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1,000 | 30,087,091 | This review is of importance given how technology has transformed delivery of conventional therapies . | BACKGROUND Traditional psychological therapies focus mainly on modification of individuals ' conscious decision-making process .
Unconscious processes , such as cognitive biases , have been found accountable for various psychiatric psychopathologies , and advances in technologies have transformed how bias modification programs are being delivered .
OBJECTIVE The primary aim of this review is to synthesize evidence of Web-based cognitive bias modification intervention for bias reduction .
The secondary aim is to determine the change in symptoms for individual psychiatric disorders following bias modification . | 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 = 2.49 ; p = .02 ; CI = 1.13 - 5.48 ) . CONCLUSION Web-based ABM training is ineffective in fostering cognitive bias reduction and continued smoking abstinence . However , the positive effects in heavy smokers-as indicated by exploratory sub sample analyses-warrant further research into the potential of multiple sessions ABM training to foster continued smoking abstinence in heavy smokers who make a quit-attempt . ( PsycINFO Data base BACKGROUND AND OBJECTIVES The biased interpretation of ambiguous social situations is considered a maintaining factor of Social Anxiety Disorder ( SAD ) . Studies on the modification of interpretation bias have shown promising results in laboratory setting s. The present study aims at pilot-testing an Internet-based training that targets interpretation and judgmental bias . METHOD Thirty-nine individuals meeting diagnostic criteria for SAD participated in an 8-week , unguided program . Participants were presented with ambiguous social situations , were asked to choose between neutral , positive , and negative interpretations , and were required to evaluate costs of potential negative outcomes . Participants received elaborate automated feedback on their interpretations and judgments . RESULTS There was a pre-to-post-reduction of the targeted cognitive processing biases ( d = 0.57 - 0.77 ) and of social anxiety symptoms ( d = 0.87 ) . Furthermore , results showed changes in depression and general psychopathology ( d = 0.47 - 0.75 ) . Decreases in cognitive biases and symptom changes did not correlate . The results held stable accounting for drop-outs ( 26 % ) and over a 6-week follow-up period . Forty-five percent of the completer sample showed clinical significant change and almost half of the participants ( 48 % ) no longer met diagnostic criteria for SAD . LIMITATIONS As the study lacks a control group , results lend only preliminary support to the efficacy of the intervention . Furthermore , the mechanism of change remained unclear . CONCLUSION First results promise a beneficial effect of the program for SAD patients . The treatment proved to be feasible and acceptable . Future research should evaluate the intervention in a r and omized-controlled setting BACKGROUND AND OBJECTIVES This two-year follow-up study evaluated the long-term outcomes of two early interventions that aim ed at reducing social and test anxiety in young adolescents at risk for developing social anxiety disorder . METHODS In this RCT , moderately socially anxious adolescents ( N=240 , mean age 13.6 years ) were r and omly assigned to a 10-week internet-based multifaceted cognitive bias modification training ( CBM ) , a 10-week school-based cognitive behavioral group training ( CBT ) , or a no-intervention control condition . Using multiple imputation , this study examined the changes in primary and secondary outcome measures from pretest to follow-up in a repeated measures design . RESULTS Primary outcome : Self-reported social and test anxiety generally decreased from pre-test to two-year follow-up , regardless of treatment condition . The percentage of adolescents who developed a social anxiety disorder was very low ( 6 % ) and similar across conditions . Secondary outcome : There were beneficial changes in self-esteem , self-reported prosocial behaviors , and fear of negative evaluation , but none of these were related to treatment condition . Automatic social-threat associations did not significantly change . The CBM intervention was effective in changing interpretative bias as indexed by the Recognition Task but this long-term effect did not transfer to the Adolescent Interpretation and Belief Question naire . LIMITATIONS There was a substantial ( 50 % ) though seemingly non-selective attrition at follow-up . CONCLUSIONS This RCT does not support the longer-term efficacy of school-based CBT or CBM as an early intervention for social and test anxiety . Rather , it emphasizes the positive ' natural ' course of highly socially anxious adolescents over two years BACKGROUND AND OBJECTIVES Cognitive Bias Modification to reduce threat interpretations ( CBM-I ) trains individuals to resolve ambiguous scenarios via completion of word fragments that assign benign meanings to scenarios . The current study tested : 1 ) whether Internet-based CBM-I can shift interpretations to be more positive/less negative , and 2 ) whether varying the number of letters missing in the word fragments ( assumed to increase task difficulty ) moderates CBM-I 's effects . METHODS Participants ( N = 350 ) completed a brief online version of CBM-I , followed by assessment s of interpretation bias , fear of negative evaluation , and anticipatory anxiety . Participants were r and omly assigned to 1 of 5 conditions : control ( half of scenarios ended positively , half negatively ) , or 4 positive conditions ( all scenarios ended positively , but word fragments varied on number of letters missing , from 0 to 3 ) . RESULTS Relative to the control condition , all positive conditions led to more positive/less negative interpretations . When analyses were re-run with only a highly socially anxious subset of the sample ( n = 100 ) , conditions in which the final word of scenarios was missing 0 , 1 , or 2 letters led to more positive/less negative interpretations compared to the control condition , but the condition missing 3 letters did not differ from the control condition . There were no differences between conditions on other outcome measures . LIMITATIONS Training was brief , and an unselected sample was used . CONCLUSIONS Results suggest a brief Internet-based CBM-I paradigm can shift interpretation bias , but not necessarily other anxiety-relevant outcomes . Making the task too difficult may blunt effects for highly socially anxious individuals Following successful outcomes of cognitive bias modification ( CBM ) programs for alcoholism in clinical and community sample s , the present study investigated whether different varieties of CBM ( attention control training and approach-bias re-training ) could be delivered successfully in a fully automated web-based way and whether these interventions would help self-selected problem drinkers to reduce their drinking . Participants were recruited through online advertising , which result ed in 697 interested participants , of whom 615 were screened in . Of the 314 who initiated training , 136 completed a pretest , four sessions of computerized training and a posttest . Participants were r and omly assigned to one of four experimental conditions ( attention control or one of three varieties of approach-bias re-training ) or a sham-training control condition . The general pattern of findings was that participants in all conditions ( including participants in the control-training condition ) reduced their drinking . It is suggested that integrating CBM with online cognitive and motivational interventions could improve results BACKGROUND AND OBJECTIVES Dual-process models posit that addictive behaviors are characterized by strong automatic processes that can be assessed with implicit measures . The present study investigated the potential of a cognitive bias modification paradigm , the Approach-Avoidance Task ( AAT ) , for retraining automatic behavioral tendencies in cigarette smoking . METHODS The study was set up as an online intervention . After completing an online survey , 257 smokers were r and omly allocated either to one of two experimental conditions ( AAT ) or a waitlist control group . Participants responded to different pictures by pushing or pulling the computer mouse , depending on the format of the picture . Pictures in portrait format depicted smoking-related items and were associated with pushing , pictures in l and scape format depicted neutral items and were associated with pulling . One version of the AAT provided individual feedback after each trial whereas the st and ard version did not . After four weeks , participants were re-assessed in an online survey . RESULTS Analyses revealed that the st and ard AAT , in particular , led to a significant reduction in cigarette consumption , cigarette dependence , and compulsive drive ; no effect was found in the control group . LIMITATIONS Interpretability of the study is constrained by the fact that no active control condition was applied . CONCLUSIONS Notwithst and ing the limitations , our findings indicate that the AAT might be a feasible instrument to reduce tobacco dependence and can be applied as an online intervention . Future studies should investigate whether the effects of behavior therapy can be augmented when combined with retraining interventions BACKGROUND Relapse is common in alcohol-dependent individuals and can be triggered by alcohol-related cues in the environment . It has been suggested that these individuals develop cognitive biases , in which cues automatically capture attention and elicit an approach action tendency that promotes alcohol seeking . The study aim was to examine whether cognitive bias modification ( CBM ) training targeting approach bias could be delivered during residential alcohol detoxification and improve treatment outcomes . METHODS Using a 2-group parallel-block ( ratio 1:1 ) r and omized controlled trial with allocation concealed to the outcome assessor , 83 alcohol-dependent in patients received either 4 sessions of CBM training where participants were implicitly trained to make avoidance movements in response to pictures of alcoholic beverages and approach movements in response to pictures of nonalcoholic beverages , or 4 sessions of sham training ( controls ) delivered over 4 consecutive days during the 7-day detoxification program . The primary outcome measure was continuous abstinence at 2 weeks postdischarge . Secondary outcomes included time to relapse , frequency and quantity of alcohol consumption , and craving . Outcomes were assessed in a telephonic follow-up interview . RESULTS Seventy-one ( 85 % ) participants were successfully followed up , of whom 61 completed all 4 training sessions . With an intention-to-treat approach , there was a trend for higher abstinence rates in the CBM group relative to controls ( 69 vs. 47 % , p = 0.07 ) ; however , a per- protocol analysis revealed significantly higher abstinence rates among participants completing 4 sessions of CBM relative to controls ( 75 vs. 45 % , p = 0.02 ) . Craving score , time to relapse , mean drinking days , and mean st and ard drinks per drinking day did not differ significantly between the groups . CONCLUSIONS This is the first trial demonstrating the feasibility of CBM delivered during alcohol detoxification and supports earlier research suggesting it may be a useful , low-cost adjunctive treatment to improve treatment outcomes for alcohol-dependent patients |
1,001 | 30,834,514 | Anti-inflammatory agents improved antidepressant treatment effects . | BACKGROUND No study has gathered evidence from all r and omized clinical trials ( RCTs ) with anti-inflammatory drugs measuring antidepressant effects including a detailed assessment of side-effects and bias . | 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 ( MDD ) , though patients suffering from severe MDD remain unstudied in this respect . The aim of the present study was therefore to investigate , in a r and omized double-blind clinical trial , the influence of adjuvant atorvastatin on symptoms of depression in patients with MDD . METHODS A total of 60 patients suffering from MDD ( mean age : 32.25 years ; 53 % males ) received a st and ard medication of 40 mg/d citalopram . Next , patients were r and omly assigned either to the atorvastatin group ( 20 mg/d ) or to the placebo group . Blood lipid values were assessed at baseline and on completion of the study 12 weeks later . Experts rated depressive symptoms via Hamilton Depression Rating Scales ( HDRS ) at baseline and 3 , 6 and 12 weeks later . RESULTS HDRS scores decreased over time ; the significant Time by Group interaction showed that symptoms of depression decreased more in the atorvastatin than in the placebo group . Compared to the placebo group , in the atorvastatin group cholesterol , triglyceride , and Low Density Lipids ( LDL ) significantly decreased , and High Density Lipids ( HDL ) significantly increased over time . HDRS scores and blood lipid values were generally not associated . CONCLUSIONS The pattern of results suggests that adjuvant atorvastatin favorably influences symptoms of depression among patients with severe MDD . Given that after 12 weeks of monotherapy and adjuvant atorvastatin patients were still moderately to severely depressed , more powerful treatment algorithms such as augmentation and change of medication are highly recommended BACKGROUND Elevated levels of C-reactive protein , even in the absence of hyperlipidemia , are associated with an increased risk of coronary events . Statin therapy reduces the level of C-reactive protein independently of its effect on lipid levels . We hypothesized that statins might prevent coronary events in persons with elevated C-reactive protein levels who did not have overt hyperlipidemia . METHODS The level of C-reactive protein was measured at base line and after one year in 5742 participants in a five-year r and omized trial of lovastatin for the primary prevention of acute coronary events . RESULTS The rates of coronary events increased significantly with increases in the base-line levels of C-reactive protein . Lovastatin therapy reduced the C-reactive protein level by 14.8 percent ( P<0.001 ) , an effect not explained by lovastatin-induced changes in the lipid profile . As expected , lovastatin was effective in preventing coronary events in participants whose base-line ratio of total cholesterol to high-density lipoprotein ( HDL ) cholesterol was higher than the median ratio , regardless of the level of C-reactive protein ( number needed to treat for five years to prevent 1 event , 47 ; P=0.005 ) . However , lovastatin was also effective among those with a ratio of total to HDL cholesterol that was lower than the median and a C-reactive protein level higher than the median ( number needed to treat , 43 ; P=0.02 ) . In contrast , lovastatin was ineffective among participants with a ratio of total to HDL cholesterol and a C-reactive protein level that were both lower than the median ( number needed to treat , 983 ; P=0.80 ) . CONCLUSIONS Statin therapy may be effective in the primary prevention of coronary events among subjects with relatively low lipid levels but with elevated levels of C-reactive protein CONTEXT Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse , and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants . OBJECTIVES To determine whether inhibition of the inflammatory cytokine tumor necrosis factor ( TNF ) reduces depressive symptoms in patients with treatment-resistant depression and whether an increase in baseline plasma inflammatory biomarkers , including high-sensitivity C-reactive protein ( hs-CRP ) , TNF , and its soluble receptors , predicts treatment response . DESIGN Double-blind , placebo-controlled , r and omized clinical trial . SETTING Outpatient infusion center at Emory University in Atlanta , Georgia . PARTICIPANTS A total of 60 medically stable out patients with major depression who were either on a consistent antidepressant regimen ( n = 37 ) or medication-free ( n = 23 ) for 4 weeks or more and who were moderately resistant to treatment as determined by the Massachusetts General Hospital Staging method . INTERVENTIONS Three infusions of the TNF antagonist infliximab ( 5 mg/kg ) ( n = 30 ) or placebo ( n = 30 ) at baseline and weeks 2 and 6 of a 12-week trial . MAIN OUTCOME MEASURES The 17-item Hamilton Scale for Depression ( HAM-D ) scores . RESULTS No overall difference in change of HAM-D scores between treatment groups across time was found . However , there was a significant interaction between treatment , time , and log baseline hs-CRP concentration ( P = .01 ) , with change in HAM-D scores ( baseline to week 12 ) favoring infliximab-treated patients at a baseline hs-CRP concentration greater than 5 mg/L and favoring placebo-treated patients at a baseline hs-CRP concentration of 5 mg/L or less . Exploratory analyses focusing on patients with a baseline hs-CRP concentration greater than 5 mg/L revealed a treatment response ( ≥50 % reduction in HAM-D score at any point during treatment ) of 62 % ( 8 of 13 patients ) in infliximab-treated patients vs 33 % ( 3 of 9 patients ) in placebo-treated patients ( P = .19 ) . Baseline concentrations of TNF and its soluble receptors were significantly higher in infliximab-treated responders vs nonresponders ( P < .05 ) , and infliximab-treated responders exhibited significantly greater decreases in hs-CRP from baseline to week 12 compared with placebo-treated responders ( P < .01 ) . Dropouts and adverse events were limited and did not differ between groups . CONCLUSIONS This proof-of-concept study suggests that TNF antagonism does not have generalized efficacy in treatment-resistant depression but may improve depressive symptoms in patients with high baseline inflammatory biomarkers . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00463580 Patients with the HIV infection are at high risk for developing depression . The aim of this study was to investigate the safety and efficacy of antidepressant effects of minocycline on HIV patients with depression . Forty-six HIV patients , with mild-to-moderate depression and a Hamilton Depression Rating Scale ( HDRS ) up to 18 , participated in a parallel , r and omized , double-blind , placebo-controlled trial and underwent 6 weeks of treatment with either minocycline ( 100 mg twice daily ) or placebo in the same manner . Patients were assessed using HDRS at baseline and at weeks 3 and 6 . The primary outcome measure was to evaluate the efficacy of minocycline in improving depressive symptoms . General linear model repeated measures showed significant effect for time × treatment interaction on the HDRS score during the trial course [ F(2 , 88)=7.50 , P=0.001 ] . There was no significant difference between the two groups regarding adverse events . No serious adverse event was reported . The administration of 100 mg minocycline twice daily seems to be safe and effective in improving depressive symptoms in HIV/AIDS patients with mild-to-moderate depression OBJECTIVE Major depressive disorder has been linked with inflammatory processes , but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial . The authors tested the hypothesis that C-reactive protein ( CRP ) , a commonly available marker of systemic inflammation , predicts differential response to escitalopram ( a serotonin reuptake inhibitor ) and nortriptyline ( a norepinephrine reuptake inhibitor ) . METHOD The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression ( GENDEP ) study , a multicenter open-label r and omized clinical trial . CRP was measured with a high-sensitivity method in serum sample s from 241 adult men and women with major depressive disorder r and omly allocated to 12-week treatment with escitalopram ( N=115 ) or nortriptyline ( N=126 ) . The primary outcome measure was the score on the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , administered weekly . RESULTS CRP level at baseline differentially predicted treatment outcome with the two antidepressants ( CRP-drug interaction : β=3.27 , 95 % CI=1.65 , 4.89 ) . For patients with low levels of CRP ( < 1 mg/L ) , improvement on the MADRS score was 3 points higher with escitalopram than with nortriptyline . For patients with higher CRP levels , improvement on the MADRS score was 3 points higher with nortriptyline than with escitalopram . CRP and its interaction with medication explained more than 10 % of individual-level variance in treatment outcome . CONCLUSIONS An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice WHAT IS KNOWN AND OBJECTIVE Depression is a debilitating complication of brucellosis and how best to treat this is a matter of debate . Inflammatory processes are involved in the pathogenesis of both brucellosis and depression . Therefore , we hypothesized that celecoxib could be beneficial for the treatment of depression due to brucellosis . METHODS Forty out patients with depression due to brucellosis with a Hamilton Depression Rating Scale score ( HDRS ) < 19 participated in a r and omized , double-blind , placebo-controlled trial and underwent 8 weeks of treatment with either celecoxib ( 200 mg bid ) or placebo as an adjunctive to antibiotic therapy . Patients were evaluated using HDRS at baseline and weeks 4 and 8 . RESULT AND DISCUSSION Repeated- measures analysis demonstrated significant effect for time × treatment interaction on the HDRS score [ F ( 1·43 , 57·41 ) = 37·22 , P < 0·001 ] . Significantly greater response to treatment occurred in the celecoxib group than in the placebo group at the study end [ 10 patients ( 50 % ) vs. no patient ( 0 % ) , respectively , P < 0·001 ] . No serious adverse event was observed . WHAT IS NEW AND CONCLUSION Celecoxib is a safe and effective treatment for depression due to brucellosis when compared with placebo BACKGROUND It has been proposed that the mechanism of the antidepressant effect of celecoxib is linked to its anti-inflammatory action and particularly its inhibitory effect on pro-inflammatory cytokines ( e.g. interleukin-6(IL-6 ) ) . We measured changes in serum IL-6 concentrations and depressive symptoms following administration of celecoxib in patients with major depressive disorder ( MDD ) . METHODS In a r and omized double-blind placebo-controlled study , 40 patients with MDD and Hamilton Depression Rating Scale-17 items ( Ham-D ) score ≥18 were r and omly assigned to either celecoxib ( 200 mg twice daily ) or placebo in addition to sertraline ( 200mg/day ) for 6 weeks . Outcome measures were serum IL-6 concentrations at baseline and week 6 , and Ham-D scores at baseline and weeks 1 , 2 , 4 , and 6 . RESULTS The celecoxib group showed significantly greater reduction in serum IL-6 concentrations ( mean difference (95%CI)=0.42(0.30 to 0.55 ) pg/ml , t(35)=6.727 , P<0.001 ) as well as Ham-D scores ( mean difference (95%CI)=3.35(1.08 to 5.61 ) , t(38)=2.99 , P=0.005 ) than the placebo group . The patients in the celecoxib group experienced more response ( 95 % ) and remission ( 35 % ) than the placebo group ( 50 % and 5 % , P=0.003 and 0.04 respectively ) . Baseline serum IL-6 levels were significantly correlated with baseline Ham-D scores ( r=0.378 , P=0.016 ) . Significant correlation was observed between reduction of Ham-D scores and reduction of serum IL-6 levels at week 6 ( r=0.673 , P<0.001 ) . LIMITATIONS We did not measure other inflammatory biomarkers . CONCLUSIONS We showed that the antidepressant activity of celecoxib might be linked to its capability of reducing IL-6 concentrations . Moreover , supporting previous studies we showed that celecoxib is both safe and effective as an adjunctive antidepressant ( Registration number : I RCT 138903124090N1 ) BACKGROUND Several lines of evidence suggest that inflammatory mechanisms may be involved in the severity and progression of depression . One pathway implicated is the production of prostagl and ins via the enzyme cyclooxygenase ( COX ) . Although late-life depression in particular has been associated with inflammation , we know of no published studies using COX inhibitors , such as nonsteroidal anti-inflammatory drugs ( NSAIDs ) , in the treatment of depressive syndromes in this population . OBJECTIVE To evaluate the effect of the NSAIDs celecoxib and naproxen on depressive symptoms in older adults . METHODS The Alzheimer 's Disease Anti-inflammatory Prevention Trial was a r and omized , placebo-controlled , double-masked clinical trial conducted at six U.S. memory clinics . Cognitively normal volunteers age 70 and older with a family history of Alzheimer-like dementia were r and omly assigned to receive celecoxib 200 mg twice daily , naproxen sodium 220 mg twice daily , or placebo . The 30-item version of the Geriatric Depression Scale ( GDS ) was administered to all participants at enrollment and at yearly follow-up visits . Participants with a GDS score greater than 5 at baseline were classified as depressed . RESULTS Of 2,528 participants enrolled , 2,312 returned for at least one follow-up visit . Approximately one-fifth had significant depressive symptoms at baseline . Mean GDS score , and the percentage with significant depressive symptoms , remained similar over time across all three treatment groups . Furthermore , there was no treatment effect on GDS scores over time in the subgroup of participants with significant depressive symptoms at baseline . In longitudinal analysis using generalized estimating equations ( GEE ) regression , higher baseline GDS scores , a prior psychiatric history , older age , time in the study , and lower cognition interacting with time , but not treatment assignment , were associated with significantly higher GDS scores over time . CONCLUSION Treatment with celecoxib or naproxen did not improve depressive symptoms over time compared with placebo . While inflammation has been implicated in late-life depression , these results do not support the hypothesis that inhibition of the COX pathway with these NSAIDs at these doses alleviates depressive symptoms in older adults OBJECTIVES : We evaluated the effects of adalimumab maintenance therapy on health-related quality of life ( HRQOL ) in patients with moderate to severe Crohn 's disease . METHODS : In a Phase III , r and omized , double-blind clinical trial ( CHARM ) of moderate to severe Crohn 's disease patients , HRQOL outcomes were compared between the adalimumab maintenance treatment groups ( every other week and weekly injection ) and the adalimumab induction-only group . The Zung Self-Rating Depression Scale , functional assessment of chronic illness therapy (FACIT)-Fatigue , visual analog pain scales , Inflammatory Bowel Disease question naire ( IBDQ ) , and Medical Outcomes Study 36-item Short Form Health Survey ( SF-36 ) were analyzed for 499 r and omized responders ( a decrease of ≥70 points from baseline in the Crohn 's Disease Activity Index [ CDAI ] ) at baseline and weeks 4 , 12 , 26 , and 56 . RESULTS : CHARM patients ' HRQOL was substantially impaired at baseline . Following a 4-week adalimumab induction therapy , patients experienced statistically significant improvements in all HRQOL measures ( P < 0.0001 ) . Compared with patients who were assigned to placebo after induction therapy , patients who continued adalimumab at 40 mg every other week maintenance therapy reported less depression ( P < 0.01 ) , fewer fatigue symptoms ( P < 0.001 ) , greater improvements in the IBDQ ( P < 0.05 ) , greater SF-36 physical component summary scores ( P < 0.05 ) , and less abdominal pain ( P < 0.05 ) from weeks 12 to 56 . They also had greater SF-36 mental component summary scores at week 56 ( P < 0.05 ) . Patients who continued adalimumab at 40-mg weekly maintenance therapy reported less depression and fewer fatigue symptoms at week 56 , greater improvement in IBDQ , and less abdominal pain from weeks 12 to 56 ( all P < 0.05 vs. placebo ) . CONCLUSIONS : Adalimumab maintenance therapy provided sustained improvements in HRQOL for patients with moderate to severe Crohn 's disease through week 56 BACKGROUND Antidepressant medication efficacy remains a major research challenge . Here , we explored four questions : whether noradrenergic antidepressants are more effective than serotonergic antidepressants ; whether the addition of 100 mg acetylsalicylic acid ( ASA ) changes antidepressant efficacy ; whether the long-term efficacy differs depending on the antidepressant and the addition of ASA ; and whether serum levels of brain-derived neurotrophic factor ( BDNF ) are clinical ly informative . SUBJECTS AND METHODS In a two-year study , forty people with major depressive disorder were r and omly assigned to groups that received an SSRI ( escitalopram ) or an SNRI ( duloxetine ) , each group received concomitant ASA ( 100 mg ) or a placebo . Sociodemographic data were recorded and patients under went regular assessment s with the Hamilton depression scale ( HDS ) and clinical global impression ( CGI ) scale . Serum levels of BDNF were measured four times per year . RESULTS There was no significant difference in efficacy between the two antidepressants or between antidepressant treatment with and without ASA . However , subgroup comparisons revealed that the duloxetine + ASA ( DASA ) subgroup showed a more rapid improvement in HDS score as early as 2 months ( t=-3.114 , p=0.01 ) , in CGI score at 5 months ( t=-2.119 , p=0.05 ) , and a better remission rate ( χ2=6.296 , p 0.012 ) than the escitalopram + placebo ( EP ) subgroup . Serum BDNF before treatment was also higher in the DASA subgroup than in the EP subgroup ( t=3.713 ; p=0.002 ) . CONCLUSION This suggest two hypotheses : either a noradrenergic agent combined with ASA is more effective in treating depression than a serotonergic agent alone , or the level of serum BDNF before treatment is a precursor marker of the response to antidepressants . Further research is needed to test these hypotheses BACKGROUND Hidradenitis suppurativa ( HS ) is a chronic , recurrent , inflammatory skin disease with frequent comorbidities of pain and depression . Adalimumab treatment for 16 weeks improved HS lesions significantly versus placebo ( NCT00918255 ) . OBJECTIVE The relationship between pain and depressive symptoms and the effects of adalimumab on each was examined in this post hoc analysis . METHODS Patients with moderate to severe HS ( N=154 ) were r and omized 1:1:1 to adalimumab 40 mg weekly ( ew ) , adalimumab 40 mg every other week ( eow ) , or placebo . Skin pain was assessed using a visual analog scale ( VAS ; 0 - 100 mm ) . Depressive symptoms were assessed using the 9-item Patient Health Question naire ( PHQ-9 ; score ≥10 indicative of depression ) . RESULTS At baseline , overall mean±SD pain VAS was 54.3±26.5 mm and 41.8 % of patients had PHQ-9 scores ≥10 . At baseline , VAS pain scores ( mean±SD ) were significantly higher ( P<0.001 ) for patients with PHQ-9 scores ≥10 ( 63.9±23.3 ) versus < 10 ( 47.4±26.7 ) . At Week 16 , clinical ly relevant pain reduction was observed for ew-treated patients with baseline PHQ-9 score ≥10 ( ew , 45.8 % ; eow , 29.4 % ; placebo , 23.8 % ) and < 10 ( ew , 50.0 % ; eow , 37.9 % ; placebo , 29.6 % ) , but did not reach statistical significance . In patients with high baseline pain ( ≥median VAS score ) , adalimumab ew significantly decreased depressivesymptoms versus placebo ( PHQ-9 scores , -34.03 % vs + 2.26 % ; P<0.01 ) . CONCLUSION Patients with moderate to severe HS had a high degree of pain and depressive symptoms at baseline . Adalimumabtherapy was associated with decreased pain and depressive symptoms compared to baseline Background : The pathophysiology of depression is associated with the hyperactivity of immune inflammatory responses . Cyclooxygenase‐2 inhibitors such as celecoxib reduce the production of pro‐inflammatory cytokines . The purpose of the present investigation was to assess the efficacy of celecoxib as an adjuvant agent in the treatment of major depression in a six‐week double blind and placebo controlled trial . Methods : Forty adult out patients who met the DSM‐IV‐TR criteria for major depression participated in the trial . Patients have a baseline Hamilton Rating Scale for Depression score of at least 18 . Patients were allocated in a r and om fashion : 20 to fluoxetine 40 mg/day plus celecoxib 400 mg/day ( 200 mg bid ) ( morning and evening ) and 20 to fluoxetine 40 mg/day plus placebo . Patients were assessed by a psychiatrist at baseline and after 1 , 2 , 4 , and 6 weeks after the medication started . Results : Although both protocol s significantly decreased the score of Hamilton Rating Scale for Depression over the trial period , the combination of fluoxetine and celecoxib showed a significant superiority over fluoxetine alone in the treatment of symptoms of major depression . There were no significant differences in the two groups in terms of observed side effects . Conclusion : The results of this study suggest that celecoxib may be an effective adjuvant agent in the management of patients with major depression and anti‐inflammatory therapies should be further investigated . Depression and Anxiety , 2009 . © 2009 Wiley‐Liss , BACKGROUND Anxiety , depression , and impaired health-related quality of life ( HRQoL ) are common in patients with psoriasis . OBJECTIVE We sought to analyze the effect of ustekinumab on these conditions in patients with moderate-to-severe psoriasis . METHODS Patients with moderate-to-severe psoriasis ( n = 1230 ) were r and omized 1:1:1 to receive 45 mg of ustekinumab , 90 mg of ustekinumab , or placebo . The Hospital Anxiety and Depression Scale was used to measure anxiety and depression , and the Dermatology Life Quality Index to measure HRQoL. RESULTS At baseline , 40.3 % and 26.7 % of patients reported symptoms of anxiety and depression , respectively , and 54.6 % reported Dermatology Life Quality Index scores greater than 10 , indicating a very high impact of disease on HRQoL. Greater improvements at week 12 in mean Hospital Anxiety and Depression Scale-Anxiety ( 13.9 % ) , Hospital Anxiety and Depression Scale-Depression ( 29.3 % ) , and Dermatology Life Quality Index ( 76.2 % ) scores were reported in ustekinumab groups compared with placebo ( P < .001 each ) . LIMITATIONS Results for these measures are reported only through 24 weeks . CONCLUSION Patients receiving ustekinumab reported significant improvements in symptoms of anxiety , depression , and BACKGROUND Approximately 25 % of patients admitted to a hospital as a result of depression are actually suffering from psychotic depression . Psychotic symptoms can be present in patients with either unipolar depression or bipolar depression and can be difficult to treat . It was reported the second-generation tetracycline may exert potential antidepressant effects through its robust neuroprotective activities , which include neurogenesis , antioxidation , and anti-glutamate excitotoxicity , and may direct regulation of pro-inflammatory agents . METHODS This was a 6-week , open-label study to evaluate the efficacy and safety of minocycline in combination with antidepressants in adult in patients ( n=25 ) diagnosed with major depression with psychotic features ( psychotic depression ) according to DSM-IV-TR . The primary endpoint was the change from baseline in the Hamilton Depression Rating Scale ( HAM-D-21 ) score from baseline to week 6 . Secondary endpoints were changes in the Brief Psychiatric Rating Scale ( BPRS ) and the Clinical Global Impression ( CGI ) Scale scores from baseline to week 6 . Spontaneously reported adverse events were recorded . RESULTS The patients ' average age was 46.9±10.2 years . Minocyline ( 150 mg/day ) in combination with antidepressants ( fulvoxamine , paroxetine , and sertraline ) provided significant improvement in depression . Mean ( ± SD ) HAM-D-21 was reduced to 6.7±1.9 at week 6 from a baseline value of 40.4±2.5 . Significant improvement of psychotic symptoms ( mean±SD ) was indicated by the decrease in BPRS scores from baseline ( 63.3±8.7 ) to week 6 ( 4.6±2.4 ) . No serious adverse events occurred . CONCLUSIONS These preliminary data suggest that minocycline in combination with antidepressants is effective and well tolerated in the treatment of unipolar psychotic depression . Further studies using larger , double-blind , parallel-group design are warranted to confirm these findings OBJECTIVES To test for simvastatin-induced changes in affect and affective processes in elderly volunteers . DESIGN R and omized , clinical trial . SETTING The Geriatric Behavioral Psychopharmacology Laboratory at the University of Pennsylvania . PARTICIPANTS Eighty older volunteers , average age 70 , with high normal/mildly elevated serum cholesterol . INTERVENTION Simvastatin up to 20 mg/d or placebo for 15 weeks . MEASUREMENTS Daily diary records of positive and negative affects and of events and biweekly measures of depressive symptoms . Affect ratings were obtained using the Lawton positive and negative affect scales ; independent raters coded the valences of events . RESULTS Thirty-one of 39 subjects assigned to placebo and 33 of 41 receiving simvastatin completed the study . During biweekly assessment s , four subjects on simvastatin and one on placebo experienced depressive symptoms , as manifest by Center for Epidemiological Studies Depression scale scores greater than 16 ( exact P=.36 ) . Diary data demonstrated significant effects on affective processes . For positive affect , there was a significant medication-by-time interaction that reflected decreases in positive affect in subjects receiving simvastatin , greatest in those patients whose final total cholesterol levels were below 148 mg/dL. For negative affect , there were significant medication-by-event , and medication-by-event-by-time interactions , reflecting a time-limited increase in the apparent effect of negative events . CONCLUSION Simvastatin has statistically significant effects on affect and affective processes in elderly volunteers . The decrease in positive affect may be significant clinical ly and relevant to the quality of life of many patients Objectives : To compare the effects of etanercept ( ETN ) 50 mg once weekly plus methotrexate ( MTX ) versus MTX alone on patient-reported outcomes ( PROs ) and the relationship between remission and PRO improvement . Methods : In this double-blind , r and omised clinical trial ( COMET ) , PROs included : the Health Assessment Question naire ( HAQ ) , EuroQoL health status , fatigue and pain visual analogue scales , Hospital Anxiety and Depression Scale , and Medical Outcomes Short-Form-36 . Mean changes from baseline were analysed by analysis of covariance using the last observation carried forward method . Results from week 52 are presented . Results : Most PROs demonstrated significantly greater improvements with ETN+MTX than MTX alone , including physical functioning , pain , fatigue and overall health status . A significantly greater improvement in HAQ score was observed in the ETN+MTX than the MTX group ( −1.02 vs −0.72 ; p<0.001 ) and a greater proportion reached the minimal clinical ly important difference of 0.22 ( 88 % vs 78 % ; p<0.006 ) . The relationship between PRO score and clinical status indicated that improvement was greatest among patients achieving remission . Conclusions : Early treatment with ETN+MTX leads to significantly greater improvements in multiple dimensions of PROs than MTX alone . The close relationship between disease activity and PRO improvement suggests that early treatment , with remission as a goal , should maximise the chance of restoring normal functioning and Epidemiological and clinical studies have suggested that powerful cholesterol lowering may have adverse effects on mood and psychological well-being . Inhibition of cholesterol bio synthesis by simvastatin ( a hydroxymethyl glutaryl coenzyme A reductase inhibitor ) may also reduce steroid hormone bio synthesis . To explore if mood changes are related with steroid hormone levels , we design ed a r and omized double-blind placebo-controlled crossover trial . The separate and combined effects of a Mediterranean-type diet intervention and treatment with simvastatin 20 mg/day PO for 12 weeks were studied in 120 hypercholesterolemic but otherwise healthy middle-aged men . Psychological functioning was assessed with question naires , and steroid hormone levels in blood were assayed radioimmunologically before and after the treatments . Simvastatin result ed in a statistically significant increase of depression and somatization without changes in the anxiety , hostility or aggression scores . Mood changes seemed to be unrelated with the statistically significant but clinical ly insignificant decline in serum testosterone levels and unrelated with the increase in serum dehydroepi and rosterone levels BACKGROUND There is controversial evidence that a low serum cholesterol level is associated with an increased risk of depression , suicide , and violence . The aim of this study was to identify or exclude any small or infrequent adverse effect of long-term reduction of serum cholesterol with pravastatin sodium on psychological well-being . METHODS The study population consisted of 1130 respondents from a representative sample of 1222 patients with stable coronary artery disease participating in the Long-term Intervention with Pravastatin in Ischaemic Disease ( LIPID ) study . Subjects were r and omized in a double-blind manner to treatment with pravastatin sodium , 40 mg/d ( n = 559 ) , or placebo ( n = 571 ) for at least 4 years . Psychological well-being was assessed with a st and ard self-administered question naire at baseline and after 6 months , 1 year , 2 years , and 4 years . The question naire assessed anxiety and depression , anger , impulsiveness , alcohol consumption , and adverse life events . RESULTS Serum cholesterol levels decreased by an average of 1.3 mmol/L ( 50 mg/dL ) with pravastatin therapy and did not change with placebo . During follow-up there was no significant difference by treatment group in measures of anxiety and depression , anger expression , or impulsiveness ( 95 % confidence interval excluded differences of > 0.2 SD ) and no difference in the proportion of subjects with excessive alcohol consumption or adverse life events ( odds ratio , 1.0 ; 95 % confidence interval , 0.8 - 1.2 ) . There was no evidence of a treatment effect for persons whose baseline serum cholesterol level was in the lowest 10 % ( < 4.6 mmol/L [ 178 mg/dL ] ) or whose scores for anxiety and depression , anger , or impulsiveness were in the highest 10 % at baseline . There was no association between change in the serum cholesterol level and measures of anxiety and depression , anger , or impulsiveness during follow-up . CONCLUSION Long-term reduction of serum cholesterol with pravastatin has no adverse effect on psychological well-being OBJECTIVE The primary objective of this investigation was to examine the acute antidepressant effects of intravenous hydrocortisone and ovine corticotropin releasing hormone ( CRH ) infusions in patients with major depression . METHOD Twenty-two patients who met DSM-III-R criteria for nonpsychotic major depression were r and omly assigned to receive intravenously 1 mg/kg of ovine CRH , 15 mg of hydrocortisone , or saline under double-blind conditions on day 1 . St and ard depression rating scales were completed on day 1 before the study medications were administered and again the following day ( day 2 ) . RESULTS Patients treated with hydrocortisone demonstrated a significantly greater reduction in total 21-item Hamilton Depression Rating Scale scores ( mean reduction=8.4 points or 37 % ) than patients given ovine CRH ( mean=1.2 points ) or placebo ( mean=1.3 points ) . CONCLUSIONS Acute hydrocortisone infusion is associated with a rapid and robust reduction in depressive symptoms . The authors discuss the therapeutic implication s of these findings OBJECTIVE Advanced cancer patients frequently experience debilitating symptoms that occur in clusters , but few pharmacological studies have targeted symptom clusters . Our objective was to examine the effects of dexamethasone on symptom clusters in patients with advanced cancer . METHODS We review ed the data from a previous r and omized clinical trial to determine the effects of dexamethasone on cancer symptoms . Symptom clusters were identified according to baseline symptoms by using principal component analysis . Correlations and change in the severity of symptom clusters were analyzed after study treatment . RESULTS A total of 114 participants were included in this study . Three clusters were identified : fatigue/anorexia-cachexia/depression ( FAD ) , sleep/anxiety/drowsiness ( SAD ) , and pain/dyspnea ( PD ) . Changes in severity of FAD and PD significantly correlated over time ( at baseline , day 8 , and day 15 ) . The FAD cluster was associated with significant improvement in severity at day 8 and day 15 , whereas no significant change was observed with the SAD cluster or PD cluster after dexamethasone treatment . CONCLUSION The results of this preliminary study suggest significant correlation over time and improvement in the FAD cluster at day 8 and day 15 after treatment with dexamethasone . These findings suggest that fatigue , anorexia-cachexia , and depression may share a common pathophysiologic basis . Further studies are needed to investigate this cluster and target anti-inflammatory therapies OBJECTIVES Current therapeutic approaches to fibromyalgia syndrome ( FMS ) do not provide satisfactory pain control to a high percentage of patients . This unmet need constantly fuels the pursuit for new modalities for pain relief . This r and omised , double-blind , controlled study assessed the efficacy and safety of adding etoricoxib vs. placebo to the current therapeutic regimen of female patients with FMS . METHODS In this double-blind , placebo-controlled study , female patients were r and omised to receive either 90 mg etoricoxib once daily or placebo for 6 weeks . Several physical and mental parameters were assessed throughout the study . The primary end-point was the response to treatment , defined as ≥ 30 % reduction in the average Brief Pain Inventory score . Secondary outcomes were changes in the Fibromyalgia Impact Question naire , SF-36 Quality of Life assessment question naire and Hamilton rating scales for anxiety and depression . RESULTS Overall , 73 patients were recruited . Although many outcome measures improved throughout the study , no difference was recorded between the etoricoxib- and placebo-treated groups . The Brief Pain Inventory , Fibromyalgia Impact Question naire , The Hamilton Anxiety and Depression scores did not differ between the two groups . CONCLUSIONS This is the first r and omised , double-blind study assessing the effect of adding etoricoxib to pre-existing medications for female patients with FMS . Although being mildly underpowered this study clearly has shown that etoricoxib did not improve pain scores and did not lead to any beneficial mental or physical effects IMPORTANCE Mood disorders frequently co-occur with medical diseases that involve inflammatory pathophysiologic mechanisms . Immune responses can affect the brain and might increase the risk of mood disorders , but longitudinal studies of comorbidity are lacking . OBJECTIVE To estimate the effect of autoimmune diseases and infections on the risk of developing mood disorders . DESIGN Nationwide , population -based , prospect i ve cohort study with 78 million person-years of follow-up . Data were analyzed with survival analysis techniques and adjusted for calendar year , age , and sex . SETTING Individual data drawn from Danish longitudinal registers . PARTICIPANTS A total of 3.56 million people born between 1945 and 1996 were followed up from January 1 , 1977 , through December 31 , 2010 , with 91 , 637 people having hospital contacts for mood disorders . MAIN OUTCOMES AND MEASURES The risk of a first lifetime diagnosis of mood disorder assigned by a psychiatrist in a hospital , outpatient clinic , or emergency department setting . Incidence rate ratios ( IRRs ) and accompanying 95 % CIs are used as measures of relative risk . RESULTS A prior hospital contact because of autoimmune disease increased the risk of a subsequent mood disorder diagnosis by 45 % ( IRR , 1.45 ; 95 % CI , 1.39 - 1.52 ) . Any history of hospitalization for infection increased the risk of later mood disorders by 62 % ( IRR , 1.62 ; 95 % CI , 1.60 - 1.64 ) . The 2 risk factors interacted in synergy and increased the risk of subsequent mood disorders even further ( IRR , 2.35 ; 95 % CI , 2.25 - 2.46 ) . The number of infections and autoimmune diseases increased the risk of mood disorders in a dose-response relationship . Approximately one-third ( 32 % ) of the participants diagnosed as having a mood disorder had a previous hospital contact because of an infection , whereas 5 % had a previous hospital contact because of an autoimmune disease . CONCLUSIONS AND RELEVANCE Autoimmune diseases and infections are risk factors for subsequent mood disorder diagnosis . These associations seem compatible with an immunologic hypothesis for the development of mood disorders in subgroups of patients Signs of an inflammatory process , in particular increased pro-inflammatory cytokines and increased levels of prostagl and ine E2 ( PGE2 ) , have repeatedly been described in major depression ( MD ) . As cyclooxygenase-2 ( COX-2 ) inhibitors inhibit the PGE2 production and the production of pro-inflammatory cytokines , we performed a therapeutic trial with the COX-2 inhibitor celecoxib . In a prospect i ve , double-blind , add-on study , 40 patients suffering from an acute depressive episode were r and omly assigned to either reboxetine and celecoxib or to reboxetine plus placebo . After a wash-out period , 20 patients received 4–10 mg reboxetine plus placebo and 20 received reboxetine plus 400 mg celecoxib for 6 weeks . The treatment effect was calculated by analysis of variance . There were no significant differences between groups in age , sex , duration or severity of disease or psychopathology , or reboxetine dose or plasma levels . Over 6 weeks , both groups of patients showed significant improvement in scores of the Hamilton Depression Scale . However , the celecoxib group showed significantly greater improvement compared to the reboxetine-alone group . Additional treatment with celecoxib has significant positive effects on the therapeutic action of reboxetine with regard to depressive symptomatology . Moreover , the fact that treatment with an anti-inflammatory drug showed beneficial effects on MD indicates that inflammation is related to the pathomechanism of the disorder , although the exact mechanisms remain to become eluci date Abstract Introduction : Concerns about the effects of HMG-CoA reductase inhibitors ( ‘ statins ’ ) on health-related quality of life may contribute to their underuse in older adults with and at risk for cardiovascular disease . These concerns also may prevent clinicians from enrolling older patients in clinical trials assessing the efficacy of statins as a preventive therapy for Alzheimer ’s disease . Objective : To determine the effects of pravastatin and tocopherol ( vitamin E ) , alone and in combination , on health-related quality of life in older adults . Study design : Double-blind , r and omised , placebo-controlled , crossover study . Participants : Forty-one community-dwelling men and women aged ≥70 years with low-density lipoprotein-cholesterol ( LDL-C ) ≥3.62 mmol/L ( 140 mg/dl ) participated . Methods : Subjects received pravastatin for 6 months then pravastatin plus tocopherol for an additional 6 months ( group 1 ) , or tocopherol for 6 months then pravastatin plus tocopherol for an additional 6 months ( group 2 ) . Dosages were pravastatin 20 mg daily and tocopherol 400IU daily . Main outcome measures : The following health-related quality -of-life measures were assessed at baseline , after 6 months and after 1 year : health perception , depression , physical function , cognitive function and sleep behaviour . In addition , data on adverse effects and laboratory abnormalities were obtained . Results : Pravastatin reduced levels of total cholesterol ( −21 % , p < 0.001 ) and LDL-C ( −29 % , p < 0.001 ) . Health-related quality -of-life scores , physical adverse effects , muscle enzyme levels and liver function tests did not change after 12 months of therapy with pravastatin , tocopherol or their combination . Conclusion : Both pravastatin and tocopherol have a good safety profile , are well tolerated and do not adversely affect health-related quality of life in older patients with hypercholesterolaemia . Given the significant beneficial cardiovascular effects of statin therapy in older adults and the potential role of statins in prevention of Alzheimer ’s disease , concerns about adverse effects on quality of life should not deter use of these medications in this population Statins have been shown to decrease depressive symptoms in certain groups of patients , an effect that is mostly attributed to their anti-inflammatory and neurotransmitter modulatory potentials . We aim ed to investigate the antidepressant effects of simvastatin as an adjuvant therapy in patients with moderate to severe depression . In this double-blind placebo-controlled clinical trial , 48 patients were r and omly allocated to receive simvastatin or placebo as an adjunct to fluoxetine for six weeks . Patients were evaluated with the Hamilton Depression Rating Scale ( HDRS ) at baseline and weeks 2 , 4 and 6 . Probable clinical and laboratory adverse events were also monitored and compared between the two groups . Simvastatin-treated patients experienced significantly more reductions in HDRS scores compared to the placebo group by the end of the trial ( p=0.02 ) . Early improvement and response rates were significantly greater in the simvastatin group than the placebo group ( p=0.02 and p=0.01 , respectively ) but remission rate was not significantly different between the two groups ( p=0.36 ) . No serious adverse event was reported during this trial . In conclusion , simvastatin seems to be a safe and effective adjuvant therapy for patients suffering from major depressive disorder . However , more confirmatory studies are warranted Background : Depression is a common comorbidity in psoriasis , and both conditions are associated with systemic inflammation . The efficacy of ixekizumab , a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A , was evaluated in patients with moderate-to-severe plaque psoriasis ( psoriasis ) and depressive symptoms that were at least moderately severe . Methods : Data were integrated from 3 r and omized , double-blind , controlled phase 3 trials . At baseline and week 12 , depressive symptoms and inflammation were assessed by the 16-item Quick Inventory of Depressive Symptomology - Self-Report ( QIDS-SR16 ) and by a high-sensitivity assay of serum C-reactive protein ( hsCRP ) , respectively . A subgroup of patients with at least moderately severe depressive symptoms at baseline ( QIDS-SR16 total score ≥11 ) was analyzed . Improvement in psoriasis was assessed by the Psoriasis Area and Severity Index ( PASI ) . Results : Approximately 10 % of the overall psoriasis population had at least moderately severe depressive symptoms at baseline . At week 12 , comorbid patients treated with ixekizumab had significantly greater improvements in their QIDS-SR16 total score ( ixekizumab 80 mg every 2 weeks [ Q2W ] , -7.1 ; ixekizumab 80 mg every 4 weeks [ Q4W ] , -6.1 ) vs. placebo ( -3.4 ) ( p < 0.001 , both comparisons ) and higher rates of remission of depressive symptoms ( ixekizumab Q2W , 45.2 % ; ixekizumab Q4W , 33.6 % ) vs. placebo ( 17.8 % ) ( p ≤ 0.01 , both comparisons ) . Patients treated with ixekizumab also had significant reductions in hsCRP and PASI compared to placebo . Etanercept treatment was not associated with significant improvements in depressive symptoms compared to placebo . Conclusions : In this comorbid population , 12 weeks of ixekizumab therapy result ed in remission of depression for approximately 40 % of patients and improved systemic inflammation as indicated by hsCRP BACKGROUND S There are contradictory evidence about the effect of statins on depression . This 6-week-r and omized placebo-controlled clinical trial assessed the efficacy and safety of lovastatin as an adjuvant agent for treating major depressive disorder ( MDD ) . METHODS The participants were 68 patients with MDD according to DSM-IV diagnostic criteria . The sample was r and omly allocated into fluoxetine ( up to 40 mg/day ) plus lovastatin ( 30 mg/day ) group or fluoxetine plus placebo group . Hamilton Depression Rating scale was used to measure depression score at baseline , week 2 , and week 6 . RESULTS Both groups showed a significant decrease of depression score on the Hamilton Depression scale . However , the treatment group decreased depression score more than placebo group [ 12.8(6.3 ) vs. 8.2(4.0 ) , t = 3.4 , df = 60 , P < .001 ] . Any serious adverse effect was not found . DISCUSSION These results suggest that lovastatin as an adjuvant treatment may be effective for treating patients with MDD OBJECTIVE To determine the effect of lovastatin therapy on health-related quality of life in older persons . DESIGN A prospect i ve , r and omized , double blind clinical trial . SETTING Four university medical center research clinics . PARTICIPANTS There were 431 men and women , primarily 65 years of age or older , with low density lipoprotein levels greater than 159 mg/dL and less than 221 mg/dL. Exclusion criteria included a Mini-Mental state score less than 24 or presence of recent cardiovascular events or other serious chronic disease likely to shorten survival . INTERVENTION All participants were administered the National Cholesterol Education Program step one diet and were then r and omized to placebo , 20 mg lovastatin , or 40 mg lovastatin . MEASUREMENTS Areas of health-related quality of life assessed in the Cholesterol Reduction in Seniors Program ( CRISP ) included : ( 1 ) physical functioning , ( 2 ) sleep behavior , ( 3 ) social support , ( 4 ) depression , ( 5 ) cognitive function , and ( 6 ) health perception . Three global change questions asked the patients to judge change in general health since starting the study diet or the study medication and change in ability to function or care for self . Although some patients were followed for a total of 12 months , all participants were followed for 6 months , and 6-month data have been used for the primary analysis in this paper . RESULTS Patients treated with 20 mg of lovastatin had a 17 % and 24 % reduction in total cholesterol and LDL-cholesterol , respectively . Patients treated with the 40-mg lovastatin dose achieved reductions of 20 % for total cholesterol and 28 % for LDL-cholesterol . Complaints of possible adverse events were remarkably similar in the two active treatment groups and the placebo group . At 6 months of follow-up there were no statistically significant differences found in mean change scores from baseline between treatment groups on the health-related quality of life measures ( physical functioning , sleep , social support , depression , cognitive function scales , health perception ) or global questions . CONCLUSIONS This study demonstrates that lovastatin was extremely well tolerated in an older cohort , both with regard to symptoms and to health-related quality of life BACKGROUND Studies have demonstrated the success of augmentation of antidepressant therapy with nonsteroidal anti-inflammatory drugs ( NSAID ) in decreasing depressive symptoms ; however , little is known about the benefit of NSAID therapy on depressive symptoms . METHODS This study pooled data from 5 postapproval trials , each trial a 6-week , multicenter , r and omized , double-blinded , placebo-controlled , active-comparator , parallel-group study in subjects with active osteoarthritis . Subjects were r and omized to placebo group , ibuprofen 800 mg 3 times daily or naproxen 500 mg twice daily group , or Celebrex 200 mg daily group . Apart from different ethnicities enrolled , these trials had identical study design s. Depression was assessed using the Patient Health Question naire-9 ( PHQ-9 ) . Outcomes measured were change in PHQ-9 score after 6 weeks of NSAID therapy and change in classification of depression with a PHQ-9 score ≥10 as a marker of depression . RESULTS There were 1497 patients included . Median PHQ-9 score was similar in all 3 groups at baseline and after 6 weeks of treatment . Multivariable regression analysis demonstrated a detectable effect in lowering PHQ-9 score in the ibuprofen or naproxen group ( -0.31 ) and Celebrex group ( -0.61 ) ( P = .0390 ) . With respect to the change in classification of depression , logistic regression analysis demonstrated a trend towards significant treatment effect of all NSAIDs compared with placebo . CONCLUSION Our analysis of pooled data from 5 postapproval trials shows that NSAID usage demonstrates a trend towards reduction of depression symptoms in patients with osteoarthritis based upon PHQ-9 scores . Future clinical trials should investigate this association with maximum dosage of drugs , increased treatment duration , and monitoring of social and environmental changes BACKGROUND Psoriasis is associated with health-related quality -of-life impairment and depression . OBJECTIVE We sought to determine the effect of adalimumab on depression symptoms in patients with psoriasis . METHODS Patients with moderate to severe psoriasis in a r and omized , placebo-controlled , double-blind clinical trial were assessed for depression symptoms at baseline and week 12 or early termination ( ET ) using the Zung Self-rating Depression Scale ( ZDS ) . The effects of adalimumab ( 40 mg every other week ) versus placebo on ZDS score at week 12/ET were assessed using analysis of covariance . Relationships between ZDS and the Psoriasis Area and Severity Index ( PASI ) , the Dermatology Life Quality Index , and the Short Form 36 Health Survey were assessed using Pearson correlations . Changes in ZDS score were compared for patients with and without a 75 % or greater reduction in baseline PASI score . RESULTS Compared with the placebo group ( n = 52 ) , the adalimumab group ( n = 44 ) experienced an additional 6-point reduction in ZDS score ( 95 % confidence interval : 2.5 - 9.5 ; P < .001 ) by week 12/ET . Depression improvement was correlated with improvement in PASI ( r = 0.5 ; P < .0001 ) and Dermatology Life Quality Index ( r = 0.5 ; P < .0001 ) . Greater ZDS score improvement was observed at week 12/ET in responders with a 75 % or greater reduction in baseline PASI score than in nonresponders ( 10.6 [ SD = 9.4 ] vs 1.4 [ SD = 9.6 ] ; P < .001 ) . LIMITATIONS This analysis can not distinguish whether adalimumab has a direct or indirect effect on depression . CONCLUSIONS Adalimumab treatment reduced psoriasis symptoms , reduced depression symptoms , and improved health-related quality of life in patients with moderate to severe psoriasis |
1,002 | 30,941,976 | 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 . | PURPOSE To evaluate the effects of radical prostatectomy ( RP ) and conservative treatment ( CT ) on the survival of localized prostate cancer by conducting a systematic review and meta- analysis . | 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 hazards models . We compared results from the benchmark trial with results from models with observational data by use of traditional multivariable survival analysis , propensity score adjustment , and instrumental variable analysis . RESULTS Prostate cancer patients receiving conservative management were more likely to be older , nonwhite , and single and to have more advanced disease than patients receiving radical prostatectomy . In a multivariable survival analysis , conservative management was associated with greater risk of prostate cancer-specific mortality ( hazard ratio [ HR ] = 1.59 , 95 % confidence interval [ CI ] = 1.27 to 2.00 ) and all-cause mortality ( HR = 1.47 , 95 % CI = 1.35 to 1.59 ) than radical prostatectomy . Propensity score adjustments result ed in similar patient characteristics across treatment groups , although survival results were similar to traditional multivariable survival analyses . Results for the same comparison from the instrumental variable approach , which theoretically equalizes both observed and unobserved patient characteristics across treatment groups , differed from the traditional multivariable and propensity score results but were consistent with findings from the subset of elderly patient with early-stage disease in the trial ( ie , conservative management vs radical prostatectomy : for prostate cancer-specific mortality , HR = 0.73 , 95 % CI = 0.08 to 6.73 ; for all-cause mortality , HR = 1.09 , 95 % CI = 0.46 to 2.59 ) . CONCLUSION Instrumental variable analysis may be a useful technique in comparative effectiveness studies of cancer treatments if an acceptable instrument can be identified Holmberg L , Bill-Axelson A , Helgesen F , Salo JO , Folmerz P , Haggman M , et al. A r and omized trial comparing radical prostatectomy with watchful waiting in early prostate cancer . N Engl J Med 2002;347 : 781 - 9 . Background : The clinical importance and disease burden of prostate cancer — the CONTEXT Prostate-specific antigen screening has led to an increase in the diagnosis and treatment of localized prostate cancer . However , the role of active treatment of low- and intermediate-risk disease in elderly men is controversial . OBJECTIVE To estimate the association between treatment ( with radiation therapy or radical prostatectomy ) compared with observation and overall survival in men with low- and intermediate-risk prostate cancer . DESIGN AND SETTING Observational US cohort from Surveillance , Epidemiology , and End Results Medicare data . PATIENTS At total of 44,630 men aged 65 to 80 years who were diagnosed between 1991 and 1999 with organ-confined , well- or moderately differentiated prostate cancer and who had survived more than a year past diagnosis . Patients were followed up until death or study end ( December 31 , 2002 ) . Patients were classified as having received treatment ( n=32,022 ) if they had cl aims for radical prostatectomy or radiation therapy during the first 6 months after diagnosis . They were classified as having received observation ( n=12,608 ) if they did not have cl aims for radical prostatectomy , radiation , or hormonal therapy . Patients who received only hormonal therapy were excluded . MAIN OUTCOME MEASURE Overall survival . RESULTS At the end of the 12-year study period , 4663 men ( 37 % ) in the observational group and 7639 men ( 23.8 % ) in the treatment group had died . The treatment group had longer 5- and 10-year survival than the observation group . After using propensity scores to adjust for potential confounders ( tumor characteristics , demographics , and comorbidities ) , there was a statistically significant survival advantage associated with treatment ( hazard ratio , 0.69 ; 95 % confidence interval , 0.66 - 0.72 ) . A benefit associated with treatment was seen in all subgroups examined , including older men ( aged 75 - 80 years at diagnosis ) , black men , and men with low-risk disease . CONCLUSIONS This study suggests a survival advantage is associated with active treatment for low- and intermediate-risk prostate cancer in elderly men aged 65 to 80 years . Because observational data can not completely adjust for potential selection bias and confounding , these results must be vali date d in r and omized controlled trials of alternative management strategies in elderly men with localized prostate cancer BACKGROUND For men with localised prostate cancer , surgery provides a survival benefit compared with watchful waiting . Treatments are associated with morbidity . Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from r and omised setting s. We report results for quality of life for men in the Sc and inavian Prostate Cancer Group Study Number 4 ( SPCG-4 ) after a median follow-up of more than 12 years . METHODS All living Swedish and Finnish men ( 400 of 695 ) r and omly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis . An additional 281 men were included in a population -based control group matched for region and age . Physical symptoms , symptom-induced stress , and self-assessed quality of life were evaluated with a study -specific question naire . Longitudinal data were available for 166 Swedish men who had answered quality -of-life question naires at an earlier timepoint . FINDINGS 182 ( 88 % ) of 208 men in the radical prostatectomy group , 167 ( 87 % ) of 192 men in the watchful-waiting group , and 214 ( 76 % ) of 281 men in the population -based control group answered the question naire . Men in SPCG-4 had a median follow-up of 12·2 years ( range 7 - 17 ) and a median age of 77·0 years ( range 61 - 88 ) . High self-assessed quality of life was reported by 62 ( 35 % ) of 179 men allocated radical prostatectomy , 55 ( 34 % ) of 160 men assigned to watchful waiting , and 93 ( 45 % ) of 208 men in the control group . Anxiety was higher in the SPCG-4 groups ( 77 [ 43 % ] of 178 and 69 [ 43 % ] of 161 men ) than in the control group ( 68 [ 33 % ] of 208 men ; relative risk 1·42 , 95 % CI 1·07 - 1·88 ) . Prevalence of erectile dysfunction was 84 % ( 146 of 173 men ) in the radical prostatectomy group , 80 % ( 122 of 153 ) in the watchful-waiting group , and 46 % ( 95 of 208 ) in the control group and prevalence of urinary leakage was 41 % ( 71 of 173 ) , 11 % ( 18 of 164 ) , and 3 % ( six of 209 ) , respectively . Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting . In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart , 38 ( 45 % ) of 85 men allocated radical prostatectomy and 48 ( 60 % ) of 80 men allocated watchful waiting reported an increase in number of physical symptoms ; 50 ( 61 % ) of 82 and 47 ( 64 % ) of 74 men , respectively , reported a reduction in quality of life . INTERPRETATION For men in SPCG-4 , negative side-effects were common and added more stress than was reported in the control population . In the radical prostatectomy group , erectile dysfunction and urinary leakage were often consequences of surgery . In the watchful-waiting group , side-effects can be caused by tumour progression . The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions . An underst and ing of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information . FUNDING US National Institutes of Health ; Swedish Cancer Society ; Foundation in Memory of Johanna Hagstr and and Sigfrid Linnér In a study by the Veterans Administration Cooperative Urological Research Group ( VACURG ) , 142 patients with localized prostate cancer , VACURG stage I and II , were r and omized between radical prostatectomy plus placebo versus placebo alone as initial treatment . 111 patients were evaluable for treatment comparison . Median follow-up for survival is 23 years . The prognostic value of Gleason histologic grading was confirmed . A difference in overall survival in favor of radical prostatectomy was observed in stage I patients . However , after adjustment for imbalance in age distribution , no statistically significant differences in survival could be demonstrated in either stage or in both stages combined . The results are discussed considering the small sample size and the limited statistical power of the study 5Although electronic search ing and publishing have made it easier to identify and obtain a report of a single r and omised trial , this can not be deemed a short-cut to obtaining an overall , balanced view of the effectiveness of the interventions investigated in the trial . Instead , similar trials need to be brought together . This bringing together needs to be done in as unbiased a way as possible . Traditional narrative review s , usually written by a recognised expert , are generally not systematic . Authors might simply not have the time to identify and bring together all relevant studies or they might actually seek to discuss and selectively combine trials that confirm their opinions and prejudices . A systematic review aims to circumvent this weakness by the use of a predefined , explicit methodology . The methods used include steps to minimise bias in the identification of relevant studies , in the selection criteria for inclusion , and in the collection of data . Guidance is available on the conduct , BACKGROUND We evaluated symptoms and self- assessment s of quality of life in men with localized prostate cancer who participated in a r and omized comparison between radical prostatectomy and watchful waiting . METHODS Between 1989 and 1999 , a group of Swedish urologists r and omly assigned men with localized prostate cancer to radical prostatectomy or watchful waiting . In this follow-up study , we obtained information from 326 of 376 eligible men ( 87 percent ) concerning certain symptoms , symptom-induced distress , well-being , and the subjective assessment of quality of life by means of a mailed question naire . RESULTS Erectile dysfunction ( 80 percent vs. 45 percent ) and urinary leakage ( 49 percent vs. 21 percent ) were more common after radical prostatectomy , whereas urinary obstruction ( e.g. , 28 percent vs. 44 percent for weak urinary stream ) was less common . Bowel function , the prevalence of anxiety , the prevalence of depression , well-being , and the subjective quality of life were similar in the two groups . CONCLUSIONS The assignment of patients to watchful waiting or radical prostatectomy entails different risks of erectile dysfunction , urinary leakage , and urinary obstruction , but on average , the choice has little if any influence on well-being or the subjective quality of life after a mean follow-up of four years BACKGROUND Robust data on patient-reported outcome measures comparing treatments for clinical ly localized prostate cancer are lacking . We investigated the effects of active monitoring , radical prostatectomy , and radical radiotherapy with hormones on patient-reported outcomes . METHODS We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment ( ProtecT ) trial who completed question naires before diagnosis , at 6 and 12 months after r and omization , and annually thereafter . Patients completed vali date d measures that assessed urinary , bowel , and sexual function and specific effects on quality of life , anxiety and depression , and general health . Cancer-related quality of life was assessed at 5 years . Complete 6-year data were analyzed according to the intention-to-treat principle . RESULTS The rate of question naire completion during follow-up was higher than 85 % for most measures . Of the three treatments , prostatectomy had the greatest negative effect on sexual function and urinary continence , and although there was some recovery , these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial . The negative effect of radiotherapy on sexual function was greatest at 6 months , but sexual function then recovered somewhat and was stable thereafter ; radiotherapy had little effect on urinary continence . Sexual and urinary function declined gradually in the active-monitoring group . Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat , except for the increasing frequency of bloody stools ; bowel function was unchanged in the other groups . Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months . Effects on quality of life mirrored the reported changes in function . No significant differences were observed among the groups in measures of anxiety , depression , or general health-related or cancer-related quality of life . CONCLUSIONS In this analysis of patient-reported outcomes after treatment for localized prostate cancer , patterns of severity , recovery , and decline in urinary , bowel , and sexual function and associated quality of life differed among the three groups . ( Funded by the U.K. National Institute for Health Research Health Technology Assessment Program ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) BACKGROUND We previously found no significant differences in mortality between men who underwent surgery for localized prostate cancer and those who were treated with observation only . Uncertainty persists regarding nonfatal health outcomes and long‐term mortality . METHODS From November 1994 through January 2002 , we r and omly assigned 731 men with localized prostate cancer to radical prostatectomy or observation . We extended follow‐up through August 2014 for our primary outcome , all‐cause mortality , and the main secondary outcome , prostate‐cancer mortality . We describe disease progression , treatments received , and patient‐reported outcomes through January 2010 ( original follow‐up ) . RESULTS During 19.5 years of follow‐up ( median , 12.7 years ) , death occurred in 223 of 364 men ( 61.3 % ) assigned to surgery and in 245 of 367 ( 66.8 % ) assigned to observation ( absolute difference in risk , 5.5 percentage points ; 95 % confidence interval [ CI ] , ‐1.5 to 12.4 ; hazard ratio , 0.84 ; 95 % CI , 0.70 to 1.01 ; P=0.06 ) . Death attributed to prostate cancer or treatment occurred in 27 men ( 7.4 % ) assigned to surgery and in 42 men ( 11.4 % ) assigned to observation ( absolute difference in risk , 4.0 percentage points ; 95 % CI , ‐0.2 to 8.3 ; hazard ratio , 0.63 ; 95 % CI , 0.39 to 1.02 ; P=0.06 ) . Surgery may have been associated with lower all‐cause mortality than observation among men with intermediate‐risk disease ( absolute difference , 14.5 percentage points ; 95 % CI , 2.8 to 25.6 ) but not among those with low‐risk disease ( absolute difference , 0.7 percentage points ; 95 % CI , ‐10.5 to 11.8 ) or high‐risk disease ( absolute difference , 2.3 percentage points ; 95 % CI , ‐11.5 to 16.1 ) ( P=0.08 for interaction ) . Treatment for disease progression was less frequent with surgery than with observation ( absolute difference , 26.2 percentage points ; 95 % CI , 19.0 to 32.9 ) ; treatment was primarily for asymptomatic , local , or biochemical ( prostate‐specific antigen ) progression . Urinary incontinence and erectile and sexual dysfunction were each greater with surgery than with observation through 10 years . Disease‐related or treatment‐related limitations in activities of daily living were greater with surgery than with observation through 2 years . CONCLUSIONS After nearly 20 years of follow‐up among men with localized prostate cancer , surgery was not associated with significantly lower all‐cause or prostate‐cancer mortality than observation . Surgery was associated with a higher frequency of adverse events than observation but a lower frequency of treatment for disease progression , mostly for asymptomatic , local , or biochemical progression . ( Funded by the Department of Veterans Affairs and others ; PIVOT Clinical Trials.gov number , NCT00007644 . |
1,003 | 27,003,123 | 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 . | BACKGROUND This is an up date of the Cochrane review " Teriflunomide for multiple sclerosis " ( first published in The Cochrane Library 2012 , Issue 12).Multiple sclerosis ( MS ) is a chronic immune-mediated disease of the central nervous system .
It is clinical ly characterized by recurrent relapses or progression , or both , often leading to severe neurological disability and a serious decline in quality of life .
Disease-modifying therapies ( DMTs ) for MS aim to prevent occurrence of relapses and disability progression .
Teriflunomide is a pyrimidine synthesis inhibitor approved by both the US Food and Drug Administration ( FDA ) and the European Medicines Agency ( EMA ) as a DMT for adults with relapsing-remitting MS ( RRMS ) .
OBJECTIVES To assess the absolute and comparative effectiveness and safety of teriflunomide as monotherapy or combination therapy versus placebo or other disease-modifying drugs ( DMDs ) ( interferon beta ( IFNβ ) , glatiramer acetate , natalizumab , mitoxantrone , fingolimod , dimethyl fumarate , alemtuzumab ) for modifying the disease course in people with MS . | 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 : Teriflunomide had a favourable safety profile for up to 8.5 years Multiple sclerosis ( MS ) relapses impose a substantial clinical and economic burden . Teriflunomide is a new oral disease-modifying therapy approved for the treatment of relapsing MS . We evaluated the effects of teriflunomide treatment on relapse-related neurological sequelae and healthcare re source use in a post hoc analysis of the Phase III TEMSO study . Confirmed relapses associated with neurological sequelae [ defined by an increase in Exp and ed Disability Status Scale/Functional System ( sequelae-EDSS/FS ) ≥30 days post relapse or by the investigator ( sequelae-investigator ) ] were analyzed in the modified intention-to-treat population ( n = 1086 ) . Relapses requiring hospitalization or intravenous ( IV ) corticosteroids , all hospitalizations , emergency medical facility visits ( EMFV ) , and hospitalized nights for relapse were also assessed . Annualized rates were derived using a Poisson model with treatment , baseline EDSS strata , and region as covariates . Risks of sequelae and hospitalization per relapse were calculated as percentages and groups were compared with a χ2 test . Compared with placebo , teriflunomide reduced annualized rates of relapses with sequelae-EDSS/FS [ 7 mg by 32 % ( p = 0.0019 ) ; 14 mg by 36 % ( p = 0.0011 ) ] and sequelae-investigator [ 25 % ( p = 0.071 ) ; 53 % ( p < 0.0001 ) ] , relapses leading to hospitalization [ 36 % ( p = 0.015 ) ; 59 % ( p < 0.0001 ) ] , and relapses requiring IV corticosteroids [ 29 % ( p = 0.001 ) ; 34 % ( p = 0.0003 ) ] . Teriflunomide-treated patients spent fewer nights in hospital for relapse ( p < 0.01 ) . Teriflunomide 14 mg also decreased annualized rates of all hospitalizations ( p = 0.01 ) and EMFV ( p = 0.004 ) . The impact of teriflunomide on relapse-related neurological sequelae and relapses requiring healthcare re sources may translate into reduced healthcare costs Background : In previous studies , teriflunomide significantly reduced the annualised relapse rate ( ARR ) and disability progression . Objective : This phase 3 , rater-blinded study ( NCT00883337 ) compared teriflunomide with interferon-beta-1a ( IFNβ-1a ) . Methods : Patients with relapsing multiple sclerosis were r and omised ( 1:1:1 ) to oral teriflunomide 7-or 14 mg , or subcutaneous IFNβ-1a 44 µg . The primary composite endpoint was time to failure , defined as first occurrence of confirmed relapse or permanent treatment discontinuation for any cause . Secondary endpoints included ARR , Fatigue Impact Scale ( FIS ) and Treatment Satisfaction Question naire for Medication ( TSQM ) . The study was completed 48 weeks after the last patient was r and omised . Results : Some 324 patients were r and omised ( IFNβ-1a : 104 ; teriflunomide 7 mg : 109 ; teriflunomide 14 mg : 111 ) . No difference in time to failure was observed . There was no difference in ARR between teriflunomide 14 mg and IFNβ-1a , but ARR was significantly higher with teriflunomide 7 mg . FIS scores indicated more frequent fatigue with IFNβ-1a , though differences were only significant with teriflunomide 7 mg . TSQM scores were significantly higher with teriflunomide . There were no unexpected safety findings . Conclusion : Effects on time to failure were comparable between teriflunomide and IFNβ-1a . There was no difference between teriflunomide 14 mg and IFNβ-1a on ARR , though ARR was higher with teriflunomide 7 mg . The teriflunomide safety profile was consistent with previous studies BACKGROUND Multiple sclerosis ( MS ) commonly affects young adults and can be associated with significant disability result ing in considerable socioeconomic burden for both patient and society . AIMS The aim was to determine the direct and indirect cost of an MS relapse . METHODS This was a prospect i ve audit composed of medical chart review and patient question naire . Relapses were stratified into 3 groups : low , moderate and high intensity . Age , gender , MS subtype , disease duration , exp and ed disability status scale ( EDSS ) score , disease modifying therapy ( DMT ) use and employment status were recorded . Direct costs included GP visits , investigations , clinic visit , consultations with medical staff , medication and admission costs . Indirect costs assessed loss of earnings , partner׳s loss of earnings , childcare , meals and travel costs . RESULTS Fifty-three patients had a clinical ly confirmed relapse . Thirteen were of low intensity ; 23 moderate intensity and 17 high intensity with mean costs of € 503 , € 1395 and € 8862 , respectively . Those with high intensity episodes tended to be older with higher baseline EDSS ( p<0.003 ) and change in EDSS ( p<0.002 ) . Direct costs were consistent in both low and moderate intensity groups but varied with length of hospital stay in the high intensity group . Loss of earnings was the biggest contributor to indirect costs . A decision to change therapy as a result of the relapse was made in 23 % of cases , further adding to annual MS related costs . CONCLUSIONS The cost of an MS relapse is dependent on severity of the episode but even low intensity episodes can have a significant financial impact for the patient in terms of loss of earnings and for society with higher annual MS related costs Objective : The purpose of this study was to determine the effects of oral teriflunomide on multiple sclerosis ( MS ) pathology inferred by magnetic resonance imaging ( MRI ) . Methods : Patients ( n=1088 ) with relapsing MS were r and omized to once-daily teriflunomide 7 mg or 14 mg , or placebo , for 108 weeks . MRI was recorded at baseline , 24 , 48 , 72 and 108 weeks . Annualized relapse rate and confirmed progression of disability ( sustained ≥12 weeks ) were the primary and key secondary outcomes . The principal MRI outcome was change in total lesion volume . Results : After 108 weeks , increase in total lesion volume was 67.4 % ( p=0.0003 ) and 39.4 % ( p=0.0317 ) lower in the 14 and 7 mg dose groups versus placebo . Other measures favoring teriflunomide were accumulated enhanced lesions , combined unique activity , T2-hyperintense and T1-hypointense component lesion volumes , white matter volume , and a composite MRI score ; all were significant for teriflunomide 14 mg and most significant for 7 mg versus placebo . Conclusions : Teriflunomide provided benefits on brain MRI activity across multiple measures , with a dose effect evident on several markers . These effects were also consistent across selected subgroups of the study population . These findings complement clinical data showing significant teriflunomide-related reductions in relapse rate and disease progression , and demonstrate containment of MRI-defined disease progression BACKGROUND most disease-modifying therapies ( DMTs ) for multiple sclerosis ( MS ) are self-injectable medications that must be taken on an ongoing basis to reduce disease activity . Thus , adherence to therapy becomes an important challenge that must be addressed to maximize benefits of therapy . This study evaluated rates of adherence to prescribed treatment and explored factors affecting adherence amongst patients with relapsing-remitting MS . METHODS this was an observational , multicenter , multinational , phase 4 study . Patients and physicians received paper question naires regarding adherence to DMTs approved at the time of the study , including intramuscular interferon beta-1a ( IFNβ-1a ) , subcutaneous IFNβ-1a , IFNβ-1b , and glatiramer acetate . Quality of life and cognition data also were collected . Multivariate analysis was conducted to identify factors associated with adherence to long-term DMTs . RESULTS two thous and six hundred and forty-eight patients were studied , revealing an average treatment duration of 31 months . Seventy-five percent of patients ( n = 1923 ) were adherent to therapy . The most common reasons for non-adherence were forgetting to administer the injection ( 50.2 % ) and other injection-related reasons ( 32.0 % ) . Adherent patients reported better quality of life ( P < 0.05 ) and fewer neuropsychological issues ( P < 0.001 ) than non-adherent patients . Adherent patients had significantly shorter duration of disease ( P < 0.001 ) and shorter duration of therapy ( P = 0.005 ) than non-adherent patients . Women were more likely than men to adhere to treatment . CONCLUSION identifying factors that affect adherence to prescribed treatments is the first step in improving adherence of patients with MS to therapy , thereby helping maximize the benefits of long-term DMTs BACKGROUND Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing-remitting multiple sclerosis . We aim ed to assess the efficacy and safety of teriflunomide in patients with a first clinical episode suggestive of multiple sclerosis . METHODS In this r and omised , double-blind , placebo-controlled , parallel-group study , we enrolled patients aged 18 - 55 years with clinical ly isolated syndrome ( defined as a neurological event consistent with demyelination , starting within 90 days of r and omisation , and two or more T2-weighted MRI lesions ≥3 mm in diameter ) from 112 centres ( mostly hospitals ) in 20 countries . Participants were r and omly assigned ( 1:1:1 ) in a double-blind manner ( by an interactive voice response system ) to once-daily oral teriflunomide 14 mg , teriflunomide 7 mg , or placebo , for up to 108 weeks . Patients , staff administering the interventions , and outcome assessors were masked to treatment assignment . The primary endpoint was time to relapse ( a new neurological abnormality separated by ≥30 days from a preceding clinical event , present for ≥24 h in the absence of fever or known infection ) , which defined conversion to clinical ly definite multiple sclerosis . The key secondary endpoint was time to relapse or new gadolinium-enhancing or T2 lesions on MRI , whichever occurred first . The primary outcome was analysed for the modified intention-to-treat population ; safety analyses included all r and omised patients who were exposed to the study drug , as treated . This trial is registered with Clinical Trials.gov , number NCT00622700 . FINDINGS Between Feb 13 , 2008 , and Aug 22 , 2012 , 618 patients were enrolled and r and omly assigned to teriflunomide 14 mg ( n=216 ) , teriflunomide 7 mg ( n=205 ) , or placebo ( n=197 ) . Two patients in each of the teriflunomide groups did not receive the study drug , so the modified intention-to-treat population comprised 214 patients in the teriflunomide 14 mg group , 203 in the teriflunomide 7 mg group , and 197 in the placebo group . Compared with placebo , teriflunomide significantly reduced the risk of relapse defining clinical ly definite multiple sclerosis at the 14 mg dose ( hazard ratio [ HR ] 0·574 [ 95 % CI 0·379 - 0·869 ] ; p=0·0087 ) and at the 7 mg dose ( 0·628 [ 0·416 - 0·949 ] ; p=0·0271 ) . Teriflunomide reduced the risk of relapse or a new MRI lesion compared with placebo at the 14 mg dose ( HR 0·651 [ 95 % CI 0·515 - 0·822 ] ; p=0·0003 ) and at the 7 mg dose ( 0·686 [ 0·540 - 0·871 ] ; p=0·0020 ) . During the study , six patients who were r and omly assigned to placebo accidently also received teriflunomide at some point : four received 7 mg and two received 14 mg . Therefore , the safety population comprised 216 patients on teriflunomide 14 mg , 207 on teriflunomide 7 mg , and 191 on placebo . Adverse events that occurred in at least 10 % of patients in either teriflunomide group and with an incidence that was at least 2 % higher than that with placebo were increased alanine aminotransferase ( 40 [ 19 % ] of 216 patients in the 14 mg group , 36 [ 17 % ] of 207 in the 7 mg group vs 27 [ 14 % ] of 191 in the placebo group ) , hair thinning ( 25 [ 12 % ] and 12 [ 6 % ] vs 15 [ 8 % ] ) , diarrhoea ( 23 [ 11 % ] and 28 [ 14 % ] vs 12 [ 6 % ] ) , paraesthesia ( 22 [ 10 % ] and 11 [ 5 % ] vs 10 [ 5 % ] ) , and upper respiratory tract infection ( 20 [ 9 % ] and 23 [ 11 % ] vs 14 [ 7 % ] ) . The most common serious adverse event was an increase in alanine aminotransferase ( four [ 2 % ] and five [ 2 % ] vs three [ 2 % ] ) . INTERPRETATION TOPIC is to our knowledge the first study to report benefits of an available oral disease-modifying therapy in patients with early multiple sclerosis . These results extend the stages of multiple sclerosis in which teriflunomide shows a beneficial effect . FUNDING Genzyme , a Sanofi company BACKGROUND Teriflunomide is an oral disease-modifying therapy approved for treatment of relapsing or relapsing-remitting multiple sclerosis . We aim ed to provide further evidence for the safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis . METHODS This international , r and omised , double-blind , placebo-controlled , phase 3 study enrolled adults aged 18 - 55 years with relapsing multiple sclerosis , one or more relapse in the previous 12 months or two or more in the previous 24 months but no relapse in the previous 30 days , and an Exp and ed Disability Status Scale ( EDSS ) score of 5.5 points or less . Patients were recruited from 189 sites in 26 countries and r and omly assigned ( 1:1:1 ) to once-daily placebo , teriflunomide 7 mg , or teriflunomide 14 mg via an interactive voice recognition system . Treatment duration was variable , ending 48 weeks after the last patient was included . The primary endpoint was annualised relapse rate ( number of relapses per patient-year ) and the key secondary endpoint was time to sustained accumulation of disability ( an EDSS score increase of at least 1 EDSS point sustained for a minimum of 12 weeks ) , both analysed in the modified intention-to-treat population ( all patients who received at least one dose of assigned study medication ) . This study is registered with Clinical Trials.gov , number NCT00751881 . FINDINGS Between Sept 17 , 2008 , and Feb 17 , 2011 , 1169 patients were r and omly assigned to a treatment group , of whom 388 , 407 , and 370 patients received at least one dose of placebo , teriflunomide 7 mg , or teriflunomide 14 mg , respectively . By the end of the study , the annualised relapse rate was higher in patients assigned to placebo ( 0.50 [ 95 % CI 0.43 - 0.58 ] ) than in those assigned to teriflunomide 14 mg ( 0.32 [ 0.27 - 0.38 ] ; p=0.0001 ) or teriflunomide 7 mg ( 0.39 [ 0.33 - 0.46 ] ; p=0.0183 ) . Compared with placebo , teriflunomide 14 mg reduced the risk of sustained accumulation of disability ( hazard ratio [ HR ] 0.68 [ 95 % CI 0.47 - 1.00 ] ; log-rank p=0.0442 ) ; however , teriflunomide 7 mg had no effect on sustained accumulation of disability ( HR 0.95 [ 0.68 - 1.35 ] ; log-rank p=0.7620 ) . The most common adverse events were alanine aminotransferase increases ( 32 [ 8 % ] of 385 patients in the placebo group vs 46 [ 11 % ] of 409 patients in the teriflunomide 7 mg group vs 52 [ 14 % ] of 371 patients in the teriflunomide 14 mg group ) , hair thinning ( 17 [ 4 % ] vs 42 [ 10 % ] vs 50 [ 13 % ] ) , and headache ( 42 [ 11 % ] vs 60 [ 15 % ] vs 46 [ 12 % ] ) . Incidence of serious adverse events was similar in all treatment groups ( 47 [ 12 % ] vs 52 [ 13 % ] vs 44 [ 12 % ] ) . Four deaths occurred , none of which was considered to be related to study drug ( respiratory infection in the placebo group , traffic accident in the teriflunomide 7 mg group , and suicide and septicaemia due to Gram-negative infection complicated by disseminated intravascular coagulopathy in the teriflunomide 14 mg group ) . INTERPRETATION Teriflunomide 14 mg was associated with a lower relapse rate and less disability accumulation compared with placebo , with a similar safety and tolerability profile to that reported in previous studies . These results confirm the dose effect reported in previous trials and support the use of teriflunomide 14 mg in patients with relapsing multiple sclerosis . FUNDING Genzyme , a Sanofi company |
1,004 | 31,700,607 | ‘ 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 . | Background Pelvic girdle pain is a common problem during pregnancy and postpartum with significant personal and societal impact and costs .
Studies examining the effectiveness of interventions for pelvic girdle pain measure different outcomes , making it difficult to pool data in meta- analysis in a meaningful and interpretable way to increase the certainty of effect measures .
A consensus-based core outcome set for pelvic girdle pain can address this issue .
As a first step in developing a core outcome set , it is essential to systematic ally examine the outcomes measured in existing studies .
Objective The objective of this systematic review was to identify , examine and compare what outcomes are measured and reported , and how outcomes are measured , in intervention studies and systematic review s of interventions for pelvic girdle pain and for lumbopelvic pain ( which includes pelvic girdle pain ) .
This core outcome set will allow for more effective comparison between future studies on pelvic girdle pain , allowing for more effective translation of findings to clinical practice .Resumen en EspañolIntroducciónEl dolor de la cintura pélvica es un problema común durante el embarazo y el posparto con un impacto personal y social significativo .
Los estudios que examinan la efectividad de intervenciones para el dolor de la cintura pélvica miden diferentes result ados , lo que dificulta el agrupamiento de los datos en un metanálisis para aumentar la certeza de las medidas del efecto .
Un conjunto de result ados principales basado en un consenso puede abordar este problema .
Primero , para desarrollar un conjunto de result ados principales , es esencial examinar sistemáticamente los result ados utilizados en los estudios existentes .
