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MS21000	*TASK* the task is to summarize an input biomedical literature in six sentences *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 : Attentional bias ( i.e. , differences in reaction time between drug and neutral cues ) has been associated with a variety of drug-use behaviors ( e.g. , craving , abstinence ) . Reduction of bias may ultimately reduce use . Objective : The current study examined whether attentional bias modification therapy ( ABMT ) reduced the frequency of drug use behaviors in individuals with cocaine use disorder ( CUD ) . Method : Participants ( n = 37 ) were r and omly assigned to ABMT or control therapy , which systematic ally varied how frequently probes replaced neutral ( ABMT = 100 % ; control therapy = 50 % ) relative to drug stimuli . Each intervention included 5 training sessions comprising a total of 2640 trials over 4 weeks . Clinical assessment s occurred at baseline , post-intervention , 2 weeks and 3 months posttreatment . Results : There were no baseline differences between groups on drug-use behaviors or other clinical measures . Contrary to predictions , both groups exhibited slower rather than faster reaction times for cocaine stimuli ( p = 0.005 ) at baseline , with no relationship between bias and baseline measures of drug-use behavior . Conclusions : ABMT was not more effective than our control therapy at reducing attentional bias , reducing craving or changing other drug use behaviors . Current results suggest additional replication studies are needed to assess ABMT ’s efficacy in reducing drug-use behaviors in CUD Introduction Anxiety and depression are highly prevalent during adolescence and characterized by negative interpretation biases . Cognitive bias modification of interpretations ( CBM-I ) may reduce such biases and improve emotional functioning . However , as findings have been mixed and the traditional scenario training is experienced as relatively boring , a picture-based type of training might be more engaging and effective . Methods The current study investigated short- and long-term effects ( up to 6 months ) and users ’ experience of two types of CBM-I procedure in adolescents with heightened symptoms of anxiety or depression ( N = 119 , aged 12–18 year ) . Participants were r and omized to eight online sessions of text-based scenario training , picture-word imagery training , or neutral control training . Results No significant group differences were observed on primary or secondary emotional outcomes . A decrease in anxiety and depressive symptoms , and improvements in emotional resilience were observed , irrespective of condition . Scenario training marginally reduced negative interpretation bias on a closely matched assessment task , while no such effects were found on a different task , nor for the picture-word or control group . Subjective evaluations of all training paradigms were relatively negative and the imagery component appeared particularly difficult for adolescents with higher symptom levels . Conclusions The current results question the preventive efficacy and feasibility of both CBM-I procedures as implemented here in adolescents BACKGROUND Alcoholism is a progressive neurocognitive developmental disorder . Recent evidence shows that computerized training interventions ( Cognitive Bias Modification , CBM ) can reverse some of these maladaptively changed neurocognitive processes . A first clinical study of a CBM , called alcohol-avoidance training , found that trained alcoholic patients showed less relapse at one-year follow-up than control patients . The present study tested the replication of this result , and questions about mediation and moderation . METHODS 509 alcohol-dependent patients received treatment as usual ( primarily Cognitive Behavior Therapy ) inpatient treatment . Before and after treatment , the implicit approach bias was measured with the Alcohol Approach-Avoidance Task . Half of the patients were r and omly assigned to CBM , the other half received treatment as usual only . Background variables , psychopathology and executive control were tested as possible moderating variables of CBM . One year after treatment , follow-up data about relapse were collected . RESULTS The group receiving CBM developed alcohol-avoidance behavior and reported significantly lower relapse rates at one-year follow-up . Change in alcohol-approach bias mediated this effect . Moderation analyses demonstrated that older patients and patients with a strong approach-bias at pretest profited most from CBM . CONCLUSIONS CBM is a promising treatment add-on in alcohol addiction and may counter some of the maladaptive neurocognitive effects of long-term alcoholism Attentional bias modification ( ABM ) to avoid smoking-related cues is a potentially new intervention in addition to existing therapy to stop smoking . We examined immediate and long-term changes in attentional bias and treatment outcomes from multiple ABM sessions in 67 smokers trying to quit . After assessing attentional bias baseline , participants were r and omly allocated to one of three training groups : three sessions of ABM ( avoid 3 ) ; two sessions of placebo-ABM and one session of ABM ( avoid 1 ) ; and three sessions of placebo-ABM ( avoid 0 ) . At baseline , all groups had similar positive attentional bias , which became negative at 24h post-training . After 1 month , avoid 1 and avoid 3 still exhibited negative attentional biases . Only avoid 3 maintained this effect at 6-month , but not at 12-month assessment s. ABM produced a long-lasting automatic and maintained avoidance to smoking-related cues which depended on number of sessions ; however its effects on treatment outcomes are uncertain 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 Based on information processing models of anxiety and depression , we investigated the efficacy of multiple sessions of online attentional bias modification training to reduce attentional bias and symptoms of anxiety and depression , and to increase emotional resilience in youth . Unselected adolescents ( N = 340 , age : 11 - 18 years ) were r and omly allocated to eight sessions of a dot-probe , or a visual search -based attentional training , or one of two corresponding placebo control conditions . Cognitive and emotional measures were assessed pre- and post-training ; emotional outcome measures also at three , six and twelve months follow-up . Only visual search training enhanced attention for positive information , and this effect was stronger for participants who completed more training sessions . Symptoms of anxiety and depression reduced , whereas emotional resilience improved . However , these effects were not especially pronounced in the active conditions . Thus , this large-scale r and omized controlled study provided no support for the efficacy of the current online attentional bias modification training as a preventive intervention to reduce symptoms of anxiety or depression or to increase emotional resilience in unselected adolescents . However , the absence of biased attention related to symptomatology at baseline , and the large drop-out rates at follow-up preclude strong conclusions Depression is a global health problem requiring treatment innovation . Targeting neglected cognitive aspects may provide a useful route . We tested a cognitive-training paradigm using positive mental imagery ( imagery cognitive bias modification , imagery CBM ) , developed via experimental psychopathology studies , in a r and omized controlled trial . Training was delivered via the Internet to 150 individuals with current major depression . Unexpectedly , there was no significant advantage for imagery CBM compared with a closely matched control for depression symptoms as a whole in the full sample . In exploratory analyses , compared with the control , imagery CBM significantly improved anhedonia over the intervention and improved depression symptoms as a whole for those participants with fewer than five episodes of depression and those who engaged to a threshold level of imagery . Results suggest avenues for improving imagery CBM to inform low-intensity treatment tools for depression . Anhedonia may be a useful treatment target for future work Social Anxiety Disorder ( SAD ) models implicate social threat cue vigilance ( i.e. , attentional biases ) in symptom development and maintenance . A modified dot-probe protocol has been shown to reduce SAD symptoms , in some but not all studies , presumably by modifying an attentional bias . The current r and omized controlled trial was design ed to replicate and extend such research . Participants included treatment-seeking adults ( n = 108 ; 58 % women ) who met diagnostic criteria for SAD . Participants were r and omly assigned to a st and ard ( i.e. , control ) or modified ( i.e. , active ) dot-probe protocol condition and to participate in-lab or at home . The protocol involved twice-weekly 15-min sessions , for 4 weeks , with question naires completed at baseline , post-treatment , 4-month follow-up , and 8-month follow-up . Symptom reports were assessed with repeated measures mixed hierarchical modeling . There was a main effect of time from baseline to post-treatment wherein social anxiety symptoms declined significantly ( p < .05 ) but depression and trait anxiety did not ( p > .05 ) . There were no significant interactions based on condition or participation location ( ps > .05 ) . Reductions were maintained at 8-month follow-up . Symptom reductions were not correlated with threat biases as indexed by the dot-probe task . The modified and st and ard protocol both produced significant sustained symptom reductions , whether administered in-lab or at home . There were no robust differences based on protocol type . As such , the mechanisms for benefits associated with modified dot-probe protocol s warrant additional research OBJECTIVE Attention bias modification ( ABM ) is a promising treatment for depression , but trial data remain restricted to adults . The present trial examined effects of ABM on adolescent depression . METHOD A total of 45 adolescents with major depressive disorder ( MDD ) , selected from a school population ( n = 2,731 ) using a 2-stage case-finding procedure , were r and omized to an active ABM intervention ( n = 23 ) or placebo ABM training ( n = 22 ) . In the active condition , participants completed a neutral ABM over 2 weeks for 8 sessions ( 320 trials each ) to shift attention away from sad words to neutral words . At a 9-week follow-up , they received a positive ABM for 2 weeks with 4 more sessions ( 480 trials each ) , shifting attention to positive words . The placebo training used the same tasks but shifted attention toward neutral and sad words equally often . Attentional biases and clinical status determined by semi-structured interviews and question naires were obtained before and after each training . Depressive symptoms were reassessed at 8- and 12-month follow-ups . RESULTS Greater reductions in attentional bias score and clinician-rated depressive symptoms were found for active ABM compared with placebo after initial neutral ABM . More participants no longer met diagnostic criteria for MDD in active ABM than in placebo . Greater reductions in self-reported depressive and anxious symptoms at the 12-month follow-up were also found in active ABM compared with placebo . CONCLUSION ABM may be a potential treatment tool for mild to moderate adolescent major depression . CLINICAL TRIAL REGISTRATION INFORMATION Attention Bias Modification Treatment for Major Depressive Disorder in Adolescents : A R and omized Controlled Trial ; http:// clinical trials.gov/ ; NCT02078258 High trait anger is associated with more severe alcohol use problems , and alcohol has been found to facilitate aggressive behavior among individuals with high trait anger . Treatments focused on a sample with alcohol use disorder with elevated anger could reduce alcohol use problems , as well as violence and aggression . We sought to examine the efficacy of interpretation bias modification for hostility ( IBM-H ) in a sample with high trait anger and alcohol use disorder ( AUD ) . Fifty-eight individuals with AUD and elevated trait anger were r and omly assigned to eight web-based sessions ( two per week ) of IBM-H or a healthy video control condition ( HVC ) . Measures of interpretation bias , anger , and alcohol use were administered at pre- and post-treatment and at one-month follow-up . IBM-H led to greater improvements in interpretation bias compared to HVC at post and follow-up . IBM-H also led to greater reductions in trait anger than HVC , though this was an indirect effect mediated by changes in interpretation bias . Further , IBM-H led to lower anger expression than HVC ; this was a direct ( non-mediated ) effect . Lastly , both conditions reported decreases in alcohol use and consequences following treatment , though there were no significant differences between them . These findings provide initial support for the utility of IBM-H as a brief non-confrontational intervention for AUD with elevated trait anger . Limitations and future research directions are discussed OBJECTIVE To assess the efficacy of a multiple-sessions Web-based Attentional Bias Modification ( ABM ) self-help intervention in 434 smokers who made a quit-attempt . METHOD Respondents were r and omized to receive 6 sessions of ABM- or placebo-training in a period of 2 weeks . Smoking-related cognitions ( e.g. , self-efficacy and intention to quit ) and cognitive biases ( i.e. , attentional and approach bias ) for smoking-cues were assessed before training ( pretest ) . Primary outcome -variable was continued abstinence , 6 months after baseline . Bias reduction at the posttraining assessment was the secondary outcome . A 2 × 2 mixed analysis of variance ( ANOVA ) and logistic regression analyses were conducted using the whole sample ( N = 434 ) as well as sub sample s of light to moderate smokers ( < 15 cigarettes , N = 115 ) and heavy smokers ( 15 or more cigarettes , N = 319 ) . Conservative analyses ( coding drop-outs as smokers ) as well as complete case analyses were conducted . RESULTS The ABM training had no significant effect regarding bias reduction and no behavioral effects in the whole sample of smokers . Sub sample analyses revealed a significant positive effect on continued abstinence in heavy smokers only ( complete case analyses : odds ratio [ OR ] = 3.15 ; p = .02 ; confidence interval [ CI ] = 1.24 - 7.99 ; conservative analyses : OR Output:	This review is of importance given how technology has transformed delivery of conventional therapies .
MS21001	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Summary Background In the 24-month MS-STAT phase 2 trial , we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive multiple sclerosis ( SPMS ) . We now describe the results of the MS-STAT cognitive sub study , in which we investigated the treatment effect on cognitive , neuropsychiatric , and health-related quality -of-life ( HRQoL ) outcome measures . Methods We did a secondary analysis of MS-STAT , a 24-month , double-blind , controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28 , 2008 , and Nov 4 , 2011 . Patients were r and omly assigned ( 1:1 ) to either 80 mg simvastatin ( n=70 ) or placebo ( n=70 ) . The cognitive assessment s done were the National Adult Reading Test , Wechsler Abbreviated Scale of Intelligence , Grade d Naming Test , Birt Memory and Information Processing Battery ( BMI PB ) , Visual Object and Space Perception battery ( cube analysis ) , Frontal Assessment Battery ( FAB ) , and Paced Auditory Serial Addition Test . Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Question naire . HRQoL was assessed using the self-reported 36-Item Short Form Survey ( SF-36 ) version 2 . Assessment s were done at study entry , 12 months , and 24 months . Patients , treating physicians , and outcome assessors were masked to treatment allocation . Analyses were by intention to treat . MS-STAT is registered with Clinical Trials.gov , number NCT00647348 . Findings Baseline assessment revealed impairments in 60 ( 45 % ) of 133 patients on the test of frontal lobe function ( FAB ) , and in between 13 ( 10 % ) and 43 ( 33 % ) of 130 patients in tests of non-verbal and verbal memory ( BMI PB ) . Over the entire trial , we noted significant worsening on tests of verbal memory ( T score decline of 5·7 points , 95 % CI 3·6–7·8 ; p<0·0001 ) and non-verbal memory ( decline of 6·8 points , 4·8–8·7 ; p<0·0001 ) . At 24 months , the FAB score was 1·2 points higher in the simvastatin-treated group than in the placebo group ( 95 % CI 0·2–2·3 ) . The simvastatin group also had a 2·5 points better mean physical component score of the SF-36 ( 95 % CI 0·3–4·8 ; p=0·028 ) . A treatment effect was not noted for any other outcomes . Interpretation To our knowledge , this SPMS cohort is the largest studied to date with comprehensive longitudinal cognitive , neuropsychiatric , and HRQoL assessment s. We found evidence of a positive effect of simvastatin on frontal lobe function and a physical quality -of-life measure . Although we found no effect of simvastatin on the other outcome measures , these potential effects warrant confirmation and underline the importance of fully assessing cognition and quality of life in progressive multiple sclerosis treatment trials . Funding The Moulton Foundation , the Berkeley Foundation , the Multiple Sclerosis Trials Collaboration , the Rosetrees Trust , a personal contribution from A W Pidgley CBE , and the National Institute for Health Research University College London Hospitals Biomedical Research Centre and University College London Thiazolidinediones have shown antidepressant effect in animal studies , as well as in some uncontrolled studies evaluating human subjects with concurrent major depressive disorder ( MDD ) and metabolic syndrome . Although these drugs are insulin sensitizers , they also have important anti-inflammatory , neuroprotective , and anti-excitotoxic properties . Thus , we hypothesized that they would show antidepressant effect in patients with MDD even if it was not accompanied by metabolic disturbances . In this double-blind placebo-controlled study , 40 patients with MDD ( DSM-IV-TR ) and Hamilton depression rating scale-17 ( Ham-D ) score ⩾22 were r and omized to citalopram plus pioglitazone ( 15 mg every 12 h ) ( n=20 ) or citalopram plus placebo ( n=20 ) for 6 weeks . Patients were evaluated using Ham-D ( weeks 0 , 2 , 4 , 6 ) . Repeated-measure analysis of variance ( ANOVA ) and analysis of covariance were used for comparison of scores between the two groups . Treatment response ( ⩾50 % reduction in Ham-D score ) , remission ( Ham-D score⩽7 ) , and early improvement ( ⩾20 % reduction in Ham-D score within the first 2 weeks ) were compared between the two groups using Fisher 's exact test . Pioglitazone showed superiority over placebo during the course of the trial ( F(1 , 38)=9.483 , p=0.004 ) . Patients in the pioglitazone group had significantly lower scores at all time points than the placebo group ( P<0.01 ) . Frequency of early improvement , response ( week 6 ) , and remission was significantly higher in the pioglitazone group ( 95 % , 95 % , 45 % , respectively ) than in the placebo ( 30 % , 40 % , 15 % respectively ) group ( P<0.001 , < 0.001 , 0.04 , respectively ) . Frequency of side effects was similar between the two groups . Pioglitazone is a safe and effective adjunctive short-term treatment in patients with moderate-to-severe MDD even in the absence of metabolic syndrome and diabetes ( http:// clinical trials.gov/ct2/show/NCT01109030 ) Background : Evidence suggests that anti-inflammatory medication may be effective in the treatment of depressive symptoms . In this study , we aim ed to investigate whether minocycline added to treatment as usual ( TAU ) for 3 months in patients with treatment-resistant depression will lead to an improvement in depressive symptoms . Methods : Multi-site , 12-week , double-blind , placebo-controlled , pilot trial of minocycline added to TAU for patients suffering from DSM-5 major depressive disorder , whose current episode has failed to respond to at least two antidepressants . The primary outcome measure was mean change in Hamilton Depression Rating Scale ( HAMD-17 ) scores from baseline to week 12 . Secondary measures were the Clinical Global Impression scale ( CGI ) , Patient Health Question naire-9 ( PHQ-9 ) , the Generalised Anxiety Disorder scale ( GAD-7 ) and EuroQoL ( EQ-5D ) quality -of-life question naire . Side-effect checklists were also used . Minocycline was started at 100 mg once daily ( OD ) and increased to 200 mg after 2 weeks . Results : A total of 41 participants were r and omised , with 21 in the minocycline group and 20 in the placebo group . A large decrease in HAMD scores was observed in the minocycline group compared to the placebo group ( st and ardised effect size ( ES ) –1.21 , p < 0.001 ) . CGI scores in the minocycline group also showed a large improvement compared with placebo ( odds ratio ( OR ) : 17.6 , p < 0.001 ) . PHQ-9 , GAD-7 and EQ-5D total showed more moderate improvements ( ES ~ 0.4–0.5 ) . Conclusion : The findings indicate that adjunctive minocycline leads to improvement in symptoms of treatment-resistant depression . However , our findings require replication in a larger sample . Trial Registration : Clinical Trials.gov identifier : NCT02263872 , registered October 2014 Cancer-related inflammation is an essential process in malignancies . Celecoxib , a nonsteroidal anti-inflammatory drug that acts via the selective inhibition of cyclooxygenase (COX)-2 , has shown favorable effects in several psychiatric disorders . The present study aim ed to assess the safety and efficacy of celecoxib single therapy on depressive symptoms of patients with colorectal cancer who underwent chemotherapy . The study was conducted as a 6-week , parallel-group , r and omized , double-blind , placebo-controlled trial . Forty participants r and omly received either 400mg/day celecoxib or placebo . Treatment effect was assessed using the Hamilton Depression Rating Scale ( HDRS ) and Visual Analogue Scale ( VAS ) score at baseline and at week 2 , 4 and 6 of the trial . Over 6 weeks , patients who received celecoxib showed significant improvement in scores of the Hamilton Depression rating Scale ( P=0.003 ) . When comparing the Mean Difference ( 95 % CI ) between the two groups of therapy , the celecoxib group demonstrated greater reduction in HDRS score during the study period at weeks 4 ( 1.95 , 95 % CI 0.27 - 3.63 , P value = 0.024 ) and 6 ( 2.60 , 95 % CI 0.96 - 4.23 , P=0.003 ) . This study indicates celecoxib as a potential monotherapy treatment strategy for mild to moderate depression in patients with colorectal cancer who underwent chemotherapy Objective : Conventional antidepressant treatments result in symptom remission in 30 % of those treated for major depressive disorder , raising the need for effective adjunctive therapies . Inflammation has an established role in the pathophysiology of major depressive disorder , and minocycline has been shown to modify the immune-inflammatory processes and also reduce oxidative stress and promote neuronal growth . This double-blind , r and omised , placebo-controlled trial examined adjunctive minocycline ( 200 mg/day , in addition to treatment as usual ) for major depressive disorder . This double-blind , r and omised , placebo-controlled trial investigated 200 mg/day adjunctive minocycline ( in addition to treatment as usual ) for major depressive disorder . Methods : A total of 71 adults with major depressive disorder ( Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition ) were r and omised to this 12-week trial . Outcome measures included the Montgomery – Asberg Depression Rating Scale ( primary outcome ) , Clinical Global Impression – Improvement and Clinical Global Impression – Severity , Hamilton Anxiety Rating Scale , Quality of Life Enjoyment and Satisfaction Question naire , Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool . The study was registered on the Australian and New Zeal and Clinical Trials Register : www.anzctr.org.au , # ACTRN12612000283875 . Results : Based on mixed- methods repeated measures analysis of variance at week 12 , there was no significant difference in Montgomery – Asberg Depression Rating Scale scores between groups . However , there were significant differences , favouring the minocycline group at week 12 for Clinical Global Impression – Improvement score – effect size ( 95 % confidence interval ) = −0.62 [ −1.8 , −0.3 ] , p = 0.02 ; Quality of Life Enjoyment and Satisfaction Question naire score – effect size ( confidence interval ) = −0.12 [ 0.0 , 0.2 ] , p < 0.001 ; and Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool score – 0.79 [ −4.5 , −1.4 ] , p < 0.001 . These effects remained at follow-up ( week 16 ) , and Patient Global Impression also became significant , effect size ( confidence interval ) = 0.57 [ −1.7 , −0.4 ] , p = 0.017 . Conclusion : While the primary outcome was not significant , the improvements in other comprehensive clinical measures suggest that minocycline may be a useful adjunct to improve global experience , functioning and quality of life in people with major depressive disorder . Further studies are warranted to confirm the potential of this accessible agent to optimise treatment outcomes Previous studies suggest that insulin-sensitizing agents could play a significant role in the treatment of major depression , particularly depression in patients with documented insulin resistance or those who are resistant to st and ard psychopharmacological approaches . This study aim ed to assess the effects on depressive symptoms with adjuvant treatment with the PPARγ-agonist pioglitazone . Patients ( N=37 ) with non-psychotic , non-remitting depression receiving st and ard psychiatric regimens for depression were r and omized across an insulin sensitivity spectrum in a 12-week double blind , r and omized controlled trial of pioglitazone or placebo . Improvement in depression was associated with improvement in glucose metabolism but only in patients with insulin resistance . An age effect was also shown in that response to pioglitazone was more beneficial in younger aged patients . Study findings suggest differential improvement in depression severity according to both glucose metabolic status and level of depression at baseline . A greater underst and ing of the reciprocal links between depression and IR may lead to a dramatic shift in the way in which depression is conceptualized and treated , with a greater focus on treating and /or preventing metabolic dysfunction BACKGROUND The administration of statins seems to be a promising new avenue in the treatment of patients suffering from major depressive disorder ( Output:	Anti-inflammatory agents improved antidepressant treatment effects .
MS21002	*TASK* the task is to summarize an input biomedical literature in six sentences *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 comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen ( PSA ) testing remains uncertain . METHODS We compared active monitoring , radical prostatectomy , and external-beam radiotherapy for the treatment of clinical ly localized prostate cancer . Between 1999 and 2009 , a total of 82,429 men 50 to 69 years of age received a PSA test ; 2664 received a diagnosis of localized prostate cancer , and 1643 agreed to undergo r and omization to active monitoring ( 545 men ) , surgery ( 553 ) , or radiotherapy ( 545 ) . The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up . Secondary outcomes included the rates of disease progression , metastases , and all-cause deaths . RESULTS There were 17 prostate-cancer-specific deaths overall : 8 in the active-monitoring group ( 1.5 deaths per 1000 person-years ; 95 % confidence interval [ CI ] , 0.7 to 3.0 ) , 5 in the surgery group ( 0.9 per 1000 person-years ; 95 % CI , 0.4 to 2.2 ) , and 4 in the radiotherapy group ( 0.7 per 1000 person-years ; 95 % CI , 0.3 to 2.0 ) ; the difference among the groups was not significant ( P=0.48 for the overall comparison ) . In addition , no significant difference was seen among the groups in the number of deaths from any cause ( 169 deaths overall ; P=0.87 for the comparison among the three groups ) . Metastases developed in more men in the active-monitoring group ( 33 men ; 6.3 events per 1000 person-years ; 95 % CI , 4.5 to 8.8 ) than in the surgery group ( 13 men ; 2.4 per 1000 person-years ; 95 % CI , 1.4 to 4.2 ) or the radiotherapy group ( 16 men ; 3.0 per 1000 person-years ; 95 % CI , 1.9 to 4.9 ) ( P=0.004 for the overall comparison ) . Higher rates of disease progression were seen in the active-monitoring group ( 112 men ; 22.9 events per 1000 person-years ; 95 % CI , 19.0 to 27.5 ) than in the surgery group ( 46 men ; 8.9 events per 1000 person-years ; 95 % CI , 6.7 to 11.9 ) or the radiotherapy group ( 46 men ; 9.0 events per 1000 person-years ; 95 % CI , 6.7 to 12.0 ) ( P<0.001 for the overall comparison ) . CONCLUSIONS At a median of 10 years , prostate-cancer-specific mortality was low irrespective of the treatment assigned , with no significant difference among treatments . Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring . ( Funded by the National Institute for Health Research ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) BACKGROUND Most localized prostate cancers are believed to have an indolent course . Within 15 yr of diagnosis , most deaths among men with prostate cancer ( PCa ) can be attributed to other competing causes . However , data from studies with extended follow-up are insufficient to determine appropriate treatment for men with localized disease . OBJECTIVE To investigate the long-term natural history of untreated , early-stage PCa . DESIGN , SETTING , AND PARTICIPANTS We conducted a population -based , prospect ive-cohort study using a consecutive sample of 223 patients with untreated , localized PCa from a regionally well-defined catchment area in central Sweden . All subjects were initially managed with observation . And rogen deprivation therapy was administered when symptomatic tumor progression occurred . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Based on > 30 yr of follow-up , the main outcome measures were : progression-free , cause-specific , and overall survival , and rates of progression and mortality per 1000 person-years . RESULTS AND LIMITATIONS After 32 yr of follow-up , all but 3 ( 1 % ) of the 223 men had died . We observed 90 ( 41.4 % ) local progression events and 41 ( 18.4 % ) cases of progression to distant metastasis . In total , 38 ( 17 % ) men died of PCa . Cause-specific survival decreased between 15 and 20 yr , but stabilized with further follow-up . All nine men with Gleason grade 8 - 10 disease died within the first 10 yr of follow-up , five ( 55 % ) from PCa . Survival for men with well-differentiated , nonpalpable tumors declined slowly through 20 yr , and more rapidly between 20 and 25 yr ( from 75.2 % [ 95 % confidence interval , 48.4 - 89.3 ] to 25 % [ 95 % confidence interval , 22.0 - 72.5 ] ) . It is unclear whether these data are relevant for tumors detected by elevated prostate-specific antigen levels . CONCLUSIONS Although localized PCa most often has an indolent course , local progression and distant metastasis can develop over the long term , even among patients considered low risk at diagnosis BACKGROUND Initial treatment options for low-risk clinical ly localized prostate cancer ( PCa ) include radical prostatectomy ( RP ) or observation . OBJECTIVE To examine cancer-specific mortality ( CSM ) after accounting for other-cause mortality ( OCM ) in PCa patients treated with either RP or observation . DESIGN , SETTING , AND PARTICIPANTS Using the Surveillance Epidemiology and End Results Medicare-linked data base , a total of 44 694 patients ≥65 yr with localized ( T1/2 ) PCa were identified ( 1992 - 2005 ) . INTERVENTION RP and observation . MEASUREMENTS Propensity-score matching was used to adjust for potential selection biases associated with treatment type . The matched cohort was r and omly divided into the development and validation sets . Competing-risks regression models were fitted and a competing-risks nomogram was developed and externally vali date d. RESULTS AND LIMITATIONS Overall , 22,244 ( 49.8 % ) patients were treated with RP versus 22450 ( 50.2 % ) with observation . Propensity score-matched analyses derived 11,669 matched pairs . In the development cohort , the 10-yr CSM rate was 2.8 % ( 2.3 - 3.5 % ) for RP versus 5.8 % ( 5.0 - 6.6 % ) for observation ( absolute risk reduction : 3.0 % ; relative risk reduction : 0.5 % ; p<0.001 ) . In multivariable analyses , the CSM hazard ratio for RP was 0.48 ( 0.38 - 0.59 ) relative to observation ( p<0.001 ) . The competing-risks nomogram discrimination was 73 % and 69 % for prediction of CSM and OCM , respectively , in external validation . The nature of observational data may have introduced a selection bias . CONCLUSIONS On average RP reduces the risk of CSM by half in patients aged ≥65 yr , relative to observation . The individualized protective effect of RP relative to observation may be quantified with our nomogram OBJECTIVE To assess the reasons for the dramatic surge in prostate cancer incidence from 1986 to 1991 . DESIGN Population -based study of incidence rates and procedures used to detect and diagnose prostate cancer derived from Medicare cl aims data and the National Cancer Institute 's Surveillance , Epidemiology , and End Results ( SEER ) program from 1986 to 1991 . SETTING Four SEER areas ( Connecticut ; Atlanta , Ga ; Detroit , Mich ; and Seattle -- Puget Sound , Wash ) covering approximately 6 % of the US population . PARTICIPANTS A 5 % r and om sample of male fee-for-service Medicare beneficiaries aged 65 years and older without cancer , and all men with prostate cancer diagnosed at 65 years of age and older residing in the four areas . MAIN OUTCOME MEASURES The age-adjusted rates of prostate cancer incidence , prostate needle biopsy , transurethral resection of the prostate , serum prostate-specific antigen ( PSA ) testing , and transrectal ultrasound . RESULTS The age-adjusted incidence rate of prostate cancer among men aged 65 years and older in the four SEER areas rose 82 % from 1986 to 1991 , with the largest annual increases occurring in 1990 ( 20 % ) and 1991 ( 19 % ) . Prostate needle biopsy rates increased while the use of transurethral resection of the prostate declined from 1986 to 1991 . The rising needle biopsy rate has been driven by an exponential increase in PSA testing in the general population from 1988 to 1991 and , to a much lesser extent , the increasing use of transrectal ultrasound since 1986 . The use of PSA or transrectal ultrasound has increased across age and race groups and in different geographic areas . However , there remain wide geographic variations in the use of PSA screening . CONCLUSIONS The recent dramatic epidemic of prostate cancer is likely the result of the increasing detection of tumors result ing from increased PSA screening . The magnitude and rapidity of the incidence rise suggest that changes in the intensity of medical surveillance is the most plausible explanation for this trend . IMPLICATION S The rapid diffusion of screening interventions that have the ability to detect latent asymptomatic disease leads to important concerns regarding costs and patient quality of life for men aged 65 years and older . Geographic variability in the adoption of PSA testing underscores uncertainty and disagreement about its value for reducing prostate cancer mortality . More research is required to determine the effectiveness of screening for prostate cancer BACKGROUND Few studies have reported on late declines and long-term health-related quality of life ( HRQOL ) after prostate cancer ( PCa ) treatment . OBJECTIVE We assessed long-term HRQOL following various treatments for localized PCa . DESIGN , SETTING , AND PARTICIPANTS This cohort study of HRQOL up to 10 yr after treatment used a prospect ively accrued , nationwide PCa registry that collects longitudinal patient-reported HRQOL . INTERVENTION Various primary treatments for localized PCa . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The Medical Outcomes Studies 36-item Short Form and the University of California , Los Angeles , Prostate Cancer Index characterized physical function , mental health , and sexual , urinary , and bowel function and bother . Repeated measures mixed-model analysis assessed change in HRQOL by treatment over time , and logistic regression was used to measure the likelihood of a clinical ly significant decline in HRQOL . RESULTS AND LIMITATIONS Among 3294 men , 1139 ( 34 % ) underwent nerve-sparing radical prostatectomy ( NSRP ) , 860 ( 26 % ) underwent non-NSRP , 684 ( 21 % ) underwent brachytherapy , 386 ( 12 % ) underwent external beam radiotherapy , 161 ( 5 % ) underwent primary and rogen deprivation therapy , and 64 ( 2 % ) pursued watchful waiting/active surveillance . Median follow-up was 74 mo ( interquartile range : 50 - 102 ) . Most treatments result ed in early declines in HRQOL , with some recovery over the next 1 - 2 yr and a plateau in scores thereafter . Surgery had the largest impact on sexual function and bother and on urinary function , radiation had the strongest effect on bowel function , and and rogen deprivation therapy had the strongest effect on physical function . The main limitation was attrition among the cohort . CONCLUSIONS Although most men experience initial declines in HRQOL in the first 2 yr after treatment , there is little change from 3 to 10 yr and most differences between treatments attenuated over time . PATIENT SUMMARY Various treatments for prostate cancer result in a distinct constellation of adverse effects on health-related quality of life , which may have a long-term impact . These findings are helpful regarding shared decision making over choice of primary treatment BACKGROUND Using observational data to assess the relative effectiveness of alternative cancer treatments is limited by patient selection into treatment , which often biases interpretation of outcomes . We evaluated methods for addressing confounding in treatment and survival of patients with early-stage prostate cancer in observational data and compared findings with those from a benchmark r and omized clinical trial . METHODS We selected 14 302 early-stage prostate cancer patients who were aged 66 - 74 years and had been treated with radical prostatectomy or conservative management from linked Surveillance , Epidemiology , and End Results -Medicare data from January 1 , 1995 , through December 31 , 2003 . Eligibility criteria were similar to those from a clinical trial used to benchmark our analyses . Survival was measured through December 31 , 2007 , by use of Cox proportional ha Output:	In the subgroup analysis according to the age and follow-up time , the results favored the RP and there was no specific factor affecting the outcomes . CONCLUSIONS RP offers a better survival rate than CT in patients with localized prostate cancer .
MS21003	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing – remitting multiple sclerosis . This post hoc analysis of the Phase III TOWER study evaluated the effects of teriflunomide treatment on five severe relapse outcomes : relapses with sequelae defined by an increase in Exp and ed Disability Status Scale (EDSS)/functional system ( FS ) score ( sequelae-EDSS/FS ) 30 days post relapse ; relapses with sequelae defined by the investigator ( sequelae-investigator ) ; relapses leading to hospitalization ; relapses treated with intravenous corticosteroids ; and intense relapses using the definition of Panitch et al. from the EVIDENCE study based on specified increases in EDSS for severe relapses . Adjusted annualized rates for the five severe relapse outcomes were derived using a Poisson model with robust error variance , with treatment , baseline EDSS strata and region as covariates . Compared with placebo , teriflunomide significantly reduced annualized rates of relapses with sequelae-EDSS/FS [ 14 mg , 36.6 % ( p = 0.0021 ) ; 7 mg , 31.3 % ( p = 0.0104 ) ] and sequelae-investigator [ 14 mg only , 53.5 % ( p = 0.0004 ) ] , relapses leading to hospitalization [ 14 mg only , 33.6 % ( p = 0.0155 ) ] , relapses requiring intravenous corticosteroids [ 14 mg , 35.7 % ( p = 0.0002 ) ; 7 mg , 21.5 % ( p = 0.0337 ) ] , and intense relapses [ 14 mg only , 52.5 % ( p = 0.0015 ) ] . Patients treated with teriflunomide 14 mg spent significantly fewer nights in hospital for relapse ( p = 0.009 ) and had lower annualized rates of all hospitalizations ( p = 0.030 ) . Taken together , the positive effects of teriflunomide on severe relapses indicate that teriflunomide may reduce relapse-related healthcare costs Objective : To evaluate teriflunomide as add-on therapy to ongoing stable-dosed interferon-&bgr ; ( IFN&bgr ; ) in patients with relapsing forms of multiple sclerosis ( RMS ) . Methods : A total of 118 patients with RMS were r and omly assigned 1:1:1 to receive oral placebo or teriflunomide , 7 or 14 mg , once daily for 24 weeks ; 86 patients entered the 24-week extension . The primary objective was to evaluate safety ; secondary objectives were to evaluate the effects of treatment on disease activity assessed by MRI and relapse rate . Results : Teriflunomide was well tolerated with a low and similar incidence of treatment-emergent adverse events ( TEAEs ) across the 3 groups ; TEAEs led to treatment discontinuation of 4.9 % , 8.1 % , and 7.9 % of patients in the placebo , 7-mg , and 14-mg groups , respectively . The number of gadolinium-enhancing T1 ( T1-Gd ) lesions was reduced in both teriflunomide groups , with relative risk reductions ( RRRs ) of 84.6 % ( p = 0.0005 ) and 82.8 % ( p < 0.0001 ) for 7 and 14 mg , respectively , compared with IFN&bgr ; alone at 48 weeks . T1-Gd lesion volume was also reduced in the 7-mg group ( RRR 72.1 % , p = 0.1104 ) and 14-mg group ( RRR 70.6 % , p = 0.0154 ) . A trend toward dose-dependent reduction in annualized relapse rate was also noted ( RRRs 32.6 % [ p = 0.4355 ] and 57.9 % [ p = 0.1005 ] for 7 and 14 mg , respectively ) . Conclusion : Teriflunomide as add-on therapy to IFN&bgr ; had acceptable safety and tolerability and reduced MRI disease activity compared with IFN&bgr ; alone . Classification of evidence : This study provides Class II evidence that teriflunomide , 7 and 14 mg , added to IFN&bgr ; , is safe . The T1-Gd lesion burden was significantly reduced with both teriflunomide doses . GLOSSARY AE : adverse event ALT : alanine aminotransferase ARR : annualized relapse rate DMT : disease-modifying therapy EDSS : Exp and ed Disability Status Scale IFN&bgr ; : interferon-&bgr ; MS : multiple sclerosis NAb : neutralizing antibody PML : progressive multifocal leukoencephalopathy RMS : relapsing multiple sclerosis RRR : relative risk reduction TEAE : treatment-emergent adverse event TEMSO : Teriflunomide Multiple Sclerosis Oral T1-Gd : gadolinium-enhancing T1 ULN : upper limit of Background : Teriflunomide , a dihydro-orotate dehydrogenase inhibitor , has immunomodulatory effects , including the ability to suppress experimental allergic encephalomyelitis . In this r and omized , double-blind , placebo-controlled Phase II study , the authors examined the safety and efficacy of oral teriflunomide in multiple sclerosis ( MS ) with relapses . Methods : Patients ( n = 179 ) with relapsing – remitting MS ( n = 157 ) or secondary progressive MS with relapses ( n = 22 ) were r and omized to receive placebo , teriflunomide 7 mg/day , or teriflunomide 14 mg/day for 36 weeks . MRI brain scans were performed every 6 weeks . The primary endpoint was the number of combined unique active lesions per MRI scan . Secondary endpoints included MRI-defined disease burden , relapse frequency , and disability increase . Results : The median number of combined unique active lesions per scan was 0.5 , 0.2 , and 0.3 in the placebo , teriflunomide 7 mg/day ( p < 0.03 vs placebo ) , and teriflunomide 14 mg/day ( p < 0.01 vs placebo ) groups during the 36-week double-blind treatment phase . Teriflunomide-treated patients also had significantly fewer T1 enhancing lesions per scan , new or enlarging T2 lesions per scan , and new T2 lesions . Patients receiving teriflunomide 14 mg/day had significantly reduced T2 disease burden . Teriflunomide treatment result ed in trends toward a lower annualized relapse rate and fewer relapsing patients ( 14 mg/day only ) vs placebo . Significantly fewer patients receiving teriflunomide 14 mg/day vs placebo demonstrated disability increase . Treatment was well tolerated ; numbers of adverse events and serious adverse events were similar in all treatment groups . Conclusion : Oral teriflunomide was effective in reducing MRI lesions and was well tolerated in patients with relapsing multiple sclerosis BACKGROUND Teriflunomide is a new oral disease-modifying therapy for relapsing forms of multiple sclerosis . METHODS We concluded a r and omized trial involving 1088 patients with multiple sclerosis , 18 to 55 years of age , with a score of 0 to 5.5 on the Exp and ed Disability Status Scale and at least one relapse in the previous year or at least two relapses in the previous 2 years . Patients were r and omly assigned ( in a 1:1:1 ratio ) to placebo , 7 mg of teriflunomide , or 14 mg of teriflunomide once daily for 108 weeks . The primary end point was the annualized relapse rate , and the key secondary end point was confirmed progression of disability for at least 12 weeks . RESULTS Teriflunomide reduced the annualized relapse rate ( 0.54 for placebo vs. 0.37 for teriflunomide at either 7 or 14 mg ) , with relative risk reductions of 31.2 % and 31.5 % , respectively ( P<0.001 for both comparisons with placebo ) . The proportion of patients with confirmed disability progression was 27.3 % with placebo , 21.7 % with teriflunomide at 7 mg ( P=0.08 ) , and 20.2 % with teriflunomide at 14 mg ( P=0.03 ) . Both teriflunomide doses were superior to placebo on a range of end points measured by magnetic resonance imaging ( MRI ) . Diarrhea , nausea , and hair thinning were more common with teriflunomide than with placebo . The incidence of elevated alanine aminotransferase levels ( ≥1 times the upper limit of the normal range ) was higher with teriflunomide at 7 mg and 14 mg ( 54.0 % and 57.3 % , respectively ) than with placebo ( 35.9 % ) ; the incidence of levels that were at least 3 times the upper limit of the normal range was similar in the lower- and higher-dose teriflunomide groups and the placebo group ( 6.3 % , 6.7 % , and 6.7 % , respectively ) . Serious infections were reported in 1.6 % , 2.5 % , and 2.2 % of patients in the three groups , respectively . No deaths occurred . CONCLUSIONS Teriflunomide significantly reduced relapse rates , disability progression ( at the higher dose ) , and MRI evidence of disease activity , as compared with placebo . ( Funded by Sanofi-Aventis ; TEMSO Clinical Trials.gov number , NCT00134563 . ) Background : The Teriflunomide Multiple Sclerosis Oral ( TEMSO ) trial , a r and omized , double-blind , placebo-controlled phase III study , demonstrated that teriflunomide significantly reduced annualized relapse rate ( ARR ) , disease progression and magnetic resonance imaging ( MRI ) activity , with a favorable safety profile in relapsing multiple sclerosis ( RMS ) patients . Objective : The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified subgroups . Methods : RMS patients ( n=1088 ) were r and omized to placebo or teriflunomide , 7 mg or 14 mg , once daily , for 108 weeks . Subgroup analyses were performed for ARR and disability progression by baseline demographics ( gender , race , age ) , disease characteristics ( Exp and ed Disability Status Scale ( EDSS ) strata , relapse history , multiple sclerosis ( MS ) subtype ) , MRI parameters ( gadolinium-enhancing lesions , total lesion volume ) and prior use of MS drugs . A generalized estimating equation method and Cox regression model were used to assess consistency of the treatment effect across subgroups , utilizing a treatment-by-subgroup interaction test for each factor separately . Results : Reductions in ARR and disability progression were consistent across subgroups in favor of teriflunomide , with no treatment-by-subgroup interaction test reaching statistical significance . Conclusion : The positive effects of teriflunomide were demonstrated consistently across subgroups in TEMSO Background : Teriflunomide , an oral disease-modifying therapy in development for patients with relapsing forms of multiple sclerosis ( RMS ) , was well tolerated and effective in reducing magnetic resonance imaging ( MRI ) lesions in 179 RMS patients in a phase 2 36-week , placebo-controlled study . Methods : A total of 147 patients who completed the core study entered an open-label extension . Teriflunomide patients continued their assigned dose , and placebo patients were re-allocated to teriflunomide , 7 mg/day or 14 mg/day . An interim analysis was performed at a cut-off on January 8 2010 . Results : The mean and median duration of study treatment , including both the core and extension phase , from baseline to the interim cut-off , was 5.6 years ( st and ard deviation : 2.7 years ) and 7.1 years ( range : 0.05–8.5 years ) , respectively . Of 147 patients , 62 ( 42.2 % ) discontinued ( 19 % due to treatment-emergent adverse events ( TEAEs ) ) . The most common TEAEs were mild infections , fatigue , sensory disturbances and diarrhoea . No serious opportunistic infections occurred , with no discontinuations due to infection . Asymptomatic alanine aminotransferase increases ( ≤3 × upper limit of normal ( ULN ) ) were common ( 7 mg , 64.2 % ; 14 mg , 62.1 % ) ; increases > 3 × ULN were similar across groups ( 7 mg , 12.3 % ; 14 mg , 12.1 % ) . Mild decreases in neutrophil counts occurred ; none led to discontinuation . The incidence of malignancies was comparable to that of the general population , and cases were not reminiscent of those observed in immunocompromised patients . Annualised relapse rates remained low , minimal disability progression was observed , with a dose-dependent benefit with teriflunomide 14 mg for several MRI parameters . Conclusion : Ter Output:	MAIN RESULTS Five studies involving 3231 people evaluated the efficacy and safety of teriflunomide 7 mg and 14 mg , alone or with add-on IFNβ , versus placebo or IFNβ-1a for adults with relapsing forms of MS and an entry Exp and ed Disability Status Scale score of less than 5.5.Overall , there were obvious clinical heterogeneities due to diversities in study design s or interventions and method ological heterogeneities across studies . When taking the effect of drop-outs into consideration , the likely-case scenario analyses still showed a benefit in reducing the number of participants with at least one relapse , but not for the number of participants with disability progression . In terms of safety profile , the most common adverse events associated with teriflunomide were diarrhoea , nausea , hair thinning , elevated alanine aminotransferase , neutropenia and lymphopenia . These adverse events had a dose-related effects and rarely led to treatment discontinuation . There was low- quality evidence to support that teriflunomide at a dose of 7 mg/day or 14 mg/day as monotherapy reduces both the number of participants with at least one relapse and the annualized relapse rate over one year or two years of treatment in comparison with placebo . The common adverse effects were diarrhoea , nausea , hair thinning , elevated alanine aminotransferase , neutropenia and lymphopenia . These adverse effects were mostly mild-to-moderate in severity , but had a dose-related effect .
MS21004	*TASK* the task is to summarize an input biomedical literature in six sentences *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 pilot r and omized controlled trial evaluated the feasibility of conducting a full scale study and compared the efficacy of exercise , spinal manipulation , and a mind-body therapy called Neuro Emotional Technique for the treatment of pregnancy-related low back pain , a common morbidity of pregnancy . Methods Healthy pregnant women with low back pain of insidious onset were eligible to enroll in the study at any point in their pregnancy . Once enrolled , they remained in the study until they had their babies . Women were r and omly allocated into one of three treatment groups using opaque envelopes . The treatment schedule paralleled the prenatal care schedule and women received individualized intervention . Our null hypothesis was that spinal manipulation and Neuro Emotional Technique would perform no better than exercise in enhancing function and decreasing pain . Our primary outcome measure was the Rol and Morris Disability Question naire and our secondary outcome measure was the Numeric Pain Rating Scale . Intention to treat analysis was conducted . For the primary analysis , regression was conducted to compare groups on the outcome measure scores . In a secondary responder analysis , difference in proportions of participants in attaining 30 % and 50 % improvement were calculated . Feasibility factors for conducting a future larger trial were also evaluated such as recruitment , compliance to study protocol s , cost , and adverse events . Results Fifty-seven participants were r and omized into the exercise ( n = 22 ) , spinal manipulation ( n = 15 ) , and Neuro Emotional Technique ( n = 20 ) treatment arms . At least 50 % of participants in each treatment group experienced clinical ly meaningful improvement in symptoms for the Rol and Morris Disability Question naire . At least 50 % of the exercise and spinal manipulation participants also experienced clinical ly meaningful improvement for the Numeric Pain Rating Scale . There were no clinical ly meaningful or statistically significant differences between groups in any analysis . Conclusions This pilot study demonstrated feasibility for recruitment , compliance , safety , and affordability for conducting a larger study in the future . Spinal manipulation and exercise generally performed slightly better than did Neuro Emotional Technique for improving function and decreasing pain , but the study was not powered to detect the between-group differences as statistically significant . Trial registration Clinical Trials.gov ( Identifier : NCT00937365 ) Background Previous publications indicate that acupuncture is efficient for the treatment of pelvic girdle pain , PGP , in pregnant women . However , the use of acupuncture for PGP is rare due to insufficient documentation of adverse effects of this treatment in this specific condition . The aim of the present work was to assess adverse effects of acupuncture on the pregnancy , mother , delivery and the fetus/neonate in comparison with women that received stabilising exercises as adjunct to st and ard treatment or st and ard treatment alone . Methods In all , 386 women with PGP entered this controlled , single-blind trial . They were r and omly assigned to st and ard treatment plus acupuncture ( n = 125 ) , st and ard treatment plus specific stabilising exercises ( n = 131 ) or to st and ard treatment alone ( n = 130 ) for 6 weeks . Acupuncture that may be considered strong was used and treatment was started as early as in the second trimester of pregnancy . Adverse effects were recorded during treatment and throughout the pregnancy . Influence on the fetus was measured with cardiotocography ( CTG ) before-during and after 43 acupuncture sessions in 43 women . A st and ardised computerized method to analyze the CTG reading numerically ( Oxford 8000 , Oxford , Engl and ) was used . After treatment , the women rated their overall experience of the treatment and listed adverse events if any in a question naire . Data of analgesia and oxytocin augmentation during labour , duration of labour , frequency of preterm birth , operative delivery , Apgar score , cord-blood gas/acid base balance and birth weight were also recorded . Results There were no serious adverse events after any of the treatments . Minor adverse events were common in the acupuncture group but women rated acupuncture favourably even despite this . The computerized or visually assessed CTG analyses of antenatal recordings in connection with acupuncture were all normal . Conclusion This study shows that acupuncture administered with a stimulation that may be considered strong led to minor adverse complaints from the mothers but had no observable severe adverse influences on the pregnancy , mother , delivery or the fetus/neonate Objective : The objective of this study was to investigate if the research process to evaluate the effect of foot manipulation on pregnancy‐related pelvic girdle pain ( PPGP ) is feasible . Methods : A r and omized , single‐blind ( patients and evaluators ) pilot trial was performed to compare foot manipulation to a comparative group at 6‐weekly treatment sessions at 5 physiotherapy outpatient clinics in Skaraborg primary care ( Skövde , Sweden ) . Women at 12 to 31 weeks of pregnancy with well‐defined PPGP ( n = 97 ) and joint dysfunction or decreased range of movement in the feet were included . Women with a twin pregnancy , low back pain , rheumatoid arthritis , or other serious diseases and those who had previous foot manipulation were excluded . Visual analog scale scores were recorded before study start , before and after each treatment session , and 3 months after delivery . Results : One‐hundred and two women were eligible , and 97 were included ( group 1 : foot manipulation , n = 47 ; group 2 : comparative treatment , n = 50 ) ; 40 and 36 in the foot manipulation and comparative treatment groups , respectively , completed the study . The foot manipulation group had a nonsignificant pain relief score compared with that of the comparative group , which had higher pain relief scores . The difference was most pronounced at the first and second treatment sessions . A power analysis showed that at least 250 individuals would be needed in each group to confirm the effect of foot manipulation . Conclusions : This study showed that it is feasible to assess the effect of foot manipulation on PPGP in a multicenter physical therapy outpatient clinic setting . A new larger study should choose a different comparative method and test this hypothesis in a full‐scale trial Background The aim of this study was to investigate the outcome of chiropractic management for a subgroup of pregnant women with dominating one-sided pelvic girdle pain ( PGP ) . Methods The study population was recruited from a prospect i ve longitudinal cohort study of pregnant women . Women reporting pelvic pain ( PP ) , and who were diagnosed with dominating one-sided PGP after a clinical examination , were invited to participate in the intervention study . Recruitment took place either at 18 weeks , or after an SMS-tracking up to week 29 . The women were r and omized into a treatment group or a control group . The treatment group received chiropractic treatment individualized to each woman with regards to treatment modality and number of treatments . The control group was asked to return to conventional primary health care . The primary outcome measure was new occurrence of full time and /or grade d sick leave due to PP and /or low back pain . Secondary outcome measures were self-reported PP , physical disability and general health status . Proportion of women reporting new occurrence of sick leave were compared using Chi squared tests . Differences in secondary outcome measures were estimated using linear regression analyses . Results Fifty-Six women were recruited , and 28 of them were r and omized into the treatment group , and 28 into the control group . There was no statistically significant difference in sick leave , PP , disability or general health status between the two groups during pregnancy or after delivery . Conclusion The study did not demonstrate superiority of chiropractic management over conventional care for dominating one-sided PGP during pregnancy . However , the analyses revealed wide confidence intervals containing both positive and negative clinical ly relevant effects . Trial registration The study was registered in Clinical Trials.gov ( NCT01098136 ; 22/03/2010 ) BACKGROUND Many pregnant women experience low back pain . Acupuncture appears to be a safe , promising intervention but evidence is needed about its clinical effectiveness and cost-effectiveness . OBJECTIVES To assess the feasibility of a future large r and omised controlled trial ( RCT ) testing the additional benefit of adding acupuncture to st and ard care ( SC ) for pregnancy-related back pain . DESIGN Phase 1 : a question naire survey described current care for pregnancy-related back pain . Focus groups and interviews with midwives , physiotherapists and pregnant women explored acceptability and feasibility of acupuncture and the proposed RCT . Phase 2 : a single-centre pilot RCT . Participants were identified using six methods and r and omised to SC , SC plus true acupuncture or SC plus non-penetrating acupuncture . PARTICIPANTS Phase 1 : 1093 physiotherapists were surveyed and 15 midwives , 21 physiotherapists and 17 pregnant women participated in five focus groups and 20 individual interviews . Phase 2 : 125 women with pregnancy-related back pain participated . INTERVENTIONS SC : a self-management booklet and onward referral for one-to-one physiotherapy ( two to four sessions ) for those who needed it . SC plus true acupuncture : the self-management booklet and six to eight treatments with a physiotherapist comprising true ( penetrating ) acupuncture , advice and exercise . SC plus non-penetrating acupuncture : the self-management booklet and six to eight treatments with a physiotherapist comprising non-penetrating acupuncture , advice and exercise . MAIN OUTCOME MEASURES Pilot RCT outcomes included recruitment rates , treatment fidelity , follow-up rate , patient-reported pain and function , quality of life and health-care re source use . Birth and neonatal outcomes were also assessed . Staff overseeing outcome data collection were blind to treatment allocation . RESULTS Phase 1 : 629 ( 57.5 % ) physiotherapists responded to the survey , 499 were experienced in treating pregnancy-related back pain and reported 16 advice and 18 treatment options . Typical treatment comprised two to four individual sessions of advice and exercise over 6 weeks . Acupuncture was reported by 24 % . Interviews highlighted the impact of back pain and paucity of effective interventions . Women and midwives strongly supported a RCT and expressed few concerns . Physiotherapists ' concerns about acupuncture in pregnancy informed a training programme prior to the pilot RCT . Phase 2 : We recruited 125 of 280 potentially eligible women ( 45 % ) in 6 months and r and omised 41 to SC and 42 each to the SC plus true acupuncture and SC plus non-penetrating acupuncture arms . Analysis was conducted with 124 participants ( 41 , 42 and 41 , respectively ) as one participant was r and omised in error . Three of six recruitment methods were the most successful . In total , 10 % of women ( n = 4 ) r and omised to SC alone accessed one-to-one physiotherapy and received an average of two treatments . The average number of treatments was six for both SC plus true acupuncture and SC plus non-penetrating acupuncture . Treatments were in line with protocol s. Eight-week follow-up was 74 % . Patient-reported outcomes ( pain , function and quality of life ) favoured the addition of acupuncture . There was no evidence of serious adverse events on mothers or birth and neonatal outcomes . The Pelvic Girdle Question naire was found to be an appropriate outcome measure for a future trial . CONCLUSIONS A future main RCT is feasible and would be welcomed by women and clinicians . Longer-term follow-up and further follow-up efforts are recommended for a main trial . TRIAL REGISTRATION Current Controlled Trials IS RCT N49955124 . FUNDING This project was funded by the National Institute of Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 20 , No. 33 . See the NIHR Journals Library website for further project information Background . Low back and pelvic pain is common in pregnancy and postpartum , but there is no well documented effect of treatment in pregnancy . The aim of the study was to assess whether a group intervention program for pregnant women with pelvic girdle pain has any effect on pain and daily function postpartum . Methods . Pregnant women with pelvic pain between the 18th and 32nd week of gestation were invited to participate in a r and omized clinical study . Among 958 examined women , 569 ( 59 % ) fulfilled the inclusion criteria . Women r and omized to the intervention group ( n = 275 ) participated in an education program that consisted of information , ergonomics , exercises , pain management , advice for daily life movement , pelvic belt/crutches , and information about delivery . Women r and omized to the control group ( n = 285 ) were not offered any treatment , but were free to seek advice or other treatment . Clinical measures and self‐evaluated utility of the intervention were measured by a visual analogue scale 0–10 . Results . Mean debut of pelvic girdle pain in pregnancy was at week 15 . Altogether 42 % of the women reported problems with low back pain earlier , and 34 % reported a family history of pelvic girdle pain in pregnancy . Median visual analogue scale score for all activities at inclusion was 6 both in the control group and the intervention group . At 6 and 12 months postpartum the score was reduced to 1.7/1.6 and 1.1/0.9 . In the intervention group , 75 % marked a self‐evaluated utility visual analogue scale score > 7 . In the control group , 60 % had search ed for alternative treatment . Conclusions . Postpartum pelvic girdle pain improved with time both in the intervention group and the control group , but there were no statistically significant differences between the groups . Self‐evaluated utility of the intervention was , Output:	‘ Pain ’ was the most commonly reported outcome in both pelvic girdle pain and lumbopelvic pain studies . Conclusions A wide variety of outcomes and outcome measurements are used in studies on pelvic girdle pain and lumbopelvic pain .
MS21005	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives —To evaluate the hormonal response to strenuous endurance exercise performed by elite athletes . Methods —Nine professional cyclists ( mean ( SD ) age 28 ( 1 ) years ; mean ( SD ) Vo2max 75.3 ( 2.3 ) ml/kg/min ) who participated in a three week tour race ( Vuelta a España 1999 ) were selected as subjects . Morning urinary levels of 6-sulphatoxymelatonin ( aMT6s ) and morning serum levels of testosterone , follicle stimulating ( FSH ) , luteinising hormone ( LH ) , and cortisol were measured in each subject at t0 ( before the competition ) , t1 ( end of first week ) , t2 ( end of second week ) , and t3 ( end of third week ) . Urine sample s of aMT6s were also evaluated in the evening at t0 , t1 , t2 , and t3 . Results —Mean urinary aMT6s levels had increased significantly ( p<0.01 ) during the day after each stage ( 1091 ( 33 ) v 683 ( 68 ) ng/ml at t1 ; 955 ( 19 ) v 473 ( 53 ) ng/ml at t2 ; 647 ( 61 ) v 337 ( 47 ) ng/ml at t3 ) . Both morning and evening aMT6s levels decreased significantly during the study . A similar pattern was observed for morning serum levels of cortisol and testosterone . Conclusions —The results suggest that the basal activity of the pineal gl and , adrenal gl and s , and testis may be decreased after consecutive days of intense , long term exercise The acute response of free salivary testosterone ( T ) and cortisol ( C ) concentrations to four resistance exercise ( RE ) protocol s in 23 elite men rugby players was investigated . We hypothesized that hormonal responses would differ among individuals after four distinct RE protocol s : four sets of 10 repetitions ( reps ) at 70 % of 1 repetition maximum ( 1RM ) with 2 minutes ' rest between sets ( 4 × 10 - 70 % ) ; three sets of five reps at 85 % 1RM with 3 minutes ' rest ( 3 × 5 - 85 % ) ; five sets of 15 reps at 55 % 1RM with 1 minute 's rest ( 5 × 15 - 55 % ) ; and three sets of five reps at 40 % 1RM with 3 minutes ' rest ( 3 × 5 - 40 % ) . Each athlete completed each of the four RE protocol s in a r and om order on separate days . T and C concentrations were measured before exercise ( PRE ) , immediately after exercise ( POST ) , and 30 minutes post exercise ( 30 POST ) . Each protocol consisted of four exercises : bench press , leg press , seated row , and squats . Pooled T data did not change as a result of RE , whereas C declined significantly . Individual athletes differed in their T response to each of the protocol s , a difference that was masked when examining the pooled group data . When individual data were retrospectively tabulated according to the protocol in which each athlete showed the highest T response , a significant protocol -dependent T increase for all individuals was revealed . Therefore , RE induced significant individual , protocol -dependent hormonal changes lasting up to 30 minutes after exercise . These individual responses may have important ramifications for modulating adaptation to RE and could explain the variability often observed in studies of hormonal response to RE PURPOSE To assess the effects of different modes of morning ( AM ) exercise on afternoon ( PM ) performance and salivary hormone responses in professional rugby union players . METHODS On 4 occasions ( r and omized , crossover design ) , 15 professional rugby players provided AM ( ~8 AM ) and PM ( ~2 PM ) saliva sample s before PM assessment s of countermovement-jump height , reaction time , and repeated-sprint ability . Control ( passive rest ) , weights ( bench press : 5 × 10 repetitions , 75 % 1-repetition maximum , 90-s intraset recovery ) , cycling ( 6 × 6-s maximal sprint cycling , 7.5 % body mass load , 54-s intraset recovery ) , and running ( 6 × 40-m maximal sprints , 20-s intraset recovery ) interventions preceded ( ~5 h ) PM testing . RESULTS PM sprint performance improved ( P < .05 ) after weights ( > 0.15 ± 0.19 s , > 2.04 % ± 2.46 % ) and running ( > 0.15 ± 0.17 s , > 2.12 % ± 2.22 % ) but not cycling ( P > .05 ) . PM jump height increased after cycling ( 0.012 ± 0.009 m , 2.31 % ± 1.76 % , P < .001 ) and running ( 0.020 ± 0.009 m , 3.90 % ± 1.79 % , P < .001 ) but not weights ( P = .936 ) . Reaction time remained unchanged between trials ( P = .379 ) . Relative to control ( 131 ± 21 pg/mL ) , PM testosterone was greater in weights ( 21 ± 23 pg/mL , 17 % ± 18 % , P = .002 ) and running ( 28 ± 26 pg/mL , 22 % ± 20 % , P = .001 ) but not cycling ( P = .072 ) . Salivary cortisol was unaffected by AM exercise ( P = .540 ) . CONCLUSIONS All modes of AM exercise improved at least 1 marker of PM performance , but running appeared the most beneficial to professional rugby union players . A rationale therefore exists for preceding PM competition with AM exercise 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 . Abstract This study assessed the acute response of salivary testosterone and cortisol concentrations to four exercise protocol s in 27 elite male rugby players . Each athlete completed four protocol s in r and om order on separate in-season weeks . Two protocol s were resistance training based consisting of four exercises ( high pull , bench press , squat and chin-ups/prone row ) : Protocol 1 consisted of 5 sets of 15 repetitions at 55 % of 1 repetition maximum ( 1 RM ) with 1-minute rest ( 5 × 15–55 % ) . Protocol 2 consisted of three sets of five repetitions at 85 % 1 RM with 2-minute rest ( 3 × 5–85 % ) . Protocol 3 was a strongman ( STRNG ) session consisting of three stations within a circuit of exercises that included exercises such as battling ropes , prowler push , farmer 's walk and tyre flips . Protocol 4 was based on boxing and wrestling inspired exercises ( combative – COMB ) . Salivary testosterone and cortisol concentrations were measured before ( PRE ) and immediately after exercise ( POST ) . Testosterone did not significantly change as a result of any intervention , whereas cortisol declined and the testosterone to cortisol ( T/C ) ratio increased significantly in both the 5 × 15–55 % and 3 × 5–85 % protocol . When results were retrospectively grouped and analysed according to the protocol that demonstrated the greatest absolute testosterone response , significant ( P < 0.01 ) increases for the 5 × 15–55 % , STRNG and COMB protocol s were observed . The individualised hormone response to exercise observed in this study highlights the importance of recognising a protocol -dependent approach to training athletes . Furthermore this study also highlights a potential usefulness of employing STRNG and COMB training protocol s as an alternative stimulus to resistance training Previous studies have shown that visual images can produce rapid changes in testosterone concentrations . We explored the acute effects of video clips on salivary testosterone and cortisol concentrations and subsequent voluntary squat performance in highly trained male athletes ( n=12 ) . Saliva sample s were collected on 6 occasions immediately before and 15 min after watching a brief video clip ( approximately 4 min in duration ) on a computer screen . The watching of a sad , erotic , aggressive , training motivational , humorous or a neutral control clip was r and omised . Subjects then performed a squat workout aim ed at producing a 3 repetition maximum ( 3RM ) lift . Significant ( P<0.001 ) relative ( % ) increases in testosterone concentrations were noted with watching the erotic , humorous , aggressive and training videos ( versus control and sad ) , with testosterone decreasing significantly ( versus control ) after the sad clip . The aggressive video also produced an elevated cortisol response ( % change ) and more so than the control and humorous videos ( P<0.001 ) . A significant ( P<0.003 ) improvement in 3RM performance was noted after the erotic , aggressive and training clips ( versus control ) . A strong within-individual correlation ( mean r=0.85 ) was also noted between the relative changes in testosterone and the 3RM squats across all video sessions ( P<0.001 ) . In conclusion , different video clips were associated with different changes in salivary free hormone concentrations and the relative changes in testosterone closely mapped 3RM squat performance in a group of highly trained males . Thus , speculatively , using short video presentations in the pre-workout environment offers an opportunity for underst and ing the outcomes of hormonal change , athlete behaviour and subsequent voluntary performance Output:	This review found that both physical and psychosocial interventions can alter testosterone and cortisol , and physical performance areas important for rugby union are affected by these changes . The limited literature in the field supports the notion that physical interventions of short duration and high intensity , and psychosocial interventions that create a positive environment may elicit a hormonal response that is associated with favorable performance outcomes . Overall , this review identified that when the testosterone responses to an intervention are notably greater than that of cortisol , favorable outcomes are likely .
MS21006	*TASK* the task is to summarize an input biomedical literature in six sentences *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 : Cardiovascular risk largely depends on diet , antioxidant status , and gene polymorphisms . Low-fat meat ( CM ) and walnut-enriched meat ( WM ) products may exert potential beneficial health effects with respect to conventional meat products . Objective : To compare the effects of consuming WM vs CM on reduced and oxidized glutathione , lipoperoxides , α- and γ-tocopherol levels , and paraoxonase ( PON-1 ) , catalase ( CAT ) , and superoxide dismutase ( SOD ) activities in 22 volunteers ( mean age 54.8 years and body mass index 29.6 kg/m2 ) at high cardiovascular risk carrying different PON-1 192/55 polymorphisms . Design : The study was a 5-week nonblinded , r and omized , crossover , controlled trial . Results : In general term , WM vs CM improved the volunteers ' antioxidant status , with several result modifications occurring after the WM period . CM consumption increased oxidized glutathione and decreased PON-1 activity ( at least p < 0.05 ) . When WM vs CM effects were compared , SOD , CAT , and PON-1 enzyme activities increased ( at least p < 0.05 ) in PON-1 192QQ carriers . γ-tocopherol levels and SOD and PON-1 activities increased in PON-1 192QR+RR carriers besides the significant decrease of lipoperoxide levels . In PON-1 55LM+MM carriers , the intervention increased significantly all the investigated enzyme activities and glutathione levels , whereas PON-1 55LL carriers increased their PON-1 activities . Conclusions : WM consumption should be preferred to CM . The intake of WM vs CM increased PON-1 but the effect upon other antioxidant enzymes and substrates varied depending on the individual 's PON-1 polymorphism . PON-1 192QR+RR carriers appear the targets for WM consumption as they increased enzyme activities and γ-tocopherol levels and decreased lipoperoxides BACKGROUND This study was conducted to determine the effect of fish oil ( FO ) supplements on high density lipoprotein cholesterol ( HDL-C ) , apolipoprotein-AI ( Apo-AI ) , malondialdehyde ( MDA ) , arylesterase ( Aryl ) , and paraoxonase-1 ( PON1 ) activity in female patients with rheumatoid arthritis ( RA ) . METHODS A total of 90 RA patients were r and omly allocated into two groups that were treated with one FO pearl ( 1 gr ) daily or placebo for three months in addition to conventional treatment . HDL-C , Apo-AI , and MDA levels as well as PON1 and Aryl activities were measured before and after treatment . Independent t-test was used to match basal parameters of case and control groups . Paired t-test was used to assess significance of the differences . Correlation was evaluated by Pearsons test and the statistical significance was set at P < 0.05 . RESULTS No significant differences were noted between FO and placebo patients with regards to age , disease duration , post-menopausal status , conventional therapy , body mass index ( BMI ) , and numbers of swollen and tender joints at the beginning of the study . There were 83 patients who completed the three-month follow up . Serum levels of HDL-C ( P = 0.018 ) , Apo-AI ( P = 0.165 ) , Aryl ( P = 0.026 ) , and PON1 ( P = 0.049 ) activity increased , whereas MDA levels decreased significantly with FO supplementation ( P = 0.077 ) . Significant correlations between increased PON1 activity and both HDL-C ( P = 0.007 , r = 0.419 ) and Apo-AI ( P < 0.001 , r = 0.742 ) concentrations as well as between HDL-C and Apo AI levels ( P = 0.01 , r = 0.403 ) were found . CONCLUSION According to the results of this study , FO could increase serum HDL-C and PON1 levels and Aryl activity in female patients with RA Paraoxonase is an enzyme associated with HDL in human serum that hydrolyzes oxidized phospholipids and inhibits LDL oxidation , which is an important step in atherogenesis . In animals , addition of oxidized lipids to the circulation reduces paraoxonase activity , and diets rich in oxidized fat accelerate the development of atherosclerosis . The current r and omized , crossover study was design ed to compare the effect of a meal rich in oxidized lipids in the form of fat that had been used for deep-frying in a fast food restaurant and a control meal rich in the corresponding unused fat on postpr and ial serum paraoxonase ( arylesterase ) activity and peroxide content of LDL and its susceptibility to copper ion catalyzed oxidation in 12 healthy men . Four hours into the postpr and ial period , serum paraoxonase activity had decreased significantly after the used fat meal ( -17 % , P=0.005 ) and had increased significantly after the meal rich in unused fat ( 14 % , P=0 . 005 ) . These changes were significantly ( P=0.003 ) different . A time-course study indicated that serum paraoxonase activity remained lower than baseline for up to 8 hours after the used fat meal . Serum apoA1 concentration tended to decrease after the unused fat meal and tended to increase after the used fat meal . These changes were different at a marginal level of significance ( P=0.07 ) . Also , a significantly ( P=0.03 ) greater decrease in apoA1 content of postpr and ial HDL was recorded after the unused fat meal . The peroxide content of LDL tended to decrease after the used fat meal and tended to increase after the control meal . These changes were significantly ( P=0.04 ) different . Susceptibility of isolated LDL to copper ion oxidation and plasma levels of malondialdehyde were unchanged during the study . These data suggest that in the postpr and ial period after a meal rich in used cooking fat , the enzymatic protection of LDL against accumulation of peroxides and atherogenic oxidative modification may be reduced , possibly due to factors associated with apoA1 , without acutely affecting the intrinsic resistance of LDL to in vitro oxidation Olive oil , rich in oleic acid , could play a particular beneficial role in the anti-atherogenic effects attributed to the Mediterranean diet . Paraoxonase ( PON1 ) has emerged as the component of high-density lipoproteins ( HDL ) most likely to explain its ability to attenuate the oxidation of low-density lipoproteins . We hypothesised that oleic acid intake might be associated with changes in PON1-HDL associated particles , and investigated the impact , if any , on this association of the PON1 - 192 polymorphism , a common polymorphism that strongly modulates PON1 activity . Six hundred and fifty-four men r and omly selected from the census were studied . Oleic acid intake was calculated from a 72-h recall question naire with specific software . Oleic acid intake groups ( low vs. high ) were created by stratifying the population according the median value as a cut-point . After adjusting for confounding variables , high oleic acid intake was associated with increased HDL cholesterol levels and PON1 activity only in subjects with the QR and the RR genotypes , respectively . Analyses of the variance showed a statistically significant interaction between PON1 - 192 genotypes and oleic acid intake for log PON1 activity ( P=0.005 ) and a marginally significant interaction for HDL cholesterol ( P=0.066 ) . These results suggest that the beneficial effect of increasing oleic acid intake on HDL and PON1 activity at population level is especially observed in subjects carrying the R allele of the PON1 - 192 polymorphism Paraoxonase-1 ( PON1 ) , a HDL-associated enzyme , may protect against the development of atherosclerosis . Serum PON1 activity and PON1-mediated capacity of HDL to prevent lipoprotein oxidation are modulated by two common polymorphisms at positions 192 ( Gln-->Arg ) and 55 ( Leu-->Met ) of the PON1 gene . We studied the effect of dietary modifications on PON1 activity and the role of PON1 gene polymorphisms in the response . A controlled , crossover dietary intervention of two 5-wk periods was conducted in 37 healthy , nonsmoking women . The two study diets were either low or high in vegetables , and thus in natural antioxidants , with some differences in fatty acid contents . The mean plasma total ( -8 % , P < 0.001 ) , LDL ( -7 % , P < 0.01 ) and HDL ( -7 % , P < 0.001 % ) cholesterol , and apolipoprotein A-I ( -8 % , P < 0.001 ) concentrations were lower after the high vegetable diet period than after the low vegetable diet period . Also , the serum PON1 activity was lower ( P < 0.05 ) after the high vegetable compared with the low vegetable diet period . The reduction of PON1 activity correlated with the reduction in HDL cholesterol ( r = 0.35 , P < 0.05 ) . High baseline PON1 activity was related to the presence of the PON1(192Arg ) allele ( P < 0.001 ) and PON1(55Leu/Leu ) genotype ( P < 0.001 ) . The reduction of PON1 activity due to the high vegetable diet was greatest among the women with the PON1(192Arg ) allele ( P < 0.05 ) and PON1(55Leu/Leu ) genotype ( P < 0.05 ) . In conclusion , a diet high in vegetables , berries and fruit reduces PON1 activity , and the response is modulated by the genetic variance of PON1 BACKGROUND Prospect i ve data relating fruit and vegetable intake to cardiovascular disease ( CVD ) risk are sparse , particularly for women . OBJECTIVE In a large , prospect i ve cohort of women , we examined the hypothesis that higher fruit and vegetable intake reduces CVD risk . DESIGN In 1993 we assessed fruit and vegetable intake among 39876 female health professionals with no previous history of CVD or cancer by use of a detailed food-frequency question naire . We subsequently followed these women for an average of 5 y for incidence of nonfatal myocardial infa rct ion ( MI ) , stroke , percutaneous transluminal coronary angioplasty , coronary artery bypass graft , or death due to CVD . RESULTS During 195647 person-years of follow-up , we documented 418 incident cases of CVD including 126 MIs . After adjustment for age , r and omized treatment status , and smoking , we observed a significant inverse association between fruit and vegetable intake and CVD risk . For increasing quintiles of total fruit and vegetable intake ( median servings/d : 2 . 6 , 4.1 , 5.5 , 7.1 , and 10.2 ) , the corresponding relative risks ( RRs ) were 1.0 ( reference ) , 0.78 , 0.72 , 0.68 , and 0.68 ( 95 % CI comparing the 2 extreme quintiles : 0.51 , 0.92 ; P : for trend = 0.01 ) . An inverse , though not statistically significant , trend remained after additional adjustment for other known CVD risk factors , with RRs of 1.0 , 0.75 , 0.83 , 0.80 , and 0.85 ( 95 % CI for extreme quintiles : 0.61 , 1.17 ) . After excluding participants with a self-reported history of diabetes , hypertension , or high cholesterol at baseline , the multivariate-adjusted RR was 0.45 when extreme quintiles were compared ( 95 % CI : 0.22 , 0.91 ; P : for trend = 0.09 ) . Higher fruit and vegetable intake was also associated with a lower risk of MI , with an adjusted RR of 0.62 for extreme quintiles ( 95 % CI : 0.37 , 1.04 ; P : for trend = 0.07 ) . CONCLUSION These data suggest that higher intake of fruit and vegetables may be protective against CVD and support current dietary guidelines to increase fruit and vegetable intake Human paraoxonase ( PON1 ) exists in 2 major polymorphic forms and has been shown to protect LDL and HDL against oxidation . The aim of this study was to assess the differences between subjects at increased risk of cardiovascular disease ( CVD ) , taking into account the effects of PON1-Q192R and PON1-L55 M polymorphisms on 1 ) basal serum arylesterase activity , lipid peroxidation ( LPO ) , and LDL-cholesterol ( LDL-C ) , HDL-C , total cholesterol ( TC ) , and oxidized-LDL ( ox-LDL ) concentrations ; 2 ) the relations between arylesterase activity and lipid variables ; and 3 ) the effect of walnut-enriched meat ( WM ) consumption on arylesterase activity and lipid variables . Twenty-three Caucasians at increased risk of CVD were r and omly assigned to diet order groups in a crossover , nonblinded , placebo-controlled trial , consisting of two 5-wk experimental periods [ WM and control meat ( C Output:	Extra virgin olive oil , the main source of fat , has been particularly effective in increasing PON1 activity , an action that could be due to low saturated fatty acid intake , oleic acid enrichment of phospholipids present in high-density lipoproteins that favor the activity , and increasing hepatic PON1 mRNA and protein expressions induced by minor components present in this oil . Other Mediterranean diet constituents , such as nuts , fruits and vegetables , have been effective in modulating the activity of the enzyme , pomegranate and its compounds being the best characterized items . Ongoing research on compounds isolated from all these natural products , mainly phenolic compounds and carotenoids , indicates that some of them are particularly effective , and this may enhance the use of nutraceuticals and functional foods capable of potentiating PON1 activity
MS21007	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospect i ve , r and omized trial to improve survival . METHODS We conducted a 12-week prospect i ve , r and omized , multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol ( formerly called prostacyclin ) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension ( New York Heart Association functional class III or IV ) . RESULTS Exercise capacity was improved in the 41 patients treated with epoprostenol ( median distance walked in six minutes , 362 m at 12 weeks vs. 315 m at base line ) , but it decreased in the 40 patients treated with conventional therapy alone ( 204 m at 12 weeks vs. 270 m at base line ; P < 0.002 for the comparison of the treatment groups ) . Indexes of the quality of life were improved only in the epoprostenol group ( P < 0.01 ) . Hemodynamics improved at 12 weeks in the epoprostenol-treated patients . The changes in mean pulmonary-artery pressure for the epoprostenol and control groups were -8 percent and + 3 percent , respectively ( difference in mean change , -6.7 mm Hg ; 95 percent confidence interval , -10.7 to -2.6 mm Hg ; P < 0.002 ) , and the mean changes in pulmonary vascular resistance for the epoprostenol and control groups were -21 percent and + 9 percent , respectively ( difference in mean change , -4.9 mm Hg/liter/min ; 95 percent confidence interval , -7.6 to -2.3 mm Hg/liter/min ; P < 0.001 ) . Eight patients died during the study , all of whom had been r and omly assigned to conventional therapy ( P = 0.003 ) . Serious complications included four episodes of catheter-related sepsis and one thrombotic event . CONCLUSIONS As compared with conventional therapy , the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement , as well as improved survival in patients with severe primary pulmonary hypertension AIM The aim of the present study was to explore the effect of hepatic or renal dysfunction on the pharmacokinetics ( PK ) , tolerability and safety of selexipag , an orally active prostacyclin receptor agonist . METHODS Two prospect i ve , open-label studies evaluated the PK of selexipag and its active metabolite ACT-333679 in healthy subjects and in subjects with mild , moderate and severe hepatic impairment or severe renal function impairment ( SRFI ) . A single dose of 200 μg or 400 μg was administered . The PK parameters were derived from plasma concentration-time profiles . RESULTS Exposure increased with the severity of hepatic impairment . Geometric mean ratios and 90 % confidence intervals of the area under the concentration-time curve from time zero to infinity ( AUC0-∞ ) for selexipag and ACT-333679 increased 2.1-fold ( 1.7 - 2.6 ) and 1.2-fold ( 0.9 - 1.6 ) in subjects with mild hepatic impairment , and 4.5-fold ( 3.4 - 5.8 ) and 2.2-fold ( 1.7 - 2.8 ) in subjects with moderate hepatic impairment when compared with healthy subjects . The two subjects with severe hepatic impairment showed similar dose-normalized exposure to that of subjects with moderate hepatic impairment . A 1.7-fold increase in the AUC0-∞ of selexipag and ACT-333679 was observed with SRFI compared with healthy subjects . Although exposure to selexipag and /or ACT-333679 was higher in subjects with mild or moderate hepatic impairment or SRFI vs. healthy subjects , no safety concerns were raised in these groups . CONCLUSIONS Based on these observations , the PK data suggest that the clinical ly used starting dose needs no adjustments in patients with mild or moderate hepatic impairment or SRFI . However , doses should be up-titrated with caution in these patients . The small number of subjects limits the interpretation of selexipag PK in subjects with severe hepatic impairment In this phase 2 proof-of-concept study we examined the safety and efficacy of selexipag , an orally available , selective prostacyclin receptor ( IP receptor ) agonist , as a treatment for pulmonary arterial hypertension ( PAH ) . 43 adult patients with symptomatic PAH ( receiving stable endothelin receptor antagonist and /or a phosphodiesterase type-5 inhibitor therapy ) were r and omised three to one to receive either selexipag or placebo . Dosage was up-titrated in 200-μg increments from 200 μg twice daily on day 1 to the maximum tolerated dose by day 35 ( maximum allowed dose of 800 μg twice daily ) . Change in pulmonary vascular resistance at week 17 expressed as a percentage of the baseline value was the primary efficacy end-point , and was analysed in the per protocol set first and then in the all-treated set to assess robustness of results . A statistically significant 30.3 % reduction in geometric mean pulmonary vascular resistance was observed after 17 weeks ' treatment with selexipag compared with placebo ( 95 % confidence limits -44.7– -12.2 ; p=0.0045 , Wilcoxon rank sum test ) . This was supported by a similar result from the all-treated set . Selexipag was well tolerated with a safety profile in line with the expected pharmacological effect . Our results encourage the further investigation of selexipag for the treatment of PAH The effects of selexipag and its active metabolite ACT-333679 on cardiac repolarization were assessed in a thorough QT study as per International Conference on Harmonisation E14 guidance . In this r and omized , double-blind , placebo/positive-controlled , parallel-group study , healthy male and female subjects were r and omized to receive escalating doses of selexipag ( n=91 ) or placebo/moxifloxacin ( n=68 ) . Ascending multiple doses of selexipag in the range of 400–1,600 μg or placebo were administered twice daily for 21 days . Following a nested crossover design , subjects in the moxifloxacin/placebo treatment group received a single oral 400 mg dose of moxifloxacin on day 2 or 24 . The primary endpoint ( QT interval correction using individualized formula [ QTcI ] ) was chosen based on a prospect ively defined test applied to on-treatment data . The mean baseline-adjusted placebo-corrected ΔQTcI ( ΔΔQTcI ) for selexipag was small at all time points and never exceeded 1.4 msec ( upper bound of 90 % confidence interval [ CI ] , 3.9 msec ) on 800 μg or –0.7 msec ( upper bound of 90 % CI , 2.1 msec ) on 1,600 μg . The mean ΔΔQTcI peak effect for moxifloxacin was 7.5 msec ( lower bound of 90 % CI , 4.8 msec ) . The exposure-response analysis did not demonstrate a relevant relationship between plasma concentrations of selexipag or ACT-333679 and ΔΔQTcI but , in contrast , a positive slope within the expected range for moxifloxacin . In conclusion , selexipag does not have an effect on cardiac repolarization Purpose The aim of this single-center , open-label study was to assess the absolute bioavailability of an oral ( tablet ) versus intravenous ( i.v . ) formulation of selexipag in healthy subjects . Methods A pilot phase in three healthy male subjects , which preceded the main study , consisted of a single 20-minute i.v . infusion of 50 μg selexipag . Its objectives were to ensure the safety of the i.v . formulation and to select the i.v . dose for the main study . The main study had a r and omized , two-way crossover design in 16 healthy male subjects . Subjects received a single oral dose of 400 μg selexipag and a single 80-minute i.v . infusion of 200 μg selexipag . Results Three subjects in the pilot and 15 in the main phase completed the study as planned , whereas one subject of the main study withdrew the consent . A geometric mean total body clearance ( 95 % confidence interval ( CI ) ) of 17.9 L/h ( 15.0–21.5 ) and a volume of distribution of 11.7 L ( 10.6–13.0 ) were determined . The absolute oral bioavailability of selexipag ( 90 % CI ) was 49.4 % ( 42.6–57.2 ) . Selexipag was well-tolerated ; no adverse event ( AE ) occurred during the pilot phase , and the main observed AEs were headache , nausea , and vomiting . Conclusion A single i.v . administration of selexipag in healthy subjects was safe and well-tolerated . The bioavailability of selexipag after oral administration is approximately 50 % Purpose Targeting the prostacyclin pathway is an effective treatment option for pulmonary arterial hypertension ( PAH ) . Patients with PAH have a deficiency of prostacyclin and prostacyclin synthase . Selexipag is an orally available and selective prostacyclin receptor ( IP receptor ) agonist . Selexipag is hydrolyzed to its active metabolite ACT-333679 , also a selective and potent agonist at the IP receptor . Methods In this phase I study the pharmacokinetics ( PK ) and tolerability of single and multiple ascending doses of selexipag were investigated in a double-blind , placebo-controlled manner in 64 healthy male subjects . An additional group of 12 subjects received an open-label dose of selexipag 400 μg in the fasted condition and after a meal . Results Maximum plasma concentrations of selexipag and ACT-333679 were reached within 2.5 and 4 h , respectively , with mean half-lives of 0.7–2.3 and 9.4–14.22 h. In the presence of food , exposure to ACT-333679 was decreased by 27 % . The most frequent adverse event was headache . Selexipag was well tolerated up to a single dose of 400 μg and multiple doses of 600 μg following an up-titration step . No relevant treatment-related effects on vital signs , clinical laboratory , and electrocardiogram ( ECG ) parameters were detected . ConclusionS elexipag exhibits a good tolerability profile and PK properties that warrant further investigation Objective : The objective of this study was to assess the safety , tolerability , pharmacokinetics , and pharmacodynamics of selexipag , an orally available selective prostacyclin receptor agonist , in development for pulmonary arterial hypertension in healthy subjects . Methods : This was a double-blind , placebo-controlled , r and omised , multiple-ascending-dose , up-titration study . Male subjects received increasing oral doses of selexipag ( 400 - 1,800 µg ; n = 12 ) or placebo ( n = 4 ) twice daily for 3 days each , using incremental steps of 200 µg between each dose level . St and ard safety and tolerability data were collected . Blood sample s were taken to assess the pharmacokinetics of selexipag and its active metabolite ACT-333679 and possible effects on platelet aggregation . Results : Dose levels of selexipag up to 1,600 μg were well tolerated and this dose was identified as the maximum tolerated dose . Plasma exposure to ACT-333679 was approximately 4 times higher than that to selexipag . Steady-state conditions for both compounds were reached on day 3 of each dose level , and no accumulation of selexipag or ACT-333679 was observed . Based on the area under the curve and the maximum plasma concentration , the pharmacokinetics of selexipag and ACT-333679 were dose proportional . At the highest dose level , the geometric mean terminal half-life of selexipag and ACT-333679 was 1.4 and 8.7 h , respectively . The observed effects on platelet aggregation were variable without obvious drug- or dose-dependent pattern . Conclusions : Oral administration of increasing doses of selexipag was well tolerated . The present results support the conduct of future clinical trials RATIONALE Although commonly used as the primary outcome measure of clinical trials in pulmonary arterial hypertension ( PAH ) , the minimal important difference ( MID ) of the 6-minute walk test ( 6MWT ) has not been well defined for this population of patients . OBJECTIVES To estimate the MID in the 6MWT in patients with PAH . METHODS Study subjects from the clinical trial of tadalafil in PAH , a 16-week , parallel-group , r and omized clinical trial of patients who were treatment naive or on background therapy with an endothelin receptor antagonist , were eligible . 6MWT was performed using a st and ardized protocol . Distributional and anchor-based methods were used to estimate the M Output:	Selexipag also improved 6-minute walk distance and lowered hospitalization risk . Common adverse events included headache , diarrhea , nausea , and jaw pain . Conclusions : The specific role of selexipag for managing PAH patients is unclear because of its modest efficacy , lack of mortality reduction , and cost similar to intravenous prostacyclins .
MS21008	*TASK* the task is to summarize an input biomedical literature in six sentences *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 aim of the present prospect i ve study was to evaluate the long-term outcome of implants placed simultaneously with guided bone regeneration ( GBR ) using resorbable and non-resorbable membranes . MATERIAL S AND METHODS The original study population consisted of 72 patients receiving a total of 265 implants . In all GBR-treated sites , demineralized bovine bone mineral ( DBBM ) was used in combination either with a collagen ( CM ) or an Exp and ed polytetrafluoroethylene ( e-PTFE ) membrane . A total of 112 implants was treated with CM , 41 implants were treated with e-PTFE membranes , and 112 served as a control group because implants were entirely surrounded by bone and did not need any GBR procedures . Clinical and radiographic analyses were performed after a period of 12 - 14 years . RESULTS The median follow-up time was 12.5 years ( range 12 - 14 years ) . A total of 58 patients participated in the present investigation , corresponding to 80.5 % of the original study population . The cumulative implant survival rate at the follow-up examination was 93.2 % . For the control group the cumulative survival rate was 94.6 % , for the CM 91.9 % , and for the e-PTFE 92.6 % . Differences among the groups were not statistically significant . The radiographically determined marginal bone level ( MBL ) amounted to : control 2.36 mm ( SD ) , CM 2.4 mm ( SD ) , e-PTFE 2.53 mm ( SD ) . There is no evidence ( P < 0.2 ) that the slope of bone level over time is different for the three treatment groups . CONCLUSION It is concluded that implants placed simultaneously with GBR procedures using resorbable or non-resorbable membranes reveal a high survival rate ranging from 91.9 % to 92.6 % , therefore it is considered to be a safe and predictable therapy . [ Correction added after online publication 30 November 2012 : the marginal bone level of CM , e-PTFE , and control was corrected to ' control 2.36 mm ( SD ) , CM 2.4 mm ( SD ) , e-PTFE 2.53 mm ( SD ) ' in the Results section ] BACKGROUND Guided bone regeneration is considered an effective tool for gaining mineralized tissue either at exposed implant surface or in deficient alveolar ridge areas before implant placement . MATERIAL AND METHODS Customized casts obtained following impression taking at surgery and re-entry allowed for morphometric assessment of alveolar ridge alterations 6 months after one-stage augmentation of bone dehiscences . In a r and omized pilot study using biphasic calcium phosphate tests ( n=17 ) received treatment with ribose cross-linked collagen membranes ( RCLM ) , whereas controls ( n=20 ) received non-cross-linked membranes . The primary endpoint was to quantify the effect of membrane type on dimensional changes in bone margins at crestal level of endosseous implants . RESULTS Soft tissue dehiscencies occurred at 70.5 % and 55 % frequency for tests and controls , respectively . Gain in clinical ly hard newly mineralized tissue at the crestal level was significantly higher in test group in lateral ( 1.8 versus 0.7 mm ; p=.046 ) and in vertical dimensions ( 1.1 versus 0.2 mm ; p=.035 ) compared with controls . Second measurement obtained at the border of reflected flap revealed no significant difference between groups ( 3.0 versus 2.1 mm ; p=0.57 ) for lateral dimension . CONCLUSIONS Both collagen devices were effective in bone augmentation . RCLMs supported mineralization process and remodelling even in sites showing compromised healing as indicated by morphometric outcome The aim of the present clinical study was to test whether or not the addition of recombinant human bone morphogenetic protein-2 ( rhBMP-2 ) to a xenogenic bone substitute mineral ( Bio-Oss ) will improve guided bone regeneration therapy regarding bone volume , density and maturation . In 11 partially edentulous patients , 34 Brånemark implants were placed at two different sites in the same jaw ( five maxillae , six m and ibles ) requiring lateral ridge augmentation . The bone defects were r and omly assigned to test and control treatments : the test and the control defects were both augmented with the xenogenic bone substitute and a resorbable collagen membrane ( Bio-Gide ) . At the test sites , the xenogenic bone substitute mineral was coated with rhBMP-2 in a lyophilization process . Following implant insertion ( baseline ) , the peri-implant bone defect height was measured from the implant shoulder to the first implant-bone contact . After an average healing period of 6 months ( SD 0.17 , range 5.7 - 6.2 ) , the residual defects were again measured and trephine burs were used to take 22 bone biopsies from the augmented regions . The healing period was uneventful except for one implant site that showed a wound dehiscence , which spontaneously closed after 4 weeks . Later at reentry , all implants were stable . At baseline , the mean defect height was 7.0 mm ( SD 2.67 , range 3 - 12 mm ) at test and 5.8 mm ( SD 1.81 , range 3 - 8 mm ) at control sites . At reentry , the mean defect height decreased to 0.2 mm ( SD 0.35 , range 0 - 1 mm ) at test sites ( corresponding to 96 % vertical defect fill ) and to 0.4 mm ( SD 0.66 , range 0 - 2 mm ) at the control site ( vertical defect fill of 91 % ) . Reduction in defect height from baseline to reentry for both test and control sites was statistically significant ( Wilcoxon P<0.01 ) . Histomorphometric analysis showed an average area density of 37 % ( SD 11.2 , range 23 - 51 % ) newly formed bone at test sites and 30 % ( SD 8.9 , range 18 - 43 % ) at control sites . The fraction of mineralized bone identified as mature lamellar bone amounted to 76 % ( SD 14.4 , range 47.8 - 94 % ) at test compared to 56 % ( SD 18.3 , range 31.6 - 91.4 % ) at control sites ( paired t-test P<0.05 ) . At BMP-treated sites 57 % ( SD 16.2 , range 29 - 81 % ) and at control sites 30 % ( SD 22.6 , range 0 - 66 % ) of the surface of the bone substitute particles were in direct contact with newly formed bone ( paired t-test P<0.05 ) . It is concluded that the combination of the xenogenic bone substitute mineral with rhBMP-2 can enhance the maturation process of bone regeneration and can increase the graft to bone contact in humans . rhBMP-2 has the potential to predictably improve and accelerate guided bone regeneration therapy The purpose of this clinical investigation was to compare the new resorbable collagen membrane , Bio-Gide , to the conventional exp and ed polytetrafluoroethylene material ( Gore-Tex ) for guided bone regeneration in situations involving exposed implant surfaces . Over a 2-year period , 25 split-mouth patients were treated r and omly : one defect site was treated with Bio-Gide and the other defect site with Gore-Tex ; all 84 defects were filled with Bio-Oss and covered with the respective membrane . The defect types , their dimensions , and their morphology were measured in detail initially and at re-entry to allow for calculation of the exposed implant surface . Changes in defect surface for both types of membranes were statistically significant ( P < .0001 ) ; however , no statistical significance ( P > .94 ) could be detected between the two membranes . The mean average percentage of bone fill was 92 % for Bio-Gide and 78 % for Gore-Tex sites . In the latter group , 44 % wound dehiscences and /or premature membrane removal occurred . The resorbable membrane , Bio-Gide , in combination with a bone graft , can be a useful alternative to the well-established exp and ed polytetrafluoroethylene membranes Two techniques of ridge augmentation using onlay bone graft alone or associated with a non-resorbable membrane have been previously described . This prospect i ve , r and omized study compared these two techniques at 6 months , in terms of bone gain , resorption and quality obtained at edentulous sites . Osseous measurements were taken using stents , callipers and CT-scans . Membrane exposure occurred at one site , 4 weeks after placement . Endosseous implants were successfully placed at all grafted sites . The mean graft thickness for all subjects was 4.7 mm ( range : 2.3 - 6.2 mm ) . Overall mean resorption was 1.5 mm ( range : 0 - 4.6 mm ) whereas overall mean width gain was 3.2 mm ( range : 0.8 - 6.2 mm ) . Six months following surgery , the membrane group experienced significantly less bone resorption than the graft alone group ( P<0.01 ) . Width augmentation did not differ significantly between the two groups . In conclusion , combining a membrane with an onlay graft demonstrates less bone resorption with a minimal risk of complications . Longer follow-up is needed to confirm the benefits of using a non-resorbable membrane OBJECTIVE The aim of this r and omized-controlled clinical trial was to evaluate the long-term outcome of implants placed in bone augmented with a xenogenic bone substitute material and a collagen membrane with or without the addition of recombinant human bone morphogenetic protein-2 ( rhBMP-2 ) . MATERIAL AND METHODS Eleven patients received a total of 34 implants placed into sites exhibiting lateral bone defects . In a split mouth design , the defects were r and omly treated with the graft material and the collagen membrane either with ( test ) or without ( control ) rhBMP-2 . The patients were examined 3 and 5 years after insertion of the prosthetic restoration . Student 's paired t-test was performed to detect differences between the two groups . RESULTS The survival rate at 3 and 5 years was 100 % for both groups . The peri-implant soft tissues were stable and healthy without any difference between the two groups . The prosthetic reevaluation demonstrated four loose prosthetic screws during the first 3 years and seven ceramic chippings after 3 and 5 years . The mean distance between the first bone to implant contact to implant abutment junction at 3 years was 1.37 mm ( test ) , 1.22 mm ( control ) , and 1.38 mm ( test ) , and 1.23 mm ( control ) at 5 years . The difference of < 0.2 mm between test and control implants was not statistically significant . The mean change of the marginal bone level between baseline and 5 years ranged from -0.07 mm ( mesial , test ) , -0.11 mm ( distal , test ) , -0.03 mm ( mesial , control ) , to + 0.13 mm ( distal , control ) . No statistically significant differences were observed between test and control sites . CONCLUSION Implants placed in bone augmented with and without rhBMP-2 revealed excellent clinical and radiological outcomes after 3 and 5 years PURPOSE This study evaluated predictability and treatment outcome of the combined application of autografts and exp and ed-polytetrafluoroethylene ( e-PTFE ) membranes for lateral ridge augmentation in partially edentulous patients using a staged approach . MATERIAL S AND METHODS Forty partially edentulous patients were consecutively treated . Emphasis was given to a lateral incision technique , perforation of the cortex to open the marrow cavity , stable placement of corticocancellous autografts and bone chips , precise adaptation of the e-PTFE membranes and stabilization with miniscrews , and a tension-free primary soft tissue closure . After 7 to 13 months , the sites were reopened for membrane removal and implant placement . RESULTS All but one patient showed complication-free soft tissue healing . After reopening , 38 patients exhibited excellent ridge augmentation , whereas two had compromised results , with soft tissue encapsulation of some bone chips . None of the applied block grafts showed clinical signs of resorption . Preaugmentation and postaugmentation measurements showed an enlargement of the crest width from a mean of 3.5 mm to 7.1 mm . This allowed the placement of nonsubmerged titanium implants in all 40 patients . CONCLUSIONS The current study demonstrates that the combined application of autografts and e-PTFE membranes is a predictable surgical procedure for lateral ridge augmentation that results in an enlargement of the alveolar crest in partially edentulous patients . The autografts support the membrane and activate bone formation with their osteoconductive and osteoinductive properties . The membrane acts as a physical barrier to nonosteogenic soft tissue cells , and protects the autografts against resorption during healing The aim of this prospect i ve 5-year longitudinal study was to follow endosteal implants in which guided bone regeneration ( GBR ) was applied during implant placement . In 75 patients , defects around implants ( Branemark System ) were treated with Bio-Oss and Bio-Gide ( 112 implants ) . In split-mouth patients in this group , Bio-Oss and Gore-Tex were used in the second defect site ( 41 implants ) . All 7 Output:	The intervention combining bone replacement grafts with barrier membranes was associated with superior outcomes The most frequently used intervention was the combination of xenograft and bioabsorbable membrane . The most frequently used intervention was the use of autogenous bone blocks . Both treatment strategies led to high survival and success rates ( > 95 % ) for the implants placed on the regenerated sites .
MS21009	*TASK* the task is to summarize an input biomedical literature in six sentences *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 describe HIV-related media events in the context of first-time HIV-1-antibody testing trends at a London genitourinary medicine clinic . Design Demographic and behavioural data were collected prospect ively for individuals tested for HIV-1 antibodies between September 1985 and September 1993 , at the genitourinary medicine clinic of St Mary 's Hospital , London . Results A total of 19242 individuals were tested of whom 37 % were women . Of the men tested 60 % were heterosexual . The women at first time of testing were significantly younger [ 29.3 years ; 95 % confidence interval ( CI ) , 28.8–29.7 ] than the men ( 32.5 years ; 95 % CI , 29.2–35.8 ) ; mean ages for both sexes did not change significantly over time . Overall , 199 women and 1539 men tested HIV-antibody-positive . The proportions of women testing positive increased significantly over time ( χ2 = 21.7 , degrees of freedom = 1 ; P < 0.001 ) , whereas the proportion of HIV-positive men remained constant for all sexual orientation groups . The proportion of heterosexual women testing positive ( 2.8 % ) was similar to the proportion of HIV-positive heterosexual men ( 2.9 % ) . HIV-positive individuals were significantly older for both sexes . Throughout the study period numerous education campaigns were run using a variety of media complemented by a number of other HIV-related media events . Conclusions Peak periods of attendance for HIV testing generally corresponded with increased HIV-related media activity and the greatest testing rates were observed when various HIV media events occurred concurrently . The increase in the number of heterosexuals tested suggests that the risk of heterosexual transmission of HIV has been recognized , at least among older individuals . The exact role of HIV-related media events , including celebrities disclosing their HIV-positive status , remains to be eluci date d. Whether the relative under-representation of younger people is due to a lack of awareness , increased use of safer sex practice s or reluctance to use the service also remains to be addressed . Given the increasing number of HIV-positive women and the relatively constant rate of HIV-positive tests in the male attendees an urgent need exists to assess the impact and effectiveness of specific HIV media campaigns BACKGROUND Access to HIV-1 voluntary counselling and testing ( VCT ) is severely limited in less-developed countries . We undertook a multisite trial of HIV-1 VCT to assess its impact , cost , and cost-effectiveness in less-developed country setting s. METHODS The cost-effectiveness of HIV-1 VCT was estimated for a hypothetical cohort of 10000 people seeking VCT in urban east Africa . Outcomes were modelled based on results from a r and omised controlled trial of HIV-1 VCT in Tanzania and Kenya . Our main outcome measures included programme cost , number of HIV-1 infections averted , cost per HIV-1 infection averted , and cost per disability-adjusted life-year ( DALY ) saved . We also modelled the impact of targeting VCT by HIV-1 prevalence of the client population , and the proportion of clients who receive VCT as a couple compared with as individuals . Sensitivity analysis was done on all model parameters . FINDINGS HIV-1 VCT was estimated to avert 1104 HIV-1 infections in Kenya and 895 in Tanzania during the subsequent year . The cost per HIV-1 infection averted was US$ 249 and $ 346 , respectively , and the cost per DALY saved was $ 12.77 and $ 17.78 . The intervention was most cost-effective for HIV-1-infected people and those who received VCT as a couple . The cost-effectiveness of VCT was robust , with a range for the average cost per DALY saved of $ 5.16 - 27.36 in Kenya , and $ 6.58 - 45.03 in Tanzania . Analysis of targeting showed that increasing the proportion of couples to 70 % reduces the cost per DALY saved to $ 10.71 in Kenya and $ 13.39 in Tanzania , and that targeting a population with HIV-1 prevalence of 45 % decreased the cost per DALY saved to $ 8.36 in Kenya and $ 11.74 in Tanzania . INTERPRETATION HIV-1 VCT is highly cost-effective in urban east African setting s , but slightly less so than interventions such as improvement of sexually transmitted disease services and universal provision of nevirapine to pregnant women in high-prevalence setting s. With the targeting of VCT to population s with high HIV-1 prevalence and couples the cost-effectiveness of VCT is improved significantly Abstract Objective : To determine the uptake and acceptability of different methods of a universal offer of voluntary HIV testing to pregnant women . Design : R and omised controlled trial involving four combinations of written and verbal communication , followed by the direct offer of a test . The control group received no information and no direct offer of a test , although testing was available on request . Setting : Hospital antenatal clinic covering most of the population of the city of Edinburgh . Subjects : 3024 pregnant women booking at the clinic over a 10 month period . Main outcome measures : Uptake of HIV testing and women 's knowledge , satisfaction , and anxiety . Results : Uptake rates were 6 % for those in the control group and 35 % for those directly offered the test . Neither the style of leaflet nor the length of discussion had an effect on uptake . Significant independent predictors of uptake were a direct test offer ; the midwife seen ; and being unmarried , previously tested , and younger age . Knowledge of the specific benefits of testing increased with the amount of information given , but neither satisfaction nor anxiety was affected by the type of offer . Conclusions : The universal offer of HIV testing is not intrusive and is acceptable to pregnant women . A policy of offering the HIV test to all women result ed in higher uptake and did not increase anxiety or dissatisfaction . Uptake depends more on the midwife than the method of offering the test . Low uptake rates and inadequate detection of HIV infection point to the need to assess a more routine approach to testing . Key messages HIV testing in pregnancy is beneficial , but uptake rates are not high Offering the test to women attending antenatal clinics increases uptake without increasing anxiety or dissatisfaction The extent of information given is not important in terms of whether women take the test and whether they find the procedure acceptable Uptake depends more on the midwife than the method of offering the test Low uptake rates and inadequate detection of HIV infection point to the need to assess a more routine approach to 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 African American women ( N = 100 ) recruited from an urban clinic were r and omly assigned to view 1 of 3 experimental videotapes promoting HIV testing : ( a ) an ethnicity-matched information control videotape ; ( b ) the same ethnicity-matched videotape presented by an African American woman ( gender-ethnicity-matched control condition ) ; or ( c ) an experimental videotape with a culturally relevant context that embedded HIV-testing information within a frame of reference emphasizing personal loss . Consistent with D. Kahneman and A. Tversky 's ( 1979 ) prospect theory , women who viewed the context -framing videotape were most likely to have been tested during a 2-week follow-up interval . Among women who expressed intentions to get tested after viewing the videotapes , 63 % of those in the message-framing condition were tested for HIV during a 2-week period compared with 23 % in the gender-ethnicity-matched condition , and none in the ethnicity-matched condition OBJECTIVES The purpose of this study was to assess the effects of an HIV antibody testing , counseling and education programme on the knowledge and practice s of low-income Los Angeles Latina women . METHODS The study design was prospect i ve and longitudinal involving pre-test , post-test and retest measures over a 2-year period . The study employed an experimental group and a comparison group which did not receive the intervention . The study group was comprised of a convenience sample of 508 low-income Latina women who were recruited from the Public Health Service nutrition programme for women , infants and children ( WIC ) . The comparison group ( n = 51 ) was recruited from the same setting . A battery of instruments was selected to measure HIV knowledge and practice s , the social support received , self-esteem , the level of acculturation and sociodemographic characteristics . The instruments were administered at pre-test , 2 weeks post-test and 1 year retest . The HIV antibody serostatus was assessed at pre-test and retest . An intervention protocol based on cultural competence , women as traditional health care givers and the major transmission categories was provided after the pre-test and was reinforced post-test . Finally , qualitative data were collected from the focus group participants ( n = 55 ) to evaluate the intervention protocol . RESULTS The participants in the study made significant improvements in HIV knowledge and reported condom use practice s from pre-test to post-test that were retained on retest . The comparison group subjects did not make significant pre-test-post-test improvements on these measures . CONCLUSIONS It should be noted that the changes in practice s made by the study group did not necessarily reduce their risk of HIV infection or transmission and were not related to the demonstrated knowledge and skills improvement . Of special significance to programme planners , educators and research ers , both the quantitative and qualitative data revealed problem areas with the intervention protocol related to cultural norms and the possible fragmentation of information based on the behavioral transmission categories Output:	Mass media interventions have immediate and overall effects in promotion of HIV testing . No long-term effects were seen .
MS21010	*TASK* the task is to summarize an input biomedical literature in six sentences *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 objective of this study was to measure the change in colonic transit time after resection rectopexy for complete rectal prolapse . Methods We prospect ively carried out isotope colonic transit studies before resection rectopexy in 38 patients with full-thickness complete rectal prolapse and invited them to attend for a postoperative transit study at least 1 year after resection rectopexy . Results Preoperatively , 27 ( 70 % ) patients had abnormally prolonged colonic transit times , while 11 had normal colonic transit . Twenty-two ( 61 % ) patients agreed to attend for a three-day colonic transit study . Resection rectopexy failed to correct delayed colonic transit in all patients with abnormal preoperative tests , while 4 patients developed new delayed transit and 2 with normal transit were unchanged . Conclusions The study suggests that most prolapse patients have a pan-colonic motility disorder that is not corrected by rectopexy and resection of most of the left colon . If resection rectopexy fails to correct abnormal transit , this study questions the rationale for continuing to offer resection and supports less invasive surgical procedures such as ventral rectopexy The objectives of this study were to compare both subjective clinical outcomes and the objective stress response of laparoscopic and open abdominal rectopexy in patients with full‐thickness rectal prolapse . Abdominal rectopexy for patients with rectal prolapse is well suited for a laparoscopic approach as no resection or anastomosis is necessary BACKGROUND A novel technique of radiofrequency ablation and plication of the rectal mucosa ( RAMP ) as a treatment for rectal mucosal prolapse is reported . The results of this technique are compared with the conventional ligature and excision procedure ( LEP ) . METHODS Radiofrequency ablation was performed using an Ellman radiofrequency generator . Patients with rectal mucosal prolapse were r and omized to undergo either LEP or RAMP . The intra- and postoperative outcomes and complications were recorded . RESULTS RAMP on average result ed in reduced operation time , shorter hospitalization , and significantly less postoperative pain . Return to work was earlier and wound healing times were shorter than that of patients in the control group . The complication rates also were significantly shorter ( 9 % in the RAMP group and 29 % in the conventional LEP group ) . CONCLUSION The procedure of radiofrequency ablation and plication of rectal mucosa is safe , effective , and swift . It can be proposed as an effective alternative to conventional surgical procedures Background More than 100 surgical approaches to treat rectal prolapse have been described . These can be done through the perineum or transabdominally . Delorme ’s procedure is the most frequently used perineal , resection rectopexy the most commonly used abdominal procedure . Recurrences seem more common after perineal compared to abdominal techniques , but the latter may carry a higher risk of peri- and postoperative morbidity and mortality . Methods / Design DeloRes is a r and omized , controlled , observer-blinded multicenter trial with two parallel groups . Patients with a full-thickness rectal prolapse ( third degree prolapse ) , considered eligible for both operative methods are included . The primary outcome is time to recurrence of full-thickness rectal prolapse during the 24 months following primary surgery . Secondary endpoints are time to and incidence of recurrence of full-thickness rectal prolapse during the 5-year follow-up , duration of surgery , morbidity , hospital stay , quality of life , constipation , and fecal incontinence . A meta- analysis was done on the basis of the available data on recurrence rates from 17 publications comprising 1,140 patients . Based on the results of a meta- analysis it is assumed that the recurrence rate after 2 years is 20 % for Delorme ’s procedure and 5 % for resection rectopexy . Considering a rate of lost to follow-up without recurrence of 30 % a total of 130 patients ( 2 x 65 patients ) was calculated as an adequate sample size to assure a power of 80 % for the confirmatory analysis . Discussion The DeloRes Trial will clarify which procedure results in a smaller recurrence rate but also give information on how morbidity and functional results compare . Trial registration German Clinical Trial Number BACKGROUND : No r and omized controlled trial has compared no rectopexy with rectopexy for external full-thickness rectal prolapse . OBJECTIVE : This study was performed to test the hypothesis that recurrence rates following no rectopexy are not inferior to those following rectopexy for full-thickness rectal prolapse . DESIGN : This was a multicenter r and omized controlled trial . Eligible patients were r and omly assigned to no rectopexy or rectopexy . The end point was recurrence rates defined as the presence of external full-thickness rectal prolapse after surgery . A prer and omized controlled trial meta- analysis suggested a sample size of 251 patients based on a 15 % expected difference in the 5-year cumulative recurrence rate . Recurrence-free curves were generated and compared using the Kaplan-Meier method and log-rank test , respectively . Data were presented as median ( range ) . SETTING : This study was conducted in 41 tertiary centers in 21 countries . PATIENTS : Patients with prior surgery for rectal prolapse or pelvic floor descent were not included . INTERVENTIONS : The no-rectopexy arm was defined as abdominal surgery with rectal mobilization only . The rectopexy arm was defined as abdominal surgery with mobilization and rectopexy . Sigmoid resection was not r and omized and was added in the presence of constipation . MAIN OUTCOME MEASURES : Two hundred fifty-two patients with external full-thickness rectal prolapse were r and omly assigned to undergo no rectopexy or rectopexy in 41 centers . All patients but one underwent the allocated intervention . One hundred sixteen no-rectopexy patients were comparable to 136 rectopexy patients for age ( P = .21 ) , body mass index ( P = .61 ) , ASA grade ( P = .29 ) , and previous abdominal surgery ( P = .935 ) , but not for sex ( P = .013 ) and external full-thickness rectal prolapse length ( 8 ( 1 - 25 ) cm vs 5 ( 1 - 20 ) cm , P = .026 ) . Sigmoid resection was performed more frequently in the no-rectopexy arm ( P < .001 ) . There was no significant difference in complication rates ( 11 % vs 17.9 % ; P = .139 ) . The mortality rate was 0.8 % . The loss of patients to 5-year follow-up was 10.3 % . Actuarial analysis demonstrated a significant difference in 5-year recurrence rates between study arms ( 8.6 % vs 1.5 % ) ( log-rank , P = .003 ) . LIMITATIONS : Limitations were the high proportion of male patients , r and omization timing , the lack of st and ardization for rectopexy technique , and the 10 % loss to follow-up . CONCLUSIONS : Recurrence rates following no rectopexy are inferior to those following rectopexy for external full-thickness rectal prolapse The introduction of new laparoscopic techniques has important cost implication s. The aim of this study was to compare the cost effectiveness of laparoscopic rectopexy with that of open abdominal rectopexy for full‐thickness rectal prolapse BACKGROUND Rectal prolapse is a distressing and socially disabling condition . controversy exists regarding the preferred surgical technique for the treatment of complete rectal prolapse . OBJECTIVE We compared Delorme operation alone or with postanal repair and levatroplasty in treating complete rectal prolapse . METHODS Consecutive patients treated for rectal prolapse at our colorectal unit were evaluated for inclusion . Participants were r and omly allocated to receive Delorme operation only ( GI ) , or Delorme operation with postanal repair and levatorplasty ( GII ) . MAIN OUTCOME MEASURES The primary outcome measure was recurrence rate ; secondary outcomes included improvement of constipation , incontinence , operative time , anal manometery and postoperative complications . RESULTS Eighty-two consecutive patients with rectal prolapse were r and omized . There was a significant difference between the two groups with longer operative time in group II . Recurrence rate after one year was ( 14.28 % in GI , and 2.43 % in GII , respectively ( P = 0.043 ) . Constipation improved in group I & II but there was a significant difference in constipation scores postoperatively between the two groups . There was improvement in continence mechanism in both groups postoperatively but being higher in group II and this produce a significant statistical difference ( 0.004 ) . Mean satisfaction score was significantly higher in group II than group I. Both groups succeed to produce a significant change in resting and squeeze pressure before & after the operation . CONCLUSIONS Delorme operation seems to be an effective procedure for treating complete rectal prolapse especially if combined with postanal repair and levatorplasty . CLINICAL TRIAL REGISTRATION NCT01656369 A r and omized trial was performed to compare abdominal resection rectopexy and pelvic floor repair ( n = 10 ) with perineal rectosigmoidectomy and pelvic floor repair ( n = 10 ) in elderly female patients with full‐thickness rectal prolapse and faecal incontinence . There were no recurrences of full‐thickness prolapse following resection rectopexy but one after rectosigmoidectomy . Continence to liquid and solid stool was achieved in nine patients , with faecal soiling reported in only two , after resection rectopexy and in eight , with soiling in six , following rectosigmoidectomy . The median ( range ) frequency of defaecation was only 1 ( 1–3 ) per day following resection rectopexy compared with 3 ( 1–6 ) per day after rectosigmoidectomy . There was an increase in the mean(s.d . ) maximum resting pressure after resection rectopexy ( 19.3(15.28 ) cmH2O ) compared with a reduction following rectosigmoidectomy ( – 3.4(13.75 ) cmH2O ) ( P = 0.003 ) . Mean(s.d . ) compliance was also greater after resection rectopexy than following rectosigmoidectomy ( 3.9(0.75 ) versus 2.2(0.78 ) ml/cmH2O , P<0.001 ) . Abdominal resection rectopexy gives better functional and physiological results than perineal rectosigmoidectomy Denervation of the rectum during rectopexy has been suggested as a reason for postoperative constipation . Bowel symptoms and anorectal function have been examined in a prospect i ve r and omized study of rectopexy with ( n = 14 ) or without ( n = 12 ) division of the lateral ligaments . Incontinence improved in both groups of patients . Division of the lateral ligaments increased the number of patients with constipation ( three before operation , ten after operation , P<0.01 ) . Mean anal canal pressures were higher after operation in all patients . Rectal electrical sensory threshold increased significantly in those in whom the ligaments had been divided ( preoperative 27.6 mA versus postoperative 56.7mA ; P<0.01 ) but not in those in whom they were preserved ( 39.0 versus 34.9 mA ; P>0.05 ) . Prolapse recurred in six patients who did not undergo division of the lateral ligaments , but in none of the group in whom the ligaments were divided OBJECTIVE To compare the efficacy of absorbable and non-absorbable mesh for rectal fixation in abdominal rectopexy . DESIGN Prospect i ve open study . SETTING University hospital , Israel . SUBJECTS 37 consecutive patients with complete rectal prolapse . INTERVENTIONS Posterior abdominal rectopexy with non-absorbable mesh ( Polypropylene , Prolene , Ethicon Ltd ) in 17 patients and with absorbable mesh ( Polyglycolic acid , Dexon , Davis & Geck ) in 20 . MAIN OUTCOME MEASURES There was no operative mortality , and there were no significant differences between the groups in the incidence of postoperative complications . Mean ( SD ) follow up was 3.6(0.5 ) years and 3.8(0.7 ) years in the Dexon and Prolene groups , respectively . Preoperative and postoperative performance indices based on the Gastrointestinal Quality of Life Index were similar in both groups . CONCLUSIONS Dexon mesh may be as effective as Prolene mesh in the treatment of complete rectal prolapse . A performance index seems to be a useful tool for evaluating the outcome of patients after repair of complete rectal prolapse BACKGROUND Laparoscopic ventral mesh rectopexy for rectal prolapse has been widely used over the past decade to reduce postoperative functional bowel disorders . We aim ed to compare changes in functional outcome 12 months after laparoscopic ventral mesh rectopexy versus laparoscopic posterior sutured rectopexy in patients with rectal prolapse . METHODS In this double-blind , r and omised trial , consecutive patients aged 18 years or older at a single centre in Denmark with full-thickness rectal prolapse were r and omly assigned ( 1:1 ) to either laparoscopic ventral mesh rectopexy or laparoscopic posterior sutured rectopexy by drawing numbers from opaque envelopes , in blocks of four for patients with or without preoperative constipation . Functional assessment was done preoperatively and 12 months postoperatively . The primary outcome was preoperative-to-postoperative change in obstructed defecation syndrome ( ODS ) score . Patients and those assessing the outcomes were masked to the procedure . The primary analysis was done in the per- protocol population . Safety outcomes were assessed in the entire cohort . The trial is registered with Clinical Trials.gov , number NCT0094 Output:	There were no detectable differences between the methods used for fixation during rectopexy . Division , rather than preservation , of the lateral ligaments was associated with less recurrent prolapse but more postoperative constipation . Laparoscopic rectopexy was associated with fewer postoperative complications and shorter hospital stay than open rectopexy . Bowel resection during rectopexy was associated with lower rates of constipation . Recurrence of full-thickness prolapse was greater for mobilisation of the rectum only compared with rectopexy . There were no differences in quality of life for patients who underwent the different kinds of prolapse surgery . It is impossible to identify or refute clinical ly important differences between the alternative surgical operations .
MS21011	*TASK* the task is to summarize an input biomedical literature in six sentences *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 sThe inflammatory response after surgery is associated with various postoperative complications . The aim of the present prospect i ve study was to evaluate the effects of Daikenchuto ( DKT ) ( a Japanese herbal medicine ) on the inflammatory response in patients following laparoscopic colorectal resection . Methods Thirty patients who underwent laparoscopic colectomy for colorectal carcinoma were divided into two groups : a DKT intake group ( D group , n = 15 ) and a control group ( C group , n = 15 ) . The D group took 7.5 g/day of DKT from the day after surgery until the 7th postoperative day . The body temperature , heart rate , WBC count , lymphocyte count , C-reactive protein ( CRP ) level , β-d-glucan level and C and ida index were compared between the two groups . Results The patients ’ mean age in the D group was significantly younger than that in the C group . D3 lymph node dissection was performed more often in the D group . The time until first flatus was significantly shorter in the D group ( 1.8 ± 0.5 days ) than in the C group ( 2.7 ± 0.5 days ) . The CRP level was significantly lower in the D group ( 4.6 ± 0.6 mg/dl ) than in the C group ( 8.3 ± 1.1 mg/dl ) on the 3rd postoperative day . Conclusions Postoperative DKT administration significantly suppressed the CRP level and shortened the time until first flatus . DKT administration also significantly suppressed postoperative inflammation following surgery for colorectal cancer Background Daikenchuto ( TJ-100 ) , a traditional Japanese herbal medicine , is widely used in Japan . Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known . The purpose of this prospect i ve r and omized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients . Methods Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained : a TJ-100 ( 15 g/day)-treated group ( n = 20 ) and a control group ( n = 20 ) . The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function . The secondary efficacy end-points were the serum C-reactive protein ( CRP ) level and adrenomedullin level during the postoperative course , the incidence of postoperative complications , and the length of hospital stay after surgery . Results We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery . The mean age of the TJ-100 group patients was significantly older than that of the control group patients .The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group ( 3.6 % vs. the control group : 7.0 % , p = 0.014 ) , but the serum albumin level was not significantly different between the groups . The recovery of gastrointestinal function regarding flatus , defecation , and oral intake showed no significant between-group differences , but postoperative bowel symptoms tended to be rare in the TJ-100 group . There was no significant between-group difference in the length of hospital stay after surgery . The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group , showing a tendency of a suppressed serum CRP level in the TJ-100 group ( p = 0.126 ) . The rate of increase in adrenomedullin tended to be high postoperatively , but there was no significant difference between the two groups . Conclusions TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss , and it might suppress the excess inflammatory reaction related to surgery Purpose This study aim ed to assess the efficacy of daikenchuto ( DKT ) , a commonly prescribed , traditional Japanese herbal medicine , on postoperative intestinal dysfunction after gastric cancer surgery . Methods Patients with gastric cancer scheduled for a total gastrectomy were r and omly assigned before surgery to receive either no treatment ( n = 40 ; control group ) or DKT ( 7.5 g/day , t.i.d . ) for 3 months ( n = 41 ) postoperatively . We examined gastrointestinal motility , stool attributes , the quantity of bowel gas , the quality of life , and the incidence of postoperative ileus . Results During the hospital stay , significant differences were observed between the DKT group and controls in the number of stools per day ( 1.1 ± 0.6 vs 0.8 ± 0.4 , respectively ; P = 0.037 ) and stool consistencies ( Bristol scale ratings were 3.7 ± 0.8 vs 3.1 ± 0.8 , respectively ; P = 0.041 ) . The DKT group showed significant reductions in gas volume scores , calculated from abdominal radiographs , at 7 days , 1 month , and 3 months after surgery . The groups did not show significant differences in quality of life scores ( based on the Gastrointestinal Symptom Rating Scale ) or in the incidence of postoperative ileus . Conclusion DKT improved bowel movements , stool properties , and bowel gas . These results suggested that DKT promoted early postoperative bowel functions after total gastrectomy Background This exploratory trial was conducted to investigate whether daikenchuto accelerates the recovery of gastrointestinal function in patients undergoing open surgery for sigmoid or rectosigmoid cancer . Methods Eighty-eight patients who underwent colectomy at one of the 11 clinical trial sites in Japan from January 2009 to June 2011 were registered in the study . Patients received either placebo or daikenchuto ( 15.0 g/day , 5 g three times a day ) from postoperative day 2 to postoperative day 8 . The study end points included the gastrointestinal tract transit time evaluated with radiopaque markers and the time to first flatus . The safety profile of daikenchuto was also evaluated until postoperative day 8 . Results Seventy-one patients ( daikenchuto , n = 38 ; placebo , n = 33 ) were statistically analyzed . Although the number of radiopaque markers in the anal side of the small intestine at 6 h was significantly greater in the daikenchuto group than in the placebo group ( 15.19 vs 10.06 , p = 0.008 ) , the total transit analysis results and the mean time to first flatus did not differ significantly between the two groups . Conclusions Daikenchuto has a positive effect on the resolution of delayed gastric emptying , but has a limited effect on the resolution of postoperative paralytic ileus after open surgery in patients with sigmoid or rectosigmoid cancer . Daikenchuto may contribute to early oral intake in the postoperative course BACKGROUND / AIMS Paralytic ileus after laparoscopic-assisted surgery often occurs . We investigated whether daikenchuto ( DKT ) , a traditional Japanese herbal medicine , improves intestinal motility in patients undergoing laparoscopic-assisted colectomy for colon cancer . METHODOLOGY Fifty-four patients who underwent colectomy at Iwate Medical University Hospital between October 2010 and March 2012 were r and omized to either the DKT group ( 7.5 g/day , p.o . ) or the control group ( lactobacillus preparation , 3g/day , p.o . ) . Primary endpoints included time to first flatus , bowel movement , and tolerance of diet after extubation . Secondary endpoints were WBC count , C-reactive protein ( CRP ) level , length of hospital stay , and postoperative ileus . Colonic transit time was measured using radiopaque markers and abdominal radiographs . RESULTS Fifty-one patients ( DKT , 26 vs. control , 25 ) were included in the per- protocol analysis . The DKT group had significantly faster time until first flatus ( 67.5 + /- 13.6h vs. 77.9 + /- 11.8h , P < 0.01 ) and bowel movement ( 82.9 + /- 17.8h vs. 99.5 + /- 18.9h , P < 0.01 ) and colonic transit time ( 91.9 + /- 19.8h vs. 115.2 + /- 12.8 h , P < 0.05 ) . There were no significant intergroup differences in secondary endpoints and adverse events . CONCLUSIONS DKT accelerates colonic motility in patients undergoing laparoscopic-assisted colectomy for colon cancer BACKGROUND Daikenchuto ( DKT ) has widely been used to improve abdominal symptoms by being expected to accelerate bowel motility . The purpose of this study is to examine the efficacy and safety of DKT for prevention of ileus and associated gastrointestinal symptoms after total gastrectomy . STUDY DESIGN Two hundred and forty-five gastric cancer patients who underwent total gastrectomy were enrolled . Patients received either DKT ( 15.0 g/d ) or matching placebo from postoperative days 1 to 12 . Primary end points were time to first flatus , time to first bowel movement ( BM ) , and frequency of BM . Secondary end points included quality of life , C-reactive protein level , symptoms indicative of a severe gastrointestinal disorder , and incidence of postoperative ileus . RESULTS A total of 195 patients ( DKT , n = 96 ; placebo , n = 99 ) were included in the per- protocol set analysis . There were no significant differences between the groups in terms of patient background characteristics . Median time to first BM was shorter in the DKT group than in the placebo group ( 94.7 hours vs 113.9 hours ; p = 0.051 ) . In patients with high medication adherence , median time to first BM was significantly shorter in the DKT group than in the placebo group ( 93.8 hours vs 115.1 hours ; p = 0.014 ) . Significantly fewer patients in the DKT group had ≥2 symptoms of gastrointestinal dysfunction than those in the placebo group on postoperative day 12 ( p = 0.026 ) . CONCLUSIONS Administration of DKT during the immediate postoperative period after total gastrectomy appears to promote early recovery of postoperative bowel function Output:	As a result of meta- analysis by all retrieved according to the registered protocol , daikenchuto was efficacious in improving postoperative bowel dysfunction in patients with gastrointestinal cancers .
MS21012	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Dog-bite wounds are often left open because of their reputation for infection if primarily closed . A prospect i ve r and omized trial comparing primary closure with leaving the wound open was performed to assess infection and cosmesis . Ninety-six patients with 169 lacerations had thorough surgical debridement and irrigation of their wounds . Ninety-two wounds were sutured and 77 left open . No prophylactic antibiotics were given . A total of 13 wounds developed infection : seven sutured and six unsutured wounds ( not statistically significant ) , giving an overall infection rate of 7.7 % . Significantly ( P less than 0.01 ) , more wound infections occurred in the h and in both groups compared to the rest of the body , indicating that particular attention should be paid to management of such wounds . It was concluded that dog-bite wounds should receive thorough surgical treatment and can be safely sutured at presentation . Special care should be given to h and wounds We prospect ively studied the management and outcome of 2,834 children , aged 1 month to 18 years , who presented to the emergency department of the Children 's Hospital of Philadelphia for laceration repair . Patients with bite wounds were excluded from the study . Eight percent ( 239 ) of all patients had complications on initial evaluation ; the most common was the presence of a foreign body ( 55 ) . Infection on presentation was diagnosed in 22 cases ( 0.8 % ) . All of these patients had delayed their initial care beyond 18 hours ( range , 18 to 288 hours ; mean , 18 hours ) . Other factors significantly associated with infection on presentation included occurrence of the injury outdoors ( 16 ; P less than .001 ) , injury due to broken " street " glass ( seven ; P less than .02 ) , and injury of an extremity ( 18 ; P less than .01 ) . The rate of prerepair infection was not influenced by the size of the wound . Infections developed subsequent to initial repair in 34 cases ( 1.2 % ) . Factors associated with development of subsequent infection included use of prophylactic antibiotics , use of subcutaneous sutures , laceration length of more than 5.0 cm , glass or ice as a causative agent , and upper- or lower-extremity involvement . The majority of injuries were repaired by ED personnel without surgical consultation . Postrepair infection rates were not influenced by the specialty of the physician managing the case . Although our study was not design ed to specifically test the issue , prophylactic antibiotics were of no proven benefit in reducing infection rates in any group of patients analyzed STUDY OBJECTIVE More than 11 million patients with traumatic wounds are seen annually in emergency departments . We developed and vali date d a data registry for traumatic wounds treated in the ED . DESIGN Prospect i ve , consecutive patient enrollment with a validation cohort of a convenience sample of 100 patients . SETTING University-affiliated hospital ED . PARTICIPANTS For all patients with traumatic wounds requiring sutures , wound registry data sheets were completed at the time of initial visit using a closed- question format . Data recorded included demographic characteristics , time from injury to evaluation , pertinent medical history , wound characteristics , type of anesthesia , details of wound-cleansing methods , details of wound closure , and postoperative care . We devised a follow-up tool to evaluate for the presence of infection and short-term cosmetic appearance . Interphysician reliability was assessed for wound description , presence of infection , and cosmetic appearance by use of the kappa statistic . RESULTS A wound registry data collection instrument that takes less than 1 minute to complete and enables the collection of most wound management techniques used by emergency physicians was found to have substantial interobserver concordance for wound description ( kappa range , .55 to .97 ) , wound infection ( kappa = 1.0 ) and overall cosmetic appearance ( kappa = .61 ) . CONCLUSION The wound registry is a reliable data collection instrument that is easy to use . It may be useful as a continuous quality -improvement tool or for st and ardization of wound surveillance and treatment data to facilitate future prospect i ve studies in wound management Background The dogma that traumatic wounds should not be sutured after 6 h is based on an animal experiment by P L Friedrich in 1898 . There is no adequately powered prospect i ve study on this cut-off of 6 h to confirm or disprove the dogma . The aim of this study was to provide evidence against the dogma that wounds should be sutured within 6 h after trauma . Method 425 patients were included in a prospect i ve cohort study . Patients ' wounds were closed , independent of time after trauma . All patients were seen after 7–10 days for removal of stitches and wound control on infection . Results Of the 425 patients , 17 were lost to follow-up . Of the remaining 408 patients , 45 had wounds older than 6 h after trauma . At follow-up 372 patients ( 91 % ) had no infection and 36 patients had redness of the suture sites or worse . 11 patients ( 2.7 % ) had general redness or pus . Of those with a wound older than 6 h , three of 45 ( 6.7 % ) wounds were infected , versus 30 of 363 ( 9.1 % ) in wounds younger than 6 h ( p=0.59 ) . Conclusion In everyday practice wounds are sutured regardless of elapsed time . Here an attempt was made to present the evidence for this daily routine , contrary to Friedrich 's Dogma In wounds of the h and and forearm treated within 4 h of injury , prophylactic clindamycin , in a dose of 150 mg 6‐hourly for 5 days , did not reduce the infection rate . In wounds treated after 4 h the infection rate was reduced , but not significantly so . There was a significant reduction in the infection rate comparing all wounds treated within 4 h with those treated after 4 h. Early treatment of wounds is more important than prophylactic antibiotics , although these may have a part to play where late treatment is unavoidable Introduction Primary wound closure in the management of open tibial fractures has generally been discouraged . Several prior studies suggest that infections are not caused by the initial contamination , but are instead the result of organisms acquired in the hospital . Primary wound closure after adequate wound care and fracture stabilisation could therefore be considered a reasonable option . Material s and methods We analysed 95 patients with open tibial fractures ( Gustilo– And erson type 1 to 3A ) treated with primary fracture stabilisation and either delayed wound closure ( group I ) or primary wound closure ( group II ) , with a minimum follow-up of 12 months . Results Group I included 46 patients with a mean age of 30.2 years ( 16–56 ) , and a mean follow-up of 13.5 months ( 12–18 ) . Group II included 49 patients with a mean age of 33.4 ( 18–69 ) , and a mean follow up of 13.7 months ( 12–16 ) . One infection developed in group I ( 2 % ) , and two infections developed in group II ( 4 % ) . This difference was not found to have any statistical significance . Conclusion Our results support other recent reports that the infection rate is not increased following primary wound closure after thorough debridement of less severe open fractures . The length of stay following primary closure ( group II ) was significantly shorter , and that should result in substantially more cost effective care of these serious injuries . We conclude that primary wound closure is a safe option in properly selected cases . Prospect i ve multi-centre studies are needed to further evaluate the safety and efficacy of this treatment alternative Uncertainty about the existence and duration of a " golden period " for suture repair of simple wounds led us to evaluate prospect ively the consequences of delayed primary closure on wound healing . Wounds were eligible for study if they were not grossly infected , and had no associated injuries to nerves , blood vessels , tendons , or bone . Three hundred seventy-two patients underwent suture repair ; 204 ( 54.8 % ) returned for review seven days later . The mean time from wounding to repair for all patients was 24.2 + /- 18.8 hours . Wounds closed at up to 19 hours after wounding had a significantly higher rate of healing than those closed later : 82 of 89 ( 92.1 % ) compared with 89 of 115 ( 77.4 % ) ( P less than .01 ) . Of 23 wounds sutured 48 or more hours ( mean , 65.3 ) after wounding , 18 ( 78.3 % ) were healing at follow-up . In contrast to wounds involving other body areas , the healing of head wounds was virtually independent of time from injury to repair : 42 of 44 ( 95.5 % ) wounds involving the head and repaired later than 19 hours after injury were healing , compared with 47 of 71 ( 66.2 % ) of all other wounds ( P less than .001 ) . On the basis of these data we conclude that there is a 19-hour " golden period " for repair of simple wounds involving body areas other than the head , after which sutured wounds are significantly less likely to heal , and the healing of clean , simple wounds involving the head is unaffected by the interval between injury and repair It is unknown whether leaving the skin wound open to heal by secondary intention is associated with a lower rate of wound infections compared with primary skin-wound closure after operations for colon injuries . From June 1998 to December 2000 at our Level I academic trauma center 48 patients entered into a r and omized controlled trial ( RCT ) and were r and omized to have their skin wound primarily closed ( CLOSED- RCT ) or left open ( OPEN- RCT ) . At the same time patients not included in the RCT were followed prospect ively . At the discretion of the surgeon their skin wounds were managed by primary closure ( CLOSED-non RCT ) or were left open ( OPEN-non RCT ) . Univariate and multivariate analysis was done to identify independent risk factors of wound infection , wound dehiscence , and necrotizing soft tissue infection . Wound infection developed in 65 per cent of CLOSED- RCT and 36 per cent of OPEN- RCT patients ( P = 0.04 ) and wound dehiscence in 31 per cent and 14 per cent respectively ( P = 0.18 ) . No remarkable differences were noted in any other variable including length of hospital stay . Wound infection developed in 29 per cent of CLOSED-non RCT and 15 per cent of OPEN-non RCT patients ( P = 0.46 ) . There were three independent risk factors of wound infection : primary wound closure [ odds ratio ( OR ) = 5.5 , 95 % confidence interval ( CI ) = 1.8 - 19.4 ] , colectomy ( OR = 3.4 , 95 % CI = 1.2 - 10.4 ) , and intraabdominal infection ( OR = 5.3 , 95 % CI = 1.3 - 24.2 ) . There were two independent risk factors for wound dehiscence and /or necrotizing soft tissue infection : wound infection ( OR = 20.9 , 95 % CI = 4.9 - 152.3 ) and intra-abdominal infection ( OR = 19.3 , 95 % CI = 4.0 - 146.9 ) . Primary closure of the wound almost doubles the rate of wound infection compared with leaving the wound open in operations for colon injuries . Primary wound closure is a risk factor for wound infection and wound infection is a risk factor for wound dehiscence or necrotizing soft tissue infection . Because of the complexity of evaluating the real clinical significance of superficial wound infection larger studies on trauma patients are required There is often a delay of more than 12 h in transferring patients with penetrating colonic injury from outlying hospitals to a regional referral centre . The aim of this prospect i ve study was to determine whether primary suture of a penetrating colonic injury in the presence of delayed presentation , shock , peritoneal contamination or associated injuries leads to increased morbidity and mortality rates BACKGROUND / AIMS To compare two non-invasive techniques of assessing wound healing , photography and high resolution ultrasound ( HRUS ) scanning , in experimentally induced full-thickness human skin wounds . METHODS Punch biopsy wounds , 4 mm in diameter , were made aseptically through locally anaesthetised skin on the anterior ( volar ) surface of the non-dominant forearm , 3 cm below the base of the cubital fossa , of 20 human participants . The wounds were treated with a topical antibiotic and covered for 3 days with Mepore sterile dressings . Wound healing was assessed on post-operative days 3 , 7 , 14 and 21 from photographs and HRUS B-scans . All photographs were taken of the wound site and adjacent intact skin under st and ardised conditions . The prints obtained were examined visually and digitised . Digital HRUS B-scans were taken through the centre of the wound bed and the adjacent intact skin parallel to the epidermis . Using the scanner 's calibrated linear measurement capability , the wound width was measured adjacent to the deep surface of the scab , at the base of the wound , and midway between these two levels . RESULTS The wound margins were more clearly defined in the HRUS scans than in the photographs of the wounds ; in some of the latter the scab masked the wound margins . Changes in the surface width of the wound were affected by the time of scab dehiscence , which varied between volunteers . There was less individual variation in the width of the base of the wound , as measured from the HRUS scans . CONCLUSIONS In contrast to photography , which Output:	There is currently no systematic evidence to guide clinical decision-making regarding the timing for closure of traumatic wounds .