ObjetivoEl objetivo de esta revisión sistemática fue identificar , examinar y comparar qué result ados se miden y reportan , y cómo se los miden , en estudios de intervención y revisiones sistemáticas de intervenciones para el dolor de la cintura pélvica y para el dolor lumbopélvico . | 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 , however , high in the intervention group OBJECTIVE To investigate the effect of an exercise program , including specific stabilizing exercises , on pain intensity and functional ability in women with pregnancy-related low back pain . METHODS Fifty women between 16 and 24 weeks of pregnancy were recruited at Tygerberg and Paarl Hospitals , Western Cape , South Africa . Twenty-six women were r and omized to a 10-week exercise program and 24 were r and omized as controls . RESULTS Overall , the most frequent type of back pain experienced was lumbar pain ( 36 [ 72.0 % ] ) . Pain intensity ( P=0.76 ) and functional ability ( P=0.29 ) were comparable between the groups on study entry . In the study group , there was a significant improvement in pain intensity ( P<0.01 ) and an improvement in functional ability ( P=0.06 ) at the end of the study . In the control group , there were no significant changes in pain intensity ( P=0.89 ) or functional ability ( P=0.70 ) at the end of the study . CONCLUSION A specific exercise program decreased back pain intensity and increased functional ability during pregnancy in South African women with lumbar and pelvic girdle pain Background For the moment , scientific evaluation of programs on treatment of pregnancy-related pelvic girdle and /or low back pain after delivery is hardly available with only one study with a positive result , suggesting uncertainty about the optimal approach . Investigators draw particular attention to biomedical factors but there is growing evidence that biopsychosocial factors appear to be even more important as a basis of an intervention program . Methods We studied the effectiveness of a tailor-made program with respect to biopsychosocial factors ( intervention group ) in women with pregnancy-related pelvic girdle and / or low back pain versus usual care based on a pain contingent basis ( control group ) shortly after delivery in a r and omized controlled trial . Women with severe complaints shortly after delivery were selected from a longitudinal prospect i ve cohort study ( n = 7526 ) , aim ed at pregnancy-related pelvic girdle and /or low back pain in the Netherl and s. A concealed block r and omization was performed after collecting baseline data . Research ers were blinded to treatment assignment . Outcomes were evaluated within the domains of the biopsychosocial approach . Primary outcome concerned limitations in activities ( RDQ ) . Follow-up measurements were performed 12 weeks after delivery . Results Since May 2001 until July 2003 , 869 women out of the cohort made a request for treatment by a physiotherapist , 10 days after delivery . Because of a quick recovery in two weeks time , we included only 126 women three weeks after delivery . There was a statistically significant and clinical ly relevant difference in improvement on the primary outcome ( RDQ ) between the two groups in favor of the experimental intervention . Conclusion The results favored the hypotheses . Women 's worries about their condition were major targets in the experimental intervention . The prognosis after delivery , especially in de first weeks , turned out to be favorable This study was undertaken to investigate the effects of acupuncture in low back and pelvic pain during pregnancy under real life conditions , as compared with patients undergoing conventional treatment alone . A total of 61 conventionally treated pregnant women were allocated r and omly into two groups to be treated or not by acupuncture . Twenty-seven patients formed the study group and 34 the control group . They reported the severity of pain using a Numerical Rating Scale from 0 to 10 , and their capacity to perform general activities , to work , and to walk . We also assessed the use of analgesic drugs . Women were followed up for eight weeks and interviewed five times , at two-week intervals . All women completed the study . In the study group the average pain during the study period showed a larger reduction ( 4.8 points ) than the control group ( −0.3 points ) ( P<0.0001 ) . Average pain scores decreased by at least 50 % over time in 21 ( 78 % ) patients in the acupuncture group and in five ( 15 % ) patients in the control group ( P<0.0001 ) . Maximum pain and pain at the moment of interview were also less in the acupuncture group compared with the control group . The capacity to perform general activities , to work and to walk was improved significantly more in the study group than in the control group ( P<0.05 ) . The use of paracetamol was lower in the acupuncture group ( P<0.01 ) . These results indicate that acupuncture seems to alleviate low back and pelvic pain during pregnancy , as well as to increase the capacity for some physical activities and to diminish the need for drugs , which is a great advantage during this period Background Pregnancy-related low back pain is considered an important health problem and potentially leads to long-lasting pain and disability . Investigators draw particular attention to biomedical factors but there is growing evidence that psychosocial and social factors might be important . It prompted us to start a large cohort study ( n = 7526 ) during pregnancy until one year after delivery and a nested r and omized controlled intervention study in the Netherl and s. Methods A r and omized controlled trial ( n = 126 ) nested within a cohort study , of brief self-management techniques versus usual care for treatment of women with persisting non-specific pregnancy-related low back pain three weeks after delivery . Women in the intervention group were referred to a participating physiotherapist . Women in the usual care group were free to choose physiotherapy , guidance by a general practitioner or no treatment . Follow up took place at 3 months , 6 months and one year after delivery . Outcomes included change in limitations in activities ( RDQ ) , pain ( VAS ) , severity of main complaints ( MC ) , global feeling of recovery ( GPE ) , impact on participation and autonomy ( IPA ) , pain-related fear ( TSK ) , SF-36 , EuroQol and a cost diary . For the outcome measures , series of mixed models were considered . For the outcome variable global perceived effect ( GPE ) a logistic regression analysis is performed . Results Intention-to-treat outcomes showed a statistical significant better estimated regression coefficient RDQ -1.6 { -2.9;-0.5 } associated with treatment , as well as better IPA subscale autonomy in self-care -1.0 { -1.9;-0.03 } and TSK -2.4 { -3.8;-1.1 } but were not clinical relevant over time . Average total costs in the intervention group were much lower than in usual care , primarily due to differences in utilization of sick leave but not statistically significant . Conclusion Brief self-management techniques applied in the first 3 months after delivery may be a more viable first-line approach but further research is needed to draw inference on costs and to determine whether no care is a better option in the long term . Trial Registration [ IS RCT N08477490 Objective . To study lumbopelvic pain in women r and omized to a regular exercise program during pregnancy in comparison to women receiving st and ard antenatal care . Design . A two‐armed , two‐center , r and omized controlled trial . Setting . St Olavs Hospital , Trondheim University Hospital and Stavanger University Hospital . Population . A total of 855 pregnant women were r and omized to intervention or control groups . Methods . The intervention was a 12 week exercise program , including aerobic and strengthening exercises , conducted between 20 and 36 weeks of pregnancy . One weekly group session was led by physiotherapists , and home exercises were encouraged twice a week . The control group received st and ard antenatal care . Main outcome measures . Self‐reports of lumbopelvic pain and sick leave due to lumbopelvic pain . The data were analysed according to the “ intention‐to‐treat ” principle . Results . There were no significant differences between groups of women reporting lumbopelvic pain at 36 weeks ( 74 vs. 75 % , p=0.76 ) . The proportion of women on sick leave due to lumbopelvic pain was lower in the intervention group ( 22 % vs 31 % , p=0.01 ) . Conclusions . Exercise during pregnancy does not influence the prevalence of lumbopelvic pain , but women offered a regular exercise course seem to h and le the disorder better Background Antenatal preparation programmes are recommended worldwide to promote a healthy pregnancy and greater autonomy during labor and delivery , prevent physical discomfort and high levels of anxiety . The objective of this study was to evaluate effectiveness and safety of a birth preparation programme to minimize lumbopelvic pain , urinary incontinence , anxiety , and increase physical activity during pregnancy as well as to compare its effects on perinatal outcomes comparing two groups of nulliparous women . Methods A r and omized controlled trial was conducted with 197 low risk nulliparous women aged 16 to 40 years , with gestational age ≥ 18 weeks . Participants were r and omly allocated to participate in a birth preparation programme ( BPP ; n=97 ) or a control group ( CG ; n=100 ) . The intervention was performed on the days of prenatal visits , and consisted of physical exercises , educational activities and instructions on exercises to be performed at home . The control group followed a routine of prenatal care . Primary outcomes were urinary incontinence , lumbopelvic pain , physical activity , and anxiety . Secondary outcomes were perinatal variables . Results The risk of urinary incontinence in BPP participants was significantly lower at 30 weeks of pregnancy ( BPP 42.7 % , CG 62.2 % ; relative risk [ RR ] 0.69 ; 95 % confidence interval [ CI ] 0.51 - 0.93 ) and at 36 weeks of pregnancy ( BPP 41.2 % , CG 68.4 % ; RR 0.60 ; 95%CI 0.45 - 0.81 ) . Participation in the BPP encouraged women to exercise during pregnancy ( p=0.009 ) . No difference was found between the groups regarding to anxiety level , lumbopelvic pain , type or duration of delivery and weight or vitality of the newborn infant . Conclusions The BPP was effective in controlling urinary incontinence and to encourage the women to exercise during pregnancy with no adverse effects to pregnant women or the fetuses . Trial registration Clinical trials.gov , ( NCT01155804 Study Design . R and omized double blind controlled clinical trial . Objective . To evaluate the pain relief effect of locally injected corticosteroid treatment in women with long-lasting sacral low back pain with onset during pregnancy . Summary of Background Data . Pregnancy-related low back pain is a global problem . Almost 1 of 10 women still experienced disabling daily back pain 2 years after childbirth with high impact on the individual , family , and society . On spite of this , the sources of pain and effective treatment are uncertain . Methods . Thirty-six women were allocated to injection treatment , with slow-release triamcinolone and lidocaine or saline and lidocaine , given at the sacrospinous ligament insertion on the ischiadic spine bilaterally with 4 weeks follow-up time . Primary outcome measure was reported pain intensity on visual analogue scale and secondary outcome measures number of pain-drawing locations and pain-provoking test results . Results . The triamcinolone treatment group had significantly reduced pain intensity , number of pain locations , and pain-provoking test results between baseline and follow-up as compared with the saline treatment group . The absolute median change of visual analogue scale score in the triamcinolone treatment group was −24 mm and in the saline group + 4.5 mm ( P < 0.05 ) . A reduced number of pain drawing locations was reported by 16 of 18 women in the triamcinolone group as compared with 10 of 18 in the saline group ( P < 0.05 ) . In the triamcinolone treatment group , 17 of 18 women had an improved pain provocation test result as compared with 9 of 18 in the saline treatment group ( P < 0.01 ) . Conclusion . The anatomic region around the sacrospinous ligament insertion on the ischial spine is suggested to be one source of long-lasting sacral low back pain with onset during pregnancy . The pain was relieved by slow-release corticosteroid injection treatment to the ischial spine OBJECTIVE Women commonly experience low back pain during pregnancy . We examined whether a multimodal approach of musculoskeletal and obstetric management ( MOM ) was superior to st and ard obstetric care to reduce pain , impairment , and disability in the antepartum period . STUDY DESIGN A prospect i ve , r and omized trial of 169 women was conducted . Baseline evaluation occurred at 24 - 28 weeks ' gestation , with follow-up at 33 weeks ' gestation . Primary outcomes were the Numerical Rating Scale ( NRS ) for pain and the Quebec Disability Question naire ( QDQ ) . Both groups received routine obstetric care . Chiropractic specialists provided manual therapy , stabilization exercises , and patient education to MOM participants . RESULTS The MOM group demonstrated significant mean reductions in Numerical Rating Scale scores ( 5.8 ± 2.2 vs 2.9 ± 2.5 ; P < .001 ) and Quebec Disability Question naire scores ( 4.9 ± 2.2 vs 3.9 ± 2.4 ; P < .001 ) from baseline to follow-up evaluation . The group that received st and ard obstetric care demonstrated no significant improvements . CONCLUSION A multimodal approach to low back and pelvic pain in mid pregnancy benefits patients more than st and ard obstetric care Many pregnant women with low back and /or pelvic pain ( LBPP ) use pain medications to manage this pain , much of which is self-prescribed and potentially harmful . Therefore , there is a need to find effective nonpharmacological treatments for the condition . Reflexology has previously been shown to help nonspecific low back pain . Therefore ; a pilot RCT was conducted investigating reflexology in the management of pregnancy-LBPP . 90 primiparous women were r and omised to either usual care , a reflexology or footbath intervention . Primary outcome measures were ; the Pain Visual Analogue Scale ( VAS ) . 64 women completed the RCT ; retention rates for the reflexology group were 80 % , usual care group 83.33 % and footbath group 50 % . The reflexology group demonstrated a Clinical ly Important Change ( CIC ) in pain frequency ( 1.64 cm ) . Results indicate it is feasible to conduct an RCT in this area , although a footbath is an unsuitable sham treatment . Reflexology may help manage pregnancy-LBPP ; however a fully powered trial is needed to confirm this Background Pregnancy-related pubic symphysis pain is relatively common and can significantly interfere with daily activities . Physiotherapist-prescribed pelvic support belts are a treatment option , but little evidence exists to support their use . This pilot compared two pelvic belts to determine effectiveness ( symptomatic relief ) , tolerance ( comfort ) and adherence ( frequency , duration of use ) . Methods Unblinded , 2-arm , single-center , r and omized ( 1:1 ) parallel-group trial . Twenty pregnant women recruited from the community ( Dunedin , New Zeal and ) , with physiotherapist-diagnosed symphyseal pain , were r and omly allocated to wear either a flexible or rigid belt for three weeks . One author , not involved in data collection , r and omized the allocation to trial group . The unblinded primary outcome was the Patient Specific Functional Scale ( PSFS ) . Secondary outcomes were pain intensity during the preceding 24 hours and preceding week ( visual analogue scale [ VAS ] ) , and disability ( Modified Oswestry Disability Question naire [ MODQ ] ) . Duration of use ( hours ) was recorded daily by text messaging . Participants were assessed at baseline , by weekly phone interviews and at intervention completion ( three weeks ) . To assess comfort , women wore the alternate belt in the fourth week . Results Twenty pregnant women ( mean ± SD age , 29.4 ± 6.5 years ; mean gestation at baseline , 30.8 ± 5.2 weeks ) were r and omized to treatment groups ( flexible = 10 , rigid = 10 ) and all were included in analysis . When adjusted for baseline , PSFS scores were not significantly different between groups at follow up ( mean difference −0.1 ; 95 % CI : −2.5 to 2.3 ; p = 0.94 ) . Pain in the preceding 24 hours reached statistical significance in favor of the flexible belt ( VAS , p = 0.049 ) . Combining both groups ’ data , function and pain were significantly improved at three weeks ( mean difference −2.3 ; 95 % CI : 1.2 to 3.5 ; p < 0.001 ) . Belts were worn for an average of 4.9 ± 2.9 hours per day ; women preferred the flexible belt . No adverse events were reported . Conclusion These preliminary results suggest the flexible pelvic support belt may be more effective in reducing pain and is potentially better tolerated than a rigid belt . Based on these data , a larger trial is both feasible and clinical ly useful . Trial registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) ACTRN12614000898651 , 25th August , 2014 Background The fusion of the pelvic joints in patients with severe pelvic girdle pain ( PGP ) is a controversial and insufficiently studied procedure . The aims of this study were to evaluate physical function and pain after sacroiliac joint ( SIJ ) fusion . Methods A single-subject research design study with repeated measurements was conducted ; pre-operatively and at 3 , 6 and 12 months post-operatively . The outcome measures considered were the Oswestry disability index ( ODI ) , visual analogue scale ( VAS ) , and SF-36 . Eight patients with severe PGP received open-accessed unilateral anterior SIJ fusion and fusion of the pubic symphysis . Results Seven patients reported positive results from the surgery . At 1 year post-operation , significant ( p < 0.001 ) reductions in ODI ( 54 to 37 ) and VAS ( 82 to 57 ) were reported . The physical functioning , bodily pain , and social functioning scores in the SF-36 were also improved . Conclusion Positive and significant changes in disability and pain at 1 year after SIJ fusion were observed . Despite these positive results , open accessed anterior fusion of the SIJ was associated with adverse events and complications such as infection and nerve damage Background Pelvic girdle pain ( PGP ) is a multifactorial condition , which can be mentally and physically compromising both during and after pregnancy . However , long-term pregnancy-related PGP has been poorly investigated . This longitudinal follow-up study uniquely aim ed to describe prevalence and predictors of PGP and its consequences on women ’s health and function up to 11 years after pregnancy . Methods / Design A postal question naire was sent to 530 women who participated in 1 of 3 r and omized controlled studies for PGP in pregnancy . Women who reported experiencing lumbopelvic pain were offered a clinical examination . Main outcome measure was the presence of long term PGP as assessed by an independent examiner . Secondary outcomes were : working hours/week , function ( the Disability Rating Index , and Oswestry Disability Index ) , self-efficacy ( the General Self-Efficacy Scale ) , HRQL ( Euro-Qol 5D and EQ-Visual scale ) , anxiety and depression , ( Hospital anxiety and depression scale , ) and pain-catastrophizing ( Pain Catastrophizing Scale ) , in women with PGP compared to women with no PGP . Results A total of 371/530 ( 70 % ) women responded and 37/ 371 ( 10 % ) were classified with long-term PGP . Pregnancy-related predictors for long-term PGP were number of positive pain provocation tests ( OR = 1.79 ) , history of low back pain ( LBP ) ( OR = 2.28 ) , positive symphysis pressure test ( OR = 2.01 ) , positive Faber ( Patrick ’s ) test ( OR = 2.22 ) , and positive modified Trendelenburg test ( OR = 2.20 ) . Women with PGP had significantly decreased ability to perform daily activities ( p < .001 ) , lower self-efficacy ( p = 0.046 ) , decreased HRQL ( p < .001 ) , higher levels of anxiety and depression ( p < .001 ) , were more prone to pain catastrophizing , and worked significantly fewer hours/week ( p = 0.032 ) compared to women with no PGP . Conclusions This unique long-term follow up of PGP highlights the importance of assessment of pain in the lumbopelvic area early in pregnancy and postpartum in order to identify women with risk of long term pain . One of 10 women with PGP in pregnancy has severe consequences up to 11 years later . They could be identified by number of positive pain provocation tests and experience of previous LBP . Access to evidence based treatments are important for individual and socioeconomic reasons Background About 45 % of all pregnant women suffer low back pain and /or pelvic girdle pain ( LBPGP ) . This study seeks to evaluate the effect of auricular acupuncture on LBPGP compared with placebo auricular acupuncture and with st and ard obstetric care in the field of primary health care . Methods and design This study will be a four-parallel-arm , multicentre , r and omised , placebo-controlled trial . A total of 212 pregnant women ( 24 to 36 weeks ’ gestation ) , aged at least 17 years , with LBPGP , will be r and omly assigned to the verum auricular acupuncture plus st and ard obstetric care group ( VAAc ) , to the non-specific auricular acupuncture plus st and ard obstetric care group ( NSAAc ) , to the non-specific placebo auricular acupuncture plus st and ard obstetric care group ( PAAc ) , or the st and ard obstetric care group ( SOC ) . The VAAc , NSAAc , and PAAc groups will receive treatment at three auricular acupuncture points ( specific points for the VAAc group or non-specific ones for the NSAAc and PAAc groups ) , once a week for 2 weeks ; the SOC group will receive only st and ard obstetric care during the same period . The primary outcome will be the reduction in pain intensity , according to the visual analogue scale ( iVAS ) , at 2 weeks after the start of treatment . The secondary outcomes will be functional status with respect to LBPGP ( according to the Rol and -Morris disability question naire ) , health-related quality of life ( SF12 ) at 2 weeks after the start of treatment , and iVAS at 12 and 48 weeks postpartum . Discussion This trial will implement a high- quality methodology and may provide evidence for the efficacy , safety , and specificity of auricular acupuncture as a treatment for pregnant women with LBPGP.Trial registration Current Controlled Trials IS RCT N41033073 ( date 20/03/2014 ) Abstract Objectives To compare the efficacy of st and ard treatment , st and ard treatment plus acupuncture , and st and ard treatment plus stabilising exercises for pelvic girdle pain during pregnancy . Design R and omised single blind controlled trial . Setting s East Hospital , Gothenburg , and 27 maternity care centres in Sweden . Participants 386 pregnant women with pelvic girdle pain . Interventions Treatment for six weeks with st and ard treatment ( n = 130 ) , st and ard treatment plus acupuncture ( n = 125 ) , or st and ard treatment plus stabilising exercises ( n = 131 ) . Main outcome measures Primary outcome measure was pain ( visual analogue scale ) ; secondary outcome measure was assessment of severity of pelvic girdle pain by an independent examiner before and after treatment . Results After treatment the stabilising exercise group had less pain than the st and ard group in the morning ( median difference = 9 , 95 % confidence interval 1.7 to 12.8 ; P = 0.0312 ) and in the evening ( 13 , 2.7 to 17.5 ; P = 0.0245 ) . The acupuncture group , in turn , had less pain in the evening than the stabilising exercise group ( −14 , −18.1 to −3.3 ; P = 0.0130 ) . Furthermore , the acupuncture group had less pain than the st and ard treatment group in the morning ( 12 , 5.9 to 17.3 ; P < 0.001 ) and in the evening ( 27 , 13.3 to 29.5 ; P < 0.001 ) . Attenuation of pelvic girdle pain as assessed by the independent examiner was greatest in the acupuncture group . Conclusion Acupuncture and stabilising exercises constitute efficient complements to st and ard treatment for the management of pelvic girdle pain during pregnancy . Acupuncture was superior to stabilising exercises in this study OBJECTIVE To investigate the efficacy of home-based specific stabilizing exercises focusing on the local stabilizing muscles as the only intervention in the treatment of persistent postpartum pelvic girdle pain . DESIGN A prospect i ve , r and omized , single-blinded , clinical ly controlled study . SUBJECTS Eighty-eight women with pelvic girdle pain were recruited 3 months after delivery . METHODS The treatment consisted of specific stabilizing exercises targeting the local trunk muscles . The reference group had a single telephone contact with a physiotherapist . Primary outcome was disability measured with Oswestry Disability Index . Secondary outcomes were pain , health-related quality of life ( EQ-5D ) , symptom satisfaction , and muscle function . RESULTS No significant differences between groups could be found at 3- or 6-month follow-up regarding primary outcome in disability . Within-group comparisons showed some improvement in both groups in terms of disability , pain , symptom satisfaction and muscle function compared with baseline , although the majority still experienced pelvic girdle pain . CONCLUSION Treatment with this home-training concept of specific stabilizing exercises targeting the local muscles was no more effective in improving consequences of persistent postpartum pelvic girdle pain than the clinical ly natural course . Regardless of whether treatment with specific stabilizing exercises was carried out , the majority of women still experienced some back pain almost one year after pregnancy Background The incidence of pelvic girdle pain ( PGP ) in pregnancy is wide ranged depending on definition , the utilised diagnostic means , and the design of the studies . PGP during pregnancy has negative effects on activities of daily living and causes long sick leave , which makes it a major public health issue . Our objectives were to explore the frequency of sick leave in pregnancy due to PGP , assess the relationship between different types of pain-related activities of daily living , examine physical workload , type of work in relation to sick leave , and to explore factors that make women less likely to take sick leave for PGP . Methods All women giving birth at the maternity ward of Stavanger University Hospital , Norway , were asked to participate and complete a question naire on demographic features , PGP , pain-related activities of daily living , sick leave in general and for PGP , frequency of exercising before and during pregnancy . Drawings of pelvic girdle and low back area were used for the localization of pain . PGP intensity was then rated retrospectively on a numerical rating scale . Non-parametric tests , multinomial logistic regression and sequential linear regression analysis were used in the statistical analysis . Results PGP is a frequent and major cause of sick leave during pregnancy among Norwegian women , which is also reflected in activities of daily living as measured with scores on all Oswestry disability index items . In the multivariate analysis of factors related to sick leave and PGP we found that work satisfaction , problems with lifting and sleeping , and pain intensity were risk factors for sick leave . In addition , women with longer education , higher work satisfaction and fewer problems with sitting , walking and st and ing , were less likely to take sick leave in pregnancy , despite the same pain intensity as women being on sick leave . Conclusions A coping factor in pregnant women with PGP was discovered , most likely dependant on education , associated with work situation and /or work posture , which decreases sick leave . We recommend these issues to be further examined in a prospect i ve longitudinal study since it may have important implication s for sick leave frequency during pregnancy Background Pregnancy-related pelvic girdle and /or low back pain is a controversial syndrome because insight in etiology and prognosis is lacking . The controversy relates to factors eliciting pain and some prognostic factors such as the interpretation of pain at the symphysis . Recent research about treatment strategies also reflects those various opinions , in fact suggesting there is professional uncertainty about the optimal approach . Currently , physiotherapists often prescribe a pain-contingent treatment regime of relative rest and avoiding several day-to-day activities . Additionally , treatment more often includes an exercise program to guide rectification of the muscle imbalance and alignment of the pelvic girdle . Effectiveness of those interventions is not proven and the majority of the studies are method ologically flawed . Investigators draw particular attention to biomedical factors but there is growing evidence that important prognostic issues such as biopsychosocial factors appear to be even more important as point of action in a treatment program . Methods / design This pragmatic r and omized controlled trial is design ed to evaluate the effectiveness of a tailor-made treatment program with respect to biopsychosocial factors in primary care . The effect of the experimental intervention and usual care are evaluated as they are applied in primary health care . The trial is embedded in a cohort study that is design ed as a longitudinal , prospect i ve study , which studies prevalence , etiology , severity and prognosis during pregnancy until one year after delivery . The present paper focuses on choices regarding recruitment procedures , in-/exclusion criteria and the development of a well-timed intervention . Discussion This section briefly discusses the actions taken to minimize bias in the design , the proper time-window for the experimental intervention and the contrast between the experimental intervention and usual care Reporting harms may cause more trouble and discredit than the fame and glory associated with successful reporting of benefits ( 1 ) . The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement , a checklist ( Table 1 ) flow diagram first published in 1996 and revised 5 years later ( 2 , 3 ) , is an effort to st and ardize , and thereby improve , published reports of r and omized , controlled trials ( RCTs ) . One of the additions to the 2001 revision was an item about reporting adverse events . This single item did not do full justice to the importance of harms-related issues . The CONSORT Group met in September 2001 to discuss how to correct this deficiency . We aim ed to provide evidence -based guidance on the reporting of harms in RCTs . First , we search ed MEDLINE , EMBASE , Web of Science , and the Cochrane Library using a wide array of terms related to harms and identified pertinent evidence . We also communicated with experts and review ed bibliographies of identified articles to find additional studies . At a meeting in Montebello , Quebec , Canada , in May 2003 , CONSORT Group members , including several journal editors and additional experts in related fields , held a structured discussion of recommendations about reporting of harms-related issues in RCTs . The discussion s led to a written document that we circulated among the team members for comment . The present manuscript describes our recommendations on the appropriate reporting of harms in RCTs . Table 1 . Original CONSORT Checklist The terminology of harms-related issues in RCTs is confusing and often misleading or misused ( see Glossary ) ( 4 , 5 ) . Safety is a reassuring term that may obscure the real and potentially major harms that drugs and other interventions may cause . We encourage authors to use the term harms instead of safety . In addition to misused terminology , reporting of harms in RCTs has received less attention than reporting of efficacy and effectiveness and is often inadequate ( 6 - 14 ) . In short , both scientific evidence and ethical necessity call for action to improve the quality of reporting of harms in RCTs ( 15 , 16 ) . Here , we present a set of recommendations and accompanying explanations for the proper reporting of harms in RCTs . These recommendations should complement the existing CONSORT statement ( Table 2 ) . Examples are presented on the Annals and CONSORT ( www.consort-statement.org ) Web sites . Table 2 . Checklist of Items To Include When Reporting Harms in R and omized , Controlled Trials Recommendations Title and Abstract Recommendation 1 . If the study collected data on harms and benefits , the title or abstract should so state . The title should mention harms if the study of harms was a key trial objective . Many phase I and phase II trials , some phase II/III trials , and most phase IV trials ( 17 , 18 ) target harms as primary outcomes . Yet , the title and abstract seldom contain the word harm . Among 375143 entries in the Cochrane Central Register of Controlled Trials ( Cochrane Library , issue 3 , 2003 ) , search ing titles with the search terms harm or harms yielded 337 references ( compared with 55374 for efficacy and 23415 for safety ) . Of the 337 , excluding several irrelevant articles on self-harm or harm reduction , only 3 trial reports and 2 abstract s contained the word harm in their titles . Authors should present information on harms in the abstract . If no important harms occurred , authors should so state . Explicit reference to the reporting of adverse events in the title or abstract is also important for appropriate data base indexing and information retrieval ( 19 ) . Introduction Background Recommendation 2 . If the trial addresses both harms and benefits , the introduction should so state . The introduction states the scientific background and rationale of an RCT . This requires a balanced presentation whereby the possible benefits of the intervention under investigation are outlined along with the possible harms associated with the treatment . R and omized , controlled trials that focus primarily on harms should clearly state this interest when describing the study objectives in the Introduction and in defining these objectives in the Methods . Methods Outcomes Recommendation 3 . List addressed adverse events with definitions for each ( with attention , when relevant , to grading , expected vs. unexpected events , reference to st and ardized and vali date d definitions , and description of new definitions ) . The Methods section should succinctly define the recorded adverse events ( clinical and laboratory ) . Authors should clarify whether the reported adverse events encompass all the recorded adverse events or a selected sample . They should explain how , why , and who selected adverse events for reporting . In trials that do not mention harms-related data , the Methods section should briefly explain the reason for the omission ( for example , the design did not include the collection of any information on harms ) . Authors should also be explicit about separately reporting anticipated and unexpected adverse events . Expectation may influence the incidence of reported or ascertained adverse events . Making participants aware in the consent form of the possibility of a specific adverse event ( priming ) may increase the reporting rate of the event ( 20 ) . Another example of priming is the finding that the rates of withdrawals due to adverse events and the rates of specific adverse events were significantly higher in trials of aspirin , diclofenac , or indomethacin with comparator drugs compared with placebo-controlled trials ( 21 ) . Presumably , participants were more eager to come forth and report an adverse event or to withdraw from treatment when they knew they could not be receiving inactive placebo . Authors should report whether they used st and ardized and vali date d measurement instruments for adverse events . Several medical fields have developed st and ardized scales ( 22 - 32 ) . Use of nonvali date d scales is common . The source document for well-established definitions and scales should be referenced . New definitions for adverse events should be explicit and clear . Authors should describe how they developed and vali date d new scales . For interventions that target healthy individuals ( for example , many preventive interventions ) , any harm , however minor , may be important to capture and report because the balance of harms and benefits may easily lean toward harms in a low-risk population . For other population s and for interventions that improve major outcomes ( for example , survival ) , severe and life-threatening adverse events may be the only ones that are important in the balance of benefits and harms . Recommendation 4 . Clarify how harms-related information was collected ( mode of data collection , timing , attribution methods , intensity of ascertainment , and harms-related monitoring and stopping rules , if pertinent ) . It is important to describe the question naires , interviews , and tests used to collect information on harms , as well as their timing during follow-up . Passive surveillance of harms leads to fewer recorded adverse events than active surveillance ( 4 ) . Open-ended questions may yield different information , both quantitatively and qualitatively , than structured question naires ( 33 ) . Studies of nonsteroidal , anti-inflammatory drugs ( NSAIDs ) exemplify how data collection methods can affect the detection and reporting of harms . When selective NSAIDs with fewer gastrointestinal adverse events became available , trials reported more than 10 times as many ulcers when comparing these drugs with older NSAIDs as when older NSAIDs were compared with placebo . In the newer trials , more ulcers were detected because participants had regular endoscopy , and the case definition of ulcers was more sensitive ( 34 ) . Authors should specify the time frame of surveillance for adverse events . Some investigators stop recording adverse events at the end of the intervention period or a certain number of days afterward ( for example , 30 days after discontinuation of drug therapy ) and miss events with long latency ( 35 ) . Surgical trials often capture only the adverse events that occur intraoperatively . Several important surgical complications are likely to occur later . Finally , in crossover trials , delayed events might occur while the patient is taking a subsequent assigned treatment . Attribution is the process of deciding whether an adverse event is related to the intervention . Whenever authors filter events through an attribution process , they should state who makes the attribution ( investigators , participants , sponsors , or combinations ) , whether the process is blinded to assigned treatment , and what definitions of adverse events they use ( 4 ) . Discontinuations and withdrawals due to adverse events are especially important because they reflect the ultimate decision of the participant and /or physician to discontinue treatment . Although treatment may occasionally be discontinued for mild or moderate adverse events , attributing discontinuation to a specific reason ( to toxicity , lack of efficacy , other reasons , or combinations of reasons ) may be difficult . For example , in psychopharmacology , dropouts may reflect treatment ineffectiveness as much as toxicity-related intolerance ( 36 ) . Trial reports should specify who gave the reasons for discontinuation ( participants or physicians ) and whether attribution was blinded to the assigned treatment . For example , even in blinded trials , participants and their clinicians are often unblinded before they decide whether to discontinue the intervention . It is important to report participants who are nonadherent or lost to follow-up because their actions may reflect their inability to tolerate the intervention . Moreover , authors should specify how they h and led withdrawals in the analyses of the data . R and omized , controlled trials should report any plan for monitoring for harms and rules for stopping the trial because of harms ( 37 ) . They should clarify whether stopping guidelines examine benefits and harms PURPOSE Despite the high prevalence of back pain and its subsequent effects in post-partum women , intervention programs are scarce . The purpose of this study was to test the effects of a back-pain-reducing program on post-partum women who experienced low-back pain during pregnancy . METHODS A non-equivalent control-group pretest-posttest design was used . Pregnant women who attended a hospital for prenatal check-ups and experienced back pain participated in an intervention program ( n=27 ) , and the results were compared with women in a control group from another hospital ( n=25 ) . RESULTS At 8 weeks post-partum , the pain intensity , functional limitations were lower in the intervention group than in the control group . However , differences in mean change of the pain intensity and functional limitations between 36 and 39 weeks of gestation and at 8 weeks post-partum were not statistically significant between the groups . Moreover , the flexibility , post-partum functional status , and post-partum depression did not differ significantly between the groups . CONCLUSIONS A back-pain-relief program in this study was not effective to reduce the back-pain intensity in post-partum women and to decrease the associated functional limitations . The implication s for nursing practice and directions for future research are discussed Background . The study was design ed to evaluate the analgesic effect and possible adverse effects of acupuncture for pelvic and low‐back pain during the last trimester of pregnancy OBJECTIVE The purpose of this study was to describe the clinical outcomes of patients with pregnancy-related lumbopelvic pain ( PRLP ) treated according to a diagnosis-based clinical decision rule . METHODS This was a prospect i ve observational cohort of consecutive patients with PRLP . Data on 115 patients were collected at baseline and on 78 patients at the end of the active treatment . Disability was measured using the Bournemouth Disability Question naire ( BDQ ) . Pain intensity was measured using the Numerical Rating Scale for pain ( NRS ) . Patients were also asked to self-rate their improvement . Care was provided by a chiropractic physician/physical therapist team . RESULTS Fifty-seven patients ( 73 % ) reported their improvement as either " excellent " or " good . " The mean patient-rated improvement was 61.5 % . The mean improvement in BDQ was 17.8 points . The mean percentage of improvement in BDQ was 39 % and the median was 48 % . Mean improvement in pain was 2.9 points . Fifty-one percent of the patients had experienced clinical ly significant improvement in disability and 67 % patients had experienced clinical ly significant improvement in pain . Patients were seen an average 6.8 visits . Follow-up data for an average of 11 months after the end of treatment were collected on 61 patients . Upon follow-up , 85.5 % of patients rated their improvement as either " excellent " or " good . " The mean patient-rated improvement was 83.2 % . The mean improvement in BDQ was 28.1 points . The mean percentage of improvement in BDQ was 68 % and the median was 87.5 % . Mean improvement in pain was 3.5 points . Seventy-three percent of the patients had experienced clinical ly significant improvement in disability and 82 % patients had experienced clinical ly significant improvement in pain . CONCLUSIONS The management strategy used in this study appeared to yield favorable outcomes in this patient population and appears to be a safe option for patients with PRLP , although because of this study 's sample size , rare complications are not likely to be detected . In addition , the absence of r and omization and a control group limits interpretation with regard to clinical effectiveness . R and omized , controlled trials are necessary to distinguish treatment effects from the natural history of PRLP OBJECTIVE To develop a clinical prediction rule ( CPR ) for identifying postpartum women with low back pain ( LBP ) and /or pelvic girdle pain ( PGP ) whose functional disability scores improve with a high-velocity thrust technique ( HVTT ) conducted by a physical therapist . DESIGN Prospect i ve cohort . SETTING Outpatient physical therapy departments . PARTICIPANTS Sixty-nine postpartum women referred to physical therapy with the complaint of LBP and /or PGP . METHODS Subjects underwent a physical examination and a HVTT to the lumbopelvic region . MAIN OUTCOME MEASURES Success with treatment was determined by the use of percent changes in disability scores and served as the reference st and ard for determining accuracy of the examination variables . Variables with univariate prediction of success and nonsuccess were combined into multivariate CPRs . RESULTS Fifty-five subjects ( 80 % ) had success with the HVTT . A CPR for success with 4 criteria was identified . The presence of 2 of 4 criteria ( positive likelihood ratio=3.05 ) increased the probability of success from 80 % to 92 % . A CPR for treatment failure with 3 criteria was identified . The presence of 2 of 3 criteria ( positive likelihood ratio=11.79 ) increased the probability of treatment failure from 20 % to 75 % . CONCLUSIONS The pretest probability of success ( 80 % ) is sufficient to reassure the clinician about the decision to use a HVTT to the lumbopelvic region in postpartum women with LBP and /or PGP . If 2 of 3 criteria for treatment failure are met in the CPR , an alternative approach is warranted . An intervention such as the HVTT is compelling , given the need to minimize pharmaceutical remedies in women who are potentially breast-feeding post partum Study Design . In this prospect i ve , consecutive , controlled cohort study , the authors analyzed the impact of a differentiated , individual‐based treatment program on sick leave during pregnancy for women experiencing lumbar back or posterior pelvic pain during pregnancy . Objective . To identify patients with pain early in pregnancy and , by means of individual information and differentiated physiotherapy , reduce sick leave during pregnancy . Summary of Background Data . Sick leave for back pain during pregnancy is common , and treatment programs have been aim ed at reducing pain , for that reason . In Sweden , the average sick leave due to back pain during pregnancy is 7 weeks . Methods . All pregnant women who attended a specific antenatal clinic and experienced lumbar back or posterior pelvic pain were included in an intervention group , and results were compared with women in a control group from another antenatal clinic . Results . The intervention group comprised 54 women , compared with 81 women in the control group . Thirty‐three women were on sick leave for an average of 30 days in the intervention group versus 45 women for an average of 54 days in the control group ( P < 0.001 ) . The reduction in sick leave reduced insurance costs by approximately $ 53,000 U.S. Conclusions . Sick leave for lumbar back and posterior pelvic pain in the intervention group was significantly reduced with the program , and the program was cost effective OBJECTIVE To investigate the effect of a supervised , structured exercise programme on the occurrence and severity of pregnancy-related lumbopelvic pain . DESIGN R and omized controlled trial . SUBJECTS A total of 45 pregnant women were r and omly assigned to 2 groups : an experimental group ( n = 20 ; mean age 32.8 ( st and ard deviation ( SD ) 3.6 ) years ) and a control group ( n = 22 ; mean age 32.2 years ( SD 4.9 ) ) . METHODS Exercise intervention for the experimental group consisted of aerobic and resistance exercises performed bi-weekly from the date of inclusion into the study until the end of pregnancy , together with at least 30 min of brisk daily walks . A numeric rating scale , Rol and -Morris Disability Question naire ( RMDQ ) , and Pelvic Girdle Question naire ( PGQ ) were used to measure outcomes . The control group received only st and ard antenatal care . RESULTS There were significant differences between the 2 groups on the numeric rating scale , PGQ and RMDQ scores in the 36th week of pregnancy ( p = 0.017 ; p = 0.005 ; p < 0.001 , respectively ) in favour of the experimental group . CONCLUSION The exercise programme had a beneficial effect on the severity of lumbopelvic pain in pregnancy , reducing the intensity of pain and the level of disability experienced as a result Background Many women have low back pain ( LBP ) or pelvic girdle pain ( PGP ) during pregnancy , but there is limited evidence of effective primary and secondary preventive strategies . Objective The purpose of this study was to investigate whether a group-based exercise program can reduce the prevalence and severity of LBP and PGP in pregnant women . Design An observer-blinded r and omized controlled trial with equal assignments to a training group and a control group was conducted . Setting The study was conducted in primary care maternity units in 2 suburban municipalities in the southeastern part of Norway . Patients The participants were 257 pregnant women who were healthy and between 18 and 40 years of age before gestation week 20 . Intervention The training group received supervised exercises in groups once a week , and the control group received st and ard care . Measurements The main outcome measures were self-reported LBP and self-reported PGP . Secondary outcome measures were pain intensity in the morning and evening , disability , and 8-Item Short-Form Health Survey ( SF-8 ) Physical Component Summary ( PCS ) and Mental Component Summary ( MCS ) scores . Follow-up measurements were performed at gestation weeks 24 , 28 , 32 , and 36 . Results Overall , there was no effect of the program on the prevalence of PGP ( odds ratio=1.03 , 95 % confidence interval [CI]=0.66 to 1.59 ) or LBP ( odds ratio=0.77 , 95 % CI=0.50 to 1.19 ) . For the secondary outcomes , the estimated mean differences between the groups were −0.4 ( 95 % CI=−0.8 to 0.1 ) for pain intensity in the morning , −0.4 ( 95 % CI=−1.0 to 0.2 ) for pain intensity in the evening , −1.0 ( 95 % CI=−2.2 to 0.0 ) for disability , 1.8 ( 95 % CI=0.0 to 3.7 ) for the SF-8 PCS , and −0.6 ( 95 % CI=−2.2 to 1.4 ) for the SF-8 MCS . Limitations Due to low statistical power , the estimates for the primary outcomes are imprecise . Conclusions Supervised group exercise did not reduce the prevalence of LBP or PGP in pregnancy BACKGROUND The purpose of this study was to assess the value of fluoroscopy-based computer-assisted surgery ( CAS ) for the insertion of iliosacral screws . The results of CAS were compared with the results of a conventionally operated prospect i ve control group . Endpoints of this study were fluoroscopy time , guide wire insertion time , operation time and complication rate . METHODS The study group consisted of 24 patients with postpartum pelvic pain syndrome . All patients were treated with a stabilization of the pelvic ring by means of an anterior plate fixation and autologous tricortical bone graft as well as two iliosacral screws bilaterally . Consequently , the results of 48 versus 48 iliosacral screw fixations could be evaluated . Conventionally operated patients were turned from the supine to the prone position intraoperatively , whereas CAS operated patients were operated in the supine position . One surgeon performed all operations . RESULTS The fluoroscopy time in the CAS group was 0.7 minutes versus 1.8 minutes in the conventionally treated group ( p < 0.01 ) . The mean insertion time for four guide wires was 20.2 minutes in the CAS versus 19.4 minutes in the conventionally operated group ( p = 0.6 ) . The mean operation time in the CAS group was 97 minutes ; 116 minutes in the conventional group ( p = 0.03 ) . In the CAS group one patient had pain and a sensory deficit of S2 postoperatively . The Fisher 's exact test showed no difference in complication rate between the two groups ( p = 0.26 ) . CONCLUSIONS The fluoroscopy time is decreased with a factor 2.5 using CAS . Guide wire insertion time was similar in both groups . The reduction in operation time using CAS was due to fact that patients were operated in the supine position during the whole procedure . This study shows that CAS is a save technique for insertion of iliosacral screws Study Design . A r and omized controlled trial with stratified block design . Objectives . To evaluate a treatment program focusing on whether specific stabilizing exercises for patients with pelvic girdle pain after pregnancy reduce pain , improve functional status , and improve quality of life . Summary of Background Data . The evidence of effectiveness of treatment for pelvic girdle pain is weak . Recent research has focused on the importance of activation of muscles for motor control and stability of the lumbopelvic region . To the authors ’ knowledge , the efficacy of applying these principles for pelvic girdle pain has not previously been evaluated in a r and omized controlled trial . Methods . Eighty-one women with pelvic girdle pain were assigned r and omly to two treatment groups for 20 weeks . One group received physical therapy with a focus on specific stabilizing exercises . The other group received individualized physical therapy without specific stabilizing exercises . Assessment s were administered by a blinded assessor , at baseline , after intervention and 1 year post partum . Main outcome measures were pain , functional status and quality of life . Results . There were no dropouts . After intervention and at 1 year post partum , the specific stabilizing exercise group showed statistically and clinical ly significant lower pain intensity , lower disability , and higher quality of life compared with the control group . Group difference in median values for evening pain after treatment was 30 mm on the Visual Analog Scale . Disability was reduced by more than 50 % for the exercise group ; changes were negligible in the control group . Significant differences were also observed for physical tests , in favor of the specific exercise group . Conclusion . An individualized treatment approach with specific stabilizing exercises appears to be more effective than physical therapy without specific stabilizing exercises for women with pelvic girdle pain after pregnancy BACKGROUND AND PURPOSE Symphysis pubis pain is a significant problem for some pregnant women . The purpose of this study was to investigate the effects of exercise , advice , and pelvic support belts on the management of symphysis pubis dysfunction during pregnancy . SUBJECTS Ninety pregnant women with symphysis pubis dysfunction were r and omly assigned to 3 treatment groups . METHODS A r and omized masked prospect i ve experimental clinical trial was conducted . Specific muscle strengthening exercises and advice concerning appropriate methods for performing activities of daily living were given to the 3 groups , and 2 of the groups were given either a rigid pelvic support belt or a nonrigid pelvic support belt . The dependent variables , which were measured before and after the intervention , were a Rol and -Morris Question naire score , a Patient-Specific Functional Scale score , and a pain score ( 101-point numerical rating score ) . RESULTS After the intervention , there was a significant reduction in the Rol and -Morris Question naire score , the Patient-Specific Functional Scale score , and the average and worst pain scores in all groups . With the exception of average pain , there were no significant differences between groups for the other measures . DISCUSSION AND CONCLUSION The findings indicate that the use of either a rigid or a nonrigid pelvic support belt did not add to the effects provided by exercise and advice OBJECTIVE The primary aim of this study was to examine whether 1 week of continuous auricular acupuncture could reduce low back and posterior pelvic pain associated with pregnancy . STUDY DESIGN A r and omized controlled trial was conducted on pregnant women who have lower back and posterior pelvic pain . These women were r and omly assigned into an acupuncture group , a sham acupuncture group , or a waiting list control group . All participants were monitored for 2 weeks . RESULTS Baseline and day 7 showed significant group differences in pain ( F = 15 ; P < .0001 ) and in the disability rating index score ( F = 7 ; P < .0001 ) . The participants in the acupuncture group reported a significant reduction of pain and improvement of functional status as compared with those in the sham acupuncture and control groups . CONCLUSION One week of continuous auricular acupuncture decreases the pain and disability experienced by women with pregnancy-related low back and posterior pelvic pain Abstract Objective To assess the efficacy of an exercise program towards reducing back pain in pregnant women . Methods In this prospect i ve control study , 145 low risk pregnant women who scored more than 20 for functional limitation assessment were recruited . The severity of back pain was assessed using the visual analoque scale ( VAS ) and the functional limitation was assessed using the Oswestry disability question naire ( ODQ ) . All participants were informed of back care measures and provided with Paracetamol as an adjunct analgesia . The intervention group will have a session with a trained physiotherapist . Subsequently , all participants will be required to fill in a similar question naire regarding pain intensity and functional limitation assessment after 6 weeks post-intervention . Results There was a significant reduction in the VAS score and improvement in functional ODQ score in the intervention group . The median usage of Paracetamol as an analgesia to control back pain in the control group was 500 mg higher than the intervention group . There was a weak association of age , parity , duration of back pain , and body mass index with functional ODQ score at 6 week following intervention . Conclusion The back pain exercise reducing program was effective in reducing back pain intensity and analgesia usage with a significant improvement in functional ability OBJECTIVE Pelvic girdle pain is a common complaint of pregnant women . There are limited data on comparison between the effectiveness of stabilizing exercises and lumbopelvic belt on the treatment of these patients . The objective of this study was to compare the effect of lumbopelvic belt plus information , home based pelvic girdle stabilizing exercises plus information and information alone on pain intensity , functional status and quality of life of pregnant women with pelvic girdle pain . METHODS In this r and omized clinical trial pregnant women with pelvic girdle pain ( n=105 ) were r and omly allocated to three groups ; Control group ( n=35 ) that received general information , exercise group ( n=31 ) that in addition to general information were asked to perform specific pelvic stabilizing exercises at home and belt group ( n=31 ) that received non-rigid lumbopelvic belt and the information . The primary outcome variables were pain intensity and functional status of the participants which were measured using visual analogue scale and Oswestry Disability Index ( ODI ) respectively . Quality of life of participants was measured using WHOQOL-BREF question naire . All measurements were performed at baseline , 3 and 6 weeks after the study conduction . RESULTS The pain intensity of patients in belt group in comparison to other groups was decreased significantly at both 3 and 6 weeks follow-ups . The mean score of ODI of patients in belt group was also improved more than exercise and control groups significantly . CONCLUSIONS On base of our results , it can be found that in short term lumbopelvic belt and information in treatment of pregnant women with pelvic girdle pain is superior to exercise plus information or information alone Background . Prevention of lumbopelvic pain in pregnancy has been sparsely studied . One aim of this study was to assess if a 12‐week training program during pregnancy can prevent and /or treat lumbopelvic pain . A r and omized controlled trial was conducted at Trondheim University Hospital and three outpatient physiotherapy clinics . Three hundred and one healthy nulliparous women were included at 20 weeks of pregnancy and r and omly allocated to a training group ( 148 ) or a control group ( 153 ) . Methods . The outcome measures were self‐reported symptoms of lumbopelvic pain ( once per week or more ) , sick leave , and functional status . Pain drawing was used to document the painful area of the body . The intervention included daily pelvic floor muscle training at home , and weekly group training over 12 weeks including aerobic exercises , pelvic floor muscle and additional exercises , and information related to pregnancy . Results . At 36 weeks of gestation women in the training group were significantly less likely to report lumbopelvic pain : 65/148 ( 44 % ) versus 86/153 ( 56 % ) ( p = 0.03 ) . Three months after delivery the difference was 39/148 ( 26 % ) in the training group versus 56/153 ( 37 % ) in the control group ( p = 0.06 ) . There was no difference in sick leave during pregnancy , but women in the training group had significantly ( p = 0.01 ) higher scores on functional status . Conclusions . A 12‐week specially design ed training program during pregnancy was effective in preventing lumbopelvic pain in pregnancy Study Design This study analyzed an education and training program concerning back and pelvic problems among pregnant women . Objective The program was aim ed at reducing tack and pelvic posterior pain during pregnancy . Summary of Background Data Low back and posterior pelvic pain accounts for the majority of sick leave among pregnant women . No previous study has suggested any type of solution to this problem . Methods Four hundred and seven consecutive pregnant women were included in the study and r and omly assigned into three groups . Group A served as controls while different degrees of interventions were made in groups B and C. Results Serious back or posterior pelvic pain developed in 47 % of all women . Pain-related problems were reduced in groups B and C ( P < 0.05 ) , and sick-leave frequency was reduced in group C ( P < 0.01 ) . For some of the women in this group pain intensity was also reduced 8 weeks post partum ( P < 0.005 ) . Weekly physical exercise before pregnancy reduced the risk for back pain problems in pregnancy ( P < 0.05 ) . A non-elastic sacro-illac belt offered some pain relief to 82 % of the women with posterior pelvic pain . Conclusions An individually design ed program reduced sick leave during pregnancy . Working with groups was less effective . Differentiation between low back and posterior pelvic pain was essential . Good physical fitness reduced the risk of back pain in a subsequent pregnency . Reduction of posterior pelvic pain by a non-elastic pelvic support was experienced by 82 % of the women with posterior pelvic pain BACKGROUND AND PURPOSE Exercises for low back and pelvic pain are supposed to increase muscle force to reduce symptoms , but they could exacerbate symptoms by loading of the spinal and pelvic structures . The purpose of this study was to investigate the value of grade d exercises of the diagonal trunk muscle systems . SUBJECTS The subjects were 44 women with persistent pelvic pain after pregnancy ( mean age=31.7 years , SD=3.2 , range=23.6 - 37.5 ; mean period postpartum=4.1 months , SD=2.2 , range=1.7 - 5.6 ) . METHODS Subjects were r and omly assigned to 1 of 3 groups : ( 1 ) a group that performed exercises to increase the force of the diagonal trunk muscle systems , ( 2 ) a group that received training of the longitudinal trunk muscle systems , and ( 3 ) a group that was instructed to refrain from exercises . Pain , fatigue , perceived general health , and mobility of the pelvic joints as measured with radiographs were the outcome measures . RESULTS After 8 weeks , no differences were found among the 3 groups . CONCLUSION AND DISCUSSION In treating patients with persistent pelvic pain , training of the diagonal trunk muscle systems , without individual coaching , has no additional value above instructions and use of a pelvic belt without exercises . Whether the treatment is ineffective or whether exacerbation of symptoms due to loading of the spinal and pelvic structures obscures any potential benefit of increased muscle force can not be determined from the study design Objective . An earlier publication showed that acupuncture and stabilising exercises as an adjunct to st and ard treatment was effective for pelvic girdle pain during pregnancy , but the post‐pregnancy effects of these treatment modalities are unknown . The aim of this follow‐up study was to describe regression of pelvic girdle pain after delivery in these women . Design . A r and omised , single blind , controlled trial . Setting . East Hospital and 27 maternity care centres in Göteborg , Sweden . Population . Some 386 pregnant women with pelvic girdle pain . Methods . Participants 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 ) . Main outcome measures . Primary outcome measures : pain intensity ( Visual Analogue Scale ) . Secondary outcome measure : assessment of the severity of pelvic girdle pain by an independent examiner 12 weeks after delivery . Results . Approximately three‐quarters of all the women were free of pain 3 weeks after delivery . There were no differences in recovery between the 3 treatment groups . According to the detailed physical examination , pelvic girdle pain had resolved in 99 % of the women 12 weeks after delivery . Conclusions . This study shows that irrespective of treatment modality , regression of pelvic girdle pain occurs in the great majority of women within 12 weeks after delivery CONTEXT Persistent low back pain ( LBP ) is a common complaint among women during and after pregnancy , and its effects on quality of life can be disabling . OBJECTIVE To evaluate the effectiveness of osteopathic manipulative therapy ( OMTh ; manipulative care provided by foreign-trained osteopaths ) in women with persistent LBP and functional disability after childbirth . METHODS A pragmatic r and omized controlled trial was conducted among a sample of women with a history of pregnancy-related LBP for at least 3 months after delivery . Participants were identified from the general population in Germany . By means of external r and omization , women were allocated to an OMTh group and a waitlist control group . Osteopathic manipulative therapy was provided 4 times at intervals of 2 weeks , with a follow-up after 12 weeks . The OMTh was tailored to each participant and based on osteopathic principles . The participants allocated to the control group did not receive OMTh during the 8-week study ; rather , they were put on a waiting list to receive OMTh on completion of the study . Further , they were not allowed to receive any additional treatment ( ie , medication , physical therapy , or other sources of pain relief ) during the study period . The main outcome measures were pain intensity as measured by a visual analog scale and the effect of LBP on daily activities as assessed by the Oswestry Disability Index ( ODI ) . RESULTS A total of 80 women aged between 23 and 42 years ( mean [ SD ] , 33.6 [ 4.5 ] years ) were included in the study , with 40 in the OMTh group and 40 in the control group . Pain intensity decreased in the OMTh group from 7.3 to 2.0 ( 95 % CI , 4.8 - 5.9 ; P<.001 ) and in the control group from 7.0 to 6.5 ( 95 % CI , -0.2 to -0.9 ; P=.005 ) . The between-group comparison of changes revealed a statistically significant improvement in pain intensity in the OMTh group ( between-group difference of means , 4.8 ; 95 % CI , 4.1 - 5.4 ; P<.001 ) and level of disability ( between-group difference of means , 10.6 ; 95 % CI , 9.9 - 13.2 ; P<.005 ) . The follow-up assessment in the OMTh group ( n=38 ) showed further improvement . CONCLUSION During 8 weeks , OMTh applied 4 times led to clinical ly relevant positive changes in pain intensity and functional disability in women with postpartum LBP . Further studies that include prolonged follow-up periods are warranted . ( German Clinical Trials Register : DRKS00006280 . ) BACKGROUND Although many pregnant women experience back pain , it has not considered an important health problem . No study has investigated the effects of a back-pain-reducing program ( BPRP ) during pregnancy for Korean women . OBJECTIVE The purpose of this study was to evaluate the effect of a program design ed to reduce back pain in pregnant women . METHODS A non-equivalent control-group pretest-posttest design was used . Pregnant women who attended an antenatal clinic and experienced back pain during their pregnancy were included in an intervention group ( n=29 ) , and their intensity of back pain , functional limitation and anxiety were compared with women in a control group from another antenatal clinic ( n=27 ) . The data were collected at three time points : prior to intervention , and 6 and 12 weeks after intervention . RESULTS At 12 weeks after intervention , the intensity of back pain experienced by the intervention group was significantly lower than that of the control group . However , there were no statistically significant differences between the groups with respect to functional limitations and anxiety . CONCLUSIONS The findings show that the pain-reducing program developed for this study was effective in reducing the intensity of back pain experienced by pregnant women . Promoting good posture and regular exercise can be recommended as a method to relieve back pain in pregnancy women . Further studies are needed to confirm the effect of the BPRP during pregnancy OBJECTIVE To compare the effect of a l and -based , physical exercise program versus water aerobics on low back or pelvic pain and sick leave during pregnancy . DESIGN R and omized controlled clinical trial . SETTING Three antenatal care centers . PARTICIPANTS 390 healthy pregnant women . INTERVENTIONS A l and -based physical exercise program or water aerobic once a week during pregnancy . MAIN OUTCOME MEASURES Sick leave , pregnancy-related low back pain or pregnancy-related pelvic girdle pain , or both . RESULTS Water aerobics diminished pregnancy-related low back pain ( p=.04 ) and sick leave due to pregnancy-related low back pain ( p=.03 ) more than a l and -based physical exercise program . CONCLUSIONS Water aerobics can be recommended for the treatment of low back pain during pregnancy . The benefits of a l and -based physical exercise program are question able and further evaluation is needed Adverse and analgesic effects of acupuncture during the second and third trimesters of pregnancy were studied retrospectively in an observational study including 167 consecutive patients with lower back pain , pelvic pain , or both . In each patient acupuncture was given on at least two different occasions by three manual stimulations of two or more acupuncture or tender points , mainly LR-3 and LI-4 together with local tender points , at 15-min intervals . Possible adverse and analgesic effects were assessed by the midwife responsible for the acupuncture given in each patient . There were no abortions and no influence on the delivery course of the infants , but transient premature labor was observed during the fourth stimulation carried out in the 15th gestational week in one woman . Other possible adverse effects , like transient dizziness or tiredness , were reported in 35 patients ( 21 % ) . Analgesia , as assessed by midwives involved , was good or excellent in 72 % of patients . Acupuncture seems to be safe and effective for pain relief in lower back pain , pelvic pain , or both during the second and third trimesters of pregnancy . Nevertheless , prospect i ve r and omized studies are needed to confirm these findings Study Design . A prospect i ve epidemiologic cohort study . Objective . To determine the incidence of clearly defined pelvic joint pain in pregnancy based on both history and objective confirmation and to classify pelvic joint pain into four groups and determine their incidence . Summary and Background Data . Pelvic and low back pain in pregnancy is a substantial problem , and the correct treatment is hampered by several factors , such as the lack of clearly defined clinical conditions , variety of nomenclature , and great variance in reported incidence ( range 4–76.4 % ) . This variation in incidence is a problem that calls for a clearly defined criteria and a study design aim ed at resolving such varying incidence rates . Methods . All pregnant women booked for delivery at two Danish hospitals over a 1-year period were offered to participate in the study in week 33 of gestation . Women who reported daily pain from pelvic joints , which could be objective ly confirmed , were divided , according to symptoms , into five subgroups : four classification groups ( pelvic girdle syndrome , symphysiolysis , one-sided sacroiliac syndrome , and double-sided sacroiliac syndrome ) and one miscellaneous . A total of 1460 women formed the incidence cohort based on geographic criteria . Results . A total of 293 women ( 20.1 % ) were found to have pelvic joint pain divided in one of the four classification groups : pelvic girdle syndrome 6.0 % , symphysiolysis 2.3 % , one-sided sacroiliac syndrome 5.5 % , and double-sided sacroiliac syndrome 6.3 % . Conclusion . This study proposes new , more precise procedures for the identification and classification of pregnancy-related pelvic joint pain based on both reports from the women and a physical examination . Presumably , the 20.1 % incidence rate , identified in the present study , represents the most precise and reliable information available hitherto , regarding the incidence of pregnancy-related pelvic joint pain OBJECTIVE To determine whether participation in a group fitness class for pregnant women can prevent and treat pelvic girdle pain and low back pain . DESIGN An observer-blinded r and omized controlled trial . PARTICIPANTS A total of 105 sedentary , nulliparous pregnant women , mean age 30.7 years ( st and ard deviation ( SD ) 4.0 ) , mean pre-pregnancy body mass index ( BMI ) 23.8 ( SD 4.3 ) , were assigned to either control or exercise groups at mean gestation week 17.7 ( SD 4.2 ) . METHODS The exercise intervention followed the guidelines of American College of Obstetricians and Gynecologists and included a 60 min general fitness class , with 40 min of endurance training and 20 min of strength training including stretching , performed at least twice per week for a minimum of 12 weeks . Outcome measures were number of women reporting pelvic girdle pain and low back pain after the intervention ( mean pregnancy week 36.6 ( SD 0.9 ) ) and postpartum ( mean 7.7 ( SD 1.7 ) ) . RESULTS There were no statistically significant differences between the exercisers and controls in numbers reporting the 2 conditions after the intervention ( pelvic girdle pain : odds ratio ( OR ) = 1.34 , CI = 0.56 - 3.20 or low back pain : OR = 1.10 , CI = 0.47 - 2.60 ) or postpartum ( pelvic girdle pain : OR = 0.38 , CI = 0.13 - 1.10 or low back pain : OR = 1.45 , CI = 0.54 - 3.94 ) . A comparison of the women who had attended at least 80 % of the weekly exercise classes with the control participants did not change the results . CONCLUSION Participation in regular group fitness classes during pregnancy did not alter the proportion of women reporting pelvic girdle pain or low back pain during pregnancy or after childbirth Study Design . Single-group prospect i ve follow-up study . Objectives . To assess the functional outcome of internal fixation of the pelvic ring in patients with severe pregnancy-related low back and pelvic pain ( PLBP ) in whom all other treatments failed . Background data . More than half of all pregnant women experience PLBP . In most cases , the pain disappears after childbirth . In some , however , the pain becomes chronic and patients may be wheelchair-bound or bedridden . After failure of all conservative treatment , surgical fixation of the pelvic ring seems to be the only remaining option for those severe cases . Material s and Methods . The postsurgical functional outcome of 58 severe PLBP patients was evaluated with the Majeed score and endurance of walking , sitting , and st and ing . Inclusion criteria were serious disability and failure of all conservative treatment . The surgical technique consisted of a symphysiodesis and bilateral percutaneous placement of two sacroiliac screws under fluoroscopic guidance . Results . With a follow-up of an average of 2.1 years , the difference between preoperative and postoperative Majeed score indicated that an improvement of more than 10 points was achieved in 69.8 % and 89.3 % of the patients at 12 and 24 months , respectively . The most important complications were irritation of nerve roots ( 8.6 % ) , nonunion of the symphysis ( 15.5 % ) , failure of the symphyseal plate ( 3.4 % ) , and pulmonary embolism ( 1.7 % ) . Conclusions . In this preliminary study , surgical fixation of the pelvic ring yielded satisfactory results in severe PLBP patients in terms of pain relief and improvement in ADL functions . These results should be confirmed in a r and omized clinical trial Study Design . A r and omized assessor-blinded clinical trial was conducted . Objective . To compare 3 different physical therapy treatments with respect to pain and activity in women with pelvic girdle pain during pregnancy and 3 , 6 , and 12 months postpartum . Summary of Background Data . In spite of the high prevalence of back pain during pregnancy , documented treatment programs are limited . Methods . Based on a clinical examination , 118 women with pelvic girdle pain diagnosed during pregnancy were r and omized into 3 different treatment groups : Information Group , use of a nonelastic sacroiliac belt and oral/written information about pelvic girdle pain ( n = 40 ) ; Home Exercise Group , same as in the Information Group , with the addition of a home exercise program ( n = 41 ) ; and the In Clinic Exercise Group , same as in the Information Group , plus participation in a training program ( n = 37 ) . Pain intensity was rated on a visual analogue scale ( 0–100 mm ) and marked on a pain drawing concerning localization . The activity ability was scored using the Disability Rating Index , covering 12 daily activity items . Outcome measures were obtained at inclusion , on average in gestation week 38 , and 3 , 6 , and 12 months postpartum . Results . There was no significant difference among the 3 groups during pregnancy or at the follow-ups postpartum regarding pain and activity . In all groups , pain decreased and the activity ability increased between gestation week 38 and at 12 months postpartum . Conclusions . Women with pelvic girdle pain seemed to improve with time in all 3 treatment groups . Neitherhome nor in clinic exercises had any additional value above giving a nonelastic sacroiliac belt and information Background Pregnancy-related low back pain is a common condition during pregnancy . Kinesio tape is a drug-free elastic therapeutic tape used for treating various musculoskeletal problems . The aim of this study was to investigate the short-term effects of lumbar Kinesio taping on pain intensity and disability in women with pregnancy-related low back pain . Material / Methods A total of 65 patients with pregnancy-related low back pain were r and omly allocated into either Kinesio taping ( n=33 ) or control ( n=32 ) groups . The intervention group was treated with paracetamol plus Kinesio taping , while the control group received only paracetamol . Kinesio taping was applied in the lumbar flexion position , and four I-shaped b and s were used . Two b and s were attached horizontally , with space correction technique . The remaining 2 b and s , 1 on each side of the lumbar spine , were placed vertically , with inhibition technique . Low back pain intensity was measured on a 10-cm visual analogue scale ( VAS ) , and the Rol and -Morris Disability Question naire ( RMDQ ) was used for evaluation of disability . Results Pain intensity and RMDQ scores improved significantly in both groups at 5 days compared with baseline . Considering the degree of treatment effect ( the change from baseline to day 5 ) , the Kinesio taping group was significantly superior than the control group in all outcome measures ( for all , P<0.001 ) . Conclusions The results of this study indicate that Kinesio taping can be used as a complementary treatment method to achieve effective control of pregnancy-related low back pain AIM To evaluate the effect of exercise programs on pregnant women with pregnancy-related low back and pelvic pain . BACKGROUND Low back and pelvic pain during pregnancy is a major health problem due to its frequent occurrence and such pain can limit pregnant women in many of their daily activities . DESIGN A r and omized trial with a control group ( n = 48 ) and an intervention group ( n = 48 ) . Trial registration number NCT02189356 . METHODS Department of Obstetrics and Gynecology , between December 2011-May 2012 , an Education and Research Hospital in Turkey . Based on the intention-to-treat principle , all pregnant women were analysed according to the group they were assigned to , regardless of whether they received the intervention or not . Participants in the intervention group received health counselling and exercised regarding low back and pelvic pain for four weeks . The pregnant women in the control group received usual care , comprised of routine clinical practice for pregnancy-related low back and pelvic pain . RESULTS According to Mann-Whitney U test analysis results , there was a statistically significant difference between the control and intervention groups ' Visual Analogue Scale during relaxation scores and Visual Analogue Scale during activity scores at the end of the study . According to Mann-Whitney U test analysis results , the change in the mean Oswestry Disability Index score for the intervention group and the difference in the mean scores between the two groups was statistically significant . CONCLUSIONS A four-week exercise program including individualized health counselling to relieve low back and pelvic pain improved the functional status in pregnant women Background . The aim of this study was to describe the effects of acupuncture in the treatment of low‐back and pelvic pain during pregnancy and compare it with physiotherapy Background . The efficacy of acupuncture on low‐back and /or pelvic pain in late pregnancy is review ed in few reports . Our aim was to evaluate the effects of two different acupuncture stimulation modes on pelvic pain intensity and some emotional symptoms due to the pain condition . Methods . In a prospect i ve r and omized controlled single‐blind study , pregnant women with pelvic pain , median gestational age 26 weeks ( range 18–35 ) , were given 10 acupuncture treatments . Needles were inserted subcutaneously over acupuncture points without further stimulation ( superficial , n=22 ) , or intramuscular and stimulated repeatedly until a perceived sensation of numbness , de qi , ( deep , n=25 ) . Self‐reported pain intensity at rest and during daily activities was assessed on a visual analog scale . The variables pain , emotional reactions , and loss of energy were assessed according to the Nottingham Health Profile question naire . Changes in assessed variables were analyzed with a nonparametric statistical method allowing for analysis of systematic group changes separated from additional individual changes . Results . After acupuncture stimulation , significant systematic group changes towards lower levels of pain intensity at rest and in daily activities as well as in rated emotional reaction and loss of energy were seen . The results also showed additional individual changes in most variables . In this study , no differences between the effects induced by the superficial and deep acupuncture stimulation modes were observed . Conclusion . Acupuncture stimulation that is individually design ed may be a valuable treatment to ameliorate suffering in the condition of pelvic pain in late pregnancy AIMS AND OBJECTIVES To analyse pain and functional capacity in women with pelvic girdle pain and to evaluate the effect of pelvic belt on these parameters . Two types of belts were to compare . BACKGROUND Pelvic girdle pain is very common during pregnancy . To prevent and relieve pelvic pain , women can use a set of techniques and tools such as a pelvic belt . While scientific evidence is lacking , commercial industries suggest the effectiveness of pelvic belts . DESIGN R and omised control trial . METHODS Forty-six pregnant women with pelvic girdle pain were evaluated . Pain analysis included a quantitative and a qualitative assessment . A daily activities question naire was used for functional capacity evaluation . Women were tested at two times during the pregnancy for a longitudinal evaluation , and they used one of the two belt models during their pregnancy . RESULTS Pelvic pain started between the 14th-21st week of pregnancy . Pain intensity was 60 ± 20 mm . Daily activities could increase pain . The use of belts reduced pain . The intensity of pain decreased by 20 mm on a visual analogue scale . The daily activities were also easier . However , all these conclusions are valid only if pregnant women used belts regularly on short periods . CONCLUSIONS The belts appear to be interesting tools to reduce pelvic pain and improve comfort of pregnant women . This effect might be explained by an analgesic effect with proprioceptive and biomechanical effect . The different types of belts could have differential effects on global , sacroiliac joint and back pain during pregnancy , but this hypothesis requires confirmation . RELEVANCE TO CLINICAL PRACTICE Relevant for patient : to use an easy and vali date d tool . Relevant for clinical practice : to suggest a tool scientifically vali date d for patient . Relevant to economic issues : belts decrease pelvic pain and increase comfort of pregnant women . Sick leave could decrease BACKGROUND Postpartum low back pain harmfully affects all parts of women 's life . OBJECTIVE To investigate the effect of kinesiotape on women with postnatal backache . METHODS Thirty participants were r and omly allocated to either group ( A ; n= 15 ) , treated by kinesiotape with exercise program , or the group ( B ; n= 15 ) , treated by exercise program . Visual analogue scale ( VAS ) and Back Pain Function Scale ( BPFS ) were evaluated.at baseline and after 2 weeks of intervention . RESULTS There were no statistically significant changes between group A and group B for baseline characteristics ( p > 0.05 ) . After two-week intervention , within group analyses revealed that VAS decreased ( p < 0.05 ) , with significant increase in BPFS ( p > 0.05 ) in the two groups . Between group analyses showed that there was significant reduction of VAS ( p < 0.05 ) and significant increase of BPFS ( p < 0.05 ) in favor to group A than group B. CONCLUSIONS Kinesiotape and postural correction exercises can be recommended as effective treatment methods for women 's postnatal back pain with better effect of kinesiotape and postural correction exercises than exercise alone Background Pelvic Girdle Pain ( PGP ) is an important cause of disability and economic cost worldwide . There is a need for effective preventative and management strategies . Emerging studies measure a variety of outcomes rendering synthesis and translation to clinical practice difficult . A Core Outcome Set ( COS ) can address this problem by ensuring that data are relevant , useful and usable for making well-informed healthcare choices . The aim of this study is to develop a consensus-based PGP-COS , including agreement on methods ( e.g. instruments ) for measuring the construct outcomes in the COS for use in research and clinical practice . Furthermore , as there is uncertainty as to whether incorporating stakeholder interviews in addition to conducting a systematic review to determine an initial list of outcomes for the Delphi survey , or , whether using different rating scales in a Delphi survey impacts on the final COS , we propose to embed two method ological studies within the PGP-COS development process to address these questions . Methods The PGP-COS study will include five phases : ( 1 ) A systematic review of the literature and semi-structured interviews with 15 patients ( three countries ) to form the initial list of outcomes for the Delphi survey ; ( 2 ) A 3-round Delphi including patients , clinicians , research ers and service providers ; ( 3 ) A systematic review of methods for measuring the outcomes in the preliminary PGP-COS identified in the Delphi survey ; ( 4 ) A face-to-face consensus meeting to agree on the final PGP-COS and methods for measuring the COS ; ( 5 ) Global dissemination . To address the method ological questions , we will assess the number and type of outcomes , in the final PGP-COS , that were exclusively derived from the interviews . Secondly , we will r and omise Delphi survey participants to either a 5-point or 9-point importance rating scale , and examine potential differences in ‘ important ’ ratings between the groups . Discussion There is currently no COS for measuring/monitoring PGP in trials and clinical practice . A PGP-COS will ensure that relevant outcomes are measured using appropriate measurement instruments for patients with PGP globally . Core outcome set registration This PGP-COS was registered with COMET ( Core Outcome Measures for Effectiveness Trials ) in January 2017 ( http://www.comet-initiative.org/ studies /details/958 ) BACKGROUND AND AIMS Post-ESD coagulation syndrome ( PECS ) occasionally occurs after colorectal endoscopic submucosal dissection ( ESD ) , presenting with localized abdominal pain and inflammation . We conducted a r and omized controlled trial ( RCT ) to assess the usefulness of endoscopic clipping closure to prevent PECS and delayed perforation ( PECS/DP ) . METHODS This is a multicenter , single-blind RCT . Prospect ively enrolled patients undergoing colorectal ESD were r and omly allocated to endoscopic clipping closure and nonclosure after ESD , stratifying by institution and tumor size . All participants received computed tomography scan after ESD . PECS was defined as visual analogue scale ( VAS ) ≥30 mm , a raise of VAS ≥20 mm from baseline , body temperature ≥37.5ºC or white blood cells ≥10,000/μL after colorectal ESD . DP was defined as PECS accompanied by extraluminal air . The pre-planned sample size was 320 patients , and the primary endpoint was the rate of PECS/DP . RESULTS At the planned interim analysis , this trial was terminated by recommendation of the independent data and safety monitoring committee because conditional power with superiority was lower than the preplanned futility limit . Finally , 155 patients were analyzed . PECS/DP 's rate was 16 ( 95 % confidence interval [ CI ] , 8%-23 % ) in the nonclosure and 24 ( 95 % CI , 14%-34 % ) in the closure groups , respectively ( P = 0.184 ) . All DP cases were within minor criteria , and all PECS/DP patients were conservatively managed without surgical treatment . Simple periluminal air without PECS was observed in 16 ( 95 % CI , 8%-23 % ) of the nonclosure and 10 ( 95 % CI , 3%-17 % ) of the closure groups . CONCLUSION Endoscopic clipping closure could not reduce the high incidence of PECS/DP after colorectal ESD |
1,005 | 28,658,074 | 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 . | Abstract Strahorn , J , Serpell , BG , McKune , A , and Pumpa , KL .
Effect of physical and psychosocial interventions on hormone and performance outcomes in professional rugby union players : a systematic review .
J Strength Cond Res 31(11 ) : 3158–3169 , 2017—This systematic review investigates the acute effects of physical or psychosocial interventions on testosterone and cortisol responses in elite male rugby union players , and the subsequent association with physical performance areas ( e.g. , strength , power , sprint performance ) or key performance indicators ( e.g. , coach-identified skills ) . | 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 |
1,006 | 26,024,295 | 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 | The Mediterranean diet has been proven to be highly effective in the prevention of cardiovascular diseases .
Paraoxonase 1 ( PON1 ) has been implicated in the development of those conditions , especially atherosclerosis .
The present work describes a systematic review of current evidence supporting the influence of Mediterranean diet and its constituents on this enzyme .
Despite the differential response of some genetic polymorphisms , the Mediterranean diet has been shown to exert a protective action on this enzyme . | 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 ( CM ) ] . Significant PON1-L55 M x PON1-Q192R interactions affected basal serum HDL-C ( P = 0.019 ) , LDL-C ( P = 0.028 ) and TC ( P = 0.022 ) and tended to affect arylesterase activity ( P = 0.083 ) . Basal arylesterase activity was positively correlated with basal HDL-C ( r = 0.53 ; P < 0.05 ) and TC ( r = 0.43 ; P < 0.05 ) and negatively correlated with LPO ( r = -0.70 ; P < 0.01 ) and the ox-LDL : LDL ratio ( r = -0.63 ; P < 0.01 ) . WM decreased arylesterase activity in PON1 - 55 M carriers ( P = 0.012 ) but not in PON1-L55 individuals , and decreased LPO concentrations in PON1 - 192R carriers ( P = 0.031 ) but not in PON1-Q192 subjects . To conclude , serum TC , HDL-C , and LDL-C concentrations and arylesterase activity depend on the interaction of PON1-L55 M and PON1-Q192R polymorphisms . However , the PON1-Q192R polymorphism is more closely related to antioxidant status . Both polymorphisms modulate the effect of WM consumption on CVD biomarkers We examined the effects of dietary fats with specific fatty acid compositions , on serum paraoxonase ( PON1 ) activity in rats . Male adult Sprague-Dawley rats were divided r and omly into four dietary groups . One group received the control diet [ AIN 93 M with soybean oil ( 5 g/100 g diet ) ] , whereas the remaining three groups received the modified control diet supplemented with ( 15 g/100 g diet ) triolein , tripalmitin or fish oil , respectively . After 20 d , blood was obtained after overnight food deprivation and PON1 activity was determined . Serum lipids and lipid components of lipoproteins were also determined . Serum PON1 activity [ micromol/(L.min ) ] was significantly ( P : < 0.05 ) higher in triolein ( 98 + /- 6 ) and lower in fish oil ( 41 + /- 4 ) , compared with tripalmitin-fed rats ( 63 + /- 11 ) . Serum PON1 activity in tripalmitin-fed rats was comparable to that of controls ( 67 + /- 9 ) . Serum PON1 activity correlated significantly with serum lecithin : cholesterol acyltransferase ( LCAT ) activity ( r = 0.77 , P : < 0.001 ) and was transported in blood principally in association with the denser subfraction of HDL , very high density lipoprotein ( VHDL ; d > 1.15 kg/L ) . Serum PON1 activity correlated strongly with serum lipids as well as lipids of VLDL , HDL and its subfractions . Multiple linear regression analysis , however , showed a significant relationship of serum PON1 activity , principally with the phospholipids of VHDL ( r = 0.47 , P : < 0.002 ) . These data suggest that the modulation of serum PON1 activity by dietary fat may be mediated via the effect of the specific fatty acids on the synthesis and secretion of VHDL , the subfraction of HDL that transports the majority of PON1 in the blood The coenzyme Q10 content of the average Danish diet was estimated from consumption data and from analysis of food items to be 3 - 5 mg coenzyme Q10 per day , primarily derived ( 64 % of the total ) from meat and poultry . To investigate if coenzyme Q10 was absorbed to any significant degree from a food item , a r and omized cross-over study with single doses of coenzyme Q10 ( 30 mg/person ) , administered either as a meal or as capsules , was carried out in healthy subjects . The serum coenzyme Q10 concentration increased significantly , and the maximum concentrations did not differ significantly for the two forms of administration . The study indicates that coenzyme Q10 is present in food items and absorbed to a significant degree . Thus , dietary coenzyme Q10 may contribute to the plasma coenzyme Q10 concentration Background High density lipoproteins ( HDL ) have many cardioprotective roles ; however , in subjects with type 2 diabetes ( T2D ) these cardioprotective properties are diminished . Conversely , increased fruit and vegetable ( F&V ) intake may reduce cardiovascular disease risk , although direct trial evidence of a mechanism by which this occurs in subjects with T2D is lacking . Therefore , the aim of this study was to examine if increased F&V consumption influenced the carotenoid content and enzymes associated with the antioxidant properties of HDL in subjects with T2D . Methods Eighty obese subjects with T2D were r and omised to a 1- or ≥6-portion/day F&V diet for 8-weeks . Fasting serum was collected pre- and post-intervention . HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation . Carotenoids were measured in serum , HDL2 and HDL3 by high performance liquid chromatography . The activity of paraoxonase-1 ( PON-1 ) was measured in serum , HDL2 and HDL3 by a spectrophotometric assay , while the activity of lecithin cholesterol acyltransferase ( LCAT ) was measured in serum , HDL2 and HDL3 by a fluorometric assay . Results In the ≥6- vs. 1-portion post-intervention comparisons , carotenoids increased in serum , HDL2 and particularly HDL3 , ( α-carotene , p = 0.008 ; β-cryptoxanthin , p = 0.042 ; lutein , p = 0.012 ; lycopene , p = 0.016 ) , as did the activities of PON-1 and LCAT in HDL3 ( p = 0.006 and 0.044 , respectively ) . Conclusion To our knowledge , this is the first study in subjects with T2D to demonstrate that increased F&V intake augmented the carotenoid content and influenced enzymes associated with the antioxidant properties of HDL . We suggest that these changes would enhance the cardioprotective properties of this lipoprotein . Clinical trial registration IS RCT The purpose of the study was to examine the effects of astaxanthin ( Asx ) on paraoxonase ( PON1 ) activities and oxidative stress status in soccer players . Forty soccer players were r and omly assigned in a double-blind fashion to Asx and placebo ( P ) group . Blood sample s were obtained before , 45 and 90 days after supplementation . PON1 activity was assessed by using two substrates : paraoxon and diazoxon . The oxidative stress biomarkers were also examined : total sulphydryl group content ( -SH groups ) , thiobarbituric acid-reactive substances ( TBARS ) , advanced oxidation protein products and redox balance . The significant interaction effect of supplementation and training ( p < 0.05 ) on PON1 activity toward paraoxon was observed . The PON1 activity toward diazoxon increased in Asx group after 90 days ( p < 0.01 ) , while there was no significant difference in P group . SH groups content rose from pre- to post-supplementation period only in Asx group ( supplementation and training , p < 0.05 ; training , p < 0.01 ) . TBARS levels decreased after 45 days and increased after 90 days of regular soccer training in both groups ( training , p < 0.001 ) . Redox balance decreased significantly in response to the regular training , regardless of treatment group ( training , p < 0.001 ) . Asx supplementation might increase total SH groups content and improve PON1 activity through protection of free thiol groups against oxidative modification CONTEXT AND OBJECTIVE Paraoxonase 1 ( PON1 ) , an enzyme associated with high-density lipoprotein ( HDL-PON1 ) , is reported to have antioxidant and cardioprotective properties . The aim of the present study was to investigate the effects of anthocyanins on the HDL-PON1 activity and cholesterol efflux capacity in hypercholesterolemic subjects . DESIGN AND PARTICIPANTS A total of 122 hypercholesterolemic subjects were given 160 mg of anthocyanins twice daily or placebo ( n = 61 of each group ) for 24 weeks in a double-blind , r and omized , placebo-controlled trial . Participants and investigators were masked to treatment allocation . RESULTS Anthocyanin consumption significantly increased HDL cholesterol and decreased low -density lipoprotein cholesterol concentrations compared with placebo ( P < .018 and P < .001 , respectively ) . Anthocyanin supplementation also increased the activity of HDL-PON1 compared with placebo ( P < .001 ) . Furthermore , cholesterol efflux capacity was increased more in the anthocyanin group ( 20.0 % increase ) than in the placebo group ( 0.2 % increase ) ( P < .001 ) . The negative correlations established between HDL-PON1 activity and the levels of lipid hydroperoxides associated with HDL confirm the relationship between PON1 activity and lipid peroxidation of lipoproteins . Furthermore , a strong positive correlation was noted between increased HDL-PON1 activity and improved cholesterol efflux capacity both before and after adjustment for HDL cholesterol and apolipoprotein AI in anthocyanin-treated subjects ( both P < .001 ) . Inhibition of HDL-PON1 activity strongly prevented the antioxidant ability of HDL and attenuated the cholesterol efflux capacity of subjects from anthocyanin group . CONCLUSIONS Our observations suggest that the alterations of PON1 activity by anthocyanin observed in hypercholesterolemic HDL reflect a shift to an improvement of cholesterol efflux capacity of HDL and may provide a link between anthocyanin and cardioprotective effects Paraoxonase 1 ( PON 1 ) has antioxidant and cardioprotective properties and is abnormally low in type 2 diabetic serum . This study aim ed to determine the effect of type 2 diabetes and meals rich in saturated fat and oleic acid on PON1 activity in chylomicrons and very low density lipoproteins ( VLDL ) . PON1 arylesterase activity was measured in chylomicrons and VLDL that were isolated in serum from 20 patients with type 2 diabetes and 20 age- and gender-matched , overweight controls 3 h after meals rich in cream or olive oil in a r and omized , cross-over study . Chylomicron – PON1 activity ( 45 % , P = 0.02 ) , ratio chylomicron – PON1/chylomicron – triacylglycerides ( TAG ) ( 42 % , P = 0.03 ) and chylomicron – protein content ( 46 % , P < 0.001 ) were significantly lower in patients with type 2 diabetes compared with controls after the olive oil meal with comparable findings after the meal rich in cream . After ingestion of olive oil , chylomicron – PON1 activity was significantly higher in controls ( P = 0.01 ) and marginally higher ( P = 0.06 ) in diabetic patients and chylomicron – TAG were significantly ( P < 0 . 05 ) higher in both groups of subjects , compared with values after ingestion of cream . VLDL – PON1 increased ( two-fold ) significantly ( P < 0.003 ) during both meals . Chylomicron-PON1 activity was correlated significantly with chylomicron – protein ( P < 0.001 , n = 40 ) and with postpr and ial serum PON1 activity ( P ≤ 0.001 , n = 40 ) . Our data suggest that type 2 diabetes is associated with abnormally low chylomicron – PON1 activity after fatty meals and this may be linked to lower chylomicron – protein content and serum PON1 activity . Switching from saturated fat to olive oil in the meal increases PON1 activity in the chylomicron fraction largely due to increased numbers of chylomicron particles Recent evidence suggests that omega-3 polyunsaturated fatty acids [ n-3 PUFAs : eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) ] , improve insulin sensitivity in humans . In a double-blind , placebo-controlled , r and omized , crossover study , we investigated the effects of EPA/DHA on paraoxonase-1 activity as well as fasting and postpr and ial levels of circulating adiponectin and leptin in 34 subjects with type 2 diabetes mellitus who received daily for 6 weeks either 2 g purified EPA/DHA or olive oil ( placebo ) , separated by a 6 weeks washout . At the end of each treatment , measurements were performed in fasting state and 2 , 4 , and 6 h following a st and ardized high-fat meal ( 600 kcal ) . No significant differences in fasting and postpr and ial circulating adiponectin , leptin , and paraoxonase-1 activity were seen between n-3 PUFAs and placebo . Our data do not support an insulin sensitizing effect of n-3 PUFAs by means of influencing circulating adipocytokines in this population . Clinical Trial Register Number : NCT00328536 There is increasing evidence that nuts have protective effects against coronary artery disease by improving lipid profile and inhibiting lipid oxidation . However , data about pistachio nuts are limited , and to our knowledge , there is no study investigating the effects of pistachio intake on lipid oxidation and serum antioxidant levels . This study , therefore , sought to determine the effects of pistachio intake on serum lipids and determine whether consumption of pistachio would alter serum antioxidant levels . Rats were r and omly divided into three groups ( n=12 for each ) : control group fed basic diet for 10 weeks and treated groups fed basic diet plus pistachio which constituted 20 % and 40 % of daily caloric intake , respectively . Consumption of pistachio as 20 % of daily caloric intake increased high-density lipoprotein ( HDL ) levels and decreased total cholesterol (TC)/HDL ratio , compared with those not taking pistachio . However , TC , low-density lipoprotein ( LDL ) cholesterol and triglyceride levels were unaffected by pistachio consumption . Consumption of pistachio as 20 % of daily caloric intake increased serum paraoxonase activity by 35 % and arylesterase activity by 60 % , which are known to inhibit LDL cholesterol oxidation , compared with the control group . However , increased antioxidant activity was blunted when pistachio intake was increased to 40 % of daily caloric intake . In conclusion , the present results show that consumption of pistachio as 20 % of daily caloric intake leads to significant improvement in HDL and TC/HDL ratio and inhibits LDL cholesterol oxidation . These results suggest that pistachio may be beneficial for both prevention and treatment of coronary artery disease BACKGROUND Despite the richness in antioxidants of the Mediterranean diet , to our knowledge , no r and omized controlled trials have assessed its effect on in vivo lipoprotein oxidation . METHODS A total of 372 subjects at high cardiovascular risk ( 210 women and 162 men ; age range , 55 - 80 years ) , who were recruited into a large , multicenter , r and omized , controlled , parallel-group clinical trial ( the Prevención con Dieta Mediterránea [ PREDIMED ] Study ) directed at testing the efficacy of the traditional Mediterranean diet ( TMD ) on the primary prevention of coronary heart disease , were assigned to a low-fat diet ( n = 121 ) or one of 2 TMDs ( TMD + virgin olive oil or TMD + nuts ) . The TMD participants received nutritional education and either free virgin olive oil for all the family ( 1 L/wk ) or free nuts ( 30 g/d ) . Diets were ad libitum . Changes in oxidative stress markers were evaluated at 3 months . RESULTS After the 3-month interventions , mean ( 95 % confidence intervals ) oxidized low-density lipoprotein ( LDL ) levels decreased in the TMD + virgin olive oil ( -10.6 U/L [ -14.2 to -6.1 ] ) and TMD + nuts ( -7.3 U/L [ -11.2 to -3.3 ] ) groups , without changes in the low-fat diet group ( -2.9 U/L [ -7.3 to 1.5 ] ) . Change in oxidized LDL levels in the TMD + virgin olive oil group reached significance vs that of the low-fat group ( P = .02 ) . Malondialdehyde changes in mononuclear cells paralleled those of oxidized LDL . No changes in serum glutathione peroxidase activity were observed . CONCLUSIONS Individuals at high cardiovascular risk who improved their diet toward a TMD pattern showed significant reductions in cellular lipid levels and LDL oxidation . Results provide further evidence to recommend the TMD as a useful tool against risk factors for CHD . Trial Registration is rct n.org Identifier : IS RCT N35739639 Summary . Background : The oxidative modification of LDL is considered to play a central role in the pathogenesis of atherosclerosis and coronary heart disease ( CHD ) . Paraoxonase ( PON1 ) protects LDL from oxidation and may therefore retard the developement of atherosclerosis . The PON1–192 polymorphism is associated with diminished PON1 concentrations and an increased risk for CHD in RR-allele subjects . Aim of the study : To investigate the effect of tomato juice consumption on PON1 activity and other parameters related to oxidative stress in healthy elderly subjects . Furthermore , the PON1–192 genotype has been determined in the volunteers in order to see whether possible treatment effects are related to the PON1–192 polymorphism . Methods : Fifty elderly subjects were r and omly assigned to control ( mineral water ) or intervention group ( tomato juice ) . Subjects of the tomato juice group consumed daily 330 mL tomato juice for 8 weeks . Antioxidant status was measured as LDL oxidation , plasma malondialdehyde , ferric reducing ability of plasma ( FRAP ) and PON1 activity . The PON1–192 polymorphism was determined by restriction fragment length polymorphism polymerase chain reaction ( RFLP-PCR ) . Plasma carotenoids were analyzed by HPLC . Results : Tomato juice consumption reduced LDL-oxidation and improved antioxidant status in R-allele carriers , but not in the QQ genotype group . PON1 activity increased irrespective of the genotype in both , control and intervention group . Conclusions : The changes in antioxidant status after tomato juice consumption seem to depend on the PON1–192 genotype . Healthy elderly , carrying the R-allele , could specificly reduce their higher cardiovascular risk by changing dietary habits BACKGROUND AND AIM Due to its high antioxidant and mono- and polyunsaturated fatty acid content virgin argan oil ( VAO ) could play a beneficial role in cardiovascular prevention . We were therefore interested in determining whether the consumption of VAO could improve plasma paraoxonase ( PON1 ) activities and antioxidant status in healthy men . METHODS AND RESULTS Sixty young men were included in this interventional study . They were given a controlled diet for 2 weeks as baseline and then received 25 g/day of butter . The group was r and omised to two diet group periods of 3 weeks each . The VAO group received 25 ml/day of oil and the extra virgin olive oil ( EVO ) group received the same quantity of EVO as control group . Plasma PON1 activities , antioxidant vitamins and LDL susceptibility to oxidation were measured . The analysis of the results shows that PON1 activities increase significantly in both groups and that lipoperoxides and conjugated dienes formation decreases significantly in VAO and EVO groups compared to baseline values ( P=0.001 and P=0.014 , respectively ) . Vitamin E concentration increases significantly only in VAO group ( P=0.007 ) . Susceptibility of LDL to lipid peroxidation shows a significant increase in lag phase and a significant decrease in maximum diene production in VAO ( P=0.005 ) and EVO groups ( P=0.041 and P=0.005 , respectively ) . CONCLUSIONS Our findings confirm the beneficial effect of EVO on plasma antioxidant status and show for the first time the same effect for VAO supplementation in man . Thus , VAO offers an additional natural food supplement to reduce cardiovascular risk AIM To evaluate the effects of different types of dietary fats on the hepatic lipid content and oxidative stress parameters in rat liver with experimental non-alcoholic fatty liver disease ( NAFLD ) . METHODS A total of 32 Sprague-Dawley rats were r and omly divided into five groups . The rats in the control group ( n = 8) were on chow diet ( Group 1 ) , rats ( n = 6 ) on methionine choline-deficient diet ( MCDD ) ( Group 2 ) , rats ( n = 6 ) on MCDD enriched with olive oil ( Group 3 ) , rats ( n = 6 ) on MCDD with fish oil ( Group 4 ) and rats ( n = 6 ) on MCDD with butter fat ( Group 5 ) . After 2 mo , blood and liver sections were examined for lipids composition and oxidative stress parameters . RESULTS The liver weight/rat weight ratio increased in all treatment groups as compared with the control group . Severe fatty liver was seen in MCDD + fish oil and in MCDD + butter fat groups , but not in MCDD and MCDD + olive oil groups . The increase in hepatic triglycerides ( TG ) levels was blunted by 30 % in MCDD + olive oil group ( 0.59 + /- 0.09 ) compared with MCDD group ( 0.85 + /- 0.04 , P < 0.004 ) , by 37 % compared with MCDD + fish oil group ( 0.95 + /- 0.07 , P < 0.001 ) , and by 33 % compared with MCDD + butter group ( 0.09 + /- 0.1 , P < 0.01 ) . The increase in serum TG was lowered by 10 % in MCDD + olive oil group ( 0.9 + /- 0.07 ) compared with MCDD group ( 1.05 + /- 0.06 ) . Hepatic cholesterol increased by 15-fold in MCDD group [ ( 0.08 + /- 0.02 , this increment was blunted by 21 % in MCDD + fish oil group ( 0.09 + /- 0.02 ) ] . In comparison with the control group , ratio of long-chain polyunsaturated fatty acids omega-6/omega-3 increased in MCDD + olive oil , MCDD + fish oil and MCDD + butter fat groups by 345- , 30- and 397-fold , respectively . In comparison to MCDD group ( 1.58 + /- 0.08 ) , hepatic MDA contents in MCDD + olive oil ( 3.3 + /- 0.6 ) , MCDD + fish oil ( 3.0 + /- 0.4 ) , and MCDD + butter group ( 2.9 + /- 0.36 ) were increased by 108 % , 91 % and 87 % , respectively ( P < 0.004 ) . Hepatic paraoxonase activity decreased significantly in all treatment groups , mostly with MCDD + olive oil group ( -68 % ) . CONCLUSION Olive oil decreases the accumulation of triglyceride in the liver of rats with NAFLD , but does not provide the greatest antioxidant activity The HDL-bound enzyme paraoxonase ( PON ) protects LDL from oxidation and may therefore attenuate the development of atherosclerosis . We examined the effect of tomato and carrot juice consumption on PON1 activity and lipid peroxidation in healthy young volunteers with different PON1 - 192 genotypes ( Q/R substitution at position 192 ) . In this r and omized cross-over study twenty-two healthy , non-smoking men on a low-carotenoid diet received 330 ml/d tomato juice ( 37.0 mg lycopene , 1.6 mg beta-carotene ) or carrot juice ( 27.1 mg beta-carotene , 13.1 mg alpha-carotene ) for 2 weeks . Intervention periods were preceded by 2-week low-carotenoid intake . We determined the PON1 - 192 genotype by restriction fragment length polymorphism-polymerase chain reaction ( RFLP-PCR ) and measured ex vivo LDL oxidation ( lag time ) , plasma malondialdehyde and PON1 activity at the beginning and end of each intervention period . At baseline , lag time was higher ( P<0.05 ) in QQ ( 111 ( sd 9 ) min ) than in QR/RR subjects ( 101 ( sd 8) min ) . Neither tomato nor carrot juice consumption had significant effects on PON1 activity . However , tomato juice consumption reduced ( P<0.05 ) plasma malondialdehyde in QR/RR ( Delta : -0.073 ( sd 0.11 ) micromol/l ) as compared to QQ subjects ( Delta:+0.047 ( sd 0.13 ) micromol/l ) . Carrot juice had no significant effect on malondialdehyde irrespective of the PON1 - 192 genotype . Male volunteers with the QR/RR genotype showed an increased lipid peroxidation at baseline . Although tomato and carrot juice fail to affect PON1 activity , tomato juice intake reduced lipid peroxidation in healthy volunteers carrying the R-allele of the PON1 - 192 genotype and could thus contribute to CVD risk reduction in these individuals Objective : A number of long-term population -based studies have tried to study fruit and vegetable consumption in relation to cardiovascular disease , cancer and total mortality . Few of these studies are based on r and omly selected population sample s. The aim of the study was to investigate the long-term effect of fruit and vegetable consumption on mortality , cardiovascular disease , cardiovascular death , cancer morbidity and cancer death among middle-aged and elderly men . Design : Prospect i ve cohort study . Setting : General community . The Study of Men Born in 1913.Subjects : 792 men at age 54 who participated in a screening examination in 1967.Main outcome measures : A food frequency question naire was used to obtain information of the dietary habits in 730 of the men ( 92 % ) . All men were followed up with repeated examinations until the age of 80 . Results : Cardiovascular as well as total mortality was significantly lower among men with high fruit consumption in univariate analysis . There was no correlation between fruit or vegetable consumption in relation to cancer incidence , cancer death and cardiovascular disease . In multivariate survival analysis where smoking , cholesterol and hypertension were taken into account , there was a significantly lower mortality among men with a high fruit consumption during 16 y follow up until the age of 70 ( P=0.042 ) , but this finding was no longer statistically significant during 26 y follow-up at the age of 80 ( P=0.051 ) . Conclusions . Daily fruit consumption seems to have positive effect on long-term survival independently of other traditional cardiovascular risk factors like smoking , hypertension and cholesterol . Sponsorship : This study was supported by grants from the Swedish Medical Research Council ( K98 - 274 - 06276 - 17 ) King Gustav V and Queen Victoria ’s Foundation , and the Göteborg University . European Journal of Clinical Nutrition ( 2000 ) 54 , Paraoxonase 1 ( PON1 ) is associated with HDL and modulates the antioxidant and anti-inflammatory role of HDL . The goals of the present study were to investigate the effect of ageing and the role of PON1 on the anti-inflammatory activity of HDL , and to determine whether extra-virgin olive oil ( EVOO ) consumption could improve the atheroprotective activity of HDL . HDL and PON1 were isolated from the plasma of ten young ( Y-HDL and Y-PON1 ) and ten elderly ( E-HDL and E-PON1 ) healthy volunteers before and after 12 weeks of EVOO consumption . Inflammation was assessed by measuring intracellular adhesion molecule 1 ( ICAM-1 ) expression . THP-1 ( human acute monocytic leukaemia cell line ) monocyte chemotaxis was measured using a Boyden chamber . Oxidative damage to HDL was assessed by measuring conjugated diene formation and changes in electrophoretic migration . Y-HDL had more anti-inflammatory activity than E-HDL . The conjugated diene content and the electrophoretic mobility of E-HDL were higher than those of Y-HDL . Y-PON1 had significant anti-inflammatory activity , reducing ICAM-1 expression by 32·64 ( SD 2·63)% , while E-PON1 had no significant effect . THP-1 chemotaxis measurements confirmed the ICAM-1 expression results . The 12 weeks of EVOO consumption significantly increased the anti-inflammatory activities of both HDL and PON1 . The anti-inflammatory activity of HDL was modulated by PON1 and was lower in the elderly volunteers . EVOO consumption increased the anti-inflammatory effect of HDL and reduced the age-related decrease in anti-atherogenic activity Objective : To investigate PON 1/Aryl activities in basketball players with or without α-T supplementation pre- and post-training . Vitamin E ( α-tocopherol , α-T ) reduces lipid peroxidation . Paraoxonase 1/arylesterase ( PON 1/Aryl ) activities are closely related to oxidation and atherogenesis . Subject/ Methods : Blood was obtained from 10 players pre- ( group A ) , post-exercise ( group B ) and after 1 month on α-T ( 200 mg per 24 h orally ) supplementation pre- ( group C ) and post-exercise ( group D ) . Lactate , pyruvate , muscle enzyme activities , creatine kinase , lactate dehydrogenase and total antioxidant status ( TAS ) were measured with commercial kits . Catecholamines and α-T were determined with high-performance liquid chromatography methods and PON 1/Aryl activities spectrophotometrically . Results : Lactate , pyruvate , muscle enzyme activities and catecholamines were increased ( P<0.001 ) in all groups post-training . Alpha-T levels remained unaltered pre- vs post-exercise . TAS was decreased in all the groups post training . PON 1/Aryl activities were significantly decreased post-exercise ( group B ) ( PON1 : 65±12 U min−1 ml−1 , Aryl : 58±14 KU min−1 ml−1 ) as compared to those pre-exercise ( group A ) ( PON1 : 142±16 U min−1 ml−1 , Aryl : 114±12 KU min−1 ml−1 , P<0.001 ) . In contrast , the studied enzyme activities remained practically unaltered after α-T supplementation pre- vs post-training . Both enzyme activities positively correlated to TAS ( r=0.60 , P<0.001 ) . Conclusions : Alpha-T supplementation may result in protection of the enzyme PON 1/Aryl activities from free radical production Objective : To determine the effects of meals rich in thermally stressed safflower ( TSAF ) and olive ( TSOL ) oils on postpr and ial serum paraoxonase ( PON1 ) arylesterase activity and low density lipoprotein ( LDL ) oxidation in patients with type 2 diabetes . Design : A r and omised cross-over study . Setting : Diabetes clinic and general practice .Subjects : Fourteen patients ( six men and eight women ) with type 2 diabetes , aged 48–67 y , glycated haemoglobin < 10 % and fasting blood glucose < 11 mmol/l were recruited . Interventions : Patients received a milkshake rich in TSAF or TSOL and at least a week later they received the alternate milkshake . These fats contained high levels of lipid oxidation and degradation products . Blood sample s were taken fasted and 4 h after consumption of the milkshake . Main outcome measures : Serum PON1 activity and lag time in LDL oxidation . Results : After the meal rich in TSOL , serum PON1 activity increased significantly in women ( 12 ( 2.22 ) µmol/ml/min , mean ( 95 % confidence interval ) , P=0.03 ) and not in men ( 0 ( −4.4 ) µmol/ml/min ) during the postpr and ial period . The increase in PON1 activity after the TSOL meal was significantly ( P=0.03 ) greater in women compared with men . In women , the increase in serum PON1 activity after the TSOL meal was significantly different ( 13 ( 1.25 ) µmol/ml/min , P=0.04 ) compared with the corresponding change ( −1 µmol/ml/min ) after the TSAF meal . The lag time in LDL oxidation and indices of oxidative stress and antioxidant capacity did not vary significantly during the meals . Conclusions : Meals rich in TSOL may increase postpr and ial serum PON1 activity in middle-aged and older diabetic women . This change is potentially anti-atherogenic and may favour the use of olive oil over polyunsaturated fats in the diet of patients with type 2 diabetes . Sponsorship : The study was supported by a grant from the National Heart Foundation of New Zeal and .European Journal of Clinical Nutrition ( 2001 ) 55 , Current advances in enzyme bioscavenger prophylactic therapy against chemical warfare nerve agent ( CWNA ) exposure are moving towards the identification of catalytic bioscavengers that can de grade large doses of organophosphate ( OP ) nerve agents without self destruction . This is a preferred method compared to therapy with the purified stoichiometric bioscavenger , butyrylcholinesterase , which binds OPs 1:1 and would thus require larger doses for treatment . Paraoxonase-1 ( PON-1 ) is one such catalytic bioscavenger that has been shown to hydrolyze OP insecticides and contribute to detoxification in animals and humans . Here we investigated the effects of a common red wine ingredient , Resveratrol ( RSV ) , to induce the expression of PON-1 in the human hepatic cell line HC04 and evaluated the protection against CWNA simulants . Dose-response curves showed that a concentration of 20 microM RSV was optimal in inducing PON-1 expression in HC04 cells . RSV at 20 microM increased the extracellular PON-1 activity approximately 150 % without significantly affecting the cells . Higher doses of RSV were cytotoxic to the cells . Resveratrol also induced PON-1 in the human lung cell line A549 . RSV pre-treatment significantly ( P = 0.05 ) protected the hepatic cells against exposure to 2x LD(50 ) of soman and sarin simulants . However , lung cells were protected against soman simulant exposure but not against sarin simulant exposure following RSV treatment . In conclusion , these studies indicate that dietary inducers , such as RSV , can up-regulate PON-1 , a catalytic bioscavenger , which can then hydrolyze and protect against CWNA-induced toxicity , providing a prospect i ve new method to protect against CWNA exposure 1 Hypothyroidism is accompanied by hyperlipidaemia and oxidative stress and is associated with several complications , such as atherosclerosis . Paraoxonase activity has been reported to decrease in several situations associated with atherosclerosis and oxidative stress . In the present study , the effects of different doses of taurine on serum paraoxonase and arylesterase activities , as well as on the serum lipid profile , were investigated in hypothyroid rats . 2 Forty male Sprague‐Dawley rats were r and omly divided into five groups as follows : Group 1 , rats received normal rat chow and tap water ; Group 2 , rats received st and ard rat chow + 0.05 % propylthiouracil ( PTU ) in the drinking water ; and Groups 3–5 , taurine‐supplemented PTU groups ( st and ard rat chow + 0.5 , 2 or 3 % taurine in the drinking water , respectively , in addition to PTU ) . Paraoxon or phenylacetate were used as substrates to measure paraoxonase and arylesterase activity , respectively . Plasma and tissue malondialdehyde ( MDA ) levels , indicators of lipid peroxidation , were determined using the thiobarbituric‐acid reactive substances method . Serum triglyceride , total cholesterol and high‐density lipoprotein – cholesterol ( following precipitation with dextran sulphate – magnesium chloride ) were determined using enzymatic methods . 3 Serum paraoxonase and arylesterase activities were increased and plasma and tissue MDA levels and serum triglyceride levels were reduced in a dose‐dependent manner in taurine‐treated hypothyroid rats . Taurine concentrations were positively correlated with enzyme activities and negatively correlated with MDA and triglyceride levels . 4 Further studies are needed to investigate the role of taurine supplementation in hypothyroidism in human subjects Background and Aim : Atherosclerosis involves oxidative and inflammatory mediators regulated by fat and antioxidants . Therefore , we studied the postpr and ial evolution of plasma lipids , carotenoids , C-reactive protein ( CRP ) , and human serum paraoxanase activity ( PON1 ) following two different fatty meals . Subjects and Methods : Eight healthy males consumed a 45 % fat 1,000 Kcal Mediterranean-like ( Med ) meal ( monounsaturated 61 % of fat ) compared to a Western-like ( Wes ) ( saturated 57 % of fat ) meal . Blood was collected at baseline ( time 0 ) 2 , 4 and 7 h postpr and ial . Plasma lipids , glucose , insulin , total carotenoids , CRP , and PON1 were analyzed . Results : There was a marginal increase in cholesterol and glucose after both meals . Triglycerides increased modestly ( to less than 200 mg/dl ) and insulin increased ( more in the Wes-like meal ) but still within normal range , indicating a low glycemic index for both meals . Only the Med-like meal result ed in a significant increase in both PON1 activity ( 16 % , p < 0.02 ) and carotenoids ( 74 % , p < 0.02 ) with a 2-hour postpr and ial decrease in CRP ( 6 % , p < 0.02 ) . Conclusion : A postpr and ial monounsaturated fatty acid rich meal increases both plasma carotenoids and PON1 with a decrease in CRP levels , thus providing a novel potential explanation to the protective properties of a Mediterranean diet against atherogenesis To test the hypothesis that cholesterol might suppress the beneficial effect of olive oil in atherosclerosis , we fed apoE KO mice diets containing extra virgin olive oil , either with or without cholesterol , for 10 weeks and assessed the development of atherosclerosis . Within each sex , mice were assigned r and omly to one of the following four experimental groups : ( 1 ) a st and ard chow diet , ( 2 ) a chow diet supplemented with 0.1 % cholesterol ( w/w ) cholesterol , ( 3 ) a chow diet enriched with 20 % ( w/w ) extra virgin olive oil and ( 4 ) a chow diet containing 0.1 % cholesterol and 20 % extra virgin olive oil . On the st and ard chow diet , average plasma cholesterol levels were higher in males than in females . Olive oil- and cholesterol-enriched diets , separately or in combination , induced hypercholesterolemia in both sexes , and abolished the difference between the sexes in plasma cholesterol levels . The addition of cholesterol to chow or olive oil diets decreased apolipoprotein A-I significantly in females and serum paraoxonase activities in males . The latter activity was higher in females than in males . In both sexes , the size of aortic atherosclerotic lesions was similar in olive oil- and chow-fed animals and smaller than in cholesterol-supplemented groups . Size of aortic lesions were positively correlated with circulating paraoxonase activity , particularly in males , and the relationship remained after adjusting for apolipoprotein A-I and HDL cholesterol levels . Our results demonstrate that the nutritional regulation of paraoxonase is an important determinant of atherosclerotic lesions dependent on sex . They also suggest that the mere inclusion of olive oil in Western diets is insufficient and the adoption of Mediterranean diet would be more effective in retarding the development of atherosclerotic lesions Diabetes is associated with increased oxidative stress and atherosclerosis development . In the present study , we investigated the effects of pomegranate juice ( PJ ; which contains sugars and potent anti-oxidants ) consumption by diabetic patients on blood diabetic parameters , and on oxidative stress in their serum and macrophages . Ten healthy subjects ( controls ) and 10 non-insulin dependent diabetes mellitus ( NIDDM ) patients who consumed PJ ( 50ml per day for 3 months ) participated in the study . In the patients versus controls serum levels of lipid peroxides and thiobarbituric acid reactive substances ( TBARS ) were both increased , by 350 % and 51 % , respectively , whereas serum SH groups content and paraoxonase 1 ( PON1 ) activity , were both decreased ( by 23 % ) . PJ consumption did not affect serum glucose , cholesterol and triglyceride levels , but it result ed in a significant reduction in serum lipid peroxides and TBARS levels by 56 % and 28 % , whereas serum SH groups and PON1 activity significantly increased by 12 % and 24 % , respectively . In the patients versus controls monocytes-derived macrophages ( HMDM ) , we observed increased level of cellular peroxides ( by 36 % ) , and decreased glutathione content ( by 64 % ) . PJ consumption significantly reduced cellular peroxides ( by 71 % ) , and increased glutathione levels ( by 141 % ) in the patients ' HMDM . The patients ' versus control HMDM took up oxidized LDL ( Ox-LDL ) at enhanced rate ( by 37 % ) and PJ consumption significantly decreased the extent of Ox-LDL cellular uptake ( by 39 % ) . We thus conclude that PJ consumption by diabetic patients did not worsen the diabetic parameters , but rather result ed in anti-oxidative effects on serum and macrophages , which could contribute to attenuation of atherosclerosis development in these patients The management of overweight subjects by interventions aim ed at reducing inflammation is highly desirable . To date , observational studies have identified a link between increased dietary antioxidant intake and reduced cardiovascular morbidity . However , direct trial evidence regarding the ability of antioxidants to influence inflammation is lacking . Therefore , this study examined lycopene 's ability to lower systemic and high-density lipoprotein (HDL)-associated inflammation in moderately overweight middle-aged subjects . Serum was collected before and after a 12-week intervention from 54 moderately overweight , middle-aged individuals . Subjects were r and omised to one of three groups : control diet ( < 10 mg lycopene/week ) , lycopene-rich diet ( 224 - 350 mg lycopene/week ) and lycopene supplement ( 70 mg lycopene/week ) . HDL was subfractionated into HDL(2&3 ) by rapid ultracentrifugation . Compliance was monitored by assessing lycopene concentration in serum and HDL(2&3 ) . Systemic and HDL-associated inflammation was assessed by measuring serum amyloid A ( SAA ) levels . HDL functionality was determined by monitoring the activities of paraoxonase-1 ( PON-1 ) , cholesteryl ester transfer protein ( CETP ) and lecithin cholesterol acyltransferase ( LCAT ) . Lycopene increased in serum and HDL(2&3 ) following both lycopene interventions ( P<.001 , for all ) , while SAA decreased in serum following the lycopene supplement and in HDL(3 ) following both lycopene interventions ( P<.05 for all ) . PON-1 activity increased in serum and HDL(2&3 ) in both lycopene groups ( P<.05 , for all ) . Furthermore , the activity of CETP decreased in serum following the lycopene supplement , while the activity of LCAT increased in serum and HDL(3 ) following both lycopene interventions ( P<.05 for all ) . These results demonstrate that in moderately overweight , middle-aged subjects , increasing lycopene intake leads to changes to HDL(2&3 ) , which we suggest enhanced their antiatherogenic properties . Overall , these results show the heart-protective properties of increased lycopene intake Thyroid hormones are associated with the oxidative and antioxidative status of the organism . Since data on the oxidative status of hypothyroidism are limited and controversial , we investigated the oxidant and antioxidant status and serum paraoxonase/arylesterase activities in propylthiouracil‐induced hypothyroidism and examined the effect of vitamin E supplementation on this experimental model . Forty male Sprague Dawley rats were r and omly divided into four groups ( group 1 , control ; group 2 , control+vitamin E ; group 3 , propylthiouracil ; group 4 , propylthiouracil+vitamin E ) . Plasma , red blood cell , liver , heart and skeletal muscle malondialdehyde levels were increased in the propylthiouracil‐treated group compared with the control rats and were decreased in propylthiouracil+vitamin E group compared with the propylthiouracil‐treated group . Vitamin E supplementation also significantly increased liver and kidney reduced glutathione levels in propylthiouracil treated animals . Serum paraoxonase and arylesterase activities were decreased in propylthiouracil treated group and vitamin E supplementation caused significant increase in serum paraoxonase activity compared with the propylthiouracil‐treated rats . These findings suggest that hypothyroidism is accompanied with increased oxidative stress and vitamin E supplementation exerts beneficial effects on this situation . Copyright © 2004 John Wiley & Sons , Objective : Conjugated linoleic acid ( CLA ) showed a wide range of beneficial biological effects with relevance for cardiovascular health in animal models and humans . Most human studies used olive oil as a reference . This study assessed the effect of CLA as compared with safflower oil on endothelial function and markers of cardiovascular risk in overweight and obese men . Heated safflower oil and olive oil were given for additional descriptive control . Methods : Eighty-five overweight men ( aged 45–68 years , body mass index 25–35 kg/m2 ) were r and omized to receive 4.5 g/d of the CLA isomeric mixture , safflower oil , heated safflower oil , or olive oil in a 4-week double-blind study . Endothelial function was assessed by peripheral arterial tonometry ( PAT ) index determination in the fasting and postpr and ial state ( i.e. , 4 hours after consumption of a fat- and sucrose-rich meal ) . Results : CLA as compared with safflower oil consumption did not impair fasting or postpr and ial PAT index but decreased body weight . CLA as compared with safflower oil did not change total , low-density lipoprotein ( LDL ) , or high-density lipoprotein ( HDL ) cholesterol ; triglycerides ; insulin sensitivity indices ; C-reactive protein ; soluble adhesion molecules ; oxidized LDL ; lipoprotein a ( Lp[a ] ) ; paraoxonase ; or platelet-activating factor acetylhydrolase ( PAF-AH ) activity , but significantly reduced arylesterase activity and increased concentrations of the F2-isoprostane 8-iso-prostagl and in F (PGF)2α . Conclusion : CLA did not impair endothelial function . Other parameters associated with metabolic syndrome and oxidative stress were not changed or were slightly improved . Results suggest that CLA does not increase cardiovascular risk . Increased F2-isoprostane concentrations in this context may not indicate increased oxidative stress The aim of this placebo-controlled study was to investigate the effects of oral vitamin E supplementation for 10 weeks on exercise-induced oxidative damage in untrained dogs . Eight dogs were r and omly assigned to a supplementation ( n=4 ) or control ( n=4 ) group and underwent two isolated submaximal exercise sessions , 10 weeks apart . Blood was collected during each session to measure erythrocyte membrane fluidity ( EMF ) , paraoxonase-1 ( PON1 ) activity , plasma malondialdehyde ( MDA ) and vitamin E concentrations . These biomarkers were measured in venous blood sample s collected before ( t(0 ) ) , just after ( t , EMF only ) and 1d ( t+1d ) and 7d ( t+7d ) after the dogs ran on a treadmill . Prior to vitamin E supplementation , exercise induced a significant decrease in PON1 activity , EMF , vitamin E concentration and a significant increase in MDA concentration at t+1d . After a 10 week vitamin E supplementation period , these exercise-induced changes in PON1 activity , EMF and MDA concentration were still significant in the control group , but not in the supplemented group . These results suggested that vitamin E supplementation had a protective effect on submaximal exercise-induced oxidative damage in sedentary dogs Serum paraoxonase 1 ( PON1 ) has been reported to be an important contributor to the antioxidant and anti-inflammatory activities of HDL , avoiding LDL oxidation . The activity of this enzyme is reduced in patients with renal insufficiency , caused by elevated oxidative stress and disturbances of apolipoprotein metabolism . Therapeutic utilization of antioxidants to control renal oxidative stress may be an effective therapy in renal protection . The aim was to investigate the protective effects of several antioxidant compounds against the oxidative stress associated to renal failure induced by ethylene glycol ( EG ) , focusing on the possible role of serum PON1 activity . Fifty-four male Wistar rats were r and omly assigned to six groups ( n = 9 ) : an untreated control ( C ) group , an EG-treated group , a catechin (CAT)-treated group , an epicatechin (EPI)-treated group , a quercetin (QUE)-treated group and a folk herbal extract (FHE)-treated group . After 16 d of treatment , calcium oxalate lithiasis was induced in the rats using EG . After eight days ( treatment + EG ) , the animals were sacrificed . EG treatment impaired kidney composition , increased oxidative damage , and decreased serum paraoxonase and arylesterase activities . CAT , QUE and the FHE Fagolitos improved oxidative status by enhancing antioxidant defenses – superoxide dismutase and PON1 activities – and reducing oxidative damage , thus reinforcing the idea of a possible role of PON1 in the protective effects of QUE against the deleterious consequences of oxidative stress in kidney To test the hypothesis that extra virgin olive oils from different cultivars added to Western diets might behave differently than palm oil in the development of atherosclerosis , apoE-deficient mice were fed diets containing different cultivars of olive oil for 10 weeks . Female mice were assigned r and omly to one of the following five groups : ( 1 - 4 ) fed chow diets supplemented with 0.15 % ( w/w ) cholesterol and 20 % ( w/w ) extra virgin olive oil from the Arbequina , Picual , Cornicabra , or Empeltre cultivars , and ( 5 ) fed a chow diet supplemented with 0.15 % cholesterol and 20 % palm oil . Compared to diets containing palm oil , a Western diet supplemented with one of several varieties of extra virgin olive oil decreased atherosclerosis lesions , reduced plaque size , and decreased macrophage recruitment . Unexpectedly , total plasma paraoxonase activity , apoA-I , plasma triglycerides , and cholesterol played minor roles in the regulation of differential aortic lesion development . Extra virgin olive oil induced a cholesterol-poor , apoA-IV-enriched lipoparticle that has enhanced arylesterase and antioxidant activities , which is closely associated with reductions in atherosclerotic lesions . Given the anti-atherogenic properties of extra virgin olive oil evident in animal models fed a Western diet , clinical trials are needed to establish whether these oils are a safe and effective means of treating atherosclerosis Background : A number of recent studies indicate that antioxidants reduce the oxidative stress associated with the development of coronary heart diseases ( CHD ) . Objective : ( i ) To investigate whether the erythrocyte catalase ( CAT ) , superoxide dismutase ( SOD ) , total glutathione , reduced glutathione ( GSH ) , oxidized glutathione ( GSSG ) , and lipid peroxidation ( LPO ) , and serum uric acid and paraoxonase-1 ( PON1 ) are modified at increased CHD-risk individuals consuming walnut-enriched meat ( WM ) , ( ii ) to evaluate whether these changes were influenced by basal serum cholesterol , body mass index or smoking habit . Design : The study was a non blinded , cross-over , placebo-controlled trial in which 22 volunteers ( 60 % overweight and 40 % obese ) with increased CHD-risk were r and omly assigned to receive WM or control meat ( CM ) during two different periods of 5 weeks . Results : A significant interaction time*treatment ( p < 0.05 ) was observed in all enzymes and substrates tested except HDL-C , uric acid and LPO . The treatment significantly increased CAT activity , total glutathione and GSSG ( p < 0.05 ) . Significant gender*time*treatment interaction ( p = 0.043 ) for total glutathione was found increasing at the end of the WM period in male but not changing in female . Total glutathione and GSH/GSSG ratio ( p < 0.05 ) were lower in smokers . Hypercholesterolemics presented higher uric acid ( p < 0.05 ) but no enzyme activities or substrate concentrations were different from those of normocholesterolemics . Conclusions : The WM tested appears to be a functional food as it improved the antioxidant status of increased CHD-risk volunteers . Despite its high energy content , it also appears adequate for overweight and obese people because did not exert negative effect upon body weight |
1,007 | 28,478,717 | 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 . | Objective : To evaluate the data supporting the approval of selexipag and discuss its potential place in therapy for managing pulmonary arterial hypertension ( PAH ) . | 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 MID ; the latter method used the Physical Component Summary Score ( PCS ) of the Medical Outcomes Study 36-item short form ( SF-36 ) . MEASUREMENTS AND MAIN RESULTS Four hundred five subjects were analyzed . Domains of the SF-36 were weakly to modestly associated with 6MWT . Change in the PCS of the SF-36 was most strongly associated with change in 6MWT ( r = 0.40 , P < 0.001 ) and thus was selected as the anchor for subsequent anchor-based analyses . Distributional analyses yielded estimates of the MID ranging from 25.1 to 38.5 m , whereas anchor-based analyses yielded an estimate of 38.6 m. CONCLUSIONS Using both distributional and anchor-based methods , the estimated consensus MID in the 6MWT for PAH is approximately 33 m. These results have important implication s for ( 1 ) assessing treatment responses from clinical trials and metaanalyses of specific PAH therapy , and ( 2 ) sample size calculations for future study design OBJECTIVE Selexipag is a novel , oral , selective prostacyclin ( PGI2 ) receptor agonist in clinical development for the treatment of pulmonary arterial hypertension . Film-coated tablets with strength between 200 and 1,600 μg were used . Bioequivalence between 8 x 200 μg and a new 1,600 μg tablet was evaluated at steady state in healthy male subjects . MATERIAL S AND METHODS This was an open-label , 2-treatment , 2-period , crossover , up-titration , phase 1 study . The treatments were selexipag at 1,600 μg b.i.d . for 4.5 days either as 8 x 200 μg tablets ( reference : A ) or 1 x 1,600 μg tablet ( test : B ) , both preceded by an up-titration phase starting from 400 μg b.i.d . doses , in 200-μg steps every 4th day . Subjects were r and omized 1 : 1 to the A-B or B-A sequence . The pharmacokinetics and tolerability of selexipag and its active metabolite , ACT-333679 , were investigated . RESULTS 80 subjects were enrolled in the study : 65 subjects completed the study according to protocol , and 15 subjects withdrew from the study . The most frequent adverse events ( AEs ) were headache ( 86 % ) , myalgia ( 73 % ) , and jaw pain ( 73 % ) . There was no difference in nature and overall frequency of AEs between the two treatments . Steady state was attained within 3 days of the selexipag 1,600 μg b.i.d . TREATMENTS The 90 % confidence intervals ( CIs ) of the geometric mean ratio ( B/A ) at steady state for AUCÏ and Cmax , ss were within ( 0.80 , 1.25 ) bioequivalence interval : ( 0.92 , 1.06 ) and ( 0.95 , 1.14 ) , respectively , for selexipag and ( 0.95 , 1.06 ) and ( 0.94 , 1.07 ) , respectively , for the active metabolite , ACT-333679 . CONCLUSIONS Bioequivalence was demonstrated between 8 x 200 μg and 1 x 1,600 μg selexipag at steady state BACKGROUND Pulmonary arterial hypertension ( PAH ) is a life-threatening disease for which both continuous IV epoprostenol and continuous subcutaneous treprostinil have proven effective . With continuous IV treprostinil having potential advantages over both of the above therapies , we investigated the safety and efficacy of this regimen in patients with PAH . METHODS We conducted a 12-week , prospect i ve , open-label , uncontrolled , multicenter study of continuous IV treprostinil in 16 patients with PAH that was idiopathic ( n = 8) , related to connective tissue disease ( n = 6 ) , or related to congenital heart disease ( n = 2 ) . The primary end point was change from baseline to week 12 in exercise capacity assessed by the 6-min walk ( 6MW ) test . RESULTS Continuous IV treprostinil increased 6MW distance ( mean + /- SE ) by 82 m from baseline ( 319 + /- 22 m ) to week 12 ( 400 + /- 26 m ) [ n = 14 ; p = 0.001 ] . There were also significant improvements in the secondary end points of Naughton-Balke treadmill time ( p = 0.007 ) , Borg dyspnea score ( p = 0.008 ) , and hemodynamics ( mean pulmonary artery pressure , p = 0.03 ; cardiac index , p = 0.002 ; pulmonary vascular resistance , p = 0.001 ) at week 12 compared with baseline . Side effects were mild and consistent with those reported with prostacyclin treatment . One death , unrelated to study drug , occurred during the 12-week study in a patient who received 3 days of treprostinil and died 2 weeks later . CONCLUSIONS Long-term IV infusion of treprostinil is safe and appears to be effective for the treatment of patients with PAH Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous prostacyclin has proven to be effective . However , this treatment requires a permanent central venous catheter with the associated risk of serious complications such as sepsis , thromboembolism , or syncope . Treprostinil , a stable prostacyclin analogue , can be administered by a continuous subcutaneous infusion , avoiding these risks . We conducted a 12-week , double-blind , placebo-controlled multicenter trial in 470 patients with pulmonary arterial hypertension , either primary or associated with connective tissue disease or congenital systemic-to-pulmonary shunts . Exercise capacity improved with treprostinil and was unchanged with placebo ; the between treatment group difference in median six-minute walking distance was 16 m ( p = 0.006 ) . Improvement in exercise capacity was greater in the sicker patients and was dose-related , but independent of disease etiology . Concomitantly , treprostinil significantly improved indices of dyspnea , signs and symptoms of pulmonary hypertension , and hemodynamics . The most common side effect attributed to treprostinil was infusion site pain ( 85 % ) leading to premature discontinuation from the study in 8 % of patients . Three patients in the treprostinil treatment group presented with an episode of gastrointestinal hemorrhage . We conclude that chronic subcutaneous infusion of treprostinil is an effective treatment with an acceptable safety profile in patients with pulmonary arterial hypertension |
1,008 | 26,215,467 | 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 . | Lateral ridge augmentation procedures are aim ed to reconstruct deficient alveolar ridges or to build up peri-implant dehiscence and fenestrations .
The objective of this systematic review was to assess the efficacy of these interventions by analyzing data from 40 clinical studies evaluating bone augmentation through either the staged or the simultaneous approach . | 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 75 patients had at least 1 implant that was entirely surrounded by bone and served as the control ( 112 implants ) . After placement of the definitive prostheses ( single-tooth , fixed , or removable implant prostheses ) , patients were recalled after 6 months and then every 12 months during a 5-year observation period . The following variables were investigated : implant survival , marginal bone level ( MBL ) , presence of plaque , peri-implant mucosal conditions , height of keratinized mucosa ( KM ) , and marginal soft tissue level ( MSTL ) . The cumulative implant survival rate after 5 years varied between 93 % and 97 % for implants treated with or without GBR . The mean MBL after 60 months was 1.83 mm for sites treated with Bio-Oss and Bio-Gide , 2.21 mm for sites treated with Bio-Oss and Gore-Tex , and 1.73 mm for the control sites . The MBL values were found to increase significantly with time and differed significantly among the treatment groups . During the observation period , KM varied between 3.16 and 3.02 mm . A slight recession of 0.1 mm was observed , and plaque was found in 15 % of all sites and was associated with inflammatory symptoms of the peri-implant mucosa . It was observed that such symptoms and recession correlated more strongly with the type of restoration than with the type of treatment . This study demonstrated that implants placed with or without GBR techniques had similar survival rates after 5 years , but that bone resorption was more pronounced in sites with GBR treatment . It was assumed that the use of GBR is indeed indicated when the initial defect size is larger than 2 mm in the vertical dimension OBJECTIVES To compare the clinical and histological outcomes of a resorbable modified polylactide/polyglycolide acid ( PLGA ) test membrane and a titanium-reinforced exp and ed polytetrafluorethylene ( ePTFE ) control membrane used for guided bone regeneration ( GBR ) around dental implants . MATERIAL S AND METHODS A total of 40 patients with peri-implant dehiscence-type defects were r and omly allocated to a GBR procedure using either a modified PLGA test or an ePTFE control membrane . Soft tissue condition , implant integration , adverse events and quality of life were recorded during the 6-month healing period . At re-entry peri-implant bone defect dimensions were measured and compared with values recorded at implant/GBR surgery . A biopsy was retrieved for qualitative and quantitative histological analyses . A comparison between the groups was conducted using non-parametric statistical tests . RESULTS Soft tissue complications were observed in five test patients and two control patients . Except for soft tissue complications and incomplete regeneration , no procedure- or device-related adverse events were observed . The vertical bone defect component was , in mean , reduced by-5.1 mm ( 95 % CI -6.8 , -3.3 ) in the test group and -6.9 mm ( 95 % CI -8.2 , -5.5 mm ) in the control group . The mean residual vertical defect height measured 1.2 ± 2.4 mm in the test group and 0.3 ± 1.1 mm in the control group meaning a mean defect resolution of 81 % in the test group and 96 % in the control group ( P = 0.161 ) . The horizontal bone thickness at implant shoulder level decreased from a mean of 3.2 mm to 1.4 mm ( -56 % , mean -1.7 mm , 95 % CI -2.3 , -1.1 ) in the test group and from 3.3 mm to 2.5 mm ( -24 % , mean -0.8 mm , 95 % CI -1.3 , -0.3 ) in the control group ( P = 0.022 ) . Qualitative and quantitative histological analyses did not show significant differences in the tissue composition between groups . CONCLUSION Peri-implant GBR was successfully performed using either of the membranes . The control membrane was able to better maintain the horizontal thickness of regenerated bone and revealed less soft tissue complications . No statistically valid evidence about the superiority of one membrane was found in any other parameters . Soft tissue dehiscences occur with both types of membranes and can impair the amount of regenerated bone OBJECTIVES This study was conducted to evaluate the effect of barrier membranes on s and wich bone augmentation ( SBA ) for the treatment of implant dehiscence defects . MATERIAL AND METHODS Twenty-six implant-associated buccal dehiscence defects in 22 patients were treated according to the SBA concept - mineralized human cancellous allograft ( inner layer ) , mineralized human cortical allograft ( outer layer ) and coverage with barrier membrane . The defects were r and omly assigned to the bovine collagen membrane ( BME ) group ; acellular dermal matrix ( ADM ) group ; and no membrane group . Measurements at baseline and 6 months re-entry included defect height ( DH : from smooth-rough junction to the most apical part of the defect ) , defect width ( DW : at the widest part of the defect ) , and horizontal defect depth ( HDD : at three locations - smooth-rough junction , middle , and most apical portion of the defect ) . All measurements were taken from a reference stent . Statistical analyses were performed for comparison of intra- and inter-group comparisons . RESULTS All implants placed were successfully osseointegrated . DH at baseline for three groups were not significantly different ( P=0.858 ) . Mean % DH reductions for ADM , BME , and control groups at 6 months were 73.9+/-17.6 % , 68.1+/-30.1 % , and 63.6+/-23.9 % , respectively , with no significant difference among the groups ( P=0.686 ) . Mean horizontal bone gain , however , was significantly greater for membrane groups ( 1.7 mm for ADM , 1.6 mm for BME ) compared with control group ( 1 mm ) ( P=0.044 ) . Implant exposure result ed in significant reduction in total height gain ( 79.1+/-14.3 % vs. 57+/-23.5 % , P=0.021 ) . CONCLUSIONS Within the limit of this study , it is concluded that SBA technique achieved predictable clinical outcomes . The addition of absorbable membranes enhanced bone gain in thickness compared with membrane-treated sites Insufficient bone volume can be a significant problem when placing dental implants . This clinical study was design ed to evaluate bone regeneration potential at dehisced dental implant sites . Nineteen titanium dental implants with exposed threads were studied . To create a secluded space for bone formation , an exp and ed polytetrafluoroethylene ( e-PTFE ) membrane was placed over the exposed implant sites secured with an implant cover screw and completely covered with the flap . Three membranes perforated the overlying soft tissue during the healing time and were removed prematurely . The remaining membranes were removed after an uneventful healing period of 4.5 to 6 months . Fourteen of 19 dehisced implant sites were completely covered with newly formed bonelike tissue ; 4 implants demonstrated partial bone fill at reentry and 1 implant showed partial fill with soft tissue . In five implant sites a reentry was performed between 6 and 9 weeks ; nonmineralized fibrous tissue was found to fill the space under the membrane . At 16 of the 19 implant sites there were similar dehiscence-type defects that were evaluated as a group . These dehiscences varied from 2.0 to 9.0 mm . The percentage of bone fill at reentry ranged from 28.4 % to 100 % ( mean 89.6 % ; SD 22.51 ; SE 5.63 ) and was highly significant ( P < .0001 ) . Six to 12 months after prosthesis connection , 12 of the 19 implants were available for radiographic interpretation and an average bone loss of 1.73 mm ( SD = 0.43 ) was measured . This surgical application of an e-PTFE membrane suggested a viable clinical method for enhancing bone formation around dental implants One of the key factors for attaining osseointegration is the presence of an adequate osseous volume . In patients with inadequate osseous width or height , a bone augmentation using the guided bone regeneration ( GBR ) concept may be applied either with a simultaneous or a staged approach . The aim of this multicenter prospect i ve case series study was to evaluate the efficacy and predictability of the GBR technique ( simultaneous approach ) in patients with peri-implant osseous defects , both dehiscences and fenestrations . Results 5 years post-treatment ( survival rates and marginal bone level ) were assessed . A total of 19 consecutive patients with 26 peri-implant osseous defects ( 20 dehiscences and six fenestrations ) were treated during the period from September 1992 to June 1993 with a simultaneous GBR approach using non-resorbable membranes combined with autogenous bone grafts or decalcified freeze-dried bone allograft . The mean osseous augmentation was 94.8 % . Marginal bone levels at re-entry and 5 years after surgery were calculated from st and ardized periapical radiographs . One implant was lost 3 months after loading . Thus , the cumulative survival rate was 96.1 % after 5 years . The mean marginal bone level after 5 years was 2.03 mm ( SD=+/-0.5 ) , without a difference between mesial and distal sites . This study demonstrates that implants with peri-implant defects that are treated with GBR had similar survival rates and crestal bone levels compared with implants in native bone The aim of this study was to determine the efficacy of a bioresorbable collagen membrane ( Bio-Gide ) in combination with autogenous bone grafts in the treatment of peri-implant dehiscences , fenestrations , or limited vertical defects . Eighteen titanium dental implants with exposed threads placed in 17 patients were studied . Autogenous bone was used in all cases to fill the defect and maintain the space underneath the barrier . The collagen membrane was trimmed and adapted to cover the defect in a saddle configuration . The membrane absorbed the blood and easily covered and adhered to the underlying bone . It was not stabilized by any retentive means . Sixteen to 32 months postoperatively , the sites were reentered and the amount of bone regenerated was measured . The results showed significant bone gain ( average 87.6 % ) in the treatment of peri-implant defects with Bio-Gide and autogenous bone Bone grafting may be required prior to implant placement , at the time of implant placement , or subsequent to it . The aim of this study was to compare the healing of onlay block grafts when deproteinized bovine bone coverage was used with the healing of the grafts without such coverage . The purpose was a clinical evaluation of deproteinized bovine bone 's ability to reduce grafted bone resorption . The results indicated that bovine bone can be placed over grafted areas , taking advantage of its osteoconductive properties and compensating for the natural bone resorption caused by remodeling OBJECTIVES To investigate the impact of residual defect height ( RDH ) following guided bone regeneration ( GBR ) in dehiscence-type defects on the long-term stability of peri-implant health after a period of 4 years . MATERIAL AND METHODS The RDH values in dehiscence-type defects at titanium implants were clinical ly assessed after 4 months of submerged healing following augmentation using a natural bone mineral ( NBM ) and a r and omized application of either a cross-linked- ( VN ) or a native collagen membrane ( BG ) ( n=12 patients each ) . The RDH values were classified as absent ( 0 mm , control ; n=8 ) , minimal ( 1 mm , test 1 ; n=8 ) , or advanced ( > 1 mm , test 2 ; n=8 ) . Clinical parameters ( i.e. bleeding on probing [ BOP ] , probing pocket depth [ PD ] , mucosal recession [ MR ] ) were recorded ( mesio- , mid- , and disto-buccal aspects ) at 4 years after prosthesis installation . RESULTS The mean PD ( 2.9±0.7 , 2.8±0.7 , 2.7±0.8 mm ) values at 4 years were comparable in all the groups investigated . The mean MR values tended to be increased in both the test groups ( 0.5±0.7 , 0.4±0.6 mm , respectively ) , when compared with the control group ( 0.2±0.3 mm ) ( P>0.05 , respectively ) . The mean BOP values were also increased in both the test groups ( 45.8±30.5 % , 54.1±24.8 % , respectively ) , even reaching statistical significance when comparing test 2 and control ( 29.1±21.3 % ) groups ( P=0.02 ) . CONCLUSION The present study indicated that ( i ) implants exhibiting RDH values > 1 mm are at a higher risk of developing peri-implant disease and ( ii ) positive RDH values may be associated with an increase in MR and may therefore compromise the overall esthetic outcome of implant therapy PURPOSE This prospect i ve case series evaluated the use of a new synthetic resorbable membrane with autogenous bone , either alone or in combination with anorganic bovine bone-derived mineral , for horizontal ridge augmentation and subsequent implant placement . MATERIAL S AND METHODS Particulated autogenous bone , either alone or in combination with anorganic bovine bone-derived mineral , was used for lateral ridge augmentation and covered with a new synthetic resorbable membrane ( glycolide and trimethylene carbonate ) to treat knife-edged ridges and prepare them for implant placement . Ridge measurements were obtained before and after augmentation , complications were recorded , and biopsy specimens were examined histologically . RESULTS Fifty-eight implants were placed in 22 patients with 25 surgical sites in knife-edged ridges . No complications were associated with this treatment . Clinical measurements revealed an average of 5.56 mm ( ± 1.45 mm ) of lateral ridge augmentation after an average of 8.12 months ( ± 2.32 months ) of graft healing . Clinical ly , all treated ridges were sufficient in width for subsequent implant placement . All implants have survived , with an average follow-up period of 45.88 months ( ± 12.43 months ) . Histologic analysis of the selected augmentation sites showed new bone formation and good incorporation of the bovine bone mineral particles . CONCLUSION The high implant survival rate and the low complication rate show the potential of this technique for the treatment of horizontal augmentation of lateral ridges and the efficacy of the new resorbable synthetic membrane OBJECTIVES The use of barrier membranes in guided bone regeneration ( GBR ) procedures for the treatment of alveolar bone defects is common practice . The objective of this study was to test whether a synthetic bioresorbable polyethylene glycol ( PEG ) hydrogel membrane could result in a similar amount of vertical bone fill as a st and ard collagen membrane , both combined with a membrane supporting material . MATERIAL AND METHODS The study enrolled 37 patients requiring implant treatment with an expected osseous defect in the posterior maxilla or m and ible . After raising a mucoperiosteal flap , the implant sites were prepared and dental implants placed . The defect height was then measured and defects <3 mm were excluded from the study . Defects were grafted with bovine bone mineral and r and omly covered with either a collagen membrane ( control group , 18 patients ) or a PEG hydrogel membrane ( test group , 19 patients ) , which is applied as a liquid . After a healing period of 6 months , surgical re-entry was performed and the change in vertical bone height from baseline evaluated . RESULTS Well-vascularized hard tissue was apparent at all sites and the regenerated bone was similar to the surrounding native bone . Mean vertical defect fill after 6 months was 5.63+/-1.84 mm at test sites and 4.25+/-1.16 mm at control sites , and the mean defect fills were 94.9 % and 96.4 % at test and control sites , respectively . More soft tissue complications were observed with the PEG membrane ( e.g. , delayed or incomplete wound healing ) but all sites recovered uneventfully . CONCLUSIONS The new PEG hydrogel membrane was as successful as a st and ard collagen membrane in the treatment of bony dehiscence defects around dental implants with simplified clinical h and ling In the present multi-center study , non-submerged ITI implants were prospect ively followed to evaluate their long-term prognosis in fully and partially edentulous patients . In a total of 1003 patients , 2359 implants were consecutively inserted . Following a healing period of 3 - 6 months , the successfully integrated implants were restored with 393 removable and 758 fixed restorations . Subsequently , all consecutive implants were documented annually up to 8 years . At each examination , the clinical status of all implants was evaluated according to predefined criteria of success . Therefore , the data base allowed the evaluation of 8-year cumulative survival and success rates for 2359 implants . In addition , cumulative success rates were calculated for implant subgroups divided per implant type , implant length , and implant location . Furthermore , the actual 5-year survival and success rates could be determined for 488 implants . During the healing period , 13 implants did not successfully integrate , whereas 2346 implants fulfilled the predefined criteria of success . This corresponds with an early failure rate of 0.55 % . During follow-up , 19 implants were classified as failures due to several reasons . In addition , 17 implants ( approximately 0.8 % ) demonstrated at the last annual examination a suppurative periimplant infection . Including 127 drop out implants (= 5.4 % drop out rate ) into the calculation , the 8-year cumulative survival and success rates result ed in 96.7 % and 93.3 % , respectively . The analysis of implant subgroups showed slightly more favorable cumulative success rates for screw type implants ( > 95 % ) compared to hollow-cylinder implants ( 91.3 % ) , and clearly better success rates for m and ibular implants ( approximately 95 % ) when compared to maxillary implants ( approximately 87 % ) . The actual 5-year survival and success rates of 488 implants with 98.2 % and 97.3 % , respectively , were slightly better than the estimated 5-year cumulative survival and success rates of 2359 implants indicating that the applied life table analysis is a reliable statistical method to evaluate the long-term prognosis of dental implants . It can be concluded that non-submerged ITI implants maintain success rates well above 90 % in different clinical centers for observation periods up to 8 years Four clinical centers , using the Brånemark System and with personnel trained in the use of Gore-Tex Augmentation Material ( GTAM ) , participated in a prospect i ve study of 45 patients 18 to 83 years of age . A total of 55 implants were placed with membranes because of local bony defects ( fenestration or dehiscence ) . Dehiscence and fenestration defects were evaluated as one group . The mean initial defect height was 4.7 mm ( SD = 3.0 ) . After healing , the remaining defect height was reduced to 1.1 mm ( SD = 2.3 ) . The decrease in surface exposure was significant . Complications were primarily attributed to exposure of six membranes during the early healing period . The cumulative survival rate was 84.7 % in maxillae and 95.0 % in m and ibles after 2 years of follow-up . The surgical application of GTAM to produce bone in localized bony defects around oral implants seems to be a predictable method that may reduce the need for extensive augmentation surgery in patients with insufficient jaw bone volume The purpose of this study was to evaluate the feasibility of using a bioactive alloplast and a physical barrier to augment localized alveolar ridge defects for the subsequent placement of dental implants . Twelve systemically healthy patients ( aged 29 to 55 years ) with inadequate dental alveolar ridge widths were selected for study . All patients completed initial therapy , which included scaling , root planing , and oral hygiene instruction . All ridge defects were augmented with a bioactive glass alloplast and a titanium-reinforced e-PTFE barrier . Vertical ( height ) and horizontal ( width ) hard tissue measurements were taken the day of ridge augmentation surgery ( baseline ) and at the 6-month reentry surgery . The change in ridge width varied from a loss of 1 mm to a gain of 4.5 mm , with a mean gain of 1.1 mm ( P < .03 ) . Eight of the 12 sites gained 1 mm or less . The difference in mean ridge width gain between maxillary and m and ibular sites was not statistically significant ( P > .08 ) . Mean ridge width gain was 1.1 mm for both maxillary and m and ibular sites . There was a loss in bone height of 0.3 mm from baseline . Four implants in four patients could not be placed because of inadequate ridge width augmentation . Histologic examination of the grafted sites revealed connective tissue encapsulation of most residual graft particles . In this study , bioactive glass particulate and an e-PTFE barrier did not consistently augment localized ridge defects for dental implant placement This prospect i ve clinical study evaluated the 5-year survival and success rates of 66 titanium implants placed in bone that had been previously augmented with autografts and nonresorbable barrier membranes . During the observation period , three patients with five implants dropped out of the study . None of the remaining 61 implants were lost during the follow-up period ( implant survival rate of 100 % ) . One implant exhibited a periimplant infection , whereas 60 implants were considered clinical ly successful at the 5-year examination , result ing in a 5-year success rate of 98.3 % . It can be concluded that the clinical results of implants in regenerated bone are comparable to those of implants in nonregenerated bone AIMS The objective of this working group was to assess and make specific recommendations to improve the quality of reporting of clinical research in implant dentistry and discuss ways to reach a consensus on choice of outcomes . MATERIAL AND METHODS Discussion s were informed by three systematic review s on quality of reporting of observational studies ( case series , case-control and cohort ) and experimental research ( r and omized clinical trials ) . An additional systematic review provided information on choice of outcomes and analytical methods . In addition , an open survey among all workshop participants was utilized to capture a consensus view on the limits of currently used survival and success-based outcomes as well as to identify domains that need to be captured by future outcome systems . RESULTS The Workshop attempted to clarify the characteristics and the value in dental implant research of different study design s. In most areas , measurable quality improvements over time were identified . The Workshop recognized important aspects that require continued attention by clinical research ers , funding agencies and peer review ers to decrease potential bias . With regard to choice of outcomes , the limitations of currently used systems were recognized . Three broad outcome domains that need to be captured by future research were identified : ( i ) patient reported outcome measures , ( ii ) peri-implant tissue health and ( iii ) performance of implant supported restorations . Peri-implant tissue health can be measured by marginal bone level changes and soft tissue inflammation and can be incorporated in time to event analyses . CONCLUSIONS The Workshop recommended that collaboration between clinicians and epidemiologists/ clinical trials specialists should be encouraged . Aspects of design aim ed at limitation of potential bias should receive attention by clinical research ers , funding agencies and journal editors . Adherence to appropriate reporting guidelines such as STROBE and CONSORT are necessary st and ards . Research on outcome measure domains is an area of top priority and should urgently inform a proper process leading to a consensus on outcome measures in dental implant research OBJECTIVE This study has been design ed to evaluate the capability of a new surgical device ( Extension Crest ) to widen narrow edentulous alveolar ridges and to allow a correct placement of endosseous implants in horizontally atrophied sites . MATERIAL AND METHODS Forty-five patients , 20 males and 25 females , aged 20 - 66 years , affected by edentulism associated to horizontal resorption of the ridges , were treated by means of a sagittal osteotomy and expansion of the ridge with a new surgical device ( Extension Crest ) to obtain a wider bony base for ideal implant placement . In the same procedure in 33 patients , and 1 week afterwards in 12 patients , 110 endosseous titanium implants ( ITI TE ) were placed . Three to four months later , the patients were rehabilitated with implant-supported prostheses . RESULTS The success rate of the expansion technique was 97.8 % . A total of 110 implants were inserted in the exp and ed ridges . The mean follow-up after the start of prosthetic loading was 20.4 months . Three implants were removed before the start of prosthetic loading , because of non-integration , while no other implants failed after the completion of the prosthetic rehabilitation . Three implants , although integrated and in function , did not fulfill success criteria : cumulative success and survival rates at the end of the observation period were 95.4 % and 97.3 % , respectively . CONCLUSION Within the limits of this study , this technique appeared to be reliable and simple , with reduction of morbidity and times of dental rehabilitation as compared with other techniques such as autogenous bone grafts and guided bone regeneration . Survival and success rates of implants placed in the treated areas are consistent with those placed in native bone OBJECTIVES The aim of the present r and omized-controlled double-blinded clinical multicenter study was to assess the use of either a new cross-linked ( VN ) or a native collagen membrane ( BG ) for the treatment of dehiscence-type defects at titanium implants . MATERIAL AND METHODS A total of n=54 patients were recruited in four German university clinics . According to a parallel-groups design , dehiscence-type defects at titanium implants were filled with a natural bone mineral and r and omly assigned to either VN or BG . Submerged sites were allowed to heal for 4 months . Primary ( e.g. , changes in defect length - DeltaDL , quality of newly formed tissue [ 0 - 4 ] - TQ ) and secondary parameters ( e.g. , membrane exposure , tissue conditions at dehisced sites ) were consecutively recorded . RESULTS Four patients were excluded due to an early wound infection ( VN:3 ; BG:1 ) , and one patient was lost during follow-up ( VN ) . The mean DeltaDL was 3.0 + /- 2.5 mm in the VN , and 1.94 + /- 2.13 mm in the BG group . The assessment of TQ revealed comparable mean values in both groups ( VN : 3.05 + /- 1.66 , BG : 3.46 + /- 1.48 ) . A significant correlation between membrane exposure and inflammation of the adjacent soft tissue was observed in the VN group . In both groups , the mean DL and TQ values were not significantly different at either non-exposed or exposed implant sites . CONCLUSION The results of the present study have indicated that VN supported bone regeneration on a level non-inferior to BG . However , in case of a premature membrane exposure , cross-linking might impair soft-tissue healing or may even cause wound infections AIM This in vivo split-mouth r and omized controlled trial compared a synthetic bone substitute with a bovine bone mineral to cover bone dehiscences after implant insertion . MATERIAL S AND METHODS Fourteen patients received four to six implants to support an overdenture . Two comparable dehiscences within the same patient were first covered with a layer of autogenous bone , followed by a layer of either Bio-Oss ® ( group 1 ; Geistlich Pharma AG , Wolhusen , Switzerl and ) or Straumann BoneCeramic ® ( group 2 ; Institut Straumann AG , Basel , Switzerl and ) and sealed by a resorbable membrane . The change in vertical dimension of the defect was measured at implant placement and at abutment connection ( 6.5 months ) . Clinical and radiological parameters were evaluated up to 1 year of loading . RESULTS The vertical size of the defect at surgery was 6.4 ± 1.6 mm for group 1 and 6.4 ± 2.2 mm for group 2 sites , measured from the implant shoulder . After 6.5 months , the depth of the defect was reduced to 1.5 ± 1.2 mm and 1.9 ± 1.2 mm for group 1 and group 2 sites , respectively ( p > 0.05 ) . No implants failed during follow-up . Mean marginal bone loss over the SLActive surface was 0.94 mm ( group 1 ) , 0.81 mm ( group 2 ) , and 0.93 mm ( group 3 , no dehiscence ) after 1 year of loading . CONCLUSION Both bone substitutes behaved equally effectively OBJECTIVES This prospect i ve clinical study investigates long-term survival and clinical parameters of non-submerged implants with large buccal dehiscences treated with a deproteinized bovine bone mineral xenograft and a non-resorbable membrane in a one-stage approach . MATERIAL AND METHODS Sixteen consecutive non-submerged implants ( ITI Straumann ) were installed in narrow alveolar ridges in 13 patients ( age range : 25 - 61 years ) . All patients were non-smokers . On the buccal site the bone dehiscence ranged between 3 and 9 mm . Primary stability was achieved in all but one implant . The exposed threads were covered with a xenograft ( Bio-Oss ) and a non-resorbable exp and ed polytetrafluoroethylene membrane . The flap was sutured leaving the implant head non-submerged . The membrane was removed when ( 1 ) the membrane became exposed or ( 2 ) after a maximum of 24 weeks . All implants received singular cemented crowns . The implants were followed for a period ranging from 12 to 114 months . Whole-mouth plaque index ( Pl ) , the % of bleeding on probing ( BOP ) , probing depth and signs of peri-implantitis were recorded . Every year periapical radiographs were taken using a long cone technique . RESULTS All but one implant integrated successfully . At the time of membrane removal , all previously exposed threads were completely covered with richly vascularized tissue except for two implants where the coverage reached 63 % and 87 % , respectively . The whole-mouth plaque score and BOP remained low in all patients during the observation period . None of the implants had plaque and , except for one implant BOP never occurred . All implants were stable and in function . Swelling , redness or purulence was never observed . On the periapical radiographs no bone resorption was observed on the mesial and distal site except for one implant in one patient with a mesial and distal bone resorption of 2 and 3 mm . Probing depth was never higher than 3 mm except for one patient where the implant was placed deeply subgingival for esthetical reasons . CONCLUSION This prospect i ve long-term study shows that with the use of non-submerged transmucosal implants , large bony dehiscences can be treated in a one-stage approach using a stiff non-resorbable membrane combined with a xenograft This prospect i ve clinical study evaluated bone regeneration around 20 dental implants placed in 15 patients ( mean age 39.7 years ) . Peri-implant bone defects were augmented with autogenous bone grafts harvested intraorally from the m and ible ( chin or retromolar area ) . Augmented sites were covered with an individually trimmed micro titanium mesh which was rigidly affixed with microscrews to the residual jaw bone . Height of implant exposure ( mean 6.5 mm ) , i.e. dehiscencies ( 80 % ) or fenestrations ( 20 % ) , and graft height ( mean 6.2 mm ) were measured in an apico-coronal direction using a periodontal probe . At re-entry ( mean interval 6.6 months ) the titanium mesh and microscrews were removed and bone regeneration assessed . The mean height of the integrated bone graft was 5.8 mm corresponding to a mean bone fill of 93.5 % . The overall postop healing course was excellent with only one site developing a soft tissue dehiscence with subsequent mesh exposure ( complication rate 5 % ) . This study demonstrated that a micro titanium mesh in combination with autogenous bone grafts is effective for treatment of peri-implant bone defects BACKGROUND Autogenous bone chips can be harvested during drilling of implant sites and may be used as a graft material for bone augmentation and coverage of exposed implant threads . PURPOSE The aim of this prospect i ve study was to evaluate the possibility of augmenting exposed implant threads with autogenous bone chips . MATERIAL S AND METHODS Twenty-one consecutive patients treated with screw-shaped oral implants with exposed threads due to buccal fenestration or marginal defects were augmented with autogenous bone harvested with a bone trap during drilling of the implant site . Both marginal ( 9 sites ) and fenestration defects ( 12 sites ) , with 4 to 14 exposed implant threads , were registered clinical ly and with photography . The number of exposed implant threads was measured before and at second-stage surgery 6 months after augmentation . RESULTS Complete bone coverage of the exposed implant threads was seen in 12 of the 21 implant sites . Six sites showed one to two remaining exposed threads , two showed about 40 % coverage , and one showed flattening of the defect but with eight of nine exposed threads at 6 months follow-up . The mean bone gain was 81 % in patients with a marginal defect and 82 % in patients with a fenestration defect . CONCLUSION The results from this clinical study show that it is possible to gain bone over exposed implant threads by augmentation with autogenous bone chips BACKGROUND Guided bone regeneration ( GBR ) is a viable treatment for osseous defects surrounding dental implants . Controversy exists regarding the choice of barrier membrane used and the method of membrane fixation to achieve GBR . METHODS This study compared the efficacy of a porcine-derived bioabsorbable collagen membrane and an exp and ed polytetrafluoroethylene ( ePTFE ) membrane ( non-resorbable ) for GBR using a bovine bone xenograft/autograft bone composite in defects surrounding dental implants . The study also examined the effect of primary barrier fixation on GBR . Defect size was recorded at Stage 1 and 2 surgeries ( performed 6 months apart ) . Forty-eight subjects ( 41 % males , 59 % females ) requiring GBR were treated with either collagen ( 23 ) or ePTFE ( 25 ) barriers , respectively . Implants were titanium self-tapping screw-type . In 34 GBR sites , barrier fixation was achieved with polylactic acid resorbable pins . The remaining barriers were secured with the implant cover screw and /or embedded beneath the flaps . RESULTS At 6 months , a decrease in defect width ( collagen barrier 1.95 + /- 0.60 mm , ePTFE barrier 2.65 + /- 0.56 mm ) , length ( collagen barrier 2.65 + /- 0.61 mm , ePTFE barrier 2.26 + /- 0.66 mm ) , and circumference ( degrees ) ( collagen barrier 57.7 + /- 18.7 , ePTFE barrier 80.2 + /- 19.9 ) was observed for both membranes . A significant number ( chi2 , P = 0.041 ) of postoperative complications occurred when barrier fixation was lacking at initial surgery . Furthermore , a significant difference ( P < 0.05 ) in the success of GBR with respect to defect size was observed when barrier fixation was taken into account . CONCLUSIONS In conclusion , both collagen and ePTFE barriers proved suitable for achieving GBR of osseous defects surrounding dental implants . The results of this study stress the importance of barrier fixation at the time of initial surgery The aim of this study was to analyse the clinical outcome of two different surgical methods for the reconstruction of narrow edentulous ridges before implant installation : guided bone regeneration with e-PTFE membranes and autologous bone chips or grafting of autologous bone blocks without e-PTFE membranes . Thirty partially edentulous patients , presenting insufficient bone width ( less than 4 mm ) in the edentulous sites for installation of screw-type titanium implants , were selected and assigned to two different treatment modalities . Fifteen patients ( group 1 ) were treated by means of guided bone regeneration with e-PTFE membranes supported by stainless steel screws and autologous bone chips taken from intraoral sites . Fifteen patients ( group 2 ) were treated by means of autologous bone blocks taken from intraoral or extraoral sites ( anterior iliac crest and calvaria ) and stabilized with titanium microscrews . Six to 8 months later , during re-entry for implant insertion , the gain of ridge width obtained was measured . In group 1 the average amount of bone gain was 2.7 mm , whereas in group 2 the value was 4.0 mm . Five to 6 months after implant placement prosthetic rehabilitation was started . The mean follow-up after prosthetic load has been 22.4 months . Success rates of implants according to Albrektsson criteria has been 93.3 % in group 1 , and 90.9 % in group 2 . Although a statistical comparison between the two treatment modalities may not be feasible , due to the bias result ing from the choice of treatment by the clinician and from the differences in donor sites and defect extension , some considerations can be made : 1 ) both methods are a reliable means for the correction of narrow edentulous ridges ; 2 ) both techniques necessitate overcorrection of the defect because of interposition of connective tissue beneath the membrane in the first group and bone resorption in the second one ; 3 ) the use of semipermeable barriers increases the costs of the surgical procedure , as compared to bone grafting without membranes ; 4 ) guided bone regeneration presents a higher risk of infection because of wound dehiscence and membrane exposure . Therefore , in case of wide edentulous areas , reconstruction of narrow ridges should be performed with bone blocks without membranes AIM The aim of the present study was to evaluate if the use of deprotenized bovine bone mineral ( DBBM ) and collagen barrier membranes ( CM ) in combination with m and ibular bone block grafts could reduce bone block graft resorption during healing . METHODS A prospect i ve r and omized controlled study has been design ed . Twenty-two ridges presenting horizontal alveolar deficiency ( crest width < 4 mm ) and at least two adjacent missing teeth were included in the study . In the control group , one or multiple m and ibular blocks were used to gain horizontal augmentation of the ridge . In the test group , DBBM granules were added at the periphery and over the graft . The reconstructions were covered by two layers of CM . Implants were placed 4 months after grafting . Direct measurements of crest width were performed before and immediately after bone augmentation , and immediately before implant placement . RESULTS Statistical analysis showed no significant differences in crest width between test and control groups at baseline and immediately after grafting . Mean augmentation at first surgery in the test group was 4.18 vs. 4.57 mm in the control group . Final gain obtained at the time of implant placement was 3.93 mm in the test and 3.67 mm in the control groups . The difference in mean graft resorption between test and control sites was statistically significant ( 0.25 mm in the test group vs. 0.89 mm in the control group , P=0.03 ) . Complications seem to occur more often in the test group ( complications recorded in three cases in the test group vs. one complication recorded in the control group ) . In all cases , implants could be placed in the planned sites and a total of 55 implants were placed ( 28 in the test group and 27 in the control group ) . All implants could be considered successfully integrated at the 24-month follow-up visit . CONCLUSION The results from this study showed that the addition of bovine bone mineral and a CM around and over a m and ibular bone block graft could minimize graft resorption during healing . On the other h and , the use of bone substitutes and barrier membranes in combination with block grafts increased the frequency of complications and the difficulty of their management |
1,009 | 16,034,948 | Mass media interventions have immediate and overall effects in promotion of HIV testing .
No long-term effects were seen . | BACKGROUND Use of the mass media is one of the important strategies in communicating behavioral change in relation to HIV/AIDS prevention .
Mass media are used to promote voluntary HIV counseling and testing and to sustain test-seeking behavior .
OBJECTIVES To assess the effect of mass media interventions and the most effective form of mass media intervention at a general population level or in specific target population s , in relation to changes in HIV testing , compared with a control group or with pre-intervention levels . | 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 |
1,010 | 26,599,079 | 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 . | BACKGROUND Complete ( full-thickness ) rectal prolapse is a lifestyle-altering disability that commonly affects older people .
The range of surgical methods available to correct the underlying pelvic floor defects in full-thickness rectal prolapse reflects the lack of consensus regarding the best operation .
OBJECTIVES To assess the effects of different surgical repairs for complete ( full-thickness ) rectal prolapse . | 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 NCT00946205 . FINDINGS From Nov 1 , 2006 , to Jan 31 , 2014 , 75 consecutive patients were assigned to laparoscopic posterior sutured rectopexy ( n=37 ) or laparoscopic ventral mesh rectopexy ( n=38 ) . Eight patients withdrew consent to follow-up , leaving 34 patients in the posterior sutured rectopexy group and 33 in the ventral mesh rectopexy groups for the primary analysis . The preoperative-to-postoperative reduction in ODS score was 1·97 ( 95 % CI 0·01 to 3·93 ) in patients who received ventral mesh rectopexy and 2·18 ( -0·14 to 4·49 ) in those who received posterior sutured rectopexy ( difference -0·21 [ -3·19 to 2·78 ] ; p=0·890 ) . Postoperative surgical complications of Clavien-Dindo grade II or worse were reported in one ( 3 % ) of 38 patients in the ventral mesh rectopexy group ( ureteral injury result ing in urine leakage , and a psoas abscess ) and one ( 3 % ) of 37 patients in the posterior sutured rectopexy group ( haematoma and pelvic abscess ) . Two ( 5 % ) patients in the posterior sutured rectopexy group developed recurrence within 12 months compared with none in the ventral mesh rectopexy group ( p=0·305 ) . INTERPRETATION Functional outcome measured by preoperative-to-postoperative change in ODS score was not significantly superior in patients who underwent ventral mesh rectopexy compared with those who had posterior sutured rectopexy . Additional , large , r and omised , multicentre studies with long-term outcomes are warranted . FUNDING None The aim of this retrospective study was to compare the functional and clinical results of laparoscopic rectopexy with those of the open technique in two similar groups of patients with complete rectal prolapse and fecal incontinence . Between November 1992 and June 1997 , 21 patients underwent abdominal rectopexy . Thirteen patients ( group A : 12 women and 1 man , mean age 52.9 years , range 28 - 70 ) and 8 patients ( group B : 8 women , mean age 58.2 years , range 20 - 76 ) were su bmi tted to Well 's rectopexy by the open technique and the laparoscopic approach , respectively , without division of the lateral rectal ligaments . Assignment to each group was done r and omly . Before the operation , a detailed clinical history was taken , and patients were studied with inspection and digital examination of the anorectum , proctosigmoidoscopy , determination of pancolonic transit time , dynamic defecography , anorectal manometry , and anal electromyography . After the operation , all patients underwent perineal physiotherapy , external electric stimulation , and perineal biofeedback . The mean follow-up time was 29.5 months ( range 6 - 54 ) in group A and 25.7 months ( range 8 - 45 ) in group B. Values were compared by chi-square , Mann-Whitney U , and Wilcoxon tests , as appropriate ; differences were considered significant at p < 0.05 . In both groups , dyschezia and fecal incontinence improved significantly ( p < 0.05 ) after the operation . Basal pressure of anal sphincter , squeezing pressure , and rectoanal reflex improved without significance , whereas anoperineal pain was not significantly reduced . In group B , the postoperative hospital stay was shorter than in group A , with a marked reduction of costs . Laparoscopic Well 's rectopexy has the same clinical and functional results as the open technique , with a shorter postoperative hospital stay and lower costs Purpose A r and omized study was performed to assess whether new technologies offer advantages over the conventional technique on the clinical and functional outcome of patients with full-thickness rectal prolapse and fecal incontinence , su bmi tted to Altemeier 's procedure with levatorplasty . Methods Between January 1999 and December 2003 , 58 patients ( 55 females ; mean age , 70.9 ± 11.3 years ) with full-thickness rectal prolapse were evaluated with continence score , colonoscopy , anorectal manometry , anal electromyography , and sacral reflex latency ; 40 of them were selected and r and omly assigned to two groups : 20 patients ( Group 1 ; 19 females , 73.4 ± 10.4 years ) were su bmi tted to a conventional operation with monopolar electrocautery and h and sewn anastomosis , and 20 ( Group 2 ; 18 females , 71.5 ± 12.2 years ) using harmonic scalpel and circular stapler . Patients were followed up with clinical examination , anorectal manometry , and anal electromyography , with mean follow-up 29.3 ± 8.5 and 27.5 ± 9.2 months in Groups 1 and 2 , respectively . Results Operative time , blood loss , and hospital stay were significantly reduced in Group 2 ( P < 0.001 ) , whereas no differences were found in pain score , time to return to normal activity , morbidity , and mortality . Complications were two ( 10 percent ) stenosis in Group 1 . Fecal continence score significantly improved in both groups ( P < 0.01 ) , whereas anorectal manometry and neurophysiologic data were not significantly modified by the operation . Recurrence rates were 15 and 10 percent in Groups 1 and 2 , respectively ( P= not significant ) . Conclusions The clinical and functional long-term results of perineal rectosigmoidectomy with levatorplasty are not influenced by surgical instruments and type of coloanal anastomosis . The clinical relevance of the short-term results in high-risk patients should be specifically investigated A prospect i ve , r and omized study comparing abdominal rectopexy and sigmoid resection ( Group I ; n=15 ) with polyglycolic acid mesh rectopexy without sigmoidectomy ( Group II ; n=15 ) for complete rectal prolapse was carried out . One patient in Group I died of myocardial infa rct ion , one patient in Group II had a small bowel obstruction and two patients in Group I an asymptomatic stricture of the anastomosis . Otherwise a safe and efficient control of the prolapse was achieved in both groups . Eleven ( 73 % ) patients in Group I and 12 ( 80 % ) patients in Group II were more or less incontinent before surgery . After correction of prolapse incontinence improved in eight and ten patients in Groups I and II , but became slightly worse in one patient in Group II . A similar rise in anal pressures was measured in both groups after surgery . Constipation disappeared in three and seven patients in Groups I and II six months after surgery , but five additional patients in Group II became severely constipated and colectomy had to be performed in one of them . Surgery caused no significant change in colonic transit times even though increased transit times were measured in each group six months postoperatively . Sigmoid resection in conjunction with rectopexy does not seem to increase operative morbidity but tends to diminish postoperative constipation possibly by causing less outlet obstruction . RésuméUne étude prospect i ve r and omisée a été faite comparant la rectopexie abdominale avec résection sigmoïdienne ( groupe I n-15 ) avec la rectopexie utilisant une mèche d'acide polyglycolique sans sigmoïdectomie ( groupe II n=15 ) pour traiter le prolapsus rectal complet . Un patient du groupe I est mort d'infa rct us du myocarde , un patient du groupe II a eu une occlusion intestinale et deux patients du groupe II une sténose asymptomatique de leur anastomose . Par ailleurs un contrôle sur et efficace du prolapsus a été obtenu dans les deux groupes . 11 ( 73 % ) patients du groupe I et 12 ( 80 % ) patients du groupe II étaient plus ou moins incontinents avant l'opération . Après correction du prolapsus l'incontinence s'est amélioré chez 8 et 10 patients respectivement , mais a augmenté légèrement chez un patient du groupe II . Une augmentation similaire des pressions anales a été constatée dans les deux groupes après chirugie . La constipation a disparu chez 3 et 7 patients des groupes I et II six mois après chirurgie mais 5 patients supplémentaires du groupe II ont développé une constipation sévère et une colectomie a dû être pratiquée chez un d'entre eux . La chirurgie n'a provoqué aucune modification significative du temps de transit colique même un temps de transit augmenté a été trouvé dans chacun des groupes six mois après l'opération . La résection sigmoïdienne associée à la rectopexie ne semble pas augmenter la morbidité opératoire mais tend à diminuer la constipation postopératoire peut-être en diminuant l'obstruction terminale PURPOSE : Colonic and anorectal function are altered after posterior rectopexy . The aim of this r and omized , prospect i ve study was to evaluate the effects of rectal mobilization and division of the lateral ligaments on colonic and anorectal function . METHODS : Posterior rectopexy was performed in 18 patients with complete rectal prolapse . Anal manometry and measurement of rectal compliance , total and segmental colonic transit time , constipation score , and defecation frequency were performed preoperatively and three months postoperatively . Ligaments were divided in ten patients . RESULTS : Mean preoperative total transit time was similar between the two patient groups and doubled postoperatively ( P=0.03 ) . Mean postoperative segmental transit time increased by a factor of 1.7 in segments I ( ascending colon ) and II ( descending colon ) and by a factor of 2.3 in segment III ( rectosigmoid ) . The same pattern was found in both groups . Mean resting pressure decreased after division of the lateral ligaments and increased after preservation . Mean rectal compliance decreased after division of the ligaments and increased when they were preserved . Mean postoperative constipation score differed little from the preoperative score . Mean defecation frequency was decreased in the group with the ligaments preserved and increased in the group with the ligaments divided . None of the effects of rectal mobilization or division of the lateral ligaments on anorectal function reached statistical significance . CONCLUSION : Rectal mobilization had a statistically significant effect on colonic function . Total and segmental colonic transit times doubled . The effects on anorectal function were not significant . Division of the lateral ligaments did not significantly influence postoperative functional outcome Ivalon sponge rectopexy is a safe reliable procedure in the management of rectal prolapse . Sutured rectopexy is simpler and avoids the use of foreign material . Sutured rectopexy is m and atory if synchronous resection is to be considered . Sixty‐three patients ( 62 women ) with fullthickness rectal prolapse were entered into a prospect i ve r and omized trial of Ivalon sponge rectopexy ( 31 patients ) versus sutured rectopexy ( 32 ) . Twenty patients ( 32 per cent ) had coexistent incontinence ( ten in each group ) . The operation was performed in the st and ard manner with a sutured rectangle of sponge or sutures alone placed along the length of the sacrum . Postoperative morbidity occurred in nine patients ( 14 per cent ) of whom three underwent a sutured procedure and six Ivalon rectopexy : wound infection in three , chest infection in two , urinary tract infection in two and thromboembolism in two . There were no deaths within 30 days . At a median follow‐up of 47 months prolapse had recurred in two patients ( 3 per cent ) , one in each group , 14 ( 22 per cent ) suffered from incontinence ( of whom five had undergone a sutured procedure ) , while 25 ( 40 per cent ) had developed constipation ( of whom 15 had received Ivalon rectopexy ) . The medium‐term results of rectopexy by suture alone are equivalent to those obtained following the conventional Ivalon procedure . These data suggest that Ivalon rectopexy could now be ab and oned |
1,011 | 31,297,704 | 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 . | The Japan Society for Oriental Medicine makes a compilation of structured abstract s of r and omized controlled trials ( RCTs ) of Kampo medicines available on its Evidence Reports of Kampo Treatment ( EKAT ) website . | 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 |
1,012 | 24,146,332 | There is currently no systematic evidence to guide clinical decision-making regarding the timing for closure of traumatic wounds . | BACKGROUND Acute traumatic wounds are one of the common reasons why people present to the emergency department .
Primary closure has traditionally been reserved for traumatic wounds presenting within six hours of injury and considered ' clean ' by the attending surgeon , with the rest undergoing delayed primary closure as a means of controlling wound infection .
Primary closure has the potential benefit of rapid wound healing but poses the potential threat of increased wound infection .
There is currently no evidence to guide clinical decision-making on the best timing for closure of traumatic wounds .
OBJECTIVES To determine the effect on time to healing of primary closure versus delayed closure for non bite traumatic wounds presenting within 24 hours post injury .
To explore the adverse effects of primary closure compared with delayed closure for non bite traumatic wounds presenting within 24 hours post injury . | 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 allows recording of changes in the superficial aspect of the wound only , HRUS scanning permits the quantitative assessment of structural changes deep within the wound . Temporal changes in the width of the base of the wound can be used as an indication of the progress of repair |
1,013 | 27,427,411 | Targeting preschool setting s and applying a comprehensive multisectoral approach may increase the effectiveness and sustainability of childhood obesity prevention programmes | The rapid economic growth in Asia in the past few decades has contributed to the global increase in childhood obesity prevalence .
Yet , little is known about obesity prevention efforts in this region .
This systematic review provides an overview of child obesity prevention programmes in Asia . | 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-component program was implemented within the intervention group , while students in the control group followed their usual health and physical education curriculum with no additional intervention program . The intervention consisted of four components : a ) classroom curriculum , ( including physical education and healthy diet education ) , b ) school environment support , c ) family involvement , and d ) fun programs/events . The primary study outcome was body composition , and secondary outcomes were behaviour and behavioural determinants . Discussion The intervention was design ed with due consideration of Chinese cultural and familial tradition , social convention , and current primary education and exam system in Mainl and China . We did our best to gain good support from educational authorities , school administrators , teachers and parents , and to integrate intervention components into schools ’ regular academic programs . The results of and lesson learned from this study will help guide future school-based childhood obesity prevention programs in Mainl and China . Trial registration Registration number : Background The prevalence of obesity increased while certain measures of physical fitness deteriorated in preschool children in China over the past decade . This study tested the effectiveness of a multifaceted intervention that integrated childcare center , families , and community to promote healthy growth and physical fitness in preschool Chinese children . Methods This 12-month study was conducted using a quasi-experimental pretest/posttest design with comparison group . The participants were 357 children ( mean age = 4.5 year ) enrolled in three grade levels in two childcare centers in Beijing , China . The intervention included : 1 ) childcare center intervention ( physical activity policy changes , teacher training , physical education curriculum and food services training ) , 2 ) family intervention ( parent education , internet website for support , and family events ) , and 3 ) community intervention ( playground renovation and community health promotion events ) . The study outcome measures included body composition ( percent body fat , fat mass , and muscle mass ) , Body Mass Index ( BMI ) and BMI z-score and physical fitness scores in 20-meter agility run ( 20M-AR ) , broad jump for distance ( BJ ) , timed 10-jumps , tennis ball throwing ( TBT ) , sit and reach ( SR ) , balance beam walk ( BBW ) , 20-meter crawl ( 20M-C ) ) , 30-meter sprint ( 30M-S ) ) from a norm referenced test . Measures of process evaluation included monitoring of children ’s physical activity ( activity time and intensity ) and food preparation records , and fidelity of intervention protocol implementation . Results Children in the intervention center significantly lowered their body fat percent ( −1.2 % , p < 0.0001 ) , fat mass ( −0.55 kg , p < 0.0001 ) , and body weight ( 0.36 kg , p < 0.02 ) and increased muscle mass ( 0.48 kg , p < 0.0001 ) , compared to children in the control center . They also improved all measures of physical fitness except timed 10-jumps ( 20M-AR : −0.74 seconds , p < 0.0001 ; BJ : 8.09 cm , p < 0.0001 ; TBT : 0.52 meters , p < 0.006 ; SR : 0.88 cm , p < 0.03 ; BBW : −2.02 seconds , p < 0.0001 ; 30M-S : −0.45 seconds , p < 0.02 ; 20M-C : −3.36 seconds , p < 0.0001 ) . Process evaluation data showed that the intervention protocol was implemented with high fidelity . Conclusions The study demonstrated that a policy-driven multi-faceted intervention can improve preschool children ’s body composition and physical fitness . Program efficacy should be tested in a r and omized trial . Trial registration ChiCTR-ONRC-14004143 INTRODUCTION Family- and school-based interventions for childhood obesity have been widely applied ; however , the prevalence of childhood obesity remains high . The purpose of this RCT is to evaluate the effectiveness of a family-individual-school-based comprehensive intervention model . DESIGN Cluster RCT . SETTING / PARTICIPANTS Fourteen primary schools were selected from 26 primary schools in a district of Shanghai , China , and then r and omly divided into intervention and control groups with seven schools in each . The trial started with first- grade students . A total of 1,287 students in the intervention group and 1,159 in the control group were studied overall . INTERVENTION The baseline study was conducted in January 2011 , and family-individual-school-based interventions started in March 2011 and ended in December 2013 for intervention group students . Three follow-up studies were conducted in January 2012 , January 2013 , and January 2014 . Data analysis was conducted in March 2014 . MAIN OUTCOME MEASURES Students ' weight and height were measured . The prevalence of obesity/overweight and BMI z-scores were calculated and analyzed using a generalized estimating equation approach . RESULTS The overall prevalence of overweight/obesity declined from 28.92 % in 2011 to 24.77 % in 2014 , with a difference of 4.15 % in the intervention group compared with a 0.03 % decline ( from 30.71 % to 30.68 % ) in the control group . The intervention group had significantly lower odds of developing obesity or overweight and had decreased average BMI z-scores compared with the control group , especially for obese or overweight students . CONCLUSIONS The family-individual-school-based comprehensive intervention model is effective for controlling childhood obesity and overweight BACKGROUND Childhood obesity has become a health problem in urban areas in China . Intervention to reduce childhood obesity should be of high priority . School-based intervention programmes are needed to deal with the growing prevalence of childhood obesity in China . METHODS Five primary schools were selected r and omly for this study in the Beijing urban area in China ; two were allocated to the intervention group and three to the control group . A total of 2425 children ( 1029 children in intervention schools and 1396 children in control schools ) took part in the study for 3 years . In the intervention group , children and their parents were involved in a programme of nutrition education and physical activity . Control school students followed their usual health and physical education curriculum with no extra intervention . RESULTS After the 3-year intervention , the prevalence of overweight and obesity were significantly lower in the intervention schools than in the control schools ( overweight : 9.8 % vs. 14.4 % , P < 0.01 ; obesity : 7.9 % vs. 13.3 % , P < 0.01 ) . The prevalence of overweight and obesity decreased by 26.3 % and 32.5 % in intervention schools respectively after intervention . The prevalence of overweight and obesity increased in control schools . There was also significant difference in body mass index between intervention and control schools ( 18.2 + /- 2.6 vs. 20.3 + /- 3.4 , P < 0.01 ) after intervention . More non-obese children became obese in the control schools ( 7.0 % ) than in the intervention schools ( 2.4 % ) at end line ( P < 0.01 ) . Among the children who were obese at baseline , 49.2 % remained obese at end line in intervention schools while 61.9 % remained obese in control schools ( P < 0.01 ) . CONCLUSIONS Our study showed that an intervention programme could be feasible in schools in Beijing , China . The prevalence of overweight and obesity was reduced in schoolchildren in Beijing through an intervention focused on nutrition education and physical activity . Overweight and obesity children as well as normal weight children and their parents should be involved in such an intervention programme Background Effective strategies to combat childhood obesity are challenging , especially among South Asian girls . We conducted a pilot cluster trial of a school-based physical activity programme among preadolescent girls to determine the feasibility ( recruitment , retention and implementation ) of the programme and influence on blood pressure ( BP ) and body mass index ( BMI ) . Methods This two-arm parallel cluster intervention trial was conducted in four similar all-girls public sector schools in Karachi over a 20-week period . All girls aged 9–11 years were included . Intervention was a physical activity programme of 30 min duration four times a week . Primary outcome was to assess the feasibility of the physical activity programme defined as recruitment and retention > 70 % and treatment fidelity of > 80 % of physical activity programme . Secondary outcomes were changes in systolic BP ( SBP ) , diastolic BP ( DBP ) and BMI from baseline to follow-up . Results A total of 360 participants were invited to participate , 280 girls met eligibility criteria , and were recruited ; 131 ( 77 % ) in the intervention group and 146 ( 87 % ) in control group . At follow-up , the overall retention of participants was 222 ( 79.2 % ) ; 105 ( 80.1 % ) in the intervention group and 117 ( 78.5 % ) in the control group . The difference in mean change from baseline to follow-up in SBP , DBP and BMI score was 1.9 mm Hg , 0.7 mm Hg and 0.55 kg/m2 between intervention and control arms , respectively . Conclusions A school-based physical activity programme in a public sector girls school of urban Pakistan is feasible . There was a favourable trend in BP and BMI at follow-up . ( Clinical trial ID NCT 00533819 ) |
1,014 | 25,832,699 | 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 . | PURPOSE Studies of the association between ataxia telangiectasia-mutated ( ATM ) gene polymorphisms and acute radiation injuries are often small in sample size , and the results are inconsistent .
We conducted the first meta- analysis to provide a systematic review of published findings . | 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 |
1,015 | 28,681,192 | 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 | Background Non-Small Cell Lung Cancer ( NSCLC ) is characterized by aggressiveness and includes the majority of thorax malignancies .
The possibility of early stratification of patients as responsive and non-responsive to radiotherapy with a non-invasive method is extremely appealing .
The distribution of the Fluorodeoxyglucose ( 18F – FDG ) in tumours , provided by Positron-Emission-Tomography ( PET ) images , has been proved to be useful to assess the initial staging of the disease , recurrence , and response to chemotherapy and chemo-radiotherapy ( CRT ) .
Objectives In the last years , particular efforts have been focused on the possibility of using ad interim 18F – FDG PET ( FDGint ) to evaluate response already in the course of radiotherapy .
However , controversial findings have been reported for various malignancies , although several results would support the use of FDGint for individual therapeutic decisions , at least in some pathologies .
The objective of the present review is to assemble comprehensively the literature concerning NSCLC , to evaluate where and whether FDGint may offer predictive potential . | 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 ardized uptake value ( SUV ) on post-treatment [(18)F]fluorodeoxyglucose positron emission tomography ( FDG-PET ) correlates with survival in stage III non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients received conventional concurrent platinum-based chemoradiotherapy without surgery ; postradiotherapy consolidation chemotherapy was allowed . Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy . SUVs were analyzed both as peak SUV ( SUVpeak ) and maximum SUV ( SUVmax ; both institutional and central review readings ) , with institutional SUVpeak as the primary end point . Relationships between the continuous and categorical ( cutoff ) SUVs and survival were analyzed using Cox proportional hazards multivariate models . RESULTS Of 250 enrolled patients ( 226 were evaluable for pretreatment SUV ) , 173 patients were evaluable for post-treatment SUV analyses . The 2-year survival rate for the entire population was 42.5 % . Pretreatment SUVpeak and SUVmax ( mean , 10.3 and 13.1 , respectively ) were not associated with survival . Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0 , respectively . Post-treatment SUVpeak was associated with survival in a continuous variable model ( hazard ratio , 1.087 ; 95 % CI , 1.014 to 1.166 ; P = .020 ) . When analyzed as a prespecified binary value ( ≤ v > 3.5 ) , there was no association with survival . However , in exploratory analyses , significant results for survival were found using an SUVpeak cutoff of 5.0 ( P = .041 ) or 7.0 ( P < .001 ) . All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak . CONCLUSION Higher post-treatment tumor SUV ( SUVpeak or SUVmax ) is associated with worse survival in stage III NSCLC , although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time PURPOSE As Radiation-Induced Lung Toxicity ( RILT ) is dose-limiting for radiotherapy ( RT ) of lung cancer and current parameters are only moderately associated with RILT , we sought for novel parameters associated with RILT . PATIENTS AND METHODS In this prospect i ve study , FDG-PET-CT scans were taken on days 0 , 7 and 14 after initiation of high-dose RT in 18 patients with stage III non-small cell lung cancer . The maximal St and ardized Uptake Value ( SUV(max ) ) in the lung outside of the GTV was used as a measure of FDG uptake . At the same time-points , the serum IL-6 concentrations were measured . RILT was defined as dyspnea score 2 ( CTCAE3.0 ) . RESULTS Six of 18 patients developed RILT . Before RT , SUV(max ) in the lung was not significantly different between patients who developed RILT and those who did not develop RILT . Patients who developed RILT post-radiation had a significant increased SUV on days 7 and 14 during RT , whereas the group that did not experience RILT showed no significant SUV changes . The SUV(max ) of the lungs increased significantly more in the group that later developed RILT compared to those who did not develop RILT . Neither the IL-6 concentration nor the mean lung dose was associated with RILT . CONCLUSIONS The increase in FDG uptake in the normal lung early during RT was highly associated with the subsequent development of clinical RILT . This may help to identify patients at high risk for RILT at a time when adjustments of the treatment or strategies to prevent RILT are still possible Objectives : Our aim was to assess FDG-PET/CT as a surrogate biomarker of the pathological complete response in locally advanced rectal cancer treated with neoadjuvant chemoradiation . Methods : T3–4 and /or N+ rectal cancer patients were treated prospect ively with capecitabine-based chemoradiation and total mesorectal excision 7–8 weeks later . FDG-PET/CT uptake was obtained at baseline , after 2 weeks , and 6 weeks following treatment completion , calculating the maximum st and ardized uptake value ( SUV ) and percentage difference to identify the early and late metabolic ‘ response index ’ . Results : Thirty-one patients were treated from January 2009 to January 2012 at the Istituto Nazionale dei Tumori of Milan . One patient was excluded due to surgery refusal . The pathological complete response rate was 30 % . Early FDG-PET/CT was performed in 24 consenting patients and failed to show predictive utility . On the contrary , significant differences in late SUV value and response index were observed between complete and noncomplete pathological responders ( p = 0.0006 and 0.03 ) . In multivariate analysis including most relevant SUV parameters , none of them was independently associated with a pathological complete response . With receiver operating characteristic curve analysis , a late SUV threshold < 5.4 had 81 % sensitivity and 100 % specificity , with 90 % overall accuracy . Conclusions : We evidence d a possible predictive role of late FDG-PET/CT for the assessment of pathological response in locally advanced rectal cancer following neoadjuvant chemoradiation UNLABELLED 18F-FDG PET has gained acceptance for staging of esophageal cancer . However , FDG is not tumor specific and false-positive results may occur by accumulation of FDG in benign tissue . The tracer 18F-fluoro-3'-deoxy-3'-L-fluorothymidine ( 18F-FLT ) might not have these drawbacks . The aim of this study was to investigate the feasibility of 18F-FLT PET for the detection and staging of esophageal cancer and to compare 18F-FLT PET with 18F-FDG PET . Furthermore , the correlation between 18F-FLT and 18F-FDG uptake and proliferation of the tumor was investigated . METHODS Ten patients with biopsy-proven cancer of the esophagus or gastroesophageal junction were staged with CT , endoscopic ultrasonography , and ultrasound of the neck . In addition , all patients underwent a whole-body 18F-FLT PET and 18F-FDG PET . St and ardized uptake values were compared with proliferation expressed by Ki-67 positivity . RESULTS 18F-FDG PET was able to detect all esophageal cancers , whereas 18F-FLT PET visualized the tumor in 8 of 10 patients . Both 18F-FDG PET and 18F-FLT PET detected lymph node metastases in 2 of 8 patients . 18F-FDG PET detected 1 cervical lymph node that was missed on 18F-FLT PET , whereas 18F-FDG PET showed uptake in benign lesions in 2 patients . The uptake of 18F-FDG ( median st and ardized uptake value [ SUV(mean ) ] , 6.0 ) was significantly higher than 18F-FLT ( median SUV(mean ) , 3.4 ) . Neither 18F-FDG maximum SUV ( SUV(max ) ) nor 18F-FLT SUV(max ) correlated with Ki-67 expression in the linear regression analysis . CONCLUSION In this study , uptake of 18F-FDG in esophageal cancer is significantly higher compared with 18F-FLT uptake . 18F-FLT scans show more false-negative findings and fewer false-positive findings than do 18F-FDG scans . Uptake of 18F-FDG or 18F-FLT did not correlate with proliferation BACKGROUND Intensity modulated radiotherapy for stage III lung cancer has become commonplace in the United States in the absence of r and omized controlled trials . We used a large , population -based data base to determine which factors led to increased utilization of IMRT and to evaluate associations of IMRT with toxicities . METHODS The Surveillance , Epidemiology , and End Results (SEER)-Medicare records identified 3986 individuals aged 66 years or older diagnosed with stage III lung cancer between 2001 and 2007 and treated with IMRT or 3D conformal radiotherapy . Predictors of IMRT use were determined using logistic regression . Associations of IMRT use with diagnosis codes for radiation-related toxicities were evaluated with multivariate proportional hazards regression and propensity-score matching . RESULTS Among the 3986 patients studied , the median age was 75 years , 54.1 % were male , and 62 % had IIIA disease . Two hundred and fifty seven ( 6.5 % ) patients received IMRT , with use increasing from 0.5 % in 2001 to 14.7 % in 2007 ( P < 0.001 ) . Key predictors of IMRT delivery included increasing year of diagnosis and treatment in a freest and ing center ( odds ratio , 2.10 ; 95 % confidence interval [ CI ] , 1.59 - 2.77 , P < 0.001 ) ; tumor size , stage , and number of radiotherapy fractions delivered were not associated with IMRT use . IMRT use was not associated with a higher burden of lung or esophagus toxicities when compared to 3DCRT . CONCLUSION These findings suggest that practice environment strongly influenced adoption of IMRT for lung cancer . Patient and tumor factors were not significant predictors of IMRT use . Esophagus and lung toxicity rates were similar between IMRT and 3DCRT AIMS Computed tomography (CT)-based radiotherapy dose escalation for locally advanced non-small cell lung cancer ( LA-NSCLC ) has had limited success . In this planning study , we investigated the potential for adaptive dose escalation using respiratory-gated 18F-fluorodeoxyglucose ( FDG ) positron emission tomography/computed tomography scans ( 4DPET/4DCT ) acquired before and during a course of chemoradiotherapy ( CRT ) . MATERIAL S AND METHODS We prospect ively enrolled patients with LA-NSCLC receiving curative intent CRT . Radiotherapy was delivered using intensity-modulated radiotherapy ( IMRT ) using the week 0 4DCT scan . Three alternative , dose-escalated IMRT plans were developed offline based on the week 0 , 2 and 4 4DPET/4DCT scans . The FDG-avid primary ( PET-T ) and nodal disease ( PET-N ) volumes defined by the 50 % of maximum st and ard uptake value threshold were dose escalated to as high as possible while respecting organ at risk constraints . RESULTS Thirty-two patients were recruited , 27 completing all scans . Twenty-five patients ( 93 % ) were boosted successfully above the clinical plan doses at week 0 , 23 ( 85 % ) at week 2 and 20 ( 74 % ) at week 4 . The median dose received by 95 % of the planning target volume ( D95 ) at week 0 , 2 and 4 to PET-T were 74.4 Gy , 75.3 Gy and 74.1 Gy and to PET-N were 74.3 Gy , 71.0 Gy and 69.5 Gy . CONCLUSIONS Using 18F-FDG-4DPET/4DCT , it is feasible to dose escalate both primary and nodal disease in most patients . Choosing week 0 images to plan a course with an integrated boost to PET-avid disease allows for more patients to be successfully dose escalated with the highest boost dose |
1,016 | 27,833,728 | 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 . | OBJECTIVES The purpose of this review was to evaluate whether history of periodontitis and smoking habits could represent a risk factor for peri-implantitis and implant loss . | 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 r and omly allocated to three groups and received an implant on average 10 days ( Ea ) , 3 months ( De ) , or 17 months ( La ) after tooth extraction . Second-stage surgery was performed after 3 months of submerged healing ; metal-ceramic crowns were cemented after one additional month . St and ardized periapical radiographs were taken 1 week after implant placement ( TP ) , 1 week ( TC ) and 1 - 1.5 year ( T1 ) after crown delivery , and 10 years after implant placement ( T10 ) . Pocket depth ( PD ) and bleeding on probing were registered during controls ( TC - T10 ) . RESULTS Two Ea and one De implants failed to osseointegrate . Seven patients ( 4 Ea , 1 De , and 2 La ) were not available at T10 . No significant differences were found among groups regarding implant survival or radiographic peri-implant marginal bone levels ( Ea : 1.15 ± 0.77 ; De : 1.53 ± 1.06 ; La : 1.42 ± 1.07 ) at T10 . Similarly , no differences were observed among groups in the number of implants with PD ≥ 5 mm ( Ea : 29 % ; De : 35 % ; La : 44 % ) or the average depth of the sites with PD ≥ 5 mm ( Ea : 5.4 ± 0.7 ; De : 6.1 ± 1.4 ; La : 5.4 ± 0.5 ) at T10 . Peri-implant mucositis was found in 70 % of the cases ; peri-implantitis was diagnosed only in two implants ( 1 De , 1 La ) corresponding to 4.3 % . CONCLUSION Single-tooth implants placed early or delayed after tooth extraction show high survival rates and limited peri-implant marginal bone resorption or biological complications , similar to what is observed with implants placed according to the conventional ( late ) protocol BACKGROUND It has been reported in many articles that marginal bone resorptions are prevented by platform-switching design . However , what occurs when these implants are placed in the apical position is not completely known . PURPOSE This report describes a r and omized controlled clinical trial study that aims to test the hypothesis that less resorption will occur when platform-switching implants are placed 1 mm below bone level . MATERIAL S AND METHODS A total of 56 r and omly selected implants were inserted bilaterally , either 1 mm below bone level ( test group , 28 implants ) or at bone level ( control group , 28 implants ) of the patients ' posterior regions . Marginal bone resorptions were examined through periapical radiographies taken with the parallel technique at the time of crown cementation and the third , sixth , 12th , and 36th months after prosthetic loading . The modified plaque index , gingival index , bleeding on probing , and probing depths were used for follow-up periodontal care of the implants . RESULTS After 3 years , the mean radiographic vertical bone loss in the control group was significantly lower than in the test group ( 0.56 ± 0.35 mm and 1.21 ± 1.05 mm , respectively ) ( p < .01 ) . In terms of periodontal indexes , there were no statistically significant differences between the two groups ( p > .05 ) . No peri-implantitis or peri-implant mucositis was observed around the test or control implants . CONCLUSIONS More marginal bone resorptions occurred after the third year of loading in implants placed 1 mm below bone level . However , the resorptions did not reach the implants thread . In the control group , the first bone implant contact was placed under the level of the first threads . Therefore , the present r and omized clinical trial confirmed the hypothesis that placing platform-switching implants 1 mm below bone level reduced marginal bone loss . It can be noted that to reduce resorption , platform-switching implants should be placed below bone level PURPOSE To evaluate aged partially and fully edentulous patients who received dental implants and were maintained over time . Further , to determine how the partially and edentulous ageing population s ( 65 and above ) with dental implants maintain bone levels , proper oral hygiene , and perceive benefits of dental implants . MATERIAL S AND METHODS Since 1995 , patients receiving dental implants have been prospect ively entered into an Access-based computerized program ( Triton Tacking System ) . Patient demographics ( age , sex ) , bone quality , quantity , implant location , and type of surgery have been continuously entered into the data base . The data base was queried for patients receiving implants ( first stage ) between 66 and 93 years of age . Thirty-one patients were within this age group . Twenty-five patients returned to the clinic for periodontal and dental implant evaluation . The Periodontal Index was used to evaluate selected teeth in terms of probing depth , bleeding on probing , plaque accumulation , and mobility . Using NIH Image J , radiographs taken at second stage and last examination were measured for changes in interproximal bone levels . Once identified , each patient anomalously filled out an abbreviated quality of health life form . Due to small sample size , descriptive statistics were used to compare clinical findings . RESULTS Fifteen males ranging from 78 to 84 ( mean age 84 years ) years and 16 females from 66 to 93 ( mean age 83 years ) ( age range 66 - 93 ) were contacted by phone or mail and asked to return to our office for a re-examination . For this group , the first dental implants were placed in 1996 ( n = initial two implants ) and continuously recorded through 2013 ( n = last seven implants ) . Thirty-one patients received a total of 84 implants . Two patients were edentulous , and the remaining were partially edentulous . Four implants were lost . Between implant placement and 6- to 7-year interval , 13 patients with 40 implants had a cumulative survival rate of 94.6 % . Of the original group ( n = 33 ) , three were deceased , two were in nursing homes , and three could not be located . CONCLUSIONS Aged patients receiving dental implants had excellent implant survival rates , low periodontal disease index scores with minimal changes in interproximal bone levels . Results from this study indicate that patients with advanced age , in reasonably good health , have excellent implant survival rates , excellent quality of life scores , and can be maintained in good oral health OBJECTIVE The objective of this prospect i ve study was to determine the prevalence and incidence of marginal bone loss and , in addition , peri-implantitis in subjects and implant sites after 10 years in function . MATERIAL AND METHODS One hundred and thirty-three subjects with a total of 407 implants that had been in function for about 5 years attended a follow-up visit in 2007 ( visit 2 ; V2 ) . 100 of the 133 subjects returned for a new clinical and radiographic examination in 2012 ( visit 3 ; V3 ) . The clinical examination included assessment of " bleeding on probing " ( BoP+ ) and " probing pocket depth . " Subjects with implant sites that in the radiograph exhibited crater-shaped marginal bone loss of > 0.5 mm were identified as losers . RESULTS During the interval between V2 and V3 ( about 5 years ) , 13 implants in 7 subjects exhibited progressive bone loss and were removed . The overall amount of crestal bone loss that had occurred at the remaining implants between visit 1 ( V1 ; ≥1 year of loading ) and V3 ( 10 years ) was small ( 0.36 ± 1.4 mm ) . The bone-level reduction was twice as great between V2 and V3 as between V1 and V2 . Forty subjects and 75 ( 26 % ) implant sites exhibited marginal bone loss of > 0.5 mm between V1 and V3 . In the interval between V2 and V3 , 37 new implant sites lost significant amounts of bone . During the entire 10-year period ( V1-V3 ) , 12 % of patients and 5 % of implants displayed signs of peri-implantitis ( bone loss > 0.5 mm , BoP+ , PPD ≥6 mm ) , while in the V2-V3 interval , the corresponding numbers were 10 % ( patients ) and 4 % ( implant sites ) . CONCLUSION Sites with marginal bone loss of ≥1 mm were not common among implant patients . Peri-implantitis occurred in about 10 % of patients and 4 % of implant sites BACKGROUND The insertion torque value has been extensively used as an indicator for implant primary stability , which is considered a determining parameter for the implants success . PURPOSE The primary goal of the present r and omized clinical trial was to evaluate and compare the clinical outcome for implants placed with high insertion torque ( between 50 Ncm and 100 Ncm ) and regular insertion torque ( within 50 Ncm ) in healed ridges . MATERIAL S AND METHODS Partially edentulous patients , missing one or more m and ibular or maxillary teeth , having an adequate amount of bone , requiring implant placement , were r and omized to receive Blossom CT implants with regular insertion torque ( < 50 Ncm ) or CT implants with high insertion torque ( ≥50 Ncm ) . Implants were left to heal submerged for 3 months . Implants were restored with individualized abutments and cemented metal-ceramic crowns . Acquired measurements were : insertion torque values ( IT ) , thickness of buccal bone plate after implant osteotomy preparation ( BBT ) , marginal bone level ( MBL ) , and facial soft tissue level ( FST ) . All patients were followed 12 months after implant placement . RESULTS One hundred sixteen implants were placed in one hundred sixteen patients and enrolled for the study . Fifty-eight implants were r and omly allocated in regular-IT and high-IT groups with a mean insertion torque ranging from 20 Ncm to 50 Ncm and from 50 Ncm to 100 Ncm , respectively . Three implants failed , and another five implants showed at the 12-month evaluation a marginal bone loss ( ΔMBL ) greater than 1.5 mm , being considered unsuccessful . CONCLUSIONS The findings suggested that implants inserted with high-IT ( ≥50 Ncm ) in healed bone ridges showed more peri-implant bone remodeling and buccal soft tissue recession than implants inserted with a regular-IT ( < 50 Ncm ) . Moreover , sites with a thick buccal bone wall ( ≥1 mm ) - after implant osteotomy site preparation - seemed to be less prone to buccal soft tissue recession after 12 months than sites with a thin buccal bone wall ( < 1 mm ) OBJECTIVE The aim of this study was to evaluate prospect ively the 12-year outcome of implant-supported single-tooth restorations . MATERIAL AND METHODS Originally 45 self-tapping Astra Tech TiOblast ® ST-implants were installed by a two-stage protocol in 40 subjects requiring single-tooth prosthetic replacement for a missing tooth . Clinical and radiologic examinations were performed at completion of the prosthetic treatment 4 - 7 months after implant installation surgery and after 5 and 12 years in function . RESULTS At 12 years 31 patients and 35 implants were available for evaluation . The overall failure rate after 12 years was 10.3 % on the subject level and 9.1 % on the implant level . The mean bone loss amounted to 0.67 mm ( SD 2.20 ) on a subject level and 0.47 mm ( 1.72 ) on an implant level . Three subjects ( 10 % ) and three implants ( 8.6 % ) were diagnosed with peri-implantitis . Five subjects had experienced technical complications ; three incidences of loosening of the abutment retention screw during the first 5 years and two minor porcelain fracture of the crown ( two patients ) between 5- and 12-years of follow-up . CONCLUSION The findings reported in this 12-year prospect i ve case series suggest that the use of the Astra Tech dental implants may be a valid treatment alternative for single-tooth replacement prostheses BACKGROUND Peri-implant marginal bone-level ( MBL ) alteration represents one of the parameters included in the criteria for determining implant health . OBJECTIVE Factors affecting peri-implant MBL alteration for 4-implant-supported fixed m and ibular prostheses ( 4-ISFMP ) were assessed . MATERIAL & METHODS A 3-year prospect i ve , cohort study was conducted on 44 m and ibularly edentulous patients treated with 4-ISFMP . Peri-implant MBL alteration was evaluated radiographically at the 12- , 24- and 36-month follow-ups considering to patient-related risk factors [ age , gender , diabetes mellitus , smoking , cardiovascular disease ( CVD ) , rheumatic disorders ( RD ) ] and implant/prosthesis-related features ( implant location , keratinized gingiva , denture cantilever length , prosthesis supporting zone , opposing dentition ) as well as to peri-implant biological parameters ( plaque- , bleeding- , calculus index ) . RESULTS 148/176 implants ( 37 patients , drop-out : 15 % ) were followed for 3 years showing significant ( p < 0.001 ) annual differences of MBL alterations over time . The univariate analysis demonstrated differences of MBL alterations for smokers ( p = 0.014 ) , for patients with CVD ( p = 0.001 ) and RD ( p = 0.011 ) . In the 3-year multivariate analysis , MBL alteration was influenced by time ( p < 0.001 ) and showed relationship with risk factors as smoking ( p < 0.002 ; OR = 18.965 ) , CVD ( p < 0.021 ; OR = 5.172 ) , RD ( p < 0.006 ; OR = 50.171 ) and plaque-index ( p = 0.034 ; OR = 3.252 ) . CONCLUSIONS Although peri-implant MBL alteration increased annually , significant odds ratios , were found for patients -related risk factors identifying them potentiating the alterations BACKGROUND The successful use of osseointegrated implants in periodontally healthy patients has been documented in numerous longitudinal studies in recent years . However , the extent to which these positive results apply to periodontally diseased patients remains unclear . The aim of the present prospect i ve longitudinal study of partially edentulous patients treated for generalized chronic periodontitis and generalized aggressive periodontitis was a clinical , microbiological , and radiographic comparison of teeth and implants and assessment of the implant success rate . METHODS Five partially edentulous patients treated for generalized aggressive periodontitis ( GAgP ) and 5 treated for generalized chronic periodontitis ( GCP ) were enrolled in this study . The GAgP patients received 36 implants , and the GCP patients 12 implants . The teeth were examined 2 to 4 weeks before extraction of the non-retainable teeth ( baseline ) , and 3 weeks after insertion of the final abutments ( second examination ) . All further examinations were performed during a 3-month recall schedule over a 5-year period for the GAgP patients and over a 3-year period for the GCP patients . At each session clinical parameters were recorded at teeth and implants and the composition of the subgingival microflora was determined by dark-field microscopy and DNA analysis . Intraoral radiographs of the teeth and implants were taken for control purpose s at baseline ; after insertion of the superstructure ; and 1 , 3 , and 5 years later . RESULTS The clinical findings indicated healthy periodontal and peri-implant conditions in both patient groups throughout the study . However , an increased probing depth and an attachment loss were recorded in the GAgP patients after the third year ( P<0.001 ) . The distribution of the microorganisms revealed no significant differences between the patient groups or between implants and teeth . Moderate bone loss at teeth and implants was registered in both groups . The success rates recorded were 100 % in the GCP patients and 88.8 % ( maxilla : 85.7 % ; m and ible : 93.3 % ) in the GAgP patients . CONCLUSIONS The 3-year and 5-year follow-ups show that osseointegrated implants may be successful in oral rehabilitation of partially edentulous patients treated for generalized aggressive periodontitis and generalized chronic periodontitis . However , as no significant differences were recorded between conditions at teeth and at implants , progression of the disease can not be ruled out A quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been drawn from a different population , depending on the particular patients chosen and the interventions and conditions unique to the study . Therefore , even if each study enrolled a large patient sample , the treatment effect would be expected to differ . These differences , called r and om effects , describe the between- study variation with regard to an overall mean of the effects of all of the studies that could be undertaken . The test most commonly used to assess the statistical significance of between- study heterogeneity is based on the chi-square distribution [ 6 ] . It provides a measure of the sum of the squared differences between the results observed and the results expected in each study , under the assumption that each study estimates the same common treatment effect . A large total deviation indicates that a single common treatment effect is unlikely . Any pooled estimate calculated must account for the between- study heterogeneity . In practice , this test has low sensitivity for detecting heterogeneity , and it has been suggested that a liberal significance level , such as 0.1 , should be used [ 6 ] . Estimating a Common Effect The questions that this step tries to answers are , 1 ) To the extent that data are similar , what is their best common point estimate of a therapeutic effect , and 2 ) how precise is this estimate ? The mathematical process involved in this step generally involves combining ( pooling ) the results of different studies into an overall estimate . Compared with the results of individual studies , pooled results can increase statistical power and lead to more precise estimates of treatment effect . Each study is given a weight according to the precision of its results . The rationale is that studies with narrow CIs should be weighted more heavily than studies with greater uncertainty . The precision is generally expressed by the inverse of the variance of the estimate of each study . The variance has two components : the variance of the individual study and the variance between different studies . When the between- study variance is found to be or assumed to be zero , each study is simply weighted by the inverse of its own variance , which is a function of the study size and the number of events in the study . This approach characterizes a fixed-effects model , as exemplified by the Mantel-Haenszel method [ 7 , 8 ] or the Peto method [ 9 ] for dichotomous data . The Peto method has been particularly popular in the past . It has the advantage of simple calculation ; however , although it is appropriate in most cases , it may introduce large biases if the data are unbalanced [ 10 , 11 ] . On the other h and , r and om-effects models also add the between- study variance to the within- study variance of each individual study when the pooled mean of the r and om effects is calculated . The r and om-effects model most commonly used for dichotomous data is the DerSimonian and Laird estimate of the between- study variance [ 12 ] . Fixed- and r and om-effects models for continuous data have also been described [ 13 ] . Pooled results are generally reported as a point estimate and CI , typically a 95 % CI . Other quantitative techniques for combining data , such as the Confidence Profile Method [ 14 ] , use Bayesian methods to calculate posterior probability distributions for effects of interest . Bayesian statistics are based on the principle that each observation or set of observations should be viewed in conjunction with a prior probability describing the prior knowledge about the phenomenon of interest [ 15 ] . The new observations alter this prior probability to generate a posterior probability . Traditional meta- analysis assumes that nothing is known about the magnitude of the treatment effect before r and omized trials are performed . In Bayesian terms , the prior probability distribution is noninformative . Bayesian approaches may also allow the incorporation of indirect evidence in generating prior distributions [ 14 ] and may be particularly helpful in situations in which few data from r and omized studies exist [ 16 ] . Bayesian analyses may also be used to account for the uncertainty introduced by estimating the between- study variance in the r and om-effects model , leading to more appropriate estimates and predictions of treatment efficacy [ 17 ] . Exploring and Explaining Heterogeneity The next important issue is whether the common estimate obtained in the previous step is robust . Sensitivity analyses determine whether the common estimate is influenced by changes in the assumptions and in the protocol for combining the data . A comparison of the results of fixed- and r and om-effects models is one such sensitivity analysis [ 18 ] . Generally , the r and om-effects model produces wider CIs than does the fixed-effects model , and the level of statistical significance may therefore be different depending on the model used . The pooled point estimate per se is less likely to be affected , although exceptions are possible [ 19 ] . Other sensitivity analyses may include the examination of the residuals and the chi-square components [ 13 ] and assessment of the effect of deleting each study in turn . Statistically significant results that depend on a single study may require further exploration . Cumulative Meta- Analysis PURPOSE This prospect i ve cohort study evaluates the 10-year survival and incidence of peri-implant disease at implant and patient level of s and blasted , large grid , and acid-etched titanium dental implants ( Straumann , soft tissue level , SLA surface ) in fully and partially edentulous patients . MATERIAL AND METHODS Patients who had dental implant surgery in the period between November 1997 and June 2001 , with a follow-up of at least 10 years , were investigated for clinical and radiological examination . Among the 506 inserted dental implants in 250 patients , 10-year data regarding the outcome of implants were available for 374 dental implants in 177 patients . In the current study , peri-implantitis was defined as advanced bone loss ( ≧1.5 mm . postloading ) in combination with bleeding on probing . RESULTS At 10-year follow-up , only one implant was lost ( 0.3 % ) 2 months after implant surgery due to insufficient osseointegration . The average bone loss at 10 year postloading was 0.52 mm . Advanced bone loss at 10-year follow-up was present in 35 dental implants ( 9.8 % ) . Seven percent of the observed dental implants showed bleeding on probing in combination with advanced bone loss and 4.2 % when setting the threshold for advanced bone loss at 2.0 mm . Advanced bone loss without bleeding on probing was present in 2.8 % of all implants . CONCLUSION In this prospect i ve study , the 10-year survival rate at implant and patient level was 99.7 % and 99.4 % , respectively . Peri-implantitis was present in 7 % of the observed dental implants according to the above-mentioned definition of peri-implantitis . This study shows that SLA implants offer predictable long-term results as support in the treatment of fully and partially edentulous patients BACKGROUND The aim of this prospect i ve 10-year study of partially edentulous subjects treated for generalized aggressive periodontitis and periodontally healthy subjects was a clinical , microbiologic , and radiographic comparison of teeth and implants and assessment of the implants ' success rate . METHODS Five subjects treated for generalized aggressive periodontitis ( GAgP ) and five periodontally healthy subjects who were orally rehabilitated with osseointegrated implants participated in the study . First , they were examined 2 to 4 weeks before extraction of the non-retainable teeth ( baseline ) and 3 weeks after insertion of the final abutments . All further examinations were performed during a 3-month recall schedule over a 10-year period . At every session , clinical parameters were recorded , and the composition of the subgingival microflora was determined . Radiographs were taken at baseline after insertion of the superstructure and 1 , 3 , 5 , 8 , and 10 years later . RESULTS Throughout the follow-up period , the peri-implant gingival index of GAgP subjects was significantly higher than in periodontally healthy subjects . There was no difference in plaque index between teeth and implants or between the two groups . The peri-implant probing depths were comparable in the two groups and remained < or = 4 mm throughout the follow-up . The probing depth was significantly higher around the teeth of the GAgP subjects compared to periodontally healthy subjects . Implants of GAgP subjects showed a significantly higher attachment loss ( Ø 2.4 mm ) . The attachment level at teeth and implants of the periodontally healthy subjects and at teeth of the GAgP subjects was almost unchanged . Microbiologically , GAgP subjects had fewer cocci and more motile rods and filaments at teeth and implants than periodontally healthy subjects . GAgP subjects showed significantly more peri-implant bone loss in the first year ( Ø 2.07 mm ) and in the subsequent 9 years ( total 1.3 mm ) . Bone loss at teeth also was significantly higher at baseline ( Ø 26.39 % ) and in the following years ( total 9.3 % ) . Implant survival rates were 100 % in periodontally healthy subjects versus 83.33 % in GAgP subjects . CONCLUSIONS This 10-year study showed that partially edentulous subjects treated for GAgP can be rehabilitated successfully with osseointegrated implants . However , the bone and attachment loss at the implants were higher than in periodontally healthy subjects This study evaluated the efficacy of implant supported dental restorations in patients with chronic periodontal diseases at various stages within 2 years of completing treatment . 30 patients with periodontal diseases and 30 patients without periodontal diseases were studied . Total counts of 276 implant bodies were divided into group A ( patients with periodontal diseases ; a total of 149 implants ) and group B ( patients with healthy periodontium ; a total of 127 implants ) . In group A subjects , periodontitis was treated prior to implant placement . The study focused on patients ' modified sulcus bleeding index , modified plaque index , implant mobility index , periodontal probing depth and implant success rate 12 and 24 months after the completion of the treatment . The result show : there were no significant differences in implant success rate between groups A and B ; modified sulcus bleeding index scores showed differences between the groups 24 months after treatment ; there were no significant differences in other clinical indexes during the study between the groups ; there were no significant differences in periodontal probing depth between the groups ; modified plaque index and modified sulcus bleeding index were positively correlated in implant supported dental restoration patients with chronic periodontal diseases PURPOSE To evaluate the clinical and radiological performance of an immediately loaded novel implant design over a 3-year period . MATERIAL S AND METHODS This prospect i ve study includes 54 consecutive partially edentulous patients treated between December 2010 and October 2011 . Outcome measures were : implant and prosthetic failures ; biological and mechanical complications ; marginal bone loss ( MBL ) ; sulcus bleeding index ( SBI ) ; and plaque score ( PS ) . RESULTS A total of 118 ( 29 narrow platform , 70 regular platform and 19 wide platform ) NobelReplace Conical Connection implants were placed in both post- extraction sockets and healed sites and immediately loaded . The mean insertion torque was 63.4 ± 7.1 Ncm . One hundred out of 118 implants ( 84.7 % ) were inserted with a torque ranging between 55 and 70 Ncm . Each patient received a single prosthesis . At the 3-year follow-up , no patient dropped out and only two post-extractive implants failed ( 1.7 % ) in two patients ( 3.7 % ) . The only complication ( 1.9 % ) observed was an event of periimplantitis , consisting of a mean mesiodistal peri-implant bone loss of 3.2 mm reported in a healed site of a smoker patient at the 2-year follow-up examination . No prosthesis failures were detected . The cumulative mean MBL between implant placements at the 3-year follow-up was 0.68 mm ( 95 % CI : 0.44 , 0.92 ) . At the 3-year follow-up session , the SBI and PS were 5.7 % and 15.4 % , respectively . CONCLUSIONS The NobelReplace Conical Connection implant can be considered as a valuable treatment option for immediate implant placement and loading in the partially edentulous patients over a 3-year period . Insertion torques ranging between 55 and 70 Ncm are not detrimental to osseointegration BACKGROUND Various causes of facial bone loss around dental implants are reported in the literature ; however , reports on the influence of residual facial bone thickness on the facial bone response ( loss or gain ) have not been published . This study measured changes in vertical dimension of facial bone between implant insertion and uncovering and compared these changes to facial bone thickness for more than 3,000 hydroxyapatite (HA)-coated and non-HA-coated root-form dental implants . METHODS Subjects were predominantly white males , 18 to 80 + years of age ( mean 62.9 years ) , who were patients at 30 Department of Veterans Affairs Medical Centers and two university dental clinics . Alveolar ridges ranged from normal to resorbed with intact basal bone . Following preparation of the osteotomy site , direct measurements with calipers were made of the residual facial bone thickness , approximately 0.5 mm below the crest of the bone . The distance from the top of the implants to the crest of the facial bone was also measured using periodontal probes . Implants were uncovered between 3 to 4 months in the m and ible and 6 to 8 months in the maxilla after insertion . Facial bone response was the difference between the height of facial bone at Stage 1 ( insertion ) and Stage 2 ( uncovering ) . RESULTS The mean facial bone thickness after osteotomies were made was 1.7 + /- 1.13 mm . When a mean facial bone thickness of 1.8 + /- 1.41 mm or larger remained after site preparation , bone apposition was more likely to occur . The mean facial bone response for 2,685 implants was -0.7 + /- 1.70 mm . For implants integrated at uncovering , the mean bone response was -0.7 + /- 1.69 mm , and -2.8 + /- 1.57 mm for implants mobile at uncovering . Bone quality -4 had the least facial bone response , -0.5 + /- 2.11 mm . Bone responses were similar for both HA-coated and non-HA-coated implants . CONCLUSIONS Significantly greater amounts of facial bone loss were associated with implants that failed to integrate . As the bone thickness approached 1.8 to 2 mm , bone loss decreased significantly and some evidence of bone gain was seen . There was no statistically or clinical ly significant difference in bone response between HA-coated and non-HA-coated implants OBJECTIVES The aim of this sub- analysis of two prospect i ve studies was to assess the incidence of peri-implant mucositis and peri-implantitis in fully edentulous patients with an implant-retained m and ibular overdenture during a 10-year follow-up period . MATERIAL AND METHODS One hundred and fifty edentulous patients with two endosseous implants to support a m and ibular overdenture were available from two prospect i ve studies . Clinical and radiographic parameters were assessed at 5 and 10 years of functional loading . Incidence of peri-implant mucositis and peri-implantitis were calculated at implant level and patient level following the Consensus of the Seventh European Workshop on Periodontology on peri-implant diseases . RESULTS Incidence of peri-implant mucositis at patient level was 51.9 % after 5 years of evaluation and 57.0 % after 10 years . Incidence of peri-implantitis at patient level was 16.9 % after 5 years of evaluation and 29.7 % after 10 years . CONCLUSION Peri-implant mucositis and peri-implantitis do occur in totally edentulous patients and incidence numbers are high OBJECTIVES The specific aim of this study was to assess sintered porous-surfaced ( SPS ) implant system from a biological point of view , through a prospect i ve study of the health status and the evolution of the peri-implant tissues over time and analysis of the changes observed in the various peri-implant parameters . MATERIAL AND METHODS Hundred and fifty-one patients were treated consecutively from 2005 to 2007 using 280 SPS implants , which were restored with a single crown or a partial fixed denture . To accurately monitor the health and biological evolution of peri-implant soft and hard tissues , a number of clinical parameters were adopted , such as the modified Plaque Index ( mPI ) , the modified sulcus Bleeding Index ( mBI ) , Peri-implant Probing Depth ( PPD ) , and Crestal Bone Level ( CBL ) . Clinical and radiographic examinations were scheduled over a 36-month follow-up of functional loading according to a well-established protocol generally applied to determine implant success rates and Peri-implant Bone Loss ( PBL ) . Statistical analysis was used to determine any significant differences or correlations ( P = 0.05 ) . RESULTS A total of 259 SPS implants in 136 patients were followed up for 36 months . According to Buser 's success criteria , the overall implant-based success rate was 98.1 % and the mean PBL was 0.48 ± 0.29 mm . MBI and mPI mean values showed statistically significant differences between baseline and follow-up analyses ( P < 0.001 ) . No statistically significant differences in mean PPD values were found between baseline and control analyses ( P = 0.060 ) . CONCLUSION This prospect i ve cohort study revealed that the biological behavior of SPS implant system was characterized by high tissue stability during the observation period , both as regards soft and hard tissues . In particular , the crestal bone remodeling pattern was very similar to that reported in other studies , confirming that the bone loss around SPS implants , at least at 36 months , seems to be predictable |
1,017 | 24,532,151 | 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 | Background Economy , velocity/power at maximal oxygen uptake ( $ $ { \text { v } } \dot{V}{\text{O}}_{2 \ , \hbox{max } } /{\text w}\dot{V}{\text{O}}_{2 \ , \hbox{max } } $ $ vV˙O2max/wV˙O2max ) and endurance-specific muscle power tests ( i.e. maximal anaerobic running velocity ; vMART ) , are now thought to be the best performance predictors in elite endurance athletes .
In addition to cardiovascular function , these key performance indicators are believed to be partly dictated by the neuromuscular system .
One technique to improve neuromuscular efficiency in athletes is through strength training .
Objective The aim of this systematic review was to search the body of scientific literature for original research investigating the effect of strength training on performance indicators in well-trained endurance athletes — specifically economy , $ $ { \text{v}}\dot{V}{\text{O}}_{2 \ , \hbox{max } } /\,{\text{w}}\dot{V}{\text{O}}_{2 \ , \hbox{max } } $ $ vV˙O2max/wV˙O2max and muscle power ( vMART ) . | 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 exhaustion at MAS were examined . METHODS Seventeen well-trained ( nine male and eight female ) runners were r and omly assigned into either an intervention or a control group . The intervention group ( four males and four females ) performed half-squats , four sets of four repetitions maximum , three times per week for 8 wk , as a supplement to their normal endurance training . The control group continued their normal endurance training during the same period . RESULTS The intervention manifested significant improvements in 1RM ( 33.2 % ) , RFD ( 26.0 % ) , RE ( 5.0 % ) , and time to exhaustion at MAS ( 21.3 % ) . No changes were found in V[spacing dot above]O2max or body weight . The control group exhibited no changes from pre to post values in any of the parameters . CONCLUSION Maximal strength training for 8 wk improved RE and increased time to exhaustion at MAS among well-trained , long-distance runners , without change in maximal oxygen uptake or body weight The aim of this experiment was to examine the effects of maximal strength training with emphasis on neural adaptations on strength- and endurance-performance for endurance trained athletes . Nineteen male cross-country skiers about 19.7 + /- 4.0 years of age and a maximal oxygen uptake ( VO(2 max ) ) of 69.4 + /- 2.2 mL x kg(-1 ) x min(-1 ) were r and omly assigned to a training group ( n = 9 ) or a control group ( n = 10 ) . Strength training was performed , three times a week for 8 weeks , using a cable pulley simulating the movements in double poling in cross-country skiing , and consisted of three sets of six repetitions at a workload of 85 % of one repetition maximum emphasizing maximal mobilization of force in the concentric movement . One repetition maximum improved significantly from 40.3 + /- 4.5 to 44.3 + /- 4.9 kg . Time to peak force ( TPF ) was reduced by 50 and 60 % on two different submaximal workloads . Endurance performance measured as time to exhaustion ( TTE ) on a double poling ski ergometer at maximum aerobic velocity , improved from 6.49 to 10.18 min ; 20.5 % over the control group . Work economy changed significantly from 1.02 + /- 0.14 to 0.74 + /- 0.10 mL x kg(-0.67 ) x min(-1 ) . Maximal strength training with emphasis on neural adaptations improves strength , particularly rate of force development , and improves aerobic endurance performance by improved work economy PURPOSE To determine whether the magnitude of improvement in athletic performance and the mechanisms driving these adaptations differ in relatively weak individuals exposed to either ballistic power training or heavy strength training . METHODS Relatively weak men ( n = 24 ) who could perform the back squat with proficient technique were r and omized into three groups : strength training ( n = 8 ; ST ) , power training ( n = 8 ; PT ) , or control ( n = 8) . Training involved three sessions per week for 10 wk in which subjects performed back squats with 75%-90 % of one-repetition maximum ( 1RM ; ST ) or maximal-effort jump squats with 0%-30 % 1RM ( PT ) . Jump and sprint performances were assessed as well as measures of the force-velocity relationship , jumping mechanics , muscle architecture , and neural drive . RESULTS Both experimental groups showed significant ( P < or = 0.05 ) improvements in jump and sprint performances after training with no significant between-group differences evident in either jump ( peak power : ST = 17.7 % + /- 9.3 % , PT = 17.6 % + /- 4.5 % ) or sprint performance ( 40-m sprint : ST = 2.2 % + /- 1.9 % , PT = 3.6 % + /- 2.3 % ) . ST also displayed a significant increase in maximal strength that was significantly greater than the PT group ( squat 1RM : ST = 31.2 % + /- 11.3 % , PT = 4.5 % + /- 7.1 % ) . The mechanisms driving these improvements included significant ( P < or = 0.05 ) changes in the force-velocity relationship , jump mechanics , muscle architecture , and neural activation that showed a degree of specificity to the different training stimuli . CONCLUSIONS Improvements in athletic performance were similar in relatively weak individuals exposed to either ballistic power training or heavy strength training for 10 wk . These performance improvements were mediated through neuromuscular adaptations specific to the training stimulus . The ability of strength training to render similar short-term improvements in athletic performance as ballistic power training , coupled with the potential long-term benefits of improved maximal strength , makes strength training a more effective training modality for relatively weak individuals BACKGROUND Altered neuromotor control during running after cycling has been associated with exercise-related leg pain and may have performance implication s for triathletes . OBJECTIVE To investigate the effectiveness of adding plyometric training to regular endurance training on triathletes ' neuromotor control and running economy in those in which it is aberrant . DESIGN R and omised controlled trial . SETTING Institutional . PARTICIPANTS 15 moderately-trained triathletes . INTERVENTIONS Eight-week endurance only ( control group ) or endurance plus plyometric ( plyometric group ) training program . MAIN OUTCOME MEASURES Neuromotor control and running economy during running after cycling . RESULTS Eight of the fifteen triathletes exhibited aberrant neuromotor control and were r and omised to control or plyometric groups . Combined plyometric and endurance training produced favourable neuromotor adaptations during running after cycling beyond that of endurance training at 8 weeks ( numbers needed to treat 2 ) . There were significant differences between control and plyometric groups at eight weeks for the coefficient of multiple correlation ( p=0.03 ) and root mean square error ( p = 0.01 ) between control and transition runs . Running economy was not different between groups at follow-up . CONCLUSION Our results provide some support for the utility of plyometrics as an intervention to correct altered neuromotor control in those triathletes in which it is aberrant 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 . The purpose of this study was to investigate the effect of heavy strength training on thigh muscle cross-sectional area ( CSA ) , determinants of cycling performance , and cycling performance in well-trained cyclists . Twenty well-trained cyclists were assigned to either usual endurance training combined with heavy strength training [ E + S ; n = 11 ( ♂ = 11 ) ] or to usual endurance training only [ E ; n = 9 ( ♂ = 7 , ♀ = 2 ) ] . The strength training performed by E + S consisted of four lower body exercises [ 3 × 4–10 repetition maximum ( RM ) ] , which were performed twice a week for 12 weeks . Thigh muscle CSA , maximal force in isometric half squat , power output in 30 s Wingate test , maximal oxygen consumption ( VO2max ) , power output at 2 mmol l−1 blood lactate concentration ( [ la− ] ) , and performance , as mean power production , in a 40-min all-out trial were measured before and after the intervention . E + S increased thigh muscle CSA , maximal isometric force , and peak power in the Wingate test more than E. Power output at 2 mmol l−1 [ la− ] and mean power output in the 40-min all-out trial were improved in E + S ( P < 0.05 ) . For E , only performance in the 40-min all-out trial tended to improve ( P = 0.057 ) . The two groups showed similar increases in VO2max ( P < 0.05 ) . In conclusion , adding strength training to usual endurance training improved determinants of cycling performance as well as performance in well-trained cyclists . Of particular note is that the added strength training increased thigh muscle CSA without causing an increase in body mass Sunde , A , Støren , Ø , Bjerkaas , M , Larsen , MH , Hoff , J , and Helgerud , J. Maximal strength training improves cycling economy in competitive cyclists . J Strength Cond Res 24(8 ) : 2157 - 2165 , 2010-The purpose of the present study was to investigate the effect of maximal strength training on cycling economy ( CE ) at 70 % of maximal oxygen consumption ( & OV0312;o2max ) , work efficiency in cycling at 70 % & OV0312;o2max , and time to exhaustion at maximal aerobic power . Responses in 1 repetition maximum ( 1RM ) and rate of force development ( RFD ) in half-squats , & OV0312;o2max , CE , work efficiency , and time to exhaustion at maximal aerobic power were examined . Sixteen competitive road cyclists ( 12 men and 4 women ) were r and omly assigned into either an intervention or a control group . Thirteen ( 10 men and 3 women ) cyclists completed the study . The intervention group ( 7 men and 1 woman ) performed half-squats , 4 sets of 4 repetitions maximum , 3 times per week for 8 weeks , as a supplement to their normal endurance training . The control group continued their normal endurance training during the same period . The intervention manifested significant ( p < 0.05 ) improvements in 1RM ( 14.2 % ) , RFD ( 16.7 % ) , CE ( 4.8 % ) , work efficiency ( 4.7 % ) , and time to exhaustion at pre-intervention maximal aerobic power ( 17.2 % ) . No changes were found in & OV0312;o2max or body weight . The control group exhibited an improvement in work efficiency ( 1.4 % ) , but this improvement was significantly ( p < 0.05 ) smaller than that in the intervention group . No changes from pre- to postvalues in any of the other parameters were apparent in the control group . In conclusion , maximal strength training for 8 weeks improved CE and efficiency and increased time to exhaustion at maximal aerobic power among competitive road cyclists , without change in maximal oxygen uptake , cadence , or body weight . Based on the results from the present study , we advise cyclists to include maximal strength training in their training programs |
1,018 | 25,279,204 | 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 | Colorectal cancer is one of the main malignant tumors threatening human health .
Surgery plays a pivotal role in treating colorectal cancer .