MS21013	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To evaluate the impact of nutrition education in kindergartens and to promote healthy dietary habits in children . DESIGN Prospect i ve cohort study . Four kindergartens with 1252 children were r and omized to the intervention group and three with 850 children to the control group . The personal nutritional knowledge , attitudes and dietary behaviours of the parents were also investigated . Each month , children and parents in the intervention group participated in nutrition education activities . The main outcome measures were anthropometrics and diet-related behaviours of the children and the nutritional knowledge and attitudes of the parents at baseline , 6 months ( mid-term ) and 1 year ( post-test ) . Baseline demographic and socio-economic characteristics were also collected . SETTING Seven kindergartens from Hefei , the capital city of Anhui Province , eastern China . SUBJECTS Two thous and one hundred and two 4- to 6-year-old pre-schoolers from seven kindergartens participated . RESULTS The prevalence of children 's unhealthy diet-related behaviours decreased significantly and good lifestyle behaviours increased in the group receiving nutrition education compared with controls . Parental eating habits and attitudes to planning their children 's diets also changed appreciably in the intervention group compared with the control group ( P < 0.05 ) . However , there were no statistically significant differences in children 's height , weight , height-for-age Z-score or weight-for-age Z-score between the two groups . CONCLUSIONS Kindergarten-based nutrition education improves pre-schoolers ' lifestyle behaviours and brings about beneficial changes in parents ' attitudes to planning their children 's diets and their own personal eating habits Background The dramatic rise of overweight and obesity among Chinese children has greatly affected the social economic development . However , no information on the cost-effectiveness of interventions in China is available . The objective of this study is to evaluate the cost and the cost-effectiveness of a comprehensive intervention program for childhood obesity . We hypothesized the integrated intervention which combined nutrition education and physical activity ( PA ) is more cost-effective than the same intensity of single intervention . Methods And Findings : A multi-center r and omized controlled trial conducted in six large cities during 2009 - 2010 . A total of 8301 primary school students were categorized into five groups and followed one academic year . Nutrition intervention , PA intervention and their shared common control group were located in Beijing . The combined intervention and its ’ control group were located in other 5 cities . In nutrition education group , ‘ nutrition and health classes ’ were given 6 times for the students , 2 times for the parents and 4 times for the teachers and health workers . " Happy 10 " was carried out twice per day in PA group . The comprehensive intervention was a combination of nutrition and PA interventions . BMI and BAZ increment was 0.65 kg/m2 ( SE 0.09 ) and 0.01 ( SE 0.11 ) in the combined intervention , respectively , significantly lower than that in its ’ control group ( 0.82±0.09 for BMI , 0.10±0.11 for BAZ ) . No significant difference were found neither in BMI nor in BAZ change between the PA intervention and its ’ control , which is the same case in the nutrition intervention . The single intervention has a relative lower intervention costs compared with the combined intervention . Labor costs in Guangzhou , Shanghai and Jinan was higher compared to other cities . The cost-effectiveness ratio was $ 120.3 for BMI and $ 249.3 for BAZ in combined intervention , respectively . Conclusions The school-based integrated obesity intervention program was cost-effectiveness for children in urban China . Trial Registration Chinese Clinical Trial Registry ChiCTR-PRC-09000402 URL : Exercise has been found to be effective for prevention of weight gain and maintenance of a stable weight in adults . The objective of this study was to evaluate the effect of a school-based aerobic exercise program on the obesity indexes of preschool children . Subjects were 292 second-year elementary school pupils from 2 kindergartens in Hat Yai municipality , Songkhla province , southern Thail and . A specially design ed exercise program , including a 15-min walk before beginning the morning class and a 20-min aerobic dance session after the afternoon nap , 3 times a week , was conducted for 29.6 wk . Weight , height , and triceps skinfold thickness were measured 4 times . At the end of the study , the prevalence of obesity , using 95th percentile National Center for Health Statistics triceps-skinfold-thickness cutoffs , of both the exercise and control groups decreased . That of the exercise group decreased from 12.2 % at baseline to 8.8 % ( Wilcoxon signed-rank test , P = 0.058 ) , whereas that of the control group decreased from 11.7 % to 9.7 % ( Wilcoxon signed-rank test , P = 0.179 ) . A sex difference in the response of body mass index ( BMI ) to exercise was observed . Girls in the exercise group had a lower likelihood of having an increasing BMI slope than the control girls did ( odds ratio : 0.32 ; 95 % CI : 0.18 , 0.56 ) . In conclusion , our study suggests that a 29.6-wk school-based exercise program can prevent BMI gain in girls and may induce a remission of obesity in preschool-age children The development of the ToyBox-intervention was based on the outcomes of the preliminary phase of the ToyBox- study , aim ing to identify young children 's key behaviours and their determinants related to early childhood obesity . The ToyBox-intervention is a multi-component , kindergarten-based , family-involved intervention with a cluster-r and omized design , focusing on the promotion of water consumption , healthy snacking , physical activity and the reduction/ breaking up of sedentary time in preschool children and their families . The intervention was implemented during the academic year 2012 - 2013 in six European countries : Belgium , Bulgaria , Germany , Greece , Pol and and Spain . St and ardized protocol s , methods , tools and material were used in all countries for the implementation of the intervention , as well as for the process , impact , outcome evaluation and the assessment of its cost-effectiveness . A total sample of 7,056 preschool children and their parents/caregivers , stratified by socioeconomic level , provided data during baseline measurements and participated in the intervention . The results of the ToyBox- study are expected to provide a better insight on behaviours associated with early childhood obesity and their determinants and identify effective strategies for its prevention . The aim of the current paper is to describe the design of the ToyBox-intervention and present the characteristics of the study sample as assessed at baseline , prior to the implementation of the intervention Increasing prevalence of childhood obesity calls for comprehensive and cost-effective educative measures in developing countries such as India . School-based educative programmes greatly influence children 's behaviour towards healthy living . We aim ed to evaluate the impact of a school-based health and nutritional education programme on knowledge and behaviour of urban Asian Indian school children . Benchmark assessment of parents and teachers was also done . We educated 40 196 children ( aged 8 - 18 years ) , 25 000 parents and 1500 teachers about health , nutrition , physical activity , non-communicable diseases and healthy cooking practice s in three cities of North India . A pre-tested question naire was used to assess r and omly selected 3128 children , 2241 parents and 841 teachers before intervention and 2329 children after intervention . Low baseline knowledge and behaviour scores were reported in 75 - 94 % government and 48 - 78 % private school children , across all age groups . A small proportion of government school children gave correct answers about protein ( 14 - 17 % ) , carbohydrates ( 25 - 27 % ) and saturated fats ( 18 - 32 % ) . Private school children , parents and teachers performed significantly better than government school subjects ( P < 0.05 ) . Following the intervention , scores improved in all children irrespective of the type of school ( P < 0.001 ) . A significantly higher improvement was observed in younger children ( aged 8 - 11 years ) as compared with those aged 12 - 18 years , in females compared with males and in government schools compared with private schools ( P < 0.05 for all ) . Major gaps exist in health and nutrition-related knowledge and behaviour of urban Asian Indian children , parents and teachers . This successful and comprehensive educative intervention could be incorporated in future school-based health and nutritional education programmes Background Childhood obesity has been a serious public health problem . An effective school-based physical activity ( PA ) intervention is still lacking in China . This study aim ed to assess the effectiveness of a school-based physical activity intervention during 12 weeks on obesity and related health outcomes in school children . Methods It was a non-r and omized controlled trial . Altogether 921 children aged 7 to 15 years were recruited at baseline survey . Children in the intervention group ( n = 388 ) participated in a multi-component physical activity intervention during 12 weeks that included improvement of physical education , extracurricular physical activities for overweight/obese students , physical activities at home , and health education lectures for students and parents . Children ( n = 533 ) in the control group participated in usual practice . Results Participants had mean age of 10.4 years , mean body mass index ( BMI ) of 19.59 kg/m2 , and 36.8 % of them were overweight or obese at baseline survey . The change in BMI in intervention group ( −0.02 ± 0.06 kg/m2 ) was significantly different from that in control group ( 0.41 ± 0.08 kg/m2 ) . The adjusted mean difference was −0.43 kg/m2 ( 95 % CI : −0.63 to −0.23 kg/m2 , P < 0.001 ) . The effects on triceps , subscapular , abdominal skinfold thickness and fasting glucose were also significant in intervention group compared with control group ( all P < 0.05 ) . The change in duration of moderate to vigorous physical activity ( MVPA ) in intervention group ( 8.9 ± 4.3 min/day ) was significantly different from that in control group ( −13.8 ± 3.3 min/day ) . The adjusted mean difference was 22.7 min/day ( 95 % CI : 12.2 to 33.2 min/day , P < 0.001 ) . Conclusions The school-based , multi-component physical activity intervention was effective to decreasing levels of BMI , skinfold thickness , fasting glucose and increasing duration of MVPA . These findings provided evidence for the development of effective and feasible school-based obesity interventions .Trial registration Clinical trials.gov Identifier : NCT02074332 ( 2014 - 02 - 26 OBJECTIVES To determine whether a large-scale physical activity intervention could affect body composition in primary school students in Beijing , China . METHODS The study design was one-year cluster r and omized controlled trial of physical activity intervention ( 20 min of daily exercise in the classroom ) with an additional year of follow-up among 4 700 students aged 8 - 11 years at baseline . RESULTS After the one-year intervention , BMI increased by 0.56 kg/m(2 ) ( SD 1.15 ) in the intervention group and by 0.72 kg/m(2 ) ( SD 1.20 ) in the control group , with a mean difference of -0.15 kg/m(2 ) ( 95 % CI : -0.28 to -0.02 ) . BMI z score decreased by -0.05 ( SD 0.44 ) in the intervention group , but increased by 0.01 ( SD 0.46 ) in the control group , with a mean difference of -0.07 ( -0.13 to -0.01 ) . After another year of follow up , compared to the control group , children in the intervention group had significantly lower BMI ( -0.13 , -0.25 to -0.01 ) , BMI z score ( -0.05 , -0.10 to -0.01 ) , fat mass ( -0.27 kg , -0.53 to -0.02 ) and percent body fat ( -0.53 , -1.00 to -0.05 ) . The intervention had a more pronounced effect on weight , height , BMI , BMI z score , and body composition among obese children than among normal weight or overweight children . Compared to the control group , the intervention group had a significantly higher percentage of children who maintained or reduced their BMI z score at year 1 ( P=0.008 ) and year 2 ( P=0.04 ) . CONCLUSIONS These findings suggest that 20 min of daily moderate to vigorous physical activity during the school year is a feasible and effective way to prevent excessive gain of body weight , BMI , and body fatness in primary school students Background The prevalence of childhood obesity among adolescents has been rapidly rising in Mainl and China in recent decades , especially in urban and rich areas . There is an urgent need to develop effective interventions to prevent childhood obesity . Limited data regarding adolescent overweight prevention in China are available . Thus , we developed a school-based intervention with the aim of reducing excess body weight in children . This report described the study design . Methods / design We design ed a cluster r and omized controlled trial in 8 r and omly selected urban primary schools between May 2010 and December 2013 . Each school was r and omly assigned to either the intervention or control group ( four schools in each group ) . Participants were the 4th grade rs in each participating school . The multi Output:	Targeting preschool setting s and applying a comprehensive multisectoral approach may increase the effectiveness and sustainability of childhood obesity prevention programmes
MS21014	*TASK* the task is to summarize an input biomedical literature in six sentences *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 last quarter of the twentieth century has brought about sweeping changes in the loco-regional treatment of breast cancer . R and omised trials have consistently established that survival rates after conservation surgery and breast irradiation are equivalent to those observed after modified radical mastectomy [ 1 ] . Moreover , during the same period the use of mammography in asymptomatic women has led to a relative increase in small tumours , ideally suitable for breast conservation . As a consequence , the use of conservation surgery has risen progressively during the 1980s and 1990s , with a corresponding increase in the importance of breast irradiation . In addition , recent meta-analyses of r and omised trials have established that breast cancer mortality can be significantly reduced by loco-regional radiotherapy ( RT ) , and that the increased intercurrent mortality observed in older trials was caused by an excess in cardiovascular deaths , presumably avoidable , associated with the earlier techniques [ 2,3 ] . Newer trials of postmastectomy radiotherapy ( PMRT ) have demonstrated a clear survival improvement , without excess cardiac morbidity , leading to an increased confidence in the use of adjuvant loco-regional RT [ 4,5 ] . The extent of the swing to conservative surgery varies amongst geographical regions , depending , at least in part , on the availability of radiotherapy services . With the increasing diffusion of medical technology throughout Europe , this factor will probably assume a decreasing importance for the choice of primary breast cancer therapy . In urban areas with a high socio-economic st and ard , it is likely that mastectomy will come to be practised in a dwindling minority of patients . According to the Geneva Tumour Registry , the proportion of all curative breast operations that were conservative rose from 3 % before 1985 , to 51 % in 1990 , then to 67 % since 1998 ( Registre genevois des tumeurs , unpublished data , 2000 ) . As a consequence , patients currently requiring mastectomy are likely to have larger tumours and positive lymph nodes , and will frequently be considered for PMRT . In such a setting , a substantial majority of primary breast cancer patients will therefore receive RT as part of their initial treatment . These changes come at a time when the prevalence of breast cancer is increasing significantly due , at least partly , to the ageing of the European population . For Geneva , an increase of more than 50 % in the number of new breast cancer cases is projected for the period between 2000 and 2010 ( Registre genevois des tumeurs , unpublished data , 1998 ) . The dem and for radiotherapy services required to treat breast cancer patients may thus be expected to increase substantially . Accordingly , the European Society of Mastology ( EUSOMA ) believes that a position paper regarding the use of RT in breast cancer is timely and useful . This document discusses the indications for adjuvant RT in operable breast cancer ( clinical stages T0 - 3 , N0 - 1 , M0 ) , the technical principles for its proper execution , and where possible , notions of its optimal co-ordination with other treatment modalities . As the breast cancer literature is vast , analysis was necessarily restricted to data having a high likelihood of being reliable , making every effort to draw conclusions likely to be pertinent PURPOSE To test for an association between in vitro fibroblast radiosensitivity and complication risk in a case-control study of breast cancer patients treated under st and ard conditions in a clinical trial of radiotherapy dose fractionation . PATIENTS AND METHODS A cohort of patients participating in a r and omised clinical trial of radiotherapy dose fractionation was selected on the basis of treatment-induced changes in the breast several years later . Thirty-nine cases with marked normal tissue changes were matched on several variables with 65 controls with no changes attributable to radiotherapy . Dermal fibroblast strains were established from duplicate skin biopsies , and clonogenic cell survival assays performed in triplicate after both high ( approximately 1.6 Gy/min ) and low ( approximately 1 cGy/min ) dose-rate irradiation . Laboratory studies were blind to patient identity , treatment outcome and radiotherapy schedule . RESULTS Analysis of 1128 clonogenic survival curves confirmed significant inter-patient variation in fibroblast radiosensitivity as measured by clonogenic survival . However , no association between fibroblast radiosensitivity and the development of late radiotherapy normal tissue effects was detected . CONCLUSIONS Inter-individual variation in cellular radiosensitivity may not be the main determinant of complication risk in patients undergoing radiotherapy for breast cancer . Other biological and technical factors may be more important in explaining the marked inter-patient differences in normal tissue damage evident several years after curative radiotherapy PURPOSE Concurrent chemoradiation therapy ( CCRT ) for squamous cell carcinoma of the head and neck ( SCCHN ) increases local tumor control but at the expense of increased toxicity . We recently showed that several clinical /pretreatment factors were associated with the occurrence of severe late toxicity . This study evaluated the potential relationship between radiation dose delivered to the pharyngeal wall and toxicity . METHODS AND MATERIAL S This was an analysis of long-term survivors from 3 previously reported Radiation Therapy Oncology Group ( RTOG ) trials of CCRT for locally advanced SCCHN ( RTOG trials 91 - 11 , 97 - 03 , and 99 - 14 ) . Severe late toxicity was defined in this secondary analysis as chronic grade 3 - 4 pharyngeal/laryngeal toxicity and /or requirement for a feeding tube≥2 years after registration and /or potential treatment-related death ( eg , pneumonia ) within 3 years . Radiation dosimetry ( 2-dimensional ) analysis was performed central ly at RTOG headquarters to estimate doses to 4 regions of interest along the pharyngeal wall ( superior oropharynx , inferior oropharynx , superior hypopharynx , and inferior hypopharynx ) . Case-control analysis was performed with a multivariate logistic regression model that included pretreatment and treatment potential factors . RESULTS A total of 154 patients were evaluable for this analysis , 71 cases ( patients with severe late toxicities ) and 83 controls ; thus , 46 % of evaluable patients had a severe late toxicity . On multivariate analysis , significant variables correlated with the development of severe late toxicity , including older age ( odds ratio , 1.062 per year ; P=.0021 ) and radiation dose received by the inferior hypopharynx ( odds ratio , 1.023 per Gy ; P=.016 ) . The subgroup of patients receiving ≤60 Gy to the inferior hypopharynx had a 40 % rate of severe late toxicity compared with 56 % for patients receiving > 60 Gy . Oropharyngeal dose was not associated with this outcome . CONCLUSIONS Severe late toxicity following CCRT is common in long-term survivors . Age is the most significant factor , but hypopharyngeal dose also was associated BACKGROUND Several studies have reported associations between radiation toxicity and single nucleotide polymorphisms ( SNPs ) in c and i date genes . Few associations have been tested in independent validation studies . This prospect i ve study aim ed to vali date reported associations between genotype and radiation toxicity in a large independent data set . METHODS 92 ( of 98 attempted ) SNPs in 46 genes were successfully genotyped in 1613 patients : 976 received adjuvant breast radiotherapy in the Cambridge breast IMRT trial ( IS RCT N21474421 , n=942 ) or in a prospect i ve study of breast toxicity at the Christie Hospital , Manchester , UK ( n=34 ) . A further 637 received radical prostate radiotherapy in the MRC RT01 multicentre trial ( IS RCT N47772397 , n=224 ) or in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer ( CHHiP ) trial ( IS RCT N97182923 , n=413 ) . Late toxicity was assessed 2 years after radiotherapy with a vali date d photographic technique ( patients with breast cancer only ) , clinical assessment , and patient question naires . Association tests of genotype with overall radiation toxicity score and individual endpoints were undertaken in univariate and multivariable analyses . At a type I error rate adjusted for multiple testing , this study had 99 % power to detect a SNP , with minor allele frequency of 0·35 , associated with a per allele odds ratio of 2·2 . FINDINGS None of the previously reported associations were confirmed by this study , after adjustment for multiple comparisons . The p value distribution of the SNPs tested against overall toxicity score was not different from that expected by chance . INTERPRETATION We did not replicate previously reported late toxicity associations , suggesting that we can essentially exclude the hypothesis that published SNPs individually exert a clinical ly relevant effect . Continued recruitment of patients into studies within the Radiogenomics Consortium is essential so that sufficiently powered studies can be done and method ological challenges addressed . FUNDING Cancer Research UK , The Royal College of Radiologists , Addenbrooke 's Charitable Trust , Breast Cancer Campaign , Cambridge National Institute of Health Research ( NIHR ) Biomedical Research Centre , Experimental Cancer Medicine Centre , East Midl and s Innovation , the National Cancer Institute , Joseph Mitchell Trust , Royal Marsden NHS Foundation Trust , Institute of Cancer Research NIHR Biomedical Research Centre for Cancer BACKGROUND AND PURPOSE We have performed a case-control study among prostate cancer patients treated with three-dimensional conformational radiotherapy ( 3D-CRT ) in order to investigate the association between single nucleotide polymorphisms ( SNPs ) , treatment and patient features with gastrointestinal and genitourinary acute toxicity . MATERIAL AND METHODS A total of 698 patients were screened for 14 SNPs located in the ATM , ERCC2 , LIG4 , MLH1 and XRCC3 genes . Gastrointestinal and genitourinary toxicities were recorded prospect ively using the Common Terminology Criteria for Adverse Events v3.0 . RESULTS The XRCC3 SNP rs1799794 ( G/G OR=5.65 ; 95 % CI : 1.95 - 16.38 ; G/A OR=2.75 ; 95 % CI : 1.25 - 6.05 ; uncorrected p-value=2.8 × 10(-03 ) ; corrected p-value=0.03 ; FDR q-value=0.06 ) as well as the mean dose received by the rectum ( OR=1.06 ; 95 % CI : 1.02 - 1.1 ; uncorrected p-value=2.49 × 10(-03 ) ; corrected p-value=0.03 ; FDR q-value=0.06 ) were significantly associated with gastrointestinal toxicity after correction for multiple testing . Those patients who undergone previous prostatectomy were less prone to develop genitourinary toxicity ( OR=0.38 ; 95 % CI : 0.18 - 0.71 ; uncorrected p-value=4.95 × 10(-03 ) ; corrected p-value=0.03 ; FDR q-value=0.08 ) . Our study excludes the possibility of a > 2-fold risk increase in genitourinary acute toxicity being due to rs1801516 ATM SNP , the rs1805386 and rs1805388 LIG4 markers , as well as all the SNPs evaluated in the ERCC2 , MLH1 and XRCC3 genes . CONCLUSIONS The XRCC3 rs1799794 SNP and the mean dose received by the rectum are associated with the development of gastrointestinal toxicity after 3D-CRT Output:	In the sensitivity analyses , small studies did not show larger effects than large studies . In addition , studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence . We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was dependent on the incidence of the injury .
MS21015	*TASK* the task is to summarize an input biomedical literature in six sentences *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 prospect ively the prognostic value of FDG PET/CT during curative-intent radiotherapy ( RT ) with or without concomitant chemotherapy in patients with non-small-cell lung cancer ( NSCLC ) . Methods Patients with histological proof of invasive localized NSCLC and evaluable tumour , and who were c and i date s for curative-intent radiochemotherapy ( RCT ) or RT were preincluded after providing written informed consent . Definitive inclusion was conditional upon significant FDG uptake before RT ( PET1 ) . All included patients had a FDG PET/CT scan during RT ( PET2 , mean dose 43 Gy ) and were evaluated by FDG PET/CT at 3 months and 1 year after RT . The main endpoint was death ( from whatever cause ) or tumour progression at 1 year . Results Of 77 patients preincluded , 52 were evaluable . Among the evaluable patients , 77 % received RT with induction chemotherapy and 73 % RT with concomitant chemotherapy . At 1 year , 40 patients ( 77 % ) had died or had tumour progression . No statistically significant association was found between stage ( IIIB vs. other ) , histology ( squamous cell carcinoma vs. other ) , induction or concomitant chemotherapy , and death/tumour progression at 1 year . The SUVmax in the PET2 scan was the single variable predictive of death or tumour progression at 1 year ( odds ratio 1.97 , 95 % CI 1.25 – 3.09 , p = 0.003 ) in multivariate analysis . The area under the receiver operating characteristic curve was 0.85 ( 95 % CI 0.73 – 0.94 , p < 10−4 ) . A SUVmax value of 5.3 in the PET2 scan yielded a sensitivity of 70 % and a specificity of 92 % for predicting tumour progression or death at 1 year . Conclusion This prospect i ve multicentre study demonstrated the prognostic value in terms of disease-free survival of SUVmax assessed during the 5th week of curative-intent RT or RCT in NSCLC patients ( NCT01261598 ; RTEP2 study ) The potential of 18F-FDG PET changes was evaluated for prediction of response to concomitant chemoradiotherapy in patients with locally advanced non – small cell lung cancer ( NSCLC ) . Methods : For 28 patients , 18F-FDG PET was performed before treatment , at the end of the second week of treatment , and at 2 wk and 3 mo after the completion of treatment . St and ardized uptake value ( SUV ) , maximum SUV , metabolic tumor volume ( MTV ) , and total lesion glycolysis ( TLG ) were obtained . Early metabolic changes were defined as fractional change ( ΔTLG ) when 18F-FDG PET at the end of the second week was compared with pretreatment 18F-FDG PET . In-treatment metabolic changes , as measured by serial 18F-FDG PET , were correlated with st and ard criteria of response evaluation of solid tumors by means of CT imaging ( Response Evaluation Criteria In Solid Tumors 1.1 ) . Parameters were analyzed for stratification in progression-free survival ( PFS ) . Results : When compared with early metabolic nonresponders , a ΔTLG decrease of 38 % or more was associated with a significantly longer PFS ( 1-y PFS 80 % vs. 36 % , P = 0.02 ) . Pretreatment TLG was found to be a prognostic factor for PFS . Conclusion : The degree of change in TLG was predictive for response to concomitant chemoradiotherapy as early as the end of the second week into treatment for patients with locally advanced NSCLC . Pretreatment TLG was prognostic for PFS OBJECTIVES The objectives were ( i ) to confirm that diagnostic FDG-PET images could be obtained during thoracic radiotherapy , ( ii ) to verify that significant changes in FDG uptake or volume could be measured early enough to adapt the radiotherapy plan and ( iii ) to determine an optimal time window during the radiotherapy course to acquire a single FDG-PET examination that would be representative of tumour response . METHODS Ten non-small cell lung carcinoma ( NSCLC ) patients with significant PET/CT-FDG tumour radioactivity uptake ( versus the background level ) , c and i date s for curative radiotherapy ( RT , n=4 ; 60 - 70 Gy , 2 Gray per fraction , 5 fractions per week ) or RT plus chemotherapy ( CT-RT , n=6 ) , were prospect ively evaluated . Using a Siemens Biograph , 5 or 6 PET/CT scans ( PET(n ) , n=0 - 5 ) were performed for each patient . Each acquisition included a 15-min thoracic PET with respiratory gating ( RG ) 60±5 min post-injection of the FDG ( 3.5 MBq/kg ) , followed by a st and ard , 5-min non-gated ( STD ) thoracic PET . PET(0 ) was performed before the first RT fraction . During RT , PET(1 - 5 ) were performed every 7 fractions , i.e. , at 14 Gy total dose increment . FDG uptake was measured as the variation of SUV(max , PETn ) versus SUV(max , PET0 ) . Each lesions ' volume was measured by ( i ) visual delineation by an experienced nuclear physician , ( ii ) 40 % SUV(max ) fixed threshold and ( iii ) a semi-automatic adaptive threshold method . RESULTS A total of 53 FDG-PET scans were acquired . Seventeen lesions ( 6 tumours and 11 nodes ) were visible on PET(0 ) in the 10 patients . The lesions were located either in or near the mediastinum or in the apex , without significant respiratory displacements at visual inspection of the gated images . Healthy lung did not cause motion artefacts in the PET images . As measured on 89 lesions , both the absolute and relative SUV(max ) values decreased as the RT dose increased . A 50 % SUV(max ) decrease was obtained around a total dose of 45 Gy . Out of the 89 lesions , 75 remained visually identifiable during the entire course of treatment . The 40 % fixed threshold and adaptive threshold methods failed to delineate otherwise visible lesions in 16/33 ( 48 % ) and 3/33 ( 9 % ) lesions , respectively . The failure rate increased with increasing RT doses . Restricting the analysis to the manually-defined volumes in 89 visible lesions , the relative volumes decreased with increased dose . CONCLUSIONS FDG-PET images can be analysed during thoracic RT , given either alone or with chemotherapy , without disturbing radiation-induced artefacts . An average 50 % decrease in SUV(max ) was observed around 40 - 45 Gy ( i.e. , during week 5 of RT ) . The three delineation methods yielded consistent volume measurements before RT and during the first week of RT , while manual delineation appeared to be more reliable later on during RT The objectives of this study were to investigate the relationship between CT- and 18F-FDG PET – based tumor volumes in non – small cell lung cancer ( NSCLC ) and the impact of tumor size and uptake heterogeneity on various approaches to delineating uptake on PET images . Methods : Twenty-five NSCLC cancer patients with 18F-FDG PET/CT were considered . Seventeen underwent surgical resection of their tumor , and the maximum diameter was measured . Two observers manually delineated the tumors on the CT images and the tumor uptake on the corresponding PET images , using a fixed threshold at 50 % of the maximum ( T50 ) , an adaptive threshold methodology , and the fuzzy locally adaptive Bayesian ( FLAB ) algorithm . Maximum diameters of the delineated volumes were compared with the histopathology reference when available . The volumes of the tumors were compared , and correlations between the anatomic volume and PET uptake heterogeneity and the differences between delineations were investigated . Results : All maximum diameters measured on PET and CT images significantly correlated with the histopathology reference ( r > 0.89 , P < 0.0001 ) . Significant differences were observed among the approaches : CT delineation result ed in large overestimation ( + 32 % ± 37 % ) , whereas all delineations on PET images result ed in underestimation ( from −15 % ± 17 % for T50 to −4 % ± 8 % for FLAB ) except manual delineation ( + 8 % ± 17 % ) . Overall , CT volumes were significantly larger than PET volumes ( 55 ± 74 cm3 for CT vs. from 18 ± 25 to 47 ± 76 cm3 for PET ) . A significant correlation was found between anatomic tumor size and heterogeneity ( larger lesions were more heterogeneous ) . Finally , the more heterogeneous the tumor uptake , the larger was the underestimation of PET volumes by threshold-based techniques . Conclusion : Volumes based on CT images were larger than those based on PET images . Tumor size and tracer uptake heterogeneity have an impact on threshold-based methods , which should not be used for the delineation of cases of large heterogeneous NSCLC , as these methods tend to largely underestimate the spatial extent of the functional tumor in such cases . For an accurate delineation of PET volumes in NSCLC , advanced image segmentation algorithms able to deal with tracer uptake heterogeneity should be preferred Background We studied whether maximum st and ardized uptake values ( SUV ) from [ 18 F ] PET/CT predict clinical outcome after concurrent proton/chemotherapy for stage III non-small cell lung cancer ( NSCLC ) . Methods Eighty-four patients were treated prospect ively with 74 Gy(RBE ) proton therapy and concurrent chemotherapy . PET/CT scans were available before ( SUV1 ) and within 6 months after ( SUV2 ) treatment . The predictive value of clinical and PET/CT factors were analyzed with univariate and multivariate Cox regression models . Results Median survival time was 29.9 months . At 3 years , the local recurrence-free survival ( LRFS ) rate was 34.8 % ; distant metastasis-free survival ( DMFS ) , 35.4 % ; progression-free survival ( PFS ) , 31.2 % ; and overall survival ( OS ) , 37.2 % . Patients with SUV2 ≥3.6 ( the median ) had high rates of LR ( p = 0.021 ) . Of 12 clinicopathologic features evaluated in univariate analysis , only KPS , SUV1 , and SUV2 predicted LRFS , DMFS , PFS , and OS ( p < 0.05 ) . Multivariate analysis showed that KPS ( p = 0.025 ) and SUV2 ( p = 0.017 ) were independently prognostic for LRFS and that SUV1 , SUV2 , and KPS were independently prognostic for DMFS , PFS , and OS ( p < 0.05 ) . Conclusions SUV2 predicted LRFS , and SUV1 and SUV2 predicted DMFS , PFS , and OS , in patients with stage III NSCLC treated with concurrent chemotherapy and high-dose proton therapy PURPOSE To develop a positron emission tomography (PET)-based response prediction model to differentiate pathological responders from nonresponders . The predictive strength of the model was vali date d in a second patient group , treated and imaged identical to the patients on which the predictive model was based . METHODS AND MATERIAL S Fifty-one rectal cancer patients were prospect ively included in this study . All patients underwent fluorodeoxyglucose ( FDG ) PET-computed tomography ( CT ) imaging both before the start of chemoradiotherapy ( CRT ) and after 2 weeks of treatment . Preoperative treatment with CRT was followed by a total mesorectal excision . From the resected specimen , the tumor regression grade ( TRG ) was scored according to the M and ard criteria . From one patient group ( n = 30 ) , the metabolic treatment response was correlated with the pathological treatment response , result ing in a receiver operating characteristic ( ROC ) curve based cutoff value for the reduction of maximum st and ardized uptake value ( SUV(max ) ) within the tumor to differentiate pathological responders ( TRG 1 - 2 ) from nonresponders ( TRG 3 - 5 ) . The applicability of the selected cutoff value for new patients was vali date d in a second patient group ( n = 21 ) . RESULTS When correlating the metabolic and pathological treatment response for the first patient group using ROC curve analysis ( area under the curve = 0.98 ) , a cutoff value of 48 % SUV(max ) reduction was selected to differentiate pathological responders from nonresponders ( specificity of 100 % , sensitivity of 64 % ) . Applying this cutoff value to the second patient group result ed in a specificity and sensitivity of , respectively , 93 % and 83 % , with only one of the pathological nonresponders being false positively predicted as pathological responding . CONCLUSIONS For rectal cancer , an accurate PET-based prediction of the pathological treatment response is feasible already after 2 weeks of CRT . The presented predictive model could be used to select patients to be considered for less invasive surgical interventions or even a " wait and see " policy . Also , based on the predicted response , early modifications of the treatment protocol are possible , which might result in an improved clinical outcome PURPOSE In this prospect i ve National Cancer Institute-funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial , we hypothesized that st and ard Output:	Conclusion Certainly , the lack of univocal PET parameters was identified as a major drawback , while st and ardization would be required for best practice . In any case , all these papers denoted FDGint as promising and a challenging examination for early assessment of outcomes during CRT , sustaining its predictivity in lung cancer
MS21016	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The aim of the present prospect i ve longitudinal study of periodontally diseased and periodontally healthy patients was a clinical , microbiological , and radiographic comparison of teeth and implants and an assessment of the implant success rate . METHODS Thirty-nine partially edentulous patients provided with a total of 150 implants were enrolled in the study . Oral rehabilitation was undertaken in 15 patients treated for generalized aggressive periodontitis ( GAgP ) , 12 patients treated for generalized chronic periodontitis ( GCP ) , and 12 periodontally healthy patients . The examinations of the teeth and implants were carried out within the framework of a 3-month recall schedule over a 3-year period . At each session , clinical parameters for probing depth ( PD ) , gingival recession ( GR ) , attachment level ( AL ) , gingival index ( GI ) , and plaque index ( PI ) were recorded , and the composition of the subgingival microflora determined by dark-field microscopy . In the periodontally diseased patients , Actinobacillus actinomycetemcomitans ( A.a . ) , Porphyromonas gingivalis ( P.g . ) , and Prevotella intermedia ( P.i . ) were detected at teeth and implants by DNA analysis in the first and third years after insertion of the superstructure . Intraoral radiographs of the teeth and implants were taken at baseline , immediately after insertion of the superstructure , and then 1 and 3 years later . RESULTS The GI and PI at implants and teeth remained below 0.25 and 0.6 , respectively , in all patient groups throughout the study period . At the implants and teeth , a slight increase in PD and a continuous attachment loss was recorded in the GAgP patients . The attachment loss was greater at the implants than at the teeth in all groups . The morphological distribution of the microorganisms revealed virtually healthy conditions in all groups . A.a . was detected in two GAgP patients , whereas P.g . and P.i . were found more frequently both in the GAgP and in the GCP patients . Radiographically detected bone loss was higher after 3 years at implants and teeth in the GAgP patients than in the other two groups . The implant success rates recorded were 100 % in the periodontally healthy and GCP patients , and 95.7 % in the maxilla and 100 % in the m and ible of the GAgP patients . CONCLUSIONS The results show that oral rehabilitation can be performed with implants in patients treated for generalized aggressive and chronic periodontitis . However , slight attachment loss and bone loss were registered at the implants and teeth in the patients with aggressive periodontitis OBJECTIVES To evaluate healing of marginal defects in immediate transmucosal implants grafted with anorganic bovine bone , and to assess mucosal and radiographic outcomes 3 - 4 years following restoration . MATERIAL AND METHODS Thirty immediate transmucosal implants in maxillary anterior extraction sites of 30 patients r and omly received BioOss ( N=10 ; BG ) , BioOss and resorbable collagen membrane ( N=10 ; BG+M ) or no graft ( N=10 ; control ) . RESULTS Vertical defect height ( VDH ) reductions of 81.2+/-5 % , 70.5+/-17.4 % and 68.2+/-16.6 % , and horizontal defect depth ( HDD ) reductions of 71.7+/-34.3 % , 81.7+/-33.7 % and 55+/-28.4 % were observed for BG , BG+M and control groups , respectively , with no significant inter-group differences . Horizontal resorption was significantly greater in control group ( 48.3+/-9.5 % ) when compared with BG ( 15.8+/-16.9 % ) and BG+M ( 20+/-21.9 % ) groups ( P=0.000 ) . Ten sites ( 33.3 % ) exhibited recession of the mucosa after 6 months ; eight ( 26.7 % ) had an unsatisfactory esthetic result post-restoration due to recession . Mucosal recession was significantly associated ( P=0.032 ) with buccally positioned implants ( HDD 1.1+/-0.3 mm ) when compared with lingually positioned implants ( HDD 2.3+/-0.6 mm ) . In 19 patients followed for a mean of 4.0+/-0.7 years , marginal mucosa and bone levels remained stable following restoration . CONCLUSION BioOss significantly reduced horizontal resorption of buccal bone . There is a risk of mucosal recession and adverse soft tissue esthetics with immediate implant placement . However , this risk may be reduced by avoiding a buccal position of the implant in the extraction socket PURPOSE The aim of this investigation was to evaluate the 3-year outcomes regarding crestal bone level , clinical parameters , and patient satisfaction , following submerged and transmucosal implant placement for two-piece implants in the anterior maxilla and m and ible . MATERIAL S AND METHODS Patients requiring dental implants for single-tooth replacement in the anterior maxilla or m and ible were enrolled in a r and omized , controlled , multicenter clinical trial . The implants were r and omized at placement to either submerged or transmucosal healing , with final restorations placed after 6 months . Radiographic and clinical parameters were recorded after 1 , 2 , and 3 years ; a question naire was also used to assess patient satisfaction . A two-sided , unpaired T-test ( significance level p ≤ .05 ) was used to statistically evaluate the differences between the two groups . RESULTS A total of 106 patients were included in the 3-year analysis . The mean change in crestal bone level from implant placement to 3 years was 0.68 ± 0.98 mm ( p < .001 ) and 0.58 ± 0.77 mm ( p < .001 ) in the submerged and transmucosal groups , respectively ; the differences between the groups were not significant . Clinical parameters remained stable throughout the study , with no significant differences between the groups , and patient satisfaction was good or excellent for over 90 % of subjects in both groups . CONCLUSIONS The results demonstrate excellent clinical and radiographic conditions after 3 years for implants supporting single-tooth restorations , regardless of whether a submerged or transmucosal surgical technique was used BACKGROUND The aim of this prospect i ve study is to evaluate the prevalence of mucositis , peri-implantitis , implant success , and survival in partially edentulous patients treated for generalized aggressive periodontitis ( GAgP ) and in periodontally healthy individuals . METHODS Thirty-five patients treated for GAgP and 18 periodontally healthy patients orally rehabilitated with osseointegrated implants participated in the study . They were first examined 2 to 4 weeks before extraction of the non-retainable teeth ( baseline ) and 3 weeks after insertion of the final abutments . Additional examinations were performed during a 3-month recall schedule over a 5- to 16-year period ( mean , 8.25 years ) . At every session , clinical parameters were recorded . At 1 , 3 , 5 , 10 , and 15 years after insertion of the superstructure , a microbiological and radiographic examination was performed . RESULTS The results show implant survival rates of 100 % in periodontally healthy individuals versus 96 % in GAgP patients . The implant success rate was 33 % in GAgP patients and 50 % in periodontally healthy individuals . In GAgP patients , mucositis was present in 56 % and peri-implantitis in 26 % of the implants . In periodontally healthy individuals , 40 % of the implants showed mucositis and 10 % peri-implantitis . GAgP patients had a five times greater risk of implant failure , a three times greater risk of mucositis , and a 14 times greater risk of peri-implantitis . CONCLUSION These results suggest that patients with treated GAgP are more susceptible to mucositis and peri-implantitis , with lower implant survival and success rates OBJECTIVES To evaluate the long-term survival rates of dental implants according to the patient 's periodontal status , as well as to estimate if the effect of periodontal status regarding implant failure is constant throughout the long-term follow-up . MATERIAL S AND METHODS This was a historical prospect i ve cohort study design of all consecutive patients operated from 1996 to 2006 at a periodontal clinic . The cohort consisted of 736 patients , with a total of 2336 dental implants . An extended Cox proportional hazards model , which includes interaction terms between survival time and variables of interest , was used . RESULTS Patients ' mean ( SD ) age was 51.13 ( 12.35 ) . The follow-up time was up to 144 months , with a mean ( SD ) of 54.4 ( 35.6 ) months . The overall implant raw survival rate was 95.9 % . The Kaplan-Meier estimates for the cumulative survival rate ( CSR ) at 108 months were 0.96 and 0.95 for implants inserted into healthy and moderate chronic periodontal patients , respectively . The CSR declined to 0.88 at 108 months for the severe periodontitis group . The extended Cox model revealed that severe chronic status turned out to be a significant risk factor for implant failure after 50 months of follow-up [ hazard ratio (HR)=8.06 ; p<0.01 ] . The extended Cox model for smoking indicates a near-significant effect after 50 months ( HR=2.76 ; p=0.061 ) . CONCLUSIONS Periodontal status and smoking are significant risk factors for late implant failures . The HR for periodontal and smoking status are not constant throughout the follow-up period AIM To determine the incidence of peri-implantitis in individuals with mucositis in a 5-year follow-up study . MATERIAL AND METHODS A sample of 212 partially edentulous individuals , rehabilitated with dental implants , underwent periodontal and peri-implant clinical examinations in 2005 ( baseline ) . Five years later , 80 individuals who had been diagnosed with mucositis in the baseline examination were re-examined . These individuals were divided into two groups : one group with preventive maintenance during the study period ( GTP ; n = 39 ) , and another group without preventive maintenance ( GNTP ; n = 41 ) . The following parameters were clinical ly evaluated : plaque index , bleeding on periodontal and peri-implant probing , periodontal and peri-implant probing depth , suppuration and peri-implant bone loss . The influence of biological and behavioural risk variables associated with the occurrence of peri-implantitis was analysed using univariate and multivariate logistic regression analyses . RESULTS The incidence of peri-implantitis in the global sample was 31.2 % ( GNTP = 43.9 % and GTP = 18.0 % ) . CONCLUSION The absence of preventive maintenance in individuals with pre-existing peri-implant mucositis was associated with a high incidence of peri-implantitis . Clinical parameters , such as bleeding on peri-implant probing , periodontal probing depth and the presence of periodontitis were associated with a higher risk of developing peri-implantitis PURPOSE To evaluate 1-year implant survival and marginal bone loss around implants that support fixed partial dentures loaded immediately or after 3 months , and effects from abutment usage . MATERIAL S AND METHODS In this 2005 to 2009 r and omized , parallel-group , clinical trial , 50 partially edentulous patients each received three Brånemark TiUnite ™ implants ( Nobel Biocare ® , Göteborg , Sweden ) , mostly in the posterior maxilla . Two implants were fitted with abutments : a TiUnite ™ surface and a machine-milled surface ; the suprastructure was attached directly at implant level for the third implant . After r and omized allocation , implants were immediately loaded with a fixed temporary bridge ( test group ) or left unloaded for 3 months ( control group ) . A permanent fixed suprastructure replaced the temporary bridge after 6 months ( test ) . Hard and soft tissues were examined during pretreatment and surgery plus 2 days , 14 days , 4 weeks , 3 months , and 1 year after surgery . RESULTS After 1 year , four implants were lost in the test and two in the control groups ( 1-year survival rates of 94.9 % [ test ] and 97.2 % [ control ] , with no significant intergroup difference ) . Resonance frequency analysis values indicated a similar pattern in both groups , with implant stability quotient ( ISQ ) reduction between 2 and 4 weeks . The test group had a significantly lower ISQ than the control group at these appointments . After 1 year , marginal bone losses around the implants were , on average , 1.32 mm ( test , st and ard error of the mean [ SEM ] 0.08 ) and 1.24 mm ( control , SEM 0.08 ) , with no significant intergroup difference . Significantly larger marginal bone loss was observed at implants without abutment compared with implants with abutment . CONCLUSIONS For both groups , this study showed similar implant survival rates and marginal bone loss . Larger bone loss was found at implants loaded without attached abutments AIM The aim of this study was to present the 10-year clinical and radiographic data from a RCT on single-tooth implants placed early , delayed , or late after tooth extraction . MATERIAL S AND METHODS Sixty-three patients were Output:	Both implant and patient-based meta-analyses revealed a significantly higher risk of developing peri-implantitis in patients with a history of periodontitis compared with periodontally healthy subjects , but not a statistically significant increased risk for implant loss . CONCLUSIONS The outcomes of this systematic review indicate history of periodontitis as a possible risk factor for peri-implantitis , while insufficient data are present in literature to evaluate the role of smoking .
MS21017	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To investigate the effects of simultaneous explosive-strength and endurance training on physical performance characteristics , 10 experimental ( E ) and 8 control ( C ) endurance athletes trained for 9 wk . The total training volume was kept the same in both groups , but 32 % of training in E and 3 % in C was replaced by explosive-type strength training . A 5-km time trial ( 5 K ) , running economy ( RE ) , maximal 20-m speed ( V20 m ) , and 5-jump ( 5J ) tests were measured on a track . Maximal anaerobic ( MART ) and aerobic treadmill running tests were used to determine maximal velocity in the MART ( VMART ) and maximal oxygen uptake ( VO2 max ) . The 5 K time , RE , and VMART improved ( P < 0.05 ) in E , but no changes were observed in C. V20 m and 5J increased in E ( P < 0.01 ) and decreased in C ( P < 0.05 ) . VO2 max increased in C ( P < 0.05 ) , but no changes were observed in E. In the pooled data , the changes in the 5 K velocity during 9 wk of training correlated ( P < 0.05 ) with the changes in RE [ O2 uptake ( r = -0.54 ) ] and VMART ( r = 0.55 ) . In conclusion , the present simultaneous explosive-strength and endurance training improved the 5 K time in well-trained endurance athletes without changes in their VO2 max . This improvement was due to improved neuromuscular characteristics that were transferred into improved VMART and running economy Fifteen highly trained distance runners ( & OV0312;O2max 71.1 ± 6.0 ml·min−1·kg−1 , mean ± SD ) were r and omly assigned to a plyometric training ( PLY ; n = 7 ) or control ( CON ; n = 8) group . In addition to their normal training , the PLY group undertook 3 × 30 minutes PLY sessions per week for 9 weeks . Running economy ( RE ) was assessed during 3 × 4 minute treadmill runs ( 14 , 16 , and 18 km·h−1 ) , followed by an incremental test to measure & OV0312;O2max . Muscle power characteristics were assessed on a portable , unidirectional ground reaction force plate . Compared with CON , PLY improved RE at 18 km·h−1 ( 4.1 % , p = 0.02 ) , but not at 14 or 16 km·h−1 . This was accompanied by trends for increased average power during a 5-jump plyometric test ( 15 % , p = 0.11 ) , a shorter time to reach maximal dynamic strength during a strength quality assessment test ( 14 % , p = 0.09 ) , and a lower & OV0312;O2-speed slope ( 14 % , p = 0.12 ) after 9 weeks of PLY . There were no significant differences in cardiorespiratory measures or & OV0312;O2max as a result of PLY . In a group of highly-trained distance runners , 9 weeks of PLY improved RE , with likely mechanisms residing in the muscle , or alternatively by improving running mechanics The purpose of this study was to determine if changes in triceps-surae tendon stiffness ( TST K ) could affect running economy ( RE ) in highly trained distance runners . The intent was to induce increased TST K in a subgroup of runners by an added isometric training program . If TST K is a primary determinant of RE , then the energy cost of running ( EC ) should decrease in the trained subjects . EC was measured via open-circuit spirometry in 12 highly trained male distance runners , and TST K was measured using ultrasonography and dynamometry . Runners were r and omly assigned to either a training or control group . The training group performed 4 × 20 s isometric contractions at 80 % of maximum voluntary plantarflexion moment three times per week for 8 weeks . All subjects ( mean $ $ \dot{V}{\text{O } } _ { 2 } { \max } $ $ = 67.4 ± 4.6 ml kg−1 min−1 ) continued their usual training for running . TST K was measured every 2 weeks . EC was measured in both training and control groups before and after the 8 weeks at three submaximal velocities , corresponding to 75 , 85 and 95 % of the speed at lactate threshold ( sLT ) . Isometric training did neither result in a mean increase in TST K ( 0.9 ± 25.8 % ) nor a mean improvement in RE ( 0.1 ± 3.6 % ) ; however , there was a significant relationship ( r2 = 0.43 , p = 0.02 ) between the change in TST K and change in EC , regardless of the assigned group . It was concluded that TST K and EC are somewhat labile and change together Berryman , N , Maurel , D , and Bosquet , L. Effect of plyometric vs. dynamic weight training on the energy cost of running . J Strength Cond Res 24(7 ) : 1818 - 1825 , 2010-The purpose of this study is to compare the effects of 2 strength training methods on the energy cost of running ( Cr ) . Thirty-five moderately to well-trained male endurance runners were r and omly assigned to either a control group ( C ) or 2 intervention groups . All groups performed the same endurance-training program during an 8-week period . Intervention groups added a weekly strength training session design ed to improve neuromuscular qualities . Sessions were matched for volume and intensity using either plyometric training ( PT ) or purely concentric contractions with added weight ( dynamic weight training [ DWT ] ) . We found an interaction between time and group ( p < 0.05 ) and an effect of time ( p < 0.01 ) for Cr . Plyometric training induced a larger decrease of Cr ( 218 ± 16 to 203 ± 13 ml·kg−1·km−1 ) than DWT ( 207 ± 15 to 199 ± 12 ml·kg−1·km−1 ) , whereas it remained unchanged in C. Pre-post changes in Cr were correlated with initial Cr ( r = −0.57 , p < 0.05 ) . Peak vertical jump height ( VJHpeak ) increased significantly ( p < 0.01 ) for both experimental groups ( DWT = 33.4 ± 6.2 to 34.9 ± 6.1 cm , PT = 33.3 ± 4.0 to 35.3 ± 3.6 cm ) but not for C. All groups showed improvements ( p < 0.05 ) in Perf3000 ( C = 711 ± 107 to 690 ± 109 seconds , DWT = 755 ± 87 to 724 ± 77 seconds , PT = 748 ± 81 to 712 ± 76 seconds ) . Plyometric training were more effective than DWT in improving Cr in moderately to well-trained male endurance runners showing that athletes and coaches should include explosive strength training in their practice s with a particular attention on plyometric exercises . Future research is needed to establish the origin of this adaptation Abstract .Previous research has reported that plyometric training improves running economy ( RE ) and ultimately distance-running performance , although the exact mechanism by which this occurs remains unclear . This study examined whether changes in running performance result ing from plyometric training were related to alterations in lower leg musculotendinous stiffness ( MTS ) . Seventeen male runners were pre- and post-tested for lower leg MTS , maximum isometric force , rate of force development , 5-bound distance test ( 5BT ) , counter movement jump ( CMJ ) height , RE , V˙O2max , lactate threshold ( Thla ) , and 3-km time . Subjects were r and omly split into an experimental ( E ) group which completed 6 weeks of plyometric training in conjunction with their normal running training , and a control ( C ) group which trained as normal . Following the training period , the E group significantly improved 3-km performance ( 2.7 % ) and RE at each of the tested velocities , while no changes in V˙O2max or Thla were recorded . CMJ height , 5BT , and MTS also increased significantly . No significant changes were observed in any measures for the C group . The results clearly demonstrated that a 6-week plyometric programme led to improvements in 3-km running performance . It is postulated that the increase in MTS result ed in improved RE . We speculate that the improved RE led to changes in 3-km running performance , as there were no corresponding alterations in V˙O2max or Thla Abstract . Maximal strength-training with an emphasis on maximal mobilization during cross-country skiing increases exercise economy when double-poling . The aim of this experiment was to investigate whether the mechanism of this increase is a change in the force-velocity relationship and the mechanical power output . A group of 19 cross-country skiers having an average peak oxygen uptake of 255 ml·kg–0.67 body mass·min–1 or 61 ml·kg–1·min–1 were r and omly assigned to either a high resistance-training group ( n=10 ) or a control group ( n=9 ) . Upper body endurance was tested on a ski ergometer . The high-resistance-training group trained for 15 min on three occasions a week for 9 weeks . Training consisted of three series of five repetitions using 85 % of one repetition maximum ( 1RM ) , with emphasis on high velocity in the concentric part of the movement . Upper body exercise economy , 1RM and time to exhaustion increased significantly in the high resistance-training group , but was unchanged in the control group . Peak power and the velocities for a given load increased significantly , except for the two lowest loads . We conclude that the increased exercise economy after a period of upper body high resistance-training can be partly explained by a specific change in the force-velocity relationship and the mechanical power output PURPOSE It has been suggested that endurance training influences the running economy ( CR ) and the oxygen uptake ( .VO(2 ) ) kinetics in heavy exercise by accelerating the primary phase and attenuating the .VO(2 ) slow component . However , the effects of heavy weight training ( HWT ) in combination with endurance training remain unclear . The purpose of this study was to examine the influence of a concurrent HWT+endurance training on CR and the .VO(2 ) kinetics in endurance athletes . METHODS Fifteen triathletes were assigned to endurance+strength ( ES ) or endurance-only ( E ) training for 14 wk . The training program was similar , except ES performed two HWT sessions a week . Before and after the training period , the subjects performed 1 ) an incremental field running test for determination of .VO(2max ) and the velocity associated ( V(.VO2max ) ) , the second ventilatory threshold ( VT(2 ) ) ; 2 ) a 3000-m run at constant velocity , calculated to require 25 % of the difference between .VO(2max ) and VT(2 ) , to determine CR and the characteristics of the VO(2 ) kinetics ; 3 ) maximal hopping tests to determine maximal mechanical power and lower-limb stiffness ; 4 ) maximal concentric lower-limb strength measurements . RESULTS After the training period , maximal strength were increased ( P < 0.01 ) in ES but remained unchanged in E. Hopping power decreased in E ( P < 0.05 ) . After training , economy ( P < 0.05 ) and hopping power ( P < 0.001 ) were greater in ES than in E. .VO(2max ) , leg hopping stiffness and the .VO(2 ) kinetics were not significantly affected by training either in ES or E. CONCLUSION Additional HWT led to improved maximal strength and running economy with no significant effects on the .VO(2 ) kinetics pattern in heavy exercise We investigated the effects of strength maintenance training on thigh muscle cross-sectional area ( CSA ) , leg strength , determinants of cycling performance , and cycling performance . Well-trained cyclists completed either ( 1 ) usual endurance training supplemented with heavy strength training twice a week during a 12-week preparatory period followed by strength maintenance training once a week during the first 13 weeks of a competition period ( E + S ; n = 6 [ ♂ = 6 ] ) , or ( 2 ) usual endurance training during the whole intervention period ( E ; n = 6 [ ♂ = 5 , ♀ = 1 ] ) . Following the preparatory period , E + S increased thigh muscle CSA and 1RM ( p < 0.05 ) , while no changes were observed in E. Both groups increased maximal oxygen consumption and mean power output in the 40-min all-out trial ( p < 0.05 ) . At 13 weeks into the competition period , E + S had preserved the increase in CSA and strength from the preparatory period . From the beginning of the preparatory period to 13 weeks into the competition period , E + S increased peak power output in the Wingate test , power output at 2 mmol l−1 [ la− ] , maximal aerobic power output ( Wmax ) , and mean power output in the 40-min all-out trial ( p < 0.05 ) . The relative improvements in the last two measurements were larger than in E ( p < 0.05 ) . For E , Wmax and power output at 2 mmol l−1 [ la− ] remained unchanged . In conclusion , in well-trained cyclists , strength maintenance training in a competition period preserved increases in thigh muscle CSA and leg strength attained in a preceding preparatory period and further improved cycling performance determinants and performance PURPOSE The present study investigated the effect of maximal strength training on running economy ( RE ) at 70 % of maximal oxygen consumption ( V[spacing dot above]O2max ) and time to exhaustion at maximal aerobic speed ( MAS ) . Responses in one repetition maximum ( 1RM ) and rate of force development ( RFD ) in half-squats , maximal oxygen consumption , RE , and time to Output:	Results The results showed that strength training improved time-trial performance , economy , $ $ { \text{v}}\dot{V}{\text{O}}_{2 \ , \hbox{max } } /{\text{w}}\dot{V}{\text{O}}_{2 \ , \hbox{max } } $ $ vV˙O2max/wV˙O2max and vMART in competitive endurance athletes . Conclusion The present research available supports the addition of strength training in an endurance athlete ’s programme for improved economy , $ $ { \text{v}}\dot{V}{\text{O}}_{2 \ , \hbox{max } } /{\text{w}}\dot{V}{\text{O}}_{2 \ , \hbox{max } } $ $ vV˙O2max/wV˙O2max , muscle power and performance . Future investigations should include valid strength assessment s ( i.e. squats , jump squats , drop jumps ) through a range of velocities ( maximal-strength ↔ strength-speed ↔ speed-strength ↔ reactive-strength ) , and administer appropriate strength programmes ( exercise , load and velocity prescription ) over a long-term intervention period ( > 6 months ) for optimal transfer to performance
MS21018	*TASK* the task is to summarize an input biomedical literature in six sentences *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 advantage and disadvantage of laparoscopic abdomino-perineal resection and open abdominoperineal resection for low rectal cancer . METHODS Patients with low rectal cancer , collected from July 2003 to April 2006 , were r and omly divided into laparoscopic abdominoperineal resection group ( 37 cases ) and open abdominoperineal resection group ( 37 cases ) . Operation time , number of lymph node removed , intra-operative blood loss , time to pass flatus , time to ambulate , time to discharge , complications , early recurrence , and economical cost were compared between the 2 groups . RESULTS All patients were performed successfully . For the first 10 patients , operation time of laparoscopic group was significantly longer than that of open group , but there was no significant difference between the 2 groups . Intra-operative blood loss of laparoscopic group was significantly less than that of open group , but it was reverse for the first 10 patients . There was no significant difference in time to pass flatus between the 2 groups . Time to ambulate in laparoscopic group was significantly earlier than that in open group . There was no significant difference in time to discharge between the 2 groups , but it was earlier for perineum closure in laparoscopic group . Relative complications of laparoscopic group , including pulmonary infection , abdominal wound infection or split , were significantly less than those of open group . There was no significant difference in number of lymph nodes removed , early recurrence between the 2 groups . Operation cost of laparoscopic group was significantly higher than that of open group , but there was no significant difference . CONCLUSION Advantages of laparoscopic abdominoperineal resection were characterized for not only minimal invasion and good cosmetic outcome but also less blood loss , complications , and earlier postoperative recovery . The operation time , total costs and oncological clearance of laparoscopic abdominoperineal resection patients were comparable with those of open procedure patients OBJECTIVE The aims of this study were to evaluate the safety and efficacy of laparoscopic abdominoperineal resection compared to conventional approach for surgical treatment of patients with distal rectal cancer presenting with incomplete response after chemoradiation . METHOD Twenty eight patients with distal rectal adenocarcinoma were r and omized to undergo surgical treatment by laparoscopic abdominoperineal resection or conventional approach and evaluated prospect ively . Thirteen underwent laparoscopic abdominoperineal resection and 15 conventional approach . RESULTS There was no significant difference ( p<0,05 ) between the two studied groups regarding : gender , age , body mass index , patients with previous abdominal surgeries , intra and post operative complications , need for blood transfusion , hospital stay after surgery , length of resected segment and pathological staging . Mean operation time was 228 minutes for the laparoscopic abdominoperineal resection versus 284 minutes for the conventional approach ( p=0.04 ) . Mean anesthesia duration was shorter ( p=0.03 ) for laparoscopic abdominoperineal resection when compared to conventional approach : 304 and 362 minutes , respectively . There was no need for conversion to open approach in this series . After a mean follow-up of 47.2 months and with the exclusion of two patients in the conventional abdominoperineal resection who presented with unsuspected synchronic metastasis during surgery , local recurrence was observed in two patients in the conventional group and in none in the laparoscopic group . CONCLUSIONS We conclude that laparoscopic abdominoperineal resection is feasible , similar to conventional approach concerning surgery duration , intra operative morbidity , blood requirements and post operative morbidity . Larger number of cases and an extended follow-up are required to adequate evaluation of oncological results for patients undergoing laparoscopic abdominoperineal resection after chemoradiation for radical treatment of distal rectal cancer Purpose This study evaluated differences in stress response and immunological function following laparoscopic and conventional total mesorectal excision ( TME ) for rectal cancer . Methods Patients with non-metastasized rectal cancer were prospect ively r and omized to open ( n = 18 ) or laparoscopic ( n = 22 ) TME . Blood sample s were taken preoperatively ( baseline ) , 2 , 24 , and 72 h following surgery . Systemic white blood cell and monocyte count , C-reactive protein , interleukin-6 ( IL-6 ) , interleukin-8 ( IL-8 ) , HLA-DR expression on monocytes , growth hormone , prolactin , and cortisol were measured . Results Forty patients with a median age of 66 years ( interquartile range , 60–74 years ) were included . Eighteen patients ( 45 % ) were r and omized to open surgery and 22 patients ( 55 % ) to laparoscopic surgery . Patient demographics in terms of gender , age , BMI , ASA classification , localization of the tumor , and type of neoadjuvant therapy were comparable for both groups . Laparoscopic surgery result ed in a significantly better short-term preservation of postoperative immune function . HLA-DR expression on monocytes was significantly higher ( 64 % vs 50 % , P = 0.014 ) and IL-6 level increase was significantly lower ( 4.6 vs 10.8 , P = 0.003 ) 2 h after laparoscopic surgery . No differences between the open and laparoscopic technique were observed in postoperative white blood cell count , monocyte count , C-reactive protein , IL-8 , growth hormone , prolactin , and cortisol levels . ConclusionS hort-term postoperative immune and inflammatory functions tended to be better after laparoscopic rectal surgery . However , the differences were not consistent at all time intervals , making a definitive conclusion difficult . Better preserved inflammatory function 2 h after surgery may reflect a reduction in operative trauma when the laparoscopic technique is compared with open rectal procedures Purpose This study was design ed to evaluate the impact of laparoscopic rectal resection on short-term postoperative morbidity and costs . Methods A total of 168 patients with rectal cancer were r and omly assigned to laparoscopic ( n = 83 ) or open ( n = 85 ) resection . Outcome parameters were : postoperative morbidity , length of hospital stay , quality of life , long-term survival , and local recurrences . The mean follow-up period was 53.6 months . Cost-benefit analysis was based on hospital costs . Results Operative time was 53 minutes longer in the laparoscopic group ( P < 0.0001 ) . Postoperative morbidity rate was 28.9 percent in the laparoscopic vs. 40 percent in the open group ( P = 0.18 ) . The mean length of hospital stay was 10 ( 4.9 ) days in the laparoscopic group and 13.6 ( 10 ) days in the open group ( P = 0.004 ) . Local recurrence rate and five-year survival were similar in both groups ; however , the limited number of patients does not allow firm conclusions . Quality of life was better in the laparoscopic group only in the first year after surgery ( P < 0.0001 ) . The additional charge in the laparoscopic group was $ 1,748 per patient r and omized ( $ 1,194 the result of surgical instruments and $ 554 the result of longer operative time ) . The saving in the laparoscopic group was $ 1,396 per patient r and omized ( $ 647 the result of shorter length of hospital stay and $ 749 the result of the lower cost of postoperative complications ) . The net balance result ed in $ 351 extra cost per patient r and omly allocated to the laparoscopic group . Conclusions Short-term postoperative morbidity was similar in the two groups . Laparoscopic resection reduced length of hospital stay , improved first-year quality of life , and slightly increased hospital costs Background : Laparoscopic resection of the rectum is still under scrutiny for its adequacy of oncological clearance . Aim : To assess lymph node yield after laparoscopic total mesorectal excision ( TME ) for rectal cancer as compared to the open approach . Methods : 74 patients with middle and low rectal cancer were prospect ively r and omized in two groups . Group A included 39 patients who had an open TME ( 35 with low anterior resection of the rectum ( LARR ) and 4 with abdominoperineal resection of the rectum ( APR ) ) . In group B , there were 34 patients who had a laparoscopic TME ( 27 with LARR and 7 with APR ) . 10 of the LARR patients in group A and 14 of the LARR patients in group B had a defunctioning ileostomy . All operations were performed by one surgeon or under his supervision . Results : Gender and age distribution were similar for both groups ( group A : 23 males ; mean age 69 ( 41–85 ) ; group B : 20 males ; mean age 72 ( 31–84 ) ) . The mean distance of the tumor from the dentate line was 7.6 cm ( 1–12 cm ) for group A and 6.1 cm ( 1–12 cm ) for group B. Anastomosis was formed at a mean distance of 5.5 cm ( 1.5–8.5 cm ) from the dentate line in group A and 3.5 cm ( 1–4.5 cm ) in group B. At histology , in group A there were 5 T4 tumors , 9 T3 , 10 T3 + ( < 1 mm distance from the circumferential resection margin ) , 13 T2 and 2 T1 . In group B , there were 3 T4 tumors , 14 T3 , 8 T3 + , 7 T2 and 2 T1 . Differences between groups were not significant . The mean number of lymph nodes retrieved in group A specimens was 19.2 ( 5–45 ) and in group B 19.2 ( 8–41 ) ( p = 0.2 ) . In group A , 3.9 ( 1–9 ) regional , 13.9 ( 3–34 ) intermediate and 1.5 ( 1–3 ) apical lymph nodes were retrieved . The respective values in group B were 3.7 ( 3–7 ) , 14.4 ( 4–33 ) and 1.3 ( 1–3 ) . Differences between groups were not significant . Also , the incidence of lymph node involvement by the tumor was not significantly different between groups ( group A : 23 ; group B : 19 ) . Conclusions : Laparoscopic resection of the rectum can achieve similar lymph node clearance to the open approach . Also , distribution of the lymph nodes along the resected specimens is similar between the two approaches Background The Laparoscopic approach has been applied to colorectal surgery for many years ; however , there are only a few reports on laparoscopic low and ultralow anterior resection with construction of coloanal anastomosis . This study compares open versus laparoscopic low and ultralow anterior resections , assesses the feasibility and efficacy of the laparoscopic approach of total mesorectal excision ( TME ) with anal sphincter preservation ( ASP ) , and analyzes the short-term results of patients with low rectal cancer . Methods We analyzed our experience via a prospect i ve , r and omized control trail . From June 2001 to September 2002 , 171 patients with low rectal cancer underwent TME with ASP , 82 by the laparoscopic procedure and 89 by the open technique . The lowest margin of tumors was below peritoneal reflection and 1.5–8 cm above the dentate line ( 1.5–4.9 cm in 104 cases and 5–8 cm in 67 cases ) . The grouping was r and omized . Results Results of operation , postoperative recovery , and short-term oncological follow-up were compared between 82 laparoscopic procedures and 89 controls who underwent open surgery during the same period . In the laparoscopic group , 30 patients in whom low anterior resection was performed had the anastomosis below peritoneal reflection and more than 2 cm above the dentate line , 27 patients in whom ultralow anterior resection was performed had anastomotic height within 2 cm of the dentate line , and 25 patients in whom coloanal anastomosis was performed had the anastomosis at or below the dentate line . In the open group , the numbers were 35 , 27 , and 27 , respectively . There was no statistical difference in operation time , administration of parenteral analgesics , start of food intake , and mortality rate between the two groups . However , blood loss was less , bowel function recovered earlier , and hospitalization time was shorter in the laparoscopic group . Conclusion Totally laparoscopic TME with ASP is feasible , and it is a minimally invasive technique with the benefits of much less blood loss during operation , earlier return of bowel function , and shorter hospitalization Bladder and sexual dysfunction , secondary to pelvic nerve injury , are recognized complications of rectal resection . This study investigated the frequency of these complications following laparoscopically assisted and conventional open mesorectal resection for cancer Local recurrence after resection for rectal cancer remains common despite growing acceptance that inadequate local excision may be implicated . In a prospect i ve study of 190 patients with rectal cancer , we examined the circumferential margin of excision of resected specimens for tumour presence , to examine its frequency and its relation to subsequent local recurrence . Tumour involvement of the circumferential margin was seen in 25 % ( 35/141 ) of specimens for which the surgeon Output:	Therefore , laparoscopy for the treatment of patients with rectal cancer has the advantage of recovery and the same complications and prognosis as laparotomy , which indicates that laparoscopy may provide a potential survival benefit for patients with rectal cancer
MS21019	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Multiple daily injection ( MDI ) therapy of bolus insulin aspart and basal insulin glargine was compared with continuous subcutaneous insulin infusion ( CSII ) with aspart in type 1 diabetic patients previously treated with CSII . RESEARCH DESIGN AND METHODS One hundred patients were enrolled in a r and omized , multicenter , open-label , crossover study . After a 1-week run-in period with aspart by CSII , 50 subjects were r and omly assigned to MDI therapy ( aspart immediately before each meal and glargine at bedtime ) and 50 subjects continued CSII . After 5 weeks of the first treatment , subjects crossed over to the alternate treatment for 5 weeks . During the last week of each treatment period , subjects wore a continuous glucose monitoring system for 48 - 72 h. RESULTS Mean serum fructosamine levels were significantly lower after CSII therapy than after MDI therapy ( 343 + /- 47 vs. 355 + /- 50 micromol/l , respectively ; P = 0.0001 ) . Continuous glucose monitoring profiles over a 24-h time period showed that glucose exposure was 24 and 40 % lower for CSII than MDI as measured by area under the curve ( AUC ) glucose > /=80 mg/dl ( 1,270 + /- 742 vs. 1,664 + /- 1,039 mg . h . dl(-1 ) ; P < 0.001 ) and AUC glucose > /=140 mg/dl ( 464 + /- 452 vs. 777 + /- 746 mg . h . dl(-1 ) , CSII vs. MDI , respectively ; P < 0.001 ) . Similar percentages of subjects reported hypoglycemic episodes ( CSII : 92 % , MDI : 94 % ) and nocturnal ( 12:00 a.m. to 8:00 a.m. ) hypoglycemic episodes ( CSII : 73 % , MDI : 72 % ) . Major hypoglycemia was infrequent ( CSII : two episodes , MDI : five episodes ) . CONCLUSIONS In a trial of short duration , CSII therapy with insulin aspart result ed in lower glycemic exposure without increased risk of hypoglycemia , as compared with MDI with insulin aspart and glargine Urinary albumin was studied in 45 patients with insulin-dependent diabetes in a 4-year prospect i ve r and omized trial , comparing continuous sc insulin infusion ( CSII ) , multiple insulin injections , and conventional treatment with twice daily injections . Strict blood glucose control was obtained with CSII and multiple injections , better than with conventional treatment ( 2P less than 0.01 ) : mean glycosylated haemoglobin ( % HbA1 + /- SEM ) after 4 years : CSII 9.0 + /- 0.4 % ; multiple injections 9.4 + /- 0.4 % ; conventional treatment 10.5 + /- 0.5 . A total of 696 24-h urine specimens were collected . After 4 years of CSII from the time of r and omization , urinary albumin excretion was reduced ( 26 + /- 5 to 16 + /- 4 mg/24 h , mean + /- SEM , 2P less than 0.01 ) , when compared with conventional treatment ( 2P = 0.01 ) , when compared with conventional treatment ( 2P = 0.01 ) where no change was observed ( 21 + /- 4 to 22 + /- 6 mg/24 h , n.s . ) . The reduction observed during multiple injection treatment was not significant ( 17 + /- 3 to 14 + /- 3 mg/24 h ) . Long-term near-normoglycaemia may influence the mechanisms leading to albuminuria in diabetes , if introduced at an early stage of the disease AIMS The goal of the study was to determine whether continuous subcutaneous insulin infusion ( CSII ) differs from a multiple daily injection ( MDI ) regimen based on neutral protamine hagedorn ( NPH ) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes . METHODS The 5-Nations trial was a r and omized , controlled , crossover trial conducted in 11 European centres . Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period , respectively . The quality of glycaemic control was assessed by HbA(1c ) , blood glucose values , and the frequency of hypoglycaemic events . For the evaluation of the quality of life , three different self-report question naires have been assessed . RESULTS CSII treatment result ed in lower HbA(1c ) ( 7.45 vs. 7.67 % , P < 0.001 ) , mean blood glucose level ( 8.6 vs. 9.4 mmol/l , P < 0.001 ) and less fluctuation in blood glucose levels than MDI ( + /- 3.9 vs. + /- 4.3 mmol/l , P < 0.001 ) . There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI , with an incidence ratio of 1.12 [ 95 % confidence interval ( CI ) : 1.08 - 1.17 ] and 2.61 ( 95 % CI : 1.59 - 4.29 ) for mild and severe hypoglycaemia , respectively . The overall score of the diabetes quality of life question naire was higher for CSII ( P < 0.001 ) , and an improvement in pump users ' perception of mental health was detected when using the SF-12 question naire ( P < 0.05 ) . CONCLUSION CSII usage offers significant benefits over NPH-based MDI for individuals with Type 1 diabetes , with improvement in all significant metabolic parameters as well as in patients ' quality of life . Additional studies are needed to compare CSII with glargine- and detemir-based MDI Summary We investigated in a r and omized , prospect i ve study the influence of improved blood glucose control during 2 - 3 years in young insulin-dependent diabetic ( IDDM ) patients with microalbuminuria , which is indicative of early nephropathy . Patients were r and omized either to intensive treatment by continuous subcutaneous insulin infusion ( CSII ) ( n = 9 ) or CT ( n = 9 ) . Kidney biopsies were taken at baseline and after 26 - 34 months . End points were structural changes in the glomeruli . Sensitive , quantitative , mor-phometric methods were used . The blood glucose control improved significantly ( p = 0.01 ) during the study in the CSII-group as glycated haemoglobin ( HbAlc ) fell from 10.1 % ( [ 95 % CI ] 8.9 - 11.3 ) to 8.6 % ( 7.9 - 9.2 ) , but not in the CT-group , 10.1 % ( 8.3 - 11.9 ) vs 9.7 % ( 8.7 - 10.8 ) . Mean HbAlc during the study period was significantly lower in the CSII-group than in the CT-group , 8.7 % ( 8.1 - 9.3 ) vs 9.9 % ( 8.5 - 11.3 ) , p = 0.04 . Basement membrane thickness ( BMT ) increased in both groups , most ( CT vs CSII , p = 0.03 ) in the CT-group : 140 nm ( 50 - 230 ) vs CSII : 56 nm ( 27 - 86 ) . In the CT-group only an increase was seen in matrix/mesan-gial volume fraction ( p = 0.006 ) and matrix star volume ( p = 0.04 ) . Furthermore , a positive correlation between mean HbAlc during the study and change from baseline in BMT ( r = 0.70 , p = 0.001 ) and ma-trix/glomerular volume fraction ( r = 0.33 , p = 0.09 , NS ) was demonstrated . Albumin excretion rate correlated significantly to BMT and most of the matrix parameters . The present study shows that during a period of only 2.5 years , a close relationship between the level of mean blood glucose and progression of glomerular morphological changes in early diabetic nephropathy can be demonstrated . [ Diabetologia ( 1994 ) 37 : 483 - 490 OBJECTIVE To evaluate glycemic control , hypoglycemic events , and quality of life in patients treated with continuous subcutaneous insulin infusion ( CSII ) and multiple daily insulin injection ( MDI ) , with insulin lispro as the principal insulin . RESEARCH DESIGN AND METHODS This clinical trial enrolled 27 patients with type 1 diabetes . They were r and omly assigned to CSII ( n = 13 ) or MDI ( n = 14 ) treatment regimens . Glycemic control ( HbA(1c ) level ) was the primary outcome and was measured monthly for 9 months . Secondary outcomes were patient reports of hypoglycemic events ( recorded monthly for 9 months ) and quality of life assessed at 9 months using the Diabetes Quality of Life ( DQOL ) question naire . RESULTS A significant decrease in HbA(1c ) from baseline was shown for both groups . However , the overall treatment effect ( CSII - MDI ) for HbA(1c ) was + 0.08 % ( 95 % CI -0.23 to + 0.39 , P > 0.10 ) . This was significantly less than the a priori limit of + /-0.5 % ( P = 0.004 ) . The relative treatment effect ( [ CSII - MDI]/MDI ) for the overall number of hypoglycemic events was + 9 % ( 95 % CI -37 to + 87 , P > 0.10 ) . There were no statistically significant differences between treatment groups for any of the DQOL subscales . CONCLUSIONS No statistically significant differences in glycemic control , reported hypoglycemic events , or quality of life were found in this study . Furthermore , a clinical ly significant difference of more than + /-0.5 % HbA(1c ) between the two regimens can be confidently ruled out . We conclude that the choice of intensive insulin therapy should be a matter of patient preference , consistent with lifestyle OBJECTIVE Compare the efficacy , safety , and patient satisfaction of continuous subcutaneous insulin infusion ( CSII ) therapy with multiple daily injection ( MDI ) therapy for patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 132 CSII-naive type 2 diabetic patients were r and omly assigned ( 1:1 ) to CSII ( using insulin aspart ) or MDI therapy ( bolus insulin aspart and basal NPH insulin ) in a multicenter , open-label , r and omized , parallel-group , 24-week study . Efficacy was assessed with HbA(1c ) and eight-point blood glucose ( BG ) profiles . Treatment satisfaction was determined with a self-administered question naire . Safety assessment s included adverse events , hypoglycemic episodes , laboratory values , and physical examination findings . RESULTS HbA(1c ) values decreased similarly for both groups from baseline ( 8.2 + /- 1.37 % for CSII , 8.0 + /- 1.08 % for MDI ) to end of study ( 7.6 + /- 1.22 % for CSII , 7.5 + /- 1.22 % for MDI ) . The CSII group showed a trend toward lower eight-point BG values at most time points ( only significant 90 min after breakfast ; 167 + /- 48 vs. 192 + /- 65 mg/dl for CSII and MDI , respectively ; P = 0.019 ) . A total of 93 % of CSII-treated subjects preferred the pump to their previous injectable insulin regimen for reasons of convenience , flexibility , ease of use , and overall preference . Safety assessment s were comparable for both treatment groups . CONCLUSIONS Insulin aspart in CSII therapy provided efficacy and safety comparable to MDI therapy for type 2 diabetes . Patients with type 2 diabetes can be trained as out patients to use CSII and prefer CSII to injections , indicating that pump therapy should be considered when initiating intensive insulin therapy for type 2 diabetes OBJECTIVE To compare the efficacy of 2 intensified insulin regimens , continuous subcutaneous insulin infusion ( CSII ) and multiple daily injections ( MDI ) , by using the short-acting insulin analog lispro in type 1 diabetic patients . RESEARCH DESIGN AND METHODS A total of 41 C-peptide-negative type 1 diabetic patients ( age 43.5+/-10.3 years ; 21 men and 20 women , BMI 24.0+/-2.4 kg/m2 , diabetes duration 20.0+/-11.3 years ) on intensified insulin therapy ( MDI with regular insulin or lispro , n = 9 , CSII with regular insulin , n = 32 ) were included in an open-label r and omized crossover study comparing two 4-month periods of intensified insulin therapy with lispro : one period by MDI and the other by CS Output:	Total daily insulin requirements were lower with CSII than with MDI therapy . In patients with type 2 diabetes mellitus , CSII and MDI treatment showed no statistically significant difference for HbA1c . The incidence of mild hypoglycaemic events was comparable between the treatment groups . Conclusions /interpretationCSII therapy in adults and adolescents with type 1 diabetes mellitus result ed in a greater reduction of glycated haemoglobin , in adult patients without a higher rate of hypoglycaemia . No beneficial effect of CSII therapy could be detected for patients with type 2 diabetes mellitus
MS21020	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In this review we sought to appraise the true method ological quality of nutritional support studies conducted in critically ill patients and to compare these findings to the method ological quality of sepsis trials . An extensive literature search revealed 111 r and omized controlled trials conducted in critically ill patients evaluating the impact of nutritional support interventions on clinical ly meaningful outcomes . Compared with sepsis trials , nutritional support studies were significantly less likely to use blinding ( 32 of 40 versus 35 of 111 , P < 0.001 ) or present an intention-to-treat analysis ( 37 of 40 versus 64 of 111 , P < 0.001 ) . There was a trend toward the less frequent use of r and omization methods that are known to maintain allocation concealment ( 12 of 40 versus 19 of 111 , P = 0.10 ) . Although nutritional support studies demonstrated a significant increase in the use of blinding after the publication of the CONSORT statement in 1996 ( 9 of 47 versus 26 of 64 post-CONSORT , P = 0.023 ) , there were no improvements in other key areas . Previous publications have described the overall method ological quality of sepsis trials as “ poor . ” Nutritional support studies were significantly worse than sepsis trials in all aspects of method ological quality , and there were few improvements noted over time . To detect important differences in clinical ly meaningful outcomes in critical care , the method ological quality of future studies must be improved BACKGROUND AND AIMS To determine whether the inclusion of 20 g free glutamine as part of the nitrogen source of parenteral feeds reduces length of hospital stay or mortality . METHODS In a r and omised , double blind , controlled trial in 168 patients clinical ly accepted for parenteral nutrition , st and ard feeds were compared with feeds in which 3.8 g of the total nitrogen was replaced with the equivalent 20 g glutamine . A minimum of 11 g nitrogen/day was used in all patients . Daily intakes of energy and nitrogen were determined using a vali date d computer protocol and were similar for the two groups . All feeds included trace elements , vitamins , electrolytes , and minerals . RESULTS A total of 85 patients received a median of eight ( interquartile range 5–13 ) daily feeds containing glutamine while 83 received a median of eight ( 5–15 ) st and ard feeds . No difference between groups was detected for infective complications . Twenty control patients and 14 who had received glutamine died during their hospital stay ( NS ) . Median length of stay was 32 ( 23–52 ) days on glutamine , which was not significantly different from the control value of 35 ( 25–55 ) days . Glutamine was associated with a significant ( p<0.03 ) reduction in length of stay in surgical patients ( 45 days ( range 29–81 ) versus 30 days ( range 19–54 ) ) . CONCLUSION The benefit from glutamine supplementation of parenteral feeds as used in this trial has not been proved . Supplementation may have advantages in surgical patients and in haematological malignancy . Further trials are required Objective To determine the effect of intravenous glutamine supplementation vs. an isonitrogenous control on infectious morbidity in severely burned patients . Previous clinical studies in seriously ill patients suggest a beneficial effect of glutamine on infectious morbidity , but no trials have examined possible clinical benefits in severely burned patients . Design Prospect i ve , double-blind , r and omized trial . Setting Burn intensive care unit of a university hospital . Patients Twenty-six severe burn patients with total burn surface area of 25 % to 90 % and presence of full-thickness burns . Patients were evaluated for occurrence of bacteremia and antibiotic use during the first 30 days of their burn unit admission . Nutritional status and overall inflammation were also measured . Intervention Either intravenous glutamine or an isonitrogenous control amino acid solution was administered as a continuous infusion during burn intensive care unit stay . Measurements and Main Results The incidence of Gram-negative bacteremia was significantly reduced in the glutamine-supplemented group ( 8 % ) vs. control ( 43%;p < .04 ) . No difference was seen in the incidence of Gram-positive bacteremia or fungemia . Average number of positive blood cultures , antibiotic usage , and mortality rates also were reduced but did not reach statistical significance . Significant improvements in serum transferrin and prealbumin were observed in glutamine-supplemented patients at 14 days after burn injury ( p < .01 and .04 , respectively ) . C-reactive protein was also significantly reduced at 14 days after burn injury in the glutamine group ( p < .01 ) . Conclusions Significantly fewer bacteremic episodes with Gram-negative organisms occurred in the glutamine-supplemented patients . Glutamine supplementation improved measures of nutrition and decreased measures of overall inflammation . In addition , a trend toward lower mortality rate , decreased overall bacteremia incidence , and antibiotic usage in the glutamine group was observed . Glutamine ’s beneficial effects may be a result of improved gut integrity or immune function , but the precise mechanism of glutamine ’s protection is unknown We investigated the effect of a glutamine-enriched enteral diet on intestinal permeability and infectious morbidity and mortality in critically ill patients who developed systemic inflammatory response syndrome after an acute event . Eleven intensive care units in tertiary-care hospitals participated in a prospect i ve , r and omized , single blind , multicenter trial . Eighty-four patients with systemic inflammatory response syndrome of any etiology were r and omly allocated to receive a glutamine-enriched enteral diet or a control diet without glutamine . Most patients received the planned caloric intake . The number of infected patients was smaller in the glutamine group than in the control group ( 11 versus 17 patients , P < 0.05 ) , with a relative risk of 0.5 ( 95 % confidence interval = 0.3 - 0.9 ) . The most frequent infection was nosocomial pneumonia , with 11 ( 33 % ) patients in the control group and 6 ( 14 % ) in the glutamine group . There were no differences with respect to other infections , mortality , or length of stay . Intestinal permeability as assessed by the lactulose-mannitol test was unchanged in both groups . Glutamine-enriched enteral diets can decrease nosocomial infections in patients with systemic inflammatory response syndrome Objective : To evaluate the effect of four doses of intravenous glutamine supplementation on skeletal muscle metabolism . Design : A prospect i ve , blinded , r and omized study . Setting : The general Intensive Care Unit ( ICU ) of a university hospital . Patients : ICU patients with multiple organ failure ( n=40 ) , who were expected to stay in the unit for more than five days . Intervention : Patients received 0 , 0.28 , 0.57 or 0.86 g of glutamine per kg bodyweight per day intravenously for five days as part of an isocaloric , isonitrogenous and isovolumetric diet . Results : Plasma glutamine concentration responded to glutamine supplementation with normalization of plasma levels in a dose-dependent way , while free muscle glutamine concentration , as well as muscle protein synthesis and muscle protein content , did not change significantly . Conclusion : Intravenous glutamine supplementation to ICU patients for a period of five days result ed in normalization of plasma glutamine concentrations in a dose-dependent way whereas muscle glutamine concentrations were unaffected Objective The authors determined the effect of glutamine-supplementation of TPN on postoperative peripheral blood T-cell response and proinflammatory cytokine production in patients undergoing colorectal resection . Summary Background Data Several vital tissues , including the immune system , are very dependent on glutamine ; however , this amino acid , which may be essential in conditions of stress , only now is becoming formulated suitably for incorporation into TPN . The effects of such supplementation on the immune function of stressed surgical patients is unknown . Methods Patients ( n = 20 ) were r and omized to receive conventional TPN ( 0.2 g nitrogen/kg/d ) or an isonitrogenous/isocaloric regimen with 0.18 g of glutamine/kg/d from days 1 to 6 postoperatively . T-cell DNA synthesis and interleukin (IL)-2 production and peripheral blood mononuclear cell IL-6 and tumor necrosis factor ( TNF ) production were measured in vitro preoperatively and on days 1 and 6 postoperatively . Results T-cell DNA synthesis after 5 days of TPN was increased compared with preoperative values in the glutamine-supplemented group ( median preoperative tritiated thymidine uptake : 78.3 X 103 cpm , day 6 : 95.0 X 103 cpm , p < 0.05 ) . There was no such increase in the control TPN group ( preoperative : 89.0 X 103 cpm , day 6 : 69.4 X 103 cpm , p > 0.05 ) . Glutamine supplementation did not influence IL-2 production or the production of TNF or IL-6 . Conclusions Glutamine supplementation may be a method of enhancing T-cell function in the surgical patient receiving TPN OBJECTIVE To examine the effect of enteral administration of glutamine in patients with peritonitis or abdominal trauma . METHODS In a prospect i ve , interventional , observer-blind , r and omized clinical trial , 120 patients , aged 18 - 60 years , were r and omized to receive either enteral glutamine 45 g/day for 5 days in addition to st and ard care ( n=63 ; group A ) or st and ard care alone ( n=57 ; group B ) . Surgical intervention was done as needed . RESULTS The two groups were comparable for sex and severity of illness scores . Following treatment , serum malondialdehyde ( MDA ) levels in group A increased from 4.4 ( 8.0 ) to 7.2 ( 4.8 ) mmol/mL , whereas those in group B decreased from 3.9 ( 4.9 ) to 3.1 ( 5.0 ) mmol/mL ; these changes were not statistically significant . Reduced glutathione levels increased from 0.03 ( 0.04 ) to 0.06 ( 0.12 ) mg/g Hb ( p=0.032 ) after treatment in group A and from 0.03 ( 0.03 ) to 0.05 ( 0.04 ) mg/g Hb ( p=0.001 ) in group B. Infectious complications were equally frequent in the two groups ( group A : 44 ; group B : 37 ; p=0.571 ) . Survival rate and duration of hospital stay were also comparable in the two groups . CONCLUSION Enteral glutamine supplementation offers no advantage in patients with peritonitis or abdominal trauma Abstract Background & Aim : to analyze the clinical impact and cost-effectiveness of parenteral immunonutrition ( PN ) . Methods : prospect i ve clinical trial of a group of 105 patients operated on for gastric carcinoma between 2001 - 2003 . During the postoperative period , patients were r and omly allocated to one of three groups : st and ard PN ( A ) , PN + glu-tamine ( B ) and PN + omega-3-FA ( C ) . The rate and type of complications , hepatic and renal function , cost and treatment tolerance in all groups were analyzed . Results : postoperative complications were observed in 11 patients ( 36,6 % ) in group A , in 7 ( 23,3 % ) in B and in 8 ( 26,6 % ) in C. The most common complication was pneumonia . Prealbumin concentration and TLC increased faster in groups B and C. The length of hospital stay was significantly shorter in the immunonutrition groups . The cost of PN was highest in C group , while cost of hospital stay was longer in A. Conclusions : immunostimulating parenteral nutrition helps to reduce the number of infectious complications , improves the function of the immune system , and has no influence on surgical complications , hepatic and renal function and protein synthesis . The cost of immunostimulating treatment based on omega-3-unsaturated fatty acids is higher than st and ard Objective Heat shock protein 70 ( HSP-70 ) is protective against cellular and tissue injury . Increased serum HSP-70 levels are associated with decreased mortality in trauma patients . Glutamine ( Gln ) administration increases serum and tissue HSP-70 expression in experimental models of sepsis . Gln has been safely administered to critically ill patients and can improve clinical outcomes , but the effect of Gln administration on HSP-70 expression in humans is unknown . We examined whether Gln-supplemented parenteral nutrition ( PN ) increases serum HSP-70 levels in critically ill patients . Design and setting R and omized , controlled , double-blind study in surgical intensive care units ( SICU ) in a university hospital . Patients 29 patients admitted to the SICU and requiring PN for more than 7 days . Interventions Patients received either Gln-PN ( containing alanyl-glutamine dipeptide ; 0 Output:	There is no evidence to suggest that glutamine is harmful in terms of organ failure and parenteral glutamine may reduce the development of organ failure
MS21021	*TASK* the task is to summarize an input biomedical literature in six sentences *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 A new technique for assessing the effects of dentifrices on the growth of human dental plaque is described . Laboratory personnel brushed their teeth with the dentifrices and a new plaque index , the Gingival margin Plaque Index , was used to measure plaque growth over the next 16 hours . The index estimates the proportion of the length of the buccal gingival margin in contact with disclosed plaque on the surface of each tooth . Dentifrices containing 0.4 , 0.8 and 1.2 % chlorhexidine digluconate caused a lower plaque growth than a placebo paste . The differences were highly significant ( P < 0.001 ) . The size of the reduction depended on the concentration of chlorhexidine in the dentifrices . The disclosing reagent had no major effect on plaque growth . The coefficient of linear correlation between results from two examiners was 0.89 for the measurement of plaque growth . Dentifrices containing a quaternary ammonium salt also reduced plaque growth A method measuring plaque by area has been developed which can be used to evaluate the antiplaque effect of agents such as dentifrices when used in combination with toothbrushing . The extent of disclosed plaque 24 hours after treatment on tooth surfaces previously cleaned of all observable plaque was drawn by the examiner onto accurate enlarged scale drawings of the outline of the labial surfaces of all incisors , canines , premolars and 1st molars . Areas were then measured by an electronically recording planimeter . Three separate blind crossover trials were performed using this plaque area measurement in which a minimum of 15 subjects brushed normally on one occasion only , with either a calcium carbonate dentifrice or water . Compared with when subjects brushed with water , a statistically significant reduction of 45%-52 % in plaque was observed in subjects 24 hours after brushing with the dentifrice in each of the three trials . In a study with 27 subjects , the periodontal condition of the papillae was found to be related to plaque present on labial surfaces on adjacent teeth as measured by this method . The teeth adjacent to papillae which bled on probing had 77 % greater plaque area than teeth adjacent to papillae which did not bleed . Plaque area measured by this method on a continuous scale has a sensitivity advantage over the commonly used four-point plaque indices , especially when comparing effective antiplaque treatments or combination of treatments BACKGROUND Inconclusive evidence exists in the literature with regard to the additional effect of the use of dentifrice on plaque removal . The present study was undertaken to test whether the use of dentifrice during toothbrushing contributes to the instant cleaning efficacy of the brushing procedure . METHODS Three groups of patients , 40 subjects each , were r and omly assigned to one of three dentifrices that differed with respect to the relative dentin abrasivity ( RDA ) value . After a 48-hour plaque accumulation , subjects brushed under supervision in a split-mouth order with or without the use of dentifrice ( total time=2 minutes ) . RESULTS Plaque reductions varied between 51 % and 58 % for the three dentifrices . The overall analysis showed a mean difference of 3 % in plaque reduction in favor of brushing without dentifrice ( P=0.017 ) . The type of dentifrice did not influence this observed difference ( P=0.506 ) . Also , the order of the brushing procedure ( starting the brushing procedure with or without dentifrice ) had no interaction with the effect of dentifrice on the brushing ( P=0.187 ) . CONCLUSIONS The use of dentifrice does not contribute to the instant mechanical plaque removal during manual toothbrushing . A higher dentifrice abrasivity does not seem to contribute to increased plaque removal with a manual toothbrush . It appears that the mechanical action provided by the use of a toothbrush is the main factor in the plaque-removing process The purpose of this study was to evaluate whether the home care of noncompliant adolescent orthodontic patients with " poor " oral hygiene could be improved through the use of a deception strategy design ed to intentionally induce the Hawthorne effect . This effect is often cited as being responsible for oral health improvements of control groups that receive placebo treatments . It is thought that participating in and fulfilling the requirements of a study alters subjects ' behavior , thereby contributing to the improvement . Forty patients with histories of poor oral hygiene were assigned , in a quasi-r and om fashion , to two groups . Experimental subjects ( n = 20 ) were presented with a situation that simulated participation in an experiment . These included the use of a consent form ; distribution of tubes of toothpaste labeled " experimental " ; instructions to brush twice a day for two minutes using a timer ; and a request to return unused toothpaste . Control subjects ( n = 20 ) had no knowledge of study participation . Tooth surface area covered with plaque was used as a proxy measure of home care behavior . It was measured at baseline , three months , and six months . Mean percentages of tooth surface covered with plaque for the experimental and control groups were 71 ( + /- 11.52 ) and 74 ( + /- 11.46 ) at baseline ; 54 ( + /- 13.79 ) and 78 ( + /- 12.18 ) at three months ; and 52 ( + /- 13.04 ) and 79 ( + /- 10.76 ) at six months . No statistically significant difference ( p > .05 ) was obtained between groups at baseline . Statistically significant differences ( p < .05 ) were found between groups at three and six months . Significant differences ( p < .05 ) were also found only for the experimental subjects between baseline and each of the two subsequent observation periods . The efficiency and potential effectiveness of this strategy suggest that additional research be conducted to assess oral health improvements and possible applications to the private practice setting Abstract Evidence suggests that brushing with a toothpaste may slow plaque reformation over 24 h. This study measured the effect of toothpaste alone on plaque regrowth over a 96 h period and compared the effect with water and the known antiplaque agent chlorhexidine . At 9 a.m. at the beginning of 7,4-day no oral hygiene periods , 10 volunteers were scaled and polished . Al 5 p.m. subjects brushed their own teeth with water until plaque free . Each subject rinsed for I min with 10 ml of a r and omly allocated rinse . Rinsing was repeated at 10 a.m. and 10 p.m. on subsequent days . The rinses were water , chlorhexidine 0.2 % or 3 g/10 ml slurries of toothpastes containing ( 1 ) monofluorophosphate(MFP ) , ( 2 ) monofluorophosphate + sodium fluoride ( MFP+NaF ) ( 3 ) monofluorophosphate + zinc citrate ( MFP+ZCT ) ( 4 ) stannous fluoride ( SnF2 ) ( 5 ) sodium fluoride ( NaF ) . At 16 , 24 , 48 and 72 h plaque on the buccal surface of the upper and lower premolars , canines and incisors was scored by the Gingival Margin Plaque Index ( GMPI ) and gram films of plaque sample s made . At 96 h plaque was recorded diagraromatically and areas of coverage measured visually ( Debris Index ) and by planimetry . Progressive plaque formation to a Gingival Margin Plaque Index of 100 % at 72 h was observed for toothpaste and water rinses . For chlorhexidine the Gingival Margin Plaque Index at 72 h was 6 % , At 96 h plaque areas were significantly less with toothpaste rinses compared with water . Chlorhexidine very significantly reduced plaque areas compared with toothpaste and water . The bacteriological assessment of smears revealed essentially similar plaque development during toothpaste and water rinses and was consistent with previous reports . However , with chlorhexidine the densities of organisms in the smears were greatly reduced . It was concluded that the small effect of toothpaste rinses on plaque accumulation compared with chlorhexidine would not alone represent a true antiplaque effect result ing in therapeutic benefit The aim of this study was to evaluate clinical ly three commercially available dentifrices and to determine any surface effects on tooth or gingival surfaces . Sixty-four participants were included in this study and were allocated r and omly to one of four treatment groups by an independent person to ensure the investigators were unaware of the brushing material used . All toothbrushes and dentifrices were distributed by this independent person . The treatment groups were : Group 1 - -brush with water ; Group 2 - -brush with Colgate ( Baking Soda and Peroxide ) ; Group 3 - -brush with Macleans ( Whitening ) ; Group 4 - -brush with Colgate ( Sensation Whitening ) . All participants were requested to brush both morning and evening in their customary fashion using only the design ated toothpaste , or water , for four weeks . All participants were required to use the same toothbrush type . No other oral hygiene products such as mouth rinses or dental floss were used during the trial period . Prior to commencement of the brushing period , all participants received a full clinical examination recording the status of the soft and hard tissues including a gingival index ( Löe and Silness ) to record gingival condition . A polyvinyl siloxane impression was taken of the six anterior teeth and gingival tissues at the commencement of the trial . After four weeks , a second full clinical examination was made and further silicone impressions were taken of the anterior teeth . All impressions were cast in epoxy resin for investigation with light and electron microscopy . Participants were also asked to answer a question naire relating to the toothpaste used . The results of this study indicated that no significant clinical differences were recorded for any dentifrice or water and there was no significant difference in gingival index scores over the four week period . Patient responses to each dentifrice varied according to individual patient preferences and expectations and no consistent findings could be determined . Light and electron microscopy indicated that tooth and gingival surface changes that occurred over the four week period with any of the dentifrices were similar to , and not significantly different from , changes seen with the use of water alone . These results indicate that none of the dentifrices tested was harmful to teeth or soft tissues AIM This study assessed the plaque inhibiting effect of a 0.2 % chlorhexidine ( CHX ) solution ( Corsodyl ) with three different rinsing times following a 72 h non-brushing period . MATERIAL AND METHODS The clinical investigation was a single-blind , r and omised study involving 90 volunteer students ( 40 male and 50 female , mean age 23.2 years ) . Subjects were r and omly allocated to one of three groups for which the protocol only differed with respect to the duration of rinsing . At the start of the trial , all participants received a dental prophylaxis to remove all plaque deposits . Subjects refrained from all mechanical oral hygiene procedures , but rinsed two times per day for the allocated duration with CHX mouth rinse over a period of 72 h. The chlorhexidine preparation was of 0.2 % concentration used at a dose of 10 ml for either 15 , 30 or 60 s. After 72 h , the Quigley & Hein plaque index ( PI ) from all volunteers was recorded at six sites per tooth . All participants received a question naire to evaluate their perception of rinsing duration . RESULTS After 72 h , the mean whole-mouth PI was 1.33 , 1.18 and 1.24 , respectively , for the 15 , 30 and 60 s rinsing group . The difference in plaque scores between the three groups was not statistically significant . Results from the question naire showed a significant difference between the groups for their perception of rinsing duration . CONCLUSIONS No significant difference was observed in the level of plaque after 72 h of non-brushing whether the subjects rinsed for 15 , 30 or 60 s with 0.2 % chlorhexidine Toothpastes have been shown to have an antimicrobial activity both in vitro and in vivo ; this activity variably translates into a plaque inhibitory effect in vivo . Commercially available toothpastes have a complex chemical make-up and some contain additional chemicals for which improved effects against plaque have been cl aim ed . The aim of this study was to assess the plaque inhibitory properties of 5 commercially available toothpastes compared to a rinse of water over 4 days . The study was a r and omised , single-blind , cross-over design balanced for residual effects . Volunteers were rendered plaque-free at each baseline and rinsed for 1 min , under the supervision of an assistant , 2x a day with the allocated mouthrinse or toothpaste slurry . At the end of the 4-day test period , the plaque was disclosed and measured by plaque index and plaque area . The plaque measurements indicated a significant difference between the toothpastes . The order of efficacy was Colgate Total , Crest regular , Crest Tartar , Colgate regular , Colgate 0 - 6 gel and water . This confirms previously reported data confirming the plaque inhibitory properties of certain toothpastes compared to water . These data indicate that the choice of control toothpaste with which to compare toothpastes formulated for plaque control is important and could influence conclusions drawn from clinical trials of such products Dentifrices have typically been formulated as pastes . Recently however , a number of liquid products have become available . The chemical plaque inhibitory activity of such products has so far received little attention . The aim of this study was to determine the plaque inhibitory effect of a proprietary liquid dentifrice by comparison to a negative control ( water ) and a conventional fluoride toothpaste . The study design was a r and omised single centre , single blind 3-way cross-over trial with the objective of validating cl aims of plaque inhibition for the liquid dentifrice . Volunteers were rendered plaque free then asked to brush for one minute with one of the three test products , following which they abstained from oral hygiene for the subsequent 24 Output:	Based on three different indices , overall plaque regrowth was significantly ( P < 0.01 ) inhibited for 0.25 or more by the use of a dentifrice slurry as compared to water . The results of this review demonstrate moderate- quality evidence for a weak inhibitory effect on plaque regrowth in favour of the use of a dentifrice intended for daily use
MS21022	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract : This study compared the effects of olanzapine ( OLZ ) with those of quetiapine ( QUE ) for improving negative symptoms in patients diagnosed with schizophrenia or schizoaffective disorder who had prominent negative symptoms and marked deficits in social or occupational functioning . In this 6-month , multicenter , double-blind clinical trial , patients were r and omized to treatment with OLZ ( n = 171 , 10 - 20 mg/d ) or QUE ( n = 175 , 300 - 700 mg/d ) . Patients were treated at community mental health centers and assigned case managers who developed individualized psychosocial treatment plans . The primary efficacy measure was the reduction in negative symptoms using the Scale for the Assessment of Negative Symptoms . Secondary measures assessed changes in functioning , psychopathology , and treatment tolerability . Treatment with OLZ or QUE led to a significant reduction in negative symptoms , with no between-group difference ( P = 0.09 ) . Both treatment groups also showed significant improvement on most efficacy measures . Olanzapine-treated patients showed significantly greater improvement on positive symptoms and on several measures of functioning including Global Assessment of Functioning Scale , Quality of Life Instrumental Role domain , and level of effort in psychosocial or occupational rehabilitation programs . Significantly more OLZ-treated patients completed the study ( 52.6 % OLZ , 37.7 % QUE , P = 0.007 ) . Treatment differences in safety were relatively small and not thought to be clinical ly relevant . Patients with schizophrenia who manifest prominent negative symptoms and marked functional deficits demonstrated significant improvement in negative symptoms after treatment with OLZ or QUE . Greater improvement in positive symptoms and a greater study completion rate may hold relevance to enhanced functional outcomes observed after OLZ therapy Background Bitopertin , a glycine reuptake inhibitor , was investigated as a novel treatment for schizophrenia . We report all the results of a double-blind r and omized study assessing safety and efficacy following 52-week adjunctive treatment with bitopertin in Japanese patients with schizophrenia . Methods This study enrolled Japanese out patients with schizophrenia who met criteria for either “ negative symptoms ” , i.e. , patients with persistent , predominant negative symptoms of schizophrenia even after long-term treatment with antipsychotics or “ sub-optimally controlled symptoms ” , i.e. , patients with insufficiently improved symptoms of schizophrenia even after long-term treatment with antipsychotics , respectively . One hundred sixty-one patients were r and omly assigned to receive 52-week treatments with bitopertin doses of 5 , 10 , or 20 mg/day at ratio of 1:5:5 , where existing antipsychotics were concomitantly administered . Efficacy endpoints included Positive and Negative Syndrome Scale ( PANSS ) , Clinical Global Impression ( CGI ) , and Personal and Social Performance ( PSP ) . The purpose of the present study is primarily to evaluate the safety , and secondarily to investigate the clinical efficacy of bitopertin . Results One hundred fourteen patients ( 71 % ) completed 52-week treatment with bitopertin . Most of the adverse events were mild or moderate in their severity . The patients in the 20-mg group experienced more adverse events than the patients in the other two groups . Common dose-dependent adverse events were somnolence and insomnia associated with worsening schizophrenia . The blood hemoglobin levels gradually decreased from baseline in a dose-dependent manner , but there were no patients with the decrease below 10 g/dL that would have led to their discontinuation . All the efficacy endpoints gradually improved in all the treatment groups for both of the two symptoms , while there were no clear differences among the three dose groups . Conclusions Altogether , bitopertin was found to be generally safe and well-tolerated for the treatment of patients with schizophrenia . All three bitopertin treated groups showed improvements in all the efficacy endpoints for both of the two symptoms , i.e. , “ negative symptoms ” and “ sub-optimally controlled symptoms ” , throughout the duration of the study .Trial registration Japan Pharmaceutical Information Center , number JapicCTI-111627 ( registered on September 20 , 2011 Background Based on experiences and empirical evidence gained in studies using the Lancashire Quality of Life Profile ( LQLP ) , the Manchester Short Assessment of Quality of Life ( MANSA ) has been developed as a condensed and slightly modified instrument for assessing quality of life . Its properties have been tested in a sample of community care patients . Method Fifty-five r and omly selected patients on the Care Programme Approach were interviewed using the LQLP , the MANSA and the Brief Psychiatric Rating Scale . Results Correlations between subjective quality of life scores on MANSA and LQLP were all 0.83 or higher ( 0.94 for the satisfaction mean score ) . Cronbach 's alpha for satisfaction ratings was 0.74 , and association with psychopathology was in line with results for LQLP as reported in the literature . Conclusions The MANSA is a brief instrument for assessing quality of life focusing on satisfaction with life as a whole and with life domains . Its psychometric properties appear satisfactory We developed a self-administered instrument to assess health-related quality of life ( HRQL ) among people with schizophrenia . The S-QoL , based on Calman 's approach to the subject 's point of view , is a multidimensional instrument that is sensitive to change . The scale is a 41-item question naire with eight subscales ( psychological well-being , self-esteem , family relationships , relationships with friends , resilience , physical well-being , autonomy and sentimental life ) and a total score . In-depth interviews with patients determined the pertinent issues for item development . The validation study , performed with 207 patients , showed high internal consistency reliability , reproducibility and responsiveness . Construct validity was confirmed using established clinical and HRQL measures . S-QoL covers domains that differ from areas tapped in other measures , with greater responsiveness . The S-QoL is an efficient instrument for the measurement of the impact of schizophrenia on individuals ' lives Recent research indicates that subjective well-being is a major determinant of medication compliance in schizophrenia . However , it is yet unresolved whether atypical neuroleptics differ regarding subjective side-effects . A self-report instrument has been constructed to evaluate ' subjective well-being under neuroleptics ' ( SWN ) . The primary aims of the present study were to develop a short form of the SWN and to investigate the extent to which the atypical antipsychotic improves the patient 's subjective well-being . The short form of the SWN was constructed following an item analysis based on data from 212 schizophrenic patients medicated with either typical or atypical antipsychotics . The short form of the SWN showed sufficient internal consistency and good construct validity . The SWN was only moderately correlated with positive and negative syndrome scale ( PANSS ) scores or changes in psychopathology ( r=-0.20 to -0.37 ) . SWN-ratings in patients receiving olanzapine were superior compared to those of patients medicated with either clozapine or risperidone on three of five domains of well-being . Clozapine reduced global psychiatric symptoms significantly more than risperidone . It is concluded that the assessment of subjective well-being under antipsychotic treatment provides an independent outcome measure which is relevant to compliance Current meta- analysis revealed small , but significant effects of repetitive transcranial magnetic stimulation ( rTMS ) on negative symptoms in patients with schizophrenia . There is a need for further controlled , multicenter trials to assess the clinical efficacy of rTMS on negative symptoms in schizophrenia in a larger sample of patients . The objective of this multicenter , r and omized , sham-controlled , rater- and patient-blind clinical trial is to investigate the efficacy of 3-week 10-Hz high frequency rTMS add on to antipsychotic therapy , 15 sessions per 3 weeks , 1,000 stimuli per session , stimulation intensity 110 % of the individual motor threshold ) of the left dorsolateral prefrontal cortex for treating negative symptoms in schizophrenia , and to evaluate the effect during a 12 weeks of follow-up . The primary efficacy endpoint is a reduction of negative symptoms as assessed by the negative sum score of the positive and negative symptom score ( PANSS ) . A sample size of 63 in each group will have 80 % power to detect an effect size of 0.50 . Data analysis will be based on the intention to treat population . The study will be conducted at three university hospitals in Germany . This study will provide information about the efficacy of rTMS in the treatment of negative symptoms . In addition to psychopathology , other outcome measures such as neurocognition , social functioning , quality of life and neurobiological parameters will be assessed to investigate basic mechanisms of rTMS in schizophrenia . Main limitations of the trial are the potential influence of antipsychotic dosage changes and the difficulty to ensure adequate blinding Abstract Using a selective glycine uptake inhibitor as adjunctive to second-generation antipsychotic ( SGA ) was hypothesized to ameliorate negative and /or cognitive symptoms in subjects with schizophrenia . Subjects with predominant persistent negative symptoms ( previously stabilized ≥3 months on an SGA ) were enrolled in a r and omized , placebo-controlled trial to investigate adjunctive treatment with Org 25935 , a selective inhibitor of type 1 glycine transporter , over 12 weeks in a flexible dose design . Org 25935 was tested at 4 to 8 mg twice daily and 12 to 16 mg twice daily versus placebo . Primary efficacy outcome was mean change from baseline in Scale for Assessment of Negative Symptoms composite score . Secondary efficacy end points were Positive and Negative Syndrome Scale total and subscale scores , depressive symptoms ( Calgary Depression Scale for Schizophrenia ) , global functioning ( Global Assessment of Functioning scale ) , and cognitive measures using a computerized battery ( Central Nervous System Vital Signs ) . Responder rates were assessed post hoc . A total of 215 subjects were r and omized , of which 187 ( 87 % ) completed the trial . Both dose groups of Org 25935 did not differ significantly from placebo on Scale for Assessment of Negative Symptoms , Positive and Negative Syndrome Scale ( total or subscale scores ) , Global Assessment of Functioning , or the majority of tested cognitive domains . Org 25935 was generally well tolerated within the tested dose range , with no meaningful effects on extrapyramidal symptoms and some reports of reversible visual adverse effects . Org 25935 did not differ significantly from placebo in reducing negative symptoms or improving cognitive functioning when administered as adjunctive treatment to SGA . In our study population , Org 25935 appeared to be well tolerated in the tested dose ranges BACKGROUND The treatment and measurement of negative symptoms are currently at issue in schizophrenia , but the clinical meaning of symptom severity and change is unclear . AIM To offer a clinical ly meaningful interpretation of severity and change scores on the Scale for the Assessment of Negative Symptoms ( SANS ) . METHOD Patients were intention-to-treat participants ( n=383 ) in two double-blind r and omized placebo-controlled clinical trials that compared amisulpride with placebo for the treatment of predominant negative symptoms . Equipercentile linking was used to examine extrapolation from ( a ) CGI-S to SANS severity ratings , and ( b ) CGI-I to SANS percentage change ( n=383 ) . Linking was conducted at baseline , 8 - 14 days , 28 - 30 days , and 56 - 60 days of the trials . RESULTS Across visits , CGI-S ratings of ' not ill ' linked to SANS scores of 0 - 13 , and ranged to ' extreme ' ratings that linked to SANS scores of 102 - 105 . The relationship between the CGI-S and the SANS severity scores assumed a linear trend ( 1=0 - 13 , 2=15 - 56 , 3=37 - 61 , 4=49 - 66 , 5=63 - 75 , 6=79 - 89 , 7=102 - 105 ) . Similarly the relationship between CGI-I ratings and SANS percentage change followed a linear trend . For instance , CGI-I ratings of ' very much improved ' were linked to SANS percent changes of -90 to -67 , ' much improved ' to -50 to -42 , and ' minimally improved ' to -21 to -13 . CONCLUSIONS The current results uniquely contribute to the debate surrounding negative symptoms by providing clinical meaning to SANS severity and change scores and so offer direction regarding clinical ly meaningful response cut-off scores to guide treatment targets of predominant negative symptoms Output:	Conclusion : No HRQoL instrument has been vali date d in patients with SNS only ; for the remaining instruments identified , it remains unclear whether they were intended to capture HRQoL in patients with SNS
MS21023	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Oral controlled-release oxycodone has been available for the treatment of chronic pain in Germany since 1998 . Controlled trials have shown good clinical efficacy and tolerability . This survey reports results from six open prospect i ve multicenter trials . In these trials 4196 patients suffering from cancer pain and non-cancer-related pain with inadequate pain relief were treated with oral controlled-release oxycodone for 3 - 4 weeks . Only a few participating physicians were pain specialists . A total of 356 patients suffering from pain of the musculoskeletal system and receiving oxycodone therapy were monitored for 6 months . Exclusion from the studies was due mainly to inadequate analgesia , side effects , and noncompliance . The efficacy of oxycodone was rated to be better than moderate by most of the patients , quality of life parameters increased significantly , and patient satisfaction was high . The treatment with oral controlled-release oxycodone was a safe and effective option even when used by nonspecialized physicians BACKGROUND : Current clinical guidelines have identified the need for studies comparing the effect of different short-acting or rapid-onset opioids for the treatment of breakthrough pain ( BTP ) . In this study we evaluated the efficacy and safety of treatment with fentanyl buccal tablet ( FBT ) in comparison with immediate-release oxycodone in alleviating BTP in opioid-tolerant patients with chronic pain . METHODS : In this cross-over design study , opioid-tolerant patients were r and omized to open-label titration with FBT ( 200 , 400 , 600 , 800 & mgr;g ) followed by oxycodone ( 15 , 30 , 45 , 60 mg ) or vice versa for the management of BTP . After titration to a successful dose of both study drugs , patients were rer and omized to double-blind treatment for 10 BTP episodes with 1 of the already identified successful doses of study drug followed by cross-over to double-blind treatment for 10 BTP episodes with the other study drug . The primary efficacy measure was the difference in pain intensity ( based on an 11-point numerical scale ) 15 minutes after administration of study drug ( PID15 ) . Other efficacy measures included PID at other time points postdose ( 5 through 60 minutes ) , the sum of pain intensity differences ( SPID ) at 30 and 60 minutes postdose , pain relief ( 5 through 60 minutes ) , proportion of BTP episodes for which patients experienced meaningful reduction in pain intensity , and patient preference for BTP medication . Adverse events were also recorded . RESULTS : Of the 323 patients enrolled , 203 achieved a successful dose of both study drugs , 191 completed the titration phase , and 180 completed the double-blind phase . PID15 was significantly greater after FBT versus oxycodone ( mean [ SD ] , 0.82 [ 1.12 ] vs. 0.60 [ 0.88 ] ; 95 % confidence interval [ CI ] = 0.18 , 0.29 ; P < 0.0001 ) . Secondary efficacy measures favored FBT and showed differences versus oxycodone from 5 minutes postdose for PID and 10 minutes postdose for pain relief . SPID30 and SPID60 were greater with FBT than with oxycodone ( P < 0.0001 for both measures ) . A ≥33 % improvement in pain intensity occurred in a larger proportion of FBT-treated episodes versus oxycodone beginning 15 through 45 minutes postdose ( P < 0.05 ) . FBT was preferred by 52 % of patients , oxycodone by 33 % . Adverse events with both study drugs were generally typical of opioids , and the majority occurred during titration . Two serious adverse events ( pneumonia ) were reported in 1 patient ; both occurrences were considered unrelated to study drug . CONCLUSION : FBT result ed in more rapid onset of analgesia and was generally well tolerated in comparison with oxycodone for the treatment of BTP in opioid-tolerant patients Opioid use has been reported to be associated with increased fracture risks . In a nested case-control study using the United Kingdom-based General Practice Research Data base , we tested the hypotheses that fracture risk was associated with 1 ) an elevated risk of falls caused by the acute central nervous system effects of opioids including sedation and dizziness , and 2 ) osteoporosis caused by chronic opioid-induced hypogonadism . Among a cohort of adults aged 18 - 80 years without cancer who received ≥1 opioid prescription during 1990 - 2008 , we selected cases with a first diagnosed fracture of the hip , humerus , or wrist ; up to 4 controls , matched by age , sex , index date ( date of the first diagnosed fracture ) , and general practice , were r and omly selected for each case . Adjusted odds ratios and 95 % confidence intervals were estimated by using conditional logistic regression . Current use of 1 prescription was associated with a strong risk of fracture ( adjusted odds ratio = 2.70 , 95 % confidence interval : 2.34 , 3.13 ) . The risk decreased with increasing use . There was no association with current use of > 20 opioid prescriptions . The findings were consistent for all study fractures and for most common opioids , suggesting that acute central nervous system effects of opioids rather than chronic opioid-induced hypogonadism play a key role in fracture risk BACKGROUND S With increasing use of opioids for chronic noncancer pain comes concern about safety of this class of drugs . Opioid-induced hypogonadism , which could increase the risk for myocardial infa rct ion ( MI ) , has recently come to the attention of clinicians . To evaluate this concern we examined the association between opioid use for noncancer pain and risk of MI amongst adults . METHODS We conducted a nested case-control study using the UK General Practice Research Data base . Amongst 1.7 million opioid users during 1990 - 2008 , we identified 11 693 incident MI cases aged 18 - 80 years , and r and omly selected up to four controls matched by age , gender , index date ( date of onset symptoms or diagnosis of first-ever MI ) and general practice via risk-set sampling . Cases and controls were required to have no cancer and no major risk factors for MI before the index date . Adjusted odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) were estimated from conditional logistic regression . RESULTS Compared with nonuse , current use of opioids was associated with a 1.28-fold ( 95 % CI 1.19 - 1.37 ) risk of MI . Cumulative use of opioids with 11 - 50 ( OR = 1.38 , 95 % CI : 1.28 - 1.49 ) or > 50 ( OR = 1.25 , 95 % CI : 1.11 - 1.40 ) prescriptions , was also marginally associated with increased risk of MI . The risk was particularly increased in users of morphine ( OR = 1.71 , 95 % CI : 1.09 - 2.68 ) , meperidine ( OR = 2.15 , 95 % CI : 1.24 - 3.74 ) and polytherapy ( OR = 1.46 , 95 % CI : 1.22 - 1.76 ) . CONCLUSIONS Current use of any opioids and cumulative use of 11 or more prescriptions are associated with a small increased risk for MI compared to nonuse and the risk was greater in morphine , meperidine and polytherapy users . Residual confounding , particularly confounding by indication , should be considered in interpreting our results & NA ; Data on comparative safety of opioid analgesics are limited , but some reports suggest disproportionate mortality risk associated with methadone . Our objective was to compare mortality rates among patients who received prescribed methadone or long‐acting morphine for pain . This is a retrospective observational cohort drawn from Department of Veterans Affairs ( VA ) health care data bases , January 1 , 2000 , to December 31 , 2007 . We included 28,554 patients who received methadone and 79,938 who received long‐acting morphine from VA pharmacies . Compared with those who received long‐acting morphine , patients who received methadone were younger , less likely to have some medical comorbidities , and more likely to have psychiatric and substance use disorders . Patients were stratified into quintiles according to propensity score ; the probability of receiving methadone was conditional on demographic , clinical , and VA service area variables . Overall propensity‐adjusted mortality was lower for methadone than for morphine . Hazard ratios varied across propensity score quintiles ; the magnitude of the between‐drug difference in mortality decreased as the propensity to receive methadone increased . Mortality was significantly lower for methadone in all but the last quintile , in which there was no between‐drug difference in mortality ( hazard ratio = 0.92 , 95 % confidence interval = 0.74 , 1.16 ) . Multiple sensitivity analyses found either no difference in mortality between methadone and long‐acting morphine or lower mortality rates among patients who received methadone . In summary , we found no evidence of excess all‐cause mortality among VA patients who received methadone compared with those who received long‐acting morphine . R and omized trials and prospect i ve observational research are needed to better underst and the relative safety of long‐acting opioids . Among patients who received methadone or long‐acting morphine for pain from Department of Veterans Affairs pharmacies in 2000–2007 , no evidence of excess all‐cause mortality associated with methadone was found Driving has been regarded as an activity of daily living that is important in maintaining a person 's independence in the community , access to employment , and social activities . Many patients , however , using opioid medications on a regular basis ( Chronic Opioid Analgesic Therapy : COAT ) to ameliorate their intractable pain have been restricted from driving out of concern that skills would be impaired and driving safety compromised by these medications . Yet there are no driving studies which have explored the effects of using opioid analgesics for an extended period of time . This pilot study was design ed to determine the effects of medically prescribed , stable opioid use on the driving abilities of patients with persistent , nonmalignant pain . Sixteen patients with chronic nonmalignant pain on COAT , who met criteria for participation in the study , underwent a comprehensive off-road driving evaluation using measures which have been shown to be sensitive in predicting on-road driving performance . The evaluation consisted of a pre-driver evaluation ( PDE ) , a simulator evaluation ( SDE ) , and behavioral observation during simulator performance . Patients in the COAT group were compared to a historical control group of 327 cerebrally compromised patients ( CComp ) who had undergone the same evaluation and then passed an on-road , behind-the-wheel evaluation ( BTW Pass ; n = 162 ) or failed ( BTW Fail ; n = 165 ) . Results revealed that COAT patients generally outperformed the CComp patients as a group by equaling or exceeding PDE and SDE scores of the BTW Fail patients as well as the BTW Pass patients on all measures that differentiated the groups . Notably , COAT patients had a relatively poorer performance than CComp patients on specific neuropsychometric tests in the PDE ; however , the differences were not statistically significant and did not imply a systematic pattern of scores that reflected domain-specific deficits . Behaviorally , COAT patients were generally superior to CComp patients , also ; however , COAT patients had greater difficulty in following instructions and as well as a tendency toward impulsivity , like the BTW fail group . While there was general support for the notion that COAT did not significantly impair the perception , cognition , coordination , and behavior measured in off-road tests that have been regarded as requisite for on-road driving , method ological problems may limit the generalizability of results and recommendations are made for research beyond a pilot study Prer and omization run-in periods are being used to select or exclude patients in an increasing number of clinical trials , but the implication s of run-in periods for interpreting the results of clinical trials and applying these results in clinical practice have not been systematic ally examined . We analyzed illustrative examples of reports of clinical trials in which run-in periods were used to exclude noncompliant subjects , placebo responders , or subjects who could not tolerate or did not respond to active drug . The Physicians ' Health Study exemplifies the use of a prer and omization run-in period to exclude subjects who are nonadherent , while recent trials of tacrine for Alzheimer disease and carvedilol for congestive heart failure typify the use of run-in periods to exclude patients who do not tolerate or do not respond to the study drug . The reported results of these studies are valid . However , because the reported results apply to subgroups of patients who can not be defined readily based on demographic or clinical characteristics , the applicability of the results in clinical practice is diluted . Compared with results that would have been observed without the run-in period , the reported results overestimate the benefits and underestimate the risks of treatment , underestimate the number needed to treat , and yield a smaller P value . The Cardiac Arrhythmia Suppression Trial exemplifies the use of an active-drug run-in period that enhances clinical applicability by selecting a group of study subjects who closely resembled patients undergoing active clinical management for this problem . Run-in periods can dilute or enhance the clinical applicability of the results of a clinical trial , depending on the patient group to whom the results will be applied . Reports of clinical trials using run-in periods should indicate how this aspect of their design affects the application of the results to clinical practice Output:	Evidence on long-term opioid therapy for chronic pain is very limited but suggests an increased risk of serious harms that appears to be dose-dependent .