The present study aim ed to compare the clinical effect in patients with rectal cancer undergoing laparoscopic versus open surgery by meta- analysis of the r and omized controlled trials ( RCTs ) published in the past 20 years . | 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 thought the resection was potentially curative , and in 36 % ( 69/190 ) of all cases . After a median 5 years ' follow-up ( range 3.0 - 7.7 years ) , the frequency of local recurrence after potentially curative resection was 25 % ( 95 % CI 18 - 33 % ) . The frequency of local recurrence was significantly higher for patients who had had tumour involvement of the circumferential margin than for those without such involvement ( 78 [ 95 % CI 62 - 94 ] vs 10 [4 - 16]% ) . By Cox 's regression analysis tumour involvement of the circumferential margin independently influenced both local recurrence ( hazard ratio = 12.2 [ 4.4 - 34.6 ] ) and survival ( 3.2 [ 1.6 - 6.53 ] ) . These results show the importance of wide local excision during resection for rectal cancer , and the need for routine assessment of the circumferential margin to assess prognosis PURPOSE The aim of the current study is to report the long-term outcomes after laparoscopic-assisted surgery compared with conventional open surgery within the context of the UK MRC CLASICC trial . Results from r and omized trials have indicated that laparoscopic surgery for colon cancer is as effective as open surgery in the short term . Few data are available on rectal cancer , and long-term data on survival and recurrence are now required . METHODS The United Kingdom Medical Research Council Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer ( UK MRC CLASICC ; clinical trials number IS RCT N 74883561 ) trial study comparing conventional versus laparoscopic-assisted surgery in patients with cancer of the colon and rectum . The r and omization ratio was 2:1 in favor of laparoscopic surgery . Long-term outcomes ( 3-year overall survival [ OS ] , disease-free survival [ DFS ] , local recurrence , and quality of life [ QoL ] ) have now been determined on an intention-to-treat basis . RESULTS Seven hundred ninety-four patients were recruited ( 526 laparoscopic and 268 open ) . Overall , there were no differences in the long-term outcomes . The differences in survival rates were OS of 1.8 % ( 95 % CI , -5.2 % to 8.8 % ; P = .55 ) , DFS of -1.4 % ( 95 % CI , -9.5 % to 6.7 % ; P = .70 ) , local recurrence of -0.8 % ( 95 % CI , -5.7 % to 4.2 % ; P = .76 ) , and QoL ( P > .01 for all scales ) . Higher positivity of the circumferential resection margin was reported after laparoscopic anterior resection ( AR ) , but it did not translate into an increased incidence of local recurrence . CONCLUSION Successful laparoscopic-assisted surgery for colon cancer is as effective as open surgery in terms of oncological outcomes and preservation of QoL. Long-term outcomes for patients with rectal cancer were similar in those undergoing abdominoperineal resection and AR , and support the continued use of laparoscopic surgery in these patients INTRODUCTION Histologic examination of circumferential margins is an important predictor of local and distant relapse in non-radiated rectal cancer . However , for patients who received preoperative chemoradiotherapy this role has not yet been addressed . METHODS From January 1995 to December 1997 , 61 patients with rectal adenocarcinoma located between 0 and 10 cm from anal verge with invasion into perirectal fat assessed by rectal ultrasound were included . All patients received 45 Gy + bolus infusion of 5-FU ( 450 mg/m(2)/days 1 - 5 , 28 - 33 of RT ) ; 4 - 6 weeks later , surgery was performed . Circumferential margin was assessed ( < 2 mm was considered as positive ) . Five-year survival was calculated by Kaplan-Meier method and comparison of groups with log-rank test . Multivariate Cox regression analysis was performed to find risk factors affecting local control and survival . RESULTS There were 35 males and 26 females , mean age 60.3 years . Twelve patients ( 19.7 % ) had circumferential margin involvement . Median follow-up was 44 months . Overall local recurrence was observed in 6 of 61 patients ( 9.8 % ) ; in patients without circumferential margin involvement this was 8 % , whereas it was 16 % in those with circumferential margin involvement ( P = 0.33 ) . Distant recurrence was observed in 22 % of patients without circumferential margin involvement ; conversely , it was 58.3 % in those with involvement ( P = 0.02 ) . Five-year survival of patients without circumferential resection involvement margin was 81 % , while it was 42 % in patients with circumferential involvement ( P = 0.006 ) . CONCLUSIONS In patients with rectal cancer treated by preoperative chemoradiation plus total mesorectal excision ( TME ) and sphincter saving surgery , circumferential margin involvement is associated with high incidence of distant recurrence and cancer-related death PURPOSE : We have previously reported the five-year results of a r and omized trial comparing laparoscopic and open resection for cancer of the upper rectum and rectosigmoid junction . The aim of this follow-up study is to report on the long-term morbidity and ten-year oncologic outcomes among the subgroup of patients with upper rectal cancer . METHODS : From September 1993 to October 2002 , 153 patients with upper rectal cancer were r and omly assigned to receive either laparoscopic-assisted ( n = 76 ) or open ( n = 77 ) anterior resection . Patients were last followed up in December 2007 . Long-term morbidity , survival , and disease-free interval were prospect ively recorded . Data were analyzed by intention-to-treat principle . RESULTS : The demographic data of the two groups were comparable . More patients in the open group developed adhesion-related bowel obstruction requiring hospitalization ( P = 0.001 ) and intervention . The overall long-term morbidity rate was also significantly higher in the open group ( P = 0.012 ) . After curative resection , the probabilities of cancer-specific survival at ten years of the laparoscopic-assisted and open groups were 83.5 percent and 78.0 percent , respectively ( P = 0.595 ) , and their probabilities of being disease-free at ten years were 82.9 percent and 80.4 percent , respectively ( P = 0.698 ) . CONCLUSION : Laparoscopic-assisted anterior resection for upper rectal cancer is associated with fewer long-term complications and similar ten-year oncologic outcomes when compared with open surgery BACKGROUND The safety and short-term efficacy of laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy has not been demonstrated . The aim of the r and omised Comparison of Open versus laparoscopic surgery for mid and low REctal cancer After Neoadjuvant chemoradiotherapy ( COREAN ) trial was to compare open surgery with laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy . METHODS Between April 4 , 2006 , and Aug 26 , 2009 , patients with cT3N0 - 2 mid or low rectal cancer without distant metastasis after preoperative chemoradiotherapy were enrolled at three tertiary-referral hospitals . Patients were r and omised 1:1 to receive either open surgery ( n=170 ) or laparoscopic surgery ( n=170 ) , stratified according to sex and preoperative chemotherapy regimen . Short-term outcomes assessed were involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , recovery of bowel function , perioperative morbidity , postoperative pain , and quality of life . Analyses were based on the intention-to-treat population . Patients continue to be followed up for the primary outcome ( 3-year disease-free survival ) . This study is registered with Clinical Trials.gov , number NCT00470951 . FINDINGS Two patients ( 1.2 % ) in the laparoscopic group were converted to open surgery , but were included in the laparoscopic group for analyses . Estimated blood loss was less in the laparoscopic group than in the open group ( median 217.5 mL [ 150.0 - 400.0 ] in the open group vs 200.0 mL [ 100.0 - 300.0 ] in the laparoscopic group , p=0.006 ) , although surgery time was longer in the laparoscopic group ( mean 244.9 min [ SD 75.4 ] vs 197.0 min [ 62.9 ] , p<0.0001 ) . Involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , and perioperative morbidity did not differ between the two groups . The laparoscopic surgery group showed earlier recovery of bowel function than the open surgery group ( time to pass first flatus , median 38.5 h [ 23.0 - 53.0 ] vs 60.0 h [ 43.0 - 73.0 ] , p<0.0001 ; time to resume a normal diet , 85.0 h [ 66.0 - 95.0 ] vs 93.0 h [ 86.0 - 121.0 ] , p<0.0001 ; time to first defecation , 96.5 h [ 70.0 - 125.0 ] vs 123 h [ 94.0 - 156.0 ] , p<0.0001 ) . The total amount of morphine used was less in the laparoscopic group than in the open group ( median 107.2 mg [ 80.0 - 150.0 ] vs 156.9 mg [ 117.0 - 185.2 ] , p<0.0001 ) . 3 months after proctectomy or ileostomy takedown , the laparoscopic group showed better physical functioning score than the open group ( 0.501 [ n=122 ] vs -4.970 [ n=128 ] , p=0.0073 ) , less fatigue ( -5.659 [ n=122 ] vs 0.098 [ n=129 ] , p=0.0206 ) , and fewer micturition ( -2.583 [ n=122 ] vs 4.725 [ n=129 ] , p=0.0002 ) , gastrointestinal ( -0.400 [ n=122 ] vs 4.331 [ n=129 ] , p=0.0102 ) , and defecation problems ( 0.535 [ n=103 ] vs 5.327 [ n=99 ] , p=0.0184 ) in repeated measures analysis of covariance , adjusted for baseline values . INTERPRETATION Laparoscopic surgery after preoperative chemoradiotherapy for mid or low rectal cancer is safe and has short-term benefits compared with open surgery ; the quality of oncological resection was equivalent BACKGROUND The long-term survival and safety of laparoscopic surgery in patients with rectal cancer remain unclear . The aim of this trial was to assess the efficacy and safety of laparoscopic surgery for treatment of rectal cancer . METHODS We undertook a r and omized , controlled trial in 343 patients with rectal cancer between May 2004 and April 2008 . One hundred sixty-nine patients were r and omly assigned to laparoscopic surgery and 174 patients to open surgery . The main endpoint was 3-year survival . Data were analyzed according to the intention-to-treat principle . RESULTS Laparoscopic surgery was associated with earlier recovery of bowel movement compared with open surgery . The average time to first discharge , bowel movement , resumption of fluid intake , and activity out of bed in laparoscopic surgery were shorter by 0.63 , 0.32 , 0.33 , and 0.63 day , respectively ( P < .001 ) . The incidences of postoperative morbidities such as infectious complications , anastomotic leakage , anastomotic stenosis , and deep vein thrombosis have no differences . No differences were found in the comparison of long-term survival . INTERPRETATION Laparoscopic surgery for rectal cancer is as safe and effective as open surgery in terms of oncology outcomes . Long-term survival for patients with rectal cancer undergoing laparoscopic surgery were similar to those undergoing conventional open surgery , thus supporting the continued use of laparoscopic surgery in Chinese patients with rectal cancer BACKGROUND Laparoscopic surgery for colon cancer has been proven safe , but debate continues over whether the available long-term survival data justify implementation of laparoscopic techniques in surgery for colon cancer . The aim of the COlon cancer Laparoscopic or Open Resection ( COLOR ) trial was to compare 3-year disease-free survival and overall survival after laparoscopic and open resection of solitary colon cancer . METHODS Between March 7 , 1997 , and March 6 , 2003 , patients recruited from 29 European hospitals with a solitary cancer of the right or left colon and a body-mass index up to 30 kg/m(2 ) were r and omly assigned to either laparoscopic or open surgery as curative treatment in this non-inferiority r and omised trial . Disease-free survival at 3 years after surgery was the primary outcome , with a prespecified non-inferiority boundary at 7 % difference between groups . Secondary outcomes were short-term morbidity and mortality , number of positive resection margins , local recurrence , port-site or wound-site recurrence , and blood loss during surgery . Neither patients nor health-care providers were blinded to patient groupings . Analysis was by intention-to-treat . This trial is registered with Clinical Trials.gov , number NCT00387842 . FINDINGS During the recruitment period , 1248 patients were r and omly assigned to either open surgery ( n=621 ) or laparoscopic surgery ( n=627 ) . 172 were excluded after r and omisation , mainly because of the presence of distant metastases or benign disease , leaving 1076 patients eligible for analysis ( 542 assigned open surgery and 534 assigned laparoscopic surgery ) . Median follow-up was 53 months ( range 0.03 - 60 ) . Positive resection margins , number of lymph nodes removed , and morbidity and mortality were similar in both groups . The combined 3-year disease-free survival for all stages was 74.2 % ( 95 % CI 70.4 - 78.0 ) in the laparoscopic group and 76.2 % ( 72.6 - 79.8 ) in the open-surgery group ( p=0.70 by log-rank test ) ; the difference in disease-free survival after 3 years was 2.0 % ( 95 % CI -3.2 to 7.2 ) . The hazard ratio ( HR ) for disease-free survival ( open vs laparoscopic surgery ) was 0.92 ( 95 % CI 0.74 - 1.15 ) . The combined 3-year overall survival for all stages was 81.8 % ( 78.4 - 85.1 ) in the laparoscopic group and 84.2 % ( 81.1 - 87.3 ) in the open-surgery group ( p=0.45 by log-rank test ) ; the difference in overall survival after 3 years was 2.4 % ( 95 % CI -2.1 to 7.0 ; HR 0.95 [ 0.74 - 1.22 ] ) . INTERPRETATION Our trial could not rule out a difference in disease-free survival at 3 years in favour of open colectomy because the upper limit of the 95 % CI for the difference just exceeded the predetermined non-inferiority boundary of 7 % . However , the difference in disease-free survival between groups was small and , we believe , clinical ly acceptable , justifying the implementation of laparoscopic surgery into daily practice . Further studies should address whether laparoscopic surgery is superior to open surgery in this setting Background Laparoscopic resection of colonic cancer has been shown to improve postoperative recovery without jeopardizing tumor clearance and survival , but information on low rectal cancer is scarce . The aim of this r and omized trial was to compare postoperative recovery between laparoscopic-assisted versus open abdominoperineal resection ( APR ) in patients with low rectal cancer . Recurrence and survival data were also recorded and compared between the two groups . Methods Between September 1994 and February 2005 , 99 patients with low rectal cancer were r and omized to receive either laparoscopic-assisted ( 51 patients ) or conventional open ( 48 patients ) APR . The median follow-up time of living patients was about 90 months for both groups . The primary and secondary endpoints of the study were postoperative recovery and survival , respectively . Data were analyzed by intention-to-treat principle . Results The demographic data of the two groups were comparable . Postoperative recovery was better after laparoscopic surgery , with earlier return of bowel function ( P < .001 ) and mobilization ( P = .005 ) , and less analgesic requirement ( P = .007 ) . This was at the expense of longer operative time and higher direct cost . There were no differences in morbidity and operative mortality rates between the two groups . After curative resection , the probabilities of survival at 5 years of the laparoscopic-assisted and open groups were 75.2 % and 76.5 % respectively ( P = .20 ) . The respective probabilities of being disease-free were 78.1 % and 73.6 % ( P = .55 ) . Conclusions Laparoscopic-assisted APR improves postoperative recovery and seemingly does not jeopardize survival when compared with open surgery for low rectal cancer . A larger sample size is needed to fully assess oncological outcomes BACKGROUND Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale r and omised trials to support its use . We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes . METHODS Between July , 1996 , and July , 2002 , we undertook a multicentre , r and omised clinical trial in 794 patients with colorectal cancer from 27 UK centres . Patients were allocated to receive laparoscopic-assisted ( n=526 ) or open surgery ( n=268 ) . Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins , proportion of Dukes ' C2 tumours , and in-hospital mortality . Analysis was by intention to treat . This trial has been assigned the International St and ard R and omised Controlled Trial Number IS RCT N74883561 . FINDINGS Six patients ( two [ open ] , four [ laparoscopic ] ) had no surgery , and 23 had missing surgical data ( nine , 14 ) . 253 and 484 patients actually received open and laparoscopic-assisted treatment , respectively . 143 ( 29 % ) patients underwent conversion from laparoscopic to open surgery . Proportion of Dukes ' C2 tumours did not differ between treatments ( 18 [ 7 % ] patients , open vs 34 [ 6 % ] , laparoscopic ; difference -0.3 % , 95 % CI -3.9 to 3.4 % , p=0.89 ) , and neither did in-hospital mortality ( 13 [ 5 % ] vs 21 [ 4 % ] ; -0.9 % , -3.9 to 2.2 % , p=0.57 ) . Apart from patients undergoing laparoscopic anterior resection for rectal cancer , rates of positive resection margins were similar between treatment groups . Patients with converted treatment had raised complication rates . INTERPRETATION Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes . However , impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use |
1,019 | 18,351,320 | 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 | Aims We compared the effects of continuous subcutaneous insulin infusion ( CSII ) with those of multiple daily insulin ( MDI ) injections on glycaemic control , risk of hypoglycaemic episodes , insulin requirements and adverse events in type 1 and type 2 diabetes mellitus . | 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 CSII . Blood glucose ( BG ) was monitored before and after each of the 3 meals each day . RESULTS The basal insulin regimen had to be optimized in 75 % of the patients during the MDI period ( mean number of NPH injections per day = 2.65 ) . HbA1c values were lower when lispro was used in CSII than in MDI ( 7.89+/-0.77 vs. 8.24+/-0.77 % , P<0.001 ) . BG levels were lower with CSII ( 165+/-27 vs. 175+/-33 mg/dl , P<0.05 ) . The SD of all the BG values ( 73+/-15 vs. 82+/-18 mg/dl , P<0.01 ) was lower with CSII . The frequency of hypoglycemic events , defined as BG levels < 60 mg/dl , did not differ significantly between the 2 modalities ( CSII 3.9+/-4.2 per 14 days vs. MDI 4.3+/-3.9 per 14 days ) . Mean insulin doses were significantly lower with CSII than with MDI ( 38.5+/-9.8 vs. 47.3+/-14.9 U/day . respectively , P < 0.0001 ) . CONCLUSIONS When used with external pumps versus MDI , lispro provides better glycemic control and stability with much lower doses of insulin and does not increase the frequency of hypoglycemic episodes Forty five insulin dependent diabetics were r and omised to treatment with continuous subcutaneous insulin infusion ( CSII ) , multiple insulin injections ( five or six daily ) , or conventional twice daily insulin injections . Near normoglycaemia was obtained with CSII and multiple injections but not with conventional treatment ( p less than 0.01 ) . Hypoglycaemic coma was observed less frequently with CSII than with multiple injections and conventional treatment ( p less than 0.001 ) , but blood glucose concentrations below 2.5 mmol/l ( 45 mg/100 ml ) were more common . After two years fewer retinal microaneurysms and haemorrhages had developed in the patients given CSII and multiple injections compared with those given conventional treatment , in whom the number had increased significantly ( p less than 0.01 ) . Motor nerve conduction velocity deteriorated in the patients given conventional treatment ; in those given CSII it was unchanged during the first year but had improved after two years ( p less than 0.01 ) . Glomerular hyperfiltration was reduced with CSII , but no change occurred in urine albumin excretion rates . Long term near normoglycaemia may prevent the progression of early stages of late diabetic complications OBJECTIVE To assess in a r and omized crossover trial the efficacy of continuous subcutaneous insulin infusion in improving glycemic control and health-related quality of life in type 1 diabetic patients with long-st and ing poor glycemic control . RESEARCH DESIGN AND METHODS A total of 79 patients in 11 Dutch centers were r and omized to 16 weeks of continuous subcutaneous insulin infusion followed by 16 weeks intensive injection therapy or the reverse order . Glycemic control was assessed by HbA(1c ) , self-reported hypoglycemic events , and blood glucose memory meter read outs . Changes in quality of life were assessed by self-report question naires administered at baseline and 16 weeks . RESULTS As the drop-out rate after crossover was high ( 17 of 79 patients [ 22 % ] ) , we analyzed the trial as a parallel clinical trial , using data of the first half of the crossover phase only . At 16 weeks , mean HbA(1c ) was 0.84 % ( 95 % CI -1.31 to -0.36 ) lower in the continuous subcutaneous insulin infusion group compared with the insulin injection group ( P = 0.002 ) . Stability of blood glucose self-measurement values , expressed as SD of the nine-point blood glucose profiles , improved in the insulin pump group by 29.3 + /- 41.1 vs. 8.2 + /- 36.5 % in the injection group ( P = 0.039 ) . The number of mild hypoglycemic episodes per patient-week was 0.99 ( 95 % CI 0.11 - 1.87 ) higher in the insulin pump group ( P = 0.028 ) . Weight gain was similar in both groups . Scores on the Short-Form 36-Item subscales ' general health ' and ' mental health ' improved in the continuous subcutaneous insulin infusion group , compared with stable values in the injection group ( P = 0.048 and 0.050 , respectively ) . CONCLUSIONS Continuous subcutaneous insulin infusion improves glycemic control and some aspects of health-related quality of life in patients with a history of long-term poor glycemic control OBJECTIVE The efficacy of the insulin analogs now available for multiple daily injection ( MDI ) and continuous subcutaneous insulin infusion ( CSII ) therapy in type 1 diabetes has not yet been established in pediatric patients . Our principal aim in this short-term study was to compare the efficacy of CSII to MDI with glargine in lowering HbA(1c ) levels in children and adolescents with type 1 diabetes . RESEARCH DESIGN AND METHODS Thirty-two youth with type 1 diabetes ( age 8 - 21 years ) were r and omly assigned to receive either MDI treatment with once-daily glargine and premeal/snack insulin aspart or CSII with insulin aspart . Dose titration in both groups was based on home self-monitored blood glucose measurements and monthly HbA(1c ) . HbA(1c ) , total daily insulin dose ( TDD ) , self-monitored blood glucose readings , and adverse events were compared after 16 weeks of therapy . RESULTS While there was no significant change in the glargine group ( HbA(1c ) 8.2 % at baseline vs. 8.1 % at 16 weeks ) , youth r and omized to CSII had a sharp reduction in HbA(1c ) levels , from 8.1 to 7.2 % after 16 weeks of therapy ( P < 0.02 vs. baseline and < 0.05 vs. glargine group ) . TDD was unchanged in the glargine group , but significantly dropped with CSII ( 1.4 units/kg at baseline vs. 0.9 units/kg at 16 weeks , P < 0.01 ) . Both groups had similar basal doses and insulin-to-carbohydrate ratios . Fasting self-monitored blood glucose was similar in both groups , but lunch , dinner , and bedtime readings were significantly lower in the CSII group ( P < 0.01 ) . CONCLUSIONS Lower HbA(1c ) and premeal glucose levels were more achievable in this short-term study with CSII than with glargine-based MDI treatment . CSII is an efficacious treatment to improve metabolic control in youth with type 1 diabetes Ten insulin-dependent C-peptide-negative diabetic subjects , whose control had been optimized on twice-daily injection therapy , were treated for periods of 10 wk in a crossover study , with either a thrice-daily subcutaneous insulin injection regimen ( Actrapid + Ultratard ) or by continuous subcutaneous insulin infusion ( CSII ) . On CSII insulin dose stabilized at 51 + /- 5 U/day , compared with 80 + /- 9 U/day ( P = 0.004 ) on the thrice-daily injection regimen , having been 60 + /- 6 U/day on twice-daily therapy . After 10 wk glycosylated hemoglobin was 11.7 + /- 0.6 % on injection therapy and 10.0 + /- 0.7 % ( P = 0.026 ) on CSII . Mean blood glucose concentration and urinary glucose excretion were lower at most points during the study on CSII than on injection therapy . Patients on pumps gained weight compared with the thrice-daily injection regimen ( P = 0.023 at 10 wk ) and the previous twice-daily regimen , despite the reduction in insulin dose . Considering individual patients , four markedly improved on CSII compared with the previous twice-daily regimen and five compared with Actrapid + Ultratard . No patient showed impaired control on CSII compared with either injection regimen . The benefits of portable insulin infusion pumps over injection therapy are thus clearly demonstrable under outpatient conditions even with equal and intensive medical attention Summary We first compared glomerular charge selectivity index in two matched groups of Type 1 ( insulin-dependent ) diabetic patients with micro and normoalbuminuria respectively , and secondly , investigated prospect ively in a r and omized clinical trial , the influence of improved metabolic control on selectivity index in diabetic patients with microalbuminuria . In Study 1 , 27 patients with microalbuminuria ( albumin excretion > -15 μg/min in at least two out of three overnight urine sample s ) were matched ( age , diabetes duration , mean 1-year HbA1c , gender ) with normoalbuminuria patients ( n=24 ) , and in Study 2 , 23 microalbuminuric patients were r and omly allocated to either intensive ( continuous subcutaneous insulin infusion ) or conventional treatment . Glomerular charge selectivity index was measured as IgG/IgG4 selectivity index , i.e. total IgG/IgG4 clearance ratio in timed overnight urine sample s. The microalbuminuric patients had a significantly reduced selectivity index compared to the normoalbuminuric patients : 1.20 ( 0.92–1.40 ) vs 1.68 ( 1.22–2.21 ) , median and 95 % confidence interval ( p<0.01 ) . In Study 2 , the HbA1c improved in the intensive-treatment group compared to the conventional-treatment group : at 2 , 6 and 12 months the difference in mean percentage HbA1c between the groups was 1.1 , 1.2 and 1.4 , respectively ( p<0.01 ) . A sharp 50 % increment in IgG/IgG4 selectivity index was seen in the intensive-treatment group during the first 6 months ( p<0.05 compared to the conventional group ) . We conclude that adolescents and young adults in an early stage of diabetic nephropathy have reduced glomerular charge selectivity , which may be improved by reducing the mean blood glucose level Glycaemic control on pump versus pen treatment was evaluated and the effects of optimised metabolic control on kidney function was studied in very long-term uncomplicated insulin-dependent diabetes mellitus ( IDDM ) . Ten otherwise healthy patients participated , age : 36.5 yr + /- 7.9 , diabetes duration : 23.7 yr + /- 2.9 , urinary albumin excretion ( UAE ) : 5.8 micrograms/min x/ divided by 2.2 , se-creatinine and blood pressure were normal and only background retinopathy was present . A 2 x 6 months r and omised cross-over study was performed using continuous subcutaneous insulin infusion ( CSII ) and multiple injection technique ( MIT ) . Glycaemic control was evaluated by a six point profile every two weeks and by measuring HbA1c monthly . At 0 , 6 and 12 months , glomerular filtration rate ( GFR ) and renal plasma flow ( RPF ) were measured by the constant infusion technique , and UAE by radioimmunoassay . Glycaemic control was significantly better on CSII as compared to MIT ( p = 0.01 ) or pre- study conventional treatment ( CT ) , p = 0.03 , whereas there was no difference between MIT and CT . There was no change in kidney function during either treatment . Thus , in these very long-term uncomplicated patients , glycaemic control was significantly improved during CSII . In spite of this , no change was found in GFR , which might suggest that in long-st and ing diabetes , kidney function is unaltered by changes in metabolic control OBJECTIVE To compare the efficacy and safety of continuous subcutaneous insulin infusion ( CSII ) and multiple daily injection ( MDI ) in older adults with insulin-treated type 2 diabetes and to assess treatment satisfaction and quality of life . RESEARCH DESIGN AND METHODS Adults ( n = 107 ) > or = 60 years of age ( mean age 66 years ) with insulin-treated type 2 diabetes ( mean duration 16 years , BMI 32 kg/m(2 ) , and HbA(1C ) [ A1C ] 8.2 % ) were r and omized to CSII ( using insulin lispro ) or MDI ( using insulin lispro and insulin glargine ) in a two-center , 12-month , prospect i ve , r and omized , controlled clinical trial . Efficacy was assessed with A1C , safety by frequency of hypoglycemia , and treatment satisfaction and quality of life with the Diabetes Quality of Life Clinical Trial Question naire and the 36-item short-form health survey , version 2 . RESULTS Forty-eight CSII subjects ( 91 % ) and 50 MDI subjects ( 93 % ) completed the study . Mean A1C fell by 1.7 + /- 1.0 % in the CSII group to 6.6 % and by 1.6 + /- 1.2 % in the MDI group to 6.4 % . The difference in A1C between treatment groups was not statistically significant ( P = 0.20 ) . Eighty-one percent of CSII subjects and 90 % of MDI subjects experienced at least one episode of minor ( self-treated ) hypoglycemia ( P = 0.17 ) , and three CSII and six MDI subjects experienced severe hypoglycemia ( P = 0.49 ) . Rates of severe hypoglycemia were similarly low in the two groups ( CSII 0.08 and MDI 0.23 events per person-year , P = 0.61 ) . Weight gain did not differ between groups ( P = 0.70 ) . Treatment satisfaction improved significantly with both CSII and MDI ( P < 0.0001 ) , and the difference between groups was not statistically significant ( P = 0.58 ) . CONCLUSIONS In older subjects with insulin-treated type 2 diabetes , both CSII and MDI achieved excellent glycemic control with good safety and patient satisfaction Forty-five diabetic patients , 18 to 45 years of age , with mild or no retinopathy , were r and omly assigned to continuous subcutaneous insulin infusion ( CSII ) , multiple injections ( Mls ) , and conventional insulin treatment ( CIT ) . The effects of near-normoglycemia ( CSII and MI ) on oscillatory potentials ( electroretinography [ ERG ] ) and macular recovery time ( nyctometry ) were studied prospect ively for 41 months . Before r and omization , the amplitudes of oscillatory potentials were negatively correlated to age ( P = 0.002 ) and positively correlated to the diameter of retinal veins ( P less than 0.05 ) . Men had shorter macular recovery time than women ( P = 0.03 ) . Nyctometry and oscillatory potentials were not related to mean blood glucose values , glycosylated hemoglobin ( HbA1 ) , retinopathy , blood pressure levels , or duration of diabetes . Changes in metabolic control ( MI and CSII ; P less than 0.01 ) and in microaneurysms and hemorrhages ( CSII and CIT ) during the study did not affect oscillatory potentials or nyctometry . Soft exu date s ( 15 patients ) and proliferative retinopathy ( 1 patient ) transiently developed with MI and CSII regimens . No changes in oscillatory potentials or nyctometry were observed and no pretreatment characteristics of these parameters predicted the occurrence of these ischemic lesions . At the stage of proliferation , however , lowered amplitudes of oscillatory potentials and lengthened macular recovery time were observed OBJECTIVE Our goals were to determine if continuous subcutaneous insulin infusion ( CSII ) , compared with those continuing multiple daily injections ( MDIs ) , can be safely used in young children , if those on CSII will have superior glycemic control , if subjects using CSII will have less hypoglycemia for their level of control , and if families using CSII will report an improved quality of life . RESEARCH DESIGN AND METHODS We conducted a r and omized 1-year feasibility trial comparing CSII with continuing MDIs in preschool children with a history of type 1 diabetes for at least 6 months ' duration . Prospect i ve outcomes included measures of overall glycemic control ( HbA1c and continuous glucose monitoring system ) , the incidence of severe hypoglycemia and diabetic ketoacidosis , the percent of glucose values below 3.9 mmol/l , and the parents ' report of quality of life . RESULTS The 19 subjects ' ages ranged from 1.7 to 6.1 ( mean 3.6 ) years , duration of diabetes ranged from 0.6 to 2.6 ( mean 1.4 ) years , and baseline HbA1c ranged from 6.7 to 9.6 % ( mean 7.9 % ) . Seven subjects were male . Nine subjects were r and omized to start CSII and 10 to continue on MDI . All baseline characteristics were well balanced . Overall metabolic control , diabetes quality of life , and the incidence of hypoglycemia were similar in the two groups . No subject had diabetic ketoacidosis , while one subject in each group had an episode of severe hypoglycemia . No CSII subject discontinued using the pump during or after the study . CONCLUSIONS CSII can be a safe and effective method to deliver insulin in young children Forty-five insulin-dependent diabetics were r and omized to 1 yr treatment with either continuous subcutaneous insulin infusion ( CSII ) , multiple insulin injections ( MI ) , or continued conventional treatment . The CSII group used regular insulin only , the MI group used 4 - 6 premeal injections of regular insulin and intermediate insulin at night , and the conventional group used two daily injections of combined regular and intermediate insulin . Only highly purified porcine insulin was used . Near normoglycemia was obtained during CSII and MI but not during conventional treatment . Antibodies against insulin were measured in serum sample s by measuring the binding of iodinated porcine insulin to serum after removal of free and antibodybound insulin from the sample s by acid charcoal . The percent binding of 125I-labeled insulin increased significantly during MI and CSII , in contrast to conventional treatment . Nineteen patients had sufficient binding capacity for Scatchard analysis . In the CSII and MI groups , high- or low-affinity antibodies or both were induced . When insulin was administered subcutaneously during MI or CSII for 1 yr , the insulin antibody production increased , in contrast with conventional treatment A fast and precise method for routine , large scale measurements of HbA1 , with elimination of pre-Alc , was established . Near normal blood glucose levels were obtained during treatment with CSII and MI ; significantly better than during conventional treatment with two daily injections of mixed regular/intermediate insulin . On most parameters of glycemic control , CSII was slightly better than MI ( n.s . ) . The frequency of hypoglycemic coma was significantly reduced , but blood glucose values below 2.5 mmol/l were more frequent on CSII , compared to conventional treatment . The frequency on MI was similar to that of conventional treatment . CSII patients have an increased risk of developing ketoacidosis by accidental cessation of insulin infusion , and of developing cutaneous infections at the infusion site . Insulin antibodies increased during one year of CSII and MI , when compared to conventional treatment . Rapid tightening of blood glucose control may lead to transient deterioration of retinopathy , mainly by the occurrence of cotton wool spots . Patients who already have background retinopathy are at higher risk for such changes . A significant increase in the number of microaneurysms and haemorrhages was observed on conventional treatment whilst no significant change was found on CSII and MI . Less progression of retinopathy ( elevated by fluorescein angiograms ) was observed on CSII and MI ( n.s . ) when compared to conventional treatment . Thus long term near-normoglycemia may retard the progression of early retinopathy . Urinary albumin excretion was reduced during CSII and MI ( n.s . ) , but no change was observed during conventional treatment . Glomerular hyperfiltration improved during intensified treatment . Motor nerve conduction velocity deteriorated on conventional treatment , but improved during CSII . No change occurred on MI The effect of prolonged restoration of near-normoglycemia on the progression of diabetic nephropathy was evaluated in a controlled study in which 10 insulin-dependent ( type 1 ) diabetic patients with clinical proteinuria were r and omized to continue with conventional insulin treatment ( CIT ) or to undertake more intensive diabetic therapy using continuous subcutaneous insulin infusion ( CSII ) . The patients , mean age 33 + /- 8 yr , mean duration of diabetes 15 + /- 4 yr , were studied before and during 12 months of either CIT or CSII therapy . Glycemic control was assessed by means of mean blood glucose ( MBG ) + /- St and ard deviation ( SD ) , urinary glucose excretion and glycosylated hemoglobin , while renal function was assessed by albumin , IgG and beta-2-microglobulin urinary excretion rates , serum creatinine and creatinine clearance . Blood glucose level , urinary glucose excretion and glycosylated hemoglobin fell significantly in the CSII group , while no differences were found in the CIT group after the 12 months observation period . Both groups showed a deterioration in all indices of renal function , as illustrated by an increase of protein excretion rates and of serum creatinine , and by a decline in creatinine clearance . Comparison of the rate of increase of urinary albumin and IgG excretion and of serum creatinine and of the rate of fall in creatinine clearance between CIT and CSII groups demonstrated that the rate of progression of diabetic nephropathy may be slowed by correction of hyperglycemia . Our study , with due reservations because of the small number of examined patients and differences in kidney function at the beginning of the trial shows that intensive diabetic care may play a role in the proteinuric stage of diabetes in slowing further destruction of residual glomerular structure and in delaying end stage renal failure We studied 45 IDDM without c-peptide response , duration 7 - 22 years , without proliferative retinopathy . After 2 months run-in period , they were r and omly assigned to : ( P ) 15 received CSII : ( C ) 15 received multiple s.c . injections via butterfly 5 - 6x daily ; : ( M ) 15 received twice daily mixed rapid and long acting insulin . All groups improved blood glucose control in the run-in period ( p less than 0.0001 ) . After change of treatment ( P ) and ( M ) improved further ( p less than 0.01 ) but ( C ) was unchanged . GFR was supranormal and decreased in ( P ) and ( M ) . No regression of retinopathy was shown in any group . One in ( P ) had transient florid pre-proliferative retinopathy which regressed spontaneously without laser treatment . We conclude that retinal response to strict control is complex . A transient deterioration may been seen A study was performed to examine the feasibility of achieving long periods of near-normoglycaemia in patients with diabetes mellitus by giving a continuous subcutaneous infusion of insulin solution from a miniature , battery-driven , syringe pump . Twelve insulin-dependent diabetics had their insulin pumped through a subcutaneously implanted , fine nylon cannula ; the basal infusion rate was electronically stepped up eightfold before meals . The blood glucose profile of these patients was closely monitored during the 24 hours of the subcutaneous infusion and compared with the profile on a control day , when the patients were managed with their usual subcutaneous insulin . Diet and exercise were st and ardised on both days . In five out of 14 studies the subcutaneous insulin infusion significantly lowered the mean blood glucose concentration without producing hypoglycaemic symptoms ; in another six patients the mean blood glucose concentration was maintained . As assessed by the M value the level of control was statistically improved in six out of 14 studies by the infusion method and maintained in six other patients . To assess the effects of blood glucose control on diabetic microvascular disease it will be necessary to achieve long-term normoglycaemia in selected diabetics . The results of this preliminary study suggest that a continuous subcutaneous insulin infusion may be a means of maining physiological glucose concentrations in diabetics . Though several problems remain -- for example , in determining the rate of infusion -- longer-term studies with the miniature infusion pumps are now needed Continuous subcutaneous insulin infusion ( CSII ) of 6 months duration was compared with 6 months of multiple insulin injections ( MII ) using a pen injector ( NovoPen ) in a prospect i ve cross-over study with 20 young insulin dependent diabetics by evaluating metabolic control , insulin requirements and patient acceptability . Following both intensified regimens ( CSII/MII ) serum fructosamine declined significantly from 4.1 + /- 0.7 to 3.4 + /- 0.5 mmol/l and 3.6 + /- 0.7 mmol/l respectively ( normal range : 2.2 + /- 0.2 mmol/l ) . When comparing CSII and MII no significant differences could be demonstrated in mean blood glucose ( MBG ) , fasting plasma ketone bodies , fasting plasma free fatty acids ( FFA ) , fasting plasma human growth hormone ( HGH ) , fasting plasma glucagon or serum fructosamine . Mean insulin requirement was 11.4 % higher during MII and glucose instability -- demonstrated by the M-values and by the frequency of blood glucose values below 4 mmol/l -- was significantly ( p less than 0.02 ) higher during the MII treatment . All of the patients reported a better well-being on both treatment regimens and none of them wanted to go back to conventional therapy ( CT ) . In conclusion , on a long-term basis both regimens result in identical metabolic control , but due to physical discomfort during pump treatment , the insulin pen injector was preferred by the majority ( 80 % ) of the patients The effects of continuous subcutaneous insulin infusion ( CSII ) , intensified conventional therapy ( ICT ) , and a combination of CSII and ICT ( CSII-ICT ) on metabolic control were compared in a group of twenty type I diabetic adolescents who had previously failed to respond to twice-daily injections and home glucose monitoring . A marked improvement in control was observed when mean glycemia and glycosylated hemoglobin A1 ( HbA1 ) were compared with conventional therapy ( CT ) . In the course of CSII , a lower HbA1 ( P < 0.05 ) and mean capillary blood glucose ( CBG ) ( P < 0.04 ) were observed than during ICT and CSII-ICT . Acceptability of CSII was greater that of ICT and CSII-ICT , with 50 % of the patients opting for this therapy at the end of the 1-yr trial . The marked improvement of control observed under CSII for the group as a whole was maintained after 6 mo of completion of the study . Thus , it appears that in type I diabetic adolescents CSII is more effective and acceptable than ICT and CSII-ICT Twenty insulin-dependent diabetic patients participated in a 1-yr prospect i ve r and omized cross-over study comparing multiple subcutaneous injections ( MSI ) and continuous subcutaneous insulin infusion ( CSII ) complemented by home blood glucose monitoring . While 4 patients dropped out early , 16 patients completed the study . Patients had severe insulin deficiency documented by absent C-peptide response to glucagon stimulation . A marked improvement in control was observed when mean blood glucose and glycosylated hemoglobin A1 were compared with conventional therapy . No significant differences in the degree of metabolic control achieved , as measured by mean fasting , prepr and ial , and postpr and ial capillary blood glucose ( CBG ) , M values , glycosylated hemoglobin A1 concentration , cholesterol and triglyceride levels were seen between MSI and CSII in the sixteen patients who completed the study . However , individual comparisons showed that fasting CBG and M-values were lower under CSII than MSI in seven patients ( P < 0.05 ) . In contrast , two patients exhibited lower M values under MSI than under CSII ( P < 0.01 ) , while for the remaining seven patients the results were similar . After completion of the study , two patients went back to conventional insulin therapy , seven patients remained on the pump , and seven patients chose to stay on MSI . In conclusion , on a long-term basis , the two methods can produce comparable levels of blood glucose and glycosylated hemoglobin in ambulatory insulin-dependent diabetics In a study of retinopathy during one year of tight blood glucose control 45 type I ( insulin dependent ) diabetics without proliferative retinopathy were r and omised to receive either continuous subcutaneous insulin infusion , multiple insulin injections , or conventional insulin treatment ( controls ) . Near normoglycaemia was achieved with continuous infusion and multiple injections but not with conventional treatment . Blind evaluation of fluorescein angiograms performed three monthly showed progression of retinopathy in the control group , transient deterioration in the continuous infusion group , and no change in the multiple injection group . Half the patients receiving continuous infusion and multiple injections developed retinal cotton wool spots after three to six months . These changes regressed in all but four patients after 12 months . Control patients did not develop cotton wool spots . Patients who developed cotton wool spots are characterised by a larger decrement in glycosylated haemoglobin and blood glucose values , more frequent episodes of hypoglycaemia , a longer duration of diabetes , and more severe retinopathy at onset . A large and rapid fall in blood glucose concentration may promote transient deterioration of diabetic retinopathy Mild background retinopathy was studied prospect ively during long-term strict blood glucose control in insulin-dependent diabetes mellitus . Forty-five subjects ( 21 women and 24 men with a mean age of 26.3 years and a mean duration of diabetes of 12.8 years ) were r and omly assigned to continuous subcutaneous insulin infusion , multiple injections , and conventional two-injection treatment . Eyes were examined two months before treatment , at the beginning of treatment , and after three , six , and 12 months . A progressive deterioration was found in the two-injection group during the study , but no significant changes were found in patients receiving multiple injections . A transient deterioration occurred after three months of continuous subcutaneous insulin infusion . Soft exu date s appeared in 50 % of the patients on the two intensified regimens , but no exu date s were found in patients given conventional treatment . The morphologic changes seemed to be related to a large and rapid decrease in mean blood glucose or to an increased frequency of hypoglycemia , or both OBJECTIVE An association between reactive oxygen species and diabetic micro- and macrovascular complications has been proposed . In the present study , we have examined the effect of an improved blood glucose control on plasma levels of hydroperoxides in patients with IDDM . RESEARCH DESIGN AND METHODS Subjects included 30 young IDDM patients with microalbuminuria who were r and omized to receive either continuous subcutaneous insulin infusion ( CSII ) by a portable insulin pump ( n = 15 ) or conventional insulin treatment ( CIT ) ( n = 15 ) for 24 months . Plasma levels of hydroperoxides were measured by the ferrous oxidation with Xylenol Orange , version 2 ( FOX2 ) assay . This method measures total lipid hydroperoxides and , unlike other methods , does not suffer from extraction losses . RESULTS The mean HbA1c level was lower in the CSII group at the end of the study than in the CIT group : ( mean [ 95 % CI ] ) 8.6 ( 8.1–9.1 ) vs. 9.6 (9.0–10.3)% , respectively ( P < 0.002 ) . The level of plasma hydroperoxides was very similar at the start of the study but was significantly lower in the CSII group compared with the CIT group at the end of the study : 2.9 ( 2.1–3.7 ) vs. 4.3 ( 3.2–5.4 ) μmol/l , respectively ( P < 0.02 ) . In the CSII group , hydroperoxides were reduced by 31 % from baseline ( P < 0.001 ) , whereas there was no change in levels of hydroperoxides in the CIT group . Mean hydroperoxide levels correlated with mean HbA1c during the study ( r = 0.39 , P < 0.04 ) . Hydroperoxide levels were associated with the levels of microalbuminuria ( r = 0.45 , P < 0.02 ) . CONCLUSIONS This study provides support for the hypothesis that hyperglycemia is an important factor in the generation of hydroperoxides , and , thus , reactive oxygen species , in the circulation of IDDM patients In a prospect i ve study with cross-over design 20 patients with insulin-dependent diabetes mellitus of more than 2 years duration were treated for 6 months with continuous subcutaneous insulin infusion ( CSII ) and multiple insulin injections ( MII ) . Metabolic control , platelet aggregability , thromboxane B2 levels in serum and plasma as well as antithrombin III ( ATIII ) activity and von Willebr and factor antigen were evaluated . A good metabolic control was obtained by both intensified regimens . No difference could be demonstrated between either platelet function tests or serum level of von Willebr and factor antigen during treatment with CSII and MII . However , the plasma level of ATIII activity was significantly higher ( P less than 0.01 ) during MII treatment as compared to CSII treatment . There was no correlation between ATIII activity and daily insulin requirement or serum fructosamine . In conclusion , long-term metabolic control with MII has a favourable effect on ATIII activity in plasma . This may be important for a delay in onset and progression of diabetic vascular complications Nineteen insulin-dependent diabetic adolescents who had poor control on twice daily injections and home glucose monitoring participated in a study assessing the feasibility of improved control . Using a r and omized crossover protocol , we examined the relative efficacy of continuous subcutaneous insulin infusion and of intensive conventional therapy with three or four daily injections of insulin . Both therapies were regulated with home glucose monitoring . A marked improvement in control with both therapies was observed when mean blood glucose and glycosylated hemoglobin A1 were compared with conventional therapy . However , pump therapy result ed in significantly lower HbA1 than intensive therapy ( P less than 0.05 ) , despite a significantly lower total insulin dose ( P less than 0.01 ) . We conclude that in adolescents with type I diabetes , continuous subcutaneous insulin infusion is more effective in achieving improvement of diabetes control than is intensive conventional therapy in the outpatient setting Twenty-one patients with insulin-dependent diabetes mellitus ( IDDM ) participated in a 20-week r and omized cross-over comparison of continuous subcutaneous insulin infusion ( CSII ) with intensified conventional treatment ( ICT ) using the NovoPen . The Medix or the Auto-Syringe pumps were used for CSII and , during ICT with NovoPen , conventional plastic syringes were used for injections of intermediate-acting insulin at bedtime . At entry HbA1c , was 8.7 + /- 0.4 % ( mean + /- SE ) in CSII patients and 8.8 + /- 0.5 % in the ICF group . HbA1c declined significantly in both groups ( ICT 7.6 + /- 0.2 % ; CSII 7.6 + /- 0.2 % ) though there was no significant difference between the responses . Overall mean blood glucose was slightly but significantly lower during CSII than during ICT ( CSII : 7.6 + /- 0.2 mmol/l ; ICT : 8.7 + /- 0.4 mmol/l , p less than 0.05 ) . The number of hypoglycaemic episodes did not differ significantly between patients treated with NovoPen and CSII . At the end of the study , a question naire revealed that all but one patient preferred ICT with NovoPen to conventional therapy . Given the choice for future treatment , 6 patients chose CSII , 12 patients preferred ICT with NovoPen and 1 was unsure |
1,020 | 19,490,739 | 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 | The amino acid glutamine has numerous important roles including particularly antioxidant defence , immune function , the inflammatory response , acid-base balance and N economy . | 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 ; 0.5 g/kg per day ; n=15 ) or st and ard Gln-free PN ( control-PN ) that was iso-nitrogenous to Gln-PN ( n=14 ) . Serum HSP-70 concentrations were measured at enrollment and at 7 days . Clinical outcome measures were also determined . Results HSP-70 concentrations were unchanged in control-PN subjects from baseline to day 7 . In marked contrast , Gln-PN subjects demonstrated significantly higher ( 3.7-fold ) serum HSP-70 concentrations than control subjects . In Gln-PN patients there was a significant correlation between increases in HSP-70 levels over baseline and decrease in ICU length of stay . Conclusions Gln-PN significantly increases serum HSP-70 in critically ill patients . The magnitude of HSP-70 enhancement in Gln-treated patients was correlated with improved clinical outcomes . These data indicate the need for larger , r and omized trials of the Gln effect on serum and tissue HSP-70 expression in critical illness and relationship to clinical outcomes BACKGROUND The effect of parenteral GLN on recovery from severe acute pancreatitis has not been thoroughly investigated . The aims of this study were to determine whether parenteral GLN improves nutrition status and immune function , and to determine its ability to reduce morbidity and mortality in patients with this condition . METHODS In a r and omized clinical trial , 44 patients with severe acute pancreatitis were r and omly assigned to receive either st and ard PN ( n = 22 ) or l-alanyl-l-glutamine-supplemented PN ( n = 22 ) after hospital admission . Nitrogen balance , counts of leukocytes , total lymphocytes , and CD4 and CD8 sub population s , and serum levels of immunoglobulin A , total protein , albumin , C-reactive protein , and serum interleukin (IL)-6 and IL-10 were measured on days 0 , 5 , and 10 . Hospital stay , infectious morbidity , and mortality were also evaluated . RESULTS Demographics , laboratory characteristics , and pancreatitis etiology and severity at entry to the study were similar between groups . The study group exhibited significant increases in serum IL-10 levels , total lymphocyte and lymphocyte sub population counts , and albumin serum levels . Nitrogen balance also improved to positive levels in the study group and remained negative in the control group . Infectious morbidity was more frequent in the control group than in the study group . The duration of hospital stay was similar between groups , as was mortality . CONCLUSION The results suggest that treatment of patients with GLN-supplemented PN may decrease infectious morbidity rate compared with those who treated with nonenriched PN Glutamine seems to play an important role in metabolism and function of immunologic cells and therefore could also influence postoperative immunosuppression in surgical patients . Nevertheless , the influence of glutamine substitution in postoperative total parenteral nutrition on immunologic function and postoperative morbidity of patients is still unknown . Therefore , the impact of glutamine substitution on postoperative immunosuppression and incidence of complications was investigated in patients with surgical interventions on esophagus or stomach and total parenteral nutrition in a prospect i ve r and omized trial . To analyse the immunologic competence of the patients , the expression of CD-3 , CD-4 , and CD-8 on lymphocytes as well as the expression of HLA-DR and CD-14 on monocytes were evaluated before , 1 , 2 , 4 , 7 days after surgery . Furthermore , plasma levels of IL-6 and IL-10 were analysed during the perioperative course . Actually , 34 patients have been included ( with glutamine : n = 18 vs. without glutamine : n = 16 ) in the study . Patients with glutamine substitution showed non significantly decreased systemic inflammation ( IL-6-plasma levels , leucocytosis ) and significantly faster compensation of postoperative immunosuppression ( HLA-DR-monocytes ) . Incidence of postoperative complications was decreased after glutamine substitution compared with the control group . Patients without postoperative complications showed no significant difference in postoperative immunosuppression . Although additional substitution of the amino acid glutamine might possibly decrease incidence of postoperative complications in patients with total parenteral nutrition a general advantage in postoperative immune function could not be demonstrated BACKGROUND Supplementation with glutamine and antioxidants may be associated with an improvement in clinical outcomes , but the optimal dose of these substrates is unknown . The purpose of this study was to determine the safety of high doses of glutamine combined with antioxidants in critically ill patients . METHODS We conducted a single-center , open-label , dose-escalating clinical trial . Mechanically ventilated adult patients with clinical evidence of hypoperfusion were sequentially enrolled to 1 of 5 groups . Group 1 ( n = 30 ) : no supplementation ; group 2 ( n = 7 ) : 0.35 g/kg/d of glutamine IV ; group 3 ( n = 7 ) : same as group 2 plus 15 g/d of glutamine and 150 microg of selenium enterally ; group 4 ( n = 7 ) : same as group 2 plus 30 g/d of glutamine and 300 microg of selenium enterally ; and group 5 ( n = 7 ) : same as group 4 plus an additional 500 microg of selenium IV . After enrollment , nutrients were started as soon as possible . All patients were fed enterally according to clinical practice guidelines . RESULTS The primary outcomes for this study were change in sequential organ function assessment ( SOFA ) score and safety parameters . Secondary outcomes included whole blood glutathione ( GSH ) , thiobarbituric acid reactive substances ( TBARS ) , and blood cells ' mitochondrial DNA/nuclear DNA ratio ( RATIO ) . There were no adverse events attributable to the study nutrients , and the maximum and Delta SOFA did not differ across groups . In group 2 , a significant decrease in GSH levels was observed ( p = .03 ) . With subsequent groups , the slopes straighten out and the p values are no longer significant , suggesting a greater preservation of GSH levels with escalating doses . In group 2 , the slope of the line representing TBARS was horizontal . With subsequent groups , the slopes decrease , and by group 5 , this decrease reaches statistical significance ( p = .03 ) , suggesting a greater reduction in oxidative stress with the higher doses in group 5 . The difference in slopes across all groups describing the mitochondrial RATIO is statistically significant ( p = .001 ) , again suggesting that , with higher doses , there is increased mitochondrial function . CONCLUSIONS The doses of glutamine and antioxidants tested in this study seem to be safe and may have positive effects on some mechanistic endpoints . A larger trial will be necessary to confirm their therapeutic effects Glutamine is normally an abundant amino acid in the body . It has many important metabolic roles , which may protect or promote tissue integrity and enhance the immune system . Low plasma and tissue levels of glutamine in the critically ill suggest that dem and may exceed endogenous supply . A relative deficiency of glutamine could compromise recovery , result ing in prolonged illness and an increase in late mortality , morbidity , and consequently hospital costs . Using a prospect i ve block-r and omized , double-blind treatment study design , we tested whether a glutamine-containing enteral feed compared with an isonitrogenous , isoenergetic control feed would influence outcome . The study endpoints were morbidity , mortality , and hospital cost at 6 mo postintervention . In one general intensive care unit ( ICU ) , to ensure consistency of management policies , 78 critically ill adult patients with Acute Physiological and Chronic Health Evaluation ( APACHE ) II score of 11 and greater and who were considered able to tolerate introduction of enteral nutrition were studied . Fifty patients successfully received enteral nutrition ( 26 glutamine , 24 control ) . There was no mortality difference between those patients receiving glutamine-containing enteral feed and the controls . However , there was a significant reduction in the median postintervention ICU and hospital patient costs in the glutamine recipients $ 23,000 versus $ 30,900 in the control patients ( P = 0.036 ) . For patients given glutamine there was a reduced cost per survivor of 30 % . We conclude that in critically ill ICU patients enteral feeds containing glutamine have significant hospital cost benefits Glutamine , a conditionally essential amino acid , is important for immune function . It is now being formulated for incorporation into total parenteral nutrition ( TPN ) . The aims of this study were to examine the effect of glutamine administration on lymphocyte proliferation and proinflammatory cytokine release in patients with severe acute pancreatitis . Fourteen patients were r and omized ( in a double-blind fashion ) to receive either conventional or isocaloric , isonitrogenous glutamine-supplemented ( 0.22 g glutamine x kg(-1 ) x d(-1 ) as glycyl-glutamine ) TPN for 7 d. DNA synthesis ( index of lymphocyte proliferation ) and the 24-h release of tumor necrosis factor ( TNF ) , interleukin (IL)-6 , and IL-8 from peripheral blood mononuclear cells were measured in vitro on days 0 , 4 , and 7 . Thirteen patients completed the study protocol ( 6 glutamine TPN , 7 conventional TPN ) . Glutamine supplementation increased median DNA synthesis by 3099 cpm over the study period against 219 cpm in the conventional group ( increase not significantly different between the two groups ) . Glutamine supplementation did not significantly influence TNF or IL-6 release , but , in contrast , median IL-8 release was reduced by day 7 in the glutamine group while it was increased in the conventional group ( -17.7 ng/mL ( median change over study period ) versus + 43.3 ng/mL , respectively ; P=0.045 ) . Small patient numbers and substantial interindividual variation limit the conclusions , but there is a trend for the glutamine group to have improved lymphocyte proliferation , and in the case of IL-8 , reduced proinflammatory cytokine release Background Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high . Infections in Intensive Care are associated with a 2–3 times increased risk of death . It is thought that under conditions of severe metabolic stress glutamine becomes " conditionally essential " . Selenium is an essential trace element that has antioxidant and anti-inflammatory properties . Approximately 23 % of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts . Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways . Systematic review s suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality . Pilot data has shown that more than 50 % of participants developed infections , typically resistant organisms . We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients . Methods / design 2 × 2 factorial , pragmatic , multicentre , double-blind , r and omised controlled trial . The trial has an enrolment target of 500 patients . Inclusion criteria include : expected to be in critical care for at least 48 hours , aged 16 years or over , patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route . Allocation is to one of four iso-caloric , iso-nitrogenous groups : glutamine , selenium , both glutamine & selenium or no additional glutamine or selenium . Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable . The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality . Secondary outcomes include antibiotic usage , length of hospital stay , quality of life and cost-effectiveness . Discussion To date more than 285 patients have been recruited to the trial from 10 sites in Scotl and . Recruitment is due to finish in August 2008 with a further six months follow up . We expect to report the results of the trial in summer 2009.Trial registration This trial is registered with the International St and ard R and omised Controlled Trial Number system . IS RCT BACKGROUND & AIMS A growing number of r and omized clinical trials suggest that glutamine ( Gln ) supplementation may be beneficial in a selected group of patients and conditions . However , the effects of Gln-enriched total parenteral nutrition ( TPN ) on recovery from acute intra-abdominal infection have not been thoroughly investigated . Therefore , the aim of this study was to investigate whether the provision of Gln-enriched TPN after surgical and medical treatment of secondary peritonitis improves infectious morbidity . METHODS Thirty-three patients with secondary peritonitis were r and omly assigned to receive either st and ard ( n=16 ) TPN or L-alanyl-L-glutamine-supplemented ( n=17 ) TPN , after medical and surgical treatment of the infectious focus . The two TPN formulae were isonitrogenous and isocaloric , which commenced the morning after surgery and ran continuously for 10 consecutive days . The control group received st and ard TPN , while the treatment group was given L-alanyl-L-glutamine , 0.40 g/kg/d ( Dipeptiven , Fresenius Kabi , Bad Homburg , Germany ) . Infectious morbidity , nitrogen balance , leukocytes , lymphocytes , sub population s CD(4 ) and CD(8 ) , Immunoglobulin A ( IgA ) , total proteins , albumin , hospital and intensive care unit ( ICU ) stays , and mortality were evaluated . Statistical analysis included one-way ANOVA , the unpaired Student 's t-test , the Mann-Whitney U-test , chi(2 ) test , or Fisher 's exact test . RESULTS Patients in both groups were comparable prior to the operation . Nitrogen balance and the levels of albumin and IgA were significantly better than those in the control group . Also , a significant reduction in the infectious morbidity was found in the Gln-treated group . Lymphocyte counts as well as sub population s CD(4 ) and CD(8 ) , and proteins showed a propensity to improvement and a tendency to reduced rates of mortality were observed when comparing the groups . Hospital and ICU stays were similar . CONCLUSION L-alanyl-L-glutamine-supplemented TPN improved the infectious morbidity of patients with secondary peritonitis . Gln supplementation to parenteral nutrition may be an alternative for enhancing host defenses and improving infectious morbidity BACKGROUND AND AIMS Surgery , trauma and inflammation reduce HLA-DR expression on monocytes , which is associated with an increased susceptibility to infection and sepsis . Furthermore , surgery decreases plasma glutamine ( GLN ) levels . The expression of HLA-DR on human monocytes in vitro is dependent on the concentration of GLN in the culture medium . We therefore hypothesized that postoperative infusions of glutamine-dipeptides would prevent the decreased HLA-DR expression on monocytes . METHODS Thirty patients undergoing major abdominal surgery were r and omly allocated to receive either 1500 ml Vamin ( control ) or an isonitrogenic formulation containing Vamin and 500 ml glycyl-glutamine ( 35 g GLN ; 0.5g/kg BW ) ( GLY-GLN ) , or Vamin and 500 ml alanyl-glutamine ( 35 g GLN ; 0.5 g/kg BW ) ( ALA-GLN ) as a continuous infusion over 48 h post-operatively . Immediately and 48 h after surgery blood sample s were collected to determine HLA-DR expression on monocytes by flow cytometry . RESULTS The groups were comparable with respect to age , gender distribution and operation time . In patients receiving GLY-GLN mean HLA-DR expression on monocytes at 48 h was significantly better preserved than in controls ( 65.0 % + /-7 % vs 42.5 % + /-4 % ; P<0.05 ) , whereas HLA-DR expression on monocytes in patients receiving ALA-GLN was not significantly different . CONCLUSION This is the first study comparing the dipeptides GLY-GLN and ALA-GLN in the postoperative setting . The GLY-GLN induced preservation of HLA-DR on monocytes following surgery may prevent infectious complications in these patients BACKGROUND The management of acute pancreatitis ( AP ) frequently includes parenteral nutrition , but conditionally essential amino acids such as glutamine are not included in conventional total parenteral nutrition ( TPN ) . AIM This study was conducted to determine whether the inclusion of glutamine has a beneficial effect in patients with AP receiving TPN . METHODS In a r and omized , controlled study 28 patients with AP received either a st and ard TPN with 1.5 g/kg body weight protein or an isonitrogen , isocaloric TPN which contains 0.3 g/kg L -alanine- L -glutamine . Patients were assessed for nutritional and inflammatory parameters , infectious complications , length of TPN , length of hospital stay ( LOS ) and cost of TPN . RESULTS There were no side-effects related to glutamine substitution observed . Glutamine was associated with a significant increase of cholinesterase , albumin and lymphocyte count in AP as well a decrease of C-reactive protein compared to st and ard TPN at day 14 . There was a reduced length of TPN ( 10 [ 6 - 16 ] vs 16 [ 10 - 18 ] days , P<0.05 ) and a trend of reduced LOS ( 21 [ 14 - 32 ] vs 25 [ 19 - 40 ] days ) in AP patients receiving glutamine . The overall cost per patient for TPN did not differ ( gln+ : 929+/-586 vs gln- : 981+/-507 euro/patient ) . CONCLUSION Our results suggest that glutamine substitution is beneficial and does not increase the overall cost of parenteral feeding in patients with acute pancreatitis BACKGROUND Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit ( SICU ) . Clinical benefits of glutamine-supplemented parenteral nutrition may occur in hospitalized surgical patients , but efficacy data in different surgical subgroups are lacking . The objective was to determine whether glutamine-supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients . METHODS This was a double-blind , r and omized , controlled study of alanyl-glutamine dipeptide-supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis , cardiac , vascular , or colonic surgery . Subjects ( n = 59 ) received isocaloric/isonitrogenous parenteral nutrition , providing 1.5 g/kg/d st and ard glutamine-free amino acids ( STD-PN ) or 1.0 g/kg/d st and ard amino acids + 0.5 g/kg/d glutamine dipeptide ( GLN-PN ) . Enteral feedings were advanced as tolerated . Nosocomial infections were determined until hospital discharge . RESULTS Baseline clinical /metabolic data were similar between groups . Plasma glutamine concentrations were low in all groups and were increased by GLN-PN . GLN-PN did not alter infection rates after pancreatic necrosis surgery ( 17 STD-PN and 15 GLN-PN patients ) . In nonpancreatic surgery patients ( 12 STD-PN and 15 GLN-PN ) , GLN-PN was associated with significantly decreased total nosocomial infections ( STD-PN 36 vs GLN-PN 13 , P < .030 ) , bloodstream infections ( 7 vs 0 , P < .01 ) , pneumonias ( 16 vs 6 , P < .05 ) , and infections attributed to Staphylococcus aureus ( P < .01 ) , fungi , and enteric Gram-negative bacteria ( each P < .05 ) . CONCLUSIONS Glutamine dipeptide-supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac , vascular , and colonic surgery BACKGROUND Feeding the hemodynamically unstable patient is increasingly practice d , yet few data exist on its safety . Because enteral glutamine is protective to the gut in experimental models of shock and improves clinical outcomes , it may benefit trauma patients undergoing shock resuscitation and improve tolerance if administered early . This pilot study aim ed to evaluate gastrointestinal tolerance and safety of enteral feeding with glutamine , beginning during shock resuscitation in severely injured patients . METHODS In a prospect i ve r and omized trial , 20 patients were r and omly assigned to either an enteral glutamine group ( n = 10 ) or a control group ( n = 10 ) . Patients with severe trauma meeting st and ardized shock resuscitation criteria received enteral glutamine 0.5 g/kg/d during the first 24 hours of resuscitation and 10 days thereafter . Immune-enhancing diet began on postinjury day 1 , with a target of 25 kcal/kg/d . Control patients received isonitrogenous whey powder plus immune-enhancing diet . Tolerance ( vomiting , nasogastric output , diarrhea , and distention ) was assessed throughout the study . RESULTS Glutamine was well tolerated and no adverse events occurred . Treated patients had significantly fewer instances of high nasogastric output ( 5 vs 23 ; p = .010 ) , abdominal distention ( 3 vs 12 ; p = .021 ) , and total instances of intolerance ( 8 vs 42 ; p = .011 ) . Intensive care unit ( ICU ) and hospital length of stay were comparable . Control patients required supplemental parenteral nutrition ( PN ) to meet goals at day 7 . CONCLUSIONS Enteral glutamine administered during active shock resuscitation and through the early postinjury period is safe and enhances gastrointestinal tolerance . A large clinical trial is warranted to determine if enteral glutamine administered to the hemodynamically unstable patient can reduce infectious morbidity and mortality An abundant amino acid in the human body , glutamine ( Gln ) has many important metabolic roles that may protect or promote tissue integrity and enhance the immune system . Low plasma and tissue levels of Gln in the critically ill suggest that dem and may exceed endogenous supply . A relative deficiency of Gln in such patients could compromise recovery and result in prolonged illness and an increase in late mortality . This study examines this hypothesis . Using a prospect i ve , block-r and omized , double-blind treatment study design , we tested whether a Gln-containing parenteral nutrition ( PN ) compared with an isonitrogenous , isoenergetic control feed would influence outcome , with the endpoints of morbidity , mortality , and cost at 6 mo postintervention . In one general intensive care unit ( ICU ) , to ensure consistency of management policies , 84 critically ill adult patients , with Acute Physiological and Chronic Health Evaluation II score > 10 , requiring nutritional support received PN only if enteral nutrition was contraindicated or unsuccessful . Survival at 6 mo was significantly improved in those receiving Gln PN ( 24/42 versus 14/42 ; P = 0.049 ) . Significantly more deaths occurred in patients requiring control PN for > 10 d ( P = 0.03 ) . The excess control deaths occurred later and those patients had had a significantly longer postintervention stay ( P = 0.012 ) and use of ICU . In the Gln recipients , the total ICU and hospital cost per survivor was reduced by 50 % . In critically ill ICU patients unable to receive enteral nutrition , a Gln-containing PN solution improves survival at 6 mo and reduces the hospital costs per survivor Objective To assess the influence of enteral glutamine on the incidence of severe sepsis and death in critically ill patients . Design This two-armed clinical trial was triple blind ( patients , attending staff , research nurse ) . Setting The 10 bed general ICU at Royal Perth Hospital , Western Australia . Patients This trial evaluated 363 patients requiring mechanical ventilation ( median APACHE II score=14 ) ; of these , 85 had trauma . InterventionThe intervention solution contained 20 g/l glutamine and the control solution was isojoulic and isonitrogenous . Measurements and results The groups had similar characteristics at baseline , and they also received equivalent amounts of protein and energy . Patients in the glutamine group received a median of 19 g/glutamine per day and 91 % ( 332 of 363 ) of the patients were fed via a nasogastric tube ( median duration = 10 days ) . The outcomes were similar in the two groups : ( a ) death within 6 months : glutamine group 15 % ( 27 of 179 ) vs control group 16 % ( 30 of 184 ) ; p=0.75 ; relative risk , 0.95 ( 95 % confidence interval , 0.71–1.28 ) ; and ( b ) severe sepsis : glutamine group 21 % ( 38 of 179 ) vs control group 23 % ( 43 of 184 ) ; p=0.62 ; relative risk , 0.94 ( 95 % confidence interval , 0.72–1.22 ) . There was also no discernable difference in the secondary outcomes relating to infections , febrile period , antimicrobial therapy , and consumption of inotropes . Conclusion This clinical trial did not support the use of enteral glutamine supplements in similar cohorts of critically ill patients OBJECTIVE We evaluated the expression of Toll-like receptors 2 and 4 ( TLR-2 and TLR-4 ) in circulating monocytes from peripheral blood of critical care patients treated with and without glutamine . Because no research has been published to date on the effect of glutamine on TLR receptors in critical patients , it was determined in an initial sample of 30 patients . METHODS This was a prospect i ve , r and omized , single-blind study with 15 patients assigned to receive parenteral nutrition with a daily glutamine supplement of 0.35 g/kg . The control group received isocaloric-isonitrogenous parenteral nutrition . Blood sample s were extracted before beginning the treatment and at 5 and 14 d. Expressions of CD14 , TLR-2 , and TLR-4 were determined by flow cytometry . Levels of TLRs were expressed as mean fluorescence intensity ( mfi ) . RESULTS Basal characteristics were similar in both groups . The expressions of TLR-2 in the treatment group with glutamine were 4.67 + /- 3.82 mfi before treatment , 3.91 + /- 2.04 mfi at 5 d , and 4.28 + /- 2.47 mfi at 14 d. The expressions of TLR-2 in the control group were 5.49 + /- 3.20 mfi before treatment , 4.48 + /- 2.15 mfi at 5 d , and 4.36 + /- 2.36 mfi at 14 d. The expressions of TLR-4 in the treatment group were 1.65 + /- 1.89 mfi before treatment , 1.23 + /- 1.10 mfi at 5 d , and 1.77 + /- 1.97 at 14 d. The expressions of TLR-4 in the control group were 1.51 + /- 1.76 mfi before treatment , 1.36 + /- 0.99 mfi at 5 d , and 1.26 + /- 0.59 mfi at 14 d. Infections were detected in 11 patients who received glutamine and 13 control patients ( P = 0.51 ) . CONCLUSION In critical care patients , parenteral nutrition supplemented with glutamine does not increase the expression of TLR-2 or TLR-4 in peripheral blood monocytes Objective Enteral glutamine supplements have been shown to reduce infectious morbidity in trauma patients , but their effect on burn patients is not known . The objective of this study was to measure the impact of enteral glutamine supplementation on infectious morbidity , length of care , and the immune system in burn patients . Design Double-blinded , r and omized clinical trial . Setting Burn center . Patients Forty-five adults with severe burns . Interventions Patients were r and omized to receive either glutamine or an isonitrogenous control mixture until complete healing occurred . Length of care , incidence of positive blood culture , and mortality were recorded . Phagocytosis by circulating polymorphonuclear cells was measured every 3 days . Measurements and Main Results Patient characteristics were similar in both groups . Four patients were excluded from the analysis , because three of them died within 72 hrs and the fourth could not receive enteral nutrition and amino acid supplements for the first 10 days . Of the remaining 41 patients , length of care in the survivors was not different between groups ( 0.9 vs. 1.0 days/percent total body surface area for glutamine vs. control , respectively ) , positive blood culture was three times more frequent in control than in glutamine treatment ( 4.3 vs. 1.2 days/patient , p < .05 ) , and Pseudomonas aeruginosa was detected in six patients on control and zero on glutamine ( p < .05 ) . Phagocytosis by polymorphonuclear cells was not different between groups . Mortality rate was significantly lower in glutamine than in control : intention to treat , two vs. 12 ( p < .05 ) ; per protocol analysis , zero vs. eight ( p < .01 ) . Conclusions Enteral glutamine supplementation in adult burn patients reduces blood infection by a factor of three , prevents bacteremia with P. aeruginosa , and may decrease mortality rate . It has no effect on level of consciousness and does not appear to influence phagocytosis by circulating polymorphonuclear cells BACKGROUND & AIMS Glutamine is recognized as a conditionally essential amino acid . Recent studies indicate that glutamine-containing total parenteral nutrition improves nitrogen economy , enhances gastrointestinal and immune functions and shortens hospital stay . METHODS Thirty-seven patients ( 19 w and 18 m ; age 61 . 4+/-10.4 years ; BMI 23.7+/-2.8 kg/m(2 ) ) following major abdominal surgery receiving an isonitrogenous isoenergetic TPN with or without alanyl-glutamine supplementation ( 0.5 g/kg BW/day ) , were evaluated in a double-blind , r and omized , controlled trial over a five-day period by measuring nitrogen balance , selected biochemical parameters and length of hospital stay . RESULTS Supplemental alanyl-glutamine improved the overall mean ( -3.5+/-1.6 vs. -5.5+/-1 . 4 g N;P<0.05 ) and cumulative nitrogen balance ( -14.1+/-9.1 vs. -21.7+/-11.4 g N;P<0.05 ) compared with the isonitrogenous , isoenergetic st and ard regimen . Alanyl-glutamine normalized plasma glutamine concentration and reduced the length of hospital stay ( 12.8+/-2.6 vs. 17.5+/-6.4 days;P<0.05 ) . CONCLUSIONS The results of the study confirm that supplementation with synthetic alanyl-glutamine dipeptide is associated with cost containment due to shortened hospitalization and improved nitrogen economy BACKGROUND Infections are an important cause of morbidity and mortality in patients with multiple trauma . Studies in both animals and human beings have suggested that glutamine-enriched nutrition decreases the number of infections . METHODS Patients with multiple trauma with an expected survival of more than 48 h , and who had an Injury Severity Score of 20 or more , were r and omly allocated glutamine supplemented enteral nutrition or a balanced , isonitrogenous , isocaloric enteral-feeding regimen along with usual care . Each patient was assessed every 8 h for infection , the primary endpoint . Data were analysed both per protocol , which included enteral feeding for at least 5 days , and by intention to treat . FINDINGS 72 patients were enrolled and 60 received enteral feeding ( 29 glutamine-supplemented ) for at least 5 days . Five ( 17 % ) of 29 patients in the glutamine-supplemented group had pneumonia compared with 14 ( 45 % ) of 31 patients in the control group ( p<0.02 ) . Bacteraemia occurred in two ( 7 % ) patients in glutamine group and 13 ( 42 % ) in the control group ( p<0.005 ) . One patient in the glutamine group had sepsis compared with eight ( 26 % ) patients in the control group ( p<0.02 ) . INTERPRETATION There was a low frequency of pneumonia , sepsis , and bacteraemia in patients with multiple trauma who received glutamine-supplemented enteral nutrition . Larger studies are needed to investigate whether glutamine-supplemented enteral nutrition reduces mortality |
1,021 | 30,169,912 | 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 | OBJECTIVES The aim of this systematic review was to establish in studies with human participants the effect of a regular fluoride dentifrice compared to water or saline on dental plaque inhibition . | 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 h. The plaque area was recorded and then measured planimetrically . The results showed that more plaque accumulated with water and the liquid dentifrice compared with the fluoride toothpaste . Thus , there was a statistically significant difference between the fluoride toothpaste and water and between the fluoride toothpaste and the liquid dentifrice . There was no significant difference between the liquid dentifrice and water . It is concluded that in this particular model system , the liquid dentifrice provided little chemical plaque inhibitory action Short-term method ologies have been developed to screen chemical agents for plaque inhibitory effects . Most measure inhibition of plaque regrowth over several days . A method was described to study agents over 16 - 24 h periods , although some difficulties with the index used were reported . The aim of this study was to determine whether more conventional plaque scoring methods could be used . These 2 crossover studies measured plaque regrowth over 24 h in 20 subjects and in response to single brushings with either a chlorhexidine and minus active toothpaste or to a fluoride toothpaste product and water . Significantly less plaque had reformed after brushing with the chlorhexidine toothpaste compared with its control and with the fluoride toothpaste compared with water . 18 subjects participated in both studies and using their data for an inter study comparison , less plaque developed with the chlorhexidine compared with the fluoride toothpaste . These studies had the advantage that longer-term trials already demonstrated the same differences . This permits one to conclude with some certainty that the 24-h plaque regrowth study design , using conventional measures of plaque accumulation , could be a useful and rapid method of screening potential plaque inhibitory agents and formulations This study was a first stage evaluation of the plaque inhibitory properties of an experimental cetylpyridinium chloride (CPC)/essential oil mouthrinse . The study was a formulation , not ingredient , evaluation and comparisons were made with established mouthrinse products . The 5 rinses tested were : the experimental formulation ; a triclosan/copolymer prebrushing mouthrinse ; two negative control rinses , which differed only in color ; and as a positive control , a 0.2 % chlorhexidine mouthrinse . The study used a 5 cell , 4-day plaque regrowth , double-blind crossover design in which 15 subjects participated . Allocation of mouthrinse sequences was accomplished using 3 replicates of a 5 x 5 Latin square , incorporating balance for carryover . On Day 1 , subjects received a scaling and polishing to reduce plaque , ceased toothcleaning , and commenced rinsing twice daily , under supervision , with the r and omly assigned rinse . Rinsing time for the experimental and one negative control rinse was 30 seconds and for the other rinses was 60 seconds . On Day 5 , plaque was scored by both index and area . Differences in plaque regrowth between the rinse groups were highly significant . The order of efficacy from the most effective was : chlorhexidine rinse ( positive control ) ; experimental CPC/essential oil rinse ; triclosan/copolymer rinse ; and the negative control rinses . From the calculated confidence intervals each rinse differed significantly from each other rinse , except for the two negative control rinses which were comparable to each other . Proportionately , the CPC/essential oil rinse was positioned 30 to 50 % between the triclosan/copolymer rinse and the chlorhexidine ( positive control ) . These findings suggest that the CPC/phenolic rinse would seem worthy of further evaluation for adjunctive benefits to oral hygiene Many compounds could be added to toothpaste to assist plaque inhibition , but ionic interactions can cause formulation difficulties . Moreover , the actual chemical action of a plaque inhibitory agent added to a toothpaste is difficult to assess when the product is used in the conventional manner , i.e. , in addition to toothbrushing . The non-ionic antimicrobial triclosan has been incorporated in toothpastes and shown to have variable plaque inhibitory activity both alone and in conjunction with certain polymers or metal ions . Little is known of the efficacy of triclosan toothpastes compared to conventional fluoride toothpastes . The aim of this study was to compare a commercially available toothpaste containing 0.3 % triclosan/co-polymer with a sodium fluoride toothpaste for chemical plaque inhibitory effects over a 4-day period . The study was design ed to stratify the relative efficacy plaque inhibitory action of the products , comparisons were made with a positive control , chlorhexidine rinse and a negative control , saline . The study design was a r and omised single blind crossover design balanced for first-order carryover . A total of 18 healthy , dentate volunteers participated in the study . On day 1 of each period the volunteers suspended toothcleaning and rinsed 2 x daily with the allocated mouthrinse or toothpaste slurry . On day 5 , the plaque on the teeth was disclosed and scored by index and area . Increasing plaque scores were in the order chlorhexidine , triclosan toothpaste , fluoride toothpaste , and saline . Chlorhexidine was significantly more effective than all the other agents tested , and both toothpaste preparations were significantly better than the saline rinse . There was no significant difference between the two toothpaste rinses . Consistent with other studies the triclosan toothpaste offers only moderate plaque inhibitory properties when compared to a conventional toothpaste AIM To examine the effect of amine fluoride/stannous fluoride ( AmF/SnF(2))-containing dentifrice and mouth rinse on plaque formation and gingivitis as compared with habitual oral hygiene procedures with a regular sodium fluoride ( NaF ) dentifrice . MATERIAL AND METHODS In total , 22 general practice s participated in this research project . The participants ( N=281 ) were r and omly assigned into two groups : the test group received an AmF/SnF(2 ) dentifrice-mouth rinse combination and the control group received a NaF-containing dentifrice . The patients were requested to brush twice daily for approximately 2 min . The subjects of the test group had to rinse additionally in the evening for 30 s with 10 ml of the mouth rinse . RESULTS Both groups started with comparable scores of plaque , bleeding and staining . At 6 months , the plaque scores were 0.95 for the AmF/SnF(2 ) group and 0.99 for the NaF group ( decrease of 16 % and 10 % , respectively ) . Bleeding scores , although significantly different from baseline , did not show differences between the two regimes . At the end of the experimental period , the overall staining was more pronounced in the AmF/SnF(2 ) group ( 41 % ) than the NaF group ( 26 % ) . Both plaque reduction and increase in staining seemed to be correlated to the amount of mouth rinse used in the test group . CONCLUSION In instruction-resistant patients recruited from dental practice s , the combined use of AmF/SnF(2 ) did not decrease gingivitis at a significant level in comparison with the regular regime of two times daily brushing with an NaF-containing dentifrice . However , the above-mentioned combination result ed in greater plaque reduction than that observed with the use of the conventional dentifrice . When used according to the manufacturer 's instructions , this effect on plaque scores was more pronounced Delmopinol is a morpholinoethanol derivative which , in mouthrinses used in the absence of normal oral hygiene , has been shown effective in the inhibition of plaque and gingivitis . The aim of this study was to determine the adjunctive oral hygiene benefits and safety of delmopinol rinses when used alongside normal toothcleaning . This 6-month home use study was a placebo-controlled , double-blind , r and omised parallel design evaluating 0.1 % and 0.2 % delmopinol rinses and structured to conform with the ADA Council of Dental Therapeutics guidelines . A total of 450 dentate male and female subjects were recruited who had no relevant medical or pharmacotherapy histories determined from a full medical examination , including haematological and biochemical tests . Subjects had moderate levels of plaque and gingivitis . At baseline , 3 and 6 months subjects were scored for plaque , gingivitis , tooth stain and supragingival calculus , with plaque sample d for microbiological analysis . Additionally , oral mucosal examinations were performed and subjects question ed for adverse symptoms . Baseline special tests were repeated at the end of the study . After baseline examinations , the subjects received a professional prophylaxis , provided with the allocated mouthwash and instructed to use 10-ml volumes for 60 s 2 x daily and where appropriate after toothbrushing and meals . Demographic features of the 3 groups were similar and losses to trial were small . Adverse signs and symptoms included transitory numbness of the tongue , tooth and tongue staining , taste disturbance and rarely mucosal soreness and erosion . All local side-effects were less commonly reported at 6 compared to 3 months and only 6 subjects were withdrawn because of adverse event . No systemic effects attributable to the agent were observed and no significant shifts in haematological or biochemical parameters occurred . All groups showed considerable improvements in oral hygiene and gingival health with some significant differences in favour of 0.2 % delmopinol compared to placebo for gingivitis and more particularly plaque . Staining was also significantly increased in the delmopinol groups but not calculus . In the present study , a considerable Hawthorne effect occurred , which must in part explain why only a modestly significant effect was achieved It has previously been shown that a toothpaste which contains triclosan and polydimethylsiloxane ( silicone oil ) improved gingival health in a test panel with established gingivitis more markedly than usually observed when testing commercial triclosan-containing toothpastes . In the present study the mode of action of combinations of silicone oil and triclosan was investigated . An in vitro experiment showed that triclosan was retained in a thin layer of silicone oil on the inner surfaces of test tubes that had been treated with the combination of triclosan and silicone oil . This triclosan was slowly released and inhibited the growth of bacteria in the test tubes . Silicone oil alone and in combination with triclosan was able to inhibit polysaccharide adhesion to the test tubes in the presence of a strain of Streptococcus sobrinus and a sucrose-containing medium . Corresponding in vivo experiments showed similar results ; teeth topically treated with silicone oil and triclosan showed a marked plaque reduction , and those treated with silicone oil alone showed a moderate reduction , as compared with a placebo . The silicone oil plus 0.3 % triclosan combination inhibited plaque formation also on proximal surfaces . It appears likely that this combination provides a reservoir of triclosan in the thin layer of silicone oil which binds strongly to teeth because of its low surface tension . Triclosan is then slowly released into saliva because of its low solubility in this fluid OBJECTIVES The present study assessed whether 3-month-old used manual toothbrushes are less effective in reducing plaque scores compared with new toothbrushes with or without the use of dentifrice . MATERIAL AND METHODS The present study was performed employing a single-use , examiner-blinded , professional brushing model . Four brushing modalities were r and omly allocated to one of four quadrants , that is , 3-month-old used toothbrushes and new toothbrushes both with and without the use of dentifrice . Prebrushing and post-brushing plaque scores ( Quigley Hein plaque index ) and gingival abrasion ( GA ) scores were obtained . A dental hygienist performed the professional brushing procedure . The 3-month-old used toothbrushes were assessed for wear . RESULTS No significant differences were observed among the treatments with regard to the prebrushing scores . The post-brushing plaque scores ranged from 1.59 for the new brush with dentifrice to 1.76 for the old brush with dentifrice . There was a significant difference ( P = 0.036 ) among the four treatments regarding the old brush with dentifrice , which removed less plaque than the other treatment modalities . Regarding GA scores , no significant differences were observed . With regard to toothbrush wear after 3 months of use , the scores varied widely among the individually evaluated brushes . CONCLUSION The present study did not show a clinical ly relevant difference in plaque score reductions following a 2-minute brushing exercise among 3-month-old used and new manual toothbrushes . However , the wear rate of the brushes seemed to be the determining factor in loss of efficacy , rather than the age of the toothbrush . Furthermore , dentifrice did not show an additional effect on instant plaque removal Triclosan is a lipophilic antimicrobial agent which , when present in an aqueous dentifrice vehicle , is complexed by or in close contact with polymers and surface-active molecules , emulsifying agents , flavoring oils and other hydrophobic ingredients . Because of this , dentifrice products containing triclosan may not have triclosan in a bioavailable state and , hence , the products themselves can not be assumed to possess antimicrobial activity . In order to determine the antimicrobial effects on dental plaque of a triclosan/pyrophosphate dentifrice relative to a negative control ( without triclosan or pyrophosphate ) , a crossover 4-day non-brushing study was conducted . Thirty-four subjects were enrolled in this r and omized two-period , double-blind crossover investigation with thirty-three subjects completing all aspects . Following a baseline plaque examination and complete plaque removal at the start of the first 4-day treatment period , subjects initiated a twice-daily supervised dosing regimen , during which they rinsed with their first assigned dentifrice in slurry form while refraining from tooth-brushing and all other oral hygiene procedures . Evaluations to quantify test product effects on plaque were conducted on Day 5 . After a week-long interim washout period , subjects repeated the twice daily rinsing regimen over Days 1 - 4 of Treatment Period 2 with their second assigned product , again with examinations on Day 5 . Analysis of data demonstrated subjects had significantly ( p = 0.0296 ) less plaque when rinsing with the triclosan/pyrophosphate dentifrice slurry as compared to the negative control dentifrice slurry ; the relative treatment difference as determined by the primary examiner was 12.7 % . A trainee examiner observed a 16.0 % reduction on a subset of subjects ( p = 0.0139 ) . This efficacy result compares favorably with results from other studies of triclosan-containing products . The examinations for oral safety demonstrated no meaningful clinical differences between the triclosan/pyrophosphate dentifrice and control dentifrice A number of substances have been incorporated into toothpastes or gels to inhibit plaque regrowth . The aim of this study was to evaluate triclosan and stannous fluoride products for plaque inhibitory properties by comparison with a chlorhexidine or saline rinse and a control product which was a conventional commercially available toothpaste . In a blind 8 cell cross-over study , 15 volunteers rinsed 2 x a day for 4 days with slurries of the products or the saline and chlorhexidine solutions . No other form of oral hygiene was performed and plaque regrowth from a zero baseline was recorded by plaque score and plaque area . Plaque regrowth was significantly less with the chlorhexidine rinse and significantly greater with the saline rinse compared to the toothpaste and gel products . No significant differences were found between the test and control products . The results again demonstrate that commercially available toothpastes have plaque inhibitory effects which so far appear difficult to improve upon by the addition of specific ingredients , in this case stannous fluoride or triclosan . Commercially available products of known activity would appear useful benchmarks for comparison of experimental formulations BACKGROUND The biofilm that forms and remains on tooth surfaces is the main etiological factor in caries and periodontal disease . Prevention of caries and periodontal disease must be based on means that counteract this bacterial plaque . OBJECTIVE To monitor the incidence of tooth loss , caries and attachment loss during a 30-year period in a group of adults who maintained a carefully managed plaque control program . In addition , a comparison was made regarding the oral health status of individuals who , in 1972 and 2002 , were 51 - 65 years old . MATERIAL AND METHODS In 1971 and 1972 , more than 550 subjects were recruited . Three hundred and seventy-five subjects formed a test group and 180 a control group . After 6 years of monitoring , the control group was discontinued but the participants in the test group was maintained in the preventive program and was finally re-examined after 30 years . The following variables were studied at Baseline and after 3 , 6 , 15 and 30 years : plaque , caries , probing pocket depth , probing attachment level and CPITN . Each patient was given a detailed case presentation and education in self-diagnosis . Once every 2 months during the first 2 years , once every 3 - 12 months during years 3 - 30 , the participants received , on an individual need basis , additional education in self-diagnosis and self-care focused on proper plaque control measures , including the use of toothbrushes and interdental cleaning devices ( brush , dental tape , toothpick ) . The prophylactic sessions that were h and led by a dental hygienist also included ( i ) plaque disclosure and ( ii ) professional mechanical tooth cleaning including the use of a fluoride-containing dentifrice/paste . RESULTS Few teeth were lost during the 30 years of maintenance ; 0.4 - 1.8 in different age cohorts . The main reason for tooth loss was root fracture ; only 21 teeth were lost because of progressive periodontitis or caries . The mean number of new caries lesions was 1.2 , 1.7 and 2.1 in the three groups . About 80 % of the lesions were classified as recurrent caries . Most sites , buccal sites being the exception , exhibited no sign of attachment loss . Further , on approximal surfaces there was some gain of attachment between 1972 and 2002 in all age groups . CONCLUSION The present study reported on the 30-year outcome of preventive dental treatment in a group of carefully monitored subjects who on a regular basis were encouraged , but also enjoyed and recognized the benefit of , maintaining a high st and ard of oral hygiene . The incidence of caries and periodontal disease as well as tooth mortality in this subject sample was very small . Since all preventive and treatment efforts during the 30 years were delivered in one private dental office , caution must be exercised when comparisons are made with longitudinal studies that present oral disease data from r and omly selected subject sample This double-blind , controlled clinical study compared the effectiveness of 30- and 60-s listerine rinses in both inhibiting the development of , and reducing existing , supragingival plaque and gingivitis , using an experimental gingivitis model . 94 subjects completed this study . For each subject , a modified gingival index , modified Quigley-Hein plaque index and Eastman interdental bleeding index were recorded at baseline and at 2 weeks . Following the baseline examinations , subjects received half-mouth prophylaxes , and began 2 x daily supervised rinsing either with listerine for 30 or 60 s or with a control mouthrinse for 30 s as their sole oral hygiene measure . Statistical analysis ( ANCOVA ) showed that both the 30- and 60-s listerine rinses were significantly ( p < 0.01 ) more effective than the control in inhibiting and reducing plaque , gingivitis and gingival bleeding . Although 60-s rinses with listerine were significantly more effective ( p < 0.01 ) than 30-s rinses in controlling plaque , the 2 rinse duration s were similarly effective in controlling interdental bleeding and gingivitis . This study confirms the recommendation of 2x daily rinsing with listerine for 30 s as an effective regimen for gingivitis control OBJECTIVES Toothpastes are good vehicles for antibacterial substances to exert a prolonged effect . This effect depends on the substantivity and ability to interfere with plaque metabolism and /or vitality . It was the purpose of this clinical , r and omized 2 x 4 cell crossover study to evaluate and to compare the antibacterial effects of two toothpastes ( Colgate Total(R ) , COL and Parodontax(R ) , PAR ) applied as slurries on established plaque over 24 h ( Part I ) and their effect on 4-day plaque regrowth ( Part II ) . Chlorhexamed(R ) ( 0.1 % ; CHX ) and water served as positive and negative controls . MATERIAL AND METHODS After professional toothcleaning eight students were asked to refrain from all mechanical hygiene measures for the next 72 h. After 48 h plaque was sample d and vitality of the plaque flora examined ( baseline , VF0 % ) . The subjects then rinsed for 1 min with 15 mL of one of the test or control solutions . Every second hour up to 14 h and 24 h after rinsing , plaque sampling and staining was performed to assess plaque vitality ( VF2 - 24 , Part I ) . In Part II , the classical 4-day plaque regrowth design was used with two rinses ( 1 min ) a day as the only oral hygiene measure . Vitality values were assessed on day 1 and day 4 ( VF1 , VF2 ) . At day 4 , teeth were stained to assess the whole mouth plaque index ( PlI ) and to evaluate the percentage of plaque area ( PA ) of the anterior teeth . RESULTS Compared to placebo , all active rinses reduced plaque vitality significantly over a period of 24 h ( Part I ) . PAR , COL and CHX revealed reductions of 18 - 31 % , 28 - 50 % and 19 - 50 % , respectively . In Part II , similar reductions of all parameters were found for all active rinses ( PAR 12 - 30 % , COL 34 - 51 % , CHX 40 - 64 % ) . CONCLUSIONS Colgate Total has shown a significant action on plaque regrowth and a high substantivity during 24 h , while Parodontax revealed a more moderate but still significant effect A staining index has been proposed which is simple to use clinical ly and yet is sensitive enough to detect small changes in staining levels between different groups . Accurate scale drawings from An atlas of tooth form were reproduced . Outlines of the labial and lingual surfaces of all eight incisor teeth were enlarged to scale ( magnification X 4 ) and each tooth face divided into 4-mm squares . All areas of extrinsic stain were drawn by the examiner on the grid system . This method has been tested in three clinical trials and the reproducibility investigated . In 161 duplicate examinations a total of 1,830 stained squares were scored by one examiner , compared with 1,853 squares by the second examiner ; the reproducibility ratio was 0.155 and the coefficient of correlation was 0.956 . The method proved sufficiently sensitive to record differences in staining levels in groups using two dentifrices ; one was a normal commercial product with an abrasivity against dentin approximately two-thirds that of the other paste . The proposed Extrinsic Stain Index provides data which can be analyzed by appling parametric or nonparametric tests The purpose of the present study was to test the effectiveness of a new type of BRAUN electric toothbrush ( D5 ) in comparison with the traditional BRAUN electric toothbrush ( D3 ) and to a manual toothbrush ( M ) . For this study , 60 dental students were selected who had no previous experience with the use of an electric toothbrush . The study consisted of 3 experiments . Prior to each experiment , all students were asked to abstain from all oral hygiene procedures for at least 24 h. In Exp I , the efficacy of toothbrushing was studied when one of the investigators brushed the teeth of the students . No toothpaste was used in this first part of the study . In Exp II , the efficacy of brushing was evaluated when the brushing was carried out by the students themselves . In Exp III , the efficacy of the brushing was studied after the students had received a professional instruction and oral prophylaxis . The available time for the brushing amounted to a total of 2 min per mouth . The amount of dental plaque was evaluated by means of the Silness and Löe plaque index at 6 sites around the tooth . Results showed in Exp I that both electric toothbrushes proved to remove significantly more plaque than the manual toothbrush ( M 78 % ; D3 85 % ; D5 86 % ) . In Exp II , no significant differences in plaque-removing efficacy were found between the 3 brushes ( M 73 % ; D3 72 % ; D5 73 % ) . In Exp III , the D5 proved to remove significantly more plaque than the other two brushes ( M 77 % ; D3 77 % ; D5 83 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES The study was design ed to test the efficacy in plaque removal of three toothbrushes : two manual brushes , the Butler GUM 311 and the Dr Best X-Active , and one electric toothbrush the Braun Oral-B 3D Plaque Remover ( 3D ) . METHOD The study was a split-mouth , single-blind , r and omized clinical study consisting of three identical experiments testing three combinations of toothbrushes ( experiment 1 : 3D versus Butler ; experiment 2 : 3D versus Dr Best ; experiment 3 : Butler versus Dr Best ) , in which the teeth of the panellists were brushed by a dental hygienist . In a fourth experiment , the panellists brushed their own teeth ( 3D versus Dr Best ) . Thirty-five subjects participated in the study and received a professional prophylaxis prior to the first experiment . They were requested to refrain from brushing their teeth for 48 h prior to each experiment . Plaque was assessed according to the Silness & Löe plaque index at six sites per tooth . Next , the dental hygienist ( experiments 1 - 3 ) or the panellist ( experiment 4 ) brushed for 60 s with their first assigned brush in two r and omly selected contralateral quadrants . Brushing was repeated ( 60 s ) with the second brush in the opposing two contralateral quadrants . Prior to experiment 4 , panellists were given two thorough h and s-on professional instructions in the use of the 3D and the Dr Best toothbrushes . RESULTS In experiment 1 , the 3D showed a mean plaque reduction of 72 % compared to 63 % with the Butler ( P<0.01 ) . In experiment 2 , the 3D showed a mean plaque reduction of 79 % and the Dr Best 76 % ( P<0.05 ) . In experiment 3 , the Butler showed a mean plaque reduction of 81 % and the Dr Best 85 % ( P=0.01 ) . In the h and s of the panellists ( experiment 4 ) , the 3D showed a mean plaque reduction of 88 % and the Dr Best 84 % ( P<0.05 ) . CONCLUSIONS A 5-week training period with repeated h and s-on instruction gives panellists the skill to perform brushing with efficacy comparable to that of professional brushing . In agreement with a previous study , the 3D was more effective than a flat-trimmed manual toothbrush ( Van der Weijden et al. 1994 ) . Brushing with the criss-cross result ed in small statistical differences with the 3D and the flat-trimmed manual toothbrush . The clinical relevance of these statistically significant results should be the subject of a longitudinal study Some triclosan and stannous fluoride toothpastes have been shown effective in reducing plaque and more particularly gingivitis in home use studies . There have been few comparisons of such products for their chemical plaque inhibitory action divorced from the indeterminate variable of toothbrushing . This study was a r and omised , single-blind , cross-over comparison of 4 products , in a 4-day plaque regrowth design , balanced for residual effects and involving 12 healthy dentate subjects . The test agents were a stannous fluoride toothpaste , a triclosan/copolymer toothpaste , a triclosan/zinc citrate toothpaste and water . On day 1 of each study period , subjects were rendered plaque free . For the following 4 days , each subject suspended normal toothcleaning and rinsed 2 x daily with the allocated treatment for 60 s under supervision . On day 5 , plaque was scored by index . Washout periods of 2 1/2 days brushing with water alone , followed each treatment period . Pseudo treatment periods of 4 days , involving 2 x daily rinsing with water in the absence of toothbrushing , followed the normal washouts after the stannous fluoride and triclosan/zinc citrate treatments , giving a total of 6 treatment periods . This design permitted analyses for 1st-order-carry-over . Intention to treat analyses revealed all toothpastes were more effective than water but that there were no differences between the active treatments . Per protocol analysis gave essentially similar findings except that the difference in plaque in favour of the triclosan/zinc citrate toothpaste over water did not reach significance . There was no evidence of 1st-order-carry-over effects for the stannous fluoride or triclosan/zinc citrate toothpastes . Consistent with other studies it appears that stannous fluoride and triclosan can be formulated into toothpaste vehicles to provide plaque inhibitory effects The removal of plaque by toothbrushing with toothpaste is the most common form of plaque control in the developed world . However , the use of chemical adjuncts such as mouthrinses is increasing . In practice mouthrinses and toothpaste are used together , however , in many clinical trials , employed to assess mouthrinse activity , toothpaste use is suspended . This fails to measure the effect of chemical interactions which are known to occur between toothpaste ingredients and mouthrinses . The objective of this trial was to develop a methodology which would assess the adjunctive chemical plaque inhibitory action of mouthrinses , when used with toothpaste but without the indeterminate variable of toothbrushing . The study was a single blind , r and omised , 7-way crossover design , based on a variation of a 4 day plaque regrowth model . The 2 x daily rinsing regimens produced increasing plaque scores in the following order : ( 1 ) water/chlorhexidine , ( 2 ) chlorhexidine/water , ( 3 ) chlorhexidine/toothpaste slurry , ( 4 ) toothpaste slurry/chlorhexidine , ( 5 ) water/toothpaste slurry , ( 6 ) toothpaste slurry/water , ( 7 ) water/water . Chlorhexidine and water or chlorhexidine and toothpaste slurry combinations produced significantly lower plaque scores than water alone . Slurry and water combinations result ed in less plaque than water alone , but differences were not significant . Toothpaste slurry and chlorhexidine produced significantly increased plaque scores compared to chlorhexidine and water . The study suggests that , outside the Hawthorne effect , chlorhexidine rinses would be less effective in reducing plaque when used with toothpaste than when used alone . The methodology could be employed as a screening tool for the evaluation of mouthrinses expected to be used as adjuncts to normal oral hygiene methods . The same could be used to optimise oral hygiene regimens which include the use of mouthrinses A three-way blind cross-over study was done to compare the plaque removing effects of a double-headed toothbrush with a popular single-headed toothbrush in 30 patients . Both brushes were used with the modified Bass technique for one week each . The results of this study indicated that the double-headed toothbrush is more effective in plaque removal especially when dentifrices were used Mouthwashes are frequently used as adjuncts to oral hygiene . However , for some products there is little supportive evidence that rinses provide greater benefits than plain water or additional benefits to the plaque inhibitory action provided by toothpaste . This study was a single blind , r and omized , cross-over design in which 6 rinses were compared for inhibitory action against plaque regrowth . The formulations were a cetylpyridinium chloride rinse , a prebrushing detergent rinse , a peroxyborate rinse a toothpaste slurry rinse , a chlorhexidine rinse , and a saline rinse . From a zero baseline , plaque regrowth at day 5 was significantly reduced by chlorhexidine compared to peroxyborate ; and , in turn , significantly reduced by peroxyborate compared to the other rinses . There were no significant differences between saline or a toothpaste slurry and the cetylpyridinium chloride or prebrushing rinse products . The findings would appear pertinent to the value of the respective rinses as adjuncts to oral hygiene |
1,022 | 30,275,939 | 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 | ABSTRACT Background : Schizophrenia negative symptoms ( SNS ) contribute substantially to poor functional outcomes , loss in productivity and poor quality of life .
It is unclear which instruments may be used for assessing quality of life in patients with SNS .
Objective : The objective of this review was to identify instruments assessing health-related quality of life ( HRQoL ) vali date d in patients with SNS and to assess their level of validation . | 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 |
1,023 | 30,313,000 | 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 . | OBJECTIVES Chronic pain is common and use of long-term opioid therapy for chronic pain has increased dramatically .
This report review s the current evidence on effectiveness and harms of opioid therapy for chronic pain , focusing on long-term ( ≥1 year ) outcomes . | 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 Objective To evaluate the outcomes associated with the use of controlled-release ( CR ) oxycodone for up to 3 years in the treatment of noncancer pain . Methods Adult patients who previously participated in controlled trials of CR oxycodone for osteoarthritis pain , diabetic neuropathy pain , or low back pain , and who continued to require opioid analgesia for moderate or severe pain , were enrolled in an open-label , uncontrolled , registry study . Data collected over time included dose , pain severity on a numeric scale , treatment acceptability , adverse events , and descriptions of problematic drug-related behavior . Results Two hundred thirty-three patients were enrolled . When the study closed , 141 , 86 , and 39 patients had taken CR oxycodone for at least 1 , 2 , and 3 years , respectively ; mean duration of treatment was 541.5 days . Among the 219 intent-to-treat patients ( received at least 1 dose and provided at least 1 postdose study observation ) , the mean ( SD , range ) daily dose was 52.5 ( ±38.5 , 10.0 to 293.5 ) mg . Before the end of month 3 , 44 % required an increase in total daily dose ; this dropped to 23 % during months 4 to 6 , to 17 % during months 10 to 12 , and remained at approximately 10 % for each time interval thereafter ( range 8 % to 13 % ) . Among the large majority of patients with stable or lower dose requirements after the initial 3 months of treatment , the average pain intensity ratings were unchanged or improved for approximately 70 % to 80 % of patients at all subsequent time points through month 33 , and for 54 % ( 7/13 patients ) at month 36 . A decrease in pain was initially seen by the end of month 3 , and for the majority of patients , the Average Pain Intensity score remained the same , better , or minimally worse ( <3 points ) for the remainder of the 3-year study period . The most common adverse events were constipation and nausea , and the incidence of these events declined over time on treatment . Investigators reported 6 cases ( 2.6 % ) of possible drug misuse but no evidence of de novo addiction was observed . Discussion These registry data demonstrate that a subgroup of patients with noncancer pain experienced prolonged relief with tolerable side effects and modest need for dose escalation during long-term therapy with CR oxycodone ABSTRACT Background : Short-acting opioids are commonly used to treat breakthrough pain ( BTP ) and rapid-onset formulations are being developed to improve the effectiveness of this approach . Fentanyl buccal tablet ( FBT ) is a new formulation of fentanyl that enhances transbuccal drug delivery via an effervescent reaction and may provide relatively rapid-onset analgesia . FBT was evaluated for BTP in opioid-treated patients with chronic low back pain – the first such study in a population with chronic non-cancer pain . Design : R and omized , double-blind , placebo-controlled . Patients and setting : Patients with chronic low back pain receiving long-term opioid therapy at 16 pain treatment centers in the United States . Procedures : Following open-label titration to identify an effective FBT dose , patients were r and omly assigned to one of three double-blind dose sequences ( six doses of FBT , three placebo ) to treat nine BTP episodes . Pain intensity ( PI ) , measured on an 11-point scale ( 0 = no pain ; 10 = worst pain ) , and other outcomes were assessed for 2 h after dosing . Data analysis : The primary efficacy measure was the sum of pain intensity differences ( PIDs ) for the first 60 min ( SPID60 ) ; secondary efficacy measures included PIDs at other time points , pain relief ( PR ) , meaningful PR , time to meaningful PR , use of supplementary BTP medication , and self/investigator-reported adverse events . Results : Of the 124 patients screened , 105 patients were enrolled , 84 identified an effective FBT dose , and 77 entered the double-blind phase . SPID60 significantly favored FBT ( p < 0.0001 ) . All secondary measures also favored FBT , with PIDs and PR showing significant differences versus placebo as early as 10 and 15 min , respectively . An improvement in PI score of ≥ 33 % occurred in a significantly larger proportion of FBT-treated episodes versus placebo from 15 min ( 20 % vs. 11 % , p < 0.01 ) through 2 h ( 65 % vs. 28 % , p < 0.0001 ) . Patients were approximately four times more likely to require supplemental opioids for BTP episodes following administration of placebo compared with episodes treated with FBT . AEs were typical for opioids , and were mostly reported during dose titration . Limitations of this study may be related to its open-label dose-titration phase ( which has the potential to compromise blinding ) and the recruitment of patients from pain clinics , which could potentially yield a study population that is not representative of the general population with BTP . Conclusions : FBT was efficacious and well tolerated in the treatment of BTP in opioid-treated patients with chronic low back pain OBJECTIVE Buprenorphine and fentanyl transdermal patches are used widely for the management of persistent malignant and nonmalignant pain . Buprenorphine and fentanyl transdermal patches , both potent opioids , are considered to be equally efficacious in managing persistent pain . Various retrospective studies comparing dosage changes of buprenorphine and fentanyl patches in persistent pain patients have been completed ; however , no long-term prospect i ve , r and omized , clinical study has compared the effectiveness of these patches . The objective of the present study was to satisfy this need . AIMS This study aims to compare prospect ively the long-term efficacy , acceptability , and side effects of both of these patches in patients with persistent pain . This study would examine the feasibility and lay the groundwork for a larger , multicenter study where such efficacy and safety outcomes of the two medications can be adequately assessed . DESIGN The participants were 46 adults ( range 22 - 80 years . ) with nonmalignant persistent pain ( mean = 11 years ) , predominantly with lower back pain . Data were obtained monthly for 12 months . Participants recruited were opioid-naïve patients , having pain for the greater part of the day and night , and appropriate for treatment with transdermal patches . After initial assessment , participants were r and omly allocated to either buprenorphine or fentanyl patch treatment . Participants were then titrated to optimal doses of medication . Patients with adverse effects or unsatisfactory pain relief were treated alternatively and discontinued from the study . RESULTS Nearly one-third of all patients , 41 % ( 8 of 22 ) of the transdermal buprenorphine ( TDB ) group and 37.5 % ( 8 of 24 ) of the transdermal fentanyl ( TDF ) group stopped treatment due to unacceptable side effects or inadequate pain relief . The remaining participants showed a similar trend in the improvement of pain intensity , physical activity , sleep , and mood throughout the study . Significant relief in the intensity of pain was achieved for the initial 6 months and the effects stabilized in the remainder of the study in both groups . There were no significant group differences over time . However , a higher equipotent dose of fentanyl was required for comparable pain relief . Compared with TDF group , the TDB group initially experienced relatively less side effects . However , a greater number of buprenorphine users suffered from local skin reactions . Buprenorphine users had significant improvement in mood . Thirty-one percent ( 5 of 16 ) of the buprenorphine group and 57 % ( 8 of 14 ) of the fentanyl users needed additional pain relief medications by the end of 3 months . By the end of 12 months , a significant number 78 % ( 7 of 9 ) of buprenorphine users but comparatively fewer 44 % ( 4 of 9 ) of the fentanyl group used rescue medicines . Both had more doctor visits in the latter half of the study . CONCLUSION Thirty percent of the total number of patients discontinued treatment because of side effects or unsatisfactory pain relief . For those continuing treatment , clinical improvements were seen in the initial 6 months in both groups . Fifty percent of the TDB and 43 % of TDF groups had significant relief in 3 months , which persisted up to 6 months . Only 11 % and 13 % of patients , respectively , had sustained relief after 6 months . Twenty percent more patients in the TDB group benefited significantly in symptoms of depression from TDB compared with the TDF group . Interestingly , switching of patches seemed to increase acceptability by preventing adverse effects and tolerance . Confirmation of these effects should be studied in future with a multicenter study and larger sample BACKGROUND Opioids are used extensively for chronic pain management in the United States . The frequency of opioid use prior to presenting to interventional pain management setting s and in interventional pain management setting s has been shown to be above 90 % . Given that controlled substance abuse and illicit drug use are prevalent phenomena , adherence monitoring of patients that are prescribed opioids is becoming common . Adherence monitoring is carried out by an appropriate history , periodic evaluation of appropriate intake of drugs , r and om drug testing , and pill counts . Crucial to adherence monitoring is an initial controlled substance agreement and repeated review of the terms of this agreement with on-going education . However , the effect of adherence monitoring on drug abuse is unclear . OBJECTIVE To identify controlled substance abuse through implementation of the terms of a controlled substance agreement , including periodic review and monitoring outside the organization . STUDY DESIGN Prospect i ve evaluation with historical controls . METHODS Five hundred consecutive patients receiving prescription controlled substances were followed in a prospect i ve manner . The evaluation consisted of a chart review to monitor controlled substance intake , with special attention to drugs obtained from outside the organization . Data collection for this purpose included information from records , pharmacies , referring physicians , and all the physicians involved in the treatment of the patient . RESULTS Results from 500 consecutive patients were evaluated . Controlled substance abuse was seen in 9 % of patients ; overall , 5 % of patients were obtaining controlled substances from other physicians , and 4 % from illegal sources . CONCLUSION Adherence monitoring , including controlled substance agreements and various periodic measures of compliance was associated with a 50 % reduction in opioid abuse BACKGROUND Prescription drug abuse and illicit drug use are common in chronic pain patients . Adherence monitoring with screening tests , and urine drug testing , periodic monitoring with prescription monitoring programs , has become a common practice in recent years . R and om drug testing for appropriate use of opioids and use of illicit drugs is often used in pain management practice s. Thus , it is expected that r and om urine drug testing will deter use of illicit drugs , and also improve compliance . OBJECTIVES To study the prevalence of illicit drug use in patients receiving opioids for chronic pain management and to compare the results of illicit drug use with the results from a previous study . DESIGN A prospect i ve , consecutive study . SETTING Interventional pain management practice setting in the United States . METHODS A total of 500 consecutive patients on opioids , considered to be receiving stable doses of opioids supplemental to their interventional techniques , were studied by r and om drug testing . Testing was performed by rapid drug screen . Results were considered positive if one or more of the monitored illicit drugs including cocaine , marijuana ( THC ) , methamphetamine or amphetamines were present . RESULTS Illicit drug use was evident in 80 patients , or 16 % , with marijuana in 11 % , cocaine in 5 % , and methamphetamine and /or amphetamines in 2 % . When compared with previous data , the overall illicit drug use was significantly less . Illicit drug use in elderly patients was absent . CONCLUSION The prevalence of illicit drug abuse in patients with chronic pain receiving opioids continues to be a common occurence . This study showed significant reductions in overall illicit drug use with adherence monitoring combined with r and om urine drug testing OBJECTIVE To evaluate driving performance , cognition , and balance in patients with chronic nonmalignant pain before and after the addition of transdermal fentanyl to their treatments . DESIGN Prospect i ve , one-group pretest-posttest design . SETTING Outpatient pain center associated with a large , urban medical school . INTERVENTIONS Patients taking less than a 15-mg equivalent of oxycodone per day took baseline driving performance , cognitive , and balance tests . Transdermal fentanyl was initiated and titrated in 25-microg/hour increments , weighing benefits and side effects . At the end of a 1-month period , the achieved dose was maintained for another month . After they were stabilized for 1 month , patients repeated driving , cognitive , and balance tests . RESULTS Twenty three patients completed the study ; three discontinued secondary to side effects . The median dose at the end of the titration period was 50 microg/hour ( 48 % ) . No differences were found in driving simulation measures between the pretreatment and posttreatment periods . No decrements in cognitive performance were found . Improvements in visual motor tracking , visual memory , and attention were found during treatment with transdermal fentanyl . No differences in balance or body sway were found . Pain decreased over the course of treatment . CONCLUSIONS The addition of transdermal fentanyl to a treatment regimen containing no opiates or small amounts of opiates for patients with chronic nonmalignant pain did not negatively affect their driving performances , reaction times , cognition , or balance . Future studies in this area are needed to guide treatment decisions OBJECTIVE To measure the impact of a structured opioid renewal program for chronic pain run by a nurse practitioner ( NP ) and clinical pharmacist in a primary care setting . PATIENTS AND SETTING Patients with chronic noncancer pain managed with opioid therapy in a primary care clinic staffed by 19 providers serving 50,000 patients at an urban academic Veterans hospital . DESIGN Naturalistic prospect i ve outcome study . INTERVENTION Based on published opioid prescribing guidelines and focus groups with primary care providers ( PCPs ) , a structured program , the Opioid Renewal Clinic ( ORC ) , was design ed to support PCPs managing patients with chronic noncancer pain requiring opioids . After training in the use of opioid treatment agreements ( OTAs ) and r and om urine drug testing ( UDT ) , PCPs worked with a pharmacist-run prescription management clinic supported by an onsite pain NP who was backed by a multi-specialty Pain Team . After 2 years , the program was evaluated for its impact on PCP practice and satisfaction , patient adherence , and pharmacy cost . RESULTS A total of 335 patients were referred to the ORC . Of the 171 ( 51 % ) with documented aberrant behaviors , 77 ( 45 % ) adhered to the OTA and resolved their aberrant behaviors , 65 ( 38 % ) self-discharged , 22 ( 13 % ) were referred for addiction treatment , and seven ( 4 % ) with consistently negative UDT were weaned from opioids . The 164 ( 49 % ) who were referred for complexity including history of substance abuse or need for opioid rotation or titration , with no documented aberrant drug-related behaviors , continued to adhere to the OTA . Use of UDT and OTAs by PCPs increased . Significant pharmacy cost savings were demonstrated . CONCLUSION An NP/ clinical pharmacist-run clinic , supported by a multi-specialty team , can successfully support a primary care practice in managing opioids in complex chronic pain patients OBJECTIVE Evaluate analgesic efficacy , functional benefit , and patient satisfaction with fentanyl buccal tablet vs immediate-release oxycodone for breakthrough pain ( BTP ) . DESIGN R and omized , double-blind , active-controlled crossover trial and 12-week open-label extension . SETTING Forty-two U.S. sites . PATIENTS Opioid-tolerant patients with predominantly chronic noncancer pain experiencing BTP . INTERVENTION Patients were r and omized to open-label titration periods with fentanyl buccal tablet followed by oxycodone or vice versa for BTP management . After titrating to a successful dose of both medications ( single dose providing adequate analgesia without unacceptable adverse events ) , patients were re-r and omized to treat 10 BTP episodes with one medication and 10 with the other . OUTCOME MEASURES The primary efficacy measure was pain intensity ( PI ) difference 15 minutes postdose . Secondary measures included PI difference 5 , 10 , 30 , 45 , and 60 minutes postdose ; sum of PI differences 30 and 60 minutes postdose ; ≥33 % and ≥50 % reduction in PI ; and pain relief . Question naires assessed functional status/satisfaction . RESULTS Of 213 patients enrolled , 149 achieved a successful dose of both medications ; 131 completed the double-blind phase and 112 the open-label phase . PI difference at 15 minutes ( mean [ st and ard deviation ] ) was greater with fentanyl buccal tablet ( 0.88 [ 1.20 ] ) vs oxycodone ( 0.76 [ 1.13 ] ; P < 0.001 ) . Patients preferred fentanyl buccal tablet ( 47 % ) over oxycodone ( 35 % ) ; 18 % had no preference . Patients and clinicians reported consistently better functional improvement and satisfaction with fentanyl buccal tablet vs short-acting opioids ( P < 0.05 ) . CONCLUSIONS Fentanyl buccal tablet was associated with rapid onset of analgesia and improvements in functional status and patient satisfaction compared with immediate-release oxycodone Study Design . Open , r and omized , parallel group multicenter study . Objectives . To compare the efficacy and safety of transdermal fentanyl ( TDF ) and sustained release morphine ( SRM ) in strong-opioid naïve patients with chronic low back pain ( CLBP ) . Summary of Background Data . Most studies of TDF and SRM have involved patients already receiving strong opioids . This is the first large-scale study focusing on strong-opioid naïve patients with CLBP . Methods . Adults with CLBP requiring regular strong opioid therapy received either TDF or SRM for 13 months . Starting doses were 25 & mgr;g/hr fentanyl patches every 72 hours or 30 mg oral morphine every 12 hours . Doses were adjusted according to response . Participants assessed pain relief and bowel function using weekly diaries . Other assessment s , including quality of life , disease progression , and side effects , were made by patients and investigators . Results . Data from 680 patients showed that TDF and SRM provided similar levels of pain relief , but TDF was associated with significantly less constipation than SRM , indicating a greater likelihood of satisfactory pain relief without unmanageable constipation for patients receiving TDF . Other ratings were similar for TDF and SRM , but TDF provided greater relief of pain at rest and at night . Conclusions . TDF and SRM provided equivalent levels of pain relief , but TDF was associated with less constipation . This study indicates that sustained-release strong opioids can safely be used in strong-opioid naïve patients BACKGROUND Tapentadol is a novel , central ly acting analgesic with 2 mechanisms of action : µ-opioid receptor agonism and norepinephrine reuptake inhibition . This r and omized , open-label phase 3 study ( Clinical Trials.gov Identifier : NCT00361504 ) assessed the long-term safety and tolerability of tapentadol extended release ( ER ) in patients with chronic knee or hip osteoarthritis pain or low back pain . METHODS Patients were r and omized 4:1 to receive controlled , adjustable , oral , twice-daily doses of tapentadol ER ( 100 to 250 mg ) or oxycodone HCl controlled release ( CR ; 20 to 50 mg ) for up to 1 year . Efficacy evaluations included assessment s at each study visit of average pain intensity ( 11-point numerical rating scale ) over the preceding 24 hours . Treatment-emergent adverse events ( TEAEs ) and discontinuations were monitored throughout the study . RESULTS A total of 1,117 patients received at least 1 dose of study drug . Mean ( st and ard error ) pain intensity scores in the tapentadol ER and oxycodone CR groups , respectively , were 7.6 ( 0.05 ) and 7.6 ( 0.11 ) at baseline and decreased to 4.4 ( 0.09 ) and 4.5 ( 0.17 ) at endpoint . The overall incidence of TEAEs was 85.7 % in the tapentadol ER group and 90.6 % in the oxycodone CR group . In the tapentadol ER and oxycodone CR groups , respectively , TEAEs led to discontinuation in 22.1 % and 36.8 % of patients ; gastrointestinal TEAEs led to discontinuation in 8.6 % and 21.5 % of patients . CONCLUSION Tapentadol ER ( 100 to 250 mg bid ) was associated with better gastrointestinal tolerability than oxycodone HCl CR ( 20 to 50 mg bid ) and provided sustainable relief of moderate to severe chronic knee or hip osteoarthritis or low back pain for up to 1 year OBJECTIVE To provide clinicians with a brief screening tool to predict accurately which individuals may develop aberrant behaviors when prescribed opioids for chronic pain . DESIGN One hundred and eighty-five consecutive new patients treated in one pain clinic took the self-administered Opioid Risk Tool ( ORT ) . The ORT measured the following risk factors associated in scientific literature with substance abuse : personal and family history of substance abuse ; age ; history of preadolescent sexual abuse ; and certain psychological diseases . Patients received scores of 0 - 3 ( low risk ) , 4 - 7 ( moderate risk ) , or > or= 8 ( high risk ) , indicating the probability of their displaying opioid-related aberrant behaviors . All patients were monitored for aberrant behaviors for 12 months after their initial visits . RESULTS For those patients with a risk category of low , 17 out of 18 ( 94.4 % ) did not display an aberrant behavior . For those patients with a risk category of high , 40 out of 44 ( 90.9 % ) did display an aberrant behavior . The authors used the c statistic to vali date the ORT , because it simultaneously assesses sensitivity and specificity . The ORT displayed excellent discrimination for both the male ( c = 0.82 ) and the female ( c = 0.85 ) prognostic models . CONCLUSION In a preliminary study , among patients prescribed opioids for chronic pain , the ORT exhibited a high degree of sensitivity and specificity for determining which individuals are at risk for opioid-related , aberrant behaviors . Further studies in a variety of pain and nonpain setting s are needed to determine the ORT 's universal applicability BACKGROUND Patients with chronic noncancer pain , including neuropathic pain , may have transitory exacerbations of pain ( median duration , 60 minutes ) , termed breakthrough pain ( BTP ) , that may reach peak intensity within minutes . Typical short-acting oral opioids may not provide sufficiently rapid relief ( 30- to 60-minute onset of analgesia ) . The fentanyl buccal tablet ( FBT ) provides a rapid onset of analgesia ( 10 - 15 minutes ) by enhancing fentanyl absorption across the buccal mucosa . OBJECTIVE This study evaluated the efficacy and tolerability of FBT in opioid-tolerant patients with BTP associated with chronic noncancer neuropathic pain . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled study in men and women aged 18 to 80 years who were opioid tolerant ; had a > /= 3-month history of chronic persistent neuropathic pain associated with diabetic peripheral neuropathy , postherpetic neuralgia , traumatic injury , or complex regional pain syndrome ; and reported having episodes of BTP . After an open-label titration period to identify an effective FBT dose ( the dose at which the patient reported receiving adequate pain relief within 30 minutes after administration of a single tablet of that dose during at least 2 of 3 BTP episodes ) , patients were r and omly assigned to treat 9 consecutive episodes of BTP over the next 21 days with 1 of 3 double-blind dose sequences of FBT and placebo tablets . Pain intensity ( PI ) ( rated on an 11-point pain scale , from 0 = no pain to 10 = worst pain ) and other outcomes were assessed before dosing and for 2 hours after dosing . The primary efficacy measure was the sum of PI differences ( PIDs ) for the first 60 minutes ( SPID(60 ) ) . Secondary efficacy measures included the proportion of BTP episodes with > /= 33 % and > /= 50 % improvement in PI from baseline ; PID at other time points ( 5 , 10 , 15 , 30 , 45 , 60 , 90 , and 120 minutes after dosing ) ; pain relief ( PR ) at the same time points ( rated on a 5-point Likert scale from 0 = none to 4 = complete ) ; proportion of BTP episodes with meaningful PR ; time to meaningful PR ; and proportion of BTP episodes in which supplemental medication was required after administration of study drug . Adverse events ( AEs ) spontaneously reported by the patient or elicited by the investigator were recorded throughout the study . RESULTS Of 102 patients in the open-label titration period , 80 identified an effective dose of FBT and 79 entered the double-blind phase . Of these 79 patients , 77 ( 97 % ) completed the study and 75 ( 95 % ) were evaluable for efficacy . Of the 79 patients who entered the double-blind phase , 63 % were women and 92 % were white ; their mean ( SD ) age was 48.3 ( 10.42 ) years , and their mean weight was 96.8 ( 33.42 ) kg . Baseline demographic and pain characteristics were similar between the overall population and the double-blind population . SPID(60 ) was significantly greater for BTP episodes treated with FBT compared with those in which placebo was administered ( mean [ SE ] , 9.63 [ 0.75 ] vs 5.73 [ 0.72 ] , respectively ; P < 0.001 ) . Significant differences between FBT and placebo were seen beginning at 10 minutes for PID ( mean , 0.740 [ 0.149 ] vs 0.427 [ 0.081 ] ; P < 0.047 ) and PR ( mean , 0.561 [ 0.087 ] vs 0.324 [ 0.056 ] ; P < 0.001 ) . A > /= 33 % improvement in PI from baseline was seen in a greater proportion of BTP episodes treated with FBT compared with placebo from 10 minutes ( 9 % vs 3 % ; P = 0.008 ) through 2 hours ( 66 % vs 37 % ; P < 0.001 ) . Patients were almost 4 times less likely to require supplemental opioids when BTP episodes were treated with FBT compared with placebo ( odds ratio = 0.28 ; 95 % Cl , 0.18 - 0.42 ) . AEs were reported by 64 ( 63 % ) of 102 patients . The most commonly reported AEs were those typical of opioids ( nausea [ 13 % ] , dizziness [ 13 % ] , somnolence [ 10 % ] , and vomiting [ 5 % ] ) and occurred more often during the dose-titration phase ( 55/102 [ 54 % ] ) than during the double-blind phase ( 22/79 [ 28 % ] ) . CONCLUSION In these opioid-tolerant patients with chronic neuropathic pain who identified an effective FBT dose , FBT had a rapid onset of action and was effective and well tolerated in the treatment of BTP CONTEXT We recently reported that fentanyl pectin nasal spray ( FPNS ) provides superior pain relief from breakthrough cancer pain ( BTCP ) compared with immediate-release morphine sulfate ( IRMS ) , with significant effects by five minutes and clinical ly meaningful pain relief from 10 minutes postdose . OBJECTIVES To report the consistency of efficacy , tolerability , and patient acceptability of FPNS vs. IRMS . METHODS Patients ( n=110 ) experiencing one to four BTCP episodes/day while taking ≥60 mg/day oral morphine ( or equivalent ) for background pain entered a double-blind , double-dummy ( DB/DD ) , multiple-crossover study . Those who completed an open-label titration phase ( n=84 ) continued to a DB/DD phase ; 10 episodes were r and omly treated with FPNS and overencapsulated placebo or IRMS and nasal spray placebo ( five episodes each ) . Pain intensity ( PI ) and pain relief scores were assessed . Patient acceptability scores were assessed at 30 and 60 minutes . Safety and tolerability were assessed by adverse events ( AEs ) and nasal assessment s. RESULTS Per-episode analysis revealed that FPNS consistently provided relief from pain more rapidly than IRMS ; by 10 minutes , there were significant differences in PI difference scores and in the percentages of episodes showing clinical ly meaningful pain relief ( P<0.05 ) . Overall acceptability scores were significantly greater for FPNS than for IRMS at 30 ( P<0.01 ) and 60 ( P<0.05 ) minutes . Patients were " satisfied/very satisfied " with the convenience ( 79.8 % ) and ease of use ( 77.2 % ) of FPNS . Only 4.7 % of patients withdrew from titration because of AEs ; no significant nasal effects were reported . CONCLUSION This study demonstrates that FPNS is efficacious , well accepted , and well tolerated by patients with BTCP The Prescription Drug Use Question naire ( PDUQ ) is one of several published tools developed to help clinicians better identify the presence of opioid abuse or dependence in patients with chronic pain . This paper introduces a patient version of the PDUQ ( PDUQp ) , a 31-item question naire derived from the items of the original tool design ed for self-administration , and describes evidence for its validity and reliability in a sample of patients with chronic nonmalignant pain and on opioid therapy . Further , this study examines instances of discontinuation from opioid medication treatment related to violation of the medication agreement in this population , and the relationship of these with problematic opioid misuse behaviors , PDUQ and PDUQp scores . A sample of 135 consecutive patients with chronic nonmalignant pain was recruited from a multidisciplinary Veterans Affairs chronic pain clinic , and prospect ively followed over one year of opioid therapy . Using the PDUQ as a criterion measure , moderate to good concurrent and predictive validity data for the PDUQp are presented , as well as item-by-item comparison of the two formats . Reliability data indicate moderate test stability over time . Of those patients whose opioid treatment was discontinued due to medication agreement violation-related discontinuation ( MAVRD ) ( n=38 or 28 % of sample ) , 40 % of these ( n=11 ) were due to specific problematic opioid misuse behaviors . Based upon specificity and sensitivity analyses , a suggested cutoff PDUQp score for predicting MAVRD is provided . This study supports the PDUQp as a useful tool for assessing and predicting problematic opioid medication use in a chronic pain patient sample Clinical experience shows that neuropsychological side effects due to opioid therapy usually decrease during the first weeks of therapy . However , the effect of long-term treatment with transdermal fentanyl on complex activities , such as driving , is not yet clear . In a prospect i ve trial , patients with continuous noncancer pain , who had received stable doses of transdermal fentanyl for at least 2 weeks , completed a series of computerized tests to measure attention , reaction , visual orientation , motor coordination and vigilance . Data from 90 healthy volunteers were matched to 30 patients ; 9 patients were excluded from the per- protocol analysis because they took additional drugs in violation of the protocol . None of the performance measures for the 21 remaining fentanyl patients was significantly inferior to the controls . We conclude that stable doses of transdermal fentanyl for the treatment of chronic non-cancer pain are not associated with significant impairments in psychomotor and cognitive performance . The threshold for fitness to drive as defined by German law did not differ significantly between the groups UNLABELLED The use of opioid medications for treating chronic noncancer pain is growing ; however , there is a lack of good evidence regarding their long-term effectiveness , association with substance abuse , and proper prescribing guidelines . The current study directly compares for the first time in a r and omized trial the effectiveness of a conservative , hold the line ( Stable Dose ) prescribing strategy for opioid medications with a more liberal dose escalation ( Escalating Dose ) approach . This 2-arm , parallel , r and omized pragmatic clinical trial followed 135 patients referred to a specialty pain clinic at a Veterans Affairs Hospital for 12 months ( 94 % male and 74 % with musculoskeletal pain ) . Primary outcomes included monthly or quarterly evaluations of pain severity , pain relief from medications , pain-related functional disability , and opioid misuse behaviors . All subjects received identical pain treatment except for the application of treatment group specific strategies for opioid prescriptions . No group differences were found for primary outcomes of usual pain or functional disability although the Escalating Dose group did show a small but significantly larger increase in self-rated pain relief from medications . About 27 % of patients were discharged over the course of the study due to opioid misuse/noncompliance , but there were no group differences in rate of opioid misuse . PERSPECTIVE The results of this study demonstrate that even in carefully selected patients there is a significant risk of problematic opioid misuse . Although in general there were no statistically significant differences in the primary outcomes between groups , the escalating dose strategy did lead to small improvements in self-reported acute relief from medications without an increase in opioid misuse , compared to the stable dose strategy BACKGROUND Use of opioids for chronic noncancer pain is increasing , but st and ards of care for this practice are poorly defined . Psychiatric disorders are associated with increased physical symptoms such as pain and may be associated with opioid use , but no prospect i ve population -based studies have addressed this issue . METHODS Analysis of longitudinal data from 6439 participants in the 1998 and 2001 waves of Healthcare for Communities , a nationally representative telephone community survey . RESULTS Two hundred thirty-seven subjects ( 3.6 % ) reported regular prescription opioid use in 2001 . In unadjusted logistic regression models , respondents with a common mental health disorder in 1998 ( 1165 [ 12.6 % ] ; major depression , dysthymia , generalized anxiety disorder , or panic disorder ) were more likely to report opioid use in 2001 than those without any of these disorders ( odds ratio [ OR ] , 4.43 ; 95 % confidence interval [ CI ] , 3.64 - 5.38 ; P<.001 ) . Risk was increased for initiation ( OR , 3.26 ; 95 % CI , 2.44 - 4.34 ; P<.001 ) and continuation ( OR , 2.30 ; 95 % CI , 1.02 - 5.17 ; P = .04 ) of opioids . Respondents reporting problem drug use ( 136 [ 2.0 % ] ; OR , 3.57 ; 95 % CI , 2.32 - 5.50 ; P<.001 ) but not problem alcohol use ( 401 [ 6.5 % ] ; OR , 0.73 ; 95 % CI , 0.43 - 1.24 ; P = .25 ) reported higher rates of prescribed opioid use than those without problem use . In multivariate logistic regression models controlling for 1998 demographic and clinical variables , common mental health disorder ( OR , 1.96 ; 95 % CI , 1.47 - 2.62 ; P<.001 ) and problem drug use ( OR , 2.98 ; 95 % CI , 1.68 - 5.30 ; P<.001 ) remained significant predictors of opioid use in 2001 . CONCLUSIONS Common mental health disorders and problem drug use are associated with initiation and use of prescribed opioids in the general population . Attention to psychiatric disorders is important when considering opioid therapy |
1,024 | 31,094,857 | 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 | null | null |
1,025 | 22,592,679 | 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 . | BACKGROUND Despite differences in how it is defined , there is a general consensus amongst clinicians and research ers that the sexual abuse of children and adolescents ( ' child sexual abuse ' ) is a substantial social problem worldwide .
The effects of sexual abuse manifest in a wide range of symptoms , including fear , anxiety , post-traumatic stress disorder and various externalising and internalising behaviour problems , such as inappropriate sexual behaviours .
Child sexual abuse is associated with increased risk of psychological problems in adulthood .
Cognitive-behavioural approaches are used to help children and their non-offending or ' safe ' parent to manage the sequelae of childhood sexual abuse .
This review up date s the first Cochrane review of cognitive-behavioural approaches interventions for children who have been sexually abused , which was first published in 2006 .
OBJECTIVES To assess the efficacy of cognitive-behavioural approaches ( CBT ) in addressing the immediate and longer-term sequelae of sexual abuse on children and young people up to 18 years of age . | 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 therapeutic relationship and the therapist 's perception of parental involvement were measured but were not related to outcome . Discussion focuses on characteristics of effective child therapy and the need for further research on treatment components and alternative treatment methods OBJECTIVE Treatment outcome in sexually abused preschool children was evaluated 6 and 12 months after treatment . METHOD Forty-three sexually abused preschool children and their parents were evaluated 6 and 12 months after completion of either Cognitive-Behavioral Therapy for Sexually Abused Preschoolers ( CBT-SAP ) or nondirective supportive therapy ( NST ) . Parents completed the Child Behavior Checklist , Child Sexual Behavior inventory , and Weekly Behavior Report to measure a variety of symptoms in their children . RESULTS Repeated- measures analyses indicated that there were significant group by time interactions on several outcome measures from the beginning of the study to the end of the 12-month follow-up period , with the CBT-SAP group exhibiting significantly more improvement over time than the NST group . Clinical findings also indicated the superior effectiveness of CBT-SAP over NST in reducing sexually inappropriate behavior . CONCLUSIONS Findings support the superior efficacy of CBT-SAP over NST in maintaining symptom reduction in the year after treatment completion . The importance of using cognitive-behavioral interventions for sexually inappropriate behaviors and including nonoffending parents in the treatment of sexually abused preschool children is discussed OBJECTIVE To evaluate the efficacy of child and caregiver participation in the cognitive-behavioral treatment of sexually abused children with posttraumatic stress symptoms . METHOD Thirty-six sexually abused children ( aged 5 - 17 years ) were r and omly assigned to a child-alone cognitive-behavioral treatment condition , a family cognitive-behavioral treatment condition , or a waiting-list control condition . RESULTS Compared with controls , children who received treatment exhibited significant improvements in posttraumatic stress disorder symptoms and self-reports of fear and anxiety . Significant improvements also occurred in relation to parent-completed measures and clinician ratings of global functioning . In general , parental involvement did not improve the efficacy of cognitive-behavioral therapy . Maintenance of improvement was evident at a 12-week follow-up assessment . CONCLUSIONS Cognitive-behavioral treatment was useful , but further research is required on caregiver involvement OBJECTIVE To evaluate sexually abused children and their families at intake and 18 months later , in comparison with a control group . METHODS Eighty-four sexually abused children aged 5 to 15 years were assessed at intake , with 64 being able to be reassessed at 18 months , the assessment using measures of self-esteem relevant to their age ; the Children 's Depression Inventory , and the Achenbach Child Behavior Checklist . Parents were assessed with the McMaster Family Assessment Device and the General Health Question naire . Control children and families were similarly assessed . Additional measures at follow-up were a structured interview with the parents , the Indices of Coping Responses , and the Newcastle Child and Family Life Events Schedule . Therapists were contacted to obtain information on type and duration of therapy . RESULTS While the control children 's self-esteem , depression , and behavior scores showed little change over time , the abused children 's scores were more likely to move toward the normal range although 56 % remained in the dysfunctional range for self-esteem , 48 % for behavior , and 35 % for depression . Improvement in child behavior was related to improvement in family function . While there was no direct relationship between child outcome and the relationship of the abuser to the child , family dysfunction , which was related to child outcome , did correlate with the closeness of the abuser to the child . Sixty-five percent of abused children had received therapy for an average of 9 months . No relationship was found between therapy and outcome . CONCLUSIONS The major variable relating to improvement in sexually abused children appears to be adequacy of family functioning . There is a need for increased emphasis on the evaluation of treatment OBJECTIVE Recent literature has emphasized the simultaneous assessment of multiple physiological stress response systems in an effort to identify biobehavioral risk factors of psychopathology in maltreated population s. The current study assessed whether an asymmetrical stress response , marked by activation in one system and a blunted response in another system , predicted higher levels of psychopathology over time . METHODS Data were collected from an ongoing , prospect i ve study of females with a substantiated history of childhood sexual abuse ( n=52 ) and a non-abused comparison group ( n=77 ) . Childhood sexual abuse was determined at the initial study visit . Vagal tone and cortisol were measured 7 years later to assess physiological response to a laboratory stressor across these systems . Depressive symptoms and antisocial behaviors were assessed 6 years after the completion of the laboratory stressor . RESULTS Structural equation modeling indicated that a prior history of childhood sexual abuse predicted an asymmetrical physiological response to stress in late adolescence . In turn , this asymmetrical response predicted both higher levels of depression and antisocial behaviors in young adulthood . CONCLUSIONS Childhood sexual abuse may sensitize females to respond to moderate daily stressors in a manner that places them at higher risk for experiencing depressive symptoms and antisocial behaviors over time . PRACTICE IMPLICATION S The management of mild to moderate stress in the everyday lives of maltreated females may be a particularly useful point of intervention in order to protect against later psychopathology |
1,026 | 29,363,105 | LMWH is possibly superior to UFH in the initial treatment of VTE in people with cancer . | BACKGROUND Compared with people without cancer , people with cancer who receive anticoagulant treatment for venous thromboembolism ( VTE ) are more likely to develop recurrent VTE .
OBJECTIVES To compare the efficacy and safety of three types of parenteral anticoagulants ( i.e. fixed-dose low molecular weight heparin ( LMWH ) , adjusted-dose unfractionated heparin ( UFH ) , and fondaparinux ) for the initial treatment of VTE in people with cancer . | 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 initial treatment of acute proximal DVT . This effect is maintained during a 6-months follow-up of treatment with oral anticoagulation BACKGROUND Body weight-adjusted subcutaneous low-molecular-weight heparin ( LMWH ) has been proven to be at least as effective and safe as dose-adjusted intravenous unfractionated heparin ( UFH ) for the treatment of patients with venous thromboembolism . However , body weight-adjusted dosage of low-molecular-weight heparin may be cumbersome and could lead possibly to incorrect dosing . Therefore a fixed LMWH dose , independent of body-weight , might rationalize initial treatment for venous thromboembolism . METHODS Patients with proven proximal deep-vein thrombosis were r and omly assigned to fixed dose subcutaneous LMWH Certoparin ( 8,000 anti-factor Xa U b.i.d . ; 265 patients ) or to adjusted dose i.v . UFH ( 273 patients ) for 12 days . Vitamin K antagonists were started between day 3 and 7 and continued for up to 6 months . The primary outcome measure was a 30 percent or greater improvement in the Marder Score , as revealed by repeated venography on day 12 ( end of the initial treatment ) . The secondary composite outcome measure included death , recurrent venous thromboembolism and major bleeding and was assessed at day 12 and after 6 months by a blinded adjunction committee . RESULTS The Marder score improved by 30 % or more in 30.3 % and 25.0 % of patients assigned to LMWH ( 198 paired venograms ) and UFH ( 192 paired venograms ) , respectively ( 2p = 0.26 ) . At the end of the initial treatment , the composite outcome was observed in 4 of the 265 patients ( 1.5 % ) r and omized to LMWH , as compared with 14 of the 273 patients ( 5.1 % ) r and omized to UFH ( 2p = 0.03 ) . At 6 months these figures were 6.8 % and 12.8 % , respectively ( risk reduction 0.53 , confidence interval 0.31 - 0.90 , 2p = 0.02 ) . CONCLUSION Fixed dose subcutaneous LMWH certoparin is at least as efficacious as UFH in resolving proximal vein thrombosis We performed a prospect i ve , r and omized , double-blind trial in 194 unselected patients to determine the safety and efficacy of low molecular weight heparin ( Fragmin ) compared with st and ard heparin as the initial treatment of acute venous thromboembolism . Ninety-eight patients received continuous intravenous heparin , and 96 patients received Fragmin for 5 - 10 days . Doses were adjusted to maintain anti-Xa levels between 0.3 and 0.6 unit/ml for patients with a high risk for a bleeding complication and between 0.4 and 0.9 unit/ml for patients with a low risk for bleeding . Treatment was stopped when a therapeutic level of anticoagulation ( International Normalized Ratio greater than 3.5 ) was reached with coumarins . Thirteen patients in the heparin group and 10 patients in the Fragmin group had a major bleeding complication . The incidence of major and minor bleeding complications combined decreased from 48.9 % to 38.5 % ( 95 % confidence interval for the difference , -3.5 % to + 24.2 % ) , corresponding with a relative bleeding risk reduction of 21.2 % . There were no significant differences in efficacy as defined by new high-probability defects on repeat ventilation-perfusion scintigraphy of the lung in 80 patients : six of 46 patients in the heparin group and 3 of 34 patients in the Fragmin group had new defects ( 95 % confidence interval for the difference , -9.4 % to + 17.8 % ) . We conclude that low molecular weight heparin ( Fragmin ) given in adjusted , continuous , and intravenous doses is safe and effective as initial treatment of acute venous thromboembolism compared with heparin . There is a trend in risk reduction for bleeding in favor of low molecular weight heparin , a trend , however , that is smaller than expected compared with animal studies In a prospect i ve , double-blind , r and omized multicenter trial the efficacy and safety of low molecular weight heparin and unfractionated heparin were compared for the prevention of postoperative deep vein thrombosis in patients undergoing abdominal surgery . Six hundred and seventy-three patients were r and omly allocated to the two prophylaxis groups ; 20 of these , however , did not undergo surgery and did not receive any prophylaxis . Of the remaining 653 patients 323 received one subcutaneous injection of 3,000 anti-Xa units of low molecular weight heparin and 330 received subcutaneously 5,000 U heparin three times a day . Treatment was initiated 2 h preoperatively and continued for 7 to 10 days . The occurrence of DVT was determined by the 125I-labelled fibrinogen uptake test and phlebography . Venous thrombosis was diagnosed in 24 of 323 patients ( 7.4 % ) treated with low molecular weight heparin and in 26 of 330 patients ( 7.9 % ) treated with low-dose heparin . DVT of proximal veins was detected in four patients of the low molecular weight heparin group and in three patients of the low-dose heparin group . During the observation period three pulmonary emboli - one fatal and two non-fatal - occurred in patients receiving prophylaxis with low-dose heparin . No pulmonary embolism was found in patients treated with low molecular weight heparin . Both prophylactic schemes were well tolerated . Intra- and postoperative blood loss , incidence of wound hematoma , frequency and volume of intra- and postoperative blood transfusion were similar in both groups with a slight advantage for the low molecular weight heparin group . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE Prophylactic therapies have demonstrated efficacy in reducing the incidence of deep venous thrombosis ( DVT ) in neurosurgical patients . Retrospective analysis of patients undergoing neurosurgical procedures at the University of Michigan demonstrated a high incidence ( 14 % ) of postoperative DVT among patients with intracranial neoplasms treated with sequential compression device ( SCD ) prophylaxis alone . Therefore , we investigated the efficacy and safety of the low-molecular weight heparin enoxaparin in preventing DVT in patients with brain tumors . The goal of the study was to compare SCD , enoxaparin , and combined SCD/enoxaparin prophylaxis among patients requiring surgery for treatment of intracranial neoplasms . METHODS Eligible patients were r and omized to SCD , enoxaparin , or combined therapy . Treatment was initiated before the induction of anesthesia and was continued throughout the hospital stay . Patients were screened for DVT , using duplex imaging , on four occasions in the first 1 month after surgery . The incidences of DVT and serious adverse events were compared between groups using analysis of variance and the Dunnet two-sided t test . RESULTS Sixty-eight patients completed the study . Postoperative DVT occurred in 3 of 22 ( 13.6 % ) SCD-treated patients , 1 of 23 ( 4.3 % ) enoxaparin-treated patients , and 4 of 23 ( 17.4 % ) SCD/enoxaparin-treated patients . Differences were not statistically significant . Postoperative intracranial hemorrhage did not occur in patients in the SCD-treated group , whereas 5 of 46 patients receiving low-molecular weight heparin suffered clinical ly significant intracranial hemorrhage . The study was terminated because of the increased incidence of adverse events in the enoxaparin-treated groups . CONCLUSION Enoxaparin therapy initiated at the time of anesthesia induction increases postoperative intracranial hemorrhage BACKGROUND An intravenous course of st and ard ( unfractionated ) heparin with the dose adjusted to prolong the activated partial-thromboplastin time to a desired length is the st and ard initial in-hospital treatment for patients with deep-vein thrombosis , but fixed-dose subcutaneous low-molecular-weight heparin appears to be as effective and safe . Because the latter treatment can be given on an outpatient basis , we compared the two treatments in symptomatic out patients with proximal-vein thrombosis but no signs of pulmonary embolism . METHODS We r and omly assigned patients to adjusted-dose intravenous st and ard heparin administered in the hospital ( 198 patients ) or fixed-dose subcutaneous low-molecular-weight heparin administered at home , when feasible ( 202 patients ) . We compared the treatments with respect to recurrent venous thromboembolism , major bleeding , quality of life , and costs . RESULTS Seventeen of the 198 patients who received st and ard heparin ( 8.6 percent ) and 14 of the 202 patients who received low-molecular-weight heparin ( 6.9 percent ) had recurrent thromboembolism ( difference , 1.7 percentage points ; 95 percent confidence interval , -3.6 to 6.9 ) . Major bleeding occurred in four patients assigned to st and ard heparin ( 2.0 percent ) and one patient assigned to low-molecular-weight heparin ( 0.5 percent ; difference , 1.5 percentage points ; 95 percent confidence interval , -0.7 to 2.7 ) . Quality of life improved in both groups . Physical activity and social functioning were better in the patients assigned to low-molecular-weight heparin . Among the patients in that group , 35 percent were never admitted to the hospital at all , and 40 percent were discharged early . This treatment was associated with a mean reduction in hospital days of 67 percent , ranging from 29 percent to 86 percent in the various study centers . CONCLUSIONS In patients with proximal-vein thrombosis , treatment with low-molecular-weight heparin at home is feasible , effective , and safe In view of the potential of low-molecular-weight heparins ( LMWH ) to simplify initial therapy and allow outpatient treatment of proximal deep-vein thrombosis , we undertook a r and omised comparison of fixed-dose subcutaneous LMWH with adjusted-dose intravenous st and ard heparin in the initial treatment of this disorder . Our main objectives were to compare the efficacy of these regimens for 6 months of follow-up and to assess the risk of clinical ly important bleeding . Of 170 consecutive symptomatic patients with venographically proven proximal deep-venous thrombosis , 85 received st and ard heparin ( to achieve an activated partial thromboplastin time of 1.5 to 2.0 times the pretreatment value ) and 85 LMWH ( adjusted only for body weight ) for 10 days . Oral coumarin was started on day 7 and continued for at least 3 months . The frequency of recurrent venous thromboembolism diagnosed objective ly did not differ significantly between the st and ard-heparin and LMWH groups ( 12 [ 14 % ] vs 6 [ 7 % ] ; difference 7 % [ 95 % confidence interval -3 % to 15 % ] ; p = 0.13 ) . Clinical ly important bleeding was infrequent in both groups ( 3.5 % for st and ard heparin vs 1.1 % for LMWH ; p greater than 0.2 ) . We conclude that fixed-dose subcutaneous LMWH is at least as effective and safe as intravenous adjusted-dose heparin in the initial treatment of symptomatic proximal-vein thrombosis . Since there is no need for laboratory monitoring with the LMWH regimen , patients with venous thrombosis can be treated at home PURPOSE A substantial clinical need exists for an alternative to vitamin K antagonists for treating deep-vein thrombosis in cancer patients who are at high risk of both recurrent venous thromboembolism and bleeding . Low-molecular-weight heparin , body-weight adjusted , avoids anticoagulant monitoring and has been shown to be more effective than vitamin-K-antagonist therapy . SUBJECTS AND METHODS Subjects were patients with cancer and acute symptomatic proximal-vein thrombosis . We performed a multi-centre r and omized , open-label clinical trial using objective outcome measures comparing long-term therapeutic tinzaparin subcutaneously once daily with usual-care long-term vitamin-K-antagonist therapy for 3 months . Outcomes were assessed at 3 and 12 months . RESULTS Of 200 patients , 100 received tinzaparin and 100 received usual care . At 12 months , the usual-care group had an excess of recurrent venous thromboembolism ; 16 of 100 ( 16 % ) versus 7 of 100 ( 7 % ) receiving low-molecular-weight heparin ( P=.044 ; risk ratio=.44 ; absolute difference -9.0 ; 95 % confidence interval [ CI ] , -21.7 to -0.7 ) . Bleeding , largely minor , occurred in 27 patients ( 27 % ) receiving tinzaparin and 24 patients ( 24 % ) receiving usual care ( absolute difference -3.0 ; 95 % CI , -9.1 to 15.1 ) . In patients without additional risk factors for bleeding at the time of r and omization , major bleeding occurred in 0 of 51 patients ( 0 % ) receiving tinzaparin and 1 of 48 patients ( 2.1 % ) receiving usual care . Mortality at 1 year was high , reflecting the severity of the cancers ; 47 % in each group died . CONCLUSION Our findings confirm the limited but benchmark data in the literature that long-term low-molecular-weight heparin is more effective than vitamin-K-antagonist therapy for preventing recurrent venous thromboembolism in patients with cancer and proximal venous thrombosis BACKGROUND The safety and efficacy of taking low-molecular-weight heparin at home was previously demonstrated in a clinical trial in which patients with acute proximal deep vein thrombosis were r and omized to receive either intravenous st and ard heparin in the hospital or subcutaneous low-molecular-weight heparin administered primarily at home . Treatment in the home has the potential to substantially reduce the cost to the health care system . METHODS To conduct an economic evaluation we prospect ively collected data on re source use and health-related quality of life ( Medical Outcomes Study Short-Form 36 ) on the 300 patients who formed the trial stratum presenting with proximal vein thrombosis as out patients , of whom 151 received st and ard heparin and 149 received low-molecular-weight heparin . The primary viewpoint of the analysis was societal , and costs included health care costs , patient travel costs , and productivity costs as a result of time off work . Costs were assessed over a period of 3 months from r and omization . Quality of life was assessed as the change in Short-Form 36 domain scores from baseline to day 7 for each treatment group . All costs are reported in 1997 Canadian dollars . RESULTS There were 11 recurrent thromboembolic events and 1 bleed in the 151 patients who received st and ard heparin ; the corresponding data for the 149 patients receiving low-molecular-weight heparin were 10 and 4 , respectively . The mean cost per patient who received st and ard heparin was Can $ 5323 compared with Can $ 2278 for low-molecular-weight heparin , a total societal cost savings per patient using low-molecular-weight heparin of Can $ 3045 ( 95 % confidence interval , Can $ 2012-$4050 ) . There was no difference in quality of life between the 2 groups except for the domain of social functioning , where a greater improvement from baseline to day 7 was observed for the low-molecular-weight heparin group vs the st and ard heparin group ( P = .005 ) . CONCLUSIONS For patients with acute proximal deep vein thrombosis , treatment at home with low-molecular-weight heparin is less costly than hospital-based treatment with st and ard heparin . The economic evidence in favor of outpatient treatment with low-molecular-weight heparin exhibits dominance ; a situation of reduced cost is created with no compromise in clinical outcomes or patients ' quality of life Summary Two studies have been done to establish recommendations for dosage and dose adjustment in the treatment of deep vein thrombosis ( DVT ) with low molecular weight heparin ( LMWH ) . In the first , 56 patients were r and omized in a double blind study to be treated either with unfractionated heparin ( UFH ) or LMWH s. c. every 12 h. Initial doses were given according to age and sex , disregarding bodyweight , and the dose was then adjusted when the peak plasma heparin concentration fell outside the desired range of 0.5–0.8 anti-FXa U/ml . There were fewer dose adjustments in the LMWH group . The correlation between injected dose ( U/kg bodyweight ) and the heparin concentration was higher in the LMWH group ( r=0.59 ) than in the UFH group ( r=0.38 ) . The results suggest that , in order to obtain the desired heparin concentration , the initial dose of LMWH should be about 100 U/kg bodyweight every 12 h . In the second , open study , this dosage plan was followed in 15 patients . The peak heparin concentration on Day 2 ranged from 0.40 to 0.75 anti-FXa U/ml and adjustment was only required in 3 patients . Day to day variation in peak heparin activity in the individual patient varied little ( CV 11–22 % ) , and there was no accumulation . The results indicate that plasma heparin concentration is more predictable using LMWH than UFH , and they point to definite advantages in the use of LMWH in a bodyweight adjusted dosage BACKGROUND Dabigatran , which is administered in a fixed dose and does not require laboratory monitoring , may be suitable for extended treatment of venous thromboembolism . METHODS In two double-blind , r and omized trials , we compared dabigatran at a dose of 150 mg twice daily with warfarin ( active-control study ) or with placebo ( placebo-control study ) in patients with venous thromboembolism who had completed at least 3 initial months of therapy . RESULTS In the active-control study , recurrent venous thromboembolism occurred in 26 of 1430 patients in the dabigatran group ( 1.8 % ) and 18 of 1426 patients in the warfarin group ( 1.3 % ) ( hazard ratio with dabigatran , 1.44 ; 95 % confidence interval [ CI ] , 0.78 to 2.64 ; P=0.01 for noninferiority ) . Major bleeding occurred in 13 patients in the dabigatran group ( 0.9 % ) and 25 patients in the warfarin group ( 1.8 % ) ( hazard ratio , 0.52 ; 95 % CI , 0.27 to 1.02 ) . Major or clinical ly relevant bleeding was less frequent with dabigatran ( hazard ratio , 0.54 ; 95 % CI , 0.41 to 0.71 ) . Acute coronary syndromes occurred in 13 patients in the dabigatran group ( 0.9 % ) and 3 patients in the warfarin group ( 0.2 % ) ( P=0.02 ) . In the placebo-control study , recurrent venous thromboembolism occurred in 3 of 681 patients in the dabigatran group ( 0.4 % ) and 37 of 662 patients in the placebo group ( 5.6 % ) ( hazard ratio , 0.08 ; 95 % CI , 0.02 to 0.25 ; P<0.001 ) . Major bleeding occurred in 2 patients in the dabigatran group ( 0.3 % ) and 0 patients in the placebo group . Major or clinical ly relevant bleeding occurred in 36 patients in the dabigatran group ( 5.3 % ) and 12 patients in the placebo group ( 1.8 % ) ( hazard ratio , 2.92 ; 95 % CI , 1.52 to 5.60 ) . Acute coronary syndromes occurred in 1 patient each in the dabigatran and placebo groups . CONCLUSIONS Dabigatran was effective in the extended treatment of venous thromboembolism and carried a lower risk of major or clinical ly relevant bleeding than warfarin but a higher risk than placebo . ( Funded by Boehringer Ingelheim ; RE-MEDY and RE-SONATE Clinical Trials.gov numbers , NCT00329238 and NCT00558259 , respectively . ) Context Are selective inhibitors of factor Xa as good as low-molecular-weight heparin in treating deep venous thrombosis ? Contribution In this large , multicenter , double-blind trial , patients with symptomatic deep venous thrombosis were r and omly assigned to receive either fondaparinux ( a selective inhibitor of factor Xa ) or enoxaparin given subcutaneously for at least 5 days plus an oral vitamin K antagonist for 3 months . In both groups , about 1 % of the patients experienced major bleeding during initial treatment and about 4 % had recurrent thromboembolic events within 3 months . Implication s Fondaparinux and enoxaparin have similar safety and efficacy for initial treatment of symptomatic deep venous thrombosis . The Editors Low-molecular-weight heparin ( LMWH ) therapy has exp and ed the options for initial management of patients presenting with deep venous thrombosis ( 1 , 2 ) . Low-molecular-weight heparin treatment is simple and consists of once- or twice-daily subcutaneous injection of a dose adjusted only for body weight . Treating suitable patients at home , often with self-injection , is effective and safe and has become st and ard practice in many setting s ( 2 - 4 ) . Clinical ly relevant aspects of LMWH treatment of venous thromboembolism remain uncertain , which may influence usage and recurrence or bleeding . First , LMWHs differ among themselves . Second , data on whether once- or twice-daily LMWH may be superior are conflicting ( 5 , 6 ) , suggesting that a once-daily regimen of enoxaparin may be less effective in patients with higher body mass index and patients with cancer ( 7 ) . Third , since LMWHs are eliminated in the urine and plasma levels are higher in patients with even modest renal insufficiency ( 8) , some clinicians administer lower dosages when the patient 's creatinine clearance is less than 0.84 mL/s ( 9 ) , despite few outcome data to guide such alterations . Finally , in addition to the clinical and economic circumstances , practical issues surround drug administration , including the patient 's capacity to administer the desired dosage from a fixed-volume syringe or multidose vial ; these issues can affect the feasibility of early discharge and home treatment . Fondaparinux is a synthetic and selective inhibitor of factor Xa that has proven efficacy and safety for preventing venous thromboembolism in orthopedic surgery . Although laboratory observations and theory suggested that such a compound might not be effective for treating established thrombosis ( 10 ) , a dose-ranging study of deep venous thrombosis treatment found that a once-daily subcutaneous injection of fondaparinux , 7.5 mg , may be effective and safe across a broad range of body weights ( 50 kg and 100 kg ) ( 11 ) . Pharmacokinetic analyses suggested that daily doses of 5 mg and 10 mg are appropriate for patients less than and more than that weight range , respectively . Moreover , the predictable and sustained anticoagulant effect of fondaparinux for 24 hours allows once-daily injection , and since fondaparinux does not cross-react with heparin-induced antibodies , platelet count monitoring may no longer be needed ( 12 ) . This may further simplify treatment . Therefore , we design ed this r and omized , double-blind study of 2205 symptomatic patients to determine whether the efficacy and safety of a once-daily subcutaneous fixed-dose regimen of fondaparinux are similar to those of the st and ard therapy of a twice-daily , subcutaneous , body weightadjusted regimen of enoxaparin . Early discharge was encouraged in both treatment groups . The large sample size allowed outcome assessment in patients with a broad range of body weights and renal function . Methods Patients Consecutive patients ( > 18 years of age ) who presented with acute symptomatic deep venous thrombosis involving the popliteal , femoral , or iliac veins or the trifurcation of the calf veins and who required antithrombotic therapy were eligible for the study . Diagnostic criteria for deep venous thrombosis were a noncompressible vein found on ultrasonography or an intraluminal filling defect found on venography ( 11 , 13 ) . Patients were ineligible for the study if they had symptomatic pulmonary embolism ; received therapeutic doses of anticoagulants or oral anticoagulant therapy for more than 24 hours ; required thrombolysis , thrombectomy , or a vena cava filter ; had contraindication to anticoagulant therapy ( for example , active bleeding , thrombocytopenia [ platelet count < 100 109 cells/L ] ) ; had elevated serum creatinine levels ( > 177 mol/L [ > 2 mg/dL ] ) ; had contraindication to contrast medium ; had uncontrolled hypertension ( systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg ) ; were pregnant ; or had a life expectancy of less than 3 months . After giving informed consent , patients were r and omly assigned by a computerized interactive voice response system that recorded information about patients before treatment assignment . R and omization was stratified by center in balanced blocks of 4 patients . The respective institutional review boards approved the study protocol , and an independent data safety monitoring board monitored the study . We assessed 5141 patients for eligibility : 2205 patients were r and omly assigned to study groups , 2416 patients were excluded , and 520 patients declined to participate ( Figure ) . The most common reasons for exclusion were the use of therapeutic anticoagulation for more than 24 hours , thrombolytic therapy , or vena cava filter ( 580 patients ) ; contraindication to anticoagulant therapy ( 395 patients ) ; symptomatic pulmonary embolism ( 387 patients ) ; and a life expectancy of less than 3 months ( 228 patients ) . Figure . Flow of patients through the study . Treatment Regimens The patients allocated to fondaparinux ( Arixtra , NV Organon , Oss , the Netherl and s , and Sanofi-Synthlabo , Paris , France ) received a once-daily subcutaneous injection of 5.0 mg if they weighed less than 50 kg , 7.5 mg if they weighed between 50 and 100 kg , or 10.0 mg if they weighed more than 100 kg . They also received twice-daily subcutaneous injections of placebo that appeared identical to enoxaparin . The patients allocated to enoxaparin ( Lovenox , Clexane , Aventis Pharmaceuticals , Bridgewater , New Jersey ) received a twice-daily subcutaneous dose of 1 mg/kg of body weight and a once-daily subcutaneous injection of placebo that appeared identical to fondaparinux . Although home treatment with the study drug was allowed , the treating physician made this decision and the drug had to be administered by a home care service . In both groups , vitamin K antagonist therapy was started as soon as possible but within 72 hours of initiation of fondaparinux or enoxaparin therapy . The investigator chose the type of vitamin K antagonist therapy according to local hospital practice . The same type of vitamin K antagonist was recommended for all patients in a particular center . During initial treatment , prothrombin times were measured at least every other day and the dose of vitamin K antagonist was adjusted to maintain the international normalized ratio between 2.0 and 3.0 . Double-blind , initial treatment was continued for at least 5 days and until the international normalized ratio was greater than 2.0 for 2 consecutive days . Treatment with vitamin K antagonists was continued for 3 months , and the international normalized ratio was determined at least once per month . Surveillance and Follow-up All patients were contacted daily during initial treatment and at 1 and 3 months . At each contact , patients were evaluated for symptomatic recurrence of deep venous thrombosis or pulmonary embolism and bleeding and were informed about the symptoms and signs of these conditions . They were instructed to report to the study center on an emergency basis if any of these conditions occurred . If recurrent deep venous thrombosis or pulmonary embolism was suspected , the protocol required objective testing for confirmation . Outcome Assessment The primary efficacy outcome was the incidence of symptomatic recurrent venous thromboembolism during the 3-month study period . Symptomatic recurrent venous thromboembolism was defined as objective ly documented recurrent deep venous thrombosis or pulmonary embolism or death in which pulmonary embolism was a contributing cause or could not be excluded . Without objective test results to adequately confirm or exclude recurrent venous thromboembolism , this diagnosis was accepted if the physician managed the patient with therapeutic doses of LMWH for more than 2 days , thrombolysis , a vena cava filter , or thrombectomy ( 3 , 13 ) . The criteria for the objective diagnosis of recurrent deep venous thrombosis were a new noncompressible venous segment or a substantial increase ( 4 mm ) in diameter of the thrombus during full compression in a previously abnormal segment on ultrasonography ( 14 , 15 ) or a new intraluminal filling defect found on venography . The criteria for the objective diagnosis of pulmonary embolism were an intraluminal filling defect on spiral computed tomography or pulmonary angiography , cut-off of a vessel of more than 2.5 mm in diameter on pulmonary angiography , perfusion defect of at least 75 % of a segment with corresponding normal ventilation ( high-probability lung scan ) , nondiagnostic lung scan associated with new deep venous thrombosis documented by ultrasonography or venography , or pulmonary embolism confirmed by autopsy . The main safety outcomes were major bleeding during the initial treatment period and 3-month mortality . Bleeding was defined as major if it was clinical ly overt and associated with a decrease in the hemoglobin level of 20 g/L or more , led to transfusion of 2 or more units of red blood cells or whole blood cells , was retroperitoneal or intracranial , occurred in a critical organ , or contributed to death . Bleeding episodes that were clinical ly relevant but not major ( for example , epistaxis that required intervention or spontaneous macroscopic hematuria ) were an additional safety outcome . The cause of PURPOSE Venous thromboembolism ( VTE ) is common in cancer patients . Evidence has suggested that low molecular weight heparin ( LMWH ) might improve survival in patients with cancer by preventing both VTE and the progression of metastases . No trial in a single cancer type has been powered to demonstrate a clinical ly significant survival difference . The aim of this trial was to investigate this question in patients with lung cancer . PATIENTS AND METHODS We conducted a multicenter , open-label , r and omized trial to evaluate the addition of a primary prophylactic dose of LMWH for 24 weeks to st and ard treatment in patients with newly diagnosed lung cancer of any stage and histology . The primary outcome was 1-year survival . Secondary outcomes included metastasis-free survival , VTE-free survival , toxicity , and quality of life . RESULTS For this trial , 2,202 patients were r and omly assigned to the two treatment arms over 4 years . The trial did not reach its intended number of events for the primary analysis ( 2,047 deaths ) , and data were analyzed after 2,013 deaths after discussion with the independent data monitoring committee . There was no evidence of a difference in overall or metastasis-free survival between the two arms ( hazard ratio [ HR ] , 1.01 ; 95 % CI , 0.93 to 1.10 ; P = .814 ; and HR , 0.99 ; 95 % CI , 0.91 to 1.08 ; P = .864 , respectively ) . There was a reduction in the risk of VTE from 9.7 % to 5.5 % ( HR , 0.57 ; 95 % CI , 0.42 to 0.79 ; P = .001 ) in the LMWH arm and no difference in major bleeding events but evidence of an increase in the composite of major and clinical ly relevant nonmajor bleeding in the LMWH arm . CONCLUSION LMWH did not improve overall survival in the patients with lung cancer in this trial . A significant reduction in VTE is associated with an increase in clinical ly relevant nonmajor bleeding . Strategies to target those at greatest risk of VTE are warranted BACKGROUND For many patients with venous thromboembolism , secondary prevention with vitamin K antagonists is not extended beyond six months , since the risk of recurrence may be outweighed by the risk of major bleeding . METHODS In a double-blind , multicenter trial , we r and omly assigned 1233 patients with venous thromboembolism who had undergone six months of anticoagulant therapy to extended secondary prevention with the oral direct thrombin inhibitor ximelagatran ( 24 mg ) or placebo , taken twice daily , for 18 months without monitoring of coagulation . At base line , bilateral ultrasonography of the legs and perfusion lung scanning were performed . RESULTS Data from 612 patients in the ximelagatran group and 611 in the placebo group were analyzed . The occurrence of the primary end point , symptomatic recurrent venous thromboembolism , was confirmed in 12 patients assigned to ximelagatran and 71 patients assigned to placebo ( hazard ratio , 0.16 ; 95 percent confidence interval , 0.09 to 0.30 ; P<0.001 ) . Death from any cause occurred in 6 patients in the ximelagatran group and 7 patients in the placebo group , and bleeding occurred in 134 patients and 111 patients , respectively ( hazard ratio , 1.19 ; 95 percent confidence interval , 0.93 to 1.53 ; P=0.17 ) . The incidence of major hemorrhage was low ( six events in the ximelagatran group and five in the placebo group ) , and none of these hemorrhages were fatal . The cumulative risk of a transient elevation of the alanine aminotransferase level to more than three times the upper limit of normal was 6.4 percent in the ximelagatran group , as compared with 1.2 percent in the placebo group ( P<0.001 ) . CONCLUSIONS Oral ximelagatran was superior to placebo for the extended prevention of venous thromboembolism . There was no significant increase in the frequency of bleeding complications , but there was an increase in the number of patients with a transient elevation in the alanine aminotransferase level Background Venous thromboembolism ( VTE ) occurs when blood clots in the leg , pelvic or other deep vein ( deep vein thrombosis ) with or without transport of the thrombus into the pulmonary arterial circulation ( pulmonary embolus ) . VTE is common in patients with cancer and is increased by surgery , chemotherapy , radiotherapy and disease progression . Low molecular weight heparin ( LMWH ) is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect , by reduction in the incidence of metastases . The FRAGMATIC trial will assess the effect of adding dalteparin ( FRAGMIN ) , a type of LMWH , to st and ard treatment for patients with lung cancer . Methods / Design The study design is a r and omised multicentre phase III trial comparing st and ard treatment and st and ard treatment plus daily LMWH for 24 weeks in patients with lung cancer . Patients eligible for this study must have histopathological or cytological diagnosis of primary bronchial carcinoma ( small cell or non-small cell ) within 6 weeks of r and omisation , be 18 or older , and must be willing and able to self-administer 5000 IU dalteparin by daily subcutaneous injection or have it administered to themselves or by a carer for 24 weeks . A total of 2200 patients will be recruited from all over the UK over a 3 year period and followed up for a minimum of 1 year after r and omisation . Patients will be r and omised to one of the two treatment groups in a 1:1 ratio , st and ard treatment or st and ard treatment plus dalteparin . The primary outcome measure of the trial is overall survival . The secondary outcome measures include venous thrombotic event ( VTE ) free survival , serious adverse events ( SAEs ) , metastasis-free survival , toxicity , quality of life ( QoL ) , levels of breathlessness , anxiety and depression , cost effectiveness and cost utility . Trial registration Current Controlled Trials IS RCT We initiated a prospect i ve , partially r and omized trial of the effects of perioperative prophylactic mini-dose heparin on the incidence of clinical ly evident pulmonary emboli , intraoperative blood loss , blood transfusions , duration of postoperative pelvic drainage , and lymphocele formation in 68 consecutive patients undergoing radical retropubic prostatectomy . We treated 32 patients with mini-dose heparin and 36 without it . We detected pulmonary emboli in 4 ( 11 % ) patients not treated with mini-dose heparin and in none treated with heparin ( p = 0.052 ) . Anesthesiologists estimated a mean intraoperative blood loss of 2,152 cc in the heparinized patients compared with 1,886 cc in controls ( p = 0.2 ) . At a time when our policy was to replace all blood loss , we transfused a mean of 3.9 units to heparinized patients and 3.2 units to controls ( p = 0.1 ) . Persistent lymphatic drainage requiring more than six days of closed suction drainage occurred in 12 of 32 ( 38 % ) heparinized patients as compared with 4 of 36 ( 11 % ) controls ( p = 0.01 ) . We discontinued the study after 68 patients because of the morbidity associated with mini-dose heparin . Because of the associated morbidity we do not recommend the routine use of mini-dose heparin in patients undergoing radical prostatectomy Background Low-molecular-weight heparin ( LMWH ) is recommended and commonly used for extended treatment of cancer-associated thrombosis ( CAT ) , but its superiority over warfarin has been demonstrated in only one r and omised study . We report here the rationale , design and a priori analysis plans of Comparison of Acute Treatments in Cancer Haemostasis ( CATCH ; NCT01130025 ) , a multinational , Phase III , open-label , r and omised controlled trial comparing tinzaparin with warfarin for extended treatment of CAT . Methods / Design The primary objective is to assess the efficacy of tinzaparin in preventing recurrent venous thromboembolism ( VTE ) in patients with active cancer and acute , symptomatic proximal deep vein thrombosis and /or pulmonary embolism . The secondary objectives are to determine : safety of tinzaparin given over 6 months ; clinical and laboratory markers for recurrent VTE and /or major bleeding ; 6-month overall mortality ; incidence and severity of post-thrombotic syndrome ; patient-reported quality of life ; and healthcare re source utilisation . Nine hundred patients are r and omised to receive tinzaparin 175 IU/kg once daily for 6 months or initial tinzaparin 175 IU/kg once daily for 5–10 days and dose-adjusted warfarin ( target INR 2.0–3.0 ) for 6 months . The primary composite outcome is time to recurrent VTE , including incidental VTE and fatal pulmonary embolism . All patients are followed up to 6 months or death , whichever comes sooner . Blinded adjudication will be performed for all reported VTE , bleeding events and causes of death . Efficacy will be analysed using central ly adjudicated results of all patients according to intention-to-treat analysis . An independent Data Safety Monitoring Board is review ing data at regular intervals and an interim analysis is planned after 450 patients have completed the study . Discussion The results will add significantly to the knowledge of the efficacy , safety and cost effectiveness of tinzaparin in the prevention of recurrent VTE in patients with cancer and thrombosis . Prospect i ve data will emerge on the clinical significance of incidental VTE and risk stratification in patients with CAT . Results on post-thrombotic syndrome , quality of life and healthcare re source utilisation will inform decision makers on how to secure better patient care . If tinzaparin is shown to be more effective than warfarin , CATCH will provide valuable confirmatory data to support the use of the LMWH tinzaparin for extended treatment of CAT Elevated levels of circulating tissue factor‐bearing microparticles ( TFMP ) have been associated with an increased risk of developing venous thromboembolism ( VTE ) in cancer patients . We performed a r and omized phase II study to evaluate the cumulative incidence of VTE in advanced cancer patients with lower levels of TFMP not receiving thromboprophylaxis and those with higher levels of circulating TFMP r and omized to enoxaparin or observation . The cumulative incidence of VTE at 2 months in the higher TFMP group r and omized to enoxaparin ( N = 23 ) was 5·6 % while the higher TFMP group observation arm ( N = 11 ) was 27·3 % ( Gray test P = 0·06 ) . The cumulative incidence of VTE in the low TFMP was 7·2 % ( N = 32 ) . No major haemorrhages were observed in the enoxaparin arm . The median survival for patients with higher levels of TFMP followed by observation was 11·8 months compared with 17·8 months on enoxaparin ( P = 0·58 ) . In a prospect i ve r and omized trial , increased numbers of circulating TFMP detected by impedance flow cytometry identified cancer patients with a high incidence of VTE . Enoxaparin demonstrated a clear trend towards reducing the rate of VTE in patients with elevated levels of TFMP , with an overall rate of VTE similar in magnitude to the lower TFMP group BACKGROUND Few reports have addressed the value of unfractionated heparin ( UFH ) or low-molecular-weight heparin in treating the full spectrum of patients with venous thromboembolism ( VTE ) , including recurrent VTE and pulmonary embolism . METHODS In an open , multicenter clinical trial , 720 consecutive patients with acute symptomatic VTE , including 119 noncritically ill patients ( 16.5 % ) with pulmonary embolism and 102 ( 14.2 % ) with recurrent VTE , were r and omly assigned to treatment with subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm ( preceded by an intravenous loading dose ) , or fixed-dose ( adjusted only to body weight ) subcutaneous nadroparin calcium . Oral anticoagulant therapy was started concomitantly and continued for at least 3 months . We recorded the incidence of major bleeding during the initial heparin treatment and that of recurrent VTE and death during 3 months of follow-up . RESULTS Fifteen ( 4.2 % ) of the 360 patients assigned to UFH had recurrent thromboembolic events , as compared with 14 ( 3.9 % ) of the 360 patients assigned to nadroparin ( absolute difference between rates , 0.3 % ; 95 % confidence interval , -2.5 % to 3.1 % ) . Four patients assigned to UFH ( 1.1 % ) and 3 patients assigned to nadroparin ( 0.8 % ) had episodes of major bleeding ( absolute difference between rates , 0.3 % ; 95 % confidence interval , -1.2 % to 1.7 % ) . Overall mortality was 3.3 % in each group . CONCLUSIONS Subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm is as effective and safe as fixed-dose nadroparin for the initial treatment of patients with VTE , including those with pulmonary embolism and recurrent VTE A small proportion of patients with deep vein thrombosis develop recurrent venous thromboembolic complications or bleeding during anticoagulant treatment . These complications may occur more frequently if these patients have concomitant cancer . This prospect i ve follow-up study sought to determine whether in thrombosis patients those with cancer have a higher risk for recurrent venous thromboembolism or bleeding during anticoagulant treatment than those without cancer . Of the 842 included patients , 181 had known cancer at entry . The 12-month cumulative incidence of recurrent thromboembolism in cancer patients was 20.7 % ( 95 % CI , 15.6%-25.8 % ) versus 6.8 % ( 95 % CI , 3.9%- 9.7 % ) in patients without cancer , for a hazard ratio of 3.2 ( 95 % CI , 1.9 - 5.4 ) The 12-month cumulative incidence of major bleeding was 12.4 % ( 95 % CI , 6.5%-18.2 % ) in patients with cancer and 4.9 % ( 95 % CI , 2.5%-7.4 % ) in patients without cancer , for a hazard ratio of 2.2 ( 95 % CI , 1.2 - 4.1 ) . Recurrence and bleeding were both related to cancer severity and occurred predominantly during the first month of anticoagulant therapy but could not be explained by sub- or overanticoagulation . Cancer patients with venous thrombosis are more likely to develop recurrent thromboembolic complications and major bleeding during anticoagulant treatment than those without malignancy . These risks correlate with the extent of cancer . Possibilities for improvement using the current paradigms of anticoagulation seem limited and new treatment strategies should be developed Introduction Systematic review er authors intending to include all r and omized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data . Objective The objective of this paper is to provide systematic review er authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of r and omized trials . Methods This guide is based on a review of the Cochrane h and book and published method ological research . The guide deals with participants excluded from the analysis who were considered ‘ non-adherent to the protocol ’ but for whom data are available , and participants with missing data . Results Systematic review er authors should include data from ‘ non-adherent ’ participants excluded from the primary study authors ' analysis but for whom data are available . For missing , unavailable participant data , authors may conduct a complete case analysis ( excluding those with missing data ) as the primary analysis . Alternatively , they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data . When the primary analysis suggests important benefit , sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis . The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta- analysis . The proposed guide does not take into account the uncertainty associated with assumed events . Conclusions This guide proposes methods for h and ling participants excluded from analyses of r and omized trials . These methods can help in establishing the extent to which risk of bias impacts meta- analysis results Abstract Objective To determine the efficacy and safety of the anticoagulant fondaparinux in older acute medical in patients at moderate to high risk of venous thromboembolism . Design Double blind r and omised placebo controlled trial . Setting 35 centres in eight countries . Participants 849 medical patients aged 60 or more admitted to hospital for congestive heart failure , acute respiratory illness in the presence of chronic lung disease , or acute infectious or inflammatory disease and expected to remain in bed for at least four days . Interventions 2.5 mg fondaparinux or placebo subcutaneously once daily for six to 14 days . Outcome measure The primary efficacy outcome was venous thromboembolism detected by routine bilateral venography along with symptomatic venous thromboembolism up to day 15 . Secondary outcomes were bleeding and death . Patients were followed up at one month . Results 425 patients in the fondaparinux group and 414 patients in the placebo group were evaluable for safety analysis ( 10 were not treated ) . 644 patients ( 75.9 % ) were available for the primary efficacy analysis . Venous thrombembolism was detected in 5.6 % ( 18/321 ) of patients treated with fondaparinux and 10.5 % ( 34/323 ) of patients given placebo , a relative risk reduction of 46.7 % ( 95 % confidence interval 7.7 % to 69.3 % ) . Symptomatic venous thromboembolism occurred in five patients in the placebo group and none in the fondaparinux group ( P = 0.029 ) . Major bleeding occurred in one patient ( 0.2 % ) in each group . At the end of follow-up , 14 patients in the fondaparinux group ( 3.3 % ) and 25 in the placebo group ( 6.0 % ) had died . Conclusion Fondaparinux is effective in the prevention of asymptomatic and symptomatic venous thromboembolic events in older acute medical patients . The frequency of major bleeding was similar for both fondaparinux and placebo treated patients BACKGROUND A low-molecular-weight heparin , enoxaparin sodium , has been shown to be effective and safe in preventing deep vein thrombosis both in general surgery and in high-risk orthopedic surgery . We conducted a controlled , r and omized trial with enoxaparin in the treatment of established deep vein thrombosis . METHODS In a multicenter trial , we compared fixed-dose subcutaneous enoxaparin , given twice daily , with adjusted-dose intravenous unfractionated heparin ( UFH ) given by continuous intravenous infusion for the initial 10 days of treatment of patients with proximal vein thrombosis . The primary efficacy outcome was the change of the size of the thrombus assessed by repeated venograms between day 0 and day 10 . The primary analysis of safety was based on the incidence of major bleeding during 10 days of treatment . RESULTS There were 67 patients in each group . Venographic assessment of clot size evolution between day 0 and day 10 showed a statistically significant superiority ( P < .002 ) of enoxaparin over the reference treatment with UFH . Moreover , the incidence of overall recurrent thromboembolic events during 10 days of treatment was significantly higher ( P < .002 ) in the UFH group ( seven of 67 ) than in the enoxaparin group ( one of 67 ) . There were no serious bleeding complications in either group . CONCLUSIONS Enoxaparin is at least as effective and safe as UFH under the conditions of this study . Moreover , it is more comfortable for patients and less time-consuming for nurses and laboratories . Thus , our study confirmed , with the use of enoxaparin , other observations that low-molecular-weight heparin provides a real therapeutic advance in the treatment of deep vein thrombosis The Medical Patients with Enoxaparin ( MEDENOX ) trial was a r and omized , placebo-controlled study that defined the risk of venous thromboembolism ( VTE ) in acutely ill , immobilized , general medical patients and the efficacy of the low-molecular-weight heparin , enoxaparin , in preventing thrombosis . We performed a post-hoc analysis to evaluate the effect of 40 mg enoxaparin once daily on MEDENOX patient outcome in different types of acute medical illness ( heart failure , respiratory failure , infection , rheumatic disorder and inflammatory bowel disease ) and pre-defined risk factors ( chronic heart and chronic respiratory failure , age , immobility , previous VTE and cancer ) . The primary outcome was the occurrence of documented VTE between days 1 and 14 . The relative risk reduction [ 95 % confidence intervals ( CI ) ] for VTE comparing 40 mg enoxaparin with placebo in the subgroups were : acute heart failure , 0.29 ( 95 % CI , 0.10–0.84 ) ; acute respiratory failure , 0.25 ( 95 % CI , 0.10–0.65 ) ; acute infectious disease , 0.28 ( 95 % CI , 0.09–0.81 ) ; and acute rheumatic disorder , 0.48 ( 95 % CI , 0.11–2.16 ) . The relative risk reduction for VTE in the pre-defined risk factor subgroups were : chronic heart failure , 0.26 ( 95 % CI , 0.08–0.92 ) ; chronic respiratory failure , 0.26 ( 95 % CI , 0.10–0.68 ) ; age , 0.22 ( 95 % CI , 0.09–0.51 ) ; immobility , 0.53 ( 95 % CI , 0.14–1.72 ) ; previous VTE , 0.49 ( 95 % CI , 0.15–1.68 ) ; and cancer , 0.50 ( 95 % CI , 0.14–1.72 ) . The beneficial effects of enoxaparin extend to a wide range of acutely ill medical patients External pneumatic compression ( EPC ) devices prevent lower extremity deep venous thrombosis ( DVT ) by reducing stasis . There is a widely held belief that they also enhance endogenous fibrinolysis ; however , recent studies of tissue plasminogen activator ( the primary activator of fibrinolysis ) and plasminogen activator inhibitor-1 ( the primary inhibitor of fibrinolysis ) failed to confirm this . The hypothesis of this study was that EPC devices increase the level of urokinase plasminogen activator ( uPA ) , a second activator of fibrinolysis . This was a prospect i ve trial in which 44 subjects who underwent major abdominal surgery were r and omized to receive unfractionated heparin injections , thigh-length sequential EPC devices , or both for DVT prophylaxis . Prophylaxis was begun immediately before surgical incision and continued until postoperative day 5 or discharge . Venous blood sample s were collected from an antecubital vein for measurement of systemic uPA levels and from the common femoral vein for measurement of regional uPA levels . Sample s were collected the day before surgery , after induction of anesthesia but before surgical incision , and on postoperative days 1 , 3 , and 5 . uPA levels ( ng/mL ) were measured with an enzyme-linked immunoassay . Baseline uPA levels ( 0.41 to 0.56 ng/mL ; P > .05 , analysis of variance with repeated measures ) were similar among the three groups . uPA levels did not change after surgery in systemic or regional blood sample s in any group . There were no significant differences in systemic or regional uPA levels in the groups treated with EPC devices relative to those treated with heparin at any time point ( P > .05 , analysis of variance with repeated measures ) . Enhancement of fibrinolysis with EPC devices remains unproven ; the findings reported here suggest that effective DVT prophylaxis can only be assured when the devices are used in a manner that reduces venous stasis Outpatient treatment of deep vein thrombosis ( DVT ) has become a common practice in uncomplicated patients . Few data are still present in patients with comorbidity ( such as cancer ) or concomitant symptomatic pulmonary embolism . Cancer patients with DVT are often excluded from home treatment because they have a higher risk of both bleeding and recurrent DVT . We tested the feasibility and safety of the Home Treatment ( HT ) program for acute DVT a PE in cancer patients . Patients were treated as out patients unless they required admission for other medical problems , were actively bleeding or had pain that requires parenteral narcotics . Outpatient treatment was with low molecular weight heparin ( LMWH ) followed by warfarin or with LMWH alone . An educational program for patients was implemented . Two-hundred and seven patients with cancer were evaluated , 36 ( 17.4 % ) of whom had metastatic disease . Treatment with LMWH and warfarin was prescribed to 106 ( 51.2 % ) and LMWH alone to 102 ( 48.8 % ) . One hundred and twenty-seven patients ( 61.3 % ) were entirely treated at home . There were no differences between patients treated at home and hospitalized patients with regard to gender , mean age , site of cancer , presence of metastases , and treatment . After 6 months , recurrent thrombo-embolism occurred in 8.7 % of patients treated at home and in 5.6 % of hospitalized patients ( P=0.58 ) ; major bleeding in 2.0 % and 1.5 % , respectively ( P=0.06 ) . Twenty-seven patients ( 33 % ) in the hospitalized , and 33 ( 26 % ) in the home-treatment group , died after a follow-up of 6 months . These results indicate that , regarding cancer patients with acute DVT and /or PE , there is no difference between hospitalised and home-treated patients in terms of major outcomes PURPOSE In this multicenter , r and omized , placebo-controlled clinical trial , we studied whether warfarin 1 mg daily reduces the incidence of symptomatic central venous catheter ( CVC ) -associated thrombosis in patients with cancer . PATIENTS AND METHODS Two hundred fifty-five patients with cancer who required a CVC for at least 7 days were r and omly assigned to receive warfarin 1 mg or placebo . RESULTS There were 11 ( 4.3 % ) symptomatic CVC-associated thromboses among 255 patients , with no difference in the incidence of symptomatic CVC-associated thrombosis between patients taking warfarin 1 mg daily ( six of 130 patients ; 4.6 % ) and patients taking placebo ( five of 125 patients ; 4.0 % ; hazard ratio , 1.20 ; 95 % CI , 0.37 to 3.94 ) . Warfarin had no effect on CVC life span ( 84 days v 63 days in control and warfarin groups , respectively ; 95 % confidence limit , -16 to 55 days ; P = .09 ) , and it did not affect the number of premature CVC removals ( 23.2 % v 25.4 % in control and warfarin groups , respectively ; 95 % confidence limit of difference -8.34 to 12.71 ; P = .68 ) or the frequency of major bleeding episodes ( 2 % v 0 % in control and warfarin groups , respectively ; P = .5 , Fisher 's exact test ) . CONCLUSION Symptomatic CVC-associated thrombosis in patients with cancer , although significant , is less common than previously reported . In this study , the administration of warfarin 1 mg daily did not reduce the incidence of symptomatic CVC-associated thrombosis in patients with cancer . However , the low rate of symptomatic CVC-associated thrombosis means that a much larger trial is required to address this issue definitively BACKGROUND Low-molecular-weight heparin appears to be at least as effective and safe as st and ard , unfractionated heparin for the treatment of deep-vein thrombosis , but only limited data are available on the use of low-molecular-weight heparin to treat acute symptomatic pulmonary embolism . METHODS We r and omly assigned 612 patients with symptomatic pulmonary embolism who did not require thrombolytic therapy or embolectomy to either subcutaneous low-molecular-weight heparin ( tinzaparin ) given once daily in a fixed dose or adjusted-dose , intravenous unfractionated heparin . Oral anticoagulant therapy was begun between the first and the third day and was given for at least three months . We compared the treatments at day 8 and day 90 with respect to a combined end point of recurrent thromboembolism , major bleeding , and death . RESULTS In the first eight days of treatment , 9 of 308 patients assigned to receive unfractionated heparin ( 2.9 percent ) reached at least one of the end points , as compared , with 9 of 304 patients assigned to low-molecular-weight heparin ( 3.0 percent ; absolute difference , 0.1 percentage point ; 95 percent confidence interval , -2.7 to 2.6 ) . By day 90 , 22 patients assigned to unfractionated heparin ( 7.1 percent ) and 18 patients assigned to low-molecular-weight heparin ( 5.9 percent ) had reached at least one end point ( P=0.54 ; absolute difference , 1.2 percentage points ; 95 percent confidence interval , -2.7 to 5.1 ) . The risk of major bleeding was similar in the two treatment groups throughout the study . CONCLUSIONS Under the conditions of this study , initial subcutaneous therapy with the low-molecular-weight heparin tinzaparin appeared to be as effective and safe as intravenous unfractionated heparin in patients with acute pulmonary embolism INTRODUCTION External pneumatic compression ( EPC ) devices prevent lower extremity deep venous thrombosis by increasing venous flow and thereby reducing stasis . Early studies suggested that they also enhance systemic fibrinolytic activity and thus prevent thrombus formation ; more recent studies have been conflicting . The hypothesis of this study was that EPC devices enhance systemic fibrinolysis or reduce postoperative fibrinolytic impairment in patients undergoing abdominal surgical procedures . METHODS Each of 48 patients ( 98 % male ; mean age , 67 years ) undergoing major intra-abdominal surgical procedures ( 36 bowel procedures , 12 aortic reconstructions ) was prospect ively r and omized to one of three treatments for deep venous thrombosis prophylaxis : subcutaneous heparin injections ( HEP group ) , use of a thigh-length sequential EPC device ( EPC group ) , or both ( HEP + EPC group ) . Antecubital venous sample s were collected for measurement of systemic fibrinolytic activity on the day before surgery , after induction of anesthesia but before prophylaxis was initiated , and on postoperative days 1 , 3 , and 5 . Fibrinolysis was assessed through measurement of the activities of the rate limiting fibrinolytic activator , tissue plasminogen activator , and its inhibitor plasminogen activator inhibitor-1 with amidolytic methods . RESULTS On the day before surgery , plasminogen activator inhibitor-1 activity was elevated in all groups in comparison with that in age-matched and sex-matched controls ( 20.3 + /- 0.6 AU/mL ) . In the HEP group , plasminogen activator inhibitor-1 activity was further elevated above the value for the day before surgery on postoperative day 1 ( 28.5 + /- 4.3 AU/mL ; P = .04 ) and postoperative day 3 ( 25.1 + /- 1.9 AU/mL ; P = .07 ) . No significant decrease in plasminogen activator inhibitor-1 activity occurred in either group treated with EPC devices in comparison with the HEP group at any time . There were no changes in tissue plasminogen activator activity postoperatively in the HEP group and no significant increases in either EPC group at any point . CONCLUSIONS Reduced systemic fibrinolytic activity ( " fibrinolytic shutdown " ) occurred in these patients after abdominal surgery ; it was manifested as increased plasminogen activator inhibitor-1 activity . EPC devices did not enhance systemic fibrinolysis or prevent postoperative shutdown either by decreasing plasminogen activator inhibitor-1 activity or by increasing tissue plasminogen activator activity . These data suggest that EPC devices do not prevent deep venous thrombosis by fibrinolytic enhancement ; effective prophylaxis is achieved only when the devices are used in a manner that reduces lower extremity venous stasis Objective : To compare the efficacy and safety of antithrombotic prophylaxis given for 1 week or 4 weeks in patients undergoing laparoscopic surgery for colorectal cancer . Background : Extending antithrombotic prophylaxis beyond 1 week reduces the incidence of venous thromboembolism ( VTE ) after open abdominal surgery for cancer . Methods : In consecutive patients who underwent laparoscopic surgery for colorectal cancer , complete compression ultrasonography of the lower limbs was performed after 8 ± 2 days of antithrombotic prophylaxis . Patients with no evidence of VTE were r and omized to short ( heparin withdrawal ) or to extended ( heparin continued for 3 additional weeks ) prophylaxis . Complete compression ultrasonography was repeated at day 28 ± 2 after surgery by investigators blinded to treatment allocation . The primary outcome of the study was the composite of symptomatic and ultrasonography-detected VTE at day 28 ± 2 after surgery . Results : Overall , 301 patients were evaluated for inclusion in the study and 225 were r and omized . VTE occurred in 11 of 113 patients r and omized to short ( 9.7 % ) and in none of the 112 patients r and omized to extended heparin prophylaxis ( P = 0.001 ) . The incidence of VTE at 3 months was 9.7 % and 0.9 % in patients r and omized to short or to extended heparin prophylaxis , respectively ( relative risk reduction : 91 % , 95 % confidence interval : 30%–99 % ; P = 0.005 ) . The rate of bleeding was similar in the 2 treatment groups . Two patients died during the study period , 1 in each treatment group . Conclusions : After laparoscopic surgery for colorectal cancer , extended antithrombotic prophylaxis is safe and reduces the risk for VTE as compared with 1-week prophylaxis ( NCT01589146 ) Patients with severe renal insufficiency ( sRI ) have been suggested to be at an increased risk of bleeding with low-molecular-weight heparins ( LMWH ) . We aim ed at assessing the benefits and risks of certoparin in comparison to unfractionated heparin ( UFH ) in these patients . In this subgroup analysis of the CERTIFY trial , acutely ill , non-surgical patients ≥70 years received certoparin 3,000U aXa o.d . or UFH 5,000 IU t.i.d . One hundred eighty-nine patients had a glomerular filtration rate ( GFR ) ≤30 ml/min/1.73 m2 , 3,050 patients served as controls . Patients with sRI had a mean age of 85.9 ± 6.6 years ( controls 78.4 ± 6.0 ) and were treated for a mean of 9.3 ± 3.7 days ( 9.9 ± 4.3 ) . Thromboembolic event rates were comparable ( 4.55 vs. 4.21 % ; OR1.08 ; 95%CI 0.5 - 2.37 ) but bleeding was increased in sRI ( 9.52 vs. 3.54 % ; OR2.87 ; 95%CI 1.70 - 4.83 ) . The incidence of the combined end-point of proximal DVT , symptomatic non-fatal PE and VTE related death was 6.49 % with certoparin and 2.60 % with UFH ( OR2.60 ; 95%CI 0.49 - 13.85 ) . There was a decrease in total bleeding with certoparin ( OR0.33 ; 95%CI 0.11 - 0.97 ) , which was non-significant in patients with GFR > 30 ml/min/1.73 m2 . In two multivariable regression models certoparin and immobilisation < 10 days were associated with less bleeding while a GFR ≤30 ml/min/1.73 m2 was associated with increased bleeding . A total of 11.3 % of certoparin- and 18.5 % of UFH-treated patients experienced serious adverse events ( 14.8 in patients with a GFR ≤30 vs. 5.6 % vs. > 30 ml/min/1.73 m2 ) . In conclusion , certoparin 3,000U anti Xa o.d . was as efficacious as 5,000 IU UFH t.i.d . in patients with sRI but had a reduced risk of bleeding BACKGROUND Low-molecular-weight heparins are frequently used to treat venous thromboembolism , but optimal dosing regimens and clinical outcomes need further definition . METHODS In this multicenter , open-label study with blinded adjudication of end points , we r and omly assigned patients with acute deep-vein thrombosis to one of three treatment regimens : intravenous administration of unfractionated heparin ; subcutaneous administration of a low-molecular-weight heparin , reviparin , twice a day for one week ; or subcutaneous administration of reviparin once a day for four weeks . The primary end point was evidence of regression of the thrombus on venography on day 21 ; secondary end points were recurrent venous thromboembolism , major bleeding within 90 days after enrollment , and death . RESULTS Of the patients receiving unfractionated heparin , 40.2 percent ( 129 of 321 ) had thrombus regression , as compared with 53.4 percent ( 175 of 328 ) of patients receiving reviparin twice daily and 53.5 percent ( 167 of 312 ) of the patients receiving reviparin once daily . With regard to thrombus regression , reviparin administered twice daily was significantly more effective than unfractionated heparin ( relative likelihood of thrombus regression , 1.28 ; 97.5 percent confidence interval , 1.08 to 1.52 ) , as was reviparin administered once daily ( relative likelihood , 1.29 ; 97.5 percent confidence interval , 1.08 to 1.53 ) . Mortality and the frequency of episodes of major bleeding were similar in the three groups . CONCLUSIONS In acute deep-vein thrombosis , reviparin regimens are more effective than unfractionated heparin in reducing the size of the thrombus . Reviparin is also more effective than unfractionated heparin for the prevention of recurrent thromboembolism and equally safe PURPOSE In patients with myeloma , thalidomide significantly improves outcomes but increases the risk of thromboembolic events . In this r and omized , open-label , multicenter trial , we compared aspirin ( ASA ) or fixed low-dose warfarin ( WAR ) versus low molecular weight heparin ( LMWH ) for preventing thromboembolism in patients with myeloma treated with thalidomide-based regimens . PATIENTS AND METHODS A total of 667 patients with previously untreated myeloma who received thalidomide-containing regimens and had no clinical indication or contraindication for a specific antiplatelet or anticoagulant therapy were r and omly assigned to receive ASA ( 100 mg/d ) , WAR ( 1.25 mg/d ) , or LMWH ( enoxaparin 40 mg/d ) . A composite primary end point included serious thromboembolic events , acute cardiovascular events , or sudden deaths during the first 6 months of treatment . RESULTS Of 659 analyzed patients , 43 ( 6.5 % ) had serious thromboembolic events , acute cardiovascular events , or sudden death during the first 6 months ( 6.4 % in the ASA group , 8.2 % in the WAR group , and 5.0 % in the LMWH group ) . Compared with LMWH , the absolute differences were + 1.3 % ( 95 % CI , -3.0 % to 5.7 % ; P = .544 ) in the ASA group and + 3.2 % ( 95 % CI , -1.5 % to 7.8 % ; P = .183 ) in the WAR group . The risk of thromboembolism was 1.38 times higher in patients treated with thalidomide without bortezomib . Three major ( 0.5 % ) and 10 minor ( 1.5 % ) bleeding episodes were recorded . CONCLUSION In patients with myeloma treated with thalidomide-based regimens , ASA and WAR showed similar efficacy in reducing serious thromboembolic events , acute cardiovascular events , and sudden deaths compared with LMWH , except in elderly patients where WAR showed less efficacy than LMWH Two hundred and four consecutive patients with venographically confirmed deep vein thrombosis ( DVT ) were r and omised either to a low molecular weight heparin , Fragmin , administered subcutaneously ( s.c . ) once daily as a fixed dose of 200 IU anti-factor Xa/kg or to continuous intravenous infusion of unfractionated heparin ( UFH ) . The UFH dose was adjusted to maintain the activated partial thromboplastin time between 1.5 and 3.0 times the upper limit of the reference value at each centre . Fragmin or UFH was given for a minimum of 5 days until anticoagulation with warfarin , given from day 1 , was established ( i.e. an Internation Normalised Ratio , of 2.0 - 3.0 ) . A second venogram was obtained after Fragmin or UFH treatment . There were no significant differences in the change in mean Marder score before and after treatment between the two treatment groups , irrespective of thrombus localisation . No major bleeding events , symptomatic pulmonary embolism , symptomatic thrombosis progression or death occurred during hospitalisation . Eight documented venous thromboembolic events occurred before the follow-up visit 6 months after r and omisation : 5 in patients treated with Fragmin and 3 in those treated with UFH . Six of these events occurred after cessation of warfarin treatment . In conclusion Fragmin given s.c . once daily in a fixed dose adjusted for body weight , is no less effective or safe than a continuous infusion of UFH in the initial treatment of acute DVT OBJECTIVE The aim of this study was to compare the efficacy of low molecular weight heparin ( LMWH ) combined with graduated compression stockings ( GCS ) with GCS alone as prophylactic measures for venous thromboembolism ( VTE ) in post-operative patients with gynecologic cancer . METHODS Patients diagnosed with gynecologic cancer undergoing primary major surgery between 2010 and 2011 in our institute were r and omized to receive LMWH+GCS or GCS as VTE prophylaxis post-operatively . RESULTS Altogether 247 patients were enrolled . The incidence of VTE in patients treated with LMWH + GCS was significantly lower than that in patients using GCS alone ( 0.8 % Vs . 8.1 % , P = 0.01 ) . There were no severe bleeding complications in the patients with prophylactic use of LMWH and the occurrence rate of wound dehiscence was comparable between the two groups ( P > 0.05 ) . Multivariable logistic regression analysis revealed that age over 60 years ( P = 0.015 ) , duration of operation over 3 hours ( P = 0.04 ) and without prophylactic use of LMWH ( P = 0.02 ) were independent risk factors for VTE . CONCLUSIONS Dual prophylaxis with LMWH and GCS should be recommended for gynecologic cancer patients undergoing major surgery for its better efficacy than GCS . Prophylactic use of LMWH is safe and convenient . Patients with older age and prolonged operation time are at highest risk of developing VTE post-operatively CONTEXT Venous thromboembolism ( VTE ) is the most frequent complication following craniotomy for brain tumors . At Brigham and Women 's Hospital , VTE after craniotomy for brain tumor is the leading cause of deep vein thrombosis ( DVT ) and pulmonary embolism ( PE ) among patients hospitalized for conditions other than VTE . OBJECTIVE To minimize VTE among patients undergoing craniotomy for brain tumor . DESIGN R and omized , prospect i ve , double-blind clinical trial . SETTING Brigham and Women 's Hospital . PATIENTS One hundred fifty patients undergoing craniotomy for brain tumor r and omized to enoxaparin , 40 mg/d , vs heparin , 5,000 U bid , with all patients receiving graduated compression stockings and intermittent pneumatic compression . MAIN OUTCOME MEASURES The rate of DVT detected by venous ultrasonography prior to hospital discharge . RESULTS Symptomatic DVT or PE developed in none of the patients . The overall rate of asymptomatic VTE was 9.3 % , with no significant difference in the rates between the two prophylaxis groups . Ten of the 14 patients identified with VTE had thrombus limited to the deep veins of the calf . CONCLUSIONS Enoxaparin , 40 mg/d , or unfractionated heparin , 5,000 U bid , in combination with graduated compression stockings , intermittent pneumatic compression , and predischarge surveillance venous ultrasonography of the legs , result ed in 150 consecutive patients without symptomatic VTE . The low 9.3 % frequency of asymptomatic VTE comprised mostly isolated calf DVT . Therefore , this comprehensive , multimodality approach to VTE prophylaxis achieved excellent efficacy and safety BACKGROUND Patients with venous thromboembolism and cancer have a substantial risk of recurrent venous thromboembolism and bleeding during anticoagulant therapy . Although monotherapy with low-molecular-weight heparin is recommended in these patients , in clinical practice many patients with venous thromboembolism and cancer do not receive this treatment . We aim ed to assess the efficacy and safety of a single-drug regimen with oral rivaroxaban compared with enoxaparin followed by vitamin K antagonists , in the subgroup of patients with cancer enrolled in the EINSTEIN-DVT and EINSTEIN-PE r and omised controlled trials . METHODS We did a subgroup analysis of patients with active cancer ( either at baseline or diagnosed during the study ) , a history of cancer , or no cancer who were enrolled in the EINSTEIN-DVT and EINSTEIN-PE trials . Eligible patients with deep-vein thrombosis ( EINSTEIN-DVT ) or pulmonary embolism ( EINSTEIN-PE ) were r and omly assigned in a 1:1 ratio to receive rivaroxaban ( 15 mg twice daily for 21 days , followed by 20 mg once daily ) or st and ard therapy ( enoxaparin 1·0 mg/kg twice daily and warfarin or acenocoumarol ; international normalised ratio 2·0 - 3·0 ) . R and omisation with a computerised voice-response system was stratified according to country and intended treatment duration ( 3 , 6 , or 12 months ) . The prespecified primary efficacy and safety outcomes of both the trials and this sub analysis were symptomatic recurrent venous thromboembolism and clinical ly relevant bleeding , respectively . We did efficacy and mortality analyses in the intention-to-treat population , and bleeding analyses for time spent receiving treatment plus 2 days in the safety population ( all patients who received at least one dose of study drug ) . The EINSTEIN-DVT and EINSTEIN-PE studies are registered at Clinical Trials.gov , numbers NCT00440193 and NCT00439777 . FINDINGS In patients with active cancer ( diagnosed at baseline or during treatment ) , recurrent venous thromboembolism occurred in 16 ( 5 % ) of 354 patients allocated to rivaroxaban and 20 ( 7 % ) of 301 patients allocated to enoxaparin and vitamin K antagonist ( hazard ratio [ HR ] 0·67 , 95 % CI 0·35 to 1·30 ) . Clinical ly relevant bleeding occurred in 48 ( 14 % ) of 353 patients receiving rivaroxaban and in 49 ( 16 % ) of 298 patients receiving st and ard therapy ( HR 0·80 , 95 % CI 0·54 to 1·20 ) . Major bleeding occurred in eight ( 2 % ) of 353 patients receiving rivaroxaban and in 15 ( 5 % ) of 298 patients receiving st and ard therapy ( HR 0·42 , 95 % CI 0·18 to 0·99 ) . The overall frequency of recurrent venous thromboembolism in patients with only a history of cancer ( five [ 2 % ] of 233 patients in the rivaroxaban group vs five [ 2 % ] of 236 in the st and ard therapy group ; HR 0·98 , 95 % CI 0·28 - 3·43 ) was similar to that of patients without cancer ( 65 [ 2 % ] of 3563 vs 70 [ 2 % ] of 3594 , respectively ; HR 0·93 , 95 % CI 0·66 - 1·30 ) , but the frequency was increased in patients with active cancer at baseline ( six [ 2 % ] of 258 vs eight [ 4 % ] of 204 , respectively ; HR 0·62 , 95 % CI 0·21 - 1·79 ) and most markedly increased in patients whose diagnosis of cancer was made during the study ( ten [ 10 % ] of 96 vs 12 [ 12 % ] of 97 , respectively ; HR 0·80 , 95 % CI 0·34 - 1·88 ) . The overall frequency of major bleeding in patients with only a history of cancer ( one [ < 1 % ] patient in the rivaroxaban group vs four [ 2 % ] patients in the st and ard therapy group ; HR 0·23 , 95 % CI 0·03 - 2·06 ) was similar to that of patients without cancer ( 31 [ 1 % ] vs 53 [ 1 % ] , respectively ; HR 0·58 , 95 % CI 0·37 - 0·91 ) , but was increased in patients with active cancer at baseline ( five [ 2 % ] vs eight [ 4 % ] , respectively ; HR 0·47 , 95 % CI 0·15 - 1·45 ) and was highest in those with cancer diagnosed during the study ( three [ 3 % ] vs seven [ 7 % ] , respectively ; HR 0·33 , 95 % CI 0·08 - 1·31 ) . INTERPRETATION In patients with active cancer and venous thromboembolism , rivaroxaban had similar efficacy to prevent recurrence of venous thromboembolism and reduced the number major bleeding events compared with treatment with enoxaparin and a vitamin K antagonist , although there was no difference between groups for clinical ly relevant bleeding . Based on these results , a head-to-head comparison of rivaroxaban with long-term low-molecular-weight heparin in patients with cancer is warranted . FUNDING Bayer HealthCare Pharmaceuticals and Janssen Research & Development Perioperative anticoagulant prophylaxis for postoperative venous thromboembolism ( VTE ) in neurosurgical patients has not gained wide acceptance due to the fear of intracranial bleeding . Physical methods give a worthwhile reduction of postoperative VTE but there still remains a substantial residual incidence . In other clinical indications , low molecular weight heparins have proven to be effective for prophylaxis of VTE when administered postoperatively , with the advantage of no bleeding enhancement during surgery . Therefore , we performed a multicentre , r and omized , double-blind trial in neurosurgical patients to investigate the efficacy and safety of adding a low molecular weight heparin ( LMWH ) , nadroparin , initiated postoperatively , to graduated compression stockings in the prevention of VTE . Deep-vein thrombosis was detected by m and atory venography . Bleeding was determined according to pre-defined objective criteria for major and minor episodes . An adequate bilateral venogram was obtained in 166 of 241 LMWH patients ( 68.9 % ) and 179 of 244 control patients ( 73.4 % ) . A total of 31 of 166 LMWH patients ( 18.7 % ) and 47 of 179 controls patients ( 26.3 ) had VTE up to Day 10 postoperatively ( p = 0.047 ) . The relative risk reduction ( RRR ) was 28.9 % . The rates for proximal deep-vein thrombosis/pulmonary embolism were 6.9 % and 11.5 % for the two groups , respectively ( RRR : 40.2 % ; p = 0.065 ) . Secondary analyses involved all VTE up to day 56 post-surgery which was detected in 33 patients of 241 in the LMWH group ( 13.7 % ) and 51 of 244 control patients ( 20.9 % ; RRR 34.5 % ; p = 0.018 ) . The corresponding percentages for proximal deep-vein thrombosis/pulmonary embolism were 5.8 % and 10.2 % for the two groups , respectively , giving a RRR of 43.3 % ; p = 0.36 . Major bleeding complications , during the treatment period , occurred in six low molecular weight heparin treated patients ( 2.5 % ) and in two control patients ( 0.8 % ) ; p = 0.87 . A higher mortality was observed in the low molecular weight heparin group over the 56-day follow-up period ( 22 versus 10 ; p = 0.026 ) . However , none of these deaths was judged by a blinded adjudication committee to be related to the study drug . In conclusion , this study demonstrates that the low molecular weight heparin , nadroparin , added to graduated compression stockings results in a clinical ly significant decrease in VTE without inducing any significant increase of major bleeding Objective : To compare efficacy and safety of thromboprophylaxis with semuloparin started postoperatively versus enoxaparin started preoperatively in major abdominal surgery . Background : Venous thromboembolism is an important complication following major abdominal surgery . Semuloparin is a novel ultra-low-molecular-weight heparin with high antifactor Xa and minimal antifactor IIa activity . Methods : In this double-blind noninferiority trial , adult patients undergoing major abdominal or pelvic operation under general anesthesia lasting more than 45 minutes were assigned to either daily enoxaparin 40 mg commenced preoperatively or daily semuloparin 20 mg commenced postoperatively , for 7 to 10 days . Patients underwent bilateral leg venography between 7 and 11 days postsurgery . The primary efficacy end point was the composite of any deep vein thrombosis , nonfatal pulmonary embolism , or all-cause death . The primary safety outcome was bleeding . Both were independently adjudicated . Results : In total , 4413 patients were r and omized ; 3030 ( 1499 in the enoxaparin and 1531 in the semuloparin groups ) were evaluable for the primary efficacy end point , which occurred in 97 patients ( 6.3 % ) in the semuloparin group and 82 patients ( 5.5 % ) in the enoxaparin group [ odds ratio ( OR ) = 1.16 , 95 % confidence interval ( CI ) : 0.84–1.59 ] . On the basis of a noninferiority margin of 1.25 , postoperative semuloparin did not demonstrate noninferiority to preoperative enoxaparin . Major bleeding occurred in 63 of 2175 patients ( 2.9 % ) in the semuloparin group and 98 of 2177 patients ( 4.5 % ) in the enoxaparin group ( OR = 0.63 , 95 % CI : 0.46–0.87 ) . Conclusions : Semuloparin commenced postoperatively did not demonstrate noninferiority to enoxaparin initiated preoperatively for thromboprophylaxis after major abdominal surgery . Study registered with clinical trials.gov : NCT00679588 Abstract Background Whereas routine prophylaxis for venous thromboembolism ( VTE ) is frequently utilized in the West , Asian physicians employ it much less often , based on its recorded rarity amongst their patients . This study was design ed to examine the incidence of VTE and to determine the optimal method of thromboembolic prophylaxis following gastrectomy for cancer . Methods In this prospect i ve , r and omized trial , patients were assigned to either an intermittent pneumatic compression ( IPC ) only or an IPC plus enoxaparin . The primary end point of this study was to determine the VTE incidence rate within 30 days of surgery . A history with physical examinations for VTE and a serum d-dimer test was scheduled on postoperative days ( POD ) 0 , 1 , 4 , and 7 . Duplex ultrasonography ( DUS ) was performed as an objective test for deep vein thrombosis at POD 4 . An interim analysis was performed to determine if it was ethical to continue the study . This clinical trial was registered at www . clinical trials.gov ( NCT01448746 ) . Results Among the 220 patients , 3 ( all from the IPC group ) were diagnosed with VTE ; these cases were asymptomatic , having been detected only on DUS 4 days after surgery . Postoperative bleeding occurred in 12 cases , among which 11 patients were in the IPC plus enoxaparin group . Conclusions This interim analysis showed a higher incidence of VTE in the IPC group but a higher bleeding rate in the IPC plus enoxaparin group . We expect that this study , once completed , will provide information key to the determination of the optimal method for preventing VTE in Korean gastric cancer patients BACKGROUND The AMPLIFY trial compared apixaban with enoxaparin followed by warfarin for the treatment of acute venous thromboembolism ( VTE ) . OBJECTIVE To perform a subgroup analysis to compare the efficacy and safety of apixaban and enoxaparin followed by warfarin for the treatment of VTE in patients with cancer enrolled in AMPLIFY . PATIENTS / METHODS Patients with symptomatic VTE were r and omized to a 6-month course of apixaban or enoxaparin followed by warfarin . The primary efficacy outcome and principal safety outcome were recurrent VTE or VTE-related death and major bleeding , respectively . RESULTS Of the 5395 patients r and omized , 169 ( 3.1 % ) had active cancer at baseline , and 365 ( 6.8 % ) had a history of cancer without active cancer at baseline . Among patients with active cancer , recurrent VTE occurred in 3.7 % and 6.4 % of evaluable patients in the apixaban and enoxaparin/warfarin groups , respectively ( relative risk [ RR ] 0.56 , 95 % confidence interval [ CI ] 0.13 - 2.37 ) ; major bleeding occurred in 2.3 % and 5.0 % of evaluable patients , respectively ( RR 0.45 , 95 % CI 0.08 - 2.46 ) . Among patients with a history of cancer , recurrent VTE occurred in 1.1 % and 6.3 % of evaluable patients in the apixaban and enoxaparin/warfarin groups , respectively ( RR 0.17 , 95 % CI 0.04 - 0.78 ) ; major bleeding occurred in 0.5 % and 2.8 % of treated patients , respectively ( RR 0.20 , 95 % CI 0.02 - 1.65 ) . CONCLUSIONS The results of this subgroup analysis suggest that apixaban is a convenient option for cancer patients with VTE . However , additional studies are needed to confirm this concept and to compare apixaban with low molecular weight heparin in these patients BACKGROUND The efficacy and safety of thromboprophylaxis in patients with acute medical illnesses who may be at risk for venous thromboembolism have not been determined in adequately design ed trials . METHODS In a double-blind study , we r and omly assigned 1102 hospitalized patients older than 40 years to receive 40 mg of enoxaparin , 20 mg of enoxaparin , or placebo subcutaneously once daily for 6 to 14 days . Most patients were not in an intensive care unit . The primary outcome was venous thromboembolism between days 1 and 14 , defined as deep-vein thrombosis detected by bilateral venography ( or duplex ultrasonography ) between days 6 and 14 ( or earlier if clinical ly indicated ) or documented pulmonary embolism . The duration of follow-up was three months . RESULTS The primary outcome could be assessed in 866 patients . The incidence of venous thromboembolism was significantly lower in the group that received 40 mg of enoxaparin ( 5.5 percent [ 16 of 291 patients ] ) than in the group that received placebo ( 14.9 percent [ 43 of 288 patients ] ) ( relative risk , 0.37 ; 97.6 percent confidence interval , 0.22 to 0.63 ; P < 0.001 ) . The benefit observed with 40 mg of enoxaparin was maintained at three months . There was no significant difference in the incidence of venous thromboembolism between the group that received 20 mg of enoxaparin ( 43 of 287 patients [ 15.0 percent ] ) and the placebo group . The incidence of adverse effects did not differ significantly between the placebo group and either enoxaparin group . By day 110 , 50 patients had died in the placebo group ( 13.9 percent ) , 51 had died in the 20-mg group ( 14.7 percent ) , and 41 had died in the 40-mg group ( 11.4 percent ) ; the differences were not significant . CONCLUSIONS Prophylactic treatment with 40 mg of enoxaparin subcutaneously per day safely and effectively reduces the risk of venous thromboembolism in patients with acute medical illnesses Danaparoid ( Org 10172 ; Organon Scientific Development Group , Oss , the Netherl and s ) , a heparinoid with a mean molecular weight of 5500 d , is obtained from the intestinal mucosa of the pig after removal of heparin . It is a mixture of sulfated glycosaminoglycans with low molecular weight : heparan sulfate ( 84 % ) , dermatan sulfate ( 12 % ) , and chondroitin sulfate ( 4 % ) [ 1 , 2 ] . Only a subfraction ( 4 % ) of heparan sulfate contains the pentasaccharide sequence , common to heparin and to low-molecular-weight heparins , that has a high affinity to antithrombin III . This subfraction acts through the selective inhibition of factor Xa through antithrombin III , which leads to the inhibition of thrombin generation . The fraction of heparan sulfate with a low affinity for antithrombin III does not affect coagulation factors Xa and IIa but contributes substantially to antithrombotic activity , probably through an endothelial cellular mechanism [ 3 ] . The dermatan sulfate component of danaparoid activates heparin cofactor II , which acts at the level of factor IIa . The synergistic activity of these three components determines the antithrombotic profile . As reflected in its anti-factor Xa : anti-factor IIa inhibitory ratio of more than 28:1 , danaparoid is a more selective inhibitor of factor Xa than heparin or the low-molecular-weight heparins . The dose-related response to danaparoid remains gradual and linear over a wide dosing range , which may contribute to its safety as an antithrombotic drug . Compared with heparin and low-molecular-weight heparins , danaparoid has almost no effect on physiologic platelet function and has low cross-reactivity with heparin-induced antibodies against platelets . The wide therapeutic range of danaparoid and its minimal effect on platelets may render it a safer anticoagulant than heparin or low-molecular-weight heparins . Treatment with unfractionated heparin is limited by the drug 's pharmacokinetic , biophysical , and antihemostatic ( nonanticoagulant ) properties . Heparin must be given in sufficient quantities under frequent monitoring , its dose-response curve is nonlinear and unpredictable in individual persons , and the risk for bleeding increases with increasing doses and duration of treatment . Danaparoid has been shown in animal studies to be more effective than st and ard heparin or two different low-molecular-weight heparin preparations in preventing the extension of experimentally induced venous thrombi [ 4 ] . It has been both safe and effective in the prophylaxis of deep venous thrombosis in patients having cancer surgery [ 5 ] , hip-fracture surgery [ 6 ] , or hip-replacement surgery [ 7 ] and in patients with nonhemorrhagic stroke [ 8 ] . It has been used as an anticoagulant during hemodialysis [ 9 , 10 ] and in patients with heparin-induced thrombocytopenia [ 11 , 12 ] or disseminated intravascular coagulation [ 13 ] . Data from studies of the treatment of deep venous thrombosis in patients with hemorrhagic stroke indicate that treatment with danaparoid can prevent the extension of venous thromboembolism without aggravating cerebral bleeding [ 14 ] . No study has yet assessed the efficacy and safety of danaparoid in the treatment of patients presenting with acute deep venous thrombosis or pulmonary embolism . Danaparoid has a bioavailability of 100 % after subcutaneous administration ; the bioavailability of unfractionated heparin after subcutaneous injection is only 20 % to 30 % . Therefore , danaparoid is particularly suitable for subcutaneous administration , much like the low-molecular-weight heparin preparations [ 15 - 19 ] , which have a bioavailablity of approximately 90 % . Our study was design ed to assess the efficacy and safety of two doses of subcutaneously administered danaparoid and of continuous intravenous administration of unfractionated heparin as initial treatment in patients presenting with acute proximal deep venous thrombosis of the leg , pulmonary embolism , or both . Methods Study Design Our study was a r and omized , open , parallel-group clinical trial done in one university hospital and two university-affiliated hospitals in the Netherl and s. The study protocol and forms giving informed consent were approved by the institutional review board at each hospital . Patients All patients gave witnessed informed consent before being entered into the study . Men and women 18 years of age or older who presented with clinical symptoms of acute proximal deep venous thrombosis of the leg or pulmonary embolism of no more than 7 days duration were eligible . Patients were excluded if they had had intracranial bleeding within 2 months or resuscitation by external chest compression within 48 hours ; if they were allergic to heparin ; if they were pregnant ; if they were receiving treatment with coumarin derivatives ; if they had been treated with thrombolytic drugs within 7 days ; or if they were receiving ongoing treatment with aspirin , nonsteroidal anti-inflammatory drugs , dextran , or fibrinolytic drugs . The provisional diagnosis of venous thrombosis or pulmonary embolism had to be confirmed within 48 hours after the start of study treatment by compression ultrasonography or contrast venography ( whichever could be done soonest ) or by ventilation-perfusion lung scan . Treatment was discontinued and the patient was excluded from the study if the clinical diagnosis was not confirmed . Enrollment began in March 1991 and continued through August 1992 . Dosing Schedule The efficacy and safety of two dosing schedules of danaparoid were compared with the efficacy and safety of continuous intravenous unfractionated heparin . The schedule for low-dose danaparoid was 1250 anti-factor Xa units given as an intravenous bolus , followed by subcutaneous doses of 1250 anti-factor Xa units every 12 hours . The schedule for high-dose danaparoid was 2000 anti-factor Xa units given as an intravenous bolus , followed by subcutaneous doses of 2000 anti-factor Xa units every 12 hours . The first subcutaneous injection was simultaneous with the intravenous bolus injection . The second subcutaneous injection was given at the time of the first of the routine twice-daily injections , unless this was within 6 hours of the first injection . Unfractionated heparin was given intravenously as a loading dose of 2500 U and was followed by an initial maintenance dose of 30 000 U every 24 hours . This maintenance dose was adjusted to reach activated partial thromboplastin 2.5 to 3.5 times the control values ; these times were equivalent to a heparin level of 0.25 to 0.40 U/mL. This was measured daily and 4 hours after any dose adjustment . Study treatment was given for at least 5 days and was continued until an international normalized ratio of at least 3.0 was achieved with oral anticoagulation therapy , which was started 48 hours after the initiation of study treatment . The oral anticoagulant dose was calculated daily using the Thrombotest ( Nyegaard and Co. , Oslo , Norway ; international sensitivity index , 0.94 ) ; this was done each morning using plasma sample s taken before the morning dose had been given . If the international normalized ratio was below the target level after 8 days of study treatment , the attending physician decided whether to continue heparin therapy , continue danaparoid therapy , or switch patients being treated with danaparoid to intravenous heparin . Study treatment was r and omized as follows . Consecutively numbered , identical boxes were kept in each hospital pharmacy ; each box contained one of the three treatments , r and omized per hospital . After giving informed consent , a patient was treated with medication from the next consecutive box . The investigators were blinded to the r and omization schedule . Only when the study medication for one individual patient was delivered did the treatment become known . After being assigned to treatment , patients were excluded from the efficacy analysis only if diagnosis of deep venous thrombosis or pulmonary embolism could not be confirmed within 48 hours of admission . Evaluations and Scheduling The primary method of assessment for recurrence or extension was repeated ultrasonography of the leg , contrast venography , ventilation-perfusion scanning , or both contrast venography and ventilation-perfusion scanning . Assessment was done after at least 5 days and at most 8 days of study treatment , within 24 hours after stopping treatment , or if clinical ly indicated . Institutional physicians , who were blinded to treatment assignments , interpreted venograms , ultrasonograms , and lung scans . Clinical evidence of recurrence or extension was defined as documented clinical circumstances suggestive of venous thromboembolic disease leading to the discontinuation of study treatment . A daily physical examination ( including tests for hemoglobin level , platelet count , and leukocyte count ) and a urinalysis to test for erythrocyte count were done . Liver function tests were done and creatinine levels were measured before and at the end of study treatment . Plasma used to measure amidolytic anti-factor Xa activity was collected at the time of screening and at treatment days 2 and 4 ( before and 2.5 hours after the morning injection on both days ) . This plasma was frozen at 20C and stored until assay . Plasma sample s were collected at the time of screening for determination of activated partial thromboplastin times before study treatment . Follow-up assessment was done 2 months after the initiation of study treatment to gather information on state of health , recurrence or extension of venous thromboembolism , and bleeding complications . Compression Ultrasonography To establish the extent of thrombosis using ultrasonography [ 20 ] , the deep venous system was divided into six segments : lower popliteal , upper popliteal , inferior femoral , mid-femoral , upper femoral , and common femoral veins . Each patient was first examined in the supine position so that the superficial femoral , common femoral , and iliac vein segments could be assessed . Patients were then examined in the prone position In a prospect i ve , r and omized , open study 119 consecutive patients with phlebographically verified deep venous thrombosis ( DVT ) of the leg ( 36 % distal and 64 % proximal ) were treated either with a low molecular weight heparin ( Fragmin , Kabi-Vitrum ) subcutaneously ( 120 anti-FXa U/kg ) twice daily or st and ard heparin ( SH ) as continuous intravenous infusion ( 480 IU kg-1 day-1 ) . The Fragmin doses were adjusted to achieve an anti-FXa activity of 0.2 - 0.4 U/ml before injection and not greater than 1.5 U/ml 4 h after the morning injection . The SH dose was modified to prolong the APTT 2 - 3 times . Repeat phlebography after 5 - 7 days showed improvement in 34/45 patients ( 76 % ) in the Fragmin group and in 30/49 patients ( 61 % ) in the SH group and progress in 2/45 ( 4 % ) and 3/49 ( 6 % ) , respectively . The mean Marder scores decreased from 18.7 + /- 12.1 to 15.7 + /- 12.7 in the Fragmin group and from 16.9 + /- 12.0 to 14.4 + /- 11.8 in the SH group ( ns ) . Two patients in the SH group and none in the Fragmin group had major bleedings . After 22 + /- 7 months follow up 6 rethromboses had occurred in the SH group and 4 in the Fragmin group . Postthrombotic signs and symptoms were similar in both groups . We conclude that two daily sc Fragmin doses seem as effective and safe as continuous SH in the treatment of DVT of the leg BACKGROUND There is not enough clinical evidence to make a strong recommendation on the optimal duration of thromboprophylaxis using low-molecular weight heparins ( LMWH ) in patients undergoing major cancer surgery . PATIENTS AND METHODS CANBESURE is a r and omized , double-blind study which enrolled patients admitted for abdominal or pelvic surgery for cancer . They received 3500 IU of bemiparin subcutaneously once daily for 8 days and were then r and omized to receive either bemiparin or placebo for 20 additional days . Bilateral venography was performed after 20 days and evaluated blinded . The primary efficacy outcome was the composite of deep vein thrombosis ( DVT ) , non-fatal pulmonary embolism ( PE ) and all-cause mortality at the end of double-blind period . Major venous thromboembolism ( proximal deep-vein thrombosis , non-fatal pulmonary embolism and venous thromboembolism-related deaths ) was also evaluated . The primary safety outcome was major bleeding . RESULTS Six hundred and twenty-five and 488 patients were included in the safety and main efficacy analyzes , respectively . The primary efficacy outcome occurred in 25 out of 248 patients ( 10.1 % ) in the bemiparin group and 32 out of 240 ( 13.3 % ) in the placebo group ( relative risk reduction 24.4 % ; 95 % CI : -23.7 - 53.8 % ; P = 0.26 ) . At the end of double-blind period , major venous thromboembolism occurred in 2 ( 0.8 % ) and 11 ( 4.6 % ) patients , respectively ( relative risk reduction 82.4 % ; 95 % CI : 21.5 - 96.1 % ; P = 0.010 ) . No significant difference was found in major bleedings . CONCLUSIONS Four weeks compared with 1 week of prophylaxis with bemiparin after abdominal or pelvic cancer surgery did not significantly reduce the primary efficacy outcome , but decreased major venous thromboembolism ( VTE ) without increasing hemorrhagic complications The efficacy and safety of dabigatran for treatment of venous thromboembolism ( VTE ) were demonstrated in two trials . It is unclear if the results pertain to patients with cancer and VTE . Data from two r and omised trials comparing dabigatran and warfarin for acute VTE were pooled . Primary efficacy outcome was symptomatic recurrent VTE and related death from r and omisation to the end of the treatment period . Safety outcomes were major , major and clinical ly relevant non-major , and any bleeding during the oral-only treatment period . Patients with active cancer ( = within 5 years ) at baseline or diagnosed during the study were analysed . Compared with 4,772 patients without cancer , recurrent VTE occurred more frequently in 335 patients with cancer at any time ( hazard ratio [ HR ] 3.3 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) and more often in 114 with cancer diagnosed during the study compared to 221 with cancer at baseline ( HR 2.6 ; 95 % CI , 1.1 - 6.2 ) . There was no significant difference in efficacy between dabigatran and warfarin for cancer at baseline ( HR 0.75 ; 95 % CI , 0.20 - 2.8 ) or diagnosed during the study ( HR 0.63 ; 95 % CI , 0.20 - 2.0 ) . Major bleeding ( HR 4.1 ; 95 % CI , 2.2 - 7.5 ) and any bleeding ( HR 1.5 ; 95 % CI , 1.2 - 2.0 ) were more frequent in patients with cancer than without , but with similar incidence in cancer with dabigatran or warfarin . In conclusion , in cancer patients , dabigatran provided similar clinical benefit as warfarin . VTE recurrence or bleeding were similar in patients on dabigatran or warfarin . The efficacy of dabigatran has not been assessed in comparison with low-molecular-weight heparin BACKGROUND In patients with venous thromboembolism ( VTE ) , identifying clinical risk factors for recurrence during the initial 3 months of anticoagulant therapy and knowledge of the time course of recurrence may help clinicians decide about the frequency of clinical surveillance and the appropriateness of outpatient treatment . METHODS Analysis of a r and omized controlled trial data base involving 1021 patients with VTE ( 750 with deep vein thrombosis [ DVT ] and 271 with pulmonary embolism [ PE ] ) who were followed up for 3 months after the start of anticoagulant therapy . All patients received initial treatment with unfractionated heparin or a low-molecular-weight heparin ( reviparin ) and a coumarin derivative starting the first or second day of treatment , with a target international normalized ratio of 2.0 to 3.0 . RESULTS Four independent clinical risk factors for recurrent VTE were identified : ( 1 ) cancer ( odds ratio [ OR ] , 2.72 ; 95 % confidence interval [ CI ] , 1 . 39 - 5.32 ) , ( 2 ) chronic cardiovascular disease ( OR , 2.27 ; 95 % CI , 1 . 08 - 4.97 ) , ( 3 ) chronic respiratory disease ( OR , 1.91 ; 95 % CI , 0.85 - 4 . 26 ) , and ( 4 ) other clinical ly significant medical disease ( OR , 1.79 ; 95 % CI , 1.00 - 3.21 ) . Older age was associated with a decreased risk for recurrent VTE ( OR , 0.76 ; 95 % CI , 0.64 - 0.92 ) . Previous VTE , sex , and idiopathic VTE were not risk factors for recurrence . In patients with DVT or PE , there was no significant difference in the rates of recurrent nonfatal VTE ( 4.8 % vs 4.1 % ; P = .62 ) , major bleeding ( 2.9 % vs 2.2 % ; P = .53 ) , and non-VTE death ( 6.4 % vs 7.8 % ; P = .45 ) , but recurrent fatal PE was more frequent in patients with PE than DVT ( 2 . 2 % vs 0 % ; P<.01 ) . There was a clustering of recurrent VTE episodes during the initial 2 to 3 weeks after the start of treatment . CONCLUSIONS During the initial 3 months of anticoagulant therapy , recurrent VTE is more likely to occur in patients with cancer , chronic cardiovascular disease , chronic respiratory disease , or other clinical ly significant medical disease . Patients with PE are as likely to develop recurrent VTE as those with DVT ; however , recurrence is more likely to be fatal in patients who initially present with PE . Arch Intern Med . 2000;160:3431 - 3436 The aim of this study was to assess whether the synthetic factor Xa inhibitor fondaparinux reduced the risk of venous thromboembolism more efficiently than the low molecular weight heparin dalteparin in patients undergoing major abdominal surgery In this study , 294 patients with acute proximal DVT ( deep venous thrombosis ) were r and omly assigned to receive intravenous st and ard heparin in the hospital ( 98 patients ) or low-molecular-weight heparin ( LMWH ) ( nadroparin 0.1 mL [ equivalent to 100 AXa IU ] per kg of body weight subcutaneously twice daily ) administered primarily at home ( out patients ) or alternatively in hospital ( 97 patients ) or subcutaneous calcium heparin ( SCHep ) ( 99 patients , 0.5 mL bid ) administered directly at home . The study design allowed out patients taking LMWH heparin to go home immediately and hospitalized patients taking LMWH to be discharged early . Patients treated with st and ard heparin or LMWH received the oral anticoagulant starting on the second day , and heparin was discontinued when the therapeutic range ( INR 2 - 3 ) had been reached . Anticoagulant treatment was maintained for 3 months . Patients treated with SCHep were injected twice daily for 3 months without oral anticoagulants . Patients were evaluated for inclusion and follow-up with color duplex scanning . Venography was not used . In case of suspected pulmonary embolism ( PE ) a ventilatory-perfusional lung scan was performed . Endpoints of the study were recurrent or extension of DVT , bleeding , the number of days spent in hospital , and costs of treatments . Of the 325 patients included , 294 completed the study . Dropouts totaled 31 ( 10.5 % ) ; six of the 325 included patients ( 1.8 % ) died from the related , neoplastic illness . Recurrence or extension of DVT was observed in 6.1 % of patients in the LMWH group , in 6.2 % in the st and ard heparin group , and in 7.1 % in the SCHep group . Most recurrences ( 11/17 ) were in the first month in all groups . Bleedings were all minor , mostly during hospital stay . Hospital stay in patients treated with LMWH was 1.2 ± 1.4 days in comparison with 5.4 ± 1.2 in those treated with st and ard heparin . There was no hospital stay in the SCHep group . Average treatment costs in 3 months in the st and ard heparin group ( US $ 2,760 ) were considered to be 100 % ; in comparison costs in the LMWH group was 28 % of the st and ard heparin and 8 % in the SCHep group . This study indicated that LMWH and SCHep can be used safely and effectively to treat patients with proximal DVT at home at a lower cost OBJECTIVE Our aim was to determine the relative efficacy and complications of low-dose heparin and intermittent pneumatic calf compression for the prevention of postoperative venous thrombosis in patients undergoing surgery for gynecologic malignancy . STUDY DESIGN R and omized trial comparing 107 patients treated with low-dose heparin to 101 patients treated with intermittent pneumatic calf compression was performed . All patients were evaluated with iodine-125 fibrinogen scanning of the legs . Clinical and laboratory variables associated with bleeding complications were recorded prospect ively . RESULTS Venous thrombosis was diagnosed in seven patients receiving low-dose heparin and in four receiving intermittent pneumatic calf compression ( p = 0.54 ) . Low-dose heparin patients received more blood transfusions postoperatively ( p = 0.02 ) , had increased volume of retroperitoneal drainage ( p = 0.02 ) , and the activated partial thromboplastin time was more frequently prolonged ( p = 0.001 ) . CONCLUSIONS Low-dose heparin and intermittent pneumatic calf compression provide similar reduction in reducing the incidence of postoperative venous thrombosis . However , low-dose heparin is more frequently associated with postoperative bleeding complications PURPOSE The extent of venous thromboembolism ( VTE ) associated with central vein catheters ( CVC ) in cancer patients remains unclear . The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin , enoxaparin , in the prevention of VTE . PATIENTS AND METHODS In a multicenter , double-blind study , consecutive cancer patients scheduled for CVC insertion were r and omly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo . Treatment was started 2 hours before CVC insertion and continued for 6 weeks . The primary end points of the study were deep vein thrombosis ( DVT ) , confirmed by venography of the CVC limb performed 6 weeks after r and omization , or clinical ly overt pulmonary embolism , confirmed by objective testing during the study drug administration . Patients were assessed for bleeding complications . RESULTS Three hundred eighty-five patients were r and omized , of which 321 ( 83.4 % ) underwent venography . A venography was adequate for adjudication in 155 patients in each treatment group . A DVT was observed in 22 patients ( 14.1 % ) treated with enoxaparin and in 28 patients ( 18.0 % ) treated with placebo , corresponding to a relative risk of 0.78 ( 95 % CI , 0.47 to 1.31 ) . No major bleeding occurred . Five patients ( 2.6 % ) in the enoxaparin group and two patients ( 1.0 % ) in the placebo group died during the treatment period . CONCLUSION In this study , no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo . The dose of enoxaparin used in this study proved to be safe . Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication OBJECTIVE Identification of risk factors for bleeding and prospect i ve evaluation of two bleeding risk scores in the treatment of acute venous thromboembolism . DESIGN Secondary analysis of a prospect i ve , r and omized , assessorblind , multicenter clinical trial . SETTING One university and 2 regional teaching hospitals . PATIENTS 188 patients treated with heparin or danaparoid for acute venous thromboembolism . MEASUREMENTS The presenting clinical features , the doses of the drugs , and the anticoagulant responses were analyzed using univariate and multivariate logistic regression analysis in order to evaluate prognostic factors for bleeding . In addition , the recently developed Utrecht bleeding risk score and L and efeld bleeding risk index were evaluated prospect ively . RESULTS Major bleeding occurred in 4 patients ( 2.1 % ) and minor bleeding in 101 patients ( 53.7 % ) . For all ( major and minor combined ) bleeding , body surface area < or = 2 m2 ( odds ratio 2.3 , 95 % CI 1.2 - 4.4 ; p = 0.01 ) , and malignancy ( odds ratio 2.4 , 95 % CI 1.1 - 4.9 ; p = 0.02 ) were confirmed to be independent risk factors . An increased treatment-related risk of bleeding was observed in patients treated with high doses of heparin , independent of the concomitant activated partial thromboplastin time ratios . Both bleeding risk scores had low diagnostic value for bleeding in this sample of mainly minor bleeders . CONCLUSIONS A small body surface area and malignancy were associated with a higher frequency of bleeding . The bleeding risk scores merely offer the clinician a general estimation of the risk of bleeding . In patients with a small body surface area or in patients with malignancy , it may be of interest to study whether limited dose reduction of the anticoagulant drug may cause less bleeding without affecting efficacy The Heparin Study in Internal Medicine ( HESIM ) compares the efficacy and safety of an unfractionated ( UF ) heparin with a low molecular weight ( LMW ) heparin ( CY 216 D ) for prevention of proximal deep vein thrombosis ( DVT ) and pulmonary embolism ( PE ) in medical in patients with a high risk for development of thromboembolism . Patients are r and omized and receive three times daily 5000 IU UF heparin or once daily 3100 IU LMW heparin and two placebo injections subcutaneously for 10 days . All patients are screened for the presence of proximal DVT at day 1 and 10 by real-time B-mode compression sonography and for PE by repeated clinical examinations . Perfusion scintigraphy is used for confirmation of the clinical diagnosis of PE . The study protocol includes a stratified r and omization of patients on admission to the hospital according to one of the following main diagnoses : malignant disease , cardiovascular disease , bronchopulmonary disease , neurologic disease , and other diseases . The present study may serve as a model for further clinical trials in medical in patients using the biometric approach of statistical analysis for proving equivalence of drug efficacy , and to adopt less sensitive but noninvasive methods for the detection of primary endpoints The st and ard treatment of deep vein thrombosis is given by continuous intravenous infusion of unfractionated heparin . This entails hospitalisation , nursing care , immobility and repeated laboratory tests ( e.g. activated partial thromboplastin time [ APTT ] , platelet count ) . In addition approximately 10 % of patients suffer major haemorrhages . The potential advantages of a low molecular weight heparin ( CY 216 ) given subcutaneously were explored in a r and omised trial with blind quantitative evaluation of venograms . The study included 166 patients and both " therapeutic efficacy " and " intention to-treat " analyses showed that subcutaneous CY 216 in fixed doses based only on body weight was more effective on the Arnesen and Marder phlebographic scores than continuous i.v . st and ard heparin with daily dose adjustment according to results of coagulation tests . There was no increase in the risks of pulmonary embolism , haemorrhage or clot extension In order to study whether a low molecular weight heparin ( LMWH ) of mw 4000 D is effective in the treatment of deep venous thrombosis ( DVT ) , patients with DVT verified by phlebography were r and omized to treatment by continuous intravenous infusion of either unfractionated heparin ( UFH ) or LMWH . The initial dose was 240 U ( anti F Xa)/kg/12 h. This study ( study I ) was stopped because of major bleeding in 2 newly operated patients in the LMWH group after 27 patients had been treated . The heparin activity measured as F Xa inhibition assayed in retrospect , was found to be much higher in the LMWH group ( mean 1.6 - 2.0 anti F Xa U/ml ) than in the UFH group ( mean 0.5 - 0.8 anti F Xa U/ml ) . A second study was therefore initiated in which the DVT patients were r and omly given UFH ( 240 U/kg/12 h ) or LMWH only 120 U ( anti F Xa)/kg/12 h , as initial doses ( study II ) . In this study 27 patients could be evaluated , the mean heparin activity still being higher in the LMWH group ( 0.9 - 1.2 anti F Xa U/ml ) than in the UFH group ( 0.5 - 0.7 anti F Xa U/ml ) . A second phlebographic investigation showed progression of thrombus size in 3 ( 11 % ) of the UFH patients of studies I and II ( n = 29 ) and improvement in 14 ( 48 % ) . There was no progression in any LMWH patient , 6 ( 50 % ) had improved in study I and 10 ( 77 % ) in study II . The mean decrease of thrombus size score ( according to Marder ) during treatment did not differ between the 3 groups . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Heparin-induced thrombocytopenia , defined by the presence of heparin-dependent IgG antibodies , typically occurs five or more days after the start of heparin therapy and can be complicated by thrombotic events . The frequency of heparin-induced thrombocytopenia and of heparin-dependent IgG antibodies , as well as the relative risk of each in patients given low-molecular-weight heparin , is unknown . METHODS We obtained daily platelet counts in 665 patients in a r and omized , double-blind clinical trial comparing unfractionated heparin with low-molecular-weight heparin as prophylaxis after hip surgery . Heparin-induced thrombocytopenia was defined as a decrease in the platelet count below 150,000 per cubic millimeter that began five or more days after the start of heparin therapy , and a positive test for heparin-dependent IgG antibodies . We also tested a representative subgroup of 387 patients for heparin-dependent IgG antibodies regardless of their platelet counts . RESULTS Heparin-induced thrombocytopenia occurred in 9 of 332 patients who received unfractionated heparin and in none of 333 patients who received low-molecular-weight heparin ( 2.7 percent vs. 0 percent ; P = 0.0018 ) . Eight of the 9 patients with heparin-induced thrombocytopenia also had one or more thrombotic events ( venous in 7 and arterial in 1 ) , as compared with 117 of 656 patients without heparin-induced thrombocytopenia ( 88.9 percent vs. 17.8 percent ; odds ratio , 36.9 ; 95 percent confidence interval , 4.8 to 1638 ; P < 0.001 ) . In the subgroup of 387 patients , the frequency of heparin-dependent IgG antibodies was higher among patients who received unfractionated heparin ( 7.8 percent , vs. 2.2 percent among patients who received low-molecular-weight heparin ; P = 0.02 ) . CONCLUSIONS Heparin-induced thrombocytopenia , associated thrombotic events , and heparin-dependent IgG antibodies are more common in patients treated with unfractionated heparin than in those treated with low-molecular-weight heparin The primary objective of this retrospective study was to describe the frequency of a post-thrombotic syndrome in 265 patients previously treated for deep venous thrombosis ( DVT ) . The secondary objectives were to document the frequency of recurrent venous thromboembolism ( VTE ) and mortality , especially from malignant disease . The patients were evaluated 5 - 14 years after inclusion in three r and omized trials comparing continuous intravenous ( i.v . ) infusion of unfractionated heparin ( UFH ) ( n = 85 ) with a low molecular weight heparin ( LMWH ) , dalteparin ( n = 180 ) . The median post-thrombotic score at follow-up was 2 ( range 0 - 8 ) . In a multiple step-wise regression analysis the postthrombotic score was significantly higher among patients with initial proximal DVT ( p = 0.0001 ) as compared with those who had distal DVT . A recurrent venous thromboembolic event was diagnosed in 29.4 % of the patients treated with dalteparin and in 23.5 % of the patients treated with UFH ( ns ) . A secondary risk factor for venous thromboembolism and a longer duration of treatment with oral anticoagulants ( OAC ) were significantly associated with a lower risk for recurrent VTE , whereas malignant disease diagnosed during follow-up was associated with a higher risk . During follow-up a total of 40.7 % of patients had died . No difference in total mortality or mortality from malignant disease was demonstrated between the two drugs . In conclusion , a severe post-thrombotic syndrome occured relatively infrequent . considering the long observation period . Proximal DVT was significantly associated with a more severe post-thrombotic syndrome . After 14 years follow-up , no significant differences were observed in overall mortality , mortality from malignant disease or recurrent VTE between UFH- and dalteparin-treated patients . Malignant disease was a risk factor for recurrent VTE , the presence of a secondary risk factor and a longer duration of treatment with OAC decreased the risk for recurrent VTE In a prospect i ve multicenter trial , 149 consecutive patients with phlebographically proven proximal and /or distal deep vein thrombosis of the leg were r and omly allocated to receive subcutaneously for 10 days either low molecular weight heparin CY 216 ( Fraxiparine ) in a fixed dose or unfractionated heparin ( UFH ) in doses adjusted according to the activated partial thromboplastin time . Pre- and post-treatment phlebograms were assessed blindly using the Arnesen 's score system in 134 patients available for analysis of the treatment efficacy . The mean phlebographic score after 10 days of treatment was significantly decreased in both groups ( p less than 0.001 ) in comparison with the baseline score but the difference in score changes between the two groups was not statistically significant . There was an improvement in 45/68 patients ( 66 % ) in the Fraxiparine group and in 32/66 patients ( 48 % ) in the UFH group , and an increase in the thrombus size in 10/68 ( 15 % ) and 12/66 ( 18 % ) , respectively . One symptomatic non-fatal pulmonary embolism and one major bleeding episode were observed in the UFH group . During a follow-up period of 3 months , two rethromboses had occurred in the UFH group and none in the Fraxiparine group . It is concluded that subcutaneous fixed dose Fraxiparine is safe and at least as effective as subcutaneous adjusted UFH in the treatment of deep vein thrombosis AIM The aim of this study was to compare the efficacy and safety of enoxaparin and intermittent pneumatic compression ( IPC ) for venous thromboembolism ( VTE ) prevention in Japanese surgical patients with gynecologic malignancy . MATERIAL AND METHODS Patients ≥ 40 years old undergoing major surgery for gynecologic malignancy without preoperative VTE were included . Written informed consent was obtained . Enrolled patients received IPC immediately before surgery . After surgery , they were r and omly assigned to either an enoxaparin group or an IPC-alone group . The enoxaparin group received enoxaparin injection ( 20 mg , subcutaneous , every 12 h ) from postoperative day 2 to 8 . IPC was discontinued after the first injection . In the IPC-alone group , IPC was continued until full ambulation . The primary end-point was incidence of VTE , including pulmonary embolism and deep vein thrombosis , regardless of symptoms . An interim analysis was to be conducted when the first 30 patients had completed the study protocol . A Data and Safety Monitoring Board was established for making recommendation on the continuation or termination of the study based on the interim results . RESULTS At the time of the interim analysis , six cases of VTE were found : five in the IPC-alone group and one in the enoxaparin group ( Fisher 's exact test , P = 0.08 ) . Three patients in the IPC-alone group developed pulmonary embolism , but none in the enoxaparin group did so ( Fisher 's exact test , P = 0.10 ) . The study was terminated following the Data and Safety Monitoring Board 's recommendation . CONCLUSION Enoxaparin might have lowered the risk of VTE among surgical patients with gynecologic malignancy . Further studies are necessary to confirm this OBJECTIVE To categorize the challenges in determining the extent of missing participant data in r and omized trials and suggest potential solutions for systematic review authors . STUDY DESIGN AND SETTING During the process of updating a series of Cochrane systematic review s on the topic of anticoagulation in patients with cancer , we identified challenges and used an iterative approach to improve , and a consensus process to agree on the challenges identified , and to suggest potential ways of dealing with them . The five systematic review s included 58 trials and 75 meta-analyses for patient-important dichotomous outcomes with 27,037 r and omized participants . RESULTS We identified three categories of challenges : ( 1 ) Although systematic review ers require information about missing data to be reported by outcome , trialists typically report the information by participant ; ( 2 ) It is not always clear whether the trialists followed up participants in certain categories ( e.g. , noncompliers ) , that is , whether some categories of participants did or did not have missing data ; ( 3 ) It is not always clear how the trialists dealt with missing data in their analysis ( e.g. , exclusion from the denominator vs. assumptions made for the numerator ) . We discuss potential solutions for each one of these challenges and suggest further research work . CONCLUSION Current reporting of missing data is often not explicit and transparent , and although our potential solutions to problems of suboptimal reporting may be helpful , reliable and valid characterization of the extent and nature of missing data remains elusive . Reporting of missing data in trials needs further improvement In the initial treatment of venous thromboembolism ( VTE ) fondaparinux , a pentasaccharide , is a good alternative to heparin . Whether this is also true for cancer patients is unknown . We performed two post-hoc analyses of two r and omized studies to compare efficacy , safety and overall survival of fondaparinux to st and ard initial ( low-molecular-weight ) heparin ( LMWH ) treatment in cancer patients with venous thromboembolism . Two hundred thirty-seven cancer patients with deep venous thrombosis ( DVT ) were initially treated with fondaparinux or enoxaparin . Two hundred forty cancer patients with pulmonary embolism ( PE ) received fondaparinux or unfractionated heparin . The initial treatment was followed by vitamin K antagonists . In DVT patients , the three-month recurrence rate was 5.4 % in the enoxaparin recipients compared to 12.7 % in those treated with fondaparinux [ absolute difference 7.3 % , 95 % CI 0.1 , 14.5 ] . A recurrence was observed in 8.9 % of the PE patients treated with fondaparinux compared to 17.2 % in the unfractionated heparin recipients [ absolute difference -8.3 , 95 % CI -16.7 , 0.1 ] . In both studies no difference in bleeding and overall survival was observed . Regarding overall survival and bleeding fondaparinux is comparable to enoxaparin and unfractionated heparin in cancer patients . No significant differences in recurrent VTE were observed when comparing fondaparinux with unfractionated or LMWH . Because of study limitations these results should be considered hypothesis-generating Venous thromboembolic disease causes significant morbidity and mortality in both hospitalized and nonhospitalized patients . The mean annual incidence in the United States is 48 per 100 000 for deep venous thrombosis and 23 per 100 000 for pulmonary embolism , according to an epidemiologic study conducted in Massachusetts ( 1 ) . A similar study in Sweden showed an annual incidence of 160 new cases of deep venous thrombosis per 100 000 inhabitants ( 2 ) . Five to 10 days of unfractionated heparin is a common recommended initial treatment for deep venous thrombosis . This treatment maintains the activated partial thromboplastin time above 1.5 times its control value ( 3 , 4 ) , as calibrated by protamine titration or an antifactor Xa assay . Another recommended initial treatment is 5 to 10 days of weight-adjusted low-molecular-weight heparin followed by at least 3 months of oral anticoagulant therapy ( 3 - 7 ) . Low-molecular-weight heparins are now frequently being used in place of unfractionated heparin for both prevention and treatment of venous thromboembolism ( 3 , 8) . R and omized trials and meta-analyses have shown subcutaneously administered low-molecular-weight heparins to have antithrombotic efficacy equal to ( 9 - 12 ) or greater than ( 13 - 16 ) that of continuously infused unfractionated heparin in the initial treatment of deep venous thrombosis and equal to that of unfractionated heparin in the treatment of pulmonary embolism ( 17 , 18 ) . However , many of these studies enrolled small numbers of patients ( 9 - 13 , 15 , 16 ) , used primarily venographic plethysmographic or scintigraphic end points ( 9 - 11 , 13 , 16 ) , and sometimes excluded patients with pulmonary embolism ( 11 , 15 ) . Most trials of twice-daily low-molecular-weight heparin adjusted treatment regimens according to patient weight without laboratory monitoring . However , several studies suggest that once-daily weight-adjusted dosage of a low-molecular-weight heparin is as effective in the treatment of proximal deep venous thrombosis as adjusted dosages of intravenous unfractionated heparin ( 14 , 19 ) or twice-daily low-molecular-weight heparin ( 20 ) . Since low-molecular-weight heparins differ in their physicochemical and pharmacologic characteristics , study results that apply to one can not be extended to another ( 21 , 22 ) . We conducted the present study to determine whether enoxaparin administered subcutaneously once or twice per day is as effective as continuously infused unfractionated heparin in the treatment of patients with acute , symptomatic venous thromboembolic disease . Methods Study Description This parallel-group , r and omized , partially blinded , international , multicenter clinical trial compared continuously infused unfractionated heparin ( adjusted to maintain activated partial thromboplastin time within a defined range ) with two weight-adjusted dosages of enoxaparin administered subcutaneously once or twice daily . The study was conducted in 74 hospitals in 16 countries , including the United States , several European countries , Australia , and Israel , and was approved by the institutional review board or ethics committees at each location . Written informed consent was obtained from each patient . Four committees participated in this study : an Advisory Committee ; an Outcome Adjudication Committee , which provided blinded outcome assignments for incidence of recurrent venous thromboembolic disease , major or minor hemorrhage , immune thrombocytopenia , and cause of death ; an independent Safety Committee ; and a Vascular Imaging Committee , which review ed all baseline venograms and all vascular imaging studies in a blinded manner to determine whether deep venous thrombosis was present at baseline and whether objective evidence of recurrence existed . Patient Characteristics Patients were required to be at least 18 years of age and willing to remain hospitalized during r and omized therapy . The primary inclusion criteria were symptomatic lower-extremity deep venous thrombosis confirmed by venography or ultrasonography ( if venography was inconclusive ) , symptomatic pulmonary embolism confirmed by high-probability ventilationperfusion scanning , or positive pulmonary angiography with confirmation of lower-extremity deep venous thrombosis . All eligible patients underwent baseline lung scanning or angiography . Exclusion criteria were more than 24 hours of previous treatment with heparin or warfarin ; need for thrombolytic therapy ; known hemorrhagic risk , including active hemorrhage , active intestinal ulcerative disease , known angiodysplasia , or eye , spinal , or central nervous system surgery within the previous month ; renal insufficiency ( serum creatinine concentration>180 mol/L [ 2.03 mg/dL ] ) ; severe hepatic insufficiency ; allergy to heparin , protamine , porcine products ( both heparin and enoxaparin are derived from pork intestinal mucosa ) , iodine , or contrast media ; history of heparin-associated thrombocytopenia or heparin- or warfarin-associated skin necrosis ; treatment with other investigational therapeutic agents within the previous 4 weeks ; inferior vena cava interruption ; or known pregnancy or lactation . Treatments Within each center , consecutive eligible patients were r and omly assigned sequentially to one of three treatment groups . R and omization was done without stratification in blocks of six , according to ascending r and omization number . The numbers were affixed to sealed treatment kits that contained study medication and were provided by the study sponsor . Patients assigned to enoxaparin received a weight-adjusted subcutaneous dose . Two blinded regimens were tested : 1.0 mg/kg of body weight twice daily or 1.5 mg/kg once daily . Several clinical trials have shown the twice-daily regimen to be effective and safe ( 16 , 23 , 24 ) . The once-daily dosage was chosen on the basis of results of pharmacokinetic studies that showed it to have a suitable pharmacokinetic profile in healthy volunteers and to be well tolerated in the treatment of patients with venous thromboembolism ( 25 , 26 ) . In these previous studies , therapeutic antifactor Xa levels were present for up to 18 hours in both volunteers and patients , and measurable levels were present for up to 24 hours . A total of three injections , study drug and placebo , were given each day to maintain blinding for volume of solutions and frequency of administration . Patients assigned to the nonblinded unfractionated heparin group received an intravenous bolus dose and infusion on the basis of an approved institution-specific nomogram . In most cases , administration was as follows : Six hours after the initial bolus , the activated partial thromboplastin time was measured and the dose was adjusted to maintain the specified value , which was between 55 and 80 seconds in most centers ( 4 - 7 ) . Activated partial thromboplastin time was measured at least daily during unfractionated heparin treatment . Enoxaparin and heparin treatments were continued for at least 5 days , and warfarin was started within 72 hours of initial study drug administration . Forty-three patients received phenprocoumon in place of warfarin sodium . Prothrombin time was measured daily , and patients could be discharged from the hospital after the international normalized ratio was found to be between 2.0 and 3.0 on 2 consecutive days . Oral anticoagulation was continued for at least 3 months . Study Assessment s Observers who were aware of treatment assignment assessed patients daily and monthly during the 3-month follow-up for worsening or recurrence of deep venous thrombosis or pulmonary embolism , hemorrhage , adverse events , changes in concomitant medications and adequacy of warfarin use , and warfarin adherence . For patients receiving unfractionated heparin , adherence was defined as an activated partial thromboplastin time within or above the therapeutic range on the second day of treatment . For patients receiving enoxaparin , adherence was defined as at least 10 doses of study medication given with no dosing errors . Adherence to warfarin therapy was defined as having at least one international normalized ratio value greater than or equal to 2.0 between day 4 and the last dose of study treatment during the initial treatment period . These definitions of treatment adherence were established before the analysis of the study outcomes . Efficacy Analysis The efficacy analysis was performed on two study sample s : all treated patients , who received at least one dose of study medication , and evaluable patients , which excluded all patients who met at least one of the criteria for nonevaluability . These criteria were no confirmed deep venous thrombosis at baseline , insufficient study therapy , placement of an inferior vena cava filter , two r and om assignments , and no 3-month follow-up . Insufficient study therapy was defined as one or more missed enoxaparin doses among at least eight consecutive enoxaparin doses or less than 4 consecutive days of heparin infusion . The definition of insufficient study therapy was established before analysis of study outcomes . These two study sample s were analyzed to strengthen the conclusion of equivalence among the treatment groups . The homogeneity of the results of the two analyses is considered to be more supportive of the conclusion of equivalence than the results of either analysis alone . Primary clinical end points were recurrent deep venous thrombosis or pulmonary embolism within 3 months of r and omization . Patients with symptoms of recurrent thrombosis underwent confirmatory testing with venography , ultrasonography , or both . Patients presenting with signs or symptoms of pulmonary embolism underwent lung perfusion scanning , pulmonary angiography , or both . Clinical symptoms and supportive findings on objective tests ; extension of existing thrombi or new thrombi for venography , angiography , or ultrasonography ; or high-probability defect patterns on perfusion scans were required to confirm recurrent thrombosis . Prespecified subgroup analyses were performed on the basis of patient PURPOSE Advanced pancreatic cancer ( APC ) , in addition to its high mortality , accounts for the highest rates of venous thromboembolic events ( VTEs ) . Enoxaparin , a low-molecular weight heparin , is effective in prevention and treatment of VTEs . Some small studies have indicated that this benefit might extend to patients with cancer . PATIENTS AND METHODS Patients with histologically proven APC were r and omly assigned to ambulant first-line chemotherapy and prophylactic use of enoxaparin or chemotherapy alone to investigate the probable reduction in symptomatic VTEs and the impact on survival . RESULTS A total of 312 patients were recruited as one of the protocol end points was reached . Within the first 3 months , the numbers of symptomatic VTEs were as follows : 15 of 152 patients in the observation group and two of 160 patients in the enoxaparin group ( hazard ratio [ HR ] , 0.12 ; 95 % CI , 0.03 to 0.52 ; χ(2 ) P = .001 ) . The numbers of major bleeding events were as follows : five of 152 patients in the observation arm and seven of 160 patients in the enoxaparin arm ( HR , 1.4 ; 95 % CI , 0.35 to 3.72 ; χ(2 ) P = 1.0 ) . Overall cumulative incidence rates of symptomatic VTEs were 15.1 % ( observation ) and 6.4 % ( enoxaparin ; HR , 0.40 ; 95 % CI , 0.19 to 0.83 ; P = .01 ) . Progression-free ( HR , 1.06 ; 95 % CI , 0.84 to 1.32 ; P = .64 ) and overall survival ( HR , 1.01 ; 95 % CI , 0.87 to 1.38 ; P = .44 ) did not differ between groups . CONCLUSION This study demonstrates the high efficacy and feasibility of primary pharmacologic prevention of symptomatic VTEs in out patients with APC . Treatment efficacy was not affected by simultaneous treatment with enoxaparin in this trial setting Background —Considerable variability exists in the use of pharmacological thromboprophylaxis among acutely ill medical patients , partly because clinical ly relevant end points have not been fully assessed in this population . We undertook an international , multicenter , r and omized , double-blind , placebo-controlled trial using clinical ly important outcomes to assess the efficacy and safety of dalteparin in the prevention of venous thromboembolism in such patients . Methods and Results — Patients ( n=3706 ) were r and omly assigned to receive either subcutaneous dalteparin 5000 IU daily or placebo for 14 days and were followed up for 90 days . The primary end point was venous thromboembolism , defined as the combination of symptomatic deep vein thrombosis , symptomatic pulmonary embolism , and asymptomatic proximal deep vein thrombosis detected by compression ultrasound at day 21 and sudden death by day 21 . The incidence of venous thromboembolism was reduced from 4.96 % ( 73 of 1473 patients ) in the placebo group to 2.77 % ( 42 of 1518 patients ) in the dalteparin group , an absolute risk reduction of 2.19 % or a relative risk reduction of 45 % ( relative risk , 0.55 ; 95 % CI , 0.38 to 0.80 ; P=0.0015 ) . The observed benefit was maintained at 90 days . The overall incidence of major bleeding was low but higher in the dalteparin group ( 9 patients ; 0.49 % ) compared with the placebo group ( 3 patients ; 0.16 % ) . Conclusions —Dalteparin 5000 IU once daily halved the rate of venous thromboembolism with a low risk of bleeding The aim of the study was to compare the efficacy and safety of once-daily subcutaneous injection of dalteparin , a low molecular weight heparin , with that of intravenous unfractionated heparin in the treatment of deep venous thrombosis ( DVT ) . Patients were included if they had deep venous thrombosis distal to inguinal ligament and were r and omised either before , if it was considered necessary , or after phlebographic verification of the diagnosis . There was no pre- inclusion treatment with unfractionated heparin . One hundred and twenty patients received dalteparin , administered subcutaneously once-daily at a fixed dose of 200 IU anti-factor Xa/kg , and 133 patients received a continuous intravenous infusion of unfractionated heparin ( UFH ) . Oral anticoagulation was started on the first or second day , and initial treatment with dalteparin or UFH discontinued when the prothrombin time was in the therapeutic range ( 2 < INR < 3 ) on two consecutive days . Control phlebograms were taken within 4 days , thereafter . There were no significant differences between the two initial treatment groups in improvements in Marder score . Two major bleeding events occurred in the UFH group versus none in the dalteparin group . One patient in each group experienced clinical ly significant pulmonary embolism . During a mean follow-up period of 6.9 + /- 1.5 months , recurrent DVT occurred in four patients in the dalteparin group and in two of the UFH group . These results confirm those of a previous study on dalteparin in the initial treatment of DVT , and suggest that dalteparin administered once-daily at a fixed dose of 200 UI/kg is as effective and well-tolerated as UFH in patients with DVT below the inguinal ligament . The present study also demonstrates that dalteparin can be started as soon as the diagnosis of DVT is suspected and without pre-treatment with UFH . Given that the administration of once-daily subcutaneous injections needs not require a patient to be hospitalised , studies to investigate the possibility of using dalteparin for the initial treatment of DVT in the outpatient setting are warranted BACKGROUND Low-molecular-weight heparin is known to be safe and effective for the initial treatment of patients with proximal deep-vein thrombosis . However , its application to pulmonary embolism or previous episodes of thromboembolism has not been studied . METHODS We r and omly assigned 1021 patients with symptomatic venous thromboembolism to fixed-dose , subcutaneous low-molecular-weight heparin ( reviparin sodium ) or adjusted-dose , intravenous unfractionated heparin . Oral anticoagulant therapy with a coumarin derivative was started concomitantly and continued for 12 weeks . Approximately one third of the patients had associated pulmonary embolism . The outcome events studied over the 12 weeks were symptomatic recurrent venous thromboembolism , major bleeding , and death . We sought to determine whether low-molecular-weight heparin is at least equivalent to unfractionated heparin in patients with venous thromboembolism . RESULTS Twenty-seven of the 510 patients assigned to low-molecular-weight heparin ( 5.3 percent ) had recurrent thromboembolic events , as compared with 25 of the 511 patients assigned to unfractionated heparin ( 4.9 percent ) . The difference of 0.4 percentage point indicates that the two therapies have equivalent value according to our predetermined definition of equivalence . Sixteen patients assigned to low-molecular-weight heparin ( 3.1 percent ) and 12 patients assigned to unfractionated heparin ( 2.3 percent ) had episodes of major bleeding ( P= 0.63 ) , and the mortality rates in the two groups were 7.1 percent and 7.6 percent , respectively ( P=0.89 ) . CONCLUSIONS Fixed-dose , subcutaneous low-molecular-weight heparin is as effective and safe as adjusted-dose , intravenous unfractionated heparin for the initial management of venous thromboembolism , regardless of whether the patient has pulmonary embolism or a history of venous thromboembolism BACKGROUND Enoxaparin sodium ( enoxaparin ) is used worldwide for the prevention of venous thromboembolism ( VTE ) . Registration trials of enoxaparin have been conducted primarily in Caucasian population s , and its preventive use in Japanese patients has yet to be established . To address this , we evaluated the efficacy and safety of postoperative enoxaparin in Japanese patients undergoing surgery for abdominal cancer . METHODS This multicenter , open-label study r and omized 151 Japanese patients undergoing curative surgery for abdominal cancer to enoxaparin 20 mg twice daily for 14 days , started 24 - 36 hours after surgery ( n=113 ) or intermittent pneumatic compression ( IPC ) as a reference ( n=38 ) . IPC was performed at least once in both groups between r and omization and surgery . The primary efficacy endpoint was the incidence of VTE in the modified intention-to-treat ( mITT ) population . The primary safety outcome was the incidence of any bleeding during treatment and follow-up . RESULTS Incidence of VTE was 1.2 % ( 95 % CI , 0.03 - 6.53 % ) ( 1/83 patients ) in the enoxaparin group and 19.4 % ( 95 % CI , 7.45 - 37.47 % ) ( 6/31 patients ) in the IPC group . In the safety population , 10/109 patients in the enoxaparin group ( 9.2 % ; 95 % CI , 4.49 - 16.23 % ) and 3/38 patients in the IPC group ( 7.9 % ; 95 % CI , 1.66 - 21.38 % ) experienced a bleeding event . There were no cases of fatal bleeding or bleeding into any critical organ . CONCLUSIONS These favorable efficacy and safety data support the use of enoxaparin ( 20 mg twice daily for 14 days started 24 - 36 hours after surgery ) in Japanese patients undergoing abdominal or pelvic cancer surgery BACKGROUND Patients undergoing major abdominal surgery are at risk of both bleeding and thrombotic complications and usually receive heparin thromboprophylaxis . PATIENTS AND METHODS Risk factors for perioperative bleeding were examined in 3,809 patients in a double-blind , r and omized trial investigating heparin thromboprophylaxis . The risk factors were modeled by logistic regression , and a risk score was calculated using the significant factors in the model . RESULTS Bleeding was associated with the following factors in the model , given as adjusted odds ratios ( ORa [ 95 % confidence interval ] ) : male sex ( ORa 1.68 [ 1.21 to 2.34 ] P = 0.003 ) , malignancy ( ORa 1.69 [ 1.21 to 2.34 ] P = 0.008 ) , gynecological surgery ( ORa 1.62 [ 1.12 to 2.35 ] P = 0.011 ) , and complex surgery ( ORa 2.7 [ 2.02 to 3.62 ] P < 0.001 ) . The risk of excessive bleeding for 0 , 1 , 2 , and 3 risk factors was 2 % , 6 % , 11 % , and 21 % , respectively . CONCLUSIONS The recognition of patients with these risk factors associated with perioperative bleeding should result in increased vigilance and may lead to modification of surgical and medical therapy OBJECTIVES To compare the efficacy and safety of the low molecular weight heparin ( LMWH ) dalteparin with unfractionated heparin ( UFH ) in the acute treatment of DVT patients who had not previously received UFH . DESIGN An open r and omized multicentre trial with blinded analysis of venograms . SETTING Seven hospitals in Sweden , Finl and and the USA . SUBJECTS A total of 330 patients , of 20 years or older , with suspected DVT , verified using venography . INTERVENTIONS Fixed-dose dalteparin ( 200 IU kg-1 ) given as a once-daily subcutaneous injection , or aPTT adjusted i.v . UFH infusion for 6 to 10 days . MAIN OUTCOME MEASURES Change in Marder score in patients with confirmed DVT and two evaluable venograms ; PE , bleeding events and follow-up . RESULTS Marder scores improved in 51 % ( 95 % CI 42 - 60 % ) of 92 patients treated with dalteparin and in 62 % ( 95 % CI 53 - 70 % ) of 98 patients treated with UFH ( P = 0.152 ) . One dalteparin-treated patient had a PE confirmed by V/Q scan ; another had progressive thrombosis with swelling in the affected limb . Bleeding complications occurred in six patients in each group . One patient treated with dalteparin and five treated with UFH died during the 6-month follow-up period as a result of underlying malignancy or heart disease . The 6-month recurrence rate was low with both treatments ( dalteparin , 3/97 ; UFH , 2/103 ) . CONCLUSIONS Fixed-dose subcutaneous dalteparin given once daily from the start of treatment is of equivalent efficacy and safety to conventional UFH therapy in the routine management of DVT In a multicenter , double-blind clinical trial in 1,968 in patients 1 daily subcutaneous administration of LMW heparin plus 2 placebo injections or 3 x 5,000 IU unfractionated ( UF ) heparin was given for 10 ( 8 - 11 ) days . The primary end point was the incidence of proximal deep-vein thrombosis or pulmonary embolism . Patients were assessed during the study period for development of proximal deep-vein thrombosis by compression sonography at days 1 and 10 and for pulmonary embolism by scintigraphy in symptomatic patients . Aim of the study was to demonstrate the equivalence of both treatment regimens . A total of 1,968 patients were r and omized to receive UF or LMW heparin . Of these , 378 patients were excluded during the study period , so that 780 patients on UF and 810 on LMW heparin were included in the efficacy analysis . Four primary end points were observed with UF and 6 with LMW heparin , demonstrating the equivalence of treatments ( p = 0.012 ) . Additionally , pulmonary embolism was suspected as the cause of death in 6 patients who died during the study ( 3 per treatment group ) . A higher frequency of death ( n = 32 ) was observed in the LMW-heparin group ( p = 0.02 ) particularly documented in a part of the centers . Safety analysis showed a higher frequency of local pruritus , local erythema and subcutaneous hematoma , a higher increase in plasma levels of triglycerides , total cholesterol , alanine aminotransferase and aspartate aminotransferase , and a decrease of antithrombin III in patients receiving UF heparin . A decrease in platelet count ( values ranging between 40,000 and 80,000/microliter ) was observed in 4 patients with UF and in none with LMW heparin . No severe thrombocytopenia was observed . Subcutaneous LMW heparin is as effective as UF heparin for prophylaxis of thromboembolism in bedridden , hospitalized medical patients OBJECTIVES To prospect ively evaluate the safety of postoperative fondaparinux in comparison with low molecular weight heparin in patients undergoing uro-oncological surgery . METHODS The present study was a prospect i ve , single-blind , non-inferiority r and omized trial . A total of 359 patients undergoing surgery for urological malignancy were enrolled from January 2011 to December 2012 . A total of 298 of these patients ( fondaparinux group , 152 ; low molecular weight heparin group , 146 ) were evaluable for the intention-to-treat- analysis . Patients were r and omly assigned to low-dose unfractionated heparin , 5000 units twice daily until postoperative day 1 plus either fondaparinux 2.5 mg once daily or low molecular weight heparin 2000 units twice daily until postoperative day 5 . The primary end-point was postoperative bleeding as by independent review , and the study was powered to show the non-inferiority of fondaparinux versus low molecular weight heparin . The other adverse events were evaluated . D-dimer and soluble fibrin monomer complex levels were measured perioperatively . RESULTS Bleeding occurred in 21 patients ( 12 in the fondaparinux group and 9 in low molecular weight heparin group , respectively ) . No significant differences were detected in the incidence of postoperative bleeding and the other adverse events between the two groups . The D-dimer was elevated on postoperative day 1 in one patient ( 16.6 μg/mL ) . In another patient , the soluble fibrin monomer complex was elevated ( 109 μg/mL ) . CONCLUSIONS Fondaparinux is non-inferior to low molecular weight heparin with respect to risk of bleeding . The favorable safety profile of fondparinux supports its prophylactic use as an alternative to low molecular weight heparin after surgery for urological malignancy BACKGROUND Venous thromboembolism occurs commonly in patients with cancer . Direct oral anticoagulants are non-inferior to conventional anticoagulants for the treatment of venous thromboembolism . We hypothesised that edoxaban , a direct oral inhibitor of activated clotting factor Xa , might be more suitable than conventional anticoagulants in the management of cancer-associated venous thromboembolism . The aim of this study was to assess the efficacy and safety of edoxaban compared with warfarin in a subgroup of patients with cancer enrolled in the Hokusai-VTE trial . METHODS We did a prespecified subgroup analysis in August , 2013 , and a post-hoc analysis of non-inferiority and safety in March , 2016 , of the patients with cancer enrolled in the r and omised , double-blind , double-dummy , multicentre , Hokusai-VTE trial done between Jan 28 , 2010 , and Oct 31 , 2012 . In this study , patients aged at least 18 years with acute symptomatic deep-vein thrombosis or acute symptomatic pulmonary embolism ( with or without deep-vein thrombosis ) were assigned to receive edoxaban 60 mg once per day ( or 30 mg once per day for patients with a creatinine clearance of 30 - 50 mL/min , bodyweight < 60 kg , or who were receiving concomitant treatment with the P-glycoprotein inhibitors quinidine or verapamil ) or warfarin ( dose adjusted to maintain the international normalised ratio between 2·0 and 3·0 ) or placebos for either group for at least 3 months up to 12 months . All patients received initial therapy with open-label enoxaparin or unfractionated heparin for at least 5 days . Edoxoban ( or placebo ) was started after discontinuation of initial heparin ; warfarin ( or placebo ) started concurrently with the study regimen of heparin . In our analysis we examined data for a subgroup of these patients who had a history of cancer or who had been categorised as having active cancer by the study physician at the time of enrolment . Additionally , all patients with a history of cancer were review ed post hoc and categorised according to the presence or absence of active cancer . The primary efficacy outcome was the proportion of these patients with symptomatic recurrent venous thromboembolism during the 12-month study period , analysed in the modified intention-to-treat population , with an upper limit of the CI for the hazard ratio ( HR ) of 1·5 . The principal safety outcome was the proportion of patients who had clinical ly relevant bleeding in the population of patients who received at least one dose of the study drug . This study is registered with Clinical Trials.gov , number NCT00986154 . FINDINGS Of 771 patients with cancer enrolled in the trial , 378 were assigned to edoxaban and 393 to warfarin . Recurrent venous thromboembolism occurred in 14 ( 4 % ) of 378 patients given edoxaban and in 28 ( 7 % ) of 393 patients given warfarin ( hazard ratio [ HR ] 0·53 , 95 % CI 0·28 - 1·00 ; p=0·0007 ) . The upper limit of this 95 % CI did not exceed the non-inferiority margin of 1·5 that was prespecified for the trial . Clinical ly relevant bleeding ( major or non-major ) occurred in 47 ( 12 % ) of 378 patients who received edoxaban and in 74 ( 19 % ) of 393 patients who received warfarin ; HR for clinical ly relevant bleeding 0·64 , 95 % CI 0·45 - 0·92 ; p=0·017 . Major bleeding occurred in ten ( 3 % ) of 378 patients with a history of cancer who received edoxaban and in 13 ( 3 % ) of 393 who received warfarin ( HR 0·80 , 95 % CI 0·35 - 1·83 ) . INTERPRETATION Edoxaban might be as effective as warfarin for the treatment of patients with cancer with venous thromboembolism , and with less clinical ly relevant bleeding . Additional clinical trials of edoxaban versus low-molecular-weight heparin for the treatment of venous thromboembolism in patients with cancer are warranted . FUNDING Daiichi Sankyo Deep vein thrombosis of upper limb is a common complication of CVC in patients with cancer . In these patients the risk factors for CVC-related thrombosis are not completely defined . The purpose of this study was to identify the risk factors for CVC-related thrombosis in patients included in a r and omized , double-blind , placebo-controlled study aim ed at assessing the efficacy and safety of enoxaparin for the prophylaxis of CVC-related thrombosis . CVC-related thrombosis was screened by m and atory venography after 6 weeks of study treatment . A number of patient baseline characteristics were assessed as potential risk factors for CVC-related deep vein thrombosis . Crude associations between risk factors and clinical outcomes were assessed by χ2 test or Fisher ’s exact test . Multiple logistic regression analysis was used to identify independent risk factors . A CVC-related thrombosis was found in 50 out of 310 patients ( 16.1 % ) . At multiple logistic regression analysis , CVC tip misplaced in the upper half of superior vena cava ( OR 4.05 , 95%CI 1.64–10.02 ) , left-sided CVC insertion ( OR 2.29 , 95%CI 1.01–5.51 ) and chest radiotherapy ( OR 7.01 , 95%CI 1.42–34.66 ) were independent risk factors for thrombosis . In addition to these risk factors , the presence of distant metastases ( OR 9.36 , 95%CI 1.53–57.05 ) increased the risk of thrombosis in patients who received placebo . An inadequate position of the CVC tip , left-sided CVC insertion and chest radiotherapy are independent risk factors for CVC-related thrombosis in cancer patients . Patients with distant metastases have an increased risk for thrombosis in absence of antithrombotic prophylaxis |
1,027 | 26,004,350 | From this review the authors concluded that multimodal , st and ardized perioperative gastrectomy care appears feasible , safe and cost effective | This systematic review and meta- analysis was performed to determine the influence of enhanced recovery programmes ( ERPs ) on outcomes after gastric cancer surgery . | 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 . PATIENTS AND METHODS Patients with locally advanced adenocarcinoma of the stomach or esophagogastric junction ( AEG II and III ) were r and omly assigned to preoperative chemotherapy followed by surgery or to surgery alone . To detect with 80 % power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant , 282 events were required . RESULTS This trial was stopped for poor accrual after 144 patients were r and omly assigned ( 72:72 ) ; 52.8 % patients had tumors located in the proximal third of the stomach , including AEG type II and III . The International Union Against Cancer R0 resection rate was 81.9 % after neoadjuvant chemotherapy as compared with 66.7 % with surgery alone ( P = .036 ) . The surgery-only group had more lymph node metastases than the neoadjuvant group ( 76.5 % v 61.4 % ; P = .018 ) . Postoperative complications were more frequent in the neoadjuvant arm ( 27.1 % v 16.2 % ; P = .09 ) . After a median follow-up of 4.4 years and 67 deaths , a survival benefit could not be shown ( hazard ratio , 0.84 ; 95 % CI , 0.52 to 1.35 ; P = .466 ) . CONCLUSION This trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit . Possible explanations are low statistical power , a high rate of proximal gastric cancer including AEG and /or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area ( celiac trunc , hepatic ligament , lymph node at a. lienalis ; D2 ) For patients with gastric cancer deemed curable the only treatment option is surgery , but there is disagreement about whether accompanying lymph-node dissection should be limited to the perigastric nodes ( D1 ) or should extend to regional lymph nodes outside the perigastric area ( D2 ) . We carried out a multicentre r and omised comparison of D1 and D2 dissection . 1078 patients were r and omised ( 539 to each group ) . 26 allocated D1 and 56 allocated D2 were found not to satisfy eligibility criteria ( histologically confirmed adenocarcinoma of the stomach without clinical evidence of distant metastasis ) . Each of the remainder was attended by one of eleven supervising surgeons who decided whether curative resection was possible and , if so , assisted with the allocated procedure . Among the 711 patients ( 380 D1 , 331 D2 ) judged to have curable lesions , D2 patients had a higher operative mortality rate than D1 patients ( 10 vs 4 % , p = 0.004 ) and experienced more complications ( 43 vs 25 % , p < 0.001 ) . They also needed longer postoperative hospital stays ( median 25 [ range 7 - 277 ] vs 18 [ 7 - 143 ] days , p < 0.001 ) . Morbidity and mortality differences persisted in almost all subgroup analyses . While we await survival results , D2 dissection should not be used as st and ard treatment for western patients Objective The authors determined if more radical surgery with extended lymphadenectomy improves the results of gastrectomy in patients with adenocarcinoma of the gastric antrum . Summary Background Data The overall survival in patients with gastric cancer is disappointing . Improved survival has been reported by Japanese authors . Whether this is because of a higher number of early gastric cancers in the Japanese series , different biologic behavior in Asians , or the adoption of radical surgery with lymphadenectomy remains unclear . Methods R1 subtotal gastrectomy with omentectomy and R3 total gastrectomy ( omentectomy , splenectomy , distal pancreatectomy , lymphatic clearance of the celiac axis , and skeletonization of vessels in the porta hepatis ) were evaluated in a prospect i ve , r and omized comparison . Results Fifty-five patients were r and omized—25 to the R1 group and 30 to the R3 group . The two groups were comparable for age , sex , tumor size , TNM stage , and length of follow-up . The R3 group had a longer operating time ( 140 vs. 260 min ; p < 0.05 ) , a greater transfusion requirement ( 0 vs. 2 units , p < 0.05 ) and a longer hospital stay ( 8 vs. 16 days ; p < 0.05 ) ( medians ; Mann-Whitney U test ) . The only postoperative death was in the R3 group and was caused by intra-abdominal sepsis . Fourteen patients in the R3 group developed left subphrenic abscesses . There were no major complications in the R1 group . Overall survival was significantly better in the R1 group ( median survival estimated by Kaplan-Meier method , 1511 vs. 922 days , p < 0.05 , log-rank test ) . Conclusions R3 total gastrectomy can be performed with a low mortality , but it has a high morbidity because of intra-abdominal sepsis . The data do not support the routine use of R3 total gastrectomy for treatment of patients with antral cancer AIM To assess the impact of fast-track surgery ( FTS ) on hospital stay , cost of hospitalization and complications after radical total gastrectomy . METHODS A r and omized , controlled clinical trial was conducted from November 2011 to August 2012 in the Department of Digestive Surgery , Xijing Hospital of Digestive Diseases , the Fourth Military Medical University . A total of 122 gastric cancer patients who met the selection criteria were r and omized into FTS and conventional care groups on the first day of hospitalization . All patients received elective st and ard D2 total gastrectomy . Clinical outcomes , including duration of flatus and defecation , white blood cell count , postoperative pain , duration of postoperative stay , cost of hospitalization and complications were recorded and evaluated . Two specially trained doctors who were blinded to the treatment were in charge of evaluating postoperative outcomes , discharge and follow-up . RESULTS A total of 119 patients finished the study , including 60 patients in the conventional care group and 59 patients in the FTS group . Two patients were excluded from the FTS group due to withdrawal of consent . One patient was excluded from the conventional care group because of a non-resectable tumor . Compared with the conventional group , FTS shortened the duration of flatus ( 79.03 ± 20.26 h vs 60.97 ± 24.40 h , P = 0.000 ) and duration of defecation ( 93.03 ± 27.95 h vs 68.00 ± 25.42 h , P = 0.000 ) , accelerated the decrease in white blood cell count [ P < 0.05 on postoperative day ( POD ) 3 and 4 ] , alleviated pain in patients after surgery ( P < 0.05 on POD 1 , 2 and 3 ) , reduced complications ( P < 0.05 ) , shortened the duration of postoperative stay ( 7.10 ± 2.13 d vs 5.68 ± 1.22 d , P = 0.000 ) , reduced the cost of hospitalization ( 43783.25 ± 8102.36 RMB vs 39597.62 ± 7529.98 RMB , P = 0.005 ) , and promoted recovery of patients . CONCLUSION FTS could be safely applied in radical total gastrectomy to accelerate clinical recovery of gastric cancer patients Summary Controversy still exists on the optimal surgical resection for potentially curable gastric cancer . Much better long-term survival has been reported in retrospective/non-r and omized studies with D2 resections that involve a radical extended regional lymphadenectomy than with the st and ard D1 resections . In this paper we report the long-term survival of patients entered into a r and omized study , with follow-up to death or 3 years in 96 % of patients and a median follow-up of 6.5 years . In this prospect i ve trial D1 resection ( removal of regional perigastric nodes ) was compared with D2 resection ( extended lymphadenectomy to include level 1 and 2 regional nodes ) . Central r and omization followed a staging laparotomy . Out of 737 patients with histologically proven gastric adenocarcinoma registered , 337 patients were ineligible by staging laparotomy because of advanced disease and 400 were r and omized . The 5-year survival rates were 35 % for D1 resection and 33 % for D2 resection ( difference –2 % , 95 % CI = –12%–8 % ) . There was no difference in the overall 5-year survival between the two arms ( HR = 1.10 , 95 % CI 0.87–1.39 , where HR > 1 implies a survival benefit to D1 surgery ) . Survival based on death from gastric cancer as the event was similar in the D1 and D2 groups ( HR = 1.05 , 95 % CI 0.79–1.39 ) as was recurrence-free survival ( HR = 1.03 , 95 % CI 0.82–1.29 ) . In a multivariate analysis , clinical stages II and III , old age , male sex and removal of spleen and pancreas were independently associated with poor survival . These findings indicate that the classical Japanese D2 resection offers no survival advantage over D1 surgery . However , the possibility that D2 resection without pancreatico-splenectomy may be better than st and ard D1 resection can not be dismissed by the results of this trial |
1,028 | 27,112,357 | EN after major abdominal surgery provided better outcomes compared with TPN in patients with gastrointestinal cancer | To clarify the benefits of enteral nutrition ( EN ) versus total parenteral nutrition ( TPN ) in patients with gastrointestinal cancer who underwent major abdominal surgery . | 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 outcomes in the short term . Whether feeding out of hospital is of benefit is unknown . Local experience has identified that between 15 and 20 % of patients required ‘ rescue ’ jejunostomy feeding for nutritional problems and weight loss while at home . This weight loss and poor nutrition may contribute to the detrimental effect on the overall quality of life ( QoL ) reported in these patients . Methods / Design This r and omized pilot and feasibility study will provide preliminary information on the routine use of jejunostomy feeding after hospital discharge in terms of clinical benefits and QoL. Sixty participants undergoing esophagectomy or total gastrectomy will be r and omized to receive either a planned program of six weeks of home jejunostomy feeding after discharge from hospital ( intervention ) or treatment-as-usual ( control ) . The intention of this study is to inform a multi-centre r and omized controlled trial . The primary outcome measures will be recruitment and retention rates at six weeks and six months . Secondary outcome measures will include disease specific and general QoL measures , nutritional parameters , total and oral nutritional intake , hospital readmission rates , and estimates of healthcare costs . Up to 20 participants will also be enrolled in a qualitative sub- study that will explore participants ’ and carers ’ experiences of home tube feeding . The results will be disseminated by presentation at surgical , gastroenterological and dietetic meetings and publication in appropriate peer review journals . A patient-friendly lay summary will be made available on the University of Leicester and the University Hospitals of Leicester NHS Trust websites . The study has full ethical and institutional approval and started recruitment in July 2012.Trial registration UK Clinical Research Network ID # 12447 ( Main study ) ; UKCRN ID#13361 ( Qualitative sub study ) ; Clinical Trials.gov # NCT01870817 ( First registered 28 May 2013 Background : The current trend in postoperative nutrition is to promote a normal oral diet as early as possible . However , postoperative ileus is a frequent and common problem after major abdominal surgery . This study was design ed to investigate whether early enteral nutrition ( EEN ) , as a bridge to a normal diet , can reduce postoperative ileus . Methods : Patients undergoing major rectal surgery for locally advanced primary or recurrent rectal carcinoma ( after neoadjuvant (chemo)-radiation , with or without intraoperative radiotherapy ) were r and omly assigned to EEN ( n = 61 ) or early parenteral nutrition ( EPN , n = 62 ) in addition to an oral diet . Early nutrition was started 8 hours after surgery . Early parenteral nutrition was given as control nutrition to obtain caloric equivalence and minimize confounding . The primary endpoint was time to first defecation ; secondary outcomes were morbidity , other ileus symptoms , and length of hospital stay . Results : Baseline characteristics were similar for both groups . In intention-to-treat analysis , the time to first defecation was significantly shorter in the enteral nutrition arm than in the control arm ( P = 0.04 ) . Moreover , anastomotic leakage occurred significantly less frequently in the enteral group ( 1 patient ) compared with parenteral supplementation ( 9 patients , P = 0.009 ) . Mean length of stay in the enteral group was 13.4 ± 2.2 days versus 16.7 ± 2.3 days in the parenteral group ( P = 0.007 ) . Conclusions : Early enteral nutrition is safe and associated with significantly less ileus . Early enteral nutrition is associated with less anastomotic leakage in patients undergoing extensive rectal surgery Background Enteral immunodiet has been gaining increasing attention , but experimental data of its clinical effects in patients with gastric cancer are inconsistent , contradictory , and poorly investigated . The aim of this study was to assess the impact of early postoperative enteral immunonutrition on clinical and immunological outcomes in a homogeneous group of gastric cancer patients su bmi tted to total gastrectomy . Methods A total of 109 patients with gastric cancer were r and omized to receive early postoperative enteral immunonutrition ( formula supplemented with arginine , omega-3 fatty acids and ribonucleic acid [ RNA ] ) , or an isocaloric – isonitrogenous control . The postoperative outcome was evaluated based on clinical variables , including postoperative infectious complications , anastomotic leak rate , and length of hospitalization . In addition , state of cellular immunity was evaluated and compared between the 2 groups . Results The incidence of postoperative infectious complications in the immunodiet group ( 7.4 % ) was significantly ( p < .05 ) lower than that of the control group ( 20 % ) , as well as the anastomotic leak rate ( 3.7 % in immunodiet group vs 7.3 % in st and ard nutrition group , p < .05 ) . Mortality rate did not show any significant differences ; patients of the immunodiet group were found to have a significantly reduced length of hospitalization ( 12.7 ± 2.3 days ) when compared with st and ard diet group ( 15.9 ± 3.4 days , p = .029 ) . The data on cellular immunity showed that the postoperative CD4 + T-cell counts decreased in both groups , but the reduction in the IED group was significantly higher ( p = .032 ) compared with the SND group . Conclusions Early postoperative enteral immunonutrition significantly improves clinical and immunological outcomes in patients undergoing gastrectomy for gastric cancer OBJECTIVE To explore the optimal postoperative nutritional support in elderly patients with gastric cancer . METHODS One hundred and twenty elderly patients with gastric cancer undergoing radical gastrectomy were prospect ively enrolled from January 2010 to March 2013 and r and omly divided into total parenteral nutrition group(TPN , n=40 ) , early total enteral nutrition group ( TEN , n=40 ) and enteral plus parenteral nutrition group(EN+PN , n=40 ) . Clinical charasteristics including treatment tolerance , nutritional indexes , immune indexes , time to first flatus , incidence of postoperative infection and anastomotic leakage , were analyzed and compared . RESULTS Treatment tolerance in EN+PN group(97.5 % , 39/40 ) was significantly higher than that in TPN group(82.5 % , 33/40 ) and TEN group(80.0 % , 32/40)(both P<0.05 ) . The nutritional indices , including prealbumin , albumin , transferrin , body mass index , and the incidence of anastomotic leakage were similar in the 3 groups(P>0.05 ) . The immune indices , including CD3 , CD4 , CD4/CD8 , were significantly reduced after operation in each group . However , they were significantly higher in EN+PN group and TEN group than those in TPN group(both P<0.05 ) . Furthermore , compared to the TPN group , the incidence of postoperative infection(surgical site infection , pulmonary infection , abdominal infection ) was significantly lower and time to first flatus was significantly shorter in EN+PN group and TEN group . CONCLUSIONS Early enteral nutrition after gastric cancer surgery is safe , simple and feasible . EN plus PN is the best way to administer postoperative nutritional support in elderly patients with gastric cancer OBJECTIVE To evaluate the impact of the route of administration of artificial nutrition and the composition of the diet on outcome . DESIGN Prospect i ve , r and omized , clinical trial . SETTING Department of surgery , university hospital . PATIENTS One hundred sixty-six consecutive patients undergoing curative surgery for gastric or pancreatic cancer . INTERVENTIONS At operation , the patients were r and omized into three groups to receive : a ) a st and ard enteral formula ( control group ; n = 55 ) ; b ) the same enteral formula enriched with arginine , RNA , and omega-3 fatty acids ( enriched group ; n = 55 ) ; and c ) total parenteral nutrition ( TPN group ; n = 56 ) . The three regimens were isocaloric and isonitrogenous . Enteral nutrition was started within 12 hrs following surgery . The infusion rate was progressively increased to reach the nutritional goal ( 25 kcal/kg/day ) on postoperative day 4 . MEASUREMENTS AND MAIN RESULTS Tolerance of enteral feeding , rate and severity of postoperative complications , and length of hospital stay were recorded . Early enteral infusion was well tolerated . Side effects were recorded in 22.7 % of the patients , but only 6.3 % did not reach the nutritional goal . The enriched group had a lower severity of infection than the parenteral group ( 4.0 vs. 8.6 ; p < .05 ) . In subgroups of malnourished ( n = 78 ) and homologous transfused patients ( n = 42 ) , the administration of the enriched formula significantly reduced both severity of infection and length of stay compared with the parenteral group ( p < .05 ) . Moreover , in transfused patients , the rate of septic complications was 20.0 % in the enriched group , 38.4 % in the control group , and 42.8 % in the TPN group . CONCLUSIONS Early enteral feeding is a suitable alternative to TPN after major abdominal surgery . The use of the enriched diet appears to be more beneficial in malnourished and transfused patients BACKGROUND / AIMS Early enteral nutrition ( EEN ) has benefits in reducing infectious complication , length of stay ( LOS ) and preserving liver function . There are few data about the effect of EEN in the patients who had total gastrectomy . The aim of this r and omized and prospect i ve study was to evaluate the effect of EEN after total gastrectomy on nutritional status , liver function , complications and LOS , compared to total parenteral nutrition ( TPN ) in patients with gastric cancer . METHODS Among 56 patients with gastric cancer , 36 and 20 were r and omly assigned to EEN and TPN groups , and finally 17 and 16 completed EEN and TPN schedules , respectively . The nutritional parameters , liver function , LOS and abdominal symptoms were compared between 2 groups on pre-operative day and post-operative 7th day . RESULTS There was no significant difference in the nutritional parameters , liver function between EEN and TPN groups . Vomiting and abdominal distention were more frequent in EEN than TPN group ( 2 vs. 0 cases , p=0.485 ; 1 vs. 0 case , p=1.000 , respectively ) , while increased AST , ALT and total bilirubin were more common in TPN than EEN group ( 4 vs. 2 cases , p=0.398 ; 1 vs. 0 case , p=0.485 , respectively without statistical significance ) . LOS was shorter in EEN than TPN group without statistical significance ( 12 vs. 13 days , p=0.289 ) . CONCLUSIONS No significant differences were found in the nutritional status parameters , liver function , complications and LOS between EEN and TPN groups on 7th day after total gastrectomy . Further large scale studies on the advantages and disadvantages of EEN after total gastrectomy are warranted AIM To investigate ( 1 ) the effect of hyperthermic intraoperative intraperitoneal chemotherapy ( HIIC ) on intestinal permeability of patients with advanced gastric cancer and ( 2 ) the protective effect of postoperative enteral nutrition ( EN ) on patients . METHODS All patients were divided r and omly into 3 groups : the EN group , treated with EN during postoperative period ; the EN+HIIC group , treated with HIIC and postoperative EN ; and the PN+HIIC group , treated with HIIC and postoperative parenteral nutrition . The lactulose/mannitol ( L/M ) ratio was used to evaluate the permeability of intestinal mucous . RESULTS Compared with the ratio of L/M on the day before operation ( POD-1 ) , the ratio of L/M on POD+3 increased significantly in all 3 groups ( P < .0001 ) and then decreased gradually . The L/M ratio of the EN and EN+HIIC groups recovered to the baseline on POD+12 . In contrast , the PN+HIIC group still had an elevated L/M ratio until POD+12 . The ratios of L/M in the EN+HIIC group on POD+7 and POD+12 were significantly different from those of the PN+HIIC group ( 0.0855 ± 0.0462 vs 0.1298 ± 0.063 , P = .007 ; 0.0336 ± 0.0235 vs 0.0616 ± 0.0430 , P = .038 , respectively ) . CONCLUSION Gastric cancer radical resection result ed in a significant increase in intestinal permeability . HIIC aggravated the injury of intestinal mucous permeability , which could be reversed by EN PURPOSE The aim of this study was to determine whether the type of postoperative feeding , glutamine-supplemented parenteral nutrition or enteral immunonutrition , can modify morbidity and outcome in malnourished cancer patients undergoing major surgery in the gastrointestinal tract . PATIENTS AND METHODS Twenty-nine consecutive malnourished patients undergoing major elective surgery for carcinoma of the stomach ( n=8 ) , pancreas ( n=8 ) , liver ( n=1 ) , and colon ( n=12 ) , were r and omly assigned to receive from the first postoperative day either enteral immunonutrition or glutamine-supplemented parenteral nutrition , for at least 5 consecutive days . Postoperative major and minor morbidity and mortality were recorded . Data analysis was done using the Fisher 's exact test . RESULTS Fifteen patients received glutamine-supplemented parenteral nutrition and 14 received enteral immunonutrition . The overall incidence of postoperative complications was 33.3 % in the parenteral nutrition group versus 50 % in the enteral nutrition group ( p=0.2 ) . Subdividing postoperative complications into different types , the rates of major complications were similar in both groups of patients ( 13.3 and 21.4 % respectively , p=0.4 ) . Similarly , there were no significant differences between the two groups considering minor postoperative noninfectious complications , infectious complications , and mortality . CONCLUSION In malnourished cancer patients undergoing major gastrointestinal surgery , morbidity and mortality are not significantly influenced by the type of postoperative feeding OBJECTIVE To determine the effects of total parenteral nutrition ( TPN ) and enteral nutrition ( EN ) on biochemical and clinical outcomes in pancreatic cancer patients who underwent pancreaticoduodenectomy . METHODS From the year 2006 to 2008 , 60 patients who underwent pancreaticoduodenectomy in Tianjin Third Central Hospital were enrolled in this study . They were r and omly divided into the EN group and the TPN group . The biochemical and clinical parameters were recorded and analyzed between the two groups . RESULTS There was no significant difference in the nutritional status , liver and kidney function , and blood glucose levels between the TPN and EN groups on the preoperative day , the 1st and 3 rd postoperative days . However , on the 7th postoperative day , there was significant difference between the two groups in 24 h urinary nitrogen , serum levels of , total protein ( TP ) , transferrin ( TF ) , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , alkaline phosphatase ( ALP ) , and γ-glutamyl transpeptadase ( GGT ) , blood urea nitrogen ( BUN ) and creatinine ( Cr ) . On the 14th postoperative day , there was a significant difference between the two groups in terms of urinary levels of 24 h nitrogen , TP , TF , retinol binding protein , ALT , AST , ALP , GGT , total bilirubin , direct bilirubin , BUN , Cr , and glucose . The incidence of delayed gastric emptying in the EN and TPN groups was 0 % and 20 % , respectively . Moreover , the incidence of pancreatic fistulas and hemorrhages in the EN group were 3.6 % and 3.6 % , versus 26.7 % and 30 % in the TPN group , respectively . CONCLUSIONS EN is better than TPN for pancreatic cancer patients who received pancreaticoduodenectomy Meeting the increased metabolic dem and s in the critically injured is a continuing challenge . Benefits of early enteral feeding after abdominal trauma have been previously reported , but the frequency of patient intolerance due to GI complaints remains unclear . One hundred twenty-three patients undergoing emergent laparotomy for major abdominal trauma with an abdominal trauma index greater than or equal to 15 were prospect ively r and omized to either a control group ( n = 52 , no enteral nutrition during the first 5 days ) or an enteral-fed group ( n = 71 ) . The enteral group had a needle catheter jejunostomy ( NCJ ) placed at laparotomy and an elemental diet begun 12 h postoperatively , advanced in volume and concentration at 8-h intervals to 100 - 125 ml/h of full-strength diet . Symptoms of GI complaints ( nausea , vomiting , cramping , distention , and diarrhea ) were monitored daily and grade d as minimal , moderate , or significant . Fifty percent of the control group had one or more GI complaints during the study period ; six ( 12 % ) developed moderate discomfort . In the enteral group , 59 ( 83 % ) patients reported some GI discomfort ; 11 had significant complaints ( two nausea , seven cramping , six distention , two diarrhea ) . Nine ( 13 % ) of the enteral-fed patients ultimately required total parenteral nutrition supplementation due to GI complaints . The remaining 62 ( 87 % ) enteral patients were maintained on the elemental diet for a mean of 7 days ( range 5 to 20 ) . By postoperative day 5 , patients received an average of 35 kcal/kg and 14.5 g N/day ; 66 % ( 41/62 ) were in positive N balance . ( ABSTRACT TRUNCATED AT 250 WORDS HYPOTHESIS Immediate enteral feeding following major abdominal surgery reduces postoperative complications and mortality when compared with parenteral nutrition . DESIGN A prospect i ve multicenter r and omized trial . SETTING A university hospital department of digestive surgery . PATIENTS AND INTERVENTIONS Two hundred forty-one malnourished patients undergoing major elective abdominal surgery were r and omly assigned to receive , after surgery , either enteral ( enteral nutrition group : 119 patients ) or parenteral nutrition ( total parenteral nutrition group : 122 patients ) . The patients were monitored for postoperative complications and mortality . RESULTS The rate of major postoperative complications was similar in the enteral and parenteral groups ( enteral nutrition group : 37.8 % ; total parenteral nutrition group : 39.3 % ; P was not significant ) , as were the overall postoperative mortality rates ( 5.9 % and 2.5 % , respectively ; P was not significant ) . CONCLUSION The present study failed to demonstrate that enteral feeding following major abdominal surgery reduces postoperative complications and mortality when compared with parenteral nutrition OBJECTIVE To study the effect of the route of delivery and formulation of postoperative nutritional support on host defense , protein metabolism , infectious complications , and outcome . DESIGN Prospect i ve , r and omized , clinical trial . SETTING Department of Surgery at a university hospital . PATIENTS Two hundred sixty c and i date s for pancreaticoduodenectomy or gastrectomy for cancer . INTERVENTIONS Patients were r and omly allocated into 3 groups during surgery . Starting 6 hours after operation , the first group received a st and ard enteral formula ( st and ard group ; n = 87 ) ; the second , the same enteral formula enriched with arginine , omega-3 fatty acids , and RNA ( immunonutrition group ; n = 87 ) ; and the third , total parenteral nutrition ( parenteral group ; n = 86 ) . The 3 regimens were isocaloric and isonitrogenous . The nutritional goal was 105 kJ/kg per day . MAIN OUTCOME MEASURES Immune response by phagocytosis ability of polymorphonuclear cells , interleukin (IL)-2 receptor levels , and delayed hypersensitivity response ; protein synthesis by IL-6 and prealbumin ; tolerance of enteral feeding ; incidence of postoperative complications ; and length of hospital stay . RESULTS The immunonutrition group had a significantly better recovery of the immune parameters on postoperative day 8 compared with the other groups . Linear regression analysis showed an inverse correlation between IL-6 and preambulin levels ( r = 0.766 ) only in the immunonutrition group . Only 11 patients ( 6.3 % ) in both enteral groups did not reach the nutritional goal . Postoperative infection rate was 14.9 % ( 13/87 ) in the immunonutrition group , 22.9 % ( 20/87 ) in the st and ard group , and 27.9 % ( 24/86 ) in the parenteral group ( P = .06 ) . Mean + /- SD length of hospital stay was 16.1 + /- 6.2 , 19.2 + /- 7.9 , and 21.6 + /- 8.9 days in the immunonutrition , st and ard , and parenteral groups , respectively ( P = .01 vs st and ard group ; P = .004 vs parenteral group ) . CONCLUSIONS Early postoperative enteral feeding is a valid alternative to parenteral feeding in patients undergoing major surgery . Immunonutrition enhances the host response , induces a switch from acute-phase to constitutive proteins , and improves outcome Bacterial translocation from the gut may be the primary event in many disease processes . The purpose of this study was to examine the route of nutrient administration on bacterial translocation from the gut . Each of 90 female Fischer rats underwent placement of a central venous catheter and was r and omized to one of three groups . Group I ( control ) received food and water ad libitum . Group II received st and ard TPN solution orally from a bottle sipper and drank the solution ad libitum . Group III underwent TPN via the central catheter by pair feeding of the animals with group II . Animals were fed for 2 weeks , and liver , spleen , mesenteric lymph nodes , blood , and cecum were aseptically obtained for culture . A statistically significant difference ( p less than 0.014 ) was found between translocation rates of parenterally fed animals compared with enterally fed animals . Two thirds of the animals ( 18/27 ) fed parenterally had culture-positive mesenteric lymph nodes compared with one third ( 9/27 ) of the enterally fed group and none ( 0/30 ) of the control group . A statistically significant increase in the cecal bacterial count was demonstrated in the animals fed the TPN solution , independent of route . Parenteral nutrition promotes bacterial translocation from the gut by increasing the cecal bacterial count and impairing intestinal defense OBJECTIVE To evaluate the benefits of reducing insulin resistance by early enteral nutrition ( EEN ) in gastric cancer patients after surgery . METHODS Gastric cancer patients were managed to r and omly accept traditional total parenteral nutrition ( group A ) or EEN ( group B ) after surgical treatment . The patients in group B were fed by tubes with 250 - 500 mL 5 % sodium chloride and glucose injection at 24 h post-surgery , and were fed enteral nutritional emulsion with constant infusion by pump slowly increasing from 20 mL/h to 100 mL/h from 48 h , and then transiting to total enteral nutrition . Insulin sensitivity of patients was detected by Quicki method before operation and at 24 h , 48 h , 72 h , 120 h and 168 h post-surgery . RESULTS A total of 77 patients were enrolled , with 42 patients in group A , and 35 patients in group B. Baseline characteristics , biochemical indexes and operational characteristics were well balanced between two groups . The time-insulin sensitivity curves of the two groups indicated that IR was present early ( day 1 to day 7 ) in gastric cancer patients and was significantly different between patients who had undergone surgical treatment and those who had not . Insulin sensitivity ( SI ) of patients in group B were higher than patients in group A with adjusting BMI , age and SI preoperative at 72 h , 120 h and 168 h post-surgery . CONCLUSIONS The management of EEN can alleviate insulin resistance in gastric cancer patients with surgical treatment Cancer surgery is a major challenge for patients to develop immune depression in postoperative period . Several cytokines can depress immune cell sub population s. Increased cytokine response after surgery is assumed to arise mainly from lipooxygenase pathway acting on membrane arachidonic acid . Therefore ; investigators focused their efforts to alter the membrane fatty acid profile by changing the nutritional regimen with epsilon-3 fatty acid supplementation and encouraging results were obtained after surgery . Despite the theoretical and clinical advantage of enteral nutrition many surgeons remain committed to parenteral nutrition for feeding of patients due to maintain bowel rest and fear of anastomosis leakage at the postoperative period . Several studies investigating role of the postoperative immunonutrition reported that beneficial immunological changes were associated with reduction of infectious complications . Interestingly ; these findings were observed at least five days after the surgery in which the highest incidence of complications was seen . In this prospect i ve study including 42 patients eligible for curative gastric or colon cancer surgery ; we investigated the beneficial effect of enteral immunonutrition ( EEN ) compared to total parenteral hyperalimentation ( TPN ) beginning from the preoperative period . Cortisol and CRP levels as stress parameters significantly increased one day after surgery in both groups but they rapidly returned to ( on POD1 ) preoperative baseline level in EEN group whereas these values remained high in the TPN group . Additionally a significant decrease in natural killer ( NK ) cells and CD8 + levels were observed in both groups . However they recovered on POD3 in EEN group and on POD6 in TPN group . CD4 + subset remained almost same as preoperative value in the TPN group whereas it increased from ( % ) 40.14 to 46.40 , 51.29 and 54.7 on PO 6th hr , POD3 and POD6 in the EEN group . Our findings suggest that preoperative nutrition via the enteral route provided better regulation of postoperative immune system restoration than parenteral nutrition . On the basis of our findings we recommend enteral immunonutrition to be started at the preoperative period rather than postoperatively before a major operation whenever the enteral route is feasible AIM To investigate the effect of early postoperative enteral nutrition enriched with arginine , RNA and omega-3 fatty acids on immunological and nutritional variables after elective curative operations for gastric or pancreatic cancer . DESIGN R and omised controlled trial . SETTING University hospital , Italy . SUBJECTS 78 Consecutive patients who were to undergo curative operations for gastric or pancreatic cancer , 60 of whom were suitable for the study . INTERVENTIONS Patients were r and omly allocated to three groups ( n = 20 each ) according to the type of postoperative nutritional support : st and ard enteral diet , the same diet enriched with arginine , RNA , and omega-3 fatty acids or total parenteral nutrition . The daily nutritional goal was 25 kcal ( 105 kJ)/kg and 0.25 g nitrogen/kg for all patients . MAIN OUTCOME MEASURES Serum concentrations of immunoglobulins , albumin , transferrin , prealbumin , retinol binding protein ( RBP ) ; cholinesterase activity , weight loss , duration of operation , operative blood loss ; blood transfusion ; delayed hypersensitivity responses , number of lymphocyte subsets , phagocytic ability of monocytes , number of interleukin-2 ( IL-2 ) plasma receptors , interleukin-6 ( IL-6 ) plasma concentrations , postoperative infections and sepsis scores . RESULTS All enterally fed patients but one completed the nutritional programme . There were significant postoperative reductions in both nutritional and immunological variables in all groups . On postoperative days 4 and 8 prealbumin concentration ( p < 0.05 ) , RBP concentration ( p < 0.05 ) , delayed hypersensitivity responses ( p < 0.05 ) , phagocytic ability of monocytes ( p < 0.01 ) and concentration of IL-2 receptors ( p < 0.009 ) had all recovered more in the group receiving the enriched solution . There was no difference in the postoperative infection rates among the three groups , but the infections were less severe in the enriched group ( p < 0.005 ) . CONCLUSION Early enteral feeding was well tolerated . Patients who received the enriched solution recovered both their nutritional and immunological status quicker than those in the other two groups OBJECTIVE To evaluate the effect of the early postoperative administration of an enriched enteral diet in cancer patients . DESIGN R and omised controlled study . SETTING Surgical intensive care unit of a university hospital . PATIENTS 77 consecutive patients undergoing curative surgery for gastric or pancreatic cancer . INTERVENTIONS Patients were r and omised into 3 groups to receive : a st and ard enteral formula ( n=24 ) ; the same formula enriched with arginine , RNA , and omega-3 fatty acids ( n = 26 ) , isonitrogen isocaloric total parenteral nutrition ( n = 27 ) . Enteral nutrition was started within 12 h following surgery . Infusion rate was progressively increased reaching the full regimen on postoperative day ( POD ) 4 . On admission and on POD 1 and 8 , the following measurements were performed : serum level of total iron-binding capacity , albumin , prealbumin , retinol-binding protein ( RBP ) , and cholinesterase . Delayed hypersensitivity response ( DHR ) , IgG , IgM , IgA , lymphocyte subsets . and monocyte phagocytosis ability were also evaluated . Bioelectrical impedance analysis was performed preoperatively and on POD 2 , 7 , and 11 . The rate and severity of postoperative infections and the length of hospital stay were evaluated . RESULTS In all patients , a significant drop of nutritional and immunologic parameters was observed on POD 1 . A significant increase of prealbumin ( p<0.02 ) , RBP ( p<0.005 ) , monocyte phagocytosis ability ( p<0.001 ) , and DHR ( p<0.005 ) was found on POD 8 only in the group fed with the enriched diet . A significant reduction of severity of postoperative infections and length of postoperative stay was found in the group with the enriched diet compared to the other groups . CONCLUSIONS These data are suggestive of an improvement of the nutritional and immunologic status and clinical outcome in cancer patients who receive an enriched enteral diet in the early postoperative course Background and Aim : Immunomodulating nutrition is supposed to reduce the number of complications and lengthen of hospital stay during the postoperative period in patients after major gastrointestinal surgery . The aim of the study was to assess the clinical effect of immunostimulatory enteral and parenteral nutrition in patients undergoing resection for gastrointestinal cancer in the group of well-nourished patients . Material and Methods : Between June 1 , 2001 , and December 31 , 2005 , a group of 214 well-nourished patients was initially assessed ( 150 men , 64 women , mean age 61.2 years ) to participate in the study . Nine patients were subsequently excluded and the remaining 205 subjects were r and omly assigned in a 2 × 2 factorial design into 4 study groups , ie , st and ard enteral nutrition ( n = 53 ) , immunomodulating enteral nutrition ( n = 52 ) , st and ard parenteral nutrition ( n = 49 ) , and immunomodulating enteral nutrition ( n = 51 ) . The study was design ed to test the hypothesis that immunonutrition and enteral nutrition would reduce the incidence of infectious complications after upper gastrointestinal surgery ; the secondary objective of the study was to evaluate the effect of nutritional intervention on overall morbidity and mortality rates , and hospital stay . The study was registered in the Clinical Trials Data base – number NCT 00558155 . Results : The overall morbidity rate was 33 % and the incidence of individual complications was comparable between all groups . Infectious complications occurred in 26 of 102 patients given st and ard diets and in 22 of 103 patients receiving immunomodulatory formulas ( odds ratio 0.81 ; 95 % CI , 0.43–1.50 ) . There were no significant differences between infectious complications in patients using parenteral nutrition ( 22 of 100 patients ) and parenteral formulas ( 26 of 105 , odds ratio 1.14 ; 95 % CI , 0.61–2.14 ) . Neither immunostimulating formulas nor enteral feeding significantly affected secondary outcome measures , including overall morbidity and mortality rates , and hospital stay . Conclusions : Our study failed to demonstrate any clear advantage of routine postoperative immunonutrition in patients undergoing elective upper gastrointestinal surgery . Both enteral and parenteral treatment options showed similar efficacy , tolerance , and effects on protein synthesis . Parenteral nutrition composed according to contemporary rules showed similar efficiency to enteral nutrition . However , because of its cost-efficiency , enteral therapy should be considered as the treatment of choice in all patients requiring nutritional therapy OBJECTIVE To evaluate the effect of the combined use of Shenmai Injection ( SMI ) and enteral nutrition on postoperative fatigue syndrome ( POFS ) in patients with gastric cancer ( GC ) . METHODS Fifty-eight GC patients were r and omized into the parenteral nutrition group ( PNG , 19 cases ) , enteral nutrition group ( ENG , 19 cases ) and combined treatment group ( CTG , 20 cases ) . The post-operative recovery in patients was observed ; patients ' conditions of fatigue , mood and sleep were evaluated respectively by visual analogue scale of fatigue , profile of mood states ( POMS ) and Pittsburgh sleep quality index ( PSQI ) . Meanwhile , nutritional variables , such as serum contents of total protein , albumin , pre-albumin , were measured at different time points : before operation ( d0 ) and the 1st , 5th , and 9th day ( d1 , d5 and d9 ) after operation . Immune variables such as subsets of lymphocytes ( CD3 , CD4 , CD8 ) , serum immunoglobulins ( IgG , IgM , IgA ) were also determined . RESULTS Conditions of recovery , POMS and PSQI were better and the postoperative fatigue reduced more significantly in CTG than those in the other two groups ( P < 0.05 ) . On d9 , levels of pre-albumin , CD3 , CD4 , CD4/CD8 in CTG were significantly higher than those in the PNG and ENG ( P < 0.05 ) , meantime , levels of albumin and IgA were higher in CTG than those in PNG ( P < 0.05 ) . CONCLUSION Combined treatment of SMI and enteral nutrition can regulate mood and sleep to some extents , and reduce the postoperative fatigue through improving nutritional status and immune function , thus speeding up the recovery of patients |
1,029 | 25,844,368 | 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 . | BACKGROUND Childhood obesity is a public health concern .
One-third of North American children and youth are overweight or obese .
We review ed the evidence of behavioural and pharmacological weight-management interventions on body mass index ( BMI ) , BMI z-score and the prevalence of overweight and obesity in children and youth . | 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/C ) group , but not in the control/intervention ( C/I ) group . The difference between groups was 0.3 , which was borderline significant ( 95 % confidence interval ( 95 % CI ) −0.62 to 0.02 , P=0.06 ) before adjusting for potential confounding factors . Thirty-three percent of the I/C group and 12 % of the C/I group achieved the target reduction of 0.5 BMI SDS . The I/C group had a significantly greater reduction in the percentage with a BMI above the 99.6th centile at 24 months ( P=0.04 ) and gained 5.7 kg less over the time of the study . There were no significant differences between groups for mean percentage attendance at physical activity sessions ( I/C group=24.1 % , 95 % CI , 15.4–32.9 ; C/I group=31.7 % , 95 % CI , 22.4–41.1 , P=0.229 ) . Conclusions : Children given active intervention followed by body composition monitoring alone reduced their BMI SDS , and fewer children were classified as grossly overweight by the end of the study . If these findings are true , there are important implication s for the provision of services managing overweight in the community OBJECTIVE To evaluate the efficacy of orlistat to enhance weight loss in obese adolescents . METHODS The study was a 6-month r and omized , double-blind , placebo-controlled trial to compare the effects of orlistat ( 120 mg orally 3 times a day ) and placebo on reduction of body mass index ( BMI ) . Forty adolescents between 14 and 18 years of age with a mean BMI of 40 kg/m2 entered the protocol between December 2002 and February 2003 . Study subjects stayed overnight in the General Clinical Research Center , during which dietary records were review ed and lifestyle recommendations were given . The study participants received either orlistat ( 120 mg orally 3 times a day ) or placebo and were assessed monthly for 6 months . At 0 , 3 , and 6 months , fasting laboratory tests were performed . The primary end point was the change in BMI from baseline to 6 months . Secondary outcomes included changes in weight , lean body mass , and results of blood chemistry studies . RESULTS No statistically significant difference was noted between the 2 study groups for decrease in BMI from baseline to 6 months ( P = 0.39 ) . The decrease in BMI within the orlistat group ( -1.3 + /- 1.6 kg/m2 ; P = 0.04 ) and within the placebo group ( -0.8 + /- 3.0 kg/m2 ; P = 0.02 ) , however , was statistically significant . Laboratory measurements did not differ between the 2 groups . In comparison with the placebo group , the orlistat group had increased adverse events , primarily gastrointestinal symptoms and findings . CONCLUSION In this study of obese adolescents , orlistat did not significantly reduce BMI in comparison with placebo at 6 months CONTEXT The negative effects of childhood overweight and obesity on quality of life ( QOL ) have been shown in clinical sample s but not yet in population -based community sample s. OBJECTIVE To determine relationships between weight and health-related QOL reported by parent-proxy and child self-report in a population sample of elementary school children . DESIGN , SETTING , AND PARTICIPANTS Cross-sectional data collected in 2000 within the Health of Young Victorians Study , a longitudinal cohort study commenced in 1997 . Individuals were recruited via a r and om 2-stage sampling design from primary schools in Victoria , Australia . Of the 1943 children in the original cohort , 1569 ( 80.8 % ) were resurveyed 3 years later at a mean age of 10.4 years . MAIN OUTCOME MEASURES Health-related QOL using the PedsQL 4.0 survey completed by both parent-proxy and by child self-report . Summary scores for children 's total , physical , and psychosocial health and subscale scores for emotional , social , and school functioning were compared by weight category based on International Obesity Task Force cut points . RESULTS Of 1456 participants , 1099 ( 75.5 % ) children were classified as not overweight ; 294 ( 20.2 % ) overweight ; and 63 ( 4.3 % ) obese . Parent-proxy and child self-reported PedsQL scores decreased with increasing child weight . The parent-proxy total PedsQL mean ( SD ) score for children who were not overweight was 83.1 ( 12.5 ) ; overweight , 80.0 ( 13.6 ) ; and obese , 75.0 ( 14.5 ) ; P<.001 . The respective child self-reported total PedsQL mean ( SD ) scores were 80.5 ( 12.2 ) , 79.3 ( 12.8 ) , and 74.0 ( 14.2 ) ; P<.001 . At the subscale level , child and parent-proxy reported scores were similar , showing decreases in physical and social functioning for obese children compared with children who were not overweight ( all P<.001 ) . Decreases in emotional and school functioning scores by weight category were not significant . CONCLUSION The effects of child overweight and obesity on health-related QOL in this community-based sample were significant but smaller than in a clinical sample using the same measure Background . Obesity has become the most common pediatric chronic disease in the modern era . Early prevention and treatment of childhood and adolescent obesity is m and ated . Surprisingly , however , only a minor fraction of obese children participate in weight reduction interventions , and the longer-term effects of these weight-reduction interventions among children have not been eluci date d. Objective . To examine prospect ively the short- and long-term effects of a 3-month , combined dietary-behavioral-physical activity intervention on anthropometric measures , body composition , dietary and leisure-time habits , fitness , and lipid profiles among obese children . Methods . In this r and omized prospect i ve study , 24 obese subjects completed the 3-month intervention and were compared with 22 obese , age- and gender-matched , control subjects . Results . At 3 months , there were significant differences in changes in body weight ( −2.8 ± 2.3 kg vs 1.2 ± 2.2 kg ) , BMI ( −1.7 ± 1.1 kg/m2 vs −0.2 ± 1.0 kg/m2 ) , body fat percentage ( from skinfold tests ; −3.3 ± 2.6 % vs 1.4 ± 4.7 % ) , serum total cholesterol level ( −24.6 ± 15.1 mg/dL vs 0.8 ± 18.7 mg/dL ) , low-density lipoprotein cholesterol level ( −23.3 ± 15.2 mg/dL vs −3.7 ± 17.3 mg/dL ) , and fitness ( 215 ± 107 seconds vs 50 ± 116 seconds ) in the intervention group versus the control group . After a 1-year follow-up period , there were significant differences between the intervention group ( n = 20 ) and the control group ( n = 20 ) in body weight ( 0.6 ± 6.0 kg vs 5.3 ± 2.7 kg ) , BMI ( −1.7 ± 2.3 kg/m2 vs 0.6 ± 0.9 kg/m2 ) , and body fat percentage . There was a significant increase in leisure-time physical activity among the intervention participants , compared with a decrease among the control subjects . Conclusions . Our data demonstrate the short- and longer-term beneficial effects of a combined dietary-behavioral-physical activity intervention among obese children . These results highlight the importance of multidisciplinary programs for the treatment of childhood obesity and emphasize their encouraging long-term effects Background In the evaluation of childhood obesity interventions , few research ers undertake a rigorous feasibility stage in which the design and procedures of the evaluation process are examined . Consequently , phase III studies often demonstrate method ological weaknesses . Purpose Our aim was to conduct a feasibility trial of the evaluation of WATCH IT , a community obesity intervention for children and adolescents . We sought to determine an achievable recruitment rate ; acceptability of r and omisation , assessment procedures , and dropout rate ; optimal outcome measures for the definitive trial ; and a robust sample size calculation . Method Our goal was to recruit 70 participants over 6 months , r and omise them to intervention or control group , and retain participation for 12 months . Assessment s were taken prior to r and omisation and after 6 and 12 months . Procedures mirrored those intended for a full-scale trial , but multiple measures of similar outcomes were included as a means to determine those most appropriate for future research . Acceptability of the research and impact of the research on the programme were ascertained through interviewing participants and staff . Results We recruited 70 participants and found that r and omisation and data collection procedures were acceptable . Self-referral ( via media promotion ) was more effective than professional referral . Blinding of assessors was sustained to a reasonable degree , and optimal outcome measures for a full-scale trial were identified . Estimated sample size was significantly greater than sample sized reported in published trials . There was some negative impact on the existing programme as a result of the research , a lesson for design ers of future trials . Limitations We successfully recruited socially disadvantaged families , but the majority of families were of White British nationality . The composition of the participants was an added valuable lesson , suggesting that recruitment strategies to obtain a more heterogeneous ethnic sample warrant consideration in future research . Conclusions This study provided us with confidence that we can run a phase III multi-centre trial to test the effectiveness of WATCH IT . Importantly , it was invaluable in informing the design not only of that trial but also of future evaluations of childhood obesity treatment interventions Background The prevalence of childhood obesity , which has seen a rapid increase over the last decade , is now considered a major public health problem . Current treatment options are based on the two important frameworks of school- and family-based interventions ; however , most research has yet to compare the two frameworks in the treatment of childhood obesity . The objective of this review is to compare the effectiveness of school-based intervention with family-based intervention in the treatment of childhood obesity . Methods Data bases such as Medline , Pub med , CINAHL , and Science Direct were used to execute the search for primary research papers according to inclusion criteria . The review included a r and omised controlled trial and quasi-r and omised controlled trials based on family- and school-based intervention frameworks on the treatment of childhood obesity . Results The review identified 1231 articles of which 13 met the criteria . Out of the thirteen studies , eight were family-based interventions ( n = 8) and five were school-based interventions ( n = 5 ) with total participants ( n = 2067 ) . The participants were aged between 6 and 17 with the study duration ranging between one month and three years . Family-based interventions demonstrated effectiveness for children under the age of twelve and school-based intervention was most effective for those aged between 12 and 17 with differences for both long-term and short-term results . Conclusions The evidence shows that family- and school-based interventions have a considerable effect on treating childhood obesity . However , the effectiveness of the interventional frameworks depends on factors such as age , short- or long-term outcome , and method ological quality of the trials . Further research studies are required to determine the effectiveness of family- and school-based interventions using primary outcomes such as weight , BMI , percentage overweight and waist circumference in addition to the aforementioned factors BACKGROUND / PURPOSE The prevalence of obesity and overweight among children and adolescents is increasing rapidly . The present research was performed to determine the influence of a ' ' behavior modification ' ' program on body mass index ( BMI ) in obese public high school students in Iran . METHODS In this study , 152 adolescence and their parents were selected from 12 high schools of Khorram Abad from 2004 to 2006 , and they were r and omly assigned to either the intervention or the control groups . The " behavior modification " interventional program consisted of nutritional education , modifying dietary habits , teaching exercise programs , teaching nutritional facts to the parents , and performing exercises 3 days a week . The height and weight as well as waist , hip , and wrist circumferences of the participants were measured before and after implementing the interventional program . BMI and waist to hip ratio ( WHR ) were calculated . The adolescents and parents completed a nutrition knowledge question naire . Adolescents also completed the Beck 's Depression Question naire . RESULTS Adolescent 's mean weight , BMI , and waist and hip circumferences decreased significantly after implementing the interventional program , in the intervention group ( p≤0.001 ) . In addition , the students ' and parents ' nutrition knowledge increased in the intervention group after implementing the interventional program ( p<0.046 ) . The symptoms of depression decreased and the frequency of students without symptoms of depression increased in the case group , but it did not reveal a statistically significant difference between case and control groups . CONCLUSION The ' ' behavior modification ' ' interventional program is effective in reducing BMI in obese students , and therefore , school principals and planners can play an important role in controlling obesity by implementing this program via the students , their parents , and the school staff Purpose To evaluate the effect of multidisciplinary treatment on obesity and health-related quality of life ( HRQOL ) . Methods Obese children were r and omized to a multidisciplinary lifestyle treatment , including medical , nutritional , physical , and psychological counseling during 3 months , ( n = 40 , BMI -SDS ; 4.2 ± 0.7 , age ; 13.3 ± 2.0 ) or st and ard care , including an initial advice on nutrition and physical activity by the pediatrician ( n = 39 , BMI -SDS ; 4.3 ± 0.7 , age ; 13.1 ± 1.9 ) . At baseline , after 3 months of treatment and at 12 months follow-up , data were collected for BMI -SDS and a European vali date d question naire for assessing HRQOL ( DISABKIDS ) . Results A significantly reduced BMI -SDS was found for the intervention group after 3 months treatment ( 4.0 ± 0.9 vs. 4.2 ± 0.7 , P = 0.02 ) and at 12 months follow-up ( 3.8 ± 1.1 vs. 4.2 ± 0.7 , P = 0.03 ) . HRQOL in the intervention group was significantly improved at 12 months follow-up and unchanged in the obese control group . Agreement between child and parent report was moderate ( 67–85 % ) , with parents reporting a lower HRQOL for their obese children than children themselves in both groups . Conclusion Multidisciplinary treatment is effective in reducing BMI -SDS and improving HRQOL after 12 months follow-up Objectives : To reduce gain in body mass index ( BMI ) in overweight/mildly obese children in the primary care setting . Design : R and omized controlled trial ( RCT ) nested within a baseline cross-sectional BMI survey . Setting : Twenty nine general practice s , Melbourne , Australia . Participants : ( 1 ) BMI survey : 2112 children visiting their general practitioner ( GP ) April – December 2002 ; ( 2 ) RCT : individually r and omized overweight/mildly obese ( BMI z-score < 3.0 ) children aged 5 years 0 months–9 years 11 months ( 82 intervention , 81 control).Intervention : Four st and ard GP consultations over 12 weeks , targeting change in nutrition , physical activity and sedentary behaviour , supported by purpose - design ed family material s . Main outcome measures : Primary : BMI at 9 and 15 months post-r and omization . Secondary : Parent-reported child nutrition , physical activity and health status ; child-reported health status , body satisfaction and appearance/self-worth . Results : Attrition was 10 % . The adjusted mean difference ( intervention – control ) in BMI was −0.2 kg/m2 ( 95 % CI : −0.6 to 0.1 ; P=0.25 ) at 9 months and −0.0 kg/m2 ( 95 % CI : −0.5 to 0.5 ; P=1.00 ) at 15 months . There was a relative improvement in nutrition scores in the intervention arm at both 9 and 15 months . There was weak evidence of an increase in daily physical activity in the intervention arm . Health status and body image were similar in the trial arms . Conclusions : This intervention did not result in a sustained BMI reduction , despite the improvement in parent-reported nutrition . Brief individualized solution-focused approaches may not be an effective approach to childhood overweight . Alternatively , this intervention may not have been intensive enough or the GP training may have been insufficient ; however , increasing either would have significant cost and re source implication s at a population level PURPOSE To compare the costs of parent-only and family-based group interventions for childhood obesity delivered through Cooperative Extension Services in rural communities . METHODS Ninety-three overweight or obese children ( aged 8 to 14 years ) and their parent(s ) participated in this r and omized controlled trial , which included a 4-month intervention and 6-month follow-up . Families were r and omized to either a behavioral family-based intervention ( n = 33 ) , a behavioral parent-only intervention ( n = 34 ) , or a waitlist control condition ( n = 26 ) . Only program costs data for the parent-only and family-based programs are reported here ( n = 67 ) . Assessment s were completed at baseline , post-treatment ( month 4 ) and follow-up ( month 10 ) . The primary outcome measures were total program costs and cost per child for the parent-only and family interventions . FINDINGS Twenty-six families in the parent-only intervention and 24 families in the family intervention completed all 3 assessment s. As reported previously , both intervention programs led to significantly greater decreases in weight status relative to the control condition at month 10 follow-up . There was no significant difference in weight status change between the parent-only and family interventions . Total program costs for the parent-only and family interventions were 13,546 US dollars and 20,928 , US dollars respectively . Total cost per child for the parent-only and family interventions were 521 US dollars and 872 US dollars , respectively . CONCLUSIONS Parent-only interventions may be a cost-effective alternative treatment for pediatric obesity , especially for families in medically underserved setting BACKGROUND The primary care setting offers the opportunity to reach children and parents to encourage healthy lifestyle behaviours , and improve weight status among children . OBJECTIVE Test the feasibility of Helping H AND ( Healthy Activity and Nutrition Directions ) , an obesity intervention for 5- to 8-year-old children in primary care clinics . METHODS A r and omized controlled pilot study of Helping H AND , a 6-month intervention , targeted children with body mass index 85 - 99%tile and their parents . Intervention group attended monthly sessions and self-selected child behaviours and parenting practice s to change . Control group received regular paediatric care and was wait-listed for Helping H AND . Session completion , participant satisfaction , child anthropometrics , dietary intake , physical activity , TV viewing and behaviour-specific parenting practice s were measured pre and post intervention . RESULTS Forty parent-child dyads enrolled : 82.5 % were Hispanic , 80 % had a girl and 65 % reported income ≤ $ 30 , 000/year . There was 20 % attrition from Helping H AND ( attended < 4/6 sessions ) . Families self-selected 4.35 ( SD 1.75 ) behaviours to target during the 6-month programme and each of the seven behaviours was selected by 45 - 80 % of the families . There were no between group differences in the child 's body mass index z-score , dietary intake or physical activity post intervention . Intervention group viewed 14.9 ( SE 2.3 ) h/week of TV post intervention versus control group 23.3 ( SE 2.4 ) h/week ( P < 0.05 ) . CONCLUSION Helping H AND is feasible , due to low attrition , good programme attendance , and clinical ly relevant improvements in some child and parenting behaviours OBJECTIVE To assess the effects of reducing television viewing and computer use on children 's body mass index ( BMI ) as a risk factor for the development of overweight in young children . DESIGN R and omized controlled clinical trial . SETTING University children 's hospital . PARTICIPANTS Seventy children aged 4 to 7 years whose BMI was at or above the 75th BMI percentile for age and sex . INTERVENTIONS Children were r and omized to an intervention to reduce their television viewing and computer use by 50 % vs a monitoring control group that did not reduce television viewing or computer use . MAIN OUTCOME MEASURES Age- and sex-st and ardized BMI ( z BMI ) , television viewing , energy intake , and physical activity were monitored every 6 months during 2 years . RESULTS Children r and omized to the intervention group showed greater reductions in targeted sedentary behavior ( P < .001 ) , z BMI ( P < .05 ) , and energy intake ( P < .05 ) compared with the monitoring control group . Socioeconomic status moderated z BMI change ( P = .01 ) , with the experimental intervention working better among families of low socioeconomic status . Changes in targeted sedentary behavior mediated changes in z BMI ( P < .05 ) . The change in television viewing was related to the change in energy intake ( P < .001 ) but not to the change in physical activity ( P = .37 ) . CONCLUSIONS Reducing television viewing and computer use may have an important role in preventing obesity and in lowering BMI in young children , and these changes may be related more to changes in energy intake than to changes in physical activity BACKGROUND Consumption of sugar-sweetened beverages may cause excessive weight gain . We aim ed to assess the effect on weight gain of an intervention that included the provision of noncaloric beverages at home for overweight and obese adolescents . METHODS We r and omly assigned 224 overweight and obese adolescents who regularly consumed sugar-sweetened beverages to experimental and control groups . The experimental group received a 1-year intervention design ed to decrease consumption of sugar-sweetened beverages , with follow-up for an additional year without intervention . We hypothesized that the experimental group would gain weight at a slower rate than the control group . RESULTS Retention rates were 97 % at 1 year and 93 % at 2 years . Reported consumption of sugar-sweetened beverages was similar at baseline in the experimental and control groups ( 1.7 servings per day ) , declined to nearly 0 in the experimental group at 1 year , and remained lower in the experimental group than in the control group at 2 years . The primary outcome , the change in mean body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) at 2 years , did not differ significantly between the two groups ( change in experimental group minus change in control group , -0.3 ; P=0.46 ) . At 1 year , however , there were significant between-group differences for changes in BMI ( -0.57 , P=0.045 ) and weight ( -1.9 kg , P=0.04 ) . We found evidence of effect modification according to ethnic group at 1 year ( P=0.04 ) and 2 years ( P=0.01 ) . In a prespecified analysis according to ethnic group , among Hispanic participants ( 27 in the experimental group and 19 in the control group ) , there was a significant between-group difference in the change in BMI at 1 year ( -1.79 , P=0.007 ) and 2 years ( -2.35 , P=0.01 ) , but not among non-Hispanic participants ( P>0.35 at years 1 and 2 ) . The change in body fat as a percentage of total weight did not differ significantly between groups at 2 years ( -0.5 % , P=0.40 ) . There were no adverse events related to study participation . CONCLUSIONS Among overweight and obese adolescents , the increase in BMI was smaller in the experimental group than in the control group after a 1-year intervention design ed to reduce consumption of sugar-sweetened beverages , but not at the 2-year follow-up ( the prespecified primary outcome ) . ( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; Clinical Trials.gov number , NCT00381160 . ) OBJECTIVE This study evaluates the post-treatment and short-term follow-up efficacy of , as well as participant satisfaction for , a 4-month behavioral weight control program for overweight adolescents initiated in a primary care setting and extended through telephone and mail contact . RESEARCH METHODS AND PROCEDURES 44 overweight adolescents were r and omly assigned to either a multiple component behavioral weight control intervention ( Healthy Habits [ HH ] ; n = 23 ) or a single session of physician weight counseling ( typical care [ TC ] ; n = 21 ) . Weight , height , dietary intake , physical activity , sedentary behavior , and problematic weight-related and eating behaviors and beliefs were assessed before treatment , after the 4-month treatment , and at 3-month follow-up . Participant satisfaction and behavioral skills use were measured . RESULTS HH adolescents evidence d better change in body mass index z scores to post-treatment than TC adolescents . Body mass index z scores changed similarly in the conditions from post-treatment through follow-up . Behavioral skills use was higher among HH than TC adolescents , and higher behavioral skills use was related to better weight outcome . Energy intake , percentage of calories from fat , physical activity , sedentary behavior , and problematic weight-related or eating behaviors/beliefs did not differ by condition or significantly change over time independent of condition . The behavioral intervention evidence d good feasibility and participant satisfaction . DISCUSSION A telephone- and mail-based behavioral intervention initiated in primary care result ed in better weight control efficacy relative to care typically provided to overweight adolescents . Innovative and efficacious weight control intervention delivery approaches could decrease provider and participant burden and improve dissemination to the increasing population of overweight youth The aim of this study was to evaluate the effectiveness of the Mind , Exercise , Nutrition , Do it ( MEND ) Program , a multicomponent community-based childhood obesity intervention ( www.mend central .org ) . One hundred and sixteen obese children ( BMI > or= 98 th percentile , UK 1990 reference data ) were r and omly assigned to intervention or waiting list control ( 6-month delayed intervention ) . Parents and children attended eighteen 2-h group educational and physical activity sessions held twice weekly in sports centers and schools , followed by a 12-week free family swimming pass . Waist circumference , BMI , body composition , physical activity level , sedentary activities , cardiovascular fitness , and self-esteem were assessed at baseline and at 6 months . Children were followed up 12 months from baseline ( 0 and 6 months postintervention for the control and intervention group , respectively ) . Participants in the intervention group had a reduced waist circumference z-score ( -0.37 ; P < 0.0001 ) and BMI z-score ( -0.24 ; P < 0.0001 ) at 6 months when compared to the controls . Significant between-group differences were also observed in cardiovascular fitness , physical activity , sedentary behaviors , and self-esteem . Mean attendance for the MEND Program was 86 % . At 12 months , children in the intervention group had reduced their waist and BMI z-scores by 0.47 ( P < 0.0001 ) and 0.23 ( P < 0.0001 ) , respectively , and benefits in cardiovascular fitness , physical activity levels , and self-esteem were sustained . High-attendance rates suggest that families found this intensive community-based intervention acceptable . Further larger controlled trials are currently underway to confirm the promising findings of this initial trial OBJECTIVE The aim of this study was to compare the effect of a hospital clinic group- versus home-based combined exercise-diet program for the treatment of childhood obesity . METHODS One hundred ten overweight/obese Spanish children and adolescents ( 6 - 16 years ) in 2 intervention groups ( hospital clinic group-based [ n = 45 ] and home-based [ n = 41 ] ) and a sex-age-matched control group ( n = 24 ) were r and omly assigned to participate in a 6-month combined exercise ( aerobic and resistance training ) and Mediterranean diet program . Anthropometric values ( including body weight , height , body mass index , BMI -Z score , and waist circumference ) were measured pre- and postintervention for all the participants . Percentage body fat was also determined with a body fat analyzer ( TANITA TBF-410 M ) . RESULTS Our study showed a significant reduction in percentage body fat and body mass index Z-score among both intervention-group participants ( 4 % , 0.16 , hospital clinic group-based ; 4.4 % , 0.23 , home-based ; P < .0001 ) . There was also a significant reduction in waist circumference in the home-based group ( 4.4 cm ; P = .019 ) . Attendance rates at intervention sessions were equivalent for both intervention groups ( P = .805 ) . CONCLUSIONS The study findings indicate that a simple home-based combined exercise and Mediterranean diet program may be effective among overweight and obese children and adolescents , because it improves body composition , is feasible and can be adopted on a large scale without substantial expenses CONTEXT Few r and omized controlled trials ( RCTs ) of interventions for the treatment of childhood obesity have taken place outside the Western world . AIM To test whether a good practice intervention for the treatment of childhood obesity would have a greater impact on weight status and other outcomes than a control condition in Kuala Lumpur , Malaysia . METHODS Assessor-blinded RCT of a treatment intervention in 107 obese 7- to 11-year olds . The intervention was relatively low intensity ( 8 hours contact over 26 weeks , group based ) , aim ing to change child sedentary behavior , physical activity , and diet using behavior change counselling . Outcomes were measured at baseline and six months after the start of the intervention . Primary outcome was BMI z-score , other outcomes were weight change , health-related quality of life ( Peds QL ) , objective ly measured physical activity and sedentary behavior ( Actigraph accelerometry over 5 days ) . RESULTS The intervention had no significant effect on BMI z score relative to control . Weight gain was reduced significantly in the intervention group compared to the control group ( + 1.5 kg vs. + 3.5 kg , respectively , t-test p < 0.01 ) . Changes in health-related quality of life and objective ly measured physical activity and sedentary behavior favored the intervention group . CONCLUSIONS Treatment was associated with reduced rate of weight gain , and improvements in physical activity and quality of life . More substantial benefits may require longer term and more intensive interventions which aim for more substantive lifestyle changes OBJECTIVE The authors performed a group-based program for obese children and adolescents in Bavaria , Germany to enable them to establish a health-oriented lifestyle and to reduce overweight . The authors compared this program with a control approach based on the patients ' own initiative . DESIGN This is a controlled clinical trial . SETTING A nutrition program for out patients in a German university hospital . PARTICIPANTS Seventy-three obese patients aged 7 to 15 years ( mean 11.2 years ) were recruited by pediatricians and local newspaper reports and r and omized into intervention and control groups . Children and adolescents in each group were divided into 3 groups according to age--7 - 8 years , 9 - 10 years , and 11 - 13 years . Children were classified overweight ( defined as body mass index ( BMI ) > 90th percentile for age and gender ) , obese ( BMI > 97th percentile ) , and extremely obese ( BMI > 99.5th percentile ) , according to the European Childhood Obesity Group and the German Working Group on Pediatric Obesity , congruent with adult st and ards used to assess overweight and obesity . INTERVENTION Thirty-seven patients ( age 7 - 13 years , mean 10.9 years ) for the 1-year intervention . This intervention consisted of modules for physical activity , nutritional education , and coping strategies . The program was performed twice each week and incorporated parental participation and medical supervision , including laboratory tests . The obese controls ( n = 36 , age 8 - 15 years , mean 11.6 years ) received written therapeutic advice during a visit at 0 and 6 months in the outpatient clinic . MAIN OUTCOME MEASURE The primary outcome variable was the body mass index ( BMI ) z score . ANALYSIS Analysis of variance and t test were used , and a P value < .05 was considered significant . RESULTS There was a reduction of BMI z score in the active treatment group ( P < .05 ) , but not for controls . Moreover , the active group showed beneficial effects for body mass index ( BMI ) , fat mass , and systolic blood pressure 12 months after beginning the intervention . CONCLUSIONS AND IMPLICATION S Group-based programs for young , obese patients can be effective tools for establishing a health-oriented lifestyle and reducing the burden of obesity BACKGROUND . Parenting-skills training may be an effective age-appropriate child behavior-modification strategy to assist parents in addressing childhood overweight . OBJECTIVE . Our goal was to evaluate the relative effectiveness of parenting-skills training as a key strategy for the treatment of overweight children . DESIGN . The design consisted of an assessor-blinded , r and omized , controlled trial involving 111 ( 64 % female ) overweight , prepubertal children 6 to 9 years of age r and omly assigned to parenting-skills training plus intensive lifestyle education , parenting-skills training alone , or a 12-month wait-listed control . Height , BMI , and waist-circumference z score and metabolic profile were assessed at baseline , 6 months , and 12 months ( intention to treat ) . RESULTS . After 12 months , the BMI z score was reduced by ∼10 % with parenting-skills training plus intensive lifestyle education versus ∼5 % with parenting-skills training alone or wait-listing for intervention . Waist-circumference z score fell over 12 months in both intervention groups but not in the control group . There was a significant gender effect , with greater reduction in BMI and waist-circumference z scores in boys compared with girls . CONCLUSION . Parenting-skills training combined with promoting a healthy family lifestyle may be an effective approach to weight management in prepubertal children , particularly boys . Future studies should be powered to allow gender sub analysis Objective To determine whether ascertainment of childhood obesity by surveillance followed by structured secondary prevention in primary care improved outcomes in overweight or mildly obese children . Design R and omised controlled trial nested within a baseline cross sectional survey of body mass index ( BMI ) . R and omisation and outcomes measurement , but not participants , were blinded to group assignment . Setting 45 family practice s ( 66 general practitioners ) in Melbourne , Australia . Participants 3958 children visiting their general practitioner in May 2005-July 2006 were surveyed for BMI . Of these , 258 children aged 5 years 0 months up to their 10th birthday who were overweight or obese by International Obesity Taskforce criteria were r and omised to intervention ( n=139 ) or control ( n=119 ) groups . Children who were very obese ( UK BMI z score ≥3.0 ) were excluded . Intervention Four st and ard consultations over 12 weeks targeting change in nutrition , physical activity , and sedentary behaviour , supported by purpose design ed family material s. Main outcomes measures Primary measure was BMI at 6 and 12 months after r and omisation . Secondary measures were mean activity count/min by 7-day accelerometry , nutrition score from 4-day abbreviated food frequency diary , and child health related quality of life . Differences were adjusted for socioeconomic status , age , sex , and baseline BMI . Results Of 781 eligible children , 258 ( 33 % ) entered the trial ; attrition was 3.1 % at 6 months and 6.2 % at 12 months . Adjusted mean differences ( intervention − control ) at 6 and 12 months were , for BMI , −0.12 ( 95 % CI −0.40 to 0.15 , P=0.4 ) and −0.11 ( −0.45 to 0.22 , P=0.5 ) ; for physical activity in counts/min , 24 ( −4 to 52 , P=0.09 ) and 11 ( −26 to 49 , P=0.6 ) ; and , for nutrition score , 0.2 ( −0.03 to 0.4 , P=0.1 ) and 0.1 ( −0.1 to 0.4 , P=0.2 ) . There was no evidence of harm to the child . Costs to the healthcare system were significantly higher in the intervention arm . Conclusions Primary care screening followed by brief counselling did not improve BMI , physical activity , or nutrition in overweight or mildly obese 5 - 10 year olds , and it would be very costly if universally implemented . These findings are at odds with national policies in countries including the US , UK , and Australia . Trial registration IS RCT N 52511065 ( www.is rct n.org OBJECTIVE To examine the effectiveness of a primary care-based obesity intervention over the first year ( 6 intervention contacts ) of a planned 2-year study . DESIGN Cluster r and omized controlled trial . SETTING Ten pediatric practice s , 5 intervention and 5 usual care . PARTICIPANTS Four hundred seventy-five children aged 2 to 6 years with body mass index ( BMI ) in the 95th percentile or higher or 85th to less than 95th percentile if at least 1 parent was overweight ; 445 ( 93 % ) had 1-year outcomes . INTERVENTION Intervention practice s received primary care restructuring , and families received motivational interviewing by clinicians and educational modules targeting television viewing and fast food and sugar-sweetened beverage intake . OUTCOME MEASURES Change in BMI and obesity-related behaviors from baseline to 1 year . RESULTS Compared with usual care , intervention participants had a smaller , nonsignificant change in BMI ( -0.21 ; 95 % confidence interval [ CI ] , -0.50 to 0.07 ; P = .15 ) , greater decreases in television viewing ( -0.36 h/d ; 95 % CI , -0.64 to -0.09 ; P = .01 ) , and slightly greater decreases in fast food ( -0.16 serving/wk ; 95 % CI , -0.33 to 0.01 ; P = .07 ) and sugar-sweetened beverage ( -0.22 serving/d ; 95 % CI , -0.52 to 0.08 ; P = .15 ) intake . In post hoc analyses , we observed significant effects on BMI among girls ( -0.38 ; 95 % CI , -0.73 to -0.03 ; P = .03 ) but not boys ( 0.04 ; 95 % CI , -0.55 to 0.63 ; P = .89 ) and among participants in households with annual incomes of $ 50 000 or less ( -0.93 ; 95 % CI , -1.60 to -0.25 ; P = .01 ) but not in higher-income households ( 0.02 ; 95 % CI , -0.30 to 0.33 ; P = .92 ) . CONCLUSION After 1 year , the High Five for Kids intervention was effective in reducing television viewing but did not significantly reduce BMI BACKGROUND & AIMS R and omized controlled trials ( RCT ) have demonstrated the effectiveness of lifestyle interventions in obese children . However , the effectiveness of interventions for overweight , but no obese children has not been demonstrated yet by RCTs . METHODS A total of 66 overweight ( BMI > 90th < or = 97th percentile ) children ( mean age 11.5+/-1.6 years , 58 % females , mean BMI 23.4+/-1.5kg/m(2 ) ) were r and omized into a control group ( CG ) ( n=32 ; no intervention for a duration of 6 months ) or intervention group ( IG ) ( n=34 ; 6 months intervention " Obeldicks light " based on physical activity , nutrition education , and behaviour counselling ) . BMI , waist circumference , skinfold thickness , bioimpedance analyses , blood pressure , physical activity based on question naires , and three-day-weighed dietary records were determined at baseline ( T0 ) and 6 months ( T1 ) later . Degree of overweight was calculated as BMI -SDS . Comparisons were performed on an intention-to-treat approach . RESULTS The drop-out rate was 3 % in IG and 16 % in CG . At T1 , 94 % of the children in IG decreased their BMI -SDS and 24 % of them were normal weight . The changes between T0 and T1 in BMI -SDS differed significantly ( p<0.001 ) between IG and CG ( CG : + 0.05+/-0.19 BMI -SDS ; IG : -0.26+/-0.22 BMI -SDS ) . Similar findings were observed for blood pressure , waist circumference , skinfold thickness , and fat mass based on bioimpedance analyses . In the IG , energy , fat and sugar intake decreased significantly between T0 and T1 , while no significant changes were observed in the CG . CONCLUSIONS The lifestyle intervention was associated with an improvement of dietary patterns and was effective in reducing degree of overweight , fat mass , waist circumference , and blood pressure BACKGROUND The association of body-mass index ( BMI ) from adolescence to adulthood with obesity-related diseases in young adults has not been completely delineated . METHODS We conducted a prospect i ve study in which we followed 37,674 apparently healthy young men for incident angiography-proven coronary heart disease and diabetes through the Staff Periodic Examination Center of the Israeli Army Medical Corps . The height and weight of participants were measured at regular intervals , with the first measurements taken when they were 17 years of age . RESULTS During approximately 650,000 person-years of follow-up ( mean follow-up , 17.4 years ) , we documented 1173 incident cases of type 2 diabetes and 327 of coronary heart disease . In multivariate models adjusted for age , family history , blood pressure , lifestyle factors , and biomarkers in blood , elevated adolescent BMI ( the weight in kilograms divided by the square of the height in meters ; mean range for the first through last deciles , 17.3 to 27.6 ) was a significant predictor of both diabetes ( hazard ratio for the highest vs. the lowest decile , 2.76 ; 95 % confidence interval [ CI ] , 2.11 to 3.58 ) and angiography-proven coronary heart disease ( hazard ratio , 5.43 ; 95 % CI , 2.77 to 10.62 ) . Further adjustment for BMI at adulthood completely ablated the association of adolescent BMI with diabetes ( hazard ratio , 1.01 ; 95 % CI , 0.75 to 1.37 ) but not the association with coronary heart disease ( hazard ratio , 6.85 ; 95 % CI , 3.30 to 14.21 ) . After adjustment of the BMI values as continuous variables in multivariate models , only elevated BMI in adulthood was significantly associated with diabetes ( β=1.115 , P=0.003 ; P=0.89 for interaction ) . In contrast , elevated BMI in both adolescence ( β=1.355 , P=0.004 ) and adulthood ( β=1.207 , P=0.03 ) were independently associated with angiography-proven coronary heart disease ( P=0.048 for interaction ) . CONCLUSIONS An elevated BMI in adolescence -- one that is well within the range currently considered to be normal -- constitutes a substantial risk factor for obesity-related disorders in midlife . Although the risk of diabetes is mainly associated with increased BMI close to the time of diagnosis , the risk of coronary heart disease is associated with an elevated BMI both in adolescence and in adulthood , supporting the hypothesis that the processes causing incident coronary heart disease , particularly atherosclerosis , are more gradual than those result ing in incident diabetes . ( Funded by the Ch aim Sheba Medical Center and the Israel Defense Forces Medical Corps . ) Objective To determine whether general practice surveillance for childhood obesity , followed by obesity management across primary and tertiary care setting s using a shared care model , improves body mass index and related outcomes in obese children aged 3 - 10 years . Design R and omised controlled trial . Setting 22 family practice s ( 35 participating general practitioners ) and a tertiary weight management service ( three paediatricians , two dietitians ) in Melbourne , Australia . Participants Children aged 3 - 10 years with body mass index above the 95th centile recruited through their general practice between July 2009 and April 2010 . Intervention Children were r and omly allocated to one tertiary appointment followed by up to 11 general practice consultations over one year , supported by shared care , web based software ( intervention ) or “ usual care ” ( control ) . Research ers collecting outcome measurements , but not participants , were blinded to group assignment . Main outcome measures Children ’s body mass index z score ( primary outcome ) , body fat percentage , waist circumference , physical activity , quality of diet , health related quality of life , self esteem , and body dissatisfaction and parents ’ body mass index ( all 15 months post-enrolment ) . Results 118 ( 60 intervention , 56 control ) children were recruited and 107 ( 91 % ) were retained and analysed ( 56 intervention , 51 control ) . All retained intervention children attended the tertiary appointment and their general practitioner for at least one ( mean 3.5 ( SD 2.5 , range 1 - 11 ) ) weight management consultation . At outcome , children in the two trial arms had similar body mass index ( adjusted mean difference −0.1 ( 95 % confidence interval −0.7 to 0.5 ; P=0.7 ) ) and body mass index z score ( −0.05 ( −0.14 to 0.03 ) ; P=0.2 ) . Similarly , no evidence was found of benefit or harm on any secondary outcome . Outcomes varied widely in the combined cohort ( mean change in body mass index z score −0.20 ( SD 0.25 , range −0.97 - 0.47 ) ; 26 % of children resolved from obese to overweight and 2 % to normal weight . Conclusions Although feasible , not harmful , and highly rated by both families and general practitioners , the shared care model of primary and tertiary care management did not lead to better body mass index or other outcomes for the intervention group compared with the control group . Improvements in body mass index in both groups highlight the value of untreated controls when determining efficacy . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12608000055303 |
1,030 | 28,353,074 | 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 | Background It remains controversial whether the addition of a second cytotoxic agent can further improve the therapeutic effect of gemcitabine monotherapy in advanced or metastatic pancreatic cancer ( LA/MPC ) .