MS21024	*TASK* the task is to summarize an input biomedical literature in six sentences *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 This paper is a report of a study to assess the effect of an adapted arthritis self-management programme with an added focus on exercise practice among osteoarthritic knee sufferers . BACKGROUND Osteoarthritis of the knee is a major source of loss of function in older people . Previous studies have found self-management programmes to be effective in increasing arthritis self-efficacy and in mastery of self-management practice . METHOD A r and omized control trial was carried out from December 2002 to May 2003 and 120 participants ( 65.9 % , including 67 in intervention group and 53 in control group ) completed the 16-week postintervention assessment s. Outcome measures included arthritis self-efficacy , use of self-management techniques , pain intensity and daily activity . FINDINGS At 16 weeks , there was a ' statistically ' significant improvement in the arthritis self-efficacy level ( P < or= 0.001 ) , in most of the self-management skills , i.e. use of cold and hot compresses , in two of three joint protective practice s ( P < or= 0.001 ; P = 0.01 ) , an increase in the duration of light exercise practice ( P < or= 0.001 ) , reduction of current arthritis pain ( P < or= 0.001 ) and in the ability to perform daily activities ( P < or= 0.001 ) among the intervention group but not for the control group ( P-range from 0.04 to 0.95 ) . One joint protective practice showed a statistically significant increase in both groups ( P < or= 0.001 ) . CONCLUSION Our findings add to evidence showing short-term beneficial effects of self-efficacy theory in education programmes . Self-efficacy theory has great potential for empowering sufferers of chronic conditions to live with their illness 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 test the effects of a high intensity home-based progressive strength training program on the clinical signs and symptoms of osteoarthritis ( OA ) of the knee . METHODS Forty-six community dwelling patients , aged 55 years or older with knee pain and radiographic evidence of knee OA , were r and omized to a 4 month home based progressive strength training program or a nutrition education program ( attention control ) . Thirty-eight patients completed the trial with an adherence of 84 % to the intervention and 65 % to the attention control . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index pain and physical function subscales . Secondary outcomes included clinical knee examination , muscle strength , physical performance measures , and question naires to measure quality of life variables . RESULTS Patients in the strength training group who completed the trial had a 71 % improvement in knee extension strength in the leg reported as most painful versus a 3 % improvement in the control group ( p < 0.01 ) . In a modified intent to treat analysis , self-reported pain improved by 36 % and physical function by 38 % in the strength training group versus 11 and 21 % , respectively , in the control group ( p = 0.01 for between group comparison ) . In addition , those patients in the strength training group who completed the trial had a 43 % mean reduction in pain ( p = 0.01 vs controls ) , a 44 % mean improvement in self-reported physical function ( p < 0.01 vs controls ) , and improvements in physical performance , quality of life , and self-efficacy when compared to the control group . CONCLUSION High intensity , home based strength training can produce substantial improvements in strength , pain , physical function and quality of life in patients with knee OA BACKGROUND People with osteoarthritis ( OA ) of the knee experience pain and deconditioning that lead to disability . This study challenged the clinical belief that repetitive lower extremity exercise is not indicated in persons with knee OA . The effects of high-intensity and low-intensity stationary cycling on functional status , gait , overall and acute pain , and aerobic capacity were examined . METHODS Thirty-nine adults ( 71+/-6.9 years old ) with complaints of knee pain and diagnosis of OA were r and omized to either a high-intensity ( 70 % heart rate reserve [ HRR ] ) or low-intensity ( 40 % HRR ) exercise group for 10 weeks of stationary cycling . Participants cycled for 25 minutes , 3 times per week . Before and after the exercise intervention they completed the Arthritis Impact Measurement Scale 2 for overall pain assessment , underwent timed chair rise , 6-minute walk test , gait , and grade d exercise treadmill tests . Acute pain was reported daily with a visual analog scale and the Western Ontario and McMaster Universities Osteoarthritis Index scale . RESULTS Analysis of variance revealed that participants in both groups significantly improved in the timed chair rise , in the 6-minute walk test , in the range of walking speeds , in the amount of overall pain relief , and in aerobic capacity . No differences between groups were found . Daily pain reports suggested that cycling did not increase acute pain in either group . CONCLUSIONS Cycling may be considered as an alternative exercise modality for patients with knee OA . Low-intensity cycling was as effective as high-intensity cycling in improving function and gait , decreasing pain , and increasing aerobic capacity Background Osteoarthritis ( OA ) is a common problem in older women that is associated with pain and disabilities . Although yoga is recommended as an exercise intervention to manage arthritis , there is limited evidence documenting its effectiveness , with little known about its long term benefits . This study ’s aims were to assess the feasibility and potential efficacy of a Hatha yoga exercise program in managing OA-related symptoms in older women with knee OA . Methods Eligible participants ( N = 36 ; mean age 72 years ) were r and omly assigned to 8-week yoga program involving group and home-based sessions or wait-list control . The yoga intervention program was developed by a group of yoga experts ( N = 5 ) . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) total score that measures knee OA pain , stiffness , and function at 8 weeks . The secondary outcomes , physical function of the lower extremities , body mass index ( BMI ) , quality of sleep ( QOS ) , and quality of life ( QOL ) , were measured using weight , height , the short physical performance battery ( SPPB ) , the Pittsburgh Sleep Quality Index ( PSQI ) , the Cantril Self-Anchoring Ladder , and the SF12v2 Health Survey . Data were collected at baseline , 4 weeks and 8 weeks , and 20 weeks . Results The recruitment target was met , with study retention at 95 % . Based on ANCOVAs , participants in the treatment group exhibited significantly greater improvement in WOMAC pain ( adjusted means [ SE ] ) ( 8.3 [ .67 ] , 5.8 [ .67 ] ; p = .01 ) , stiffness ( 4.7 [ .28 ] , 3.4 [ .28 ] ; p = .002 ) and SPPB ( repeated chair st and s ) ( 2.0 [ .23 ] , 2.8 [ .23 ] ; p = .03 ) at 8 weeks . Significant treatment and time effects were seen in WOMAC pain ( 7.0 [ .46 ] , 5.4 [ .54 ] ; p = .03 ) , function ( 24.5 [ 1.8 ] , 19.9 [ 1.6 ] ; p = .01 ) and total scores ( 35.4 [ 2.3 ] , 28.6 [ 2.1 ] ; p = .01 ) from 4 to 20 weeks . Sleep disturbance was improved but the PSQI total score declined significantly at 20 weeks . Changes in BMI and QOL were not significant . No yoga related adverse events were observed . Conclusions A weekly yoga program with home practice is feasible , acceptable , and safe for older women with knee OA , and shows therapeutic benefits .Trial registration Clinical Trials.gov : Background Strengthening exercises of the quadriceps femoris muscle ( QFM ) are beneficial for patients with knee osteoarthritis ( OA ) . Studies reporting short-term effects of neuromuscular electrical stimulation ( NMES ) of the QFM in this population support the use of this modality as an adjunct treatment . The objectives of this follow-up study are to compare the effects of an exercise program with and without NMES of the QFM on pain , functional performance , and muscle strength immediately posttreatment and 12 weeks after completion of the intervention . Methods Sixty-three participants with knee OA were r and omly assigned into two groups receiving 12 biweekly treatments : An exercise-only program or an exercise program combined with NMES . Results A significantly greater reduction in knee pain was observed immediately after treatment in the NMES group , which was maintained 12 weeks postintervention in both groups . Although at this stage NMES had no additive effect , both groups demonstrated an immediate increase in muscle strength and in functional abilities , with no differences between groups . Although the improvements in gait velocity and in self-report functional ability were maintained at the follow-up session , the noted improvements in muscle strength , time to up and go , and stair negotiation were not maintained . Conclusion Supplementing an exercise program with NMES to the QFM increased pain modulation immediately after treatment in patients with knee OA . Maintenance of the positive posttreatment effects during a 12-week period was observed only for pain , self-reported functional ability , and walk velocity , with no difference between groups . Clinical rehabilitation effect The effects of a comprehensive group exercise program with or without NMES are partially maintained 12 weeks after completion of the intervention . The addition of NMES is recommended primarily for its immediate effect on pain . Further studies are necessary to determine the effects of repeated bouts of exercise with and without NMES in this population This observer-blinded , r and omized controlled trial compared the short- and long-term effects of 4 months of supervised strength training ( ST ) in a local fitness center , supervised Nordic Walking ( NW ) in a local park , and unsupervised home-based exercise ( HBE , control ) on functional performance in 60 + -year-old persons ( n = 152 ) with hip osteoarthritis ( OA ) not awaiting hip replacement . Functional performance [ i.e. , 30-s chair st and test ( primary outcome ) , timed stair climbing , and 6-min walk test ] and self-reported outcomes ( i.e. , physical function , pain , physical activity level , self-efficacy , and health-related quality of life ) were measured at baseline and at 2 , 4 , and 12 months . Based on intention-to-treat-analyses improvements [ mean ( 95 % CI ) ] after intervention in number of chair st and s were equal in all three groups at 4 months [ ST : 0.9 ( 0.2 - 1.6 ) , NW : 1.9 ( 0.8 - 3.0 ) , HBE : 1.1 ( 0.1 - 2.0 ) ] but greater in the NW group [ 1.4 ( 0.02 - 2.8 ) ] than in the ST group at 12 months . Generally , improvements in functional performance were greater ( P < 0.001-P < 0.03 ) after NW compared with HBE and ST at all follow-up time points . Furthermore , NW was superior ( P < 0.01 ) to HBE for improving vigorous physical activity and to both ST and HBE for improving ( P < 0.01 ) mental health . These data suggest that NW is the recommended exercise modality compared with ST and HBE Objective : To evaluate the effects of tai chi consisting of group and home-based sessions in elderly subjects with knee osteoarthritis . Design : A r and omized , controlled , single-blinded 12-week trial with stratification by age and sex , and six weeks of follow-up . Setting : General community . Participants : Forty-one adults ( 709 / 9.2 years ) with knee osteoarthritis . Interventions : The tai chi programme featured six weeks of group tai chi sessions , 40 min/session , three times a week , followed by another six weeks ( weeks 7 -12 ) of home-based tai chi training . Subjects were requested to discontinue tai chi training during a six-week follow-up detraining period ( weeks 13 - 18 ) . Subjects in the attention control group attended six weeks of health lectures following the same schedule as the group-based tai chi intervention ( weeks 0 -6 ) , followed by 12 weeks of no activity ( weeks 7 - 18 ) . Main outcome measures : Knee pain measured by visual analogue scale , knee range of motion and physical function measured by Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) were recorded at baseline and every three weeks throughout the 18-week study period . Data were analysed using a mixed model ANOVA . Results : The six weeks of group tai chi followed by another six weeks of home tai chi training showed significant improvements in mean overall knee pain ( P = 0.0078 ) , maximum knee pain ( P = 0.0035 ) and the WOMAC subscales of physical function ( P = 0.0075 ) and stiffness ( P = 0.0206 ) compared to the baseline . No significant change of any outcome measure was noted in the attention control group throughout the study . The tai chi group reported lower overall pain and better WOMAC physical function than the attention control group at weeks 9 and 12 . All improvements disappeared after detraining OBJECTIVE To determine the effects of structured exercise programs Output:	In subgroup analyses , resistance training still ranked the most effective pain reduction intervention , followed by strengthening exercise and yoga . Among female subjects with intervention adherence rate more than 90 % , the most effective intervention was yoga . Strengthening exercise was superior to all other forms of interventions when comparing long-term effect of selected interventions . Among older adults with osteoarthritis , resistance training can be considered a treatment option for pain relief . Yoga is an effective intervention strategy for female elderly , and strengthening exercise has a better long-term beneficial effect
MS21025	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE This study examined the prevalence and psychological sequelae of childhood sexual and physical abuse in adults from the general population . METHOD A national sampling service generated a geographically stratified , r and om sample of 1,442 subjects from the United States . Subjects were mailed a question naire that included the Traumatic Events Survey ( TES ) [ Traumatic Events Survey , Unpublished Psychological Test , Harbor-UCLA Medical Center , Los Angeles ] and the Trauma Symptom Inventory ( TSI ) [ Trauma Symptom Inventory Professional Manual , Psychological Assessment Re sources , Odessa , FL ] . Of all potential subjects , 935 ( 64.8 % ) returned substantially completed surveys . RESULTS Sixty-six men and 152 women ( 14.2 % and 32.3 % , respectively ) reported childhood experiences that satisfied criteria for sexual abuse , and 103 males and 92 females ( 22.2 % and 19.5 % , respectively ) met criteria for physical abuse . Twenty-one percent of subjects with one type of abuse also had experienced the other type , and both types were associated with subsequent adult victimization . After controlling for demographics , adult history of interpersonal violence , and other child abuse , childhood sexual abuse was associated with all 10 scales of the TSI , and physical abuse was related to all TSI scales except those tapping sexual issues . Sexual abuse predicted more symptom variance than did physical abuse or adult interpersonal victimization . Various aspects of both physical and sexual abuse experiences were predictive of TSI scores . Abuser sex , however , both alone and in interaction with victim sex , was not associated with additional TSI symptomatology . CONCLUSIONS Childhood sexual and physical abuse is relatively common in the general population , and is associated with a wide variety of psychological symptoms . These relationships remain even after controlling for relevant background variables OBJECTIVE The present study sought to determine whether the 12-session pre- to posttest therapeutic gains that had been found by Deblinger , Lippmann . and Steer ( 1996 ) for an initial sample of 100 sexually abused children suffering posttraumatic stress disorder ( PTSD ) symptoms would be sustained 2 years after treatment . METHOD These sexually abused children , along with their nonoffending mothers , had been r and omly assigned to one of three cognitive-behavioral treatment conditions , child only , mother only , or mother and child , or a community comparison condition , and were followed for 3 months , 6 months , 1 year , and 2 years after treatment . RESULTS A series of repeated MANCOVAs , controlling for the pre-test scores , indicated that for the three measures of psychopathology that had significantly decreased in the original study ( i.e. , externalizing behavior problems , depression , and PTSD symptoms ) , these measures at 3 months , 6 months , 1 year , and 2 years were comparable to the posttest scores . CONCLUSIONS These findings suggest that the pre- to post-treatment improvements held across the 2-year follow-up period . The clinical and research implication s of these findings are discussed The objective of this study was to evaluate and compare the efficacy of two short-term individual therapy interventions for sexually abused girls and their nonoffending female caretakers . Thirty-two girls , ages 8 to 13 , and their caretakers from primarily low-income , African-American families were r and omly assigned to a theoretically based , structured experimental treatment program or to a relatively unstructured comparison intervention . Measures of child outcome were completed before and after the treatment program by each parent and child , and by a clinician blind to treatment condition . Pre- and post measures of maternal outcome were completed by the caretaker and a clinician not involved in the treatment . Both treatment programs yielded decreases in children 's posttraumatic stress disorder symptoms and traumagenic beliefs reflecting self-blame and powerlessness , and increases in children 's overall psychosocial functioning . The experimental intervention was more effective than the comparison program in increasing abuse-related caretaker support of the child and in decreasing caretaker self-blame and expectations of undue negative impact of the abuse on the child . Clinical impfications of these findings include the development of interventions targeting sexually abused children 's traumagenic beliefs and nonoffending parents ' support of their victimized children OBJECTIVE Treatment outcome for sexually abused preschool-age children and their parents was assessed , comparing the effectiveness of a cognitive-behavioral intervention to nondirective supportive treatment . METHOD Sixty-seven sexually abused preschool children and their parents were r and omly assigned to either ( 1 ) cognitive-behavioral therapy adapted for sexually abused preschool children ( CBT-SAP ) or ( 2 ) nondirective supportive therapy ( NST ) . Treatment consisted of 12 individual sessions for both the child and parent , monitored for integrity with the therapeutic model through intensive training and supervision , use of treatment manuals , and rating of audiotaped sessions . Parents completed the Child Behavior Checklist , the Child Sexual Behavior Inventory , and the Weekly Behavior Report to measure a variety of emotional and behavioral symptoms . RESULTS Within-group comparison of pretreatment and posttreatment outcome measures demonstrated that while the NST group did not change significantly with regard to symptomatology , the CBT-SAP group had highly significant symptomatic improvement on most outcome measures . Repeated- measures analyses of variance demonstrated group x time interactions on some variables as well . Clinical findings also supported the effectiveness of the CBT-SAP intervention over NST . CONCLUSIONS Findings provide strong preliminary evidence for the effectiveness of a specific cognitive-behavioral treatment model for sexually abused preschool children and their parents OBJECTIVE To determine the rate and risk of clinical and personality disorders diagnosed in childhood and adulthood in those known to have been sexually abused during childhood . METHODS Forensic medical records of 2,759 sexually abused children assessed between 1964 and 1995 were linked with a public psychiatric data base between 12 and 43 years later . Cases were compared to control subjects matched on gender and age groupings drawn from the general population through a r and om sample of the national electoral data base . RESULTS A lifetime record of contact with public mental health services was found in 23.3 % of cases compared to 7.7 % of controls . The rate of contact among child sexual abuse victims was 3.65 times higher ( 95 % CI , 3.09 - 4.32 , p<0.001 ) . It was estimated that child sexual abuse accounted for approximately 7.83 % of mental health contact . Exposure to sexual abuse increased risks for the majority of outcomes including psychosis , affective , anxiety , substance abuse , and personality disorders . Rates of clinical disorders diagnosed in adulthood and childhood remained significantly higher among child sexual abuse cases . Older age at sexual abuse and those exposed to severe abuse involving penetration or multiple offenders were associated with greater risk for psychopathology . CONCLUSIONS This study confirms that child sexual abuse is a substantial risk factor for a range of mental disorders in both childhood and adulthood . PRACTICE IMPLICATION S Those treating victims of sexual abuse must assess not only disorders commonly associated with trauma , but also low prevalence disorders such as psychosis OBJECTIVE To measure the durability of improvement in response to two alternative treatments for sexually abused children . METHOD Eighty-two sexually abused children ages 8 - 15 years old and their primary caretakers were r and omly assigned to trauma-focused cognitive-behavioral therapy ( TF-CBT ) or non-directive supportive therapy ( NST ) delivered over 12 sessions ; this study examines symptomatology during 12 months posttreatment . DATA ANALYSIS Intent-to-treat and treatment completer repeated measures analyses were conducted . RESULTS Intent-to-treat indicated significant group x time effects in favor of TF-CBT on measures of depression , anxiety , and sexual problems . Among treatment completers , the TF-CBT group evidence d significantly greater improvement in anxiety , depression , sexual problems and dissociation at the 6-month follow-up and in PTSD and dissociation at the 12-month follow-up . CONCLUSION This study provides additional support for the durability of TF-CBT effectiveness OBJECTIVE To examine the differential efficacy of trauma-focused cognitive-behavioral therapy ( TF-CBT ) and child-centered therapy for treating posttraumatic stress disorder ( PTSD ) and related emotional and behavioral problems in children who have suffered sexual abuse . METHOD Two hundred twenty-nine 8- to 14-year-old children and their primary caretakers were r and omly assigned to the above alternative treatments . These children had significant symptoms of PTSD , with 89 % meeting full DSM-IV PTSD diagnostic criteria . More than 90 % of these children had experienced traumatic events in addition to sexual abuse . RESULTS A series analyses of covariance indicated that children assigned to TF-CBT , compared to those assigned to child-centered therapy , demonstrated significantly more improvement with regard to PTSD , depression , behavior problems , shame , and abuse-related attributions . Similarly , parents assigned to TF-CBT showed greater improvement with respect to their own self-reported levels of depression , abuse-specific distress , support of the child , and effective parenting practice s. CONCLUSIONS This study adds to the growing evidence supporting the efficacy of TF-CBT with children suffering PTSD as a result of sexual abuse and suggests the efficacy of this treatment for children who have experienced multiple traumas The differential efficacies of supportive and cognitive behavioral group therapy models design ed for young children ( ages 2 to 8) who have experienced sexual abuse and their nonoffending mothers were compared . Forty-four mothers and their respective children participated in either supportive or cognitive behavioral therapy groups with the group format being r and omly determined . Repeated measures MANOVAs indicated that compared to mothers who participated in the support groups , the mothers who participated in cognitive behavioral groups reported greater reductions at posttest in ( a ) their intrusive thoughts and ( b ) their negative parental emotional reactions regarding the sexual abuse . The children treated with cognitive behavioral therapy demonstrated greater improvement in their knowledge regarding body safety skills at posttest than did the children who received supportive therapy The present study evaluated alternative treatments for children ( N = 112 , ages 7 - 13 ) referred for severe antisocial behavior . Children were r and omly assigned to one of three treatments : problem-solving skills training ( PSST ) , problem-solving skills training with in vivo practice ( PSST-P ) , which included therapeutically planned activities to extend training to setting s outside of treatment , or client-centered relationship therapy ( RT ) . PSST and PSST-P children showed significantly greater reductions in antisocial behavior and overall behavior problems , and greater increases in prosocial behavior than RT children . These effects were evident on measures obtained immediately after treatment and at a 1-year follow-up , and on measures of child performance at home and at school . PSST-P children showed greater changes than PSST children on measures of functioning at school at posttreatment , but these differences were no longer evident at follow-up . Children in both PSST conditions showed significant reductions in deviant behavior and improvements in prosocial behavior from pretreatment to follow-up , whereas RT children tended to remain at their pretreatment level of functioning . Notwithst and ing the significant improvements , comparisons with nonclinic ( normative ) sample s revealed that the majority of youth remained outside of the normal range of deviant behavior . Possible directions for improving treatment for antisocial youth are highlighted BACKGROUND Evidence is accumulating that child sexual abuse ( CSA ) is associated with many psychiatric disorders in adulthood . This paper uses the detailed information available from the 2007 Adult Psychiatric Morbidity Survey of Engl and ( APMS 2007 ) to quantify links between CSA and a range of psychiatric conditions . METHOD The prevalence of psychiatric disorder was established in a r and om sample of the English household population ( n=7403 ) , which also provided sociodemographic and experiential information . RESULTS We analyzed six types of common mental disorder , alcohol abuse and drug abuse , and people who screened positively for post-traumatic stress disorder ( PTSD ) and eating disorders . All were strongly and highly significantly associated with CSA , particularly if non-consensual sexual intercourse was involved , for which odds ratios ( ORs ) ranged from 3.7 to 12.1 . These disorders were also related to adult sexual abuse ( ASA ) , although the likelihood of reverse causality is then increased . Revictimization in adulthood was common , and increased the association of CSA with disorder . For several disorders , the relative odds were higher in females but formal tests for moderation by gender were significant only for common mental disorders and only in relation to non-consensual sexual intercourse . The population attributable fraction ( PAF ) was higher in females in all cases . CONCLUSIONS The detailed and high- quality data in APMS 2007 provided important confirmation both of the strength of association of CSA with psychiatric disorder and of its relative non-specificity . Our results have major implication s at the public health level and the individual level , in particular the need for better recognition and treatment of the sequelae of CSA In this study a psychosocial treatment for 47 Ss ( aged 9 - 13 years ) with anxiety disorders was investigated . A 16-session cognitive-behavioral treatment was compared with a wait-list condition . Outcome was evaluated using child self-report , parent report , teacher report , cognitive assessment , and behavioral observations . Pretreatment-posttreatment changes and maintenance of gains at 1-year follow-up were examined . Results revealed that many treated Ss were found to be without a diagnosis at posttest and at follow-up and to be within normal limits on many measures . The child 's perception of the Output:	Treatment as usual was , for the most part , supportive , unstructured psychotherapy . Data suggest that CBT may have a positive impact on the sequelae of child sexual abuse , but most results were not statistically significant . Strongest evidence for positive effects of CBT appears to be in reducing PTSD and anxiety symptoms , but even in these areas effects tend to be ' moderate ' at best .
MS21026	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Lenalidomide plus dexamethasone is effective in the treatment of multiple myeloma ( MM ) but is associated with an increased risk of venous thromboembolism ( VTE ) . This prospect i ve , open-label , r and omized sub study of a phase 3 trial compared the efficacy and safety of thromboprophylaxis with low-dose aspirin ( ASA ) or low-molecular-weight heparin ( LMWH ) in patients with newly diagnosed MM , treated with lenalidomide and low-dose dexamethasone induction and melphalan-prednisone-lenalidomide consolidation . Overall , 342 patients who did not have clinical indications or contraindications to antiplatelet or anticoagulant therapy were r and omly assigned to receive ASA 100 mg/d ( n = 176 ) or LMWH enoxaparin 40 mg/d ( n = 166 ) . The incidence of VTE was 2.27 % in the ASA group and 1.20 % in the LMWH group . Compared with LMWH , the absolute difference in the proportion of VTE was 1.07 % ( 95 % confidence interval , -1.69 - 3.83 ; P = .452 ) in the ASA group . Pulmonary embolism was observed in 1.70 % of patients in the ASA group and none in the LMWH group . No arterial thrombosis , acute cardiovascular events , or sudden deaths were reported . No major hemorrhagic complications were reported . In previously untreated patients with MM receiving lenalidomide with a low thromboembolic risk , ASA could be an effective and less-expensive alternative to LMWH thromboprophylaxis Summary : A r and omized controlled trial was undertaken comparing the efficacy and safety of low molecular weight ( LMW ) heparin ( Fragmin ) with sodium heparin for prophylaxis against postoperative thromboembolic disease after major gynaecological surgery . Women were r and omized to receive subcutaneous injections of 5,000 U of either once daily LMW heparin or twice daily sodium heparin . A total of 566 women were recruited , of whom 552 completed the study . Most women ( 461 ) had malignant disease and 430 of these underwent radical surgery . The remainder underwent major , but not radical surgery . There were 5 thromboembolic events in the LMW heparin group and 2 in the sodium heparin group , with no significant difference between these groups . No significant difference was found in the incidence of intraoperative or postoperative transfusion in the 2 groups . The decision of which heparin to use in routine practice can not be made on clinical grounds PURPOSE Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism . There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment . Furthermore , the incidence of such events in these patients is dependent on the achieved International Normalized Ratio ( INR ) . The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR . PATIENTS AND METHODS In a retrospective analysis , the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy . Eligible patients participated in two multicenter , r and omized clinical trials on the initial treatment of venous thromboembolism . Patients were initially treated with heparin ( st and ard or low-molecular weight ) . Treatment with vitamin K antagonists was started within 1 day and continued for 3 months , with a target INR of 2.0 to 3.0 . RESULTS In 1,303 eligible patients ( 264 with malignancy ) , 35 recurrences and 12 bleeds occurred . Patients with malignancy , compared with nonmalignant patients , had a clinical ly and statistically significantly increased overall incidence of recurrence ( 27.1 v 9.0 , respectively , per 100 patient-years ) as well as bleeding ( 13.3 v 2.1 , respectively , per 100 patient-years ) . In both groups of patients , the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0 . CONCLUSION Although adequately dosed vitamin K antagonists are effective in patients with malignant disease , the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy Background Advanced pancreatic cancer ( APC ) , beside its high mortality , causes the highest rates of venous thromboembolic events ( VTE ) . Enoxaparin , a low molecular weight heparin ( LMWH ) , is effective in prevention and treatment of VTE . Some small studies indicated that this benefit might extend to patients with cancer and probably prolong survival due to independent mechanisms . We initiated this safety investigation to get feasibility information on intensified chemotherapy combined with LMWH in out patients with APC treated in 1st line . Methods The trial was a prospect i ve , open-label , single center investigation in out patients with inoperable pancreatic cancer who were treated with intensified first-line chemotherapy along with concomitant application of subcutaneous LMWH . The combined chemotherapy consisted of gemcitabine 1 g/m2 ( 30 min ) , 5-FU 750 mg/m2 ( 24 h ) , folinic acid 200 mg/m2 ( 30 min ) , and Cisplatin 30 mg/m2 ( 90 min ) on day 1 and 8 ; q3w for the first 12 weeks ( GFFC ) followed by gemcitabine alone in patients without cancer progression . The simultaneous application of prophylactic enoxaparin started on day 1 of chemotherapy with a fixed dose of 40 mg daily . Statistical analyses were performed using R 3.01 with software package CMPRSK and SPSS software v19.0 . Results The investigation was stopped after recruitment of 19 patients . At this time 15 patients had completed the required 12 weeks of treatment . Based on 71 cycles of GFFC + enoxaparin ( median 4/pt [ range : 2–4 ] ) and 108 cycles of single-agent gemcitabine + enoxaparin ( median 4/pt [ range : 0–18 ] ) the cumulative frequency of NCI-CTC toxicities grade 3/4 was below 10 % . One case ( 5 % ) of a symptomatic non-lethal thromboembolic event was observed while receiving LMWH treatment . No severe bleeding event as defined in the protocol has been observed . The median overall survival was 10.05 [ 95 % CI : 8.67 - 18.14 ] months . Conclusions The addition of enoxaparin to GFFC chemotherapy is feasible , safe and does not appear to affect the efficacy or the toxicity profile of the chemotherapy regimen in patients with advanced pancreatic adenocarcinoma . Based on these findings we have initiated the r and omized CONKO-004 trial to examine whether enoxaparin reduces the incidence of thromboembolic events or increases overall outcome .Trial registration Clinical Trials NCT01945879 BACKGROUND Patients with acute proximal deep-vein thrombosis are usually treated first in the hospital with intravenous st and ard ( unfractionated ) heparin . However , the longer plasma half-life , better bioavailability after subcutaneous administration , and more predictable anticoagulant response of low-molecular-weight heparins make them attractive for possible home use . We compared these two approaches . METHODS Patients with acute proximal deep-vein thrombosis were r and omly assigned to receive either intravenous st and ard heparin in the hospital ( 253 patients ) or low-molecular-weight heparin ( 1 mg of enoxaparin per kilogram of body weight subcutaneously twice daily ) administered primarily at home ( 247 patients ) . The study design allowed out patients taking low-molecular-weight heparin to go home immediately and hospitalized patients taking low-molecular-weight heparin to be discharged early . All the patients received warfarin starting on the second day . RESULTS Thirteen of the 247 patients receiving low-molecular-weight heparin ( 5.3 percent ) had recurrent thromboembolism , as compared with 17 of the 253 patients receiving st and ard heparin ( 6.7 percent ; P=0.57 ; absolute difference , 1.4 percentage points ; 95 percent confidence interval , -3.0 to 5.7 ) . Five patients receiving low-molecular-weight heparin had major bleeding , as compared with three patients receiving st and ard heparin . After r and omization , the patients who received low-molecular-weight heparin spent a mean of 1.1 days in the hospital , as compared with 6.5 days for the st and ard-heparin group ; 120 patients in the low-molecular-weight- heparin group did not need to be hospitalized at all . CONCLUSIONS Low-molecular-weight heparin can be used safely and effectively to treat patients with proximal deep-vein thrombosis at home Background Advanced pancreatic cancer , in addition to its high mortality , is characterized by one of the highest rates of venous thromboembolic events ( VTE ) as compared to other types of cancer . Enoxaparin , a low molecular weight heparin ( LMWH ) , has proven to be effective for the prevention and treatment of VTE in surgical and general medical patients . Results of some small studies suggest that this benefit might extend to patients with cancer , however , enoxaparin is not currently indicated for this use . This phase IIb study was design ed to analyze the efficacy of enoxaparin in patients with locally advanced or metastatic pancreatic cancer undergoing systemic chemotherapy . Methods The aim of this prospect i ve multicenter trial is to compare concomitant treatment with enoxaparin to no anticoagulation in 540 patients . Primary endpoint is the incidence of clinical ly relevant VTE ( symptomatic deep venous thrombosis ( DVT ) of the leg and /or pelvic and /or pulmonary embolism ( PE ) ) within the first 3 months . Secondary endpoints include the incidence of symptomatic and asymptomatic VTE after 6 , 9 and 12 months as well as remission at 3 , 6 , 9 and 12 months , overall survival and bleeding . Trial registration : is rct n.org identifier CCT-NAPN-16752 , controlled-trials.com identifier : IS RCT N02140505 . Results An interim analysis for safety performed after inclusion of 152 patients revealed no increased risk of bleeding ( 5 pts vs. 6 pts , Chi2 : 0.763 ) . Conclusion PROSPECT is a pivotal study in elucidating the role of low molecular weight heparins in advanced pancreatic cancer . Its results will lead to a new underst and ing of the role of heparins in the prevention of venous thromboembolism and of their effect on survival , remission rates and toxicity of chemotherapeutic regimens Subcutaneous body weight-adjusted low molecular weight heparin ( LMWH ) has been proven as effective and safe as intravenous aPTT-adjusted unfractionated heparin ( UFH ) for the treatment of patients with acute deep venous thrombosis ( DVT ) . In this study we evaluate the efficacy of the initial treatment of proximal DVT with a fixed-dose , body weight-independent application of the LMWH Certoparin with a six month follow-up . In a prospect i ve , multicentre , r and omized , active-controlled study 1220 patients with objective ly diagnosed proximal DVT were r and omly assigned to subcutaneous 8000 U anti-factor Xa of Certoparin twice daily for 10 to 14 days or intravenous aPTT-adjusted UFH for 5 to 8 days . Both regimen were followed by oral anticoagulation for 6 months . The primary end point was the rate of symptomatic and objective ly confirmed thromboembolic events within 6 months . The aim of the study was to demonstrate the non-inferiority of the Certoparin regimen as compared to UFH . The per- protocol analysis revealed 22 ( 3.8 % ) thromboembolic events in the Certoparin group and 24 ( 4.3 % ) in patients assigned to UFH within 6 months , thereby proving the non-inferiority ( p<0.01 ) , confirmed by intent-to-treat analysis ( p<0.001 ) . Major bleeding occurred in 6 and 7 patients started on Certoparin or UFH during the treatment period . Thromboembolic events were equally distributed in body weight categories with < 50 , 50 - 80 and > 80 kg as followed : 0 , 3.6 % and 4.1 % of patients for the Certoparin group and 0 , 4.6 % and 4.2 % of patients for the UFH group . The same was true for major bleeding complications with 0 , 2.9 % and 1.5 % for Certoparin and 0 , 3.5 % and 4.2 % for UFH . Overall mortality was 1.9 % in the Certoparin group and 2.7 % in the UFH group . Fixed-dose body weight-independent subcutaneous LMWH Certoparin is at least as efficacious and safe as intravenous aPTT-adjusted UFH for the Output:	LMWH is possibly superior to UFH in the initial treatment of VTE in people with cancer .
MS21027	*TASK* the task is to summarize an input biomedical literature in six sentences *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 contention that the R2 radical gastrectomy for localized and potentially curable gastric carcinoma may be superior to gastrectomy without lymphadenectomy ( R1 ) was assessed by r and omized trial . Five years after commencement 403 patients have been evaluated at surgery and only 43 ( 11 per cent ) found eligible ( S0–2 , P0 , H0 , N0–1 ) , 22 of whom underwent R1 and 21 R2 gastrectomy . Seven patients had final histological stages in excess of the protocol . The R2 group had a longer operating time ( P<0.005 ) , a greater blood transfusion requirement ( P<0.005 ) , a longer hospital stay ( 0.05>P>0.025 ) and required reoperation in four cases . There were no postoperative deaths . Four patients have died from the disease in the R1 group and five in the R2 group , there being no difference in the probability of survival at a median follow‐up of 3.1 years . The small proportion of patients suitable for radical R2 surgery , the high associated morbidity and the fact that survival advantage has yet to be proven in trial suggest that this procedure should not yet be performed outside of controlled clinical trials BACKGROUND The aim of this trial was to compare multimodal optimization with conventional perioperative management in a consecutive series of patients undergoing gastrectomy procedures . METHODS According to r and omized controlled studies and conclusions made by meta-analyses in colorectal surgery , optimized perioperative measures were design ed and applied in gastrectomy surgery . Thirty-three patients were r and omized to the optimized group and 30 patients to a control group . Two groups were treated in 1 center by a single surgical team in different wards . Both groups used patient-controlled intravenous analgesia for postoperative analgesia . The primary end point was length of postoperative hospital stay . Secondary outcomes included bowel function recovery after surgery , perioperative changes of inflammatory factors , glucocorticoid , insulin resistance , and body composition . Perioperative complications and adverse events were also recorded . RESULTS The groups were similar in terms of age , sex ratio , and Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity ( POSSUM score ) . The optimized group was associated with a significantly shorter postoperative hospital stay compared with the conventional care group ( P < .001 ) . Duration s of urinary catheterization and abdominal drainage were also less ( P < .001 ) . The diet program in the optimization group was well tolerated and was associated with an earlier recovery of gut function ( P < .001 ) . Proinflammatory factors were less elevated and body composition was more stable in the optimized group than in controls . There were no differences in morbidity or mortality between the groups . CONCLUSIONS Optimization of care in gastrectomy can shorten postoperative hospital stay and provides multiple beneficial outcomes , including hastening the return of gut function , without increasing morbidity Background Fast-track surgery has been shown to enhance postoperative recovery in several surgical fields . This study aim ed to evaluate the safety and efficacy of fast-track surgery in laparoscopic distal gastrectomy . Methods The present study was design ed as a single-center , r and omized , unblinded , parallel-group trial . Patients were eligible if they had gastric cancer for which laparoscopic distal gastrectomy was indicated . The fast-track surgery protocol included intensive preoperative education , a short duration of fasting , a preoperative carbohydrate load , early postoperative ambulation , early feeding , and sufficient pain control using local anesthetics perfused via a local anesthesia pump device , with limited use of opioids . The primary endpoint was the duration of possible and actual postoperative hospital stay . Results We r and omized 47 patients into a fast-track group ( n = 22 ) and a conventional pathway group ( n = 22 ) , with three patients withdrawn . The possible and actual postoperative hospital stays were shorter in the fast-track group than in the conventional group ( 4.68 ± 0.65 vs. 7.05 ± 0.65 ; P < 0.001 and 5.36 ± 1.46 vs. 7.95 ± 1.98 ; P < 0.001 ) . The time to first flatus and pain intensity were not different between groups ; however , a greater frequency of additional pain control was needed in the conventional group ( 3.64 ± 3.66 vs. 1.64 ± 1.33 ; P = 0.023 ) . The fast-track group was superior to the conventional group in several factors of the European Organization for Research and Treatment of Cancer Quality of Life Question naire , including : fatigue , appetite loss , financial problems , and anxiety . The complication and readmission rates were similar between groups . Conclusions Fast-track surgery could enhance postoperative recovery , improve immediate postoperative quality of life , and be safely applied in laparoscopic distal gastrectomy UNLABELLED In traditional practice patterns , physicians take care of all clinical decisions , such as diagnosis , treatment , and recovery . In the Nippon Medical School Hospital a clinical pathway for distal gastrectomy patients , recorded as a post-operative care map , was introduced in August 2000 . In January 2001 the post-operative management was analyzed and st and ardization of practice was carried out with printed order sets , such as drugs and infusion solutions . The aim of this study was to evaluate the clinical significance of the clinical pathway for gastrectomy patients by employing st and ardized postoperative management and printed order sets . PATIENTS AND METHODS From January 2001 to December 2001 , 87 patients underwent distal ( 43 ) , total ( 28 ) , proximal ( 7 ) and partial gastrectomy ( 9 ) for gastric cancer ( stage IA : 47 , IB : 9 , II : 7 , IIIA : 8 , IIIB 2 , IV : 10 ) and gastrointestinal stromal tumor ( 4 ) . These patients were r and omly assigned to either the main building or the east building of our hospital . In the main building 38 patients were looked after using traditional practice ( control group ) . In the east building 47 patients were looked after according to the clinical pathway ( path group ) and 2 patients were excluded from the path group because of neo-adjuvant chemotherapy and severe heart failure . Aspects of the patients ' outcomes , including length of stay , the first day of the diet , morbidity , and medical costs , were compared between the path group and the control group . All data were expressed as means+/-st and ard deviation . Statistical analyses were made using Student t-test , Mann-Whitney U-test , and chi(2 ) test , and the 5%level was chosen for statistical significance . RESULTS The length of the hospital stay was 27.1+/-10.0 and 40.8+/-26.1 days ( p<0.005 ) and the length of post-operative stay was 18.1+/-9.5 and 28.2+/-22.3 days ( p<0.01 ) in the path group and the control group , respectively . The post-operative day when the diet was started for the path and control groups was 6.8+/-8.9 and 8.2+/-7.2 , respectively ; however , the length of the intravenous infusion for the two groups was 11.8+/-1.1 and 16.5+/-1.2 days ( p<0.01 ) , respectively . There was no statistically significant difference in the morbidity rate between the path group ( 3/47 ) and the control group ( 5/38 ) . The total cost was 1,502,587 yen + /-41,650 in the path group and 1,932,197 yen + /-131,030 in the control ( p<0.001 ) . CONCLUSION A clinical pathway for gastrectomy patients proved useful to optimize their postoperative care , including medication management and diet education . It is suggested that the implementation of a st and ardized clinical pathway for gastrectomy patients reduced the length of the hospital stay and the medical costs Background Fast-track surgery is a new , promising comprehensive program for surgical patients and is beneficial to recovery . Prospect i ve r and omized , controlled clinical trials involving fast-track surgery for gastric cancer are lacking . Patient and methods Ninety-two patients with gastric cancer were r and omly divided into a fast-track surgery group ( n = 45 ) and conventional surgery group ( n = 47 ) . We compared outcomes ( duration of postoperative stay in hospital , fever , and flatus , complications , and medical costs ) ; postoperative serum levels of tumor necrosis factor-α , interleukin-6 , and C-reactive protein ; and resting energy expenditure between two groups . Results Compared with the conventional surgery group , the fast-track surgery group had no more complications ( P > 0.05 ) with a significantly shorter duration of fever , flatus , and hospital stay , and less medical costs as well as a higher quality of life score on hospital discharge ( all P < 0.05 ) . With a significantly lower resting energy expenditure ( days 1 and 3 ) postoperatively ( P < 0.05 ) , the fast-track surgery group showed a lower serum level of tumor necrosis factor-α ( days 1 and 3 ) , interleukin-6 ( days 1 and 3 ) , and C-reactive protein ( days 1 , 3 , and 7 ) than the conventional surgery group ( all P < 0.05 ) . Conclusions Fast-track surgery can lessen postoperative stress reactions and accelerate rehabilitation for patients with gastric cancer Objective The aim of this study was to evaluate the safety and effectiveness of fast-track surgery combined with laparoscopy-assisted radical distal gastrectomy for gastric cancer . Methods Eighty-eight eligible patients were r and omly assigned into four groups : ( 1 ) fast-track surgery ( FTS ) + laparoscopy-assisted radical distal gastrectomy ( LADG ) , treated with LADG and FTS treatment ; ( 2 ) LADG , treated with LADG and traditional treatment ; ( 3 ) FTS + open distal grastectomy ( ODG ) , treated with ODG and FTS treatment ; and ( 4 ) ODG , treated with ODG and traditional treatment . The clinical parameters and serum indicators were compared . Results Compared with the ODG group , the other three groups had earlier first flatus and shorter postoperative hospital stay ( all P < 0.01 ; all P < 0.05 ) , especially in the FTS + LADG group . The level of ALB was higher in the FTS + LADG group than in the LADG group at 4 and 7 days after surgery ( P < 0.05 , P < 0.01 ) . The level of CRP in the FTS + LADG group was lower than in the FTS+ODG group at 4 and 7 days after surgery ( P < 0.05 , P < 0.05 ) . The FTS + ODG group had lowest medical costs . Conclusion Combination of FTS and LADG in gastric cancer is safe , feasible , and efficient and can improve nutritional status , lessen postoperative stress , and accelerate postoperative rehabilitation . Compared with FTS + ODG and LADG , its advantages were limited in short-term follow-up OBJECTIVE To investigate the safety and efficacy of fast track surgery ( FTS ) management in gastric cancer undergoing D2 gastrectomy . METHODS Eighty gastric cancer patients undergoing D2 gastrectomy were recruited prospect ively . Patients were assigned to receive FTS management ( n = 40 ) or conventional perioperative care ( n = 40 ) . The FTS care included shorten preoperative fasting time , no nasogastric decompressing tubes and abdominal drainage placed , early postoperative oral feeding , multimodal analgesia , and early mobilisation . The length of postoperative hospital stay , medical cost , nutritional status , gut function , and postoperative complications in the two groups were recorded and compared . RESULTS FTS group was associated with a significantly shorter postoperative hospital stay compared with conventional care group [ ( 5.6 + /- 1.3 ) d vs. ( 9.4 + /- 1.9 ) d , P < 0.05 ] . Medical cost was less [ ( 18 620 + /- 2360 ) Yuan vs. ( 20 370 + /- 2440 ) Yuan , P < 0.05 ] and duration of intravenous infusion [ ( 3.5 + /- 1.4 ) d vs. ( 5.8 + /- 1.9 ) d , P < 0.05 ] was also shorter . First passage of flatus was earlier in FTS group than in conventional care group [ ( 4.3 + /- 0.4 ) d vs. ( 5.5 + /- 0.9 ) d , P < 0.05 ] . Loss of body weight in the postoperative period was less in FTS group [ ( 3.2 + /- 0.8 ) kg vs. ( 4.3 + /- 1.6 ) kg , P < 0.05 ] . There was no difference in morbidity or mortality between the two groups . CONCLUSION FTS in D2 gastrectomy is safe and efficient , and it can shorten postoperative hospital stay and hasten return of gut function PURPOSE Patients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy , although fewer than 50 % could receive postoperative chemotherapy . We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines . P Output:	From this review the authors concluded that multimodal , st and ardized perioperative gastrectomy care appears feasible , safe and cost effective
MS21028	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective To evaluate the potential clinical , metabolic , and economic advantages of enteral nutrition over total parenteral nutrition . Design Prospect i ve , r and omized clinical trial . Setting Department of surgery in a university hospital . Patients Two hundred and fifty-seven patients with cancer of the stomach ( n = 121 ) , pancreas ( n = 110 ) , or esophagus ( n = 26 ) were r and omized to receive postoperative total parenteral nutrition ( TPN group , n = 131 ) or early enteral nutrition ( EEN group , n = 126 ) . The nutritional goal was 25 kcal/kg/day . The two nutritional formulas were isocaloric and isonitrogenous , and they were continued until oral intake was at least 800 kcal/day . Measurements Morbidity , mortality , length of hospital stay , and treatment costs were evaluated in all patients . In 40 consecutive patients , selected nutritional , immunologic and inflammatory variables were studied . Moreover , intestinal oxygen tension was evaluated by micropolarographic implantable probes . Main Results The nutritional goal was reached in 100/126 ( 79.3 % ) patients in the EEN group and in 128/131 ( 97.7 % ) patients in the TPN group ( p < .001 ) . In the EEN group , hyperglycemia ( serum glucose , > 200 mg/dL ) was observed in 4.7 % of the patients vs. 9.1 % in the TPN group ( p = NS ) . Alteration of serum electrolyte levels was 3.9 % in the EEN group vs. 13.7 % in the TPN group ( p < .01 ) . No significant difference was found in nutritional , immunologic , and inflammatory variables between the two groups . The overall complication rate was similar ( 40.4 % for TPN vs. 35.7 % , for EEN;p = .52 ) . No difference was detected for either infectious or noninfectious complications , length of hospital stay , and mortality . From postoperative day 5 , intestinal oxygen tension recovered faster in the EEN group than in the TPN group ( 43 ± 5 mm Hg vs. 31 ± 4 mm Hg at day 7;p < .001 ) . EEN was four-fold less expensive than TPN ( $ 25 vs. $ 90.60/day , respectively ) . Conclusion EEN represents a rational alternative to TPN in patients who undergo upper gastrointestinal tract surgery for cancer and who clinical ly require postoperative artificial nutrition Glutamine has been demonstrated to be an important source of fuel for the gut . The purpose of this study was to evaluate the effect of glutamine-supplemented hyperalimentation on gut immune function . Thirty-six female Fischer rats were r and omized into three groups : group 1 ( chow ) was fed rat chow and water ad libitum , group 2 ( total parenteral nutrition ) received a st and ard hyperalimentation formula , and group 3 ( total parenteral nutrition-glutamine ) received a hyperalimentation solution that contained 2 % glutamine . Animals were maintained on their respective diets for 2 weeks and then killed . Mesenteric lymph nodes were harvested for culture , bile was assayed for secretory IgA , and bowel was excised to assay bacterial adherence . Results indicated that glutamine-supplemented total parenteral nutrition protects against bacterial translocation from the gut seen with st and ard formulas . This effect may be mediated by the secretory IgA immune system We investigated the impact of early enteral nutrition ( EEN ) and parenteral nutrition ( PN ) on prealbumin ( PA ) and high-sensitivity C-reactive protein ( hs-CRP ) in patients after gastric cancer surgery . Sixty-eight selected patients undergoing gastric cancer surgery were r and omly divided into the EEN ( N = 34 ) and PN ( N = 34 ) groups . Body weight ( BW ) , serum albumin ( ALB ) , transferrin ( TF ) , PA , hs-CRP , length of hospital stay , cost of postoperative nutritional support , and incidence of complications were compared between groups . On postoperative day 7 , the BW , TF , ALB , and PA for both groups were significantly decreased compared with the values obtained on preoperative day 1 ( P < 0.01 ) . A significant decrease was observed in TF and PA in the PN group compared with the EEN group ( P < 0.01 ) . There was no significant difference in BW and ALB between the two groups ( P > 0.05 ) . The hs-CRP level of both groups was significantly higher than on preoperative day 1 . There was a significant increase in hs-CRP in the PN group compared with the EEN group ( P < 0.01 ) . The anal exhaust time , length of hospital stay , and nutritional support cost were significantly shorter or lower in the EEN group than in the PN group ( P < 0.01 ) . There was no significant difference in the incidence of complications between the two groups ( P > 0.05 ) . EEN helps regulate the postoperative response of patients after gastric cancer surgery , promotes rehabilitation , and accelerates the recovery of gastrointestinal function . Furthermore , EEN has the advantage of being inexpensive The benefits of early enteral feeding ( EEN ) have been demonstrated in gastrointestinal surgery . But , the impact of EEN has not been eluci date d yet . We assessed the postoperative nutritional status of patients who had undergone pancreaticoduodenectomy ( PD ) according to the postoperative nutritional method and compared the clinical outcomes of two methods . A prospect i ve r and omized trial was undertaken following PD . Patients were r and omly divided into two groups ; the EEN group received the postoperative enteral feed and the control group received the postoperative total parenteral nutrition ( TPN ) management . Thirty-eight patients were included in our analyses . The first day of bowel movement and time to take a normal soft diet was significantly shorter in EEN group than in TPN group . Prealbumin and transferrin were significantly reduced on post-operative day ( POD ) 7 and were slowly recovered until POD 90 in the TPN group than in the EEN group . EEN group rapidly recovered weight after POD 21 whereas it was gradually decreased in TPN group until POD 90 . EEN after PD is associated with preservation of weight compared with TPN and impact on recovery of digestive function after PD AIM To investigate the potential role of perioperative nutrition in reducing complications and mortality in malnourished gastrointestinal cancer patients . METHODS Four hundred and sixty-eight elective moderately or severely malnourished surgical patients with gastric or colorectal cancers defined by the subjective global assessment ( SGA ) were r and omly assigned to 7 d preoperative and 7 d postoperative parenteral or enteral nutrition vs a simple control group . The nutrition regimen included 24.6+/-5.2 kcal /kg per d non-protein and 0.23+/-0.04 g nitrogen /kg per d. Control patients did not receive preoperative nutrition but received 600+/-100 kcal non-protein plus or not plus 62+/-16 g crystalline amino acids postoperatively . RESULTS Complications occurred in 18.3 % of the patients receiving nutrition and in 33.5 % of the control patients ( P=0.012 ) . Fourteen patients died in the control group and 5 in those receiving nutrition . There were significant differences in the mortality between the two groups ( 2.1 % vs 6.0 % , P=0.003 ) . The total length of hospitalization and postoperative stay of control patients were significantly longer ( 29 vs 22 d , P=0.014 ) than those of the studied patients ( 23 vs 12 d , P=0.000 ) . CONCLUSION Perioperative nutrition support is beneficial for moderately or severely malnourished gastrointestinal cancer patients and can reduce surgical complications and mortality BACKGROUND Enteral nutrition ( EN ) is now used more frequently than total parenteral nutrition ( TPN ) for nutritional support after resection for esophageal cancer . But consensus regarding which type of nutrition should be used does not exist . We studied the effect of TPN and EN on patients ' nutritional status and immune function in the immediate postoperative period after esophageal cancer resection . METHODS We enrolled 30 patients ( 27 men and 3 women ) who underwent subtotal esophagectomy . The patients were r and omly assigned to TPN or EN group . Either TPN or EN was begun on postoperative day 1 . On postoperative days 1 , 3 , and 7 , three endpoints were measured : albumin , C-reactive protein , and Th1/Th2 balance . RESULTS All patients completed the study . Anastomotic leaks occurred in 6 patients in the TPN group and 7 patients in the EN group . Albumin , Th1/Th2 balance , and C-reactive protein did not differ between the groups . Th1/Th2 balance was not different regardless of the preoperative treatment or complications . CONCLUSIONS No differences in immune function , nutritional state , or inflammatory response were seen between patients supported with TPN and those supported with EN . The results of our study suggest that perioperative nutritional support can be safely performed either with TPN or EN BACKGROUND Although current opinion favours the use of enteral over parenteral nutrition , the clinical benefits of early postoperative nutrition in patients undergoing elective surgery have never been clearly shown . We aim ed to test the hypothesis that postoperative enteral nutrition is better ( fewer postoperative complications ) than parenteral nutrition containing similar energy and nitrogen amounts ( 112 kJ kg(-1 ) day(-1 ) and 1.4 g aminoacid kg(-1 ) day(-1 ) ) . METHODS We did a r and omised multicentre clinical trial in patients with gastrointestinal cancer who were malnourished and c and i date s for major elective surgery . 159 patients were assigned to enteral nutrition and 158 to parenteral nutrition . The primary endpoint was the occurrence of postoperative complications , and secondary endpoints were length of postoperative hospital stay , adverse effects , and treatment crossover . Analysis was by intention to treat . FINDINGS Postoperative complications occurred in 54 ( 34 % ) patients fed enterally versus 78 ( 49 % ) fed parenterally ( relative risk 0.69 , 95 % CI 0.53 - 0.90 , p=0.005 ) . Length of postoperative stay was 13.4 days and 15.0 days in the enteral nutrition and parenteral nutrition groups , respectively ( p=0.009 ) . Adverse effects occurred in 56 ( 35 % ) patients fed enterally versus 22 ( 14 % ) patients fed parenterally ( 2.50 , 1.61 - 3.86 , p<0.0001 ) . 14 ( 9 % ) patients on enteral nutrition had to switch to parenteral nutrition , whereas none of those fed parenterally crossed over to enteral feeding . INTERPRETATION We conclude that early enteral nutrition significantly reduces the complication rate and duration of postoperative stay compared with parenteral nutrition , although parenteral nutrition is better tolerated than enteral nutrition OBJECTIVE To investigate the potential benefits of postoperative nutrition in malnourished patients with gastrointestinal cancer . METHODS A total of 646 malnourished patients with gastrointestinal cancer defined by the subjective global assessment ( SGA ) were r and omly divided into parenteral nutrition group ( n=215 ) , enteral nutrition group ( n=215 ) and conventional group ( n=216 ) . Two nutritional regimens were design ed to be isocaloric 125.5 kJ(30 kcal).kg(-1).d(-1 ) and isonitrogenous 0.25 g.kg(-1).d(-1 ) for 7 postoperative days . Conventional group did not receive artificial nutrition before and after surgery . Postoperative complications , mortality and postoperative length of hospital stay were compared . RESULTS All baseline and surgical characteristics were comparable among 3 groups . Overall postoperative mortality was 1.5 % , and no difference was observed among 3 groups . Postoperative complications occurred in 61(28.4 % ) patients in enteral nutrition group , 72(33.5 % ) in parenteral nutrition group , and 97 ( 44.9 % ) in conventional group ( P=0.000 vs enteral nutrition group ; P=0.001 vs parenteral nutrition group ) . Postoperative length of hospital stay was ( 9.8+/-3.4 ) d in enteral nutrition group , ( 11.2+/-5.0 ) d in parenteral nutrition group , and ( 14.5+/-7.1 ) d in conventional group ( P=0.001 vs enteral nutrition group ; P=0.003 vs parenteral nutrition group ) . CONCLUSIONS Postoperative artificial nutrition support is beneficial to the malnourished patients with gastrointestinal cancer , which improves postoperative outcome . Early enteral nutrition significantly reduces the infectious complication rate and length of postoperative hospital stay as compared with parenteral nutrition Background Each year approximately 3000 patients in the United Kingdom undergo surgery for esophagogastric cancer . Jejunostomy feeding tubes , placed at the time of surgery for early postoperative nutrition , have been shown to have a positive impact on clinical out Output:	EN after major abdominal surgery provided better outcomes compared with TPN in patients with gastrointestinal cancer
MS21029	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND OBJECTIVE : Most clinic-based weight control treatments for youth have been design ed for preadolescent children by using family-based care . However , as adolescents become more autonomous and less motivated by parental influence , this strategy may be less appropriate . This study evaluated a primary care – based , multicomponent lifestyle intervention specifically tailored for overweight adolescent females . METHODS : Adolescent girls ( N = 208 ) 12 to 17 years of age ( mean ± SD : 14.1 ± 1.4 years ) , with a mean ± SD BMI percentile of 97.09 ± 2.27 , were assigned r and omly to the intervention or usual care control group . The gender and developmentally tailored intervention included a focus on adoptable healthy lifestyle behaviors and was reinforced by ongoing feedback from the teen ’s primary care physician . Of those r and omized , 195 ( 94 % ) completed the 6-month posttreatment assessment , and 173 ( 83 % ) completed the 12-month follow-up . The primary outcome was reduction in BMI z score . RESULTS : The decrease in BMI z score over time was significantly greater for intervention participants compared with usual care participants ( −0.15 in BMI z score among intervention participants compared with −0.08 among usual care participants ; P = .012 ) . The 2 groups did not differ in secondary metabolic or psychosocial outcomes . Compared with usual care , intervention participants reported less reduction in frequency of family meals and less fast-food intake . CONCLUSIONS : A 5-month , medium-intensity , primary care – based , multicomponent behavioral intervention was associated with significant and sustained decreases in BMI z scores among obese adolescent girls compared with those receiving usual care CONTEXT The prevalence of overweight and obesity in children and adolescents is increasing rapidly . In this population , behavioral therapy alone has had limited success in providing meaningful , sustained weight reduction , and pharmacological treatment has not been extensively studied . OBJECTIVE To determine the efficacy and safety of orlistat in weight management of adolescents . DESIGN , SETTING , AND PATIENTS Multicenter , 54-week ( August 2000-October 2002 ) , r and omized , double-blind study of 539 obese adolescents ( aged 12 - 16 years ; body mass index [ BMI ] > or=2 units above the 95th percentile ) at 32 centers in the United States and Canada . INTERVENTIONS A 120-mg dose of orlistat ( n = 357 ) or placebo ( n = 182 ) 3 times daily for 1 year , plus a mildly hypocaloric diet ( 30 % fat calories ) , exercise , and behavioral therapy . MAIN OUTCOME MEASURES Change in BMI ; secondary measures included changes in waist and hip circumference , weight loss , lipid measurements , and glucose and insulin responses to oral glucose challenge . RESULTS There was a decrease in BMI in both treatment groups up to week 12 , thereafter stabilizing with orlistat but increasing beyond baseline with placebo . At the end of the study , BMI had decreased by 0.55 with orlistat but increased by 0.31 with placebo ( P = .001 ) . Compared with 15.7 % of the placebo group , 26.5 % of participants taking orlistat had a 5 % or higher decrease in BMI ( P = .005 ) ; 4.5 % and 13.3 % , respectively , had a 10 % or higher decrease in BMI ( P = .002 ) . At study end , weight had increased 0.53 kg with orlistat and 3.14 kg with placebo ( P<.001 ) . Dual-energy x-ray absorptiometry showed that this difference was explained by changes in fat mass . Waist circumference decreased in the orlistat group but increased in the placebo group ( -1.33 cm vs + 0.12 cm ; P<.05 ) . Generally mild to moderate gastrointestinal tract adverse events occurred in 9 % to 50 % of the orlistat group and in 1 % to 13 % of the placebo group . CONCLUSIONS In combination with diet , exercise , and behavioral modification , orlistat statistically significantly improved weight management in obese adolescents compared with placebo . The use of orlistat for 1 year in this adolescent population did not raise major safety issues although gastrointestinal adverse events were more common in the orlistat group BACKGROUND Sedentary activities such as video gaming are independently associated with obesity . Active video games , in which players physically interact with images on screen , may help increase physical activity and improve body composition . OBJECTIVE The aim of this study was to evaluate the effect of active video games over a 6-mo period on weight , body composition , physical activity , and physical fitness . DESIGN We conducted a 2-arm , parallel , r and omized controlled trial in Auckl and , New Zeal and . A total of 322 overweight and obese children aged 10 - 14 y , who were current users of sedentary video games , were r and omly assigned at a 1:1 ratio to receive either an active video game up grade package ( intervention , n = 160 ) or to have no change ( control group , n = 162 ) . The primary outcome was the change from baseline in body mass index ( BMI ; in kg/m(2 ) ) . Secondary outcomes were changes in percentage body fat , physical activity , cardiorespiratory fitness , video game play , and food snacking . RESULTS At 24 wk , the treatment effect on BMI ( -0.24 ; 95 % CI : -0.44 , -0.05 ; P = 0.02 ) favored the intervention group . The change ( ±SE ) in BMI from baseline increased in the control group ( 0.34 ± 0.08 ) but remained the same in the intervention group ( 0.09 ± 0.08 ) . There was also evidence of a reduction in body fat in the intervention group ( -0.83 % ; 95 % CI : -1.54 % , -0.12 % ; P = 0.02 ) . The change in daily time spent playing active video games at 24 wk increased ( 10.03 min ; 95 % CI : 6.26 , 13.81 min ; P < 0.0001 ) with the intervention accompanied by a reduction in the change in daily time spent playing nonactive video games ( -9.39 min ; 95 % CI : -19.38 , 0.59 min ; P = 0.06 ) . CONCLUSION An active video game intervention has a small but definite effect on BMI and body composition in overweight and obese children . This trial was registered in the Australian New Zeal and Clinical Trials Registry at http://www.anzctr.org.au/ as ACTRN12607000632493 BACKGROUND Conjugated linoleic acid ( CLA ) is a supplemental dietary fatty acid that decreases fat mass accretion in young animals . OBJECTIVE The aim of this study was to determine CLA 's efficacy with regard to change in fat and body mass index ( BMI ; in kg/m(2 ) ) in children . DESIGN We conducted a 7 + /- 0.5-mo r and omized , double-blind , placebo-controlled trial of CLA in 62 prepubertal children aged 6 - 10 y who were overweight or obese but otherwise healthy . The subjects were r and omly assigned to receive 3 g/d of 80 % CLA ( 50:50 cis-9,trans-11 and trans-10,cis-12 isomers ) or placebo in chocolate milk . RESULTS Fifty-three subjects completed the trial ( n = 28 in the CLA group , n = 25 in the placebo group ) . CLA attenuated the increase in BMI ( 0.5 + /- 0.8 ) compared with placebo ( 1.1 + /- 1.1 ) ( P = 0.05 ) . The percentage change in body fat measured by dual-energy X-ray absorptiometry was smaller ( P = 0.001 ) in the CLA group ( -0.5 + /- 2.1 % ) than in the placebo group ( 1.3 + /- 1.8 % ) . The change in abdominal body fat as a percentage of total body weight was smaller ( P = 0.02 ) in the CLA group ( -0.09 + /- 0.9 % ) than in the placebo group ( 0.43 + /- 0.6 % ) . There were no significant changes in plasma glucose , insulin , or LDL cholesterol between groups . Plasma HDL cholesterol decreased significantly more ( P = 0.05 ) in the CLA group ( -5.1 + /- 7.3 mg/dL ) than in the placebo group ( -0.7 + /- 8 mg/dL ) . Bone mineral accretion was lower ( P = 0.04 ) in the CLA group ( 0.05 + /- 0.03 kg ) than in the placebo group ( 0.07 + /- 0.03 kg ) . Reported gastrointestinal symptoms did not differ significantly between groups . CONCLUSIONS CLA supplementation for 7 + /- 0.5 mo decreased body fatness in 6 - 10-y-old children who were overweight or obese but did not improve plasma lipids or glucose and decreased HDL more than in the placebo group . Long-term investigation of the safety and efficacy of CLA supplementation in children is recommended Background : The best outcomes for treating childhood obesity have come from comprehensive family-based programmes . However there are questions over their generalizability . Objective : To examine the acceptability and effectiveness of ‘ family-based behavioural treatment ’ ( FBBT ) for childhood obesity in an ethnically and socially diverse sample of families in a UK National Health Service ( NHS ) setting . Methods : In this parallel group , r and omized controlled trial , 72 obese children were r and omized to FBBT or a waiting-list control . Primary outcomes were body mass index ( BMI ) and BMI s.d . scores ( SDSs ) . Secondary outcomes were weight , weight SDSs , height , height SDSs , waist , waist SDSs , FM index , FFM index , blood pressure ( BP ) and psychosocial measures . The outcomes were assessed at baseline and after treatment , with analyses of 6-month data performed on an intent-to-treat ( ITT ) basis . Follow-up anthropometric data were collected at 12 months for the treatment group . Results : ITT analyses included all children with baseline data ( n=60 ) . There were significant BMI SDS changes ( P<0.01 ) for the treatment and control groups of −0.11 ( 0.16 ) and −0.10 ( 1.6 ) . The treatment group showed a significant reduction in systolic BP ( −0.24 ( 0.7 ) , P<0.05 ) and improvements in quality of life and eating attitudes ( P<0.05 ) , with no significant changes for the control group . However the between-group treatment effects for BMI , body composition , BP and psychosocial outcomes were not significant . There was no overall change in BMI or BMI SDSs from 0–12 months for the treatment group . No adverse effects were reported . Conclusions : Both treatment and control groups experienced significant reductions in the level of overweight , but with no significant difference between them . There were no significant group differences for any of the secondary outcomes . This trial was registered at http://www.controlled-trials.com/ under IS RCT N 51382628 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 Background / Objectives : To determine if a multi-component family focused education package is more effective than a waiting list control group in treating overweight and obese children . Subjects/ Methods : A 2-year r and omised controlled trial ; 65 overweight and obese children aged 6–14 years were allocated to active intervention in either the first or second year , with body composition monitoring alone in the control period . Anthropometric measurements were undertaken at six monthly intervals and a 7-day food and activity diary were issued . Results : Over the 2 years of the study body mass index ( BMI ) SDS ( z score ) fell significantly in the intervention/control ( I/ Output:	Studies reported no significant difference between groups in the likelihood of reduced prevalence of overweight or overweight and obesity . INTERPRETATION Low- to moderate- quality evidence suggests behavioural treatments are associated with a medium effect in terms of reduced BMI or BMI z-score compared with a small effect shown by combined pharmacological-behavioural interventions .
MS21030	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This study was performed to determine the activity of adding continuous infusion ( CI ) of 5-fluorouracil ( 5-FU ) to gemcitabine ( GEM ) vs GEM alone in advanced pancreatic cancer ( APC ) . In all , 94 chemo-naïve patients with APC were r and omised to receive GEM alone ( arm A : 1000 mg m−2 per week for 7 weeks followed by a 2 week rest period , then weekly for 3 consecutive weeks out of every 4 weeks ) or in combination with CI 5-FU ( arm B : CI 5-FU 200 mg m−2 day−1 for 6 weeks followed by a 2 week rest period , then for 3 weeks every 4 weeks ) . Overall response rate ( RR ) was the primary end point and criteria for decision were planned according to the Simon 's optimal two-stage design . The overall RR was 8 % ( arm A ) and 11 % ( arm B ) ( 95 % confidence interval : 0.5–16 % and 2–22 % ) , respectively , and stable disease was 29 and 28 % . The median duration of RR was 34 weeks ( range 25–101 weeks ) for GEM and 26 weeks ( range 16–46 weeks ) for the combination . The median progression-free survival ( PFS ) was 14 weeks ( range 2–65 weeks ) and 18 weeks ( range 4–51 weeks ) , respectively . The median overall survival ( OS ) was 31 weeks ( range 1–101 weeks ) and 30 weeks ( 1–101 weeks ) . Toxicity was mild in both arms . This study does not show promising activity in terms of RR , PFS and OS for the double combination arm in APC PURPOSE This phase III trial compared the efficacy and safety of gemcitabine ( Gem ) plus capecitabine ( GemCap ) versus single-agent Gem in advanced/metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive GemCap ( oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks ) or Gem ( 1,000 mg/m2 by 30-minute infusion weekly for 7 weeks , followed by a 1-week break , and then weekly for 3 weeks every 4 weeks ) . Patients were stratified according to center , Karnofsky performance score ( KPS ) , presence of pain , and disease extent . RESULTS A total of 319 patients were enrolled between June 2001 and June 2004 . Median overall survival ( OS ) time , the primary end point , was 8.4 and 7.2 months in the GemCap and Gem arms , respectively ( P = .234 ) . Post hoc analysis in patients with good KPS ( score of 90 to 100 ) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm ( 10.1 v 7.4 months , respectively ; P = .014 ) . The overall frequency of grade 3 or 4 adverse events was similar in each arm . Neutropenia was the most frequent grade 3 or 4 adverse event in both arms . CONCLUSION GemCap failed to improve OS at a statistically significant level compared with st and ard Gem treatment . The safety of GemCap and Gem was similar . In the subgroup of patients with good performance status , median OS was improved significantly . GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status BACKGROUND In a phase 1 - 2 trial of albumin-bound paclitaxel ( nab-paclitaxel ) plus gemcitabine , substantial clinical activity was noted in patients with advanced pancreatic cancer . We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer . METHODS We r and omly assigned patients with a Karnofsky performance-status score of 70 or more ( on a scale from 0 to 100 , with higher scores indicating better performance status ) to nab-paclitaxel ( 125 mg per square meter of body-surface area ) followed by gemcitabine ( 1000 mg per square meter ) on days 1 , 8 , and 15 every 4 weeks or gemcitabine monotherapy ( 1000 mg per square meter ) weekly for 7 of 8 weeks ( cycle 1 ) and then on days 1 , 8 , and 15 every 4 weeks ( cycle 2 and subsequent cycles ) . Patients received the study treatment until disease progression . The primary end point was overall survival ; secondary end points were progression-free survival and overall response rate . RESULTS A total of 861 patients were r and omly assigned to nab-paclitaxel plus gemcitabine ( 431 patients ) or gemcitabine ( 430 ) . The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group ( hazard ratio for death , 0.72 ; 95 % confidence interval [ CI ] , 0.62 to 0.83 ; P<0.001 ) . The survival rate was 35 % in the nab-paclitaxel-gemcitabine group versus 22 % in the gemcitabine group at 1 year , and 9 % versus 4 % at 2 years . The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group , as compared with 3.7 months in the gemcitabine group ( hazard ratio for disease progression or death , 0.69 ; 95 % CI , 0.58 to 0.82 ; P<0.001 ) ; the response rate according to independent review was 23 % versus 7 % in the two groups ( P<0.001 ) . The most common adverse events of grade 3 or higher were neutropenia ( 38 % in the nab-paclitaxel-gemcitabine group vs. 27 % in the gemcitabine group ) , fatigue ( 17 % vs. 7 % ) , and neuropathy ( 17 % vs. 1 % ) . Febrile neutropenia occurred in 3 % versus 1 % of the patients in the two groups . In the nab-paclitaxel-gemcitabine group , neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days . CONCLUSIONS In patients with metastatic pancreatic adenocarcinoma , nab-paclitaxel plus gemcitabine significantly improved overall survival , progression-free survival , and response rate , but rates of peripheral neuropathy and myelosuppression were increased . ( Funded by Celgene ; Clinical Trials.gov number , NCT00844649 . ) Background : This r and omised phase II trial compared gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer . Methods : Patients were r and omly assigned to 4-week treatment with gemcitabine alone ( 1000 , mg m−2 gemcitabine by 30-min infusion on days 1 , 8 , and 15 ) or gemcitabine and S-1 combination therapy ( 1000 , mg m−2 gemcitabine by 30-min infusion on days 1 and 15 and 40 mg m−2 S-1 orally twice daily on days 1–15 ) . The primary end point was progression-free survival ( PFS ) . Results : Between July 2006 and February 2009 , 106 patients were enrolled . The PFS in gemcitabine and S-1 combination arm was significantly longer than in gemcitabine arm ( 5.4 vs 3.6 months ) , with a hazard ratio of 0.64 ( P=0.036 ) . Overall survival ( OS ) for gemcitabine and S-1 combination was longer than that for gemcitabine monotherapy ( 13.5 vs 8.8 months ) , with a hazard ratio of 0.72 ( P=0.104 ) . Overall , grade 3 or 4 adverse events were similar in both arms . Conclusion : Gemcitabine and S-1 combination therapy demonstrated longer PFS in advanced pancreatic cancer . Improved OS duration of 4.7 months was found for gemcitabine and S-1 combination therapy , though this was not statistically significant PURPOSE To compare clinical benefit response ( CBR ) and quality of life ( QOL ) in patients receiving gemcitabine ( Gem ) plus capecitabine ( Cap ) versus single-agent Gem for advanced/metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive GemCap ( oral Cap 650 mg/m(2 ) twice daily on days 1 through 14 plus Gem 1,000 mg/m(2 ) in a 30-minute infusion on days 1 and 8 every 3 weeks ) or Gem ( 1,000 mg/m(2 ) in a 30-minute infusion weekly for 7 weeks , followed by a 1-week break , and then weekly for 3 weeks every 4 weeks ) for 24 weeks or until progression . CBR criteria and QOL indicators were assessed over this period . CBR was defined as improvement from baseline for > or= 4 consecutive weeks in pain ( pain intensity or analgesic consumption ) and Karnofsky performance status , stability in one but improvement in the other , or stability in pain and performance status but improvement in weight . RESULTS Of 319 patients , 19 % treated with GemCap and 20 % treated with Gem experienced a CBR , with a median duration of 9.5 and 6.5 weeks , respectively ( P < .02 ) ; 54 % of patients treated with GemCap and 60 % treated with Gem had no CBR ( remaining patients were not assessable ) . There was no treatment difference in QOL ( n = 311 ) . QOL indicators were improving under chemotherapy ( P < .05 ) . These changes differed by the time to failure , with a worsening 1 to 2 months before treatment failure ( all P < .05 ) . CONCLUSION There is no indication of a difference in CBR or QOL between GemCap and Gem . Regardless of their initial condition , some patients experience an improvement in QOL on chemotherapy , followed by a worsening before treatment failure Purpose The aim of this study was to evaluate efficacy and safety of gemcitabine plus S-1 ( GS ) combination chemotherapy in patients with unresectable pancreatic cancer . Methods Patients were r and omly assigned to receive GS ( oral S-1 60 mg/m2 daily on days 1–15 every 3 weeks and gemcitabine 1,000 mg/m2 on days 8 and 15 ) or gemcitabine ( 1,000 mg/m2 on days 1 , 8 , and 15 every 4 weeks ) . The primary endpoint was progression-free survival ( PFS ) . Results One hundred and one patients were r and omly assigned . PFS was significantly longer in the GS arm with an estimated hazard ratio ( HR ) of 0.65 ( 95 % CI 0.43–0.98 ; P = 0.039 ; median 5.3 vs 3.8 months ) . Objective response rate ( ORR ) was also better in the GS arm ( 21.6 vs 6 % , P = 0.048 ) . Median survival was 8.6 months for GS and 8.6 months for GEM ( HR 0.93 ; 95 % CI 0.61–1.41 ; P = 0.714 ) . Grade 3–4 neutropenia ( 44 vs 19.6 % , P = 0.011 ) and thrombocytopenia ( 26 vs 8.7 % , P = 0.051 ) were more frequent in the GS arm . Conclusions GS therapy improved PFS and ORR with acceptable toxicity profile in patients with unresectable pancreatic cancer PURPOSE The combination of gemcitabine plus bevacizumab produced a 21 % response rate and a median survival of 8.8 months in a multicenter phase II trial in patients with metastatic pancreatic cancer . These encouraging data led Cancer and Leukemia Group B ( CALGB ) to conduct a double-blind , placebo-controlled , r and omized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients . PATIENTS AND METHODS Eligible patients had no prior therapy for advanced disease , Eastern Cooperative Oncology Group ( ECOG ) performance status 0 to 2 , no tumor invasion of adjacent organs , and no increased bleeding risk . The primary end point was overall survival . Patients were stratified by performance status , extent of disease , and prior radiotherapy . Patients received gemcitabine at 1,000 mg/m(2 ) over 30 minutes on days 1 , 8 , and 15 every 28 days and bevacizumab at 10 mg/kg or placebo on days 1 and 15 every 28 days . RESULTS Between June 2004 and April 2006 , 602 patients were enrolled onto the study and 535 were treated . Median overall survival was 5.8 months for gemcitabine/bevacizumab and 5.9 months for gemcitabine/placebo ( P = .95 ) . Median progression-free survival was 3.8 and 2.9 months , respectively ( P = .07 ) . Overall response rates were 13 % and 10 Output:	However , the combination of gemcitabine with other cytotoxic agents , such as platinum compounds or topoisomerase inhibitors failed to reduce the mortality risk . Combination therapy caused more grade 3/4 toxicities , including neutropenia , thrombocytopenia , vomiting , diarrhea , and fatigue . Conclusions Gemcitabine-based doublet regimens demonstrated superiority over gemcitabine monotherapy in overall efficacy , but were associated with increased toxicity . Different gemcitabine-based combinations showed different antitumor activity , and doublet regimens of gemcitabine in combination with a taxoid or a fluoropyrimidine , in particular an oral fluoropyrimidine provided significant survival benefits in the first-line treatment of unresectable LA/MPC
MS21031	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Management of degenerative spondylolisthesis with spinal stenosis is controversial . Surgery is widely used , but its effectiveness in comparison with that of nonsurgical treatment has not been demonstrated in controlled trials . METHODS Surgical c and i date s from 13 centers in 11 U.S. states who had at least 12 weeks of symptoms and image-confirmed degenerative spondylolisthesis were offered enrollment in a r and omized cohort or an observational cohort . Treatment was st and ard decompressive laminectomy ( with or without fusion ) or usual nonsurgical care . The primary outcome measures were the Medical Outcomes Study 36-Item Short-Form General Health Survey ( SF-36 ) bodily pain and physical function scores ( 100-point scales , with higher scores indicating less severe symptoms ) and the modified Oswestry Disability Index ( 100-point scale , with lower scores indicating less severe symptoms ) at 6 weeks , 3 months , 6 months , 1 year , and 2 years . RESULTS We enrolled 304 patients in the r and omized cohort and 303 in the observational cohort . The baseline characteristics of the two cohorts were similar . The one-year crossover rates were high in the r and omized cohort ( approximately 40 % in each direction ) but moderate in the observational cohort ( 17 % crossover to surgery and 3 % crossover to nonsurgical care ) . The intention-to-treat analysis for the r and omized cohort showed no statistically significant effects for the primary outcomes . The as-treated analysis for both cohorts combined showed a significant advantage for surgery at 3 months that increased at 1 year and diminished only slightly at 2 years . The treatment effects at 2 years were 18.1 for bodily pain ( 95 % confidence interval [ CI ] , 14.5 to 21.7 ) , 18.3 for physical function ( 95 % CI , 14.6 to 21.9 ) , and -16.7 for the Oswestry Disability Index ( 95 % CI , -19.5 to -13.9 ) . There was little evidence of harm from either treatment . CONCLUSIONS In nonr and omized as-treated comparisons with careful control for potentially confounding baseline factors , patients with degenerative spondylolisthesis and spinal stenosis treated surgically showed substantially greater improvement in pain and function during a period of 2 years than patients treated nonsurgically . ( Clinical Trials.gov number , NCT00000409 [ Clinical Trials.gov ] . ) BACKGROUND Lumbar-disk surgery often is performed in patients who have sciatica that does not resolve within 6 weeks , but the optimal timing of surgery is not known . METHODS We r and omly assigned 283 patients who had had severe sciatica for 6 to 12 weeks to early surgery or to prolonged conservative treatment with surgery if needed . The primary outcomes were the score on the Rol and Disability Question naire , the score on the visual-analogue scale for leg pain , and the patient 's report of perceived recovery during the first year after r and omization . Repeated- measures analysis according to the intention-to-treat principle was used to estimate the outcome curves for both groups . RESULTS Of 141 patients assigned to undergo early surgery , 125 ( 89 % ) underwent microdiskectomy after a mean of 2.2 weeks . Of 142 patients design ated for conservative treatment , 55 ( 39 % ) were treated surgically after a mean of 18.7 weeks . There was no significant overall difference in disability scores during the first year ( P=0.13 ) . Relief of leg pain was faster for patients assigned to early surgery ( P<0.001 ) . Patients assigned to early surgery also reported a faster rate of perceived recovery ( hazard ratio , 1.97 ; 95 % confidence interval , 1.72 to 2.22 ; P<0.001 ) . In both groups , however , the probability of perceived recovery after 1 year of follow-up was 95 % . CONCLUSIONS The 1-year outcomes were similar for patients assigned to early surgery and those assigned to conservative treatment with eventual surgery if needed , but the rates of pain relief and of perceived recovery were faster for those assigned to early surgery . ( Current Controlled Trials number , IS RCT N26872154 [ controlled-trials.com ] . ) Summary of Background Data . The Spine Patient Outcomes Research Trial ( SPORT ) was design ed to assess the relative efficacy and cost-effectiveness of surgical and nonsurgical approaches to the treatment of common conditions associated with low back and leg pain . Objectives . To describe the rationale and design of the SPORT project and to discuss its strengths and limitations . Study Design . Descriptive . Methods . First , the authors explain the rationale for embarking on SPORT , i.e. , deficiencies in the existing scientific knowledge base for treatment of these conditions . Second , the authors describe the design of SPORT , including topics such as specific aims , participating sites , study population , recruitment and enrollment , study interventions , follow-up , outcomes , statistical analysis , and study governance and organization . Finally , issues that complicate the performance of r and omized trials in surgery as they relate to the design and conduct of SPORT are discussed . Results . The SPORT project is being conducted at 11 clinical centers around the United States . It involves the simultaneous conduct of three multicenter , r and omized , controlled clinical trials . The study includes patients with the three most common diagnoses for which spine surgery is performed : intervertebral disc herniation , spinal stenosis , and degenerative spondylolisthesis , and it compares the most commonly used st and ard surgical and nonsurgical treatments for patients with these diagnoses . By the end of enrollment the authors anticipate a total of 500 patients with intervertebral disc herniation , 370 patients with spinal stenosis , and 300 patients with degenerative spondylolisthesis in the r and omized trials . Patients who meet the eligibility criteria but decline to be r and omized are invited to participate in an observational cohort study . Patients are being followed for a minimum of 24 months with visits scheduled at 6 weeks and at 3 , 6 , 12 , and 24 months . Conclusions . The results of this study will provide high- quality scientific evidence to aid clinical decision-making and improve treatment outcomes for these common , costly , and , in some instances , debilitating conditions Study Design . R and omized trial and concurrent observational cohort study . Objective . To compare 4 year outcomes of surgery to nonoperative care for spinal stenosis . Summary of Background Data . Surgery for spinal stenosis has been shown to be more effective compared to nonoperative treatment over 2 years , but longer-term data have not been analyzed . Methods . Surgical c and i date s from 13 centers in 11 US states with at least 12 weeks of symptoms and confirmatory imaging were enrolled in a r and omized cohort ( RC ) or observational cohort ( OC ) . Treatment was st and ard decompressive laminectomy or st and ard nonoperative care . Primary outcomes were SF-36 bodily pain ( BP ) and physical function scales and the modified Oswestry Disability index assessed at 6 weeks , 3 months , 6 months , and yearly up to 4 years . Results . A total of 289 patients enrolled in the RC and 365 patients enrolled in the OC . An as-treated analysis combining the RC and OC and adjusting for potential confounders found that the clinical ly significant advantages for surgery previously reported were maintained through 4 years , with treatment effects ( defined as mean change in surgery group minus mean change in nonoperative group ) for bodily pain 12.6 ( 95 % confidence interval [ CI ] , 8.5–16.7 ) ; physical function 8.6 ( 95 % CI , 4.6–12.6 ) ; and Oswestry Disability index −9.4 ( 95 % CI , −12.6 to −6.2 ) . Early advantages for surgical treatment for secondary measures such as bothersomeness , satisfaction with symptoms , and self-rated progress were also maintained . Conclusion . Patients with symptomatic spinal stenosis treated surgically compared to those treated nonoperatively maintain substantially greater improvement in pain and function through 4 years Objectives To evaluate the effects of early lumbar disc surgery compared with prolonged conservative care for patients with sciatica over two years of follow-up . Design R and omised controlled trial . Setting Nine Dutch hospitals . Participants 283 patients with 6 - 12 weeks of sciatica . Interventions Early surgery or an intended six months of continued conservative treatment , with delayed surgery if needed . Main outcome measures Scores from Rol and disability question naire for sciatica , visual analogue scale for leg pain , and Likert self rating scale of global perceived recovery . Results Of the 141 patients assigned to undergo early surgery , 125 ( 89 % ) underwent microdiscectomy . Of the 142 patients assigned to conservative treatment , 62 ( 44 % ) eventually required surgery , seven doing so in the second year of follow-up . There was no significant overall difference between treatment arms in disability scores during the first two years ( P=0.25 ) . Improvement in leg pain was faster for patients r and omised to early surgery , with a significant difference between “ areas under the curves ” over two years ( P=0.05 ) . This short term benefit of early surgery was no longer significant by six months and continued to narrow between six months and 24 months . Patient satisfaction decreased slightly between one and two years for both groups . At two years 20 % of all patients reported an unsatisfactory outcome . Conclusions Early surgery achieved more rapid relief of sciatica than conservative care , but outcomes were similar by one year and these did not change during the second year . Trial Registry IS RCT No 26872154 Objective This study describes the 5 years ’ results of the Sciatica trial focused on pain , disability , (un)satisfactory recovery and predictors for unsatisfactory recovery . Design A r and omised controlled trial . Setting Nine Dutch hospitals . Participants Five years ’ follow-up data from 231 of 283 patients ( 82 % ) were collected . Intervention Early surgery or an intended 6 months of conservative treatment . Main outcome measures Scores from Rol and disability question naire , visual analogue scale ( VAS ) for leg and back pain and a Likert self-rating scale of global perceived recovery were analysed . Results There were no significant differences between groups on the 5 years ’ primary outcome scores . Despite at least 6 months of conservative treatment 46 % of the conservatively allocated patients were treated surgically because of severe leg pain and disability . Forty-nine ( 21 % ) patients had an unsatisfactory recovery at 5 years and the recovery pattern showed that there was a variable group of 66 patients ( 31 % ) with at least one unsatisfactory outcome at 1 , 2 or 5 years of follow-up . Multivariate logistic regression showed that age ( > 40 ; OR 2.42 ( 95 % CI 1.16 to 5.02 ) ) , severity of leg pain ( VAS > 70 ; OR 3.32 ( 95 % CI 1.69 to 6.54 ) ) and the Mc Gill affective score ( score > 3 ; OR 6.23 ( 95 % CI 2.23 to 17.38 ) ) were the only significant predictors for an unsatisfactory outcome at 5 years . Conclusions In the long term , 8 % of the patients with sciatica never showed any recovery and in at least 23 % , sciatica appears to result in ongoing complaints , which fluctuate over time , irrespective of treatment . Prolonged conservative care might give patients a fair chance for pain and disability to resolve without surgery , but with the risk to receive delayed surgery after prolonged suffering of sciatica . Age above 40 years , severe leg pain at baseline and a higher affective Mc Gill pain score were predictors for unsatisfactory recovery . Trial Registry IS RCT No 26872154 BACKGROUND The management of degenerative spondylolisthesis associated with spinal stenosis remains controversial . Surgery is widely used and has recently been shown to be more effective than nonoperative treatment when the results were followed over two years . Questions remain regarding the long-term effects of surgical treatment compared with those of nonoperative treatment . METHODS Surgical c and i date s from thirteen centers with symptoms of at least twelve weeks ' duration as well as confirmatory imaging showing degenerative spondylolisthesis with spinal stenosis were offered enrollment in a r and omized cohort or observational cohort . Treatment consisted of st and ard decompressive laminectomy ( with or without fusion ) or usual nonoperative care . Primary outcome measures were the Short Form-36 ( SF-36 ) bodily pain and physical function scores and the modified Oswestry Disability Index at six weeks , three months , six months , and yearly up to four years . RESULTS In the r and omized cohort ( 304 patients enrolled ) , 66 % of those r and omized to receive surgery received it by four years whereas 54 % of those r and omized to receive nonoperative care received surgery by four years . In the observational cohort ( 303 patients enrolled ) , 97 % of those who chose surgery received it whereas 33 % of those who chose nonoperative care eventually received surgery . The intent-to-treat analysis of the r and omized cohort , which was limited by nonadherence to the assigned treatment , showed no significant differences in treatment outcomes between the operative and nonoperative groups at three or four years . An as-treated analysis combining the r and omized and observational cohorts that adjusted for potential confounders demonstrated that the clinical ly relevant advantages of surgery that had been previously reported through two years were maintained at four years , with treatment effects of 15.3 ( 95 % confidence Output:	Long-term and greater than 2-year post-r and omisation results favoured surgery for spondylolisthesis and stenosis , although the size of the effects reduced with time . For disc herniation , no significant effect was shown for leg and back pain comparing surgery to physical activity . For spondylolisthesis and spinal stenosis , surgery is superior to physical activity up to greater than 2 years follow-up .
MS21032	*TASK* the task is to summarize an input biomedical literature in six sentences *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 purpose of this r and omized study was to compare sirolimus-eluting stenting with coronary artery bypass grafting ( CABG ) for patients with unprotected left main ( ULM ) coronary artery disease . BACKGROUND CABG is considered the st and ard of care for treatment of ULM . Improvements in percutaneous coronary intervention ( PCI ) with use of drug-eluting stents might lead to similar results . The effectiveness of drug-eluting stenting versus surgery has not been established in a r and omized trial . METHODS In this prospect i ve , multicenter , r and omized trial , 201 patients with ULM disease were r and omly assigned to undergo sirolimus-eluting stenting ( n = 100 ) or CABG using predominantly arterial grafts ( n = 101 ) . The primary clinical end point was noninferiority in freedom from major adverse cardiac events , such as cardiac death , myocardial infa rct ion , and the need for target vessel revascularization within 12 months . RESULTS The combined primary end point was reached in 13.9 % of patients after surgery , as opposed to 19.0 % after PCI ( p = 0.19 for noninferiority ) . The combined rates for death and myocardial infa rct ion were comparable ( surgery , 7.9 % vs. stenting , 5.0 % ; noninferiority p < 0.001 ) , but stenting was inferior to surgery for repeat revascularization ( 5.9 % vs. 14.0 % ; noninferiority p = 0.35 ) . Perioperative complications including 2 strokes were higher after surgery ( 4 % vs. 30 % ; p < 0.001 ) . Freedom from angina was similar between groups ( p = 0.33 ) . CONCLUSIONS In patients with ULM stenosis , PCI with sirolimus-eluting stents did not show noninferiority [ corrected ] to CABG at 12-month follow-up with respect to freedom from major adverse cardiac events , which is mainly influenced by repeated revascularization , whereas for hard endpoints , [ corrected ] PCI results are favorable . A longer follow-up is warranted . [ corrected Background — The prospect i ve , multinational , r and omized Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery ( SYNTAX ) trial was design ed to assess the optimal revascularization strategy between percutaneous coronary intervention ( PCI ) and coronary artery bypass grafting ( CABG ) , for patients with left main ( LM ) and /or 3-vessel coronary disease . Methods and Results — This observational hypothesis-generating analysis reports the results of a prespecified powered subgroup of 705 r and omized patients who had LM disease among the 1800 patients with de novo 3-vessel disease and /or LM disease r and omized to PCI with paclitaxel-eluting stents or CABG in the SYNTAX trial . Major adverse cardiac and cerebrovascular event rates at 1 year in LM patients were similar for CABG and PCI ( 13.7 % versus 15.8 % ; & Dgr;2.1 % [ 95 % confidence interval −3.2 % to 7.4 % ] ; P=0.44 ) . At 1 year , stroke was significantly higher in the CABG arm ( 2.7 % versus 0.3 % ; & Dgr;−2.4 % [ 95 % confidence interval −4.2 % to −0.1 % ] ; P=0.009 ] ) , whereas repeat revascularization was significantly higher in the PCI arm ( 6.5 % versus 11.8 % ; & Dgr;5.3 % [ 95 % confidence interval 1.0 % to 9.6 % ] ; P=0.02 ) ; there was no observed difference between groups for other end points . When patients were scored for anatomic complexity , those with higher baseline SYNTAX scores had significantly worse outcomes with PCI than did patients with low or intermediate SYNTAX scores ; outcomes for patients with CABG did not correlate with baseline SYNTAX score , but baseline EuroSCORE significantly predicted outcomes for both treatments . Conclusions — Patients with LM disease who had revascularization with PCI had safety and efficacy outcomes comparable to CABG at 1 year ; longer follow-up is required to determine whether these 2 revascularization strategies offer comparable medium-term outcomes in this group of complex patients . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT00114972 BACKGROUND Percutaneous coronary intervention ( PCI ) is increasingly used to treat unprotected left main coronary artery stenosis , although coronary-artery bypass grafting ( CABG ) has been considered to be the treatment of choice . METHODS We r and omly assigned patients with unprotected left main coronary artery stenosis to undergo CABG ( 300 patients ) or PCI with sirolimus-eluting stents ( 300 patients ) . Using a wide margin for noninferiority , we compared the groups with respect to the primary composite end point of major adverse cardiac or cerebrovascular events ( death from any cause , myocardial infa rct ion , stroke , or ischemia-driven target-vessel revascularization ) at 1 year . Event rates at 2 years were also compared between the two groups . RESULTS The primary end point occurred in 26 patients assigned to PCI as compared with 20 patients assigned to CABG ( cumulative event rate , 8.7 % vs. 6.7 % ; absolute risk difference , 2.0 percentage points ; 95 % confidence interval [ CI ] , -1.6 to 5.6 ; P=0.01 for noninferiority ) . By 2 years , the primary end point had occurred in 36 patients in the PCI group as compared with 24 in the CABG group ( cumulative event rate , 12.2 % vs. 8.1 % ; hazard ratio with PCI , 1.50 ; 95 % CI , 0.90 to 2.52 ; P=0.12 ) . The composite rate of death , myocardial infa rct ion , or stroke at 2 years occurred in 13 and 14 patients in the two groups , respectively ( cumulative event rate , 4.4 % and 4.7 % , respectively ; hazard ratio , 0.92 ; 95 % CI , 0.43 to 1.96 ; P=0.83 ) . Ischemia-driven target-vessel revascularization occurred in 26 patients in the PCI group as compared with 12 patients in the CABG group ( cumulative event rate , 9.0 % vs. 4.2 % ; hazard ratio , 2.18 ; 95 % CI , 1.10 to 4.32 ; P=0.02 ) . CONCLUSIONS In this r and omized trial involving patients with unprotected left main coronary artery stenosis , PCI with sirolimus-eluting stents was shown to be noninferior to CABG with respect to major adverse cardiac or cerebrovascular events . However , the noninferiority margin was wide , and the results can not be considered clinical ly directive . ( Funded by the Cardiovascular Research Foundation , Seoul , Korea , and others ; PRECOMBAT Clinical Trials.gov number , NCT00422968 . ) Background — Current guidelines recommend coronary artery bypass graft surgery ( CABG ) when treating significant de novo left main coronary artery ( LM ) stenosis ; however , percutaneous coronary intervention ( PCI ) has a class IIa indication for unprotected LM disease in selected patients . This analysis compares 5-year clinical outcomes in PCI- and CABG-treated LM patients in the Synergy Between PCI With Taxus and Cardiac Surgery ( SYNTAX ) trial , the largest trial in this group to date . Methods and Results — The SYNTAX trial r and omly assigned 1800 patients with LM or 3-vessel disease to receive either PCI ( with TAXUS Express paclitaxel-eluting stents ) or CABG . The unprotected LM cohort ( N=705 ) was predefined and powered . Major adverse cardiac and cerebrovascular event rates at 5 years was 36.9 % in PCI patients and 31.0 % in CABG patients ( hazard ratio , 1.23 [ 95 % confidence interval , 0.95–1.59 ] ; P=0.12 ) . Mortality rate was 12.8 % and 14.6 % in PCI and CABG patients , respectively ( hazard ratio , 0.88 [ 95 % confidence interval , 0.58–1.32 ] ; P=0.53 ) . Stroke was significantly increased in the CABG group ( PCI 1.5 % versus CABG 4.3 % ; hazard ratio , 0.33 [ 95 % confidence interval , 0.12–0.92 ] ; P=0.03 ) and repeat revascularization in the PCI arm ( 26.7 % versus 15.5 % ; hazard ratio , 1.82 [ 95 % confidence interval , 1.28–2.57 ] ; P<0.01 ) . Major adverse cardiac and cerebrovascular events were similar between arms in patients with low/intermediate SYNTAX scores but significantly increased in PCI patients with high scores ( ≥33 ) . Conclusions — At 5 years , no difference in overall major adverse cardiac and cerebrovascular events was found between treatment groups . PCI-treated patients had a lower stroke but a higher revascularization rate versus CABG . These results suggest that both treatments are valid options for LM patients . The extent of disease should accounted for when choosing between surgery and PCI , because patients with high SYNTAX scores seem to benefit more from surgery compared with those in the lower tertiles . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00114972 Background — The objective of the present study was to compare the midterm follow-up results of percutaneous coronary intervention ( PCI ) and coronary bypass graft surgery ( CABG ) for the treatment of unprotected left main coronary artery disease in octogenarians . Methods and Results — A total of 249 consecutive patients ≥80 years of age diagnosed with left main coronary artery disease underwent coronary revascularization in our center between January 2002 and January 2008 ; 145 patients underwent CABG , and 104 patients had PCI . Major adverse cardiac and cerebrovascular events ( MACCE [ cardiac death , myocardial infa rct ion , cerebrovascular event , revascularization ] ) were evaluated at a mean follow-up of 23±16 months . Patients who underwent PCI were older ; had higher creatinine levels , lower ejection fraction , and higher EuroSCORE ; and presented more frequently with an acute coronary syndrome . Drug-eluting stents were used in 48 % of PCI patients . A propensity score analysis was performed to adjust for baseline differences between the 2 groups . Survival free of cardiac death or myocardial infa rct ion ( PCI , 65.4 % ; CABG , 69.7 % ) and MACCE-free survival ( PCI , 56.7 % ; CABG , 64.8 % ) at follow-up were similar between the groups ( adjusted hazard ratio for survival free of cardiac death or myocardial infa rct ion , 1.28 ; 95 % CI , 0.64 to 2.56 ; P=0.47 ; adjusted hazard ratio for MACCE-free survival , 1.11 ; 95 % CI , 0.59 to 2.0 ; P=0.73 ) . The EuroSCORE value was an independent predictor of MACCE regardless of the type of revascularization ( hazard ratio , 1.17 for each EuroSCORE increase of 1 point ; 95 % CI , 1.09 to 1.25 ; P<0.0001 ) . Conclusions — In this single-center , nonr and omized study , there were no significant differences in cardiac death or myocardial infa rct ion and MACCE between CABG and PCI for the treatment of left main coronary artery disease in octogenarians after a mean follow-up of 2 years . Baseline EuroSCORE was the most important predictor of MACCE regardless of the type of revascularization . R and omized studies comparing both revascularization strategies in this high-risk coronary population are warranted BACKGROUND Currently available r and omized data on the comparison between percutaneous coronary intervention ( PCI ) and coronary artery bypass graft ( CABG ) for the treatment of unprotected left main coronary disease ( LMD ) lacks statistical power due to low numbers of patients enrolled . OBJECTIVES This study assessed long-term outcomes of PCI and CABG for the treatment of LMD in specific subgroups according to disease anatomic complexity . METHODS We conducted a pooled analysis of individual patient-level data of the LMD patients included in the PRECOMBAT ( Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease ) and SYNTAX ( Synergy Between PCI With TAXUS and Cardiac Surgery ) trials . Incidences of major adverse cardiac events were assessed at 5 years follow-up . RESULTS Study population comprised 1,305 patients . The incidence of major adverse cardiac and cerebrovas Output:	Stratified analysis based on stent types showed that the increased risk for myocardial infa rct ion associated with PCI was only evident in patients with bare-metal stents or early-generation drug-eluting stents ( DES ) , but not newer-generation DES . Conclusions Compared with CABG , PCI with newer-generation DES might be a safe alternative revascularization strategy for treatment of left main CAD , but is associated with more repeat revascularization
MS21033	*TASK* the task is to summarize an input biomedical literature in six sentences *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 article evaluates the effects and use of adjuncts to a televised smoking cessation program , based on the American Lung Association 's " Freedom From Smoking in 20 Days . " Subjects were r and omized to maintenance and control conditions . The maintenance condition received newsletters with information and support addressing different stages in the cessation process and information about a telephone hotline . The maintenance condition did not increase cessation at any wave of interviewing , assessed by multiple point or point prevalence of abstinence . Those abstinent at 6 months and those who had made an attempt to stop smoking by that time were more likely to have used the newsletters and were more likely to have used the sections relevant to their cessation stage . Rates of use of the telephone hotline were low . The newsletters appear to be useful to smokers who are predisposed to use written material OBJECTIVE To evaluate the effect of the middle and junior high school Drug Abuse Resistance Education ( D.A.R.E. ) and D.A.R.E. Plus programs on drug use and violence . DESIGN R and omized controlled trial of 24 schools , with 3 conditions : D.A.R.E. only , D.A.R.E. Plus , and delayed program control . SETTING Schools and neighborhoods , primarily in Minneapolis-St Paul . PARTICIPANTS All seventh- grade students in 24 schools in the academic year 1999 - 2000 ( N = 6237 at baseline , 67.3 % were white , and there was 84.0 % retention at final follow-up ) . INTERVENTIONS The middle and junior high school D.A.R.E. curriculum in the 16 schools that received D.A.R.E. only and D.A.R.E. Plus . In the 8 schoolts that received D.A.R.E. Plus , additional components included a peer-led parental involvement classroom program called " On the VERGE , " youth-led extracurricular activities , community adult action teams , and postcard mailings to parents . The interventions were implemented during 2 school years , when the cohort was in the seventh and eighth grade s. MAIN OUTCOME MEASURES Self-reported tobacco , alcohol , and marijuana use ; multidrug use ; violence ; and victimization , assessed at the beginning and end of seventh grade and at the end of eighth grade . Growth curve analytic methods were used to assess changes over time by condition . RESULTS There were no significant differences between D.A.R.E. only and the controls ; significant differences among boys between D.A.R.E. Plus and controls for tobacco , alcohol , and multidrug use and victimization ; significant differences among boys between D.A.R.E. Plus and D.A.R.E. only in tobacco use and violence ; and no significant behavioral differences among girls . CONCLUSION D.A.R.E. Plus significantly enhanced the effectiveness of the D.A.R.E. curriculum among boys and was more effective than the delayed program controls , underscoring the potential for multiyear , multicomponent prevention programs and demonstrating sex differences in response to intervention programs OBJECTIVES : Media Detective is a 10-lesson elementary school substance use prevention program developed on the basis of the message interpretation processing model design ed to increase children 's critical thinking skills about media messages and reduce intent to use tobacco and alcohol products . The purpose of this study was to conduct a short-term , r and omized , controlled trial to evaluate the effectiveness of Media Detective for achieving these goals . METHODS : Elementary schools were r and omly assigned to conditions to either receive the Media Detective program ( n = 344 ) or serve in a waiting list control group ( n = 335 ) . RESULTS : Boys in the Media Detective group reported significantly less interest in alcohol-br and ed merch and ise than boys in the control group . Also , students who were in the Media Detective group and had used alcohol or tobacco in the past reported significantly less intention to use and more self-efficacy to refuse substances than students who were in the control group and had previously used alcohol or tobacco . CONCLUSIONS : This evaluation provides evidence that Media Detective can be effective for substance use prevention in elementary school – aged children . Notably , media-related cognitions about alcohol and tobacco products are malleable and relevant to the development and maintenance of substance use behaviors during late childhood . The findings from this study suggest that media literacy – based interventions may serve as both a universal and a targeted prevention program that has potential for assisting elementary school children in making healthier , more informed decisions about use of alcohol and tobacco products A population -based , r and omized universal classroom intervention trial for the prevention of disruptive behavior ( i.e. , attention-deficit/hyperactivity problems , oppositional defiant problems , and conduct problems ) is described . Impact on developmental trajectories in young elementary schoolchildren was studied . Three trajectories were identified in children with high , intermediate , or low levels of problems on all 3 disruptive behaviors at baseline . The intervention had a positive impact on the development of all disruptive behavior problems in children with intermediate levels of these problems at baseline . Effect sizes of mean difference at outcome were medium or small . In children with the highest levels of disruptive behavior at baseline , a positive impact of the intervention was found for conduct problems This study evaluates a youth subject-directed smoking prevention and cessation program titled Breathe Easy ! The program was delivered at two sites and a control group was recruited from two additional sites . Surveys were administered prior to the program and either 1 month or 6 months after completion at the exposure sites . The same survey administration procedure was used as the control . After controlling for invalid responses and including only those that completed both surveys , 251 exposure subjects and 159 control subjects remained for analysis . At sites with 1-month follow-up , no significant difference was noted between intervention and control groups . At the sites with 6-month follow-up , prevalence dropped from 18.7 % to 8.9 % , which is statistically significant , while at the control site prevalence changed from 14.1 % to 9.4 % , which is not significant . Additional outcomes examined in the exposed group showed trends toward smoking cessation and prevention at higher rates than those of the unexposed group In India , 57 % of men between 15 and 54 years and 10.8 % of women between 15 and 49 years use tobacco . A wide variety of tobacco gets used and the poor and the underprivileged are the dominant victims of tobacco and its adverse consequences . Project MYTRI ( Mobilizing Youth for Tobacco-Related Initiatives in India ) was a tobacco prevention intervention program , a cluster-r and omized trial in 32 Indian schools which aim ed to decrease susceptibility to tobacco use among sixth- to ninth- grade students in urban setting s in India . This culture-specific intervention , which addressed both smokeless and smoked forms of tobacco , was Indian in content and communication . We qualitatively developed indicators which would help accurately measure the dose of the intervention given , received and reached . A multi-staged process evaluation was done through both subjective and objective measures . Training the teachers critically contributed toward a rigorous implementation and also correlated with the outcomes , as did a higher proportion of students participating in the classroom discussion s and better peer-leader-student communication . A sizeable proportion of subjective responses were ' socially desirable ' , making objective assessment a preferred methodology even for ' dose received ' . The peer-led health activism was successful . Teachers ' manuals need to be concise BACKGROUND No long-term impact has yet been observed with the use of the social-influences approach to school-based smoking prevention for youth . However , whether this lack of impact is due to method ologic problems with the studies or to the failure of the interventions is unclear . The Hutchinson Smoking Prevention Project ( HSPP ) , conducted from September 1984 through August 1999 , aim ed to attain the most rigorous r and omized trial possible to determine the long-term impact of a theory-based , social-influences , grade 3 - 12 intervention on smoking prevalence among youth . METHODS Forty Washington school districts were r and omly assigned to the intervention or to the control condition . Study participants were children enrolled in two consecutive 3rd grade s in the 40 districts ( n = 8388 ) ; they were followed to 2 years after high school . The trial achieved high implementation fidelity and 94 % follow-up . Data were analyzed with the use of group-permutation methods , and all statistical tests were two-sided . RESULTS No significant difference in prevalence of daily smoking was found between students in the control and experimental districts , either at grade 12 ( difference [ Delta ] = 0.2 % , 95 % confidence interval [ CI ] = -4.6 % to 4.4 % , and P = .91 for girls ; Delta = 0.3 % , 95 % CI = -5.0 % to 5.5 % , and P = .89 for boys ) or at 2 years after high school ( Delta = -1.4 % , 95 % CI = -5.0 % to 1.6 % , and P = .38 for girls ; Delta = 2.6 % , 95 % CI = -2.5 % to 7.7 % , and P = .30 for boys ) . Moreover , no intervention impact was observed for other smoking outcomes , such as extent of current smoking or cumulative amount smoked , or in subgroups that differ in a priori specified variables , such as family risk for smoking . CONCLUSION The rigor of the HSPP trial suggests high credence for the intervention impact results . Consistent with previous trials , there is no evidence from this trial that a school-based social-influences approach is effective in the long-term deterrence of smoking among youth This study examined the effects of the Iowa Strengthening Families Program ( ISFP ) and the Preparing for the Drug-Free Years program ( PDFY ) on young adolescent transitions from nonuse of substances to initiation and progression of substance use . Analyses incorporated 3 waves of data collected over a 2.5-year period from 329 rural young adolescents . Outcomes were analyzed by using log-linear models that incorporated substance use status frequencies derived from latent transition analyses . Effects on delayed substance use initiation were shown for both the ISFP and the PDFY at a 2-year follow-up . Also at this follow-up , the PDFY showed effects on delayed progression of use among those previously reporting initiation This paper described the short-term results from an ongoing r and omized controlled efficacy study of Click City ® : Tobacco , a tobacco prevention program design ed for 5th grade rs , with a booster in sixth grade . Click City ® : Tobacco is an innovative school-based prevention program delivered via an intranet , a series of linked computers with a single server . The components of the program target theoretically based and empirically supported etiological mechanisms predictive of future willingness and intentions to use tobacco and initiation of tobacco use . Each component was design ed to change one or more etiological mechanisms and was empirically evaluated in the laboratory prior to inclusion in the program . Short-term results from 47 elementary schools ( 24 schools who used Click City ® : Tobacco , and 23 who continued with their usual curriculum ) showed change in intentions and willingness to use tobacco from baseline to 1-week following the completion of the 5th grade sessions . The results demonstrate the short-term efficacy of this program and suggest that experimentally evaluating components prior to including them in the program contributed to the efficacy of the program . The program was most efficacious for students who were most at risk Recent studies have suggested that a prevention program that addresses the social influences that encourage smoking can be effective in deterring cigarette use by adolescents . This study presents 1- , 2- , and 3-year follow-up results from two studies which evaluated three variations of the social influences curriculum and compared them to a health consequences program and a usual-care comparison group . These results suggest that a peer-led , social influences program can restrain smoking among both baseline nonsmokers and baseline experimental smokers at 2 years postintervention . Analyses of attrition data suggest no evidence to threaten the internal validity of these findings , although their generalizability to baseline smokers may be limited This study reports the evaluation of an intervention design edto reinforcetobacco abstinence amongelementary schoolchildren in a school transition period . This intervention was developed according to the principles of Intervention Mapping . A total of 765 grade 5 students ( ages 10 - 12 ) was recruited in 32 elementary schools . A quasi-experimental longitudinal design was used to evaluate the outcomes . Results observed 2 and 8 months postintervention are reported here . It is shown that although the behavior remained largely unchanged by the intervention , some of its determinants were modified . Behavioral intention , behavioral and normative beliefs , perceived self-efficacy , and role beliefs were changed at one or both postintervention measures . An interesting feature of these results relates to the fact that the most positive outcomes were seen among at-risk children . Discussion considers the advisability to develop , implement , and evaluate evidence -based interventions targeting the psychosocial factors underlying maintenance of tobacco smoking abstinence in elementary school Most school-based smoking prevention studies employ design s in which schools or classrooms are assigned to different treatment conditions while observations are made on individual students . This design requires that the treatment effect be assessed against the between-school variance . However , the between-school variance is usually larger than the variance that would be obtained if students were individually r and omized to different conditions . Consequently , the power of the test for a treatment effect is reduced , and it becomes difficult to detect important treatment effects . To assess the potential loss of power or to calculate appropriate sample sizes , investigators need good estimates of the intraclass correlations for the variables of interest . The authors calculated intraclass correlations for some common outcome variables in a school-based smoking prevention study , using a three-level model-i.e . , students nested within classrooms and classrooms nested within schools . The authors present the intraclass correlation estimates for the entire data set , as well as separately by Output:	Pure Prevention cohorts showed a significant effect at longest follow-up , with an average 12 % reduction in starting smoking compared to the control groups . However , no overall effect was detected at one year or less . The combined social competence and social influences interventions showed a significant effect at one year and at longest follow-up . Studies that deployed a social influences programme showed no overall effect at any time point ; multimodal interventions and those with an information-only approach were similarly ineffective . Studies reporting Change in Smoking Behaviour over time did not show an overall effect , but at an intervention level there were positive findings for social competence and combined social competence and social influences interventions
MS21034	*TASK* the task is to summarize an input biomedical literature in six sentences *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 efficacy of ceritinib in patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer ( NSCLC ) is not known . We assessed the efficacy and safety of ceritinib versus platinum-based chemotherapy in these patients . METHODS This r and omised , open-label , phase 3 study in untreated patients with stage IIIB/IV ALK-rearranged non-squamous NSCLC was done in 134 centres across 28 countries . Eligible patients were assigned via interactive response technology to oral ceritinib 750 mg/day or platinum-based chemotherapy ( [ cisplatin 75 mg/m2 or carboplatin AUC 5 - 6 plus pemetrexed 500 mg/m2 ] every 3 weeks for four cycles followed by maintenance pemetrexed ) ; r and omisation was stratified by World Health Organization performance status ( 0 vs 1 - 2 ) , previous neoadjuvant or adjuvant chemotherapy , and presence of brain metastases as per investigator 's assessment at screening . Investigators and patients were not masked to treatment assignment . The primary endpoint was blinded independent review committee assessed progression-free survival , based on all r and omly assigned patients ( the full analysis set ) . Efficacy analyses were done based on the full analysis set . All safety analyses were done based on the safety set , which included all patients who received at least one dose of study drug . This trial is registered with Clinical Trials.gov , number NCT01828099 . FINDINGS Between Aug 19 , 2013 , and May 11 , 2015 , 376 patients were r and omly assigned to ceritinib ( n=189 ) or chemotherapy ( n=187 ) . Median progression-free survival ( as assessed by blinded independent review committee ) was 16·6 months ( 95 % CI 12·6 - 27·2 ) in the ceritinib group and 8·1 months ( 5·8 - 11·1 ) in the chemotherapy group ( hazard ratio 0·55 [ 95 % CI 0·42 - 0·73 ] ; p<0·00001 ) . The most common adverse events were diarrhoea ( in 160 [ 85 % ] of 189 patients ) , nausea ( 130 [ 69 % ] ) , vomiting ( 125 [ 66 % ] ) , and an increase in alanine aminotransferase ( 114 [ 60 % ] ) in the ceritinib group and nausea ( in 97 [ 55 % ] of 175 patients ) , vomiting ( 63 [ 36 % ] ) , and anaemia ( 62 [ 35 % ] ) in the chemotherapy group . INTERPRETATION First-line ceritinib showed a statistically significant and clinical ly meaningful improvement in progression-free survival versus chemotherapy in patients with advanced ALK-rearranged NSCLC . FUNDING Novartis Pharmaceuticals Corporation PURPOSE The purpose of this study was to determine whether the addition of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ( Iressa , ZD1839 ; AstraZeneca , Wilmington , DE ) to st and ard first-line gemcitabine and cisplatin provides clinical benefit over gemcitabine and cisplatin alone in patients with advanced or metastatic non-small-cell lung cancer ( NSCLC ) . Gefitinib has demonstrated encouraging efficacy in advanced NSCLC in phase II trials in pretreated patients , and a phase I trial of gefitinib in combination with gemcitabine and cisplatin showed favorable tolerability . PATIENTS AND METHODS This was a phase III r and omized , double-blind , placebo-controlled , multicenter trial in chemotherapy-naive patients with unresectable stage III or IV NSCLC . All patients received up to six cycles of chemotherapy ( cisplatin 80 mg/m(2 ) on day 1 and gemcitabine 1,250 mg/m(2 ) on days 1 and 8 of the 3-week cycle ) plus either gefitinib 500 mg/d , gefitinib 250 mg/d , or placebo . Daily gefitinib or placebo was continued until disease progression . End points included overall survival ( primary ) , time to progression , response rates , and safety evaluation . RESULTS A total of 1,093 patients were enrolled . There was no difference in efficacy end points between the treatment groups : for the gefitinib 500 mg/d , gefitinib 250 mg/d , and placebo groups , respectively , median survival times were 9.9 , 9.9 , and 10.9 months ( global ordered log-rank [ GOLrank ] P = .4560 ) , median times to progression were 5.5 , 5.8 , and 6.0 months ( GOLrank ; P = .7633 ) , and response rates were 49.7 % , 50.3 % , and 44.8 % . No significant unexpected adverse events were seen . CONCLUSION Gefitinib in combination with gemcitabine and cisplatin in chemotherapy-naive patients with advanced NSCLC did not have improved efficacy over gemcitabine and cisplatin alone . The reasons for this remain obscure and require further pre clinical testing BACKGROUND The efficacy of the ALK inhibitor crizotinib as compared with st and ard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer ( NSCLC ) is unknown . METHODS We conducted an open-label , phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease . Patients were r and omly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy ( pemetrexed , 500 mg per square meter of body-surface area , plus either cisplatin , 75 mg per square meter , or carboplatin , target area under the curve of 5 to 6 mg per milliliter per minute ) every 3 weeks for up to six cycles . Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy . The primary end point was progression-free survival as assessed by independent radiologic review . RESULTS Progression-free survival was significantly longer with crizotinib than with chemotherapy ( median , 10.9 months vs. 7.0 months ; hazard ratio for progression or death with crizotinib , 0.45 ; 95 % confidence interval [ CI ] , 0.35 to 0.60 ; P<0.001 ) . Objective response rates were 74 % and 45 % , respectively ( P<0.001 ) . Median overall survival was not reached in either group ( hazard ratio for death with crizotinib , 0.82 ; 95 % CI , 0.54 to 1.26 ; P=0.36 ) ; the probability of 1-year survival was 84 % with crizotinib and 79 % with chemotherapy . The most common adverse events with crizotinib were vision disorders , diarrhea , nausea , and edema , and the most common events with chemotherapy were nausea , fatigue , vomiting , and decreased appetite . As compared with chemotherapy , crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life . CONCLUSIONS Crizotinib was superior to st and ard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC . ( Funded by Pfizer ; PROFILE 1014 Clinical Trials.gov number , NCT01154140 . ) BACKGROUND In single-group studies , chromosomal rearrangements of the anaplastic lymphoma kinase gene ( ALK ) have been associated with marked clinical responses to crizotinib , an oral tyrosine kinase inhibitor targeting ALK . Whether crizotinib is superior to st and ard chemotherapy with respect to efficacy is unknown . METHODS We conducted a phase 3 , open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen . Patients were r and omly assigned to receive oral treatment with crizotinib ( 250 mg ) twice daily or intravenous chemotherapy with either pemetrexed ( 500 mg per square meter of body-surface area ) or docetaxel ( 75 mg per square meter ) every 3 weeks . Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study . The primary end point was progression-free survival . RESULTS The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group ( hazard ratio for progression or death with crizotinib , 0.49 ; 95 % confidence interval [ CI ] , 0.37 to 0.64 ; P<0.001 ) . The response rates were 65 % ( 95 % CI , 58 to 72 ) with crizotinib , as compared with 20 % ( 95 % CI , 14 to 26 ) with chemotherapy ( P<0.001 ) . An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy ( hazard ratio for death in the crizotinib group , 1.02 ; 95 % CI , 0.68 to 1.54 ; P=0.54 ) . Common adverse events associated with crizotinib were visual disorder , gastrointestinal side effects , and elevated liver aminotransferase levels , whereas common adverse events with chemotherapy were fatigue , alopecia , and dyspnea . Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy . CONCLUSIONS Crizotinib is superior to st and ard chemotherapy in patients with previously treated , advanced non-small-cell lung cancer with ALK rearrangement . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00932893 . ) BACKGROUND Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase ( ALK ) are present in a subgroup of non-small-cell lung cancers , representing 2 to 7 % of such tumors . We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib ( PF-02341066 ) , an orally available small-molecule inhibitor of the ALK tyrosine kinase . METHODS After screening tumor sample s from approximately 1500 patients with non-small-cell lung cancer for the presence of ALK rearrangements , we identified 82 patients with advanced ALK-positive disease who were eligible for the clinical trial . Most of the patients had received previous treatment . These patients were enrolled in an exp and ed cohort study instituted after phase 1 dose escalation had established a recommended crizotinib dose of 250 mg twice daily in 28-day cycles . Patients were assessed for adverse events and response to therapy . RESULTS Patients with ALK rearrangements tended to be younger than those without the rearrangements , and most of the patients had little or no exposure to tobacco and had adenocarcinomas . At a mean treatment duration of 6.4 months , the overall response rate was 57 % ( 47 of 82 patients , with 46 confirmed partial responses and 1 confirmed complete response ) ; 27 patients ( 33 % ) had stable disease . A total of 63 of 82 patients ( 77 % ) were continuing to receive crizotinib at the time of data cutoff , and the estimated probability of 6-month progression-free survival was 72 % , with no median for the study reached . The drug result ed in grade 1 or 2 ( mild ) gastrointestinal side effects . CONCLUSIONS The inhibition of ALK in lung tumors with the ALK rearrangement result ed in tumor shrinkage or stable disease in most patients . ( Funded by Pfizer and others ; Clinical Trials.gov number , NCT00585195 . ) PURPOSE Erlotinib is a potent reversible HER1/epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor with single-agent activity in patients with non-small-cell lung cancer ( NSCLC ) . Erlotinib was combined with chemotherapy to determine if it could improve the outcome of patients with NSCLC . PATIENTS AND METHODS TRIBUTE r and omly assigned patients with good performance status and previously untreated advanced ( stage IIIB/IV ) NSCLC to erlotinib 150 mg/d or placebo combined with up to six cycles of carboplatin and paclitaxel , followed by maintenance monotherapy with erlotinib . R and om assignment was stratified by stage , weight loss in the previous 6 months , measurable disease , and treatment center . The primary end point was overall survival ( OS ) . Secondary end points included time to progression ( TTP ) , objective response ( OR ) , and duration of response . RESULTS There were 1,059 assessable patients ( 526 erlotinib Output:	The use of ALK-TKIs significantly increases the risk of developing high- grade ILD and QTc prolongation in lung cancer patients .
MS21035	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Since there is no consensus on the anticaries effectiveness of low-fluoride ( F ) dentifrice , this r and omized clinical trial evaluated its effect in children at different caries activity status . One hundred and twenty 2- to 4-year-old children , half with and half without active caries lesions , were r and omly divided into 2 groups which used 500- or 1,100-µg F/g ( NaF ) dentifrices during 1 year . Caries progression or regression were evaluated as the number of lesions becoming active/cavities or inactive , respectively . The anticaries effect of the low-F dentifrice was similar to the conventional F dentifrice when used by caries-inactive children . However , in children with active caries lesions the low-F dentifrice was less effective than the 1,100-µg F/g dentifrice in controlling the progression of lesions . The data suggest that the child caries activity may be taken into account to recommend a low-F dentifrice BACKGROUND The authors investigated the associations between enamel fluorosis , caries and early fluoride use among Norwegian children who received fluoride supplementation under a protocol similar to the current U.S. protocol . METHODS Two examiners whose techniques were calibrated examined r and omly selected middle-school-aged children living in Bergen , Norway-where the water supply contains less than 0.10 milligrams of fluoride per liter-for both enamel fluorosis and caries by using the Fluorosis Risk Index and modified National Institute of Dental and Craniofacial Research criteria . The authors ascertained past fluoride exposure via a follow-up question naire mailed to parents . RESULTS The question naire had an 88 percent response rate and 87 percent reliability . Adjusted analyses revealed a strong association between regular supplementation ( given in the form of lozenges ) and mild to moderate enamel fluorosis ( odds ratio [ OR ] , 6.85 ; P < .05 ) , as well as fluorosis of lesser severity ( OR , 3.07 ; P < .05 ) . No children who had exclusively used only a pea-sized amount of toothpaste ( 0.1 percent fluoride ) had mild to moderate fluorosis . The authors found a 40 percent reduction in caries risk associated with early use of pea-sized amounts of fluori date d toothpaste and a 46 percent reduction associated with regular use of fluoride supplement lozenges . CONCLUSIONS These findings suggest that both risk of fluorosis development and caries-preventive benefit are associated with regular use of fluoride supplements , and caries prevention was associated with early use of a pea-sized amount of toothpaste . CLINICAL IMPLICATION S These findings underscore the need for clinicians to consider thoroughly- and discuss with a child 's parent or guardian-both the benefit and the potential risk of fluorosis development associated with preventive fluoride agents before introducing them . Clinicians also should emphasize the proper use of such agents PURPOSE To describe oral health status and to evaluate the effectiveness of a caries prevention programme in preschool children . MATERIAL S AND METHODS A sample of 1656 3- to 7-year-old children were examined in kindergartens in 2002 , and 411 3-year-old children were then selected to participate in the prevention programme . The test group A ( n = 156 ) , group B ( n = 118 ) , and the control group ( n = 137 ) were defined for the study . For test group A , supervised toothbrushing was prescribed and for test group B , fluoride gel applications were used . For the control group , children did not undergo any of the aforementioned procedures . Dental caries was assessed according to the World Health Organization ( WHO ) criteria , and oral hygiene according to the Greene-Vermillion simplified oral hygiene index . Preventive programmes were based on oral hygiene instructions , supervised daily toothbrushing , and fluoride gel applications . The relationship between oral hygiene and severity of dental caries was determined by using Fisher 's test . RESULTS The prevalence of dental caries varied between 39.7 % and 90.8 % , and the decayed , missing , and filled teeth ( dmf-t ) varied between 1.3 + /- 0.16 and 5.0 + /- 0.24 . Oral hygiene was satisfactory in 43.2 % of children . During the 3 years of the programme , a significant difference was found between the test and the control groups . The reduction in test group A was 45.4 % and in test group B was 60.1 % . CONCLUSIONS The prevalence and severity of dental caries among the examined children increased with age , and was lower in both the test groups compared with the control group . The professional fluoride applications and proper oral hygiene showed the most effective results in caries prevention OBJECTIVE To assess the impact of a programme regularly supplying free fluoride toothpaste to children on the prevalence and severity of fluorosis and other developmental defects of enamel . DESIGN R and omised , controlled , parallel three-group clinical trial . Two groups received toothpaste containing either 440 or 1450 ppm F ; the third group received no intervention . Children were supplied with toothpaste and advice on its use from the age of 12 months until they were 5 - 6 years old . The participants were a sub sample of those involved in a study that considered the caries benefits of providing free fluoride toothpaste . They were eligible if they completed the main study , lived in four of the nine districts involved and attended schools with 6 or more eligible participants . SETTING Children from the north west of Engl and consuming drinking water containing less than 0.1 ppm F were examined in primary schools . PARTICIPANTS 3731 children completed the main study . Of the 1833 children in the four selected districts , 927 were from schools with six or more participants . METHOD Digital images encompassing the upper and lower anterior sextants were taken of each child when they were 8 - 9 years old . MAIN OUTCOME MEASURES Developmental defects of enamel and dental fluorosis ( TF index ) were recorded on upper central incisors from wet and dry images . RESULTS A total of 703 children were included in the data analysis . In the 1450 ppm F ( n=218 ) , 440 ppm F ( n = 226 ) and control ( n = 259 ) groups the prevalence of dental fluorosis ( TF > 0 ) was 17 % , 15 % and 12 % for the wet ( p > 0.05 ) and 26 % , 24 % and 25 % for the dry ( p > 0.05 ) photographs respectively . The prevalence of TF scores 2 or 3 ( highest score ) was 5 % , 4 % and 2 % and for the wet ( p > 0.05 ) and 7 % , 4 % and 5 % for the dry ( p > 0.05 ) photographs respectively . All subjects identified with TF score 3 were found in the group using the 1450 ppm F toothpaste ( 3 wet and 4 dry ) and there were statistically significant differences between the three groups for both wet ( p = 0.03 ) and dry photographs ( p < 0.01 ) . However , the pairwise comparisons between the groups failed to attain statistical significance . The highest prevalence and severity of demarcated opacities was seen in the control group and for the wet photographs the difference between the three groups attained statistical significance ( p = 0.04 ) . For both the wet and dry photographs the prevalence of any enamel defects ( including fluorosis ) and large demarcated or TF score 3 was similar for the three groups ( p > 0.05 ) . CONCLUSION Previously it has been reported that only the provision of 1450 ppm F toothpaste provides anticaries benefits in a programme of this type . This benefit is accompanied by a slight increase in prevalence of TF score 3 but not the overall prevalence of developmental defects of enamel . Careful targeting and implementation of a programme of this type is required to maximise benefits and minimise risks of fluoride exposure Abstract s on this page have been chosen and edited by Dr Trevor Watts Abstract A low-fluoride dentifrice gave measurable benefit only in the most deprived groups , but a high-fluoride dentifrice improved health in less deprived groups as well OBJECTIVE To assess the impact of regularly supplying free fluoride toothpaste regularly to children , initially aged 12 months , and living in deprived areas of the north west of Engl and on the level of caries in the deciduous dentition at 5 - 6 years of age . A further aim was to compare the effectiveness of a programme using a toothpaste containing 440 ppmF ( Colgate 0 - 6 Gel ) with one containing 1,450 ppmF ( Colgate Great Regular Flavour ) in reducing caries . DESIGN R and omised controlled parallel group clinical trial . Clinical data were collected from test and control groups when the children were 5 - 6 years old . SETTING A programme of posting toothpaste with dental health messages to the homes of children initially aged 12 months . Clinical examinations took place in primary schools . PARTICIPANTS 7,422 children born in 3-month birth cohorts living in high caries areas in nine health districts in north west Engl and . Within each district children were r and omly assigned to test or control groups . INTERVENTIONS Toothpaste , containing either 440 ppmF or 1450 ppmF , and dental health literature posted at three monthly intervals to children in test groups until they were aged 5 - 6 years . MAIN OUTCOME MEASURES The dmft index , missing teeth and the prevalence of caries experience . RESULTS An analysis of 3,731 children who were examined and remained in the programme showed the mean dmft to be 2.15 for the group who had received 1,450 ppmF toothpaste and 2.49 for the 440 ppmF group . The mean dmft for the control group was 2.57 . This 16 % reduction between the 1,450 ppmF and control group was statistically significant ( P<0.05 ) . The difference between the 440 ppmF group and control was not significant . Further analyses to estimate the population effect of the programme also confirmed this relationship . CONCLUSION This study demonstrates that a programme distributing free toothpaste containing 1,450 ppmF provides a significant clinical benefit for high caries risk children living in deprived , non-fluori date d districts OBJECTIVE The objective of this two-year comparative investigation was to assess the anticaries efficacy of three dentifrices commercially available in China . Two products contained the stated active agent sodium monofluorophosphate ( SMFP ) at a concentration of 1.14 % ; one was calcium carbonate-based , the second was silica-based . The third dentifrice tested contained no fluoride and was calcium carbonate-based . METHODS Prior to the start of this double-blind , parallel-group study , all aspects of the study were review ed and approved by the human review committee of the West China College of Stomatology , Sichuan University . All parents signed the approved consent form before the initial evaluations . A total of 1200 qualifying children living in the Chengdu , China area entered the study , and 998 children completed all aspects of the study . Subjects were r and omly assigned to use one of the three dentifrices : 328 participants used the non-fluoride calcium carbonate-based dentifrice ; 341 participants used the 1.14 % SMFP silica-based dentifrice ; and 329 participants used the 1.14 % SMFP calcium carbonate-based dentifrice . Participants were instructed to brush their teeth with their assigned dentifrice twice daily . Brushing instructions were reinforced . RESULTS At the baseline examination , the mean dfs ( decayed and filled tooth surfaces ) scores of the non-fluoride dentifrice group ( 3.60 + /- 6.07),the 1.14 % SMFP silica-based dentifrice group ( 3.53 + /- 5.62 ) , and the 1.14 % SMFP calcium carbonate-based dentifrice group ( 3.54 + /- 5.34 ) were not statistically different ( p > 0.05 ) . After one year , the mean dfs increment of the non-fluoride dentifrice group was 2.19 + /- 4.12 , 1.69 + /- 3.12 for the 1.14 % for the SMFP silica-based dentifrice group , and 1.53 + /- 3.09 for the 1.14 % SMFP calcium carbonate-based dentifrice group ; after two years , the mean dfs increments were 4.73 + /- 5.17 , 2.98 + /- 4.42 , and 2.75 + /- 4.33 , respectively . Both the 1.14 % SMFP calcium carbonate-based and the 1.14 % SMFP silica-based dentifrices provided significantly more caries reduction than the non-fluoride silica-based dentifrice after one year ( -30 % and -23 % ) and two years ( -42 % and -37 % ) of product use . The 1.14 % SMFP calcium carbonate-based dentifrice was not significantly different from the 1.14 % SMFP silica-based dentifrice after one and two years of use . CONCLUSION The results of this clinical study indicate that the 1.14 % SMFP calcium carbonate-based and the 1.14 % SMFP silica-based dentifrices are effective against tooth decay compared to brushing with a non-fluoride toothpaste In Output:	Limited scientific evidence demonstrates that for children younger than 6 years , fluoride toothpaste use is effective in caries control . Ingesting pea-sized amounts or more can lead to mild fluorosis .
MS21036	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Focal therapy is an emerging approach to the treatment of localized prostate cancer . The purpose of this study was to report the 6-month follow-up oncologic and functional data of the initial phase 1 trial of patients treated with focal transrectal MRI-guided focused ultrasound in North America . SUBJECTS AND METHODS Four patients with a prostate-specific antigen ( PSA ) level of 10 ng/mL or less , tumor classification cT2a or less , and a Gleason score of 6 ( 3 + 3 ) were prospect ively enrolled in the study and underwent multiparametric MRI and transrectal ultrasound-guided prostate systematic biopsy . Under MRI guidance and real-time monitoring with MR thermography , focused high-frequency ultrasound energy was delivered to ablate the target tissue . The incidence and severity of treatment-related adverse events were recorded along with responses to serial quality -of-life question naires for 6 months after treatment . Oncologic outcomes were evaluated with multiparametric MRI and repeat transrectal ultrasound-guided biopsy 6 months after treatment . RESULTS Four patients with a total of six target lesions were treated and had complications grade d Clavien-Dindo I or less . Quality -of-life parameters were similar between baseline and 6-months . All four patients had normal MRI findings in the treated regions ( 100 % ) , biopsy showed that three patients ( 75 % ) were clear of disease in the treated regions , representing complete ablation of five target lesions ( 83 % ) . All patients had at least one Gleason 6-positive core outside of the treated zone . CONCLUSION MRI-guided focused ultrasound is a feasible method of noninvasively ablating low-risk prostate cancers with low morbidity . Further investigation and follow-up are warranted in a larger patient series with appropriate statistical analysis of oncologic and functional outcome measures BACKGROUND Tissue preservation by means of focal therapy offers some men with clinical ly significant prostate cancer an alternative to st and ard care that appears to confer favourable genito-urinary outcomes . The precise estimates of these outcomes have so far been based on small series . OBJECTIVE This analysis pools the sexual domain related patient reported outcomes from three prospect i ve , registered studies that represent a range of inclusion criteria . DESIGN , SETTING , AND PARTICIPANTS One-hundred and eighteen men with localised prostate cancer ( prostate specific antigen ≤ 15ng/ml , Gleason ≤ 4 + 3 , stage ≤ T3aN0M0 ) treated in a tissue-preserving manner using high intensity focused ultrasound from three registered studies were included . Data on International Index of Erectile Function ( IIEF-5 ) scores and use of phosphodiesterase-5-inhibitors were collected at baseline , and 1 mo , 3 mo , 6 mo , 9 mo , and 12 mo postoperatively . The IIEF-15 total and individual domain scores were used to assess overall sexual function . Urinary function was assessed with the International Prostate Symptom Score ( IPSS ) , IPSS quality -of-life , and UCLA-Exp and ed Prostate Cancer Index Composite continence question naires . General health status was derived by means of the Charlson score . Multiple linear regression was used to assess whether age , grade , stage , qualitative scores ( IIEF , IPSS , Exp and ed Prostate Cancer Index Composite , Charlson ) , or focal therapy type duration were associated with IIEF-5 and IIEF-15 scores at 12 mo . RESULTS AND LIMITATIONS Median age was 63 yr ( interquartile range [ IQR ] 52 - 70 yr ) . Median IIEF-erectile score at baseline was 23 ( IQR 11 - 28 ) . This declined significantly to 9 ( IQR 3 - 22 , p<0.01 ) at 1 mo , but improved to 20 ( IQR 9 - 29 , p=0.30 ) at 1 yr posttreatment . Changes in total IIEF and other IIEF domains were only significantly different from preoperative values at 1 mo and 3 mo postoperatively . In the same period , the proportion of men using phosphodiesterase-5-inhibitors was 10 % preoperatively , reaching 43 % and 42 % at 6 mo and 9 months before declining to 37 % at 1 yr . The only baseline determinants of postoperative erectile function were total IIEF and IIEF-erectile function scores ( p=0.002 ) . The primary limitation of our study is the relatively short follow-up of 1 yr . CONCLUSION Men who received a range of tissue preserving therapies from the three pertinent studies experienced small decreases in total IIEF , erectile , and individual sexual domain scores that are not significantly different to those recorded at baseline . The only determinant of erectile dysfunction after tissue preserving therapy was preoperative erectile dysfunction status . Tissue preservation confers a high probability of maintaining erectile function that appears independent of all perioperative factors with the exception of baseline status . PATIENT SUMMARY In this report , the largest prospect ively collected and published set of patients with erectile dysfunction outcomes post-focal therapy for prostate cancer , we have found a return to baseline International Index of Erectile Function-erectile and total International Index of Erectile Function scores by 6 mo post-focal therapy which was maintained at 1 yr , with the majority of patients not on any form of medical treatment for their erectile dysfunction at that point . Focal therapy may represent a suitable alternative for men of any age or comorbidity wishing to maintain erectile function BACKGROUND High-intensity focused ultrasound ( HIFU ) is a nonsurgical therapy for selected patients with localized prostate cancer ( PCa ) . OBJECTIVE The long-term oncologic and morbidity outcomes of primary HIFU therapy for localized PCa were evaluated in a prospect i ve , single-arm , single-institution cohort study . DESIGN , SETTING , AND PARTICIPANTS Participants were patients treated with HIFU for localized PCa from 1997 to 2009 . Excluded were patients with local recurrence following radiotherapy . A second HIFU session was systematic ally performed in patients with biopsy-proven local recurrence . INTERVENTION Whole-gl and prostate ablation with transrectal HIFU . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Incontinence was assessed using the Ingelman-Sundberg score , and potency was assessed using the five-item version of the International Index of Erectile Function ( IIEF-5 ) scores . Primary outcomes were survival rates ( biochemical-free , cancer-specific , metastasis-free , and overall survival ) . Secondary outcomes were morbidity rates . Median follow-up was 6.4 yr ( range : 0.2 - 13.9 ) . The Kaplan-Meier method was used to determine survival estimates , and multivariate analysis was used to determine predictive factors of biochemical progression . RESULTS AND LIMITATIONS A total of 1002 patients were included . The median nadir prostate-specific antigen ( PSA ) was 0.14 ng/ml , with 63 % of patients reaching a nadir PSA ≤0.3 ng/ml . Sixty percent of patients received one HIFU session , 38 % received two sessions , and 2 % received three sessions . The 8-yr biochemical-free survival rates ( Phoenix definition ) were 76 % , 63 % , and 57 % for low- , intermediate- , and high-risk patients , respectively ( p < 0.001 ) . At 10 yr , the PCa-specific survival rate and metastasis-free survival rate ( MFSR ) were 97 % and 94 % , respectively . Salvage therapies included external-beam radiation therapy ( EBRT ) ( 13.8 % ) , EBRT plus and rogen-deprivation therapy ( ADT ) ( 9.7 % ) , and ADT alone ( 12.1 % ) . Severe incontinence and bladder outlet obstruction decreased with refinement in the technology , from 6.4 % and 34.9 % to 3.1 % and 5.9 % , respectively . Limitations included the fact that the study was a single-arm study without a comparison group , technological improvements , changes in surgical protocol during the study , and the use of ADT to downsize the prostate in 39 % of patients . CONCLUSIONS HIFU is a potentially effective treatment of localized PCa , with a low PCa-specific mortality rate and a high MFSR at 10 yr as well as acceptable morbidity BACKGROUND In selected patients with unilateral , organ-confined prostate cancer ( PCa ) , hemiablation of the affected lobe might be feasible to achieve acceptable cancer control with fewer complications . OBJECTIVES To assess the oncologic and functional outcomes of focal high-intensity focused ultrasound ( HIFU ) hemiablation in unilateral organ-confined PCa . DESIGN , SETTING AND PATIENTS Single-center prospect i ve evaluation of HIFU hemiablation for unilateral organ-confined PCa was performed from July 2009 through December 2013 . INTERVENTION Cancer localization was done with transrectal ultrasound-guided biopsy and multiparametric magnetic resonance imaging followed by HIFU hemiablation . OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS Oncologic outcomes were analyzed with control biopsies and prostate-specific antigen ( PSA ) measurement . Functional outcomes were assessed with vali date d question naires for genitourinary symptoms . RESULTS AND LIMITATIONS Of 71 HIFU hemiablation patients , 67 completed the study protocol . The mean age was 70.2 yr ( st and ard deviation : 6.8 yr ) , and median PSA was 6.1 ng/ml ( interquartile range [ IQR ] : 1.6 - 15.5 ng/ml ) . Median maximum cancer-core length was 3 mm ( IQR : 2 - 10 mm ) , and total cancer length was 6.5 mm ( IQR : 2 - 24 mm ) . Gleason score was 6 ( 3 + 3 ) in 58 patients ( 86.6 % ) and 7 ( 3 + 4 ) in 9 patients ( 13.4 % ) . Median follow-up was 12 mo ( IQR : 6 - 50 mo ) , and at 12 mo , 56 of 67 patients had a negative control biopsy in the treated lobe . At 3 mo , all patients were continent , and potency was maintained in 11 of 21 preoperatively potent patients ( confidence interval , 0.18 - 0.69 ) . Complications included 8 % Clavien-Dindo grade 2 and 2.8 % grade 3 events . CONCLUSIONS Focal HIFU hemiablation appears to achieve acceptable oncologic outcomes with low morbidity and minimal functional changes . Longer follow-up will establish future considerations . PATIENT SUMMARY This study showed that high-intensity focused ultrasound hemiablation in selected patients with unilateral organ-confined prostate cancer can be used for satisfactory cancer control with minimal effect on genitourinary functions PURPOSE Multiparametric magnetic resonance imaging and magnetic resonance imaging targeted biopsy may improve the detection of clinical ly significant prostate cancer . However , st and ardized prospect i ve evaluation is limited . MATERIAL S AND METHODS A total of 294 consecutive men with suspicion of prostate cancer ( 186 primary , 108 repeat biopsies ) enrolled in 2013 underwent 3 T multiparametric magnetic resonance imaging ( T2-weighted , diffusion weighted , dynamic contrast enhanced ) without endorectal coil and systematic transperineal cores ( median 24 ) independently of magnetic resonance imaging suspicion and magnetic resonance imaging targeted cores with software registration ( median 4 ) . The highest Gleason score from each biopsy method was compared . McNemar 's tests were used to evaluate detection rates . Predictors of Gleason score 7 or greater disease were assessed using logistic regression . RESULTS Overall 150 cancers and 86 Gleason score 7 or greater cancers were diagnosed . Systematic , transperineal biopsy missed 18 Gleason score 7 or greater tumors ( 20.9 % ) while targeted biopsy did not detect 11 ( 12.8 % ) . Targeted biopsy of PI-RADS 2 - 5 alone overlooked 43.8 % of Gleason score 6 tumors . McNemar 's tests for detection of Gleason score 7 or greater cancers in both modalities were not statistically significant but showed a trend of superiority for targeted primary biopsies ( p=0.08 ) . Sampling efficiency was in favor of magnetic resonance imaging targeted prostate biopsy with 46.0 % of targeted biopsy vs 7.5 % of systematic , transperineal biopsy cores detecting Gleason score 7 or greater cancers . To diagnose 1 Gleason score 7 or greater cancer , 3.4 targeted and 7.4 systematic biopsies were needed . Limiting biopsy to men with PI-RADS 3 - 5 would have missed 17 Gleason score 7 or greater tumors ( 19.8 % ) , demonstrating limited magnetic resonance imaging sensitivity . PI-RADS scores , digital rectal examination findings and prostate specific antigen greater than 20 ng/ml were predictors of Gleason score 7 or greater disease . CONCLUSIONS Compared to systematic , transperineal biopsy as a reference test , magnetic resonance imaging targeted biopsy alone detected as many Gleason score 7 Output:	Conclusions : Early evidence suggests that partial gl and ablation is a safe treatment option for men with localized disease .
MS21037	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background — For patients with ischemic mitral regurgitation ( MR ) , it is not clear whether adjunctive mitral valve ( MV ) repair at the time of coronary artery bypass graft surgery ( CABG ) is beneficial . We sought to test the hypothesis that MV repair with CABG is superior to CABG alone in improving MR without increasing operative or long-term mortality . Methods and Results — A total of 107 consecutive patients with moderate or severe ischemic MR , as determined by preoperative echocardiography , underwent CABG with concomitant MV repair ( repair group , n=50 ) or CABG only ( CABG group , n=57 ) . Degree of MR was grade d as none , mild , moderate , or severe by the proximal isovelocity surface area method . The groups were similar with respect to age , gender , baseline New York Heart Association class , ejection fraction , and number of bypass grafts . The repair group had a higher percentage of patients with atrial fibrillation or severe MR than the CABG group . The operative mortality was significantly higher for the repair group ( 12 % ) than the CABG group ( 2 % ) , whereas the 5-year actuarial survival rate of the 2 groups was similar ( 88%±5 % versus 87%±6 % ) . On multivariate logistic regression analysis , older age , higher New York Heart Association class , and atrial fibrillation were independent predictors of operative mortality ( P<0.05 ) . Among patients with severe MR , ischemic MR was improved in all patients of the repair group and in 67 % of patients in the CABG group ( P<0.001 ) , whereas improvement rates in patients with moderate MR were similar in the 2 groups ( 75 % versus 67 % , P = NS ) . Conclusions — Although MV repair appears to be more effective at reducing ischemic functional MR , CABG alone may be a preferable treatment option for patients with moderate MR and high operative risk factors such as old age or atrial fibrillation Background —The optimal management of moderate ( 3 + on a scale of 0 to 4 + ) ischemic mitral regurgitation ( MR ) remains controversial . Some advocate CABG alone , whereas others favor concomitant mitral annuloplasty . To clarify the optimal management of these patients , we evaluated the early impact of isolated CABG on moderate ischemic MR . Methods and Results —Between January 1992 and August 1999 , 136 patients ( 54 % male , mean age 70.5 years , mean New York Heart Association class 2.7 , mean ejection fraction 38.1 % ) with a preoperative diagnosis of moderate ischemic MR , without leaflet prolapse or pathology , underwent isolated CABG . Thirty-eight ( 28 % ) of 136 patients had intraoperative transesophageal echocardiography ( TEE ) before CABG , and 68 ( 50 % ) had postoperative transthoracic echocardiography ( TTE ) within 6 weeks of surgery . The subgroups of patients undergoing intraoperative TEE and postoperative TTE had preoperative characteristics similar to the overall group . The 30-day operative mortality was 2.9 % ( 4/136 ) . Intraoperative TEE down grade d the severity of MR to mild or less ( 0 to 2 + ) in 89 % ( 34/38 ) . On postoperative TTE , 40 % ( 27/68 ) continued to have at least moderate MR ( 3 to 4 + ) , 51 % ( 35/68 ) improved somewhat to mild ( 2 + ) MR , and only 9 % ( 6/68 ) had resolution of their MR ( 0 to 1 + ) . The mean preoperative , intraoperative , and postoperative MR grade s were 3.0±0.0 , 1.4±1.0 , and 2.3±0.8 , respectively ( P < 0.001 ) . Conclusions —CABG alone for moderate ischemic MR leaves many patients with significant residual MR and may not be the optimal therapy for most patients . Intraoperative TEE may significantly underestimate the severity of ischemic MR . A preoperative diagnosis of moderate MR may warrant concomitant mitral annuloplasty OBJECTIVE To investigate mitral regurgitation occurring early in the course of acute myocardial infa rct ion with respect to its incidence , the impact of infa rct size and location , the accuracy of clinical detection , the contribution of global and regional left ventricular performance , and its influence on prognosis . DESIGN Prospect i ve observational study derived from patients entering Phase I of the Thrombolysis in Myocardial Infa rct ion ( TIMI ) trial . SETTING Multicenter trial involving 13 university-affiliated medical centers . PATIENTS A total of 206 patients studied within 7 hours of symptom onset during their first myocardial infa rct ion . MEASUREMENTS Contrast left ventriculography was used to document mitral regurgitation . RESULTS Mitral regurgitation was present in 27 patients ( 13 % ) . Although the presence of regurgitation correlated with the site of infa rct ion ( 20 of 27 had anterior infa rct ions ) and the number of akinetic chords , it was not statistically related to the peak creatine kinase value or to left ventricular chamber size or filling pressure . A murmur of mitral regurgitation was heard in only 2 patients ( 1 incorrectly ) . The presence of early mitral regurgitation predicted cardiovascular mortality at 1 year by univariate ( relative risk , 12.2 ; 95 % Cl , 3.5 to 42 ; P less than 0.0001 ) and multivariate ( relative risk , 7.5 ; Cl , 2.0 to 28.6 ; P = 0.0008 ) analyses . CONCLUSIONS Mitral regurgitation in early myocardial infa rct ion is generally clinical ly " silent , " is more common in anterior infa rct ion , is associated with regional dysfunction but not early ventricular dilation or peak enzyme release , and is an important predictor of cardiovascular mortality Background — Whether mitral valve repair during coronary artery bypass grafting ( CABG ) improves survival in patients with ischemic mitral regurgitation ( MR ) remains unknown . Methods and Results — Patients with ejection fraction ⩽35 % and coronary artery disease amenable to CABG were r and omized at 99 sites worldwide to medical therapy with or without CABG . The decision to treat the mitral valve during CABG was left to the surgeon . The primary end point was mortality . Of 1212 r and omized patients , 435 ( 36 % ) had none/trace MR , 554 ( 46 % ) had mild MR , 181 ( 15 % ) had moderate MR , and 39 ( 3 % ) had severe MR . In the medical arm , 70 deaths ( 32 % ) occurred in patients with none/trace MR , 114 ( 44 % ) in those with mild MR , and 58 ( 50 % ) in those with moderate to severe MR . In patients with moderate to severe MR , there were 29 deaths ( 53 % ) among 55 patients r and omized to CABG who did not receive mitral surgery ( hazard ratio versus medical therapy , 1.20 ; 95 % confidence interval , 0.77–1.87 ) and 21 deaths ( 43 % ) among 49 patients who received mitral surgery ( hazard ratio versus medical therapy , 0.62 ; 95 % confidence interval , 0.35–1.08 ) . After adjustment for baseline prognostic variables , the hazard ratio for CABG with mitral surgery versus CABG alone was 0.41 ( 95 % confidence interval , 0.22–0.77 ; P=0.006 ) . Conclusion — Although these observational data suggest that adding mitral valve repair to CABG in patients with left ventricular dysfunction and moderate to severe MR may improve survival compared with CABG alone or medical therapy alone , a prospect i ve r and omized trial is necessary to confirm the validity of these observations . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00023595 BACKGROUND The development of ischemic mitral regurgitation ( MR ) after myocardial infa rct ion may impose hemodynamic load during a period of active left ventricular remodeling and promote heart failure ( HF ) . However , few data are available on the relationship between ischemic MR and the long-term risk for HF . METHODS We prospect ively studied 1190 patients admitted for acute myocardial infa rct ion . Mitral regurgitation was assessed by echocardiography and was considered mild , moderate , and severe when the regurgitant jet area occupied less than 20 % , 20 % to 40 % , and greater than 40 % of the left atrial area , respectively . The median duration of follow-up was 24 months ( range , 6 - 48 months ) . RESULTS Mild and moderate or severe ischemic MR was present in 39.7 % and 6.3 % of patients , respectively . After adjusting for ejection fraction and clinical variables ( age , sex , Killip class , previous infa rct ion , hypertension , diabetes mellitus , anterior infa rct ion , ST-elevation infa rct ion , and coronary revascularization ) , compared with patients without MR , the hazard ratios for HF were 2.8 ( 95 % confidence interval [ CI ] , 1.8 - 4.2 ; P<.001 ) and 3.6 ( 95 % CI , 2.0 - 6.4 ; P<.001 ) in patients with mild and moderate or severe ischemic MR , respectively . The adjusted hazard ratios for death were 1.2 ( 95 % CI , 0.8 - 1.8 ; P = .43 ) and 2.0 ( 95 % CI , 1.2 - 3.4 ; P = .02 ) in patients with mild and moderate or severe MR , respectively . CONCLUSIONS There is a grade d independent association between the severity of ischemic MR and the development of HF after myocardial infa rct ion . Even mild ischemic MR is associated with an increase in the risk of HF OBJECTIVE Surgical management of moderate chronic ischemic mitral valve regurgitation is still debated . The aim of this study was to evaluate the effect of adding mitral valve repair to coronary artery bypass grafting on clinical outcomes and left ventricular remodeling in patients who underwent coronary artery bypass grafting alone versus coronary artery bypass grafting plus mitral valve repair in a r and omized trial . METHODS Between February 2003 and May 2007 , 102 patients were eligible for this study and were r and omly assigned to one of 2 groups by means of card allocation : coronary artery bypass grafting plus mitral valve repair ( CABG plus MVR group ; 48 patients , 47 % ) or coronary artery bypass grafting alone ( CABG group ; 54 patients , 53 % ) . The 2 groups were similar regarding demographics , perioperative clinical data , and outcomes . There were differences regarding cardiopulmonary bypass ( P < .0001 ) and aortic crossclamp ( P < .0001 ) times . Exercise tests were performed for all survivors to evaluate tolerance to exercise and variability on grade of mitral regurgitation and systolic pulmonary arterial pressure . The study was blinded for physicians and nurses involved in postoperative care and clinical follow-up . The mean follow-up was 32 + /- 18 months . RESULTS Overall in-hospital mortality was 3 % ( 3 patients ) . One ( 1.8 % ) patient died in the CABG group , and 2 ( 4.1 % ) patients died in the CABG plus MVR group . Survival rates + /- st and ard error at 5 years for patients in the CABG and CABG plus MVR groups were 88.8 % + /- 3.2 % and 93.7 % + /- 3.1 % , respectively . A significant difference was found between the 2 groups with regard to mean New York Heart Association class ( P < .0001 ) , left ventricular end-diastolic diameter ( P < .01 ) , left ventricular end-systolic diameter ( P < .01 ) , pulmonary arterial pressure ( P < .0001 ) , and left atrial size ( P < .01 ) . At follow-up , coronary artery bypass grafting alone was able to reduce mitral regurgitation grade in 40 % of patients , whereas in the remaining patients mitral regurgitation grade remained stable or worsened . In the CABG group , among the 17 patients with mild mitral regurgitation and 12 patients with moderate mitral regurgitation at rest , 7 ( 40 % ) and 9 ( 75 % ) patients , respectively , had worsening in mitral regurgitation grade and pulmonary artery pressure during exercise . CONCLUSIONS The efficacy of adding mitral valve repair to coronary artery bypass grafting is well demonstrated by the improvement of New York Heart Association functional class and percentage of left ventricular ejection fraction and by the decrease of mitral regurgitation grade , left ventricular end-diastolic diameter , left ventricular end-systolic diameter , pulmonary artery pressure , and left atrial size . Moreover , coronary artery bypass grafting alone left more patients with heart failure Output:	Review of current literature showed mixed results in terms of improvement in functional status but failed to show any survival benefit of performing MVR along with CABG .
MS21038	*TASK* the task is to summarize an input biomedical literature in six sentences *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 paper aims to describe factors associated with HIV sero-status in young , rural South African women and the relationship between intimate partner violence ( IPV ) and HIV . METHODS A total of 1295 sexually active female volunteers , aged 15 - 26 , from 70 villages were recruited to participate in a cluster r and omized controlled trial of an HIV behavioural intervention . The main measures were HIV sero-status , and IPV and sexual practice s measured using a question naire administered during baseline interviews . RESULTS About 12.4 % of women had HIV and 26.6 % had experienced more than one episode of physical or sexual IPV . After adjusting for age , HIV infection was associated with having three or more past year partners [ odds ratio ( OR ) 2.39 ; 95 % confidence interval ( 95 % CI ) 1.48 - 3.85 ] , sex in past 3 months ( OR 3.33 ; 95 % CI 1.87 - 5.94 ) , a partner three or more years older ( OR 1.69 ; 95 % CI 1.16 - 2.48 ) , and a more educated partner ( OR 1.91 ; 95 % CI 1.30 - 2.78 ) . IPV was associated with HIV in two-way analyses ( OR 1.56 ; 95 % CI 1.08 - 2.23 ) , but the effect was non-significant after adjusting for HIV risk behaviours . The experience of IPV was strongly associated with past year partner numbers , time of last sex , and partner 's education ; it was also marginally associated with partner age difference . Adverse experiences in childhood , including sexual abuse , increased the likelihood of having more past year partners ( OR 1.43 ; 95 % CI 1.21 - 1.69 ) . CONCLUSIONS IPV was strongly associated with most of the identified HIV risk factors . Our findings provide further evidence of links between IPV and HIV among women and the importance of joint prevention OBJECTIVE To describe factors associated with HIV infection in men aged 15 - 26 years . SETTING Rural Eastern Cape Province , South Africa . SAMPLE A total of 1277 sexually experienced Xhosa male volunteers from 70 villages participating in a cluster r and omized controlled trial of an HIV behavioural intervention . Xhosas circumcise during manhood initiation rituals . DESIGN Cross-sectional , analysis of the study 's baseline interviews . MAIN MEASURE HIV sero-status , sexual practice s measured with an interviewer-administered question naire . RESULTS About 2 % of the men were HIV positive . A logistic regression model showed HIV positivity to be associated with age ( OR 1.55 ; 95%CI 1.22 - 1.95 ) , having made a woman pregnant ( OR 2.93 ; 95 % CI 1.28 - 6.68 ) , having been circumcised ( OR 0.40 ; 95 % CI 0.16 - 0.98 ) , and having had sex with a man ( OR 3.61 ; 95 % CI 1.0 - 13.0 ) . CONCLUSIONS Our findings provide further evidence to suggest that circumcision is protective . There was much heterosexual risk taking among men but only pregnancy ( with its association with sexual frequency ) predicted HIV sero-positivity . Although relatively rare , same-sex sexual experiences were a risk factor . Male-male sexual contact is rarely assessed in HIV research in Africa and almost never addressed in general HIV prevention programming . Our findings suggest that it should be given more attention To better underst and the prevalence , incidence , and risk factors for sexually transmitted diseases ( STDs ) among female adolescents , a prospect i ve 6-month cohort study was conducted at four teen clinics in a southeastern city . At enrollment , 260 ( 40 % ) of 650 sexually active females ages 14 - 19 years had an STD : chlamydia , 27 % ; herpes simplex virus type 2 ( HSV-2 ) , 14 % ; gonorrhea , 6 % ; trichomoniasis , 3 % ; and hepatitis B , 2 % . At follow-up , 112 ( 23 % ) of 501 participants had an incident infection : chlamydia , 18 % ; HSV-2 , 4 % ; gonorrhea , 4 % ; and trichomoniasis , 3 % . At either enrollment or follow-up , 53 % had > /=1 STD ; of those with 1 lifetime partner , 30 % had an STD . Having a new partner ( odds ratio [ OR ] , 2.2 ; 95 % confidence interval [ CI ] , 1 . 1 - 4.2 ) or friends who sell cocaine ( OR , 1.6 ; CI , 1.0 - 2.6 ) was independently associated with incident infection . STD incidence and prevalence were extremely high in this population , even in teenagers with only 1 lifetime partner . Individual risk behaviors appeared less important for STD risk than population factors Objectives : To evaluate tolerance for the oral administration of zidovudine ( ZDV ) during labor and measure the result ing ZDV concentrations in umbilical cord blood . Design : A cross-sectional study of women in a placebo-controlled trial of short-course ZDV ( twice a day from 36 weeks ' gestation until labor and every 3 h during labor ) to prevent perinatal HIV transmission in Bangkok . Methods : Umbilical cord blood was collected . Sixty control specimens and specimens from 372 women ( 182 in the ZDV group , 190 in the placebo group ) were tested for ZDV by radioimmunoassay ( lower detection limit < 1 ng/ml ) . Results : All women in the ZDV group took one or more labor dose , 170 ( 93 % ) took their last dose within 3 h of delivery , and only five ( 3 % ) experienced nausea or vomiting , a proportion similar to the placebo group . The median concentration of ZDV in the cord blood in the ZDV group was 252 ng/ml ( range , < 1–1133 ng/ml ) ; 31 ( 17 % ) specimens were less than 130 ng/ml ( 0.5 μM ) , the concentration thought to be active against HIV in vitro . Median concentrations were 189 ng/ml in specimens from women taking one or two labor doses , 290 ng/ml in those taking three or four doses , and 293 ng/ml in those taking more than four doses ( P < 0.01 ) . The ZDV concentration was not associated with time since the last dose , body weight , or perinatal transmission . Conclusion : Oral intrapartum ZDV was feasible and well tolerated . Most ZDV concentrations in the cord blood after oral dosing during labor were at therapeutic concentrations but were lower than those reported after continuous intravenous administration . Although concentrations were not associated with perinatal transmission , these data do not exclude the possibility that intrapartum and neonatal chemoprophylaxis is effective Objectives : To determine risk factors for HIV-1 infection in young men in northern Thail and . Methods : At enrollment into a prospect i ve study , data were collected from a self-administered question naire and serologic testing on a cohort of 1115 young men selected by lottery for conscription . Results : The overall HIV-1 infection rate was 6.9 % ; however , the rate was 15.3 % among the 387 ( 34.7 % ) men who had been living in the upper north subregion of Thail and compared with 2.5 % for the remaining 728 men ( P < 0.001 ) . A history of sex with female prostitutes was reported by 74.7 % of men and increased frequency of this type of sex was highly associated with HIV-1 infection and a history of sexually transmitted disease ( STD ) symptoms ( x2 for trend , P < 0.001 ) . In stratified and multivariate analyses , however , history of STD symptoms , reported by 42.5 % of the cohort , was most strongly associated with HIV-1 infection . Only 42.8 % of men who reported sex with prostitutes had used condoms more than half the time . Conclusions : Young men in the general population in northern Thail and are at high risk for HIV-1 infection via sex with female prostitutes ; STD are highly associated with HIV-1 infection . Increasing condom use and controlling STD should be immediate goals of HIV control programs Background : To treat chlamydial infection , the Centers for Disease Control and Prevention recommends either a single dose of azithromycin or a 7‐day course of doxycycline . Cost is a concern with the single‐dose regimen ; compliance is a concern with the multidose regimen . Goal : To compare the use‐effectiveness of azithromycin and doxycycline for preventing persistence or recurrence of Chlamydia trachomatis infection in women and to evaluate associated risk behaviors . Study Design : One hundred and ninety‐six chlamydia‐infected women and their sex partners were recruited into a r and omized controlled trial of single‐dose versus multidose regimens in seven public health clinics , with no incentives for enrollment , compliance , or follow‐up . The outcome measure was a positive test for C. trachomatis by polymerase chain reaction testing at 1 month after treatment . Results : C. trachomatis positivity at 1 month was similar for women receiving single‐dose ( 5.1 % , 5/98 ) and multidose therapy ( 4.1 % , 4/98 ) . Reported compliance among 73 women taking multidose therapy was 94.5 % . A twofold to threefold increased risk of chlamydial persistence or recurrence was observed among women who were ≤24 and white or who reported : a recent new partner , multiple partners , or a partner who may have had multiple partners at the time of enrollment or that not all partners were treated during the 1‐month follow‐up period after initiation of treatment . Conclusions : The use‐effectiveness of single‐dose and multidose therapy was comparably high . Observed rates of persistence or recurrence were consistent with reported rates of pharmacological treatment failure . However , all women with C. trachomatis detected at 1 month had behavioral risk factors that may have contributed to reinfection Objective To determine the incidence of HIV-1 infection and associated risk factors among young , seronegative , and sexually active women in a mixed rural and urban population in southern Rw and a. Design A prospect i ve cohort study . Methods Between October 1991 and April 1993 , we completed a 2-year follow-up survey among HIV-1-seronegative women aged ≤30 years at the time of their initial HIV-1 screening during pregnancy . All women aged ≤25 years and a r and omly selected sample of 26–30-year olds were invited to participate from five prenatal clinics in the Butare region . The interview focused on potential risk factors for HIV-1 acquisition during the 2-year interval between blood collection . Results Out of 1524 women selected , 1150 ( 75 % ) participated in the follow-up survey . The 2-year incidence of HIV-1 infection was 2.7 % [ 95 % confidence interval ( CD , 1.8–3.9 ] . Teenage women were at the highest risk ( incidence , 10.5 % ; 95 % Cl , 5.2–19.4 ) , with incidence leveling off with increasing age ( P < 0.001 ) . Women who began sexual activity recently were also at higher risk ; the lowest risk category consisted of women aged 26–30 years with 5 or more years of sexual experience . The more urban the geographic residence of the woman , the more likely she was to have acquired HIV-1 infection ( P < 0.001 ) . In the urban and peri-urban zones , the poorest women were at significantly higher risk of incident HIV-1 infection than women reporting higher household income . In a multivariate analysis , young maternal age , marital status ( being single , divorced or widowed ) , multiple sexual partners , and a history of sexually transmitted diseases remained strongly associated with incident HIV-1 infection . Geographic residence , hormonal contraception , and receipt of injections were no longer significantly associated with incident HIV-1 infection when these other factors were accounted for simultaneously . Conclusion Among young Rw and an women , the early years of sexual activity are particularly dangerous for acquisition of HIV-1 infection . Interventions should focus on young teenagers before they become sexually active Introduction : Little is known regarding whether partner characteristics explain sex differences in sexually transmitted infection ( STI ) rates in nonclinic-based , school-aged African American youth . Material s and Methods : A r and om digit dial household sample of 14- to 19-year-old youth in San Francisco reported the total number , age , race , and perceived history of incarceration , gang membership , and level of sexual activity of their partners . Youth were tested for gonorrhea and chlamydia . Results : Female participants were more likely than male participants to have a partner who was older or had been incarcerated and less likely to have a non-African American partner . Controlling for partner number , female 's odds ratio ( OR ) for having an STI was 1.39 ( 95 % confidence interval [ CI ] = 0.98–1.98 ; P = 0.07 ) . Controlling for partner incarceration and number of partners , the borderline sex difference was eliminated ( OR = 1.07 ; 95 % CI = 0.70–1.63 ) . Conclusion : Sex differences in STI rates among African American adolescents may be determined more by the risk of the partner than the risk of the individual Objectives : To examine differences in population based rates Output:	Partner attributes assessed most frequently included the following : age , race/ethnicity , multiple sex partners , and STI symptoms . Older partners were associated with prevalent STIs but largely unrelated to incidence . Black race was associated with STIs but not uniformly . Partners with multiple partners and STI symptoms seem to be associated with STIs predominantly among females . Although significant associations were reported , weaker evidence exists for the following : other partner sociodemographics , sexual and other behaviors ( sexual concurrency , intimate partner violence , substance use , travel ) , and STI history . There were no apparent differences by STI . Partner attributes are independently associated with STIs among male and female adolescents worldwide .
MS21039	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Some studies have suggested that helminth infections increase the risk of malaria infection and are associated with increased number of malaria attacks and anaemia . Thus interventions to control helminth infections may have an impact on incidence of clinical malaria and anaemia . The current study assessed the impact of two anthelmintic treatment approaches on malaria infection and on anaemia in school and pre-school children in Magu district , Tanzania . Methods A total of 765 children were enrolled into a prospect i ve r and omized anthelmintic intervention trial following a baseline study of 1546 children . Enrolled children were r and omized to receive either repeated treatment with praziquantel and albendazole four times a year ( intervention group , 394 children ) or single dose treatment with praziquantel and albendazole once a year ( control group , 371 children ) . Follow up examinations were conducted at 12 and 24 months after baseline to assess the impact of the intervention . Stool and urine sample s were collected and examined for schistosome and soil transmitted helminth infections . Blood sample s were also collected and examined for malaria parasites and haemoglobin concentrations . Monitoring of clinical malaria attacks was performed at each school during the two years of the intervention . Results Out of 1546 children screened for P. falciparum , S. mansoni , S. haematobium , hookworm and T. Trichiura at baseline , 1079 ( 69.8 % ) were infected with at least one of the four parasites . There was no significant difference in malaria infection ( prevalence , parasite density and frequency of malaria attacks ) and in the prevalence of anaemia between the repeated and single dose anthelmintic treatment groups at 12 and 24 months follow up ( p > 0.05 ) . However , overall , there was significant improvement in mean haemoglobin concentrations ( p < 0.001 ) from baseline levels of 122.0g/L and 123.0g/L to 136.0g/L and 136.8g/L for the repeated and single dose treatment groups , respectively , at 24 months follow-up which result ed in significant reduction in prevalence of anaemia . Conclusions These results suggest that repeated anthelmintic treatment did not have an impact on malaria infection compared to single dose treatment . However , both treatment approaches had overall impact in terms of improvements of haemoglobin levels and hence reductions in prevalence of anaemia OBJECTIVES This study hypothesized that besides iron deficiency , intestinal parasites infection is also a determinant of anemia in schoolchildren in rural Vietnam . METHODS 400 primary schoolchildren from 20 primary schools in Tam Nong district , a poor rural area in Vietnam , were r and omly selected from enrollment lists . Venous blood ( 5ml ) was collected in a cross sectional study and analyzed for hemoglobin ( Hb ) , serum ferritin ( SF ) , serum transferrin receptor ( TfR ) , serum C-reactive protein ( CRP ) and total immunoglobulin E ( IgE ) . Stools sample s were examined for hookworm , Trichuris , and Ascaris infection . Logistic regression was used to assess the effect of intestinal parasites on anemia . RESULTS The prevalence of anemia ( Hb < 115g/l ) was 25 % . Iron deficiency ( TfR > 8.5mg/L ) occurred in 2 % of the children . The prevalence of intestinal parasites was 92 % with the highest prevalence for Trichuris ( 76 % ) and Ascaris ( 71 % ) . More than 30 % and 80 % of the children showed an elevated CRP ( > or = 8 mg/L ) and IgE ( > 90 IU/ml ) concentration . Anemia status was borderline significantly associated with SF and not associated with TfR and CRP . The prevalence odds ratio for Trichuris infection was 1.96 ( 95 % CI 1.07 - 3.59 ) and 2.00 ( 95 % CI 1.08 - 3.65 ) with iron deficiency reflected by TfR and SF , respectively . CONCLUSION Anemia is highly prevalent among schoolchildren in Vietnam but may not be associated with iron deficiency . Trichuris infection is associated with a doubled risk of anemia , not mediated through iron deficiency . Chronic infection may play a role in anemia , but needs further investigation We evaluated the effects of the Zanzibar school-based deworming program on the iron status of primary school children . Parasitologic and nutritional assessment s were carried out at baseline , 6 mo , and 12 mo in 4 nonprogram schools ( n = 1002 ) , 4 schools in which students received twice-yearly deworming ( n = 952 ) , and 4 schools in which students received thrice-yearly deworming ( n = 970 ) with 500 mg generic mebendazole . Schools were r and omly selected for evaluation and allocated to program groups . Relative to no treatment , thrice-yearly deworming caused significant decreases in protoporphyrin concentrations and both deworming regimens caused marginally significant increases in serum ferritin concentrations . The average annual changes in protoporphyrin concentrations were -5.9 and -23.5 micromol/mol heme in the control and thrice-yearly deworming groups , respectively ( P < 0.001 ) . The average changes in ferritin concentration were 2.8 and 4.5 microg/L , respectively ( P = 0.07 ) . Deworming had no effect on annual hemoglobin change or prevalence of anemia . However , the relative risk of severe anemia ( hemoglobin < 70 g/L ) was 0.77 ( 95 % confidence limits : 0.39 , 1.51 ) in the twice-yearly deworming group and 0.45 ( 0.19 , 1.08 ) in the thrice-yearly deworming group . The effects on prevalence of high protoporphyrin values and incidence of moderate-to-severe anemia ( hemoglobin < 90 g/L ) were significantly greater in children with > 2000 hookworm eggs/g feces at baseline . We estimate that this deworming program prevented 1260 cases of moderate-to-severe anemia and 276 cases of severe anemia in a population of 30,000 schoolchildren in 1 y. Where hookworm is heavily endemic , deworming programs can improve iron status and prevent moderate and severe anemia , but deworming may be needed at least twice yearly BACKGROUND Iron deficiency and its consequent anemia constitute the commonest micronutrient deficiency in the world . OBJECTIVE We investigated whether long-term , weekly iron-folate supplements administered at school would improve hemoglobin and ferritin concentrations in adolescent girls , including those with mild-to-moderate anemia and hemoglobin concentrations indicating borderline anemia . DESIGN Subjects were 266 girls with hemoglobin concentrations of 80 - 119.9 g/L ( group A ) and 358 girls with hemoglobin concentrations of 120 - 130 g/L ( group B ) who were otherwise healthy . Two hundred sixty-six girls in group A and 268 girls in group B were r and omly assigned to receive either 60 or 120 mg Fe plus 3.5 mg folic acid weekly for 22 wk . Ninety of the girls in group B were r and omly assigned to receive only 5 mg folic acid weekly . Capillary hemoglobin and plasma ferritin were measured at baseline and after 12 and 22 wk of supplementation . RESULTS By the end of the study , 2 % of the girls had dropped out and > 96 % had taken > or = 20 of the 22 tablets ; side effects were minimal . Mean plasma ferritin increased significantly in all iron-supplemented groups , independently of initial hemoglobin values and iron doses . Ferritin concentrations decreased in the girls supplemented with folic acid only . As expected , hemoglobin responses to iron were higher in group A than in group B and increases were positively correlated with initial plasma ferritin . Hemoglobin failed to respond to folate supplementation if initial plasma ferritin concentrations were low . Mean hemoglobin increased significantly and consistently in relation to the length of treatment . CONCLUSION Long-term , weekly iron-folate supplementation was found to be a practical , safe , effective , and inexpensive method for improving iron nutrition in adolescent schoolgirls A study to determine the effect of antihelminthic treatment on growth and nutritional status was undertaken on 103 children in the second grade of primary school , 71 of whom were found to be infected with Ascaris lumbricoides or Trichuris trichiura . The median Ascaris and Trichuris intensities in the infected group were 19,600 ( range ; 0 - 488,000 ) and 2,800 ( range ; 0 - 84,600 ) eggs per gram of feces respectively . Forty-three children harbored both types of worm . Fourteen weeks after two 400 mg doses of albendazole were administered to infected children , the increases in weight , height , weight for age , height for age and weight for height were significantly higher among infected children than controls who were uninfected at baseline . The observed gains were independent of sex and socioeconomic status . Decrease in log transformed Trichuris intensity correlated with increases in weight ( r=0.24 ; p=0.02 ) and weight for age ( r=0.20 ; p=0.06 ) but decrease in Ascaris intensity did not correlate with increases in any of the anthropometric parameters . The results suggest that antihelminthic treatment has beneficial short-term effects on growth and nutritional status of a modest magnitude among early primary schoolchildren in the area Introduction : Helminth ( worm ) infections cause morbidity among poor communities worldwide . An influential study conducted in Kenya in 1998–99 reported that a school-based drug- and -educational intervention had benefits for worm infections and school attendance . Methods : In this statistical replication , we re-analysed data from this cluster quasi-r and omized stepped-wedge trial , specifying two co- primary outcomes : school attendance and examination performance . We estimated intention-to-treat effects using year-stratified cluster- summary analysis and observation-level r and om-effects regression , and combined both years with a r and om-effects model accounting for year . The participants were not blinded to allocation status , and other interventions were concurrently conducted in a sub-set of schools . A protocol guiding outcome data collection was not available . Results : Quasi-r and omization result ed in three similar groups of 25 schools . There was a substantial amount of missing data . In year-stratified cluster- summary analysis , there was no clear evidence for improvement in either school attendance or examination performance . In year-stratified regression models , there was some evidence of improvement in school attendance [ adjusted odds ratios ( aOR ) : year 1 : 1.48 , 95 % confidence interval ( CI ) 0.88–2.52 , P = 0.147 ; year 2 : 1.23 , 95 % CI 1.01–1.51 , P = 0.044 ] , but not examination performance ( adjusted differences : year 1 : −0.135 , 95 % CI −0.323–0.054 , P = 0.161 ; year 2 : −0.017 , 95 % CI −0.201–0.166 , P = 0.854 ) . When both years were combined , there was strong evidence of an effect on attendance ( aOR 1.82 , 95 % CI 1.74–1.91 , P < 0.001 ) , but not examination performance ( adjusted difference −0.121 , 95 % CI −0.293–0.052 , P = 0.169 ) . Conclusions : The evidence supporting an improvement in school attendance differed by analysis method . This , and various other important limitations of the data , caution against over-interpretation of the results . We find that the study provides some evidence , but with high risk of bias , that a school-based drug-treatment and health-education intervention improved school attendance and no evidence of effect on examination performance Summary Background In north India many pre-school children are underweight , many have intestinal worms , and 2–3 % die at ages 1·0–6·0 years . We used the state-wide Integrated Child Development Service ( ICDS ) infrastructure to help to assess any effects of regular deworming on mortality . Methods Participants in this cluster-r and omised study were children in catchment areas of 8338 ICDS-staffed village child-care centres ( under-5 population 1 million ) in 72 administrative blocks . Groups of four neighbouring blocks were cluster-r and omly allocated in Oxford between 6-monthly vitamin A ( retinol capsule of 200 000 IU retinyl acetate in oil , to be cut and dripped into the child 's mouth every 6 months ) , albendazole ( 400 mg tablet every 6 months ) , both , or neither ( open control ) . Analyses of albendazole effects are by block ( 36 vs 36 clusters ) . The study spanned 5 calendar years , with 11 6-monthly mass-treatment days for all children then aged 6–72 months . Annually , one centre per block was r and omly selected Output:	The prevalence of anemia was markedly changed after the program , particularly in the studies which implemented deworming with hygiene program , co-administration of iron and retinol . Conclusion and Recommendation School based deworming program decreases prevalence of anemia and will contribute to reduction of anemia in the community .
MS21040	*TASK* the task is to summarize an input biomedical literature in six sentences *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 novel translational pharmacology investigation was conducted by combining an in vitro efficacy target with mucosal tissue pharmacokinetic ( PK ) data and mathematical modeling to determine the number of doses required for effective human immunodeficiency virus ( HIV ) preexposure prophylaxis ( PrEP ) . METHODS A PK/pharmacodynamic ( PD ) model was developed by measuring mucosal tissue concentrations of tenofovir , emtricitabine , their active metabolites ( tenofovir diphosphate [ TFVdp ] and emtricitabine triphosphate [ FTCtp ] , respectively ) , and competing endogenous nucleotides ( dATP and dCTP ) in 47 healthy women . TZM-bl and CD4(+ ) T cells were used to identify 90 % effective concentration ( EC90 ) ratios of TFVdp to dATP and FTCtp to dCTP ( alone and in combination ) for protection against HIV . Monte-Carlo simulations were then performed to identify minimally effective dosing strategies to protect lower female genital tract and colorectal tissues . RESULTS The colorectal TFVdp concentration was 10 times higher than that in the lower female genital tract , whereas concentrations of endogenous nucleotides were 7 - 11 times lower . Our model predicted that ≥98 % of the population achieved protective mucosal tissue exposure by the third daily dose of tenofovir disoproxil fumarate plus emtricitabine . However , a minimum adherence to 6 of 7 doses/week ( 85 % ) was required to protect lower female genital tract tissue from HIV , while adherence to 2 of 7 doses/week ( 28 % ) was required to protect colorectal tissue . CONCLUSIONS This model is predictive of recent PrEP trial results in which 2 - 3 doses/week was 75%-90 % effective in men but ineffective in women . These data provide a novel approach for future PrEP investigations that can optimize clinical trial dosing strategies Background As pre-exposure prophylaxis ( PrEP ) becomes more widely used in heterosexual population s , an important consideration is its safety in infants who are breastfed by women taking PrEP . We investigated whether tenofovir and emtricitabine are excreted into breast milk and then absorbed by the breastfeeding infant in clinical ly significant concentrations when used as PrEP by lactating women . Methods and Findings We conducted a prospect i ve short-term , open-label study of daily oral emtricitabine – tenofovir disoproxil fumarate PrEP among 50 HIV-uninfected breastfeeding African mother – infant pairs between 1–24 wk postpartum ( Clinical Trials.gov Identifier : NCT02776748 ) . The primary goal was to quantify the steady-state concentrations of tenofovir and emtricitabine in infant plasma ingested via breastfeeding . PrEP was administered to women through daily directly observed therapy ( DOT ) for ten consecutive days and then discontinued thereafter . Non-fasting peak and trough sample s of maternal plasma and breast milk were obtained at drug concentration steady states on days 7 and 10 , and a single infant plasma sample was obtained on day 7 . Peak blood and breast milk sample s were obtained 1–2 h after the maternal DOT PrEP dose , while maternal trough sample s were obtained at the end of the PrEP dosing interval ( i.e. , 23 to 24 h ) after maternal DOT PrEP dose . Tenofovir and emtricitabine concentrations were quantified using liquid chromatography-t and em mass spectrometry ( LC-MS/MS ) assays . Of the 50 mother – infant pairs enrolled , 48 % were ≤12 wk and 52 % were 13–24 wk postpartum , and median maternal age was 25 y ( interquartile range [ IQR ] 22–28 ) . During study follow-up , the median ( IQR ) daily reported frequency of infant breastfeeding was 15 times ( 12 to 18 ) overall , 16 ( 14 to 19 ) for the ≤12 weeks , and 14 ( 12 to 17 ) for the 13–24 wk infant age groups . Overall , median ( IQR ) time-averaged peak concentrations in breast milk were 3.2 ng/mL ( 2.3 to 4.7 ) for tenofovir and 212.5 ng/mL ( 140.0 to 405.0 ) for emtricitabine . Similarly , median ( IQR ) time-averaged trough concentrations in breast milk were 3.3 ng/mL ( 2.3 to 4.4 ) for tenofovir and 183.0 ng/mL ( 113.0 to 250.0 ) for emtricitabine , reflecting trough-to-peak breast milk concentration ratios of 1.0 for tenofovir and 0.8 for emtricitabine , respectively . In infant plasma , tenofovir was unquantifiable in 46/49 sample s ( 94 % ) , but emtricitabine was detectable in 47/49 ( 96 % ) ( median [ IQR ] concentration : 13.2 ng/mL [ 9.3 to 16.7 ] ) . The estimated equivalent doses an infant would ingest daily from breastfeeding were 0.47 μg/kg ( IQR 0.35 to 0.71 ) for tenofovir and 31.9 μg/kg ( IQR 21.0 to 60.8 ) for emtricitabine , translating into a < 0.01 % and 0.5 % relative dose when compared to the 6 mg/kg dose that is proposed for therapeutic treatment of infant HIV infection and for prevention of infant postnatal HIV infection ; a dose that has not shown safety concerns . No serious adverse effects were recorded during study follow-up . The key study limitation was that only a single infant sample was collected to minimize venipunctures for the children . However , maternal daily DOT and specimen collection at drug concentration steady state provided an adequate approach to address the key research question . Importantly , there was minimal variation in breast milk concentrations of tenofovir and emtricitabine ( respective median trough-to-peak concentration ratio ~1 ) , demonstrating that infants were exposed to consistent drug dosing via breast milk . Conclusion In this short-term study of daily directly observed oral PrEP in HIV-uninfected breastfeeding women , the estimated infant doses from breast milk and result ant infant plasma concentrations for tenofovir and emtricitabine were 12,500 and > 200-fold lower than the respective proposed infant therapeutic doses , and tenofovir was not detected in 94 % of infant plasma sample s. These data suggest that PrEP can be safely used during breastfeeding with minimal infant drug exposure . Trial Registration Clinical Trials.gov , Identifier : ABSTRACT The objective of the study was to measure antiretroviral exposures in four physiological compartments during pregnancy , delivery , and postpartum . This prospect i ve , open-label , longitudinal study collected paired blood plasma ( BP ) and genital tract ( GT ) aspirates antepartum , at delivery , and up to 12 weeks postpartum . Antiretroviral cord BP and amniotic fluid concentrations were also measured . Drug concentrations were analyzed by vali date d high-performance liquid chromatography/UV and liquid chromatography/t and em mass spectrometry methods , with secondary compartment concentrations presented as the percentage of BP . Fourteen women taking lamivudine plus zidovudine and either lopinavir-ritonavir ( n = 7 ) , nelfinavir ( n = 6 ) , or nevirapine ( n = 1 ) were enrolled ; four also received tenofovir . GT penetration relative to BP was highest for the nucleoside reverse transcriptase inhibitors compared to the protease inhibitors and nevirapine . Only antepartum nelfinavir GT penetration was significantly higher than in the second trimester ( geometric mean ratio [ GMR ] , 179.3 ) or third trimester ( GMR , 41.9 ) . Compared to nonpregnant historical controls , antepartum GT penetration was significantly lower ( P < 0.05 ) for zidovudine ( GMR , 0.25 ) and lopinavir ( GMR , 0.03 ) ; postpartum lopinavir GT penetration continued to be significantly lower ( GMR , 0.27 ) . Cord BP exposures were highest for lamivudine and tenofovir ( ≥100 % ) , with cord BP levels of the remaining drugs ranging from 49 to 86 % of that of the respective BP level . Amniotic exposures for lamivudine , zidovudine , tenofovir , and nelfinavir were ≥100 % , nevirapine exposure was 53 % , and lopinavir and ritonavir exposures were ≤6 % that of BP . We conclude that GT , cord BP , and amniotic fluid exposures vary within and between antiretroviral drug classes and biologic sites . Measurement of antiretroviral exposure in maternal genital secretions , cord BP , and amniotic fluid may be needed to identify signals of subtherapeutic or supratherapeutic drug exposure BACKGROUND & AIMS Fetal safety of antiviral therapies is important given the long-term treatment of women with chronic hepatitis B ( CHB ) infection who may become pregnant . We analyzed neonatal safety data from the Antiretroviral Pregnancy Registry ( APR ) , the largest safety data base in pregnancy for antivirals used for HIV and CHB . METHODS Data were extracted from APR cases prospect ively enrolled between 1989 and 2011 . Primary outcomes were major birth defects rates with exposure to all antivirals , individual classes , and drugs compared to population -based controls . Relevant to CHB , only lamivudine ( LAM ) and tenofovir disoproxil fumarate ( TDF ) had sufficient individual data for review ( ≥200 cases ) . RESULTS Of 13,711 cases analyzed , the overall birth defect prevalence ( 2.8 % , 95 % CI 2.6 - 3.1 % ) was comparable to Centers for Disease Control population -based data ( 2.72 % , 2.68 - 2.76 % , p=0.87 ) and two prospect i ve antiretroviral exposed newborn cohorts ( 2.8 % , 2.5 - 3.2 % , p=0.90 and 1.5 % , 1.1 - 2.0 % , p<0.001 ) . The birth defects prevalence between first and second/third trimesters exposure was similar ( 3.0 % vs. 2.7 % ) . No increased risk of major birth defects with LAM or TDF exposure compared to population -based controls was observed . No specific pattern of major birth defects was observed for individual antivirals or overall . CONCLUSIONS No increased risk of major birth defects including in non-live births was observed for pregnant women exposed to antivirals relevant to CHB treatment overall or to LAM or TDF compared to population -based controls . Continued safety and efficacy reporting on antivirals in pregnancy are essential to inform patients on their risks and benefits during pregnancy ABSTRACT Tenofovir DF is an antiviral nucleotide with activity against human immunodeficiency virus type 1 ( HIV-1 ) . The pharmacokinetics , safety , and activity of oral tenofovir DF in HIV-1-infected adults were evaluated in a r and omized , double-blind , placebo-controlled , escalating-dose study of four doses ( 75 , 150 , 300 , and 600 mg given once daily ) . Subjects received a single dose of tenofovir DF or a placebo , followed by a 7-day washout period . Thereafter , subjects received their assigned study drug once daily for 28 days . Pharmacokinetic parameters were dose proportional and demonstrated no change with repeated dosing . Reductions in plasma HIV-1 RNA were dose related at tenofovir DF doses of 75 to 300 mg , but there was no increase in virus suppression between the 300- and 600-mg dose cohorts , despite dose-proportional increases in drug exposure . Grade III or IV adverse events were limited to laboratory abnormalities , including elevated creatine phosphokinase and liver function tests , which resolved with or without drug discontinuation and without sequelae . No patients developed detectable sequence changes in the reverse transcriptase gene BACKGROUND Few data are available regarding the use of tenofovir disoproxil fumarate ( TDF ) during pregnancy for the prevention of mother-to-child transmission of hepatitis B virus ( HBV ) . METHODS In this trial , we included 200 mothers who were positive for hepatitis B e antigen ( HBeAg ) and who had an HBV DNA level higher than 200,000 IU per milliliter . Participants were r and omly assigned , in a 1:1 ratio , to receive usual care without antiviral therapy or to receive TDF ( at an oral dose of 300 mg per day ) from 30 to 32 weeks of gestation until postpartum week 4 ; the participants were followed until postpartum week 28 . All the infants received immunoprophylaxis . The primary outcomes were the rates of mother-to-child Output:	In none of the manuscripts was the non-pregnant HBV threshold of Cmax of 300 ng/ml reached , but the EC50 of TFV is lower for treatment of HBV compared to HIV . Most knowledge of pharmacokinetic of TFV in pregnancy results from studies on HIV involving multiple antiretrovirals . Increased TFV clearance occurred in the second and third trimester when optimal TFV concentrations are required to maximize suppression of HBV in the window before birth .
MS21041	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Protein-energy wasting ( PEW ) is common in patients undergoing hemodialysis ( HD ) . Studies have assessed the positive effect of oral nutritional supplementation ( ONS ) or resistance exercise ( RE ) on nutritional status ( NS ) markers in patients undergoing HD . METHODS The aim of this study was to assess the effect of ONS and RE on NS and the quality of life ( QOL ) of 36 patients undergoing HD . In a r and omized clinical trial , patients were divided into the following two groups : a control group ( ONS ) that received a can of ONS during their HD sessions and an intervention group ( ONS + RE ) that received a can of ONS and underwent a 40-min session of RE during their HD sessions . Both interventions lasted 12 weeks . The patients ' anthropometric , biochemical , dietetic and bioelectrical impedance measurements as well as their QOL , evaluated using the Kidney Disease Quality of Life Short Form , were recorded . RESULTS At baseline , 55.5 % of patients presented with PEW according to International Society of Renal Nutrition and Metabolism criteria ( 20 patients ) . We found statistically significant changes from baseline in both groups , such as increases in body weight , body mass index , midarm circumference , midarm muscle circumference , triceps skinfold thickness , fat mass percentage , h and grip strength , phase angle and serum albumin . A decrease in the prevalence of PEW was observed in both groups at the end of the intervention . A delta comparison between groups showed no statistically significant differences in the anthropometric and biochemical parameters . No significant improvement was observed in QOL and body composition measured by bioimpedance vector analysis . Dietary energy and protein intake increased significantly during the study period for all patients . CONCLUSION Oral nutritional supplementation during HD improves NS . The addition of RE during HD does not seem to augment the acute anabolic effects of intradialytic ONS on NS INTRODUCTION Maintenance hemodialysis ( MHD ) patients suffer from a number of co-morbidities including declines in muscle mass and physical function . Beta-hydroxy-beta-methylbutyrate ( HMB ) is a metabolite of the amino acid leucine that has been shown to improve lean mass and physical function in elderly and clinical population s , but had not been studied in MHD patients . The purpose of this study was to investigate the efficacy of HMB in this population . METHODS We performed a double-blind , placebo-controlled , r and omized trial to assess the effects of daily HMB supplementation on co-morbidities in MHD patients . MHD patients were recruited and assigned to either daily supplementation with HMB ( n = 16 ) or placebo ( n = 17 ) for 6 months . Measurements of body composition , bone density , strength , physical function , fall risk , quality of life , and blood parameters were measured at baseline and 6 months . Blood was drawn at baseline , 3 , and 6 months to measure compliance . FINDINGS No significant effects of HMB on body composition , bone density , strength , physical function , fall risk , quality of life , or blood parameters were observed . On analysis of plasma HMB concentrations , 5 of 16 patients ( 31 % ) in the HMB group were found to be noncompliant at 3 or 6 months . Therefore , we performed a per- protocol analysis with compliant participants only and observed no significant differences in our outcomes of interest . DISCUSSION These results do not support the efficacy of HMB to attenuate co-morbid conditions in MHD patients . Moreover , this highlights the need for future interventions targeted at reducing pill burden and improving pill compliance in this population BACKGROUND Malnutrition is highly prevalent in peritoneal dialysis ( PD ) patients and is associated with a poor prognosis . Attempts to improve nutritional status with enteral supplements have yielded poor results . METHODS We performed a crossover- design trial on 13 PD patients to investigate whether these patients reduce their food intake after drinking oral nutritional supplements . Patients attended three visits in which they were administered a st and ard oral nutritional supplement either 2 hours or 30 minutes before lunch or a placebo drink 30 minutes before lunch . Lunch was provided as a self-select buffet-style meal , and food intake was measured . Total intake was calculated by adding the nutritional content of the oral supplement . RESULTS Patients showed poor food intake , with mean values equaling only 18 % of the recommended daily intake for calories and 34 % for protein . Drinking the supplement 2 hours before lunch result ed in a significant increase compared with the placebo visit in total caloric ( 430 to 843 kcal ; P < 0.001 ) and protein intake ( 27.6 to 41.3 g ; P = 0.006 ) . No significant difference in total intake was detected between drinking the supplement 2 hours versus 30 minutes before lunch . CONCLUSION These results indicate that oral nutritional supplements administered before a meal may significantly increase caloric and protein intakes of PD patients BACKGROUND Malnutrition is a significant problem in those undergoing peritoneal dialysis ( PD ) . Factors such as gastrointestinal ( GI ) symptoms and the need for a fluid reduced diet can limit tolerance and thereby the efficacy of oral nutritional supplements to treat malnutrition . OBJECTIVES To evaluate the acceptability and impact of two different forms of oral nutrition supplementation for 16 weeks on nutritional markers and quality of life of malnourished patients undergoing PD . DESIGN A r and omised , within-subject cross-over study . Patients assessed as malnourished or with serum albumin < 35 g/l were recruited . Participants were r and omised to receive either 200 ml of a 1.25 kcal/ml nutrition supplement or a high protein nutrition supplement bar , for eight weeks . Each group then crossed over to receive the alternative supplement for eight weeks . Total intervention time was 16 weeks . Serum albumin , serum transthyretin and food intake were evaluated at baseline , at 8 and 16 weeks . Subjective Global Assessment , the presence of GI symptoms and quality of life were evaluated at baseline and 16 weeks . RESULTS Sixteen weeks of nutritional support was associated with statistically significant improvements in weight and a reduction in the proportion of patients who were malnourished . There was no difference in the impact of bars compared with liquid oral nutrition supplementation . Patients preferred the fluid supplement to the bars . CONCLUSION Sixteen weeks of nutritional support improved nutritional status in malnourished patients on PD OBJECTIVE We examined the protein anabolic effects of Pro-Stat 64 , a high nitrogen-containing , enzyme-hydrolyzed , tryptophan-fortified , collagen protein supplement administrated during hemodialysis , at two different dosing regimens . DESIGN This was a r and omized , controlled , prospect i ve study with 3 different groups : control , single dose of supplementation , and double dose of supplementation . SETTING This study was performed at a clinical research center . PATIENTS Six prevalent chronic hemodialysis ( HD ) patients were enrolled : 5 males , 1 female , 4 African Americans , and 2 Caucasians . Their mean age was 45 + /- 11 years ( S.D. ) . Two patients were diabetic . METHODS Protein turnover studies were performed using amino-acid ( AA ) balance and primed constant infusion of L-(1-(13)C ) leucine . MAIN OUTCOME MEASURE Whole-body protein balance was determined according to substrate kinetics . RESULTS There were no statistically significant difference at any time point between protocol s for blood chemistries and hormonal markers , except for minor variations in plasma glucose . All plasma AA groups displayed decreases during a control study , in which no supplementation was given . Compared with the control group , plasma nonessential AA and total AA concentrations were statistically significantly higher during HD after both single and double doses of supplementation . The forearm arteriovenous AA balance was statistically significantly better for essential , nonessential , and total AA uptake after both single-dose and double-dose supplementation compared with the control group , except for nonessential AA , which was significantly better only after a double dose . Whole-body protein breakdown and net protein balance were statistically significantly better during HD with a double-dose administration in a dose-dependent manner , compared with the control and single-dose groups . CONCLUSIONS Oral AA supplementation alone improves whole-body and skeletal muscle protein anabolism in a dose-dependent manner in chronic HD patients . These data should be taken into account during clinical decision-making or when design ing clinical trials of nutritional supplementation BACKGROUND Hypoalbuminemia is associated with substantial morbidity and mortality in dialysis patients . METHODS Subjects with a mean three-month pre study serum albumin of 3.8 g/dL or less and who demonstrated > /=90 % compliance during a two-week run-in period were r and omized to 3.6 g of essential amino acids ( EAAs ) or placebo three times daily with meals for three months . R and omization was stratified by dialysis modality and by severity of the hypoalbuminemia . The primary study outcome was change in the average of three monthly serum albumin measurements between baseline and follow-up . RESULTS Fifty-two patients were r and omized ; 47 patients ( 29 hemodialysis and 18 peritoneal dialysis ) met the predetermined primary analysis criteria . The mean compliance rates averaged 75 , 70 , and 50 % at months 1 , 2 , and 3 , respectively , and were similar for EAAs and placebo . Serum albumin in the hemodialysis patients , EAA versus placebo , improved [ ( mean + /- SE ) 0.22 + /- 0.09 g/dL , P = 0.02 ] . Changes in peritoneal dialysis patients were not significant ( 0.01 + /- 0.15 g/dL ) , but approached significance for the total study group ( 0.14 + /- 0.08 g/dL , P = 0.08 ) . Patients in the very low albumin strata ( < 3.5 g/dL ) improved more than those in the low albumin strata ( 3.5 to 3.8 g/dL , P < 0.01 ) . There was a significant correlation ( r = 0.83 , P = 0.001 ) within the hemodialysis EAA group between the baseline C-reactive protein level and improvement in serum albumin . Improvements were also seen in grip strength and SF-12 mental health score , but not in serum amino acid levels , SF-12 physical health score , or anthropometric measurements . CONCLUSIONS Oral EAAs induce a significant improvement in the serum albumin concentration in hemodialysis but not peritoneal dialysis subjects . Further study of their long-term effects on morbidity and mortality is warranted Uremic malnutrition is associated with increased risk of hospitalization and death in chronic hemodialysis ( CHD ) patients . Most nutritional intervention studies in CHD patients traditionally have used concentrations of serum albumin as the primary outcome measure and showed slight or no significant improvements . A recent study showed that intradialytic parenteral nutrition ( IDPN ) improves whole-body protein synthesis in CHD patients . On the basis of this observation , it was hypothesized that the anabolic effects of IDPN are associated with increases in the fractional synthetic rate of albumin , a direct estimate of acute changes in hepatic albumin synthesis . Seven CHD patients were studied during two hemodialysis ( HD ) sessions , with and without IDPN , using primed-constant infusion of ( 13C ) leucine 2 h before , during , and 2 h after HD . Plasma enrichments of ( 13C ) leucine and ( 13C ) ketoisocaproate were examined to determine the fractional synthetic rate of albumin . The results indicate that administration of IDPN significantly improves the fractional synthetic rate of albumin during HD ( 16.2 + /- 1.5%/d versus 12.8 + /- 1.7%/d ; P < 0.05 ) in CHD patients in parallel with significant improvements in whole-body protein synthesis ( 5.05 + /- 1.3 mg/kg fat-free mass/min versus 3.22 + /- 0.3 mg/kg fat-free mass/min ; P < 0.05 ) . IDPN is protein anabolic in the acute setting in CHD patients , as evidence d by significant concomitant increases in the fractional synthetic rate of albumin and whole-body protein synthesis OBJECTIVE This controlled trial was undertaken to evaluate the benefits of short-term enteral nutrient supplementation in maintenance hemodialysis ( MHD ) patients using a high-calorie and high-protein blend formula ( low-cost home-prepared [ HP ] blend or a commercially available supplement ) and to study its effect on selected parameters of nutritional status . The acceptability and palatability of the HP blend formula , ease of use , and cost were also assessed in comparison with the commercial nutritional supplement ( CNS ) . DESIGN R and omized controlled trial . SETTING Hemodialysis ( HD ) unit of a tertiary referral care hospital in Southern India . PATIENTS Nondiabetic adult MHD patients with no intercurrent illness , on regular thrice weekly MHD for at least 1 month before recruitment , with a body mass index ( BMI ) < 20 and a serum albumin level of < 4.0 g/dL. Patients were r and omized into control group and experimental group , the latter in turn to recieve either CNS or HP blend . INTERVENTION The control group received appropriate monitoring , including di Output:	Overall , it is likely that oral protein-based nutritional supplements increase both mean change in serum albumin and serum albumin at end of intervention and may improve serum prealbumin and mid-arm muscle circumference . The improvement in serum albumin was more evident in haemodialysis and malnourished participants . However , it remains uncertain whether these results translate to improvement in nutritional status and clinical ly relevant outcomes such as death .
MS21042	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The European Society of Thoracic Surgeons ( ESTS ) organized a workshop dealing with lymph node staging in non-small cell lung cancer . The objective of this workshop was to develop guidelines for definitions and the surgical procedures of intraoperative lymph node staging , and the pathologic evaluation of resected lymph nodes in patients with non-small cell lung cancer ( NSCLC ) . Relevant peer- review ed publications on the subjects , the experience of the participants , and the opinion of the ESTS members contributing on line , were used to reach a consensus . Systematic nodal dissection is recommended in all cases to ensure complete resection . Lobe-specific systematic nodal dissection is acceptable for peripheral squamous T1 tumors , if hilar and interlobar nodes are negative on frozen section studies ; it implies removal of , at least , three hilar and interlobar nodes and three mediastinal nodes from three stations in which the subcarinal is always included . Selected lymph node biopsies and sampling are justified to prove nodal involvement when resection is not possible . Pathologic evaluation includes all lymph nodes resected separately and those remaining in the lung specimen . Sections are done at the site of gross abnormalities . If macroscopic inspection does not detect any abnormal site , 2-mm slices of the nodes in the longitudinal plane are recommended . Routine search for micrometastases or isolated tumor cells in hematoxylin-eosin negative nodes would be desirable . R and omized controlled trials to evaluate adjuvant therapies for patients with these conditions are recommended . The adherence to these guidelines will st and ardize the intraoperative lymph node staging and pathologic evaluation , and improve pathologic staging , which will help decide on the best adjuvant therapy Summary Background The diagnosis and staging of lung cancer is an important process that identifies treatment options and guides disease prognosis . We aim ed to assess endobronchial ultrasound-guided transbronchial needle aspiration as an initial investigation technique for patients with suspected lung cancer . Methods In this open-label , multicentre , pragmatic , r and omised controlled trial , we recruited patients who had undergone a CT scan and had suspected stage I to IIIA lung cancer , from six UK centres and r and omly assigned them to either endobronchial ultrasound-guided transbronchial needle aspiration ( EBUS-TBNA ) or conventional diagnosis and staging ( CDS ) , for further investigation and staging . If a target node could not be accessed by EBUS-TBNA , then endoscopic ultrasound-guided fine needle aspiration ( EUS-FNA ) was allowed as an alternative procedure . R and omisation was stratified according to the presence of mediastinal lymph nodes measuring 1 cm or more in the short axis and by recruiting centre . We used a telephone r and omisation method with permuted blocks of four generated by a computer . Because of the nature of the intervention , masking of participants and consenting investigators was not possible . The primary endpoint was the time-to-treatment decision after completion of the diagnostic and staging investigations and analysis was by intention-to-diagnose . This trial is registered with Clinical Trials.gov , number NCT00652769 . Findings Between June 10 , 2008 , and July 4 , 2011 , we r and omly allocated 133 patients to treatment : 66 to EBUS-TBNA and 67 to CDS ( one later withdrew consent ) . Two patients from the EBUS-TBNA group underwent EUS-FNA . The median time to treatment decision was shorter with EBUS-TBNA ( 14 days ; 95 % CI 14–15 ) than with CDS ( 29 days ; 23–35 ) result ing in a hazard ratio of 1·98 , ( 1·39–2·82 , p<0·0001 ) . One patient in each group had a pneumothorax from a CT-guided biopsy sample ; the patient from the CDS group needed intercostal drainage and was admitted to hospital . Interpretation Transbronchial needle aspiration guided by endobronchial ultrasound should be considered as the initial investigation for patients with suspected lung cancer , because it reduces the time to treatment decision compared with conventional diagnosis and staging techniques . Funding UK Medical Research Council BACKGROUND To compare surgical results , pathological staging , and survival between complete and minimal mediastinal lymph node dissection for non-small cell lung cancer ( NSCLC ) . METHODS A r and omized controlled trial was carried out in 202 patients who were assigned to undergo either skeletonized complete mediastinal lymph node dissection ( CLD ) or minimal mediastinal lymph node dissection ( MLD ) . Clinical and pathological characteristics , surgical results , postoperative staging , and five-year survival were recorded for statistical analysis . RESULTS Significantly more stations of lymph nodes were harvested through CLD , than MLD ( 8.9 vs. 6.2 , P < 0.001 ) . There was no difference in major complications ( CLD 14.7 % vs. MLD 14.0 % , P = 0.884 ) or postoperative death ( CLD 2.1 % vs. MLD 1.9 % , P = 0.904 ) . No significant difference was detected in pathological staging between the two groups . The pN2 rates ( 27.1 % vs. 24.2 % ) , skip-mediastinal metastasis ( 9.3 % vs. 7.4 % ) , and multi-stational mediastinal involvement ( 15.0 % vs. 16.8 % ) were similar between MLD and CLD . However , CLD had significantly better five-year survival than MLD ( 55.7 % vs. 37.7 % , P = 0.005 ) , especially in patients with a tumor size > 3 cm , pleural invasion , pN1-N2 , stage II-III , adenocarcinoma , and low-differentiation carcinoma . Upon multivariate analysis , CLD , along with stage I and high-differentiation , were independent prognostic factors for better overall survival . CONCLUSIONS Complete and minimal mediastinal dissections have similar surgical risks and mediastinal staging effect in patients with NSCLC . Minimal dissection is enough for early stage high-differentiation tumors . For patients with stage II-III or low-differentiation carcinoma , skeletonized complete mediastinal dissection may improve survival compared with minimal dissection OBJECTIVES Nodal upstaging is a quality indicator for oncological thoracic surgery and is found in up to 25 % of patients with clinical stage I ( cStage-I ) non-small-cell lung cancer ( NSCLC ) . In large retrospective series , lower N1 upstaging was reported after video-assisted thoracic surgery ( VATS ) resections . We studied the impact of central primary tumour location on nodal upstaging in cStage-I NSCLC . METHODS Consecutive patients operated for cStage-I NSCLC were selected from a prospect ively managed surgical data base . Tumour location was classified as central if the lesion was visible during st and ard video bronchoscopy . A nodal station mapping was drawn for each patient based on final pathological examination . Univariable and additive multivariable binary logistic regression analyses were performed . RESULTS Between 2007 - 2014 , 334 patients underwent anatomical resection for cStage-I NSCLC , either by open thoracotomy ( n = 158 ) or by VATS ( n = 176 ; conversion rate 1.7 % ) . All patients underwent imaging with [(18)F]-fluorodeoxyglucose positron emission tomography and computer tomography . Invasive mediastinal staging was performed in 24.6 % of patients . There were more central tumours in the open group ( 24.1 % , n = 38 ) compared with the VATS group ( 4.5 % , n = 8) . There was no significant difference between the number ( mean ± st and ard deviation ) of nodal stations examined ( open 5 ± 1.9 vs VATS 5 ± 1.7 , P = 0.99 ) . Pathological nodal upstaging was found in 15.9 % ( n = 53 ) of cStage-I patients . Nodal pN1 and pN2 upstaging were 13.3 and 8.2 % , respectively , for the open group , and 6.3 and 4.5 % , respectively , for the VATS group . In 32.6 % ( n = 15/46 ) of patients with a central cStage-I tumour pN1 , upstaging was found . A binary logistic regression model ( including tumour location , technique , tumour size , gender and histology ) showed that only tumour location had a significant impact on pN1 upstaging [ peripheral versus central ; odds ratio ( OR ) 5.07 ( confidence interval , CI : 1.89 - 13.60 ) , P = 0.001 ] , while surgical technique had no significant impact [ VATS versus open ; OR 0.74 ( CI : 0.31 - 1.78 ) , P = 0.50 ] . CONCLUSIONS The number of lymph node stations examined during VATS resections is similar to open resections for cStage-I NSCLC . Almost one-third of the patients with a central cStage-I NSCLC were upstaged to pN1 . Tumour location was the only independent variable for pN1 upstaging in logistic regression analysis . It is a potential bias in retrospective studies and should therefore be accounted for when comparing different surgical resection techniques for cStage-I NSCLC We design ed a prospect i ve trial to determine the long-term prognosis of video-assisted thoracoscopic ( VATS ) lobectomy versus conventional lobectomy for patients with clinical stage IA ( T1N0M0 ) lung cancer . Between January 1993 and June 1994 , 100 consecutive patients with clinical stage IA non-small cell lung carcinoma underwent either conventional lobectomy through an open thoracotomy ( open group ; n= 52 ) or VATS lobectomy ( VATS group ; n= 48 ) . Lymph node dissections were performed in a similar manner in both groups . No significant differences were observed in the number of dissected lymph nodes between the 2 groups . Pathologic N1 and N2 disease was found in 3 and 1 patients , respectively , from the open group , and in 2 and 1 patients , respectively , from the VATS group . During the follow-up period , distant metastases and local or regional recurrences developed in 7 and 3 of the open group patients , respectively , and in 2 and 3 of the VATS group patients , respectively . Two and one of the open and VATS group patients developed second primary cancers , respectively . The overall survival rates 5 years after surgery were 85 % and 90 % in the open and VATS groups , respectively ( log-rank test , p= 0.74 ; generalized Wilcoxon test , p= 0.91 ) . VATS lobectomy with lymph node dissection achieved an excellent 5-year survival , similar to that achieved by the conventional approach BACKGROUND Little prospect i ve , multiinstitutional data exist regarding the morbidity and mortality after major pulmonary resections for lung cancer or whether a mediastinal lymph node dissection increases morbidity and mortality . METHODS Prospect ively collected 30-day postoperative data was analyzed from 1,111 patients undergoing pulmonary resection who were enrolled from July 1999 to February 2004 in a r and omized trial comparing lymph node sampling versus mediastinal lymph node dissection for early stage lung cancer . RESULTS Of the 1,111 patients r and omized , 1,023 were included in the analysis . Median age was 68 years ( range , 23 to 89 years ) ; 52 % were men . Lobectomy was performed in 766 ( 75 % ) and pneumonectomy in 42 ( 4 % ) . Pathologic stage was IA in 424 ( 42 % ) , IB in 418 ( 41 % ) , IIA in 37 ( 4 % ) , IIB in 97 ( 9 % ) , and III in 45 ( 5 % ) . Lymph node sampling was performed in 498 patients and lymph node dissection in 525 . Operative mortality was 2.0 % ( 10 of 498 ) for lymph node sampling and 0.76 % ( 4 of 525 ) for lymph node dissection . Complications occurred in 38 % of patients in each group . Lymph node dissection had a longer median operative time and greater total chest tube drainage ( 15 minutes , 121 mL , respectively ) . There was no difference in the median hospitalization , which was 6 days in each group ( p = 0.404 ) . CONCLUSIONS Complete mediastinal lymphadenectomy adds little morbidity to a pulmonary resection for lung cancer . These data from a current , multiinstitutional cohort of patients who underwent a major pulmonary resection constitute a new baseline with which to compare results in the future PURPOSE We conducted a r and omized trial to investigate whether systematic nodal dissection ( SND ) is superior to mediastinal lymph nodal sampling ( MLS ) in surgical treatment of non-small cell lung cancer ( NSCLC ) . METHODS The patients resectable clinical Stage I-IIIA NSCLC were r and omly assigned to lung resection combined with SND or lung resection combined with MLS . Output:	The finding of clinical ly important surgically related morbidities but lower perioperative mortality with lymphadenectomy seems inconsistent .
MS21043	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Ketoprofen , 25 , 50 , and 100 mg , was compared with 90 mg codeine and placebo for relief of pain due to removal of impacted third molar teeth . Treatment was self-administered as a single oral dose under double-blind conditions in five parallel groups established by a r and om code in healthy young adults . Based on 129 patient evaluations of pain experience and pain relief , ketoprofen was shown to have a more rapid onset and longer duration of action than codeine . In the derived variables of SPID ( Sum of Pain Intensity Differences ) and TOPAR ( Total Pain Relief ) , all three doses of ketoprofen , with no dose-related differences among them , were found to provide statistically superior analgesia to codeine and placebo . All five treatments were associated with some adverse reactions Background Dexketoprofen trometamol plus tramadol hydrochloride is a new oral combination of two analgesics , which have different mechanisms of action for the treatment of moderate to severe acute pain . Methods R and omised , double-blind , parallel , placebo and active-controlled , single and multiple-dose study to evaluate the analgesic efficacy and safety of dexketoprofen/tramadol 25 mg/75 mg in comparison with the single agents ( dexketoprofen 25 mg and tramadol 100 mg ) in moderate to severe acute pain after abdominal hysterectomy . Patients received seven consecutive doses of study drug within a 3-day period , each dose separated by an 8-hour interval . A placebo arm was included during the single-dose phase to vali date the pain model . Efficacy assessment s included pain intensity , pain relief , patient global evaluation and use of rescue medication . The primary endpoint was the mean sum of pain intensity differences over the first 8 h ( SPID8 ) . Results The efficacy analysis included 606 patients , with a mean age of 48 years ( range 25–73 ) . The study results confirmed the superiority of the combination over the single agents in terms of the primary endpoint ( p < 0.001 ) . Secondary endpoints were generally supportive of the superiority of the combination for both single and multiple doses . Most common adverse drug reactions ( ADRs ) were nausea ( 4.6 % ) and vomiting ( 2.3 % ) . All other ADRs were experienced by less than 2 % of patients . Conclusions The study results provided robust evidence of the superiority of dexketoprofen/tramadol 25 mg/75 mg over the single components in the management of moderate to severe acute pain , as confirmed by the single-dose efficacy , repeated-dose sustained effect and good safety profile observed . Trial registration EU Clinical Trials Register ( EudraCT number 2012 - 004545 - 32 , registered 04 October 2012 ) ; Clinical trials.gov ( NCT01904149 , registered 17 July 2013 ) Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Background . The aim was to evaluate the analgesic efficacy and safety of the dexketoprofen/tramadol 25 mg/75 mg fixed-dose combination vs dexketoprofen ( 25 mg ) and tramadol ( 100 mg ) in moderate-to-severe acute pain after total hip arthroplasty . Methods . This was a r and omized , double-blind , parallel-group study in patients experiencing pain of at least moderate intensity on the day after surgery , compared with placebo at first administration to vali date the pain model . The study drug was administered orally every 8 h throughout a 5 day period . Rescue medication , metamizole 500 mg , was available during the treatment period . The evaluation of efficacy was based on patient assessment s of pain intensity and pain relief . The primary end point was the mean sum of the pain intensity difference values throughout the first 8 h ( SPID8 ) . Results . Overall , 641 patients , mean age 62 ( range 29–80 ) yr , were analysed ; mean ( sd ) values of SPID8 were 247 ( 157 ) for dexketoprofen/tramadol , 209 ( 155 ) for dexketoprofen , 205 ( 146 ) for tramadol , and 151 ( 159 ) for placebo . The primary analysis confirmed the superiority of the combination over dexketoprofen 25 mg ( P=0.019 ; 95 % confidence interval 6.4–73 ) and tramadol 100 mg ( P=0.012 ; 95 % confidence interval 9.5–76 ) . The single components were superior to placebo ( P<0.05 ) , confirming model sensitivity . Most secondary analyses supported the superiority of the combination . The incidence of adverse drug reactions was low and similar among active treatment groups . Conclusion . The efficacy results confirmed the superiority of dexketoprofen/tramadol over its single components , even at higher doses ( tramadol ) , with a safety profile fully in line with that previously known for these agents in monotherapy . Clinical trial registration . EudraCT 2012 - 004548 - 31 ( https://www . clinical trialsregister.eu/ctr- search / search ? query = eudract_number:2012 - 004548 - 31 ) ; Clinical Trials.gov NCT01902134 ( https://www . clinical trials.gov/ct2/show/NCT01902134?term=NCT01902134&rank=1 ) One hundred sixty-one patients with postoperative pain were treated at a single center in a double-blind , r and omized , parallel study design ed to compare the efficacy and safety of single oral doses of ketoprofen ( 50 and 150 mg ) , an acetaminophen ( 650 mg ) plus codeine ( 60 mg ) combination , and placebo . From 1 through 4 hours after administration of the study drugs , the mean summed pain intensity difference ( SPID ) and time-weighted total pain relief ( TOPAR ) scores for the three active treatments generally were significantly ( P less than 0.05 ) higher than those for placebo but not significantly different from each other . At the 6-hour evaluation , the ketoprofen groups , but not the acetaminophen-codeine group , had higher ( P less than 0.05 ) mean SPID and TOPAR scores than the placebo group , as a result of a shorter duration of pain relief in the acetaminophen-codeine group . The 6-hour TOPAR scores were significantly ( P less than 0.05 ) higher for both ketoprofen groups than for the acetaminophen-codeine group ; the ketoprofen 150 mg group also had significantly ( P less than 0.05 ) higher mean 6-hour SPID and global subjective assessment scores . As a result of a higher frequency of somnolence , there was a significantly ( P less than 0.05 ) greater incidence of central nervous system adverse drug reactions among patients treated with acetaminophen plus codeine than among those treated with 150 mg of ketoprofen . These results indicate that the analgesic efficacy of both 50 and 150 mg doses of ketoprofen equals that of acetaminophen 650 mg plus codeine 60 mg and the duration of the analgesic effect of ketoprofen is significantly longer Background Combination analgesics are effective in acute pain , and a theoretical framework predicts efficacy for combinations . The combination of dexketoprofen and tramadol is untested , but predicted to be highly effective . Methods This was a r and omised , double-blind , double-dummy , parallel-group , placebo-controlled , single-dose trial in patients with moderate or severe pain following third molar extraction . There were ten treatment arms , including dexketoprofen trometamol ( 12.5 mg and 25 mg ) and tramadol hydrochloride ( 37.5 mg and 75 mg ) , given as four different fixed combinations and single components , with ibuprofen 400 mg as active control as well as a placebo control . The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo . The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours . Results 606 patients were r and omised and provided at least one post-dose assessment . All combinations were significantly better than placebo . The highest percentage of responders ( 72 % ) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group ( NNT 1.6 , 95 % confidence interval 1.3 to 2.1 ) . Addition of tramadol to dexketoprofen result ed in greater peak pain relief and greater pain relief over the longer term , particularly at times longer than six hours ( median duration of 8.1 h ) . Adverse events were unremarkable . Conclusions Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain . The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae . Trial registration EudraCT ( 2010 - 022798 - 32 ) ; Clinical trials.gov ( NCT01307020 ) Our purpose was to evaluate the analgesic efficacy of single oral doses of ketoprofen 25 , 50 , and 100 mg compared with aspirin 650 mg and placebo in the relief of moderate to severe postepisiotomy , uterine cramping , or cesarean section pain . One hundred and fifty-six patients participated in a r and omized , double-blind , stratified , parallel-group study . They were observed over a six-hour period by one nurse-observer . Several of the st and ard summary measures of analgesia were derived from the interview data , including the sum of pain intensity differences ( SPID ) and the sum of the hourly relief values ( TOTAL ) . The study showed significant differences between aspirin and placebo for four-hour SPID and several other parameters and between ketoprofen at all dose levels and placebo for the four- and six-hour SPID and many other parameters . The two higher doses of ketoprofen were significantly more effective than aspirin as as assessed by the four- and six-hour SPID , TOTAL , and other summary measures . The low dose of ketoprofen , although not significantly different from aspirin for SPID and TOTAL , showed a significantly faster onset of relief and had a better global rating . This study suggests that 50 mg of ketoprofen may be the clinical dose of choice as an analgesic . There were no adverse effects reported & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely Output:	Differential efficacy between dental surgery and other types of surgery seen for both drugs is unusual . Both drugs were well tolerated in single doses
MS21044	*TASK* the task is to summarize an input biomedical literature in six sentences *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 reported data on surgery plus radiotherapy for retroperitoneal soft tissue sarcomas ( RPS ) have been mostly from retrospective studies . We evaluated the long-term outcome of patients with operable RPS who were treated with protocol -based preoperative radiotherapy followed by complete surgical resection . Methods Data from two prospect i ve trials that included preoperative radiotherapy and surgery for patients with radiographically resectable RPS were combined to define long-term relapse rates and survival . Results Seventy-two patients with intermediate- or high- grade RPS were treated with preoperative radiotherapy ( median dose , 45 Gy ; range , 18.0–50.4 Gy ) . Fifty-four patients ( 75 % ) had primary RPS , whereas 18 ( 25 % ) had recurrent disease . The median tumor size was 15.5 cm . Sixty-four patients completed the planned preoperative radiotherapy ; 57 ( 89 % ) underwent laparotomy with curative intent , and 54 ( 95 % ) had a macroscopically complete ( R0 or R1 ) resection . With a median follow-up of 40.3 months , 28 patients ( 52 % ) who received preoperative radiotherapy and underwent a macroscopically complete resection had recurrences . For the 54 patients who underwent R0 or R1 resection after preoperative radiotherapy , the 5-year local recurrence – free , disease-free , and overall survival rates were 60 % , 46 % , and 61 % , respectively . The median overall survival has not been reached ( > 60 months ) . Conclusions Patients with intermediate- or high- grade RPS treated with preoperative radiotherapy plus complete resection had a median survival > 60 months . This compares favorably to historical data for similar patients treated with surgery alone Complete surgical resection is the most effective modality for the treatment of retroperitoneal sarcomas . Previous studies of all types of retroperitoneal sarcomas have not shown a survival benefit of incomplete resection over no resection . Because death often occurs as a result of local progression in retroperitoneal liposarcomas ( RPLS ) , it is possible that incomplete resection may be beneficial in this histologic type . In this study we have sought to determine the clinical outcomes in patients with incompletely resected and unresected RPLS with the aim of defining patients who may benefit from palliative resection . From a prospect i ve clinical data base 55 patients with incompletely resected ( n = 43 ) or unresected ( n = 12 ) RPLS were identified between 1982 and 1999 . Statistical analyses were performed using the log-rank test and Kaplan-Meier estimates with disease-specific survival as the primary end point . Variables studied included age , gender , recurrent versus primary disease , tumor grade , and tumor size . The patient population consisted of 34 men and 21 women with a mean age of 61 + /- 14 ( SD ) years . The median time to death was 10 months ( range 1 to 83 months ) with a median followup of 12 months ( range 1 to 60 months ) for survivors . Partial resection was an independent factor for increased survival as compared with exploration or biopsy only ( median survival 26 versus 4 months , p < 0.0001 ) . Of patients who received incomplete resections , locally recurrent presentation ( n = 19 ) versus primary disease ( n = 24 ) was a negative prognostic variable ( median survival 17 versus 46 months , p = 0.009 ) . Successful palliation of symptoms was achieved in 24 of 32 patients ( 75 % ) with preoperative symptoms . In select patients with unresectable RPLS , incomplete surgical resection can provide prolongation in survival and successful symptom palliation . Most likely to benefit are those patients presenting with primary tumors , suggesting that surgical resection should be attempted in the majority of patients PURPOSE The primary objective of this phase I trial was to define the maximum-tolerated dose of continuous-infusion doxorubicin administered with st and ard preoperative radiation for patients with localized , potentially resectable soft tissue sarcomas of the extremities or body wall . PATIENTS AND METHODS Twenty-seven patients with radiographically resectable intermediate- or high- grade soft tissue sarcomas were treated . Preoperative external-beam radiation was administered in 25 2-Gy fractions ( total dose , 50 Gy ) . Concurrent continuous-infusion doxorubicin was administered by an initial bolus ( 4 mg/m(2 ) ) and subsequent 4-day continuous infusion ( 12.5 , 15.0 , 17.5 , or 20.0 mg/m(2)/wk ) . Radiographic restaging was performed 4 to 7 weeks after chemoradiation , and patients with localized disease underwent surgical resection . RESULTS Chemoradiation was completed as an outpatient procedure in 25 patients ( 93 % ) . The maximum-tolerated dose of continuous-infusion doxorubicin combined with st and ard preoperative radiation was 17.5 mg/m(2)/wk ; at this dose level , seven ( 30 % ) of 23 patients had grade 3 dermatologic toxicity . Macroscopically complete resection ( R0 or R1 ) was performed in all 26 patients who underwent surgery . Among 22 patients who were treated with doxorubicin 17.5/mg/m(2)/wk with concurrent radiation and subsequent surgery , 11 patients ( 50 % ) had 90 % or greater tumor necrosis , including two patients who had complete pathologic responses . CONCLUSION Preoperative doxorubicin-based chemoradiation appears safe and feasible . The maximum-tolerated dose of continuous-infusion doxorubicin with st and ard preoperative radiation was 17.5 mg/m(2)/wk . Pathologic response rates with this regimen are encouraging Background Surgical resection alone does not cure the majority of patients with retroperitoneal sarcoma ( RPS ) . We evaluated the effects of preoperative external-beam radiotherapy ( XRT ) and postoperative brachytherapy ( BT ) combined with complete surgical resection . Methods Fifty-five patients with primary or locally recurrent RPS judged to be resectable were entered onto a trial of combined therapy and observed prospect ively . Forty-six patients underwent complete gross resection with curative intent . Of these , 41 patients completed preoperative XRT and 23 patients received BT . Outcome measures were treatment toxicity , overall survival , and disease-free survival ( DFS ) . Results Preoperative XRT was very well tolerated and was associated with Radiation Therapy Oncology Group acute toxicity scores of ≤2 in all patients . Acute postoperative and BT-related toxicity result ed in modified RTOG scores of ≥3 in 39.1 % ( 18 of 46 ) of patients . Late toxicity was associated with death in 4.3 % ( 2 of 46 ) and with life-threatening illness in 2.2 % ( 1 of 46 ) of patients , all of whom had been treated with BT to the upper abdomen . The 2-year overall survival and DFS for resected RPS were 88 % and 80 % , respectively . Significantly better 2-year DFS was achieved in patients with primary RPS and in those with low- grade tumors ( 93 % and 95 % , respectively ) . Conclusions The initial results of combined therapy are promising . Although preoperative XRT was very well tolerated , BT to the upper abdomen was associated with substantial toxicity . Our current protocol includes selective application of BT to the lower abdomen only Retroperitoneal sarcomas ( RPSs ) are rare tumors with poor survival rates due to difficult resectability and high local and distant recurrence rates . Preoperative radiation therapy appears to have dosimetric advantages to utilize the tumor as a tissue exp and er to limit exposure of small bowel to higher radiation doses Retroperitoneal sarcomas ( RPS ) are rare tumours that typically present late and carry a poor prognosis even following grossly complete resection . In an attempt to improve the outlook for patients with RPS , sarcoma specialists have employed various adjuvant therapies , including extermal beam radiation , intraoperative radiation , brachyradiation and systemic chemotherapy . This article review s the presentation and prognosis of RPS , and focuses on the results of new treatment strategies compared with conventional management . A Medline search of the English literature was performed to identify all retrospective and prospect i ve reports relating to the management of adult RPS published since 1980 . Series that did not analyse RPS separately from other intra-abdominal or extra-abdominal sarcomas or other malignancies were excluded , and information on investigation , presentation , prognostic factors , treatment and outcome was extracted from the remaining reports . Survival and local control data were collected from reports that contained at least 30 cases of RPS ( n = 31 ) . While surgical resection remains the cornerstone of treatment for RPS , the majority of patients will relapse and die from sarcoma within 5 years of resection . Adjuvant radiation may improve these results , but further trials are required to definitively demonstrate its benefit . Possible reasons for the failure of conventional treatment are discussed , and alternative strategies design ed to overcome these obstacles are presented PURPOSE Few published studies have analyzed risk factors for sarcoma-specific death . We developed and internally vali date d a nomogram that combines the factors to predict the probability of 12-year sarcoma-specific death using a data base of 2,136 prospect ively followed adult patients treated at a single institution . PATIENTS AND METHODS Nomogram predictor variables included age at diagnosis , tumor size ( < or = 5 , 5 to 10 , or > 10 cm ) , histologic grade ( high or low ) , histologic subtype ( fibrosarcoma , leiomyosarcoma , liposarcoma , malignant fibrous histiocytoma , malignant peripheral nerve tumor , synovial , or other ) , depth ( superficial or deep ) , and site ( upper extremity , lower extremity , visceral , thoracic or trunk , retrointraabdominal , or head or neck ) . Death from sarcoma or treatment complication was the predicted end point . Three prediction methods were compared , Kaplan-Meier analysis of all possible subsets , recursive partitioning , and Cox proportional hazards regression analysis . The concordance index was used as an accuracy measure with bootstrapping to correct for optimistic bias . RESULTS Sarcoma-specific death at 12 years was 36 % ( 95 % confidence interval , 33 % to 39 % ) . The bootstrap-corrected concordance indices were as follows : Kaplan-Meier , 0.69 ; recursive partitioning , 0.74 ; and Cox regression , 0.77 . A nomogram was drawn on the basis of the Cox regression model . This nomogram was internally vali date d using bootstrapping and shown to have excellent calibration . CONCLUSION A nomogram has been developed to predict 12-year sarcoma-specific death . This tool may be useful for patient counseling , follow-up scheduling , and clinical trial eligibility determination Thirty-five patients with surgically resected sarcomas of the retroperitoneum were enrolled in a prospect i ve , r and omized , clinical trial comparing 20-Gy intraoperative radiotherapy in combination with postoperative low-dose ( 35- to 40-Gy ) external-beam radiotherapy with postoperative high-dose ( 50- to 55-Gy ) external-beam radiotherapy alone . Chemotherapy with doxorubicin hydrochloride , cyclophosphamide ( anhydrous ) , and methotrexate sodium was used for a portion of the trial . Fifteen patients who received intraoperative radiotherapy and 20 control patients were followed up for a minimum of 5 years ( median follow-up , 8 years ) . Median survival times were similar for the group that received intraoperative radiotherapy ( 45 months ) and the control group ( 52 months ) . There were no indications of benefit from adjunctive chemotherapy . The number of locoregional recurrences was significantly lower among those who received intraoperative radiotherapy ( six of 15 ) than control patients ( 16 of 20 ) . Patients who received intraoperative radiotherapy had fewer complications of disabling radiation-related enteritis ( two of 15 ) than control patients ( 10 of 20 ) , but radiation-related peripheral neuropathy was more frequent among those who received intraoperative radiotherapy ( nine of 15 ) than among control patients ( one of 20 ) PURPOSE Retroperitoneal soft tissue sarcomas are rare tumors . Studies characterizing long-term follow-up and patterns of recurrence are limited . The purpose of this analysis is to identify patterns of recurrence and prognostic factors associated with long-term survival after resection of retroperitoneal soft tissue sarcomas . METHODS Between July 1 , 1982 , and June 30 , 1990 , 198 adult patients were identified from our prospect i ve soft tissue sarcoma data base carrying the diagnosis of retroperitoneal soft tissue sarcoma who were eligible for > or = 5 years of follow-up . Of these , 48 patients ( 25 % ) were documented to be alive > or = 5 years from the time of operation . Statistical analysis was by log-rank or Wilcoxon test for univariate analysis . Multivariate analysis was by the Cox model . RESULTS The recurrence rate during the follow-up period was approximately 5 % per year from the time of initial operation . Of the patients who were disease-free for > or = 5 years from initial surgery Output:	The authors concluded that there is good evidence from multiple single-institutions studies that RT improves the LCR in patients with retroperitoneal sarcoma . The current results indicated that preoperative external-beam RT followed by radical surgery seems to be the preferred sequence , and adding intraoperative RT is a safe procedure for dose escalation in the upper abdomen
MS21045	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: & NA ; A series of health surveys are conducted every sixth to seventh year in Denmark . In the most recent survey of 2000 , a national r and om sample ( > 16 years ) was drawn from the Danish Central Personal Register . Out of the original sample 12,333 ( 74 % ) were interviewed and of these 10,066 returned a completed question naire ( SF‐36 ) . The present study includes only those who both took part in the interview and the postal question naire . Cancer patients were excluded . Persons suffering from chronic pain ( PG ) were identified through the question ‘ Do you have chronic/long lasting pain lasting 6 months or more ’ ? An overall chronic pain prevalence of 19 % was found −16 % for men and 21 % for women . Prevalence of chronic pain increased with increasing age . Persons ≥67 years had 3.9 higher odds of suffering from chronic pain than persons in the age group 16–24 years . Compared with married persons , divorced or separated persons had 1.5 higher odds of chronic pain . Odds for chronic pain were 1.9 higher among those with an education of less than 10 years compared with individuals with an education of 13 years or more . During a 14‐day period reporters of chronic pain had an average of 0.8 days ( range 0–10 ) lost due to illness compared with an average of 0.4 days ( range 0–10 ) for the control group ( CG ) ( Odds Ratio ( OR ) ) 2.0 ) . Persons with a job which required high physical strain were more likely to report chronic pain compared with those with a sedentary job ( OR 2.2 ) . The odds of quitting one 's job because of ill health were seven times higher among people belonging to the PG . A strong association between chronic pain and poor self‐rated health was also demonstrated . The PG had twice as many contacts with various health professionals compared with the CG , and the health care system was , on average , utilised 25 % more ( overall contacts ) by the PG than by the general population . Among the persons in the PG , 33 % were not satisfied with the examinations carried out in connection with their pain condition and 40 % were not satisfied with the treatment offered . Nearly 130,000 adults , corresponding to 3 % of the Danish population , use opioids on a regular basis . Opioids are used by 12 % of the PG The role of gonadal hormones on pain sensations was investigated in normally menstruating women ( n = 16 ) using the cold pressor test . Tolerance time , pain threshold , and pain intensity were examined once a week during a 4-wk period , and serum concentrations of 17beta-estradiol and progesterone were determined at each test session , which were classified into the early follicular phase , late follicular phase , early luteal phase , and late luteal phase , as determined by the first day of menses and the actual hormone levels recorded . A group of men ( n = 10 ) of the same age interval was examined for comparison . The data show that pain threshold was reduced during the late luteal phase compared with the late follicular phase , and hormone analyses showed significant positive correlation between the progesterone concentration and lowered pain threshold and increasing pain intensity . Hormone analysis also showed an interaction between S-estradiol and S-progesterone on pain intensity , demonstrating that the increased perceived pain intensity that was associated with high progesterone concentrations was significantly reduced with increasing levels of estradiol . While no statistically significant sex differences in pain measurements were found , women displayed much more pronounced , and statistically significant , session-to-session effects than men , with increased pain threshold and decreased pain intensity with each test session . Hence , these data suggest that the changes in the serum concentration of gonadal hormones that occur during the menstrual cycle influence pain sensations elicited by noxious tonic cold stimulation and show that adaptation to the cold pressor test may be sex dependent & NA ; Gender differences in pain habituation , temporal summation , and pressure hyperalgesia evoked by repeated injections of glutamate into the dominant trapezius muscle were investigated . The glutamate‐evoked muscle pain intensity and pressure pain threshold ( PPT ) were assessed . The PPTs were measured bilaterally in the trapezius muscles ( local pain area ) and posterolateral neck muscles ( referred pain area ) after glutamate injection in healthy and age‐matched males and females ( each n=14 ) . Two glutamate injections ( 0.4 ml , 2 M each ) were injected with an interval of 5 min . One injection of glutamate ( 0.4 ml , 2 M ) served as a control . Males , but not females , rated the second injection ( maximal pain intensity ) significantly less painful than the first injection . The area under the visual analogue scale pain curve of the second injection was significantly larger than the first injection in females . Repeated glutamate injections , but not one‐glutamate injection , significantly decreased PPTs in the local pain area , with no significant gender differences . No PPTs changes were observed either in the contralateral trapezius muscle or bilaterally in the referred pain areas in either sex . These results suggest that a less efficient pain habituation and a greater susceptibility to the development of temporal summation of muscle pain in females , but not in males , might be one of the contributing factors to the higher incidence of neck shoulder pain in females . In addition , the reduction of PPTs in the local pain area evoked by intramuscular glutamate injection may represent an early process of peripheral pressure hyperalgesia , which is most likely gender independent & NA ; Aims of investigation : To quantify the magnitude of putative gender differences in experimental pressure pain threshold ( PPT ) , and to establish the relevance of repeated measurements to any such differences . Methods : Two separate studies were undertaken . A pressure algometer was used in both studies to assess PPT in the first dorsal interosseous muscle . Force was increased at a rate of 5 N /s . In study 1 , two measurements were taken from 240 healthy volunteers ( 120 males , 120 females ; mean age 25 years ) giving a power for statistical analysis of & bgr;=0.80 at & agr;=0.01 . In study two , 30 subjects ( 15 males , 15 females mean age 28 years ) were r and omly selected from study one . Fourteen repeated PPT measurements were recorded at seven , 10 min intervals . Mean PPT data for gender groups , from both studies , were analysed using analysis of covariance with repeated measures , and age as the covariate . Results : The mean PPT for each of the two measurements in study one showed a difference between gender of 12.2 N ( f=30.5 N , m=42.7 N ) and 12.8 N ( f=29.5 N , m=42.3 N ) , respectively , representing a difference of 28 % with females exhibiting a lower threshold . In study two , the mean difference calculated from 14 PPT repeated measurements over a 1 h period was comparable to that in study one at 12.3 N ( range 10.4–14.4 N ) again females exhibited the lower threshold . The differences in mean PPT values between gender were found to be significant in both study one , at ( P<0.0005 , F=37.8 , df=1 ) and study two ( P=0.01 , F=7.6 , df=1 ) . No significant differences were found in either study with repeated measurement ( P=0.892 and P=0.280 ) , or on the interaction of gender and repeated measurement after controlling for age ( P=0.36 and P=0.62 ) . Conclusion : Healthy females exhibited significantly lower mean PPTs in the first dorsal interosseous muscle than males , which was maintained for fourteen repeated measures within a 1 h period . This difference is likely to be above clinical ly relevant levels of change , and it has clear implication s for the use of different gender subjects in laboratory based experimental design s utilising PPT as an outcome measure BACKGROUND AND PURPOSE Palpation of peripheral nerve trunks has been advocated as a method of assessing the presence of hyperalgesic nerve tissue as a contributing factor to pain syndromes in musculoskeletal disorders of the upper quadrant . This study investigated , in the first instance , the pressure pain thresholds of the median , radial and ulnar nerve trunks of the upper limb in healthy , asymptomatic subjects . METHOD Forty-five male and 50 female healthy volunteer subjects participated in this study which involved measurement of pressure pain thresholds by use of pressure algometry bilaterally over the three peripheral nerve trunks in the upper limbs . RESULTS Pressure pain thresholds were shown to be lowest in the median nerve ( p = 0.001 ) and lower in female subjects ( p = 0.001 ) . Laterality ( p = 0.077 ) or the age of the subject ( p = 0.254 ) did not significantly influence results . CONCLUSIONS The study demonstrated differences in pressure pain thresholds in the three nerve trunks of the upper limb . These findings should be taken into account when interpreting the findings of nerve palpation in musculoskeletal upper quadrant disorders Objectives : Evidence has accumulated that men and women show different responses to noxious stimuli , with women exhibiting greater sensitivity to pain than men . Data concerning sex differences in Cortisol response patterns have revealed inconsistent results so far . The purpose of the present study was to examine sex differences in subjective pain and Cortisol response to a noxious stressor . Methods : Seventy‐six subjects ( 39 male and 37 female ) were investigated by a modification of the cold pressor test that consisted of intermittent immersion of the h and into ice water ( plunge test , PT ) . The PT was conducted twice , in consecutive trials , to guarantee a sufficient exposure to the noxious stressor for eliciting Cortisol responses . In each trial , tolerance time and pain ratings visual analog scale ( VAS ) were assessed . Seven saliva sample s ( c1‐c7 ) were collected to determine Cortisol levels at baseline ( c1‐c2 ) , directly before ( c3 ) and 20 minutes after noxious stress ( c4 ) , and during recovery period ( c5‐c7 ) . Results : We found no significant sex differences in tolerance time in trial 1 , but highly significant differences in tolerance time in trial 2 , with higher tolerance times in men . No significant sex differences were found for the VAS ratings of pain intensity and unpleasantness in the 2 trials . In contrast , a significantly larger Cortisol increase in men was observed compared with women . Analysis of covariance revealed that this result could not be attributed to sex differences in Cortisol level at baseline and in tolerance time . Discussion : The present study demonstrates that men show a larger Cortisol response to a noxious stressor than women that is not attributable to sex differences in subjective pain . The conclusion of a causal relation between larger Cortisol responses and higher pain tolerance thresholds in men is tempting but yet speculative & NA ; The purpose of the present study was to determine whether gender differences exist in the forebrain cerebral activation patterns of the brain during pain perception . Accordingly , positron emission tomography ( PET ) with intravenous injection of H2 15O was used to detect increases in regional cerebral blood flow ( rCBF ) in normal right‐h and ed male and female subjects as they discriminated differences in the intensity of innocuous and noxious heat stimuli applied to the left forearm . Each subject was instructed in magnitude estimation based on a scale for which 0 indicated ‘ no heat sensation ’ ; 7 , ‘ just barely painful ’ and 10 , ‘ just barely tolerable ’ . Thermal stimuli were 40 ° C or 50 ° C heat , applied with a thermode as repetitive 5‐s contacts to the volar forearm . Both male and female subjects rated the 40 ° C stimuli as warm but not painful and the 50 ° C stimuli as painful but females rated the 50 ° C stimuli as significantly more intense than did the males ( P=0.0052 ) . Both genders showed a bilateral activation of premotor cortex in addition to the activation of a number of contralateral structures , including the posterior insula , anterior cingulate cortex and the cerebellar vermis , during heat pain . However , females had significantly greater activation of the contralateral prefrontal cortex when compared to the males by direct image subtraction . Volume of interest comparison ( t‐statistic ) also suggested greater activation of the contralateral insula and thalamus in the females ( P<0.05 ) . These pain‐related differences in brain activation may be attributed to gender , perceived pain intensity , or to both factors Objective : In contrast to the research using typical experimental pain stimuli , there is no consensus that women are more sensitive to delayed onset muscle pain than men . The purpose of this study was to examine sex differences in delayed onset muscle pain with use of a quantified stimulus intensity and multidimensional and valid pain measures . Methods : Ninety-five participants ( 49.5 % women ) completed eccentric exercise and then returned to the laboratory at 24 and 48 hours postexercise . The same relative intensity of the eccentric exercise was administered to women and men based on their eccentric strength . Results : The occurrence of muscle pain was confirmed by increases in intensity , F2 , 182 = 162.28 , P<0.01 , η2 = 0.64 , and unpleasantness , F2 , 182 = 204.03 , P < 0.01 , η2 = 0.69 , and st and ardized pain ratings , F2 , 180 = 67.44 , P < 0.01 , η2 = 0.43 . The affective ratios indicated that the muscle pain was more unpleasant than intense . No sex differences were detected except that men reported higher affective ratios than women , F1 , 92 = 4.06 , P < 0.05 , η2 = 0.04 . Discussion : The absence of higher muscle pain ratings in women than men in this investigation Output:	This review suggests that females ( F ) and males ( M ) have comparable thresholds for cold and ischemic pain , while pressure pain thresholds are lower in F than M. There is strong evidence that F tolerate less thermal ( heat , cold ) and pressure pain than M but it is not the case for tolerance to ischemic pain , which is comparable in both sexes . The majority of the studies that measured pain intensity and unpleasantness showed no sex difference in many pain modalities . In summary , 10 years of laboratory research have not been successful in producing a clear and consistent pattern of sex differences in human pain sensitivity , even with the use of deep , tonic , long-lasting stimuli , which are known to better mimic clinical pain .
MS21046	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A double blind trial , was design ed , in which 118 patients undergoing the removal of impacted wisdom teeth were r and omly divided into the following groups ; 41 patients received Metronidazole , 39 patients received Arnica Montana , 38 patients received the placebo . Metronidazole was more effective in pain control than Arnica ( p less than 0.001 ) and placebo ( p less than 0.01 ) . It prevented swelling better than Arnica ( p less than 0.01 ) and placebo ( p less than 0.05 ) and was more effective in promoting healing than Arnica ( p less than 0.01 ) and placebo ( p greater than 0.02 ) . Arnica Montana appeared to give rise to greater pain than placebo ( p less than 0.05 ) and caused more swelling than the placebo ( p less than 0.01 ) Output:	On balance , they do not suggest that homeopathic arnica is more efficacious than placebo . CONCLUSION The cl aim that homeopathic arnica is efficacious beyond a placebo effect is not supported by rigorous clinical trials
MS21047	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Therapies that target the programmed death-1 ( PD-1 ) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types . One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 lig and ( PD-L1 ) and its ligation to PD-1 on antigen-specific CD8 + T cells ( termed adaptive immune resistance ) . Here we show that pre-existing CD8 + T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy . We analysed sample s from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy ( pembrolizumab ) using quantitative immunohistochemistry , quantitative multiplex immunofluorescence , and next-generation sequencing for T-cell antigen receptors ( TCRs ) . In serially sample d tumours , patients responding to treatment showed proliferation of intratumoral CD8 + T cells that directly correlated with radiographic reduction in tumour size . Pre-treatment sample s obtained from responding patients showed higher numbers of CD8- , PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours , with close proximity between PD-1 and PD-L1 , and a more clonal TCR repertoire . Using multivariate analysis , we established a predictive model based on CD8 expression at the invasive margin and vali date d the model in an independent cohort of 15 patients . Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8 + T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel . Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of 578 patients ) . One treatment-related death from a respiratory tract infection was reported in the docetaxel group . INTERPRETATION To our knowledge , OAK is the first r and omised phase 3 study to report results of a PD-L1-targeted therapy , with atezolizumab treatment result ing in a clinical ly relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer , regardless of PD-L1 expression or histology , with a favourable safety profile . FUNDING F. Hoffmann-La Roche Ltd , Genentech , The development of human cancer is a multistep process characterized by the accumulation of genetic and epigenetic alterations that drive or reflect tumour progression . These changes distinguish cancer cells from their normal counterparts , allowing tumours to be recognized as foreign by the immune system . However , tumours are rarely rejected spontaneously , reflecting their ability to maintain an immunosuppressive microenvironment . Programmed death-lig and 1 ( PD-L1 ; also called B7-H1 or CD274 ) , which is expressed on many cancer and immune cells , plays an important part in blocking the ‘ cancer immunity cycle ’ by binding programmed death-1 ( PD-1 ) and B7.1 ( CD80 ) , both of which are negative regulators of T-lymphocyte activation . Binding of PD-L1 to its receptors suppresses T-cell migration , proliferation and secretion of cytotoxic mediators , and restricts tumour cell killing . The PD-L1–PD-1 axis protects the host from overactive T-effector cells not only in cancer but also during microbial infections . Blocking PD-L1 should therefore enhance anticancer immunity , but little is known about predictive factors of efficacy . This study was design ed to evaluate the safety , activity and biomarkers of PD-L1 inhibition using the engineered humanized antibody MPDL3280A . Here we show that across multiple cancer types , responses ( as evaluated by Response Evaluation Criteria in Solid Tumours , version 1.1 ) were observed in patients with tumours expressing high levels of PD-L1 , especially when PD-L1 was expressed by tumour-infiltrating immune cells . Furthermore , responses were associated with T-helper type 1 ( TH1 ) gene expression , CTLA4 expression and the absence of fractalkine ( CX3CL1 ) in baseline tumour specimens . Together , these data suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1 , and is re-invigorated on antibody treatment BACKGROUND Nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , disrupts PD-1-mediated signaling and may restore antitumor immunity . METHODS In this r and omized , open-label , international phase 3 study , we assigned patients with nonsquamous non-small-cell lung cancer ( NSCLC ) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS Overall survival was longer with nivolumab than with docetaxel . The median overall survival was 12.2 months ( 95 % confidence interval [ CI ] , 9.7 to 15.0 ) among 292 patients in the nivolumab group and 9.4 months ( 95 % CI , 8.1 to 10.7 ) among 290 patients in the docetaxel group ( hazard ratio for death , 0.73 ; 96 % CI , 0.59 to 0.89 ; P=0.002 ) . At 1 year , the overall survival rate was 51 % ( 95 % CI , 45 to 56 ) with nivolumab versus 39 % ( 95 % CI , 33 to 45 ) with docetaxel . With additional follow-up , the overall survival rate at 18 months was 39 % ( 95 % CI , 34 to 45 ) with nivolumab versus 23 % ( 95 % CI , 19 to 28 ) with docetaxel . The response rate was 19 % with nivolumab versus 12 % with docetaxel ( P=0.02 ) . Although progression-free survival did not favor nivolumab over docetaxel ( median , 2.3 months and 4.2 months , respectively ) , the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel ( 19 % and 8 % , respectively ) . Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression ( ≥1 % , ≥5 % , and ≥10 % ) of the PD-1 lig and . Treatment-related adverse events of grade 3 or 4 were reported in 10 % of the patients in the nivolumab group , as compared with 54 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy , overall survival was longer with nivolumab than with docetaxel . ( Funded by Bristol-Myers Squibb ; CheckMate 057 Clinical Trials.gov number , NCT01673867 . ) BACKGROUND Patients with advanced squamous-cell non-small-cell lung cancer ( NSCLC ) who have disease progression during or after first-line chemotherapy have limited treatment options . This r and omized , open-label , international , phase 3 study evaluated the efficacy and safety of nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , as compared with docetaxel in this patient population . METHODS We r and omly assigned 272 patients to receive nivolumab , at a dose of 3 mg per kilogram of body weight every 2 weeks , or docetaxel , at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS The median overall survival was 9.2 months ( 95 % confidence interval [ CI ] , 7.3 to 13.3 ) with nivolumab versus 6.0 months ( 95 % CI , 5.1 to 7.3 ) with docetaxel . The risk of death was 41 % lower with nivolumab than with docetaxel ( hazard ratio , 0.59 ; 95 % CI , 0.44 to 0.79 ; P<0.001 ) . At 1 year , the overall survival rate was 42 % ( 95 % CI , 34 to 50 ) with nivolumab versus 24 % ( 95 % CI , 17 to 31 ) with docetaxel . The response rate was 20 % with nivolumab versus 9 % with docetaxel ( P=0.008 ) . The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel ( hazard ratio for death or disease progression , 0 Output:	Conclusion The use of anti-PD-1/anti-PD-L1 therapy in patients with progressive advanced NSCLC is significantly better than the use of docetaxel in terms of OS , PFS , duration of response and overall response rate
MS21048	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A double-blind , 18-center , balanced trial of diflunisal vs. cyclobenzaprine HCl vs. these two drugs combined vs. placebo produced complete results from 175 patients . They had sought treatment at the cooperating centers for acute painful spasms of the back within a day or two of trauma or strain . Global results over the 7 to 10 days of observations revealed a clinical ly and statistically significant superiority of the combined therapy by Day 4 ( P=0.006 ) and almost all patients recovered within a week to 10 days . A combination therapy with an effective safe analgesic and a true muscle relaxant for less than a week appears to be an excellent relief measure for acute back problems Therapeutic trials often attempt to “ blind ” patient and investigator to the true nature of treatments received , reducing the influences of conscious or subconscious prejudices . In drug trials , this is accomplished with placebo tablets , but blinding in trials of physical treatments is more problematic . This issue arose in a clinical trial of transcutaneous electrical nerve stimulation ( TENS ) for patients with chronic low back pain . Several study design features were incorporated to promote blinding : use of sham TENS units visually identical with real units , exclusion of potential subjects with previous TENS experience , avoidance of a crossover design and use of identical visit frequency , instructions and modifications in electrode placement . Subjects were asked not to discuss treatments with the clinicians who performed outcome assessment s. Both patients and clinicians were asked to guess actual treatment assignments at the trial 's end . Every patient in the true TENS group believed the unit was functioning properly , but the degree of certainty varied . In the sham TENS group , 84 % also believed they had functioning units , but their certainty was significantly less than in the active treatment group . Differences in patient perceptions did not affect compliance , as the two groups had similar dropout rates , appointment compliance , days of TENS use and daily duration of TENS use . Clinicians guessed treatments correctly 61 % of the time ( as opposed to 50 % expected by chance ) , again suggesting partial success in blinding . These efforts at blinding may partly explain the negative trial results for TENS efficacy . We conclude that complete blinding is difficult to achieve because of sensory difference in treatment and unintended communication between patient and examiner . Nonetheless , trials of physical treatments can achieve partial blinding with the techniques described here , and the success of blinding can be assessed with simple questions at study completion PURPOSE Herbal medicines are widely used for the treatment of pain , although there is not much information on their effectiveness . This study was design ed to evaluate the effectiveness of willow ( Salix ) bark extract , which is widely used in Europe , for the treatment of low back pain . SUBJECTS AND METHODS We enrolled 210 patients with an exacerbation of chronic low back pain who reported current pain of 5 or more ( out of 10 ) on a visual analog scale . They were r and omly assigned to receive an oral willow bark extract with either 120 mg ( low dose ) or 240 mg ( high dose ) of salicin , or placebo , with tramadol as the sole rescue medication , in a 4-week blinded trial . The principal outcome measure was the proportion of patients who were pain-free without tramadol for at least 5 days during the final week of the study . RESULTS The treatment and placebo groups were similar at baseline in 114 of 120 clinical features . A total of 191 patients completed the study . The numbers of pain-free patients in the last week of treatment were 27 ( 39 % ) of 65 in the group receiving high-dose extract , 15 ( 21 % ) of 67 in the group receiving low-dose extract , and 4 ( 6 % ) of 59 in the placebo group ( P < 0.001 ) . The response in the high-dose group was evident after only 1 week of treatment . Significantly more patients in the placebo group required tramadol ( P < 0.001 ) during each week of the study . One patient suffered a severe allergic reaction , perhaps to the extract . CONCLUSION Willow bark extract may be a useful and safe treatment for low back pain Study Design . Two replicate , 4-week , r and omized , double-blind , placebo-controlled , trials of rofecoxib 25 and 50 mg versus placebo for chronic low back pain . Objectives . To determine the efficacy and safety of two doses of rofecoxib compared to placebo in the treatment of chronic low back pain . Summary of Background Data . Although nonsteroidal anti-inflammatory drugs are commonly prescribed for chronic low back pain , their efficacy is unproven and toxicity can be serious . These studies evaluated the efficacy and tolerability of rofecoxib , a selective COX-2 inhibitor , in the treatment of chronic low back pain . Methods . Patients with chronic low back pain were r and omized 1:1:1 to rofecoxib 25 mg , 50 mg , or placebo once daily . Primary endpoint : Low Back Pain Intensity . Secondary endpoints : Pain Bothersomeness , Global Assessment s of Response to Therapy , Global Assessment of Disease Status , Rol and -Morris Disability Question naire , SF-12 Health Survey , Use of Rescue Acetaminophen , and Discontinuations Due to Lack of Efficacy . Results . Combining both studies , 690 patients were r and omized to placebo ( N = 228 ) , rofecoxib 25 mg ( N = 233 ) , or rofecoxib 50 mg ( N = 229 ) . Mean ( ± SD ) age was 53.4 ( ± 12.9 ) years , pain duration 12.1 ( ± 11.8 ) years , 62.3 % female . Both rofecoxib groups improved significantly . Mean differences from placebo in pain intensity were −13.50 mm , −13.81 mm ( 25 , 50 mg doses ) respectively ( P < 0.001 ) . Both regimens were superior to placebo in eight of nine secondary endpoints . Fifty mg provided no advantage over 25 mg . Both rofecoxib regimens were well tolerated , although 25 mg had a slightly better safety profile . Conclusions . Rofecoxib significantly reduced chronic low back pain in adults and was well tolerated Objective Chronic low back pain ( CLBP ) is a widespread ailment . The aim of this study was to assess the efficacy of topiramate in the treatment of CLBP and the changes in anger status and processing , body weight , subjective pain-related disability and health-related quality of life during the course of treatment . Methods We conducted a 10-week , r and omized , double-blind , placebo-controlled study of topiramate in 96 ( 36 women ) patients with CLBP . The subjects were r and omly assigned to topiramate ( n=48 ) or placebo ( n=48 ) . Primary outcome measures were changes on the McGill Pain Question naire , State-Trait Anger Expression Inventory , Oswestry Low Back Pain Disability Question naire and SF-36 Health Survey scales , and in body weight . Results In comparison with the placebo group ( according to the intent-to-treat principle ) , significant changes on the pain rating index of McGill Pain Question naire ( Ps<0.001 ) , State-Trait Anger Expression Inventory Scales ( all Ps<0.001 ) , Oswestry Low Back Pain Disability Question naire ( P<0.001 ) , and SF-36 Health Survey scales ( all P<0.001 , except on the role-emotional scale ) were observed after 10 weeks in the patients treated with topiramate . Weight loss was also observed and was significantly more pronounced in the group treated with topiramate than in those treated with placebo ( P<0.001 ) . Most patients tolerated topiramate relatively well but 2 patients dropped out because of side effects . Discussion Topiramate seems to be a relatively safe and effective agent in the treatment of CLBP . Significantly positive changes in pain sensitivity , anger status and processing , subjective disability , health-related quality of life , and loss of weight were observed UNLABELLED Opioid-experienced ( N = 250 ) patients with chronic , moderate to severe low back pain ( LBP ) were converted from their pre study opioid(s ) to an approximately equianalgesic dose of OPANA ER ( oxymorphone extended release ) . Patients continued slow titration , with 56 % stabilized within 1 month to a dose of OPANA ER that reduced average pain to < 40 mm on a visual analog scale with good tolerability . Stabilized patients ( n = 143 ) were r and omized to placebo or their stabilized dose of OPANA ER every 12 hours for a 12-week double-blind period . Pain intensity increased significantly more for patients r and omized to placebo than for patients who continued their stabilized dose of OPANA ER ; the increase from baseline ( at r and omization ) to final visit was 31.6 mm for placebo versus 8.7 mm with OPANA ER ( P < .0001 ) . During double-blind treatment , placebo patients were approximately 8-fold more likely than OPANA ER patients to discontinue because of lack of efficacy ( P < .001 ) . Discontinuations as a result of adverse events were similar between groups , 10 % with placebo and 11 % with OPANA ER . Opioid-related adverse events included constipation ( 6 % ) , somnolence ( 3 % ) , and nausea ( 3 % ) . Fifty-seven percent of opioid-experienced patients with chronic , moderate to severe LBP achieved a stable dose of OPANA ER that was efficacious and generally well-tolerated for up to 12 weeks . PERSPECTIVE In a 12-week , double-blind , r and omized , placebo-controlled trial in opioid-experienced patients with chronic , moderate to severe LBP , OPANA ER provided efficacious , long-term analgesia and was generally well-tolerated . OPANA ER may provide clinicians with a new treatment option for patients experiencing suboptimal analgesic responses or poor tolerability with other opioids Previous studies have shown a positive association between pain and depression , though evidence supporting a direct link between these two variables is less robust . Using a placebo-controlled trial , the authors examined the analgesic and antidepressant efficacy of paroxetine ( 20 mg ) in chronic low back pain sufferers . The authors examined the associations among pain , depression , disability , and illness attitudes . Paroxetine showed no effects on pain or depression compared with placebo ; however , subjects r and omized to paroxetine were more likely to reduce concomitant analgesic medication . The cross-sectional association of depression and pain at baseline ( r = 0.2 , P = 0.02 ) was weaker than the association between depression and disability ( r = 0.3 , P = 0.004 ) . Similarly , the association of change in depression scores with change in pain ( r = 0.25 , P = 0.016 ) was weaker than change between depression and disability ( r = 0.49 , P<0.0005 ) . Whereas the relationship between pain and depression became nonsignificant when disability and illness attitudes were controlled , the relationship between depression and disability remained highly significant when pain and illness attitudes were controlled . These data are consistent with the association between pain and depression being wholly modulated by disability and illness attitudes , with no direct relationship between pain and depression BACKGROUND The effectiveness of massage therapy for low-back pain has not been documented . This r and omized controlled trial compared comprehensive massage therapy ( soft-tissue manipulation , remedial exercise and posture education ) , 2 components of massage therapy and placebo in the treatment of subacute ( between 1 week and 8 months ) low-back pain . METHODS Subjects with subacute low-back pain were r and omly assigned to 1 of 4 groups : comprehensive massage therapy ( n = 25 ) , soft-tissue manipulation only ( n = 25 ) , remedial exercise with posture education only ( n = 22 ) or a placebo of sham laser therapy ( n = 26 ) . Each subject received 6 treatments within approximately 1 month . Outcome measures obtained at baseline , after treatment and at 1-month follow-up consisted of the Rol and Disability Question naire ( RDQ ) , the McGill Pain Question naire ( PPI and PRI ) , the State Anxiety Index and the Modified Schober test ( lumbar range of motion ) . RESULTS Of the 107 subjects who passed screening , 98 ( 92 % ) completed post-treatment tests and 91 ( 85 % ) completed follow-up tests . Statistically significant differences were noted after treatment and at follow-up . The comprehensive massage therapy group had improved function ( mean RDQ score 1.54 v. 2.86 - 6.5 , p < 0.001 ) , less intense pain ( mean PPI score 0.42 v. 1.18 - 1.75 , p < 0.001 ) and a decrease in the quality of pain ( mean PRI score 2.29 v. 4.55 - 7.71 , p = 0.006 ) compared with the other 3 groups . Clinical significance was evident for the comprehensive massage therapy group and the soft-tissue manipulation group on the measure of function . At 1-month follow-up 63 % of subjects in the comprehensive massage therapy group reported no pain as compared with 27 % of the soft-tissue manipulation group , 14 % of the remedial exercise group and 0 % of the sham laser therapy group . INTERPRETATION Patients with Output:	Although the evidence from studies using sham laser was inconclusive , the present review did find a clinical ly meaningful change in LBP scores following the use of sham oral medications . CONCLUSIONS The present best- evidence review found a clinical ly meaningful change in pain scores following the use of sham oral medications for the treatment of nonspecific LBP .
MS21049	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Some studies in first-episode schizophrenia correlate shorter duration of untreated psychosis ( DUP ) with better prognosis , suggesting that timing of treatment may be important . A three-site prospect i ve clinical trial in Norway and Denmark is underway to investigate the effect of the timing of treatment in first-episode psychosis . One health care sector ( Rogal and , Norway ) is experimental and has developed an early detection ( ED ) system to reduce DUP . Two other sectors ( Ullevål , Norway , and Roskilde , Denmark ) are comparison sectors and rely on existing detection and referral systems for first-episode cases . The study ultimately will compare early detected with usual detected patients . This paper describes the study 's major independent intervention variable , i.e. a comprehensive education and detection system to change DUP in first onset psychosis . System variables and first results from the four-year inclusion period ( 1997 - 2000 ) are described . It includes targeted information towards the general public , health professionals and schools , and ED teams to recruit appropriate patients into treatment as soon as possible . This plus easy access to psychiatric services via ED teams systematic ally changed referral patterns of first-episode schizophrenia . DUP was reduced by 1.5 years ( mean ) from before the time the ED system was instituted ( to 0.5 years ) . The ED strategies appear to be effective and to influence directly the community 's help-seeking behaviour BACKGROUND There are few evaluations of strategies to improve rates of early detection and treatment of patients with first-episode psychosis . AIMS To evaluate the effectiveness of a general practitioner ( GP ) education programme and an early detection assessment team ( the Lambeth Early Onset Crisis Assessment Team ; LEO CAT ) in reducing delays in accessing treatment for first-episode psychosis patients . METHOD 46 clusters of GP practice s r and omised to GP education in early detection with direct access to LEO CAT v. care as usual . Primary outcome measures were GP referral rates , duration of untreated psychosis ( DUP ) and delays in receiving treatment . RESULTS 150 patients with first-episode psychosis were recruited ; 113 were registered with the study GPs , who referred 54 ( 47.7 % ) directly to mental health services . Significantly more intervention group GPs ( 86.1 % v. 65.7 % ) referred their patients directly to mental health services and fewer patients experienced long delays in receiving treatment . However , their overall DUP was unaffected . CONCLUSIONS Educating GPs improves detection and referral rates of first-episode psychosis patients . An early detection team reduces the long delays in initial assessment and treatment . However , these only impact on the later phases of the DUP . Broader measures , such as public health education , are needed to reduce the earlier delays in DUP Background The Mental Health First Aid training course was favorably evaluated in an uncontrolled trial in 2002 showing improvements in participants ' mental health literacy , including knowledge , stigmatizing attitudes , confidence and help provided to others . This article reports the first r and omized controlled trial of this course . Methods Data are reported on 301 participants r and omized to either participate immediately in a course or to be wait-listed for 5 months before undertaking the training . The participants were employees in two large government departments in Canberra , Australia , where the courses were conducted during participants ' work time . Data were analyzed according to an intention-to-treat approach . Results The trial found a number of benefits from this training course , including greater confidence in providing help to others , greater likelihood of advising people to seek professional help , improved concordance with health professionals about treatments , and decreased stigmatizing attitudes . An additional unexpected but exciting finding was an improvement in the mental health of the participants themselves . Conclusions The Mental Health First Aid training has shown itself to be not only an effective way to improve participants ' mental health literacy but also to improve their own mental health . It is a course that has high applicability across the community CONTEXT Most studies on first-episode psychosis show an association between a long duration of untreated psychosis ( DUP ) and poorer short-term outcome , but the mechanisms of this relationship are poorly understood . OBJECTIVE To determine whether it is possible to reduce the DUP for first-episode patients in a defined health care area through the introduction of an early detection ( ED ) program , compared with parallel health care areas without an ED program ( No-ED ) . SETTING AND PATIENTS We included consecutive patients with a DSM-IV diagnosis of nonorganic , nonaffective psychosis coming to their first treatment in the study health care areas between January 1 , 1997 , and December 31 , 2000 . A total of 281 patients ( 76 % of the total ) gave informed consent . INTERVENTIONS The ED and No-ED health care areas offered an equivalent assessment and treatment program for first-episode psychosis . The ED area also carried out an intensive ED program . RESULTS The DUP was significantly shorter for the group of patients coming from the ED area , compared with patients from the No-ED areas ( median , 5 weeks [ range , 0 - 1196 weeks ] vs 16 weeks [ range , 0 - 966 weeks ] ) . Clinical status measured by the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale was significantly better for patients from the ED area at start of treatment and , with the exception of Positive and Negative Syndrome Scale positive subscale , at 3 months . Multiple linear regression analyses gave no indication that confounders were responsible for these differences . CONCLUSIONS It is possible to reduce the DUP through an ED program . The reduction in DUP is associated with better clinical status at baseline that is maintained after 3 months This study evaluates the ability of a safer sex televised public service announcement ( PSA ) campaign to increase safer sexual behavior among at-risk young adults . Independent , monthly r and om sample s of 100 individuals were surveyed in each city for 21 months as part of an interrupted-time-series design with a control community . The 3-month high-audience-saturation campaign took place in Lexington , KY , with Knoxville , TN , as a comparison city . Messages were especially design ed and selected for the target audience ( those above the median on a composite sensation-seeking/impulsive-decision-making scale ) . Data indicate high campaign exposure among the target audience , with 85%-96 % reporting viewing one or more PSAs . Analyses indicate significant 5-month increases in condom use , condom-use self-efficacy , and behavioral intentions among the target group in the campaign city with no changes in the comparison city . The results suggest that a carefully targeted , intensive mass media campaign using televised PSAs can change safer sexual behaviors BACKGROUND Delays in accessing care for young people with a first episode of psychosis are significantly associated with poorer treatment response and higher relapse rates . AIM To assess the effect of an educational intervention for GPs on referral rates to early-intervention services and the duration of untreated psychosis for young people with first-episode psychosis . DESIGN OF STUDY Stratified cluster r and omised controlled trial , clustered at practice level . SETTING Birmingham , Engl and . METHOD Practice s with access to the three early-intervention services in three inner-city primary care trusts in Birmingham were eligible for inclusion . Intervention practice s received an educational intervention addressing GP knowledge , skills , and attitudes about first-episode psychosis . The primary outcome was the difference in the number of referrals to early-intervention services between practice s. Secondary outcomes were duration of untreated psychosis , time to recovery , use of the Mental Health Act , and GP consultation rate during the developing illness . RESULTS A total of 110 of 135 eligible practice s ( 81 % ) were recruited ; 179 young people were referred , 97 from intervention and 82 from control practice s. The relative risk of referral was not significant : 1.20 ( 95 % confidence interval [ CI ] = 0.74 to 1.95 ; P = 0.48 ) . No effect was observed on secondary outcomes except for ' delay in reaching early-intervention services ' , which was statistically significantly shorter in patients registered in intervention practice s ( 95 % CI = 83.5 to 360.5 ; P = 0.002 ) . CONCLUSION GP training on first-episode psychosis is insufficient to alter referral rates to early-intervention services or reduce the duration of untreated psychosis ; however , there is a suggestion that training facilitates access to the new specialist teams for early psychosis R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community Output:	Evidence suggests that general practitioner education campaigns and dedicated early intervention services do not by themselves reduce DUP or generate more treated cases . Evidence for multifocus initiatives is mixed : intensive campaigns targeting the general public as well as relevant professionals may be needed . CONCLUSIONS How early detection can be achieved is not clear .