Objective The objective of the present systematic review and meta- analysis was to investigate the efficacy and safety of gemcitabine-based doublet chemotherapy regimens compared to single-agent gemcitabine in the first-line treatment of unresectable LA/MPC . | 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 % , respectively . Patients with a performance status of 0 , 1 , and 2 survived a median of 7.9 , 4.8 , and 2.4 months , respectively . The only statistically significant differences in grade s 3 and 4 toxicity occurred for hypertension ( 10 % v 3 % ; P < .001 ) and proteinuria ( 5 % v 1 % ; P = .002 ) ; venous thrombosis grade > or = 3 was equivalent in both arms ( 14 % and 15 % , respectively ) . CONCLUSION The addition of bevacizumab to gemcitabine does not improve survival in advanced pancreatic cancer patients 4006 BACKGROUND : DX is a novel hexacyclic , water-soluble , topoisomerase-1 inhibitor . DX has single-agent and combination activity with GEM in APC ( D'Adamo , et al. ASCO , 2001 ; O'Reilly , et al. ASCO , 2002 ) . A multicenter , r and omized phase III trial comparing DX + GEM to GEM alone in APC was conducted . METHODS Eligibility included KPS ≥ 60 % ; locally advanced or metastatic pancreatic adenocarcinoma ; no prior chemotherapy . Radiation ( RT ) alone for locally advanced disease was permitted . Patients ( pts ) were r and omized on a 1 : 1 basis to DX + GEM or GEM alone . Pts were stratified by KPS , 60 % , 70 - 80 % , ≥ 90 % , locally advanced vs metastatic disease , prior RT vs. no RT . For the DX + GEM arm , DX was dosed at 2.0mg/m2 ; GEM at 1,000mg/m2 on a days 1 and 8 , q 3 weeks . GEM alone was dosed at 1,000mg/m2 up to 7 weeks in the 1st cycle , then weekly x 3 , q 4 weeks . Tumor assessment was performed every 6 weeks . The primary endpoint was overall survival . An intent-to-treat analysis was used . An independent data safety monitoring board monitored the trial . RESULTS From 8/01 to 1/03 , 349 patients were r and omized , 175 to DX + GEM , and 174 to GEM alone . Twenty-four pts ( 6.9 % ) were not treated . The treatment arms were well-balanced for extent of disease , KPS , and prior RT . The median survival time was 6.7 months for DX + GEM and 6.2 months for GEM alone ( p=0.52 ) . The median TTP for DX + GEM was 3.7 months and 3.8 months for GEM alone ( p=0.22 ) . There was an improvement in time-to-worsening of pain and analgesic consumption for DX + GEM compared to GEM alone . However , time-to-worsening of KPS and weight were similar for both treatment arms . Tumor response rates were 8.2 % for DX + GEM and 6.3 % for GEM alone . Grade 3 - 4 toxicity was higher for the DX + GEM arm for neutropenia ( 30 % vs 15 % , p=0.001 ) , thrombocytopenia ( 17 % vs 4 % , p=0.0004 ) and vomiting ( 11 % vs 5 % , p=0.04 ) . The rates of febrile neutropenia were 4 % for DX + GEM and 2 % for GEM alone , p=0.24 . The relative dose-intensities were similar for both arms : 83 % and 81 % of projected doses for the DX and GEM arm compared to 92 % for GEM alone . CONCLUSIONS DX + GEM was not superior to GEM alone with respect to overall survival in the front-line treatment of APC . There was a trend in favor of clinical benefit for the combination arm . The results do not alter the st and ard of care for treatment of APC . [ Table : see text ] PURPOSE Gemcitabine is generally considered to constitute first-line therapy for pancreatic cancer . To determine whether the addition of fluorouracil ( 5-FU ) improves on the results from single-agent gemcitabine , the Eastern Cooperative Oncology Group ( ECOG ) compared gemcitabine plus bolus 5-FU with gemcitabine alone for patients with advanced pancreatic carcinoma . PATIENTS AND METHODS This trial involved patients with biopsy-proven , advanced carcinoma of the pancreas not amenable to surgical resection . Patients were r and omized to receive either gemcitabine alone ( 1,000 mg/m(2)/wk ) weekly for 3 weeks of every 4 or to receive gemcitabine ( 1,000 mg/m(2)/wk ) followed by 5-FU ( 600 mg/m(2)/wk ) weekly on the same schedule . The primary end point of the trial was survival , with secondary end points of time to progression and response rate . RESULTS Of 327 patients enrolled over 18 months , 322 were eligible . Overall , the median survival was 5.4 months for gemcitabine alone and 6.7 months for gemcitabine plus 5-FU ( P = .09 ) . Progression-free survival for gemcitabine alone was 2.2 months , compared with 3.4 months for gemcitabine plus 5-FU ( P = .022 ) . Objective responses were uncommon and were observed in only 5.6 % of patients treated with gemcitabine and 6.9 % of patients treated with gemcitabine plus 5-FU . Most toxicities were hematologic or gastrointestinal ; no significant differences were noted between the two treatment arms . CONCLUSION 5-FU , administered in conjunction with gemcitabine , did not improve the median survival of patients with advanced pancreatic carcinoma compared with single-agent gemcitabine . Further studies with other combinations of gemcitabine and 5-FU are not compelling , and clinical trial re sources should address other combinations and novel agents PURPOSE Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies . Pre clinical and early clinical evidence has supported targeting the epidermal growth factor receptor ( EGFR ) signaling pathway in patients with pancreas cancer . This trial was conducted to evaluate the contribution of an EGFR-targeted agent to st and ard gemcitabine therapy . Cetuximab is a monoclonal antibody against the lig and -binding domain of the receptor . PATIENTS AND METHODS Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were r and omly assigned to receive gemcitabine alone or gemcitabine plus cetuximab . The primary end point was overall survival . Secondary end points included progression-free survival , time to treatment failure , objective response , and toxicity . RESULTS A total of 745 eligible patients were accrued . No significant difference was seen between the two arms of the study with respect to the median survival time ( 6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm ; hazard ratio = 1.06 ; 95 % CI , 0.91 to 1.23 ; P = .23 , one-sided ) . Objective responses and progression-free survival were similar in both arms of the study . Although time to treatment failure was longer in patients on gemcitabine plus cetuximab ( P = .006 ) , the difference in length of treatment was only 2 weeks longer in the combination arm . Among patients who were studied for tumoral EGFR expression , 90 % were positive , with no treatment benefit detected in this patient subset . CONCLUSION In patients with advanced pancreas cancer , the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone . Alternate targets other than EGFR should be evaluated for new drug development PURPOSE Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms . To date , no treatment has had a significant impact on the disease . In early studies with gemcitabine , patients with pancreas cancer experienced an improvement in disease-related symptoms . Based on those findings , a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer . PATIENTS AND METHODS One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were r and omized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest , then weekly x 3 every 4 weeks thereafter ( 63 patients ) , or to fluorouracil ( 5-FU ) 600 mg/m2 once weekly ( 63 patients ) . The primary efficacy measure was clinical benefit response , which was a composite of measurements of pain ( analgesic consumption and pain intensity ) , Karnofsky performance status , and weight . Clinical benefit required a sustained ( > or = 4 weeks ) improvement in at least one parameter without worsening in any others . Other measures of efficacy included response rate , time to progressive disease , and survival . RESULTS Clinical benefit response was experienced by 23.8 % of gemcitabine-treated patients compared with 4.8 % of 5-FU-treated patients ( P = .0022 ) . The median survival duration s were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients , respectively ( P = .0025 ) . The survival rate at 12 months was 18 % for gemcitabine patients and 2 % for 5-FU patients . Treatment was well tolerated . CONCLUSION This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced , symptomatic pancreas cancer . Gemcitabine also confers a modest survival advantage over treatment with 5-FU BACKGROUND Paclitaxel embedded in cationic liposomes ( EndoTAG ™ -1 ; ET ) is an innovative agent targeting tumor endothelial cells . This r and omized controlled phase II trial evaluated the safety and efficacy of ET in combination with gemcitabine ( GEM ) in advanced pancreatic cancer ( PDAC ) . PATIENTS AND METHODS Chemotherapy-naive patients with locally advanced or metastatic disease were r and omly assigned to receive weekly GEM 1000 mg/m(2 ) or GEM plus twice-weekly ET 11 , 22 or 44 mg/m(2 ) for 7 weeks . After a safety run-in of 100 patients , a second cohort continued treatment . End points included overall survival ( OS ) , progression-free survival ( PFS ) , tumor response and safety . RESULTS Two hundred and twelve patients were r and omly allocated to the study and 200 were treated ( 80 % metastatic , 20 % locally advanced ) . Adverse events were manageable and reversible . Transient thrombocytopenia and infusion reactions with chills and pyrexia mostly grade 1 or 2 occurred in the ET groups . Disease control rate after the first treatment cycle was 43 % with GEM and 60 % , 65 % and 52 % in the GEM + ET cohorts . Median PFS reached 2.7 compared with 4.1 , 4.6 and 4.4 months , respectively . Median OS was 6.8 compared with 8.1 , 8.7 and 9.3 months , respectively . CONCLUSIONS Treatment of advanced PDAC with GEM + ET was generally well tolerated . GEM + ET showed beneficial survival and efficacy . A r and omized phase III trial should confirm this positive trend BACKGROUND Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways . A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and had activity in advanced pancreatic cancer ( APC ) patients . The BAYPAN study was a multicentric , placebo-controlled , double-blind , r and omized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC . PATIENTS AND METHODS The patient eligibility criteria were locally advanced or metastatic pancreatic adenocarcinoma , no prior therapy for advanced disease and a performance status of zero to two . The primary end point was progression-free survival ( PFS ) . The patients received gemcitabine 1000 mg/m(2 ) i.v . , weekly seven times followed by 1 rest week , then weekly three times every 4 weeks plus sorafenib 200 mg or placebo , two tablets p.o . , twice daily continuously . RESULTS Between December 2006 and September 2009 , 104 patients were enrolled on the study ( 52 pts in each arm ) and 102 patients were treated . The median and the 6-month PFS were 5.7 months and 48 % for gemcitabine/placebo and 3.8 months and 33 % for gemcitabine/sorafenib ( P = 0.902 , stratified log-rank test ) , respectively . The median overall survivals were 9.2 and 8 months , respectively ( P = 0.231 , log-rank test ) . The overall response rates were similar ( 19 and 23 % , respectively ) . CONCLUSION The addition of sorafenib to gemcitabine does not improve PFS in APC patients 4007 Background : S-1 , an oral fluoropyrimidine , is one of the key drugs for PC in Japan . Phase II studies of S-1 alone as well as those of GS have shown high efficacy against the tumor as the first-line treatment of metastatic PC . METHODS The GEST study was a r and omized , prospect i ve , open-label , 3-arm , phase III study . Chemotherapy-naive patients with unresectable advanced PC , an ECOG PS of 0 - 1 , with adequate organ functions were r and omly assigned to receive GEM ( 1000 mg/m2 , iv , d1 , 8 and 15 , q4w ) , S-1 ( 80/100/120 mg/day based on BSA , po , d1 - 28 , q6w ) or GS ( GEM 1000 mg/m2 , iv , d1 and 8 plus S-1 60/80/100 mg/day based on BSA po , d1 - 14 , q3w ) . The primary endpoint was overall survival ( OS ) to assess the non-inferiority of S-1 alone and the superiority of GS to GEM , with a 90 % power and a 1-sided alpha value of 0.0125 for each multiplicity-adjusted comparison . Secondary endpoints were progression-free survival ( PFS ) , response rate ( RR ) , safety , and quality of life ( EQ-5D ) . RESULTS A total of 834 patients were enrolled from July 2007 to October 2009 . We conducted this analysis after confirming over 680 events as expected . Demographic factors were well balanced . S-1 was confirmed to be non-inferior to GEM with respect to OS . There was no significant difference in OS between GEM and GS , while PFS differed significantly between these arms . ( 4.1M/5.7 M , p value<0.0001 ) RR was 13.3 % , 21.0 % , and 29.3 % in GEM , S-1 , and GS respectively . Grade 3/4 toxicities ( % ) in GEM/S-1/GS were neutropenia 41.0/8.8/62.2 , thrombocytopenia 11.0/1.5/17.2 , anorexia 7.3/11.4/9.4 , diarrhea 1.1/5.5/4.5 . EQ-5D QOL score in S-1 was similar to GEM ( p value=0.67 ) , and that in GS was significantly better than that in GEM ( p value=0.003 ) . CONCLUSIONS Without compromising QOL , oral S-1 provided similar efficacy and tolerable toxicity to GEM as the first-line treatment for PC . Our results suggested that GS contribute better QOL than GEM . Further clinical investigation might be needed to ensure the efficacy of GS . [ Table : see text ] 4029 Background : Combination chemotherapy with gemcitabine ( GEM ) and S-1 has been reported to be promising treatment for advanced pancreatic cancer . In order to evaluate its efficacy and safety , we conducted a multicenter r and omized phase II study in patients ( pts ) with unresectable pancreatic cancer , comparing the combination of GEM and S-1 ( GS ) with GEM alone ( G ) . METHODS Eligible pts had histologically or cytologically confirmed locally advanced or metastatic pancreatic adenocarcinoma with measurable lesion . Other main inclusion criteria were an age between 20 and 80 years , no prior anticancer treatment , well preserved function of major organs and Eastern Cooperative Oncology Group ( ECOG ) PS of 0 - 2 . Pts were r and omly assigned to receive either GS or G. GS regimen consists of intravenous GEM 1,000 mg/m2 over 30 minutes on days 1 and 8 , combined with oral S-1 80 mg/m2 twice daily on days 1 - 14 , repeated every 3 weeks . On the other h and , G includes intravenous GEM 1,000 mg/m2on days 1 , 8 and 15 , repeated every 4 weeks . These therapies were continued until disease progression . The primary endpoint was objective response rate ( ORR ) . Secondary endpoints included disease control rate ( DCR ; complete response , partial response , and stable disease ) , progression-free survival ( PFS ) , overall survival ( OS ) , and safety . RESULTS Between Jun. 2007 and Aug. 2010 , 117 pts from 16 institutions were registered . Patient characteristics in GS and G were : median age ; 64.1 and 62.4 years , PS 0 ; 83 % and 77 % , locally advanced ; 23 % and 24 % , respectively . ORR of GS was 22.6 % , whereas that of G was 3.4 % . This difference was statistically significant ( p = 0.0029 ) . DCR was 60.4 % in GS and 44.1 % in G. Median PFS was 8.0 months in GS and 4.9 month in G. This was also statistically significant ( p=0.02 ) . Moreover , median OS of GS was significantly likely to be longer than that of G ( 13.0 months vs. 7.9 months ; p = 0.04 ) . The major grade 3 - 4 adverse events were neutropenia ( 24.5 % in GS and 5.1 % in G ) , thrombocytopenia ( 13.2 % in GS and 5.1 % in G ) , and skin rash ( 9.4 % in GS ) . CONCLUSIONS Our study showed the possibility that GS could be a first line therapy for unresectable pancreatic cancer . Larger r and omized phase III study is warranted 4131 Background : GEM is a st and ard drug for chemotherapy in patients with APC . But they should be offered better therapy aim ed more effective response and prolonging survival . UFT is also available for treatment of APC . In order to evaluate the efficacy of GEM in combination with UFT , we performed following study . METHODS Eligibility : no pretreatment ( chemotherapy and irradiation ) , good performance status ( 50 - 100 in Karnofsky Performance Status ) and less than 75 years old in APC patients such as locally advanced or with distant metastasis . The study is r and omized trial comparing two arms , arm A in which patients are treated by GEM plus UFT ( day 1 , 8 , 15 : gemcitabine 1000 mg/m2 , d.i.v./30min ; everyday : UFT 300 mg/day , oral ; every 4 weeks as 1 course ) , arm B in which patients are treated by GEM alone ( day 1 , 8 , 15 : gemcitabine 1000 mg/m2 , div/30min ; every 4 weeks as 1 course ) . Primary endpoints are response rate ( RR ) and survival time ( MST ) . Time to progression ( TTP ) and Clinical benefit response ( CBR ) were also evaluated . RESULTS During July in 2001 to March in 2003 , 19 patients ( A : B=10 : 9 ) were r and omized from two centers.depends on document review Pretreatment characteristics were well balanced between the two groups ; A vs B as median age , 60.5 vs 58.4 , stage ( locally advanced : metastatic ) , 3:7 vs 2:7 , sex difference ( male : female ) , 7:3 vs 7:2 . RR ( 0/10 vs 3/9 ) and MST ( 5.0±0.6 months vs 7.6±2.1 ) were not significant ( NS ) . CBR ( 25 % vs 33.3 % ) was NS . But TTP ( 1.9±0.5 months vs 5.0±1.5 ) was significantly different ( p=0.0408 , Logrank ) . So , from a point of ethics , the study has already stopped . Toxicity ( NCI-CTC grade 3/4 ) ; leucocytes ( 20.0%:33.3 % ) , neutrophils ( 10.0%:11.1 % ) , platelets ( 10.0%:0 % ) , diarrhea ( 10.0%:0 % ) , anorexia ( 40.0%:11.1 % ) Conclusions : The chemotherapy by GEM plus UFT in this method may not be effective compared with GEM alone . No significant financial relationships to disclose PURPOSE Exatecan mesylate is a hexacyclic , water-soluble , topoisomerase-1 inhibitor . Exatecan has single-agent and combination activity with gemcitabine in advanced pancreatic cancer . A multicenter , r and omized , phase III trial comparing exatecan plus gemcitabine versus gemcitabine alone in advanced pancreatic cancer was conducted . PATIENTS AND METHODS Eligibility criteria included Karnofsky performance status > or = 60 % , locally advanced or metastatic pancreatic adenocarcinoma , and no prior chemotherapy . Radiation alone for locally advanced disease was permitted . Patients were r and omly assigned on a 1:1 basis . For the exatecan plus gemcitabine arm , exatecan 2.0 mg/m2 and gemcitabine 1,000 mg/m2 were administered on days 1 and 8 , every 3 weeks . Gemcitabine alone was dosed at 1,000 mg/m2 up to 7 weeks in the first cycle , then once a week for the first 3 weeks of a 4-week cycle . Tumor assessment was performed every 6 weeks . The primary end point was overall survival . An intent-to-treat analysis was used . RESULTS From August 2001 to January 2003 , 349 patients were r and omly assigned , 175 to exatecan plus gemcitabine and 174 to gemcitabine alone . Twenty-four patients ( 6.9 % ) were not treated . The median survival time was 6.7 months for exatecan plus gemcitabine and 6.2 months for gemcitabine alone ( P = .52 ) . One complete response ( CR ; < 1 % ) and 11 partial responses ( PRs ; 6.3 % ) were observed in the exatecan plus gemcitabine treatment group , and one CR ( < 1 % ) and eight PRs ( 4.6 % ) were observed in the gemcitabine-alone group . Grade 3 and 4 toxicities were higher for the exatecan plus gemcitabine arm versus the gemcitabine alone arm ; neutropenia ( 30 % v 15 % ) and thrombocytopenia ( 15 % v 4 % ) . CONCLUSION Exatecan plus gemcitabine was not superior to gemcitabine alone with respect to overall survival in the first-line treatment of advanced pancreatic cancer BACKGROUND Patients with advanced pancreatic adenocarcinoma have a poor response , progression-free survival , and overall survival with st and ard treatment . We aim ed to assess whether a four-drug regimen could improve 4 month progression-free survival compared with gemcitabine alone . METHODS In a r and omised multicentre phase III trial , 52 patients were r and omly assigned to 40 mg/m2 cisplatin and 40 mg/m2 epirubicin both given on day 1 , 600 mg/m2 gemcitabine given intravenously over 1 h on days 1 and 8 , and 200 mg/m2 fluorouracil a day given by continuous infusion on days 1 - 28 of a 4-week cycle ( PEFG regimen ) , and 47 were assigned to 1000 mg/m2 gemcitabine given intravenously over 30 min once a week for 7 of 8 consecutive weeks in cycle 1 and for 3 of 4 weeks thereafter . The primary endpoint was 4-month progression-free survival . Secondary endpoints were overall survival , objective response , safety , and quality of life . Analyses were by intention to treat . FINDINGS 51 patients assigned PEFG and 46 assigned gemcitabine alone had disease progression . 49 patients in the PEFG group and 46 in the gemcitabine group died from progressive disease . More patients allocated PEFG than gemcitabine alone were alive without progressive disease at 4 months ( 60 % [ 95 % CI 46 - 72 ] vs 28 % [ 17 - 42 ] ; hazard ratio [ HR ] 0.46 [ 0.26 - 0.79 ] ) . 1-year overall survival in the PEFG group was 38.5 % ( 25.3 - 51.7 ) and in the gemcitabine group was 21.3 % ( 9.6 - 33.0 ; HR 0.68 [ 0.42 - 1.09 ] ) . More patients assigned PEFG showed disease response than did those assigned gemcitabine ( 38.5 % [ 25.3 - 51.7 ] vs 8.5 % [ 0.5 - 16.5 ] ; odds ratio 6.60 [ 2.11 - 20.60 ] , p=0.0008 ) . More patients in the PEFG group had grade 3 - 4 neutropenia and thrombocytopenia than in the gemcitabine group ( p<0.0001 ) . INTERPRETATION The PEFG regimen could be considered for treatment of advanced pancreatic adenocarcinoma PURPOSE Single-agent gemcitabine became st and ard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil . The Gruppo Italiano Pancreas 1 r and omized phase III trial aim ed to compare gemcitabine plus cisplatin versus gemcitabine alone ( Clinical Trials.gov ID NCT00813696 ) . PATIENTS AND METHODS Patients with locally advanced or metastatic pancreatic cancer , age 18 to 75 years , and Karnofsky performance status ( KPS ) > or = 50 , were r and omly assigned to receive gemcitabine ( arm A ) or gemcitabine plus cisplatin ( arm B ) . Arm A : gemcitabine 1,000 mg/m(2 ) weekly for 7 weeks , and , after a 1-week rest , on days 1 , 8 , and 15 every 4 weeks . Arm B : cisplatin 25 mg/m(2 ) added weekly to gemcitabine , except cycle 1 day 22 . Primary end point was overall survival . To have 8 % power of detecting a 0.74 hazard ratio ( HR ) of death , with bilateral alpha .05 , 355 events were needed and 400 patients planned . RESULTS Four hundred patients were enrolled ( arm A : 199 ; arm B : 201 ) . Median age was 63 , 59 % were male , 84 % had stage IV , and 83 % had KPS > or = 80 . Median overall survival was 8.3 months versus 7.2 months in arm A and B , respectively ( HR , 1.10 ; 95 % CI , 0.89 to 1.35 ; P = .38 ) . Median progression-free survival was 3.9 months versus 3.8 months in arm A and B , respectively ( HR , 0.97 ; 95 % CI , 0.80 to 1.19 ; P = .80 ) . The objective response rate was 10.1 % in A and 12.9 % in B ( P = .37 ) . Clinical benefit was experienced by 23.0 % in A and 15.1 % in B ( P = .057 ) . Combination therapy produced more hematologic toxicity , without relevant differences in nonhematologic toxicity . CONCLUSION The addition of weekly cisplatin to gemcitabine failed to demonstrate any improvement as first-line treatment of advanced pancreatic cancer PURPOSE To compare the effectiveness and tolerability of gemcitabine plus cisplatin with single-agent gemcitabine as first-line chemotherapy for locally advanced or metastatic pancreatic cancer . PATIENTS AND METHODS Patients with advanced adenocarcinoma of the pancreas were r and omly assigned to receive either gemcitabine 1,000 mg/m2 and cisplatin 50 mg/m2 given on days 1 and 15 of a 4-week cycle ( GemCis arm ) or gemcitabine alone at a dose of 1,000 mg/m2 on days 1 , 8 , and 15 of a 4-week regimen ( Gem arm ) . The primary end point was overall survival ; secondary end points were progression-free survival , response rate , safety , and quality of life . RESULTS One hundred ninety-five patients were enrolled and showed baseline characteristics well balanced between treatment arms . Combination treatment in the GemCis arm was associated with a prolonged median progression-free survival ( 5.3 months v 3.1 months ; hazard ratio [ HR ] = 0.75 ; P = .053 ) . Also , median overall survival was superior for patients treated in the GemCis arm as compared with the Gem arm ( 7.5 v 6.0 months ) , an advantage which did not , however , reach statistical significance ( HR = 0.80 ; P = .15 ) . Tumor response rates were comparable between treatment arms ( 10.2 % v 8.2 % ) . The rate of stable disease was , however , greater in the combination arm ( 60.2 % v 40.2 % ; P < .001 ) . Grade 3 to 4 hematologic toxicity did not exceed 15 % in both treatment arms . CONCLUSION These results support the efficacy and safety of an every-2-weeks treatment with gemcitabine plus cisplatin . Median overall survival and progression-free survival were more favorable in the combination arm as compared with gemcitabine alone , although the difference did not attain statistical significance PURPOSE Single-agent gemcitabine ( GEM ) is st and ard treatment of metastatic pancreatic cancer . Fixed-dose rate ( FDR ) GEM and GEM plus oxaliplatin have shown promise in early clinical trials . E6201 was design ed to compare overall survival ( OS ) of st and ard weekly GEM 1,000 mg/m(2)/30 minutes versus GEM FDR 1,500 mg/m(2)/150 minutes or GEM 1,000 mg/m(2)/100 minutes/day 1 plus oxaliplatin 100 mg/m(2)/day 2 every 14 days ( GEMOX ) . METHODS This trial included patients with metastatic or locally advanced pancreatic cancer , normal organ function , and performance status of 0 to 2 . The study was design ed to detect a 33 % difference in median survival ( hazard ratio [ HR ] < or = 0.75 for either of the experimental arms ) with 81 % power while maintaining a significance level of 2.5 % in a two-sided test for each of the two primary comparisons . RESULTS Eight hundred thirty-two patients were enrolled . The median survival and 1-year survival were 4.9 months ( 95 % CI , 4.5 to 5.6 ) and 16 % for GEM , 6.2 months ( 95 % CI , 5.4 to 6.9 ) , and 21 % for GEM FDR ( HR , 0.83 ; stratified log-rank P = .04 ) , and 5.7 months ( 95 % CI , 4.9 to 6.5 ) and 21 % for GEMOX ( HR , 0.88 ; stratified log-rank P = .22 ) . Neither of these differences met the prespecified criteria for significance . Survival was 9.2 months for patients with locally advanced disease , and 5.4 months for those with metastatic disease . Grade 3/4 neutropenia and thrombocytopenia were greatest with GEM FDR . GEMOX caused higher rates of nausea , vomiting , and neuropathy . CONCLUSION Neither GEM FDR nor GEMOX result ed in substantially improved survival or symptom benefit over st and ard GEM in patients with advanced pancreatic cancer PURPOSE The trial objectives were to identify the maximum-tolerated dose ( MTD ) of first-line gemcitabine plus nab-paclitaxel in metastatic pancreatic adenocarcinoma and to provide efficacy and safety data . Additional objectives were to evaluate positron emission tomography ( PET ) scan response , secreted protein acidic and rich in cysteine ( SPARC ) , and CA19 - 9 levels in relation to efficacy . Subsequent pre clinical studies investigated the changes involving the pancreatic stroma and drug uptake . PATIENTS AND METHODS Patients with previously untreated advanced pancreatic cancer were treated with 100 , 125 , or 150 mg/m(2 ) nab-paclitaxel followed by gemcitabine 1,000 mg/m(2 ) on days 1 , 8 , and 15 every 28 days . In the pre clinical study , mice were implanted with human pancreatic cancers and treated with study agents . RESULTS A total of 20 , 44 , and three patients received nab-paclitaxel at 100 , 125 , and 150 mg/m(2 ) , respectively . The MTD was 1,000 mg/m(2 ) of gemcitabine plus 125 mg/m(2 ) of nab-paclitaxel once a week for 3 weeks , every 28 days . Dose-limiting toxicities were sepsis and neutropenia . At the MTD , the response rate was 48 % , with 12.2 median months of overall survival ( OS ) and 48 % 1-year survival . Improved OS was observed in patients who had a complete metabolic response on [(18)F]fluorodeoxyglucose PET . Decreases in CA19 - 9 levels were correlated with increased response rate , progression-free survival , and OS . SPARC in the stroma , but not in the tumor , was correlated with improved survival . In mice with human pancreatic cancer xenografts , nab-paclitaxel alone and in combination with gemcitabine depleted the desmoplastic stroma . The intratumoral concentration of gemcitabine was increased by 2.8-fold in mice receiving nab-paclitaxel plus gemcitabine versus those receiving gemcitabine alone . CONCLUSION The regimen of nab-paclitaxel plus gemcitabine has tolerable adverse effects with substantial antitumor activity , warranting phase III evaluation |
1,031 | 26,210,309 | 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 . | Abstract Purpose Previous review s have compared surgical to non-surgical management of sciatica , but have overlooked the specific comparison between surgery and physical activity-based interventions . | 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 interval , 11 to 19.7 ) for bodily pain , 18.9 ( 95 % confidence interval , 14.8 to 23 ) for physical function , and -14.3 ( 95 % confidence interval , -17.5 to -11.1 ) for the Oswestry Disability Index . Early advantages ( at two years ) of surgical treatment in terms of the secondary measures of bothersomeness of back and leg symptoms , overall satisfaction with current symptoms , and self-rated progress were also maintained at four years . CONCLUSIONS Compared with patients who are treated nonoperatively , patients in whom degenerative spondylolisthesis and associated spinal stenosis are treated surgically maintain substantially greater pain relief and improvement in function for four years Study Design . A prospect i ve cohort study . Objective . To assess 10-year outcomes of patients with sciatica result ing from a lumbar disc herniation treated surgically or nonsurgically . Summary of Background Data . There is little information comparing long-term outcomes of surgical and conservative therapy of lumbar disc herniation in contemporary clinical practice . Prior studies suggest that these outcomes are similar . Methods . Patients recruited from the practice s of orthopedic surgeons , neurosurgeons , and occupational medicine physicians throughout Maine had baseline interviews with follow-up question naires mailed at regular intervals over 10 years . Clinical data were obtained at baseline from a physician question naire . Primary analyses were based on initial treatment received , either surgical or nonsurgical . Secondary analyses examined actual treatments received by 10 years . Outcomes included patient-reported symptoms of leg and back pain , functional status , satisfaction , and work and disability compensation status . Results . Of 507 eligible consenting patients initially enrolled , 10-year outcomes were available for 400 of 477 ( 84 % ) surviving patients ; 217 of 255 ( 85 % ) treated surgically , and 183 of 222 ( 82 % ) treated nonsurgically . Patients undergoing surgery had worse baseline symptoms and functional status than those initially treated nonsurgically . By 10 years , 25 % of surgical patients had undergone at least one additional lumbar spine operation , and 25 % of nonsurgical patients had at least one lumbar spine operation . At 10-year follow-up , 69 % of patients initially treated surgically reported improvement in their predominant symptom ( back or leg pain ) versus 61 % of those initially treated nonsurgically ( P = 0.2 ) . A larger proportion of surgical patients reported that their low back and leg pain were much better or completely gone ( 56 % vs. 40 % , P = 0.006 ) and were more satisfied with their current status ( 71 % vs. 56 % , P = 0.002 ) . Treatment group differences persisted after adjustment for other determinants of outcome in multivariate models . Change in the modified Rol and back-specific functional status scale favored surgical treatment , and the relative benefit persisted over the follow-up period . Despite these differences , work and disability status at 10 years were comparable among those treated surgically or nonsurgically . Conclusions . Surgically treated patients with a herniated lumbar disc had more complete relief of leg pain and improved function and satisfaction compared with nonsurgically treated patients over 10 years . Nevertheless , improvement in the patient ’s predominant symptom and work and disability outcomes were similar regardless of treatment received . For patients in whom elective discectomy is a treatment option , an individualized treatment plan requires patients and their physicians to integrate clinical findings with patient preferences based on their symptoms and goals STUDY DESIGN A prospect i ve r and omized study was performed . OBJECTIVE To determine whether posterolateral fusion in patients with adult isthmic spondylolisthesis results in an improved outcome compared with an exercise program . SUMMARY OF BACKGROUND DATA In spondylolisthesis , satisfactory results have been reported with both surgical and conservative management . The evidence for treatment efficacy , however , is weak because prospect i ve r and omized studies are lacking . METHODS In this study , 111 patients were r and omly allocated to an exercise program ( n = 34 ) or posterolateral fusion with or without transpedicular fixation ( n = 77 ) . The inclusion criteria were lumbar isthmic spondylolisthesis of any grade , at least 1 year of low back pain or sciatica , and a severely restricted functional ability in individuals 18 to 55 years of age . Pain and functional disability were quantified before treatment and at 1- and 2-year follow-up assessment s by visual analog scales ( VAS ) . RESULTS The 2-year follow-up rate was 93 % . The functional outcome , as assessed by the Disability Rating Index and the pain reduction , was better in the surgically treated group than in the exercise group at both the 1- and 2-year follow-up assessment s ( P < 0.01 ) . In the longitudinal analysis , the mean Disability Rating Index and pain improved in the surgical group ( P < 0.0001 ) . In the exercise group , the Disability Rating Index did not change at all , whereas the pain decreased slightly ( P < 0.02 ) . CONCLUSIONS Surgical management of adult isthmic spondylolisthesis improves function and relieves pain more efficiently than an exercise program STUDY DESIGN A cohort of 100 patients with symptomatic lumbar spinal stenosis , characterized in a previous article , were given surgical or conservative treatment and followed for 10 years . OBJECTIVES To identify the short- and long-term results after surgical and conservative treatment , and to determine whether clinical or radiologic predictors for the treatment result can be defined . SUMMARY OF BACKGROUND DATA Surgical decompression has been considered the rational treatment . However , clinical experience indicates that many patients do well with conservative treatment . METHODS In this study , 19 patients with severe symptoms were selected for surgical treatment and 50 patients with moderate symptoms for conservative treatment , whereas 31 patients were r and omized between the conservative ( n = 18 ) and surgical ( n = 13 ) treatment groups . Pain was decisive for the choice of treatment group . All patients were observed for 10 years by clinical evaluation and question naires . The results , evaluated by patient and physician , were rated as excellent , fair , unchanged , or worse . RESULTS After a period of 3 months , relief of pain had occurred in most patients . Some had relief earlier , whereas for others it took 1 year . After a period of 4 years , excellent or fair results were found in half of the patients selected for conservative treatment , and in four fifths of the patients selected for surgery . Patients with an unsatisfactory result from conservative treatment were offered delayed surgery after 3 to 27 months ( median , 3.5 months ) . The treatment result of delayed surgery was essentially similar to that of the initial group . The treatment result for the patients r and omized for surgical treatment was considerably better than for the patients r and omized for conservative treatment . Clinical ly significant deterioration of symptoms during the final 6 years of the follow-up period was not observed . Patients with multilevel afflictions , surgically treated or not , did not have a poorer outcome than those with single-level afflictions . Clinical or radiologic predictors for the final outcome were not found . There were no dropouts , except for 14 deaths . CONCLUSIONS The outcome was most favorable for surgical treatment . However , an initial conservative approach seems advisable for many patients because those with an unsatisfactory result can be treated surgically later with a good outcome Study Design . A r and omized controlled trial . Objectives . To assess the effectiveness of decompressive surgery as compared with nonoperative measures in the treatment of patients with lumbar spinal stenosis . Summary of Background Data . No previous r and omized trial has assessed the effectiveness of surgery in comparison with conservative treatment for spinal stenosis . Methods . Four university hospitals agreed on the classification of the disease , inclusion and exclusion criteria , radiographic routines , surgical principles , nonoperative treatment options , and follow-up protocol s. A total of 94 patients were r and omized into a surgical or nonoperative treatment group : 50 and 44 patients , respectively . Surgery comprised undercutting laminectomy of the stenotic segments in 10 patients augmented with transpedicular fusion . The primary outcome was based on assessment of functional disability using the Oswestry Disability Index ( scale , 0–100 ) . Data on the intensity of leg and back pain ( scales , 0–10 ) , as well as self-reported and measured walking ability were compiled at r and omization and at follow-up examinations at 6 , 12 , and 24 months . Results . Both treatment groups showed improvement during follow-up . At 1 year , the mean difference in favor of surgery was 11.3 in disability ( 95 % confidence interval [ CI ] , 4.3–18.4 ) , 1.7 in leg pain ( 95 % CI , 0.4–3.0 ) , and 2.3(95 % CI , 1.1–3.6 ) in back pain . At the 2-year follow-up , the mean differences were slightly less : 7.8 in disability ( 95 % CI , 0.8–14.9 ) 1.5 in leg pain ( 95 % CI , 0.3–2.8 ) , and 2.1 in back pain ( 95 % CI , 1.0–3.3 ) . Walking ability , either reported or measured , did not differ between the two treatment groups . Conclusions . Although patients improved over the 2-year follow-up regardless of initial treatment , those undergoing decompressive surgery reported greater improvement regarding leg pain , back pain , and overall disability . The relative benefit of initial surgical treatment diminished over time , but outcomes of surgery remained favorable at 2 years . Longer follow-up is needed to determine if these differences persist Objective To determine whether the faster recovery after early surgery for sciatica compared with prolonged conservative care is attained at reasonable costs . Design Cost utility analysis alongside a r and omised controlled trial . Setting Nine Dutch hospitals . Participants 283 patients with sciatica for 6 - 12 weeks , caused by lumbar disc herniation . Interventions Six months of prolonged conservative care compared with early surgery . Main outcome measures Quality adjusted life years ( QALYs ) at one year and societal costs , estimated from patient reported utilities ( UK and US EuroQol , SF-6D , and visual analogue scale ) and diaries on costs ( healthcare , patient ’s costs , and productivity ) . Results Compared with prolonged conservative care , early surgery provided faster recovery , with a gain in QALYs according to the UK EuroQol of 0.044 ( 95 % confidence interval 0.005 to 0.083 ) , the US EuroQol of 0.032 ( 0.005 to 0.059 ) , the SF-6D of 0.024 ( 0.003 to 0.046 ) , and the visual analogue scale of 0.032 ( −0.003 to 0.066 ) . From the healthcare perspective , early surgery result ed in higher costs ( difference € 1819 ( £ 1449 ; $ 2832 ) , 95 % confidence interval € 842 to € 2790 ) , with a cost utility ratio per QALY of € 41 000 ( € 14 000 to € 430 000 ) . From the societal perspective , savings on productivity costs led to a negligible total difference in cost ( € −12 , € −4029 to € 4006 ) . Conclusions Faster recovery from sciatica makes early surgery likely to be cost effective compared with prolonged conservative care . The estimated difference in healthcare costs was acceptable and was compensated for by the difference in absenteeism from work . For a willingness to pay of € 40 000 or more per QALY , early surgery need not be withheld for economic reasons . Trial registration Current Controlled Trials IS RCT N 26872154 Study Design . Combined prospect i ve r and omized controlled trial and observational cohort study of intervertebral disc herniation ( IDH ) , an as-treated analysis . Objective . To determine modifiers of the treatment effect ( TE ) of surgery ( the difference between surgical and nonoperative outcomes ) for intervertebral disc herniation ( IDH ) using subgroup analysis . Summary of Background Data . The Spine Patient Outcomes Research Trial demonstrated a positive surgical TE for IDH at the group level . However , individual characteristics may affect TE . No prior studies have evaluated TE modifiers in IDH . Methods . IDH patients underwent either discectomy ( n = 788 ) or nonoperative care ( n = 404 ) and were analyzed according to treatment received . Thirty-seven baseline variables were used to define subgroups for calculating the time-weighted average TE for the Oswestry Disability Index ( ODI ) across 4 years ( TE = & Dgr;ODIsurgery −&Dgr;ODInonoperative ) . Variables with significant subgroup-by-treatment interactions ( P < 0.1 ) were simultaneously entered into a multivariate model to select independent TE predictors . Results . All analyzed subgroups improved significantly more with surgery than with nonoperative treatment ( P < 0.05 ) . In minimally adjusted univariate analyses , being married , absence of joint problems , worsening symptom trend at baseline , high school education or less , older age , no worker 's compensation , longer duration of symptoms , and an SF-36 mental component score ( MCS ) less than 35 were associated with greater TEs . Multivariate analysis demonstrated that being married ( TE , −15.8 vs. −7.7 single , P < 0.001 ) , absence of joint problems ( TE , −14.6 vs. −10.3 joint problems , P = 0.012 ) , and worsening symptoms ( TE , −15.9 vs. −11.8 stable symptoms , P = 0.032 ) were independent TE modifiers . TEs were greatest in married patients with worsening symptoms ( −18.3 ) vs. single patients with stable symptoms ( −7.8 ) . Conclusion . IDH patients who met strict inclusion criteria improved more with surgery than with nonoperative treatment , regardless of specific characteristics . However , being married , without joint problems , and worsening symptom trend at baseline were associated with a greater TE PURPOSE To compare short- , intermediate- , and long-term functional results concerning pain reduction and mobility improvement between conservative therapy and percutaneous disk decompression ( PDD ) in patients with intervertebral disk herniations . MATERIAL S AND METHODS The study received approval from both the university ethics panel and the institutional review board . Patients provided informed consent for the study . Over the past 4 years , two r and omized groups of 31 patients with sciatica due to intervertebral disk herniation were prospect ively studied and compared with the t test . The control group underwent conservative therapy ( administration of analgesics , antiinflammatory drugs , muscle relaxants , and physiotherapy ) for 6 weeks . The decompression group underwent fluoroscopically guided PDD . Pain reduction and mobility improvement were recorded at 3- , 12- , and 24-month follow-up on a numeric visual scale ( NVS ) ( range , 0 - 10 ) . RESULTS The control group had a mean pain score of 6.9 NVS units ± 1.9 prior to conservative therapy . This was reduced to 0.9 NVS units ± 2.0 3 months after therapy ; however , it increased to 4.0 NVS units ± 3.4 at 12-month follow-up and further increased to 4.0 NVS units ± 3.4 at 24-month follow-up . The decompression group had a mean pain score of 7.4 NVS units ± 1.4 prior to PDD . This was reduced to 3.0 NVS units ± 2.4 at 3-month follow-up and further reduced to 1.7 NVS units ± 2.4 at 12-month follow-up and 1.6 NVS units ± 2.5 at 24-month follow-up . No complications were noted . CONCLUSION When compared with conservative therapy , PDD shows improved amelioration of symptoms at 12- and 24-month follow-up 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 . Study Design . Combined prospect i ve r and omized controlled trial and observational cohort study of spinal stenosis ( SpS ) with an as-treated analysis . Objective . To determine modifiers of the treatment effect ( TE ) of surgery ( the difference between surgical and nonoperative outcomes ) for SpS using subgroup analysis . Summary of Background Data . The Spine Patient Outcomes Research Trial demonstrated a positive surgical TE for SpS at the group level . However , individual characteristics may affect TE . No previous studies have evaluated TE modifiers in SpS. Methods . SpS patients were treated with either surgery ( n = 419 ) or nonoperative care ( n = 235 ) and were analyzed according to treatment received . Fifty-three baseline variables were used to define subgroups for calculating the time-weighted average TE for the Oswestry Disability Index ( ODI ) over 4 years ( TE = & Dgr;ODIsurgery – & Dgr;ODInonoperative ) . Variables with significant subgroup × treatment interactions ( P < 0.05 ) were simultaneously entered into a multivariate model to select independent TE predictors . Results . Other than smokers , all analyzed subgroups including at least 50 patients improved significantly more with surgery than with nonoperative treatment ( P < 0.05 ) . Multivariate analysis demonstrated : baseline ODI ⩽ 56 ( TE −15.0 vs. −4.4 , ODI > 56 , P < 0.001 ) , not smoking ( TE −11.7 vs. −1.6 smokers , P < 0.001 ) , neuroforaminal stenosis ( TE −14.2 vs. −8.7 no neuroforaminal stenosis , P = 0.002 ) , predominant leg pain ( TE −11.5 vs. −7.3 predominant back pain , P = 0.035 ) , not lifting at work ( TE −12.5 vs. −0.5 lifting at work , P = 0.017 ) , and the presence of a neurological deficit ( TE −13.3 vs. −7.2 no neurological deficit , P < 0.001 ) were associated with greater TE . Conclusion . With the exception of smokers , patients who met strict inclusion criteria improved more with surgery than with nonoperative treatment , regardless of other specific characteristics . However , TE varied significantly across certain subgroups , and these data can be used to individualize shared decision making discussion s about likely outcomes . Smoking cessation should be considered before surgery for BACKGROUND Surgery for spinal stenosis is widely performed , but its effectiveness as compared with nonsurgical treatment has not been shown in controlled trials . METHODS Surgical c and i date s with a history of at least 12 weeks of symptoms and spinal stenosis without spondylolisthesis ( as confirmed on imaging ) were enrolled in either a r and omized cohort or an observational cohort at 13 U.S. spine clinics . Treatment was decompressive surgery or usual nonsurgical care . The primary outcomes were measures of bodily pain and physical function on the Medical Outcomes Study 36-item Short-Form General Health Survey ( SF-36 ) and the modified Oswestry Disability Index at 6 weeks , 3 months , 6 months , and 1 and 2 years . RESULTS A total of 289 patients were enrolled in the r and omized cohort , and 365 patients were enrolled in the observational cohort . At 2 years , 67 % of patients who were r and omly assigned to surgery had undergone surgery , whereas 43 % of those who were r and omly assigned to receive nonsurgical care had also undergone surgery . Despite the high level of nonadherence , the intention-to-treat analysis of the r and omized cohort showed a significant treatment effect favoring surgery on the SF-36 scale for bodily pain , with a mean difference in change from baseline of 7.8 ( 95 % confidence interval , 1.5 to 14.1 ) ; however , there was no significant difference in scores on physical function or on the Oswestry Disability Index . The as-treated analysis , which combined both cohorts and was adjusted for potential confounders , showed a significant advantage for surgery by 3 months for all primary outcomes ; these changes remained significant at 2 years . CONCLUSIONS In the combined as-treated analysis , patients who underwent surgery showed significantly more improvement in all primary outcomes than did patients who were treated nonsurgically . ( Clinical Trials.gov number , NCT00000411 [ Clinical Trials.gov ] . ) We r and omised a total of 94 patients with long-st and ing moderate lumbar spinal stenosis ( LSS ) into a surgical group and a non-operative group , with 50 and 44 patients , respectively . The operative treatment comprised undercutting laminectomy of stenotic segments , augmented with transpedicular-instrumented fusion in suspected lumbar instability . The primary outcome was the Oswestry disability index ( ODI ) , and the other main outcomes included assessment s of leg and back pain and self-reported walking ability , all based on question naire data from 85 patients at the 6-year follow-up . At the 6-year follow-up , the mean difference in ODI in favour of surgery was 9.5 ( 95 % confidence interval 0.9–18.1 , P-value for global difference 0.006 ) , whereas the intensity of leg or back pain did not differ between the two treatment groups any longer . Walking ability did not differ between the treatment groups at any time . Decompressive surgery of LSS provided modest but consistent improvement in functional ability , surpassing that obtained after non-operative measures Study Design . Concurrent , prospect i ve , r and omized , and observational cohort study . Objective . To assess the 4-year outcomes of surgery versus nonoperative care . Summary of Background Data . Although r and omized trials have demonstrated small short-term differences in favor of surgery , long-term outcomes comparing surgical to nonoperative treatment remain controversial . Methods . Surgical c and i date s with imaging-confirmed lumbar intervertebral disc herniation meeting SPORT eligibility criteria enrolled into prospect i ve , r and omized ( 501 participants ) , and observational cohorts ( 743 participants ) at 13 spine clinics in 11 US states . Interventions were st and ard open discectomy versus usual nonoperative care . Main outcome measures were changes from baseline in the SF-36 Bodily Pain ( BP ) and Physical Function ( PF ) scales and the modified Oswestry Disability Index ( ODI - AAOS/Modems version ) assessed at 6 weeks , 3 months , 6 months , and annually thereafter . Results . Nonadherence to treatment assignment caused the intent-to-treat analyses to underestimate the treatment effects . In the 4-year combined as-treated analysis , those receiving surgery demonstrated significantly greater improvement in all the primary outcome measures ( mean change surgery vs. nonoperative ; treatment effect ; 95 % CI ) : BP ( 45.6 vs. 30.7 ; 15.0 ; 11.8 to 18.1 ) , PF ( 44.6 vs. 29.7 ; 14.9;12.0 to 17.8 ) and ODI ( −38.1 vs. −24.9 ; −13.2 ; −15.6 to −10.9 ) . The percent working was similar between the surgery and nonoperative groups , 84.4 % versus 78.4 % respectively . Conclusion . In a combined as-treated analysis at 4 years , patients who underwent surgery for a lumbar disc herniation achieved greater improvement than nonoperatively treated patients in all primary and secondary outcomes except work status Study Design . Prospect i ve r and omized controlled trial . Objective . To assess effectiveness of microdiscectomy in lumbar disc herniation patients with 6 to 12 weeks of symptoms but no absolute indication for surgery . Summary of Background Data . There is limited evidence in favor of discectomy for prolonged symptoms of lumbar disc herniation . However , only one r and omized trial has directly compared discectomy with conservative treatment . Methods . Fifty-six patients ( age range , 20–50 years ) with a lumbar disc herniation , clinical findings of nerve root compression , and radicular pain lasting 6 to 12 weeks were r and omized to microdiscectomy or conservative management . Fifty patients ( 89 % ) were available at the 2-year follow-up . Leg pain intensity was the primary outcome measure . Results . There were no clinical ly significant differences between the groups in leg or back pain intensity , subjective disability , or health-related quality of life over the 2-year follow-up , although discectomy seemed to be associated with a more rapid initial recovery . In a subgroup analysis , discectomy was superior to conservative treatment when the herniation was at L4–L5 . Conclusions . Lumbar microdiscectomy offered only modest short-term benefits in patients with sciatica due to disc extrusion or sequester . Spinal level of the herniation may be an important factor modifying effectiveness of surgery , but this hypothesis needs verification The authors performed single- or multiple-level unilateral laminectomy to treat lumbar spinal stenosis in patients with mild to moderate leg pain and compared the results with those from patients treated with conservative therapy in a prospect i ve study . This decompression technique produced a 68 % rate of improvement compared with a 33 % rate for conservatively treated patients . The surgical group exhibited significant and sustained improvement , whereas the functional and clinical status of the conservatively managed group had returned to baseline during the same period . The preoperative dural sac cross-sectional area at the level of the most stenosis was 70.76 + /- 28.2 mm(2 ) for the surgical group , whereas on postoperative scans it was 108.12 + /- 31.5 mm(2 ) , with an average correction rate of 65 % . Neither new degenerative spondylolisthesis nor any evidence of instability was detected in any patient during the study Study Design . Combined prospect i ve r and omized controlled trial and observational cohort study of degenerative spondylolisthesis ( DS ) with an as-treated analysis . Objective . To determine modifiers of the treatment effect ( TE ) of surgery ( the difference between surgical and nonoperative outcomes ) for DS using subgroup analysis . Summary of Background Data . Spine Patient Outcomes Research Trial demonstrated a positive surgical TE for DS at the group level . However , individual characteristics may affect TE . Methods . Patients with DS were treated with either surgery ( n = 395 ) or nonoperative care ( n = 210 ) and were analyzed according to treatment received . Fifty-five baseline variables were used to define subgroups for calculating the time-weighted average TE for the Oswestry Disability Index during 4 years ( TE = [ INCREMENT ] Oswestry Disability Indexsurgery− [ INCREMENT ] Oswestry Disability Indexnonoperative ) . Variables with significant subgroup-by-treatment interactions ( P < 0.05 ) were simultaneously entered into a multivariate model to select independent TE predictors . Results . All analyzed subgroups that included at least 50 patients improved significantly more with surgery than with nonoperative treatment ( P < 0.05 ) . Multivariate analyses demonstrated that age 67 years or less ( TE −15.7 vs.−11.8 for age > 67 , P= 0.014 ) ; female sex ( TE −15.6 vs.−11.2 for males , P= 0.01 ) ; the absence of stomach problems ( TE −15.2 vs.−11.3 for those with stomach problems , P= 0.035 ) ; neurogenic claudication ( TE −15.3 vs.−9.0 for those without claudication , P= 0.004 ) ; reflex asymmetry ( TE −17.3 vs.−13.0 for those without asymmetry , P= 0.016 ) ; opioid use ( TE −18.4 vs.−11.7 for those not using opioids , P < 0.001 ) ; not taking antidepressants ( TE −14.5 vs.−5.4 for those on antidepressants , P= 0.014 ) ; dissatisfaction with symptoms ( TE −14.5 vs.−8.3 for those satisfied or neutral , P= 0.039 ) ; and anticipating a high likelihood of improvement with surgery ( TE −14.8 vs.−5.1 for anticipating a low likelihood of improvement with surgery , P= 0.019 ) were independently associated with greater TE . Conclusion . Patients who met strict inclusion criteria improved more with surgery than with nonoperative treatment , regardless of other specific characteristics . However , TE varied significantly across certain subgroups . Level of Evidence : CONTEXT For patients with lumbar disk herniation , the Spine Patient Outcomes Research Trial ( SPORT ) r and omized trial intent-to-treat analysis showed small but not statistically significant differences in favor of diskectomy compared with usual care . However , the large numbers of patients who crossed over between assigned groups precluded any conclusions about the comparative effectiveness of operative therapy vs usual care . OBJECTIVE To compare the treatment effects of diskectomy and usual care . DESIGN , SETTING , AND PATIENTS Prospect i ve observational cohort of surgical c and i date s with imaging-confirmed lumbar intervertebral disk herniation who were treated at 13 spine clinics in 11 US states and who met the SPORT eligibility criteria but declined r and omization between March 2000 and March 2003 . INTERVENTIONS St and ard open diskectomy vs usual nonoperative care . MAIN OUTCOME MEASURES Changes from baseline in the Medical Outcomes Study Short-Form Health Survey ( SF-36 ) bodily pain and physical function scales and the modified Oswestry Disability Index ( American Academy of Orthopaedic Surgeons/MODEMS version ) . RESULTS Of the 743 patients enrolled in the observational cohort , 528 patients received surgery and 191 received usual nonoperative care . At 3 months , patients who chose surgery had greater improvement in the primary outcome measures of bodily pain ( mean change : surgery , 40.9 vs nonoperative care , 26.0 ; treatment effect , 14.8 ; 95 % confidence interval , 10.8 - 18.9 ) , physical function ( mean change : surgery , 40.7 vs nonoperative care , 25.3 ; treatment effect , 15.4 ; 95 % CI , 11.6 - 19.2 ) , and Oswestry Disability Index ( mean change : surgery , -36.1 vs nonoperative care , -20.9 ; treatment effect , -15.2 ; 95 % CI , -18.5 . to -11.8 ) . These differences narrowed somewhat at 2 years : bodily pain ( mean change : surgery , 42.6 vs nonoperative care , 32.4 ; treatment effect , 10.2 ; 95 % CI , 5.9 - 14.5 ) , physical function ( mean change : surgery , 43.9 vs nonoperavtive care 31.9 ; treatment effect , 12.0 ; 95 % CI ; 7.9 - 16.1 ) , and Oswestry Disability Index ( mean change : surgery -37.6 vs nonoperative care -24.2 ; treatment effect , -13.4 ; 95 % CI , -17.0 to -9.7 ) . CONCLUSIONS Patients with persistent sciatica from lumbar disk herniation improved in both operated and usual care groups . Those who chose operative intervention reported greater improvements than patients who elected nonoperative care . However , nonr and omized comparisons of self-reported outcomes are subject to potential confounding and must be interpreted cautiously . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000410 Study Design . Cost-effectiveness analysis of a r and omized plus observational cohort trial . Objective . Analyze cost-effectiveness of Spine Patient Outcomes Research Trial data over 4 years comparing surgery with nonoperative care for three common diagnoses : spinal stenosis ( SPS ) , degenerative spondylolisthesis ( DS ) , and intervertebral disc herniation ( IDH ) . Summary of Background Data . Spine surgery rates continue to rise in the United States , but the safety and economic value of these procedures remain uncertain . Methods . Patients with image-confirmed diagnoses were followed in r and omized or observational cohorts with data on re source use , productivity , and EuroQol EQ-5D health state values measured at 6 weeks , 3 , 6 , 12 , 24 , 36 , and 48 months . For each diagnosis , cost per quality -adjusted life year ( QALY ) gained in 2004 US dollars was estimated for surgery relative to nonoperative care using a societal perspective , with costs and QALYs discounted at 3 % per year . Results . Surgery was performed initially or during the 4-year follow-up among 414 of 634 ( 65.3 % ) SPS , 391 of 601 ( 65.1 % ) DS , and 789 of 1192 ( 66.2 % ) IDH patients . Surgery improved health , with persistent QALY differences observed through 4 years ( SPS QALY gain 0.22 ; 95 % confidence interval , CI : 0.15 , 0.34 ; DS QALY gain 0.34 , 95 % CI : 0.30 , 0.47 ; and IDH QALY gain 0.34 , 95 % CI : 0.31 , 0.38 ) . Costs per QALY gained decreased for SPS from $ 77,600 at 2 years to $ 59,400 ( 95 % CI : $ 37,059 , $ 125,162 ) at 4 years , for DS from $ 115,600 to $ 64,300 per QALY ( 95 % CI : $ 32,864 , $ 83,117 ) , and for IDH from $ 34,355 to $ 20,600 per QALY ( 95 % CI : $ 4,539 , $ 33,088 ) . Conclusion . Comparative effectiveness evidence for clearly defined diagnostic groups from Spine Patient Outcomes Research Trial shows good value for surgery compared with nonoperative care over 4 years |
1,032 | 28,427,392 | 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 | Background The optimal revascularization technique in patients with left main coronary artery disease ( CAD ) remains controversial .
We aim ed to compare the long-term performance of percutaneous coronary intervention ( PCI ) versus coronary artery bypass graft ( CABG ) surgery in treatment of left main CAD . | 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 cerebrovascular events at 5 years was 28.3 % in the PCI group and 23.0 % in the CABG group ( hazard ratio [ HR ] : 1.23 ; 95 % confidence interval [ CI ] : 1.01 to 1.55 ; p = 0.045 ) . This difference is mainly driven by a higher rate of repeat revascularization associated with PCI ( HR : 1.85 ; 95 % CI : 1.38 to 2.47 ; p < 0.001 ) . The 2 strategies showed similar rates of the safety composite endpoint of death , myocardial infa rct ion , or stroke ( p = 0.45 ) . In patients with isolated LM or LM + 1-vessel disease , PCI was associated with a 60 % reduction in all-cause mortality ( HR : 0.40 ; 95 % CI : 0.20 to 0.83 ; p = 0.029 ) and 67 % reduction in cardiac mortality ( HR : 0.33 ; 95 % CI : 0.12 to 0.88 ; p = 0.025 ) when compared with CABG . CONCLUSIONS In patients with unprotected LMD , CABG , and PCI result in similar rates of the safety composite endpoint of death , myocardial infa rct ion , or stroke . In patients with isolated LM or LM + 1-vessel disease , PCI is associated with lower all-cause and cardiac mortality when compared to CABG OBJECTIVES This study has reported 10-year clinical follow-up of patients enrolled in the prospect i ve , r and omized LE MANS ( Left Main Stenting ) trial . BACKGROUND The very long-term outcome after left main stenting in comparison with surgical revascularization remains unknown . METHODS In this prospect i ve , multicenter trial , we r and omly assigned 105 patients with unprotected left main coronary artery stenosis with low and medium complexity of coexisting coronary artery disease according to SYNTAX ( Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery ) score to percutaneous coronary intervention ( PCI ) with stenting ( n = 52 ) or coronary artery bypass grafting ( CABG ) ( n = 53 ) . Drug-eluting stents were implanted in 35 % , whereas arterial grafts to the left anterior descending artery were utilized in 81 % . Currently , the mean long-term follow-up was collected at 9.8 ± 1.0 years . Follow up for all-cause mortality is complete , whereas the incidence of major adverse cardiovascular and cerebral events ( MACCE ) was reported from 90 % of patients . Ambulatory follow-up was completed in 46 ( 43.9 % ) patients . RESULTS At 10 years , there was a trend toward higher ejection fraction in stenting when compared with surgery ( 54.9 ± 8.3 % vs. 49.8 ± 10.3 % ; p = 0.07 ) . The mortality ( 21.6 % vs. 30.2 % ; p = 0.41 ) and MACCE ( 51.1 % vs. 64.4 % ; p = 0.28 ) were statistically not different between groups ; however , numerically the difference was in favor of stenting . Similarly , there was no difference in the occurrence of myocardial infa rct ion ( 8.7 vs. 10.4 % ; p = 0.62 ) , stroke ( 4.3 vs. 6.3 % ; p = 0.68 ) , and repeated revascularization rates ( 26.1 % vs. 31.3 % ; p = 0.64 ) . The probability of very long-term survival up to 14 years was comparable between PCI and CABG ( 74.2 % vs. 67.5 % ; p = 0.34 ; hazard ratio : 1.45 , 95 % confidence interval : 0.67 to 3.13 ) ; however , there was a trend toward higher MACCE-free survival in the PCI group ( 34.7 % vs. 22.1 % ; p = 0.06 ; hazard ratio : 1.71 , 95 % confidence interval : 0.97 to 2.99 ) . CONCLUSIONS In patients with unprotected left main coronary artery stenosis with low and medium complexity of coexisting coronary artery disease , stenting offers numerically , but statistically nonsignificant , favorable long-term outcome up to 10 years in terms of safety and efficacy outcome measures , therefore , constitutes an alternative therapy for CABG BACKGROUND Coronary artery bypass grafting ( CABG ) is the st and ard treatment for revascularisation in patients with left main coronary artery disease , but use of percutaneous coronary intervention ( PCI ) for this indication is increasing . We aim ed to compare PCI and CABG for treatment of left main coronary artery disease . METHODS In this prospect i ve , r and omised , open-label , non-inferiority trial , patients with left main coronary artery disease were enrolled in 36 centres in northern Europe and r and omised 1:1 to treatment with PCI or CABG . Eligible patients had stable angina pectoris , unstable angina pectoris , or non-ST-elevation myocardial infa rct ion . Exclusion criteria were ST-elevation myocardial infa rct ion within 24 h , being considered too high risk for CABG or PCI , or expected survival of less than 1 year . The primary endpoint was major adverse cardiac or cerebrovascular events ( MACCE ) , a composite of all-cause mortality , non-procedural myocardial infa rct ion , any repeat coronary revascularisation , and stroke . Non-inferiority of PCI to CABG required the lower end of the 95 % CI not to exceed a hazard ratio ( HR ) of 1·35 after up to 5 years of follow-up . The intention-to-treat principle was used in the analysis if not specified otherwise . This trial is registered with Clinical Trials.gov identifier , number NCT01496651 . FINDINGS Between Dec 9 , 2008 , and Jan 21 , 2015 , 1201 patients were r and omly assigned , 598 to PCI and 603 to CABG , and 592 in each group entered analysis by intention to treat . Kaplan-Meier 5 year estimates of MACCE were 29 % for PCI ( 121 events ) and 19 % for CABG ( 81 events ) , HR 1·48 ( 95 % CI 1·11 - 1·96 ) , exceeding the limit for non-inferiority , and CABG was significantly better than PCI ( p=0·0066 ) . As-treated estimates were 28 % versus 19 % ( 1·55 , 1·18 - 2·04 , p=0·0015 ) . Comparing PCI with CABG , 5 year estimates were 12 % versus 9 % ( 1·07 , 0·67 - 1·72 , p=0·77 ) for all-cause mortality , 7 % versus 2 % ( 2·88 , 1·40 - 5·90 , p=0·0040 ) for non-procedural myocardial infa rct ion , 16 % versus 10 % ( 1·50 , 1·04 - 2·17 , p=0·032 ) for any revascularisation , and 5 % versus 2 % ( 2·25 , 0·93 - 5·48 , p=0·073 ) for stroke . INTERPRETATION The findings of this study suggest that CABG might be better than PCI for treatment of left main stem coronary artery disease . FUNDING Biosensors , Aarhus University Hospital , and participating sites BACKGROUND Patients with obstructive left main coronary artery disease are usually treated with coronary-artery bypass grafting ( CABG ) . R and omized trials have suggested that drug-eluting stents may be an acceptable alternative to CABG in selected patients with left main coronary disease . METHODS We r and omly assigned 1905 eligible patients with left main coronary artery disease of low or intermediate anatomical complexity to undergo either percutaneous coronary intervention ( PCI ) with fluoropolymer-based cobalt-chromium everolimus-eluting stents ( PCI group , 948 patients ) or CABG ( CABG group , 957 patients ) . Anatomic complexity was assessed at the sites and defined by a Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery ( SYNTAX ) score of 32 or lower ( the SYNTAX score reflects a comprehensive angiographic assessment of the coronary vasculature , with 0 as the lowest score and higher scores [ no upper limit ] indicating more complex coronary anatomy ) . The primary end point was the rate of a composite of death from any cause , stroke , or myocardial infa rct ion at 3 years , and the trial was powered for noninferiority testing of the primary end point ( noninferiority margin , 4.2 percentage points ) . Major secondary end points included the rate of a composite of death from any cause , stroke , or myocardial infa rct ion at 30 days and the rate of a composite of death , stroke , myocardial infa rct ion , or ischemia-driven revascularization at 3 years . Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses . RESULTS At 3 years , a primary end-point event had occurred in 15.4 % of the patients in the PCI group and in 14.7 % of the patients in the CABG group ( difference , 0.7 percentage points ; upper 97.5 % confidence limit , 4.0 percentage points ; P=0.02 for noninferiority ; hazard ratio , 1.00 ; 95 % confidence interval , 0.79 to 1.26 ; P=0.98 for superiority ) . The secondary end-point event of death , stroke , or myocardial infa rct ion at 30 days occurred in 4.9 % of the patients in the PCI group and in 7.9 % in the CABG group ( P<0.001 for noninferiority , P=0.008 for superiority ) . The secondary end-point event of death , stroke , myocardial infa rct ion , or ischemia-driven revascularization at 3 years occurred in 23.1 % of the patients in the PCI group and in 19.1 % in the CABG group ( P=0.01 for noninferiority , P=0.10 for superiority ) . CONCLUSIONS In patients with left main coronary artery disease and low or intermediate SYNTAX scores by site assessment , PCI with everolimus-eluting stents was noninferior to CABG with respect to the rate of the composite end point of death , stroke , or myocardial infa rct ion at 3 years . ( Funded by Abbott Vascular ; EXCEL Clinical Trials.gov number , NCT01205776 . ) We carried out a systematic overview using individual patient data from the seven r and omised trials that have compared a strategy of initial coronary artery bypass graft ( CABG ) surgery with one of initial medical therapy to assess the effects on mortality in patients with stable coronary heart disease ( stable angina not severe enough to necessitate surgery on grounds of symptoms alone , or myocardial infa rct ion ) . 1324 patients were assigned CABG surgery and 1325 medical management between 1972 and 1984 . The proportion of patients in the medical treatment group who had undergone CABG surgery was 25 % at 5 years , 33 % at 7 years , and 41 % at 10 years : 93.7 % of patients assigned to the surgery group underwent CABG surgery . The CABG group had significantly lower mortality than the medical treatment group at 5 years ( 10.2 vs 15.8 % ; odds ratio 0.61 [ 95 % CI 0.48 - 0.77 ] , p = 0.0001 ) , 7 years ( 15.8 vs 21.7 % ; 0.68 [ 0.56 - 0.83 ] , p < 0.001 ) , and 10 years ( 26.4 vs 30.5 % ; 0.83 [ 0.70 - 0.98 ] ; p = 0.03 ) . The risk reduction was greater in patients with left main artery disease than in those with disease in three vessels or one or two vessels ( odds ratios at 5 years 0.32 , 0.58 , and 0.77 , respectively ) . Although relative risk reductions in subgroups defined by other baseline characteristics were similar , the absolute benefits of CABG surgery were most pronounced in patients in the highest risk categories . This effect was most evident when several prognostically important clinical and angiographic risk factors were integrated to stratify patients by risk levels and the extension of survival at 10 years was examined ( change in survival -1.1 [ SE 3.1 ] months in low-risk group , 5.0 [ 4.2 ] months in moderate-risk group , and 8.8 [ 5.4 ] months in high-risk group ; p for trend < 0.003 ) . A strategy of initial CABG surgery is associated with lower mortality than one of medical management with delayed surgery if necessary , especially in high-risk and medium-risk patients with stable coronary heart disease . In low-risk patients , the limited data show a non-significant trend towards greater mortality with CABG Introduction The aim of this study was to prospect ively assess the clinical outcome and quality of life of elderly patients who underwent either coronary artery bypass grafting ( CABG ) or percutaneous coronary intervention ( PCI ) with drug-eluting stents ( DES ) for treatment of significant left main disease ( LMD ) compared to a younger patient population . Methods Consecutive patients , admitted into our institution between 04/2004 and 12/2007 with LMD and a life expectancy of > 1 year were prospect ively included and stratified in two groups ( either CABG or left main stenting [ LMS ] with DES ) based on the patients ’ age at inclusion ( > or ≤75 years ) . Rates of death , myocardial infa rct ion ( MI ) , stroke , and target lesion revascularization ( TLR ) were evaluated over a 12 month follow-up . Six months after the initial procedure , additionally , quality of life was assessed using the SF-36 question naire . Results A total of 300 patients was included ; 56 of the 95 PCI patients ( 59 % ) were ≤75 years and 39 ( 44 % ) > 75 years , whereas 155 of 205 patients in the CABG group were ≤75 years ( 76 % ) , and 50 patients ( 24 % ) were > 75 years . Mean follow-up was 312 ± 226 days in the PCI and 377 ± 286 in the CABG group . Rates of death and MI were not significantly different between the four groups at the end of follow-up . There was no difference in quality of life after 6 months . Conclusion In this prospect i ve trial , PCI of LM with DES in elderly patients was feasible with a short- and intermediate term outcome comparable to CABG procedure and to a younger patient cohort BACKGROUND In a previous r and omized trial , we found that percutaneous coronary intervention ( PCI ) was not inferior to coronary artery bypass grafting ( CABG ) for the treatment of unprotected left main coronary artery stenosis at 1 year . OBJECTIVES This study sought to determine the 5-year outcomes of PCI compared with CABG for the treatment of unprotected left main coronary artery stenosis . METHODS We r and omly assigned 600 patients with unprotected left main coronary artery stenosis to undergo PCI with a sirolimus-eluting stent ( n = 300 ) or CABG ( n = 300 ) . The primary endpoint was a major adverse cardiac or cerebrovascular event ( MACCE : a composite of death from any cause , myocardial infa rct ion , stroke , or ischemia-driven target vessel revascularization ) and compared on an intention-to-treat basis . RESULTS At 5 years , MACCE occurred in 52 patients in the PCI group and 42 patients in the CABG group ( cumulative event rates of 17.5 % and 14.3 % , respectively ; hazard ratio [ HR ] : 1.27 ; 95 % confidence interval [ CI ] : 0.84 to 1.90 ; p = 0.26 ) . The 2 groups did not differ significantly in terms of death from any cause , myocardial infa rct ion , or stroke as well as their composite ( 8.4 % and 9.6 % ; HR , 0.89 ; 95 % CI , 0.52 to 1.52 ; p = 0.66 ) . Ischemia-driven target vessel revascularization occurred more frequently in the PCI group than in the CABG group ( 11.4 % and 5.5 % , respectively ; HR : 2.11 ; 95 % CI : 1.16 to 3.84 ; p = 0.012 ) . CONCLUSIONS During 5 years of follow-up , our study did not show significant difference regarding the rate of MACCE between patients who underwent PCI with a sirolimus-eluting stent and those who underwent CABG . However , considering the limited power of our study , our results should be interpreted with caution . ( Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease [ PRECOMBAT ] ; NCT00422968 ) OBJECTIVES The purpose of this study was to compare the early and late results of percutaneous and surgical revascularization of left main coronary artery stenosis . BACKGROUND Unprotected left main coronary artery ( ULMCA ) stenting is being investigated as an alternative to bypass surgery . METHODS We r and omly assigned 105 patients with ULMCA stenosis to percutaneous coronary intervention ( PCI ; 52 patients ) or coronary artery bypass grafting ( CABG ; 53 patients ) . The primary end point was the change in left ventricular ejection fraction ( LVEF ) 12 months after the intervention . Secondary end points included 30-day major adverse events ( MAE ) , major adverse cardiac and cerebrovascular events ( MACCE ) , length of hospitalization , target vessel failure ( TVF ) , angina severity and exercise tolerance after 1 year , and total and MACCE-free survival . RESULTS A significant increase in LVEF at the 12-month follow-up was noted only in the PCI group ( 3.3 + /- 6.7 % after PCI vs. 0.5 + /- 0.8 % after CABG ; p = 0.047 ) . Patients performed equally well on stress tests , and angina status improved similarly in the 2 groups . PCI was associated with a lower 30-day risk of MAE ( p < 0.006 ) and MACCE ( p = 0.03 ) and shorter hospitalizations ( p = 0.0007 ) . Total and MACCE-free 1-year survival was comparable . Left main TVF was similar in the 2 groups . During the 28.0 + /- 9.9-month follow-up , there were 3 deaths in the PCI group and 7 deaths in the CABG group ( p = 0.08 ) . CONCLUSIONS Patients with ULMCA disease treated with PCI had favorable early outcomes in comparison with the CABG group . At 1 year , LVEF had improved significantly only in the PCI group . After more than 2 years , MACCE-free survival was similar in both groups with a trend toward improved survival after PCI OBJECTIVES The purpose of this study was to compare outcomes for drug-eluting stents ( DES ) and coronary artery bypass graft ( CABG ) surgery in patients with unprotected left main coronary artery ( ULMCA ) stenosis . BACKGROUND Expert guidelines recommend coronary artery bypass graft ( CABG ) surgery for the treatment of significant stenosis of the unprotected left main coronary artery ( ULMCA ) if the patient is eligible for CABG ; however , treatment by percutaneous coronary intervention ( PCI ) is common . METHODS Details of patients ( n = 343 , ages 69.9 + /- 11.9 years ) undergoing coronary revascularization for ULMCA stenosis ( April 2003 to January 2007 ) were recorded . A total of 223 patients were treated with CABG ( mean [ interquartile range ] : follow-up 600 [ 226 to 977 ) days ) and 120 by PCI ( follow-up 362 [ 192 to 586 ) days ) . The hazard ratios ( HRs ) for death and major adverse cardiovascular and cerebrovascular events ( MACCE ) were calculated incorporating propensity score adjustment . Survival comparisons were conducted in propensity-matched subjects ( n = 134 ) , and in low- and high-risk subjects for CABG . RESULTS Patients treated by PCI were more likely to be > or=75 years of age ( 49 % vs. 33 % ; p = 0.005 ) , and of greater surgical risk ( Parsonnet score 17.2 + /- 11.2 vs. 13.0 + /- 9.3 ; p < 0.001 ) than patients treated by CABG . Overall , the propensity-adjusted HR for death was not statistically different ( HR 1.93 , 95 % confidence interval [ CI ] 0.89 to 4.19 , p = 0.10 ) , but MACCE was greater in the PCI group ( HR 1.83 , 95 % CI 1.01 to 3.32 , p = 0.05 ) . In propensity-matched individuals , neither survival nor MACCE-free survival were different . Survival was equivalent among low-risk c and i date s , but PCI had a tendency to inferior survival in high-risk c and i date s ( Ellis category IV , log-rank p = 0.05 ) . Interaction testing , however , failed to demonstrate a difference in outcomes of the 2 revascularization techniques as a function of baseline risk assessment . CONCLUSIONS Overall , the propensity-adjusted risk of mortality for treatment of ULMCA disease does not differ between PCI- and CABG-treated groups . There appears to be sufficient equipoise that a r and omized clinical trial to compare the techniques would not be ethically contraindicated OBJECTIVES This study sought to analyze stroke rates in the SYNTAX ( Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery ) trial 's r and omized and registry cohorts of patients being treated with coronary artery bypass grafting ( CABG ) or percutaneous coronary intervention ( PCI ) for treatment of complex coronary artery disease . BACKGROUND The SYNTAX trial compared PCI to CABG in patients with de novo 3-vessel and /or left main coronary disease . METHODS The SYNTAX r and omized trial was conducted at 85 U.S. and European sites ( n = 1,800 ) . All strokes ( up to 4 years ) were independently adjudicated by a clinical events committee that included a neurologist . An additional 1,077 ( of which 644 were followed for 5 years ) and 198 patients were included in the CABG and PCI registries , respectively . RESULTS In the r and omized cohort , 31 CABG and 19 PCI patients experienced 33 and 20 strokes post-r and omization at 4-year follow-up , respectively ( p = 0.062 ) . Three strokes occurred pre-procedurally but following r and omization in CABG-treated patients . After CABG , a large proportion of strokes occurred acutely ( 0 to 30 days : 9 of 33 ) , whereas in the PCI arm , most strokes occurred > 30 days after the procedure ( 18 of 20 ) . Stroke result ed in death in 3 patients in both the PCI and CABG groups . Of the patients who developed stroke , 68 % ( 21 of 31 ) in the CABG group had residual deficits at discharge ; in the PCI group , 47 % ( 9 of 19 ) had residual deficits . In a multivariate analysis , treatment with CABG was not significantly associated with increased stroke rates ( odds ratio : 1.67 , 95 % confidence interval : 0.93 to 3.01 , p = 0.089 ) . The incidence and outcomes of stroke were similar in the r and omized trial and registries . CONCLUSIONS There is a higher risk of periprocedural stroke in patients undergoing CABG versus PCI ; however , the risk converges over the first 4 years of follow-up . ( SYNTAX Study : TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries ; NCT00114972 ) |
1,033 | 23,633,306 | 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 | BACKGROUND Helping young people to avoid starting smoking is a widely endorsed public health goal , and schools provide a route to communicate with nearly all young people .
School-based interventions have been delivered for close to 40 years .
OBJECTIVES The primary aim of this review was to determine whether school smoking interventions prevent youth from starting smoking .
Our secondary objective was to determine which interventions were most effective .