MS21050	*TASK* the task is to summarize an input biomedical literature in six sentences *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 most common site of venous reflux is the long saphenous vein ( LSV ) . The preferred treatment for reflux in the LSV is surgical stripping of the LSV . However , the complications of surgical stripping are well documented and undesirable . The constant search for treatment options with less morbidity , which are also cosmetically more acceptable , has result ed in the endovenous treatment for primary varicose veins , developed by VNUS Medical Technologies , Inc ( Sunnyvale , Calif ) . We hereby present our first treatment experiences and propose refinements to the procedure . METHODS Two types of heat-generating endovenous catheters were used to treat incompetence of the LSV with a diameter of up to 12 mm . The procedure was performed on a blood-empty limb . RESULTS Twenty-six limbs , in 26 patients , were treated , and the follow-up period was 1 year . The mean preoperative CEAP score was 4 , and the postoperative score was 1.26 , which was statistically significantly less ( P < .0001 , with Wilcoxon nonparametric matched pair test ) . Five patients had postoperative paresthesia of the saphenous nerve , and one patient had a burn from the procedure . The overall complication rate was 23 % . All complications occurred in the first half of the studied population ( P = .015 , with Fisher exact test ) , indicating the learning curve effect . In one patient ( 3.8 % ) , was total recanalization of the treated segment occurred , one patient ( 3.8 % ) could not be treated at all ( technical failure ) , and one patient ( 3.8 % ) had partial recanalization of the LSV . Eight patients ( 30.8 % ) had closure of the entire LSV but with persisting reflux in the saphenofemoral junction ( SFJ ) . Two patients had a competent SFJ with occlusion of the LSV . In 13 patients ( 50 % ) , closure of both the LSV and the SFJ was seen . The LSV was successfully occluded in 88 % of the patients . CONCLUSION The endovenous catheter should not be used more than 5 to 10 cm below the knee to prevent saphenous nerve damage . Performance of the procedure with bloodlessness is preferable . A result of 88 % of successfully treated LSV segments indicates a promising alternative for surgical stripping of the LSV OBJECTIVE The aim of this r and omized study was to compare a new method of endovenous saphenous vein obliteration ( Closure System , VNUS Medical Technologies , Inc , Sunnyvale , Calif ) with the conventional stripping operation in terms of short-term recovery and costs . METHODS Twenty-eight selected patients for operative treatment of primary greater saphenous vein tributary varicose veins were r and omly assigned to endovenous obliteration ( n = 15 ) or stripping operation ( n = 13 ) . Postoperative pain was daily assessed during the 1st week and on the 14th postoperative day . The length of sick leave was determined . The R AND -36 health survey was used to assess the patient health-related quality of life . The patient conditions were controlled 7 to 8 weeks after surgery , and patients underwent examination with duplex ultrasonography . The comparison of costs included both direct medical costs and costs result ing from lost of productivity of the patients . Costs that were similar in the study groups were not considered in the analysis . RESULTS All operations were successful , and the complication rates were similar in the two groups . Postoperative average pain was significantly less severe in the endovenous obliteration group as compared with the stripping group ( at rest : 0.7 , st and ard deviation [ SD ] 0.5 , versus 1.7 , SD 1.3 , P = .017 ; on st and ing : 1.3 , SD 0.7 , versus 2.6 , SD 1.9 , P = .026 ; on walking : 1.8 , SD 0.8 , versus 3.0 , SD 1.8 , P = .036 ; with t test ) . The sick leaves were significantly shorter in the endovenous obliteration group ( 6.5 days , SD 3.3 days , versus 15.6 days , SD 6.0 days ; 95 % CI , 5.4 to 12.9 ; P < .001 , with t test ) . Physical function was also restored faster in the endovenous obliteration group . The estimated annual investment costs of the closure operation were US $ 3360 . The other direct medical costs of the Closure operation were about $ 850 , and those of the conventional treatment were $ 360 . With inclusion of the value of the lost working days , the Closure treatment was cost-saving for society , and when 40 % of the patients are retired ( or 60 % of the productivity loss was included ) , the Closure procedure became cost-saving at a level of 43 operations per year . CONCLUSION Endovenous obliteration may offer advantages over the conventional stripping operation in terms of reduced postoperative pain , shorter sick leaves , and faster return to normal activities , and it appears to be cost-saving for society , especially among employed patients . Because the procedure is also associated with shorter convalescence , this new method may potentially replace conventional varicose vein surgery BACKGROUND Despite adequate training in the surgical treatment of varicose veins , recurrence continues to be a problem and a burden to the vascular services . A major cause of recurrence is reported to be neo-vascularisation at the sapheno-femoral junction ( SFJ ) . The aim of this study was to compare the incidence of neo-vascularisation at the SFJ following radiofrequency ablation ( RFA ) and open high saphenous tie and stripping ( HSTS ) . MATERIAL S AND METHODS Fifty-one patients ( 55 legs ) underwent st and ardised HSTS as part of a prospect i ve study . These were compared with an age ( range 28 - 83 , mean 54.4 ) and sex ( male : female 31:20 ) matched group of patients treated during the same time period , by the same consultant vascular surgeon , using RFA ( VNUS closure ) . Each patient had a pre-operative duplex scan to confirm SFJ reflux , a one-week scan to confirm successful surgery and a one-year post-operative scan to assess neo-vascularisation . The same vascular technologist performed all scans . Neo-vascularisation was identified by the presence of refluxing tortuous vessels arising from the area of the SFJ . RESULTS AND CONCLUSION Six of 55 ( 11 % ) legs in the open surgery group showed clear evidence of tortuous refluxing veins related to the SFJ . None of the 55 in the RFA group showed any neo-vascularisation at the SFJ ( Fischer exact test P = 0.028 ) . Further r and omised controlled trials are necessary to confirm these observations The study was planned to evaluate efficacy and costs of endovascular sclerotherapy ( ES ) in comparison with surgery and surgery associated with sclerotherapy in a prospect i ve ( 10-year follow-up ) , good- clinical - practice study . Patients with varicose veins and pure , superficial venous incompetence were included . Of the patients r and omized into the three groups 39 ( group A ) were treated with ES , 40 ( B ) with surgery + sclerotherapy , and 42 with surgery only ( C ) . Surgery consisted of ligation of the SFJ ( saphenofemoral junction ) and of incompetent veins detected with color duplex . Of the preselected 150 patients , 121 subjects entered the study ; 96 completed the 10-year follow-up ( mean age 52.6 ±6 years ; 51 men , 45 women ) . Dropouts were due to nonmedical problems . At 10 years no incompetence was observed in subjects treated with SPJ ligation ( B and C ) . In the ES group 18.8 % of the SFJs were patent and incompetent and in 43.8 % of limbs the distal ( below-knee ) venous system was still incompetent [ 16.1 % in the surgery + scle rotherapy group ( p < 0.05 ) and 36 % in the group treated with surgery only ( p < 0.05 vs B and 0.05 vs A ) ] . Color duplex of the long saphenous vein indicated atrophy or obstruc tion of a segment ( average 6.7 cm ) after SFJ ligation ( 4.2 cm after ES ) . The cost of ES was 68 % of surgery while the cost of surgery and sclerotherapy was 122 % of surgery only . Endovascular sclerotherapy is an effective , cheaper treatment option , but surgery after 10 years is superior OBJECTIVE This study aim ed to assess the outcome of endoluminal thermal ablation ( VNUS ) and traditional redo groin surgery ( RGS ) and long saphenous vein ( LSV ) stripping in patients with bilateral recurrent long saphenous varicose veins . METHODS This was a r and omised patient controlled double blind study . Sample size calculations required 16 patients . Their median age was 54 and 11 were women . The median CEAP class was 3 . At operation one leg , chosen at r and om , was treated with VNUS and avulsions using intra-operative duplex control . The other leg was treated with traditional RGS , exposure of the femoral vein , stripping of the LSV and multiple avulsions . Post-operatively patients completed 10 cm visual analogue scales for pain and bruising . Digital Image analysis was used to objective ly assess bruising . Statistical analysis was done using Wilcoxon signed rank test for paired data . Results are expressed as median values ( inter-quartile ranges ) . RESULTS Time to perform VNUS was 25.5 ( 20.5 - 31.3 ) min compared with 40 ( 34.5 - 45.5 ) min it took for RGS ( p=0.02 ) . Pain score for VNUS was 1.7 ( 0.2 - 4 ) , significantly lower than that for RGS 3.8 ( 0.6 - 6.3 ) ( p=0.02 ) . Bruise score for VNUS was 1.7 ( 0.4 - 4.4 ) , and that for RGS was 5.2 ( 2.6 - 7 ) ( p=0.03 ) . All LSVs were sealed by VNUS at duplex follow up . Three legs in the RGS group and two in the VNUS group had a minor complication . CONCLUSIONS VNUS caused less pain and bruising and was performed more quickly than RGS . VNUS should be considered the treatment of choice for recurrent long saphenous varicose veins PURPOSE This study was design ed as a prospect i ve multicenter r and omized comparison of procedure-related complications , patient recuperation , and quality -of-life outcomes between patients undergoing vein stripping with high ligation and patients undergoing great saphenous vein ( GSV ) obliteration with temperature-controlled radiofrequency ablation without adjunctive high ligation ( Closure procedure ) . METHODS Eighty-five patients ( 86 limbs ) from five sites ( France , 2 ; Austria , 1 ; United States , 2 ) were r and omly allocated to undergo radiofrequency obliteration ( RFO ) or stripping and high ligation ( S&L ) . Final analysis included data for 44 limbs in the RFO group and 36 limbs in the S&L group . Follow-up examinations were performed at 72 hours , 1 week , 3 weeks , and 4 months . All patients completed the CIVIQ2 quality -of-life ( QOL ) question naire and underwent clinical and ultrasound examinations at each follow-up visit . RESULTS Immediate success on the day of treatment was reported for 95 % ( 42 of 44 ) of limbs in the RFO group and 100 % ( 36 of 36 ) of limbs in the S&L group . In seven RFO limbs ( 16.3 % ) a scan obtained 72 hours after the procedure showed flow in the proximal GSV . Five of these segments had reflux in the open segment . At 1 week two of these closed , and an additional segment closed at 3 weeks . In no cases did flow reappear after complete occlusion of the GSV . Time to return to normal activities was significantly less in the RFO group ( mean , 1.15 days ; 95 % confidence interval [ CI ] , 0.05 - 2.34 ) compared with the S&L group ( mean , 3.89 days ; CI , 2.67 - 5.12 ; P = .02 ) . In the RFO group , 80.5 % of patients returned to routine activities of daily living within 1 day , compared with 46.9 % of patients in the S&L group ( P < .01 ) . Patients in the RFO group were able to return to work in 4.7 days ( CI , 1.16 - 8.17 ) , compared with 12.4 days ( CI , 8.66 - 16.23 ) for the S&L group ( P < .05 ) . Analysis of the QOL surveys showed statistically significant differences in favor of the RFO group for global score and pain score during follow-up . The magnitude of the difference , however , progressively decreased between 1 week and 4 months . CONCLUSIONS In the absence of significant complications , such as deep vein thrombosis and pulmonary embolism , severe neuritic sequelae , and skin burns , there are significant early advantages to endovascular obliteration of the GSV compared with conventional vein stripping Endovenous laser therapy ( EVLT ) is a minimally invasive treatment for varicose veins . This study compares early quality -of-life ( QoL ) outcomes following EVLT and surgery . Two nonr and omized groups were studied : an EVLT group with 70 patients , median age 49 ( interquart Output:	Serious adverse events were rare . Minor adverse events were more common but generally self-limiting . All treatments displayed levels of effectiveness depending on the extent of the vein in question . Short-term advantages appeared to be associated with sclerotherapy and endovenous treatments , and long-term effectiveness was more apparent following surgical intervention . Evidence suggests conservative therapy is less effective than sclerotherapy and surgery for the treatment of varicose veins . Sclerotherapy and surgery both appear to have a place in the management of varicose veins . Sclerotherapy and phlebectomy may also be more appropriate in patients with minor superficial varicose veins not related to reflux of the saphenous system or as a post- or adjunctive treatment to other procedures , such as surgery . Current evidence suggests endovenous laser therapy and radiofrequency ablation are as safe and effective as surgery , particularly in the treatment of saphenous veins .
MS21051	*TASK* the task is to summarize an input biomedical literature in six sentences *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 AND OBJECTIVES The use of levosimendan to treat postoperative low cardiac output syndrome ( LCOS ) has been studied in only small patient series and in r and omized trials focusing on hemodynamic variables . The objective of the present study was to assess the effectiveness of levosimendan , compared with dobutamine , as a treatment for postoperative LCOS . METHODS Patients with LCOS were r and omly assigned to receive either levosimendan ( loading dose , 10 microg/kg , followed by 0.1 microg/kg per min for 24 h ) or dobutamine ( starting dose , 5 microg/kg per min ) . Hemodynamic and clinical parameters ( including postoperative mortality and major complications ) , the need for the coadministration of another drug ( such as an inotrope or a vasopressor ) or for balloon counterpulsation , and length of stay in intensive care were all monitored . RESULTS The study included 137 patients : 69 received levosimendan , while 68 were treated with dobutamine . Although both agents improved hemodynamic parameters , the effect of levosimendan was greater and occurred earlier than that of dobutamine . In addition , levosimendan use result ed in lower postoperative mortality ( 8.7 % vs. 25 % ; P < .05 ) , a lower incidence of major postoperative complications , and less need for an additional inotropic drug ( 8.7 % vs. 36.8 % ; P < .05 ) , a vasopressor ( 11.6 % vs. 30.9 % ; P < .05 ) , or balloon counterpulsation ( 2.9 % vs. 14.7 % ; P<0.05 ) . The length of stay in intensive care was also less ( 66 vs. 158 h ; P < .05 ) . CONCLUSIONS In this r and omized study , levosimendan proved more effective than dobutamine . Postoperative morbidity and mortality were lower , fewer patients required either an additional inotropic drug , a vasopressor or intra-aortic balloon counterpulsation , and the length of stay in intensive care was shorter The calcium sensitizer levosimendan may counteract stunning after reperfusion of ischaemic myocardium , but no r and omized placebo‐controlled trials exist regarding its use in PCI‐treated ST‐segment elevation infa rct ion ( STEMI ) . We evaluated the efficacy and safety of levosimendan in patients with a primary PCI‐treated STEMI complicated by symptomatic heart failure ( HF ) Background Clinical evidence continues to exp and and is increasingly difficult to overview . We aim ed at conceptualizing a visual assessment tool , i.e. , a matrix for overviewing studies and their data in order to assess the clinical evidence at a glance . Methods A four-step matrix was constructed using the three dimensions of systematic error , r and om error , and design error . Matrix step I ranks the identified studies according to the dimensions of systematic errors and r and om errors . Matrix step II orders the studies according to the design errors . Matrix step III assesses the three dimensions of errors in studies . Matrix step IV assesses the size and direction of the intervention effect . Results The application of this four-step matrix is illustrated with two examples : peri-operative beta-blockade initialized in relation to surgery versus placebo for major non-cardiac surgery , and antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation . When clinical evidence is deemed both internally and externally valid , the size of the intervention effect is to be assessed . Conclusion The error matrix provides an overview of the validity of the available evidence at a glance , and may assist in deciding which interventions to use in clinical practice INTRODUCTION Although beta-blockers are highly effective in the treatment of heart failure ( HF ) , many patients with HF receiving a beta-blocker continue to become decompensated and require hospitalization for worsening HF . Levosimendan and dobutamine are used to manage decompensated HF , but their comparative effects on left ventricular ( LV ) function in patients prescribed beta-blockers are unknown . AIMS The aim of this study was to compare the effects of dobutamine and levosimendan on LV systolic and diastolic functions in chronic HF patients treated chronically with carvedilol . Forty patients with chronic HF who had NYHA class III to IV symptoms , a LV ejection fraction ( LVEF ) < 40 % , and ongoing treatment with carvedilol were enrolled in this r and omized ( 1:1 ) , dobutamine controlled , open-label study . Before and 24 h after treatment , LVEF , mitral inflow peak E and A wave velocity , E/A ratio , the deceleration time of the E wave ( DT ) , isovolumic relaxation time ( IVRT ) , peak systolic ( Sm ) and early diastolic ( Em ) mitral annular velocity , and systolic pulmonary artery pressure ( SPAP ) were measured by echocardiography . RESULTS Levosimendan produced a statistically significant increase in LVEF ( 28+/-5 % vs. 33+/-3 % ) , Sm ( 6.5+/-1.2 cm/s vs. 7.4+/-0.9 cm/s ) , DT ( 120+/-10 ms vs. 140+/-15 ms ) , and Em ( 7.5+/-0.4 cm/s vs. 8.1+/-0.5 cm/s ) and significant decrease in E/A ratio ( 2.1+/-0.3 vs. 1.7+/-0.4 ) and SPAP ( 55+/-5 mmHg vs. 40+/-7 mmHg ) . No significant change occurred in LV systolic and diastolic function parameters , or SPAP with dobutamine treatment . Levosimendan did not significantly alter the heart rate ( 72+/-4 bpm vs. 70+/-3 bpm ) , systolic ( 105+/-5 mmHg vs. 102+/-4 mmHg ) , or diastolic blood pressure ( 85+/-5 mmHg vs. 83+/-5 mmHg ) whereas with dobutamine treatment , all these parameters significantly increased . CONCLUSIONS Dobutamine and levosimendan have different effects on LV functions in patients treated chronically with carvedilol . These differences should be considered when selecting inotropic therapy for decompensated HF receiving long-term carvedilol Introduction The purpose of the present study was to investigate microcirculatory blood flow in patients with septic shock treated with levosimendan as compared to an active comparator drug ( i.e. dobutamine ) . The primary end point was a difference of ≥ 20 % in the microvascular flow index of small vessels ( MFIs ) among groups . Methods The study was design ed as a prospect i ve , r and omized , double-blind clinical trial and performed in a multidisciplinary intensive care unit . After achieving normovolemia and a mean arterial pressure of at least 65 mmHg , 40 septic shock patients were r and omized to receive either levosimendan 0.2 μg·kg-1·min-1 ( n = 20 ) or an active comparator ( dobutamine 5 μg·kg-1·min-1 ; control ; n = 20 ) for 24 hours . Sublingual microcirculatory blood flow of small and medium vessels was assessed by sidestream dark-field imaging . Microcirculatory variables and data from right heart catheterization were obtained at baseline and 24 hours after r and omization . Baseline and demographic data were compared by means of Mann-Whitney rank sum test or chi-square test , as appropriate . Microvascular and hemodynamic variables were analyzed using the Mann-Whitney rank sum test . Results Microcirculatory flow indices of small and medium vessels increased over time and were significantly higher in the levosimendan group as compared to the control group ( 24 hrs : MFIm 3.0 ( 3.0 ; 3.0 ) vs. 2.9 ( 2.8 ; 3.0 ) ; P = .02 ; MFIs 2.9 ( 2.9 ; 3.0 ) vs. 2.7 ( 2.3 ; 2.8 ) ; P < .001 ) . The relative increase of perfused vessel density vs. baseline was significantly higher in the levosimendan group than in the control group ( dMFIm 10 ( 3 ; 23)% vs. 0 ( -1 ; 9)% ; P = .007 ; dMFIs 47 ( 26 ; 83)% vs. 10 ( -3 ; 27 ) ; P < .001 ) . In addition , the heterogeneity index decreased only in the levosimendan group ( dHI -93 ( -100 ; -84)% vs. 0 ( -78 ; 57)% ; P < .001 ) . There was no statistically significant correlation between systemic and microcirculatory flow variables within each group ( each P > .05 ) . Conclusions Compared to a st and ard dose of 5 μg·kg-1·min-1 of dobutamine , levosimendan at 0.2 μg·kg-1·min-1 improved sublingual microcirculatory blood flow in patients with septic shock , as reflected by changes in microcirculatory flow indices of small and medium vessels . Trial registration NCT00800306 BACKGROUND Atrial fibrillation ( AF ) often occurs after coronary artery bypass grafting ( CABG ) and can result in increased morbidity and mortality due to complications . In the present study , our goal was to investigate whether the use of levosimendan can reduce the frequency of AF after coronary artery bypass grafting in patients with poor left ventricle function . MATERIAL AND METHODS To investigate the effectiveness of levosimendan in the prophylaxis of AF , we conducted a prospect i ve , r and omized , placebo-controlled clinical study on 200 consecutive patients in whom we performed elective CABG operations . Baseline characteristics were similar in both groups . A control group of 100 patients were treated with placebo ( 500 mL saline solution ) , whereas the levosimendan group ( n = 100 patients ) was treated with levosimendan . High-sensitivity C-reactive protein , cardiac troponin , and creatine kinase – MB levels were measured before surgery and 5 days postoperatively . RESULTS AF occurred in 12 % of the levosimendan group and 36 % of the control group . The occurrence of AF was significantly lower in the levosimendan group ( P < 0.05 ) . The duration of AF in the levosimendan group was significantly shorter than that in the control group ( 4.83 ± 1.12 and 6.50 ± 1.55 hours , respectively ; P = 0.028 ) . Our research showed that C-reactive protein was higher postoperatively in the control group than in the levosimendan group ( P < 0.05 ) . CONCLUSIONS The incidence of postoperative AF in the levosimendan group was reduced significantly in patients with poor left ventricle function after CABG operations Background We determined the short-term hemodynamic and clinical effects of levosimendan , a novel calcium-sensitizing agent , in patients with decompensated heart failure . Methods and Results One hundred forty-six patients with New York Heart Association functional class III or IV heart failure ( mean left ventricular ejection fraction 21±1 % ) who had a pulmonary capillary wedge pressure ≥15 mm Hg and a cardiac index ≤2.5 L · min−1 · m−2 were enrolled in a multicenter , double-blind , placebo-controlled study and r and omized 2:1 to intravenous infusion of levosimendan or placebo . Drug infusions were uptitrated over 4 hours from an initial infusion rate of 0.1 & mgr;g · kg−1 · min−1 to a maximum rate of 0.4 & mgr;g · kg−1 · min−1 and maintained at the maximal tolerated infusion rate for an additional 2 hours . Levosimendan caused dose-dependent increases in stroke volume and cardiac index beginning with the lowest infusion rate and achieving maximal increases in stroke volume and cardiac index of 28 % and 39 % , respectively . Heart rate increased modestly ( 8 % ) at the maximal infusion rate and was not increased at the 2 lowest infusion rates . Levosimendan caused dose-dependent decreases in pulmonary capillary wedge , right atrial , pulmonary arterial , and mean arterial pressures . Levosimendan appeared to improve dyspnea and fatigue , as assessed by the patient and physician , and was not associated with a significant increase in adverse events . Conclusions Levosimendan caused rapid dose-dependent improvement in hemodynamic function in patients with decompensated heart failure . These hemodynamic effects appeared to be accompanied by symptom improvement and were not associated with a significant increase in the number of adverse events . Levosimendan may be of value in the short-term management of patients with decompensated heart failure CONTEXT Because acute decompensated heart failure causes substantial morbidity and mortality , there is a need for agents that at least improve hemodynamics and relieve symptoms without adversely affecting survival . OBJECTIVE To assess the effect of a short-term intravenous infusion of levosimendan or dobutamine on long-term survival . DESIGN , SETTING , AND PATIENTS The Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support ( SURVIVE ) study was a r and omized , double-blind trial comparing the efficacy and safety of intravenous levosimendan or dobutamine in 1327 patients hospitalized with acute decompensated heart failure who Output:	Conclusions The available evidence is inconclusive whether or not levosimendan may have a beneficial effect on mortality due to risks of systematic errors and r and om errors .
MS21052	*TASK* the task is to summarize an input biomedical literature in six sentences *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 enzyme heme oxygenase-1 ( HO-1 ) de grade s heme and protects against ischemia-reperfusion injury . Monocytes/macrophages are the major source of HO-1 and higher levels improve renal transplant outcomes . Heme arginate ( HA ) safely induces HO-1 in humans . Methods The Heme Oxygenase-1 in renal Transplantation study was a r and omized , placebo-controlled , IIb trial to evaluate HA effect on HO-1 upregulation after deceased donor kidney transplantation . 40 recipients were r and omized to either 3 mg kg−1 HA or placebo ( 0.9 % NaCl ) , given preoperatively ( day 0 ) and again on day 2 . Recipient blood and urine were collected daily . Graft biopsies were taken preoperatively and on day 5 . Primary outcome was HO-1 upregulation in peripheral blood mononuclear cells ( P BMC s ) . Secondary outcomes were graft HO-1 upregulation and injury , urinary biomarkers , and renal function . Results The HA upregulated P BMC HO-1 protein more than placebo at 24 hours : HA 11.1 ng/mL versus placebo 0.14 ng/mL ( P = < 0.0001 ) . The P BMC HO-1 messenger RNA also increased : HA 2.73-fold versus placebo 1.41-fold ( P = 0.02 ) . Heme arginate increased day 5 tissue HO-1 protein immunopositivity compared with placebo : HA 0.21 versus placebo −0.03 ( P = 0.02 ) and % HO-1–positive renal macrophage also increased : HA 50.8 cells per high power field versus placebo 22.3 ( P = 0.012 ) . Urinary biomarkers were reduced after HA but not significantly . Histological injury and renal function were similar but the study was not powered for this . Adverse events were equivalent between groups . Conclusions The primary outcome was achieved and demonstrated for the first time that HA safely induces HO-1 in transplant recipients . Planned larger studies will determine the impact of HO-1 upregulation on clinical outcomes and evaluate the benefit to patients at risk of ischemia-reperfusion injury Objective To investigate the adrenocortical function in brain-dead patients , potential organ donors . Design Prospect i ve study . Setting Intensive care units in two teaching hospitals . Patients A total of 37 patients ( 28 men , nine women ) with severe brain injury , having a mean age of 42 ± 18 yrs , were included in the study . Group A consisted of 20 brain-injured patients who did not deteriorate to brain death . Group B included 17 brain-injured patients who were brain dead ; of these , ten patients developed brain death during ICU stay and seven patients were admitted to the ICU after clinical brain death . Interventions In all patients ( group A and group B ) , a morning blood sample was obtained at admission to the ICU to determine baseline plasma cortisol . Subsequently , 1 & mgr;g of corticotropin ( adrenocorticotropic hormone , Synacthen ) was administered intravenously , and a blood sample was taken 30 mins after the injection . In group B patients who became brain dead while being treated in the ICU ( n = 10 ) , the same procedure was repeated the morning after the confirmation of brain death . Patients having a cortisol level of at least 18 & mgr;g/dL after the administration of adrenocorticotropic hormone were defined as responders . Measurements and Main Results After the occurrence of brain death , group B patients had significantly lower values for baseline ( 8.5 ± 6.2 vs. 17.0 ± 6.6 & mgr;g/dL , p < .001 ) and stimulated ( 16.9 ± 6.3 vs. 23.9 ± 5.7 & mgr;g/dL , p = .001 ) plasma cortisol compared with group A patients . Thirteen group B patients ( 76 % ) and two group A patients ( 10 % ) were nonresponders to adrenocorticotropic hormone ( p < .001 ) . In group B patients , baseline and stimulated cortisol concentrations were significantly related ( r = .71 , p = .001 ) , whereas there was no correlation between baseline cortisol and the increment in cortisol ( r = −.37 , p = .15 ) . Mean hormonal data of the ten brain-dead patients studied at admission in the ICU and after the occurrence of brain death were the following : baseline plasma cortisol ( 23.5 ± 11.4 vs. 6.8 ± 4.2 & mgr;g/dL , p = .003 ) and stimulated serum cortisol ( 28.8 ± 9.9 vs. 16.3 ± 4.3 & mgr;g/dL , p = .008 ) . Conclusions Adrenal cortisol secretion after dynamic stimulation is deficient in a substantial proportion of brain-dead potential organ donors CONTEXT After brain stem death ( BSD ) , a low T(3 ) state is common , and T(3 ) supplementation has been advocated to improve heart function and yield for transplantation . OBJECTIVES The aim of the study was to assess the effects of T(3 ) on expression of mRNAs encoding T(3)-responsive genes in the post-BSD human heart . DESIGN Within a prospect i ve double-blind trial , potential BSD cardiac donors undergoing hemodynamic optimization were r and omized to T(3 ) ( 0.8 microg . kg(-1 ) bolus ; infusion 0.113 microg . kg(-1 ) . h(-1 ) ) or placebo ( 5 % dextrose ) for up to 6 h. Left ventricular biopsies were obtained at end- assessment from 30 donors ( T(3 ) ; n=16 ) . TaqMan real-time PCR was performed to investigate mRNA expression of the voltage-gated potassium channel Kv1.5 , beta-1 adrenergic receptor ( ADRB1 ) , sarcoplasmic reticulum calcium ATPase type 2a ( SERCA2a ) , and phospholamban ( PLB ) . RESULTS Time between diagnosis of BSD and donor management was 13.2 h ( range , 9.7 - 16.8 h ) . T(3 ) donors were managed for 7.6 ( 6.9 - 8.3 ) h. Median serum free T(3 ) ( fT3 ) at baseline was 2.9 ( 2.3 - 3.8 ) pmol . liter(-1 ) ( reference range , 3.3 - 7.5 pmol . liter(-1 ) ) . At baseline , 19 of 30 ( 56.7 % ) had low serum fT3 , and T(3 ) treatment increased fT3 to supraphysiological levels ( P < 0.001 ) . Expression of mRNAs encoding Kv1.5 and SERCA2a was increased 1.99-fold and 1.51-fold ( P = 0.015 and 0.043 ) . There was no significant change in the expression of mRNAs encoding ADRB1 and PLB . Treatment with T(3 ) did not improve hemodynamic function compared with placebo . CONCLUSIONS Acute administration of T(3 ) in the BSD cardiac donor reverses the low T(3 ) state and increases expression of the mRNAs encoding Kv1.5 and SERCA2a , but not ADRB1 or PLB and is not associated with any improvement in hemodynamic performance 34 cadaveric donor grafts were r and omized in a blind study of the effect of pretreatment of 5 g each of methylprednisolone and cyclophosphamide on kidney graft outcome . There was no difference in overall survival or functioning after 3 , 6 or 12 months between grafts from pretreated ( 33 kidneys ) or control ( 29 kidneys ) cadaveric donors . In addition , this pretreatment protocol did not modify the recipient immune response against B-lymphocyte alloantigens which developed in unsuccessful transplants . Our data , thus , neither confirm the high rate of kidney graft survival attributed to cadaveric donor treatment nor the supposition that treatment is effective in suppressing recipient antidonor B-lymphocyte antibodies BACKGROUND Posttransplantation acute renal failure ( ARF ) occurs in roughly 25 % of recipients of organs from deceased donors . Inflammation in the donor organ is associated with risk for ARF . OBJECTIVE To determine whether administering corticosteroids to deceased organ donors reduces the incidence and duration of ARF in organ recipients more than placebo . DESIGN Parallel , blocked r and omized trial , performed between February 2006 and November 2008 , with computer-generated r and omization and central ized allocation . Investigators were masked to group assignment . ( Controlled-trials.com registration number : IS RCT N78828338 ) SETTING : 3 renal transplantation centers in Austria and Hungary . PATIENTS 306 deceased heart-beating donors and 455 renal transplant recipients . INTERVENTIONS Organ donors were administered an intravenous infusion of either 1000 mg of methylprednisolone ( 136 donors ) or placebo ( 0.9 % saline ) ( 133 donors ) at least 3 hours before organ harvesting . MEASUREMENTS Incidence of ARF , defined as more than 1 dialysis session in the first week after transplantation , was the primary end point . Secondary and other end points included duration of ARF and trajectories of serum creatinine level . The suppression of immune response and inflammation by the intervention was assessed in the donor organ on a genome-wide basis . RESULTS 52 of 238 recipients ( 22 % ) of kidneys from steroid-treated donors and 54 of 217 recipients ( 25 % ) of kidneys from placebo-treated donors had ARF ( difference , 3 percentage points [ 95 % CI , -11 to 5 percentage points ] ) . One graft was lost on day 1 in each group , and 1 recipient in the placebo group died of cardiac arrest on day 2 . The median duration of ARF was 5 days ( interquartile range , 2 days ) in the steroid group and 4 days ( interquartile range , 2 days ) in the placebo group ( P = 0.31 ) . The groups had similar trajectories of serum creatinine level in the first week ( P = 0.72 ) . Genomic analysis showed suppressed inflammation and immune response in kidney biopsies from deceased donors who received corticosteroids . LIMITATION Donors and recipients were mainly white , and all were from 3 transplantation centers in central Europe , which may limit generalizability . CONCLUSION Systemic suppression of inflammation in deceased donors by corticosteroids did not reduce the incidence or duration of posttransplantation ARF in allograft recipients . PRIMARY FUNDING SOURCE Austrian Science Fund and Austrian Academy of Science BACKGROUND Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome . We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients . METHODS Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter , r and omized trial . The trial compared traditional ventilation treatment , which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration ( plateau pressure ) of 50 cm of water or less , with ventilation with a lower tidal volume , which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less . The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28 . RESULTS The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes ( 31.0 percent vs. 39.8 percent , P=0.007 ) , and the number of days without ventilator use during the first 28 days after r and omization was greater in this group ( mean [ + /-SD ] , 12+/-11 vs. 10+/-11 ; P=0.007 ) . The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight ( P<0.001 ) , respectively , and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water ( P<0.001 ) , respectively . CONCLUSIONS In patients with acute lung injury and the acute respiratory distress syndrome , mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use AIMS The aim of this study was to assess the haemodynamic effects of tri-iodothyronine ( T3 ) and methylprednisolone in potential heart donors . METHODS AND RESULTS In a prospect i ve r and omized double-blind trial , 80 potential cardiac donors were allocated to receive T3 ( 0.8 microg kg(-1 ) bolus ; 0.113 microg kg(- Output:	The remaining meta-analyses ( seven studies , 334 participants ) compared the effects of 10 min of ischaemic preconditioning on outcomes after liver transplantation and showed that ischaemic preconditioning improved short-term liver function , but not long-term transplant outcomes . CONCLUSIONS There is currently insufficient evidence to conclude that any particular drug treatment or any intervention in the deceased donor improves long-term graft or patient survival after transplantation
MS21053	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Kidney transplantation is associated with an increased risk of bone fracture and rapid loss of bone mineral density after kidney transplantation . STUDY DESIGN R and omized controlled trial . SETTING & PARTICIPANTS Patients were r and omly assigned to treatment ( n = 46 ) or control ( no treatment ; n = 47 ) groups . Patients were stratified according to parathyroid hormone level and sex . Those with parathyroid hormone level less than 150 pg/mL were excluded . INTERVENTION The treatment and control groups received pamidronate , 1 mg/kg , perioperatively and then at 1 , 4 , 8 , and 12 months or no treatment , respectively . All received calcium ( 500 mg ) and vitamin D ( 400 units ) daily . Immunosuppression was cyclosporine and prednisolone , with no difference in dosing between the 2 groups . OUTCOMES & MEASUREMENTS Bone mineral density was evaluated by means of dual-energy x-ray absorptiometry of the lumbar spine and hip at baseline and 3 , 6 , 12 , and 24 months , with the primary end point at 1 year of percentage of change in bone mineral density from baseline . Clinical fractures were recorded and also evaluated by means of spinal radiographs at baseline and 1 and 2 years . RESULTS Pamidronate protected bone mineral density at the lumbar spine ; bone mineral density increased by 2.1 % in the treatment group and decreased by 5.7 % in the control group at 12 months ( P = 0.001 ) . Protection was also seen in Ward 's area of the hip ( P = 0.002 ) and the total hip ( P = 0.004 ) . There was no difference in femoral neck bone mineral density loss between the 2 groups . Fracture rates in the treatment and control groups were 3.3 % and 6.4 % per annum , respectively . LIMITATIONS This study was not powered to detect differences in fracture rates . CONCLUSION Pamidronate protects against posttransplantation bone loss at the lumbar spine and Ward 's area of the hip Severe osteoporosis frequently is observed after organ transplantation . In kidney transplantation , it adds to pre-existing renal bone disease and strategies to prevent osteoporosis are not established . Eighty kidney recipients were included in a r and omized controlled prospect i ve intervention trial . Treated patients ( n = 40 ) received an injection of ib and ronate , a bisphosphonate , immediately before and at 3 , 6 , and 9 mo after transplantation . The primary outcome measured was the change in bone mineral density . Secondary measures included graft outcome , spinal deformities , fracture rate , body height , and hormonal and metabolic data . Loss of spongy and cortical bone after transplantation was prevented by ib and ronate . Changes of bone mineral density ( ib and ronate versus controls ) were as follows : lumbar spine , -0.9 + /- 6.1 % versus -6.5 + /- 5.4 % ( P < 0.0001 ) ; femoral neck , + 0.5 + /- 5.2 % versus -7.7 + /- 6.5 % ( P < 0.0001 ) ; and midfemoral shaft , + 2.7 + /- 12.2 % versus -4.0 + /- 10.9 % ( P = 0.024 ) . Fewer spinal deformities developed with ib and ronate ( 7 patients with 7 deformities versus 12 patients with 23 deformities ; P = 0.047 ) . Loss of body height was 0.5 + /- 1.0 cm versus 1.1 + /- 1.0 cm in control subjects ( P = 0.040 ) . Two bone fractures occurred in each group . There were fewer acute rejection episodes with ib and ronate ( 11 versus 22 ; P = 0.009 ) . Graft function after 1 yr was comparable . Bone loss , spinal deformation , and loss of body height during the first year after kidney transplantation are prevented by injection of ib and ronate at intervals of 3 mo . The smaller number of rejection episodes of the ib and ronate-treated group should be confirmed and its mechanism should be explored in additional studies The clinical profile of ib and ronate as add‐on to calcitriol and calcium was studied in this double‐blind , placebo‐controlled trial of 129 renal transplant recipients with early stable renal function ( ≤ 28 days posttransplantation , GFR ≥ 30 mL/min ) . Patients were r and omized to receive i.v . ib and ronate 3 mg or i.v . placebo every 3 months for 12 months on top of oral calcitriol 0.25 mcg/day and calcium 500 mg b.i.d . At baseline , 10 weeks and 12 months bone mineral density ( BMD ) and biochemical markers of bone turnover were measured . The primary endpoint , relative change in BMD for the lumbar spine from baseline to 12 months was not different , + 1.5 % for ib and ronate versus + 0.5 % for placebo ( p = 0.28 ) . Ib and ronate demonstrated a significant improvement of BMD in total femur , + 1.3 % versus −0.5 % ( p = 0.01 ) and in the ultradistal radius , + 0.6 % versus −1.9 % ( p = 0.039 ) . Bone formation markers were reduced by ib and ronate , whereas the bone resorption marker , NTX , was reduced in both groups . Calcium and calcitriol supplementation alone showed an excellent efficacy and safety profile , virtually maintaining BMD without any loss over 12 months after renal transplantation , whereas adding ib and ronate significantly improved BMD in total femur and ultradistal radius , and also suppressed biomarkers of bone turnover . Ib and ronate was also well tolerated The aim of this study was to investigate the effects of alendronate , calcitriol , and calcium in bone loss after kidney transplantation . We enrolled 40 patients ( 27 men and 13 women , aged 44.2 + /- 11.6 years ) who had received renal allograft at least 6 months before ( time since transplant , 61.2 + /- 44.6 months ) . At baseline , parathyroid hormone ( PTH ) was elevated in 53 % of the patients and the Z scores for bone alkaline phosphatase ( b-ALP ) and urinary type I collagen cross-linked N-telopeptide ( u-NTX ) were higher than expected ( p < 0.001 ) . T scores for the lumbar spine ( -2.4 + /- 1.0 ) , total femur ( -2.0 + /- 0.7 ) , and femoral neck ( -2.2 + /- 0.6 ) were reduced ( p < 0.001 ) . After the first observation , patients were advised to adhere to a diet containing 980 mg of calcium daily and their clinical , biochemical , and densitometric parameters were reassessed 1 year later . During this period , bone density decreased at the spine ( -2.6 + /- 5.7%;p < 0.01 ) , total femur ( -1.4 + /- 4.2 % ; p < 0.05 ) , and femoral neck ( -2.0 + /- 3.0 % ; p < 0.001 ) . Then , the patients were r and omized into two groups : ( 1 ) group A-10 mg/day of alendronate , 0.50 microg/day of calcitriol , and 500 mg/day of calcium carbonate ; and ( 2 ) group B-0.50 microg/day of calcitriol and 500 mg/day of calcium carbonate . A further metabolic and densitometric reevaluation was performed after the 12-month treatment period . At the r and omization time , group A and group B patients did not differ as to the main demographic and clinical variables . After treatment , bone turnover markers showed a nonsignificant fall in group B patients , while both b-ALP and u-NTX decreased significantly in alendronate-treated patients . Bone density of the spine ( + 5.0 + /- 4.4 % ) , femoral neck ( + 4.5 + /- 4.9 % ) , and total femur ( + 3.9 + /- 2.8 % ) increased significantly only in the alendronate-treated patients . However , no trend toward further bone loss was noticed in calcitriol and calcium only treated subjects . No drug-related major adverse effect was recorded in the two groups . We conclude that renal transplanted patients continue to loose bone even in the long-term after the graft . Alendronate normalizes bone turnover and increases bone density . The association of calcitriol to this therapy seems to be advantageous for better controlling the complex abnormalities of skeletal metabolism encountered in these subjects We performed a prospect i ve , r and omized , double-blind study to determine whether calcium and calcitriol prevents posttransplant bone loss . Thirty-eight nondiabetic and 26 diabetic patients without prior steroid exposure undergoing their first kidney or kidney-pancreas transplant were r and omized to calcium , calcium plus calcitriol , or placebo . Lumbar spine ( LS ) , femoral neck ( FN ) , and distal radius ( DR ) bone mineral density scans ( BMDs ) were obtained at baseline , 6 , and 12 months . At 1 year , patients treated with placebo experienced a 2 % decline in BMD at the LS and DR and a 1.3 % increase at the FN . In contrast , patients treated with calcium and vitamin D had a 0.1 % decline at the LS and 2.9 % and 4.8 % increases at the DR and FN , respectively . Patients receiving cyclosporine had more bone loss than those receiving tacrolimus . Our results demonstrate a small therapeutic effect of calcium and calcitriol and suggest that tacrolimus is less osteotoxic than cyclosporine Bisphosphonates may prevent or treat the bone loss promoted by the immunosuppressive regimens used in renal transplantation . Risedronate is a commonly used third-generation amino-bisphosphonate , but little is known about its effects on the bone health of renal transplant recipients . We r and omly assigned 42 new living-donor kidney recipients to either 35 mg of risedronate weekly or placebo for 12 months . We obtained bone biopsies at the time of renal transplant and after 12 months of protocol treatment . Treatment with risedronate did not affect bone mineral density ( BMD ) in the overall cohort . In subgroup analyses , it tended to preserve BMD in female participants but did not significantly affect the BMD of male participants . Risedronate did associate with increased osteoid volume and trabecular thickness in male participants , however . There was no evidence for the development of adynamic bone disease . In summary , further study is needed before the use of prophylactic bisphosphonates to attenuate bone loss can be recommended in renal transplant recipients BACKGROUND Very rapid bone loss , osteopenia and skeletal morbidity after renal transplantation have been well documented and found to occur in a sex dependent fashion . Glucocorticoids , cyclosporine and pre-existing uremic osteodystrophy have been implicated in the pathogenesis of the skeletal lesions . Glucocorticoid induced osteopenia is also a serious clinical problem in patients with various nonrenal diseases and can be prevented , or at least attenuated , by pamidronate and other bisphosphonates . METHOD We prospect ively studied 26 male patients undergoing renal transplantation , and r and omized them to receive either placebo or intravenous pamidronate ( 0.5 mg/kg ) at the time of transplantation and again one month later . All patients received immunosuppression comprising prednisolone , cyclosporine and azathioprine . The bone mineral density ( BMD ) of the second , third and fourth lumbar vertebrae and of the femoral neck was measured at the time of transplantation and at three months and 12 months after transplantation using dual energy X-ray absorptiometry ( DXA ) . RESULTS Twelve months after transplantation , the mean ( + /- SEM ) BMD of the lumbar vertebrae in patients who received placebo had decreased 6.4 % ( P < 0.05 ) . In contrast , patients who received pamidronate experienced no significant reduction of BMD at the lumbar vertebrae . At the femoral neck , placebo-treated patients showed a reduction of BMD of 9 % ( P < 0.005 ) , whereas there was no significant change in the pamidronate treated group . The two study groups had similar patient profiles , serum parathyroid hormone ( PTH ) and aluminium concentrations . After transplantation , comparable falls in the serum creatinine and PTH concentration were found in the two groups . Apart from transient hypocalcemia in two patients , no significant adverse effects of pamidronate were noted . CONCLUSION This study has shown that the early rapid bone loss that occurs in men during the first 12 months after renal transplantation can be prevented by two intravenous doses of pamidronate given at transplantation and one month later . The regimen was simple to administer , well tolerated and potentially applicable to other clinical groups of glucocorticoid treatment patients BACK Output:	Conclusions Our study suggested that additional use of bisphosphonate was well-tolerated and more favorable in KTRs to improve BMD
MS21054	*TASK* the task is to summarize an input biomedical literature in six sentences *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 — Thrombolytic therapy with intravenous alteplase within 4.5 hours of ischemic stroke onset increases the overall likelihood of an excellent outcome ( no , or nondisabling , symptoms ) . Any improvement in functional outcome distribution has value , and herein we provide an assessment of the effect of alteplase on the distribution of the functional level by treatment delay , age , and stroke severity . Methods — Prespecified pooled analysis of 6756 patients from 9 r and omized trials comparing alteplase versus placebo/open control . Ordinal logistic regression models assessed treatment differences after adjustment for treatment delay , age , stroke severity , and relevant interaction term(s ) . Results — Treatment with alteplase was beneficial for a delay in treatment extending to 4.5 hours after stroke onset , with a greater benefit with earlier treatment . Neither age nor stroke severity significantly influenced the slope of the relationship between benefit and time to treatment initiation . For the observed case mix of patients treated within 4.5 hours of stroke onset ( mean 3 hours and 20 minutes ) , the net absolute benefit from alteplase ( ie , the difference between those who would do better if given alteplase and those who would do worse ) was 55 patients per 1000 treated ( 95 % confidence interval , 13–91 ; P=0.004 ) . Conclusions — Treatment with intravenous alteplase initiated within 4.5 hours of stroke onset increases the chance of achieving an improved level of function for all patients across the age spectrum , including the over 80s and across all severities of stroke studied ( top versus bottom fifth means : 22 versus 4 ) ; the earlier that treatment is initiated , the greater the benefit Background Limited efficacy of IV recombinant tissue plasminogen activator ( rt-PA ) for large vessel occlusions ( LVO ) raises doubts about its utility prior to endovascular therapy . Purpose To compare outcomes and hospital costs for anterior circulation LVOs ( middle cerebral artery , internal carotid artery terminus ( ICA-T ) ) treated with either primary endovascular therapy alone ( EV-Only ) or bridging therapy ( IV+EV ) ) . Methods A single-center retrospective analysis was performed . Clinical and demographic data were collected prospect ively and relevant cost data were obtained for each patient in the study . Results 90 consecutive patients were divided into EV-Only ( n=52 ) and IV+EV ( n=38 ) groups . There was no difference in demographics , stroke severity , or clot distribution . The mean ( SD ) time to presentation was 5:19 ( 4:30 ) hours in the EV-Only group and 1:46 ( 0:52 ) hours in the IV+EV group ( p<0.0001 ) . Recanalization : EV-Only 35 ( 67 % ) versus IV+EV 31 ( 81.6 % ) ( p=0.12 ) . Favorable outcome : EV-Only 26 ( 50 % ) versus IV+EV 22 ( 58 % ) ( p=0.45 ) . For patients presenting within 4.5 hours ( n=64 ) : Recanalization : EV-Only 21/26 ( 81 % ) versus IV+EV 31/38 ( 81.6 % ) ( p=0.93 ) . Favorable outcome : EV-Only 14/26 ( 54 % ) versus IV+EV 22/38 ( 58 % ) ( p=0.75 ) . There was no significant difference in rates of hemorrhage , mortality , home discharge , or length of stay . A stent retriever was used in 67 cases ( 74.4 % ) , with similar recanalization , outcomes , and number of passes in the EV-Only and IV+EV groups . The mean ( SD ) total hospital cost was $ 33 810 ( 13 505 ) for the EV-Only group and $ 40 743 ( 17 177 ) for the IV+EV group ( p=0.02 ) . The direct cost was $ 23 034 ( 8786 ) for the EV-Only group and $ 28 711 ( 11 406 ) for the IV+EV group ( p=0.007 ) . These significantly higher costs persisted for the subgroup presenting in < 4.5 hours and the stent retriever subgroup . IV rt-PA administration independently predicted higher hospital costs . Conclusions IV rt-PA did not improve recanalization , thrombectomy efficacy , functional outcomes , or length of stay . Combined therapy was associated with significantly higher total and direct hospital costs than endovascular therapy alone Importance Intravenous thrombolysis ( IVT ) followed by mechanical thrombectomy ( MT ) is recommended to treat acute ischemic stroke ( AIS ) with a large vessel occlusion ( LVO ) . Most hospitals do not have on-site MT facilities , and most patients need to be transferred secondarily after IVT ( drip and ship ) , which may have an effect on the neurologic outcome . Objective To compare the functional independence at 3 months between patients treated under the drip- and -ship paradigm and those treated on site ( mothership ) . Design , Setting , and Participants This study used a prospect ively gathered registry of patients with AIS to select patients admitted through the Saint-Antoine and Tenon ( drip and ship ) or the Fondation Rothschild ( mothership ) hospitals from January 1 , 2013 , through April 30 , 2016 . The study included patients older than 18 years treated with bridging therapy for AIS with LVO of the anterior circulation . Among the 159 patients who received MT at the mothership , 100 had been transferred after IVT from the drip- and -ship hospitals and 59 had received IVT on site . Main Outcomes and Measures The main outcome was 3-month functional independence ( modified Rankin scale score ⩽2 ) . Both groups were compared using a multivariate linear model , including variables that were significantly different in the 2 groups . Results During the study period , 497 patients were hospitalized at the drip- and -ship and mothership hospitals for an AIS eligible to reperfusion therapy ; 11 patients had a basilar artery occlusion and were excluded , leaving 100 patients in the drip- and -ship group ( mean age , 73 years ; age range , 60 - 81 years ; 57 men [ 57.0 % ] ) and 59 in the mothership group ( mean age , 70 years ; age range , 58 - 82 years ; 29 men [ 49.2 % ] ) . The proportion of patients with a favorable neurologic outcome at 3 months was similar in both groups ( drip and ship , 61 [ 61.0 % ] ; mothership , 30 [ 50.8 % ] ; P = .26 ) , even after adjusting the analysis for the baseline National Institutes of Health Stroke Scale score , diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score , and general anesthesia ( P = .82 ) . Patients had less severe conditions in the drip- and -ship group ( median baseline National Institutes of Health Stroke Scale score , 15 vs 17 [ P = .03 ] ; median diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score , 7.5 vs 7 [ P = .05 ] ) . Process times were longer in the drip- and -ship group ( onset-to-needle time , 150 vs 135 minutes ; onset-to-puncture time , 248 vs 189 minutes ; and onset-to-recanalization time , 297 vs 240 minutes ; P < .001 ) . Both groups were similar in terms of substantial recanalization ( Thrombolysis in Cerebral Ischemia scores 2B to 3 ; drip and ship , 84 [ 84.0 % ] ; mothership , 47 [ 79.7 % ] ; P = .49 ) and symptomatic hemorrhagic transformation ( drip and ship , 2 [ 2.0 % ] ; mothership , 2 [ 3.4 % ] ; P = .63 ) . Conclusions and Relevance This study found that patients treated under the drip- and -ship paradigm also benefit from bridging therapy , with no statistically significant difference compared with those treated directly in a comprehensive stroke center Background Recent studies suggested that preinterventional intravenous ( i. v. ) recombinant tissue plasminogen activator ( rtPA ) as bridging therapy facilitates successful and fast vessel recanalization in endovascular stroke treatment ( EST ) ; however , data on this effect and the associated clinical value are discrepant . Objective This study examined if this discrepancy could be related to an effect-modifying variable , specifically to the exact occlusion site . Methods Retrospective analysis of 239 patients with acute occlusion of the middle cerebral artery ( MCA ) treated with up to date endovascular techniques . Effects of i. v.-rtPA bridging on clinical outcomes and safety/efficacy of EST , defined as the respective rates of successful , first pass and thrombolysis in cerebral infa rct ion ( TICI ) scale 3 recanalization , were evaluated and stratified according to distal versus proximal occlusion sites . Results Overall , i. v.-rtPA bridging was associated with a significantly higher rate of successful recanalization ( 86.9 % vs. 75.7 % , p = 0.028 ) . i. v.-rtPA bridging-related effects , however , were observable only in distal , but not in proximal MCA-occlusions . In distal occlusions , i. v.-rtPA clearly favored successful recanalization ( adj . OR 4.6 , 95 % -CI 1.5–13.6 , p = 0.006 ) and first-pass successes ( adj . OR 2.8 , 95 % -CI 1.0–7.6 , p = 0.042 ) , but tended to be associated with lower rates of complete ( TICI-3 ) reperfusion ( adj . OR 0.4 , 95 % -CI 0.2–1.1 , p = 0.068 ) . The net effect was a small clinical benefit , reflected in higher rates of strong neurological improvement ( adj . OR : 2.8 , 95 % -CI : 1.1–6.9 , p = 0.03 ) . Conclusion i. v.-rtPA-bridging-related effects are occlusion site-dependent , paralleling similar effects of systemic i. v.-rtPA when applied without subsequent endovascular therapy . In distal occlusions , i. v.-rtPA facilitates thrombectomy , but may also promote distal embolization , with a small clinical benefit as overall net effect . R and omized trials assessing i.v-rtPA bridging need to be stratified according to occlusions sites Background Current guidelines suggest treating blood pressure above 180/105 mm Hg during the first 24 hours in patients with acute ischemic stroke undergoing any form of recanalization therapy . Currently , no studies exist to guide blood pressure management in patients with stroke treated specifically with mechanical thrombectomy . We aim ed to determine the association between blood pressure parameters within the first 24 hours after mechanical thrombectomy and patient outcomes . Methods and Results We retrospectively studied a consecutive sample of adult patients who underwent mechanical thrombectomy for acute ischemic stroke of the anterior cerebral circulation at 3 institutions from March 2015 to October 2016 . We collected the values of maximum , minimum , and average values of systolic blood pressure , diastolic blood pressure , and mean arterial pressures in the first 24 hours after mechanical thrombectomy . Primary and secondary outcomes were patients ’ functional status at 90 days measured on the modified Rankin scale and the incidence and severity of intracranial hemorrhages within 48 hours . Associations were explored using an ordered multivariable logistic regression analyses . A total of 228 patients were included ( mean age 65.8±14.3 ; 104 males , 45.6 % ) . Maximum systolic blood pressure independently correlated with a worse 90‐day modified Rankin scale and hemorrhagic complications within 48 hours ( adjusted odds ratio=1.02 [ 1.01–1.03 ] , P=0.004 ; 1.02 [ 1.01–1.04 ] , P=0.002 ; respectively ) in multivariable analyses , after adjusting for several possible confounders . Conclusions Higher peak values of systolic blood pressure independently correlated with worse 90‐day modified Rankin scale and a higher rate of hemorrhagic complications . Further prospect i ve studies are warranted to identify whether systolic blood pressure is a therapeutic target to improve outcomes BACKGROUND AND PURPOSE Whether intravenous thrombolysis prior to endovascular treatment in patients with anterior circulation large-vessel occlusion ( LVO ) is indispensable remains unclear . The aim was to retrospectively compare , in a Chinese population , the effectiveness and safety of direct endovascular treatment ( DEVT ) initiated within 4.5 h after onset with bridging therapy in acute anterior circulation LVO stroke patients . METHODS A total of 363 patients , 160 in the bridging therapy group and 203 in the DEVT group , were enrolled between 2014 and 2016 . Using propensity score matching analysis , 276 patients were matched . A modified Rankin Scale score of 0 - 2 was considered as good functional outcome . RESULTS Good functional outcome at 90 days in the DEVT group [ 40.6 % ( 56/138 ) ] did not significantly differ from that in the bridging group [ 44.9 % ( 62/138 ) ] ( P = Output:	Conclusion : The findings of our meta- analysis confirmed that bridging strategies improved functional outcomes , successful recanalization rate and reduced mortality rates . Moreover , the incidence of sICH showed no differences between the bridging strategies and MT alone treatments .
MS21055	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To examine the value of additional transrectal ultrasonography (TRUS)‐guided r and om biopsy ( RB ) in patients with negative magnetic resonance imaging (MRI)/ultrasonography ( US ) fusion‐guided targeted biopsy ( TB ) and to identify possible reasons for TB failure To analyse the performance of the Prostate Cancer Prevention Trial Risk Calculator ( PCPT‐RC ) and two iterations of the European R and omised Study of Screening for Prostate Cancer ( ERSPC ) Risk Calculator , one of which incorporates prostate volume ( ERSPC‐RC ) and the other of which incorporates prostate volume and the prostate health index ( PHI ) in a referral population ( ERSPC‐PHI ) PURPOSE To evaluate the role of a 3 T biparametric magnetic resonance imaging ( bpMRI ) , T2 -weighted imaging , and three separate diffusion-weighted imaging acquisitions combined with targeted biopsy ( TB ) for improving risk stratification of men with elevated prostate-specific antigen ( PSA ) . MATERIAL S AND METHODS Between March 2013 and February 2015 , 175 men with a clinical suspicion of prostate cancer ( PCa ) were offered bpMRI ( NCT01864135 ) based on a suspicion of PCa ( two repeated PSA measurements in the range 2.5 - 20.0 ng/ml and /or abnormal digital rectal examination ) . Men with an equivocal to high suspicion of PCa had two TBs of the dominant lesion using cognitive ultrasound guidance , followed by systematic biopsy ( SB ) . Men with a low to very low suspicion had only SB . In total , 161 ( 161/175 , 92 % ) prospect ively enrolled men completed the trial and were included in the final analyses . The primary endpoint of the trial was the cancer detection rate ( CDR ) of TB and SB . Clinical ly significant cancer ( SPCa ) was defined as Gleason score ≥3 + 4 . RESULTS TB compared with SB had higher CDR for SPCa ( 45 % , 72/161 vs. 39 % , 63/161 , respectively ; P > 0.05 ) and a lower CDR for Gleason score 3 + 3 ( 8 % , 15/161 vs. 16 % , 30/161 ; P < 0.05 ) . Restricting biopsy to men with equivocal to highly suspicious bpMRI findings would have result ed in a 24 % ( 38/161 ) reduction in the number of men undergoing biopsy , while missing 4 ( 2 % ) with SPCa . All anonymized data sets , including bpMRI reports and follow up information , are freely available on the trial server . CONCLUSION Prebiopsy bpMRI and TB in men with a clinical suspicion of PCa improved risk stratification . LEVEL OF EVIDENCE 1 Technical Efficacy : Stage 5 J. Magn . Reson . Imaging 2017;46:1089 - 1095 Purpose To compare prostate cancer detection rates between 12 cores transrectal ultrasound-guided prostate biopsy ( TRUS-Bx ) and visually estimated multiparametric magnetic resonance imaging (mp-MRI)-targeted prostate biopsy ( MRI-visual-Bx ) for patients with prostate specific antigen ( PSA ) level less than 10 ng/mL. Material s and Methods In total , 76 patients with PSA levels below 10 ng/mL underwent 3.0 Tesla mp-MRI and TRUS-Bx prospect ively in 2014 . In patients with abnormal lesions on mp-MRI , we performed additional MRI-visual-Bx . We compared pathologic results , including the rate of clinical ly significant prostate cancer cores ( cancer length greater than 5 mm and /or any Gleason grade greater than 3 in the biopsy core ) . Results The mean PSA was 6.43 ng/mL. In total , 48 of 76 ( 63.2 % ) patients had abnormal lesions on mp-MRI , and 116 targeted biopsy cores , an average of 2.42 per patient , were taken . The overall detection rates of prostate cancer using TRUS-Bx and MRI-visual-Bx were 26/76 ( 34.2 % ) and 23/48 ( 47.9 % ) , respectively . In comparing the pathologic results of TRUS-Bx and MRI-visual-Bx cores , the positive rates were 8.4 % ( 77 of 912 cores ) and 46.6 % ( 54 of 116 cores ) , respectively ( p<0.001 ) . Mean cancer core lengths and mean cancer core percentages were 3.2 mm and 24.5 % , respectively , in TRUS-Bx and 6.3 mm and 45.4 % in MRI-visual-Bx ( p<0.001 ) . In addition , Gleason score ≥7 was noted more frequently using MRI-visual-Bx ( p=0.028 ) . The detection rate of clinical ly significant prostate cancer was 27/77 ( 35.1 % ) and 40/54 ( 74.1 % ) for TRUS-Bx and MRI-visual-Bx , respectively ( p<0.001 ) . Conclusion MRI-visual-Bx showed better performance in the detection of clinical ly significant prostate cancer , compared to TRUS-Bx among patients with a PSA level less than 10 Background Multiparametric-magnetic resonance imaging ( mpMRI ) can accurately detect high- grade and larger prostate cancers ( PC ) . Aims To evaluate the ability of 1.5 T magnetic field mpMRI-targeted Prostate Biopsies ( PBx ) in predicting PC in comparison with blind 24-core saturation PBx ( sPBx ) . Methods We prospect ively collected data from patients undergoing transrectal sPBx and , if needed , targeted PBx of suspected lesions based on the 16-‘region-of-interest ’ ( ROI ) PI-RADS graph . Data remodeling : for each ‘ target ’ ( each suspected lesion at mpMRI ) , we identified all the 16 ‘ ROIs ’ into which the lesion extended : these single ‘ ROIs ’ were identified as ‘ macro-targets ’ . For each ‘ ROI ’ and ‘ macro-target ’ , we compared the mpMRI result with that of a saturation and targeted biopsy ( if performed ) . Results 1.5 T mpMRI showed a PI-RADS value ≥ 3 in 101 patients ( 82.1 % ) . We found a PC in 50 ( 40.6 % ) . Negative-positive predictive values for mpMRI were 82–45 % , respectively . Of the 22 patients with normal mpMRI , four had a PC , but none had a clinical ly significant cancer . After the data remodeling , we demonstrated the presence of PC in 228 ‘ ROIs ’ : ( a ) only in targeted biopsies in 15 ‘ ROIs’/’macro-targets ’ ( 6.6 % ) ; ( b ) only in sPBx in 177 ‘ ROIs ’ ( 77.6 % ) ; ( c ) in both targeted and sPBx in 36 ‘ ROIs ’ ( 15.8 % ) . Discussion 81.8 % of patients with normal 1.5 T mpMRI were negative at PBx . Performing only targeted PBx may lead to lack of PC diagnosis in about 50 % of patients . Conclusions In patients with suspected PC and a previous negative PBx , a normal mpMRI may exclude a clinical ly significant PC , avoiding sPBx Purpose To characterize clinical ly important prostate cancers missed at multiparametric ( MP ) magnetic resonance ( MR ) imaging . Material s and Methods The local institutional review board approved this HIPAA-compliant retrospective single-center study , which included 100 consecutive patients who had undergone MP MR imaging and subsequent radical prostatectomy . A genitourinary pathologist blinded to MP MR findings outlined prostate cancers on whole-mount pathology slices . Two readers correlated mapped lesions with reports of prospect ively read MP MR images . Readers were blinded to histopathology results during prospect i ve reading . At histopathologic examination , 80 clinical ly unimportant lesions ( < 5 mm ; Gleason score , 3 + 3 ) were excluded . The same two readers , who were not blinded to histopathologic findings , retrospectively review ed cancers missed at MP MR imaging and assigned a Prostate Imaging Reporting and Data System ( PI-RADS ) version 2 score to better underst and false-negative lesion characteristics . Descriptive statistics were used to define patient characteristics , including age , prostate-specific antigen ( PSA ) level , PSA density , race , digital rectal examination results , and biopsy results before MR imaging . Student t test was used to determine any demographic differences between patients with false-negative MP MR imaging findings and those with correct prospect i ve identification of all lesions . Results Of the 162 lesions , 136 ( 84 % ) were correctly identified with MP MR imaging . Size of eight lesions was underestimated . Among the 26 ( 16 % ) lesions missed at MP MR imaging , Gleason score was 3 + 4 in 17 ( 65 % ) , 4 + 3 in one ( 4 % ) , 4 + 4 in seven ( 27 % ) , and 4 + 5 in one ( 4 % ) . Retrospective PI-RADS version 2 scores were assigned ( PI-RADS 1 , n = 8 ; PI-RADS 2 , n = 7 ; PI-RADS 3 , n = 6 ; and PI-RADS 4 , n = 5 ) . On a per-patient basis , MP MR imaging depicted clinical ly important prostate cancer in 99 of 100 patients . At least one clinical ly important tumor was missed in 26 ( 26 % ) patients , and lesion size was underestimated in eight ( 8 % ) . Conclusion Clinical ly important lesions can be missed or their size can be underestimated at MP MR imaging . Of missed lesions , 58 % were not seen or were characterized as benign findings at second-look analysis . Recognition of the limitations of MP MR imaging is important , and new approaches to reduce this false-negative rate are needed . © RSNA , 2017 Online supplemental material is available for this article BACKGROUND Multiparametric magnetic resonance imaging ( mpMRI ) is gaining widespread acceptance in prostate cancer ( PC ) diagnosis and improves significant PC ( sPC ; Gleason score≥3 + 4 ) detection . Decision making based on European R and omised Study of Screening for PC ( ERSPC ) risk-calculator ( RC ) parameters may overcome prostate-specific antigen ( PSA ) limitations . OBJECTIVE We added pre-biopsy mpMRI to ERSPC-RC parameters and developed risk models ( RMs ) to predict individual sPC risk for biopsy-naïve men and men after previous biopsy . DESIGN , SETTING , AND PARTICIPANTS We retrospectively analyzed clinical parameters of 1159 men who underwent mpMRI prior to MRI/transrectal ultrasound fusion biopsy between 2012 and 2015 . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariate regression analyses were used to determine significant sPC predictors for RM development . The prediction performance was compared with ERSPC-RCs , RCs refitted on our cohort , Prostate Imaging Reporting and Data System ( PI-RADS ) v1.0 , and ERSPC-RC plus PI-RADSv1.0 using receiver-operating characteristics ( ROCs ) . Discrimination and calibration of the RM , as well as net decision and reduction curve analyses were evaluated based on resampling methods . RESULTS AND LIMITATIONS PSA , prostate volume , digital-rectal examination , and PI-RADS were significant sPC predictors and included in the RMs together with age . The ROC area under the curve of the RM for biopsy-naïve men was comparable with ERSPC-RC3 plus PI-RADSv1.0 ( 0.83 vs 0.84 ) but larger compared with ERSPC-RC3 ( 0.81 ) , refitted RC3 ( 0.80 ) , and PI-RADS ( 0.76 ) . For postbiopsy men , the novel RM 's discrimination ( 0.81 ) was higher , compared with PI-RADS ( 0.78 ) , ERSPC-RC4 ( 0.66 ) , refitted RC4 ( 0.76 ) , and ERSPC-RC4 plus PI-RADSv1.0 ( 0.78 ) . Both RM benefits exceeded those of ERSPC-RCs and PI-RADS in the decision regarding which patient to receive biopsy and enabled the highest reduction rate of unnecessary biopsies . Limitations include a monocentric design and a lack of PI-RADSv2.0 . CONCLUSIONS The novel RMs , incorporating clinical parameters and PI-RADS , performed significantly better compared with RMs without PI-RADS and provided measurable benefit in making the decision to biopsy men at a suspicion of PC . For biopsy-naïve patients , both our RM and ERSPC-RC3 plus PI-RADSv1.0 exceeded the prediction performance compared with clinical parameters alone . PATIENT SUMMARY Combined risk models including clinical and imaging parameters predict clinical ly relevant prostate cancer significantly better than clinical risk calculators and multiparametric magnetic resonance imaging Output:	Among the diagnostic strategies considered , the MRI pathway has the most favourable diagnostic accuracy in clinical ly significant prostate cancer detection . Compared to systematic biopsy , it increases the number of significant cancer detected while reducing the number of insignificant cancer diagnosed .
MS21056	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Despite the psychosocial difficulties common among young adults with autism spectrum disorders ( ASD ) , little to no evidence -based social skills interventions exist for this population . Using a r and omized controlled trial ( RCT ) design , the current study tested the effectiveness of an evidence -based , caregiver-assisted social skills intervention known as PEERS for Young Adults with high-functioning young adults with ASD ( ages 18–23 ) using self- and caregiver-report measures . Results revealed that treated young adults reported significantly less loneliness and improved social skills knowledge , while caregivers reported significant improvements in young adults ’ overall social skills , social responsiveness , empathy , and frequency of get-togethers . Results support the effectiveness of using this caregiver-assisted , manualized intervention for young adults with ASD BACKGROUND AND AIMS This pilot study tested the efficacy of a developmentally modified CBT for young children with Autism Spectrum Disorders ( ASD ) to teach emotion regulation strategies for reducing anger and anxiety , commonly noted problems in this population . METHOD Eleven 5 - 7 year-old children participated in a CBT-group while parents participated in psychoeducation . Children were r and omly assigned to an experimental or delayed-treatment control group . RESULTS From pre- to post-treatment , all children had less parent reported negativity/lability , better parent reported emotion regulation , and shorter outbursts , and also generated more coping strategies in response to vignettes . Parents also reported increases in their own confidence and their child 's ability to deal with anger and anxiety . CONCLUSIONS This study suggests that young children with high functioning ASD may benefit from CBT to improve regulation of anger and anxiety , and parent training may improve parental self-efficacy . Future studies are needed to make conclusions about its efficacy Although melatonin and cognitive-behavioural therapy have shown efficacy in treating sleep disorders in children with autism spectrum disorders , little is known about their relative or combined efficacy . One hundred and sixty children with autism spectrum disorders , aged 4 - 10 years , suffering from sleep onset insomnia and impaired sleep maintenance , were assigned r and omly to either ( 1 ) combination of controlled-release melatonin and cognitive-behavioural therapy ; ( 2 ) controlled-release melatonin ; ( 3 ) four sessions of cognitive-behavioural therapy ; or ( 4 ) placebo drug treatment condition for 12 weeks in a 1 : 1 : 1 : 1 ratio . Children were studied at baseline and after 12 weeks of treatment . Treatment response was assessed with 1-week actigraphic monitoring , sleep diary and sleep question naire . Main outcome measures , derived actigraphically , were sleep latency , total sleep time , wake after sleep onset and number of awakenings . The active treatment groups all result ed in improvements across all outcome measures , with moderate-to-large effect sizes from baseline to a 12-week assessment . Melatonin treatment was mainly effective in reducing insomnia symptoms , while cognitive-behavioural therapy had a light positive impact mainly on sleep latency , suggesting that some behavioural aspects might play a role in determining initial insomnia . The combination treatment group showed a trend to outperform other active treatment groups , with fewer dropouts and a greater proportion of treatment responders achieving clinical ly significant changes ( 63.38 % normative sleep efficiency criterion of > 85 % and 84.62 % , sleep onset latency < 30 min ) . This study demonstrates that adding behavioural intervention to melatonin treatment seems to result in a better treatment response , at least in the short term OBJECTIVE Examine the efficacy of a personalized , modular cognitive-behavioral therapy ( CBT ) protocol among early adolescents with high-functioning autism spectrum disorders ( ASDs ) and co-occurring anxiety relative to treatment as usual ( TAU ) . METHOD Thirty-one children ( 11 - 16 years ) with ASD and clinical ly significant anxiety were r and omly assigned to receive 16 weekly CBT sessions or an equivalent duration of TAU . Participants were assessed by blinded raters at screening , posttreatment , and 1-month follow-up . RESULTS Youth r and omized to CBT demonstrated superior improvement across primary outcomes relative to those receiving TAU . Eleven of 16 adolescents r and omized to CBT were treatment responders , versus 4 of 15 in the TAU condition . Gains were maintained at 1-month follow-up for CBT responders . CONCLUSIONS These data extend findings of the promising effects of CBT in anxious youth with ASD to early adolescents Aim : To investigate the acceptability and feasibility of adapted group therapy for anxiety in children with autism spectrum disorder in a pilot r and omised controlled trial . Method : A total of 32 children aged 9–13 years were r and omised to immediate or delayed therapy using the ‘ Exploring Feelings ’ manual ( Attwood , 2004 ) . Child and parent groups were run in parallel , for seven weekly sessions , under the supervision of experienced psychologists . The primary blinded outcome measures addressed change in overall functioning and in severity of the primary anxiety diagnosis after 3 months . Results : Children met diagnostic criteria for 1–6 anxiety disorders ( median 3 ) . At end point , both parents and children in the immediate therapy group were more likely to report a reduction in anxiety symptoms . Fidelity of delivery of the group therapy was high , and attendance was 91 % . Conclusions : This pilot trial established that children and families were willing to be recruited and r and omised , the outcome measures were acceptable , the format and content of the groups were feasible within UK child and adolescent mental health services , the intervention was appreciated by families and attrition was very small BACKGROUND The study aim ed to investigate the effectiveness of a new multi-component social skills intervention for children with Asperger syndrome ( AS ) : The Junior Detective Training Program . This 7-week program included a computer game , small group sessions , parent training sessions and teacher h and outs . METHOD Forty-nine children with AS were recruited to participate and r and omly assigned to intervention ( n = 26 ) or wait-list control ( n = 23 ) conditions . RESULTS Relative to children in the wait-list group , program participants showed greater improvements in social skills over the course of the intervention , as indicated by parent-report measures . Teacher-report data also confirmed that children receiving the intervention made significant improvements in social functioning from pre- to post-treatment . Treatment group participants were better able to suggest appropriate emotion-management strategies for story characters at post-intervention than at pre-intervention , whereas control participants were not . However , there was no difference in the improvements made by children in the intervention and control conditions on facial expression and body-posture recognition measures . Follow-up data suggested that treatment gains were maintained by children at 5-months post-intervention . CONCLUSIONS The Junior Detective Training Program appeared to be effective in enhancing the social skills and emotional underst and ing of children with AS . Limitations and suggestions for future research are discussed Background Although social skills training programs for people with high-functioning autism ( HFA ) are widely practice d , the st and ardization of curricula , the examination of clinical effectiveness , and the evaluation of the feasibility of future trials have yet to be done in Asian countries . To compensate for this problem , a Japanese pilot r and omized controlled trial ( RCT ) of the Treatment and Education of Autistic and Related Communication H and icapped Children (TEACCH)-based group social skills training for children with HFA and their mothers was conducted . Methods Eleven children with HFA , aged 5–6 years , and their mothers were r and omly assigned to the TEACCH program ( n=5 ) or a waiting-list control group ( n=6 ) . The program involved comprehensive group intervention and featured weekly 2-hour sessions , totaling 20 sessions over six months . The adaptive behaviors and social reciprocity of the children , parenting stress , and parent – child interactions were assessed using the Strengths and Difficulties Question naire ( SDQ ) , Parenting Stress Index ( PSI ) , Beck depression inventory-II ( BDI-II ) , and Interaction Rating Scale ( IRS ) . Results Through this pilot trial , the intervention and evaluation of the program has been shaped . There were no dropouts from the program and the mothers ’ satisfaction was high . The outcome measurements improved more in the program group than in the control group , with moderate effect sizes ( SDQ , 0.71 ; PSI , 0.58 ; BDI-II , 0.40 ; and IRS , 0.69 ) . This pilot trial also implied that this program is more beneficial for high IQ children and mothers with low stress than for those who are not . Conclusion We have st and ardized the TEACCH program , confirmed the feasibility of a future trial , and successfully estimated the positive effect size . These findings will contribute to a larger trial in the future and to forthcoming systematic review s with meta-analyses . Trial registration Background There is a growing interest in using cognitive – behavioural therapy ( CBT ) with people who have Asperger syndrome and comorbid mental health problems . Aims To examine whether modified group CBT for clinical ly significant anxiety in an Asperger syndrome population is feasible and likely to be efficacious . Method Using a r and omised assessor-blind trial , 52 individuals with Asperger syndrome were r and omised into a treatment arm or a waiting-list control arm . After 24 weeks , those in the waiting-list control arm received treatment , while those initially r and omised to treatment were followed up for 24 weeks . Results The conversion rate for this trial was high ( 1.6:1 ) , while attrition was 13 % . After 24 weeks , there was no significant difference between those r and omised to the treatment arm compared with those r and omised to the waiting-list control arm on the primary outcome measure , the Hamilton Rating Scale for Anxiety . Conclusions Trials of psychological therapies with this population are feasible . Larger definitive trials are now needed . Declaration of interest None . Copyright and usage © The Royal College of Psychiatrists 2016 . This is an open access article distributed under the terms of the Creative Commons Attribution ( CC BY ) licence This study examined the relationship between therapist factors and child outcomes in anxious youth who received cognitive-behavioral therapy ( CBT ) as part of the Child-Adolescent Anxiety Multimodal Study ( CAMS ) . Of the 488 youth who participated in the CAMS project , 279 were r and omly assigned to one of the CBT conditions ( CBT only or CBT plus sertraline ) . Participants included youth ( ages 7 - 17 ; M = 10.76 ) who met criteria for a principal anxiety disorder . Therapists included 38 cognitive-behavioral therapists . Therapist style , treatment integrity , and therapist experience were examined in relation to child outcome . Child outcome was measured via child , parent , and independent evaluator report . Therapists who were more collaborative and empathic , followed the treatment manual , and implemented it in a developmentally appropriate way had youth with better treatment outcomes . Therapist " coach " style was a significant predictor of child-reported outcome , with the collaborative " coach " style predicting fewer child-reported symptoms . Higher levels of therapist prior clinical experience and lower levels of prior anxiety-specific experience were significant predictors of better treatment outcome . Findings suggest that although all therapists used the same manual-guided treatment , therapist style , experience , and clinical skills were related to differences in child outcome . Clinical implication s and recommendations for future research are discussed Many children with Autism Spectrum Disorders ( ASD ) participate in social skills or Theory of Mind ( ToM ) treatments . However , few studies have shown evidence for their effectiveness . The current study used a r and omized controlled design to test the effectiveness of a 16-week ToM treatment in 8–13 year old children with ASD and normal IQs ( n = 40 ) . The results showed that , compared to controls , the treated children with ASD improved in their conceptual ToM skills , but their elementary underst and ing , self reported empathic skills or parent reported social behaviour did not improve . Despite the effects on conceptual underst and ing , the current study does not indicate strong evidence for the effectiveness of a ToM treatment on the daily life mindreading skills A r and omized controlled design was employed to evaluate a social skills intervention for children with pervasive developmental disorders . Aims included evaluating the acceptability of the program and gathering preliminary evidence on efficacy . Forty-four children , ages 8–11 years , were r and omly assigned to treatment or wait list . Treatment consisted of a 16-week group intervention design ed to teach appropriate social behavior . Between group comparisons showed that children in treatment were rated as improved on the primary outcome measure , ( unblinded parent report ) , but not on the secondary outcome measure , a parent question naire . Parents reported a high level of satisfaction with the intervention . The study supports the feasibility of this intervention to families and highlights challenges for future research in social skills intervention OBJECTIVE This study explores the relationships between therapist variables ( cognitive behavioral therapy [ CBT ] competence , and CBT adherence ) and clinical outcomes of computer-assisted CBT for anxiety disorders delivered by novice therapists in a primary care setting . METHODS Participants were recruited for a r and omized controlled trial of evidence -based treatment , including computer-assisted CBT , versus treatment as usual . Therapists ( anxiety clinical specialists ; ACSs ) were nonexpert clinicians , many of whom had no prior experience in delivering psychotherapy ( and in particular , very little experience with CBT ) . Trained raters review ed r and omly selected treatment sessions from 176 participants and rated therapists on measures of CBT competence and CBT adherence . Patients were assessed at baseline and at 6- , 12- , and 18-month follow-ups on measures of anxiety , depression , and functioning , and an average Reliable Change Index was calculated as a composite measure of outcome . CBT competence and CBT adherence were entered as Output:	Definitive trials are needed to demonstrate that CBT is an empirically vali date d treatment for use with people who have ASDs
MS21057	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Systolic dysfunction in septic shock is well recognized and , paradoxically , predicts better outcome . In contrast , diastolic dysfunction is often ignored and its role in determining early mortality from sepsis has not been adequately investigated . METHODS AND RESULTS A cohort of 262 intensive care unit patients with severe sepsis or septic shock underwent two echocardiography examinations early in the course of their disease . All clinical , laboratory , and survival data were prospect ively collected . Ninety-five ( 36 % ) patients died in the hospital . Reduced mitral annular e'-wave was the strongest predictor of mortality , even after adjusting for the APACHE-II score , low urine output , low left ventricular stroke volume index , and lowest oxygen saturation , the other independent predictors of mortality ( Cox 's proportional hazards : Wald = 21.5 , 16.3 , 9.91 , 7.0 and 6.6 , P < 0.0001 , < 0.0001 , 0.002 , 0.008 , and 0.010 , respectively ) . Patients with systolic dysfunction only ( left ventricular ejection fraction ≤50 % ) , diastolic dysfunction only ( e'-wave < 8 cm/s ) , or combined systolic and diastolic dysfunction ( 9.1 , 40.4 , and 14.1 % of the patients , respectively ) had higher mortality than those with no diastolic or systolic dysfunction ( hazard ratio = 2.9 , 6.0 , 6.2 , P= 0.035 , < 0.0001 , < 0.0001 , respectively ) and had significantly higher serum levels of high-sensitivity troponin-T and N-terminal pro-B-type natriuretic peptide ( NT-proBNP ) . High-sensitivity troponin-T was only minimally elevated , whereas serum levels of NT-proBNP were markedly elevated [ median ( inter-quartile range ) : 0.07 ( 0.02 - 0.17 ) ng/mL and 5762 ( 1001 - 15 962 ) pg/mL , respectively ] , though both predicted mortality even after adjusting for highest creatinine levels ( Wald = 5.8 , 21.4 and 2.3 , P= 0.015 , < 0.001 and 0.13 ) . CONCLUSION Diastolic dysfunction is common and is a major predictor of mortality in severe sepsis and septic shock Objectives : To describe the quality of life among sepsis survivors . Design : Secondary analyses of two international , r and omized clinical trials ( A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis [ derivation cohort ] and PROWESS-SHOCK [ validation cohort ] ) . Setting : ICUs in North and South America , Europe , Africa , Asia , and Australia . Patients : Adults with severe sepsis . We analyzed only patients who were functional and living at home without help before sepsis hospitalization ( n = 1,143 and 987 from A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis and PROWESS-SHOCK , respectively ) . Interventions : None . Measurements and Main Results : In A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis and PROWESS-SHOCK , the average age of patients living at home independently was 63 and 61 years ; 400 ( 34.9 % ) and 298 ( 30.2 % ) died by 6 months . In A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis , 580 patients had a quality of life measured using EQ-5D at 6 months . Of these , 41.6 % could not live independently ( 22.7 % were home but required help , 5.1 % were in nursing home or rehabilitation facilities , and 5.3 % were in acute care hospitals ) . Poor quality of life at 6 months , as evidence d by problems in mobility , usual activities , and self-care domains were reported in 37.4 % , 43.7 % , and 20.5 % , respectively , and the high incidence of poor quality of life was also seen in patients in PROWESS-SHOCK . Over 45 % of patients with mobility and self-care problems at 6 months in A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis died or reported persistent problems at 1 year . Conclusions : Among individuals enrolled in a clinical trial who lived independently prior to severe sepsis , one third had died and of those who survived , a further one third had not returned to independent living by 6 months . Both mortality and quality of life should be considered when design ing new interventions and considering endpoints for sepsis trials BACKGROUND Recent clinical data suggest that treatment with terlipressin ( TP ) may be more advantageous for septic shock than catecholamines . However , it is unknown whether TP would be effective for acute respiratory distress syndrome ( ARDS ) patients with shock . OBJECTIVES The aim of this study was to compare the impact of TP vs. dopamine on hemodynamic variables and vascular endothelial growth factor ( VEGF ) in ARDS patients with shock . METHODS We studied 32 ARDS patients with shock despite fluid loading , who were r and omized to receive TP ( 16 patients ) or dopamine ( 16 patients ) . TP was administered as a continuous intravenous dose of 1.3 μg/kg/h and dopamine was administered in doses up to 20 μg/kg/min to maintain a mean arterial pressure of 70 ± 5 mm Hg for 48 h. Hemodynamic changes , ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ( PaO(2)/FiO(2 ) ) , and VEGF were recorded prospect ively . RESULTS There was a significant correlation between the plasma VEGF level and the lung injury score at baseline ( r = 0.387 , p < 0.01 ) . VEGF concentrations significantly decreased from baseline levels in the TP group ( p < 0.05 ) at 48 h ; there was no difference in the dopamine group ( p > 0.05 ) at 48 h vs. baseline . There was no significant difference in the tumor necrosis factor-α concentration between the groups . CONCLUSIONS TP treatment has the potential to inhibit VEGF and improve oxygenation in patients with shock in the early stage of ARDS Introduction Recent clinical data suggest that early administration of vasopressin analogues may be advantageous compared to a last resort therapy . However , it is still unknown whether vasopressin and terlipressin are equally effective for hemodynamic support in septic shock . The aim of the present prospect i ve , r and omized , controlled pilot trial study was , therefore , to compare the impact of continuous infusions of either vasopressin or terlipressin , when given as first-line therapy in septic shock patients , on open-label norepinephrine requirements . Methods We enrolled septic shock patients ( n = 45 ) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation . Patients were r and omized to receive continuous infusions of either terlipressin ( 1.3 μg·kg-1·h-1 ) , vasopressin ( .03 U·min-1 ) or norepinephrine ( 15 μg·min-1 ; n = 15 per group ) . In all groups , open-label norepinephrine was added to achieve a mean arterial pressure between 65 and 75 mmHg , if necessary . Data from right heart and thermo-dye dilution catheterization , gastric tonometry , as well as laboratory variables of organ function were obtained at baseline , 12 , 24 , 36 and 48 hours after r and omization . Differences within and between groups were analyzed using a two-way ANOVA for repeated measurements with group and time as factors . Time-independent variables were compared with one-way ANOVA . Results There were no differences among groups in terms of systemic and regional hemodynamics . Compared with infusion of .03 U of vasopressin or 15 μg·min-1 of norepinephrine , 1.3 μg·kg-1·h-1 of terlipressin allowed a marked reduction in catecholamine requirements ( 0.8 ± 1.3 and 1.2 ± 1.4 vs. 0.2 ± 0.4 μg·kg-1·min-1 at 48 hours ; each P < 0.05 ) and was associated with less rebound hypotension ( P < 0.05 ) . At the end of the 48-hour intervention period , bilirubin concentrations were higher in the vasopressin and norepinephrine groups as compared with the terlipressin group ( 2.3 ± 2.8 and 2.8 ± 2.5 vs. 0.9 ± 0.3 mg·dL-1 ; each P < 0.05 ) . A time-dependent decrease in platelet count was only observed in the terlipressin group ( P < 0.001 48 hours vs. BL ) . Conclusions The present study provides evidence that continuous infusion of low-dose terlipressin – when given as first-line vasopressor agent in septic shock – is effective in reversing sepsis-induced arterial hypotension and in reducing norepinephrine requirements . Trial registration Clinical Trial.gov NCT00481572 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 Purpose To determine the incidence of and risk factors for adverse cardiac events during catecholamine vasopressor therapy in surgical intensive care unit patients with cardiovascular failure . Methods The occurrence of any of seven predefined adverse cardiac events ( prolonged elevated heart rate , tachyarrhythmia , myocardial cell damage , acute cardiac arrest or death , pulmonary hypertension-induced right heart dysfunction , reduction of systemic blood flow ) was prospect ively recorded during catecholamine vasopressor therapy lasting at least 12 h. Results Fifty-four of 112 study patients developed a total of 114 adverse cardiac events , an incidence of 48.2 % ( 95 % CI , 38.8–57.6 % ) . New-onset tachyarrhythmia ( 49.1 % ) , prolonged elevated heart rate ( 23.7 % ) , and myocardial cell damage ( 17.5 % ) occurred most frequently . Aside from chronic liver diseases , factors independently associated with the occurrence of adverse cardiac events included need for renal replacement therapy , disease severity ( assessed by the Simplified Acute Physiology Score II ) , number of catecholamine vasopressors ( OR , 1.73 ; 95 % CI , 1.08–2.77 ; p = 0.02 ) and duration of catecholamine vasopressor therapy ( OR , 1.01 ; 95 % CI , 1–1.01 ; p = 0.002 ) . Patients developing adverse cardiac events were on catecholamine vasopressors ( p < 0.001 ) and mechanical ventilation ( p < 0.001 ) for longer and had longer intensive care unit stays ( p < 0.001 ) and greater mortality ( 25.9 vs. 1.7 % ; p < 0.001 ) than patients who did not . Conclusions Adverse cardiac events occurred in 48.2 % of surgical intensive care unit patients with cardiovascular failure and were related to morbidity and mortality . The extent and duration of catecholamine vasopressor therapy were independently associated with and may contribute to the pathogenesis of adverse cardiac events Objectives To determine the effects of an intravenous bolus dose of a vasopressin analogue , terlipressin ( 1 mg ) , on systemic haemodynamic parameters and gastric mucosal perfusion ( GMP ) in patients with catecholamine-treated septic shock using a gastric tonometry and laser-Doppler flowmetry technique . Design Prospect i ve open label study . Setting sTwo multidisciplinary intensive care units . Patients Fifteen patients with norepinephrine-treated septic shock . Interventions Every patient with mean arterial pressure between 50 and 55 mmHg treated with high dose norepinephrine received an intravenous bolus dose of terlipressin as last resort therapy . A laser-Doppler probe and tonometer were introduced into the gastric lumen . Measurements and main results Terlipressin produced a decrease in cardiac output ( p<0.05 ) , a progressive increase in mean arterial pressure ( p<0.05 ) and in GMP , detected by laser-Doppler flowmetry ( p<0.05 ) over 30 min and sustained for at least 24 h. The ratio of GMP to systemic oxygen delivery increased after terlipressin bolus dose ( p<0.05 ) . The gradient between gastric mucosal and arterial PCO2 tended to be lower after terlipressin , and the difference was statistically significant ( p<0.05 ) after 8 h. Terlipressin administration significantly increased ( p<0.05 ) urine output compared to baseline and higher values were found at Output:	Additionally , TP improved renal function . The use of TP was associated with reduced mortality in septic shock patients less than 60 years old . TP may also improve renal function and cause more peripheral ischaemia .
MS21058	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Malarial infection during pregnancy increases the risks of severe sequelae for the pregnant woman and the risk of delivering a low birthweight baby . The aim of this intervention study was to reduce significantly the prevalence of malaria parasitaemia in adolescent parturients in Matola and Boane in Mozambique . The study was focused upon the most malaria-vulnerable group , adolescent nulliparous and primiparous women . After completing the usual antenatal clinic and giving informed consent , 600 pregnant women were r and omly chosen in a double blind manner to one of two regimens comparing the prevailing routine ( placebo ) for malaria prevention with a two dose regimen of sulphadoxine-pyrimethamine ( SP ) . The first dose was given at enrollment with a second dose at the beginning of the third trimester . At delivery maternal and placental malaria parasitaemia as well as birthweight and gestational duration were analysed . At booking the prevalence of malaria parasitaemia was 35.3 % in the placebo group and 30.6 % in the SP group . At the second dose , the prevalence of malaria parasitaemia in the placebo group and SP group was 19.7 % and 8.7 % , respectively . This implies a relative risk ( RR ) of 2.24 with 95 % CI ( 1.34 , 3.75 ) . The corresponding figures at delivery were 13.6 % and 6.3 % with an RR of 2.22 ( 1.07 , 4.60 ) and in placenta 13.3 % and 2.4 % with an RR of 4.87 ( 1.58 , 15.0 ) . Newborns with malaria within 7 days were significantly more frequent in the placebo group , 6.4 % and 0.7 % respectively , with an RR of 6.55 ( 1.20 , 35.7 ) . Almost all ( approximately 98 % ) of the women studied had Plasmodium falciparum , the remainder had P. malariae and P. ovale . The mean birthweight in the SP group was 3077 g and in the placebo group 2926 g. The estimated mean difference between the two groups was 151 g with 95 % CI ( 51 , 252 ) . The mean placental weight in the placebo group was 596 and 645 g in the SP group , implying a difference of 49 g with a 95 % CI ( 11 , 88 ) . The mean gestational duration was 6.1 days longer in the SP group , 95 % CI ( 1.5 , 10.6 ) . In the placebo group there were two cases of urticaria and one case of nausea ; in the SP group there was one case of vomiting . No newborn showed any sign of serious SP side-effect . Two doses of SP were enough to significantly reduce the prevalence of peripheral and placental malaria parasitaemia among young nulliparous and primiparous pregnant women in Matola and Boane 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 BACKGROUND Malaria during pregnancy contributes to maternal anemia and low birth weight . In East Africa , several studies have demonstrated that intermittent preventive treatment ( IPT ) with sulfadoxine-pyrimethamine ( SP ) is more efficacious than week Output:	Chemoprophylaxis or IPT reduces antenatal parasite prevalence and placental malaria when given to women in all parity groups . They also have positive effects on birthweight and possibly on perinatal death in low-parity women
MS21059	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The authors compared ultrasonography with electrophysiology for the diagnosis of carpal tunnel syndrome ( CTS ) on 110 clinical ly affected wrists . An increased cross sectional area in the proximal carpal tunnel larger than 0.11 cm2 in combination with compression signs on longitudinal scans proved to be highly predictive for CTS ( sensitivity , 89.1 % ; specificity , 98.0 % ) . Ultrasound was comparable to electrophysiology in the diagnosis of CTS , and in 35 % of cases changes in morphology suggested a specific therapeutic strategy PURPOSE To compare the diagnostic value of high-resolution ultrasound ( US ) with nerve conduction studies ( NCS ) in patients with clinical ly defined carpal tunnel syndrome ( CTS ) . METHODS A prospect i ve study was conducted on 66 consecutive patients investigated for sensory h and symptoms . The gold st and ard was the clinical diagnosis of CTS . RESULTS NCS showed greater diagnostic sensitivity ( 82 % ) than US ( 62 % ) in supporting a diagnosis of CTS . With increasing neurophysiologic severity of median neuropathy , there was increasing convergence of the two test methods . Abnormal US as the only diagnostic supportive evidence of CTS was rare . However , the positive predictive value of US for CTS was 100 % . CONCLUSION NCS show better sensitivity than US in supporting a diagnosis of CTS . However , because of its high positive predictive value , one may consider using US as a screening test , eliminating the need for NCS in the majority of clinical suspicion of CTS and reserving NCS for cases in which US is negative OBJECTIVE The few papers published on the use of sonography in carpal tunnel syndrome suggest it may be a useful diagnostic test . This study aims to prospect ively evaluate the use of sonographic measurements of the median nerve in the diagnosis of carpal tunnel syndrome . SUBJECTS AND METHODS Patients with documented carpal tunnel syndrome and a group of asymptomatic control subjects were enrolled and underwent high-resolution sonography of the carpal tunnel . A small-footprint linear array transducer was used to scan and measure the median nerve cross-sectional area and the maximum transverse and anteroposterior diameters . Data from the patient group and the control group were compared to establish optimal diagnostic criteria for carpal tunnel syndrome . RESULTS Sixty-eight carpal tunnel syndrome patients ( 50 women , 18 men ) with 102 affected nerves and 68 nerves in 36 asymptomatic controls ( 23 women , 13 men ) were examined . Qualitative assessment alone was found to be unreliable . All measurements showed significant differences between patients and controls . The most predictive measurement was swelling of the median nerve , which was significantly greater in carpal tunnel syndrome patients compared with controls ( mean , 0.13 cm2 versus 0.07 cm2 ) . Thus , quantitative assessment of the median nerve provides an accurate diagnostic test ( sensitivity , 82 % ; specificity , 97 % ) , with an area larger than 0.09 cm2 being highly predictive of carpal tunnel syndrome . CONCLUSION We confirm that median nerve cross-sectional area measurement correlates well with the presence of carpal tunnel syndrome and is both sensitive and specific for the diagnosis OBJECTIVE The aim of this study is twofold . First , to assess the relationships between the cross-sectional area ( CSA ) of the median nerve ( MN ) calculated at ultrasound ( US ) and : ( 1 ) patient 's perception of his/her symptoms and h and function ; ( 2 ) clinical severity of CTS ; ( 3 ) neurophysiological classification ; ( 4 ) h and distribution of symptoms . Second , to assess the sensitivity of ultrasonography ( US ) and neurophysiology in the diagnosis of CTS using clinical measures as gold st and ard . METHODS We performed a prospect i ve study by using multidimensional assessment : clinical ( Historic and Objective scale , Hi-Ob ) , neurophysiological , patient-oriented measures ( Boston Carpal Tunnel Question naire , BCTQ ) and high-resolution US . The dominant h and s of 54 consecutive patients who were referred to our neurophysiologic laboratory with clinical signs of CTS ( 43 females , mean age 53.3 , range 30 - 80 , SD : 13.1 ) were examined . RESULTS A statistically significant correlation was found between the CSA of the MN at wrist and ( 1 ) h and function ( according to BCTQ , r=0.35 , p=0.01 ) , ( 2 ) clinical scale ( Hi-Ob scale , r=0.51 , p<0.00007 ) , ( 3 ) neurophysiologic classification ( r=0.80 , p<0.0000001 ) , and ( 4 ) h and distribution of symptoms ( p=0.017 ) . Neurophysiology showed higher sensitivity than US but in one of 3 cases with normal neurophysiological results , US showed data suggestive of CTS . CONCLUSIONS A positive correlation exists between US findings and all the conventional measures of CTS severity . The sensitivity of the combination of US and neurophysiology is higher than the sensitivity of neurophysiology or US alone . US is a useful complementary tool for CTS assessment . SIGNIFICANCE Information on the contribution of US in CTS and the interpretation of severity measurements in CTS PURPOSE To determine whether sonography can be an alternative method to nerve conduction study ( NCS ) in the diagnosis of carpal tunnel syndrome ( CTS ) , by comparing sonography with nerve conduction study using clinical diagnosis as the reference st and ard . METHODS Forty-one wrists of 29 patients were enrolled , along with the same number of age- and gender-matched controls . All patients had sonographic measurement of the cross-sectional area ( CSA ) of the median nerve and NCS . Sensitivity and specificity were obtained and compared between sonography and NCS . RESULTS There were no significant differences in age , gender , body mass index and involved side between patients and controls ( p<.05 ) . The CSA at the tunnel inlet was significantly larger in patients than in controls ( p=.03 ) . The best cutoff value of CSA at the tunnel inlet was 10.7 mm(2 ) , which had a sensitivity of 66 % and a specificity of 63 % . NCS showed a sensitivity of 78 % and a specificity of 83 % . Sensitivity was similar between sonography and NCS ( p=0.27 ) , whereas specificity was significantly lower in sonography than in NCS ( p=0.02 ) . CONCLUSIONS Sonography is not accurate enough to replace NCS for the diagnosis of CTS . TYPE OF STUDY /LEVEL OF EVIDENCE Diagnostic III OBJECTIVE To evaluate the diagnostic value of ultrasonography in patients with electrophysiologically confirmed carpal tunnel syndrome . DESIGN A prospect i ve ultrasonographic study of 70 wrists with electrophysiologically confirmed carpal tunnel syndrome and of 80 normal wrists . Receiver-operating-characteristics curves for the ultrasonographic measurements of median nerve were plotted to identify the most optimal cutoff values . RESULTS The ultrasonographic measurements of median nerves were found to be increased significantly in patients with carpal tunnel syndrome when compared with controls , particularly in terms of cross-sectional area ( P < 0.001 ) . According to receiver-operating-characteristics curve results , the most optimal cutoff value for the cross-sectional area of the median nerve was obtained at the level of middle carpal tunnel , which was 9.3 mm2 , with a sensitivity of 80 % and specificity of 77.5 % . CONCLUSION Ultrasonographic examination of the median nerve seems to be a promising method in the diagnosis of carpal tunnel syndrome , evaluating the morphologic changes of the median nerve in patients with clinical signs and symptoms . Further studies with wider series are needed to confirm our preliminary results Background : Carpal tunnel syndrome ( CTS ) is a common entrapment neuropathy . Electrodiagnostic testing ( EMG ) is used to confirm the diagnosis . It is not known what the diagnostic accuracy of high-resolution sonography is in comparison to EMG . Objective : The aim of this study was to compare the diagnostic accuracy of both tests in CTS patients . Methods : A prospect i ve cohort of 207 patients with possible CTS underwent high-resolution sonography and EMG . The diagnosis of CTS was based on clinical signs and symptoms . The cross-sectional area of the median nerve at the carpal tunnel inlet and at the distal one-third level of the forearm was assessed by an investigator , blinded to the clinical and EMG data . Normal sonographic values were obtained from 137 controls . All patients and 40 controls underwent a st and ardised nerve conduction study . The kappa coefficient was used to evaluate the relationship between sonography , EMG and clinical diagnosis . Results : The cross-sectional area at the distal one-third of the forearm was not significantly different between the controls and patients ( p = 0.59 ) , whereas the cross-sectional area at the carpal tunnel inlet was significantly increased in the patient group ( p<0.0001 ) . The kappa coefficient for EMG using the median-ulnar distal sensory latency difference versus clinical evaluation was 0.64 and , for sonography , this coefficient was 0.69 ; these were not statistically different ( p = 0.37 ) . Combining the two tests result ed in a kappa coefficient of 0.72 , which was not significantly different from sonography alone ( p = 0.73 ) . Conclusion : In patients with a clinical diagnosis of CTS , the accuracy of sonography is similar to that for EMG . Sonography is probably preferable because it is painless , easily accessible and preferred by the patients BACKGROUND There is no clear-cut consensus on the best diagnostic criteria for carpal tunnel syndrome . The objective of this study was to compare the probability of carpal tunnel syndrome being present following electrodiagnostic testing with the probability of it being present after the diagnosis was established on the basis of a clinical evaluation alone . METHODS The study sample included patients with any peripheral nerve diagnosis who had been referred to the electrodiagnostic laboratory of an academic health-care center . The probability of carpal tunnel syndrome before electrodiagnostic testing ( pretest probability ) was estimated with use of the CTS-6 , a vali date d clinical diagnostic aid that is used to estimate the probability of carpal tunnel syndrome on the basis of the presence or absence of six clinical findings recorded as part of the history or noted on physical examination . All patients then underwent a st and ard electrodiagnostic assessment of the median nerve by a neurologist blinded to the result of the CTS-6 evaluation . Sensory nerve conduction velocity was used to classify the result of the electrodiagnostic testing as either positive or negative for carpal tunnel syndrome with use of two different criteria ( one stringent and one lax ) derived from the literature . The main outcome measure was the difference between the pretest and posttest probabilities of carpal tunnel syndrome . RESULTS One hundred and forty-three patients were studied . The pretest probability of carpal tunnel syndrome ranged between 0.10 and 0.99 ( mean [ and st and ard deviation ] , 0.81 + /- 0.22 ) . Seventy-three percent of the patients had a pretest probability of at least 0.80 . The average change in probability for these patients was -0.02 when the stringent electrodiagnostic criterion was used and -0.06 when the lax criterion was used . With either electrodiagnostic criterion , the majority of the large changes in probability were for patients for whom the pretest probability was < or = 0.50 . The probability of carpal tunnel syndrome was lowered after the electrodiagnostic testing in most of these cases . CONCLUSIONS For the majority of patients who are considered to have carpal tunnel syndrome on the basis of their history and physical examination alone , electrodiagnostic tests do not change the probability of diagnosing this condition to an extent that is clinical ly relevant The utility of electrodiagnostic testing in the evaluation of carpal tunnel syndrome ( CTS ) has been question ed . We studied patients who met the clinical criteria for CTS and compared patients who had normal nerve conduction studies ( NCS ) with patients who had abnormal NCS . We found that 25 % of the CTS patients without confounding neurologic disorders had normal NCS with median palmar nerve stimulation . Patients with abnormal NCS were older and heavier and had more clinical features of CTS . NCS results could not be predicted accurately from clinical features by use of logistic regression models . This was especially true in clinical ly borderline cases . NCS did not predict the outcome of conservative management . We concluded that NCS provide independent information in the evaluation of suspected CTS , especially when fewer clinical criteria are present , but that NCS are not helpful in predicting the outcome of nonsurgical management The diagnosis of carpal tunnel syndrome ( CTS ) is mainly based on clinical findings and electrodiagnostic tests ( EDT ) . However , EDT results do not support clinical findings in some cases . It has been recently suggested that ultrasonography ( US ) can be used to diagnose CTS . In this study , we aim ed to investigate whether US has a diagnostic value for CTS in patients with negative EDT findings or not . EDT was performed on 319 wrists with clinical CTS findings in electrophysiology laboratory . Median and ulnar nerve conduction velocities were measured in all cases and electromyography was performed in patient with tenar atrophy and having suspicion involvement of brachial plexus as EDT . Fifty-nine wrists with negative EDT ( study group ) and 30 wrists from 15 healthy individuals ( control group ) were examined using US . The mean of cross-sectional areas ( CSAs ) measurements were found 8.83+/-3.05 mm2 by tracing method ( TM ) and 8.51+/-3.13 mm2 by ellipsoid formula ( EF ) in study group , and 7.63+/-1.52 mm2 by TM and 7.66+ Output:	Conclusions The wide variations of sensitivities and specificities reported in the literature have prevented meaningful analysis of ultrasound as either a screening or confirmatory tool in the diagnosis of CTS . Although ultrasound may not replace electrodiagnostic testing as the most sensitive and specific test for the diagnosis of CTS given the values reported in this meta- analysis , it may be a feasible alternative to electrodiagnostic testing as the first-line confirmatory test .
MS21060	*TASK* the task is to summarize an input biomedical literature in six sentences *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 muscle torque , lower extremity coordination , and knee laxity after ACL reconstruction comparing patients operated on with semitendinosus graft ( ST ) and patients with combined semitendinosus and gracilis ( STGR ) grafts . Methods Forty-six subjects who underwent ST ( n = 23 ) or STGR harvest ( n = 23 ) ACL reconstruction participated in this study . Quadriceps and hamstring torque were recorded using an isokinetic dynamometer . The anterior tibial translation was measured using the Kneelax 3 Arthrometer . The eccentric and concentric motor coordination was tested by multi-joint lower-limb tracking-trajectory test . All measurements were taken 12 months after surgery . Side-to-side differences were determined for all subjects . Results Side-to-side differences in extensor peak torque at 180 ° /s and 60 ° /s did not differ between semitendinosus ( ST ) and semitendinosus + gracilis ( STGR ) groups ( n.s . ) . However , side-to-side differences in flexor peak torque were significantly higher at 60 ° /s for the STGR group than the ST group ( P = 0.002 ) . Side-to-side differences in eccentric and concentric parts of tracking-trajectory test and anterior tibial translation did not differ between the STGR and the ST groups ( n.s . ) . Conclusion The outcomes of this study suggested that additional harvest of gracilis did not influence lower extremity motor control , quadriceps muscle torque , and anterior tibial translation ; however , it affected knee flexion isokinetic torque negatively at low angular velocity . This finding could be important for functional activity or sports with high dem and s on hamstring muscle strength . It is recommended that gracilis muscle should be preserved as possible during ACL reconstruction . Level of evidence Prospect i ve comparative study , Level II Purpose The purpose of this prospect i ve study was to describe the variability in leg muscle power and hop performance up to 2 years among patients following ACL reconstruction and specifically to illustrate the effects of various criteria for an acceptable level of muscle function . Methods Eighty-two patients ( 56 men and 26 women ) with a mean age of 28 years , who underwent ACL reconstruction using either hamstring tendons ( n = 46 ) or a patellar tendon ( n = 36 ) , were assessed pre-operatively and 3 , 6 , 12 and 24 months post-surgery with a battery of three lower extremity muscle power tests and a battery of three hop tests . Results Leg symmetry index ( LSI ) values at group level ranged between 73 and 100 % at all follow-ups . When the tests were evaluated individually , patients reached an average LSI of ≥90 % at 24 months . The success rate at 24 months for the muscle power test battery , that is , patients with an LSI of ≥90 % in all three tests , was 48 and 44 % for the hop test battery . The success rate at 24 months for both test batteries on all six muscle function tests was 22 % . The criterion of an LSI of ≥80 % result ed in 53 % of the patients having an acceptable level on all six tests , while with a criterion of an LSI of ≥100 % , none of the patients reached an acceptable level . Conclusion At group level and in single muscle function tests , the muscle function outcome 1 and 2 years after ACL reconstruction is satisfactory in the present study and on a par with the results presented in the literature . However , when using more dem and ing criteria for a successful muscle function outcome , using batteries of tests or increasing the acceptable LSI level from ≥90 % to ≥95 % or ≥100 % , the results are considered to be poor . It is suggested that this should be taken into consideration when presenting results after ACL rehabilitation , deciding on the criteria for a safe return to sports , or design ing rehabilitation programmes after ACL reconstruction . Level of evidence Prognostic prospect i ve cohort study , Level BACKGROUND The diagnosis of clinical ly important meniscal tears of the knee remains challenging , and it is unknown why only some injuries become painful . The role of inflammatory cytokines in generating pain following meniscal injury remains unclear . This study aim ed to investigate the cytokine profile in patients with acute knee pain believed to be secondary to meniscal damage . METHODS This prospect i ve cohort study included thirty-two patients without rheumatoid arthritis who had knee pain for less than six months , with either an acute or insidious onset , and elected to have arthroscopic treatment after nonoperative management had failed . Twenty-three of these patients elected to have the contralateral , nonoperatively treated knee lavaged at the time of arthroscopy . Fifteen asymptomatic control subjects also contributed sample s of knee joint fluid , for a total of seventy sample s from forty-seven subjects . Lavage of the operatively treated , contralateral , and control knees was performed with the patient under regional anesthesia prior to arthroscopy , if applicable , by the infusion of sterile saline solution into the knee followed by the immediate withdrawal into a syringe . The concentrations of seventeen inflammatory cytokines and chemokines were measured with use of a multiplexed immunoassay panel . Preoperative magnetic resonance imaging findings and cytokine assay results were compared with intraoperative findings . RESULTS Multivariate analysis of variance detected significantly greater concentrations of interferon gamma ( IFN-gamma ) ; interleukins 2 , 4 , 6 , 10 , and 13 ( IL-2 , IL-4 , IL-6 , IL-10 , and IL-13 ) ; monocyte chemotactic protein-1 ( MCP-1 ) ; and macrophage inflammatory protein-1 beta ( MIP-1beta ) in fluid sample s from painful knees than in sample s from nonpainful knees . Correlation analysis demonstrated a significant positive correlation between patient-reported pain scores and concentrations of IL-6 ( Spearman rho = 0.7 ) , MCP-1 ( rho = 0.8 ) , MIP-1beta ( rho = 0.6 ) , and IFN-gamma ( rho = 0.6 ) . These four cytokines also demonstrated a positive correlation with each other ( rho = 0.5 to 0.7 ) . The presence of IFN-gamma , IL-6 , MCP-1 , or MIP-1beta performed as well as magnetic resonance imaging in the prediction of intraoperative findings . CONCLUSIONS Intra-articular concentrations of four inflammatory cytokines IFN-gamma , IL-6 , MCP-1 , and MIP-1beta correlated to pain in patients with symptomatic meniscal tears in the knee but were markedly lower in asymptomatic normal knees and in asymptomatic knees with meniscal tears . These cytokines may be involved in the generation of pain following meniscal injury STUDY DESIGN Descriptive , prospect i ve , longitudinal single-cohort study . OBJECTIVE To investigate the rate of force development to 30 % ( RFD(30 ) ) , 50 % ( RFD(50 ) ) , and 90 % ( RFD(90 ) ) of maximal voluntary isometric contraction ( MVIC ) as an adjunct outcome measure for determining readiness for return to sport following an anterior cruciate ligament ( ACL ) reconstruction . BACKGROUND One criterion of full recovery following an ACL reconstruction is the ability to achieve 85 % or 90 % of the maximal strength of the contralateral limb . However , the time required to develop muscular strength in many types of daily and sports activities is considerably shorter than that required to achieve maximal strength . Therefore , in addition to maximal strength , neuromuscular functions such as RFD should also be considered in the definition of recovery . METHODS Forty-five male professional soccer players who underwent an ACL reconstruction were recruited . Assessment with the International Knee Documentation Committee ( IKDC ) Subjective Knee Evaluation Form , Tegner score , and KT1000 instrumented arthrometer was performed postinjury/prereconstruction and at 6 and 12 months after ACL reconstruction . MVIC , RFD(30 ) , RFD(50 ) , and RFD(90 ) testing was performed preinjury , as part of st and ard preseason assessment , and at 6 and 12 months post-ACL reconstruction . RESULTS The average MVIC value 6 months postreconstruction was 97 % of the preinjury average value . In contrast , at 6 months , the RFD(30 ) , RFD(50 ) , and RFD(90 ) values were 80 % ( P = .04 ) , 77 % ( P = .03 ) , and 63 % ( P = .007 ) , respectively , of the preinjury values . The mean RFD values for the reconstructed knee attained or exceeded 90 % of the preinjury mean values only at the 12-month post-ACL reconstruction assessment ( RFD(30 ) , P = .86 ; RFD(50 ) , P = .51 ; RFD(90 ) , P = .56 ) . CONCLUSION Despite the near recovery of MVIC strength to preinjury levels , there were still significant deficits in RFD at 6 months post-ACL reconstruction . An RFD similar to the preinjury RFD was achieved at 12 months post-ACL reconstruction , following a rehabilitation program focusing on muscle power . These results suggest that , following an ACL reconstruction , RFD criteria may be a useful adjunct outcome measure for the decision to return athletes to sports . J Orthop Sports Phys Ther 2012;42(9):772 - 780 , Epub 19 July 2012 . doi:10.2519/jospt.2012.3780 Background and Purpose Although various hop tests have been proposed as performance-based outcome measures following anterior cruciate ligament ( ACL ) reconstruction , limited reports of their measurement properties exist . The purpose of this study was to investigate the reliability and longitudinal validity of data obtained from hop tests during rehabilitation after ACL reconstruction . Subjects Forty-two patients , 15 to 45 years of age , who had undergone ACL reconstruction participated in the study . Methods and Measures The study design was prospect i ve and observational with repeated measures . The subjects performed a series of 4 hop tests on 3 separate occasions within the 16th week following surgery and on a fourth occasion 6 weeks later . The tests were a single hop for distance , a 6-m timed hop , a triple hop for distance , and crossover hops for distance . Performance on the ACL-reconstructed limb was expressed as a percentage of the performance on the nonoperative limb , termed the “ limb symmetry index . ” Subjects also completed the Lower Extremity Functional Scale and a global rating of change question naire . Results Intraclass correlation coefficients for limb symmetry index values ranged from .82 to .93 . St and ard errors of measurement were 3.04 % to 5.59 % . Minimal detectable changes , at the 90 % confidence level , were 7.05 % to 12.96 % . Changes in hop test scores on the operative limb were statistically greater than changes on the nonoperative limb . Pearson correlations ( r ) between change in hop performances and self-reported measures ranged from .26 to .58 . Discussion and Conclusion The results show that the described series of hop tests provide a reliable and valid performance-based outcome measure for patients undergoing rehabilitation following ACL reconstruction . These findings support the use and facilitate the interpretation of hop tests for research and clinical practice CONTEXT The development pattern of motor coordination , strength , and functional ability during recovery from anterior cruciate ligament ( ACL ) reconstruction . OBJECTIVE To investigate the relationship between motor coordination , functional ability , and strength after ACL reconstruction . DESIGN Prospect i ve clinical follow-up study . SETTING Sports-injury research laboratory . PARTICIPANTS 20 subjects who underwent ACL reconstruction . INTERVENTIONS Real-time eccentric and concentric motor coordination were tested by a multijoint lower limb tracking-trajectory test , quadriceps and hamstring isokinetic strength were assessed by isokinetic dynamometer , and functional performance was tested with a single-leg-hop test 6 and 12 mo after ACL reconstruction . MAIN OUTCOME MEASURES Percentage deficits of the involved lower extremity for target-tracking ability , peak torque , total work parameters of isokinetic strength , and single-leg-hop distance . RESULTS Deficits in hamstring-quadriceps isokinetic muscle strength and single-leg-hop distance significantly decreased from the 6th to the 12th mo after surgery ( P < .05 ) . There were no significant differences in muscle concentric and eccentric motor-coordination deficits of the involved side ( P > .05 ) . CONCLUSIONS Although muscle strength and functional performance clearly increased from the 6th to the 12th mo after surgery , coordination characteristics of involved side remained low . This pattern demonstrated that motor-coordination progression was not affected by strength development . Patients continued to have significant motor-coordination deficits even 12 mo postsurgery . Therefore , the authors recommend that neuromuscular-coordination exercises be included in long-term rehabilitation programs to improve motor coordination Objective To evaluate the effectiveness of neuromuscular training in reducing the rate of acute knee injury in adolescent female football players . Design Stratified cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 230 Swedish football clubs ( 121 in the intervention group , 109 in the control group ) were followed for one season ( 2009 , seven months ) . Participants 4564 players aged 12 - 17 years ( 2479 in the intervention group , 2085 in the control group ) completed the study . Intervention Output:	The most commonly reported functional tests were the hop tests . The knee flexion strength deficit was significantly less in the BPTB autograft group as compared with those having hamstring autograft at 1 year postoperatively , while no significant differences were found in isokinetic extension strength between the 2 groups . Conclusion : Hop testing was the most commonly reported functional test following ACL reconstruction . Increases in performance on functional tests were predictably seen as time increased following surgery . Those with hamstring autografts may experience increased strength deficits with knee flexion versus those having BPTB autograft .
MS21061	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Among apparently healthy men , elevated levels of C-reactive protein ( CRP ) , a marker for systemic inflammation , predict risk of myocardial infa rct ion and thromboembolic stroke . Whether increased levels of CRP are also associated with the development of symptomatic peripheral arterial disease ( PAD ) is unknown . METHODS AND RESULTS Using a prospect i ve , nested , case-control design , we measured baseline levels of CRP in 144 apparently healthy men participating in the Physicians ' Health Study who subsequently developed symptomatic PAD ( intermittent claudication or need for revascularization ) and in an equal number of control subjects matched on the basis of age and smoking habit who remained free of vascular disease during a follow-up period of 60 months . Median CRP levels at baseline were significantly higher among those who subsequently developed PAD ( 1.34 versus 0.99 mg/L ; P=.04 ) . Furthermore , the risks of developing PAD increased significantly with each increasing quartile of baseline CRP concentration such that relative risks of PAD from lowest ( referent ) to highest quartile of CRP were 1.0 , 1.3 , 2.0 , and 2.1 ( Ptrend=.02 ) . Compared with those with no clinical evidence of disease , the subgroup of case patients who required revascularization had the highest baseline CRP levels ( median= 1.75 mg/L ; P= .04 ) ; relative risks from lowest to highest quartile of CRP for this end point were 1.0 , 1.8 , 3.8 , and 4.1 ( Ptrend=.02 ) . Risk estimates were similar after additional control for body mass index , hypercholesterolemia , hypertension , diabetes , and a family history of premature atherosclerosis . CONCLUSIONS These prospect i ve data indicate that among apparently healthy men , baseline levels of CRP predict future risk of developing symptomatic PAD and thus provide further support for the hypothesis that chronic inflammation is important in the pathogenesis of atherothrombosis In 1998 , the American Heart Association convened Prevention Conference V to examine strategies for the identification of high-risk patients who need primary prevention . Among the strategies discussed was the measurement of markers of inflammation.1 The Conference concluded that “ many of these markers ( including inflammatory markers ) are not yet considered applicable for routine risk assessment because of : ( 1 ) lack of measurement st and ardization , ( 2 ) lack of consistency in epidemiological findings from prospect i ve studies with endpoints , and ( 3 ) lack of evidence that the novel marker adds to risk prediction over and above that already achievable through the use of established risk factors . ” The National Cholesterol Education Program Adult Treatment Panel III Guidelines identified these markers as emerging risk factors,1a which could be used as an optional risk factor measurement to adjust estimates of absolute risk obtained using st and ard risk factors . Since these publications , a large number of peer- review ed scientific reports have been published relating inflammatory markers to cardiovascular disease ( CVD ) . Several commercial assays for inflammatory markers have become available . As a consequence of the exp and ing research base and availability of assays , the number of inflammatory marker tests ordered by clinicians for CVD risk prediction has grown rapidly . Despite this , there has been no consensus from professional societies or governmental agencies as to how these assays of markers of inflammation should be used in clinical practice . On March 14 and 15 , 2002 , a workshop titled “ CDC/AHA Workshop on Inflammatory Markers and Cardiovascular Disease : Applications to Clinical and Public Health Practice ” was convened in Atlanta , Ga , to address these issues . The goals of this workshop were to determine which of the currently available tests should be used ; what results should be used to define high risk ; which patients should be tested ; and the indications for which the tests would be most useful . These BACKGROUND The objective of this study was to examine the association of Joint National Committee ( JNC-V ) blood pressure and National Cholesterol Education Program ( NCEP ) cholesterol categories with coronary heart disease ( CHD ) risk , to incorporate them into coronary prediction algorithms , and to compare the discrimination properties of this approach with other noncategorical prediction functions . METHODS AND RESULTS This work was design ed as a prospect i ve , single-center study in the setting of a community-based cohort . The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up . During the 12 years of follow-up , a total of 383 men and 227 women developed CHD , which was significantly associated with categories of blood pressure , total cholesterol , LDL cholesterol , and HDL cholesterol ( all P<.001 ) . Sex-specific prediction equations were formulated to predict CHD risk according to age , diabetes , smoking , JNC-V blood pressure categories , and NCEP total cholesterol and LDL cholesterol categories . The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used . After adjustment for other factors , approximately 28 % of CHD events in men and 29 % in women were attributable to blood pressure levels that exceeded high normal ( > or = 130/85 ) . The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ( > or = 200 mg/dL ) was 27 % in men and 34 % in women . CONCLUSIONS Recommended guidelines of blood pressure , total cholesterol , and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample . A simple coronary disease prediction algorithm was developed using categorical variables , which allows physicians to predict multivariate CHD risk in patients without overt CHD AIMS Recently , markers of inflammation , haemostasis , and blood rheology have received much attention as risk factors for coronary heart disease and stroke . However , their role in peripheral arterial disease ( PAD ) is not well established and some of them , including the pro-inflammatory cytokine interleukin-6 ( IL-6 ) , have not been examined before in prospect i ve epidemiological studies . METHODS AND RESULTS In the Edinburgh Artery Study , we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD . At baseline ( 1987 ) , 1519 men and women free of PAD aged 55 - 74 were recruited . After 17 years , 208 subjects had developed symptomatic PAD . In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease ( CVD ) , only C-reactive protein , fibrinogen , lipoprotein ( a ) , and haematocrit [ hazard ratio ( 95 % CI ) corresponding to an increase equal to the inter-tertile range 1.30 ( 1.08 , 1.56 ) , 1.16 ( 1.05 , 1.17 ) , 1.22 ( 1.04 , 1.44 ) , 1.22 ( 1.08 , 1.38 ) ] were significantly ( P < 0.01 ) associated with PAD . However , these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index . Other markers including IL-6 , intracellular adhesion molecule 1 , d-dimer , tissue plasminogen activator antigen , and plasma and blood viscosities showed weak associations , which were considerably attenuated when CVD risk factors were accounted for . CONCLUSIONS Our prospect i ve data showed that several inflammatory , haemostatic , and rheological markers are associated with incident PAD ; however , their clinical utility is likely to be limited . Future research is necessary to vali date the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations CONTEXT Despite improved underst and ing of atherothrombosis , cardiovascular prediction algorithms for women have largely relied on traditional risk factors . OBJECTIVE To develop and vali date cardiovascular risk algorithms for women based on a large panel of traditional and novel risk factors . DESIGN , SETTING , AND PARTICIPANTS Thirty-five factors were assessed among 24 558 initially healthy US women 45 years or older who were followed up for a median of 10.2 years ( through March 2004 ) for incident cardiovascular events ( an adjudicated composite of myocardial infa rct ion , ischemic stroke , coronary revascularization , and cardiovascular death ) . We used data among a r and om two thirds ( derivation cohort , n = 16 400 ) to develop new risk algorithms that were then tested to compare observed and predicted outcomes in the remaining one third of women ( validation cohort , n = 8158 ) . MAIN OUTCOME MEASURE Minimization of the Bayes Information Criterion was used in the derivation cohort to develop the best-fitting parsimonious prediction models . In the validation cohort , we compared predicted vs actual 10-year cardiovascular event rates when the new algorithms were compared with models based on covariates included in the Adult Treatment Panel III risk score . RESULTS In the derivation cohort , a best-fitting model ( model A ) and a clinical ly simplified model ( model B , the Reynolds Risk Score ) had lower Bayes Information Criterion scores than models based on covariates used in Adult Treatment Panel III . In the validation cohort , all measures of fit , discrimination , and calibration were improved when either model A or B was used . For example , among participants without diabetes with estimated 10-year risks according to the Adult Treatment Panel III of 5 % to less than 10 % ( n = 603 ) or 10 % to less than 20 % ( n = 156 ) , model A reclassified 379 ( 50 % ) into higher- or lower-risk categories that in each instance more accurately matched actual event rates . Similar effects were achieved for clinical ly simplified model B limited to age , systolic blood pressure , hemoglobin A(1c ) if diabetic , smoking , total and high-density lipoprotein cholesterol , high-sensitivity C-reactive protein , and parental history of myocardial infa rct ion before age 60 years . Neither new algorithm provided substantive information about women at very low risk based on the published Adult Treatment Panel III score . CONCLUSION We developed , vali date d , and demonstrated highly improved accuracy of 2 clinical algorithms for global cardiovascular risk prediction that reclassified 40 % to 50 % of women at intermediate risk into higher- or lower-risk categories CONTEXT Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus ( DM ) ; however , clinical data addressing this issue are limited . OBJECTIVE To determine whether elevated levels of the inflammatory markers interleukin 6 ( IL-6 ) and C-reactive protein ( CRP ) are associated with development of type 2 DM in healthy middle-aged women . DESIGN Prospect i ve , nested case-control study . SETTING The Women 's Health Study , an ongoing US primary prevention , r and omized clinical trial initiated in 1992 . PARTICIPANTS From a nationwide cohort of 27 628 women free of diagnosed DM , cardiovascular disease , and cancer at baseline , 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls . MAIN OUTCOME MEASURES Incidence of confirmed clinical ly diagnosed type 2 DM by baseline levels of IL-6 and CRP . RESULTS Baseline levels of IL-6 ( P<.001 ) and CRP ( P<.001 ) were significantly higher among cases than among controls . The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 ( 95 % confidence interval [ CI ] , 3.7 - 15.4 ) and 15.7 for CRP ( 95 % CI , 6.5 - 37.9 ) . Positive associations persisted after adjustment for body mass index , family history of diabetes , smoking , exercise , use of alcohol , and hormone replacement therapy ; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 ( 95 % CI , 0.9 - 5.6 ; P for trend = .07 ) and 4.2 for CRP ( 95 % CI , 1.5 - 12.0 ; P for trend = .001 ) . Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c ) of 6.0 % or less and after adjustment for fasting insulin level . CONCLUSIONS Elevated levels of CRP and IL-6 predict the development of type 2 DM . These data support a possible role for inflammation in diabetogenesis BACKGROUND C-reactive protein is an inflammatory marker believed to be of value in the prediction of coronary events . We report data from a large study of C-reactive protein and other circulating inflammatory markers , as well as up date d meta-analyses , to evaluate their relevance to the prediction of coronary heart disease . METHODS Measurements were made in sample s obtained at base line from up to 2459 patients who had a nonfatal myocardial infa rct ion or died of coronary heart disease during the study and from up to 3969 controls without a coronary heart disease event in the Reykjavik prospect i ve study of 18,569 participants . Measurements were made in paired sample s obtained an average of 12 years apart from 379 of these participants in order to quantify within-person fluctuations in inflammatory marker levels Output:	CRP does not perform better than the Framingham risk equation for discrimination . The improvement in risk stratification or reclassification from addition of CRP to models based on established risk factors is small and inconsistent .
MS21062	*TASK* the task is to summarize an input biomedical literature in six sentences *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 regenerative potential of brain has led to emerging therapies that can cure clinico-motor deficits after neurological diseases . Bone marrow mononuclear cell therapy is a great hope to mankind as these cells are feasible , multipotent and aid in neurofunctional gains in Stroke patients . Aims : This study evaluates safety , feasibility and efficacy of autologous mononuclear ( MNC ) stem cell transplantation in patients with chronic ischemic stroke ( CIS ) using clinical scores and functional imaging ( fMRI and DTI ) . Design : Non r and omised controlled observational study Study : Twenty four ( n=24 ) CIS patients were recruited with the inclusion criteria as : 3 months-2years of stroke onset , h and muscle power ( MRC grade ) at least 2 ; Brunnstrom stage of recovery : II-IV ; NIHSS of 4 - 15 , comprehendible . Fugl Meyer , modified Barthel Index ( mBI ) and functional imaging parameters were used for assessment at baseline , 8 weeks and at 24 weeks . Twelve patients were administered with mean 54.6 million cells intravenously followed by 8 weeks of physiotherapy . Twelve patients served as controls . All patients were followed up at 24 weeks . Outcomes : The laboratory and radiological outcome measures were within normal limits in MNC group . Only mBI showed statistically significant improvement at 24 weeks ( p<0.05 ) whereas the mean FM , MRC , Ashworth tone scores in the MNC group were high as compared to control group . There was an increased number of cluster activation of Brodmann areas BA 4 , BA 6 post stem cell infusion compared to controls indicating neural plasticity . Cell therapy is safe and feasible which may facilitate restoration of function in CIS Background and Purpose — Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells ( BMSCs ) in stroke . We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke . Methods — This was a phase II , multicenter , parallel group , r and omized trial with blinded outcome assessment that included 120 patients . Patients with subacute ischemic stroke were r and omly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm . Co primary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180 . Secondary outcomes were change in infa rct volume , National Institute of Health Stroke Scale ( NIHSS ) at day 90 and 180 . Main safety outcomes were adverse events , any new area of 18fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days . Results — Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset . There was no significant difference between BMSCs arm and control arm in the Barthel Index score ( 63.1 versus 63.6 ; P=0.92 ) , modified Rankin scale shift analysis ( P=0.53 ) or score > 3 ( 47.5 % versus 49.2 % ; P=0.85 ) , NIHSS score ( 6.3 versus 7.0 ; P=0.53 ) , change in infa rct volume ( −11.1 versus −7.36 ; P=0.63 ) at day 180 . Adverse events were also similar in the 2 arms , and no patient showed any new area of 18fluorodeoxyglucose uptake . Conclusions — With the methods used , results of this hitherto first r and omized controlled trial indicate that intravenous infusion of BMSCs is safe , but there is no beneficial effect of treatment on stroke outcome . Clinical Trial Registration — URLs : http://ctri.nic.in/ Clinical trials and http://www . clinical trials.gov . Unique identifiers : CTRI-ROVCTRI/2008/091/0004 and NCT0150177 AIMS To assess the biodistribution of bone marrow mononuclear cells ( BMMNC ) delivered by different routes in patients with subacute middle cerebral artery ischemic stroke . PATIENTS & METHODS This was a nonr and omized , open-label Phase I clinical trial . After bone marrow harvesting , BMMNCs were labeled with technetium-99 m and intra-arterially or intravenously delivered together with the unlabeled cells . Scintigraphies were carried out at 2 and 24 h after cell transplantation . Clinical follow-up was continued for 6 months . RESULTS Twelve patients were included , between 19 and 89 days after stroke , and received 1 - 5 × 10(8 ) BMMNCs . The intra-arterial group had greater radioactive counts in the liver and spleen and lower counts in the lungs at 2 and 24 h , while in the brain they were low and similar for both routes . CONCLUSION BMMNC labeling with technetium-99 m allowed imaging for up to 24 h after intra-arterial or intravenous injection in stroke patients Background and Purpose — Bone marrow mononuclear cell ( BM-MNC ) intra-arterial transplantation improves recovery in experimental models of ischemic stroke . We aim ed to assess the safety , feasibility , and biological effects of autologous BM-MNC transplantation in patients with stroke . Methods — A single-blind ( outcomes assessor ) controlled Phase I/II trial was conducted in patients with middle cerebral artery stroke . Autologous BM-MNCs were injected intra-arterially between 5 and 9 days after stroke . Follow-up was done for up to 6 months and blood sample s were collected for biological markers . The primary outcome was safety and feasibility of the procedure . The secondary outcome was improvement in neurological function . Results — Ten cases ( BM-MNC-treated ) and 10 control subjects ( BM-MNC-nontreated ) were consecutively included . Mean National Institutes of Health Stroke Scale before the procedure was 15.6 . Mean BM-MNCs injected were 1.59 × 108 . There was no death , stroke recurrence , or tumor formation during follow-up , although 2 cases had an isolate partial seizure at 3 months . After transplantation , higher plasma levels of beta nerve growth factor ( & bgr;-nerve growth factor ) were found compared with control subjects ( P=0.02 ) . There were no significant differences in neurological function at 180 days . A trend to positive correlation between number of CD34 + cells injected and Barthel Index was found ( r=0.56 , P=0.09 ) . Conclusions — Intra-arterial BM-MNC transplantation in subacute ischemic stroke is feasible and seems to be safe . Larger r and omized trials are needed to confirm the safety and eluci date the efficacy of BM-MNC transplantation . Clinical Trial Registration -URL— www . clinical trials.gov . Unique identifier : NCT00761982 Background and Purpose — Pre clinical data suggest that cell-based therapies have the potential to improve stroke outcomes . Methods — Eighteen patients with stable , chronic stroke were enrolled in a 2-year , open-label , single-arm study to evaluate the safety and clinical outcomes of surgical transplantation of modified bone marrow – derived mesenchymal stem cells ( SB623 ) . Results — All patients in the safety population ( N=18 ) experienced at least 1 treatment-emergent adverse event . Six patients experienced 6 serious treatment-emergent adverse events ; 2 were probably or definitely related to surgical procedure ; none were related to cell treatment . All serious treatment-emergent adverse events resolved without sequelae . There were no dose-limiting toxicities or deaths . Sixteen patients completed 12 months of follow-up at the time of this analysis . Significant improvement from baseline ( mean ) was reported for : ( 1 ) European Stroke Scale : mean increase 6.88 ( 95 % confidence interval , 3.5–10.3 ; P<0.001 ) , ( 2 ) National Institutes of Health Stroke Scale : mean decrease 2.00 ( 95 % confidence interval , −2.7 to −1.3 ; P<0.001 ) , ( 3 ) Fugl-Meyer total score : mean increase 19.20 ( 95 % confidence interval , 11.4–27.0 ; P<0.001 ) , and ( 4 ) Fugl-Meyer motor function total score : mean increase 11.40 ( 95 % confidence interval , 4.6–18.2 ; P<0.001 ) . No changes were observed in modified Rankin Scale . The area of magnetic resonance T2 fluid-attenuated inversion recovery signal change in the ipsilateral cortex 1 week after implantation significantly correlated with clinical improvement at 12 months ( P<0.001 for European Stroke Scale ) . Conclusions — In this interim report , SB623 cells were safe and associated with improvement in clinical outcome end points at 12 months . Clinical Trial Registration — URL : https://www . clinical trials.gov . Unique identifier : NCT01287936 Background and objective . Proportional recovery of upper-extremity motor function and aphasia after stroke may suggest common mechanisms for spontaneous neurobiological recovery . This study aim ed to investigate if the proportional recovery rule also applies to visuospatial neglect ( VSN ) in right-hemispheric first-ever ischemic stroke patients and explored the possible common underlying mechanisms . Methods . Patients with upper-limb paresis and VSN were included . Recovery defined as the change in Letter Cancellation Test ( LCT ) score at ~8 days and 6 months poststroke . Potential recovery defined as LCTmax-LCTinitial = 20 − LCTinitial . Hierarchical clustering separated fitters and nonfitters of the prediction rule . A cutoff value on LCTmax-LCTinitial was determined . The change in LCT and Fugl-Meyer Assessment Upper Extremity was expressed as a percentage of the total possible score to investigate the communality of proportional recovery . Results . Out of 90 patients , 80 displayed proportional recovery of VSN ( ie , “ fitters , ” 0.97 ; 95 % CI = 0.82 - 1.12 ) . All patients who did not follow the prediction rule for VSN ( ie , ” nonfitters ” ) had ≥15 missing O ’s at baseline and failed to show proportional recovery of the upper limb . Conclusions . This study shows that the proportional recovery rule also applies to patients with VSN poststroke . Patients who fail to show proportional recovery of VSN are the same patients who fail to show proportional recovery of the upper limb . These findings support the idea of common intrahemispheric mechanisms underlying spontaneous neurobiological recovery in the first months poststroke . Future studies should investigate the prognostic clinical and neurobiological markers of these subgroups AIMS To assess the safety and feasibility of intra-arterial transplantation of autologous bone marrow mononuclear cells in patients with middle cerebral artery ischemic stroke within 90 days of symptom onset . PATIENTS & METHODS Six patients were included in the study , and they received 1 - 5 × 10(8 ) bone marrow mononuclear cell and were evaluated using blood tests , neurological and imaging examination before treatment , and 1 , 3 , 7 , 30 , 60 , 90 , 120 and 180 days after transplantation . Scintigraphies were carried out 2 and 24 h after the procedure to analyze the biodistribution of labeled cells . Electroencephalogram was conducted within 7 days after transplantation . RESULTS No patients exhibited any complication or adverse events during the procedure . There was no worsening in the neurological scales until the end of the follow-up . CONCLUSION Intra-arterial bone marrow mononuclear cell transplantation is feasible and safe in patients with nonacute ischemic strokes of the middle cerebral artery . Further studies are required to evaluate the efficacy of this therapy Transplantation of autologous bone marrow mononuclear cells ( BMMCs ) has been proven safe in animal and human studies . However , there are very few studies in stroke patients . In this study , intra-arterial autologous BMMCs were infused in patients with moderate to severe acute middle cerebral artery infa rcts . The subjects of this study included 20 patients with early or late spontaneous recanalization but with persistent deficits , in whom treatment could be initiated between 3 and 7 days after stroke onset . Mononuclear cells were isolated from bone marrow aspirates and infused at the proximal middle cerebral artery of the affected hemisphere . Safety analysis ( primary endpoint ) during the 6-month follow-up assessed death , any serious clinical events , neurological worsening with ≥ 4-point increase in National Institutes of Health Stroke Scale ( NIHSS ) scores , seizures , epileptogenic activity on electroencephalogram , and neuroimaging complications including new ischemic , hemorrhagic , or neoplastic lesions . Satisfactory clinical improvement ( secondary endpoint ) at 90 days was defined according to the pretreatment NIHSS scores as follows : modified Rankin Scale score of 0 in patients with NIHSS < 8 , modified Rankin Scale scores of 0 - 1 in patients with NIHSS 8 - 14 , or modified Rankin Scale scores 0 - 2 in patients with NIHSS > 14 . Good clinical outcome was defined as mRS ≤2 at 90 days . Serial clinical , laboratory , electroencephalogram , and imaging evaluations showed no procedure-related adverse events . Output:	The safety and feasibility of administering different types of stem cell therapies in stroke seem to be reasonably proven .
MS21063	*TASK* the task is to summarize an input biomedical literature in six sentences *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 calibration of serum creatinine values to st and ardized creatinine and the commutability of serum creatinine across surveys are essential to the correct use of National Health and Nutrition Examination Survey ( NHANES ) data for kidney function and for generating estimates of the burden of kidney disease in the United States . STUDY DESIGN Calibration study of serum creatinine in NHANES III ( 1988 - 1994 ) and NHANES 1999 - 2000 , 2001 - 2002 , and 2003 - 2004 to directly compare creatinine measurements from the original surveys with st and ard creatinine measured using an assay traceable to known gold-st and ard methods . We also assessed predictors of differences between methods ( potential interferences ) in this general population . SETTING & PARTICIPANTS The NHANES are ongoing cross-sectional surveys of the civilian noninstitutionalized population of the United States . We selected r and om sample s of approximately 200 stored specimens from persons aged 60 years or older from each survey ( NHANES III , 1999 - 2000 , 2001 - 2002 , and 2003 - 2004 ) . MEASUREMENTS Stored serum specimens from the 4 NHANES surveys were analyzed for serum creatinine by using a Roche enzymatic assay implemented at the Clevel and Clinic Research Laboratory ( CCRL ) . The Roche assay is traceable to gold-st and ard reference methods . The original NHANES serum creatinine values were obtained using the Jaffé method ( kinetic alkaline picrate ) implemented in several different laboratories . RESULTS Overall agreement between the original NHANES values ( Jaffé method ) and CCRL measurements ( Roche enzymatic ) was high , but substantial biases were observed in NHANES III and 1999 - 2000 . No bias was observed in NHANES 2001 - 2002 and 2003 - 2004 . Final calibration equations to correct serum creatinine values in the relevant surveys are provided . Assay differences were independent of sex , race/ethnicity , and bilirubin and triglyceride levels , but weakly related to age and glucose concentration . LIMITATIONS We were not able to examine drift in measurements over time within each survey or directly evaluate freeze-thaw effects . CONCLUSIONS The magnitude of differences in serum creatinine measurements in NHANES III and 1999 - 2000 from st and ard creatinine would result in large differences in estimates of kidney function ( 10 % to 20 % ) . Thus , correction of original creatinine values in NHANES III and 1999 - 2000 is essential , but no correction is needed for NHANES 2001 - 2002 or 2003 - 2004 BACKGROUND African American smokers are more likely to experience tobacco-related morbidity and mortality than European American smokers , and higher rates of menthol cigarette smoking may contribute to these disparities . METHODS We prospect ively measured cumulative exposure to menthol and nonmenthol cigarettes and smoking cessation behavior ( 1985 - 2000 ) , coronary calcification ( 2000 ) , and 10-year change in pulmonary function ( 1985 - 1995 ) in African American and European American smokers recruited in 1985 for the Coronary Artery Risk Development in Young Adults Study . RESULTS We identified 1535 smokers in 1985 ( 972 menthol and 563 nonmenthol ) ; 89 % of African Americans preferred menthol vs 29 % of European Americans ( P<.001 ) . After adjustment for ethnicity , demographics , and social factors , we found nonsignificant trends in menthol smokers toward lower cessation ( odds ratio [ OR ] , 0.71 ; 95 % confidence interval [ CI ] , 0.49 - 1.02 ; P = .06 ) and recent quit attempt ( OR , 0.77 ; 95 % CI , 0.56 - 1.06 ; P = .11 ) rates and a significant increase in the risk of relapse ( OR , 1.89 ; 95 % CI , 1.17 - 3.05 ; P = .009 ) . Per pack-year of exposure , however , we found no differences from menthol in tobacco-related coronary calcification ( adjusted OR , 1.27 ; 95 % CI , 1.01 - 1.60 for menthol cigarettes and 1.33 ; 95 % CI , 1.06 - 1.68 for nonmenthol cigarettes per 10-pack-year increase ; P = .75 for comparison ) or 10-year pulmonary function decline ( adjusted excess decline in forced expiratory volume in 1 second , 84 mL ; 95 % CI , 32 - 137 for menthol cigarettes and 80 mL ; 95 % CI , 30 - 129 for nonmenthol cigarettes , per 10-pack-year increase ; P = .88 for comparison ) . CONCLUSION Menthol and nonmenthol cigarettes seem to be equally harmful per cigarette smoked in terms of atherosclerosis and pulmonary function decline , but menthol cigarettes may be harder to quit smoking BACKGROUND Menthol cigarettes , preferred by African American smokers , have been conjectured to be harder to quit and to contribute to the excess lung cancer burden among black men in the Unites States . However , data showing an association between smoking menthol cigarettes and increased lung cancer risk compared with smoking nonmenthol cigarettes are limited . The Food and Drug Administration is currently considering whether to ban the sale of menthol cigarettes in the United States . METHODS We conducted a prospect i ve study among 85,806 racially diverse adults enrolled in the Southern Community Cohort Study during March 2002 to September 2009 according to cigarette smoking status , with smokers classified by preference for menthol vs nonmenthol cigarettes . Among 12,373 smokers who responded to a follow-up question naire , we compared rates of quitting between menthol and nonmenthol smokers . In a nested case-control analysis of 440 incident lung cancer case patients and 2213 matched control subjects , using logistic regression modeling we computed odds ratios ( ORs ) and accompanying 95 % confidence intervals ( CIs ) of lung cancer incidence , and applied Cox proportional hazards modeling to estimate hazard ratios ( HRs ) of lung cancer mortality , according to menthol preference . RESULTS Among both blacks and whites , menthol smokers reported smoking fewer cigarettes per day ; an average of 1.6 ( 95 % CI = 1.3 to 2.0 ) fewer for blacks and 1.8 ( 95 % CI = 1.3 to 2.3 ) fewer for whites , compared with nonmenthol smokers . During an average of 4.3 years of follow-up , 21 % of participants smoking at baseline had quit , with menthol and nonmenthol smokers having equal odds of quitting ( OR = 1.02 , 95 % CI = 0.89 to 1.16 ) . A lower lung cancer incidence was noted in menthol vs nonmenthol smokers ( for smokers of < 10 , 10 - 19 , and ≥ 20 cigarettes per day , compared with never smokers , OR = 5.0 vs 10.3 , 8.7 vs 12.9 , and 12.2 vs 21.1 , respectively ) . These trends were mirrored for lung cancer mortality . In multivariable analyses adjusted for pack-years of smoking , menthol cigarettes were associated with a lower lung cancer incidence ( OR = 0.65 , 95 % CI = 0.47 to 0.90 ) and mortality ( hazard ratio of mortality = 0.69 , 95 % CI = 0.49 to 0.95 ) than nonmenthol cigarettes . CONCLUSIONS The findings suggest that menthol cigarettes are no more , and perhaps less , harmful than nonmenthol cigarettes BACKGROUND African Americans have higher tobacco-related morbidity and mortality and are more likely to smoke menthol cigarettes than their white counterparts . This study examined differences between African American menthol and non-menthol smokers in smoking characteristics and cessation . METHODS The study sample consisted of 600 African American smokers enrolled in a clinical trial that assessed the efficacy of sustained-release bupropion for smoking cessation . Menthol ( n = 471 ) and non-menthol ( n = 129 ) smokers were compared on smoking-related characteristics and abstinence rates at 6 weeks and 6 months . RESULTS Menthol smokers were younger ( 41.2 versus 52.9 years ) , more likely to be female ( 73.7 % versus 56.6 % ) and more likely to smoke their first cigarette within 30 minutes of waking up ( 81.7 % versus 69.8 % ) compared to non-menthol smokers ( all P < 0.01 ) . Cigarette taste ( 50 % versus 40 % , P = 0.054 ) was rated non-significantly higher by menthol smokers . Seven-day point-prevalence abstinence from smoking at 6 weeks were 28 % and 42 % ( P = 0.006 ) and at 6 months were 21 % and 27 % ( P = 0.21 ) for menthol and non-menthol smokers , respectively . At 6 weeks follow-up , stepwise logistic regression revealed that among those younger than 50 years , non-menthol smokers were more likely to quit smoking ( odds ratio = 2.0 ; 95 % CI = 1.03 - 3.95 ) as were those who received bupropion ( odds ratio = 2.12 ; 95 % CI = 1.32 - 3.39 ) . CONCLUSION African American menthol smokers had lower smoking cessation rates after 6 weeks of treatment with bupropion-SR , thereby putting menthol smokers at greater risk from the health effects of smoking . Lower overall cessation rates among African Americans menthol smokers may partially explain ethnic differences in smoking-related disease risks AIMS To determine whether African American light smokers who smoked menthol cigarettes had lower cessation when treated with nicotine replacement therapy and counseling . DESIGN Data were derived from a clinical trial that assessed the efficacy of 2 mg nicotine gum ( versus placebo ) and counseling ( motivational interviewing counseling versus Health Education ) for smoking cessation among African American light smokers ( smoked < or = 10 cigarettes per day ) . PARTICIPANTS The sample consisted of 755 African American light smokers . MEASUREMENTS The primary outcome variable was verified 7-day point-prevalence smoking cessation at 26 weeks follow-up . Verification was by salivary cotinine . FINDINGS Compared to non-menthol smokers , menthol smokers were younger and less confident to quit smoking ( P = 0.023 ) . At 26 weeks post-r and omization , 7-day verified abstinence rate was significantly lower for menthol smokers ( 11.2 % versus 18.8 % for non-menthol , P = 0.015 ) . CONCLUSIONS Among African American light smokers , use of menthol cigarettes is associated with lower smoking cessation rates . Because the majority of African American smokers use menthol cigarettes , a better underst and ing of the mechanism for this lower quit rate is needed Context Guidelines recommend that laboratories estimate glomerular filtration rate ( GFR ) with equations that use serum creatinine level , age , sex , and ethnicity . St and ardizing creatinine measurements across clinical laboratories should reduce variability in estimated GFR . Contribution Using st and ardized creatinine assays , the authors calibrated serum creatinine levels in 1628 patients whose GFR had been measured by urinary clearance of 125I-iothalamate . They used these data to derive new equations for estimating GFR and to measure their accuracy . The equations were inaccurate only when kidney function was near-normal . Caution s There was no independent sample of patients for measuring accuracy . Implication s By using this equation and a st and ardized creatinine assay , different laboratories can report estimated GFR more uniformly and accurately . The Editors Chronic kidney disease is a recently recognized public health problem . Current guidelines define chronic kidney disease as kidney damage or a glomerular filtration rate ( GFR ) less than 60 mL/min per 1.73 m2 for 3 months or more , regardless of cause ( 13 ) . Kidney damage is usually ascertained from markers , such as albuminuria . The GFR can be estimated from serum creatinine concentration and demographic and clinical variables , such as age , sex , ethnicity , and body size . The normal mean value for GFR in healthy young men and women is approximately 130 mL/min per 1.73 m2 and 120 mL/min per 1.73 m2 , respectively , and declines by approximately 1 mL/min per 1.73 m2 per year after 40 years of age ( 4 ) . To facilitate detection of chronic kidney disease , gu Output:	In a representative sample of U.S. adults , menthol cigarette smoking was associated with increased all-cause , cardiovascular and cancer mortality with no differences compared to nonmenthol cigarettes . In the systematic review , menthol cigarette use was associated with inverse risk of cancer compared to nonmenthol cigarette use with some evidence of an increased risk for cardiovascular disease
MS21064	*TASK* the task is to summarize an input biomedical literature in six sentences *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 effectiveness of acupressure and vitamin B6 in the outpatient treatment of nausea and vomiting in early pregnancy . Study design Pregnant volunteers with symptoms of mild to moderate nausea and vomiting between 6 and 12 weeks ’ gestation participated in a 7-day clinical trial . Participants were r and omly assigned to receive a device for acupressure therapy and placebo drug or an otherwise identical but non-stimulating placebo device and vitamin B6 . The primary outcome measure was self-recorded symptoms according to Rhodes index . Secondary outcome measures were weight gain and medication use . Results The mean change in Rhodes index was not significantly different between the two groups . There were no statistically significant differences in weight gain and medication use between the two groups . Conclusion Acupressure therapy is not more effective than vitamin B6 in reducing nausea and vomiting in symptomatic women in the first trimester of pregnancy OBJECTIVE Our purpose was to investigate the efficacy of P6 acupressure in reducing or relieving symptoms of nausea with or without vomiting and retching during pregnancy . STUDY DESIGN Symptomatic pregnant volunteers ( n=161 ) participated in a 7-day community-based clinical trial . All participants were assigned to one of three groups ( i.e. , P6 acupressure , placebo [ acupressure b and s inappropriately placed ] , or control ) on the basis of a process of blocked r and omization . Data were analyzed by error bar charts and analysis of variance of difference scores . RESULTS Of 161 women , 149 ( 92.5 % ) completed the protocol . Irrespective of group assignment , participants reported significant decreases in nausea ( p<0.0009 ) and vomiting or retching ( p<0.0009 ) . However , there was no differential treatment effect as a result of acupressure . CONCLUSION There was no apparent medical benefit from the use of P6 acupressure . Our findings differ from other recently published studies that did not include a control group Objective : To evaluate the effectiveness of acupressure in reducing nausea and vomiting of pregnancy . Methods : Symptomatic pregnant women were r and omized to one of two acupressure groups : one treatment group using an acupressure point ( PC-6 ) and one sham control group using a placebo point . Subjects were blind to the group assignment . Each evening for 10 consecutive days , the subjects completed an assessment scale describing the severity and frequency of symptoms that occurred . Data from the first 3 days were used as pre-treatment scores . Beginning on the morning of the fourth day , each subject used acupressure at her assigned point for 10 minutes four times a day . Data from day 4 were discarded to allow 24 hours for the treatment to take effect . Data from days 5 - 7 were used to measure treatment effect . Results : Sixty women completed the study . There were no differences between groups in attrition , parity , fetal number , maternal age , gestational age at entry , or pre-treatment nausea and emesis scores . Analysis of variance indicated that both groups improved significantly over time , but that nausea improved significantly more in the treatment group than in the sham control group ( F1,58=10.4 , P = .0021 ) . There were no differences in the severity or frequency of emesis between the groups . There was a significant positive correlation ( r=0.261 , P = .044 ) between maternal age and severity of nausea . Conclusion : Our results indicate that acupressure at the PC-6 anatomical site is effective in reducing symptoms of nausea but not frequency of vomiting in pregnant women Background Nausea and vomiting of pregnancy ( NVP ) is the most common medical condition of pregnancy , affecting up to 85 % of expecting mothers . NVP can have serious adverse effects on the quality of a woman 's life , social , and domestic functioning , and her general well-being . Therefore , it is very important to treat this condition . Objectives The effectiveness of ginger and acupressure in the treatment of NVP was compared in the present study . Patients and Methods 159 eligible pregnant women with symptoms of mild to moderate nausea and /or vomiting before 16 weeks gestational age participated in a 7-day clinical trial . They were divided r and omly into three groups : the acupressure , ginger , and control . Participants did not receive any intervention for three days and interventions were performed for the women in acupressure and ginger groups for four days . No intervention was performed for the control group . Data was collected by self-recorded symptoms according to the Rhodes index . Data was analyzed by ANOVA , Kruskal-Wallis , Chi-square , and Fisher exact tests for quantitative and qualitative variables . Results There were no statistical differences in the baseline demographics between the three groups . ANOVA test showed that there were significantly differences in mean difference Rhodes index scores ( vomiting , nausea , retching and total score ) in the three groups ( P < 0.001 ) . Conclusions Ginger is more effective than acupressure to relieve mild to moderate nausea and vomiting in symptomatic pregnant women in less than 16 weeks of gestational age Background Nausea and vomiting in pregnancy is a common complaint of nearly 50 - 80 % of pregnant women . The problem begins around the 4th weeks of pregnancy and often stays up to the 12th weeks and may continue to the 16th week in a few patients . Objectives The aim of our study is to determine the effect of acupressure ( on KID21 point ) on nausea and vomiting of pregnancy . Material s and Methods This single blind clinical trial study was performed on 80 women with nausea and vomiting in the first trimester of pregnancy . Women were r and omly divided to two groups ; study group with the acupressure on KID21 point and the placebo group with pressure on sham acupressure for 20 minutes per day in four consecutive days . The intensity of nausea was assessed by visual Analogue scale ( VAS ) and vomiting frequency was evaluated by counting during these four days . Then the results compared with each other . Results The intensity of nausea and vomiting between two groups on the fourth day was shown differences ( P<0.001 ) . Conclusions Acupressure on KID21 point is more effective than sham acupressure in reduction of nausea and vomiting in pregnancy BACKGROUND Nausea and vomiting in early pregnancy are troublesome symptoms for some women . We undertook a single blind r and omized controlled trial to determine whether acupuncture reduced nausea , dry retching , and vomiting , and improved the health status of women in pregnancy . METHODS The trial was undertaken at a maternity teaching hospital in Adelaide , Australia , where 593 women less than 14 weeks ' pregnant with symptoms of nausea or vomiting were r and omized into 4 groups : traditional acupuncture , pericardium 6 ( p6 ) acupuncture , sham acupuncture , or no acupuncture ( control ) . Treatment was administered weekly for 4 weeks . The primary outcomes were nausea , dry retching , vomiting , and health status . Comparisons were made between groups over 4 consecutive weeks . RESULTS Women receiving traditional acupuncture reported less nausea ( p < 0.01 ) throughout the trial and less dry retching ( p < 0.01 ) from the second week compared with women in the no acupuncture control group . Women who received p6 acupuncture ( p < 0.05 ) reported less nausea from the second week of the trial , and less dry retching ( p < 0.001 ) from the third week compared with women in the no acupuncture control group . Women in the sham acupuncture group ( p < 0.01 ) reported less nausea and dry retching ( p < 0.001 ) from the third week compared with women in the no acupuncture group . No differences in vomiting were found among the groups at any time . CONCLUSION Acupuncture is an effective treatment for women who experience nausea and dry retching in early pregnancy . A time-related placebo effect was found for some women Objective To compare acupuncture with sham ( placebo ) acupuncture for treatment of nausea of pregnancy . Methods In a subject- and observer-masked , r and omized , controlled trial in the maternity unit at Exeter Hospital , we gave 55 women between 6 and 10 weeks ' gestation genuine , traditional-style acupuncture or sham treatment with a cocktail stick on three or four occasions over 3 weeks . The main outcome measure was nausea score , as determined by subject report on a visual analogue scale in a daily diary . Anxiety and depression also were assessed . Results Nausea scores decreased from a median of 85.5 ( interquartile range 71.25–89.75 ) to 47.5 ( interquartile range 29.25–69.5 ) in the acupuncture group and from 87.0 ( interquartile range 73.0–90.0 ) to 48.0 ( interquartile range 14.0–80.0 ) in the sham treatment group . There was strong evidence of a time effect ( P < .001 ) but no evidence of a group effect ( P = .9 ) or a group-time interaction ( P = .8 ) . Similarly , there was evidence of time effects in scores for anxiety and depression but no group differences . The study had a power of 95 % to detect significant differences in nausea scores . Conclusion Acupuncture was as effective in treating nausea of pregnancy as a sham procedure OBJECTIVE To find out whether acupressure wristb and can alleviate nausea and vomiting in early pregnancy . DESIGN Double-blind , placebo-controlled study . SUBJECTS 97 women with mean gestational length completed 8 - 12 weeks . MAIN OUTCOME MEASURES Symptoms were recorded according to intensity , duration and nature of complaints . RESULTS 71 % of women in the intervention group reported both less intensive morning sickness and reduced duration of symptoms . The same tendency was seen in the placebo group , with 59 % reporting less intensity and 63 % shorter duration of symptoms . However , a significance level of 5 % was reached only in the case of duration of symptoms , which was reduced by 2.74 hours in the intervention group compared to 0.85 hours in the placebo group ( p = 0.018 ) . CONCLUSIONS Acupressure wristb and might be an alternative therapy for morning sickness in early pregnancy , especially before pharmaceutical treatment is considered OBJECTIVE To evaluate the effectiveness of auricular acupressure in the treatment of nausea and vomiting in early pregnancy . MATERIAL AND METHOD Ninety-eight volunteer pregnant women with symptoms of nausea and vomiting in early pregnancy before 14 weeks gestation were enrolled . The participants were r and omized into two groups : treatment group and control group . Each patient in the treatment group received magnet pellets , placed at both auricles . They were taught to start acupressure from the third to the sixth day . Outcome measurement was Rhodes index score , which describe the severity and frequency of nausea and vomiting in the form of a question naire . The patients from both groups were asked to complete and return the forms including the amount of anti-emetic drug taken . Mean Rhodes index score and total number of anti-emetic drug taken from day 4 - 6 were used to compare the treatment effect . Student 's t test , Chi-square test and Mann-Whitney U test were used for statistical analysis . RESULTS Ninety-one pregnant women who returned the question naires were evaluated . The Rhodes index scores of the treatment group were lower than that of the control group especially after day 4 to day 6 when the acupressure was started . However when comparing the mean score between the two groups , there were no statistically significant differences ( p > 0.05 ) . The total amount of anti-emetic tablets in day 4 - 6 after acupressure intervention was compared and there were no statistically significant differences ( p > 0.05 ) between the groups . CONCLUSION Auricular acupressure therapy in treatment of nausea and vomiting in early pregnancy may not relieve nausea and vomiting in early pregnancy and need further clinical research to confirm the effectiveness OBJECTIVE To compare the antiemetic effect of acupressure at the Neiguan point ( P6 ) in a group of healthy women with normal pregnancy and nausea and vomiting during pregnancy ( NVP ) with a similar group receiving acupressure at a placebo point and another , similar group not receiving any treatment . STUDY DESIGN A r and omized , placebo-controlled , pilot study involving 60 women . RESULTS It is possible to reduce NVP significantly with acupressure at P6 as compared to acupressure at a placebo point or no treatment at all in healthy women with normal pregnancies . Relief from nausea appeared one day after starting treatment in both the P6 and placebo groups but lasted for only six days in the placebo group . The P6 group , however , experienced significantly less nausea after 14 days as compared to the other two groups . CONCLUSION This study involved 60 healthy women with normal pregnancy and suffering from NVP . According to the results , in healthy women with normal pregnancy it is possible to reduce NVP significantly at P6 as compared to acupressure at a placebo point and to no treatment OBJECTIVE To determine the effect of continuous acupressure at P6 applied by Sea-B and s with acupressure buttons on the frequency and severity of nausea and vomiting of pregnancy during the 1 st trimester . DESIGN A two-group , quasi-experimental , posttest-only and posttest-repeated measure . SETTING Seventeen medical clinics or offices in southern Michigan . PARTICIPANTS Convenience sample of English-speaking , healthy pregnant women in their 1 st trimester , who had at least one episode of Output:	Conclusions Although there is some evidence for an effect of acustimulation on nausea and vomiting or hyperemesis in pregnancy , results are not conclusive .
MS21065	*TASK* the task is to summarize an input biomedical literature in six sentences *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 — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies Abstract Hypoxia is an important modulator of endurance exercise‐induced oxidative adaptations in skeletal muscle . However , whether hypoxia affects resistance exercise‐induced muscle adaptations remains unknown . Here , we determined the effect of resistance exercise training under systemic hypoxia on muscular adaptations known to occur following both resistance and endurance exercise training , including muscle cross‐sectional area ( CSA ) , one‐repetition maximum ( 1RM ) , muscular endurance , and makers of mitochondrial biogenesis and angiogenesis , such as peroxisome proliferator‐activated receptor‐γ coactivator‐1α ( PGC‐1α ) , citrate synthase ( CS ) activity , nitric oxide synthase ( NOS ) , vascular endothelial growth factor ( VEGF ) , hypoxia‐inducible factor‐1 ( HIF‐1 ) , and capillary‐to‐fiber ratio . Sixteen healthy male subjects were r and omly assigned to either a normoxic resistance training group ( NRT , n = 7 ) or a hypoxic ( 14.4 % oxygen ) resistance training group ( HRT , n = 9 ) and performed 8 weeks of resistance training . Blood and muscle biopsy sample s were obtained before and after training . After training muscle CSA of the femoral region , 1RM for bench‐press and leg‐press , muscular endurance , and skeletal muscle VEGF protein levels significantly increased in both groups . The increase in muscular endurance was significantly higher in the HRT group . Plasma VEGF concentration and skeletal muscle capillary‐to‐fiber ratio were significantly higher in the HRT group than the NRT group following training . Our results suggest that , in addition to increases in muscle size and strength , HRT may also lead to increased muscular endurance and the promotion of angiogenesis in skeletal muscle We hypothesized that specific muscular transcript level adaptations participate in the improvement of endurance performances following intermittent hypoxia training in endurance-trained subjects . Fifteen male high-level , long-distance runners integrated a modified living low-training high program comprising two weekly controlled training sessions performed at the second ventilatory threshold for 6 wk into their normal training schedule . The athletes were r and omly assigned to either a normoxic ( Nor ) ( inspired O2 fraction = 20.9 % , n = 6 ) or a hypoxic group exercising under normobaric hypoxia ( Hyp ) ( inspired O2 fraction = 14.5 % , n = 9 ) . Oxygen uptake and speed at second ventilatory threshold , maximal oxygen uptake ( VO2 max ) , and time to exhaustion ( Tlim ) at constant load at VO2 max velocity in normoxia and muscular levels of selected mRNAs in biopsies were determined before and after training . VO2 max ( + 5 % ) and Tlim ( + 35 % ) increased specifically in the Hyp group . At the molecular level , mRNA concentrations of the hypoxia-inducible factor 1alpha ( + 104 % ) , glucose transporter-4 ( + 32 % ) , phosphofructokinase ( + 32 % ) , peroxisome proliferator-activated receptor gamma coactivator 1alpha ( + 60 % ) , citrate synthase ( + 28 % ) , cytochrome oxidase 1 ( + 74 % ) and 4 ( + 36 % ) , carbonic anhydrase-3 ( + 74 % ) , and manganese superoxide dismutase ( + 44 % ) were significantly augmented in muscle after exercise training in Hyp only . Significant correlations were noted between muscular mRNA levels of monocarboxylate transporter-1 , carbonic anhydrase-3 , glucose transporter-4 , and Tlim only in the group of athletes who trained in hypoxia ( P < 0.05 ) . Accordingly , the addition of short hypoxic stress to the regular endurance training protocol induces transcriptional adaptations in skeletal muscle of athletic subjects . Expressional adaptations involving redox regulation and glucose uptake are being recognized as a potential molecular pathway , result ing in improved endurance performance in hypoxia-trained subjects Twenty healthy high-altitude natives , residents of La Paz , Bolivia ( 3,600 m ) , participated in 6 wk of endurance exercise training on bicycle ergometers , 5 times/wk , 30 min/session , as previously described in normoxia-trained sea-level natives ( H. Hoppeler , H. Howald , K. E. Conley , S. L. Lindstedt , H. Claassen , P. Vock , and E. R. Weibel . J. Appl . Physiol . 59 : 320 - 327 , 1985 ) . A first group of 10 subjects was trained in chronic hypoxia ( HT ; barometric pressure = 500 mmHg ; inspired O2 fraction = 0.209 ) ; a second group of 10 subjects was trained in acute normoxia ( NT ; barometric pressure = 500 mmHg ; inspired O2 fraction = 0.314 ) . The workloads were adjusted to approximately 70 % of peak O2 consumption ( VO2peak ) measured either in hypoxia for the HT group or in normoxia for the NT group . VO2peak determination and biopsies of the vastus lateralis muscle were taken before and after the training program . VO2peak in the HT group was increased ( 14 % ) in a way similar to that in NT sea-level natives with the same protocol . Moreover , VO2peak in the NT group was not further increased by additional O2 delivery during the training session . HT or NT induced similar increases in muscle capillary-to-fiber ratio ( 26 % ) and capillary density ( 19 % ) as well as in the volume density of total mitochondria and citrate synthase activity ( 45 % ) . It is concluded that high-altitude natives have a reduced capillarity and muscle tissue oxidative capacity ; however , their training response is similar to that of sea-level residents , independent of whether training is carried out in hypobaric hypoxia or hypobaric normoxia BACKGROUND Exercise training improves physical fitness , insulin resistance , and endothelial function in type 2 diabetes . Hypoxia may further optimize these beneficial effects . The aim of this study was to compare the effects of hypoxic versus normoxic exercise training on physical fitness , endothelial function , and insulin resistance in type 2 diabetes . METHODS Peak oxygen consumption , flow mediated dilation ( endothelial function ) , and glucose homeostasis were assessed in 19 patients ( 55±7 years ) before and after an 8-week intervention . Subjects were r and omly allocated to normoxic ( 21 % O2 , n=9 ) or hypoxic ( 16.5 % O2 , n=10 ) exercise training . Endothelium-independent dilation was examined using sublingual administration of glyceryl trinitrate , and used to calculate the ratio between endothelium-dependent and -independent dilation . RESULTS Exercise training improved physical fitness and brachial artery ratio between endothelium-dependent and -independent dilation ( both p<0.05 ) , whilst these exercise training-induced changes were similar in both groups ( interaction-effects p>0.05 ) . Exercise training did not significantly change brachial artery flow-mediated dilation or glyceryl trinitrate-response , superficial femoral artery flow-mediated dilation , or glucose homeostasis , whilst hypoxia did not alter the impact of exercise training . CONCLUSION Contrary to our hypothesis , hypoxia does not potentiate the effect of exercise training on physical fitness , vascular function , or glucose homeostasis in type 2 diabetes This study was performed to explore changes in gene expression as a consequence of exercise training at two levels of intensity under normoxic and normobaric hypoxic conditions ( corresponding to an altitude of 3,850 m ) . Four groups of human subjects trained five times a week for a total of 6 wk on a bicycle ergometer . Muscle biopsies were taken , and performance tests were carried out before and after the training period . Similar increases in maximal O(2 ) uptake ( 8.3 - 13.1 % ) and maximal power output ( 11.4 - 20.8 % ) were found in all groups . RT-PCR revealed elevated mRNA concentrations of the alpha-subunit of hypoxia-inducible factor 1 ( HIF-1 ) after both high- ( + 82.4 % ) and low (+78.4%)-intensity training under hypoxic conditions . The mRNA of HIF-1alpha(736 ) , a splice variant of HIF-1alpha newly detected in human skeletal muscle , was shown to be changed in a similar pattern as HIF-1alpha . Increased mRNA contents of myoglobin ( + 72.2 % ) and vascular endothelial growth factor ( + 52.4 % ) were evoked only after high-intensity training in hypoxia . Augmented mRNA levels of oxidative enzymes , phosphofructokinase , and heat shock protein 70 were found after high-intensity training under both hypoxic and normoxic conditions . Our findings suggest that HIF-1 is specifically involved in the regulation of muscle adaptations after hypoxia training . Fine-tuning of the training response is recognized at the molecular level , and with less sensitivity also at the structural level , but not at global functional responses like maximal O(2 ) uptake or maximal power output Background and Objectives Increased central arterial stiffness is an emerging risk factor for cardiovascular disease . Acute aerobic exercise reduces arterial stiffness , while acute resistance exercise may increase arterial stiffness , but this is not a universal finding . We tested whether an acute resistance exercise program was associated with an increase in arterial stiffness in healthy young men . Subjects and Methods Thirteen healthy subjects were studied under parallel experimental conditions on 2 separate days . The order of experiments was r and omized between resistance exercise ( 8 resistance exercises at 60 % of 1 repeated maximal ) and sham control ( seated rest in the exercise room ) . Carotid-femoral pulse wave velocity ( PWV ) and aortic augmentation index as indices of aortic stiffness were measured using applanation tonometry . Measurements were made at baseline before treatments , 20 minutes , and 40 minutes after treatments ( resistance exercise and sham control ) . Results There was no difference in resting heart rate or in arterial stiffness between the two experimental conditions at baseline . At 20 minutes after resistance exercise , heart rate , carotid-femoral PWV and augmentation index@75(% ) were significantly increased in the resistance exercise group compared with the sham control ( p<0.05 ) . Brachial blood pressure , central blood pressure and pulse pressure were not significantly increased after resistance exercise . Conclusion An acute resistance exercise program can increase arterial stiffness in young healthy men . Further studies are needed to clarify the effects of long-term resistance training on arterial stiffness Background Intermittent normobaric hypoxia training , an alternative to altitude training for athletes , may be beneficial to treat overweight and obesity . The purpose of this study is to investigate whether normobaric hypoxia training combined with low-caloric diet has the additive effect on weight loss compared with normoxia training in obese young adults . Methods Twenty-two subjects ( age 17–2 Output:	Conclusion Based on current published studies , hypoxic ExT potentiates vascular adaptations related to skeletal muscle capillarization and dilator function . These findings may contribute to establishing effective exercise programs design ed to enhance vascular health
MS21066	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Seven hundred fifty-nine of 926 women in abnormal labor ( 82 % ) were entered into an open r and omized trial to compare the effects of oxytocin and saline . Patients were classified as having either primary dysfunctional labor or secondary arrest of cervical dilatation . The end points chosen were an increase in the rate of cervical dilatation or a change in cervical dilatation . Patients who failed to respond to the initial solution were crossed over to the other solution . Oxytocin was significantly superior to saline in treating both labor abnormalities . Administration of oxytocin did not increase the need for cesarean delivery for fetal distress OBJECTIVE To estimate the effect of epidural analgesia on the Friedman labor curve . METHODS This study was a secondary analysis of a previously reported r and omized trial of the effects of patient‐controlled epidural analgesia during labor compared with patient‐controlled meperidine on cesarean delivery rate . All subjects had a singleton , cephalic , nonanomalous fetus at or beyond 37 weeks ' gestation . This secondary analysis was limited to women who had cervical dilatation commencing of at least 3 cm ( ie , active phase of labor ) . RESULTS A total of 459 women were r and omized . Twenty‐five women were excluded for a cervix less than 3 cm dilated , leaving 220 women allocated to patient‐controlled epidural analgesia and 214 to patient‐controlled intravenous meperidine available for analysis . There were no significant demographic differences between the two groups , including age , race , gestational age , and cervix on admission . The active phase of labor was 1 hour longer in the epidural‐treated group ( 6.0 ± 3.2 hours versus 5.0 ± 3.2 hours , P < .001 ) . The rate of cervical dilation was significantly less with epidural analgesia ( 1.4 cm/h versus 1.6 cm/h , P < .002 ) . The duration of the second stage tended to be longer in the epidural group ( 1.1 ± 1.5 hours versus 0.9 ± 1.0 hours , P = .079 ) . CONCLUSION Epidural analgesia prolonged the active phase of labor by 1 hour compared with Friedman 's original criteria The authors have carried out a r and om study on 75 cases in order to evaluate objective ly the therapeutic methods usually employed in cases of dystocia in starting labour . These studies have shown the superiority of Syntocinon using an infusion together with epidural analgesia . This attitude goes against the methods of treatment usually used in France . The authors explain the reasons for their choice in the light of factors that they have observed using other therapeutic methods OBJECTIVE To determine whether cervical dilatation at the time of placement of patient-requested epidural affects cesarean rates or lengths of labors in actively managed parturients . METHODS The charts of 255 women r and omized to active management of labor ( n = 125 ) or control protocol s ( n = 130 ) were review ed and stratified to early epidural placement ( up to 4 cm cervical dilatation ) versus late placement ( more than 4 cm ) . RESULTS Women with early epidural placement had shorter labors than those with late placement ( 11.6 + /- 4.6 versus 13.2 + /- 5.6 hours ; P = .02 ) . Active management reduced the length of labor compared with controls regardless of epidural timing , with a reduction of 1.4 hours in early epidural placement ( 10.9 + /- 4.7 versus 12.3 + /- 4.3 hours ; P = .04 ) and 3.6 hours in those with later placement ( 11.0 + /- 3.6 versus 14.6 + /- 6.2 hours ; P = .004 ) . Cesarean rates did not vary significantly ( early 14.5 % versus late 7.9 % ; P = .21 ) . Early epidural placement did not lengthen the second stage of labor or increase operative vaginal delivery rates . CONCLUSION Early epidural placement did not affect lengths of labor or cesarean rates and was actually associated with shorter labor compared with late epidural placement . Women managed actively in labor , regardless of timing of epidural placement , had shorter labors than controls BACKGROUND Active management of labor reduces the length of labor and rate of prolonged labor , but its effect on satisfaction with care , within a r and omized controlled trial , has not previously been reported . The study objectives were to establish if a policy of active management of labor affected any aspect of maternal satisfaction , and to determine the independent explanatory variables for satisfaction with labor care in a low-risk nulliparous obstetric population . METHODS Nulliparous women at National Women 's Hospital in Auckl and , New Zeal and , in spontaneous labor at term with singleton pregnancy , cephalic presentation , and without fetal distress were r and omized after the onset of labor to active management ( n = 320 ) or routine care ( n = 331 ) . Active management included early amniotomy , two-hourly vaginal assessment s , and early use of high dose oxytocin for slow progress in labor . Routine care was not prespecified . Maternal satisfaction with labor care was assessed by postal question naire at 6 weeks postpartum . Sensitivity analyses were performed , and logistic regression models were developed to determine independent explanatory variables for satisfaction . RESULTS Of the 651 women r and omized in the trial , 482 ( 74 % ) returned the question naires . Satisfaction with labor care was high ( 77 % ) and did not significantly differ by treatment group . This finding was stable when sensitivity analysis was performed . The first logistic regression model found independent associations between satisfaction and adequate pain relief , one-to-one midwifery care , adequate information and explanations by staff , accurate expectation of length of labor , not having a postpartum hemorrhage , and fewer than three vaginal examinations during labor . The second model found fewer than three vaginal examinations and one-to-one midwifery care as significant explanatory variables for satisfaction with labor care . CONCLUSIONS Active management did not adversely affect women 's satisfaction with labor and delivery care in this trial . Future studies should concentrate on measurement of potential predictors before and during labor To establish the spontaneous miscarriage rate and compare it with the procedure related miscarriage rate for amniocentesis and chorionic villus sampling ( CVS ) by experienced operators OBJECTIVE To compare the costs of a protocol of active management of labor with those of traditional labor management . DESIGN Cost analysis of a r and omized controlled trial . METHODS From August 1992 to April 1996 , we r and omly allocated 405 women whose infants were delivered at the University of New Mexico Health Sciences Center , Albuquerque , to an active management of labor protocol that had substantially reduced the duration of labor or a control protocol . We calculated the average cost for each delivery , using both actual costs and charges . RESULTS The average cost for women assigned to the active management protocol was $ 2,480.79 compared with an average cost of $ 2,528.61 for women in the control group ( P = 0.55 ) . For women whose infant was delivered by cesarean section , the average cost was $ 4,771.54 for active management of labor and $ 4,468.89 for the control protocol ( P = 0.16 ) . Spontaneous vaginal deliveries cost an average of $ 27.00 more for actively managed patients compared with the cost for the control protocol . CONCLUSIONS The reduced duration of labor by active management did not translate into significant cost savings . Overall , an average cost saving of only $ 47.91 , or 2 % , was achieved for labors that were actively managed . This reduction in cost was due to a decrease in the rate of cesarean sections in women whose labor was actively managed and not to a decreased duration of labor Background Rates of caesarean section are progressively increasing in many parts of the world . As a result of psychosocial factors there has been an increasing tendency for pregnant women without justifiable medical indications for caesarean section to ask for this procedure in China . A critical examination of this issue in relation to maternal outcomes is important . At present there are no clinical trials to help assess the risks and benefits of caesarean section in low risk women . To fill the gap left by trials , this indication-matched cohort study was carried out to examine prospect ively the outcomes of caesarean section on women with no absolute obstetric indication compared with similar women who had vaginal delivery . Methods An indication-matched cohort study was undertaken to compare maternal outcomes following caesarean section with those undergoing vaginal delivery , in which the two groups were matched for non-absolute indications . 301 nulliparous women with caesarean section were matched successfully with 301 women who delivered vaginally in the Maternal and Children 's Hospitals ( MCHs ) in Shanghai , China . Logistic regression model or binomial regression model was used to estimate the relative risk ( RR ) directly . Adjusted RRs were calculated adjusting for propensity score and medical indications . Results The incidence of total complications was 2.2 times higher in the caesarean section group during hospitalization post-partum , compared with the vaginal delivery group ( RR = 2.2 ; 95 % CI : 1.1 - 4.4 ) . The risk of haemorrhage from the start of labour until 2 hours post-partum was significantly higher in the caesarean group ( RR = 5.6 ; 95 % CI : 1.2 - 26.9 ) . The risk of chronic abdominal pain was significantly higher for the caesarean section group ( RR = 3.6 ; 95 % CI : 1.2 - 10.9 ) than for the vaginal delivery group within 12 months post-partum . The two groups had similar incidences of anaemia and complicating infections such as wound complications or urinary tract infection . Conclusions In nulliparous women who were at low risk , caesarean section was associated with a higher rate of post-partum morbidity . Those requesting the surgical procedure with no conventional medical indication , should be advised of the potential risks OBJECTIVE Our purpose was to determine the effect of epidural analgesia on nulliparous labor and delivery . STUDY DESIGN Normal term nulliparous women in early spontaneous labor were r and omized to receive either narcotic or epidural analgesia . RESULTS When compared with the group receiving narcotic analgesia ( n = 45 ) , the group receiving epidural analgesia ( n = 48 ) had a significant prolongation in the first and second stages of labor , an increased requirement for oxytocin augmentation , and a significant slowing in the rate of cervical dilatation . Epidural analgesia was associated with a significant increase in malposition ( 4.4 % vs 18.8 % , p < 0.05 ) . Cesarean delivery occurred more frequently in the epidural group ( 2.2 % vs 25 % , p < 0.05 ) , primarily related to an increase in cesarean section for dystocia ( 2.2 % vs 16.7 % , p < 0.05 ) . CONCLUSIONS In a r and omized , controlled , prospect i ve trial epidural analgesia result ed in a significant prolongation in the first and second stages of labor and a significant increase in the frequency of cesarean delivery , primarily related to dystocia Objective . To show that early discontinuation of oxytocin will not increase the mean duration of the active labor phase in a clinical ly significant way . Design . Controlled non‐inferiority study . Setting . Department of Obstetrics and Gynecology , University of Caen , Clémenceau Hospital , France . Population . A total of 138 women with singleton pregnancy and a vertex presentation of over 34 gestational weeks , presenting a medical indication of induction of labor or a dystocia at onset of labor , from May 2005 to June 2006 . Methods . Two parallel groups were compared : continuation of oxytocin until delivery versus discontinuation of oxytocin at the onset of the active phase . The clinical ly acceptable increase in mean duration of the active phase of labor ( non‐inferiority margin ) was set at 60 minutes . Main outcome measures . Primary outcome measure was duration of the active labor phase . Secondary outcome measures included total duration of labor , parameters concerning oxytocin use , rates of uterine hyperstimulation and fetal heart rate ( FHR ) abnormalities , and mode of delivery . Some neonatal outcomes were also analyzed . Results . Equivalence of the two strategies ( continuation vs. discontinuation of oxytocin ) was not demonstrated ( p = 0.97 testing for non‐inferiority ) , the active phase even being significantly longer by a mean of 113 minutes ( p = 0.0001 testing for superiority ) . The rates of cesarean sections , alterations of FHR and delivery hemorrhage were higher when oxytocin was continued , but not significantly . There were significantly more infants hospitalized in neonatology when oxytocin was continued ( p = 0.028 ) . Conclusions . Discontinuation of oxytocin at the onset of the active phase prolongs labor . We found no argument for discontinuing the infusion of oxytocin at the onset of the active phase Background Oxytocin is widely used to speed up slow labour , especially in nulliparous women , but r and omised trials , apart from one reported only in abstract , have been too small to exclude important effects OBJECTIVE Our goal was to evaluate whether active management of labor lowers cesarean section rates , shortens the length of labor , and overcomes any negative effects of epidural analgesia on nulliparous labor . STUDY DESIGN We r and omly assigned 405 low-risk term nulliparous patients to either an active management of labor ( n = 200 ) or our usual care control protocol ( n = 205 ) Output:	There was no statistically significant difference identified between women in spontaneous labour with epidural analgesia who were augmented with oxytocin , compared with those who received placebo .
MS21067	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Acute exacerbations of chronic obstructive pulmonary disease ( AE COPD ) impair health-related quality of life ( HRQL ) . We evaluated the effect of an abbreviated repeat pulmonary rehabilitation ( PR ) program on HRQL after an AE COPD . METHODS Patients who had completed PR were followed for up to 12 months to identify an AE COPD and then placed in r and omized groups to receive a 3-week repeat-PR intervention or usual care . Measures of HRQL ( Chronic Respiratory Disease Question naire , CRQ ) and functional exercise capacity ( 6-minute walk distance , 6MWD ) were collected at 2 ( T1 ) , 5 ( T2 ) , and 12 weeks ( T3 ) post-AE COPD . The repeat-PR program was undertaken between T1 and T2 . Between-group differences were examined using repeated- measures analysis of variance or covariance . RESULTS Of the 60 patients ( 30 men , age 69±8 years , forced expiratory volume in 1 second 0.86±0.40 L , 6MWD 367±99 m ) followed , 41 experienced an AE COPD 14 ± 11 weeks after completion of the initial PR program and 33 completed the study . Of these , 16 and 17 were r and omized to the intervention and control groups , respectively . No between-group differences were demonstrated at T2 or T3 . With the exclusion of 5 subjects who experienced a second AE COPD between T1 and T3 , the participants in the intervention group demonstrated greater reduction in dyspnea when compared to those in the control group at T3 ( 0.8±1.6 vs −0.4±1.3 points per item , P = .04 ) . CONCLUSIONS The reduction in dyspnea in those who did not experience a second AE COPD provides preliminary evidence for the role of repeat programs . The application of repeat PR should be refined in larger trials A prospect i ve , r and omized and controlled study has been performed in 28 patients with severe COPD . A group of 14 has been trained with their lower limbs ( LL ) , while another similar group of 14 patients was also trained with their upper limbs ( UL ) . Results showed improvement in both groups in the endurance test for LL , dyspnea scale , efficiency and muscular working capacity . A considerable improvement was observed in the oxygen uptake at the anerobic threshold ( VO2AT ) which suggests a training effect , expressed through an improvement in exercise tolerance . Only the group who trained UL showed a remarkable improvement in the dyspnea scale , endurance test and maximal static mouth pressure , showing a better intrinsic working capacity and participation of the UL muscles producing those manoeuvres . At the end of training , quality of life was significantly increased and the hospitalization rate was lower in both groups . According to these findings , it is suggested that patients with severe COPD included in training programmes add UL exercises to the LL usually carried out Background : The evidence of benefit for pulmonary rehabilitation ( PR ) programmes is established . However , the optimal duration of a PR programme is not known . A r and omised controlled trial was undertaken in patients with chronic obstructive pulmonary disease ( COPD ) to assess whether a 4 week PR programme was equivalent to our conventional 7 week PR programme at equivalent time points of 7 weeks and 6 months . Methods : One hundred patients ( 56 men ) with stable COPD of mean ( SD ) age 70 ( 8) years and forced expiratory volume in 1 second ( FEV1 ) 1.13 ( 0.50 ) litres were r and omised to either a 7 week ( n = 50 ) or 4 week ( n = 50 ) supervised PR programme . Patients were assessed at baseline , at completion of the supervised PR programme , and 6 months later . Patients r and omised to the 4 week group were also assessed at the 7 week time point . Outcome measures were the Incremental Shuttle Walk Test , Endurance Shuttle Walk Test ( ESWT ) , Chronic Respiratory Question naire-Self Reported , and the Breathing Problems Question naire . Results : Forty one patients in each group completed the PR programme . Patients made significant within group improvements after supervised rehabilitation . There were no statistically significant differences between the groups for any other measure at the 7 week or 6 month time points , except that patients in the 4 week group attained higher ESWT times ( mean difference 124 seconds ( 95 % CI 17.00 to 232.16 ) , p = 0.024 ) at the 7 week time point . Conclusions : A shortened 4 week supervised PR programme is equivalent to a 7 week supervised PR programme at the comparable time points of 7 weeks and 6 months OBJECTIVES To compare the effectiveness of a once-weekly supervised pulmonary rehabilitation programme with a st and ard twice-weekly format . DESIGN R and omised trial of equivalency . SETTING Pulmonary rehabilitation service of a primary care trust delivered at two physiotherapy outpatient departments . PARTICIPANTS Thirty patients with chronic obstructive pulmonary disease . OUTCOME MEASURES Primary outcomes were the Incremental Shuttle Walking Test ( ISWT ) , Endurance Shuttle Walking Test ( ESWT ) and St George 's Respiratory Question naire ( SGRQ ) , assessed at baseline and at completion of the supervised programme . Secondary outcomes were home-exercise activity , attendance levels and patient satisfaction with the programme . INTERVENTIONS The once-weekly group ( n=15 ) received one supervised rehabilitation session per week , and the twice-weekly group ( n=15 ) received two sessions per week , both for 8 weeks , together with a home-exercise plan . RESULTS After pulmonary rehabilitation , the groups showed similar improvements in exercise tolerance ( median values : ISWT once-weekly 60metres , twice-weekly 50metres ; ESWT once-weekly 226seconds , twice-weekly 109seconds ) . However , for health-related quality -of-life , the once-weekly group 's score did not change ( SGRQ 0 ) , whereas an improvement was seen for the twice-weekly group ( SGRQ 3.7 ) . The number of home-exercise sessions and attendance levels were similar between the groups . Patient satisfaction with both formats was high and almost identical between the groups . CONCLUSIONS This pilot provides data to inform a larger study and shows that the methodology is feasible . The findings suggest that once-weekly supervision may be capable of producing equivalent improvements in exercise tolerance as a twice-weekly programme , but the health-related quality -of-life outcome appeared to be poorer for once-weekly supervision Limited information is available regarding the physiological responses to different types of exercise training in patients with severe chronic obstructive pulmonary disease ( COPD ) . The aim of this study was two fold : firstly , to investigate the physiological response to training at 60 % of achieved peak load in patients with severe COPD ; and secondly to study the effects of interval ( I ) versus continuous ( C ) training in these patients . Twenty-one patients with COPD ( mean+/-SD forced expiratory volume in one second : 37+/-15 % of predicted , normoxaemic at rest ) were evaluated at baseline and after 8 weeks ' training . Patients were r and omly allocated to either I or C training . The training was performed on a cycle ergometer , 5 days a week , 30 min daily . The total work load was the same for both training programmes . C training result ed in a significant increase in oxygen consumption ( V'O2 ) ( 17 % , p<0.05 ) and a decrease in minute ventilation (V'E)/V'O2 ( p<0.01 ) and V'E/carbon dioxide production ( V'CO2 ) ( p<0.05 ) at peak exercise capacity , while no changes in these measures were observed after interval training . During submaximal exercise a significant decrease was observed in lactic acid production , being most pronounced in the C-trained group ( -31 % , p<0.01 versus -20 % , p<0.05 ) . Only in the I-trained group did a significant increase in peak work load ( 17 % , p<0.05 ) and a decrease in leg pain ( p<0.05 ) occur . Training did not result in a significant improvement in lung function , but maximal inspiratory mouth pressure increased in both groups by 10 % ( C : p<0.05 ) and 23 % ( I : p<0.01 ) . The present study shows a different physiological response pattern to interval or continuous training in chronic obstruction pulmonary disease , which might be a reflection of specific training effects in either oxidative or glycolytic muscle metabolic pathways . Further work is required to determine the role of the different exercise programmes and the particular category of patients for whom this might be beneficial Fifty patients with severe chronic obstructive pulmonary disease ( FEV1 < 50 % pred . ) were r and omized to a rehabilitation group and a control group . The rehabilitation group took part in an individualized multidisciplinary , outpatient 12-month rehabilitation programme . Exercise training was intensive during the first 6 weeks and was then gradually replaced by an individual home-training programme and booster sessions . Controls received the usual outpatient care . Positive effects were found in terms of maximum symptom-limited exercise tolerance and walking distance ( 13.5 and 12.1 % increase , respectively ) in the rehabilitation group compared with the controls . Quality of life measurements showed minor beneficial effects on the Sickness Impact Profile , indicating a higher level of activity . No effect was seen on the St George 's Respiratory Question naire or the Mood Adjective Check List . Patients expressed their enthusiasm for the rehabilitation programme in a study -specific question naire The purpose of this study was to assess the effects of a particular breathing pattern training ( BPT ) on forced expiratory volume during the first second ( FEV1 ) and forced vital capacity ( FVC ) in patients with chronic obstructive pulmonary disease ( COPD ) . The subjects adjusted each breath to a target breath displayed on a video screen , by using visual feedback . This target was chosen in an individual sample recorded at rest . We used a r and omized , controlled group design . Twenty patients with stable COPD , FEV1 less than 1.5 liters , undergoing a traditional rehabilitation program were r and omly assigned to the BPT group or to the control group . Each BPT subject underwent 30–35 training sessions spread out over four weeks , in addition to the traditional program . FEV1 and FVC were performed before and after this program . ANOVAs showed that FEV1 and FVC significantly improved in BPT subjects , with a mean percent increase of 22 % and 19 % , respectively . Corresponding changes in controls were not significant . This study showed short-term increases in FEV1 and FVC in COPD patients practicing BPT in addition to respiratory rehabilitation , in comparison with controls . Further studies should incorporate outcome data to clarify the mechanisms and the duration of this effect To overcome the problem of altered breathing strategy during resistive ventilatory muscle training ( VMT ) , we used a single-orifice inspiratory resistance together with a target feedback device ( TFD ) in patients with chronic obstructive pulmonary disease ( COPD ) . In a preliminary study ( study A ) , we showed that the resistance plus TFD was effective in controlling breathing strategy . We subsequently used the resistor plus TFD in a 5-wk study ( study B ) of VMT in 17 COPD patients who were r and omized into high-intensity ( HI ) and low-intensity ( LI ) training groups . Compared with the LI group , the HI group showed significant increases in static maximal inspiratory pressure ( 21.3 vs. 5.0 cmH2O ) , maximal sustained ventilatory capacity ( MSVC , 3.2 vs -0.1 l/min , sustained maximal mouth pressure ( 12.1 vs. 0.6 cmH2O ) , mean mouth pressure ( 6.9 vs. 3.9 cmH2O ) , peak inspiratory flow rate ( 12.3 vs. 4.0 l/min ) , and maximal sustained work rate ( 12.2 vs. 4.2 cmH2O.l-1.min-1 ) . We conclude that targeted VMT with control of breathing strategy improves both ventilatory muscle strength and endurance The purpose of this study was to test the effectiveness of a taped relaxation message in reducing dyspnea and anxiety in chronic obstructive pulmonary disease ( COPD ) patients . Twenty-six adult COPD patients with dyspnea were r and omly assigned to two groups . The treatment group was taught relaxation using a prerecorded tape while the control group was instructed to sit quietly . Skin temperature , heart rate , and respiratory rate were recorded for all subjects during a total of four weekly sessions . Anxiety , dyspnea , and airway obstruction were measured at the beginning and end of the study . The relaxation group achieved the preset relaxation criteria . Dyspnea , anxiety , and airway obstruction were induced in the relaxation group while the control group remained the same or became worse Objective To evaluate an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease COPD , using St . George ’s Respiratory question naire ( SGRQ ) , the 6-minutes walking test ( 6-MWT ) and BODE index as the primary outcome measures . Methods A prospect i ve , parallel-group controlled study of an outpatient rehabilitation program in 80 patients with COPD ( 67 men and 13 women ; mean age 64.8 ± 10.6 years ; FEV1 , 42.8 % ± 7.6 % of the predicted value . The active group ( n = 40 ) took part in a 14-week rehabilitation program [ 3 h/wk , 1.5 h of education and exercise and 1.5 h of cycling ] . The control group ( n = 40 ) was review ed routinely as medical out patients . The following evaluations were Output:	A modest improvement in health-related quality of life ( HRQoL ) was identified but this was possibly biased due to high loss to follow-up . The economic model was speculative due to uncertainty in impact on readmissions . Compared with UC , post-discharge SM support ( delivered within 6 weeks of discharge ) was more costly and result ed in better outcomes ( £ 683 cost difference and 0.0831 QALY gain ) . There was little evidence of benefit of providing SM support to patients shortly after discharge from hospital , although effects observed were consistent with possible improvement in HRQoL and reduction in hospital admissions . It was not easy to tease out the most effective components of SM support packages , although interventions containing exercise seemed the most effective .
MS21068	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This study aim ed to assess the influence of different whole body vibration ( WBV ) determinants on the electromyographic ( EMG ) activity during WBV in order to identify those training conditions that cause highest neuromuscular responses and therefore provide optimal training conditions . In a r and omized cross-over study , the EMG activity of six leg muscles was analyzed in 18 subjects with respect to the following determinants : ( 1 ) vibration type ( side-alternating vibration ( SV ) vs. synchronous vibration ( SyV ) , ( 2 ) frequency ( 5–10–15–20–25–30 Hz ) , ( 3 ) knee flexion angle ( 10 ° –30 ° –60 ° ) , ( 4 ) stance condition ( forefoot vs. normal stance ) and ( 5 ) load variation ( no extra load vs. additional load equal to one-third of the body weight ) . The results are : ( 1 ) neuromuscular activity during SV was enhanced compared to SyV ( P < 0.05 ) ; ( 2 ) a progressive increase in frequency caused a progressive increase in EMG activity ( P < 0.05 ) ; ( 3 ) the EMG activity was highest for the knee extensors when the knee joint was 60 ° flexed ( P < 0.05 ) ; ( 4 ) for the plantar flexors in the forefoot stance condition ( P < 0.05 ) ; and ( 5 ) additional load caused an increase in neuromuscular activation ( P < 0.05 ) . In conclusion , large variations of the EMG activation could be observed across conditions . However , with an appropriate adjustment of specific WBV determinants , high EMG activations and therefore high activation intensities could be achieved in the selected muscles . The combination of high vibration frequencies with additional load on an SV platform led to highest EMG activities . Regarding the body position , a knee flexion of 60 ° and forefoot stance appear to be beneficial for the knee extensors and the plantar flexors , respectively BACKGROUND Low back disorders and their prevention is of great importance for companies and their employees . Whole-body vibration is thought to be a risk factor for low back disorders , but the neuromuscular , biomechanical , and /or physiological mechanisms responsible for this increased risk are unclear . The purpose of this study was to measure the acute effect of seated whole-body vibration on the postural control of the trunk during unstable seated balance . METHODS Twenty-one healthy subjects ( age : 23 years ( SD 4 years ) ) were tested on a wobble chair design ed to measure trunk postural control . Measurements of kinematic variance and non-linear stability control were based on seat angle before and after 30 min of seated whole-body vibration ( b and width=2 - 20 Hz , root-mean-squared amplitude=1.15m/s(2 ) ) . FINDINGS All measures of kinematic variance of unstable seated balance increased ( P<0.05 ) after vibration including : ellipse area ( 35.5 % ) , root-mean-squared radial lean angle ( 17.9 % ) , and path length ( 12.2 % ) . Measures of non-linear stability control also increased ( P<0.05 ) including Lyapunov exponent ( 8.78 % ) , stability diffusion analysis ( 1.95 % ) , and Hurst rescaled range analysis ( 5.2 % ) . INTERPRETATION Whole-body vibration impaired postural control of the trunk as evidence d by the increase in kinematic variance and non-linear stability control measures during unstable sitting . These findings imply an impairment in spinal stability and a mechanism by which vibration may increase low back injury risk . Future work should investigate the effects of whole-body vibration on the anatomical and neuromuscular components that contribute to spinal stability The purpose of this study was to investigate the consequences of a high-speed boat transit on physical performance . Twenty-four Royal Marines were r and omly assigned to a control ( CON ) or transit ( TRAN ) group . The CON group sat onshore for 3 h whilst the TRAN group completed a 3-h transit in open-boats running side-by-side , at 40 knots in moderate-to-rough seas , with boat deck and seat-pan acceleration recorded . Performance tests ( exhaustive shuttle-run , h and grip , vertical-jump , push-up ) were completed pre- and immediately post-transit/sit , with peak heart rate ( HRpeak ) and rating of perceived exertion ( RPE ) recorded . Serial blood sample s ( pre , 24 , 36 , 48 , 72 h ) were analyzed for creatine kinase ( CK ) activity . The transit was typified by frequent high shock impacts , but moderate mean heart rates ( < 45 % HRpeak ) . The TRAN group post-transit run distance ( −219 m , P < 0.01 ) and vertical-jump height ( 5 % , P < 0.05 ) were reduced , the CON group showed no change . The TRAN group post-transit test RPE increased ( P < 0.05 ) , however , HRpeak was similar for each group ( 98 % ) . Post-transit CK activity increased in the TRAN group up to 72 h ( P < 0.01 ) and also , but less markedly , in the CON group ( 24 and 48 h , P < 0.05 ) . Post-transit run and jump performances were reduced despite mean transit heart rates indicating low energy expenditure . The greater TRAN CK activity suggests muscle damage may have been a contributory factor . These findings have operational implication s for Special Forces/naval/police/rescue services carrying out dem and ing , high-risk physical tasks during and immediately after high-speed boat transits Underst and ing of the resonance behaviour of the human body is important in the identification of vibration frequencies and body postures associated with back problems . In this study , experimental modal analysis was applied to whole-body vibration . Eight subjects were exposed to vertical r and om vibration while adopting three different postures on a rigid seat without a backrest . Motions of the spine , pelvis and viscera in the mid-sagittal plane were derived from skin-mounted accelerometers ; head responses were measured using a bite-bar . Eight modes of vibration response were extracted below 10 Hz . A principal resonance of the human body at about 5 Hz consisted of an entire body mode , in which the skeleton moved vertically due to axial and shear deformations of buttocks tissue , in phase with a vertical visceral mode , and a bending mode of the upper thoracic and cervical spine . A bending mode of the lumbar and lower thoracic spine was found with a pitching mode of the head in the next higher mode located close to the principal mode . The second principal resonance at about 8 Hz corresponded to pitching modes of the pelvis and a second visceral mode . When subjects changed posture from erect to slouched , the natural frequency of the entire body mode decreased , result ing in a decrease in the principal resonance frequency . Shear deformation of buttocks tissue increased in the entire body mode due to the same change of posture . The complex body motions suggest that any forces causing injury from whole-body vibration will not be well-predicted by biodynamic models incapable of representing the appropriate body motions and the effects of body posture . It seems likely that the greatest risk of back problems will arise from the bending deformations of the spine STUDY DESIGN A cross-sectional study in patients with recurrent/chronic low back trouble and healthy control subjects . OBJECTIVE To evaluate the effect of paraspinal muscle fatigue on the ability to sense a change in lumbar position . SUMMARY OF BACKGROUND DATA Protection against spinal injury requires proper anticipation of events , appropriate sensation of body position , and reasonable muscular responses . Lumbar fatigue is known to delay lumbar muscle responses to sudden loads . It is not known whether the delay is because of failure in the sensation of position , output of the response , or both . METHODS Altogether , 106 subjects ( 57 patients with low back trouble [ 27 men and 30 women ] and 49 healthy control subjects [ 28 men and 21 women ] ) participated in the study . Their ability to sense a change in lumbar position while seated on a special trunk rotation unit was assessed . A motor rotated the seat with an angular velocity of 1 degree per second . The task in the test involved reacting to the perception of lumbar movement ( rotation ) by releasing a button with a finger movement . The test was performed twice , before and immediately after a fatiguing procedure . During the endurance task , the participants performed upper trunk repetitive extensions against a resistance , with a movement amplitude adjusted between 25 degrees flexion and 5 degrees extension , until exhaustion . RESULTS Patients with chronic low back trouble had significantly poorer ability than control subjects on the average to sense a change in lumbar position ( P = 0.007 ) , which was noticed before and after the fatiguing procedure . Lumbar fatigue induced significant impairment in the sensation of position change ( P < 0.000001 ) . CONCLUSIONS Lumbar fatigue impairs the ability to sense a change in lumbar position . This feature was found in patients and control subjects , but patients with low back trouble had poorer ability to sense a change in lumbar position than control subjects even when they were not fatigued . There seems to be a period after a fatiguing task during which the available information on lumbar position and its changes is inaccurate Owing to the recent interest in torso stabilization exercises together with many questions regarding the duration of prolonged isometric holds in occupational setting s , the authors attempted to assess the level of back muscle oxygenation during prolonged isometric contractions . Specifically , this study recorded relative oxygen saturation of haemoglobin/myoglobin using Near Infrared Spectroscopy ( NIRS ) in the L3 erector mass during prolonged isometric contractions at intensities from 2 to 30 % of maximum voluntary contraction ( MVC ) . It was hypothesized that available oxygen to these muscles is severely compromised even at moderate levels of activation observed in occupational work . Eight volunteers without a history of lower back pain or injury participated in this study . The exercise task involved isometric contraction of the lower erector spinae at five different levels of each subject 's maximal voluntary contraction : 2 , 5 , 10 , 20 and 30 % MVC , presented in r and om order . Subjects were placed in a sitting position , with a curved plastic plate secured horizontally to the pelvis to minimize movement at the hip joint . During extensor exertions , they were restrained with a harness that was attached at chest level to a load cell . Each isometric contraction was performed for 30 s followed by 1 min of rest . All levels of contraction demonstrated reduction in oxygen . Given the concern for motion artefact on the NIRS signal , sham trials were conducted where the subjects went through the procedure of attaching the pulling cable but no active pull was performed . These trials showed no change in the NIRS signal . At this time NIRS appears to be the only non-invasive instrumentation available to indicate total available muscle oxygen during low level , prolonged work . Although the specific tissue volume sample d by NIRS can not be positively identified , it appears that tissue oxygenation in the lumbar extensor musculature is reduced as a function of contraction intensity , even at levels as low as 2 % of MVC . These data have implication s for prolonged work where postures requiring isometric contractions are sometimes held for hours , and where musculoskeletal illness has been linked to prolonged contraction levels above 2 % MVC — these data suggest a possible biological pathway Exposure to whole-body vibration is implicated as one of the occupational risk factors for lower back disorders ; however , its influence on the lumbar muscle physiology is still poorly understood . The objective of this study was to investigate the effects of backrest support and h and grip contractions on lumbar muscle oxygenation and blood volume responses during seated whole-body vibration using continuous dual-wave near-infrared spectroscopy . Thirteen healthy men were exposed to frequencies of 3 , 4.5 and 6 Hz on a vibration simulator , in r and omized order on separate days . Each day the duration of the protocol was 30 min . During the fifth minute of vibration ' with ' and ' without ' backrest support , participants performed maximal rhythmic h and grip contractions for 1 min . In general , erector spinae oxygenation and blood volume showed a trend to decrease with vibration exposure compared to the control condition . However , these responses were not influenced by the change in vibration frequency ( P > 0.05 ) . Sitting without backrest result ed in a greater decrease in oxygenation ( by 27 % , P = 0.02 ) and blood volume ( by 11 % , P = 0.05 ) than with backrest , implying a deficiency in oxygen supply owing to the sitting posture . Compared to the vibration-only condition , h and grip work decreased both oxygenation ( by 22 % , P = 0.003 ) and blood volume responses ( by 13 % , P = 0.04 ) , suggesting that postural load due to prolonged sitting combined with physical activity during vibration might further burden paraspinal muscles . The influence of adipose tissue thickness of the lumbar muscle on optically derived oxygenation and blood volume changes was inconclusive An experiment is described in which two independent groups of eight subjects each performed a combined continuous and discrete tracking task during exposure to vertical whole-body vibration . Both groups received sinusoidal and r and om vibration at preferred third-octave centre frequencies of 0.5 - 10 Hz . One group performed the task with the display collimated by a convex lens . Without the collimation , performance was disrupted by both types of vibration at all vibration frequencies ; collimation removed the disruption at frequencies above 1.6 Hz . There were differences in the effects of r and om and sinusoidal vibration at 2.0 and 2.5 Hz , suggesting that compensatory eye movements were assisting performance during exposure to the predictable sinusoidal motion . The results show that continuous control performance was disrupted by visual interference at frequencies above 1.6 Hz ; closed-loop system transfer functions showed that visual interference increased the phase lags which impaired control performance . Possible mechan Output:	Discussion Given the inconsistency in the reported responses , the precise changes to human function remain unknown . However , there is sufficient evidence to warrant the design of studies which investigate occupationally relevant physical performance changes following WBV
MS21069	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Mycobacterium paratuberculosis is implicated as a possible cause of Crohn 's disease . However , due to lack of an appropriate diagnostic method , this has been a subject of significant controversy . Our aim was therefore to develop a multiplex polymerase chain reaction ( MPCR ) for the detection of M. paratuberculosis DNA in Crohn 's disease tissue . METHODS Biopsy sample s were collected by endoscopic forceps from terminal ileum , and genomic DNA was isolated . M. paratuberculosis-specific marker genes were amplified by using the present MPCR method . RESULTS Here we report a new MPCR for detection of M. paratuberculosis DNA in Crohn 's disease tissue . In this technique two genetic markers , IS900 and a newly described specific marker of MP2 , were amplified in a single tube simultaneously . The method was evaluated using biopsy specimens from 10 Crohn 's disease patients , 6 ulcerative colitis patients , and 21 irritable bowel syndrome patients . The patients were characterized by using st and ard clinical and histologic observations . The present MPCR method could not detect M. paratuberculosis DNA in the biopsy specimens . However , the marker genes were amplified from the sample s that were spiked with M. paratuberculosis before DNA extraction . The marker genes were also not detected in 10 closely related mycobacterial strains and human genomic DNA . CONCLUSIONS The present MPCR method is highly specific and can detect M. paratuberculosis DNA more reliably . These findings do not support an aetiologic role of M. paratuberculosis in Crohn 's disease BACKGROUND The etiology of Crohn 's disease remains unknown , but current research has concentrated on autoimmunity and /or mycobacterial infection . The polymerase chain reaction ( PCR ) enables the detection of genetic material even when very few microorganisms are present . METHODS A nested primer PCR for detection of a multi-copy insertional element ( IS900 ) specific for Mycobacterium paratuberculosis was applied to DNA extracted from fresh and from paraffin-embedded intestinal tissue obtained from patients undergoing surgery . RESULTS In fresh intestinal tissue from 11 of 24 patients with Crohn 's disease , from 2 of 10 patients with ulcerative colitis , and from 3 of 28 patients with other colonic disorders , specific M. paratuberculosis DNA was found . In paraffin-embedded Crohn 's disease tissue the presence of specific M. paratuberculosis DNA was also increased . CONCLUSIONS Whether the presence of M. paratuberculosis is connected to the inflammatory bowel disease or is a mere coincidence can not be stated . We find this presence interesting and encouraging for further investigations PURPOSE : Mycobacterium paratuberculosis has been proposed as a causative agent in patients with Crohn 's disease . The purpose of this study was to determine whether M. paratuberculosis was present in tissue from patients with Crohn 's disease in a defined geographic area . METHODS : We prospect ively evaluated , using polymerase chain reaction and culture , whether M. paratuberculosis was present in 44 specimens ( 37 from intestinal mucosal biopsies and 7 from surgical resections ) from patients with Crohn 's disease , ulcerative colitis , or normal colonic mucosa . RESULTS : Of the 25 specimens tested from the 21 Crohn 's patients , only 1 positive specimen was noted , whereas the 8 specimens from the 5 ulcerative colitis patients and the 11 specimens from the 11 control patients failed to demonstrate a positive result with polymerase chain reaction . Cultures of all specimens revealed no growth of M. paratuberculosis . CONCLUSION : M. paratuberculosis was only rarely detected in biopsy or surgical specimens from patients with Crohn 's disease . These results do not support a common causative role of M. paratuberculosis in Crohn 's disease BACKGROUND / AIMS In order to assess the potential impact of bacterial eradication on recurrence rates , the prevalence of various enteropathogenic bacteria and toxins in chronic inflammatory bowel diseases ( CIBD ) was prospect ively examined . METHODOLOGY Stool , sera and gut tissue sample s from a total of 59 patients ( 33 males , 26 females ; mean age : 42 years + /- 14 ; 21 Crohn 's disease , 14 ulcerative colitis , 24 controls ) were examined for the presence of enteropathogenic bacteria by culture , immunoblotting and PCR . RESULTS Conventional cultures failed to detect obligate pathogenic bacteria . By PCR , mycobacteria were found in 85 % of all groups , with mycobacterium paratuberculosis not detected . Yersinia species were observed in 63 % of patients with Crohn 's disease , in 46 % of patients with ulcerative colitis , and in 36 % of the control patients . Pathogenic E. coli were identified in stool sample s of three patients with ulcerative colitis ( 21 % ) by amplifying the EAE-gene , one of whom exhibited shiga-like-toxin as well . CONCLUSIONS We concluded that mycobacteria do not play a causative role in CIBD . Yersinia species seem to persist in intestinal tissue in CIBD patients without adequate immune response and might , thus , contribute to tissue destruction . E. coli infections contribute to the disease process in a small group of patients with ulcerative colitis and their eradication might eliminate the need for immediate surgical intervention Output:	The data confirms the observation that MAP is detected more frequently among CD patients compared with controls . However , the pathogenic role of this bacterium in the gut remains uncertain . Our analysis demonstrates that there is an association between MAP and CD , across many sites , by many investigators , and controlling for a number of factors ; however , this association remains controversial and inconclusive .
MS21070	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract The effect of altering the rest period on adaptations to high-repetition resistance training is not well known . Eighteen active females were matched according to leg strength and repeated-sprint ability and r and omly allocated to one of two groups . One group performed resistance training with 20-s rest intervals between sets , while the other group employed 80-s rest intervals between sets . Both groups performed the same total training volume and load . Each group trained 3 days a week for 5 weeks [ 15- to 20-repetition maximum ( RM ) , 2 – 5 sets ] . Repeated-sprint ability ( 5 × 6-s maximal cycle sprints ) , 3-RM leg press strength , and anthropometry were determined before and after each training programme . There was a greater improvement in repeated-sprint ability after training with 20-s rest intervals ( 12.5 % ) than after training with 80-s rest intervals ( 5.4 % ) ( P = 0.030 ) . In contrast , there were greater improvements in strength after training with 80-s rest intervals ( 45.9 % ) than after training with 20-s rest intervals ( 19.6 % ) ( P = 0.010 ) . There were no changes in anthropometry for either group following training . These results suggest that when training volume and load are matched , despite a smaller increase in strength , 5 weeks of training with short rest periods results in greater improvements in repeated-sprint ability than the same training with long rest periods The purpose of this study was to compare the ability of various body-composition assessment techniques to detect changes in soft tissue in older , weight-stable women ( 50 - 70 y of age ) completing a 1-y r and omized , controlled trial of progressive resistance training . The intervention group ( n = 20 ) performed high-intensity strength-training 2 d/wk with five different exercises ; the control group ( n = 19 ) was untreated . Hydrostatic weighing , 24-h urinary creatinine , computed tomography of thigh sections , total body potassium , and tritium dilution techniques were used to measure increases in total fat-free mass ( FFM ) and the muscle and water components of FFM . A decrease in fat mass ( by hydrostatic weighing ) was seen in the strength-trained women compared with the control subjects ( P - 0.01 - 0.0001 ) . Anthropometry , bioelectric impedance , dual-energy X-ray absorptiometry , and total body nitrogen and carbon did not measure any significant change in soft tissue . The choice of a body-composition technique is important when design ing a study expected to affect soft tissue , because not all techniques available are precise enough to detect small changes Piirainen , JM , Tanskanen , M , Nissilä J , Kaarela , J , Väärälä , A , Sippola , N , and Linnamo , V. Effects of a heart rate-based recovery period on hormonal , neuromuscular , and aerobic performance responses during 7 weeks of strength training in men . J Strength Cond Res 25(8 ) : 2265 - 2273 , 2011—The purpose of this study was to compare hormonal , neuromuscular , and aerobic performance changes between a constant 2-minute interset recovery time and an interset recovery time based on individual heart rate ( HR ) responses during a 7-week ( 3 sessions per week , 3 × 10 repetition maximum [ RM ] ) hypertrophic strength training period . The HR-dependent recovery time was determined with a Polar FT80 HR monitor , whereas the control groups used constant 2-minute periods between sets . From 24 male subjects who were divided in 2 equal groups , 21 completed the study ( FT80 , n = 12 ; CONTROL , n = 9 ) . Serum blood sample s analyzed for testosterone ( TES ) and cortisol ( COR ) were taken before and after the 7-week training period at rest . Concentric knee extension 1RM was measured before , after 4 weeks , and at the end of the training period . Concentric knee extension and knee flexion 10RM , central activation ratio ( CAR ) , and max&OV0312;o2 were measured before and after the training . Serum TES concentrations were significantly higher after the training period in FT80 ( p < 0.001 ) , whereas no significant changes were observed in the CONTROL . Serum COR and max&OV0312;o2 were unchanged in both groups . In FT80 ( p < 0.001 ) , the increase in 10RM was higher ( p < 0.05 ) than in CONTROL ( p < 0.001 ) . Central activation ratio increased in both groups , with the significant increase observed in FT80 ( p < 0.05 ) . The higher TES responses , 10RM , and CAR development in FT80 suggest that an HR-based recovery period system of the FT80 may be more efficient in this type of hypertrophic strength training ( 3 × 10RM ) . The protocol in this study may be considered as a metabolic training cycle that coaches and trainers can use within a longer periodized training program To examine endogenous anabolic hormone and growth factor responses to various heavy resistance exercise protocol s ( HREPs ) , nine male subjects performed each of six r and omly assigned HREPs , which consisted of identically ordered exercises carefully design ed to control for load [ 5 vs. 10 repetitions maximum ( RM ) ] , rest period length ( 1 vs. 3 min ) , and total work effects . Serum human growth hormone ( hGH ) , testosterone ( T ) , somatomedin-C ( SM-C ) , glucose , and whole blood lactate ( HLa ) concentrations were determined preexercise , midexercise ( i.e. , after 4 of 8 exercises ) , and at 0 , 5 , 15 , 30 , 60 , 90 , and 120 min postexercise . All HREPs produced significant ( P less than 0.05 ) temporal increases in serum T concentrations , although the magnitude and time point of occurrence above resting values varied across HREPs . No differences were observed for T when integrated areas under the curve ( AUCs ) were compared . Although not all HREPs produced increases in serum hGH , the highest responses were observed consequent to the H10/1 exercise protocol ( high total work , 1 min rest , 10-RM load ) for both temporal and time integrated ( AUC ) responses . The pattern of SM-C increases varied among HREPs and did not consistently follow hGH changes . Whereas temporal changes were observed , no integrated time ( AUC ) differences between exercise protocol s occurred . These data indicate that the release patterns ( temporal or time integrated ) observed are complex functions of the type of HREPs utilized and the physiological mechanisms involved with determining peripheral circulatory concentrations ( e.g. , clearance rates , transport , receptor binding ) . All HREPs may not affect muscle and connective tissue growth in the same manner because of possible differences in hormonal and growth factor release Purpose To determine if 8 weeks of periodized strength resistance training ( RT ) utilizing relatively short rest interval lengths ( RI ) in between sets ( SS ) would induce greater improvements in body composition and muscular performance , compared to the same RT program utilizing extended RI ( SL ) . Methods 22 male volunteers ( SS : n = 11 , 65.6 ± 3.4 years ; SL : n = 11 , 70.3 ± 4.9 years ) were assigned to one of two strength RT groups , following 4 weeks of periodized hypertrophic RT ( PHRT ) : strength RT with 60-s RI ( SS ) or strength RT with 4-min RI ( SL ) . Prior to r and omization , all 22 study participants trained 3 days/week , for 4 weeks , targeting hypertrophy ; from week 4 to week 12 , SS and SL followed the same periodized strength RT program for 8 weeks , with RI the only difference in their RT prescription . Results Following PHRT , all study participants experienced increases in lean body mass ( LBM ) ( p < 0.01 ) , upper and lower body strength ( p < 0.001 ) , and dynamic power ( p < 0.001 ) , as well as decreases in percentage body fat ( p < 0.05 ) . Across the 8-week strength RT phase , SS experienced significantly greater increases in LBM ( p = 0.001 ) , flat machine bench press 1-RM ( p < 0.001 ) , bilateral leg press 1-RM ( p < 0.001 ) , narrow/neutral grip lat pulldown ( p < 0.01 ) , and Margaria stair-climbing power ( p < 0.001 ) , compared to SL . Conclusions This study suggests 8 weeks of periodized high-intensity strength RT with shortened RI induces significantly greater enhancements in body composition , muscular performance , and functional performance , compared to the same RT prescription with extended RI , in older men . Applied professionals may optimize certain RT-induced adaptations , by incorporating shortened RI de Souza Jr , TP , Fleck , SJ , Simão , R , Dubas , JP , Pereira , B , de Brito Pacheco , EM , da Silva , AC , and de Oliveira , PR . Comparison between constant and decreasing rest intervals : influence on maximal strength and hypertrophy . J Strength Cond Res 24(7 ) : 1843 - 1850 , 2010-Most resistance training programs use constant rest period lengths between sets and exercises , but some programs use decreasing rest period lengths as training progresses . The aim of this study was to compare the effect on strength and hypertrophy of 8 weeks of resistance training using constant rest intervals ( CIs ) and decreasing rest intervals ( DIs ) between sets and exercises . Twenty young men recreationally trained in strength training were r and omly assigned to either a CI or DI training group . During the first 2 weeks of training , 3 sets of 10 - 12 repetition maximum ( RM ) with 2-minute rest intervals between sets and exercises were performed by both groups . During the next 6 weeks of training , the CI group trained using 2 minutes between sets and exercises ( 4 sets of 8 - 10RM ) , and the DI group trained with DIs ( 2 minutes decreasing to 30 seconds ) as the 6 weeks of training progressed ( 4 sets of 8 - 10RM ) . Total training volume of the bench press and squat were significantly lower for the DI compared to the CI group ( bench press 9.4 % , squat 13.9 % ) and weekly training volume of these same exercises was lower in the DI group from weeks 6 to 8 of training . Strength ( 1RM ) in the bench press and squat , knee extensor and flexor isokinetic measures of peak torque , and muscle cross-sectional area ( CSA ) using magnetic resonance imaging were assessed pretraining and posttraining . No significant differences ( p ≤ 0.05 ) were shown between the CI and DI training protocol s for CSA ( arm 13.8 vs. 14.5 % , thigh 16.6 vs. 16.3 % ) , 1RM ( bench press 28 vs. 37 % , squat 34 vs. 34 % ) , and isokinetic peak torque . In conclusion , the results indicate that a training protocol with DI is just as effective as a CI protocol over short training periods ( 6 weeks ) for increasing maximal strength and muscle CSA ; thus , either type of program can be used over a short training period to cause strength and hypertrophy Regular performance of resistance exercise induces an increase in skeletal muscle mass , however , the molecular mechanisms underlying this effect are not yet fully understood . The purpose of the present investigation was to examine acute changes in molecular signalling in response to resistance exercise involving different training volumes . Eight untrained male subjects carried out one , three and five sets of 6 repetition maximum ( RM ) in leg press exercise in a r and om order . Muscle biopsies were taken from the vastus lateralis both prior to and 30 min after each training session and the effect on protein signalling was studied . Phosphorylation of Akt was not altered significantly after any of the training protocol s , whereas that of the mammalian target of rapamycin was enhanced to a similar extent by training at all three volumes . The phosphorylation of p70S6 kinase ( p70S6k ) was elevated threefold after 3 × 6 RM and sixfold after 5 × 6 RM , while the phosphorylation of S6 was increased 30- and 55-fold following the 3 × 6 RM and 5 × 6 RM exercises , respectively . Moreover , the level of the phosphorylated form of the gamma isoform of p38 MAPK was enhanced three to fourfold following each of the three protocol s , whereas phosphorylation of ERK1/2 was unchanged 30 min following exercise . These findings indicate that when exercise is performed in a fasted state , the increase in phosphorylation of signalling molecules such as p70S6k and the S6 ribosomal protein in human muscle depends on the exercise volume Abstract In its last position st and about strength training , the American College of Sports Medicine recommends a rest interval ( RI ) between sets ranging between 1 and 3 min , varying in accordance with the objective . However , there is no consensus regarding the optimal recovery between sets , and most studies have investigated fixed intervals . Therefore , the aim of this study was to analyse the effects of fixed versus self-suggested RI between sets in lower and upper body exercises performance . Twenty-seven healthy subjects ( 26 ± 1.5 ; 75 ± 15 kg ; 175 ± 12 cm ) were r and omly assigned into two groups : G1 : lower body exercises and G2 : upper body exercises . Squat and leg press 1 repetition maximum ( 1RM ) were tested for the G1 and bench press and bice Output:	Current evidence indicates that both short and long inter-set rest intervals may be useful when training for achieving gains in muscle hypertrophy . Novel findings involving trained participants using measures sensitive to detect changes in muscle hypertrophy suggest a possible advantage for the use of long rest intervals to elicit hypertrophic effects .
MS21071	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Advances in technology allowed the development of a novel smoking cessation program delivered by video messages sent to mobile phones . This social cognitive theory-based intervention ( called “ STUB IT ” ) used observational learning via short video diary messages from role models going through the quitting process to teach behavioral change techniques . Objective The objective of our study was to assess the effectiveness of a multimedia mobile phone intervention for smoking cessation . Methods A r and omized controlled trial was conducted with 6-month follow-up . Participants had to be 16 years of age or over , be current daily smokers , be ready to quit , and have a video message-capable phone . Recruitment targeted younger adults predominantly through radio and online advertising . Registration and data collection were completed online , prompted by text messages . The intervention group received an automated package of video and text messages over 6 months that was tailored to self-selected quit date , role model , and timing of messages . Extra messages were available on dem and to beat cravings and address lapses . The control group also set a quit date and received a general health video message sent to their phone every 2 weeks . Results The target sample size was not achieved due to difficulty recruiting young adult quitters . Of the 226 r and omized participants , 47 % ( 107/226 ) were female and 24 % ( 54/226 ) were Maori ( indigenous population of New Zeal and ) . Their mean age was 27 years ( SD 8.7 ) , and there was a high level of nicotine addiction . Continuous abstinence at 6 months was 26.4 % ( 29/110 ) in the intervention group and 27.6 % ( 32/116 ) in the control group ( P = .8 ) . Feedback from participants indicated that the support provided by the video role models was important and appreciated . Conclusions This study was not able to demonstrate a statistically significant effect of the complex video messaging mobile phone intervention compared with simple general health video messages via mobile phone . However , there was sufficient positive feedback about the ease of use of this novel intervention , and the support obtained by observing the role model video messages , to warrant further investigation . Trial registration Australian New Zeal and Clinical Trials Registry Number : ACTRN12606000476538 ; http://www.anzctr.org.au/trial_view.aspx?ID=81688 ( Archived by WebCite at http://www.webcitation.org/5umMU4sZi Background Web-based and mobile health interventions ( also called “ Internet interventions ” or " eHealth/mHealth interventions ") are tools or treatments , typically behaviorally based , that are operationalized and transformed for delivery via the Internet or mobile platforms . These include electronic tools for patients , informal caregivers , healthy consumers , and health care providers . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed to improve the suboptimal reporting of r and omized controlled trials ( RCTs ) . While the CONSORT statement can be applied to provide broad guidance on how eHealth and mHealth trials should be reported , RCTs of web-based interventions pose very specific issues and challenges , in particular related to reporting sufficient details of the intervention to allow replication and theory-building . Objective To develop a checklist , dubbed CONSORT-EHEALTH ( Consoli date d St and ards of Reporting Trials of Electronic and Mobile HEalth Applications and onLine TeleHealth ) , as an extension of the CONSORT statement that provides guidance for authors of eHealth and mHealth interventions . Methods A literature review was conducted , followed by a survey among eHealth experts and a workshop . Results A checklist instrument was constructed as an extension of the CONSORT statement . The instrument has been adopted by the Journal of Medical Internet Research ( JMIR ) and authors of eHealth RCTs are required to su bmi t an electronic checklist explaining how they addressed each subitem . Conclusions CONSORT-EHEALTH has the potential to improve reporting and provides a basis for evaluating the validity and applicability of eHealth trials . Subitems describing how the intervention should be reported can also be used for non- RCT evaluation reports . As part of the development process , an evaluation component is essential ; therefore , feedback from authors will be solicited , and a before-after study will evaluate whether reporting has been improved Background Mobile phone-based psychological interventions enable real time self-monitoring and self-management , and large-scale dissemination . However , few studies have focussed on mild-to-moderate symptoms where public health need is greatest , and none have targeted work and social functioning . This study reports outcomes of a CONSORT-compliant r and omised controlled trial ( RCT ) to evaluate the efficacy of myCompass , a self-guided psychological treatment delivered via mobile phone and computer , design ed to reduce mild-to-moderate depression , anxiety and stress , and improve work and social functioning . Method Community-based volunteers with mild-to-moderate depression , anxiety and /or stress ( N = 720 ) were r and omly assigned to the myCompass program , an attention control intervention , or to a waitlist condition for seven weeks . The interventions were fully automated , without any human input or guidance . Participants ’ symptoms and functioning were assessed at baseline , post-intervention and 3-month follow-up , using the Depression , Anxiety and Stress Scale and the Work and Social Adjustment Scale . Results Retention rates at post-intervention and follow-up for the study sample were 72.1 % ( n = 449 ) and 48.6 % ( n = 350 ) respectively . The myCompass group showed significantly greater improvement in symptoms of depression , anxiety and stress and in work and social functioning relative to both control conditions at the end of the 7-week intervention phase ( between-group effect sizes ranged from d = .22 to d = .55 based on the observed means ) . Symptom scores remained at near normal levels at 3-month follow-up . Participants in the attention control condition showed gradual symptom improvement during the post-intervention phase and their scores did not differ from the myCompass group at 3-month follow-up . Conclusions The myCompass program is an effective public health program , facilitating rapid improvements in symptoms and in work and social functioning for individuals with mild-to-moderate mental health problems . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN Background Prevention of the onset of depression in adolescence may prevent social dysfunction , teenage pregnancy , substance abuse , suicide , and mental health conditions in adulthood . New technologies allow delivery of prevention programs scalable to large and disparate population s. Objective To develop and test the novel mobile phone delivery of a depression prevention intervention for adolescents . We describe the development of the intervention and the results of participants ’ self-reported satisfaction with the intervention . Methods The intervention was developed from 15 key messages derived from cognitive behavioral therapy ( CBT ) . The program was fully automated and delivered in 2 mobile phone messages/day for 9 weeks , with a mixture of text , video , and cartoon messages and a mobile website . Delivery modalities were guided by social cognitive theory and marketing principles . The intervention was compared with an attention control program of the same number and types of messages on different topics . A double-blind r and omized controlled trial was undertaken in high schools in Auckl and , New Zeal and , from June 2009 to April 2011 . Results A total of 1348 students ( 13–17 years of age ) volunteered to participate at group sessions in schools , and 855 were eventually r and omly assigned to groups . Of these , 835 ( 97.7 % ) self-completed follow-up question naires at postprogram interviews on satisfaction , perceived usefulness , and adherence to the intervention . Over three-quarters of participants viewed at least half of the messages and 90.7 % ( 379/418 ) in the intervention group reported they would refer the program to a friend . Intervention group participants said the intervention helped them to be more positive ( 279/418 , 66.7 % ) and to get rid of negative thoughts ( 210/418 , 50.2%)—significantly higher than proportions in the control group . Conclusions Key messages from CBT can be delivered by mobile phone , and young people report that these are helpful . Change in clinician-rated depression symptom scores from baseline to 12 months , yet to be completed , will provide evidence on the effectiveness of the intervention . If proven effective , this form of delivery may be useful in many countries lacking widespread mental health services but with extensive mobile phone coverage . Clinical Trial Australia New Zeal and Clinical Trials Registry ( ACTRN ) : 12609000405213 ; http://www.anzctr.org.au/trial_view.aspx?ID=83667 ( Archived by WebCite at http://www.webcitation.org/64aueRqOb Objective To evaluate the impacts of using SMS on improving laboratory test levels and Knowledge , Attitude , Practice ( KAP ) and Self Efficacy ( SE ) of patients with type 2 diabetes mellitus ( DM ) in Iran . Material s and methods In this r and omized controlled trial study , a total of 81 type 2 diabetes patients were r and omly assigned into two groups exp . group ( n = 43 ) and cont . group ( n = 38 ) . Only exp . group received 4 messages weekly consisted of diet , exercise , medication taking and . The research ers provided the intervention for 12 weeks . Data were collected with results of laboratory tests and KAP , SE reliable and valid question naires and demographic characteristics list . Data gathering at the baseline of the study and after 3 months intervention and was analyzed by SPSS11.5 software using descriptive and inferential statistics methods . Results The results of this study showed that exp . group compared with cont . group improved significantly in HbA1C ( p = 0.024 ) , LDL ( p = 0.019 ) , cholesterol ( p = 0.002 ) , BUN ( p ≤ 0.001 ) , micro albumin ( p ≤ 0.001 ) , knowledge ( p ≤ 0.001 ) , practice ( p ≤ 0.001 ) and self efficacy ( p ≤ 0.001 ) . Conclusion The finding of this study demonstrate the effectiveness of intervention using SMS via mobile phone in the management of type 2 diabetes mellitus ( DM ) . Thus , further studies are recommended for wide usage of distance education with mobile phone utilization Background — Indirect evidence shows that alerting users with clinical decision support systems seems to change behavior more than requiring users to actively initiate the system . However , r and omized trials comparing these methods in a clinical setting are lacking . We studied the effect of both alerting and on-dem and decision support with respect to screening and treatment of dyslipidemia based on the guidelines of the Dutch College of General Practitioners . Methods and Results — In a clustered r and omized trial design , 38 Dutch general practice s ( 77 physicians ) and 87 886 of their patients ( 39 433 men 18 to 70 years of age and 48 453 women 18 to 75 years of age ) who used the ELIAS electronic health record participated . Each practice was assigned to receive alerts , on-dem and support , or no intervention . We measured the percentage of patients screened and treated after 12 months of follow-up . In the alerting group , 65 % of the patients requiring screening were screened ( relative risk versus control=1.76 ; 95 % confidence interval , 1.41 to 2.20 ) compared with 35 % of patients in the on-dem and group ( relative risk versus control=1.28 ; 95 % confidence interval , 0.98 to 1.68 ) and 25 % of patients in the control group . In the alerting group , 66 % of patients requiring treatment were treated ( relative risk versus control=1.40 ; 95 % confidence interval , 1.15 to 1.70 ) compared with 40 % of patients ( relative risk versus control=1.19 ; 95 % confidence interval , 0.94 to 1.50 ) in the on-dem and group and 36 % of patients in the control group . Conclusion — The alerting version of the clinical decision support systems significantly improved screening and treatment performance for dyslipidemia by general practitioners Background and Aims Internet-based cognitive-behavioral therapy ( iCBT ) for social anxiety disorder has been found effective , as attested by independently conducted r and omized controlled trials in four language s. The study aim is to test the efficacy of an iCBT program in a culture where it was not tested before ( i.e. Romania ) . Methods Participants ( n = 76 ) were recruited , screened and r and omized to either a nine-week guided iCBT or a wait-list control group in April and May 2012 . Self-report measures were collected before ( April 2012 ) and after the intervention ( July 2012 ) , as well as six months later ( January 2013 ) . Although social anxiety was assessed with multiple measures , the Liebowitz Social Anxiety Scale - Self Report version ( LSAS-SR ) and Social Phobia Inventory ( SPIN ) were used as the primary outcome measures . Results A significant difference with a large between-group effect size in favor of iCBT was found ( Cohen´s d = 1.19 for LSAS-SR and d = 1.27 for SPIN ) . Recovery rates show that 36.8 % ( n = 14 ) in the treatment group score below the SPIN clinical cut-off compared to only 2.6 % ( n = 1 ) in the wait-list control group . Post-intervention clinical interviews also revealed that 34.2 % ( n = 13 ) of the treatment group was completely recovered ( full remission ) while additionally 36.8 % ( n = 14 ) retained some social anxiety symptoms ( partial remission Output:	We also confirmed that RCTs are valuable tools for assessing the effectiveness , acceptability , safety , privacy , appropriateness , satisfaction , performance , usefulness and adherence .
MS21072	*TASK* the task is to summarize an input biomedical literature in six sentences *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 : Emerging evidence suggests positive associations between serum anti-Müllerian hormone ( AMH ) , a marker of ovarian function , and breast cancer risk . Body size at young ages may influence AMH levels , but few studies have examined this . Also , no studies have examined the relation of AMH levels with breast density , a strong predictor of breast cancer risk . Methods : We examined associations of early life body fatness , AMH concentrations , and breast density among 172 women in the Dietary Intervention Study in Children ( DISC ) . Height and weight were measured at baseline ( ages 8–10 ) and throughout adolescence . Serum AMH concentrations and breast density were assessed at ages 25–29 at the DISC 2006 Follow-up visit . We used linear mixed effects models to quantify associations of AMH ( dependent variable ) with quartiles of age-specific youth body mass index ( BMI ) Z-scores ( independent variable ) . We assessed cross-sectional associations of breast density ( dependent variable ) with AMH concentration ( independent variable ) . Results : Neither early life BMI nor current adult BMI was associated with AMH concentrations . There were no associations between AMH and percent or absolute dense breast volume . In contrast , women with higher AMH concentrations had significantly lower absolute nondense breast volume ( Ptrend < 0.01 ) . Conclusions : We found no evidence that current or early life BMI influences AMH concentrations in later life . Women with higher concentrations of AMH had similar percent and absolute dense breast volume , but lower nondense volume . Impact : These results suggest that AMH may be associated with lower absolute nondense breast volume ; however , future prospect i ve studies are needed to establish temporality . Cancer Epidemiol Biomarkers Prev ; 25(7 ) ; 1151–7 . © 2016 AACR Purpose To compare two methods of automatic breast segmentation with each other and with manual segmentation in a large subject cohort . To discuss the factors involved in selecting the most appropriate algorithm for automatic segmentation and , in particular , to investigate the appropriateness of overlap measures ( e.g. , Dice and Jaccard coefficients ) as the primary determinant in algorithm selection . Methods Two methods of breast segmentation were applied to the task of calculating MRI breast density in 200 subjects drawn from the Avon Longitudinal Study of Parents and Children , a large cohort study with an MRI component . A semiautomated , bias‐corrected , fuzzy C‐means ( BC‐FCM ) method was combined with morphological operations to segment the overall breast volume from in‐phase Dixon images . The method makes use of novel , problem‐specific insights . The result ing segmentation mask was then applied to the corresponding Dixon water and fat images , which were combined to give Dixon MRI density values . Contemporaneously acquired T1‐ and T2‐weighted image data sets were analyzed using a novel and fully automated algorithm involving image filtering , l and mark identification , and explicit location of the pectoral muscle boundary . Within the region found , fat‐water discrimination was performed using an Expectation Maximization – Markov R and om Field technique , yielding a second independent estimate of MRI density . Results Images are presented for two individual women , demonstrating how the difficulty of the problem is highly subject‐specific . Dice and Jaccard coefficients comparing the semiautomated BC‐FCM method , operating on Dixon source data , with expert manual segmentation are presented . The corresponding results for the method based on T1‐ and T2‐weighted data are slightly lower in the individual cases shown , but scatter plots and interclass correlations for the cohort as a whole show that both methods do an excellent job in segmenting and classifying breast tissue . Conclusions Epidemiological results demonstrate that both methods of automated segmentation are suitable for the chosen application and that it is important to consider a range of factors when choosing a segmentation algorithm , rather than focus narrowly on a single metric such as the Dice coefficient Introduction Overweight and obesity in childhood and adolescence are associated with reduced breast cancer risk , independent of adult body mass index ( BMI ) . These associations may be mediated through breast density . Methods We prospect ively examined associations of early life body fatness with adult breast density measured by MRI in 182 women in the Dietary Intervention Study in Children ( DISC ) who were ages 25–29 at follow-up . Height , weight , and other factors were measured at baseline ( ages 8–10 ) and annual clinic visits through adolescence . We used linear mixed-effects models to quantify associations of percent breast density and dense and non-dense breast volume at ages 25–29 with quartiles of age-specific youth body mass index ( BMI ) Z-scores , adjusting for clinic , treatment group , current adult BMI , and other well-established risk factors for breast cancer and predictors of breast density . Results We observed inverse associations between age-specific BMI Z-scores at all youth clinic visits and percent breast density , adjusting for current adult BMI and other covariates ( all p values < 0.01 ) . Women whose baseline BMI Z-scores ( at ages 8–10 years ) were in the top quartile had significantly lower adult breast density , after adjusting for current adult BMI and other covariates [ least squares mean ( LSM ) : 23.4 % ; 95 % confidence interval ( CI ) : 18.0 % , 28.8 % ] compared to those in the bottom quartile ( LSM : 31.8 % ; 95 % CI : 25.2 % , 38.4 % ) ( p trend < 0.01 ) . Significant inverse associations were also observed for absolute dense breast volume ( all p values < 0.01 ) , whereas there were no clear associations with non-dense breast volume . Conclusions These results support the hypothesis that body fatness during childhood and adolescence may play an important role in premenopausal breast density , independent of current BMI , and further suggest direct or indirect influences on absolute dense breast volume . Clinical Trials Registration NumberNCT00458588 ; April 9 , The purpose of this study was to investigate prospect ively whether the apparent diffusion coefficients ( ADCs ) of both breast cancer and normal fibrogl and ular tissue vary with the menstrual cycle and menopausal status . Institutional review board approval was obtained , and informed consent was obtained from each participant . Fifty-seven women ( 29 premenopausal , 28 postmenopausal ) with newly diagnosed breast cancer underwent diffusion-weighted imaging twice ( interval 12–20 days ) before surgery . Two radiologists independently measured ADC of breast cancer and normal contralateral breast tissue , and we quantified the differences according to the phases of menstrual cycle and menopausal status . With normal fibrogl and ular tissue , ADC was significantly lower in postmenopausal than in premenopausal women ( P = 0.035 ) . In premenopausal women , ADC did not differ significantly between proliferative and secretory phases in either breast cancer or normal fibrogl and ular tissue ( P = 0.969 and P = 0.519 , respectively ) . In postmenopausal women , no significant differences were found between ADCs measured at different time intervals in either breast cancer or normal fibrogl and ular tissue ( P = 0.948 and P = 0.961 , respectively ) . The within-subject variability of the ADC measurements was quantified using the coefficient of variation ( CV ) and was small : the mean CVs of tumor ADC were 2.90 % ( premenopausal ) and 3.43 % ( postmenopausal ) , and those of fibrogl and ular tissue ADC were 4.37 % ( premenopausal ) and 2.55 % ( postmenopausal ) . Both intra- and interobserver agreements were excellent for ADC measurements , with intraclass correlation coefficients in the range of 0.834–0.974 . In conclusion , the measured ADCs of breast cancer and normal fibrogl and ular tissue were not affected significantly by menstrual cycle , and the measurements were highly reproducible both within and between observers Women with high breast density ( BD ) have a 4- to 6-fold greater risk for breast cancer than women with low BD . We found that BD can be easily computed from a mathematical algorithm using routine mammographic imaging data or by a curve-fitting algorithm using fat and nonfat suppression magnetic resonance imaging ( MRI ) data . These BD measures in a strictly defined group of premenopausal women providing both mammographic and breast MRI images were predicted as well by the same set of strong predictor variables as were measures from a published laborious histogram segmentation method and a full field digital mammographic unit in multivariate regression models . We also found that the number of completed pregnancies , C-reactive protein , aspartate aminotransferase , and progesterone were more strongly associated with amounts of gl and ular tissue than adipose tissue , while fat body mass , alanine aminotransferase , and insulin like growth factor-II appear to be more associated with the amount of breast adipose tissue . Our results show that methods of breast imaging and modalities for estimating the amount of gl and ular tissue have no effects on the strength of these predictors of BD . Thus , the more convenient mathematical algorithm and the safer MRI protocol s may facilitate prospect i ve measurements of BD Introduction During adolescence the breasts undergo rapid growth and development under the influence of sex hormones . Although the hormonal etiology of breast cancer is hypothesized , it remains unknown whether adolescent sex hormones are associated with adult breast density , which is a strong risk factor for breast cancer . Methods Percentage of dense breast volume ( % DBV ) was measured in 2006 by magnetic resonance imaging in 177 women aged 25–29 years who had participated in the Dietary Intervention Study in Children from 1988 to 1997 . They had sex hormones and sex hormone-binding globulin ( SHBG ) measured in serum collected on one to five occasions between 8 and 17 years of age . Multivariable linear mixed-effect regression models were used to evaluate the associations of adolescent sex hormones and SHBG with % DBV . Results Dehydroepi and rosterone sulfate ( DHEAS ) and SHBG measured in premenarche serum sample s were significantly positively associated with % DBV ( all Ptrend ≤0.03 ) but not when measured in postmenarche sample s ( all Ptrend ≥0.42 ) . The multivariable geometric mean of % DBV across quartiles of premenarcheal DHEAS and SHBG increased from 16.7 to 22.1 % and from 14.1 to 24.3 % , respectively . Estrogens , progesterone , and rostenedione , and testosterone in pre- or postmenarche serum sample s were not associated with % DBV ( all Ptrend ≥0.16 ) . Conclusions Our results suggest that higher premenarcheal DHEAS and SHBG levels are associated with higher % DBV in young women . Whether this association translates into an increased risk of breast cancer later in life is currently unknown . Clinical trials registration Clinical Trials.gov Identifier , NCT00458588 April 9 , 2007 ; NCT00000459 October 27 , BACKGROUND The amount of fibrogl and ular tissue ( FGT ) has been linked to breast cancer risk based on mammographic density studies . Currently , the qualitative assessment of FGT on mammogram ( MG ) and magnetic resonance imaging ( MRI ) is prone to intra and inter-observer variability . The purpose of this study is to develop an objective quantitative FGT measurement tool for breast MRI that could provide significant clinical value . METHODS An IRB approved study was performed . Sixty breast MRI cases with qualitative assessment of mammographic breast density and MRI FGT were r and omly selected for quantitative analysis from routine breast MRIs performed at our institution from 1/2013 to 12/2014 . Blinded to the qualitative data , whole breast and FGT contours were delineated on T1-weighted pre contrast sagittal images using an in-house , proprietary segmentation algorithm which combines the region-based active contours and a level set approach . FGT ( % ) was calculated by : [ segmented volume of FGT ( mm(3))/(segmented volume of whole breast ( mm(3 ) ) ] ×100 . Statistical correlation analysis was performed between quantified FGT ( % ) on MRI and qualitative assessment s of mammographic breast density and MRI FGT . RESULTS There was a significant positive correlation between quantitative MRI FGT assessment and qualitative MRI FGT ( r=0.809 , n=60 , P<0.001 ) and mammographic density assessment ( r=0.805 , n=60 , P<0.001 ) . There was a significant correlation between qualitative MRI FGT assessment and mammographic density assessment ( r=0.725 , n=60 , P<0.001 ) . The four qualitative assessment categories of FGT correlated with the calculated mean quantitative FGT ( % ) of 4.61 % ( 95 % CI , 0 - 12.3 % ) , 8.74 % ( 7.3 - 10.2 % ) , 18.1 % ( 15.1 - 21.1 % ) , 37.4 % ( 29.5 - 45.3 % ) . CONCLUSIONS Quantitative measures of FGT ( % ) were computed with data derived from breast MRI and correlated significantly with conventional qualitative assessment s. This quantitative technique may prove to be a valuable tool in clinical use by providing computer generated st and ardized measurements with limited intra or inter-observer variability Background : Lack of association between fat intake and breast cancer risk in cohort studies might be attributed to the disregard of temporal effects during adolescence when breasts develop and are particularly sensitive to stimuli . We prospect ively examined associations between adolescent fat intakes and breast density . Method : Among 177 women who participated in the Dietary Intervention Study in Children , dietary intakes at ages 10–18 years were assessed on five occasions by 24-hour recalls and averaged . We calculated geometric mean and 9 Output:	The review confirmed high levels of heterogeneity within the breast density studies , considered to be due mainly to the applications of MR breast-imaging protocol s and the use of breast density segmentation/measurement methods .
MS21073	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To evaluate the role of low-molecular weight heparin ( LMWH ) as an alternative to oral anticoagulants in the prevention of recurrent venous thromboembolism , we compared in a r and omized trial conventional warfarin treatment with a three-month course of enoxaparin 4000 anti-Xa units once a day subcutaneously . 187 patients with symptomatic deep-vein thrombosis ( DVT ) , diagnosed by strain-gauge plethysmography plus D-dimer latex assay and confirmed by venography in most cases , were treated with full-dose subcutaneous heparin for ten days and then r and omized to secondary prophylaxis . During the 3-month treatment period , 6 of the 93 patients who received LMWH ( 6 % ) and 4 of the 94 patients on warfarin ( 4 % ) had symptomatic recurrence of venous thromboembolism confirmed by objective testing ( p = 0.5 ; 95 % confidence interval [ CI ] for the difference , -3 % to 7 % ) . Four patients in the LMWH group had bleeding complications as compared with 12 in the warfarin group ( p = 0.04 ; 95 % CI for the difference , 4 % to 14 % ) . In the 9-month follow-up period , during which 34 patients on warfarin prolonged treatment for other 3 months and 14 up to one year , 10 patients in the enoxaparin group and 4 patients in the warfarin group suffered a documented recurrence of venous thromboembolism . Of these 14 late recurrences , just one occurred in patients with postoperative DVT . After one year there were 16 recurrences ( 17 % ) in the LMWH group and 8 ( 9 % ) in the warfarin group ( p = 0.07 ; 95 % CI for the difference , 1 % to 16 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this study was to assess the effectiveness of low-molecular-weight heparin ( LMWH ) treatment of deep vein thrombosis ( DVT ) in terms of the evolution of thrombosis , the incidence of adverse events , and compliance with heparin treatment using 2 types of LMWH available on the market administered in therapeutic doses throughout the period of treatment ( Nadroparin ) or at therapeutic doses only during the first month of treatment followed by a prophylactic phase at half dose ( Parnaparin ) . A r and omized prospect i ve study was carried out on patients under observation with a recent diagnosis of DVT . The objectives of the study were to confirm the effectiveness of therapy with LMWH in terms of prevention of the risk of thromboembolism , of relapse of DVT , and of hemorrhagic complications , and to complete an evaluation of venous recanalization and residual valve competence in the 2 groups of patients . From December 2002 to June 2005 , we r and omized a total of 91 patients ( 51 in the Parnaparin group and 40 in the Nadroparin group ) . Overall , there was 1 case of nonfatal pulmonary embolism ( 1.1 % ) at 7 days into therapy with LMWH . There were 3 cases ( 3.3 % ) of progression of thrombosis despite therapy with LMWH , 2 cases ( 5 % ) in the Nadroparin group , and 1 case ( 2 % ) in the Parnaparin group ( P = NS ) , and after suspension of the therapy , there was 1 case of relapse of thrombosis . Three of the 4 thrombotic events occurred in patients with active neoplasia . Moreover , only 1 major hemorrhagic event ( 1.1 % ) required blood transfusion . The Doppler ultrasound in the follow-up showed a complete resolution of 56 % of the vein thromboses at an average of 6.1 ± 4.6 ( mean ± SD ) months . Valve competence recovered in 65.9 % of cases with no significant difference between the 2 heparin groups . Home treatment of sural and femoral-popliteal DVT using LMWH represents a safe and effective method in the prevention of pulmonary embolism and encourages the process of recanalization of the thrombosed vessel , especially in cases of sural and /or popliteal DVT . Administration can be carried out with the same degree of safety at the therapeutic dose throughout the period of treatment or can be halved after the first month of treatment . In patients with active neoplasia , treatment with oral anticoagulant therapy must be considered PURPOSE The purpose of this study was to compare the efficacy and safety of treating mobile iliofemoral patients with deep venous thrombosis ( DVT ) with subcutaneous low-molecular-weight heparin ( dalteparin sodium ) either 200 IU/kg once-daily ( group 1 ) or 100 IU/kg twice-daily ( group 2 ) . METHODS Consecutive patients with suspected iliofemoral DVT diagnosed by duplex ultrasonography and verified by radionuclide venography were r and omized to one of the two low-molecular-weight heparin ( LMWH ) regimens . Perfusion and when necessary ventilation scans were performed for diagnosis of pulmonary emboli ( PE ) in all patients immediately after admission and were repeated after approximately 10 days , whereupon oral anticoagulation was started unless contraindicated . Minimal and maximal anti-factor Xa activity was measured after 2 to 3 days of therapy . All patients were kept mobile with compression b and ages . The primary end point was reduction in frequency of PE as assessed on the second lung scan . RESULTS A total of 140 patients with confirmed DVT were r and omized , 76 to group 1 and 64 to group 2 . The two groups were comparable in their baseline clinical characteristics . In the initial lung scans 36 ( 47.4 % ) patients in group 1 and 29 ( 45.3 % ) patients in group 2 had objective ly verified PE , but only 11 ( 14.5 % ) and 8 ( 12.5 % ) patients , respectively , had symptoms . After dalteparin treatment PE disappeared in two patients in group 1 , but in two other cases new PEs occurred , ( NS ) . In group 2 a resolution of PEs was observed in eight patients , whereas only one new PE could be detected . This change reflects the efficacy of therapy as defined by resolution of existing PEs and by the occurrence of new PEs and is statistically significant according to McNemar 's chi-square test with the exact binomial method pair procedure ( p < 0.05 ) . Symptomatic PE was reduced from 14.5 % to 5.3 % in group 1 ( 96 % to CI for the difference , -1.5 % to + 17.3 % ) and from 12.5 % to 1.6 % in group 2 ( 95 % CI for the difference 0.7 % to 18 % , p < 0.05 ) . There was one single fatal PE , one serious and three minor bleeding episodes in group 1 , and one minor bleeding episode in group 2 ( 95 % CI for the difference : -3.6 % to + 8.1 % ) . CONCLUSIONS Treatment of ambulant iliofemoral patients with DVT with 100 IU/kg dalteparin twice-daily appears to be moe safe and effective than 200 IU/kg given once-daily . Bed rest is not necessary for treating mobile patients Treatment of deep venous thrombosis with low molecular weight heparin ( LMWH-Novo , Logiparin ) was carried out with two different doses of Logiparin , 75 XaI U/kg b.w . twice daily and 150 XaI U/kg b.w . once daily subcutaneously for 5 days . Simultaneously warfarin was given from the first day of heparin treatment . Mean age of the twenty patients was 65 years and one third was females . No serious side effects , hematomas , pulmonary emboli or signs of recurrent thrombosis occurred during treatment with either dose regime . Venografic assessment with Marder scoring one week after initiation of Logiparin treatment showed a slight not significant improvement apparent in 40 % of the patients . The activities of F-IIaI and F-XaI in the blood plasma were found to increase after injection of Logiparin . These two parameters seem to be the most suitable for monitoring the effect during treatment . For future studies on the therapeutic effect of Logiparin in deep venous thrombosis a single dose of 150 to 200 F-XaI activity per 24 hours seems to be most suitable INTRODUCTION Trials comparing the use of full dose unfractionated heparin ( UFH ) or low molecular weight heparins ( LMWHs ) in very elderly patients with impaired renal function are lacking . IRIS aim ed to assess whether LMWH is at least as safe as UFH in this population . MATERIAL S AND METHODS The study included renally impaired patients ≥70 years with acute symptomatic lower limb deep vein thrombosis ( DVT ) . Patients were r and omized to initial treatment with either tinzaparin 175 IU/kg once daily ( n=269 ) or activated partial thromboplastin time-adjusted UFH twice daily ( n=270 ) . After acute management both groups received vitamin K antagonist to day 90 . RESULTS The trial was stopped prematurely due to a difference in mortality favoring the UFH group ( 11.5 vs. 6.3 % ; p=0.035 ) . Rates of clinical ly relevant bleedings by day 90 were similar in the tinzaparin ( 11.9 % ) and UFH ( 11.9 % ) groups , as were rates of confirmed recurrent venous thromboembolism ( VTE ) ( 2.6 vs. 1.1 % ; p=0.34 ) . As the mortality difference could not be explained by bleedings or recurrent VTE , a post-hoc analysis was performed . This identified six baseline characteristics significantly correlated with mortality , of which five were over-represented in the tinzaparin group . CONCLUSION The IRIS study was a challenging study involving patients ( mean age 83 years ) usually excluded from clinical studies , but its early termination has left questions unanswered . The mortality difference observed with tinzaparin vs. UFH in elderly , renally-impaired patients with DVT can not be explained on the basis of bleedings or recurrent VTE , and may reflect an imbalance of mortality risk factors at baseline BACKGROUND Optimal doses and duration of low-molecular-weight heparin ( LMWH ) for the treatment of superficial vein thrombosis ( SVT ) are still uncertain . OBJECTIVES To compare the efficacy and safety of different doses and duration s of LMWH parnaparin for symptomatic lower limb SVT . PATIENTS AND METHODS Out patients with at least a 4-cm-long SVT of long or short saphenous veins or their collaterals were r and omized to receive parnaparin either 8500 UI once daily ( o.d . ) for 10 days followed by placebo for 20 days ( group A ) or 8500 UI o.d . for 10 days followed by 6400 UI once daily ( o.d . ) for 20 days ( group B ) or 4250 UI o.d . for 30 days ( group C ) in a double-blind fashion in 16 clinics . Primary outcome was the composite of symptomatic and asymptomatic deep vein thrombosis ( DVT ) , symptomatic pulmonary embolism ( PE ) and relapse and /or symptomatic or asymptomatic SVT recurrence in the first 33 days with 60 days follow-up . RESULTS Among 664 patients , primary outcome occurred in 33/212 ( 15.6 % ) , 4/219 ( 1.8 % ) and 16/217 ( 7.3 % ) subjects in groups A , B and C , respectively ( B vs. A : absolute risk reduction [ ARR ] : 13.7 % , 95 % confidence intervals [ CI ] : 8 - 18.9 P<0.001 ; B vs. C : ARR : 5.5 % ; 95 % CI : 1.6 - 9.4 P= 0.011 ; C vs. A : ARR : 8.2 % , 95 % CI : 2 - 14 P=0.012 ) . During days 0 - 93 , the event rate was higher in group A ( 22.6 % ) than either in group B ( 8.7 % ; P=0.001 ) or C ( 14.3 % , P=0.034 ) . No major hemorrhages occurred . CONCLUSIONS An intermediate dose of parnaparin for 30 days is superior to either a 30-day prophylactic dose or a 10-day intermediate dose for lower limb SVT treatment Treatment monitoring based on a laboratory parameter increases the efficacy and safety of st and ard heparin therapy , but it is not known if this also applies to low-molecular-weight heparin ( LMWH ) therapy of acute deep vein thrombosis ( DVT ) . In a prospect i ve r and omized trial involving 122 consecutive patients , group A ( 58 patients ) received a weight adjusted dose of Fragmin ( 100 IU/kg ) subcutaneously twice a day throughout the treatment period ( 10 days + /- 1 ) , while in group B ( 64 patients ) the dosage was based on the results of an anti factor Xa ( anti Xa ) amidol Output:	AUTHORS ' CONCLUSIONS Once daily treatment with LMWH is as effective and safe as twice daily treatment with LMWH
MS21074	*TASK* the task is to summarize an input biomedical literature in six sentences *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 benefit of heparin anticoagulation in patients undergoing intra-aortic balloon counterpulsation ( IABP ) is unproven . Methods : We determined the net clinical benefit ( or harm ) of heparin therapy during intra-aortic balloon counterpulsation ( IABP ) in the coronary care unit ( CCU ) by conducting a prospect i ve “ before- and -after ” analysis of consecutive patients . We compared a universal heparin ( UH ) strategy ( all patients given heparin ) to a selective heparin ( SH ) strategy ( heparin only for a clinical indication ) . Results : There were 102 patients in the UH group and 150 patients in the SH group . Among the SH group , 70 patients ( 47 % ) received no heparin . Major IABP-related complications were uncommon in both groups ( 2.9 % versus 4.6 % , P=0.7 ) . Major limb ischemia occurred in one patient in the UH group ( overall incidence : 0.4 % ) . Major non-access-site bleeding was more common in the UH group ( 10.8 % versus 3.3 % , P=0.02 ) . Inclusion in the UH group was independently associated with the endpoints of : major limb ischemia or any major bleeding ( odds ratio ( OR ) 3.32 , P=0.03 ) , any major bleeding ( OR 3.35 , P=0.03 ) , and major limb ischemia , any major bleeding , or death ( OR 2.17 , P=0.03 ) . Conclusions : Among CCU patients undergoing IABP , a selective heparin strategy appears to be superior to a strategy of universal heparin use To assess the usefulness of intraaortic balloon pumping ( IABP ) in acute myocardial infa rct ion ( AMI ) , 114 patients with anterior AMI undergoing emergency percutaneous transluminal coronary angioplasty ( PTCA ) for total occlusion of the left anterior descending artery were studied . After successful PTCA 66 patients were treated with conventional therapy ( group I ) , and 48 patients were treated with IABP for 25 + /- 8 hours ( group II ) . The reocclusion rate was significantly lower in group II ( 2.4 % vs 17.7 % p less than 0.05 ) . An increase in ejection fraction in group II compared with group I was marginally significant ( 4.5 + /- 12.2 % vs 9.2 + /- 13.0 % , p = 0.08 ) . Vascular complications occurred in two patients , but there were no deaths from IABP . These results suggest that after successful PTCA for acute myocardial infa rct ion , IABP prevents reocclusion and may add strength to reperfusion in the improvement of left ventricular function Background —Recovery of myocardial function after revascularization of acutely occluded coronary arteries may require several days . During this critical time , patients in cardiogenic shock may have low output . A newly developed percutaneous left ventricular assist device ( VAD ) may offer effective treatment for these patients by providing active circulatory support . Methods and Results —Between May 2000 and May 2001 , VADs were implanted in 18 consecutive patients who had cardiogenic shock after myocardial infa rct ion . The device was connected to the patient ’s circulation by insertion of a 21F venous cannula into the left atrium by transseptal puncture ; blood was returned to the iliac artery through an arterial cannula . Mean duration of cardiac assistance was 4±3 days . Mean flow of the VAD was 3.2±0.6 L/min . Before support , cardiac index was 1.7±0.3 L/min per m2 and improved to 2.4±0.6 L/min per m2 ( P < 0.001 ) . Mean blood pressure increased from 63±8 mm Hg to 80±9 mm Hg ( P < 0.001 ) . Pulmonary capillary wedge pressure , central venous pressure , and pulmonary artery pressure were reduced from 21±4 , 13±4 , and 31±8 mm Hg to 14±4 , 9±3 , and 23±6 mm Hg ( all P < 0.001 ) , respectively . Overall 30-day mortality rate was 44 % . Conclusions —A newly developed VAD can be rapidly deployed in the catheterization laboratory setting . This device provides up to 4.0 L/min of assisted cardiac output , which may aid to revert cardiogenic shock . The left ventricle is unloaded by diverting blood from the left atrium to the systemic circulation , making recovery more likely after an ischemic event . The influence of this device on long-term prognosis warrants further investigation Intra-aortic balloon counterpulsation ( IABP ) related complications in a heterogeneous group of patients who received an IABP before or after thrombolytic therapy and mechanical revascularization or in the management of refractory unstable angina and myocardial infa rct ion related mechanical complications were evaluated prospect ively . Ninety-one patients were enrolled to the study . Mean IABP duration was 4.3+/-2.4 days . While the IABP was in place , three patients ( 3.3 % ) had femoral artery emboli , four patients ( 4.4 % ) had lower extremity ischemia that resolved after the removal of the balloon , eight patients ( 8.8 % ) had groin hematoma requiring blood transfusion ( < or = 2 units ) and four patients ( 4.4 % ) had intra-aortic balloon rupture . The relation of several risk factors to groin hematoma requiring < or = 2 units blood transfusion , emboli , lower extremity ischemia and to total complications was evaluated . A chi-squared analysis showed that nadroparine use was more often complicated with emboli ( P = 0.00005 ) and ischemic events ( emboli and /or lower extremity ischemia ) ( three patients ; 30 % of nadroparine group vs. four patients ; 4.9 % of heparin group , P = 0.005 ) and hypercholesterolemia ( > 200 mg/dl ) was more often complicated with lower extremity ischemia ( P = 0.017 ) . Forward conditional logistic regression analysis did not show any relation between the risk factors identified and emboli , lower extremity ischemia , ischemic events and groin hematoma ( P>0.05 ) , but an inverse relation was found between IABP duration and total complications ( P = 0.0198 ) . In conclusion , IABP related complications were found to remain unchanged but were not life-threatening and were inversely related to IABP duration and this suggests shorter periods of IABP use whenever possible and one must be cautious to use low molecular weight heparin in patients with an IABP in place Output:	While differences in survival were comparable in patients treated with IABP , with and without LVAD , haemodynamics and incidences of device related complications show heterogeneous results . Available evidence suggests that IABP may have a beneficial effect on the haemodynamics , however there is no convincing r and omised data to support the use of IABP in infa rct related cardiogenic shock
MS21075	*TASK* the task is to summarize an input biomedical literature in six sentences *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 is a need for a reliable marker of endometriosis , especially in early stages of peritoneal disease during which imaging is not effective . The use of serum interleukin (IL)-6 as a marker is controversial . To readdress the matter , patients undergoing laparoscopy were prospect ively evaluated for serum IL-6 levels . MATERIAL S AND METHODS A total of 119 women 31 years old who underwent laparoscopy were divided into groups : control patients ( n = 38 ) with no pathologic findings ; endometriosis sufferers ( n = 47 ) with minimal-mild ( MM , n = 11 ) or moderate-severe ( MS , n = 36 ) endometriosis ; uterine myomas ( n = 13 ) and benign ovarian pathologies ( n = 21 ) . Blood was drawn on cycles days 5 - 12 and stored for subsequent analysis of IL-6 and carbohydrate antigen (CA)-125 levels . RESULTS Serum IL-6 levels were significantly ( P = 0.002 ) higher in women with MM endometriosis ( 29.4 9.0 pg/ml ) than in controls ( 15.7 9.3 pg/ml ) . When all the non-endometriosis patients were grouped together ( n = 72 ) and serum IL-6 ( 17.8 12.1 pg/ml ) compared with MS ( n = 36 ; 17.6 10.3 pg/ml ) and MM ( n = 11 ; 29.4 9.0 pg/ml ) endometriosis significantly ( P < 0.01 ) higher levels in MM endometriosis were observed as compared to the other two groups . Serum Ca-125 levels were significantly ( P < 0.01 ) elevated in MS endometriosis . A serum IL-6 threshold of 25.75 pg/ml afforded a sensitivity of 75 % and specificity of 83 % in the diagnosis of MM endometriosis . Sensitivity and specificity for CA-125 in the diagnosis of MS endometriosis , using 35 IU/ml as the cut-off value , were 47 % and 97 % , respectively . CONCLUSIONS IL-6 is a reliable non-invasive marker of MM endometriosis , whereas Ca-125 is of use as a marker of severe cases OBJECTIVE This study was undertaken to evaluate serum leptin concentrations in women with endometriosis during treatment with danazol and with leuprolide depot . STUDY DESIGN Twenty patients aged 18 to 42 years with regular menses and documented pelvic endometriosis were recruited from a university hospital setting . Treatment was 200 mg danazol 3 times daily for 6 months or 3.75 mg leuprolide depot every 28 days for 6 months . Serum leptin concentrations were measured before , during , and after treatment . A single blood sample was taken from each of 10 control women without endometriosis for comparison . Serum leptin level was measured with a radioimmunoassay kit with human leptin , and analysis of variance and paired t tests were used for statistical analysis . RESULTS Serum leptin levels were almost the same among women with endometriosis as in the control group . Leptin levels were higher among women with endometriosis during treatment with danazol and leuprolide(P < .001 ) . Three months after treatment , leptin values remained moderately higher than before treatment . CONCLUSION Danazol and leuprolide increased serum leptin levels . The mechanism of leptin increase is unclear . Further studies are needed to determine whether an adipogonadal axis exists BACKGROUND Little is known about the precise nature of the relationship between dysmenorrhoea ( DM ) and endometriosis . Our aim was to evaluate the relationship between the severity of DM in women with posterior deep infiltrating endometriosis ( DIE ) and indicators of the extent of their disease . METHODS Various indicators of the extent of DIE were recorded during surgery in 209 women . The severity of their DM was assessed with a pain scale . The scale was retrospective for 155 women and prospect i ve for 54 . Correlations were sought with an ordinal logistic regression model with cumulative odds . RESULTS On univariate analysis the following variables were related to the severity of DM : number of previous surgical procedures for endometriosis ; revised American Fertility society classification ; extensiveness of adnexal adhesion ; Douglas obliteration ; size of the posterior DIE implant ; extent of the sub-peritoneal infiltration by the posterior DIE ( rectal , vaginal or both versus sub-peritoneal only ) . Current infertility was associated with less severe DM . After multiple regression analysis , presence of a rectal or vaginal infiltration by the posterior DIE and extensiveness of adnexal adhesion were the only factors that remained related to DM severity . CONCLUSIONS The concept of ' very deep infiltrating endometriosis ' , defined as implants invading the wall of the pelvic organ , should be tested in future classification systems specifically addressed to the prediction of endometriosis-related pain OBJECTIVE The pathogenesis of endometriosis is associated with an inflammatory process . Here , we assessed if the levels of high-sensitivity C-reactive protein ( hs-CRP ) in serum could constitute an effective method for detecting systemic inflammation during endometriosis . STUDY DESIGN This was a prospect i ve , laboratory-based study , which was carried out in a tertiary care university hospital . Patients with histologically proven endometriosis ( n = 370 ) and unaffected women ( n = 464 ) were enrolled from January 2005 through December 2009 . We performed complete surgical excision of endometriotic lesions with pathological analysis . In addition , hs-CRP levels were determined through a particle-enhanced immunoturbidimetric method . The hs-CRP levels were measured in both controls and women with endometriosis according to the established surgical classifications of endometriosis : superficial peritoneal endometriosis , endometrioma , and deep infiltration endometriosis . Also , hs-CRP levels were evaluated according to hormonal treatment and menstrual cycle . RESULTS The hs-CRP serum levels did not statistically differ between women with endometriosis and controls ( median in ng/mL [ range ] : 0.82 [ 0.04 - 42.89 ] vs 0.9 [ 0.03 - 43.73 ] , respectively ; P = .599 ) . Moreover , subgroup analysis revealed no difference among superficial peritoneal endometriosis , endometrioma , deep infiltration endometriosis , and controls : 0.8 ( 0.15 - 13.35 ) , 0.81 ( 0.04 - 38.82 ) , 0.83 ( 0.09 - 42.89 ) , and 0.9 ( 0.03 - 43.73 ) , respectively ; P = .872 . Furthermore , no effect was observed regarding hormonal treatment or menstrual cycle . CONCLUSION Although endometriosis is an inflammatory disease , we failed to identify any systemic changes in hs-CRP serum levels . Therefore , hs-CRP analysis appears to be irrelevant to the diagnosis and staging of endometriosis OBJECTIVE This study analyzed the relationship between clinical characteristics of endometriosis and Th1/Th2 immune response patterns . METHODS A prospect i ve study was performed with 65 patients with endometriosis ( Group A ) and 33 without the disease ( Group B ) . Measurement of IL 2 , 4 and 10 , TNF-alpha and IFN-gamma was carried out in peripheral blood and peritoneal fluid . RESULTS Serum TNF-alpha was higher in patients with endometriosis who had deep dyspareunia compared to controls ( mean 4.5 pg/ml and 2.3 pg/ml , p<0.05 ) . Among these patients ( n=32 ) , 65.5 % had deep endometriosis . Patients with endometriosis and infertility had higher IL-2 concentrations in peritoneal fluid than controls ( mean 5.9 pg/ml and 0.2 pg/ml , p<0.05 ) . Among these patients ( n=22 ) , 63.5 % ( n=14 ) had deep endometriosis . A higher concentration of IL-10 was also observed in patients with ovarian endometriosis when compared to those without this type of disease , as well as when compared to control group patients ( mean 50 pg/ml , 18.7 pg/ml and 25.7 pg/ml , p<0.05 ) . CONCLUSIONS These results suggest that when specific clinical data are associated with a higher production of certain cytokines , there is a Th1 response pattern that may be related to deep infiltrating endometriosis The purpose of this study was to investigate the frequency of antibodies in the serum of patients with endometriosis reacting with endometrial , ovarian , thyroid and skeletal muscle antigens . A total of 55 fertile patients with pelvic pain who had endometriosis diagnosed by laparoscopy and confirmed by histology formed the study group , while 43 fertile patients without pelvic pain and undergoing tubal sterilization formed the control group . Eutopic endometrial membrane antigen was prepared from biopsies taken from patients or controls by an ultracentrifugation technique and used in an enzyme-linked immunosorbent assay ( ELISA ) for immunoglobulin ( Ig ) G , IgA and IgM endometrial antibodies . Ovarian , thyroid and skeletal muscle antigens were prepared similarly and used in an ELISA . There was a significant difference in the prevalence of IgG antibodies to eutopic endometrial antigens derived from either control or endometriosis patients ( P < 0.05 ) . IgA or IgM antibodies against endometrial antigens were not detected . Endometrial antibodies were detectable in both the luteal and the follicular phases of the menstrual cycle . Immunoblot analysis demonstrated the presence of endometrial antigens with molecular weights of 60 and 66 kDa in the eutopic endometrium of patients with endometriosis . Antibodies to thyroid , ovary or skeletal muscle were not detected in these patients . These findings indicate that endometrial antibodies of the IgG class can be detected in approximately 50 % of patients with endometriosis but it remains unclear whether these represent a pathologically distinct subgroup of such patients OBJECTIVE To examine the expression of gremlin-1 ( GREM1 ) on the levels of messenger RNA ( mRNA ) and protein in eutopic endometrium and its serum level in patients with endometriosis . DESIGN Prospect i ve , experimental study using reverse-transcription polymerase chain reaction , Western blot , immunofluorescence , and ELISA . SETTING Gynecological oncology laboratory in a department of obstetrics and gynecology in a medical college in China . PATIENT(S ) Thirty-five patients with endometriosis and 23 healthy control women . INTERVENTION(S ) During surgery , the eutopic endometria and peripheral serum were obtained from the patients with endometriosis and the control women . MAIN OUTCOME MEASURE(S ) The cellular compartment location of GREM1 expression was examined by using immunofluorescent double staining . The expression levels of mRNA and protein for GREM1 were determined by reverse-transcription polymerase chain reaction and Western blot , respectively . The serum level of GREM1 was measured by indirect ELISA . RESULT ( S ) The expression of GREM1 was defined within endometrial blood vessel endothelium exclusively , with the concomitant expressions of GREM1 and CD146 . The expression of GREM1 on the levels of mRNA and protein was significantly higher in eutopic endometria of patients with endometriosis than in those from healthy control women . According to the ELISA established in our laboratory , the concentration of GREM1 in peripheral serum that was collected during the follicular menstrual phase of patients with endometriosis was significantly higher than that in serum from healthy control women . CONCLUSION ( S ) Gremlin-1 plays a role to some extent in the aberrant angiogenesis of eutopic endometrium in patients with endometriosis . It is possible that the peripheral serum level of GREM1 is a prospect i ve serum biomarker of endometriosis Vascular endothelial growth factor ( VEGF ) serum levels and VEGF and cellular expression were prospect ively analyzed in 60 patients ( group A consisted of asymptomatic patients or patients presenting mild dysmenorrhea ; 30 women comprised group B severe dysmenorrhea and /or chronic pelvic pain and /or dyspareunia ) who underwent surgery for cystic ovarian endometriosis to asses whether a correlation exists among VEGF serum levels , VEGF cellular expression , and pelvic pain . No differences were found in VEGF serum levels and VEGF cellular expression between both groups . Therefore , we conclude that pain symptoms in ovarian endometriosis are not correlated with VEGF serum levels and VEGF cellular expression OBJECTIVE : To test the hypothesis that differential surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein or peptide expression in plasma can be used in infertile women with or without pelvic pain to predict the presence of laparoscopically and histologically confirmed endometriosis , especially in the sub population with a normal preoperative gynecologic ultrasound examination . METHODS : Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry analysis was performed on 254 plasma Output:	A subset of blood biomarkers could prove useful either for detecting pelvic endometriosis or for differentiating ovarian endometrioma from other benign ovarian masses , but there was insufficient evidence to draw meaningful conclusions . Overall , none of the biomarkers displayed enough accuracy to be used clinical ly outside a research setting .
MS21076	*TASK* the task is to summarize an input biomedical literature in six sentences *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 prevalence of systemic hypertension and its cardiovascular consequences is higher in African-Americans than in whites . Low to moderate intensity aerobic exercise lowers blood pressure ( BP ) in African-American patients with severe hypertension . It is not known whether such exercise can improve lipid metabolism in these patients . Thirty-six African-American men with established essential hypertension , aged 35 to 76 years , were r and omly assigned to an exercise ( n = 17 ) or no exercise ( n = 19 ) group . The exercise group exercised for 16 weeks , 3 times/week , at 60 % to 80 % of maximum heart rate . After 16 weeks , peak oxygen uptake in the exercise group improved ( 21+/-4 vs 23+/-3 ml/kg/min ; p < 0.001 ) . Body weight did not change . Exercise intensity correlated with high-density lipoprotein ( HDL ) cholesterol changes from baseline to 16 weeks ( r = 0.65 ; p < 0.01 ) and was the strongest predictor of these changes ( R2 = 0.4 ; p = 0.009 ) . Lipoprotein-lipid changes in the 2 r and omized groups did not differ significantly . A 10 % increase in HDL cholesterol--42+/-19 versus 46+/-19 mg/dl ; p = 0.003 - -noted in 10 patients who exercised > or = 75 % of maximal heart rate suggested the existence of an exercise intensity threshold . Thus low to moderate intensity aerobic exercise may not be adequate to modify lipid profiles favorably in patients with severe hypertension . However , substantial changes in HDL cholesterol were noted in patients exercising at intensities > or = 75 % of age-predicted maximum heart rate , suggesting an exercise-intensity threshold Background Tailored health communications to date have been based on a rather narrow set of theoretical constructs . Purpose This study was design ed to test whether tailoring a print-based fruit and vegetable ( F & V ) intervention on relatively novel constructs from self-determination theory ( SDT ) and motivational interviewing ( MI ) increases intervention impact , perceived relevance , and program satisfaction . The study also aim ed to explore possible user characteristics that may moderate intervention response . Methods African American adults were recruited from two integrated health care delivery systems , one based in the Detroit Metro area and the other in the Atlanta Metro area , and then r and omized to receive three tailored newsletters over 3 months . One set of newsletters was tailored only on demographic and social cognitive variables ( control condition ) , whereas the other ( experimental condition ) was tailored on SDT and MI principles and strategies . The primary focus of the newsletters and the primary outcome for the study was fruit and vegetable intake assessed with two brief self-report measures . Preference for autonomy support was assessed at baseline with a single item : “ In general , when it comes to my health I would rather an expert just tell me what I should do ” . Most between-group differences were examined using change scores . Results A total of 512 ( 31 % ) eligible participants , of 1,650 invited , were enrolled , of which 423 provided complete 3-month follow-up data . Considering the entire sample , there were no significant between-group differences in daily F & V intake at 3 month follow-up . Both groups showed similar increases of around one serving per day of F & V on the short form and half a serving per day on the long form . There were , however , significant interactions of intervention group with preference for autonomy-supportive communication as well as with age . Specifically , individuals in the experimental intervention who , at baseline , preferred an autonomy-supportive style of communication increased their F & V intake by 1.07 servings compared to 0.43 servings among controls . Among younger controls , there was a larger change in F & V intake , 0.59 servings , than their experimental group counterparts , 0.29 servings . Conversely , older experimental group participants showed a larger change in F & V , 1.09 servings , than older controls , 0.48 . Conclusion Our study confirms the importance of assessing individual differences as potential moderators of tailored health interventions . For those who prefer an autonomy-supportive style of communication , tailoring on values and other motivational constructs can enhance message impact and perceived relevance We examined race-specific weight-loss results from two r and omized , multicenter trials ; the Hypertension Prevention Trial ( HPT ) and the Trials of Hypertension Prevention ( TOHP ) . Mean weight change from baseline averaged 2.2 kg less in black women than in white women during 18 mo of follow-up in TOHP and 2.7 kg less during 36 mo of follow-up in HPT . Mean weight loss averaged 2.0 kg less in black than in white men in TOHP and 1.4 kg less in HPT . Because of greater weight gain in black control subjects , a comparison of net weight loss ( change in intervention minus change in control participants , within-race ) showed a less marked difference than did black-white differences in weight loss within the actively treated group . Thus , relative to weight that would have been gained without the intervention , the experience of blacks and whites was more similar . Racial differences in weight loss may result from a combination of behavioral , sociocultural , biological , and programmatic factors OBJECTIVE To identify African American cultural characteristics that may be used to modify clinical trial design s and behavioral programs aim ed at losing weight and maintaining weight loss . DESIGN Focus group discussion s. SETTING University-affiliated biomedical research center . PARTICIPANTS Thirty-one African American men and women who completed the screening process , but were ineligible for the Weight Loss Maintenance ( WLM ) trial , participated in one of five focus group sessions . WLM is a r and omized controlled trial that compares two lifestyle interventions for preventing weight regain in individuals who have successfully lost weight in a group-based behavioral weight loss program . RESULTS Nine themes emerged as cultural characteristics specific to African Americans seeking participation in a lifestyle change program : ( 1 ) religion is a powerful force ; ( 2 ) family structure ; ( 3 ) integration dismantled the African American family ; ( 4 ) general mistrust of Caucasians ; ( 5 ) African Americans are undervalued and not respected as a people ; ( 6 ) limited re sources equal limited ability to make lifestyle changes ; ( 7 ) preservation of an explicit ethnic identity ; ( 8) education is the key to success as an African American ; and ( 9 ) communication skills are vital . CONCLUSIONS Identifying cultural characteristics specific to African Americans may help investigators design clinical trials that will enhance outcomes and improve the generalizability of results in ethnic minority population PURPOSE Communities That Care ( CTC ) is a prevention system design ed to reduce levels of adolescent delinquency and substance use through the selection and use of effective preventive interventions tailored to a community 's specific profile of risk and protection . This article describes early findings from the first group-r and omized trial of CTC . METHODS A panel of 4407 fifth- grade students was surveyed annually through seventh grade . Analyses were conducted to assess the effects of CTC on reducing levels of targeted risk factors and reducing initiation of delinquent behavior and substance use in seventh grade , 1.67 years after implementing preventive interventions selected through the CTC process . RESULTS Mean levels of targeted risks for students in seventh grade were significantly lower in CTC communities compared with controls . Significantly fewer students in CTC communities than in control communities initiated delinquent behavior between grade s 5 and 7 . No significant intervention effect on substance use initiation by spring of seventh grade was observed . CONCLUSIONS CTC 's theory of change hypothesizes that it takes from 2 to 5 years to observe community-level effects on risk factors and 5 or more years to observe effects on adolescent delinquency or substance use . The early findings indicating hypothesized effects of CTC on targeted risk factors and initiation of delinquent behavior are promising Disengagement beliefs function to reduce cognitive dissonance and a number of predictions with regard to disengagement beliefs have been tested and verified . However , the influence of disengagement beliefs on persuasion has not been studied yet . In a field-experiment , 254 smokers were r and omly assigned to a persuasive message condition or a no-information control condition . First , it was assessed to what extent disengagement beliefs influenced persuasion . In smokers with low adherence to disengagement beliefs , quitting activity ( attempting to quit ) in the control condition was high , but this was not further increased by persuasive information on the negative outcomes of smoking . In contrast , smokers who strongly adhered to disengagement beliefs showed low quitting activity in the control condition , but significantly more quitting activity when they received the persuasive message . Second , it was studied what smokers do when they experience negative affect caused by the persuasive message . The results show that in smokers who strongly adhered to disengagement beliefs , negative affect was associated with less quitting activity . Although these results show that quitting activity as assessed at 2 and 8 months follow-ups was influenced by disengagement beliefs , point prevalence seven-day quitting was not . This study shows that adherence to disengagement beliefs is a relevant individual difference in underst and ing effects of smoking cessation interventions OBJECTIVE To evaluate a weight loss and exercise program design ed to improve diabetes management in older African-Americans . RESEARCH DESIGN AND METHODS Overweight African-Americans ( n = 64 ) ages 55–79 years with NIDDM were r and omized to either an intervention ( 12 weekly group sessions , 1 individual session , and 6 biweekly group sessions ) or usual care ( 1 class and 2 informational mailings ) . Clinical and behavioral variables were assessed at 0 , 3 , and 6 months of treatment . RESULTS Significant net differences in the intervention versus usual care were observed for weight ( −2.0 kg , P = 0.006 ) , physical activity , and dietary intake of fat , saturated fat , cholesterol , and nutrition knowledge at 3 months ( all P < 0.05 ) and for weight at 6 months ( −2.4 kg ; P = 0.006 ) and mean HbA1c values at 3 and 6 months ( respectively , −1.6 and −2.4 % , both P < 0.01 ) . After the adjustment for changes in weight and activity , the intervention participants were ∼ twice as likely to have a one unit decrease in HbA1c value as those in usual care . Blood pressure increase sin usual care participants result ed in net differences ( intervention minus control ) at 3 and 6 months of −3.3 ( P = 0.09 ) and −4.0 ( P = 0.05 ) mmHg diastolic , respectively , and −8.4 ( P = 0.06 ) and −5.9 ( P > 0.10 ) mmHg systolic , respectively . Blood lipid profiles improved more in intervention than usual care participants , but not significantly . CONCLUSIONS The intervention program was effective in improving glycemic and blood pressure control . The decrease in HbA1c values was generally independent of the relatively modest changes in dietary intake , weight , and activity and may reflect indirect program effects on other aspects of self-care BACKGROUND African Americans have lower rates of physical activity ( PA ) than Caucasians . Although correlates of PA have been studied in many population s , little is known about the influences on physical activity for African Americans , particularly African-American men . METHODS Individuals were r and omly selected from 20 church rosters and participated in a telephone survey ( 165 men , 407 women ) in May to September 2003 . Participants were classified according to whether they were meeting recommendations for moderate to vigorous physical activity , walking , and strength training . Sociodemographic , health , psychosocial , and physical environment correlates were also assessed . Mixed-model logistic regression analyses were conducted . RESULTS For men , explained variance ranged from 20.8 % to 33.3 % . For women , the independent variables explained 10.8 % to 23.2 % of the variance in physical activity behavior . Significant positive correlates among men were employment , income , self-rating of health , PA self-efficacy , and PA enjoyment , and fruit and vegetable intake , with age as a negative correlate . Significant positive correlates among women were employment , education , income , self-rating of health , PA self-efficacy , PA enjoyment , fruit and vegetable intake , reporting PA programs at their church , and attempting weight loss . Negative correlates included age , number of chronic health conditions , and body mass index . CONCLUSIONS Various factors influenced PA in men and women , suggesting a need for gender targeting in addition to cultural adaptations in PA interventions for African Americans Sodium reduction is efficacious for primary prevention of hypertension , but the feasibility of achieving this effect is unclear . The objective of the paper is detailed analyses of adherence to and effects of the sodium reduction intervention among overweight adults in the Trials of Hypertension Prevention , Phase II . Sodium reduction ( comprehensive education and counselling about how to reduce sodium intake ) was tested vs no dietary intervention ( usual care ) for 36–48 months . A total of 956 white and 203 black adults , ages 30–54 years , with diastolic blood pressure 83–89 mmHg , systolic blood pressure ( SBP ) < 140 mmHg , and body weight 110–165 % of gender-specific st and ard weight were included in the study . At 36 months , urinary sodium excretion was 40.4 mmol/24 h ( 24.4 % ) lower in sodium reduction compared to usual care participants ( P<0.0001 ) , but only 21 % of sodium reduction participants achieved the targeted level of sodium excretion below 80 mmol/24 h. Adherence was positively related to attendance at face-to-face contacts . Net decreases in SBP at 6 , 1 Output:	Although the available evidence appears to show that these interventions produce positive results , the relative and the long-term effectiveness of weight loss , dietary and /or physical activity interventions for this population are unknown
MS21077	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Despite negative outcomes for depressed mothers and their children , no treatment specifically design ed to address maternal depression in the context of home visitation has emerged . In-Home Cognitive Behavioral Therapy ( IH-CBT ) is an adapted treatment that is delivered in the home , focuses on the needs of new mothers , and leverages ongoing home visiting to optimize engagement and outcomes . This study examined the efficacy of IH-CBT using a r and omized clinical trial . Subjects were 93 new mothers in a home visiting program . Mothers with major depressive disorder identified at 3months postpartum were r and omized into IH-CBT and ongoing home visitation ( n=47 ) or st and ard home visitation ( SHV ; n=46 ) in which they received home visitation alone and could obtain treatment in the community . Depression was measured at pre- and posttreatment , and 3-month follow-up using interviews , clinician ratings , and self-report . Mothers receiving IH-CBT showed improvements in all indicators of depression relative to the SHV condition and these gains were maintained at follow-up . For example , 70.7 % of mothers receiving IH-CBT were no longer depressed at posttreatment in terms of meeting criteria for major depressive disorder compared to 30.2 % in the SHV group . These findings suggest that IH-CBT is an efficacious treatment for depressed mothers in home visitation programs Abstract STUDY QUESTION How does the psychological well-being and prenatal bonding of Indian surrogates differ from a comparison group of mothers ? SUMMARY ANSWER Surrogates had higher levels of depression during pregnancy and post-birth , displayed lower emotional connection with the unborn baby , and greater care towards the healthy growth of the foetus , than the comparison group of mothers . WHAT IS ALREADY KNOWN Studies in the West have found that surrogates do not suffer long-term psychological harm . One study has shown that surrogates bond less with the foetus than expectant mothers . STUDY , DESIGN , SIZE , DURATION This study uses a prospect i ve , longitudinal and cross-sectional design . Surrogates and a matched group of expectant mothers were seen twice , during 4–9 months of pregnancy and 4–6 months after the birth . PARTICIPANTS / MATERIAL S , SETTING , METHODS Semi-structured interviews and st and ardized question naires were administered to 50 surrogates and 69 expectant mothers during pregnancy and 45 surrogates and 49 expectant mothers post-birth . All gestational surrogates were hosting pregnancies for international intended parents . MAIN RESULTS AND THE ROLE OF CHANCE Surrogates had higher levels of depression compared to the comparison group of mothers , during pregnancy and post-birth ( P < 0.02 ) . Low social support during pregnancy , hiding surrogacy and criticism from others were found to be predictive of higher depression in surrogates post-birth ( P < 0.05 ) . Regarding prenatal bonding , surrogates interacted less with and thought less about the foetus but adopted better eating habits and were more likely to avoid unhealthy practice s during pregnancy , than expectant mothers ( P < 0.05 ) . No associations were found between greater prenatal bonding and greater psychological distress during pregnancy or after relinquishment . LIMITATIONS , REASONS FOR CAUTION All surrogates were recruited from one clinic in Mumbai , and thus the representativeness of this sample is not known . Also , the possibility of socially desirable responding from surrogates can not be ruled out . WIDER IMPLICATION S OF THE FINDINGS As this is the first study of the psychological well-being of surrogates in low-income countries , the findings have important policy implication s. Providing support and counselling to surrogates , especially during pregnancy , may alleviate some of the psychological problems faced by surrogates . STUDY FUNDING /COMPETING INTEREST(S ) This study was supported by the Wellcome Trust [ 097857/Z/11/Z ] and Nehru Trust , Cambridge . K.K. is the Medical Director of Corion Fertility Clinic . All other authors have no conflict of interest to declare The prevalence of postpartum depression is approximately 13 % . Postpartum depression is associated with a higher maternal morbidity and mortality , and also with pervasive effects on the emotional , cognitive and behavioral development of the child . The aim of our study was to identify socio-demographic , psychosocial and obstetrical risk factors of postpartum depression in a middle class community sample , using a prospect i ve design . We enrolled consecutively 312 pregnant out patients in a single maternity unit . The first assessment was conducted between 32 and 41 weeks gestation , and a second time between 6 and 8 weeks after delivery . Depressive symptoms were measured using the French version of the Edinburgh Postnatal Depression Scale ( EPDS ) . A cut-off score of 12/30 or above was considered as indicative of Major Depression . Of the initial sample of 312 women , 264 ( 84.6 % ) were followed-up between 6 and 8 weeks after delivery and considered for analysis . Depression during pregnancy , migrant status , and physical abuse by the partner were independently associated with postpartum depression when considered together , whereas physical complications were significantly associated with postpartum depression only when adjusting for antenatal depression . Depression during pregnancy , history of physical abuse , migrant status and postpartum physical complications are four major risk factors for postpartum depression BACKGROUND Peripartum anxiety and depressive disorders are associated with adverse consequences for mother and child . Thus , it is important to examine risk factors , correlates and course patterns of anxiety and depressive disorders during pregnancy and after delivery . METHODS In the prospect ive-longitudinal Maternal Anxiety in Relation to Infant Development ( MARI ) Study , n=306 expectant mothers were recruited from gynaecological outpatient setting s in Germany and completed up to seven waves of assessment from early pregnancy until 16 months postpartum . Anxiety and depressive disorders and potential risk factors/correlates were assessed with the Composite International Diagnostic Interview for Women ( CIDI-V ) , medical records and additional question naires . RESULTS Although peripartum anxiety and depressive disorders appeared to be persistent in some women , others reported major changes with heterogeneous courses and shifts between diagnoses and contents . There was a considerable amount of incident disorders . Strongest predictors for peripartum anxiety and depressive disorders were anxiety and depressive disorders prior to pregnancy , but psychosocial ( e.g. maternal education ) , individual ( e.g. low self-esteem ) , and interpersonal ( e.g. partnership satisfaction , social support ) factors were also related . LIMITATION Knowing the aims of the study , some participants may have been more encouraged to report particular symptoms , but if so , this points to the importance of a comprehensive assessment in perinatal care . CONCLUSION Peripartum time is a sensitive period for a considerable incidence or persistence/recurrence of anxiety and depressive disorders albeit the course may be rather heterogeneous . Interventional studies are needed to examine whether an alteration of associated factors could help to prevent peripartum anxiety and depressive disorders OBJECTIVE To determine whether a correlation exists between prenatal and postnatal attachment . DESIGN Prospect i ve , correlational study with data collected during the second half of pregnancy and again 1 - 2 months after delivery . SETTING / PARTICIPANTS Two hundred twenty-eight women were recruited from childbirth education classes . The women were generally young , white , well educated , married , and employed . MAIN OUTCOME MEASURES The Prenatal Attachment Inventory ( PAI ) was used to measure attachment before birth . The Maternal Attachment Inventory ( MAI ) , the How I Feel About my Baby Now Scale , and the Maternal Separation Anxiety Scale were used to measure attachment after birth . RESULTS One hundred ninety-six women completed all the measures . A correlation was found between PAI and MAI scores ( r = 0.41 , p < 0.001 ) . CONCLUSIONS A correlation between prenatal and postnatal attachment was found . However , the modest size of the correlation indicated that other factors also influenced postnatal scores . Thus , caution should be exercised when promoting increased prenatal attachment in hopes of improving postnatal attachment Background While the importance of the infant-parent relationship from the child ’s perspective is acknowledged worldwide , there is still a lack of knowledge about predictors and long-term benefits or consequences of the quality of parent-infant relationships from the parent ’s perspective . The purpose of this prospect i ve study is to investigate the quality of parent-infant relationships from parents ’ perspectives , both in the prenatal and postpartum period . This study therefore focuses on prenatal ( risk ) factors that may influence the quality of pre- and postnatal bonding , the transition to parenthood , and bonding as a process within families with young children . In contrast to most research concerning pregnancy and infant development , not only the roles and experiences of mothers during pregnancy and the first two years of infants ’ lives are studied , but also those of fathers . Methods / design The present study is a prospect i ve longitudinal cohort study , in which pregnant women ( N = 466 ) and their partners ( N = 319 ) are followed from 15 weeks gestation until their child is 24 months old . During pregnancy , midwives register the presence of prenatal risk factors and provide obstetric information after the child ’s birth . Parental characteristics are investigated using self-report question naires at 15 , 26 , and 36 weeks gestational age and at 4 , 6 , 12 , and 24 months postpartum . At 26 weeks of pregnancy and at 6 months postpartum , parents are interviewed concerning their representations of the ( unborn ) child . At 6 months postpartum , the mother-child interaction is observed in several situations within the home setting . When children are 4 , 6 , 12 , and 24 months old , parents also completed question naires concerning the child ’s ( social-emotional ) development and the parent-child relationship . Additionally , at 12 months information about the child ’s physical development and well-being during the first year of life is retrieved from National Health Care Centres . Discussion The results of this study may contribute to early identification of families at risk for adverse parent-infant relationships , infant development , or parenting . Thereby this study will be relevant for the development of policy , practice , and theory concerning infant mental health BACKGROUND Depression is common in low-income pregnant women , and treatments need to be fitted to meet their needs . We conducted a r and omized controlled trial comparing brief Interpersonal Psychotherapy ( brief-IPT ) to enhanced treatment as usual ( ETAU ) for perinatal depression in low-income women . The brief-IPT model is design ed to better engage low-income women by utilizing an engagement session , providing flexible delivery of sessions , and pragmatic case management . METHODS Pregnant women , aged ≥18 , between 12 and 30 weeks gestation were recruited from an urban prenatal clinic . Women scoring ≥10 on the Edinburgh Depression Scale and meeting depressive disorder criteria were r and omized to either brief-IPT ( n=21 ) or ETAU ( n=21 ) . We assessed treatment outcomes , acceptability , and feasibility of the intervention ( measured by session attendance ) . RESULTS Depression scores significantly decreased in both brief-IPT and ETAU . Brief-IPT participants reported significant improvements in social support satisfaction as compared to ETAU participants , even after controlling for concurrent depressive symptoms . Brief-IPT participants reported high satisfaction with the program . However , many participants did not participate in the full 9-session course of treatment ( average sessions attended = 6 , range 0 - 17 ) . LIMITATIONS Small sample size , use of self-report measures , and lack of an active psychotherapy control group limits interpretation of study results . CONCLUSIONS Brief-IPT for perinatal depression is acceptable to low-income women and is helpful for improving depressive symptoms and social support . However , feasibility of the treatment was limited by relatively low session attendance in spite of efforts to maximize treatment engagement . Additional modifications to meet the needs of low-income women are discussed In this study , we investigated the psychometric qualities of the Dutch version of the Maternal Antenatal Attachment Scale ( MAAS ) . In a monocentric prospect i ve observational cohort study , 403 expectant mothers completed a booklet with question naires in the first ( T1 ) , second ( T2 ) , and third ( T3 ) pregnancy trimesters . In addition to the MAAS ( T1-T3 ) , the following measures were used : the Marlowe-Crowne Social Desirability Scale ( T1 ) , the Parental Bonding Inventory ( T1 ) , the Relationship Question naire ( T1 ) the Facilitator scale and the Regulator scale ( T3 ) , the Edinburgh Postnatal Depression Scale ( T1-T3 ) and the Pregnancy Related Anxiety Question naire ( T1-T3 ) . In this study , the mean of the MAAS scales increased as the pregnancy progressed . Good internal reliabilities were found for the Total MAAS scale , the Quality subscale and the Preoccupation subscale . Small-to-moderate correlations were found with social desirability , maternal orientation , parental care and adult attachment . Maternal mood was weakly associated with the quality but not with the intensity of the maternal attachment feelings . Overall , our findings suggest that the Dutch version of the Maternal Antenatal Attachment Scale is a reliable and valid measure of the early emotional tie between a pregnant woman and her unborn child OBJECTIVE To investigate the association between the magnitude of foetal movements and level of prenatal attachment within a 24h period among women in the third trimester of pregnancy . DESIGN a prospect i ve population -based survey . SET Output:	Specifically , prenatal depressive symptoms were found to be negatively associated with prenatal attachment . Furthermore , lower levels of prenatal attachment were related to higher postnatal depressive symptoms , although fewer studies assessed this association .
MS21078	*TASK* the task is to summarize an input biomedical literature in six sentences *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 many r and omized trials of the collaborative care model for improving depression in primary care have not described the implementation and maintenance of this model . This paper reports how and the degree to which collaborative care process changes were implemented and maintained for the 75 primary care clinics participating in the DIAMOND Initiative ( Depression Improvement Across Minnesota – Offering a New Direction ) . Methods Each clinic was trained to implement seven components of the model and participated in ongoing evaluation and facilitation activities . For this study , assessment of clinical process implementation was accomplished via completion of surveys by the physician leader and clinic manager of each clinic site at three points in time . The physician leader of each clinic completed a survey measure of the presence of various practice systems prior to and one and two years after implementation . Clinic managers also completed a survey of organizational readiness and the strategies used for implementation . Results Survey response rates were 96 % to 100 % . The systems survey confirmed a very high degree of implementation ( with large variation ) of DIAMOND depression practice systems ( mean of 24.4 ± 14.6 % ) present at baseline , 57.0 ± 21.0 % at one year ( P = < 0.0001 ) , and 55.9 ± 21.3 % at two years . There was a similarly large increase ( and variation ) in the use of various quality improvement strategies for depression ( mean of 29.6 ± 28.1 % at baseline , 75.1 ± 22.3 % at one year ( P = < 0.0001 ) , and 74.6 ± 23.0 % at two years . Conclusions This study demonstrates that under the right circumstances , primary care clinics that are prepared to implement evidence -based care can do so if financial barriers are reduced , effective training and facilitation are provided , and the new design introduces the specific mental models , new care processes , and workers and expertise that are needed . Implementation was associated with a marked increase in the number of improvement strategies used , but actual care and outcomes data are needed to associate these changes with patient outcomes and patient-reported care OBJECTIVE A r and omized trial assessed the effectiveness of a 2-level strategy for implementing evidence -based mental health treatments for delinquent youth . METHOD A 2 x 2 design encompassing 14 rural Appalachian counties included 2 factors : ( a ) the r and om assignment of delinquent youth within each county to a multisystemic therapy ( MST ) program or usual services and ( b ) the r and om assignment of counties to the ARC ( for availability , responsiveness , and continuity ) organizational intervention for implementing effective community-based mental health services . The design created 4 treatment conditions ( MST plus ARC , MST only , ARC only , control ) . Outcome measures for 615 youth who were 69 % male , 91 % Caucasian , and aged 9 - 17 years included the Child Behavior Checklist and out-of-home placements . RESULTS A multilevel , mixed-effects , regression analysis of 6-month treatment outcomes found that youth total problem behavior in the MST plus ARC condition was at a non clinical level and significantly lower than in other conditions . Total problem behavior was equivalent and at non clinical levels in all conditions by the 18-month follow-up , but youth in the MST plus ARC condition entered out-of-home placements at a significantly lower rate ( 16 % ) than youth in the control condition ( 34 % ) . CONCLUSIONS Two-level strategies that combine an organizational intervention such as ARC and an evidence -based treatment such as MST are promising approaches to implementing effective community-based mental health services . More research is needed to underst and how such strategies can be used effectively in a variety of organizational context s and with other types of evidence -based treatments OBJECTIVES We evaluated an education , distribution , and fitting program for increasing age-appropriate and correct child restraint use . METHODS We performed a cluster r and omized trial involving 28 early childhood education centers in low socioeconomic status areas in Sydney , Australia . The main outcome was optimal restraint use defined as age-appropriate restraints , installed into the vehicle correctly and used correctly . RESULTS One service withdrew after r and omization , so data are presented for 689 child passengers , aged 3 to 5 years , from 27 centers . More children attending intervention centers were optimally restrained ( 43 % vs 31 % ; P = .01 ; allowing for clustering ) . More 3-year-olds were using forward-facing seats rather than booster seats , more 4- to 5-year-olds were using booster seats instead of seat belts alone , and there were fewer errors in use at intervention centers . Among non-English-speaking families , more children attending intervention centers were optimally restrained ( 43 % vs 17 % ; P = .002 ; allowing for clustering ) . CONCLUSIONS The program increased use of age-appropriate restraints and correct use of restraints , which translates to improved crash injury protection . Multifaceted education , seat distribution , and fitting enhanced legislation effects , and the effect size was larger in non-English-speaking families PURPOSE The aim of this paper is to identify initial barriers influencing implementation of supported employment ( SE ) . SE , according to the individual placement and support ( IPS ) approach , has been recognised as an evidence -based method to help people with severe mental illness to find regular employment . DESIGN / METHODOLOGY /APPROACH A systematic implementation evaluation of the first r and omised controlled SE ( IPS ) trial in Sweden was conducted in August 2008 and August 2009 . Data were collected on a regular basis from SE employment specialists , process heads , clients and representatives from mental health care units and vocational services ( social insurance and public employment offices ) using interviews , non-participant observations and document analysis . FINDINGS SE employment specialists reported that existing regulations for social insurance and employment regulations presented major obstacles to implementation . Difficulties were reported in cooperation with h and ling officers at the vocational services . Scepticism towards persons with mental illness was common and employers expected to receive subsidies if they hired a person with mental illness . SE participants expressed fear of losing their social benefits . ORIGINALITY/VALUE The results illuminate a collision between an innovative evidence -based practice and the existing systems for social benefits and work rehabilitation PURPOSE The objective of this study was to eluci date the effect of facilitation on practice outcomes in the 2-year patient-centered medical home ( PCMH ) National Demonstration Project ( NDP ) intervention , and to describe practice s ’ experience in implementing different components of the NDP model of the PCMH . METHODS Thirty-six family practice s were r and omized to a facilitated intervention group or a self-directed intervention group . We measured 3 practice -level outcomes : ( 1 ) the proportion of 39 components of the NDP model that practice s implemented , ( 2 ) the aggregate patient rating of the practice s ’ PCMH attributes , and ( 3 ) the practice s ’ ability to make and sustain change , which we term adaptive reserve . We used a repeated- measures analysis of variance to test the intervention effects . RESULTS By the end of the 2 years of the NDP , practice s in both facilitated and self-directed groups had at least 70 % of the NDP model components in place . Implementation was relatively harder if the model component affected multiple roles and processes , required coordination across work units , necessitated additional re sources and expertise , or challenged the traditional model of primary care . Electronic visits , group visits , team-based care , wellness promotion , and proactive population management presented the greatest challenges . Controlling for baseline differences and practice size , facilitated practice s had greater increases in adaptive reserve ( group difference by time , P = .005 ) and the proportion of NDP model components implemented ( group difference by time , P=.02 ) ; the latter increased from 42 % to 72 % in the facilitated group and from 54 % to 70 % in the self-directed group . Patient ratings of the practice s ’ PCMH attributes did not differ between groups and , in fact , diminished in both of them . CONCLUSIONS Highly motivated practice s can implement many components of the PCMH in 2 years , but apparently at a cost of diminishing the patient ’s experience of care . Intense facilitation increases the number of components implemented and improves practice s ’ adaptive reserve . Longer follow-up is needed to assess the sustained and evolving effects of moving independent practice s toward OBJECTIVE People with psychiatric impairments ( primarily schizophrenia or a mood disorder ) are the largest and fastest-growing group of Social Security Disability Insurance ( SSDI ) beneficiaries . The authors investigated whether evidence -based supported employment and mental health treatments can improve vocational and mental health recovery for this population . METHOD Using a r and omized controlled trial design , the authors tested a multifaceted intervention : team-based supported employment , systematic medication management , and other behavioral health services , along with elimination of barriers by providing complete health insurance coverage ( with no out-of-pocket expenses ) and suspending disability review s. The control group received usual services . Paid employment was the primary outcome measure , and overall mental health and quality of life were secondary outcome measures . RESULTS Overall , 2,059 SSDI beneficiaries with schizophrenia , bipolar disorder , or depression in 23 cities participated in the 2-year intervention . The teams implemented the intervention package with acceptable fidelity . The intervention group experienced more paid employment ( 60.3 % compared with 40.2 % ) and reported better mental health and quality of life than the control group . CONCLUSIONS Implementation of the complex intervention in routine mental health treatment setting s was feasible , and the intervention was effective in assisting individuals disabled by schizophrenia or depression to return to work and improve their mental health and quality of life Integrating Mental Health Services for Mothers of Children With Autism Autism is one of the most common childhood mental health conditions , affecting one child per 88 children . Although up to 40 % of mothers of children with autism report clinical ly significant depressive symptoms , there has been little attention to the mental health needs of parents . Because most autism services for young children rely on active parental engagement to deliver recommended therapies , maternal functioning directly affects the intensity and quality of therapy that children with autism receive . Developing feasible and acceptable strategies to support the mental health of mothers who care for children with autism has the potential to optimize both maternal and child functioning . In 2009 , as part of a clinical trial supported by the Combating Autism Act , our groupbegan to offer abrief , manualized cognitive-behavioral intervention— problem-solving education — to mothers of children with new autism diagnoses and whowere receiving early-intervention services authorized under Part C of the Individuals With Disabilities Education Act . Problem-solving education is an adaptation of an evidence -based depression treatment known as problemsolving therapy and is tailored to mothers of young children . It aims to strengthen an individual ’s problemsolving skills as a strategy to prevent depression and improve parental involvement in intensive autism-specific therapy . Experience supports the program ’s feasibility and provides a model to engage an at-risk group of parents in mental health services in a novel , home-based setting . Problem-solving education was integrated into the existing service delivery model of early intervention , which has a national infrastructure for replication and dissemination . Early intervention provides a flexible , individualized array of therapeutic services based on a child ’s needs and a family ’s goals . Family support is an explicit but not fully realized aim of early intervention . Authorizing legislation allows parents as well as children to receive services . Mothers ( N537 ) involved in this program received six individual problem-solving education sessions ( 30–45 minutes ) delivered biweekly at home as a supplement to early-intervention services . During each workbook-based session , mothers focused on one problem and worked through a series of problem-solving steps that included defining the problem , identifying a short-term achievable goal , brainstorming multiple solutions , evaluating their pros and cons , choosing the best solution , and developing an action plan . The most common problems that mothers selected to address were related to child rearing , followed by time management . Time spent providing problemsolving education was billed and reimbursed in the same way as other family support services . This flexibility in the early-intervention service delivery model supports opportunities for integrating parental mental health services into a nonstigmatizing setting . To support future replication and dissemination , we trained multidisciplinary early-intervention staff , many of whom did not have clinical mental health training , to deliver problem-solving education . Eighteen early-intervention staff completed a st and ardized training curriculum that included one day of didactics , followed by five practice sessions . All early-intervention staff achieved reliability within eight weeks . Fidelity was assessed in 34 r and omly selected problemsolving sessions that were audiotaped and scored with a st and ardized form and predetermined criteria . All sessions were judged to be of excellent quality . A major challenge confronted at the outset of the program was the belief that mothers of young children with a new diagnosis of autism would be too busy or overwhelmed to participate . The demographic characteristics of women who received problem-solving education suggested that the program successfully engaged mothers at risk of major depression . Of the 37 mothers who received problem-solving education , 75 % had incomes,200 % of federal poverty level and were from racial-ethnic minority groups ( 54 % ) . Almost a quarter ( 24 % ) of the mothers were born outside of the United States . Although mothers were not selected on the basis of depression risk , 35 % reported they had received a depression diagnosis in their lifetime and 68%had current symptoms . Seventy-five percent of mothers completed the full six sessions , supporting the program ’s acceptability . Satisfaction with the program and continued use of the skills learned in the program were evaluated at the nine-month followup assessment . Satisfaction was high ; participants reported using the problemsolving skills , such as thinking through pros and cons of solutions , and behavioral activation strategies almost weekly . Our experience supports the feasibility and acceptability of integrating parental Output:	Conclusions This is the first study to our knowledge to use a systematic review process to identify empirically observed external context factors documented to impact implementation .
MS21079	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Mechanisms explaining the decrease in circulatory cholesterol levels after weight loss remain ill defined . The objective was to examine effects of weight loss as achieved through energy restriction upon human in vivo cholesterol bio synthesis . Six subjects ( 64 - 77 y , body mass index , 30.3 + /- 3.8 kg/m(2 ) ) were recruited into a two-phase prospect i ve clinical trial . In the first phase , subjects complied with American Heart Association ( AHA ) Step I diets for 3 mo with no change in their usual energy intake . After this weight-stable phase , subjects consumed an AHA Step I diet with a targeted reduction in energy intake of approximately 1000 kJ/d for 6 mo to achieve negative energy balance leading to weight loss . The incorporation rate of deuterium from body water into erythrocyte membrane free cholesterol over 24 h was utilized as an index of cholesterogenesis at the end of both phases . Subjects ' mean weights decreased ( P < 0.05 ) from 89.3 + /- 12.5 kg to 83.2 + /- 11.5 kg ( 6.8 + /- 2.6 % of initial body weight ) across phases . Circulating concentrations of total and LDL-cholesterol , and triglycerides also decreased ( P < 0 . 05 ) across phases . HDL-cholesterol concentrations were unchanged ( P > 0.05 ) . Cholesterol fractional synthetic rate ( FSR ) after phase 2 ( 3.04 + /- 1.90%/d ) was lower ( P < 0.05 ) than that after phase 1 ( 8 . 42 + /- 3.90%/d ) . Absolute synthesis rate ( ASR ) after phase 2 [ 0.59 + /- 0.38 g/(kg . d ) ] also was lower ( P < 0.05 ) than that after phase 1 [ 1.66 + /- 0.84 g/(kg . d ) ] . These data suggest that , in obese men , energy restriction result ing in even modest weight loss suppresses endogenous cholesterol synthesis , which contributes to a decline in circulating lipid concentrations This study examined the effects of calorie alternation and exercise on weight loss . Moderately obese women ( 130 - 160 % of ideal body weight ) were r and omly assigned to an alternating- or constant-calorie diet with or without aerobic exercise . Both diets provided an average of 1200 kcal/d over a 12-wk period ; daily intake of subjects in the alternating-diet condition varied in a prescribed pattern from 600 to 1800 kcal/d . Exercising subjects walked 5 d/wk . All subjects participated in an intensive outpatient behavior-modification program . At the end of the study , exercised subjects had greater reductions in body weight and body fat percentage than did nonexercised subjects . The type of caloric restriction did not affect weight or fat loss . Changes in resting metabolic rate did not differ among groups . Alternating calories was neither beneficial nor detrimental as a weight-loss strategy whereas exercise was clearly beneficial in weight-loss therapy BACKGROUND Since many successful dieters regain the weight they lose , programs that teach maintenance skills are needed . We developed a maintenance program based on self-regulation theory and tested the efficacy of delivering the program face to face or over the Internet . METHODS We r and omly assigned 314 participants who had lost a mean of 19.3 kg of body weight in the previous 2 years to one of three groups : a control group , which received quarterly newsletters ( 105 participants ) , a group that received face-to-face intervention ( 105 ) , and a group that received Internet-based intervention ( 104 ) . The content of the programs in the two intervention groups was the same , emphasizing daily self-weighing and self-regulation , as was the frequency of contact with the groups . The primary outcome was weight gain over a period of 18 months . RESULTS The mean ( + /-SD ) weight gain was 2.5+/-6.7 kg in the face-to-face group , 4.7+/-8.6 kg in the Internet group , and 4.9+/-6.5 kg in the control group , with a significant difference between the face-to-face group and the control group ( 2.4 kg ; 95 % confidence interval [ CI ] , 0.002 to 10.8 ; P=0.05 ) . The proportion of participants who regained 2.3 kg or more over the 18-month period was significantly higher in the control group ( 72.4 % ) than in the face-to-face group ( 45.7 % ; absolute difference , 27 % ; 95 % CI , 14 to 39 ; P<0.001 ) or the Internet group ( 54.8 % ; absolute difference , 18 % ; 95 % CI , 5 to 30 ; P=0.008 ) . Daily self-weighing increased in both intervention groups and was associated with a decreased risk of regaining 2.3 kg or more ( P<0.001 ) . CONCLUSIONS As compared with receiving quarterly newsletters , a self-regulation program based on daily weighing improved maintenance of weight loss , particularly when delivered face to face . ( Clinical Trials.gov number , NCT00067145 [ Clinical Trials.gov ] . OBJECTIVE Conflicting recommendations are prevalent regarding the appropriateness of red meat versus white meat consumption for individuals aim ing to reduce body weight and cardiovascular disease risk . METHODS We examined changes in body weight and lipid profiles in a 12-wk , r and omized , controlled trial , in which overweight women followed a hypocaloric diet with lean beef or chicken as the primary protein source , while participating in a fitness walking program . Sedentary non-smoking females ( n = 61 ) , age 43.4 + /- 7.8 years , with body mass indexes of 32.1 + /- 3.4 kg/m(2 ) ( means + /- st and ard deviation ) , followed calculated-deficit diets ( -500 kcal daily ) and were r and omly assigned to the beef-consumption or chicken-consumption dietary group , while following a fitness walking program . Body weight , body composition ( by hydrodensitometry ) , and blood lipid profiles were measured at baseline and 12 wk . RESULTS Weight loss was significant within ( P < 0.05 ) but similar between ( P > 0.05 ) the beef-consumption ( 5.6 + /- 0.6 kg , mean + /- st and ard error ) and the chicken-consumption ( 6.0 + /- 0.5 kg ) groups . Both groups showed significant reductions in body fat percentage ( P < 0.05 ) and total ( P < 0.05 ) and low-density lipoprotein ( P < 0.05 ) cholesterol , with no significant differences between groups . High-density lipoprotein cholesterol did not change significantly in either group . CONCLUSIONS These findings demonstrated that weight loss and improved lipid profile can be accomplished through diet and exercise , whether the dietary protein source is lean beef or chicken OBJECTIVES To compare two different very low calorie diet (VLCD)-based weight maintenance strategies . DESIGN AND SETTING A r and omized 2-year clinical trial performed at the Department of Body Composition and Metabolism , Sahlgrenska University Hospital , Sweden . SUBJECTS A total of 334 patients , body mass index ( BMI ) > 30 kg m-2 , aged 18 - 60 years . INTERVENTIONS All the patients started with 16 VLCD weeks . Subjects in the intermittent group were then scheduled to use VLCD for 2 weeks every third month , whilst patients in the on-dem and group were instructed to use VLCD whenever their body weight passed an individualized cut-off level . Irrespective of the treatment group , all the subjects were recommended a hypocaloric diet during VLCD-free periods . MAIN OUTCOME MEASURES Changes in body weight , body composition , anthropometric variables and cardiovascular risk factors . RESULTS Completers in both groups maintained highly significant weight losses after 2 years : 7.0 + /- 11.0 kg ( 6.2 + /- 9.5 % ) in the intermittent group and 9.1 + /- 9.7 kg ( 7.7 + /- 8.1 % ) in the on-dem and group ( P < 0.001 , ns between groups ) . Male completers in the on-dem and group lost significantly more weight than men in the intermittent group , 14.5 + /- 11.0 kg vs. 4.0 + /- 10.5 kg , respectively ( P < 0.01 ) . Most cardiovascular risk factors improved during the first year , whilst anthropometric measures , insulin , HDL- and LDL-cholesterol were also significantly improved after 2 years of treatment . CONCLUSION Clinical ly significant weight reductions were achieved after 2 years of VLCD-based treatment . The structure of VLCD treatment during the maintenance phase did not affect weight loss in the total study population , whilst male subjects might benefit from the VLCD on-dem and strategy CONTEXT Weight loss using low-calorie diets produces variable results , presumably due to a wide range of energy deficits and low-dietary adherence . OBJECTIVE Our objective was to quantify the relationship between dietary adherence , weight loss , and severity of caloric restriction . DESIGN AND SETTING Participants were r and omized to diet only , diet-endurance training , or diet-resistance training until body mass index ( BMI ) was less than 25 kg/m(2 ) . PARTICIPANTS Healthy overweight ( BMI 27 - 30 ) premenopausal women ( n = 141 ) were included in the study . INTERVENTIONS An 800-kcal/d(-1 ) diet was provided , and the exercise groups were engaged in three sessions per week . MAIN OUTCOMES Dietary adherence , calculated from total energy expenditure determined by doubly labeled water measurements and dual-energy x-ray absorptiometry body composition changes , and degree of caloric restriction were determined . RESULTS All groups had similar weight loss ( approximately 12.1 + /- 2.5 kg ) and length of time to reach target BMI ( approximately 158 + /- 70 d ) . Caloric restriction averaged 59 + /- 9 % , and adherence to diet was 73 + /- 34 % . Adherence to diet was inversely associated to days to reach target BMI ( r = -0.687 ; P < 0.01 ) and caloric restriction ( r = -0.349 ; P < 0.01 ) . Association between adherence to diet and percent weight lost as fat was positive for the diet-endurance training ( r = 0.364 ; P < 0.05 ) but negatively correlated for the diet-only group ( r = -0.387 ; P < 0.05 ) . CONCLUSIONS Dietary adherence is strongly associated with rates of weight loss and adversely affected by the severity of caloric restriction . Weight loss programs should consider moderate caloric restriction relative to estimates of energy requirements , rather than generic low-calorie diets PURPOSE To evaluate a year-long behavioral weight control program , used with and without an intermittent very-low-calorie diet ( VLCD ) in the treatment of type II diabetes mellitus . PATIENTS AND METHODS Subjects ( n = 93 ) were r and omly assigned to 50-week treatment programs that used either a balanced low-calorie diet ( LCD ) of 1,000 to 1,000 kilocalories ( kcal ) per day throughout or included 2 12-week periods of a VLCD of 400 to 500 kcal per day alternating with the balanced LCD . Weight , glycemic control , blood pressure , and lipids were assessed at baseline , at the end of the year-long treatment , and at 2-year follow-up . RESULTS Subjects in the VLCD program lost significantly more weight than did LCD subjects at the end of the 50-week program ( 14.2 kg versus 10.5 kg ; P = 0.057 ) and remained off diabetes medication longer ( P < 0.05 ) . These benefits of the VLCD were due primarily to the first 12 weeks of the diet ; the second diet maintained , but did not increase , these effects . Subjects in both groups experienced marked improvements in glycemic control and cardiovascular risk factors over the year-long program , but attendance declined in the latter weeks of treatment and weight was regained . There was also marked recidivism in both groups in the year following treatment . CONCLUSIONS The intermittent VLCD improved weight loss and glycemic control , but these effects were quite modest and do not appear to justify the clinical use of an intermittent VLCD . Moreover , lengthening treatment to a full year did not prevent relapse . Thus , further research is needed to develop a successful approach to long-term weight control OBJECTIVE : To investigate the effectiveness of intensive innovative methods for implementing dietary prescriptions on weight management and glycaemic control in overweight men with Type II diabetes . DESIGN : A r and omised clinical trial with a 12-week intervention period — three isocaloric dietary intervention groups ( intermittent energy restriction , pre-portioned meals and self-selected meals ) each with weekly dietitian contact — and a follow-up visit after 18 months . SUBJECTS : A total of 51 men with Type II diabetes ( mean age 54 y , mean body mass index ( BMI ) 31.7 kg/m2 ) . MEASUREMENTS : Weight , body composition , waist circumference Output:	The effects of intermittent energy restriction in the long term remain unclear . Blood lipid concentrations , glucose , and insulin were not altered by intermittent energy expenditure in values greater than those seen with continuous energy restriction
MS21080	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We examined the interaction of two different frequencies of aerobic exercise training ( 30 min at 50 - 60 % of maximal heart rate reserve per session ) and a self-administered caloric restriction program on the changes in subcutaneous ( SFM ) and visceral ( VFM ) fat mass over a period of 13 wk . Twenty-six sedentary young women ( 27.9 % body fat ) were r and omized into three groups : nonexercising control ( C , N = 8) ; 1 - 2 sessions/wk plus a 240 kcal caloric restriction ( 1 - 2SW , N = 9 ) ; and 3 - 4 sessions/wk without caloric restriction ( 3 - 4SW , N = 9 ) . There was a equivalent decrease in the percentage of body fat and total fat mass in both exercise groups compared with that in C. Reduction in SFM was significant in 3 - 4SW , but not in 1 - 2SW or C. A negative correlation was observed between training frequency and changes in SFM ( r = -0.65 ) . In contrast , VFM decreased significantly and equivalently in both 1 - 2SW and 3 - 4SW , but there was no correlation between training frequency and changes in VFM ( r = 0.20 ) . It is suggested that the decrease in SFM , but not VFM , is proportional to the amount of aerobic exercise training . A change in VFM appears to be related to an deficit in caloric balance either by dietary restriction ( decrease caloric intake ) or by increased caloric expenditure Background It has been suggested that exercise training results in compensatory mechanisms that attenuate weight loss . However , this has only been examined with large doses of exercise . The goal of this analysis was to examine actual weight loss compared to predicted weight loss ( compensation ) across different doses of exercise in a controlled trial of sedentary , overweight or obese postmenopausal women ( n = 411 ) . Methodology /Principal Findings Participants were r and omized to a non-exercise control ( n = 94 ) or 1 of 3 exercise groups ; exercise energy expenditure of 4 ( n = 139 ) , 8 ( n = 85 ) , or 12 ( n = 93 ) kcal/kg/week ( KKW ) . Training intensity was set at the heart rate associated with 50 % of each woman 's peak VO2 and the intervention period was 6 months . All exercise was supervised . The main outcomes were actual weight loss , predicted weight loss ( exercise energy expenditure/ 7700 kcal per kg ) , compensation ( actual minus predicted weight loss ) and waist circumference . The study sample had a mean ( SD ) age 57.2 ( 6.3 ) years , BMI of 31.7 ( 3.8 ) kg/m2 , and was 63.5 % Caucasian . The adherence to the intervention was > 99 % in all exercise groups . The mean ( 95 % CI ) weight loss in the 4 , 8 and 12 KKW groups was −1.4 ( −2.0 , −0.8 ) , −2.1 ( −2.9 , −1.4 ) and −1.5 ( −2.2 , −0.8 ) kg , respectively . In the 4 and 8 KKW groups the actual weight loss closely matched the predicted weight loss of −1.0 and −2.0 kg , respectively , result ing in no significant compensation . In the 12 KKW group the actual weight loss was less than the predicted weight loss ( −2.7 kg ) result ing in 1.2 ( 0.5 , 1.9 ) kg of compensation ( P<0.05 compared to 4 and 8 KKW groups ) . All exercise groups had a significant reduction in waist circumference which was independent of changes in weight . Conclusion In this study of previously sedentary , overweight or obese , postmenopausal women we observed no difference in the actual and predicted weight loss with 4 and 8 KKW of exercise ( 72 and 136 minutes respectively ) , while the 12 KKW ( 194 minutes ) produced only about half of the predicted weight loss . However , all exercise groups had a significant reduction in waist circumference which was independent of changes in weight . Trial Registration Clinical Trials.gov NCT OBJECTIVE : To determine the time course for changes in aerobic capacity , body weight ( BW ) , and composition in overweight adults in response to a supervised exercise trial with a targeted energy expenditure of 2000 kcal week−1 . DESIGN : The Midwest Exercise Trial ( MET ) was a r and omized , controlled , 16-month verified , supervised exercise trial . Aerobic exercise progressed to 45 min day−1 , 5 days week−1 over 6-months and was then maintained for 10 months . Controls maintained their normal physical activity and all participants maintained ad libitum diets . SUBJECTS : A total of 131 participants were r and omized to exercise or control groups and 74 completed the intervention and all laboratory testing . MEASUREMENTS : At baseline and months 4 , 9 , 12 , and 16 , aerobic capacity ( VO2max ) was measured by indirect calorimetry , BW by digital scale , and fat weight and fat-free weight by hydrostatic weighing . RESULTS : Aerobic capacity ( ml kg−1 min−1 ) increased ( P<0.05 ) from baseline ( 39.2±5.2 , mean±s.d . ) to 9 months ( 48.8±4.3 ) in exercising men as well as women ( 32.8±4.2–39.6±5.5 ) with no significant changes occurring at 12 or 16 months . From baseline to 9 months BW ( 94.0±12.6–88.7±9.7 kg ) and fat weight ( 26.8±6.8–21.8±4.5 kg ) significantly decreased in exercising men with no changes occurring at 12 or 16 months . There were no changes in fat-free weight across the 16 months for exercising men or for BW or composition in exercising women . Further , there were no significant changes for the control men for aerobic capacity , BW , or body composition across 16 months . Women in the control group showed significant increases in weight of 2.9±5.5 kg and fat weight of 2.1±4.8 kg at 16 months only . CONCLUSIONS : We recommend that investigations that use exercise without diet as the stimulus for weight loss have at least a 9-month duration to provide sufficient time for the full effects to be realized , should such effects be present The present study examined the cardiovascular health effects of 16 weeks of recreational football training in untrained premenopausal women in comparison with continuous running training . Fifty healthy women were matched and r and omized to a football ( FG , n=25 ) or a running ( RG , n=25 ) group and compared with a control group with no physical training ( CO , n=15 ) . Training was performed for 1 h twice a week . After 16 weeks , systolic and diastolic blood pressure was reduced ( P<0.05 ) in FG ( 7+/-2 and 4+/-1 mmHg ) and systolic blood pressure was lowered ( P<0.05 ) in RG ( 6+/-2 mmHg ) . After 16 weeks , resting heart rate was lowered ( P<0.05 ) by 5+/-1 bpm both in FG and RG , and maximal oxygen uptake was elevated ( P<0.05 ) by 15 % in FG and by 10 % in RG ( 5.0+/-0.7 and 3.6+/-0.6 mL/min/kg , respectively ) . Total fat mass decreased ( P<0.05 ) by 1.4+/-0.3 kg in FG and by 1.1+/-0.3 kg in RG . After 16 weeks , pulse pressure wave augmentation index ( -0.9+/-2.5 vs 4.2+/-2.4 % ) , skeletal muscle capillarization ( 2.44+/-0.15 vs 2.07+/-0.05 cap/fib ) and low-density lipoprotein/high-density lipoprotein cholesterol ratio were improved ( P<0.05 ) in FG , but not altered in RG . No changes were observed in CO . In conclusion , regular recreational football training has significant favorable effects on the cardiovascular risk profile in untrained premenopausal women and is at the least as efficient as continuous running The animal model of exercise-induced anorexia was employed in humans to develop a laboratory paradigm for study ing the acute effect of exercise on food intake . Each of nine obese and nine nonobese women exercised either strenuously ( 90 W ) or moderately ( 30 W ) on a cycle ergometer for 40 min or rested in the laboratory on each of 3 nonconsecutive days . Intake of a liquefied test meal ( 1.04 kcal/g ) eaten 15 min after exercise was significantly less after the strenuous ( 620 g ) than after the moderate ( 754 g ) exercise in the nonobese women but was no different after the two conditions ( 532 g after strenuous , 581 g after moderate ) in the obese women . Heart rate and energy expenditure were increased in proportion to the exercise by the same amount in both groups . The results demonstrate for the first time that food intake is reduced immediately after strenuous exercise in nonobese women , as it is in animals , and vali date the feasibility of this laboratory paradigm BACKGROUND It is not clear how decreased activity quantitatively affects energy balance ( EB ) in subjects feeding ad libitum . OBJECTIVE We assessed the effect of an imposed sedentary routine on appetite , energy intake ( EI ) , EB , and nutrient balance in lean men for 7 d. DESIGN Six men with a mean ( + /-SD ) age of 23.0 + /- 2.3 y , weight of 69.2 + /- 11.4 kg , and height of 1.76 + /- 0.07 m were each studied twice during a sedentary [ 1.4 x resting metabolic rate ( RMR ) ] and a moderately active ( 1.8 x RMR ) regimen . During each treatment , they resided in the whole-body indirect calorimeter for the 7 d and had ad libitum access to a medium-fat diet of constant , measurable composition . Meal size , frequency , and composition were continually monitored . Motivation to eat was recorded during waking hours . Subjects were weighed in light clothing each morning , and their weight was corrected to nude . RESULTS Energy expenditure was 9.7 and 12.8 MJ/d [ P < 0.01 ; SE of the difference between means ( SED ) = 0.41 ] during the sedentary and active regimens , respectively . EI was 13.5 and 14.4 MJ/d ( P = 0.463 , SED = 1.06 ) , respectively . There was no regimen effect on hunger , appetite , or body weight . By day 7 , cumulative EB was 26.3 and 11.1 MJ , respectively . CONCLUSIONS Reducing a level of physical activity from 1.8 to 1.4 x RMR can markedly affect EB . A sedentary routine does not induce a compensatory reduction of EI and leads to a significantly positive EB , most of which is stored as fat The study was aim ed at investigating if endurance training of moderate intensity and longer duration , intended to promote health rather than performance , evokes ultrastructural changes in skeletal muscle tissue comparable to those observed after high-intensity protocol s. Twenty healthy , middle-aged men enrolled in a 6-month , home-based jogging program of 120 min/wk at 75 % VO2max . Only 12 men showed a sufficient exercise adherence over the 6 months ( > or = 60 min/wk on average ) and were included into statistical analysis . Their average training activity was 105 + /- 31 min/wk . The results revealed significant increases in VO2max ( + 8.4 % , p < 0.01 ) and submaximal power output ( + 18.1 % , p < 0.01 ) . Total mitochondrial volume density in M. vastus lateralis increased by 20 % ( p < 0.05 ) with a larger increase in subsarcolemmal volume compared to central volume ( 50 % vs 15 % ) . No changes in volume of intracellular lipid droplets , capillary density , capillary per fiber ratio , fiber mean cross-sectional area and muscle fiber type could be observed . Body composition analysis showed a decrease in trunk fat mass ( -7.3 % , p < 0.05 ) and an increase in trunk lean mass ( + 1.7 % , p < 0.05 ) , while changes in the legs were not significant . It can be concluded that a moderate-intensity , health oriented endurance training beneficially affected cardiovascular and muscle oxidation capacity as well as body composition in the trunk area . No adaptations in capillaries or lipid metabolism could be demonstrated . The results support the hypothesis of thresholds for induction of adaptation processes in muscle skeletal tissue depending on the intensity of the exercise stimulus BACKGROUND Obesity is a major health problem due , in part , to physical inactivity . The amount of activity needed to prevent weight gain is unknown . OBJECTIVE To determine the effects of different amounts and intensities of exercise training . DESIGN R and omized controlled trial ( February 1999-July 2002 ) . SETTING AND PARTICIPANTS Sedentary , overweight men and women ( aged 40 - 65 years ) with mild to moderate dyslipidemia were recruited from Durham , NC , and surrounding communities . INTERVENTIONS Eight-month exercise Output:	The fitted model suggested that for a shorter study duration , lower energy compensation was observed in younger individuals with higher initial fat mass ( FM ) . In contrast , higher energy compensation was noted for younger individuals with lower initial FM . From 25 weeks onward , energy compensation was no longer different for these predictors . Lower energy compensation occurs with short-term exercise , and a much higher level of energy compensation accompanies long-term exercise interventions
MS21081	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The authors conducted a prospect i ve cohort study to determine whether poor glycemic control is a contraindication to implant therapy in patients with type 2 diabetes . METHODS The study sample consisted of 117 edentulous patients , each of whom received two m and ibular implants , for a total of 234 implants . Implant-retained m and ibular overdentures were loaded after a four-month healing period and followed up for an additional one year . The authors assessed implant survival and stability ( by means of resonance frequency analysis ) relative to glycated hemoglobin A1c ( HbA1c ) levels , with baseline levels up to 11.1 percent and levels as high as 13.3 percent over one year . RESULTS Implant survival rates for 110 of 117 patients who were followed up for one year after loading were 99.0 percent , 98.9 percent and 100 percent , respectively , for patients who did not have diabetes ( n = 47 ) , those with well-controlled diabetes ( n = 44 ) and those with poorly controlled diabetes ( n = 19 ) . The authors considered the seven patients lost to follow-up as having had failed implants ; consequently , their conservative estimates of survival rates in the three groups were 93.0 percent , 92.6 percent and 95.0 percent ( P = .6510 ) . Two implants failed at four weeks , one in the nondiabetes group and the other in the well-controlled diabetes group . Delays in implant stabilization were related directly to poor glycemic control . CONCLUSIONS The results of this study indicate that elevated HbA1c levels in patients with type 2 diabetes were not associated with altered implant survival one year after loading . However , alterations in early bone healing and implant stability were associated with hyperglycemia The International Journal of Implant Dentistry is a peer- review ed open access journal published under the SpringerOpen br and . The journal is dedicated to promoting the exchange and discussion of all research areas relevant to implant dentistry in the form of systematic literature or invited review s , prospect i ve and retrospective clinical studies , clinical case reports , basic laboratory and animal research , and articles on material research and engineering . Diabetes mellitus is considered a relative contra-indication for implant therapy . However , the effect of glycemic level on implant integration in persons with diabetes remains poorly understood . The hypothesis of this research was that poor glycemic control is directly related to short-term-impairment implant stabilization . This prospect i ve clinical study evaluated 10 non-diabetic individuals ( 12 implants ) and 20 persons with type 2 diabetes ( 30 implants ) . Glycated hemoglobin ( HbA1c ) levels ranged from 4.7–12.6 % . Implant stability was assessed by resonance frequency analysis over 4 months following placement . Minimum stability levels were observed 2–6 weeks following placement for all 42 implants . Persons with HbA1c ≥ 8.1 % had a greater maximum decrease in stability from baseline and required a longer time for healing , as indicated by return of stability level to baseline . This study demonstrates alterations in implant stability consistent with impaired implant integration for persons with type 2 diabetes mellitus in direct relation to hyperglycemic conditions Diabetes mellitus , a prevalent disorder worldwide , is associated with systemic adverse sequelae , such as wound healing alterations , which may affect osseointegration of dental implants . This prospect i ve multicenter study assessed the success of 2-stage endosseous root-form implants ( 3 different implant systems ) placed in the m and ibular symphysis of 89 male type 2 diabetic subjects . The implants were uncovered approximately 4 months after placement , restored with an implant-supported , Hader bar clip-retained overdenture , and maintained at scheduled follow-up data collection examinations for 60 months after loading . Sixteen ( 9.0 % ) of the 178 implants failed . Life table methods calculated implant survival at approximately 88 % , from prosthesis placement through the 60-month follow-up , and at approximately 90 % from implant placement through the observation period . No implants failed between surgical placement and uncovering , 5 failed at uncovering , 7 failed after uncovering before prosthesis placement , and 4 failed after prosthesis placement . Fasting plasma glucose ( FPG ) and glycosylated hemoglobin ( HbA1c ) values were determined before implant placement ( baseline ) and approximately 4 months later at surgical uncovering ( follow-up ) . The 5-year implant outcomes ( successes versus failures ) were analyzed against the following predictor variables : ( 1 ) baseline and follow-up FPG values , ( 2 ) baseline and follow-up HbA1c values , ( 3 ) subject age , ( 4 ) duration of diabetes ( years ) , ( 5 ) baseline diabetic therapy , ( 6 ) smoking history , and ( 7 ) implant length . Regression analysis found only duration of diabetes ( P < .025 ) and implant length ( P < .001 ) to be statistically significant predictors of implant failure . There was no statistically significant difference in failure rates between the 3 different implant systems used . This study supports the use of dental implants in type 2 diabetic patients BACKGROUND The authors conducted a prospect i ve cohort study to explore the relationship between implant success and glycemic control in patients with type 2 diabetes mellitus . METHODS The authors used a two-phased enrollment , stratified by glycated hemoglobin ( HbA1c ) levels , to evaluate 50 implants in 35 subjects . The authors assessed nonsubmerged , nonrestored implants after placement , during healing and at abutment placement ( 35 newton centimeters ) for restoration after four months . Outcomes assessed included implant success or failure , clinical complications and adverse events . RESULTS The HbA1c levels of the subjects ranged from 4.5 to 13.8 percent . All 50 implants were integrated clinical ly . The authors identified three minor complications in three patients having HbA1c levels ranging from 7.4 to 8.3 percent . None of these complications affected the clinical management of the cases , and the authors did not identify any adverse events . CONCLUSIONS There was no evidence of diminished clinical success or significant early healing complications associated with implant therapy based on the glycemic control levels of subjects with type 2 diabetes mellitus . CLINICAL IMPLICATION S These findings support the continued investigation of the effects of glycemic control on implant therapy toward the development of therapeutic guidelines that will optimize implant therapy in patients with diabetes OBJECTIVE The objective of this study was to evaluate the potential for a chemically modified S and blasted , Large grit , Acid etched ( SLA ) surface , compared with a conventional SLA surface , to enhance implant healing and integration in poorly controlled diabetic patients , a group previously demonstrated to have compromises and delays in implant stabilization during the metabolically active healing period following implant placement . MATERIAL S AND METHODS The study enrolled 24 patients with type 2 diabetes , baseline HbA1c levels between 7.5 - 11.4 % , and a minimum of two posterior m and ibular tooth sites at least 4 months following extraction and appropriate for implant placement . Each patient , at a r and omly selected site , received an implant with the conventional SLA surface ; at the second site , the patient received an implant with the chemically modified SLA ( modSLA ) surface . Thus , 48 study implants were placed . Implant stability was assessed using Resonance Frequency Analysis ( RFA ) . Readings were taken from the buccal and proximal directions for each implant . Implant stability ( ISQ ) was assessed at the time of surgical placement ( baseline ) and 2 , 3 , 4 , 6 , 8 , 10 , 12 , and 16 weeks following implant placement . RESULTS No significant differences in implant stability were observed between conventional SLA implants and modSLA implants , and the time courses of implant stabilization following implant placement were similar for the two implant types . Baseline ISQ and minimum ISQ was slightly higher in subjects with higher HbA1c levels , but were similar during 12 - 16 weeks following implant placement . Forty-seven ( 98 % ) of the 48 implants were determined to be successfully osseointegrated and continued to restoration . CONCLUSION Implant stabilization was similar for the conventional SLA and chemically modified SLA implants in type 2 diabetic patients with relatively poor glycemic control . Furthermore , this study demonstrated clinical ly successful implant placement even in poorly controlled diabetic patients PURPOSE To investigate the effect of type-2 diabetes on implant survival and complication rate . MATERIAL S AND METHODS Prospect i ve study enrolling type-2 diabetic patients suffering from edentulism , having a mean perioperative HbA1c level of 7.2 % , and compliant with a maintenance program . All the patients underwent dental and periodontal examinations and had laboratory testing for HbA1c , fasting plasma glucose , blood lipids , and microalbuminuria . Nondiabetic patients matched for implant treatment indication served as controls . The influence of clinical diabetes-related factors and periodontal parameters ( Plaque Index , bleeding on probing , probing depth ) on implant survival were assessed via univariate then multivariate methods . RESULTS Forty-five diabetic patients , followed for 1 to 12 years , mean age 64.7 years , received 255 implants : 143 following a classical protocol and 112 in cases of sinus floor elevation , immediate loading , and guided bone regeneration . Forty-five nondiabetic control patients received 244 implants : 142 following a classical protocol and 102 in cases of advanced surgery . Implant survival following conventional or advanced implant therapy was not statistically different between the well-controlled ( HbA1c < 7 % , P = .33 ) and the fairly well-controlled group ( HbA1c 7 % to 9 % , P = .37 ) . The overall survival rate for the diabetic group was 97.2 % ( control 98.8 % ) and was not significantly different for age , gender , diabetes duration , smoking , or type of hypoglycemic therapy . The mean peri-implant bone loss was 0.41 + /- 0.58 mm ( control , 0.49 + /- 0.64 mm ) . PI and BOP fairly correlated with postoperative complications . HbA1c was the only multivariate independent factor affecting the complication rate ( P = .04 ) . No statistically significant difference was found for patients ( P = .81 ) or for implants ( P = .66 ) for the advanced surgery cases or the conventional approach in diabetic patients compared to nondiabetic patients BACKGROUND Because the life expectancy of individuals continues to increase , dentists providing dental implant treatment can expect to see an increasing number of patients with diabetes mellitus . Today , there are little data available concerning the clinical outcomes involving the use of implant treatment for patients with diabetes mellitus . There are three types of diabetes mellitus : Type 1 ( insulin dependent ) , Type 2 ( non-insulin dependent ) , and gestational . Because of possible complications from patients with diabetes mellitus , they are excluded from participation in most clinical studies of endosseous dental implant survival . METHODS This study attempted to determine if Type 2 diabetes represents a significant risk factor to the long-term clinical performance of dental implants , using the comprehensive DICRG data base . Diabetes was a possible exclusion criterion ; however , the final decision on Type 2 patients was left to the dental implant team at the research center . A total of 2,887 implants ( 663 patients ) were surgically placed , restored , and followed for a period of 36 months . Of these , 2,632 ( 91 % ) implants were placed in non-diabetic patients and 255 ( 8.8 % ) in Type 2 patients . Failures ( survival ) were compared using descriptive data . Possible clustering was also studied . RESULTS A model assuming independence showed that implants in Type 2 patients have significantly more failures ( P = 0.020 ) . However , if correlations among implants within the patient are considered , the significance level becomes marginal ( P = 0.046 ) . The experience of the surgeon did not produce a clinical ly significant improvement in implant survival . The use of chlorhexidine rinses following implant placement result ed in a slight improvement ( 2.5 % ) in survival in non-Type 2 patients and a greater improvement in Type 2 patients ( 9.1 % ) ; the use of preoperative antibiotics improved survival by 4.5 % in non-Type 2 patients and 10.5 % in Type 2 patients . The use of HA-coated implants improved survival by 13.2 % in Type 2 diabetics . CONCLUSION Type 2 diabetic patients tend to have more failures than non-diabetic patients ; however , the influence was marginally significant . These findings need to be confirmed by other scientific clinical studies with a larger Type 2 diabetic sample size BACKGROUND The poor glycemic status seems to be an important factor affecting implant complication rates , including peri-implant bone loss . PURPOSE This trial evaluated the influence of glycemic control of type 2 diabetes mellitus ( T2DM ) patients on implant stabilization and on the levels of bone markers in peri-implant fluid during the healing . MATERIAL S AND METHODS Systemically healthy patients ( SH Output:	We conclude that patients with poorly controlled diabetes suffer from impaired osseointegration , elevated risk of peri-implantitis , and higher level of implant failure . The influence of duration of the disease is not fully clear . The supportive administration of antibiotics and chlorhexidine seems to improve implant success . When diabetes is under well control , implant procedures are safe and predictable with a complication rate similar to that of healthy patients
MS21082	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Scapula taping is a commonly used adjunctive treatment for shoulder im- pingement pathology . However , this intervention has not previously been subject to formal investigation . A pilot single-blind r and omized controlled trial was conducted to evaluate facilitatory taping as an adjunct to routine physiotherapy management . Twenty-two sub- jects with unilateral shoulder impingement symptoms were r and omized into a taping with routine physiotherapy or a routine physiotherapy only group . The intervention group had scapula taping applied three times per week for the first two weeks of their treatment . All subjects were assessed at baseline , then at 2 and 6 weeks after the commencement of treat- ment . Pain and functional ability were assessed using the Shoulder Pain and Disability In- dex , range of shoulder elevation , and self-reported pain on elevation . At 2 weeks , the taping group demonstrated a strong trend toward reduced pain both on self-reported activity ( SPADI pain subscale mean for taping 27.0 versus 41.5 for control ) and pain during mea- sured abduction ( mean VAS 22.8 for taped , 46.8 for control ) , statistical power being limited by small sample size . No similar trend was evident in the SPADI disability subscale . The magnitude of the differences was reduced at 6-week follow-up . This study provides prelimi- nary evidence for a short-term role for scapula taping as an adjunct to routine physiother- apy in the management of shoulder impingement symptoms but also highlights the need for consideration on a case basis relating to risk factors for skin reaction PURPOSE This study aim ed to investigate the effect of elastic taping on kinematics , muscle activity and strength of the scapular region in baseball players with shoulder impingement . SCOPE Seventeen baseball players with shoulder impingement were recruited from three amateur baseball teams . All subjects received both the elastic taping ( Kinesio Tex ) and the placebo taping ( 3 M Micropore tape ) over the lower trapezius muscle . We measured the 3-dimensional scapular motion , electromyographic ( EMG ) activities of the upper and lower trapezius , and the serratus anterior muscles during arm elevation . Strength of the lower trapezius was tested prior to and after each taping application . The results of the analyses of variance ( ANOVA ) with repeated measures showed that the elastic taping significantly increased the scapular posterior tilt at 30 degrees and 60 degrees during arm raising and increased the lower trapezius muscle activity in the 60 - 30 degrees arm lowering phase ( p<0.05 ) in comparison to the placebo taping . CONCLUSIONS The elastic taping result ed in positive changes in scapular motion and muscle performance . The results supported its use as a treatment aid in managing shoulder impingement problems The purpose of this clinical trial is to compare the effectiveness of a scapular-focused treatment with a control therapy in patients with shoulder impingement syndrome . Therefore , a r and omized clinical trial with a blinded assessor was used in 22 patients with shoulder impingement syndrome . The primary outcome measures included self-reported shoulder disability and pain . Next , patients were evaluated regarding scapular positioning and shoulder muscle strength . The scapular-focused treatment included stretching and scapular motor control training . The control therapy included stretching , muscle friction , and eccentric rotator cuff training . Main outcome measures were the shoulder disability question naire , diagnostic tests for shoulder impingement syndrome , clinical tests for scapular positioning , shoulder pain ( visual analog scale ; VAS ) , and muscle strength . A large clinical ly important treatment effect in favor of scapular motor control training was found in self-reported disability ( Cohen ’s d = 0.93 , p = 0.025 ) , and a moderate to large clinical ly important improvement in pain during the Neer test , Hawkins test , and empty can test ( Cohen ’s d 0.76 , 1.04 , and 0.92 , respectively ) . In addition , the experimental group demonstrated a moderate ( Cohen ’s d = 0.67 ) improvement in self-experienced pain at rest ( VAS ) , whereas the control group did not change . The effects were maintained at three months follow-up Purpose Neck and shoulder complaints are common among employees in occupations characterized by intensive computer use . Treatment has varied from passive rest to active treatments and active treatments have often been divided into either training of the painful area or the surrounding musculature avoiding direct training of the painful area . Our study investigates the effect of the latter approach . The purpose of this study was in a r and omised controlled trial to investigate if intensive scapular function training (SFT)—in terms of training of the lower trapezius and the serratus anterior muscle while minimizing direct training of the upper trapezius — is effective in reducing pain in adults with chronic non-specific pain in the neck/shoulder region . Methods 47 office workers with chronic non-specific pain in the neck/shoulder region were r and omized to 10 weeks 3 × 20 min SFT with training supervision or to a control group . At baseline and at follow-up the participants were tested for maximum isometric shoulder strength by a blinded tester . Further , once a week participants reported pain intensity of the neck/shoulder during the previous week . Results In intention-to-treat analysis neck- and shoulder pain decreased 2.0 ( 95 % CI 0.35 ; 3.64 ) in SFT compared with control group ( p < 0.05 ) . Pressure Pain Threshold ( PPT ) increased 129 kPa in the lower trapezius in SFT compared with the control group ( p < 0.01 ) . Shoulder elevation strength increased 7.7 kg in SFT compared with the control group ( p < 0.01 ) with no change in shoulder protraction strength . Conclusions SFT reduces pain intensity and increases shoulder elevation strength in adults with chronic non-specific pain in the neck/shoulder region . The magnitude of improvement in pain intensity was clinical ly relevant [ Purpose ] This study examined the effects of scapular stabilization exercises immediately after surgery on pain and function in patients diagnosed with shoulder impingement syndrome . [ Subjects ] The subjects were assigned by r and om sampling to an experimental group ( n=15 ) to which stabilization exercise was applied and a control group ( n=15 ) to which ordinary physical treatment was applied . [ Methods ] To evaluate the degree of pain , a 100 mm visual analogue scale ( VAS ) was used . The Constant-Murley Scale ( CMS ) was used to evaluate the functions of the shoulder joints . To determine the range of motion , a goniometer was used to measure range of shoulder motion . The simple shoulder test ( SST ) was used to determine the condition of the shoulder joints of the subjects . [ Results ] There were significant differences in all the items of the experimental group . The results of comparison of the therapeutic effect in the experimental and control groups revealed significant differences in active abduction , passive abduction , VAS , SST , and the CMS , except for pain . [ Conclusion ] The results suggest that shoulder stabilization exercise positively affects pain alleviation and functional recovery in shoulder impingement patients OBJECTIVES To identify predictors of non-recovery in non-traumatic complaints at the arm , neck and shoulder in general practice 6 months after the first consultation . METHODS A prospect i ve cohort study was set in 21 Dutch general practice s. Consulters with a first or new episode of non-traumatic arm , neck or shoulder complaints and age 18 through 64 yrs entered the cohort . Complaint , patient , physical , psychosocial and work characteristics were investigated as possible predictors of non-recovery at 6 months using multiple logistic regression analyses ( backward Wald ) . RESULTS At 6 months , 46 % of the total population ( n = 612 ) and 42 % of the working sub population ( n = 473 ) still reported complaints . Complaint characteristics ( long duration of the complaint before consultation , recurrent complaint , musculoskeletal comorbidity and complaint mainly located at wrist or h and ) were most predictive of non-recovery followed by psychosocial characteristics ( more somatization and experiencing less social support ) . Having a specific diagnosis was associated with recovery . In the working sub population , the same variables were predictors of non-recovery . Additionally , low supervisory support was associated with non-recovery . The models correctly classified 72 - 75 % of the patients ( explained variance 0.27 - 0.28 ) . CONCLUSIONS Besides questions on complaint characteristics , information on somatization and support can help a general practitioner to recognize patients at risk of persistent complaints Shoulder-related dysfunction affects individuals ' ability to function independently and thus decreases quality of life . Functional task assessment is a key concern for a clinician in diagnostic assessment , outcome measurement , and planning of treatment programs . The purpose of this study was to test the reliability of the FASTRAK 3-dimensional ( 3-D ) motion analysis and surface electromyography ( sEMG ) systems to analyze 3-D shoulder complex movements during functional tasks and compare motion patterns between subjects with and without shoulder dysfunctions (SDs).For the test , sEMG and 3-D motion analysis systems were used to characterize the functional tasks . Twenty-five asymptomatic male subjects and 21 male subjects with right shoulder disorders performed four functional tasks which involved arm reaching and raising activities with their dominant arms . Reliability was estimated by the intraclass correlation coefficient ( ICC ) . Motion pattern was compared between two groups using mixed analysis of variances ( ANOVAs ) . Shoulder complex kinematics and associated muscular activities during functional tasks were reliably quantified ( ICC=0.83 - 0.99 ) from the means of three trials . Relative to the group without SDs , the group with SDs showed significant alteration in shoulder complex kinematics ( 3 degrees -40 degrees ) and associated muscular activities ( 3 - 10 % maximum ) . Scapular tipping , scapular elevation , upper trapezius muscle function , and serratus anterior muscle function may have implication s in the rehabilitation of patients with SDs OBJECTIVE The study investigated the effectiveness of stretching , strengthening exercises , and the scapular stabilization exercises on the pain , shoulder range of motion ( ROM ) , muscle strength , joint position sense ( JPS ) , scapular dyskinesis and quality of life ( OL ) in the patients with subacromial impingement syndrome ( SIS ) . METHODS 27 women and 13 men , mean age 51 ( 24 - 71 ) years old , were included in this study . All the patients were separated into 2 groups according to simple r and om table . Stretching and strengthening exercises were given to the group I ( n=20 ) and scapular stabilization exercises were added to the group II ( n=20 ) . The pain severity , shoulder ROM , muscle strength , JPS , lateral scapular slide test ( LSST ) , Western Ontario Rotator Cuff ( WORC ) Index were evaluated before and after treatment . Patients completed a 6-week rehabilitation program , three times a week . RESULTS The results showed that all measurements improved statistically in both groups after treatment ( p < 0.05 ) . And the improvements in the muscle strength , JPS and scapular dyskinesia were significantly different in group II ( p < 0.05 ) . CONCLUSION It is suggested that in the treatment of SIS ; scapular stabilization exercises , given with stretching and strengthening exercises , can be more effective in increasing the muscle strength , developing the JPS and decreasing the scapular dyskinesis HYPOTHESIS This study tested the hypothesis that infraspinatus strength in professional volleyball players can be assessed with the scapula free ( infraspinatus strength test , IST ) and with the scapula retracted ( infraspinatus scapula retraction test , ISRT ) before and after scapular musculature training . MATERIAL S AND METHODS A prospect i ve study was performed in 31 professional volleyball players . Isometric strength ( kg ) of the infraspinatus with IST and with ISRT was recorded by a h and held dynamometer and compared with the values found after 3 and 6 months of rehabilitation . Magnetic resonance imaging was performed to exclude articular and cuff pathology . Pain scores were assessed using a visual analog scale . RESULTS The mean increase in the force values of IST was statistically significant after 3 months ( P < .01 ) and 6 months ( P < .001 ) of rehabilitation . The mean difference between IST and ISRT decreased from 4.72 ± 0.007 before rehabilitation to 1.2 ± 0.26 at 3 months and to 0.4 ± 0.006 at 6 months . The mean score for pain was 2.4 ± 1.8 at 3 months and 2.6 ± 1.4 at 6 months . DISCUSSION Acquired scapular dyskinesis in overhead athletes can lead to the rotator cuff weakness . Inhibition due to pain and the negative biomechanic effect of scapular dyskinesis results in specific infraspinatus dysfunction that arise with the ISRT . CONCLUSIONS ISRT is practical and consistent to assess the infraspinatus strength in overhead athletes with scapular dyskinesis . A functional rehabilitation protocol , design ed to restore scapular muscles balance and shoulder mobility , is essential in the training program to prevent shoulder dysfunction and improve sports performance HYPOTHESIS AND BACKGROUND Though commonly suggested as an injury risk factor , scapular dysfunction has not been established as a prospect i ve cause of throwing-related upper extremity injury in baseball players . The purpose is to determine whether scapular dysfunction identified during preseason screening is predictive of increased risk of throwing-related shoulder and elbow injuries in high school baseball players . MATERIAL S AND METHODS The presence or absence of scapular dysfunction was obtained prospect ively during preseason screenings in 246 high school baseball players over the 2010 and 2011 seasons . Exposure and injury surveillance data were then obtained weekly over the course of each season Output:	There was moderate evidence that scapular-focused treatment compared with other physiotherapeutic treatment is effective in improving scapular muscle strength in participants with SPS . Conflicting evidence was found for improvements in pain , function and clinical measures of scapular positioning . No evidence was found for improvements in shoulder range of motion or rotator cuff muscle strength . Conclusions There is some support for the use of scapular-focused exercise therapy in patients with SPS .
MS21083	*TASK* the task is to summarize an input biomedical literature in six sentences *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 authors examined which , if any , research design features and patient characteristics would significantly differ between successful and unsuccessful antidepressant trials . METHOD Clinical trial data were review ed for nine antidepressants approved by the Food and Drug Administration between 1985 and 2000 . From the antidepressant research programs on these medications , 52 clinical trials were included in the study . The authors evaluated trial design features , patient characteristics , and difference in response between placebo and antidepressant . RESULTS Nine trial design features and patient characteristics were present in the research programs for all nine of the antidepressants . The severity of depressive symptoms before patient r and omization , the dosing schedule ( flexible versus fixed ) , the number of treatment arms , and the percentage of female patients were significantly associated with the difference in response to antidepressant and placebo . The duration of the antidepressant trial , number of patients per treatment arm , number of sites , and mean age of the patients were similar in successful trials ( with a greater antidepressant-placebo difference ) and less successful trials ( with a smaller antidepressant-placebo difference ) . CONCLUSIONS These findings may help in the design of future antidepressant trials BACKGROUND The highly recurrent nature of major depression in the young and the elderly warrants long-term antidepressant treatment . AIMS To compare the prophylactic efficacy of citalopram and placebo in elderly patients ; to evaluate long-term tolerability of citalopram . METHOD Out- patients , > or = 65 years , with unipolar major depression ( DSM-IV : 296.2 x or 296.3 x ) and Montgomery-Asberg Depression Rating Scale score > or = 22 were treated with citalopram 20 - 40 mg for 8 weeks . Responders continued on their final fixed dose of citalopram for 16 weeks before r and omisation to double-blind treatment with citalopram or placebo for at least 48 weeks . RESULTS Nineteen of the 60 patients using citalopram v. 41 of the 61 patients using placebo had recurrence . Time to recurrence was significantly different between citalopram- and placebo- patients , in favour of citalopram ( log-rank test , P<0.0001 ) . Long-term treatment was well tolerated . CONCLUSIONS Long-term treatment with citalopram is effective in preventing recurrence of depression in the elderly and is well tolerated Dysthymia is one of the most prevalent problems in primary care , especially in the elderly . In this study , we evaluated the demographic and clinical predictors of nonresponse to treatment in primary care patients with dysthymia . The study sample consisted of 338 primary care patients meeting DSMIII-R criteria for dysthymia from 4 diverse geographic sites in a r and omized controlled 11-week trial of paroxetine , problem-solving therapy or placebo . Patients who attended at least 4 treatment sessions were used in the analysis . A score of less than 7 on the Hamilton was defined as a positive response to treatment . By Week 11 , 52.2 % of patients had a positive response to treatment . Patients with lower levels of education ( odds ratio 0.44 , 95 % CI 0.23 , 0.86 ) , higher scores on the personality dimension of neuroticism ( odds ratio 0.58 , 95 % CI 0.36 , 0.92 ) and those with more severe medical illness ( odds ratio 0.97 , 95 % CI 0.95 , 0.99 ) were less likely to recover with either active or placebo treatments . Elderly women ( > 60 years of age ; odds ratio 0.19 , 95 % CI 0.05 , 0.66 ) were also less likely to respond to all treatments ; however , females had a significantly higher response to placebo treatment compared to males . The factors associated with lack of response to treatment included lower-levels of education , high neuroticism , more severe medical illness and being an older female . This analysis is based on patients agreeing to participate in a r and omized controlled trial , limiting representativeness of the sample , however , the demographic and clinical characteristics are common in elderly depressed primary care patients , and may signal the need for increased mental health specialty consultation OBJECTIVE The present study examined the efficacy and tolerability of acute escitalopram treatment in depressed patients aged 60 years or older . METHODS Patients aged > or = 60 years with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition major depressive disorder were r and omized to 12 weeks of double-blind , flexible-dose treatment with escitalopram ( 10 - 20 mg/day ; N = 130 ) or placebo ( N = 134 ) . The prospect ively defined primary efficacy end point was change from baseline to week 12 in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score using the last observation carried forward approach . RESULTS A total of 109 ( 81 % ) patients in the placebo group and 96 ( 74 % ) patients in the escitalopram group completed treatment . Mean age in both groups was approximately 68 years . Mean baseline MADRS scores were 28.4 and 29.4 for the placebo and escitalopram treatment groups , respectively . Escitalopram did not achieve statistical significance compared with placebo in change from baseline on the MADRS ( least square mean difference : -1.34 ; last observation carried forward ) . Discontinuation rates result ing from adverse events were 6 % for placebo and 11 % for escitalopram . Treatment-emergent adverse events reported by > 10 % of patients in the escitalopram group were headache , nausea , diarrhea , and dry mouth . CONCLUSIONS Escitalopram treatment was not significantly different from placebo treatment on the primary efficacy measure , change from baseline to week 12 in MADRS . In patients aged 60 years or older with major depression , acute escitalopram treatment appeared to be well tolerated BACKGROUND There is suggestive evidence that depression increases risk of myocardial infa rct ion ( MI ) , but there are no prospect i ve studies in which the measure of depression corresponds to clinical criteria . This study examines prospect ively whether a major depressive episode increases the risk of incident MI and evaluates the role of psychotropic medication use in this relationship . METHODS AND RESULTS The study is based on a follow-up of the Baltimore cohort of the Epidemiologic Catchment Area Study , a survey of psychiatric disorders in the general population . A history of major depressive episode , dysphoria ( 2 weeks of sadness ) , and psychotropic medication use were assessed in 1981 , and self-reported MI was assessed in 1994 . Sixty-four MIs were reported among 1551 respondents free of heart trouble in 1981 . Compared with respondents with no history of dysphoria , the odds ratio for MI associated with a history of dysphoria was 2.07 ( 95 % CI , 1.16 to 3.71 ) , and the odds ratio associated with a history of major depressive episode was 4.54 ( 95 % CI , 1.65 to 12.44 ) , independent of coronary risk factors . In multivariate models , use of barbiturates , meprobamates , phenothiazines , and lithium was associated with an increased risk of MI , whereas use of tricyclic antidepressants and benzodiazepines was not . Among individuals with no history of dysphoria , only lithium use was significantly associated with MI . CONCLUSIONS These data suggest that a history of dysphoria and a major depressive episode increase the risk of MI . The association between psychotropic medication use and MI is probably a reflection of the primary relationship between depression and MI BACKGROUND Treatment studies of depression in residential care are limited . Reports of predictors of response are rare . In the largest nursing home prospect i ve antidepressant trial reported , we examined predictors of response . METHODS This was a 12-week open-label study of mirtazapine orally disintegrating tablets performed in 30 US nursing homes . Subjects were men and women aged > or=70 , with a Mini Mental State Exam ( MMSE ) score > or=10 , who had a depressive disorder that required antidepressant treatment . Mirtazapine was started at 15 mg at bedtime , and adjusted to 15 - 45 mg/day . A 16-item Hamilton Depression Rating Scale was used to assess depression at baseline , weeks 2 , 4 , 8 , and 12 or early termination . RESULTS One hundred and twenty-four patients received at least one dose of study drug and of these , 119 had at least one post-drug assessment . Mean age was 82.9 years and 72 % were female . Response rates at 12 weeks were 47 % on the HAMD and 54 % on the CGI . Age , sex , MMSE score , medical burden , history of prior depression , and baseline HAMD severity were not significantly associated with HAMD response ( > or=50 % improvement ) and in most cases correlations were trivial , < 0.1 . Advanced age , medical burden , and cognitive impairment did not predict adverse events . CONCLUSIONS In this sample of depressed nursing home residents treated with mirtazapine orally disintegrating tablets , advanced age , medical illness , and cognitive impairment did not predict response . The findings suggest that these variables need not be viewed as obstacles to treatment CONTEXT Few r and omized controlled trials have evaluated the efficacy of treatments for major depression in patients with coronary artery disease ( CAD ) . None have simultaneously evaluated an antidepressant and short-term psychotherapy . OBJECTIVE To document the short-term efficacy of a selective serotonin reuptake inhibitor ( citalopram ) and interpersonal psychotherapy ( IPT ) in reducing depressive symptoms in patients with CAD and major depression . DESIGN , SETTING , AND PARTICIPANTS The Canadian Cardiac R and omized Evaluation of Antidepressant and Psychotherapy Efficacy , a r and omized , controlled , 12-week , parallel-group , 2 x 2 factorial trial conducted May 1 , 2002 , to March 20 , 2006 , among 284 patients with CAD from 9 Canadian academic centers . All patients met Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria for diagnosis of major depression of 4 weeks ' duration or longer and had baseline 24-item Hamilton Depression Rating Scale ( HAM-D ) scores of 20 or higher . INTERVENTIONS Participants underwent 2 separate r and omizations : ( 1 ) to receive 12 weekly sessions of IPT plus clinical management ( n = 142 ) or clinical management only ( n = 142 ) and ( 2 ) to receive 12 weeks of citalopram , 20 to 40 mg/d ( n = 142 ) , or matching placebo ( n = 142 ) . MAIN OUTCOME MEASURES The primary outcome measure was change between baseline and 12 weeks on the 24-item HAM-D , administered blindly during central ized telephone interviews ( tested at alpha = .033 ) ; the secondary outcome measure was self-reported Beck Depression Inventory II ( BDI-II ) score ( tested at alpha = .017 ) . RESULTS Citalopram was superior to placebo in reducing 12-week HAM-D scores ( mean difference , 3.3 points ; 96.7 % confidence interval [ CI ] , 0.80 - 5.85 ; P = .005 ) , with a small to medium effect size of 0.33 . Mean HAM-D response ( 52.8 % vs 40.1 % ; P = .03 ) and remission rates ( 35.9 % vs 22.5 % ; P = .01 ) and the reduction in BDI-II scores ( difference , 3.6 points ; 98.3 % CI , 0.58 - 6.64 ; P = .005 ; effect size = 0.33 ) also favored citalopram . There was no evidence of a benefit of IPT over clinical management , with the mean HAM-D difference favoring clinical management ( -2.26 points ; 96.7 % CI , -4.78 to 0.27 ; P = .06 ; effect size , 0.23 ) . The difference on the BDI-II did not favor clinical management ( 1.13 points ; 98.3 % CI , -1.90 to 4.16 ; P = .37 ; effect size = 0.11 ) . CONCLUSIONS This trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for major depression among patients with CAD and found no evidence of added value of IPT over clinical management . Based on these results and those of previous trials , citalopram or sertraline plus clinical management should be considered as a first-step treatment for patients with CAD and major depression . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N15858091 OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are widely used to treat depression , but the rates , timing , and baseline predictors of remission in " real world " patients are not established . The authors ' primary objectives in this study were to evaluate the effectiveness of citalopram , an SSRI , using measurement-based care in actual practice , and to identify predictors of symptom remission in out patients with major depressive disorder . METHOD This clinical study included out patients with major depressive disorder who were treated in 23 psychiatric and 18 primary care Output:	In patients with an illness duration > 10 years , baseline depression severity was also significantly associated with drug-placebo differences . Older patients with a long illness duration and moderate to severe depression appear to benefit from antidepressants as compared with placebo . Antidepressants do not appear to be effective for older patients with short illness duration
MS21084	*TASK* the task is to summarize an input biomedical literature in six sentences *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 work was to test and compare the accuracy of five different morphological scoring systems to identify malignant ovarian masses in a prospect i ve multicenter study . Four of the systems had previously been reported by Granberg , Sassone , De Priest and Lerner and the fifth is newly developed . A total of 330 ovarian neoplasms were collected in three different centers , which adopted the same diagnostic procedures . Of these , 261 masses were benign ( mean diameter 50 + /- 26 mm ) and 69 were malignant ( mean diameter 69 + /- 33 mm ) ( prevalence 21 % ) . The area under the receiver operating characteristic ( ROC ) curve for the multicenter score was 0.84 . This was significantly better than the areas of the other four scores which ranged from 0.72 to 0.75 . The cut-off levels derived from the five ROC curves achieved a sensitivity that ranged from 74 % ( Sassone score ) to 88 % ( De Priest score > or = 5 ) , and a specificity from 40 % ( De Priest ) to 67 % ( multicenter ) ; the highest positive predictive value was 41 % ( multicenter ) . With a cut-off level of 9 , the accuracy of the multicenter score was significantly better than the scores of Granberg and De Priest ( McNemar 's test p < 0.0001 ) . Similar results were obtained in 207 ovarian masses of < or = 5 cm in mean diameter , and when 19 borderline and 11 stage 1 cancers only were considered . For the clinical purpose s of a screening test we also checked a possible cut-off level of > or = 8 , which increased the sensitivity to 93 % with a drop of specificity to 56 % . With the use of the same criteria for the scores of the different authors , the following values were obtained for sensitivity : 96 % , 81 % , 93 % and 90 % ; and for specificity : 23 % , 56 % , 28 % and 49 % . The multicenter score performed well at distinguishing malignant from benign lesions , and was better than the other four traditional scores , for both large and small masses . This was mainly due to the introduction of two criteria that allowed correction for typical dermoids and endohemorrhagic corpora lutea . A completely reliable differentiation of benign from malignant masses can not be obtained by sonographic imaging alone Background . In a prospect i ve study , the differential dignostic potential of peovic examination , ultrasound , and serum CA 125 assay in postmenopausal patients presenting with a pelvic mass was assessed In a prospect i ve study , 32 women with suspected pelvic masses at physical examination underwent both endovaginal ultrasound ( US ) and magnetic resonance ( MR ) imaging to compare their ability in diagnosis of adnexal masses . Criteria for the diagnosis of various types of adnexal masses with MR imaging and endovaginal US were prospect ively defined , and the ability of either modality to allow a specific diagnosis was assessed . For each modality , measures of sensitivity , specificity , and accuracy were obtained . Results indicated higher diagnostic capability of endovaginal US for simple cysts ( five of five ) , hemorrhagic cysts ( eight of nine ) , endometriomas ( nine of 14 ) , and ovarian carcinomas ( three of three ) . MR imaging demonstrated higher diagnostic capability for dermoids ( three of three ) . MR imaging and endovaginal US showed equal diagnostic capability for pedunculated fibroids ( two of two ) . For all masses , observers , and observations , the overall sensitivity of endovaginal US was 76 % versus 49 % for MR imaging , and the overall accuracy of endovaginal US was 83 % versus 70 % for MR imaging . The authors suggest that endovaginal US is a better modality than MR imaging for the assessment of suspected pelvic masses Objective : To assess the accuracy of pelvic sonography in distinguishing benign from malignant lesions in postmenopausal women , using morphologic criteria and Doppler flow characteristics . Methods : All postmenopausal patients scanned from March 1992 to April 1993 with sonographically identified and pathologically confirmed adnexal masses formed the study group . The adnexal lesions were morphologically categorized prospect ively as benign or malignant , and pulsed Doppler flow studies were measured using the lowest resistance index obtained from each mass . The sensitivity and specificity were determined for morphologic and Doppler flow assessment s , as well as for a combination of these methods , for predicting the presence of malignancy . Results : Thirty-three postmenopausal patients formed the study group ; 12 lesions were malignant and 21 were benign pathologically . Using morphologic criteria alone , the sensitivity in detecting malignancy was 91 % and specificity was 52 % . Using pulsed Doppler alone with a resistance index limit of 0.6 , the sensitivity in predicting malignancy was 66 % , with a specificity of 81 % . If a resistance index limit of 0.8 were used , the sensitivity and specificity would be the same as those for morphology alone . Combining morphology and resistance index , a single malignancy would still have been missed ( sensitivity 91 % ) . Conclusion : In our experience , Doppler flow studies did not add substantially to the prediction of malignancy using morphologic assessment alone BACKGROUND To assess the differential diagnostic potential of physical examination , ultrasound , the serum CA 125 assay , and serum CA 72 - 4 assay , and the contribution of each parameter to a logistic model predicting the probability of malignancy in postmenopausal patients presenting with a pelvic mass . PATIENTS AND METHODS In a multicenter , prospect i ve study a total of 155 patients were evaluated preoperatively using a st and ard protocol for pelvic examination , transvaginal ( occasionally additional abdominal ) ultrasound , and serum CA 72 - 4 ( cutoff level 3 U/ml ) and CA 125 ( cutoff level 35 U/ml ) . RESULTS Fifty-nine malignant ( 39 % ) and 92 benign ( 61 % ) pelvic tumors were found in addition to 4 borderline tumors ( 3 % ) . Forty-three patients appeared to have ovarian carcinoma , FIGO Stage III or IV in 28 cases . Borderline tumors were excluded from the statistical calculations . The diagnostic accuracy of each single parameter , i.e. , pelvic examination , ultrasound , and serum CA 125 and CA 72 - 4 in discriminating between benign and malignant pelvic masses gave highly similar results ( 81 , 76 , 78 , and 81 % respectively ) . Best sensitivity was found in pelvic examination ( 92 % ) ; best specificity was found in CA 72 - 4 ( 93 % ) . Using logistic regression analysis the power of pelvic examination appeared to be the most relevant ( adjusted odds ratio 12.1 ) , followed by ultrasound ( odds ratio 9.7 ) , serum CA 125 ( odds ratio 5.0 ) , and serum CA 72 - 4 ( odds ratio 4.9 ) . Age appeared to be nonpredictive . The logistic model gives a correct prediction in 87 % of all cases . CONCLUSIONS The addition of serum CA 72 - 4 to the combination of pelvic examination , ultrasound , and serum CA 125 leads to an improved discrimination between malignant and benign pelvic masses OBJECTIVE To prospect ively evaluate the accuracy of a multiparameter , ultrasound-based triage and its impact on surgical management of adnexal masses . METHODS Masses evaluated as normal according to Ferrazzi 's sonographic morphological score were considered as being at low risk of malignancy and eligible for laparoscopic treatment without further evaluation . Masses evaluated as abnormal , but without additional risk factors such as ascites , diameter > or = 10 cm , bilaterality , immobility , resistance index < or = 0.6 and serum CA 125 > 35 IU/mL were considered at moderate risk and eligible for laparoscopic evaluation and treatment . Masses with abnormal morphological score and any of these additional risk factors were considered at high risk and treated by laparotomy . The results of pathological examination were obtained for each mass . RESULTS Two hundred and four ( 87 % ) masses were benign and 30 ( 13 % ) were malignant . Among 182 low-risk , 19 moderate-risk and 33 high-risk masses , the odds of malignancy were 1 : 90 , 1 : 18 and 4.5 : 1 , respectively . To calculate the diagnostic accuracy of this algorithm , low- and moderate-risk groups were considered together : the sensitivity was 90 % , specificity 97 % , positive predictive value 82 % and negative predictive value 99 % . The new algorithm was significantly more accurate than was morphological score alone ( P = 0.0002 ) . Ninety-six percent of benign masses were treated by laparoscopy . All three patients with malignant masses that were incorrectly assigned to laparoscopy underwent laparoscopic adnexectomy and frozen section . CONCLUSIONS The accuracy of this new algorithm was higher than that of the sonographic morphological scoring system alone . In the present series , it allowed the treatment by laparoscopy of 96 % of benign adnexal masses without mismanagement of any cases of ovarian cancer Objective To determine the ability of pelvic examination , tumor marker assessment , and transvaginal ultrasonography , with selected use of Doppler ultrasonography , to predict pelvic malignancy . Methods Two hundred twenty-six women scheduled for operative removal of a pelvic mass were entered in the study prospect ively . Each woman underwent pelvic examination , tumor marker assessment , and transvaginal ultrasonography preoperatively . Women whose gray-scale findings were suspicious for malignancy underwent Doppler ultrasonography . Suspicious findings included masses that were fixed or irregular on pelvic examination ; CA 125 level greater than 35 U/mL ; elevations in serum lactic dehydrogenase , alphafetoprotein , or hCG ; and the presence of a substantial solid component on gray-scale ultrasonography . Suspicious Doppler findings included intratumoral color flow , pulsatility index less than 1.0 , or resistance index 0.4 or lower . The findings were correlated with the presence of malignancy . Results If all three indicators ( examination , tumor marker assessment , and gray-scale ultrasound findings ) were nonsuspicious , 99 % of premenopausal women and 100 % of postmenopausal women had benign masses . If all three indicators were suspicious , 77 % of premenopausal women and 83 % of postmenopausal women had malignant tumors . Logistic regression identified ultrasound impression and tumor size to be significant predictors of malignancy in premenopausal women , whereas CA 125 level and ultrasound impression were significant in postmenopausal women . In patients with suspicious gray-scale findings , recategorization based on Doppler findings result ed in inferior diagnostic indices . Conclusions Ultrasonographic tumor size and appearance are the best predictors of pelvic malignancy in premenopausal women , whereas CA 125 level and ultrasonographic appearance are the best predictors in postmenopausal women . Neither color nor spectral Doppler is useful in this setting OBJECTIVE To investigate the potential efficacy of real-time contrast-enhanced power Doppler sonography in the differentiation of benign and malignant adnexal masses in a pilot study . METHODS Before surgical treatment , adnexal masses were prospect ively evaluated with power Doppler sonography before and after injection of a contrast agent . Real-time postinjection sequences were computerized with time-intensity analysis software to determine an enhancement curve and contrast parameters . The intraobserver and interobserver reproducibilities of these criteria were assessed on a sub sample . These contrast parameters were compared between benign and malignant tumors using logistic regression . Sensitivity and specificity were used to compare contrast parameters with sonographic and Doppler variables . RESULTS Ninety-nine women were included , for a total of 101 adnexal masses . There were 23 cases of ovarian malignancies and 78 benign adnexal lesions . Our procedure had excellent intraobserver and interobserver reproducibility , with an average intraclass correlation coefficient of 0.92 . The time before enhancement and intensity ratio did not reliably differentiate between the benign and malignant masses . Washout times and areas under the curves were significantly greater in ovarian malignancies than in other benign tumors ( P < .001 ) , leading to sensitivity estimates between 96 % and 100 % and specificity estimates between 83 and 98 % . Contrast parameters had slightly higher sensitivity and slightly lower specificity when compared with transvaginal sonographic variables of the resistive index and serum cancer antigen 125 levels . CONCLUSIONS Contrast-enhanced power Doppler imaging may easily and precisely discriminate benign from malignant adnexal lesions . Larger studies are needed to determine the appropriate use and benefits of this new procedure OBJECTIVE The purpose of this study was to evaluate prospect ively the relative usefulness of color Doppler , spectral Doppler , and gray-scale sonography in differentiating benign from malignant adnexal masses . SUBJECTS AND METHODS A total of 170 adnexal masses in 161 patients were classified prospect ively as suggestive of or not suggestive of malignant tumor on the basis of gray-scale morphology , internal flow versus peripheral or no flow , and spectral Doppler pulsatility , as measured by a pulsatility index ( PI ) threshold of 1.0 and a resistive index ( RI ) threshold of 0.4 . RESULTS Surg Output:	As a st and alone modality , serum cancer antigen 125 is not recommended for distinguishing between benign and malignant adnexal masses . Fertility-preserving surgery is an acceptable alternative to more extensive surgery in patients with low-malignant-potential tumours and those with well-differentiated surgical stage i ovarian cancer .
MS21085	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Respiratory syncytial virus ( RSV ) bronchiolitis is the most common lower respiratory tract infection in infancy . To date , there is no effective therapy for RSV bronchiolitis . In order to investigate the efficacy of clarithromycin in the treatment of RSV bronchiolitis , the present authors conducted a r and omised , double-blind , placebo-controlled trial comparing clarithromycin with placebo in 21 infants with a diagnosis of RSV bronchiolitis . The infants were r and omised to receive clarithromycin or placebo daily for 3 weeks . Levels of interleukin (IL)-4 , IL-8 , eotaxin , and interferon-γ were determined in plasma , before and after treatment , using ELISA . Six months after treatment , parents were surveyed as to whether their child had experienced wheezing within the previous 6 months . Treatment with clarithromycin was associated with a statistically significant reduction in the length of hospital stay , the duration of need for supplemental oxygen and the need for β2-agonist treatment . There were significant decreases in plasma IL-4 , IL-8 and eotaxin levels after 3 weeks of treatment with clarithromycin . Readmission to the hospital within 6 months after discharge was significantly lower in the clarithromycin group . In conclusion , clarithromycin has statistically significant effects on the clinical and laboratory findings in respiratory syncytial virus bronchiolitis . Therefore , clarithromycin treatment may be helpful in reducing the short-term effects of respiratory syncytial virus bronchiolitis Background : Respiratory syncytial virus ( RSV ) is the most common cause of viral lower respiratory tract infections ( LRTI ) . Viral LRTI is a risk factor for bacterial superinfection , having an escalating incidence with increasing severity of respiratory illness . A study was undertaken to determine the incidence of pulmonary bacterial co-infection in infants and children with severe RSV bronchiolitis , using paediatric intensive care unit ( PICU ) admission as a surrogate marker of severity , and to study the impact of the co-infection on morbidity and mortality . Methods : A prospect i ve microbiological analysis was made of lower airways secretions on all RSV positive bronchiolitis patients on admission to the PICU during three consecutive RSV seasons . Results : One hundred and sixty five children ( median age 1.6 months , IQR 0.5–4.6 ) admitted to the PICU with RSV bronchiolitis were enrolled in the study . Seventy ( 42.4 % ) had lower airway secretions positive for bacteria : 36 ( 21.8 % ) were co-infected and 34 ( 20.6 % ) had low bacterial growth/possible co-infection . All were mechanically ventilated ( median 5.0 days , IQR 3.0–7.3 ) . Those with bacterial co-infection required ventilatory support for longer than those with only RSV ( p<0.01 ) . White cell count , neutrophil count , and C-reactive protein did not differentiate between the groups . Seventy four children ( 45 % ) received antibiotics prior to intubation . Sex , co-morbidity , origin , prior antibiotics , time on preceding antibiotics , admission oxygen , and ventilation index were not predictive of positive bacterial cultures . There were 12 deaths ( 6.6 % ) , five of which were related to RSV . Conclusions : Up to 40 % of children with severe RSV bronchiolitis requiring admission to the PICU were infected with bacteria in their lower airways and were at increased risk for bacterial pneumonia Routine administration of antibiotics in the treatment of pneumonia and bronchiolitis in infants and small children was evaluated in an open r and omised prospect i ve trial . From 1979 - 82 136 children between the age of 1 month and 6 years were allocated to one of two treatment groups shortly after their admission to a paediatric ward . Group A patients were to be given antibiotics but those in group B were not . None of the children had received antibiotics before hospital admission . A viral infection was diagnosed in 38 of the 72 patients from group A and in 34 of the 64 patients from group B. Respiratory syncytial virus was detected in 84 % of these patients . Sample s of tracheal secretions showed no differences between the groups in respect of cytology and bacterial flora . Nor were there any significant differences in the course of acute disease , the frequency of fever relapse and pulmonary complications . Fifteen patients from group B were subsequently treated with antibiotics : two of these developed secondary purulent infections of the middle ear and one showed a slight pleural effusion . These results do not support the routine use of antibiotics in infants and small children admitted to hospital with pneumonia and bronchiolitis OBJECTIVES . The goals were to describe the ( 1 ) frequency of sepsis evaluation and empiric antibiotic treatment , ( 2 ) clinical predictors of management , and ( 3 ) serious bacterial illness frequency for febrile infants with clinical ly diagnosed bronchiolitis seen in office setting s. METHODS . The Pediatric Research in Office Setting s network conducted a prospect i ve cohort study of 3066 febrile infants ( <3 months of age with temperatures ≥38 ° C ) in 219 practice s in 44 states . We compared the frequency of sepsis evaluation , parenteral antibiotic treatment , and serious bacterial illness in infants with and without clinical ly diagnosed bronchiolitis . We identified predictors of sepsis evaluation and parenteral antibiotic treatment in infants with bronchiolitis by using logistic regression models . RESULTS . Practitioners were less likely to perform a complete sepsis evaluation , urine testing , and cerebrospinal fluid culture and to administer parenteral antibiotic treatment for infants with bronchiolitis , compared with those without bronchiolitis . Significant predictors of sepsis evaluation in infants with bronchiolitis included younger age , higher maximal temperature , and respiratory syncytial virus testing . Predictors of parenteral antibiotic use included initial ill appearance , age of < 30 days , higher maximal temperature , and general signs of infant distress . Among infants with bronchiolitis ( N = 218 ) , none had serious bacterial illness and those with respiratory distress signs were less likely to receive parenteral antibiotic treatment . Diagnoses among 2848 febrile infants without bronchiolitis included bacterial meningitis ( n = 14 ) , bacteremia ( n = 49 ) , and urinary tract infection ( n = 167 ) . CONCLUSIONS . In office setting s , serious bacterial illness in young febrile infants with clinical ly diagnosed bronchiolitis is uncommon . Limited testing for bacterial infections seems to be an appropriate management strategy BACKGROUND Nearly half of all hospitalized infants with respiratory syncytial virus ( RSV ) lower respiratory tract disease ( LRTD ) are treated with ( parenteral ) antibiotics . The present study was design ed to test our hypothesis that the use of antibiotics would not lead to a reduced duration of hospitalization in mild to moderate RSV LRTD . METHODS Seventy-one patients < or = 24 months of age with a virologically confirmed clinical diagnosis of RSV LRTD were r and omized to azithromycin 10 mg/kg/day ( n = 32 ) or placebo ( n = 39 ) in a multicenter , r and omized , double-blind , placebo-controlled equivalence trial during three RSV seasons ( 2002 - 2004 through 2005 - 2006 ) . Primary endpoint was duration of hospitalization , secondary endpoints included duration of oxygen supplementation and nasogastric tube feeding , course of RSV symptom score , number of PICU referrals and number of patients who received additional antibiotic treatment . Data were analyzed according to the intention-to-treat principle using the Mann-Whitney U-test or chi2 test considering P < 0.05 as statistically significant . RESULTS Included patients were comparable with respect to baseline demographics , clinical characteristics , laboratory and roentgenologic investigations . The mean duration of hospitalization was not significantly different between patients treated with azithromycin or placebo ( 132.0 + /- 10.8 vs. 139.6 + /- 7.7 hr , P = 0.328 ) . Azithromycin was not associated with a stronger resolution of clinical symptoms represented by the RSV symptom score . Four patients were treated with antibiotics after 72 hr , three of them were assigned to placebo ( P = 0.406 ) . CONCLUSIONS Infants and young children with RSV LRTD do not benefit from routine treatment with antibiotics ( IS RCT N number 86554663 ) OBJECTIVES To determine the current management of bronchiolitis by five major New Zeal and hospitals and to identify areas for improvement . METHODS Lists of infants under 1 year of age admitted with bronchiolitis during 1998 were obtained from the casemix offices of the five largest New Zeal and hospitals with paediatric services . Hospital records from a r and om sample of these admissions were review ed . RESULTS Out of the 409 infants admitted overnight , 8 % had been born less than or=32 weeks gestation and 53 % were aged younger than 6 months . Overall , 59 % received oxygen , 21 % had nasogastric fluids , 22 % had intravenous fluids , 34 % were prescribed antibiotics , 42 % received bronchodilators and 60 % had a chest radiograph . Respiratory secretions were collected for viral studies from 58 % of infants and , in 59 % , respiratory syncytial virus was detected . Significant variations in management were detected between hospitals . The overall proportion of infants requiring oxygen , intravenous or nasogastric fluids ( 65 % ) was significantly higher than that found in a 1986 - 1988 Christchurch study where only 25 % received one or more of these interventions ( P < 0.001 ) . CONCLUSIONS Opportunities exist to rationalize bronchiolitis management in New Zeal and with potential cost savings , particularly by reducing the number of chest radiographs and prescribing of unnecessary antibiotics and bronchodilators Aims : To examine the frequency of and risk factors for bacteraemia in children hospitalised with respiratory syncytial virus ( RSV ) infection ; and to determine current use of antibiotics in hospitalised children with RSV infection . Methods : Retrospective study of all children , aged 0–14 years , admitted to a tertiary children ’s hospital with proven RSV infection over a four year period . Children with concurrent bacteraemia and RSV infection were identified , and risk factors examined for bacteraemia . The case notes of a r and omly selected comparison sample of 100 of these RSV infected children were examined to assess antibiotic use and population incidence of risk factors for severe RSV infection . Results : A total of 1795 children had proven RSV infection , and blood cultures were sent on 861 ( 48 % ) . Eleven ( 0.6 % ) of the 1795 RSV positive children had bacteraemia . RSV positive children had a significantly higher incidence of bacteraemia if they had nosocomial RSV infection ( 6.5 % ) , cyanotic congenital heart disease ( 6.6 % ) , or were admitted to the paediatric intensive care unit ( 2.9 % ) . Forty five ( 45 % ) of the r and om comparison sample of RSV infected children received antibiotics . Conclusions : Bacteraemia is rare in RSV infection . Children with RSV infection are more likely to be bacteraemic , however , if they have nosocomial RSV infection , cyanotic congenital heart disease , or require intensive care unit admission arthritis , particularly with actively inflamed large joints , and ankylosing spondylitis . The fact that indomethacin is a rapidly effective , non-steroidal , anti-inflammatory agent , like phenylbutazone , makes it a useful alternative to predni-steroid therapy . As with many other drugs used in the treatment of chronic rheumatic disorders , indomethacin causes undesired effects which are particularly apt to occur in the early stages of treatment . Fortunately most of these are trivial and clear rapidly after withdrawal of the drug . In view of the occurrence of severe neurological disturbance in seven of our cases we feel that it would be unwise to ignore and dangerous to suppress the headache and associated symptoms so commonly encountered . If these can not be avoided by gradual induction or by subsequent reduction of dosage , they must be taken as an indication for stopping the drug . It would seem reasonable to insist that indomethacin should only be given with caution to any patient with a history of depressive illness . Active or recent peptic ulceration should be regarded as an absolute contraindication , and therapy should not be resumed in any patient who exhibits a rash during treatment BACKGROUND Treatment of hospitalized infants with respiratory syncytial virus ( RSV ) bronchiolitis is mainly supportive . Bronchodilators and systemic steroids are often used but do not reduce the length of hospital stay . Because hypoxia and airways obstruction develop secondary to viscous mucus in infants with RSV bronchiolitis , and because free DNA is present in RSV mucus , we tested the efficacy of the mucolytic drug recombinant human deoxyribonuclease ( rhDNase ) . METHODS In a multicenter , r and omized , double-blind , controlled clinical trial , 225 oxygen-dependent infants admitted to the hospital for RSV Output:	AUTHORS ' CONCLUSIONS This review found minimal evidence to support the use of antibiotics for bronchiolitis .
MS21086	*TASK* the task is to summarize an input biomedical literature in six sentences *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 effect of a computerized medical record and other practice factors on the delivery of preventive health care . DESIGN Prospect i ve , controlled trial . SETTING University general internal medicine teaching clinic . PARTICIPANTS Forty-five internal medicine residents and their 4 supervising attending physicians . INTERVENTION The study group used a computerized ambulatory medical record system that included health care maintenance reminders . The control group used a conventional paper record with a health care maintenance flow sheet . MEASUREMENTS AND MAIN RESULTS The computer reminders significantly increased health care maintenance recommendations made to patients for proctosigmoidoscopy , tetanus vaccination , influenza vaccination , and pneumococcal vaccination , but not for fecal occult blood testing , mammography , Pap smears , or serum thyroxine screening in the elderly . First-year residents were nearly twice as successful as third-year residents in overall health care maintenance . Success scores varied markedly depending on which attending physician was supervising the residents . We found a strong interaction among group assignment , supervising attending , and level of training such that the reminders doubled success scores among first-year residents supervised by two of the attending physicians but had little effect on other subgroups . The time of year and the format of the reminder also had important effects for some of the maneuvers . CONCLUSIONS Although computerized medical records markedly improved the performance of prevention maneuvers by committed physicians , many physicians using computer systems failed to make use of the re source . The reasons for this were complex . Future work in this area should carefully control for personal behaviors and focus upon administrative changes that more effectively implement these potentially powerful tools Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions BACKGROUND Adverse drug-related events are common in the elderly , and inappropriate prescribing is a preventable risk factor . Our objective was to determine whether inappropriate prescribing could be reduced when primary care physicians had computer-based access to information on all prescriptions dispensed and automated alerts for potential prescribing problems . METHODS We r and omly assigned 107 primary care physicians with at least 100 patients aged 66 years and older ( total 12 560 ) to a group receiving computerized decision-making support ( CDS ) or a control group . Physicians in the CDS group had access to information on current and past prescriptions through a dedicated computer link to the provincial seniors ' drug-insurance program . When any of 159 clinical ly relevant prescribing problems were identified by the CDS software , the physician received an alert that identified the nature of the problem , possible consequences and alternative therapy . The rate of initiation and discontinuation of potentially inappropriate prescriptions was assessed over a 13-month period . RESULTS In the 2 months before the study , 31.8 % of the patients in the CDS group and 33.3 % of those in the control group had at least 1 potentially inappropriate prescription . During the study the number of new potentially inappropriate prescriptions per 1000 visits was significantly lower ( 18 % ) in the CDS group than in the control group ( relative rate [ RR ] 0.82 , 95 % confidence interval [ CI ] 0.69 - 0.98 ) , but differences between the groups in the rate of discontinuation of potentially inappropriate prescriptions were significant only for therapeutic duplication by the study physician and another physician ( RR 1.66 , 95 % CI 0.99 - 2.79 ) and drug interactions caused by prescriptions written by the study physician ( RR 2.15 , 95 % CI 0.98 - 4.70 ) . INTERPRETATION Computer-based access to complete drug profiles and alerts about potential prescribing problems reduces the rate of initiation of potentially inappropriate prescriptions but has a more selective effect on the discontinuation of such prescriptions Background — Indirect evidence shows that alerting users with clinical decision support systems seems to change behavior more than requiring users to actively initiate the system . However , r and omized trials comparing these methods in a clinical setting are lacking . We studied the effect of both alerting and on-dem and decision support with respect to screening and treatment of dyslipidemia based on the guidelines of the Dutch College of General Practitioners . Methods and Results — In a clustered r and omized trial design , 38 Dutch general practice s ( 77 physicians ) and 87 886 of their patients ( 39 433 men 18 to 70 years of age and 48 453 women 18 to 75 years of age ) who used the ELIAS electronic health record participated . Each practice was assigned to receive alerts , on-dem and support , or no intervention . We measured the percentage of patients screened and treated after 12 months of follow-up . In the alerting group , 65 % of the patients requiring screening were screened ( relative risk versus control=1.76 ; 95 % confidence interval , 1.41 to 2.20 ) compared with 35 % of patients in the on-dem and group ( relative risk versus control=1.28 ; 95 % confidence interval , 0.98 to 1.68 ) and 25 % of patients in the control group . In the alerting group , 66 % of patients requiring treatment were treated ( relative risk versus control=1.40 ; 95 % confidence interval , 1.15 to 1.70 ) compared with 40 % of patients ( relative risk versus control=1.19 ; 95 % confidence interval , 0.94 to 1.50 ) in the on-dem and group and 36 % of patients in the control group . Conclusion — The alerting version of the clinical decision support systems significantly improved screening and treatment performance for dyslipidemia by general practitioners OBJECTIVE Computerized physician order entry with clinical decision support has been shown to improve medication safety in adult in patients , but few data are available regarding its usefulness in the long-term care setting . The objective of this study was to examine opportunities for improving medication safety in that clinical setting by determining the proportion of medication orders that would generate a warning message to the prescriber via a computerized clinical decision support system and assessing the extent to which these alerts would affect prescribers ' actions . DESIGN The study was set within a r and omized controlled trial of computerized clinical decision support conducted in the long-stay units of a large , academically-affiliated long-term care facility . In March 2002 , a computer-based clinical decision support system ( CDSS ) was added to an existing computerized physician order entry ( CPOE ) system . Over a subsequent one-year study period , prescribers ordering drugs for residents on three resident-care units of the facility were presented with alerts ; these alerts were not displayed to prescribers in the four control units . MEASUREMENTS We assessed the frequency of drug orders associated with various categories of alerts across all participating units of the facility . To assess the impact of actually receiving an alert on prescriber behavior during drug ordering , we calculated separately for the intervention and control units the proportion of the alerts , within each category , that were followed by an appropriate action and estimated the relative risk of an appropriate action in the intervention units compared to the control units . RESULTS During the 12 months of the study , there were 445 residents on the participating units of the facility , contributing 3,726 resident-months of observation time . During this period , 47,997 medication orders were entered through the CPOE system-approximately 9 medication orders per resident per month . 9,414 alerts were triggered ( 2.5 alerts per resident-month ) . The alert categories most often triggered were related to risks of central nervous system side-effects such as over-sedation ( 20 % ) . Alerts for risk of drug-associated constipation ( 13 % ) or renal insufficiency/electrolyte imbalance ( 12 % ) were also common . Twelve percent of the alerts were related to orders for warfarin . Overall , prescribers who received alerts were only slightly more likely to take an appropriate action ( relative risk 1.11 , 95 % confidence interval 1.00 , 1.22 ) . Alerts related to orders for warfarin or central nervous system side effects were most likely to engender an appropriate action , such as ordering a recommended laboratory test or canceling an ordered drug . CONCLUSION Long-term care facilities must implement new system-level approaches with the potential to improve medication safety for their residents . The number of medication orders that triggered a warning message in this study suggests that CPOE with a clinical decision support system may represent one such tool . However , the relatively low rate of response to these alerts suggests that further refinements to such systems are required , and that their impact on medication errors and adverse drug events must be carefully assessed OBJECTIVE The aim of this study was to evaluate the impact of an integrated patient-specific electronic clinical reminder system on diabetes and coronary artery disease ( CAD ) care and to assess physician attitudes toward this reminder system . DESIGN We enrolled 194 primary care physicians caring for 4549 patients with diabetes and 2199 patients with CAD at 20 ambulatory clinics . Clinics were r and omized so that physicians received either evidence -based electronic reminders within their patients ' electronic medical record or usual care . There were five reminders for diabetes care and four reminders for CAD care . MEASUREMENTS The primary outcome was receipt of recommended care for diabetes and CAD . We created a summary outcome to assess the odds of increased compliance with overall diabetes care ( based on five measures ) and overall CAD care ( based on four measures ) . We surveyed physicians to assess attitudes toward the reminder system . RESULTS Baseline adherence rates to all quality measures were low . While electronic reminders increased the odds of recommended diabetes care ( odds ratio [ OR ] 1.30 , 95 % confidence interval [ CI ] 1.01 - 1.67 ) and CAD ( OR 1.25 , 95 % CI 1.01 - 1.55 ) , the impact of individual reminders was variable . A total of three of nine reminders effectively increased rates of recommended care for diabetes or CAD . The majority of physicians ( 76 % ) thought that reminders improved quality of care . CONCLUSION An integrated electronic reminder system result ed in variable improvement in care for diabetes and CAD . These improvements were often limited and quality gaps persist Guided dosing within a computerized provider order entry ( CPOE ) system is an effective method of individualizing therapy for patients . Physicians ' responses to guided dosing decision support have not been extensively studied . As part of a r and omized trial evaluating efficacy of dosing advice on reducing falls in the elderly , CPOE prompts to physicians for 88 drugs included tailored messages and guided dose lists with recommended initial doses and frequencies . The study captured all prescribing activity electronically . The primary outcome was the ratio between prescribed dose and recommended dose . Over 9 months , 778 providers entered 9111 study -related medication orders on 2981 patients . Physicians using guided orders chose recommended doses more often than controls(28.6 % vs. 24.1 % , p<0.001 ) . Selected doses were significantly lower in the intervention group ( median ratio of actual to recommended 2.5 , interquartile range [ 1.0,4.0 ] ) than the control group ( median 3.0 interquartile range [ 1.5,5.0 ] , p<0.001 ) . While physicians selected the recommended dose less than a third of the time , guided geriatric dosing modestly improved compliance with guidelines OBJECTIVE To assess the impact of an automated intraoperative alert to redose prophylactic antibiotics in prolonged cardiac operations . DESIGN R and omized , controlled , evaluator-blinded trial . SETTING University-affiliated hospital . PATIENTS Patients undergoing cardiac surgery that lasted more than 4 hours after the preoperative administration of cefazolin , unless they were receiving therapeutic antibiotics at the time of surgery . INTERVENTION R and omization to an audible and visual reminder on the operating room computer console at 225 minutes after the administration of preoperative antibiotics ( reminder group , n = 137 ) or control ( n = 136 ) . After another 30 minutes , the circulating nurse was required to indicate whether a follow-up dose of antibiotics had been administered . RESULTS Intraoperative redosing was significantly more frequent in the reminder group ( 93 of 137 ; 68 % ) than in the control group ( 55 of 136 ; 40 % ) ( adjusted odds ratio , 3.31 ; 95 % confidence interval , 1.97 to 5.56 ; P < .0001 ) . The impact of the reminder was even greater when compared with the 6 months preceding the study period ( 129 of 480 ; Output:	INTERPRETATION Computer reminders produced much smaller improvements than those generally expected from the implementation of computerized order entry and electronic medical record systems .
MS21087	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BDNF plays a critical role in activity-dependent neuroplasticity underlying learning and memory in the hippocampus . A frequent single nucleotide polymorphism in the targeting region of the human BDNF gene ( val66met ) has been associated with abnormal intracellular trafficking and regulated secretion of BDNF in cultured hippocampal neurons transfected with the met allele . In addition , the met allele has been associated with abnormal hippocampal neuronal function as well as impaired episodic memory in human subjects , but a direct effect of BDNF alleles on hippocampal processing of memory has not been demonstrated . We studied the relationship of the BDNF val66met genotype and hippocampal activity during episodic memory processing using blood oxygenation level-dependent functional magnetic resonance imaging and a declarative memory task in healthy individuals . Met carriers exhibited relatively diminished hippocampal engagement in comparison with val homozygotes during both encoding and retrieval processes . Remarkably , the interaction between the BDNF val66met genotype and the hippocampal response during encoding accounted for 25 % of the total variation in recognition memory performance . These data implicate a specific genetic mechanism for substantial normal variation in human declarative memory and suggest that the basic effects of BDNF signaling on hippocampal function in experimental animals are important in humans In a prospect ive-longitudinal study of a representative birth cohort , we tested why stressful experiences lead to depression in some people but not in others . A functional polymorphism in the promoter region of the serotonin transporter ( 5-HT T ) gene was found to moderate the influence of stressful life events on depression . Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms , diagnosable depression , and suicidality in relation to stressful life events than individuals homozygous for the long allele . This epidemiological study thus provides evidence of a gene-by-environment interaction , in which an individual 's response to environmental insults is moderated by his or her genetic makeup BACKGROUND Neurotrophic factors are known to play an important role in the survival and differentiation of many types of neurons during development . Both brain-derived neurotrophic factor ( BDNF ) and ciliary neurotrophic factor ( CNTF ) may act cooperatively in modulating the development and functioning of synapses . Both these neurotrophic factors were intensely investigated with regard to depression without conclusive results . METHODS We have investigated the possible use of both CNTF null-mutation and BDNF polymorphism C270 T as biomarkers for depression in the Vienna Transdanube Aging ( VITA ) study . The VITA is a prospect i ve community-based cohort study of all 75 years old inhabitants of a geographical region of Vienna . RESULTS We found no association between CNTF null-mutation and BDNF C270 T polymorphism to any depressive symptoms after exclusion of demented subjects . CONCLUSION These results call in question the hypothesis that either BDNF or CNTF can be used as molecular markers for depression or late onset depression in the elderly OBJECTIVE To compare differences in gray matter volumes , white matter and subcortical gray matter hyperintensities , neuropsychological factors , and treatment outcome between early- and late-onset late-life depressed ( LLD ) subjects . METHODS We conducted a prospect i ve , nonr and omized , controlled trial at the outpatient clinics at Washington University and Duke University on 126 subjects , aged 60 years or older , who met Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria for major depression , scored 20 or more on the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and received neuropsychological testing and magnetic resonance imaging . Subjects were excluded for cognitive impairment or severe medical disorders . After 12 weeks of sertraline treatment , subjects ' MADRS scores over time and neuropsychological factors were studied . RESULTS Left anterior cingulate thickness was significantly smaller in the late-onset depressed group than in the early-onset LLD subjects . The late-onset group also had more hyperintensities than the early-onset LLD subjects . No differences were found in neuropsychological factor scores or treatment outcome between early-onset and late-onset LLD subjects . CONCLUSION Age at onset of depressive symptoms in LLD subjects are associated with differences in cortical thickness and white matter and subcortical gray matter hyperintensities , but age at onset did not affect neuropsychological factors or treatment outcome We have developed an online catalog of SNP-trait associations from published genome-wide association studies for use in investigating genomic characteristics of trait/disease-associated SNPs ( TASs ) . Reported TASs were common [ median risk allele frequency 36 % , interquartile range ( IQR ) 21%−53 % ] and were associated with modest effect sizes [ median odds ratio ( OR ) 1.33 , IQR 1.20–1.61 ] . Among 20 genomic annotation sets , reported TASs were significantly overrepresented only in nonsynonymous sites [ OR = 3.9 ( 2.2−7.0 ) , p = 3.5 × 10−7 ] and 5kb-promoter regions [ OR = 2.3 ( 1.5−3.6 ) , p = 3 × 10−4 ] compared to SNPs r and omly selected from genotyping arrays . Although 88 % of TASs were intronic ( 45 % ) or intergenic ( 43 % ) , TASs were not overrepresented in introns and were significantly depleted in intergenic regions [ OR = 0.44 ( 0.34−0.58 ) , p = 2.0 × 10−9 ] . Only slightly more TASs than expected by chance were predicted to be in regions under positive selection [ OR = 1.3 ( 0.8−2.1 ) , p = 0.2 ] . This new online re source , together with bioinformatic predictions of the underlying functionality at trait/disease-associated loci , is well-suited to guide future investigations of the role of common variants in complex disease etiology OBJECTIVE This study compared microstructural abnormalities in depressed elders and controls and studied the association of the serotonin transporter gene status to white matter abnormalities and to remission of depression . METHODS The subjects were Caucasians with non-psychotic major depression and normal elders . Depressed subjects received escitalopram 10 mg daily for 12 weeks . Remission was defined as a HDRS score of 7 or below for 2 consecutive weeks . Diffusion tensor imaging was performed and voxel-based analysis of fractional anisotropy ( FA ) was conducted using age and mean diffusivity as covariates . RESULTS Depressed elders ( N=27 ) had lower FA than controls ( N=27 ) in several frontolimbic areas . Depressed elderly S-allele carriers also had lower FA than L homozygotes in frontolimbic brain areas , including the dorsal and rostral anterior cingulate , posterior cingulate , dorsolateral prefrontal and medial prefrontal regions , thalamus , and in other regions . S-allele carriers had a lower remission rate than L homozygotes . LIMITATIONS Small number of subjects , lack of r and om sampling , fixed antidepressant dose , short follow-up . CONCLUSIONS Lower FA was observed in several frontolimbic and other regions in depressed elders compared to controls . Depressed S-allele carriers had both microstructural white matter abnormalities in frontolimbic networks and a low remission rate . It remains unclear whether the risk for chronicity of geriatric depression in S-allele carriers is mediated by frontolimbic compromise . However , these observations set the stage for studies aim ing to identify the relationship of S allele to impairment in specific frontolimbic functions interfering with response of geriatric depression to antidepressants The recently shown association between apolipoprotein E ( APOE ) genotype and depressive illness has been challenged by subsequent studies . However , controversial results may derive from the different diagnostic criteria used for depression and from the small numbers of depressed patients included in the studies . We examined the association between depression and the genetic polymorphism of APOE in a large sample of depressed patients , Alzheimer ’s disease ( AD ) patients , and healthy controls following clear definitions for late-life depression . The cumulative incidence of depression depending on the age at onset of the first episode was examined by survival analysis . Our data do not disconfirm the hypothesis of depression sharing some common pathophysiologic features with AD , however , it seems very unlikely that the APOE genotype will eluci date the assumed common mechanisms BACKGROUND Alcoholism is a complex , genetically influenced disorder the cause of which may be better understood through the study of genetically influenced phenotypes that mediate the risk . One such intermediate phenotype is the low level of response ( LR ) to alcohol . This project used a case-control approach to search for genes that may contribute to LR . METHODS Data were available from alcohol challenges at approximately age 20 and regarding the development of alcohol use disorders over the subsequent 20 years for 85 men , including 40 reported in a previous genetic analysis . LR was evaluated using oral consumption of 0.75 ml/kg of alcohol , after which changes in subjective feelings of intoxication and body sway were measured . Alcohol abuse and dependence were diagnosed by DSM-III-R criteria through structured interviews administered to both the participant and an informant ( usually the spouse ) 10 , 15 , and 20 years after initial testing . Four polymorphisms were evaluated , including the serotonin transporter HTTLPR promoter ins/del , GABAAalpha6 Pro385Ser , NPY Leu7Pro , and catalase 262C > T. Two of these , HTTLPR and GABAAalpha6 Pro385Ser , had been previously associated with LR and alcoholism in a preliminary study . RESULTS The HTTLPR L allele was significantly related to both the LR and alcoholism in an allele-dosage ( stepwise ) manner . Furthermore , the association remained when L alleles were subdivided into recently reported functional subtypes : the lowest LR was associated with genotypes correlated with the highest serotonin transporter expression . The GABAAalpha6 Ser385 allele showed a nonsignificant trend for association to a low LR , as had been previously observed , although the Ser385 allele is uncommon , and only 18 heterozygotes were in the current group . However , the six men with both LL and Pro385/Ser385 genotypes had the lowest LR , and each had developed alcoholism during follow-up . Neither NPY nor catalase was associated with either LR or alcoholic outcomes , although the sample did not have sufficient power for definitive conclusions . CONCLUSIONS This report strengthens the support for a relationship between the HTTLPR L and GABAAalpha6 Ser385 alleles to low alcohol LR and to alcoholism in a prospect ively studied cohort evaluated for LR in young adulthood and before the onset of alcohol dependence Output:	These genes are implicated in hippocampal plasticity and stress reactivity , suggesting that dysregulation of these pathways may contribute to LLD .
MS21088	*TASK* the task is to summarize an input biomedical literature in six sentences *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 oral ciprofloxacin was compared with that of parenteral aminoglycoside for therapy of complicated urinary tract infection in a prospect i ve r and omized trial . The setting was a chronic-care Veterans Administration facility in which long-term bladder catheterization and resistant bacteria were common . Sixty-five consecutive patients were stratified for presence and type of bladder catheter , the presence of Providencia and Pseudomonas aeruginosa organisms versus other urinary pathogens , and renal dysfunction . A pharmacokinetic study of ciprofloxacin concentrations in serum and urine was performed with selected patients . Urinary catheters were present in 94 % . All patients were symptomatic , and 58.5 % had fever . Ciprofloxacin , 500 mg every 12 h orally , was compared with parenteral aminoglycoside for 7 to 10 days . Clinical response , defined by resolution of symptoms and fever at 5 to 9 days posttherapy ( short-term ) and 28 to 30 days posttherapy ( long-term ) , was essentially identical for both treatment groups . Bacteriologic response , defined by sterile urine cultures , showed that ciprofloxacin was significantly more efficacious ( P = 0.0005 ) than aminoglycoside at 5 to 9 days posttherapy . However , by 28 to 30 days , the response rate was essentially identical . Emergence of resistance to the study antibiotic was seen in 62 and 70 % of those who did not show a bacteriological response and were receiving ciprofloxacin and aminoglycosides , respectively . Concentrations of ciprofloxacin and aminoglycoside in the urine substantially exceeded the MIC for the urinary pathogens isolated , although these concentrations did not correlate with short-term bacteriologic response for either antibiotic . Ciprofloxacin was efficacious in complicated urinary tract infection compared with the current st and ard of parenteral aminoglycoside among catheterized patients with relatively resistant bacteria Abstract The aim of this trial was to compare the efficacy and safety of extended-release ciprofloxacin ( CIPRO XR ) versus the immediate-release formulation ( CIPRO IR ) in the treatment of complicated urinary tract infections ( UTIs ) . 212 patients were r and omized to CIPRO XR 1,000 mg tablet once daily or CIPROXIN IR 500 mg tablet twice daily . Treatment efficacy was evaluated by bacteriological outcome . Safety was measured by recording adverse events . The rate of bacteriological eradication was 83 % in the CIPRO XR group and 75 % in the CIPRO IR . The overall incidence of adverse events reported was higher in the CIPRO IR group . The authors conclude that CIPRO XR is a safe and effective treatment for complicated UTIs . Although the limited data available do not consent to support a statistically superior efficacy or safety compared to CIPRO IR , a trend in favor of CIPRO XR is clearly evident in all efficacy and safety variables . CIPRO XR is associated with reduced frequencies of drug-related adverse events compared to CIPRO IR OBJECTIVES Given increasing rates of co-trimoxazole resistance among uropathogens causing acute uncomplicated cystitis , fluoroquinolones , nitrofurantoin and fosfomycin are often considered as alternative empirical therapy . The choice between these drugs should depend in part on whether they are associated with the isolation of drug-resistant microbial flora . We conducted a r and omized treatment trial to assess the effects of ciprofloxacin , nitrofurantoin and fosfomycin on the rectal microbial flora of women with acute uncomplicated cystitis , including isolation of fluoroquinolone-resistant strains . METHODS Pre-menopausal women presenting with acute uncomplicated cystitis were r and omized to treatment with 3 days of ciprofloxacin , 7 days of nitrofurantoin , or a single dose of fosfomycin . Women were followed for 1 month for evaluation of clinical and microbiological responses as well as for isolation of resistant rectal E. coli . RESULTS Sixty-two women ( 25 ciprofloxacin , 17 nitrofurantoin , 20 fosfomycin ) were enrolled and eligible for analysis . All three regimens were well tolerated and result ed in > 90 % clinical and bacteriological cure . The prevalence of rectal E. coli was markedly decreased by ciprofloxacin and fosfomycin , but not by nitrofurantoin . One woman treated with ciprofloxacin had emergence of two ciprofloxacin-resistant rectal E. coli strains within 10 days of completing therapy . No emergence of resistance was observed in the other two treatment groups . CONCLUSIONS This study demonstrates that fluoroquinolone-resistant E. coli remain infrequent in the rectal flora of women with uncomplicated cystitis in Seattle . However , a 3 day course of a fluoroquinolone for treatment of uncomplicated cystitis was followed by isolation of fluoroquinolone-resistant rectal E. coli in one patient A double-blind , r and omized controlled study to evaluate the efficacy and safety of a single dose of 500 mg of ciprofloxacin versus 3 days 400 mg twice-daily of norfloxacin in uncomplicated urinary tract infection in women was design ed . Patients underwent four visits : baseline , and at 3 , 7 and 28 days . The main efficacy variables were clinical and microbiological outcome at day 7 . Analyses on both valid patients and intention-to-treat population s were performed . Two hundred and twenty-six patients ( 114 receiving ciprofloxacin and 112 receiving norfloxacin ) were considered valid for efficacy evaluation . Bacteriologic cure was 91.2 % in the ciprofloxacin group and 91.9 % in the norfloxacin group . Clinical resolution was 91.2 and 93.8 % , respectively . Both treatments were equally efficacious ( P = 0.016 ) Seventy-one adult patients with 72 infections were treated , by r and om selection , with intravenous/oral ciprofloxacin or intravenously administered ceftazidime . Twenty-seven additional patients with 29 infections who were not appropriate for r and om assignment were treated in an open study with intravenously administered ciprofloxacin only ; the latter infections were generally more serious or were caused by ceftazidime-resistant organisms . The most common doses were ciprofloxacin , 200 mg intravenously and 500 mg orally every 12 hours and ceftazidime , 1 to 2 g intravenously every eight to 12 hours . Forty-seven ciprofloxacin-treated infections and 31 ceftazidime-treated infections were evaluable for determination of efficacy . Infections included lower respiratory tract ( 21 infections ) , urinary ( 37 infections ) , skin/soft tissue ( 14 infections ) , bacteremia/endocarditis ( four infections ) , colitis ( one infection ) , and mastoiditis ( one infection ) . Median minimal inhibitory concentrations of ciprofloxacin and ceftazidime were , respectively : for Enterobacteriaceae , Haemophilus influenzae , and Branhamella catarrhalis , no more than 0.06 and no more than 0.25 micrograms/ml ; for Pseudomonas aeruginosa , 0.25 and 4 micrograms/ml ; for Enterococcus faecalis , 1 and more than 32 micrograms/ml ; and for Staphylococcus aureus , 0.25 and 8 micrograms/ml . Ciprofloxacin , 200 mg intravenously , yielded mean serum concentrations 0.5 and eight hours post-intravenous infusion of 2.3 and 0.7 micrograms/ml , respectively . Satisfactory clinical responses were achieved in 17 ( 81 percent ) of 21 patients with intravenous/oral ciprofloxacin , 22 ( 71 percent ) of 31 patients with ceftazidime , and 20 ( 77 percent ) of 26 patients with intravenous ciprofloxacin . The most common treatment failures occurred in complicated skin/soft-tissue infections treated with intravenous/oral ciprofloxacin , complicated urinary tract infections treated with ceftazidime , and necrotizing P. aeruginosa pneumonia treated with intravenous ciprofloxacin ; the pneumonia patients all had respiratory failure and had been previously unresponsive to treatment with other appropriate drugs . Serious adverse reactions were observed in three patients , seizures with intravenous ciprofloxacin in two patients , and Clostridium difficile diarrhea with ceftazidime in one patient . We conclude that sequential intravenous/oral ciprofloxacin and ceftazidime were comparable in efficacy and safety ; the ability to change from intravenous to oral therapy is a major convenience . Intravenous ciprofloxacin was useful for more serious infections , often caused by ceftazidime-resistant organisms ABSTRACT Twelve healthy volunteers participated in this r and omized crossover study to compare the concentrations and recovery levels of fleroxacin and pefloxacin in urine and to assess their bactericidal activities against 12 strains of urinary pathogens with different susceptibilities over a wide range of MICs . The volunteers received a single oral dose of 400 mg of fleroxacin or 800 mg of pefloxacin . The mean cumulative renal excretion of unchanged fleroxacin , N-demethyl-fleroxacin , and N-oxide-fleroxacin accounted for 67 , 7 , and 6 % of the total dose , respectively . The total urinary recovery of pefloxacin and the active metabolite norfloxacin was 34 % . In the time-kill and the urinary bactericidal titer ( UBT ) studies , only the subjects ’ urine not supplemented with broth was used . With most tested organisms and both quinolones it took more than 8 h to achieve a reduction in CFU of 99.9 % ( 3 log units ) . Overall , there was a good correlation between UBTs and MICs for the strains . Against Escherichia coli ATCC 25922 the median UBTs were similar for both antibiotics and at least 1:8 for 96 h ; against the E. coli strain for which the MIC was 0.5 μg/ml the UBT was at least 1:4 for 48 h. The UBTs of both drugs against Klebsiella pneumoniae were at least 1:16 for 72 h. The UBTs for Staphylococcus aureus ( the MIC for which was 16 μg/ml ) of both antibiotics were low , and in some of the sample s , no bactericidal titers were observed . UBTs for Proteus mirabilis of pefloxacin are significantly higher than those of fleroxacin . For Pseudomonas aeruginosa the median UBTs were present for the 24-to-48-h interval . The same is true forEnterococcus faecalis . Against Staphylococcus saprophyticus , UBTs were present for at least 48 h with both quinolones . Overall , a single oral dose of 400 mg of fleroxacin exhibits UBTs comparable to those of 800 mg of pefloxacin . Therefore , it may be expected that half of the dose of fleroxacin gives comparable results in the treatment of urinary tract infections ; this should be substantiated in comparative clinical trials OBJECTIVES To evaluate the prevention of urinary tract infections ( UTIs ) after transurethral resection of the prostate ( TURP ) in a prospect i ve r and omized study using a quinolone antibiotic ( fleroxacin ) to compare the efficacy of : ( 1 ) a single oral dose , ( 2 ) a single intravenous ( IV ) dose , and ( 3 ) an extended regimen consisting of an initial IV dose followed by oral therapy until removal of the urinary catheter , but for less than 6 days . METHODS We excluded from study patients who received antimicrobial agents within 48 hours of surgery . Single-dose prophylaxis consisted of 400 mg of fleroxacin given either orally or intravenously . The extended regimen consisted of an initial 400 mg IV dose followed by 400 mg oral each day ( patients older than 75 years , or with a creatinine clearance less than 40 mL/min , received 200 mg/day ) . UTI was defined as clinical evidence of infection plus the presence of more than 10 white blood cells (WBC)/mm3 in any urine specimen plus the presence of more than 10(4 ) cfu/mL in midstream urine specimens or more than 10(2 ) cfu/mL in catheter specimens . RESULTS Prior to TURP , 30 % Output:	An analysis of the remaining RGTs identified therapeutic equivalence of ciprofloxacin against other antimicrobials in terms of bacterial eradication and clinical cure at the end of treatment and in subsequent stages . The percentage of bacterial resistance was similar in both groups , while the percentage of related adverse events was significantly lower in the groups treated with ciprofloxacin . CONCLUSIONS We conclude that ciprofloxacin is a safe and effective therapeutic alternative for the treatment of acute or complicated urinary tract infections in adults
MS21089	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Well London is a multicomponent community engagement and coproduction programme design ed to improve the health of Londoners living in socioeconomically deprived neighbourhoods . To evaluate outcomes of the Well London interventions , a cluster r and omised trial ( CRT ) was conducted that included a longitudinal qualitative component , which is reported here . The aim is to explore in depth the nature of the benefits to residents and the processes by which these were achieved . Methods The 1-year longitudinal qualitative study was nested within the CRT . Purposive sampling was used to select three intervention neighbourhoods in London and 61 individuals within these neighbourhoods . The interventions comprised activities focused on : healthy eating , physical exercise and mental health and well-being . Interviews were conducted at the inception and following completion of the Well London interventions to establish both if and how they had participated . Transcripts of the interviews were coded and analysed using Nvivo . Results Positive benefits relating to the formal outcomes of the CRT were reported , but only among those who participated in project activities . The extent of benefits experienced was influenced by factors relating to the physical and social characteristics of each neighbourhood . The highest levels of change occurred in the presence of : ( 1 ) social cohesion , not only pre-existing but also as facilitated by Well London activities ; ( 2 ) personal and collective agency ; ( 3 ) involvement and support of external organisations . Where the physical and social environment remained unchanged , there was less participation and fewer benefits . Conclusions These findings show interaction between participation , well-being and agency , social interactions and cohesion and that this modulated any benefits described . Pathways to change were thus complex and variable , but personal well-being and local social cohesion emerged as important mediators of change Background We report the main results , among adults , of a cluster-r and omised-trial of Well London , a community-engagement programme promoting healthy eating , physical activity and mental well-being in deprived neighbourhoods . The hypothesis was that benefits would be neighbourhood-wide , and not restricted to intervention participants . The trial was part of a multicomponent process/ outcome evaluation which included non-experimental components ( self-reported behaviour change amongst participants , case studies and evaluations of individual projects ) which suggested health , well-being and social benefits to participants . Methods Twenty matched pairs of neighbourhoods in London were r and omised to intervention/control condition . Primary outcomes ( five portions fruit/vegetables/day ; 5 × 30 m of moderate intensity physical activity/week , abnormal General Health Question naire (GHQ)-12 score and Warwick – Edinburgh Mental Well-being Scale ( WEMWBS ) score ) were measured by postintervention question naire survey , among 3986 adults in a r and om sample of households across neighbourhoods . Results There was no evidence of impact on primary outcomes : healthy eating ( relative risk [ RR ] 1.04 , 95 % CI 0.93 to 1.17 ) ; physical activity ( RR:1.01 , 95 % CI 0.88 to 1.16 ) ; abnormal GHQ12 ( RR:1.15 , 95 % CI 0.84 to 1.61 ) ; WEMWBS ( mean difference [ MD ] : −1.52 , 95 % CI −3.93 to 0.88 ) . There was evidence of impact on some secondary outcomes : reducing unhealthy eating-score ( MD : −0.14 , 95 % CI −0.02 to 0.27 ) and increased perception that people in the neighbourhood pulled together ( RR : 1.92 , 95 % CI 1.12 to 3.29 ) . Conclusions The trial findings do not provide evidence supporting the conclusion of non-experimental components of the evaluation that intervention improved health behaviours , well-being and social outcomes . Low participation rates and population churn likely compromised any impact of the intervention . Imprecise estimation of outcomes and sampling bias may also have influenced findings . There is a need for greater investment in refining such programmes before implementation ; new methods to underst and , longitudinally different pathways residents take through such interventions and their outcomes , and new theories of change that apply to each pathway Purpose . To present an evaluation of a 5-year , community-based , chronic disease prevention project managed by a state health department to determine whether the department could replicate similar previous projects that had received more funding and other re sources . Design . The evaluation used a matched comparison design and a review of archive and interview data . Setting . Florence , South Carolina ( population : 56,240 ) . Subjects . A r and om sample of 1642 persons in Florence ( and 1551 in the comparison ) who responded to a risk factor question naire and underwent a physical assessment ; 70 . 7 % of baseline subjects participated in the postintervention . Forty key persons were interviewed concerning project effectiveness . Interventions by Project . Walk-a-thons , a speakers ' bureau , media messages , restaurant food labeling , and cooking seminars . More than 31,000 participants were involved in 585 activities . Measures . Question naires focused on hypertension , obesity , high cholesterol , smoking , and exercise . Physical assessment s determined lipid , lipoprotein , apolipoprotein , and blood pressure levels . Analysis of covariance was used for baseline and postintervention comparisons . Content analysis was used on archive and interview data . Results . The project had a slightly favorable intervention effect on cholesterol and smoking , but failed to have an effect on other risk factors for cardiovascular disease . The project influenced community awareness , enlisted influential community members , and fostered linkages among local health services . Conclusions . Health departments can be instrumental in community risk reduction programming ; however , they may not replicate projects having greater re sources Background Second-h and smoke ( SHS ) in households remains a serious public health problem in Sri Lanka , partly due to a lack of voluntary prohibitions of tobacco smoking inside houses . Women are especially at risk of being exposed . Effective community based interventions to reduce the SHS in households targeting women is scarce . The objective of this study was to examine the impact of a multi-component intervention on household SHS exposure among Sri Lankan women . Methods Thirty clusters of 25 women ( aged 18–65 ) from 750 households were r and omized into the intervention and control groups . Women in the intervention group were exposed to activities which focused on improving knowledge on the health effects of SHS , attitudes towards SHS exposure , right to a smoke-free living and women empowerment against smoking . The duration of the intervention was six months . The comparison group received no intervention . The primary outcome of interest was self-reported SHS exposure in the household within 7 days prior to data collection . The secondary outcomes were exposure in the past 30 days , knowledge of the health risks of exposure , attitudes towards exposure , right to smoke-free living , women empowerment against smoking , and smoking inside the homes . Results Final assessment was in 329 ( 89.6 % ) in the intervention group and 309 ( 85.8 % ) in the comparison group . Following the intervention , significantly lower proportion of women in the intervention group as compared to the control group reported SHS exposure in their households within 7-days ( 9.2 % vs. 15.3 % , p = 0.02 ) and 30-days ( 13.6 % vs. 21.6 % , p = 0.008 ) prior to the post survey . As compared to the control group , significantly higher median scores were observed in the intervention group on the knowledge of the health risks of exposure to SHS ( p < 0.001 ) , attitudes on exposure to SHS ( p = 0.004 ) , right to smoke free living ( p = 0.001 ) and women empowerment ( p < 0.001 ) . Conclusion Multi-component intervention activities were effective in reducing household exposure to SHS among women . Trial registration Sri Lanka Clinical Trials Registry SLCTR/2014/033 OBJECTIVE The objective of this paper is to evaluate the behavioural effects , as reported by the parents of the participating boys and girls , of the IDEFICS ( Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS ) intervention . METHODS The effectiveness of the IDEFICS intervention was evaluated through a cluster-controlled trial in eight European countries ( control and intervention communities in each country ) including more than 16,000 children . The 2- to 9.9-year-old children in the intervention group were exposed to a culturally adapted intervention that aim ed to prevent childhood obesity through the community , schools/kindergartens and family . Parents completed question naires to measure water , soft drink and fruit juice intake ; fruit and vegetable intake ; daily TV viewing and other sedentary behaviours ; daily physical activity levels and strengthening of the parent-child relationships at baseline and follow-up ( 2 years later ) . Mixed models with an additional r and om effect for country were used to account for the clustered study design , and results were stratified by sex . RESULTS The pan-European analysis revealed no significant time by condition interaction effects , neither for boys nor girls , i.e. the analysis revealed no intervention effects on the behaviours of the IDEFICS children as reported by their parents ( F = 0.0 to 3.3 , all p > 0.05 ) . Also very few significance s were found in the country-specific analyses . Positive intervention effects were only found for sport club participation in Swedish boys , for screen time in weekends for Spanish boys and for TV viewing in Belgian girls . CONCLUSION Although no expected intervention effects as reported by the parents on diet , physical activity and sedentary behaviours could be shown for the overall IDEFICS cohort , a few favourable intervention effects were found on specific behaviours in some individual countries . More in-depth analyses of the process evaluation data are needed to obtain more insight into the relationship between the level of exposure to the intervention and its effect OBJECTIVE The present study was conducted to determine the impact of a community-based intervention on the nutritional behaviour of a representative sample of Iranian adults . DESIGN The Isfahan Healthy Heart Programme ( IHHP ) , a six-year , action-oriented , integrated community-based study aim ed at health promotion through the reduction of CVD risk factors , targeted the whole population living in two intervention cities , and compared outcomes with the population of a non-intervention city considered as reference . Dietary interventions were performed as educational , environmental and /or legislative strategies . A global dietary index ( GDI ) was calculated representing the general dietary behaviour . In addition , two consumption indices were calculated for specific food groups , i.e. meat products and major sources of fat . Univariate AVOVA was conducted to evaluate the impact of the intervention on dietary behaviours . SETTING Isfahan and Najaf-Abad ( intervention cities ) and Arak ( reference city ) , central Iran . SUBJECTS The baseline survey was conducted among 12514 r and omly selected adults aged > or = 19 years in both intervention and reference areas . The survey was repeated annually among about 5000 persons ( 2002 - 2005 ) in the intervention and reference communities . RESULTS According to significant year x group interactions in mean fat consumption index ( FCI ) and meat consumption index ( MCI ) in the total population , a significant improvement in FCI and MCI was found in the intervention areas v. the reference area ( P < 0.001 ) . In addition , the GDI improved significantly in the intervention areas v. the reference area ( P < 0.001 ) . CONCLUSIONS The IHHP interventions were effective in improving dietary behaviours at the population level . The highest effectiveness was documented in the change in the type of fat consumed . Such simple and integrated interventions can be adopted in other developing countries with limited financial re sources OBJECTIVE To determine whether a health-promotion intervention increases South African men 's adherence to physical-activity guidelines . METHOD We utilized a cluster-r and omized controlled trial design . Eligible clusters , residential neighborhoods near East London , South Africa , were matched in pairs . Within r and omly selected pairs , neighborhoods were r and omized to theory-based , culturally congruent health-promotion intervention encouraging physical activity or attention-matched HIV/STI risk-reduction control intervention . Men residing in the neighborhoods and reporting coitus in the previous 3 months were eligible . Primary outcome was self-reported individual-level adherence to physical-activity guidelines averaged over 6-month and 12-month post-intervention assessment s. Data were collected in 2007 - 2010 . Data collectors , but not facilitators or participants , were blind to group assignment . RESULTS Primary outcome intention-to-treat analysis included 22 of 22 clusters and 537 of 572 men in the health-promotion intervention and 22 of 22 clusters and 569 of 609 men in the attention-control intervention . Model-estimated probability of meeting physical-activity guidelines was 51.0 % in the health-promotion intervention and 44.7 % in attention-matched control ( OR=1.34 ; 95 % CI , 1.09 - 1.63 ) , adjusting for baseline prevalence and clustering from 44 neighborhoods . CONCLUSION A theory-based culturally congruent intervention increased South African men 's self-reported physical activity , a key contributor to deaths from non-communicable diseases in South Africa . TRIAL REGISTRATION Clinical Trials.gov Identifier : NCT01490359 Citizen participation in neighbourhood development is one way to promote public health and contribute to the well-being of individuals . However , some people participate while others do not . This study examines the individual characteristics of people who during the past 2 years have participated in a neighbourhood development process compared with potential and non- participants . Socio-demographic factors , perceptions and behaviour were analysed in a cross-sectional study . A question naire was answered by 1160 r and omly chosen citizens over the age of 18 who lived in three Swedish cities . The most important single Output:	Large-scale community-based health promotion programs , however , often result ed in limited or missing population -wide changes . Our results confirm that community-based interventions are promising for health promotion and disease prevention but so far their potential is not fully realized .
MS21090	*TASK* the task is to summarize an input biomedical literature in six sentences *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 No prospect i ve surveillance systems have been available for monitoring the outcome of cruciate ligament surgery in Sc and inavia ( Denmark , Norway , and Sweden ) . In the present paper we describe the Sc and inavian ACL registries including their main function , similarities , and preliminary baseline results . Methods The Sc and inavian registries were established in 2004 ( Norway ) and 2005 ( Denmark and Sweden ) . The Danish and Swedish registries were originally based on the Norwegian registry , and there is no overriding difference between the three . In Denmark , all hospitals and clinics are legally bound to report to an approved national data base . In Norway and Sweden , the registries are based on voluntarily reporting by surgeons . Results The annual incidence of primary ACL reconstructions is higher in Denmark than in Norway , except in females younger than 20 years . Among Sc and inavian surgeons , there is a similar approach to the patients . Differences do , however , exist regarding choice of grafts , choice of implants , and choice of treatment of simultaneous meniscal and cartilage injuries ; the proportion of ACL reconstructions performed as outpatient surgery ; and the use of prophylactic anticoagulation . Clinical ly , the preoperative KOOS scores are not significantly different between the Sc and inavian registries , except that Denmark reports more symptoms both pre- and postoperatively . Interpretation The Sc and inavian national ACL registries will generate new data about ACL reconstructions . They will contribute important knowledge regarding ACL epidemiology . They will be the only source of data on the performance of a wide range of different implants and techniques . In addition , they will hopefully have an impact on the selection of methods for ACL reconstructions in Sc and inavia and elsewhere Background The choice of different graft types and surgical techniques used when reconstructing a torn anterior cruciate ligament may influence the long-term prevalence of osteoarthritis and functional outcomes . Hypothesis There are no differences in the prevalence of knee osteoarthritis or knee function in patients undergoing reconstruction of a torn anterior cruciate ligament with 4-str and hamstring autograft versus patellar tendon — bone autograft . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Seventy-two patients with subacute or chronic rupture of the anterior cruciate ligament were r and omly assigned to autograft reconstruction with 4-str and gracilis and semitendinosus tendon ( HAM ) ( N = 37 ) or with patellar tendon — bone ( PTB ) ( N = 35 ) from the ipsilateral side . Outcome measurements were the Cincinnati knee score , single-legged hop tests , isokinetic muscle strength tests , pain , knee joint laxity test ( KT-1000 arthrometer ) , and a radiologic evaluation ( Kellgren and Lawrence ) at 10-year follow-up . Results At 10 years , 57 patients ( 79 % ) were eligible for evaluation—29 in the HAM group and 28 in the PTB group . No differences were found between the 2 graft groups with respect to the Cincinnati knee score , the single-legged hop tests , pain , muscle strength measurements , or knee joint laxity . Fifty-five percent and 64 % of the patients had osteoarthritis corresponding to Kellgren and Lawrence grade 2 or more in the HAM and the PTB groups , respectively ( P = .27 ) . For the uninvolved knee , the corresponding numbers were 28 % and 22 % ( P = .62 ) . Conclusion At 10 years postoperatively , no statistically significant differences in clinical outcome between the 2 graft types were found . The prevalence of osteoarthritis was significantly higher in the operated leg than in the contralateral leg , but there were no significant differences between the 2 groups . The results indicate that the choice of graft type after an anterior cruciate ligament injury has minimal influence on the prevalence of osteoarthritis 10 years after surgery Seventy-two patients with subacute or chronic rupture of the anterior cruciate ligament were r and omly assigned to autograft reconstruction with four-str and gracilis and semitendinosus tendon ( N = 37 ) or with patellar tendon-bone ( N = 35 ) from the ipsilateral side . The groups were similar in terms of age , sex , level of activity , degree of laxity , meniscal lesions found surgically , and rehabilitation program . The follow-up was performed at another hospital by independent observers after 6 , 12 , and 24 months . Sixty-one patients ( 32 with hamstring tendon grafts and 29 with patellar tendon grafts ) complied with the follow-up routine for the full 24 months . No differences were found between the groups with respect to Cincinnati functional score , KT-1000 arthrometer measurements , or stairs hopple test results . The subjective result and the single-legged hop test result were better for the hamstring tendon group after 6 and 12 months , but no differences were found after 24 months . The hamstring tendon group showed better isokinetic knee extension strength than did the patellar tendon group after 6 months , but not after 12 and 24 months . There was a significant weakness in isokinetic knee flexion strength among the hamstring tendon group . Anterior knee pain was not significantly different between the groups , but kneeling pain was significantly less common in the hamstring tendon group after 24 months Background : R and omized controlled trials after anterior cruciate ligament reconstructions with long-term follow-up including assessment of health-related quality of life are rare . Purpose : To compare clinical outcome and health-related quality of life 8 years after anterior cruciate ligament reconstruction using 2 types of graft . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Long-term follow-up of 164 patients with anterior cruciate ligament injury r and omized to arthroscopic reconstruction with a quadrupled semitendinosus graft or a bone – patellar tendon – bone graft was undertaken . After a mean 8 years , 153 patients were available for follow-up , including instrumented laxity , 1-legged hop test , a knee-walking test , and assessment with International Knee Documentation Committee , Lysholm , Tegner , and patellofemoral pain score . Health-related quality of life was assessed with Knee Osteoarthritis Outcome Score and Short Form–36 . Results : Patients in both graft groups retained the same stability , knee function , and health-related quality of life . The patellofemoral pain score was similar for both groups ; the bone – patellar tendon – bone group had more donor site morbidity from kneeling and knee walking . In the bone – patellar tendon – bone group , 19 patients had no kneeling problems , 23 slight problems , 31 moderate problems , and 5 unable to kneel . Corresponding figures for the semitendinosus group were 25 , 32 , 16 , and 2 ( P < .001 ) . Patients with early reconstructions ( < 5 months ) had a lower risk for meniscal injuries ( 37 % ) than did later reconstructed ( 62 % , P = .008 ) . Health-related quality of life regarding physical functioning in Short Form–36 was better for the early-reconstructed patients than for the later reconstructed ( 92 vs 85 ; P = .014 ) . Patients without medial meniscal surgery had higher Knee Osteoarthritis Outcome Scores for all subscales than did patients with medial meniscal surgery , with most significant difference for sport and recreation ( 63 vs 75 , P = .008 ) . Conclusion : In the long term , the semitendinosus graft provided similar stability , knee function , and health-related quality of life but with less kneeling morbidity than did the bone – patellar tendon – bone graft Background No prospect i ve surveillance system exists for monitoring the outcome of cruciate ligament surgery . Purpose This article is intended to describe the development and procedures of the Norwegian National Knee Ligament Registry ( NKLR ) , including baseline results from the first 2 years of operation . Study Design Cohort study ( prevalence ) ; Level of evidence , 1 . Methods The NKLR was established on June 7 , 2004 to collect information prospect ively on all cases of cruciate ligament reconstruction surgery in Norway . Information on the details of surgery is gathered through a registration form completed by the surgeon postoperatively , and a vali date d knee outcome score form is completed by the patients preoperatively and at follow-ups on all patients at 2 , 5 , and 10 years postoperatively . Hospital compliance was examined in 2005 and 2006 . Results A total of 2793 primary cruciate ligament reconstruction surgeries were registered by 57 hospitals . This corresponds to an annual population incidence of primary anterior cruciate ligament reconstruction surgeries of 34 per 100 000 citizens ( 85 per 100 000 citizens in the main at-risk age group of 16–39 years ) . After 21 months of operation , the NKLR had an overall compliance of 97 % when compared with the hospital records . Conclusions A national population -based cruciate ligament registry has been developed , implemented , and maintained in Norway . The registry will each year enroll approximately 1500 primary cruciate ligament reconstruction cases . It is expected that inadequate procedures and devices can be identified , as well as prognostic factors associated with good and poor outcomes , at least for the most frequent categories In a two-centre study , 164 patients with unilateral instability of the anterior cruciate ligament were prospect ively r and omised to arthroscopic reconstruction with either a patellar tendon graft using interference screw fixation or a quadruple semitendinosus graft using an endobutton fixation technique . The same postoperative rehabilitation protocol was used for all patients and follow-up at a median of 31 months ( 24 to 59 ) was carried out by independent observers . Four patients ( 2 % ) were lost to follow-up . No significant differences were found between the groups regarding the Stryker laxity test , one-leg hop test , Tegner activity level , Lysholm score , patellofemoral pain score , International Knee Documentation Committee ( IKDC ) score or visual analogue scale , reflecting patient satisfaction and knee function . Slightly decreased extension , compared with the non-operated side , was found in the patellar tendon group ( p < 0.05 ) . Patients with associated meniscal injuries had lower IKDC , visual analogue ( p < 0.01 ) and Lysholm scores ( p < 0.05 ) than those without such injuries . Patients in whom reconstruction had been carried out less than five months after the injury had better final IKDC scores than the more chronic cases ( p < 0.05 ) . We conclude that patellar tendon and quadruple semitendinous tendon grafts have similar outcomes in the medium term . Associated meniscal pathology significantly affects the final outcome and early reconstruction seems to be beneficial Objective the aim of this study was to radiologically evaluate the femoral tunnel position in anterior cruciate ligament ( ACL ) reconstructions using the isometric and anatomical techniques . Methods a prospect i ve analytical study was conducted on patients undergoing ACL reconstruction by means of the isometric and anatomical techniques , using grafts from the knee flexor tendons or patellar tendon . Twenty-eight patients were recruited during the immediate postoperative period , at the knee surgery outpatient clinic of FCMMG-HUSJ . Radiographs of the operated knee were produced in anteroposterior ( AP ) view with the patient st and ing on both feet and in lateral view with 30 ° of flexion . The lines were traced out and the distances and angles were measured on the lateral radiograph to evaluate the sagittal plane . The distance from the center of the screw to the posterior cortical bone of the lateral condyle was measured and divided by the Blumensaat line . In relation to the height of the screw , the distance from the center of the screw to the joint surface of the lateral condyle of the knee was measured . On the AP radiograph , evaluating the coronal plane , the angle between the anatomical axis of the femur and a line traced at the center of the screw was measured . Results with regard to the p measurement ( posteriorization of the interference screw ) , the tests showed that the p-value ( 0.4213 ) was greater than the significance level used ( 0.05 ) ; the null hypothesis was not rejected and it could be stated that there was no statistically significant difference between the anatomical and isometric techniques . With regard to the H measurement ( height of the screw in relation to the lower cortical bone of the knee ) , the p-value observed ( 0.0006 ) was less than the significance level used ( 0.05 ) ; the null hypothesis was rejected and it could be stated that there was a statistically significant difference between the anatomical and isometric techniques . It can be concluded that the latter difference occurred because the isometric technique generated greater values for the H measurement than the anatomical technique . With regard to the MED variable ( position of the screw on the AP radiograph ) , the observed p-value ( 0.000 ) was less than the significance level ( 5 % ) ; the null hypothesis was rejected and it could be stated with 95 % confidence that there was a significant difference between the anatomical and isometric techniques . Conclusions there were statistically significant differences in the radiological evaluations of the femoral tunnel , both in the sagittal and in the coronal plane , between the ACL reconstruction techniques Radiographic tibial and femoral bone tunnel enlargement has been demonstrated following anterior cruciate ligament ( ACL ) reconstruction . This study investigated whether bone tunnel enlargement differs between four-str and hamstring Output:	We found significant differences in favor of the HT technique in the domains of anterior knee pain , kneeling pain , and restriction in the range of active extension ( " extension deficit " ) . We found no differences between the PT and HT technique in terms of rerupture rate . There were no clinical ly significant differences for the outcomes of Lysholm score and Tegner Activity Scale as well as the KT-1000 side-to-side at maximum manual force . Contemporary 4-str and HT ACL reconstruction is comparable with the PT technique in terms of clinical stability and postoperative functional status across most parameters studied . The HT technique carries lower risk of postoperative complications such as anterior knee pain , kneeling discomfort , and extension deficit . Primary ACL reconstruction using the 4-str and HT technique achieves clinical results that are comparable with the PT technique with significantly less postoperative complications .
MS21091	*TASK* the task is to summarize an input biomedical literature in six sentences *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 : Parkinson disease ( PD ) is a common neurodegenerative disease affecting up to 1 million individuals in the United States . Depression affects up to 50 % of these patients and is associated with a variety of poor outcomes for patients and their families . Despite this , there are few evidence -based data to guide clinical care . Methods : An NIH-funded , r and omized , controlled trial of paroxetine CR , nortriptyline , and placebo in 52 patients with PD and depression . The primary outcomes were the change in the Hamilton Depression Rating Scale ( HAM-D ) and the percentage of depression responders at 8 weeks . Results : Nortriptyline was superior to placebo for the change in HAM-D ( p < 0.002 ) ; paroxetine CR was not . There was a trend for superiority of nortriptyline over paroxetine CR at 8 weeks ( p < 0.079 ) . Response rates favored nortriptyline ( p = 0.024 ) : nortriptyline 53 % , paroxetine CR 11 % , placebo 24 % . In planned contrasts of response rates , nortriptyline was superior to paroxetine CR ( p = 0.034 ) . Nortriptyline was also superior to placebo in many of the secondary outcomes , including sleep , anxiety , and social functioning , while paroxetine CR was not . Both active drug treatments were well tolerated . Conclusions : Though relatively modest in size , this is the largest placebo-controlled trial done to date in patients with Parkinson disease ( PD ) and depression . Nortriptyline was efficacious in the treatment of depression and paroxetine CR was not . When compared directly , nortriptyline produced significantly more responders than did paroxetine CR . The trial suggests that depression in patients with PD is responsive to treatment and raises questions about the relative efficacy of dual reuptake inhibitors and selective serotonin reuptake inhibitors . ARR = absolute risk reduction ; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders , 4th edition ; HAM-A = Hamilton Anxiety Scale ; HAM-D = Hamilton Depression Rating Scale ; MMSE = Mini-Mental State Examination ; NNT = number needed to treat ; PD = Parkinson disease ; PDQ = Parkinson ’s Disease Question naire ; PSQI = Pittsburgh Sleep Quality Index ; SCID = Structured Clinical Interview ; SSRI = selective serotonin reuptake inhibitor ; TCA = tricyclic antidepressant ; UPDRS = Unified Parkinson ’s Disease Rating Scale In the context of chronic physical illness , such as breast cancer , depression is associated with increased morbidity , longer periods of hospitalization , and greater overall disability . Prompt diagnosis and effective treatment is , therefore , essential . Several small studies have established the efficacy of tricyclic antidepressants ( TCAs ) in this setting , and the selective serotonin reuptake inhibitors ( SSRIs ) would appear to be an alternative therapeutic option because of their established efficacy and better tolerability profile . This was a multicenter , double-blind , parallel-group study in which 179 women with breast cancer were r and omized to treatment with either the SSRI paroxetine ( 20–40mg/day ) , or the TCA , amitriptyline ( 75–150mg/day ) . After 8-weeks treatment , depressive symptomatology had improved markedly and to a similar extent in both groups on the Montgomery Asberg Depression Rating Scale . Clinical global impression ( CGI ) Global improvement and Patient global evaluation scales indicated that patients were minimally to much improved at study endpoint ; a change from moderately/mildly ill to borderline ill on the CGI severity of Illness scale . A steady improvement in quality of life was also observed in both groups . There were no clinical ly significant differences between the groups . In total , 47 ( 53.4 % ) patients in the paroxetine group and 53 ( 59.6 % ) patients in the amitriptyline group had adverse experiences , the most common of which were the well-recognized side-effects of the antidepressant medications or chemotherapy . Anticholinergic effects were almost twice as frequent in the amitriptyline group ( 19.1 % ) compared with paroxetine ( 11.4 % ) . This study has demonstrated that paroxetine is a suitable alternative to amitriptyline for the treatment of depression in patients with breast cancer BACKGROUND Although the underlying pathology is initially confined to the lungs , the associated emotional responses to chronic obstructive pulmonary disease ( COPD ) contribute greatly to the result ing morbidity . The objective of this study was to examine the effect of an antidepressant drug on disease-specific quality of life in patients with end-stage COPD who present significant depressive symptoms . METHODS We conducted a 12-week , r and omized double-blind placebo-controlled trial of Paroxetine in which quality of life measured by the Chronic Respiratory Question naire ( CRQ ) , an evaluative COPD -specific quality -of-life question naire , was the primary outcome . RESULTS 23 patients were r and omized and 15 completed the trial ( 8 on Paroxetine ; 7 on placebo ) . In the per- protocol analysis , we observed statistically and clinical ly significant improvements favoring the active treatment in 2 of the 4 domains of the CRQ : emotional function ( adjusted mean difference : 1.1 ; 95 % confidence interval [ CI ] : 0.0 - 2.2 ) and mastery ( difference : 1.1 ; CI : 0.4 - 1.8 ) . Dyspnea and fatigue improved , but to an extent that did not reach statistical significance . In the intention-to-treat analysis , none of the differences in CRQ scores was significant . Paroxetine was not associated to any worsening of respiratory symptoms . CONCLUSIONS The results of this small r and omized trial indicated that patients with end-stage COPD may benefit from antidepressant drug therapy when significant depressive symptoms are present . This study underlined the difficulties in conducting experimental studies in frail and elderly patients with COPD Little has been done to study the effectiveness of antidepressants in controlling anxiety/depression in a population of cancer patients . A double‐blind placebo‐controlled study was therefore design ed to assess the effectiveness of 20 mg fluoxetine . Of 115 cancer patients who fulfilled entry criteria for levels of distress , 45 patients were r and omized to a fluoxetine treatment group ( FA ) and 46 patients to a placebo group ( PA ) after a 1‐week placebo period design ed to exclude placebo responders . The Montgomery and Asberg Depression Scale ( MADRS ) , the Hamilton Anxiety Scale ( HAS ) , the Hospital Anxiety and Depression Scale ( HADS ) , the Revised Symptom Checklist ( SCL90‐R ) and the Spitzer Quality of Life Index ( SQOLI ) were used to assess the efficacy of fluoxetine . The response rate , defined by a HADS score lower than 8 after 5 weeks of treatment , was not significantly higher in the FA group ( 11 % ) compared to the PA group ( 7 % ) . Compared to the PA group , patients in the FA group showed a significantly greater decrease in SCL90‐R mean total score after 5 weeks , but not a greater decrease in HADS mean score . No difference between the two groups was found in observer‐reported assessment s ( MADRS , HAS and SQOLI ) . Significantly more drop‐outs were observed in the FA group ( n=15 ) than in the PA group ( n=7 ) , although the frequencies of side‐effects were not significantly different The efficacy of nortriptyline in the treatment of post-stroke depression was assessed by a double-blind study in thirty-four patients . Half of the patients had major depression . There was a significantly greater improvement in depression in patients treated with nortriptyline than in a similar group of placebo-treated patients . Depression was measured by the Hamilton depression scale , Zung depression scale , present state examination , and an overall depression scale . Successfully treated patients had serum nortriptyline levels in the therapeutic range . Post-stroke depressions are common , severe , and longst and ing , and the demonstrated efficacy of nortriptyline provides an important addition to the treatments available for stroke patients 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 ( HRSD ) ; LPSS was determined by the Enhancing Recovery in Coronary Heart Disease Patients ( ENRICHD ) Social Support Instrument ( ESSI ) . R and om allocation was to usual medical care or CBT-based psychosocial intervention . INTERVENTION Cognitive behavior therapy was initiated at a median of 17 days after the index MI for a median of 11 individual sessions throughout 6 months , plus group therapy when feasible , with SSRIs for patients scoring higher than 24 on the HRSD or having a less than 50 % reduction in Beck Depression Inventory scores after 5 weeks . MAIN OUTCOME MEASURES Composite primary end point of death or recurrent MI ; secondary outcomes included change in HRSD ( for depression ) or ESSI scores ( for LPSS ) at 6 months . RESULTS Improvement in psychosocial outcomes at 6 months favored treatment : mean ( SD ) change in HRSD score , -10.1 ( 7.8 ) in the depression and psychosocial intervention group vs -8.4 ( 7.7 ) in the depression and usual care group ( P<.001 ) ; mean ( SD ) change in ESSI score , 5.1 ( 5.9 ) in the LPSS and psychosocial intervention group vs 3.4 ( 6.0 ) in the LPSS and usual care group ( P<.001 ) . After an average follow-up of 29 months , there was no significant difference in event-free survival between usual care ( 75.9 % ) and psychosocial intervention ( 75.8 % ) . There were also no differences in survival between the psychosocial intervention and usual care arms in any of the 3 psychosocial risk groups ( depression , LPSS , and depression and LPSS patients ) . CONCLUSIONS The intervention did not increase event-free survival . The intervention improved depression and social isolation , although the relative improvement in the psychosocial intervention group compared with the usual care group was less than expected due to substantial improvement in usual care patients Forty-two patients with depression and epilepsy were entered into an antidepressant trial of amitriptyline , nomifensine and placebo . The dose of the active drug was 25 mg tid , which was doubled in non-responders on the active drug after 6 weeks . At that point a further 6 week follow-up was carried out . Serum antidepressant and anticonvulsant levels were assessed . The results indicated that at 6 weeks all patients showed a decline in their depression scores but at 12 weeks nomifensine was superior to amitriptyline . The possible reasons for this and the clinical implication s of this are discussed CONTEXT In patients with diabetes mellitus , depression is a prevalent and recurrent problem that adversely affects the medical prognosis . OBJECTIVE To determine whether maintenance therapy with sertraline hydrochloride prevents recurrence of major depression in patients with diabetes . DESIGN A r and omized , double-blind , placebo-controlled , maintenance treatment trial . Patients who recovered from depression during open-label sertraline treatment continued to receive sertraline ( n = 79 ) or placebo ( n = 73 ) and were followed up for up to 52 weeks or until depression recurred . SETTING Outpatient clinics at Washington University , St Louis , MO , the University of Washington , Seattle , and the University of Arizona , Tucson . PATIENTS One hundred fifty-two patients with diabetes ( mean age , 52.8 years ; 59.9 % female ; 82.9 % with type 2 diabetes ) who recovered from major depression ( 43.3 % of those initially assigned ) during 16 weeks of open-label treatment with sertraline ( mean dose , 117.9 mg/d ) . INTERVENTION Sertraline continued at recovery dose or identical-appearing placebo . MAIN OUTCOME MEASURES The primary outcome was length of time ( measured as the number of days after r and omization ) to recurrence of major depression as defined in DSM-IV . The secondary outcome was glycemic control , which was assessed via serial determinations of glycosylated hemoglobin levels . RESULTS Sertraline conferred significantly greater prophylaxis against depression recurrence than did placebo ( hazard ratio = 0.51 ; 95 % confidence interval , 0.31 - 0.85 ; P = .02 ) . Elapsed time before major depression recurred in one third of the patients increased from 57 days in patients who received placebo to 226 days in patients treated with sertraline . Glycosylated hemoglobin levels decreased during the open Output:	Only SSRIs were shown to improve quality of life . Direct comparisons of SSRIs and tricyclics revealed no advantage for either group for remission , response , effect size or tolerability . Effectiveness studies suggest a neutral or beneficial effect on mortality for antidepressants in participants with recent myocardial infa rct ion . Antidepressants are efficacious and safe in the treatment of depression occurring in the context of chronic physical health problems . The SSRIs are probably the antidepressants of first choice given their demonstrable effect on quality of life and their apparent safety in cardiovascular disease
MS21092	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Although epidemiological studies have reported protective effects of religion and spirituality on mental health , it is unknown whether spirituality can be used as an intervention to improve psychological well-being . OBJECTIVE To evaluate the efficacy of a home study -based spirituality program on mood disturbance in emotionally distressed patients . DESIGN , SETTING , AND PARTICIPANTS A non-blinded , r and omized , wait list-controlled trial of 165 individuals with mood disturbance [ score of > 40 on the Profile of Mood States ( POMS ) ] were recruited from primary care clinics in a Canadian city between August 2000 and March 2001 . INTERVENTIONS Participants were r and omized to a spirituality group ( an 8-week audiotaped spirituality home- study program ) , a mindfulness meditation-based stress reduction group ( attendance at facilitated classes for 8 weeks ) , or a wait-list control group ( no intervention for 12 weeks ) . MAIN OUTCOME MEASURES Primary outcomes were mood disturbance , measured using POMS , and quality of life , measured using the SF-36 , a short-form health survey with 36 questions . The POMS and the SF-36 were completed at baseline , at 8 weeks , and at 12 weeks . RESULTS At the end of the 8-week intervention period , the mean POMS score improvement was -43.1 ( -45.7 % ) for the spirituality group , -22.6 ( -26.3 % ) for the meditation group , and -10.3 ( 11.3 % ) for the control group ( P<.001 for spirituality vs control group ; P=.034 for spirituality vs meditation group ) . Mean improvement in the SF-36 mental component summary score was 14.4 ( 48.6 % ) for the spirituality group , 7.1 ( 22.3 % ) for the meditation group , and 4.7 ( 16.1 % ) for the control group ( P<.001 for spirituality vs control group ; P=.029 for spirituality vs meditation group ) . At 12 weeks , POMS and SF-36 scores remained significantly different from baseline for the spirituality group Background Although several studies have reported positive effects of mindfulness-based stress reduction ( MBSR ) intervention on psychological well-being , it is not known whether these effects are attributable to a change in mindfulness . Purpose The aim of this study is to compare the effects of MBSR to a waiting-list control condition in a r and omized controlled trial while examining potentially mediating effects of mindfulness . Methods Forty women and 20 men from the community with symptoms of distress ( mean age 43.6 years , SD = 10.1 ) were r and omized into a group receiving MBSR or a waiting-list control group . Before and after the intervention period , question naires were completed on psychological well-being , quality of life , and mindfulness . Results Repeated measures multiple analysis of variance ( MANCOVAs ) showed that , compared with the control group , the intervention result ed in significantly stronger reductions of perceived stress ( p = 0.016 ) and vital exhaustion ( p = 0.001 ) and stronger elevations of positive affect ( p = 0.006 ) , quality of life ( p = .009 ) , as well as mindfulness ( p = 0.001 ) . When mindfulness was included as a covariate in the MANCOVA , the group effects on perceived stress and quality of life were reduced to non significance . Conclusion Increased mindfulness may , at least partially , mediate the positive effects of mindfulness-based stress reduction intervention Objective : The underlying changes in biological processes that are associated with reported changes in mental and physical health in response to meditation have not been systematic ally explored . We performed a r and omized , controlled study on the effects on brain and immune function of a well‐known and widely used 8‐week clinical training program in mindfulness meditation applied in a work environment with healthy employees . Methods : We measured brain electrical activity before and immediately after , and then 4 months after an 8‐week training program in mindfulness meditation . Twenty‐five subjects were tested in the meditation group . A wait‐list control group ( N = 16 ) was tested at the same points in time as the meditators . At the end of the 8‐week period , subjects in both groups were vaccinated with influenza vaccine . Results : We report for the first time significant increases in left‐sided anterior activation , a pattern previously associated with positive affect , in the meditators compared with the nonmeditators . We also found significant increases in antibody titers to influenza vaccine among subjects in the meditation compared with those in the wait‐list control group . Finally , the magnitude of increase in left‐sided activation predicted the magnitude of antibody titer rise to the vaccine . Conclusions : These findings demonstrate that a short program in mindfulness meditation produces demonstrable effects on brain and immune function . These findings suggest that meditation may change brain and immune function in positive ways and underscore the need for additional research Purpose . To determine if participation in a Wellness-Based Mindfulness Stress Reduction intervention decreases the effect of daily hassles , psychological distress , and medical symptoms . Design . A r and omized controlled trial of a stress reduction intervention with a 3-month follow-up . Setting . A university setting in West Virginia . Subjects . A total of 103 adults , with 59 in the intervention group and 44 in the control group . Eight-five percent of subjects completed the intervention . Fifty-nine percent and 61 % of the intervention and control subjects completed the study , respectively . Intervention . The intervention consisted of an 8-week group stress reduction program in which subjects learned , practice d , and applied “ mindfulness meditation ” to daily life situations . The control group received educational material s and were encouraged to use community re sources for stress management . Measures . The Daily Stress Inventory assessed the effect of daily hassles , the Revised Hopkins Symptom Checklist measured psychological distress , the Medical Symptom Checklist measured number of medical symptoms , and a Follow-up Question naire measured program adherence . Results . Intervention subjects reported significant decreases from baseline in effect of daily hassles ( 24 % ) , psychological distress , ( 44 % ) , and medical symptoms ( 46 % ) that were maintained at the 3-month follow-up compared to control subjects ( repeated measures analysis of variance [ ANOVA ] ; p < .05 ) . Conclusions . Self-selected community residents can improve their mental and physical health by participating in a stress reduction intervention offered by a university wellness program OBJECTIVES Patients with chronic obstructive lung disease ( COPD ) suffer from significant dyspnea and may benefit from complementary and alternative medicine ( CAM ) therapies aim ed at mitigating symptoms . The objective of this study was to test the efficacy of a mindfulness-based breathing therapy ( MBBT ) on improving symptoms and health-related quality of life in those with COPD . DESIGN We conducted a r and omized controlled trial of 8-week mindfulness-based breathing therapy ( MBBT ) compared to support groups to test efficacy on improving symptoms and health-related quality of life in those with COPD . SETTING The setting for this study was an academic-affiliated veterans healthcare system . SUBJECTS The subjects consisted of 86 patients with COPD . INTERVENTIONS MBBT included weekly meetings practicing mindfulness mediation and relaxation response . OUTCOME MEASURES The main outcome measure was a post 6-minute-walk test ( 6MWT ) Borg dyspnea assessment . Other outcome measures included health-related quality of life measures , 6MWT distance , symptom scores , exacerbation rates , and measures of stress and mindfulness . Analysis of covariance compared differences in outcomes between groups ; paired t test evaluated changes within groups . RESULTS Participants were predominantly elderly men with moderate to severe COPD . We found no improvements in dyspnea ( post 6MWT Borg difference between the MBBT and support group was 0.3 ( 95 % confidence interval [ CI ] : -1.1 , 1.7 ) . We found no differences between groups in almost all other outcome measures by either intention-to-treat analysis or within the subset that completed assigned group sessions . For the physical summary scale of the generic Short Form-36 for Veterans , the difference between outcomes favored the support group ( 4.3 , 95 % CI : 0.4 , 8.1 ) . Participant retention was low compared to mind-body trials that r and omize from CAM wait lists . CONCLUSIONS This trial found no measurable improvements in patients with COPD receiving a mindfulness-based breathing CAM therapy compared to a support group , suggesting that this intervention is unlikely to be an important therapeutic option for those with moderate-to-severe COPD Objective : Health-related quality of life ( HRQOL ) is often much reduced among individuals with multiple sclerosis ( MS ) , and incidences of depression , fatigue , and anxiety are high . We examined effects of a mindfulness-based intervention ( MBI ) compared to usual care ( UC ) upon HRQOL , depression , and fatigue among adults with relapsing-remitting or secondary progressive MS . Methods : A total of 150 patients were r and omly assigned to the intervention ( n = 76 ) or to UC ( n = 74 ) . MBI consisted of a structured 8-week program of mindfulness training . Assessment s were made at baseline , postintervention , and 6 months follow-up . Primary outcomes included disease-specific and disease-aspecific HRQOL , depression , and fatigue . Anxiety , personal goal attainment , and adherence to homework were secondary outcomes . Results : Attrition was low in the intervention group ( 5 % ) and attendance rate high ( 92 % ) . Employing intention-to-treat analysis , MBI , compared with UC , improved nonphysical dimensions of primary outcomes at postintervention and follow-up ( p < 0.002 ) ; effect sizes , 0.4–0.9 posttreatment and 0.3–0.5 at follow-up . When analyses were repeated among subgroups with clinical ly relevant levels of preintervention depression , fatigue , or anxiety , postintervention and follow-up effects remained significant and effect sizes were larger than for the total sample . Conclusions : In addition to evidence of improved HRQOL and well-being , these findings demonstrate broad feasibility and acceptance of , as well as satisfaction and adherence with , a program of mindfulness training for patients with MS . The results may also have treatment implication s for other chronic disorders that diminish HRQOL . Classification of evidence : This trial provides Class III evidence that MBI compared with UC improved HRQOL , fatigue , and depression up to 6 months postintervention For people at risk of depressive relapse , mindfulness-based cognitive therapy ( MBCT ) has an additive benefit to usual care ( H. F. Coelho , P. H. Canter , & E. Ernst , 2007 ) . This study asked if , among patients with recurrent depression who are treated with antidepressant medication ( ADM ) , MBCT is comparable to treatment with maintenance ADM ( m-ADM ) in ( a ) depressive relapse prevention , ( b ) key secondary outcomes , and ( c ) cost effectiveness . The study design was a parallel 2-group r and omized controlled trial comparing those on m-ADM ( N = 62 ) with those receiving MBCT plus support to taper/discontinue antidepressants ( N = 61 ) . Relapse/recurrence rates over 15-month follow-ups in MBCT were 47 % , compared with 60 % in the m-ADM group ( hazard ratio = 0.63 ; 95 % confidence interval : 0.39 to 1.04 ) . MBCT was more effective than m-ADM in reducing residual depressive symptoms and psychiatric comorbidity and in improving quality of life in the physical and psychological domains . There was no difference in average annual cost between the 2 groups . Rates of ADM usage in the MBCT group was significantly reduced , and 46 patients ( 75 % ) completely discontinued their ADM . For patients treated with ADM , MBCT may provide an alternative approach for relapse prevention The inability to cope successfully with the enormous stress of medical education may lead to a cascade of consequences at both a personal and professional level . The present study examined the short-term effects of an 8-week meditation-based stress reduction intervention on premedical and medical students using a well-controlled statistical design . Findings indicate that participation in the intervention can effectively ( 1 ) reduce self-reported state and trait anxiety , ( 2 ) reduce reports of overall psychological distress including depression , ( 3 ) increase scores on overall empathy levels , and ( 4 ) increase scores on a measure of spiritual experiences assessed at termination of intervention . These results ( 5 ) replicated in the wait-list control group , ( 6 ) held across different experiments , and ( 7 ) were observed during the exam period . Future research should address potential long-term effects of mindfulness training for medical and premedical students UNLABELLED Mindfulness meditation training has stress reduction benefits in various patient population s , but its effects on biological markers of HIV-1 progression are unknown . The present study tested the efficacy of an 8-week Mindfulness-based stress reduction ( MBSR ) meditation program compared to a 1-day control seminar on CD4 + T lymphocyte counts in stressed HIV infected adults . A single-blind r and omized controlled trial was conducted with enrollment and follow-up occurring between November 2005 and December 2007 . A diverse community sample of 48 HIV-1 infected adults was r and omized and entered treatment in either an 8-week MBSR or a 1-day control stress reduction education seminar . The primary outcome was circulating counts of CD4 + T lymphocytes . Participants in the 1-day control seminar showed declines in CD4 + T lymphocyte counts whereas counts among participants in the 8-week MBSR program were Output:	Evidence supports that MBSR improves mental health and MBCT prevents depressive relapse .
MS21093	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: UNLABELLED Gastrointestinal stromal tumors ( GISTs ) are gaining the interest of research ers because of impressive metabolic response to the targeted molecular therapeutic drug imatinib mesylate . Initial reports suggest an impressive role for (18)F-FDG PET in follow-up of therapy for these tumors . However , the role of (18)F-FDG PET versus that of CT has not been established . Therefore , we compared the roles of (18)F-FDG PET and CT in staging and evaluation of early response to imatinib mesylate therapy in recurrent or metastatic GIST . METHODS The study included 54 patients who underwent (18)F-FDG PET and CT scans within 3 wk before initiation of imatinib mesylate therapy . Forty-nine of these patients underwent repeat scans 2 mo after therapy . The numbers of sites or organs containing lesions on (18)F-FDG PET and CT scans were compared . Corresponding lesions on (18)F-FDG PET and CT scans or those confirmed to be malignant in appearance by other imaging modalities or on follow-up were considered true positives . Lesions seen on (18)F-FDG PET or CT scans but not seen or confirmed to be of benign appearance with other imaging modalities or on follow-up were considered false positives . Measurements of the maximum st and ard uptake value ( SUV ) on (18)F-FDG PET scans and tumor size on CT scans were used for quantitative evaluation of early tumor response to therapy . RESULTS A total of 122 and 114 sites and /or organs were involved on pretherapy (18)F-FDG PET and CT scans , respectively . The sensitivity and positive predictive values ( PPVs ) for CT were 93 % and 100 % ; whereas these values for (18)F-FDG PET were 86 % and 98 % . However , the differences between these values for CT and (18)F-FDG PET were not statistically significant ( P = 0.27 for sensitivity and 0.25 for PPV ) . This suggests comparable performance of (18)F-FDG PET and CT in staging GISTs . Repeat scans at 2 mo after therapy showed agreement between (18)F-FDG PET and CT scans in 71.4 % of patients ( 57.1 % having a good response to therapy and 14.3 % lacking a response ) . Discrepant results between (18)F-FDG PET and CT were recorded for 28.6 % of the patients . (18)F-FDG PET predicted response to therapy earlier than did CT in 22.5 % of patients during a longer follow-up interval ( 4 - 16 mo ) , whereas CT predicted lack of response to therapy earlier than (18)F-FDG PET in 4.1 % . One patient did not undergo long-term follow-up . These findings suggest that (18)F-FDG PET is superior to CT in predicting early response to therapy in recurrent or metastatic GIST patients . CONCLUSION The performances of (18)F-FDG PET and CT are comparable in staging GISTs before initiation of imatinib mesylate therapy . However , (18)F-FDG PET is superior to CT in predicting early response to therapy . Thus , (18)F-FDG PET is a better guide for imatinib mesylate therapy AIM The aim of this study was to evaluate the utility of positron emission tomography with 18F-fluorodeoxyglucose ( FDG-PET ) in monitoring response in refractory GIST . METHODS This multicenter study prospect ively evaluated 21 patients with locally advanced and /or metastatic GIST refractory to with high-dose imatinib ( 800 mg/day ) treated with doxorubicin 15 - 20 mg/m2/weekly for 4 cycles , followed by imatinib maintenance ( 400 mg/day ) . CT and FDG-PET were performed at baseline and after completion of therapy . RESULTS Mean baseline tumor size on CT was 5.9 cm . Median progression-free survival ( PFS ) was 219 days ( range 62 - 1108 ) . Three out of 21 patients ( 14 % ) had partial responses ( PR ) under RECIST criteria , 12 patients ( 57 % ) remained stable ( SD ) and 6 showed progression ( PD ) of the disease during treatment ( 29 % ) . Six patients had PR by FDG-PET , 15 showed SD ( n=9 ) or PD ( n=6 ) based on EORTC criteria . Patients with a PFS < 6 mo showed a significantly higher ∑SUVmax at baseline ( 26.04±13.4 ) than those with PFS≥6 mo ( 9.82±5.0 ) ( P<0.05 ) . A correlation was found between PET response and PFS : PR 14±6.1 mo , SD 5.5±0.8 mo and PD 3.5±4.1 mo ( P<0.05 ) . A residual SUVmax < 5 after treatment correlated with improved PFS ( 314±315 days vs 131±91 days ) ( P<0.01 ) . Survival curves showed a significant association between PET response and PFS ( P<0.05 ) . Patients with wild-type genotype KIT ( KIT-WT ) showed a significantly lower baseline SUVmax ( 5.36±1.4 ) than non-WT KIT ( 8.40±3.6 ) ( P<0.05 ) . CONCLUSION FDG-PET is useful in assessing response of GIST refractory to imatinib and correlates with the presence of KIT-WT . Baseline ∑SUVmax can predict response to treatment in this series BACKGROUND Although most patients with gastrointestinal stromal tumor ( GIST ) treated with imatinib mesylate achieve remission or disease stabilization , a significant proportion show progressive disease ( PD ) with or without initial favorable responses . We evaluated and categorized the patterns of progression of metastatic or unresectable GIST treated with imatinib to identify the prognostic significance and contribution to further treatment decision-making . METHODS We prospect ively gathered clinical data from 62 GIST patients treated with imatinib mesylate ( 400 mg/day ) over a median period of 26 months . Twenty-one of these patients showed evidence of PD based on Response Evaluation Criteria in Solid Tumor criteria . RESULTS Four patterns of PD were defined : focal progression ( FP , N = 4 ) , general progression ( GP , N = 6 ) , new cystic lesion ( NCL , N = 6 ) and new solid lesion ( NSL , N = 5 ) . The groups were found to differ in terms of time to progression and prior response to imatinib . The proportion of patients who responded to escalated doses of imatinib ( 600 - 800 mg/day ) was significantly higher in NCL patients ( P = 0.04 ) . Overall survival and survival from the confirmation of PD were significantly better in NCL or FP patients compared with NSL or GP patients ( P = 0.0157 , P = 0.0013 ) . CONCLUSIONS We identified four patterns of disease progression based on radiographic criteria with different clinical characteristics and impact on survival . Knowledge of these patterns was relevant for early detection and may be helpful in further treatment decision-making BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies BACKGROUND HSP90 inhibition leads to proteosomal degradation of activated KIT and has in vitro activity against gastrointestinal stromal tumors ( GIST ) . BIIB021 is an oral non-ansamycin HSP90 inhibitor . We carried out a phase II study of BIIB021 in patients with GIST refractory to imatinib and sunitinib . PATIENTS AND METHODS The primary end-point was metabolic partial response ( mPR ) as assessed by fluorodeoxyglucose positron emission tomography ( FDG-PET ) . The secondary end-points were pharmacokinetic assessment s of BIIB021 and pharmacodynamic assessment s of HSP70 . Twenty-three patients were treated on two schedules : 12 pts received 600 mg twice a week ( BIW ) and 11 patients received 400 mg three times a week ( TIW ) . All had prior imatinib and sunitinib but stopped>14 days before starting BIIB021 . RESULTS The median age was 59 years ( 33 - 88 years ) , 61 % male , 44 % Eastern Cooperative Oncology Group 1 ( ECOG1 ) . The best response was PR by FDG-PET for five patients ( 3/12 at 600 mg BIW and 2/9 at 400 TIW ) for an overall response rate of 22 % . The response duration was 25 - 138 days . Adverse events ( AEs ) were mild to moderate . The mean Cmax was 1.5 µmol and the mean AUC was 2.9 µmol h. Cmax>1.5 µmol was associated with a decrease in st and ardized uptake value ( SUVmax ) . HSP70 increased substantially following treatment . CONCLUSIONS This study met its primary end-point . BIIB021 leads to objective responses in refractory GIST patients . Pharmacodynamic studies confirmed HSP90 inhibition . Further evaluation of BIIB021 in GIST is warranted Typical MRI findings for gastro-intestinal stromal tumours ( GIST ) under treatment with imatinib were evaluated . MRI was performed in 45 patients ( 25 responders , 20 non-responders ) with metastatic or locally advanced , unresectable GIST . Target lesions were selected and re-evaluated after 2 , 4 , and 6 months of therapy with imatinib . The target tumour response ( TTR ) was classified according to RECIST criteria . TTR , signal intensity in the centre and border of the lesion and the presence and the extension of a hypervascular rim were analysed . The mean diameter of the marker lesions decreased significantly ( P<0.001 ) from 7.1±2.6 cm to 5.9±2.3 cm after 6 months . Accuracy of RECIST criteria was 51 % , 69 % and 73 % on MRI 2 , 4 and 6 months for response assessment . In addition , responders had higher signal-to-noise ratios on T2-w images after 2 months ( P<0.05 ) and a decrease of vascularised areas in the lesion 4 and 6 months after treatment ( each P<0.01 ) , when compared with non-responders . Beyond the size measurement for response assessment , MRI provides additional information of tumour response using SI of T2-w images and quantification Output:	CT is still the st and ard method for the evaluation of therapy response despite its several limitations .
MS21094	*TASK* the task is to summarize an input biomedical literature in six sentences *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 compared the relative efficacy of interferon beta ( IFNβ ) products and azathioprine ( AZA ) in the treatment of relapsing- remitting multiple sclerosis ( RRMS ) . Ninety-four previously untreated patients of short duration with RRMS were r and omly allocated to the two treatment groups . The first group received IFNβ products ( Betaferon , Avonex or Rebif ) ; the second group received AZA for 12 months . Response to treatment was assessed at 3 , 6 , and 12 months after starting therapy . The mean number of relapse during one year of the study was lower in the AZA group than in the IFNβ products group ( 0.28 vs. 0.64 , P < 0.05).After 12 months , 57.4 % of patients receiving IFNβ products remained relapse free compared with 76.6 % of those given AZA . The Exp and ed Disability Status Scale ( EDSS ) decreased by 0.30 units in IFNβ-treated patients ( P < 0.05 ) and 0.46 in AZAtreated patients ( P < 0.001 ) . Treatment with IFNβ products and AZA significantly reduces the relapse rate and EDSS score in patients with RRMS , while AZA is more effective than the IFNβ formulations BACKGROUND Fingolimod has shown reductions in clinical and MRI disease activity in patients with relapsing-remitting multiple sclerosis . We further assessed the efficacy and safety of fingolimod in such patients . METHODS We did this placebo-controlled , double-blind phase 3 study predominantly in the USA ( 101 of 117 centres ) . Using a computer-generated sequence , we r and omly allocated eligible patients -those aged 18 - 55 years with relapsing-remitting multiple sclerosis-to receive fingolimod 0·5 mg , fingolimod 1·25 mg , or placebo orally once daily ( 1:1:1 ; stratified by study centre ) . On Nov 12 , 2009 , all patients assigned to fingolimod 1·25 mg were switched to the 0·5 mg dose in a blinded manner after a review of data from other phase 3 trials and recommendation from the data and safety monitoring board , but were analysed as being in the 1·25 mg group in the primary outcome analysis . Our primary endpoint was annualised relapse rate at month 24 , analysed by intention to treat . Secondary endpoints included percentage brain volume change ( PBVC ) from baseline and time-to-disability-progression confirmed at 3 months . This trial is registered with Clinical Trilals.gov , number NCT00355134 . FINDINGS Between June 30 , 2006 , and March 4 , 2009 , we enrolled and r and omly allocated 1083 patients : 370 to fingolimod 1·25 mg , 358 to fingolimod 0·5 mg , and 355 to placebo . Mean annualised relapse rate was 0·40 ( 95 % CI 0·34 - 0·48 ) in patients given placebo and 0·21 ( 0·17 - 0·25 ) in patients given fingolimod 0·5 mg : rate ratio 0·52 ( 95 % CI 0·40 - 0·66 ; p<0·0001 ) , corresponding to a reduction of 48 % with fingolimod 0·5 mg versus placebo . Mean PBVC was -0·86 ( SD 1·22 ) for fingolimod 0·5 mg versus -1·28 ( 1·50 ) for placebo ( treatment difference -0·41 , 95 % CI -0·62 to -0·20 ; p=0·0002 ) . We recorded no statistically significant between-group difference in confirmed disability progression ( hazard rate 0·83 with fingolimod 0·5 mg vs placebo ; 95 % CI 0·61 - 1·12 ; p=0·227 ) . Fingolimod 0·5 mg caused more of the following adverse events versus placebo : lymphopenia ( 27 [ 8 % ] patients vs 0 patients ) , increased alanine aminotransferase ( 29 [ 8 % ] vs six [ 2 % ] ) , herpes zoster infection ( nine [ 3 % ] vs three [ 1 % ] ) , hypertension ( 32 [ 9 % ] vs 11 [ 3 % ] ) , first-dose bradycardia ( five [ 1 % ] vs one [ < 0·5 % ] ) , and first-degree atrioventricular block ( 17 [ 5 % ] vs seven [ 2 % ] ) . 53 ( 15 % ) of 358 patients given fingolimod 0·5 mg and 45 ( 13 % ) of 355 patients given placebo had serious adverse events over 24 months , which included basal-cell carcinoma ( ten [ 3 % ] patients vs two [ 1 % ] patients ) , macular oedema ( three [ 1 % ] vs two [ 1 % ] ) , infections ( 11 [ 3 % ] vs four [ 1 % ] ) , and neoplasms ( 13 [ 4 % ] vs eight [ 2 % ] ) . INTERPRETATION Our findings exp and knowledge of the safety profile of fingolimod and strengthen evidence for its beneficial effects on relapse rates in patients with relapsing-remitting multiple sclerosis . We saw no effect of fingolimod on disability progression . Our findings substantiate the beneficial profile of fingolimod as a disease-modifying agent in the management of patients with relapsing-remitting multiple sclerosis . FUNDING Novartis Pharma AG BACKGROUND BG-12 ( dimethyl fumarate ) is in development as an oral treatment for relapsing-remitting multiple sclerosis , which is commonly treated with parenteral agents ( interferon or glatiramer acetate ) . METHODS In this phase 3 , r and omized study , we investigated the efficacy and safety of oral BG-12 , at a dose of 240 mg two or three times daily , as compared with placebo in patients with relapsing-remitting multiple sclerosis . An active agent , glatiramer acetate , was also included as a reference comparator . The primary end point was the annualized relapse rate over a period of 2 years . The study was not design ed to test the superiority or noninferiority of BG-12 versus glatiramer acetate . RESULTS At 2 years , the annualized relapse rate was significantly lower with twice-daily BG-12 ( 0.22 ) , thrice-daily BG-12 ( 0.20 ) , and glatiramer acetate ( 0.29 ) than with placebo ( 0.40 ) ( relative reductions : twice-daily BG-12 , 44 % , P<0.001 ; thrice-daily BG-12 , 51 % , P<0.001 ; glatiramer acetate , 29 % , P=0.01 ) . Reductions in disability progression with twice-daily BG-12 , thrice-daily BG-12 , and glatiramer acetate versus placebo ( 21 % , 24 % , and 7 % , respectively ) were not significant . As compared with placebo , twice-daily BG-12 , thrice-daily BG-12 , and glatiramer acetate significantly reduced the numbers of new or enlarging T(2)-weighted hyperintense lesions ( all P<0.001 ) and new T(1)-weighted hypointense lesions ( P<0.001 , P<0.001 , and P=0.002 , respectively ) . In post hoc comparisons of BG-12 versus glatiramer acetate , differences were not significant except for the annualized relapse rate ( thrice-daily BG-12 ) , new or enlarging T(2)-weighted hyperintense lesions ( both BG-12 doses ) , and new T(1)-weighted hypointense lesions ( thrice-daily BG-12 ) ( nominal P<0.05 for each comparison ) . Adverse events occurring at a higher incidence with an active treatment than with placebo included flushing and gastrointestinal events ( with BG-12 ) and injection-related events ( with glatiramer acetate ) . There were no malignant neoplasms or opportunistic infections reported with BG-12 . Lymphocyte counts decreased with BG-12 . CONCLUSIONS In patients with relapsing-remitting multiple sclerosis , BG-12 ( at both doses ) and glatiramer acetate significantly reduced relapse rates and improved neuroradiologic outcomes relative to placebo . ( Funded by Biogen Idec ; CONFIRM Clinical Trials.gov number , NCT00451451 . ) BACKGROUND Interleukin 12 ( IL-12 ) , a cytokine that promotes generation of helper T cells subtype 1 , is increased in multiple sclerosis . Albuterol sulfate , a β2-adrenergic agonist , reduces IL-12 expression , so we tested the effect of albuterol as an add-on treatment to glatiramer acetate therapy . OBJECTIVES To investigate the clinical and immunologic effects of albuterol treatment as an add-on therapy in patients starting glatiramer acetate treatment . DESIGN Single-center double-masked clinical trial . SETTING Academic research . Patients Subjects with relapsing-remitting multiple sclerosis . MAIN OUTCOME MEASURES In this single-center double-masked clinical trial , subjects with relapsing-remitting multiple sclerosis were r and omized to receive a subcutaneous injection of glatiramer acetate ( 20 mg ) plus an oral dose of placebo daily for 2 years or a subcutaneous injection of glatiramer acetate ( 20 mg ) plus an oral dose of albuterol daily for 2 years . The primary clinical efficacy measurement was the change in Multiple Sclerosis Functional Composite at 2 years , and the primary immunologic end point was the change in expression of IL-13 and interferon γ at each study time point . The classification level of evidence from this trial is C for each question , as this is the first class II clinical trial addressing the efficacy of glatiramer acetate plus albuterol . RESULTS Forty-four subjects were r and omized to receive glatiramer acetate plus albuterol or glatiramer acetate plus placebo , and 39 subjects contributed to the analysis . Improvement in the Multiple Sclerosis Functional Composite was observed in the glatiramer acetate plus albuterol group at the 6-month ( P = .005 ) and 12-month ( P = .04 ) time points but not at the 24-month time point . A delay in the time to first relapse was also observed in the glatiramer acetate plus albuterol group ( P = .03 ) . Immunologically , IL-13 and interferon-γ production decreased in both treatment groups , and a treatment effect on IL-13 production was observed at the 12-month time point ( P < .05 ) . Adverse events were generally mild , and only 3 moderate or severe events were considered related to the treatment . CONCLUSION Treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00039988 A double‐blind , r and omized , controlled study was undertaken to determine whether combined use of interferon β‐1a ( IFN ) 30μg intramuscularly weekly and glatiramer acetate ( GA ) 20 mg daily is more efficacious than either agent alone in relapsing – remitting multiple sclerosis BACKGROUND The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis . We aim ed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment . METHODS In our 2 year , rater-masked , r and omised controlled phase 3 trial , we enrolled adults aged 18 - 55 years with relapsing-remitting multiple sclerosis and at least one relapse on interferon beta or glatiramer . Eligible participants were r and omly allocated in a 1:2:2 ratio by an interactive voice response system , stratified by site , to receive subcutaneous interferon beta 1a 44 μg , intravenous alemtuzumab 12 mg per day , or intravenous alemtuzumab 24 mg per day . Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and for 3 days at 12 months . The 24 mg per day group was discontinued to aid recruitment , but data are included for safety assessment s. Co primary endpoints were relapse rate and time to 6 month sustained accumulation of disability , comparing alemtuzumab 12 mg and interferon beta 1a in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT00548405 . FINDINGS 202 ( 87 Output:	Our review shows that alemtuzumab , natalizumab , and fingolimod are the best choices for preventing clinical relapses in people with RRMS , but this evidence is limited to the first 24 months of follow-up . For the prevention of disability worsening in the short term ( 24 months ) , only natalizumab shows a beneficial effect on the basis of moderate quality evidence ( all of the other estimates were based on low to very low quality evidence ) . Currently , therefore , insufficient evidence is available to evaluate treatments for the prevention of irreversible disability worsening .
MS21095	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Patients with diabetes and anemia are at high risk of cardiovascular disease . The Anemia CORrection in Diabetes ( ACORD ) Study aim ed to investigate the effect of anemia correction on cardiac structure , function , and outcomes in patients with diabetes with anemia and early diabetic nephropathy . METHODS One hundred seventy-two patients with type 1 or 2 diabetes mellitus , mild to moderate anemia , and stage 1 to 3 chronic kidney disease were r and omly assigned to attain a target hemoglobin ( Hb ) level of either 13 to 15 g/dL ( 130 to 150 g/L ; group 1 ) or 10.5 to 11.5 g/dL ( 105 to 115 g/L ; group 2 ) . The primary end point was change in left ventricular mass index ( LVMI ) . Secondary end points included echocardiographic variables , renal function , quality of life , and safety . RESULTS Median Hb level and LVMI were similar in groups 1 and 2 ( Hb , 11.9 and 11.7 g/dL [ 119 and 117 g/L ] ; LVMI , 113.5 and 112.3 g/m(2 ) , respectively ) . At study end , Hb levels were 13.5 g/dL ( 135 g/L ) in group 1 and 12.1 g/dL ( 121 g/L ) in group 2 ( P < 0.001 ) . No significant differences were observed in median LVMI at month 15 between study groups ( group 1 , 112.3 g/m(2 ) ; group 2 , 116.5 g/m(2 ) ) . Multivariate analysis showed a nonsignificant decrease in LVMI ( P = 0.15 ) in group 1 versus group 2 . Anemia correction had no effect on the rate of decrease in creatinine clearance , but result ed in significantly improved quality of life in group 1 ( P = 0.04 ) . There were no clinical ly relevant differences in adverse events between study groups . CONCLUSION In patients with diabetes with mild to moderate anemia and moderate left ventricular hypertrophy , correction to an Hb target level of 13 to 15 g/dL ( 130 to 150 g/L ) does not decrease LVMI . However , normalization of Hb level prevented an additional increase in left ventricular hypertrophy , was safe , and improved quality of life BACKGROUND This r and omized clinical trial is design ed to assess whether the prevention and /or correction of anemia , by immediate versus delayed treatment with erythropoietin alfa in patients with chronic kidney disease , would delay left ventricular ( LV ) growth . Study design and sample size calculations were based on previously published Canadian data . METHODS One hundred seventy-two patients were r and omly assigned . The treatment group received therapy with erythropoietin alfa subcutaneously to maintain or achieve hemoglobin ( Hgb ) level targets of 12.0 to 14.0 g/dL ( 120 to 140 g/L ) . The control/delayed treatment group had Hgb levels of 9.0 + /- 0.5 g/dL ( 90 + /- 5 g/L ) before therapy was started : target level was 9.0 to 10.5 g/dL ( 90 to 105 g/L ) . Optimal blood pressure and parathyroid hormone , calcium , and phosphate level targets were prescribed ; all patients were iron replete . The primary end point is LV growth at 24 months . RESULTS One hundred fifty-two patients were eligible for the intention-to-treat analysis : mean age was 57 years , 30 % were women , 38 % had diabetes , and median glomerular filtration rate was 29 mL/min ( 0.48 mL/s ; range , 12 to 55 mL/min [ 0.20 to 0.92 mL/s ] ) . Blood pressure and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were similar in the control/delayed treatment and treatment groups at baseline . Erythropoietin therapy was administered to 77 of 78 patients in the treatment group , with a median final dose of 2,000 IU/wk . Sixteen patients in the control/delayed treatment group were administered erythropoietin at a median final dose of 3,000 IU/wk . There was no statistically significant difference between groups for the primary outcome of mean change in LV mass index ( LVMI ) from baseline to 24 months , which was 5.21 + /- 30.3 g/m2 in the control/delayed treatment group versus 0.37 + /- 25.0 g/m2 in the treatment group . Absolute mean difference between groups was 4.85 g/m2 ( 95 % confidence interval , -4.0 to 13.7 ; P = 0.28 ) . Mean Hgb level was greater in the treatment group throughout the study and at study end was 12.75 g/dL ( 127.5 g/L in treatment group versus 11.46 g/dL [ 114.6 g/L ] in control/delayed treatment group ; P = 0.0001 ) . LV growth occurred in 20.1 % in the treatment group versus 31 % in the control/delayed treatment group ( P = 0.136 ) . In patients with a stable Hgb level , mean LVMI did not change ( -0.25 + /- 26.7 g/m2 ) , but it increased in those with decreasing Hgb levels ( 19.3 + /- 28.2 g/m2 ; P = 0.002 ) . CONCLUSION This trial describes disparity between observational and r and omized controlled trial data : observed and r and omly assigned Hgb level and LVMI are not linked ; thus , there is strong evidence that the association between Hgb level and LVMI likely is not causal . Large r and omized controlled trials with unselected patients , using morbidity and mortality as outcomes , are needed Abstract A prospect i ve r and omized study of the use of recombinant human erythropoietin ( rHuEPO ) in children with chronic renal disease was conducted to assess dosing requirements and side effects . Forty-four children with chronic renal failure , aged 4 months to 21 years , were studied . Twenty-five patients were pre dialysis , 10 on peritoneal dialysis , and 9 on hemodialysis . Patients received either 150 U/kg per week or 450 U/kg per week divided thrice weekly of rHuEPO for 12 weeks or until target hemoglobin ( Hb ) was attained . Dose was then adjusted to maintain a normal Hb . Eighty-two percent of patients reached target Hb by 7.9±5.6 weeks ( mean±SD ) ; 95 % of patients in the high-dose group and 66 % in the low-dose group reached target Hb within 12 weeks . The overall median rHuEPO dose at target Hb was 150 U/kg per week . Hemodialysis patients tended to require more rHuEPO to maintain a normal Hb ( median 250 U/kg per week ) . Transfusion requirements and panel-reactive antibody levels decreased during the 12 weeks . Iron deficiency and /or hypertension occurred in 30 % of children . In conclusion , rHuEPO at 150 U/kg per week is safe and effective in treating anemia in children with chronic renal disease The investigators evaluated the impact of recombinant human erythropoietin ( r-HuEPO ) therapy on health-related quality of life ( HRQL ) in predialysis chronic renal disease patients with anemia . Eighty-three patients were entered into a r and omized , parallel-group , open-label clinical trial with follow-up evaluations over 48 weeks . Forty-three patients were assigned to r-HuEPO treatment , and 40 patients were assigned to an untreated control group . Hematocrit levels were measured at baseline and monthly . HRQL was assessed at baseline and at weeks 16 , 32 , and 48 . The HRQL assessment included measures of physical function , energy , role function , health distress , cognitive function , social function , home management , sexual dysfunction , depression , and life satisfaction . Significant improvements in hematocrit levels were observed in the r-HuEPO-treated group ( P < 0.0001 ) , and no changes were seen in the untreated group . Correction of anemia ( hematocrit > or = 36 ) occurred in 79 % of r-HuEPO-treated patients and 0 % of control patients . Significant improvements in assessment s of energy ( P < 0.05 ) , physical function ( P < 0.05 ) , home management ( P < 0.05 ) , social activity ( P < 0.05 ) , and cognitive function ( P < 0.05 ) were found for the r-HuEPO-treated group . No changes were observed in the control group , except for a decrease in physical function ( P < 0.05 ) . Between-group differences favoring the r-HuEPO-treated group were found for energy ( P < 0.05 ) and physical functioning ( P < 0.05 ) . In patients receiving r-HuEPO , significant improvements were seen in hemotocrit levels , and these increases result ed in improvements in HRQL Children with end stage renal failure and anaemia have an increased cardiac index and often gross ventricular hypertrophy . The contribution of anaemia to these abnormalities is uncertain . Eleven children with end stage renal failure and anaemia ( haemoglobin concentration < 90 g/l ) were enrolled into a single blind , placebo controlled , crossover study to assess the cardiovascular effects of reversing anaemia using subcutaneous human recombinant erythropoietin ( r-HuEpo ) . Each limb lasted 24 weeks ; seven children completed both limbs of the study . Haemoglobin increased with r-HuEpo , remaining above 100 g/l for a mean of 11 weeks . Cardiac index fell as a result of a reduction in both left ventricular stroke volume and heart rate . Left ventricular end diastolic diameter also decreased . In five children left ventricular wall thickness and left ventricular mass decreased with r-HuEpo , but this failed to reach significance for the whole group . Blood pressure did not change in six normotensive children completing an r-HuEpo limb ; the decrease in cardiac index was therefore balanced by an increase in peripheral vascular resistance . Three children were taking anti-hypertensive treatment at the start of the study ; one required an increase , and one a decrease , in treatment during the r-HuEpo limb . Short term treatment with r-HuEpo reduces cardiac index . A longer study is needed to determine whether this will , in time , result in a significant reduction in left ventricular hypertrophy BACKGROUND This study is design ed to assess the effect of early and complete correction of anemia by using recombinant human erythropoietin ( epoetin ) alfa on the progression of chronic kidney disease ( CKD ) . METHODS Patients were r and omly assigned to achieve high ( 13 to 15 g/dL [ 130 to 150 g/L ] ) or low ( 11 to 12 g/dL [ 110 to 120 g/L ] ) hemoglobin-level targets during 4 months of stabilization , followed by 36 months of maintenance . Glomerular filtration rate ( GFR ) decrease was measured by using iohexol clearance . Quality of life , nutrition , and safety also were monitored . RESULTS Because of labeling changes for subcutaneous administration of epoetin alfa ( Eprex ; Johnson and Johnson , Schaffhausen , Switzerl and ) , the study was terminated prematurely . There were 195 patients enrolled in each group ; 108 high-hemoglobin and 133 low-hemoglobin patients entered the maintenance phase . Mean maintenance duration was 7.4 months for the high-hemoglobin group and 8.3 months for the low-hemoglobin group . GFR decrease was numerically , but not statistically significantly , lower with the high-hemoglobin group ( 0.058 versus 0.081 mL/min/1.73 m2/mo [ < 0.01 mL/s/1.73 m2/mo ] ) . Physical quality -of-life measures showed trends ( Role-Physical , P = 0.055 ; Physical Function , P = 0.083 ) or statistically significant improvement ( Vitality , P = 0.042 ) with high hemoglobin levels at the end of the stabilization phase . Adverse events were similar between groups . Cardiovascular adverse events occurred in 25 % of the high-hemoglobin and 18 % of the low-hemoglobin patients ( P = 0.137 ) . Neither epoetin dosage nor hemoglobin level was associated with cardiovascular adverse events or death . CONCLUSION These data suggest that normalization of hemoglobin levels in patients with CKD is safe . Longer duration studies are needed to clarify efficacy benefits with high hemoglobin levels BACKGROUND Partial correction of renal anaemia with erythropoietin improves quality of life ( QoL ) . We aim ed to examine if normalization of haemoglobin with epoetin alfa in pre-dialysis and dialysis patients further improves QoL and is safe . METHODS 416 Sc and inavian patients with renal anaemia [ pre- Output:	Treatment effects were consistent across subgroups , including all stages of CKD . Targeting higher hemoglobin levels in CKD increases risks for stroke , hypertension , and vascular access thrombosis and probably increases risks for death , serious cardiovascular events , and end-stage renal disease .
MS21096	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This study evaluated the effects of a water exercise training program that includes perturbation exercises ( WEP ) to improve the speed of voluntary stepping reaction in older adults . Speed of voluntary stepping considered as an important skill to prevent a fall when balance is lost . In a single-blinded r and omized controlled trial with a crossover design thirty-six independent old adults ( 64 - 88 years old ) were divided into two groups . Group A received WEP for the first 12 weeks , followed by no intervention for the second 12 weeks . Group B did not receive intervention for the first 12 weeks and received WEP for the second 12 weeks . Voluntary Step Execution Test and postural stability in upright st and ing ( eyes open and closed conditions ) were measured at baseline , 12 weeks , and 24 weeks . A significant interaction effect between group and time was found for the step execution , due to improvement in initiation phase and swing phase duration s in the WEP group . Also significant improvement in postural stability parameters in eyes open and closed conditions is noted . The present results indicate that the primary benefit of WEP that include perturbations to induce stepping , was a reduction in voluntary stepping times . The WEP generalized to a better control of balance in up-right st and ing This study compared the effects of 2 types of water exercise programs on balance ability in the elderly . Thirty healthy elderly persons ( 60.7 + /- 4.1 yr ) were r and omly assigned to a deep-water-running exercise ( DWRE , n = 15 ) group or a normal water exercise ( NWE , n = 15 ) group . The participants completed a twice-weekly water exercise intervention for 12 wk . Exercise sessions comprised a 10-min warm-up on l and , 20 min of water-walking exercise , 30 min of water exercise while separated into NWE and DWRE , a 10-min rest on l and , and 10 min of recreation and relaxation in water . Postural-sway distance and t and em-walking time were decreased significantly in DWRE . Postural-sway area was decreased significantly in NWE . In both groups , simple reaction times were significantly decreased . The findings of this study show that a water exercise program including deep-water running is much better than normal water exercise for improving dynamic balance ability in the elderly BACKGROUND Recently , several studies have reported age-associated increases in muscle coactivation during postural control . A rigid posture induced by strong muscle coactivation reduces the degree of freedom to be organized by the postural control system . The purpose of this study was to clarify the effect of balance training on muscle coactivation during postural control in older adults . METHODS Forty-eight subjects were r and omized into an intervention ( mean age : 81.0 ± 6.9 years ) and a control group ( mean age : 81.6 ± 6.4 years ) . The control group did not receive any intervention . Postural control ability ( postural sway during quiet st and ing , functional reach , and functional stability boundary ) was assessed before and after the intervention . A cocontraction index was measured during the postural control tasks to assess muscle coactivation . RESULTS Cocontraction index values in the intervention group significantly decreased following the intervention phase for functional reach ( p < .0125 ) . Cocontraction index values had a tendency to decrease during functional stability boundary for forward and quiet st and ing tasks . Functional improvements were observed in some of the tasks after the intervention , that is , functional reach , functional stability boundary for forward , one-leg stance , and timed up and go ( p < .05 ) . CONCLUSIONS Our study raised the possibility that balance training for older adults was associated with decreases in muscle coactivation during postural control . Postural control exercise could potentially lead older adults to develop more efficient postural control strategies without increasing muscle coactivation . Further research is needed to clarify in greater detail the effects of changes in muscle coactivation The changes in postural control in elderly people after an 8-week training course were characterized . Static postural stability was measured during st and ing on a single force platform first with the eyes open and then with the eyes closed . Body sway was analysed on a force plate in groups of elderly and of young subjects . Half of the elderly subjects then took part in the training course . The posturographic measurements were repeated after the course . The sway in anteroposterior ( AP ) and mediolateral ( ML ) directions was subjected to spectral analysis . The frequency spectrum of the platform oscillations was calculated by fast Fourier transformation in the intervals 0.1–0.3 , 0.3–1 and 1–3 Hz . It was found that the sway path was longer and the frequency power was higher in the elderly group . The training caused a significant improvement in functional performance , but a significantly longer sway path was observed after the training in the ML direction . The frequency analysis revealed a significantly higher power after 8 weeks without visual control in the ML direction in the training group in the low and the middle frequency b and s. The results suggest that the participants ’ balance confidence and the control of ML balance improved in response to the training . The higher ML frequency power exhibited after the training may be indicative of a better balance performance . Thus , the increase in the sway path in this age group did not mean a further impairment of the postural control OBJECTIVE To compare the effect of a custom- design ed yoga program with 2 other balance training programs . DESIGN R and omized controlled trial . SETTING Research laboratory . PARTICIPANTS A group of older adults ( N=39 ; mean age , 74.15 ± 6.99 y ) with a history of falling . INTERVENTIONS Three different exercise interventions ( Tai Chi , st and ard balance training , yoga ) were given for 12 weeks . MAIN OUTCOME MEASURES Balance performance was examined during pre- and posttest using field tests , including the 8-foot up- and -go test , 1-leg stance , functional reach , and usual and maximal walking speed . The static and dynamic balances were also assessed by postural sway and dynamic posturography , respectively . RESULTS Training produced significant improvements in all field tests ( P<.005 ) , but group difference and time × group interaction were not detected . For postural sway , significant decreases in the area of the center of pressure with eyes open ( P=.001 ) and eyes closed ( P=.002 ) were detected after training . For eyes open , maximum medial-lateral velocity significantly decreased for the sample ( P=.013 ) . For eyes closed , medial-lateral displacement decreased for Tai Chi ( P<.01 ) . For dynamic posturography , significant improvements in overall score ( P=.001 ) , time on the test ( P=.006 ) , and 2 linear measures in lateral ( P=.001 ) and anterior-posterior ( P<.001 ) directions were seen for the sample . CONCLUSIONS Yoga was as effective as Tai Chi and st and ard balance training for improving postural stability and may offer an alternative to more traditional programs BACKGROUND Diabetes is the most common cause of peripheral neuropathies . No definitive treatment for diabetic neuropathies has been reported , and very few studies have been published on the role of exercise in reducing either the symptoms or incidence of diabetic neuropathies . METHODS This study assessed the effects of an exercise program on balance and trunk proprioception in older adults with diabetic neuropathies . Thirty-eight patients with diabetes having peripheral neuropathies were enrolled , r and omized , and subdivided in two groups : an experimental group of 19 participants with diabetes ( 72.9 ± 5.6 years old ) and a control group of 19 participants with diabetes ( 73.2 ± 5.4 years old ) . Both groups received health education on diabetes for 50 min/week for 8 weeks . The experimental group practice d an additional balance exercise program for 60 min , two times a week . The exercise training was performed two times per week for 8 weeks . Results were evaluated by both static and dynamic balance and trunk proprioception . RESULTS Postural sway significantly decreased ( P < 0.05 ) , the one-leg stance test significantly increased ( P < 0.05 ) , and dynamic balance from the Berg Balance Scale , Functional Reach Test , Timed Up and Go test , and 10-m walking time improved significantly after balance exercise ( P < 0.05 ) . Trunk repositioning errors also decreased with training ( P < 0.05 ) . CONCLUSION The balance exercise program improved balance and trunk proprioception . These results suggested that a balance exercise is suitable for individuals with diabetic neuropathy OBJECTIVE To determine whether a 12-week whole-body vibration ( WBV ) training program improved balance in participants with type 2 diabetes mellitus ( T2DM ) . DESIGN R and omized controlled trial . SETTING Primary health care setting . PARTICIPANTS Participants with T2DM ( N=50 ) . INTERVENTIONS Participants were r and omly allocated to either a WBV group ( n=25 ) , which performed a 12-week WBV-based exercise program on an oscillating platform ( 12 - 16Hz-4 mm ; 3 sessions/wk ) , or a usual-care control group ( n=25 ) . MAIN OUTCOME MEASURES Clinical and sociodemographic variables were recorded at baseline . Static balance and dynamic balance were also assessed at baseline by measuring postural sway ( measurement of center of pressure [ COP ] excursions in the anteroposterior and mediolateral directions ) using a Wii Balance Board and the Timed Up and Go test . RESULTS Significant between-group differences in COP excursions with participants ' eyes closed were found with their feet apart and feet together . In addition , participants in the WBV group exhibited significantly lower COP excursions with their eyes closed after the intervention , while participants in the control group experienced a nonsignificant deterioration in COP excursions ( ie , greater excursion ) with their eyes open ( mediolateral axis ) . There was no significant difference in the Timed Up and Go test values postintervention . CONCLUSIONS WBV provides a safe and well-tolerated approach to improve balance in participants with T2DM . These findings may have important implication s for falls prevention in those with T2DM in the primary health care setting Purpose The purpose of the study was to evaluate the effect of BodyBalance ® training on balance , functional task performance , fear of falling , and health-related quality of life in adults aged over 55 years . Participants and methods A total of 28 healthy , active adults aged 66±5 years completed the r and omized controlled trial . Balance , functional task performance , fear of falling , and self-reported quality of life were assessed at baseline and after 12 weeks . Participants either undertook two sessions of BodyBalance per week for 12 weeks ( n=15 ) or continued with their normal activities ( n=13 ) . Results Significant group-by-time interactions were found for the timed up and go ( P=0.038 ) , 30-second chair st and ( P=0.037 ) , and mediolateral center-of-pressure range in narrow stance with eyes closed ( P=0.017 ) . There were no significant effects on fear of falling or self-reported quality of life . Conclusion Twelve weeks of BodyBalance training is effective at improving certain balance and functional based tasks in healthy older adults OBJECTIVE To compare the impacts of Tai Chi , a st and ard balance exercise program , and a video game balance board program on postural control and perceived falls risk . DESIGN R and omized controlled trial . SETTING Research laboratory . PARTICIPANTS Independent seniors ( N=40 ; 72.5±8.40 ) began the training , 27 completed . INTERVENTIONS Tai Chi , a st and ard balance exercise program , and a video game balance board program . MAIN OUTCOME MEASURES The following were used as measures : Timed Up & Go , One-Leg Stance , functional reach , Tinetti Performance Oriented Mobility Assessment , force plate center of pressure ( COP ) and time to boundary , dynamic posturography ( DP ) , Falls Risk for Older People-Community Setting , and Falls Efficacy Scale . RESULTS No significant differences were seen between groups for any outcome measures at baseline , nor were significant time or group × time differences for any field test or question naire . No group × time differences were seen for any COP measures ; however , significant time differences were seen for total COP , 3 of 4 anterior/posterior displacement and both velocity , and 1 displacement and 1 velocity medial/lateral measure across time for the entire sample . For DP , significant improvements in the overall score ( dynamic movement analysis score ) , and in 2 of the 3 linear and angular measures were seen for the sample . CONCLUSIONS The video game balance board program , which can be performed at home , was as effective as Tai Chi and the st and ard balance exercise program in improving postural control and balance dictated by the force plate postural sway and DP measures . This finding may have implication s for exercise adherence because the at-home nature of the intervention eliminates many obstacles to exercise training BACKGROUND AND PURPOSE Loss of lower-extremity strength increases the risk of falls in older persons . The purpose of this study was to test the hypothesis that a vigorous program of lower-extremity strengthening , walking , and postural control exercises would improve the single-stance balance of healthy older women and lower their risk of falls and fall-associated injuries . SUBJECTS From a total of 38 respondents , 21 women were r and omly assigned to either a treatment group ( combined training , n = 12 ) or a control group ( flexibility training , n = 9 ) . The subjects ranged in age from 62 to 75 years ( mean = 68 , SD = 3.5 ) . METHODS A r and omized control trial compared the effects of two exercise programs on static balance . The combined training group exercised three times per week on knee extension and sitting leg press machines , walked briskly for 20 minutes , and performed postural control exercises , which included simple tai chi movements . The flexibility training group performed postural control exercises weekly . Measurements of balance were obtained on a force platform in double and single stance , at baseline and following 6 months Output:	In contrast , neither resistance nor multi-component exercise interventions affected any of the included COP measurements . Conclusions Postural control is improved by balance exercise interventions . In contrast , strength or multi-component exercise interventions did not influence postural control measurements in older adults .
MS21097	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Dietary intake of fish and the omega-3 fatty acids have been associated with lower risk of Alzheimer disease and stroke . OBJECTIVE To examine whether intakes of fish and the omega-3 fatty acids protect against age-related cognitive decline . DESIGN Prospect i ve cohort study . SETTING Geographically defined Chicago , Ill , community . PARTICIPANTS Residents , 65 years and older , who participated in the Chicago Health and Aging Project . MAIN OUTCOME MEASURE Change in a global cognitive score estimated from mixed models . The global score was computed by summing scores of 4 st and ardized tests . In-home cognitive assessment s were performed 3 times over 6 years of follow-up . RESULTS Cognitive scores declined on average at a rate of 0.04 st and ardized units per year ( SU/y ) . Fish intake was associated with a slower rate of cognitive decline in mixed models adjusted for age , sex , race , education , cognitive activity , physical activity , alcohol consumption , and total energy intake . Compared with a decline rate in score of -0.100 SU/y among persons who consumed fish less than weekly , the rate was 10 % slower ( -0.090 SU/y ) among persons who consumed 1 fish meal per week and 13 % slower ( -0.088 SU/y ) among persons who consumed 2 or more fish meals per week . The fish association was not accounted for by cardiovascular-related conditions or fruit and vegetable consumption but was modified after adjustment for intakes of saturated , polyunsaturated , and trans fats . There was little evidence that the omega-3 polyunsaturated fatty acids were associated with cognitive change . CONCLUSIONS Fish consumption may be associated with slower cognitive decline with age . Further study is needed to determine whether fat composition is the relevant dietary constituent In a test of the effects of cortisol on emotional memory , 90 men were orally administered placebo or 20 or 40 mg cortisol and presented with emotionally arousing and neutral stimuli . On memory tests administered within 1 hr of stimulus presentation , cortisol elevations caused a reduction in the number of errors committed on free-recall tasks . Two evenings later , when cortisol levels were no longer manipulated , inverted-U quadratic trends were found for recognition memory tasks , reflecting memory facilitation in the 20-mg group for both negative and neutral information . Results suggest that the effects of cortisol on memory do not differ substantially for emotional and neutral information . The study provides evidence of beneficial effects of acute cortisol elevations on explicit memory in humans BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality BACKGROUND While high adiposity in middle age appears to be related to greater dementia risk , studies exploring this association in the elderly are conflicting . OBJECTIVE To evaluate associations between midlife and late-life obesity and risk of dementia . DESIGN Prospect i ve study with mean follow-up of 5.4 years ( 1992 - 1994 through 1999 ) . SETTING Community-dwelling sample in 4 US sites recruited from Medicare eligibility files . PARTICIPANTS A total of 2798 adults without dementia ( mean age , 74.7 years ; 59.1 % women ) participating in the Cardiovascular Health Study who underwent magnetic resonance imaging were measured for height and weight at baseline at age 65 years or older ( late life ) , and self-reported weight at age 50 years ( midlife ) . Body mass index ( BMI ) ( calculated as weight in kilograms divided by height in meters squared ) was calculated at both times . MAIN OUTCOME MEASURES Dementia , Alzheimer disease , and vascular dementia classified by a multidisciplinary committee using st and ardized criteria . RESULTS Classification result ed in 480 persons with incident dementia , 245 with Alzheimer disease ( no vascular dementia ) , and 213 with vascular dementia ( with or without Alzheimer disease ) . In evaluations of midlife obesity , an increased risk of dementia was found for obese ( BMI > 30 ) vs normal-weight ( BMI 20 - 25 ) persons , adjusted for demographics ( hazard ratio [ HR ] , 1.39 ; 95 % confidence interval [ CI ] , 1.03 - 1.87 ) and for cardiovascular risk factors ( 1.36 ; 0.94 - 1.95 ) . The risk estimates were reversed in assessment s of late-life BMI . Underweight persons ( BMI < 20 ) had an increased risk of dementia ( 1.62 ; 1.02 - 2.64 ) , whereas being overweight ( BMI > 25 - 30 ) was not associated ( 0.92 ; 0.72 - 1.18 ) and being obese reduced the risk of dementia ( 0.63 ; 0.44 - 0.91 ) compared with those with normal BMI . CONCLUSION These results help explain the " obesity paradox " as differences in dementia risk across time are consistent with physical changes in the trajectory toward disability The current study used a r and omized , double-blind , placebo-controlled design to investigate the effects of saccharide supplementation on cognition and well-being in middle-aged adults . Participants ( N = 109 ; 45–60 years ) took a teaspoon of a combination of saccharides or a placebo twice daily for 12 weeks ( 3.6 g per day ) . Before and after this supplementation period , participants completed alternate forms of st and ardized tests of cognition and self-report measures of well-being . Significant beneficial effects of saccharide supplementation were found for memory performance and indicators of well-being . The potential for these nutrients to optimize cognitive function and well-being in older adults warrants ongoing investigation BACKGROUND Cognitive performance often declines under chronic stress exposure . The negative effect of chronic stress on performance may be mediated by reduced brain serotonin function . The uptake of the serotonin precursor tryptophan into the brain depends on nutrients that influence the availability of tryptophan by changing the ratio of plasma tryptophan to the sum of the other large neutral amino acids ( Trp-LNAA ratio ) . In addition , a diet-induced increase in tryptophan may increase brain serotonergic activity levels and improve cognitive performance , particularly in high stress-vulnerable subjects . OBJECTIVE We tested whether alpha-lactalbumin , a whey protein with a high tryptophan content , would increase the plasma Trp-LNAA ratio and improve cognitive performance in high stress- vulnerable subjects . DESIGN Twenty-three high stress-vulnerable subjects and 29 low stress-vulnerable subjects participated in a double-blind , placebo-controlled , crossover study . All subjects conducted a memory-scanning task after the intake of a diet enriched with either alpha-lactalbumin ( alpha-lactalbumin diet ) or sodium caseinate ( control diet ) . Blood sample s were taken to measure the effect of dietary manipulation on the plasma Trp-LNAA ratio . RESULTS A significantly greater increase in the plasma Trp-LNAA ratio after consumption of the alpha-lactalbumin diet than after the control diet ( P = 0.0001 ) was observed ; memory scanning improved significantly only in the high stress-vulnerable subjects ( P = 0.019 ) . CONCLUSION Because an increase in the plasma Trp-LNAA ratio is considered to be an indirect indication of increased brain serotonin function , the results suggest that dietary protein rich in alpha-lactalbumin improves cognitive performance in stress-vulnerable subjects via increased brain tryptophan and serotonin activities BACKGROUND Dietary carbohydrates can improve memory . Whether these effects are related to elevations in blood glucose or to energy ingestion is unknown . OBJECTIVES Our objectives were to determine 1 ) the influence of isoenergetic protein- , carbohydrate- , and fat-containing drinks on cognitive performance and 2 ) whether the time period after ingestion affects cognition . DESIGN After fasting overnight , 11 men and 11 women aged 61 - 79 y consumed either a 300-mL drink containing 774 kJ as pure protein ( whey ) , carbohydrate ( glucose ) , or fat ( safflower oil ) or a nonenergy placebo on 4 separate mornings . Cognitive tests were administered 15 and 60 min after ingestion of the drinks . Plasma glucose and serum insulin concentrations were measured . RESULTS Only the carbohydrate drink increased blood glucose ( P < 0.0001 ) . Compared with the placebo , all 3 macronutrients improved delayed paragraph recall ( PR ) ( P < 0.001 ) and improved or tended to improve immediate PR ( P < 0.04 ) 15 min after ingestion . Beneficial effects on other cognitive tests were confined to one or more of the macronutrients : carbohydrate improved Trail Making Test ( Trails ) performance at 60 min ( P = 0.02 ) and tended to improve Trails at 15 min ( P = 0.04 ) and PR at 60 min in men , carbohydrate and fat improved or tended to improve performance on Trails at 15 and 60 min in subjects with poor baseline scores ( r > -0.41 , P < 0.03 ) , fat tended to improve attention at 60 min ( P < 0.05 ) , and protein reduced the rate of forgetting on the PR at 15 min ( P = 0.002 ) . CONCLUSIONS Energy intake from protein , carbohydrate , or fat can enhance memory independently of elevations in blood glucose . Each macronutrient may also exert unique effects on cognition BACKGROUND A glucose drink has been shown to improve memory in persons with poor glucose regulation and poor cognition . OBJECTIVE The objective of this study was to determine 1 ) whether an association between cognition and glucose regulation is apparent in healthy seniors and 2 ) the effects of dietary carbohydrates on cognition . DESIGN After an overnight fast , 10 men and 10 women ( aged 60 - 82 y ) consumed 50 g carbohydrate as glucose , potatoes , or barley or a placebo on 4 separate mornings . Cognitive tests were administered 15 , 60 , and 105 min after ingestion of the carbohydrate . Plasma glucose and serum insulin were measured . RESULTS In a multiple regression analysis , poor baseline ( placebo ) verbal declarative memory ( immediate and 20-min delayed paragraph recall and word list recall ) and visuomotor task performance were predicted by poor beta cell function , high incremental area under the glucose curve , low insulin resistance , and low body mass index . The difference in plasma glucose after food consumption [ glucose > potatoes > barley > placebo ( P : < 0.03 ) ] did not predict performance . Although overall performance did not differ with consumption of the different test foods , baseline score and beta cell function correlated with improvements in immediate and delayed paragraph recall for all 3 carbohydrates ( compared with placebo ) ; the poorer the baseline memory or beta cell function , the greater the improvement ( correlation between beta cell function and improvement in delayed paragraph recall : r > -0.50 , P : < 0.03 ) . Poor beta cell function correlated with improvement for all carbohydrates in visuomotor task performance but not on an attention task . CONCLUSIONS Glucose regulation was associated with cognitive performance in elderly subjects with normal glucose tolerance . Dietary carbohydrates ( potatoes and barley ) enhanced cognition in subjects with poor memories or beta cell function independently of plasma glucose BACKGROUND Low-carbohydrate diets are often used to promote weight loss , but their effects on psychological function are largely unknown . OBJECT Output:	MAIN RESULTS There is no suitable RCT of any form of carbohydrates involving independent-living older adults with normal cognition or mild cognitive impairment . AUTHORS ' CONCLUSIONS There are no suitable RCTs on which to base any recommendations about the use of any form of carbohydrate for enhancing cognitive performance in older adults with normal cognition or mild cognitive impairment .
MS21098	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To examine the effect of treatment-induced weight loss on Health-Related Quality of Life ( HRQL ) , 38 mildly-to-moderately overweight persons recruited to participate in a study to examine the efficacy of a lifestyle modification treatment program completed a sociodemographic question naire , the Beck Depression Inventory ( BDI ) , the Medical Outcomes Study Short-Form Health Survey ( SF-36 , as an assessment of HRQL ) , and underwent a series of clinical evaluations prior to treatment . After baseline evaluations , participants were r and omly assigned to either a program of lifestyle physical activity or a program of traditional aerobic activity . Participants again completed the SF-36 and BDI after the 13-week treatment program had ended . Weight loss averaged 8.6 ± 2.8 kg over the 13-week study . We found that weight loss was associated with significantly higher scores ( enhanced HRQL ) , relative to baseline , on the physical functioning , role-physical , general health , vitality and mental health domains of the SF-36 . The largest improvements were with respect to the vitality , general health perception and role-physical domains . There were no significant differences between the lifestyle and aerobic activity groups on any of the study measures . These data indicate that , at least in the short-term , weight loss appears to profoundly enhance HRQL OBJECTIVE : To reveal whether baseline body mass index ( BMI ) , and psychobehavioral and nutritional markers were significant predictors of the change in BMI observed after 4 and 12 months in obese women enrolled in a weight reduction program , including low-energy diet , increased physical activity , cognitive behavior therapy and sibutramine . The impact of changes in psychobehavioral and nutritional markers observed after 4 and 12 months of treatment on BMI changes was also investigated . DESIGN : During a double-blind placebo-controlled 4-month period , subjects received either sibutramine ( 10 mg/day ) or placebo . Then , an open phase with sibutramine administered to all patients continued until month 12.SUBJECTS : In total , 80 obese women ( age : 43.9±10.6 y , BMI : 36.7±4.8 kg/m2 ) . MEASUREMENTS : The dependent variable was change in BMI while baseline BMI , mode of treatment , the Beck depression score , the three items ( dietary restraint , disinhibition and perceived hunger ) of the Eating Inventory ( EI ) , energy and macronutrient intakes were independent variables . At 1-week dietary records were analyzed using a computer software for assessing energy and macronutrient intake . RESULTS : Multiple regression analysis revealed that the BMI loss at month 4 was significantly influenced by mode of treatment and initial BMI , whereas a borderline negative relationship was observed with the baseline restraint score . Baseline BMI , depression score , restraint score and total energy intake predicted weight loss at month 12 . These predictive variables accounted for 43.8 % of the variance in BMI loss at 12 months . When relationships between the BMI loss and changes in all included psychobehavioral and nutritional parameters were considered after 12 months of treatment , a drop in the disinhibition score of the EI appeared the only significant factor affecting the BMI decrease . CONCLUSIONS : Our results suggest that psychobehavioral and nutritional characteristics can be used as predictors of weight loss in response to a comprehensive weight management program including pharmacological treatment with sibutramine BACKGROUND Some investigators fear that dieting may precipitate binge eating and other adverse behavioral consequences . OBJECTIVE The objective of the study was to examine whether dieting would elicit binge eating and mood disturbance in individuals free of these complications before treatment . DESIGN A total of 123 obese women were r and omly assigned to 1 ) a 1000 kcal/d diet that included 4 servings/d of a liquid meal replacement ( MR ) ; 2 ) a 1200 - 1500 kcal/d balanced deficit diet ( BDD ) of conventional foods ; or 3 ) a nondieting ( ND ) approach that discouraged energy restriction . All women attended weekly group sessions for 20 wk and biweekly sessions from week 20 to week 40 . RESULTS At week 20 , participants in the MR , BDD , and ND groups lost 12.1 + /- 6.7 % , 7.8 + /- 6.0 % , and 0.1 + /- 2.4 % of initial weight , respectively ( P < 0.001 ) . During the first 20 wk , there were no significant differences among groups in the number of persons who had objective binge episodes or in reports of hunger or dietary disinhibition . Symptoms of depression decreased significantly more ( P < 0.001 ) in the MR and BDD groups than in ND participants . At week 28 , significantly more ( P < 0.003 ) cases of binge eating were observed in MR participants than in the 2 other groups . No differences , however , were observed between groups at weeks 40 or 65 ( a follow-up visit ) . At no time did any participant meet criteria for binge-eating disorder . CONCLUSION Concerns about possible adverse behavioral consequences of dieting should not dissuade primary care providers from recommending modest energy restriction to obese individuals BACKGROUND Low-carbohydrate diets are often used to promote weight loss , but their effects on psychological function are largely unknown . OBJECTIVE We compared the effects of a low-carbohydrate , high-fat ( LCHF ) diet with a conventional high-carbohydrate , low-fat ( HCLF ) diet on mood and cognitive function . DESIGN Ninety-three overweight or obese participants [ x + /- SEM age : 50.2 + /- 0.8 y ; body mass index ( in kg/m2 ) : 33.6 + /- 0.4 ] were r and omly assigned to an energy-restricted ( approximately 6 - 7 MJ , 30 % deficit ) , planned isocaloric LCHF diet or an HCLF diet for 8 wk . Body weight and psychological well-being were measured by using the Profile of Mood States , Beck Depression Inventory , and Spielberger State Anxiety Inventory instruments at baseline and fortnightly . Cognitive functioning ( working memory and speed of processing ) was assessed at baseline and week 8 . RESULTS The LCHF diet result ed in significantly greater weight loss than did the HCLF diet ( 7.8 + /- 0.4 and 6.4 + /- 0.4 kg , respectively ; P = 0.04 ) . Both groups showed improvements in psychological well-being ( P < 0.01 for time ) , with the greatest effect occurring during the first 2 wk , but there was no significant difference between groups . There were no significant between-group differences in working memory ( P = 0.68 ) , but there was a significant time x diet interaction for speed of processing ( P = 0.04 ) , so that this measure improved less in the LCHF than in the HCLF diet group . CONCLUSIONS Both dietary patterns significantly reduced body weight and were associated with improvements in mood . There was some evidence for a smaller improvement in cognitive functioning with the LCHF diet with respect to speed of processing , but further studies are required to determine the replicability of this finding BACKGROUND The impact of a 6-month lifestyle change intervention on cardiovascular risk factors in obese , sedentary , postmenopausal women was examined . A secondary aim of this investigation was to determine whether the addition of self-control skills training to an empirically supported lifestyle change intervention would result in greater cardiovascular risk reduction . METHODS Forty-four women were r and omly assigned to receive either a lifestyle change or a lifestyle change with self-control skills intervention . Pretreatment and posttreatment weight loss , body composition , physical activity , cardiorespiratory fitness , diet , blood pressure ( BP ) , blood lipids , and psychosocial functioning were assessed . Also , at 1-year posttreatment , weight loss , body composition , self-reported physical activity , and psychosocial functioning were assessed . RESULTS The women significantly increased their physical activity ( + 39.6 % ) and cardiorespiratory fitness ( + 13.5 % ) and reduced their body weight ( -6.5 % ) , fat mass ( -7.4 % ) , body fat ( -2.4 % ) , BP ( SBP -6.2 % , DBP -9.2 % ) , total cholesterol ( -7.4 % ) , triglycerides ( -16.5 % ) , and low-density lipoprotein ( LDL ) cholesterol ( 9.1 % ) and improved their diet ( p < 0.05 ) . At the 1-year follow-up , women had regained approximately 63 % of their posttreatment weight loss ( p < 0.05 ) , but had maintained their previous increases in physical activity . Additionally , there were no significant changes in fat free mass , body fat , anxiety , or depression between the end of treatment and 1-year posttreatment . The addition of self-control skills training did not significantly improve cardiovascular risk reduction . CONCLUSIONS Lifestyle change interventions may be an effective means for reducing cardiovascular risk in obese , sedentary , postmenopausal women . However , greater attention should be devoted to the maintenance of these positive lifestyle changes Objective : To compare the effects of aerobic and resistance exercise on weight , muscle strength , cardiovascular fitness , blood pressure and mood in obese women who were not on an energy-restricted diet . Design : R and omized , prospect i ve , controlled trial . Setting : Department of Physical Medicine and Rehabilitation , University Hospital . Subjects : Sixty obese women were assigned to one of three groups : aerobic exercise ( n=20 ) , resistance exercise ( n=20 ) and control group ( n=20 ) . Interventions : The aerobic exercise group performed both walking and leg cycle exercise with increasing duration and frequency . The resistance exercise group performed progressive weight-resistance exercises for the upper and lower body . Main outcome measures : Before and after a 12-week period , all subjects were evaluated by anthropometric measurement , rating of mood , cardiorespiratory capacity and maximum strength of trained muscles . Results : After a 12-week training period , subjects in the resistance group showed significant improvement in one-repetition maximum test of hip abductors ( 7.95±3.58 kg ) , quadriceps ( 14±7.18 kg ) , biceps ( 3.37± 2.84 kg ) and pectorals ( 8.75±5.09 kg ) compared with those in the control group ( P<0.001 ) . VO2 max increased ( 0.51±0.40 ) and Beck Depression Scale scores decreased ( -5.40±4.27 ) in the aerobic exercise group compared with the control group , significantly ( P<0.001 ) . Only in hip abductor muscle strength was there a significant increase in the resistance exercise group compared with the aerobic exercise group ( P < 0.05 ) . Conclusion : Both aerobic exercise and resistance exercise result ed in improved performance and exercise capacity in obese women . While aerobic exercise appeared to be beneficial with regard to improving depressive symptoms and maximum oxygen consumption , resistance exercise was beneficial in increasing muscle strength OBJECTIVE To investigate childhood to adulthood weight change associated with anxiety and depression . DESIGN The Children in the Community Study . A prospect i ve longitudinal investigation . SETTING Albany and Saratoga Counties , New York . PARTICIPANTS Eight hundred twenty individuals ( 403 females and 417 males ) assessed at 4 time points : in 1983 when they were 9 to 18 years old ( n = 776 ) , in 1985 to 1986 when they were 11 to 22 years old ( n = 775 ) , in 1991 to 1994 when they were 17 to 28 years old ( n = 776 ) , and in 2001 to 2003 when they were 28 to 40 years old ( n = 661 ) . MAIN EXPOSURES Anxiety disorders and depression assessed by structured diagnostic interview . MAIN OUTCOME MEASURES Centers for Disease Control and Prevention body mass index z score ( BMI z ) , a measure of weight status ; and association of anxiety and depression with BMI z level and annual change . RESULTS In females , anxiety disorders were associated with higher weight status , a BMI z of 0.13 ( 95 % confidence interval , 0.01 - 0.25 ) units higher compared with females without anxiety disorders . Female depression was associated with a gain in BMI z of 0.09 units/y ( 95 % confidence interval , 0.03 - 0.15 units/y ) , modified by the age when depression was first observed , such that early depression onset was associated with a higher subsequent BMI z than depression onset at older ages . In males , childhood depression was associated with a lower BMI z ( -0.46 ; 95 % confidence interval , -0.93 to 0.02 units lower at the age of 9 years ) , but BMI z trajectories for males with or without depression converged in adulthood ; male anxiety disorders were not substantively associated with weight status . CONCLUSIONS Anxiety disorders and depression were associated with a higher BMI z in females , whereas these disorders in males were not associated with a higher BMI z. These results , if causal and confirmed in other prospect i ve studies , support treating female anxiety and depression as part of comprehensive obesity prevention efforts Objective Very-low-calorie diets have been shown to produce dramatic improvements in glycemic control in obese subjects with non-insulin-dependent ( type II ) diabetes . There have been no studies Output:	Results : R and om effects models found that lifestyle modification was superior to control and non-dieting interventions for reducing symptoms of depression , and marginally better than dietary counseling and exercise-alone programs . Exercise-alone programs were superior to controls . No differences were found for comparisons of pharmacologic agents and placebos . Within-group analyses found significant reductions in symptoms of depression for nearly all active interventions . A meta-regression found no relationship between changes in weight and changes in symptoms of depression in lifestyle modification interventions . Conclusions : On average , obese individuals in weight loss trials experienced reductions in symptoms of depression .
MS21099	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Recently , a novel allelic variant of cytochrome P450 2C19 encoding ultrarapid enzyme activity was described ( denoted CYP2C19 * 17 ) . The objective of this study was to evaluate the impact of CYP2C19 * 17 on serum concentration of escitalopram in psychiatric patients . One hundred and sixty‐six patients treated with escitalopram were divided into the following subgroups according to CYP2C19 genotype : CYP2C19 * 17/17 ( n=7 ) , CYP2C19 1/17 ( n=43 ) , CYP2C19 1/1 ( n=60 ) , CYP2C19 17/def ( n=16 ) , CYP2C19 * 1/def ( n=34 ) , and CYP2C19def/def ( n=6 ) ( def = defective allele , i.e. , CYP2C19 * 2 or * 3 ) . Dose‐adjusted serum concentrations of escitalopram were compared using the CYP2C19 * 1/1 subgroup as reference . Geometric mean of the escitalopram serum concentration was 42 % lower in patients homozygous for CYP2C19 17 ( P<0.01 ) and 5.7‐fold higher in subjects homozygous for defective CYP2C19 alleles ( P<0.001 ) . Of the heterozygous subgroups , only CYP2C19 * 1/def was significantly different from CYP2C19 * 1/1 ( P<0.001 ) . In conclusion , a homozygous CYP2C19 17 genotype is associated with lower serum concentration of escitalopram , which might imply increased risk of therapeutic failure In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite , N-desmethylescitalopram . We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP , a clinical pharmacogenomic trial . Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer ( i.e. IM/PM genotypic category ) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers ( EMs ) ( p = 0.004 ) . Older age was also associated with higher concentrations of escitalopram . Covarying for CYP2D6 and age , we found those homozygous for the CYP2C19 * 17 allele associated with ultrarapid metabolizer ( UM ) phenotype had a significantly lower mean escitalopram concentration ( 2-fold , p = 0.0001 ) and a higher mean metabolic ratio ( p = 0.0003 ) than EMs , while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs ( 1.55-fold , p = 0.008 ) . There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration ( p = 0.0003 ; p = 0.0012 Bonferroni corrected ) . In conclusion , we have demonstrated an association between CYP2C19 genotype , including the CYP2C19 * 17 allele , and steady state escitalopram concentration Sixty-nine depressive patients ( DSM III criteria : 296.2 , 296.3 , 296.5 , 300.4 ) were treated with 40 to 60 mg citalopram ( CIT ) daily for 4 weeks . Among them , 45 responded to treatment ( improvement > 50 % on the 21-item Hamilton Rating Scale for Depression [ HAM-D ] ) and continued their treatment for another week before being released from the study . The 24 nonresponders were r and omized and comedicated under double-blind conditions with lithium carbonate ( Li ) ( 2 x 400 mg/day ) ( CIT-Li group ) or with placebo ( CIT-Pl group ) from days 29 to 35 . For days 36 to 42 , the patients of both subgroups were treated openly with Li ( 800 mg/day ) in addition to the ongoing CIT treatment . On day 35 , 6 of 10 patients responded to the CIT-Li combination , whereas 2 of 14 patients only responded to the CIT-Pl combination . This group difference reached significance ( p < 0.05 ) on day 35 with lower HAM-D total scores in the CIT-Li group . No evidence was seen of a pharmacokinetic interaction between CIT and Li , and this combination was well tolerated . Patients were phenotyped with dextromethorphan and mephenytoin at baseline and at day 28 . As evaluated at baseline , three patients ( responders ) were poor metabolizers of dextromethorphan and six patients ( three responders and three nonresponders ) of mephenytoin . On day 28 , the ratio CIT/N-desmethylCIT ( DCIT ) in plasma was significantly higher in poor than in extensive metabolizers of mephenytoin ( p = 0.0001 ) , and there was a significant positive correlation between the metabolic ratio of dextromethorphan and the ratio DCIT/N-didesmethylCIT in plasma ( p < 0.001 ) . These findings illustrate the role of CYP2D6 and CYP2C19 in the metabolism of CIT . It can be concluded that Li addition to CIT is effective in patients not responding to CIT alone without any evidence of an accentuation or provocation of adverse events Background Citalopram is a selective serotonin reuptake inhibitor ( SSRI ) mainly prescribed to treat major depression . Objective The aim of this study was to compare the pharmacokinetic characteristics of a new and a br and ed citalopram 20 mg formulation to support the marketing authorization of the test formulation in China . Methods A single-dose , open-label , r and omized-sequence , two-period crossover design was used in this study . Healthy Chinese male cytochrome P450 ( CYP ) 2C19 extensive metabolizers , aged 18–40 years , were eligible to participate . CYP2C19 poor metabolizers were excluded , based on genotyping of genomic DNA from blood sample s. Twenty-four subjects were r and omly assigned to receive the test formulation followed by the reference formulation , and then vice versa . A 2-week washout occurred between study periods . Blood sample s were collected for up to 144 h post-dose . Quantification was carried out using a vali date d high-performance liquid chromatography-t and em mass spectrometry ( HPLC-MS/MS ) method . Pharmacokinetic parameters were calculated and analysed statistically . The two formulations were considered pharmacokinetically equivalent if the 90 % confidence intervals ( CIs ) of the log-transformed ratios ( test/reference ) of the maximum plasma concentration ( Cmax ) , area under the plasma concentration-time curve from time zero to the last measurable concentration ( AUClast ) , and area under the plasma concentration-time curve from time zero to infinity ( AUC∞ ) were within the predetermined acceptance range ( 70–143 % for Cmax ; 80–125 % for AUClast and AUC∞ ) according to China State Food and Drug Administration bioequivalence guidelines . Tolerability was monitored by clinical assessment , vital signs , laboratory analysis and interviews with participants about adverse events . Results A total of 24 participants , with a mean ( SD ) age of 26 ( 3 ) years ( range 22–32 years ) , body weight of 65.2 ( 5.0 ) kg ( range 53–73 kg ) , and height of 172.7 ( 4.9 ) cm ( range 159–182 cm ) , were enrolled in this study . Both formulations showed similar pharmacokinetic profiles . Mean ( SD ) AUClast , AUC∞ and Cmax were 1436 ( 341 ) ng · h/mL , 1595 ( 381 ) ng · h/mL and 32.3 ( 5.9 ) ng/mL , respectively , for the test formulation , and 1444 ( 388 ) ng · h/mL , 1648 ( 504 ) ng · h/mL , 33.1 ( 7.4 ) ng/mL , respectively , for the reference formulation . Median ( range ) time to reach Cmax ( tmax ) was 2 ( 1–12 ) hours ( test ) and 3 ( 1–6 ) hours ( reference ) . The 90 % CIs of the treatment ratios for the ln-transformed values of Cmax , AUClast and AUC∞ were 92.5–103.6 , 95.2–100.6 and 96.4–105.4 , respectively . No significant difference was found between treatments with regard to pharmacokinetic parameters . Fifteen adverse events were reported during the study but none were considered serious . Conclusion This single-dose study found that the test and reference citalopram 20 mg tablets met the regulatory criteria for assuming bioequivalence in the selected healthy Chinese male subjects . Both formulations were well tolerated A single oral dose of omeprazole ( 20 mg ) was given orally to 160 healthy Caucasian Swedish subjects and tested as a probe for CYP2C19 . The study was nonr and omized and included seven subjects previously classified as poor metabolizers ( PM ) of S-mephenytoin . The ratio between the plasma concentrations of omeprazole and hydroxyomeprazole ( metabolic ratio ; MR ) was determined by HPLC in a blood sample drawn 3 h after drug intake . In 17 subjects the test was repeated and the MRs of omeprazole on the two occasions were correlated ( rs = 0.85 ; p < 0.0001 ) . There was a significant correlation between the MR of omeprazole and the S/R mephenytoin ratio among 141 subjects , in whom both ratios were determined ( rs = 0.63 , p < 0.001 ) . All seven PMs of S-mephenytoin had higher MRs of omeprazole ( 7.1 - 23.8 ) than extensive metabolizers ( EM ) ( 0.1 - 4.9 ) . All 160 subjects and another 15 Caucasian Swedish PMs previously phenotyped with mephenytoin were analysed with respect to the presence of the CYP2C19m1 allele by PCR amplification of the intron 4/exon 5 junction followed by Sma I digestion . EMs heterozygous for the CYP2C19m1 gene had MRs of omeprazole and S/R ratios of mephenytoin that were higher than those of subjects who were homozygous for the wild-type allele ( p = 0.0001 ) . Nineteen of the 22 PMs were homozygous for the CYP2C19m1 gene . Three were heterozygous for this allele . Thus , 41 of the 44 alleles ( 93 % ) of PMs were defective CYP2C19m1 . One of the remaining three PM alleles was subsequently found to contain the CYP2C19m2 mutation , which has earlier been shown to be associated with the PM phenotype in Oriental population s. In conclusion , the phenotype determined by omeprazole correlated with that of mephenytoin , and was in good agreement with the genotype We investigate the impact of sex and genotype on citalopram disposition in 35 healthy volunteers who received an oral dose of 20 mg citalopram within a single-dose bioequivalence study . CYP2C19 * 2 and * 3 , and CYP2D6 * 4 mutations were determined by Real-Time PCR . The influence of sex and genotype was analyzed by a linear mixed model for repeated measures , including formulation , period , sequence , sex , CYP2C19 and CYP2D6 as fixed effects and subject nested sequencesexCYP2C19CYP2D6 as the r and om one . Pharmacokinetic parameters were log-transformed and AUC(infinity ) and C(max ) adjusted to the administered dose/weight . The model yields a statistical significance in AUC(infinity ) and CL/F for CYP2C19 and CYP2D6 . Gender , formulation , sequence or period effects were not statistically significant . AUC(infinity ) of CYP2C19 1/2 and CYP2C19 2/2 carriers is 44 % and 118 % higher than wild type , respectively ; CYP2D6 volunteers carrying 1/4 have an AUC 23 % higher than wild type . Our data also suggest that the influence of CYP2D6 on AUC(infinity ) is very low when it is in association with CYP2C19 1/1 while its influence is more apparent in association with CYP2C19 1/*2 . In conclusion , we demonstrate the influence of CYP2C19 and CYP2D6 in the disposition of citalopram , and we suggest Output:	In contrast , the exposure to (es)citalopram decreased by 36 % ( 95 % CI 27–46 , p < 0.0001 ) in the UM/UM ( CYP2C19 * 17/17 ) and by 14 % ( 95 % CI 1–27 , p < 0.05 ) in the UM/EM (CYP2C19 17/1).InterpretationThis is the first meta- analysis based on a systematic review of accumulated information that addresses the relationship between CYP2C19 genotypes and the exposure to citalopram or escitalopram . All functional CYP2C19 genotype groups demonstrated significant effects on (es)citalopram exposure . The findings based on our pooled analysis are likely to help in underst and ing the inter-individual variability in the exposure to citalopram and escitalopram in psychiatric patients and to facilitate dose selection , particularly for the homozygous carriers of CYP2C19 2 or * 3 ( loss of function ) and CYP2C19 * 17 ( gain of function ) alleles .

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