This included evaluating the effects of theoretical approaches ; additional booster sessions ; programme deliverers ; gender effects ; and multifocal interventions versus those focused solely on smoking . | 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 sex and ethnicity . They also illustrate the use of these estimates in the planning of future studies Outcome research has shown that drug prevention programs based on theories of social influence often prevent the onset of adolescent drug use . However , little is known empirically about the processes through which they have their effects . The purpose of the present study was to evaluate intervening mechanism theories of two program models for preventing the onset of adolescent drug use . Analyses based on a total of 3077 fifth grade rs participating in the Adolescent Alcohol Prevention Trial revealed that both normative education and resistance training activated the causal processes they targeted . While beliefs about prevalence and acceptability significantly mediated the effects of normative education on subsequent adolescent drug use , resistance skills did not significantly predict subsequent drug use . More impressively , this pattern of results was virtually the same across sex , ethnicity , context ( public versus private school students ) , drugs ( alcohol , cigarettes , and marijuana ) and levels of risk and was durable across time . These findings strongly suggest that successful social influence-based prevention programs may be driven primarily by their ability to foster social norms that reduce an adolescent 's social motivation to begin using alcohol , cigarettes , and marijuana AIM To evaluate the effectiveness of a school-based substance abuse prevention program developed in the EU-Dap study ( EUropean Drug Addiction Prevention trial ) . MATERIAL S AND METHODS Cluster R and omized Controlled Trial . Seven European countries participated in the study ; 170 schools ( 7079 pupils 12 - 14 years of age ) were r and omly assigned to one of three experimental conditions or to a control condition during the school year 2004/2005 . The program consisted of a 12-h curriculum based on a comprehensive social influence approach . A pre-test survey assessing past and current substance use was conducted before the implementation of the program , while a post-test survey was carried out about 18 months after the pre-test . The association between program condition and change in substance use at post-test was expressed as adjusted prevalence odds ratio ( POR ) , estimated by multilevel regression models . RESULTS Persisting beneficial program effects were found for episodes of drunkenness ( any , POR=0.80 ; 0.67 - 0.97 ; frequent , POR=0.62 ; 0.47 - 0.81 ) and for frequent cannabis use in the past 30 days ( POR=0.74 ; 0.53 - 1.00 ) , whereas daily cigarette smoking was not affected by the program as it was at the short-term follow-up . Baseline non-smokers that participated in the program progressed in tobacco consumption to a lower extent than those in the control condition , but no difference was detected in the proportion of quitters or reducers among baseline daily smokers . CONCLUSION The experimental evaluation of an innovative school curriculum based on a comprehensive social influence approach , indicated persistent positive effects over 18 months for alcohol abuse and for cannabis use , but not for cigarette smoking BACKGROUND Physicians ' advice to help pregnant women quit smoking during prenatal care has had mixed results . Training and prompting physicians to provide consistent advice and referral to on-site support might improve cessation rates . METHODS Pregnant women who smoked were r and omly assigned to receive structured advice from their physician and referral to individual behavior change counseling during prenatal care or to receive brief advice to stop smoking and a quit smoking booklet at their first visit . Smoking status was measured by self-report , exhaled carbon monoxide , and urinary cotinine . RESULTS Compared with usual care , greater proportions of intervention group women reported not smoking at the 36th-week visit ( 14 % vs 10 % ) and at 1 year postpartum ( 18 % vs 11 % ) , but these differences were not significant . However , significantly greater proportions of intervention group women reported either not smoking or reducing their cigarette consumption by 50 % or more at their second visit ( 43 % vs 29 % , P = 0.02 ) , at their 36th-week visit ( 40 % vs 25 % , P < 0.01 ) , and at 1 year postpartum ( 26 % vs 14 % , P = 0.02 ) . CONCLUSIONS Physician training on how to gain a pregnant smoker 's commitment to change her smoking behavior , an office prompt system , and individualized smoking behavior change counseling show promise in reducing smoking during pregnancy and postpartum , but practical methods to assist pregnant smokers between regular prenatal visits , as they attempt to quit , need to be developed This article review s major risk factors for cigarette smoking , alcohol , and other drug abuse and promising community-based approaches to primary prevention . In a longitudinal experimental study , 8 representative Kansas City communities were assigned r and omly to program ( school , parent , mass media , and community organization ) and control ( mass media and community organization only ) conditions . Programs were delivered at either 6th or 7th grade , and panels were followed through Grade 9 or 10 . The primary findings were ( a ) significant reductions at 3 years in tobacco and marijuana use and ( b ) equivalent reductions for youth at different levels of risk . This study provides evidence that a comprehensive community program-based approach can prevent the onset of substance abuse and that the benefits are experienced equally by youth at high and low risk OBJECTIVES Our study tested the effectiveness of network methods for identifying opinion leaders and for constructing groups . METHODS Three conditions-r and om , teacher , and network -- ere r and omly assigned to 84 6th- grade classrooms within 16 schools . Pre- and postcurriculum data on mediators of tobacco use were collected from 1961 students . Peer leaders in the network condition were identified by student nominations , and those leaders were matched with the students who nominated them . RESULTS Students in the network condition relative to the r and om condition liked the prevention program more and had improved attitudes ( beta = -0.06 ; P < .01 ) , improved self-efficacy ( beta = -0.10 ; P < .001 ) , and decreased intention to smoke ( adjusted odds ratio [ OR ] = 0.46 ; 95 % confidence interval [ CI ] = 0.38 , 0.55 ) . CONCLUSIONS The network method was the most effective way to structure the program . Future programs may refine this technique and use it in other setting This study examined the effects of a smoking prevention program on the acquisition of refusal skills among junior high school students . Two conditions were compared : one in which the subjects participated in a videotaped training program on resisting pressures to smoke , and the other an untreated control group . As predicted , the results showed significant improvement in the skill training group , while the untreated controls showed no change relative to their pretest performance . These findings suggest that smoking prevention programs which focus on resisting social pressures can enhance the young person 's ability to say " no " to smoking BACKGROUND Interventions design ed to prevent tobacco and alcohol use targeting high-risk adolescents are limited . In addition , few studies have attempted to improve parent-child communication skills as a way of improving and maintaining healthy youth decision-making . METHODS A total of 660 Hispanic migrant families participated in a r and omized pre-post control group study that was utilized to determine the impact of the intervention on parent-child communication . Both treatment and attention-control groups of youth were exposed to an eight-session culturally sensitive program presented by bilingual/bicultural college students . Parents jointly attended three of the eight sessions and participated in helping their child complete homework assignments supporting the content of each session . The content of the treatment intervention included ( 1 ) information about tobacco and alcohol effects , ( 2 ) social skills training ( i.e. , refusal skills ) , and ( 3 ) the specific development of parent-child communication skills to support healthy youth decisions . RESULTS Significant intervention by household size interactions for both parent and youth perceptions of communication were found indicating that the treatment was effective in increasing communication in families with fewer children . Based on the effect size and the previously established relationship between communication and susceptibility to tobacco and alcohol use , it was determined that the intervention effect could be translated into a future 5 to 10 % decrease in susceptibility for these smaller families . CONCLUSIONS A culturally sensitive family-based intervention for migrant Hispanic youth was found to be effective in increasing perceived parent-child communication in families with fewer children . It is expected that increases in this important protective factor will lead to later observed decreases in tobacco and alcohol use The present study was design ed to test the feasibility , acceptability , and effectiveness of a 15-session smoking prevention intervention with a predominantly hispanic ( 74 % ) sample of seventh- grade students ( N=471 ) in eight urban schools in the New York area . The smoking prevention curriculum teaches social resistance skills within the context of a broader intervention promoting general personal and social competence and was implemented in this study by regular classroom teachers . Results of logistic regression analyses provided preliminary evidence of the efficacy of this type of smoking prevention strategy with urban minority youth when implemented with a reasonable degree of fidelity . The significance of these findings is that they provide support for the generalizability of an approach previously found to be effective with white middle-class population s to a predominantly hispanic inner-city population Background Smoking rates are projected to increase substantially in developing countries such as South Africa . Purpose The aim of this study was to test the efficacy of two contrasting approaches to school-based smoking prevention in South African youth compared to the st and ard health education program . One experimental program was based on a skills training/peer resistance model and the other on a harm minimization model . Method Thirty-six public schools from two South African provinces , KwaZulu-Natal and the Western Cape , were stratified by socioeconomic status and r and omized to one of three groups . Group 1 ( comparison ) schools ( n = 12 ) received usual tobacco use education . Group 2 schools ( n = 12 ) received a harm minimization curriculum in grade s 8 and 9 . Group 3 schools ( n = 12 ) received a life skills training curriculum in grade s 8 and 9 . The primary outcome was past month use of cigarettes based on a self-reported question naire . Result Five thous and two hundred sixty-six students completed the baseline survey . Of these , 4,684 ( 89 % ) completed at least one follow-up assessment . The net change in 30-day smoking from baseline to 2-year follow-up in the control group was 6 % compared to 3 % in both harm minimization ( HM ) and life skills training ( LST ) schools . These differences were not statistically significant . Intervention response was significantly moderated by both gender and race . The HM intervention was more effective for males , whereas the life skills intervention was more effective for females . For black African students , the strongest effect was evident for the HM intervention , whereas the strongest intervention effect for “ colored ” students was evident for the LST group . Conclusion The two experimental curricula both produced similar overall reductions in smoking prevalence that were not significantly different from each other or the control group . However , the impact differed by gender and race , suggesting a need to tailor tobacco and drug use prevention programs . More intensive intervention , in the classroom and beyond , may be needed to further impact smoking behavior Background : Prevention of youth smoking has great potential to improve the health of Americans . There is limited information about correlates of tobacco use among adolescents from ethnic minority groups , especially Asians , Pacific Isl and ers , and Native Hawaiians . Purpose : This article examines the relationships among ethnicity , sense of coherence ( SOC ) , and tobacco use . Methods : We conducted a baseline survey of a cluster r and omized tobacco prevention trial in public middle schools in Hawaii with a multiethnic sample of 3,438 seventh- grade students . Results : Ethnic differences in smoking prevalence were very large , with high smoking rates among Native Hawaiian/Pacific Isl and er , White , and Filipino students and with low rates among Japanese and Chinese students . Higher SOC scores predicted significantly lower risk of having ever smoked and of smoking in the past 30 days , SOC was most strongly related to ever smoking among Filipino , Hawaiian/Pacific Isl and er , and While students ; Japanese students experienced the strongest protective effect from SOC for past-month smoking . Conclusions : The results suggest that SOC is strongly associated with tobacco use among this age group . It will be important to examine whether SOC can be improved by an intervention program and whether increases in SOC are associated with reduced smoking The purpose of this study was to compare longitudinal smoking prevention program effects estimated on a population -based cohort sample of sixth- and seventh- grade students ( average n per year = 4,664 ) using different schools as units of analysis ( middle/junior high school as the school of origin or high school as the endpoint school of intervention ) . Fifty schools in 15 school districts were demographically matched and assigned to either a school and community-based program for prevention of cigarette , alcohol , and marijuana use , or a health education as usual control group . Smoking was measured by question naires administered to the students . An expired air ( CO ) measure of smoking was also administered to increase accuracy of self-reports . Program effects were estimated with regression analyses , controlling for school-level socioeconomic status , racial/ethnic make-up , urbanicity , and grade . Using school of origin as the unit of analysis , program effects showed 1 year net reductions of -8 , -6 , and -5 % in prevalence rates of smoking in the last month , last week , and last 24 hr ; 2-year program effects showed similar net reductions of -6 , -5 , and -3 % ( P 's less than 0.10 - 0.001 ) . Analyses with endpoint school as the unit showed slightly weaker effects at the 2-year follow-up , the year during which 64 % of students had moved to a junior high or high school . The findings are discussed in terms of the potential contamination of experimental groups in longitudinal studies from school consolidations , family mobility , and feeder patterns to high schools , and the different smoking environments represented by middle , junior high , and high schools A major issue in smoking prevention research is that no study has tried to equate program success expectancies across experimental and placebo control conditions . Equivalent overall program success expectancies should be established to help rule out the effects of extra-theoretical variables which influence program outcomes . The present study tested whether an attention-placebo ( information based ) smoking prevention program would produce equivalent expectancies about the likelihood of program success in comparison to an experimental social influences program . To try to equate program success expectancies , the design of the two programs differed in content but was similar in procedure . Fourteen middle schools were r and omly assigned to the two conditions . As hypothesized , baseline expectancies were found to predict outcome measures , even after controlling for baseline smoking intentions , ethnic group , and gender . Second , the equivalence of program expectancies at posttest was tested . Youths held equivalent overall expectancies for success across conditions . This study suggested the need to control for program expectancies in prevention research , and showed that program expectancies could be controlled for by equating process of program delivery BACKGROUND Early use of alcohol , tobacco , and other drugs threatens the physical and mental well-being of students and continued use negatively affects many areas of development . An internet-based , tailored intervention based on the Transtheoretical Model of Behavior Change was delivered to middle school students to reduce alcohol , tobacco , and other drug use . This internet-based approach requires very little faculty and staff time , which is efficient given curricular dem and s. METHODS Twenty-two middle schools in the United States were matched and r and omly assigned to either the intervention or control conditions ( N=1590 students who had ever used substances ) . Participants received one pre-test assessment , three thirty-minute intervention sessions over three months , and two post-test assessment s ( 3 and 14 months after pre-test , respectively ) . RESULTS R and om effects logistic models showed significant treatment effects for the intervention group when compared to the control group at the 3-month post-test . CONCLUSIONS This program has the potential to be applied as st and -alone practice or as part of more intensive interventions to promote substance use cessation A grade five through eight substance abuse prevention program , later incorporated into the Michigan Model for Comprehensive School Health Education , was developed , implemented , and evaluated . Results focus on students who received seven lessons on alcohol in grade six , and eight lessons on tobacco , alcohol , marijuana , and cocaine in grade seven taught by their regular classroom teachers ( after a 6-hour training in the social pressures resistance skills curriculum ) . Students ( N = 442 ) received either two years of the program or none , and completed individually-coded question naires . Repeated measures analysis of variance result ed in significant treatment by occasion interactions on the use of alcohol , cigarettes , marijuana , cocaine , and other drugs , as well as on knowledge . At the end of grade seven , program students ' rates of substance use had increased significantly less and knowledge of alcohol pressures , effects , and skills to resist had increased significantly more than those of comparison students BACKGROUND Smoking prevention programs usually run during school hours . In our study , an out-of-school program was developed consisting of a computer-tailored intervention aim ed at the age group before school transition ( 11- to 12-year-old elementary schoolchildren ) . The aim of this study is to evaluate the additional effect of out-of-school smoking prevention . METHODS One hundred fifty-six participating schools were r and omly allocated to one of four research conditions : ( a ) the in-school condition , an existing seven-lesson program ; ( b ) the out-of-school condition , three computer-tailored letters sent to the students ' homes ; ( c ) the in-school and out-of-school condition , a combined approach ; ( d ) the control condition . Pretest and 6 months follow-up data on smoking initiation and continuation , and data on psychosocial variables were collected from 3,349 students . RESULTS Control and out-of-school conditions differed regarding posttest smoking initiation ( 18.1 and 10.4 % ) and regarding posttest smoking continuation ( 23.5 and 13.1 % ) . Multilevel logistic regression analyses showed positive effects regarding the out-of-school program . Significant effects were not found regarding the in-school program , nor did the combined approach show stronger effects than the single- method approaches . CONCLUSIONS The findings of this study suggest that smoking prevention trials for elementary schoolchildren can be effective when using out-of-school computer-tailored interventions Using a r and omized controlled effectiveness trial , we examined the effects of Project SUCCESS on a range of secondary outcomes , including the program 's mediating variables . Project SUCCESS , which is based both on the Theory of Reasoned Action and on Cognitive Behavior Theory , is a school-based substance use prevention program that targets high-risk students . We recruited two groups of alternative high schools in successive academic years , and r and omly assigned schools in each group to either receive the intervention ( n = 7 ) or serve as a control ( n = 7 ) . Students completed surveys prior to and following the administration of the program , and again 1 year later . Although participation in Project SUCCESS significantly increased students ' perceptions of harm result ing from alcohol and marijuana use , students in the control group reported greater increases in peer support . We also found conflicting evidence in two opposing trends related to students ' perceptions of the prevalence and acceptability of substance use . Therefore , the effects of Project SUCCESS on substance use-related beliefs and behaviors must be considered mixed Psychosocial tobacco use prevention programs are based on the assumption that refusal skills training will have a suppressive effect on the onset of use by enabling non-using adolescents to refuse offers of cigarettes and smokeless tobacco . The present study investigated this assumption with 389 high-risk junior high-school students involved in a prevention program during their seventh , eighth , and ninth- grade years . Direct behavioral measures of refusal skills were taken by having subjects respond to audiotaped offers of tobacco and then rating the quality of their responses . These ratings were then linked to tobacco use measures obtained at the end of each of the 3 study years . Results showed that the comprehensive prevention program produced a favorable trend in delaying or preventing the onset of tobacco use . However , the refusal skills training , which was carried out throughout the 3-year intervention period , produced significant differences in overall refusal skill quality only at the seventh grade . Moreover , refusal skill quality was not related to overall tobacco use or cigarette use at any grade As part of a larger study to evaluate the impact of a state-levied tax increase on tobacco products and the allocation of funds for smoking education , 81 schools were assigned r and omly to one of four recommended smoking prevention programs for adolescents . The four programs differed in amount of program structure and extent of teacher training required . A one-session observation was made of 106 teachers in the 81 schools to assess the percentage of time allocated to recommended activities -- those based on the social influences model . Data suggest an explicit curriculum with design ed activities and face-to-face teacher training results in greater compliance to prescribed program components Background . Achieving significant reductions in tobacco use by youth is an important challenge . There is a pressing need to develop and evaluate innovative strategies that stimulate youth involvement and are effective in multi-ethnic population s. This article describes an innovative tobacco prevention trial , and reports baseline characteristics of participants and findings about implementation of the curriculum . Methods . The aim of Project SPLASH is to evaluate the impact of a school-based smoking prevention intervention that emphasizes active involvement of middle school students , on rates of smoking initiation and regular smoking in a multi-ethnic cohort of youth in Hawaii . Project SPLASH is a group r and omized trial that compares a 2-year innovative intervention with a social influence prevention program , in 20 public schools in Hawaii . The main outcome is mean 30-day smoking prevalence rates . Results . The response rate was 78.4 % . Approximately 1 in 4 students had tried smoking and 30-day smoking prevalence at baseline was 8 % . Intervention and control groups were comparable in terms of tobacco use , gender , ethnicity , behavioral , environmental , and psychosocial characteristics . Differences in ethnic identification , socio-economic status , acculturation , and involvement in prevention activities may be due to chance . The intervention was well implemented by teachers across both the intervention and control school classes . Conclusion . For this study , 20 schools in Hawaii with close to 4000 participating students were recruited . Student smoking behavior and curriculum implementation were comparable by group status . The intervention study has the potential to eluci date how youth respond to an intervention with student involvement that incorporates cognitive and social action components This study developed and tested a gender-specific intervention for preventing substance abuse among adolescent girls . Delivered on CD-ROM by computer , the program was compared with a conventional substance abuse prevention program delivered live in a group setting . Seventh- grade girls in New York City middle schools completed pretests , and , by school , were r and omly assigned to receive either gender-specific computer intervention ( GSI ) or conventional intervention , and were posttested . Analyses of pretest to posttest gain scores showed GSI girls compared to girls receiving conventional intervention to possess a larger repertoire of stress-reduction methods , to report lower approval of cigarettes , alcohol , and drugs , to identify more unhealthy ways to deal with stress , to report lower likelihood of cigarette use or alcohol consumption if asked to do so by best friends , and to hold stronger plans to avoid cigarettes , alcohol , and drugs in the next year . These modest findings lend credence to the promise of gender-specific , computerized interventions for substance use prevention among adolescent girls The research community has criticized Drug Abuse Resistance Education ( D.A.R.E. ) because the extant literature indicates a lack of evidence that the elementary school program prevents drug use . Yet D.A.R.E. continues to be the most widely implemented drug use prevention program in the United States and has considerable community support . To date , the junior high D.A.R.E. program has not been evaluated . The Minnesota DARE PLUS Project is a r and omized trial of 24 schools and communities . During 1999 - 2001 , students in eight schools will receive the junior high D.A.R.E. curriculum in 7th grade ; eight schools also will receive the curriculum as well as additional parent involvement , peer leadership , and community components in the 7th and 8th grade s ; and eight schools will serve as controls . This article describes the background and conceptualization , the curriculum and additional intervention components , and the evaluation methods of the DARE PLUS Project The goal of this study was to assess the effects of a school-based smoking prevention programme that used both a video and peer-led discussion groups among Romanian junior high school students aged 13 - 14 years . The programme embraced the social influence approach and concentrated on enhancing self-efficacy and the acquisition of cigarette refusal skills . Twenty schools were r and omly assigned to the control and experimental conditions , result ing in 55 participating classes from the seventh grade ( 28 in the control group and 27 in the experimental group ) . Pretest and 9 months follow-up data on weekly smoking initiation and psychosocial variables were collected from 1071 students . Multilevel logistic regression analyses demonstrated a significant effect of the programme on adolescents ' smoking behaviour after 9 months . At post-test , weekly smoking onset was 4.5 % in the experimental group versus 9.5 % in the control group . Furthermore , the programme had significant effects on smoking-related beliefs . In the experimental group , this result ed in a more negative attitude towards smoking , increased social self-efficacy levels and a more negative intention towards smoking . These findings show that short-term effects of the smoking prevention programme can be realized in Romania . More studies are needed to analyse how to maintain these effects over time Background A strong increase in smoking is noted especially among adolescents . In the Netherl and s , about 5 % of all 10-year olds , 25 % of all 13-year olds and 62 % of all 17-year olds report ever smoking . In the U.S. , an intervention program called ' Smoke-free Kids ' was developed to prevent children from smoking . The present study aims to assess the effects of this home-based smoking prevention program in the Netherl and s. Methods / Design A r and omized controlled trial is conducted among 9 to 11-year old children of primary schools . Participants are r and omly assigned to the intervention and control conditions . The intervention program consists of five printed activity modules design ed to improve parenting skills specific to smoking prevention and parent-child communication regarding smoking . These modules will include additional sheets with communication tips . The modules for the control condition will include solely information on smoking and tobacco use . Initiation of cigarette smoking ( first instance of puffing on a lighted cigarette ) , susceptibility to cigarette smoking , smoking-related cognitions , and anti-smoking socialization will be the outcome measures . To collect the data , telephone interviews with mothers as well as with their child will be conducted at baseline . Only the children will be examined at post-intervention follow-ups ( 6 , 12 , 24 , and 36 months after the baseline ) . Discussion This study protocol describes the design of a r and omized controlled trial that will evaluate the effectiveness of a home-based smoking prevention program . We expect that a significantly lower number of children will start smoking in the intervention condition compared to control condition as a direct result of this intervention . If the program is effective , it is applicable in daily live , which will facilitate implementation of the prevention protocol .Trial registration Netherl and s Trial Register OBJECTIVES This paper presents the 1-year outcomes evaluation of Project Towards No Drug Abuse ( Project TND ) , a large-scale indicated drug abuse prevention program in southern California applied to continuation high school youth , who are at high risk for drug abuse . METHODS The efficacy of nine-lesson health motivation -- social skills -- decision-making curriculum was evaluated in a three-condition experimental design . Twenty-one schools were r and omly assigned by block to one of three conditions -- st and ard care ( control ) , classroom program , and classroom program plus a semester-long school-as-community component . A pretest was followed by a 3-week-long drug abuse prevention program and then a posttest at 14 continuation high schools . The 7 st and ard care schools received only the pretest followed by the posttest ( same time duration ) . Subjects were followed up 1 year later . RESULTS Changes in use of cigarettes , alcohol , marijuana , and hard drugs were assessed in a pretest-1-year follow-up time interval . The follow-up rate was 67 % ( analysis n = 1,074 ) . Indicated preventive effects were found on alcohol and hard drug use . No differences were found across the two program conditions . CONCLUSIONS Project TND is the first program to demonstrate 1-year self-reported behavioral effects on alcohol use and hard drug use among older , high-risk youth by using a school-based , limited-session model OBJECTIVES The purpose of this study was to implement and evaluate the effectiveness of a long-term tobacco use prevention program for junior high school students that used college undergraduate change agents and telephone boosters . METHODS A psychosocial intervention combining refusal skills training , contingency management , and other tobacco use prevention method ologies such as telephone and mail boosters was implemented in 11 junior high schools in San Diego County , California . Eleven other junior high schools served as controls . Of the 2668 participants , 57 % were White/non-Hispanic , 24 % were Hispanic , and 19 % were of other racial/ethnic groups . College undergraduates served as change agents for both the classroom and booster interventions , the latter of which was delivered in the third ( ninth- grade ) year of the program . RESULTS At the end of the third year , the prevalence of tobacco use within the past month was 14.2 % among the intervention students and 22.5 % among the controls , yielding an odds ratio of 0.71 for analysis at the school level . CONCLUSIONS Both college undergraduate change agents and direct one-to-one telephone interventions appear to provide cost-effective tobacco-related behavior modification OBJECTIVE To determine whether the addition of a parental monitoring intervention ( Informed Parents and Children Together [ ImPACT ] ) alone or with " boosters " could enhance ( either broaden or sustain or both ) the effect of a small group , face-to-face adolescent risk reduction intervention Focus on Kids ( FOK ) . METHODS A longitudinal , r and omized , community-based cohort study was conducted of 35 low-income , community-based , in-town setting s. A total of 817 black youths aged 12 to 16 years at baseline were studied . After completion of baseline measures , youths were r and omized to receive a face-to-face intervention alone ( FOK only ) , a face-to-face intervention and a parental monitoring intervention ( FOK plus ImPACT ) , or both of the above plus boosters ( FOK plus ImPACT plus boosters ) . Risk and protective behaviors were assessed at 6 and 12 months after intervention . RESULTS At 6 months ' follow-up , youths in families that were assigned to FOK plus ImPACT reported significantly lower rates of sexual intercourse , sex without a condom , alcohol use , and cigarette use and marginally lower rates of " risky sexual behavior " compared with youths in families that were assigned to FOK only . At 12 months after intervention , rates of alcohol and marijuana use were significantly lower and cigarette use and overall risk intention were marginally lower among FOK plus ImPACT youths compared with FOK only youths . With regard to the boosters delivered at 7 and 10 months , 2 risk behaviors -- use of crack/cocaine and drug selling -- were significantly lower among the youths who were assigned to receive the additional boosters compared with youths without the boosters . The rates of the other risk behaviors and intentions did not differ significantly . CONCLUSIONS The results of this r and omized , controlled trial indicate that the inclusion of a parental monitoring intervention affords additional protection from involvement in adolescent risk behaviors 6 and 12 months later compared with the provision of an intervention that targets adolescents only . At the same time , the results of the present study do not provide sufficient evidence that booster sessions further improve targeted behaviors enough to include them in a combined parent and youth intervention This study was design ed to create , implement , and test a school-based multiple risk factor reduction program for high school students . All tenth grade rs in four senior high schools ( N = 1447 ) from two school districts participated in the study . Within each district , one school was assigned at r and om to receive a special 20-session CVD risk reduction intervention and one school served as a control . The schools were matched for size and distribution of racial groups before r and omization . At a two-month follow-up , knowledge gains were significantly greater for students in the treatment group on each of the risk factor domains tested : nutrition/diet ( p less than 0.0001 ) , physical activity ( p less than 0.0001 ) , and cigarette smoking ( p less than 0.0001 ) . Compared to controls , a higher proportion of those in the treatment group who were not exercising regularly at baseline , reported regular exercise at follow-up ( p less than 0.0003 ) . Almost twice as many baseline experimental smokers in the treatment group reported quitting at follow-up while only 5.6 % of baseline experimental smokers in the treatment group graduated to regular smoking compared to 10.3 % in the control group ( p = 0.009 ) . Students in the treatment group were more likely to report that they would choose heart healthy snack items ( p less than 0.0001 ) . Beneficial treatment effects were observed for resting heart rate ( p less than 0.0001 ) , BMI ( p = 0.05 ) , triceps skinfold thickness ( p = 0.003 ) , and subscapular skinfold thickness ( p = 0.01 ) . The results suggest that it is feasible to provide CVD risk reduction training to a large segment of the population through school-based primary prevention approaches Sirice 1974 an anti-smoking campaign consisting of a one-day educational intervention has been carried out in primary schools in Milan by the Italian League against Cancer ( Milan Division ) . All but two of the 165 schools were r and omized to evaluate the intervention effect . A total of 8549 children aged 9 - 10 were allocated to the intervention group and 8897 to the control group . Four years later a self-administered question naire was distributed in order to investigate the children 's smoking habits . The proportion of smokers was 8.05 % and 8.72 % ( p = 0.23 ) respectively for the intervention and control groups . It was concluded that sporadic educational Intervention carried out during primary school years has little or no impact in preventing cigarette smoking in teenagers Reported are results of an independent effectiveness study of the Project ALERT drug prevention program implemented in eight Pennsylvania middle schools by outside program leaders employed by Cooperative Extension . In this r and omized , 2-cohort longitudinal evaluation , 1,649 seventh- grade students completed a pretest and four waves of posttests over the 2-year program and 1-year follow-up . Project ALERT 's effectiveness was tested through a 3-level hierarchical linear model . Analyses failed to yield any positive effects for substance use or mediators for use in the adult or teen-assisted delivery of the curriculum . An extensive set of additional analyses detected no differential program effects by student risk level , gender , school , or level of implementation quality . Potential explanations for outcomes relative to Project ALERT 's original effectiveness trial are discussed , as well as implication s for future research , including the need to conduct independent effectiveness studies of previously vali date d programs in a variety of context OBJECTIVES This study investigated the efficacy of a social-influences tobacco prevention program conducted with adolescents living in a high tobacco production area . METHODS Students in 10 experimental schools completed the tobacco prevention program and a booster intervention . Control students received health education as usual . RESULTS After 2 years of treatment , smoking rates in the treatment group ( vs the control group ) were lower for 30-day , 7-day , and 24-hour smoking . The intervention had more of an impact on those who were involved in raising tobacco than it did on those not involved in raising tobacco . CONCLUSIONS Although modest , effects were achieved with minimal intervention time in a high-risk group , indicating that social-influences prevention programs may be effective in such groups Tobacco and drug use remain major public health concerns . The aim of this study was to evaluate the effectiveness of a school health intervention program using life skills training ( LST ) to reduce tobacco and drug use among Thai high school students . A r and omized pretest and post-test comparative design was used to evaluate the effectiveness of the LST program . A total of 170 Thai students in grade s 7 - 12 were r and omly selected . The students in the control group received the tobacco and drug education curriculum normally provided ; the intervention group received a LST program that provided information and skills specifically related to drug and tobacco use . Students in the school health intervention program had statistically significant positive effects regarding knowledge level , attitudes , and the development of refusal , decision-making , and problem-solving skills . The results showed that a LST program was effective for preventing tobacco and drug use in Thai high school students BACKGROUND This paper presents the student outcomes of a large-scale , social-influences-based , school and media-based tobacco use prevention and cessation project in Southern California . METHODS The study provided an experimental comparison of classroom delivery with television delivery and the combination of the two in a 2 x 2 plus 1 design . Schools were r and omly assigned to conditions . Control groups included " treatment as usual " and an " attention control " with the same outcome expectancies as the treatment conditions . Students were surveyed twice in grade 7 and once in each of grade s 8 and 9 . The interventions occurred during grade 7 . RESULTS We observed significant effects on mediating variables such as knowledge and prevalence estimates , and coping effort . The knowledge and prevalence estimates effects decayed partially but remained significant up to a 2-year follow-up . The coping effort effect did not persist at follow-ups . There were significant main effects of both classroom training and TV programming on knowledge and prevalence estimates and significant interactions of classroom and TV programming on knowledge ( negative ) , disapproval of parental smoking , and coping effort . There were no consistent program effects on refusal/self-efficacy , smoking intentions , or behavior . CONCLUSIONS Previous reports demonstrated successful development and pilot testing of program components and measures and high acceptance of the program by students and parents . The lack of behavioral effects may have been the result of imperfect program implementation or low base rates of intentions and behavior School-based drug prevention curricula constitute the nation ’s most prevalent strategy to prevent adolescent drug use . We evaluated the effects of one such curriculum , Project ALERT , on adolescent substance use . In particular , we sought to determine if a single effect on 30-day alcohol use , noted shortly following the completion of the 2-year program , could be detected 1 year later . We also looked for delayed effects on other outcomes of interest , namely lifetime alcohol use , and 30-day and lifetime use of cigarettes , marijuana , and inhalants . We employed a r and omized controlled trial that used school as the unit of assignment . Thirty-four schools with grade s 6–8 from 11 states completed the study . Seventy-one Project ALERT instructors taught 11 core lessons to sixth grade rs and 3 booster lessons to seventh grade rs . Students were assessed prior to the onset of the intervention , as sixth grade rs , after the completion of the 2-year curriculum , as seventh grade rs , and again 1 year later as eighth grade rs . This paper examines data from the pretest and final posttest . Using hierarchical nonlinear modeling , we found that our earlier effect on 30-day alcohol use did not persist . Further , we continued to find no effects for lifetime alcohol use and both the lifetime and 30-day use of cigarettes , marijuana , and inhalants . Our findings do not support the long-term effectiveness of Project ALERT , when delivered to sixth grade rs BACKGROUND Substance misuse by adolescents and related health issues constitute a major public health problem . Community-based partnership models design ed for sustained , quality implementation of proven preventive interventions have been recommended to address this problem . There is very limited longitudinal study of such models . PURPOSE To examine the long-term findings from an RCT of a community-university partnership model design ed to prevent substance misuse and related problems . DESIGN / SETTING / PARTICIPANTS A cohort sequential design included 28 public school districts in rural towns and small cities in Iowa and Pennsylvania that were r and omly assigned to community-university partnership or usual-programming conditions . At baseline , 11,960 students participated , across two consecutive cohorts . Data were collected from 2002 to 2008 . INTERVENTION Partnerships supported community teams that implemented universal , evidence -based interventions selected from a menu . The selected family-focused intervention was implemented with 6th- grade students and their families ; school-based interventions were implemented during the 7th grade . Observations demonstrated intervention implementation fidelity . MAIN OUTCOME MEASURES Outcome measures were lifetime , past-month , and past-year use of a range of substances , as well as indices of gateway and illicit substance use ; they were administered at baseline and follow-ups , extending to 4.5 years later . RESULTS Intent-to-treat , multilevel ANCOVAs of point-in-time use at 4.5 years past baseline were conducted , with supplemental analyses of growth in use . Data were analyzed in 2009 . Results showed significantly lower substance use in the intervention group for 12 of 15 point-in-time outcomes , with relative reductions of up to 51.8 % . Growth trajectory analyses showed significantly slower growth in the intervention group for 14 of 15 outcomes . CONCLUSIONS Partnership-based implementation of brief universal interventions has potential for public health impact by reducing growth in substance use among youth ; a multistate network of partnerships is being developed . Notably , the tested model is suitable for other types of preventive interventions OBJECTIVE To provide a review of the evidence from 3 experimental trials of Project Towards No Drug Abuse ( TND ) , a senior-high-school-based drug abuse prevention program . METHODS Theoretical concepts , subjects , design s , hypotheses , findings , and conclusions of these trials are presented . A total of 2,468 high school youth from 42 schools in southern California were surveyed . RESULTS The Project TND curriculum shows reductions in the use of cigarettes , alcohol , marijuana , hard drugs , weapon carrying , and victimization . Most of these results were replicated across the 3 trials . CONCLUSION Project TND is an effective drug and violence prevention program for older teens , at least for one-year follow-up This study evaluated cigarette smoking prevention methods with a sample of adolescent females and males . Arranged by school , 331 informed and consenting sixth grade rs were r and omly divided into four groups : 1 ) pretest , skills-building methods , posttest ; 2 ) pretest , discussion methods , posttest ; 3 ) pretest and posttest ; and 4 ) posttest only . All subjects were followed for 6 and 15 months after the posttest . Outcome results on measures of non-smoking intentions , attitudes , predictions , problem-solving abilities , and peer interactions favored subjects in the skills-building group when compared with subjects in the discussion and pretest-posttest control groups . Smoking rates at posttest and at both follow-ups were lower in the skills-building group than in the other three groups . Results from posttest-only subjects did not support pretest reactivity . The study 's strengths and limits are discussed along with directions for future smoking prevention research An amenability to treatment model stipulates that interventions may be differentially effective for subgroups of individuals with similar characteristics . Using such a model , the present study tests the impact of two social-cognitive interventions implemented in the sixth ( Intervention I ) and eighth/ninth ( Intervention II ) grade s on students ' skill acquisition and on their ninth and tenth grade substance use . A r and omized factorial design was used to examine main and interaction effects within the context of student family household status and gender . Positive program effects were found for Intervention II on skill acquisition and overall drug involvement . Interaction effects of Intervention II x Family Household Status provided support for the amenability to treatment model , but no support for the model was observed based on student gender . Possible explanations for the study findings are presented and future research directions are proposed to address why differences emerge in amenability to intervention and why such differences occur for specific subgroups BACKGROUND Although numerous interventions have been demonstrated to reduce targeted adolescent risk behaviors for brief periods , sustained behavior changes covering multiple risk behaviors have been elusive . OBJECTIVE To determine whether a parental monitoring intervention ( Informed Parents and Children Together [ ImPACT ] ) with and without boosters can further reduce adolescent truancy , substance abuse , and sexual risk behaviors and can alter related perceptions 24 months after intervention among youth who have all received an adolescent risk-reduction intervention , Focus on Kids ( FOK ) . DESIGN R and omized , controlled , 3-celled longitudinal trial . SETTING Thirty-five low-income , urban community sites . PARTICIPANTS Eight hundred seventeen African American youth aged 13 to 16 at baseline . Intervention All youth participated in FOK , an 8-session , theory-based , small group , face-to-face risk-reduction intervention , 496 youth and parents received the 1-session ImPACT intervention ( a videotape and discussion ) , 238 of the ImPACT youth also received four 90-minute FOK boosters delivered in small groups . MAIN OUTCOME MEASURES Responses at baseline and 24 months after intervention to a question naire assessing risk and protective behaviors and perceptions . Analyses used General Linear Modeling , intraclass correlation coefficient , analysis of covariance , and multiple comparisons with least significant difference test adjustment . RESULTS After adjusting for the intraclass correlation coefficient , 6 of 16 risk behaviors were significantly reduced ( P < or = .05 ) among youth receiving ImPACT compared with youth who only received FOK ( respectively , mean number of days suspended , 0.65 vs 1.17 ; carry a bat as a weapon , 4.1 % vs 9.6 % ; smoked cigarettes , 12.5 % vs 22.7 % ; used marijuana , 18.3 % vs 26.8 % ; used other illicit drugs , 1.4 % vs 5.6 % ; and , asked sexual partner if condom always used , 77.9 % vs 64.9 % ) . Four of the 7 theory-based subscales reflected significant protective changes among youth who received ImPACT . ImPACT did not produce any significant adverse effects on behaviors or perceptions . CONCLUSION A parent monitoring intervention can significantly broaden and sustain protection beyond that conferred through an adolescent risk-reduction intervention Nonadherence to accepted design principles for r and omized trials has been a limitation of school-based intervention research . Design ed to overcome these limitations , the Hutchinson Smoking Prevention Project ( HSPP ) is a 15-year r and omized trial to determine the extent to which a school-based ( grade s 3 - 12 ) tobacco use prevention intervention can deter youth tobacco use throughout and beyond high school . This paper presents the HSPP experimental design , together with methods for its implementation , and an evaluation of the degree to which HSPP has adhered to principles of r and omized trials . Results from the experimental design and its conduct include ( 1 ) a recruitment rate of 97.6 % ( 40 of 41 targeted school districts ) , ( 2 ) full and active participation for the trial 's duration by 100 % of the 40 school districts recruited , ( 3 ) implementation by virtually all teachers ( 99%+ ) , with 86 % implementation fidelity , and ( 4 ) outcome determination for 94.3 % ( 7910 ) of 8388 original study participants identified 12 years previously at baseline . The high degree of rigor achieved by the HSPP experimental design ensures confidence in the trial 's soon-to-be available intervention effectiveness results . Equally important , for future school-based trials , the HSPP design and its execution have illustrated that school-based research can adhere to the principles of rigorous r and omized trials , with high rates of implementation , and very high rates of recruitment , maintenance , and follow-up of study participants , even for studies with decade-long follow-up periods . Rigor in school-based trials can be achieved through a combination of ( 1 ) commitment to the principles of r and omized trials , ( 2 ) attention to the special challenges of trials specific to the school setting , ( 3 ) adoption and meticulous execution of proven methods for trial conduct , and ( 4 ) establishment at the outset of principles for maintaining positive collaborative relationships with participating school districts for the duration of the trial . These findings are important in light of the great potential for using the nation 's schools to access youth for health promotion/risk-factor prevention This study reports findings on a combined family and school-based competency-training intervention from an in-school assessment 2.5 years past baseline , as a follow-up to an earlier study of substance initiation . Increased rates of observed alcohol use and an additional wave of data allowed evaluation of regular alcohol use and weekly drunkenness , with both point-in-time and growth curve analyses . Thirty-six rural schools were r and omly assigned to ( a ) a combined family and school intervention condition , ( b ) a school-only condition , or ( c ) a control condition . The earlier significant outcome on a substance initiation index was replicated , and positive point-in-time results for weekly drunkenness were observed , but there were no statistically significant outcomes for regular alcohol use . Discussion focuses on factors relevant to the mix of significant longitudinal results within a consistent general pattern of positive intervention-control differences Research -based substance use prevention curricula typically yield small effects when implemented by school teachers under real-world conditions . Using a r and omized controlled trial , the authors examined whether expert coaching improves the effectiveness of the All Stars prevention curriculum . Although a positive effect on students ' cigarette use was noted , this finding may be attributed to marked baseline differences on this variable across the intervention and control groups . No effects were found on students ' alcohol or marijuana use or on any of several variables thought to mediate curriculum effects . The effects of coaching on teachers may not become evident until future years , when they have moved beyond an initial mechanical delivery of the curriculum This paper evaluates a smoking prevention intervention aim ed at vocational school students , consisting of an existing Dutch in-school program ( three lessons each lasting 50 min ) and a computer-based tailored out-of-school program ( three tailored letters with smoking prevention messages mailed to students ' homes ) . Nineteen schools that already participated in the in-school program were r and omly assigned to the in-school or to the combined in-school and out-of-school condition . The remaining 17 schools were r and omly assigned to the out-of-school condition or to the control group . Effect outcomes were assessed at 6 , 12 and 18 months after a pre-test , and were based on initiation among never-smokers and continuation among ever-smokers . Twelve months after the pre-test ( post-test 2 ) , the in-school intervention was successful in preventing vocational school students from continuing to smoke , compared with students in the control condition [ odds ratio ( OR ) = 0.49 ; 95 % confidence interval ( CI ) = 0.29 - 0.84 ] . Eighteen months after the pre-test ( post-test 3 ) , the tailored out-of-school intervention was successful in preventing smoking initiation , compared with students in the control condition ( OR = 0.42 ; 95 % CI = 0.18 - 0.96 ) . The effect of the combined approach was not larger than the sum of the effects of the in-school and the out-of-school effects This study used Complier Average Causal Effect analysis ( CACE ; see G. Imbens & D. Rubin , 1997 ) to examine the impact of an adaptive approach to family intervention in the public schools on rates of substance use and antisocial behavior among students ages 11 - 17 . Students were r and omly assigned to a family-centered intervention ( N = 998 ) in 6th grade and offered a multilevel intervention that included ( a ) a universal classroom-based intervention , ( b ) the Family Check-Up ( selected ; T. J. Dishion & K. Kavanagh , 2003 ) , and ( c ) family management treatment ( indicated ) . All services were voluntary , and approximately 25 % of the families engaged in the selected and indicated levels . Participation in the Family Check-Up was predicted by 6th- grade teacher ratings of risk , youth reports of family conflict , and the absence of biological fathers from the youths ' primary home . Relative to r and omized matched controls , adolescents whose parents engaged in the Family Check-Up exhibited less growth in alcohol , tobacco , and marijuana use and problem behavior during ages 11 through 17 , along with decreased risk for substance use diagnoses and police records of arrests by age 18 It is becoming increasingly common for community teams or coalitions to implement programming for children and families design ed to promote positive youth development and prevent adolescent problem behaviors . However , there has been only limited rigorous study of the effectiveness of community teams ’ programming efforts to produce positive outcomes . This study employed a community-level r and omized control design to examine protective parent and youth skills outcomes of evidence -based preventive interventions selected from a menu and delivered by community teams supported by a community – university partnership model called PROSPER . Twenty-eight rural communities in two states were r and omized across intervention and control conditions . Data were collected through written question naires that were completed by approximately 12,000 middle school students in the fall of the 6th grade , prior to intervention delivery , and again in the spring of the 7th , 8th , and 9th grade s. Positive intervention effects were found for youth , parent , and family outcomes ( e.g. , association with antisocial peers , child management , parent – child affective quality ) at each post-intervention assessment point . Improvements in these family and youth skill outcomes are expected to support long-term reductions of adolescent problem behaviors , such as substance abuse . Editors ’ Strategic Implication s : In this important and well controlled trial , the authors demonstrate that university partnership-supported community teams , especially when supported with ongoing technical assistance , can continue to produce positive outcomes even after much of the control over delivery of programs is turned over to representatives of the communities in which they are implemented BACKGROUND Universal school-based prevention programs for alcohol , tobacco , and other drug use are typically design ed for all students within a particular school setting . However , it is unclear whether such broad-based programs are effective for youth at high risk for substance use initiation . METHOD The effectiveness of a universal drug abuse preventive intervention was examined among youth from 29 inner-city middle schools participating in a r and omized , controlled prevention trial . A sub sample of youth ( 21 % of full sample ) was identified as being at high risk for substance use initiation based on exposure to substance-using peers and poor academic performance in school . The prevention program taught drug refusal skills , antidrug norms , personal self-management skills , and general social skills . RESULTS Findings indicated that youth at high risk who received the program ( n = 426 ) reported less smoking , drinking , inhalant use , and polydrug use at the one-year follow-up assessment compared to youth at high risk in the control condition that did not receive the intervention ( n = 332 ) . Results indicate that a universal drug abuse prevention program is effective for minority , economically disadvantaged , inner-city youth who are at higher than average risk for substance use initiation . CONCLUSIONS Findings suggest that universal prevention programs can be effective for a range of youth along a continuum of risk BACKGROUND The prevention of initiation of tobacco , alcohol and drug use is a major societal challenge , for which the existing research literature is generally disappointing . This study aim ed to test the effectiveness of adaptation of Motivational Interviewing ( MI ) for universal prevention purpose s , i.e. to prevent initiation of new substance use among non-users , and to reduce risks among existing users . METHODS Cluster r and omised trial with 416 students aged 16 - 19 years old recruited in 12 London Further Education colleges without regard to substance use status . Individualised MI was compared with st and ard practice classroom-delivered Drug Awareness intervention , both delivered over the course of one lesson . Prevalence , initiation and cessation rates for the 3 target behaviours of cigarette smoking , alcohol consumption and cannabis use , along with reductions in use and harm indicators after both 3 and 12 months were assessed . RESULTS This adaptation of MI was not demonstrated to be effective in either intention-to-treat or sub-group analyses for any outcome . Unexpected lower levels of cannabis initiation and prevalence were found in the Drug Awareness control condition . CONCLUSIONS This particular adaptation of MI is ineffective as a universal drug prevention intervention and does not merit further study The Media Ready Program was design ed as a middle school , media literacy education , preventive intervention program to improve adolescents ' media literacy skills and reduce their intention to use alcohol or tobacco products . In a short-term efficacy trial , schools in North Carolina were r and omly assigned to conditions ( Media Ready : n = 214 ; control : n = 198 ) . Boys in the Media Ready group reported significantly less intention to use alcohol in the future than did boys in the control group . Also , students in the Media Ready group who had used tobacco in the past reported significantly less intention to use tobacco in the future than did students in the control group who had previously used tobacco . Multilevel multiple mediation analyses suggest that the set of logical analysis Message Interpretation Processing variables mediated the program 's effect on students ' intentions to use alcohol or tobacco in the future BACKGROUND The Good Behavior Game ( GBG ) , a method of classroom behavior management used by teachers , was tested in first- and second- grade classrooms in 19 Baltimore City Public Schools beginning in the 1985 - 1986 school year . The intervention was directed at the classroom as a whole to socialize children to the student role and reduce aggressive , disruptive behaviors , confirmed antecedents of later substance abuse and dependence disorders , smoking , and antisocial personality disorder . This article reports on impact to ages 19 - 21 . METHODS In five poor to lower-middle class , mainly African American urban areas , three or four schools were matched and within each set r and omly assigned to one of three conditions : ( 1 ) GBG , ( 2 ) a curriculum- and -instruction program directed at reading achievement , or ( 3 ) the st and ard program . Balanced assignment of children to classrooms was made , and then , within intervention schools , classrooms and teachers were r and omly assigned to intervention or control . RESULTS By young adulthood significant impact was found among males , particularly those in first grade who were more aggressive , disruptive , in reduced drug and alcohol abuse/dependence disorders , regular smoking , and antisocial personality disorder . These results underline the value of a first- grade universal prevention intervention . REPLICATION : A replication was implemented with the next cohort of first- grade children with the same teachers during the following school year , but with diminished mentoring and monitoring of teachers . The results showed significant GBG impact for males on drug abuse/dependence disorders with some variation . For other outcomes the effects were generally smaller but in the predicted direction BACKGROUND The prevalence of adolescent smoking has been increasing rapidly in China . Theory-based smoking prevention programmes in schools may be an effective approach in preventing smoking among Chinese adolescents . METHODS A school-level cluster r and omized controlled trial was conducted among 7th and 8th grade students ( N = 2343 ) in four junior high schools in southern China during 2004 - 06 . The theory-based , multi-level intervention was compared with the st and ard health curriculum . Outcome measures comprised changes in students ' smoking-related knowledge , attitudes and behaviour . RESULTS The mean knowledge scores from baseline to the 1- and 2-year follow-ups increased more in the intervention group than in the control group , whereas there was little change in attitude scores . At the 1-year follow-up ( the total sample ) , the interventions reduced the probability of baseline experimental smokers ' escalating to regular smoker [ 7.9 vs 18.3 % ; adjusted odds ratio ( OR ) 0.34 , 95 % confidence interval ( CI ) 0.12 - 0.97 , P = 0.043 ] , but did not reduce the probability of baseline non-smokers ' initiating smoking ( 7.9 vs 10.6 % ; adjusted OR 0.86 , 95 % CI 0.54 - 1.38 , P = 0.538 ) . At the 2-year follow-up ( only 7th grade students ) , similar proportions of baseline non-smokers initiated smoking in the intervention group and the control group ( 13.5 vs 13.1 % ) , while a possibly lower proportion of baseline experimental smokers escalated to regular smoking in the intervention group than the control group ( 22.6 vs 40.0 % ; adjusted OR 0.43 , 95 % CI 0.12 - 1.57 , P = 0.199 ) . CONCLUSIONS This multi-level intervention programme had a moderate effect on inhibiting the escalation from experimental to regular smoking among Chinese adolescents , but had little effect on the initiation of smoking . The programme improved adolescents ' smoking-related knowledge , but did not change their attitudes towards smoking This study investigated both substantive and method ological issues associated with school-based smoking prevention programs . Substantive issues included the efficacy of a refusal skills training curriculum and of parent messages mailed to students ' homes . Method ological issues included the effects of assigning classrooms versus entire schools to experimental conditions and determination of the effects of attrition on internal and external validity . Results revealed differential impact for different subgroups of adolescents . The refusal skills program produced lower rates of smoking than the control condition for students who were smokers at the pretreatment assessment but may have produced detrimental effects among males who were nonsmokers at pretest . The provision of parent messages did not affect outcome . Method of assignment ( schools versus classrooms ) failed to produce significant effects , and attrition did not affect internal validity . However , the above differential findings , as well as the impact of attrition on external validity , raise questions concerning the generalizability of smoking prevention programs Raising Healthy Children ( RHC ) is a preventive intervention design ed to promote positive youth development by targeting developmentally appropriate risk and protective factors . In this study , the authors tested the efficacy of the RHC intervention on reducing adolescent alcohol , marijuana , and cigarette use . Ten public schools , which comprised 959 1st- and 2nd- grade students ( 54 % male students , 18 % minority , 28 % low socioeconomic status ) , were matched and assigned r and omly to either intervention or control conditions . A 2-part latent growth modeling strategy was used to examine change in both use-versus-nonuse and frequency-of-use outcomes while students were in Grade s 6 - 10 . Results indicated significant ( p < .05 ) intervention effects in growth trajectories for frequency of alcohol and marijuana use but not for use versus nonuse . These findings provide support for preventive interventions that take a social development perspective in targeting empirically supported risk and protective factors and demonstrate the use of 2-part models in adolescent substance use research This study tested the hypothesis that cigarette smoking adoption among adolescents could be suppressed by providing school-based videotape instruction for resisting social influences to smoke . The utilization of same-age peer leaders was also varied to test whether their participation in the classroom would enhance program effects . Seventh grade students ( N = 540 ) from one junior high school in Southern California were r and omly assigned by classrooms ( N = 15 ) to : ( a ) videotape instruction , ( b ) videotape instruction plus peer leader involvement , or ( c ) survey-only . Seventh grade students ( N = 234 ) in a second junior high school served as a measurement-only control . Assessment s were conducted at the beginning and end of the academic year . Results revealed a marked suppression in the onset of both experimental and regular smoking among those students exposed to the pressure resistance training with peer leader involvement . Pressure resistance training without peer leader involvement produced a more variable and less powerful effect on students ' smoking behavior . Data collected on students ' use of alcohol and marijuana revealed a generalized suppression effect , albeit weaker than for tobacco , among those students exposed to the social resistance training with peer leader involvement . Results provide further encouraging support for the use of peer-led pressure resistance training in preventing adolescent drug use BACKGROUND The 1985 Minnesota Legislature established guidelines for school-based tobacco-use prevention programming and provided financial incentives to school districts to encourage them to adopt a broad range of preventive measures . The Minnesota-Wisconsin Adolescent Tobacco-Use Research Project was funded by the National Cancer Institute in 1986 to evaluate the Minnesota initiative through two parallel studies . METHODS The Four Group Comparison Study was a prospect i ve study of 48 school " units " which were r and omly assigned to one of four conditions in 1987 . Baseline observations were taken in the sixth grade in 1987 , interventions were delivered in the seventh grade , and follow-up observations were taken in the seventh , eighth , and ninth grade s. The Four Group Comparison Study was design ed to evaluate the three middle-school interventions that were most widely adopted by Minnesota school districts as a result of the 1985 legislation . The Two State Comparison Study was a serial cross-sectional study of representative districts in Minnesota and Wisconsin . Annual surveys of ninth grade rs were conducted from 1986 - 1990 . The Two State Comparison Study was design ed to determine whether tobacco-use patterns changed in Minnesota relative to Wisconsin following the Minnesota legislation . RESULTS The prospect i ve study indicated that none of the interventions was more effective in reducing adolescent tobacco use compared with a r and omized control group . The serial cross-sectional study revealed that there was a modest net decline in Minnesota relative to Wisconsin from 1986 to 1990 , but that it was within the range of chance variation . CONCLUSIONS Taken together , these results indicate that this legislative initiative was insufficient to reduce adolescent tobacco use statewide during the 5-year study period . Together with results from other recent studies , they suggest that even more intensive efforts may be required to effect widespread reductions in adolescent tobacco use OBJECTIVE To test the efficacy of 2 programs design ed to reduce high-risk behaviors among inner-city African American youth . DESIGN Cluster r and omized trial . SETTING Twelve metropolitan Chicago , Ill , schools and the communities they serve , 1994 through 1998 . PARTICIPANTS Students in grade s 5 through 8 and their parents and teachers . INTERVENTIONS The social development curriculum ( SDC ) consisted of 16 to 21 lessons per year focusing on social competence skills necessary to manage situations in which high-risk behaviors occur . The school/community intervention ( SCI ) consisted of SDC and school-wide climate and parent and community components . The control group received an attention-placebo health enhancement curriculum ( HEC ) of equal intensity to the SDC focusing on nutrition , physical activity , and general health care . MAIN OUTCOME MEASURES Student self-reports of violence , provocative behavior , school delinquency , substance use , and sexual behaviors ( intercourse and condom use ) . RESULTS For boys , the SDC and SCI significantly reduced the rate of increase in violent behavior ( by 35 % and 47 % compared with HEC , respectively ) , provoking behavior ( 41 % and 59 % ) , school delinquency ( 31 % and 66 % ) , drug use ( 32 % and 34 % ) , and recent sexual intercourse ( 44 % and 65 % ) , and improved the rate of increase in condom use ( 95 % and 165 % ) . The SCI was significantly more effective than the SDC for a combined behavioral measure ( 79 % improvement vs 51 % ) . There were no significant effects for girls . CONCLUSIONS Theoretically derived social-emotional programs that are culturally sensitive , developmentally appropriate , and offered in multiple grade s can reduce multiple risk behaviors for inner-city African American boys in grade s 5 through 8 . The lack of effects for girls deserves further research While most intervention studies on coronary heart disease have focused on the high-risk person only , the present study used the family as the unit of intervention . In the study 1373 high-risk men , ages 30 - 54 years , were identified on the basis of high total cholesterol ( TC ) and /or low relative high-density lipoprotein cholesterol ( HDL-C ) ( HDL-C/TC ) following the 1979/1980 survey in Tromsø . The men and their families were r and omly allocated to a control or intervention condition . The intervention families were given advice on diet , smoking , and exercise . At rescreening in 1986/1987 , significantly lower risk factor levels were found in both the intervention men and their spouses compared with those in the control group . For children , the differences were small and mostly nonsignificant . Men , spouses , and children in the intervention group reported more favorable dietary habits than those in the control group . No differences were found in smoking or leisure time physical activity AIMS To determine the impact of a school-based harm minimization smoking intervention compared to traditional abstinence-based approaches . DESIGN , SETTING AND PARTICIPANTS A school-based cluster r and omized trial was conducted in Perth , Western Australia in 30 government high schools from 1999 to 2000 . Over 4000 students were recruited to participate and schools were assigned r and omly to either the harm minimization intervention or a st and ard abstinence-based programme . INTERVENTION The harm minimization intervention comprised eight 1-hour lessons over 2 years , quitting support from school nurses and enactment of policies to support programme components . Comparison schools implemented st and ard abstinence-based programmes and policies . MEASURES Cigarette smoking was categorized at two levels : regular smoking , defined as smoking on 4 or more days in the previous week ; and 30-day smoking as any smoking within the previous month . FINDINGS At immediate post-test ( 20 months post-baseline ) , after accounting for baseline differences , school-level clustering effects , socio-economic status , gender and family smoking , intervention students were less likely to smoke regularly [ OR = 0.51 , 95 % confidence interval ( CI ) = 0.36 , 0.71 ] or to have smoked within the previous 30 days ( OR = 0.69 , 95 % CI = 0.53 , 0.91 ) . CONCLUSION The school-based adolescent harm minimization intervention appears to have been more effective than the abstinence-based social influences programme at reducing regular smoking In this article , we examine the impact of two universal , grade 1 preventive interventions on the onset of tobacco smoking as assessed in early adolescence . The classroom-centered ( CC ) intervention was design ed to reduce the risk for tobacco smoking by enhancing teachers ' behavior management skills in first grade and , thereby , reducing child attention problems and aggressive and shy behavior-known risk behaviors for later substance use . The family-school partnership ( FSP ) intervention targeted these early risk behaviors via improvements in parent-teacher communication and parents ' child behavior management strategies . A cohort of 678 urban , predominately African-American , public school students were r and omly assigned to one of three Grade 1 classrooms at entrance to primary school ( age 6 ) . One classroom featured the CC intervention , a second the FSP intervention , and the third served as a control classroom . Six years later , 81 % of the students completed audio computer-assisted self-interviews . Relative to controls , a modest attenuation in the risk of smoking initiation was found for students who had been assigned to either the CC or FSP intervention classrooms ( 26 % versus 33 % ) ( adjusted relative risk for CC/control contrast=0.57 , 95 % confidence interval ( CI ) , 0.34 - 0.96 ; adjusted relative risk for FSP/control contrast=0.69 , 95 % CI , 0.50 - 0.97 ) . Results lend support to targeting the early antecedent risk behaviors for tobacco smoking BACKGROUND The study 's objective was to examine the effects of " real-world , " community-based implementation of universal preventive interventions selected from a menu , including effects specific to higher- and lower-risk sub sample s. DESIGN School districts were selected based on size and location , and then r and omly assigned to a control condition or to an experimental condition in a cohort sequential design . SETTING / PARTICIPANTS The study included 28 public school districts in Iowa and Pennsylvania that were located in rural towns and small cities , ranging in size from 6975 to 44,510 . Sixth and seventh grade rs in these school districts participated in the study . INTERVENTION Community teams were mobilized ; each team implemented one of three evidence -based , family-focused interventions ( 5 to 12 sessions ) and one of three evidence -based school interventions ( 11 to 15 sessions ) , for 6th and 7th grade rs , respectively . Observations showed that interventions were implemented with fidelity . MAIN OUTCOME MEASURES Outcomes included student reports of past month , past year , and lifetime use of alcohol , cigarettes , marijuana , methamphetamines , ecstasy , and inhalants , as well as indices of gateway and illicit substance initiation , at pretest and at a follow-up assessment 18 months later . RESULTS Intent-to-treat analyses demonstrated significant effects on substance initiation ( marijuana , inhalants , methamphetamines , ecstasy , gateway index , illicit-use index ) , as well as past-year use of marijuana and inhalants , with positive trends for all substances measured . For three outcomes , intervention effects were stronger for higher-risk students than lower-risk students . CONCLUSIONS Community-based implementation of brief universal interventions design ed for general population s has potential for public health impact by reducing substance use among adolescents This study investigated the effects of a smoking prevention program that emphasized refusal skills training on 1730 adolescents in three high schools and six middle schools . Classes within these schools were r and omly assigned to treatment or no-treatment conditions to avoid confounding schools with treatment condition . The effects of attrition on the internal and external validity of the study were examined . Although the results indicated an apparent effect of the program at the 1-year follow-up in deterring continued smoking among those who were smoking at pretest , this result may have been due to a higher rate of attrition among high-rate smokers in the treatment condition than in the control condition . Attrition also affected external validity . Across both conditions , subjects who were smoking at pretest and who were at risk to smoke were more likely to be missing at follow-up . The program did have an effect on the refusal skills of participants and the validity of this effect was not jeopardized by differential attrition Introduction : School-based smoking prevention programmes can be effective , but evidence on cost-effectiveness is lacking . We conducted a cost-effectiveness analysis of a school-based “ peer-led ” intervention . Methods : We evaluated the ASSIST ( A Stop Smoking In Schools Trial ) programme in a cluster r and omized controlled trial . The ASSIST programme trained students to act as peer supporters during informal interactions to encourage their peers not to smoke . Fifty-nine secondary schools in Engl and and Wales were r and omized to receive the ASSIST programme or usual smoking education . Ten thous and seven hundred and thirty students aged 12–13 years attended participating schools . Previous work has demonstrated that the ASSIST programme achieved a 2.1 % ( 95 % CI = 0%–4.2 % ) reduction in smoking prevalence . We evaluated the public sector cost , prevalence of weekly smoking , and cost per additional student not smoking at 24 months . Results : The ASSIST programme cost of £ 32 ( 95 % CI = £ 29.70–£33.80 ) per student . The incremental cost per student not smoking at 2 years was £ 1,500 ( 95 % CI = £ 669–£9,947 ) . Students in intervention schools were less likely to believe that they would be a smoker at age 16 years ( odds ratio [ OR ] = 0.80 ; 95 % CI = 0.66–0.96 ) . Conclusions : A peer-led intervention reduced smoking among adolescents at a modest cost . The intervention is cost-effective under realistic assumptions regarding the extent to which reductions in adolescent smoking lead to lower smoking prevalence and /or earlier smoking cessation in adulthood . The annual cost of extending the intervention to Year 8 students in all U.K. schools would be in the region of £ 38 million and could result in 20,400 fewer adolescent smokers In a recent r and omized field trial , Ellickson et al. found the Project ALERT drug prevention curriculum curbed alcohol misuse and tobacco and marijuana use among eighth- grade adolescents . This article reports effects among ninth- grade at-risk adolescents . Comparisons between at-risk girls in ALERT Plus schools ( basic curriculum extended to ninth grade with five booster lessons ) and at-risk girls in control schools showed the program curbed weekly alcohol and marijuana use , at-risk drinking , alcohol use result ing in negative consequences , and attitudinal and perceptual factors conducive to drug use . Program-induced changes in perceived social influences , one 's ability to resist those influences , and beliefs about the consequences of drug use mediated the ALERT Plus effects on drug use . No significant effects emerged for at-risk boys or at-risk adolescents in schools where the basic ALERT curriculum ( covering seventh and eighth grade s only ) was delivered . Possible reasons for gender differences and implication s for prevention programming are discussed OBJECTIVE To examine the effectiveness of a drug abuse prevention program in reducing the initiation and escalation of smoking in a sample of predominantly minority junior high school girls . METHODS The 15-session prevention program teaches social resistance skills within the context of a broader intervention design ed to promote general personal and social competence skills , and is implemented in the seventh grade . Smoking rates in girls from 29 New York City public schools who received the program ( n = 1,278 ) were compared to smoking rates in a control group of girls ( n = 931 ) who did not . RESULTS Those who participated in the program were less likely to initiate smoking relative to controls , due in part to significant program effects on smoking intentions , smoking knowledge , perceived peer and adult smoking norms , drug refusal skills , and risk taking . Experimental smokers in the intervention group were less likely to escalate to monthly smoking relative to controls , due in part to significant program effects on smoking intentions . CONCLUSION A school-based drug abuse prevention approach previously found to be effective among white youth significantly reduced smoking initiation and escalation among urban minority girls This paper reports on the evaluation of a culturally grounded prevention intervention targeting substance use among urban middle-school students . The curriculum consists of 10 lessons promoting antidrug norms and teaching resistance and other social skills , reinforced by booster activities and a media campaign . Three versions were delivered : Mexican American , combined African American and European American , and Multicultural . Thirty-five middle schools were r and omly assigned to 1 of the 3 versions or the control . Students completed baseline and follow-up question naires over a 2-year period ( total 6,035 respondents ) . Analyses utilizing a generalized estimating equations approach assessed the overall effectiveness of cultural grounding and the cultural matching hypothesis . Support was found for the intervention 's overall effectiveness , with statistically significant effects on gateway drug use as well as norms , attitudes , and resistance strategies but with little support for the cultural matching hypothesis . Specific contrasts found the Mexican American and Multicultural versions impacted the most outcomes OBJECTIVE To evaluate the impact of a classroom-based , Web-assisted tobacco intervention addressing smoking prevention and cessation with adolescents . DESIGN A two-group r and omized control trial with 1,402 male and female students in grade s 9 through 11 from 14 secondary schools in Toronto , Canada . Participants were r and omly assigned to a tailored Web-assisted tobacco intervention or an interactive control condition task conducted during a single classroom session with e-mail follow-up . The cornerstone of the intervention was a five-stage interactive Web site called the Smoking Zine ( http://www.smokingzine.org ) integrated into a program that included a paper-based journal , a small group form of motivational interviewing , and tailored e-mails . MAIN OUTCOME MEASURE Resistance to smoking , behavioral intentions to smoke , and cigarette use were assessed at baseline , postintervention , and three- and six-month follow-up . Multilevel logistic growth modeling was used to assess the effect of the intervention on change over time . RESULTS The integrated Smoking Zine program helped smokers significantly reduce the likelihood of having high intentions to smoke and increased their likelihood of high resistance to continued cigarette use at 6 months . The intervention also significantly reduced the likelihood of heavy cigarette use adoption by nonsmokers during the study period . CONCLUSION The Smoking Zine intervention provided cessation motivation for smokers most resistant to quitting at baseline and prevented nonsmoking adolescents from becoming heavy smokers at 6 months . By providing an accessible and attractive method of engaging young people in smoking prevention and cessation , this interactive and integrated program provides a novel vehicle for school- and population -level health promotion OBJECTIVE To test whether a social network tailored substance abuse prevention program can reduce substance use among high-risk adolescents without creating deviancy training ( iatrogenic effects ) . METHODS A classroom r and omized controlled trial comparing control classes with those receiving an evidence -based substance use prevention program [ Towards No Drug Abuse ( TND ) ] and TND Network , a peer-led interactive version of TND . Students ( n = 541 , mean age 16.3 years ) in 75 classes from 14 alternative high schools completed surveys before and approximately 1 year after curriculum delivery . Past-month use of tobacco , alcohol , marijuana and cocaine were assessed . RESULTS Overall , TND Network was effective in reducing substance use . However , the program effect interacted with peer influence and was effective mainly for students who had peer networks that did not use substances . Students with classroom friends who use substances were more likely to increase their use . CONCLUSIONS A peer-led interactive substance abuse prevention program can accelerate peer influences . For students with a peer environment that supports non-use , the program was effective and reduced substance use . For students with a peer environment that supports substance use , an interactive program may have deleterious effects This paper presents the results of theory-based intervention strategies to increase the adoption of a tobacco prevention program . The adoption intervention followed a series of dissemination intervention strategies targeted at 128 school districts in Texas . Informed by Social Cognitive Theory , the intervention provided opportunities for districts to learn about and model themselves after ' successful ' school districts that had adopted the program , and to see the potential for social reinforcement through the knowledge that the program had the potential to have an important influence on students ' lives . The proportion of districts in the Intervention condition that adopted the program was significantly greater than in the Comparison condition ( P < 0.001 ) . Stepwise logistic regression indicated that the variables most closely related to adoption among intervention districts were teacher attitudes toward the innovation and organizational considerations of administrators . Recommendations for the development of effective strategies for the diffusion of innovations are presented The onset of smoking behavior in adolescents has been described as a process , beginning when children are young . Little empirical evidence is available , however , on the nature and specifics of the onset process in young children . More information is needed about the early stages of smoking onset in order to design interventions for young children and for early triers . The purpose of the present study was to describe several onset-related variables in young girls and boys and to discuss implication s for design ing prevention interventions that target young children . A total of 1,663 5th- grade students completed a question naire assessing smoking behavior , psychosocial characteristics , and perceptions of a " smoker " image . Saliva sample s for cotinine analysis were also collected . Students were classified as either never-triers ( never tried a cigarette ) or early triers ( tried one or more cigarettes ) on the basis of self-reported smoking . Most students who had tried a cigarette were in the early stages of smoking onset , because approximately 30 % had tried one cigarette and less than 10 % had tried a second . Triers versus never-triers differed on their reported images of smokers , and several psychosocial characteristics predicted trying a cigarette and intentions to smoke for boys Although media literacy represents an innovative venue for school-based antismoking programming , studies have not systematic ally compared student impressions of these and traditional programs . This study utilized data from a r and omized trial comparing these two types of programs . After each program , students responded to three open-ended questions related to their assigned curriculum . Two coders , blinded to student assignments , independently coded these data . Coders had strong inter-rater agreement ( kappa = 0.77 ) . Our primary measures were spontaneously noted overall assessment , enjoyment/interest and the likelihood of changing smoking behavior . Of the 531 participants , 255 ( 48.0 % ) were r and omized to the intervention ( media literacy ) group . Intervention participants had more net positive responses [ rate ratio ( RR ) = 1.27 , 95 % confidence interval ( CI ) = 1.05 , 1.54 ] , more responses rating the program as compelling ( RR = 1.63 , 95 % CI = 1.16 , 2.29 ) and fewer responses rating the program as non-compelling ( RR = 0.62 , 95 % CI = 0.39 , 0.97 ) . However , the intervention group was not more likely to suggest that the curriculum was likely to change behavior positively ( RR = 0.57 , 95 % CI = 0.30 , 1.06 ) . Findings suggest that although media literacy provides a compelling format for the delivery of anti-tobacco programming , integration of components of traditional programming may help media literacy programs achieve maximal efficacy This study examined the plausibility of the gateway hypothesis to account for drug involvement in a sample of middle school students participating in a drug abuse , prevention trial . Analyses focused on a single prevention approach to exemplify intervention effects on drug progression . Improvements to social competence reduced multiple drug use at 1- and 2-year follow-ups . Specific program effects disrupted drug progression by decreasing alcohol and cigarette use over 1 year and reducing cigarette use over a 2-year period . Controlling for previous drug use , alcohol was integrally involved in the progression to multiple drug use . Subgroup analyses based on distinctions of pretest use/nonuse of alcohol and cigarettes provided partial support for the gateway hypothesis . However , evidence also supported alternate pathways including cigarette use as a starting point for later alcohol and multiple drug use OBJECTIVES --To assess the effectiveness of two school based smoking education projects in delaying onset of smoking behaviour and in improving health knowledge , beliefs , and values . DESIGN --Cluster r and omised controlled trial of two projects taught under normal classroom conditions . Schools were allocated to one of four groups to receive the family smoking education project ( FSE ) ; the smoking and me project ( SAM ) ; both projects in sequence ( FSE/SAM ) ; or no intervention at all . SETTING --39 schools in Wales and Engl and matched for size and catchment profile . SUBJECTS -- All first year pupils in the schools were included and were assessed on three occasions ( 4538 before teaching ( 1988 ) , 3930 immediately after teaching ( 1989 ) , 3786 at one year follow up ( 1990 ) ) . MAIN OUTCOME MEASURES --Self reported smoking behaviour ( backed by saliva sample ) and change in relevant health knowledge , beliefs , and values . RESULTS --No consistent significant differences in smoking behaviour , health knowledge , beliefs , or values were found between the four groups . For never smokers at baseline the rate of remaining never smokers in 1990 was 74 % ( 594/804 ) in the control group , 65 % ( 455/704 ) in the FSE group , 70 % ( 440/625 ) in the SAM group , and 69 % ( 549/791 ) in the FSE/SAM group ( chi 2adj = 6.1 , df = 3 , p = 0.1 ) . Knowledge about effects of smoking rose in all groups from a mean score of 5.4 in 1988 to 6.4 in 1989 and 6.5 in 1990 . CONCLUSIONS --More comprehensive interventions than school health education alone will be needed to reduce teenage smoking . Other measures including further restrictions on access to cigarettes and on the promotion of tobacco products need to be considered . Further research will be needed to develop effective school based health education projects , which should be formally field tested under normal conditions before widespread dissemination The entire early adolescent population of the 15 communities that constitute the Kansas City ( Kansas and Missouri ) metropolitan area has participated in a community-based program for prevention of drug abuse since September 1984 . The Kansas City area is the first of two major metropolitan sites being evaluated in the Midwestern Prevention Project , a longitudinal trial for primary prevention of cigarette , alcohol , and marijuana use in adolescents . The project includes mass media programming , a school-based educational program for youths , parent education and organization , community organization , and health policy components that are introduced sequentially into communities during a 6-year period . Effects of the program are determined through annual assessment s of adolescent drug use in schools that are assigned to immediate intervention or delayed intervention control conditions . In the first 2 years of the project , 22,500 sixth- and seventh- grade adolescents received the school-based educational program component , with parental involvement in homework and mass media coverage . Analyses of 42 schools indicate that the prevalence rates of use for all three drugs are significantly lower at 1-year follow-up in the intervention condition relative to the delayed intervention condition , with or without controlling for race , grade , socioeconomic status , and urbanicity ( 17 % vs 24 % for cigarette smoking , 11 % vs 16 % for alcohol use , and 7 % vs 10 % for marijuana use in the last month ) , and the net increase in drug use prevalence among intervention schools is half that of delayed intervention schools This study evaluated the substance initiation effects of an intervention combining family and school-based competency-training intervention components . Thirty-six rural schools were r and omly assigned to 1 of 3 conditions : ( a ) the classroom-based Life Skills Training ( LST ) and the Strengthening Families Program : For Parents and Children 10 - 14 , ( b ) LST only , or ( c ) a control condition . Outcomes were examined 1 year after the intervention posttest , using a substance initiation index ( SII ) measuring lifetime use of alcohol , cigarettes , and marijuana and by rates of each individual substance . Planned intervention-control contrasts showed significant effects for both the combined and LST-only interventions on the SII and on marijuana initiation . Relative reduction rates for alcohol initiation were 30.0 % for the combined intervention and 4.1 % for LST only All tenth grade rs in four senior high schools ( N = 1447 ) from two school districts participated in a cardiovascular disease risk-reduction trial . Within each district , one school was assigned at r and om to receive a special 20-session risk-reduction intervention and one school served as a control . At a two-month follow-up , risk factor knowledge scores were significantly greater for students in the treatment group . Compared with controls , a higher proportion of those in the treatment group who were not exercising regularly at baseline reported regular exercise at follow-up . Almost twice as many baseline experimental smokers in the treatment group reported quitting at follow-up , while only 5.6 % of baseline experimental smokers in the treatment group graduated to regular smoking compared with 10.3 % in the control group . Students in the treatment group were more likely to report that they would choose " heart-healthy " snack items . Beneficial treatment effects were observed for resting heart rate , body mass index , triceps skin fold thickness , and subscapular skin fold thickness . The results suggest that it is feasible to provide cardiovascular disease risk-reduction training to a large segment of the population through school-based primary prevention approaches Studies have shown that the effectiveness of programs or curricula may depend in part on who delivers the material . In adolescent health education programs , peer leaders are often recruited to implement programs because they are more persuasive to other adolescents than adults . Teachers also systematic ally vary how groups are constructed in school-based health education programs . This study compared the effects of three leader and group selection methods within the context of two tobacco prevention programs . Eight schools received a social influences program ( Chips ) and eight received a program with a multicultural emphasis ( Flavor ) . Within these 16 schools 84 classrooms consisting of 1486 students were r and omly assigned to one of three leader and group creation conditions : ( i ) leaders defined as those who received the most nominations by students and groups created r and omly ( r and om group ) , ( ii ) same as ( i ) but groups created by assigning students to the leaders they nominated ( network ) , and ( iii ) leaders and groups created by teachers ( teacher ) . One year follow-up data showed that main effects of the curriculum and network assignments were non-significant on smoking initiation when entered alone . Interaction terms of curriculum and assignment methods , however , were significant such that the network and teacher conditions were less effective than the r and om group condition with Chips , and more effective than r and om group condition with Flavor . These data show that school-based prevention programs should be evaluated in light of who implements the program . Even a peer-led program will be differentially effective based on how leaders are selected and how groups are formed , and this effect may be curriculum dependent Background : Studies of effectiveness of school-based prevention of substance misuse have generally overlooked gender differences . The purpose of this work was to analyse gender differences in the effectiveness of a new European school-based curriculum for prevention of substance misuse among adolescents . Methods : The European Drug Abuse Prevention ( EU-Dap ) trial took place in seven European countries during the school year 2004–05 . Schools were r and omly assigned to either a control group or a 12-session st and ardised curriculum ( “ Unplugged ” ) based on a comprehensive social influence model . The analytical sample consisted of 6359 students ( 3324 boys and 3035 girls ) . The use of cigarettes , alcohol and illicit drugs , adolescents ’ knowledge and opinions about substances , as well as social and personal skills were investigated through a self-completed anonymous question naire administered at enrolment and 3 months after the end of the programme . Adjusted Prevalence Odds Ratios were calculated as the measure of association between the intervention and behavioural outcomes using multilevel regression modelling . Results : At enrolment , boys were more likely than girls to have used cannabis and illicit drugs , whereas girls had a higher prevalence of cigarette smoking . At the follow-up survey , a significant association between the programme and a lower prevalence of all behavioural outcomes was found among boys , but not among girls . Age and self-esteem emerged as possible modifiers of these gender differences , but effects were not statistically significant . Conclusions : Comprehensive social influence school curricula against substance misuse in adolescence may perform differently among girls and boys , owing to developmental and personality factors OBJECTIVE This paper reports the impact of two first- and second- grade classroom based universal preventive interventions on the risk of Suicide Ideation ( SI ) and Suicide Attempts ( SA ) by young adulthood . The Good Behavior Game ( GBG ) was directed at socializing children for the student role and reducing aggressive , disruptive behavior . Mastery Learning ( ML ) was aim ed at improving academic achievement . Both were implemented by the teacher . METHODS The design was epidemiologically based , with r and omization at the school and classroom levels and balancing of children across classrooms . The trial involved a cohort of first- grade children in 19 schools and 41 classrooms with intervention at first and second grade s. A replication was implemented with the next cohort of first grade children with the same teachers but with little mentoring or monitoring . RESULTS In the first cohort , there was consistent and robust GBG-associated reduction of risk for suicide ideation by age 19 - 21 years compared to youths in st and ard setting ( control ) classrooms regardless of any type of covariate adjustment . A GBG-associated reduced risk for suicide attempt was found , though in some covariate-adjusted models the effect was not statistically robust . No statistically significant impact on these outcomes was found for ML . The impact of the GBG on suicide ideation and attempts was greatly reduced in the replication trial involving the second cohort . CONCLUSIONS A universal preventive intervention directed at socializing children and classroom behavior management to reduce aggressive , disruptive behavior may delay or prevent onset of suicide ideation and attempts . The GBG must be implemented with precision and continuing support of teachers Background In response to India 's growing tobacco epidemic , strategies are needed to decrease tobacco use among Indian youth , particularly among those who are economically disadvantaged . The objective of this study was to assess the effectiveness of a school-based life-skills tobacco control program for youth of low socio-economic status in Mumbai and the surrounding state of Maharashtra . We hypothesized that compared to youth in control schools , youth exposed to the program would have greater knowledge of effects of tobacco use ; be more likely to take action to prevent others from using tobacco ; demonstrate more positive life skills and attitudes ; and be less likely to report tobacco use . Methods / Findings Using a quasi-experimental design , we assessed program effectiveness by comparing 8th and 9th grade students in intervention schools to 8th grade students in comparable schools that did not receive the program . Across all schools , 1851 students completed a survey that assessed core program components in early 2010 . The program consisted of activities focused on building awareness about the hazards of tobacco , developing life skills , and advocacy development . The primary outcome measure was self-reported tobacco use in the last 30 days . Findings indicate that 4.1 % of 8th grade intervention students ( OR = 0.51 ) and 3.6 % of 9th grade intervention students ( OR = 0.33 ) reported using tobacco at least once in the last 30 days , compared to 8.7 % of students in the control schools . Intervention group students were also significantly more knowledgeable about tobacco and related legislation , reported more efforts to prevent tobacco use among others , and reported stronger life skills and self-efficacy than students in control schools . Limitations to the study include schools not being r and omly assigned to condition and tobacco use being measured by self-report . Conclusions This program represents an effective model of school-based tobacco use prevention that low-income schools in India and other low- and middle-income countries can replicate OBJECTIVES We present 1-year follow-up data from a school-based tobacco use prevention project design ed to test the effectiveness of three main components of social influence programs . The components teach refusal skills , awareness of social misperceptions about tobacco use , and misconceptions about physical consequences . METHODS Four different curricula were developed and tested in a r and omized experiment involving 48 junior high schools . The outcome variables examined were changes in initial and weekly cigarette and smokeless tobacco use 1 year after the intervention . RESULTS Analyses indicated that each of the component programs were effective in decreasing both the initial and the weekly use of cigarettes except for the curriculum in which refusal skills were taught . Also , each curriculum was effective in decreasing the initial use of smokeless tobacco except for the one aim ed at correcting social misperceptions . Only the combined curriculum showed an effect on the weekly use of smokeless tobacco . CONCLUSIONS The combined intervention was the most effective overall in reducing the initial and weekly use of cigarettes and smokeless tobacco . This suggests that different reasons for use exist and need to be counteracted simultaneously . However , since single programs were also effective in reducing all but weekly smokeless tobacco use , any of these components may be worthwhile prevention tools Higher rates of smoking initiation and continuation by female compared with male adolescents , as found in many developed countries , may call for gender-specific prevention programs . Risk factors of smoking initiation and continuation were examined prospect ively ( 1997 - 2002 ) among 3205 Dutch elementary schoolchildren ( mean age 11.64 ) in an intervention trial using written question naires and multilevel logistic regression . At baseline , smoking prevalence was lower among girls than among boys ; at follow-up , smoking initiation was lower among girls than among boys . Concerning smoking initiation , girls and boys shared the following risk factors : age , modeling from parents and siblings ( ' modeling nuclear ' ) , modeling from other members in the social circle ( ' modeling diffuse ' ) and perceived pro-tobacco pressure to smoke . The only gender-specific predictor of smoking initiation was parent origin ; girls with non-Dutch parents could be targeted for prevention programs . Concerning continuation , girls and boys shared the following risk factors : older age , more modeling nuclear and diffuse , fewer smoking disadvantages and lower self-efficacy to refrain from smoking . This study confirms that social modeling , smoking attitude and self-efficacy information to refrain from smoking deserve a prominent place in smoking prevention programs for schoolchildren . Besides booster sessions , family-directed programs are suggested . No gender-specific predictors of later smoking initiation were found , apart from parent origin , which is not amenable to intervention This study examines the effects of 2 brief family-focused interventions on the trajectories of substance initiation over a period of 6 years following a baseline assessment . The 2 interventions , design ed for general- population families of adolescents , were the 7-session Iowa Strengthening Families Program ( ISFP ) ( Molgaard & Spoth , 2001 ) and the 5-session Preparing for the Drug Free Years Program ( PDFY ) ( Catalano , Kosterman , Haggerty , Hawkins , & Spoth , 1999 ) . Thirty-three rural public schools were r and omly assigned to the ISFP , the PDFY , or a minimal-contact control condition . The authors evaluated the curvilinear growth observed in school-level measures of initiation using a logistic growth curve analysis . Alcohol and tobacco composite use indices -- as well as lifetime use of alcohol , cigarettes , and marijuana-- and lifetime drunkenness , were examined . Significant intervention-control differences were observed , indicating favorable delays in initiation in the intervention groups OBJECTIVE To evaluate the impact of a theatre production on smoking-related attitudes , norms , and intentions of children in grade s 1–6 ( aged 6–12 years ) . DESIGN Seventeen schools were r and omly selected among 160 that were participating in the implementation of the theatre production 2 Smart 2 Smoke . Schools that participated in the theatre production after 3 December 1997 were assigned as control schools . Assignment of schools to a given date for the theatre production was a r and om process . Students in grade s 1–6 were surveyed before and after the theatre production and associated activities . The data were examined for pretest – posttest differences and intervention-control differences . The school was the unit of analysis . SETTING Elementary schools in the Twin Cities metropolitan area . PARTICIPANTS Students in grade s 1–6 in 17 elementary schools . INTERVENTION Two plays2 Smart 2 Smoke for grade s 1–3 ( 6–8 year olds ) and grade s 4–6 ( 9–12 year olds ) , respectively , with follow-up activities for the classroom and home . A national theatre company performed the plays at the schools . MAIN OUTCOME MEASURES Intention to smoke in the future , normative expectations about how many people smoke , functional meanings of smoking , expected outcomes of smoking . RESULTS 10 % more students reported that they would never smoke a cigarette after the theatre production . Students in grade s 4–6 showed changes in the functional meanings and expected outcomes of smoking . Students in grade s 1–3 showed changes in normative expectations . CONCLUSIONS Further research on the impact of live theatre productions as a smoking prevention strategy is recommended Using st and ard missing data taxonomy , due to Rubin and co-workers , and simple algebraic derivations , it is argued that some simple but commonly used methods to h and le incomplete longitudinal clinical trial data , such as complete case analyses and methods based on last observation carried forward , require restrictive assumptions and st and on a weaker theoretical foundation than likelihood-based methods developed under the missing at r and om ( MAR ) framework . Given the availability of flexible software for analyzing longitudinal sequences of unequal length , implementation of likelihood-based MAR analyses is not limited by computational considerations . While such analyses are valid under the comparatively weak assumption of MAR , the possibility of data missing not at r and om ( MNAR ) is difficult to rule out . It is argued , however , that MNAR analyses are , themselves , surrounded with problems and therefore , rather than ignoring MNAR analyses altogether or blindly shifting to them , their optimal place is within sensitivity analysis . The concepts developed here are illustrated using data from three clinical trials , where it is shown that the analysis method may have an impact on the conclusions of the study Summary Background Schools in many countries undertake programmes for smoking prevention , but systematic review s have shown mixed evidence of their effectiveness . Most peer-led approaches have been classroom-based , and rigorous assessment s are scarce . We assessed the effectiveness of a peer-led intervention that aim ed to prevent smoking uptake in secondary schools . Methods We undertook a cluster r and omised controlled trial of 10 730 students aged 12–13 years in 59 schools in Engl and and Wales . 29 schools ( 5372 students ) were r and omly assigned by stratified block r and omisation to the control group to continue their usual smoking education and 30 ( 5358 students ) to the intervention group . The intervention ( ASSIST [ A Stop Smoking In Schools Trial ] programme ) consisted of training influential students to act as peer supporters during informal interactions outside the classroom to encourage their peers not to smoke . Follow-up was immediately after the intervention and at 1 and 2 years . Primary outcomes were smoking in the past week in both the school year group and in a group at high risk of regular smoking uptake , which was identified at baseline as occasional , experimental , or ex-smokers . Analysis was by intention to treat . This study is registered , number IS RCT N55572965 . Findings The odds ratio of being a smoker in intervention compared with control schools was 0·75 ( 95 % CI 0·55–1·01 ) immediately after the intervention ( n=9349 students ) , 0·77 ( 0·59–0·99 ) at 1-year follow-up ( n=9147 ) , and 0·85 ( 0·72–1·01 ) at 2-year follow-up ( n=8756 ) . The corresponding odds ratios for the high-risk group were 0·79 ( 0·55–1·13 [ n=3561 ] ) , 0·75 ( 0·56–0·99 [ n=3483 ] ) , and 0·85 ( 0·70–1·02 [ n=3294 ] ) , respectively . In a three-tier multilevel model with data from all three follow-ups , the odds of being a smoker in intervention compared with control schools was 0·78 ( 0·64–0·96 ) . Interpretation The results suggest that , if implemented on a population basis , the ASSIST intervention could lead to a reduction in adolescent smoking prevalence of public-health importance . Funding MRC ( UK ) Having friends who engage in disruptive behavior in childhood may be a risk factor for childhood tobacco experimentation . This study tested the role of friends ’ disruptive behavior as a mediator of the effects of a classroom based intervention on children ’s tobacco experimentation . 433 Children ( 52 % males ) were r and omly assigned to the Good Behavior Game ( GBG ) intervention , a universal preventive intervention targeting disruptive behavior , and facilitating positive prosocial peer interactions . Friends ’ disruptive behavior was assessed from age 7–10 years . Participants ’ experimentation with tobacco was assessed annually from age 10–13 . Reduced rates in tobacco experimentation and friends ’ disruptive behavior were found among GBG children , as compared to controls . Support for friends ’ disruptive behavior as a mediator in the link between intervention status and tobacco experimentation was found . These results remained after controlling for friends ’ and parental smoking status , and child ADHD symptoms . The results support the role of friends ’ disruptive behavior in preadolescents ’ tobacco experimentation We assessed the immediate effects of two universal , first- grade preventive interventions on the proximal targets of poor achievement , concentration problems , aggression , and shy behaviors , known early risk behaviors for later substance use/abuse , affective disorder , and conduct disorder . The classroom-centered ( CC ) intervention was design ed to reduce these early risk behaviors by enhancing teachers ' behavior management and instructional skills , whereas the family-school partnership ( FSP ) intervention was aim ed at improving parent-teacher communication and parental teaching and child behavior management strategies . Over the course of first and second grade s , the CC intervention yielded the greatest degree of impact on its proximal targets , whereas the FSP 's impact was somewhat less . The effects were influenced by gender and by preintervention levels of risk . Analyses of implementation measures demonstrated that greater fidelity to the intervention protocol s was associated with greater impact on behavior ratings and on achievement scores , thus providing some evidence of specificity in the effect of the interventions Background Although the number of smokers has declined in the last decade , smoking is still a major health problem among youngsters and adolescents . For this reason , there is a need for effective smoking prevention programmes targeting primary school children . A web-based computer-tailored feedback programme may be an effective intervention to stimulate youngsters not to start smoking , and increase their knowledge about the adverse effects of smoking and their attitudes and self-efficacy regarding non-smoking . Methods & design This paper describes the development and evaluation protocol of a web-based out-of-school smoking prevention programme for primary school children ( age 10 - 13 years ) entitled ‘ Fun without Smokes ’ . It is a transformation of a postal mailed intervention to a web-based intervention . Besides this transformation the effects of prompts will be examined . This web-based intervention will be evaluated in a 2-year cluster r and omised controlled trial ( c- RCT ) with three study arms . An intervention and intervention + prompt condition will be evaluated for effects on smoking behaviour , compared with a no information control condition . Information about pupils ’ smoking status and other factors related to smoking will be obtained using a web-based question naire . After completing the question naire pupils in both intervention conditions will receive three computer-tailored feedback letters in their personal e-mail box . Attitudes , social influences and self-efficacy expectations will be the content of these personalised feedback letters . Pupils in the intervention + prompt condition will - in addition to the personalised feedback letters - receive e-mail and SMS messages prompting them to revisit the ‘ Fun without Smokes ’ website . The main outcome measures will be ever smoking and the utilisation of the ‘ Fun without Smokes ’ website . Measurements will be carried out at baseline , 12 months and 24 months of follow-up . Discussion The present study protocol describes the purpose , intervention design and study protocol of ‘ Fun without Smokes ’ . Expectations are that pupils receiving tailored advice will be less likely to smoke after 24 months in contrast to pupils in the control condition . Furthermore , tailored feedback letters and prompting is expected to be more effective than providing tailored feedback letters only . Trial registration Dutch Trial Register The objective of the study was to develop and evaluate an effective whole-community approach to identifying a diverse group of influential young people to effectively diffuse health promotion messages among their peers . A peer nomination question naire , developed through extensive piloting work , was completed by 10 730 Year 8 students ( aged 12 - 13 years ) in 59 schools ( 30 intervention , 29 control ) as part of a cluster r and omized controlled trial . Influential students identified in 30 intervention schools were trained to disseminate smoke-free health promotion messages through informal contacts with peers . This approach successfully identified , recruited and retained a diverse group of students , broadly representative of their year group , to undertake the role of ' peer supporter ' . Although students and staff expressed doubts about the suitability of some young people recruited as peer supporters , the intervention achieved a 22 % reduction in the odds of being a regular smoker in intervention compared with control schools [ odds ratio 0.78 ( 95 % CI 0.64 - 0.96 ) ] . Carefully design ed and developed peer-led interventions have potential for delivering effective smoking prevention among adolescents . Paying close attention to the way in which peer educators are identified , and involving young people themselves in this process , may be the key to increasing the effectiveness of peer education In autumn 1995 The Norwegian Cancer Society in cooperation with The Research Center for Health Promotion , University of Bergen started a study of school-based interventions aim ing at preventing smoking among pupils in Norwegian secondary schools . The study comprised a nationwide sample of 4441 students at 99 schools ( 195 classes ) . This panel of students is followed through annual data collection s till they graduate in spring 1997 . Written consensus from students and parents was obtained from 95 % . Schools were systematic ally allocated to one of four groups : Group A , control ; Group B , intervention , containing classroom program , involvement of parents and teacher courses ; Group C , like B , but without teacher courses ; Group D , like B , but without parental involvement . Baseline data were collected by question naires administered in class in November 1994 and the first follow-up survey was carried out in May 1995 . At follow-up the proportion of smokers had increased by 8.3 percentage points in Group A ( control ) and by 1.9 percentage points in Group B ( most extensive intervention ) . As expected , the recruitment of smokers was higher in Groups C and D than in the ideal intervention , but lower than in the control group . Effects of the most extensive program among subgroups of students were examined by comparing Groups A and B. Students are categorized as high risk or low risk based on scores on scales measuring sensation seeking , physical maturity , antisocial behavior and parental smoking . The effect of the program on recruitment of smokers seems to have been at least as strong or even stronger among ' high-risk ' students than among other students Objective : To assess the effect of an antismoking intervention focusing on adolescents in lower education . Students with lower education smoke more often and perceive more positive norms , and social pressure to smoke , than higher educated students . An intervention based on peer group pressure and social influence may therefore be useful to prevent smoking among these students . Design : Group r and omised controlled trial . Setting : 26 Dutch schools that provided junior secondary education . Subjects : 1444 students in the intervention and 1118 students in the control group , all in the first grade , average age 13 years . Intervention : Three lessons on knowledge , attitudes , and social influence , followed by a class agreement not to start or to stop smoking for five months and a class based competition . Main outcome measures : Comparison of smoking status before and immediately after and one year after the intervention , using multilevel analysis . Results : In the intervention group , 9.6 % of non-smokers started to smoke , in the control group 14.2 % . This leads to an odds ratio of 0.61 ( 95 % CI= 0.41 to 0.90 ) to uptake smoking in the intervention group compared with the control group . One year after the intervention , the effect was no longer significant . Conclusions : In the short-term , an intervention based on peer pressure decreases the proportion of adolescents with lower education who start smoking . Influencing social norms and peer pressure would therefore be a promising strategy in terms of preventing smoking among adolescents . The results also suggest that additional interventions in later years are needed to maintain the effect Background / Aims : Symptoms of attention deficit hyperactivity disorder ( ADHD ) have often been associated with early-onset smoking . We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking . Methods : In a universal , school-based , r and omized controlled intervention trial , we examined whether intervention-induced reductions in ADHD symptoms at age 9 mediated the reduced risk of tobacco use onset among these children at age 10 or 11 years . A sample of 477 first- grade boys and girls were r and omly assigned to the Good Behavior Game intervention ( n = 263 ) , a 2-year ( grade s 2 and 3 ) universal classroom-based intervention aim ed at reducing disruptive behavior problems , or to a control condition ( n = 214 ) . ADHD symptoms were assessed through teacher ratings . Early onset of tobacco use was assessed through self-report . Results : The intervention-induced reductions in ADHD symptoms fully mediated the distal effect of intervention on reductions in early-onset smoking . Conclusions : Our results showed that programs that target ADHD symptoms may protect children from early-onset smoking as well . Further research is needed to examine pathways from ADHD symptoms to tobacco use OBJECTIVES We evaluated the revised Project ALERT drug prevention program across a wide variety of Midwestern schools and communities . METHODS Fifty-five South Dakota middle schools were r and omly assigned to program or control conditions . Treatment group students received 11 lessons in 7th grade and 3 more in 8th grade . Program effects for 4276 8th- grade rs were assessed 18 months after baseline . RESULTS The revised Project ALERT curriculum curbed cigarette and marijuana use initiation , current and regular cigarette use , and alcohol misuse . Reductions ranged from 19 % to 39 % . Program effects were not significant for initial and current drinking or for current and regular marijuana use . CONCLUSIONS School-based drug prevention programs can prevent occasional and more serious drug use , help low- to high-risk adolescents , and be effective in diverse school environments Background To date , no school-based intervention has been proven to be effective in preventing adolescent smoking , despite continuing concern about smoking levels amongst young people in the United Kingdom . Although formal teacher-led smoking prevention interventions are considered unlikely to be effective , peer-led approaches to reducing smoking have been proposed as potentially valuable . Methods / design ASSIST ( A Stop Smoking in Schools Trial ) is a comprehensive , large-scale evaluation to rigorously test whether peer supporters in Year 8 ( age 11–12 ) can be recruited and trained to effect a reduction in smoking uptake among their fellow students . The evaluation is employing a cluster r and omised controlled trial ( RCT ) design with secondary school as the unit of r and omisation , and is being undertaken in 59 schools in South East Wales and the West of Engl and . Embedded within the trial are an economic evaluation of the intervention costs , a process evaluation to provide detailed information on how the intervention was delivered and received , and an analysis of social networks to consider whether such a peer group intervention could work amongst schoolchildren in this age group . Schools were r and omised to either continue with normal smoking education ( n = 29 schools , 5562 students ) , or to do so and additionally receive the ASSIST intervention ( n = 30 schools , 5481 students ) . No schools withdrew once the trial had started , and the intervention was successfully implemented in all 30 schools , with excellent participation rates from the peer supporters . The primary outcome is regular ( weekly ) smoking , vali date d by salivary cotinine , and this outcome has been obtained for 94.4 % , 91.0 % and 95.6 % of eligible students at baseline , immediate post-intervention , and one-year follow-up respectively . Discussion Comprehensive evaluations of complex public health interventions of this scale and nature are rare in the United Kingdom . This paper demonstrates the feasibility of conducting cluster RCTs of complex public health interventions in schools , and how the rigour of such design s can be maximised both by thorough implementation of the protocol and by broadening the scope of questions addressed in the trial by including additional evaluative components PURPOSE Toward developing attractive and effective means to reduce cancer risks faced by Native American people , this study developed and tested interactive computer software to improve dietary choices and prevent tobacco use among Native American adolescents . METHODS Based on a legend of the Seneca Nation , a cancer prevention lesson was developed and programmed for software . A sample of 368 Native American adolescents were divided r and omly into intervention and control arms . Youths in both arms were pre-tested , youths in the intervention arm interacted with the software , and all youths were post-tested . Pre-test and post-test measures covered information and attitudes about cancer risks from dietary practice s and tobacco use . RESULTS Pre-test scores differed between the two arms on youths ' age and on one outcome variable . Relative to their counterparts in the control arm , youths in the intervention arm increased their post-test scores on 8 of 12 outcome measurement variables . Process data gathered during intervention delivery indicated that nearly all youths were involved with the interactive software and lesson . CONCLUSION Interactive computer software holds promise for delivering cancer risk reduction intervention aim ed at modifying dietary habits and preventing tobacco use among Native American youth OBJECTIVES This paper presents up to 5 years post-program outcomes of Project Towards No Drug Abuse ( Project TND ) , a drug abuse prevention program conducted in South California alternative high school system during years 1994 - 1999 . METHODS The effects of a 9-session health motivation -- social skills -- decision-making curriculum were evaluated . Twenty-one schools recruited were r and omly assigned to st and ard care ( control ) , classroom only , or a classroom plus semester-long school-as-community component . Last 30-day use of cigarettes , alcohol , marijuana , and hard drugs were assessed at three time intervals : short-term ( year 1 ) , middle-term ( years 2 or 3 ) , and long-term ( years 4 or 5 ) . Multilevel r and om coefficients modeling were employed to estimate the adjusted levels of substance use . RESULTS Among 1578 baseline subjects , follow-up data were available for 68 % ( year 1 ) , 66 % ( years 2 or 3 ) , and 46 % ( years 4 or 5 ) of subjects , respectively . Results revealed significant positive long-term program effects for hard drug use at year 4 or 5 for the two program interventions ( P = 0.02 ) . CONCLUSIONS Project TND reduced hard drug use in the 46 % who were successfully followed . It is the first program to demonstrate long-term self-reported behavioral effects on hard drug use among high-risk youth by using a school-based , limited-session model A major challenge in the dissemination of evidence -based family interventions ( EBFIs ) design ed to reduce youth substance use and other problem behaviors is effective and sustainable community-based recruitment . This understudied topic is addressed by a preliminary study of 14 community-university partnership teams r and omly assigned to an intervention condition in which teams attempted sustained implementation of EBFIs with two cohorts of middle school families . This report describes attendance rates of recruited families maintained over time and across both cohorts , along with exploratory analyses of factors associated with those rates . When compared with community-based recruitment rates in the literature , particularly for multisession interventions , relatively high rates were observed ; they averaged 17 % across cohorts . Community team functioning ( e.g. , production of quality team promotional material s ) and technical assistance ( TA ) variables ( e.g. , effective collaboration with TA , frequency of TA requests ) were associated with higher recruitment rates , even after controlling for community and school district context ual influences . Results support the community-university partnership model for recruitment that was implemented in the study The aim of this study was to investigate the smoking habits of a sample of second year high school students in Romagna ( Northern Italy ) by means of an anonymous self-administered question naire and the efficiency of a previous health education campaign . A sample of 2,691 16-year-old pupils ( 74 % of the school population of this age ) was r and omly selected . Of these , 863 ( 32.1 % ) had participated in a prevention campaign while attending middle school . 19.1 % of the students who had taken part in the campaign were smokers compared to 23.2 % of those who had not . The students ' smoking habits were found to be influenced by the type of school and by the role models ( parents , siblings , friends , teachers ) . The campaign appears to have had good results , especially in places where it was carried out on a wide scale . Suggestions are made for making such campaigns more efficient OBJECTIVES This study examined the effect of an orthodontist-delivered tobacco-use prevention program for adolescents . METHODS Southern California orthodontic offices were r and omly assigned to experimental ( n = 77 ) and control ( n = 77 ) groups . R and omly selected adolescents were interviewed at baseline and 2 years later ( n = 15,644 ) . Experimental offices received tobacco prevention training , anti-tobacco material s , and 50 cents for each anti-tobacco " prescription " written . RESULTS The 30-day tobacco use 2-year incidence rates for the control and experimental groups were 12.6 % and 12.0 % , respectively ; incidence rates for using tobacco more than 100 times were 7.6 % and 6.8 % . Differences between the groups did not reach significance . Mean prescription compliance was 64.4 % . A multivariate logistic model , showed a significant dose response : patients who received more prescriptions had lower incidence rates than those who received few or none ( 10 % vs 14 % ) . CONCLUSIONS Training , payment , and support did not ensure clinician compliance with prevention services . The dose effect suggests that replication under conditions that would ensure clinician compliance and statistical power would more thoroughly test clinicians ' ability to prevent tobacco use To evaluate methods of preventing young children from experimenting with tobacco and to determine cost effectiveness , students ( n = 1005 ) in 31 primary schools , from r and omly selected higher grade -levels were recruited into a partially r and omized , single blinded controlled trial in which seven groups of schools were r and omly assigned to a combination of teaching , leaflet , and drama , in order to modify students ' knowledge , attitudes , beliefs and behaviour ( KAB ) . The eighth group ( n = 346 ) with ten schools , distantly separated from the former , was assigned to be the control , but was dropped from comparison analysis for lack of r and omness at baseline . The mean , st and ard deviation and median age of the intervention groups was 9.94 years ( 0.81 ) , 10.0 years , ( n = 669 ) at baseline ; and 10.62 years ( 0.66 ) , 11.0 years , ( n = 397 ) , at 12 months follow-up . In all , 6.6 % had ever used tobacco at least once at a median age of seven years . Teaching health education at school when combined with other methods was significantly better at improving KAB . In 2003 , after a year post-intervention , the occurrence of experimentation smoking in the last 30 days , dropped from 9.2 % to 1.2 % ( p = 0.00 ) , equivalent to 87 % ( 95 % CI 78 , 93 ) reduction in the group exposed to health education compared to none in the leaflet-only group and Numbers Needed to Treat ( NNT ) = 12.5 . Due to its cost-effectiveness ( comparable to child immunizations ) at BDS dollars 1.89 to 2.89 or US dollars 1 to 1.5 per child contacted and BDS dollars 100 to 140 ( US dollars 50 to 70 ) capital investment in other re sources per school , the experience could be utilized routinely in elementary schools This article presents the results of a mediation analysis of Project MYTRI ( Mobilizing Youth for Tobacco Related Initiatives in India ) , a r and omized , controlled trial of a multiple-component , school-based tobacco prevention program for sixth- to ninth- grade rs ( n = 14,085 ) in Delhi and Chennai , India . A mediation analysis identifies how an intervention achieves its effects . In MYTRI , changes in students ’ ( a ) knowledge about the negative health effects of tobacco , ( b ) beliefs about its social consequences , ( c ) reasons to use tobacco , ( d ) reasons not to use tobacco , ( e ) advocacy skills self-efficacy , and ( f ) normative beliefs about tobacco use were significantly associated with reductions in students ’ intentions to use tobacco and tobacco use behaviors . In contrast , changes in students ’ perceptions of the prevalence of smoking and chewing tobacco were significantly related to increases in students ’ intentions to use and use of tobacco . Implication s for intervention design are considered BACKGROUND This study aim ed at exploring the impacts of a school-wide no smoking strategy and a classroom-based smoking prevention curriculum on smoking-related knowledge , attitude , behavior , and skill of junior high school students . METHODS Using a pre-post quasi-experimental design , 469 seventh-to ninth- grade students at four junior high schools in Taiwan , were selected and separated into three groups according to class unit . Experimental group A experienced a school-wide no smoking strategy and a six-session smoking prevention curriculum . Experimental group B experienced only the school-wide no smoking strategy . The control group experienced no intervention . The students were tested 1 week before intervention began and 1 week after it ended . RESULTS Experimental group A exhibited a better underst and ing than either experimental group B or the control group of the dangers of smoking and of techniques for refusing cigarettes ; and in fact , group A indicated low smoking intention than experimental group B. Experimental group A also had a better attitudes towards resisting smoking than the control group . However , the intervention had no demonstrable effect on the smoking behavior and on the smoking substitution methods of students . CONCLUSIONS To reduce the smoking rates among junior high school students , diversified school-wide no smoking strategies and st and ardized , diversified instruments should be adopted so that outcomes of smoking prevention work may be assessed more objective ly and effectively INTRODUCTION A smoking prevention program was developed to prepare children in elementary school for secondary school . This study assessed the effects on smoking in secondary school . METHODS In 2002 , 121 schools in The Netherl and s were r and omly assigned to the intervention or control group . The intervention group received 3 lessons in 5th grade of elementary school and a second 3 lessons in 6th grade . The control group received " usual care " . Students completed 5 question naires : before and after the lessons in 5th and 6th grade and in the first class of secondary school . At baseline , 3173 students completed the question naire ; 57 % completed all question naires . RESULTS The program had limited effect at the end of elementary school . One year later in secondary school significant effects on behavioral determinants and smoking were found . The intervention group had a higher intention not to smoke ( β=0.13 , 95 % confidence interval=0.01 - 0.24 ) and started to smoke less often than the control group ( odds ratio=0.59 , 95 % confidence interval=0.35 - 0.99 ) : smoking increased from 2.5 % to 3.6 % in the intervention group and from 3.2 % to 6.5 % in the control group . Girls showed the largest differences in smoking between intervention and control condition . CONCLUSIONS A prevention program in elementary school seems to be effective in preventing smoking Primary prevention of smoking in adolescents requires effective screening instruments for identifying those adolescents who are most likely to experiment with cigarettes . This study investigated the predictive value of a measure of susceptibility to smoking ( the lack of a firm commitment not to smoke ) for predicting smoking initiation 1 and 2 years later among 687 seventh- grade nonsmokers . Results showed that susceptible adolescents were approximately two to three times more likely to experiment with cigarettes during the ensuing 2 years than were nonsusceptible adolescents . At the lower levels of smoking , these relationships persisted even after controlling for psychosocial variables . Measures of susceptibility to smoking could be an effective tool for identifying adolescents at increased risk of experimenting with cigarettes or assessing their readiness for smoking-prevention programs We reported previously on the success of an innovative approach to cigarette smoking prevention in seventh- grade students . The present report describes a 3-year follow-up of three schools and 1081 sutdents initially involved in the research program . The curriculum emphasizes the shortterm influences which affect smoking in youth , particularly social and peer influences . In the school which received this curriculum from likeaged peer leaders , the incidence of smoking remained low compared to that in a control school . Those who did smoke in this school consumed significantly fewer cigarettes . In the school where the curriculum was adult taught , smoking rates were initially lower but rose in the later years , ultimately differing little from those in the control school . Reported smoking behavior was confirmed by saliva ihiocyanate measurement in all students . Cigarette smoking behavior appears significantly inhibited by a peer-taught curriculum and that effect is retained for several years after the education program BACKGROUND This article discusses the development , implementation , and preliminary testing of an intervention to reduce cancer risks through tobacco use prevention and dietary modification among Native American youth in the Northeastern United States . METHODS The intervention outcome study includes a research design and outcome measurement instruments . In collaboration with Native American communities , reservations , and organizations in the Northeastern United States , implementation of the design quantifies the separate and combined effects of a tobacco use prevention and a dietary modification intervention . RESULTS Native American youths in the tobacco prevention intervention and in the combined tobacco and dietary intervention increased their knowledge of tobacco facts and their awareness of the motives of tobacco advertising , and showed higher ratings for an ability to resist peer pressure and to refuse offers of tobacco use between pretest and posttest . Youths in the combined intervention were significantly less apt to report smoking of any kind . Youths in the tobacco use prevention-only condition reported significantly less smoking than their counterparts in the dietary modification-only condition and control condition on 4 of 8 measurement items . As for dietary variables , pretest to posttest measurement scores showed that , after receiving the curriculum , youths in the dietary modification intervention and in the combined intervention improved their knowledge of the health implication s of consuming dietary fat , fiber , fruits , and vegetables . Youths in the dietary modification and combined intervention also improved their scores of knowledge related to cancer risk-reducing nutritional practice s , cultural dietary habits , and healthy food choices available for Native American cultures . Youths in the dietary modification-only condition report significantly increasing their consumption of complex carbohydrates and significantly decreasing their fat intake between pretest and posttest occasions . CONCLUSIONS Data from this longitudinal study suggest the value of the FACETS curriculum for helping Native American youth reduce their risks for cancer associated with tobacco use and dietary preference and consumption patterns . In particular , results indicate the enhanced effects of the combined tobacco use prevention and dietary modification intervention for preventing tobacco use and for improving youths ' knowledge and attitudes with regard to tobacco use and diet . Further , the study demonstrates the value of collaborating with Native American organizations to design a cancer risk-reducing curriculum and to implement tests of that curriculum OBJECTIVE To evaluate the process of smoking prevention and control among Chinese adolescent with a model on health promotion in junior high school . METHODS A cluster-r and omized , controlled and schooled-based trial on smoking prevention was conducted among 2343 students at four secondary schools in Huangpu District of Guangzhou . Students ' reports and investigators ' daily records were used to evaluate the intervention measures . RESULTS During the one-year period of intervention ( Dec. 2004 through Dec. 2005 ) , eighteen activities had been implemented among students , teachers , parents and cigarette retailers . Ranked by the rate of awareness , the top six activities were shown as follows : " the nicotine toxicity experiment " ( 90.7 % ) , " agreement of building families free of smoking"(77.7 % ) , " a letter to parents " ( 77.1 % ) , " no-smoking signs " ( 76.5 % ) , " Blackboard information about health and smoking " ( 75.0 % ) , and " signature on the 18th World Day of No Smoking " ( 70.2 % ) . Among all the activities , " the nicotine toxicity experiment " had the highest rate of participation ( 88.5 % ) , followed by " a letter to parents " ( 73.6 % ) , " agreement of building families free of smoking " ( 69.8 % ) , " health education through experiments"(68.6 % ) , " health education through multimedia " ( 65.7 % ) and " signature on the 18th World Day of No Smoking " ( 65.6 % ) . The top seven activities in which students showed greatest interests were " the nicotine toxicity experiment " ( 64.5 % ) , " signature on the 18th World Day of No Smoking " ( 33.0 % ) , " health education through experiments " ( 31.2 % ) , " health education through multimedia " ( 29.8 % ) , " class meetings with a thesis of smoking " ( 26.8 % ) , " health pamphlets " ( 26.6 % ) , " specific textbooks " ( 25.9 % ) . The extent of students ' general satisfaction to the work of tobacco control in school during the last year was 52.4 % . The biggest perceived shortcoming for the intervention plan was the low participation of students . CONCLUSION Some intervention measures had not been fully carried out among the students and only covered part of them . It is necessary to adjust the previous intervention measures through keeping the nicotine toxicity experiment , health education through multimedia and other measures with extensive participation of students and at the same time , to avoid literal material s , exhibition boards and traditional single-way health education program This paper describes a preventive intervention trial called EARLY ALLIANCE which is aim ed at reducing risk for three adverse outcomes in childhood and adolescence : conduct problems , substance abuse , and school failure . The structure of the prevention trial is unique because two linked design s are being implemented concurrently . The primary design focuses on children at elevated risk for adverse outcomes , and compares a targeted , multi context ual preventive intervention with family , classroom , peer relational , and academic components to a universal , schoolwide preventive intervention that emphasizes peaceful conflict management and serves as a " usual care " control condition . The secondary design focuses on children at lower risk for adverse outcomes and compares a universally administered classroom program to the control condition . The paper describes the theoretical foundation for EARLY ALLIANCE , the goals of the prevention trial , the rationale for design choices , and the methods employed An 8-month school-based smoking prevention program tested with 1526 seventh grade students result ed in a substantial reduction in the incidence of smoking relative to a comparison population . Two curriculum elements were found to have important deterrent effects on smoking onset : ( 1 ) emphasis on immediate and primarily social consequences of smoking and ( 2 ) personalization of the course material s and mode of presentation to include relevant peer role models and active individual role playing . Thiocyanate analysis of saliva sample s taken from all participants corroborated the validity of self-report measures of smoking behavior This study evaluates the effects of a school-based smoking prevention program after 1 year , using school ( 22 middle/elementary schools , 15 high schools ) as both the unit of r and omization and the unit of analysis . The multi grade level ( grade s 6 through 9 ) intervention was design ed to address comprehensively the social influence factors that encourage smoking . Teacher survey data indicated that treatment schools had a median of 10 classroom sessions devoted to tobacco/drug use education , 5 of which were the sessions design ed for this evaluation , and control schools had also dedicated a median of 10 classroom sessions to tobacco/drug education . Thus , the study evaluated the incremental effects of the social influence intervention compared to “ st and ard-care ” curricula . Among those who reported smoking one or more cigarettes in the month prior to the intervention , there was a significant treatment effect on rate of smoking at one year , but no grade level , gender , or interaction effects . The 1-year covariate-adjusted smoking rate among pretest smokers in the treatment schools was 76.6 cigarettes per month , compared to 111.6 cigarettes per month in control schools , a 31.4 % difference . These effects were not accounted for by differential subject attrition . The analyses for nonsmokers , however , showed no significant effects , and the program did not affect self-reported alcohol or marijuana use . Taken together with the results of other prevention studies , these results point to the need for the development and evaluation of new initiatives to prevent substance use This article presents the evaluation of written paragraphs which described twenty-one drug abuse prevention “ themes ” contained in thirty-five separate activities , as part of the process of curriculum development targeting Continuation High School students . The goal was to determine which activities were most preferred by these youth . The paragraphs consisted of descriptions of traditional drug abuse prevention program activities , alternative activities using the themes underlying traditional activities , and novel activities generated from newly developed themes . The study was conducted with seven Continuation High Schools . Three hundred and fifteen students participated in this study . Each student rated detailed written descriptions of five activities . Classrooms were r and omly assigned to different combinations of paragraphs . An analysis of variance indicated that there were significant differences in preferences among activities , with a marked preference for the alternative and novel activity presentations . Females , Latinos , older students , and non-marijuana users rated the activities higher overall . There were no significant interactions between demographic variables and order of activity preference . If there is a limit in amount of allotted time and re sources , the theme study is an appropriate and cost-effective tool for gaining important information for health curricula development This study assessed the immediate and short-term outcomes of adapting a culturally-grounded middle school program , keepin ' it REAL , for elementary school students . After curriculum adaptation , 10 schools were r and omly assigned to the intervention in 5th grade with follow-up boosters in 6th grade ; 13 schools were r and omly assigned to the control condition , implementing the school 's pre-existing substance use prevention programming . Students ( n = 1,566 ) completed a question naire prior to curriculum implementation and follow-up question naires toward the end of 5th and 6th grade . The 5th grade kiR curriculum generally appeared no more effective than the control schools ' programming in changing students ' resistance or decision-making skills ; substance use intentions , expectancies , or normative beliefs ; or lifetime and recent substance use . Such findings have implication s for the age appropriateness of school-based programs Objectives To examine the longitudinal relationship between exposure and receptivity to tobacco advertisements and progression towards tobacco use among adolescents in India . Design and setting A 2-year longitudinal group-r and omised trial , Mobilizing Youth for Tobacco Related Initiatives ( MYTRI ) , was undertaken from 2004 to 2006 in 32 schools in Delhi and Chennai . Among the control schools ( n=16 ) , mixed-effects regression models were used to assess the objectives . Subjects Students who were non-susceptible , never users of tobacco ( n=2782 ) at baseline ( 2004 ) in the control schools of Project MYTRI , who progressed academically and were followed up at endline ( 2006 ) . Main outcome measures Progression towards tobacco use ( on tobacco uptake continuum ) . Results Bivariate results suggest that exposure to tobacco advertisements at baseline was associated in a dose-dependent manner with progression at endline . Students exposed at more than four places were 1.5 times ( 95 % CI 1.12 to 1.94 ; p<0.05 ) more likely to progress towards tobacco use at endline versus those not exposed . Among boys , those exposed at more than four places were 1.7 times more likely to progress ( 95 % CI 1.14 to 2.62 ; p<0.05 ) . These significant results disappeared in multivariate analysis , when other psychosocial risk factors for tobacco use were controlled . In both bivariate and multivariate analyses , the risk of progression at endline was more than two times higher ( 95 % CI 1.28 to 4.32 ; p<0.05 ) among boys who were highly receptive versus non-receptive boys . The same relationship did not hold among girls . Conclusion High receptivity to tobacco advertising predicts future progression to tobacco use among boys in India . Suggestive evidence exists of a causal relationship between tobacco marketing and adolescent tobacco use BACKGROUND The present study addresses diffusion of a psychosocial-based substance abuse prevention program , including : ( a ) teacher adoption , implementation , and maintenance ; ( b ) teacher characteristics associated with implementation ; ( c ) the relationship between integrity of program delivery and program outcomes ; and ( d ) the effectiveness of teacher training and school principal involvement in increasing implementation . METHODS Participants were teachers ( n = 60 ) , school principals ( n = 25 ) , and fifth- grade students ( n = 1147 ) from four Los Angeles area school districts . Districts were r and omly assigned to an intensive or brief teacher training condition . Schools were r and omly assigned to a principal-intervention or a no-principal-intervention condition . Assessment s included teacher and principal self-reports , classroom observations of program delivery , and evaluation of immediate program outcomes . RESULTS During the first year , 78 % of trained teachers implemented one or more program lessons . During the second year , only 25 % maintained implementation of the program . Implementors reported fewer years of teaching experience and stronger self-efficacy , enthusiasm , preparedness , teaching methods compatibility , and principal encouragement than did nonimplementors . The principal intervention increased rates of implementation , but the intensive teacher training did not . Integrity of program delivery was positively associated with immediate program outcomes . CONCLUSIONS Program implementation was highly variable , suggesting that widespread teacher use of psychosocial-based programs can not be taken for granted . Strategies for increasing implementation and maintenance need to be developed OBJECTIVES We assessed the effectiveness of a 2-year multicomponent , school-based intervention design ed to reduce tobacco use rates among adolescents in an urban area of India . METHODS Students from 32 schools in Delhi and Chennai , India , were recruited and r and omly assigned to an intervention or control group . Baseline , intermediate , and outcome data were collected from 2 cohorts of 6th- and 8th- grade students in 2004 ; 14,063 students took part in the study and completed a survey in 2004 , 2005 , or 2006 . The intervention consisted of behavioral classroom curricula , school posters , a parental involvement component , and peer-led activism . The main outcome measures were self-reported use of cigarettes , bidis ( small h and -rolled , often flavored , cigarettes ) , and chewing tobacco and future intentions to smoke or use chewing tobacco . RESULTS Findings showed that students in the intervention group were significantly less likely than were students in the control group to exhibit increases in cigarette smoking or bidi smoking over the 2-year study period . They were also less likely to intend to smoke or chew tobacco in the future . CONCLUSIONS School-based programs similar to the intervention examined here should be considered as part of a multi strategy approach to reducing tobacco use among young people in India INTRODUCTION AND AIMS Declines in adolescent smoking prevalence have slowed recently , result ing in increased interest and literature in tobacco harm minimisation . To date , harm reduction strategies have focused largely on modifying the product and alternative ( safer ) mechanisms of nicotine delivery . There has been little exploration of primary harm minimisation to prevent the onset of regular smoking among young people . A major concern expressed about harm reduction interventions and young people is that they may increase experimentation among non-users . DESIGN AND METHODS The Smoking Cessation for Youth Project was a 2-year school-based cluster r and omised controlled trial conducted in 30 Western Australian schools . Results on the primary outcome showed a significant reduction in regular smoking among 4636 13 - 15-year-olds receiving a harm minimisaton versus st and ard intervention . This paper addresses the intervention effects on 2078 students who had not smoked at baseline . RESULTS At 20-month follow-up , smoking initiation was slightly lower among intervention students than comparison students ( who received a largely abstinence-based intervention ) , although this difference did not attain statistical significance ( OR=0.86 ; 95 % confidence interval : 0.68 , 1.09 ) . DISCUSSION AND CONCLUSIONS This study provided limited evidence to suggest that harm minimisation is a superior approach to abstinence-based interventions for non-smokers . However , this intervention did not contribute to increased experimentation among non-smokers . Although more trials are required , these results indicate that fears of potential negative iatrogenic effects from school-based harm minimisation interventions may be unwarranted Four years of longitudinal data from 373 families participating in a r and omized intervention-control clinical trial were used to examine whether intervention effects on adolescent alcohol and tobacco use trajectories were moderated by family risk , as defined by parental social emotional maladjustment . Consistent with earlier outcome evaluations based on analyses of covariance , analyses confirmed that both the Preparing for the Drug Free Years program and the Iowa Strengthening Families Program favorably influenced alcohol use index trajectories across the time frame of the study ; only the latter program , however , evidence d positive effects on a tobacco use index . Concerning the primary research question , analyses provided no support for family risk moderation of any intervention effect . Findings indicate the feasibility of developing universal preventive interventions that offer comparable benefits to all families Much research has been done in developing and implementing smoking prevention programs ; however , few studies have focused on urban Black population s. In November of 1989 , a comprehensive prevention program was implemented to decrease the incidence of new smokers within the adolescent population in a Black community . The program combined a school-based curriculum with a comprehensive media intervention . All components of the program were financed by business leaders from the targeted community . There were two experimental conditions : one group participated in a school-based intervention and were prompted to participate in a multi-media intervention and the other group had access to the multi-media intervention ; however , they were not prompted to participate . A key finding was that the rate of smoking decreased for all children involved in the intervention . The authors present a model that can be employed to prevent other high-risk behaviors within the Black population The primary purpose of this study was to test the efficacy of a brief , multi-health behavior intervention integrating physical activity and alcohol use prevention messages for high school-aged adolescents . A total of 604 participants , 335 9th and 269 11th grade students from a suburban high school in northeast Florida participated in this study . A r and omized control trial was conducted with participants r and omly assigned within grade levels to receive either a brief consultation and prescription with a mailed reinforcing follow-up flyer ( Project SPORT ) or a minimal intervention control consisting of a wellness brochure provided in school and a pamphlet about teen health and fitness mailed to the home . Differences between intervention groups were evaluated with a series of MANCOVA tests . Project SPORT participants demonstrated significant positive effects at 3-months postintervention for alcohol consumption , alcohol initiation behaviors , alcohol use risk and protective factors , drug use behaviors , and exercise habits , and at 12-months for alcohol use risk and protective factors , cigarette use , and cigarette initiation ( p 's < 0.05 ) . A post hoc analysis examining interactions between past 30-day use of marijuana and /or cigarettes by treatment group indicates significant positive effects for drug using adolescents who received Project SPORT on alcohol consumption , drug use behaviors , and drug use initiation at 3-months , and for drug use behaviors and exercise habits at 12-months ( p 's < 0.05 ) . A brief , 12-min one-on-one consultation integrating alcohol avoidance messages within those promoting fitness and other positive health behaviors holds promise for influencing adolescent alcohol and cigarette use and other health behaviors at posttreatment and 1 year later . Long-term sustained effects for cigarette and marijuana use , and both vigorous and moderate physical activity , were found among adolescents using marijuana and /or cigarettes prior to intervention Abstract Objective : To assess the net 5 year effects of intervention of a community based demonstration project , the Heartbeat Wales programme , on modifiable behavioural risks for prevention of cardiovascular disease . Design and setting : Quasi-experimental design comparing results from two independent cross sectional population surveys conducted in 1985 and 1990 in Wales and a matched reference area in north east Engl and . Subjects : R and om , stratified sample s of people aged 18 - 64 years ( 18 538 in 1985 and 13 045 in 1990 ) in Wales and in north east Engl and ( 1483 and 4534 , respectively ) . Intervention : A coordinated range of activities for heart health promotion in Wales entailing public education campaigns along with supportive policy and infrastructure change . In the reference area no additional community heart health promotion was planned , though considerable activity did take place , “ contaminating ” the reference area . Main outcome measures : Fifteen self reported behavioural indicators relating to dietary choice , smoking , frequency of exercise , and weight . Results : Positive changes ( for health ) in behavioural outcomes were observed among the population in Wales , including a reduction in reported smoking prevalence and improvements in dietary choice . There was no net intervention effect for the programme over and above observed change in the reference area . Conclusions : No definite conclusions can be drawn concerning the efficacy of the programme in terms of behavioural outcomes . With hindsight , the difficulties of evaluating such a complex multifaceted intervention were underestimated . Further debate on the most appropriate methods for assessing the effectiveness of community based health promotion programmes is called for . Key messages Heartbeat Wales was set up in 1985 as a community based programme to demonstrate risk reduction for cardiovascular disease Important changes were observed in modifiable risks for cardiovascular disease in Wales between 1985 and 1990 There was an unexpectedly rapid uptake of heart health promotion activity in the reference area No net intervention effects were found for the programme over and above changes in the reference area Improvements in methods of evaluation for community based health promotion programmes are The objective of this study was to evaluate the impact of a revised state-of-the-art drug prevention program , Project ALERT , on risk factors for drug use in mostly rural midwestern schools and communities . Fifty-five middle schools from South Dakota were r and omly assigned to treatment or control conditions . Treatment-group students received 11 lessons in Grade 7 and 3 more in Grade 8 . Effects for 4,276 eighth grade rs were assessed 18 months after baseline . Results indicate that Project ALERT had statistically significant effects on all the targeted risk factors associated with cigarette and marijuana use and more modest gains with the pro-alcoholrisk factors . The program helped adolescents at low , moderate , and high risk for future use , with the effect sizes typically stronger for the low- and moderate-risk groups . Thus , school-based drug prevention programs can lower risk factors that correlate with drug use , help low- to high-risk adolescents , and be effective in diverse school environments This study presents one-year follow-up data from an evaluation study testing the effectiveness of a cognitive-behavioral substance abuse prevention approach which emphasizes the teaching of social resistance skills within the larger context of an intervention design ed to enhance general social and personal competence . The follow-up study involved 998 eighth grade rs from 10 suburban New York junior high schools . Two schools were assigned to each of the following conditions ( a ) peer-led intervention , ( b ) peer-led intervention with booster sessions , ( c ) teacher-led intervention , ( d ) teacher-led intervention with booster sessions , and ( e ) control . The original intervention was implemented in the seventh grade ; the booster intervention was implemented during the eighth grade . Results indicate that this type of prevention strategy , when implemented by peer leaders in the seventh grade and when additional booster sessions are provided during the eighth grade , can reduce tobacco , alcohol , and marijuana use . Similar effects are evident for females when the prevention program is implemented with fidelity by classroom teachers . Moreover , the prevention program is also capable of producing a significant impact on several hypothesized mediating variables This article examines the impact of the school-based smoking-prevention program " BE smokeFREE " on adolescent smoking . A national representative sample of 99 schools ( 195 classes , 4,441 students ) was used when the intervention started in November 1994 . Schools were allocated to one of four groups : a comparison group ( A ) and three intervention groups ( B , C , and D ) . Group B received the most comprehensive intervention . A baseline ( autumn 1994 ) and three follow-up data collection s ( 1995 , 1996 , and 1997 ) were conducted . There were no significant differences in smoking habits among the four groups at baseline . The smoking habits in the group that was involved in the most comprehensive intervention ( group B ) changed more favourably than those of students in the comparison schools over the three follow-up data collection s. At the third follow-up , the proportion of students smoking weekly or more in the comparison group was 29.2 % , compared with 19.6 % in the model intervention group . The two less comprehensive interventions ( no teacher in-service courses in group C , and no involvement of parents in group D ) appeared to be less effective than the model intervention . Multilevel multiple logistic regression analyses , comparing changes in smoking habits between students in group B with those among students in the comparison schools , confirm the conclusion that the comprehensive intervention was the most effective . This school-based intervention , based on a social influence approach , proved to be effective at reducing smoking rates among participants This article discusses the findings of Focus Group Discussion s ( FGDs ) that were conducted as a formative assessment for Project MYTRI ( Mobilizing Youth for Tobacco Related Initiatives in India ) , a r and omized , multicomponent , school-based trial to prevent and control tobacco use among youth in India . Forty-eight FGDs were conducted with students ( N = 435 ) in sixth and eighth grade s in six schools in Delhi , India . Key findings include : ( a ) students in government schools reported as “ consumers ” of tobacco , whereas students in private schools reported as “ commentators ” ; ( b ) parents and peers have a strong influence on youth tobacco use ; ( c ) chewing gutkha is considered less harmful and more accessible than smoking cigarettes ; ( d ) schools are not promoting tobacco control activities ; and ( e ) students were enthusiastic about the role government should play in tobacco control . These findings are being used to develop a comprehensive intervention program to prevent and control tobacco use among Indian youth OBJECTIVES This study investigated the secondary prevention effects of a substance abuse primary prevention program . METHODS Logistic regression analyses were conducted on 4 waves of follow-up data from sixth- and seventh- grade baseline users of cigarettes , alcohol , and marijuana taking part in a school-based program in Indianapolis . RESULTS The program demonstrated significant reductions in cigarette use at the initial follow-up ( 6 months ) and alcohol use at the first 2 follow-ups ( up to 1.5 years ) . Models considering repeated measures also showed effects on all 3 substances . CONCLUSIONS Primary prevention programs are able to reach and influence high-risk adolescents in a nonstigmatizing manner As no similar study has been conducted in Italy , the Local Health District ( USL ) of Rozzano ( Milano ) , decided to carry on a r and omized controlled trial on the efficacy of a Smoking Prevention Program . In this article we describe study protocol and give data related to program steps already carried out . A team of four MDs involved in school health and a Health Research consultant were in charge for the study . 1013 students from the second class of the secondary school ( 12y age ) were stratified into four subgroups , according to their risk of becoming a smoker and their teachers smoking status . They were subsequently r and omized ( with blocking ) to two groups : the smoking prevention ( which was based on the Waterloo Smoking Program ) and the cardiovascular risk prevention ( based on an ad hoc program by the USL ) which was the control group . Both interventions consisted in six weekly lessons which were delivered in 37 classrooms ( 777 students or 61 % of all the eligible student population , 72 % of r and omized students ) by an equal number of teacher who voluntarily joined the program , during school hours . A larger number of teachers ( 53 ) formerly joined the program but not all accomplished it . Problems with program planning and delivering are described , together with the criteria which guided this approach In a r and omized controlled trial , we evaluated the effect on tobacco use onset among middle school students of Family Communications ( FC ) activities design ed to mobilize parental influences against tobacco use and Youth Anti-tobacco Activities ( YAT ) design ed to market anti-tobacco norms to adolescents . We conducted a simple , two-condition experimental design in which 40 middle schools , with a prevalence of tobacco use at or above the Oregon median , received , by r and om assignment , either the intervention or no intervention . State , county , and local prevention coordinators around Oregon served as liaisons to schools . To generate interest , staff made presentations to these groups and distributed marketing packets at several conferences . Dependent variables were indices of smoking prevalence and use of smokeless tobacco ( ST ) in the prior month . Additionally , we created an intervention manual so that other communities could replicate this study . The findings suggest that efforts to influence parents to discourage their children ’s tobacco use and efforts to market an anti-tobacco perspective to teens are effective in preventing smoking . The impact of YAT is consistent with experimental and nonexperimental evaluations of media campaigns to influence young people not to smoke OBJECTIVE : We describe the design and baseline data of the Prevention Education Program ( PEP ) , a home-based and family oriented intervention program , aim ed to assess and improve cardiovascular risk factors in school children and their families during an intervention period of 10 y. DESIGN AND METHODS : At study entry all participants were r and omized either to an intervention group ( screening and intervention program ) or to a control group ( risk screening , general advice ) . Cardiovascular risk factors ( hypertension , elevated lipids , smoking , obesity ) as well as dietary behaviour are evaluated yearly using structured interview , physical examination , laboratory analysis , and seven-day dietary protocol . RESULTS : During the years 1993–1998 , 3547 adults ( age 36.2±7 y ) and 3495 children ( age 6.5±2 y ) were recruited . Adults show a high prevalence of risk factors : hypertension 21 % ; active smoking 39 % , elevated LDL-cholesterol 19 % ; and obesity 42 % . Children exhibit these risk factors in comparable frequency : hypertension 20 % ; passive smoking 44 % ; elevated LDL-cholesterol 17 % ; and obesity 19 % . The analysis of the dietary protocol s ( 1926 adults , 1569 children ) shows that both generations adhere to a diet exceeding the recommended fat intake ( adults 38 % of total energy , children 38 % ) , while carbohydrate intake ( adults 43 % of total energy intake , children 50 % ) is reduced compared to NCEP-(step I)- guidelines . CONCLUSION : The finding , that children show a prevalence of risk factors which is comparable to that found in adults , supports the need for an early beginning of intervention . Since both generations adhere to an unhealthy diet which contributes to cardiovascular risk , dietary intervention may be a promising method in primary prevention of cardiovascular risk This article represents a replication and extension of previous studies of the effects of Project ALERT , a school-based substance use prevention program , on the prodrug beliefs of adolescents . Specifically , the authors ’ research examined Project ALERT ’s effects on adolescents ’ intentions to use substances in the future , beliefs about substance use consequences , normative beliefs , and resistance self-efficacy . In all , 34 schools with Grade s 6 to 8 completed this r and omized controlled trial and 71 Project ALERT instructors taught 11 core lessons to 6th grade rs and 3 booster lessons to 7th grade rs ( one grade level earlier than in previous studies ) . Students were assessed in 6th grade prior to the onset of the intervention , in 7th grade after the completion of the 2-year curriculum , and again 1 year later in 8th grade . The authors found no evidence to suggest that Project ALERT had a positive impact on any alcohol , cigarette , or marijuana prodrug beliefs . Implication s for school-based substance use prevention are discussed This case study has two aims . First , it describes intervention strategies from two school-based programs design ed to prevent tobacco use among adolescents in India . Second , it explains how evidence from r and omized controlled trials of these intervention programs was used by a local non-governmental organization in Delhi to advocate for scaling up the Government of India ’s tobacco control efforts to include school health interventions as one of the components of India ’s National Tobacco Control Program . This case study illustrates the need for developing countries to conduct rigorous evaluation in order to provide context -relevant evidence prior to scaling up interventions AIMS This study sought to more precisely delineate the mechanisms by which two early elementary school-based , universal ( i.e. , applied to the entire population regardless of risk status ) preventive interventions increased survival to first tobacco cigarette smoked . Specifically , we examined whether the interventions ' effect on survival to first use was via the reduction of offers to smoke and /or through preventing the transition from first offer to smoking . METHODS A total of 678 urban first- grade rs were assigned r and omly to the classroom-centered ( CC ) , or the family-school partnership ( FSP ) , or a control classroom condition . Youth were followed annually until 1 year beyond their anticipated high school graduation ( mean age ∼18 years ) . Discrete-time survival analyses on 628 youth evaluated the impact of the CC and FSP interventions on first tobacco offer and initial tobacco smoking once offered . FINDINGS The risk of being offered tobacco was reduced among both CC and FSP intervention groups relative to the control group , although the reduction was only statistically significant for the CC intervention . Neither intervention condition reduced the transition to smoking once offered tobacco to smoke . CONCLUSION The CC intervention appeared to have its effect on survival to first cigarette smoked by delaying the first offer to smoke . Preventive interventions focused on refusal skills during the middle school years may be necessary to reduce the likelihood of the transition to smoking once offered One of the important research issues in the emerging area of research on dissemination of prevention programs relates to the type and extent of training needed by program providers to prepare them to implement effective programs with fidelity . The present paper describes the immediate outcomes of a dissemination and implementation trial of Project Toward No Drug Abuse , an evidence -based prevention program for high school students . A total of 65 high schools in 14 school districts across the USA were recruited and r and omly assigned to one of three experimental conditions : comprehensive implementation support for teachers , regular workshop training only , or st and ard care control . The comprehensive intervention was comprised of on-site coaching , web-based support , and technical assistance , in addition to the regular workshop . Students ( n = 2,983 ) completed self-report surveys before and immediately after program implementation . Fidelity of implementation was assessed with a classroom observation procedure that focused on program process . Results indicated that relative to the controls , both intervention conditions produced effects on hypothesized program mediators , including greater gains in program-related knowledge ; greater reductions in cigarette , marijuana and hard drug use intentions ; and more positive changes in drug-related beliefs . There were stronger effects on implementation fidelity in the comprehensive , relative to the regular , training condition . However , seven of the ten immediate student outcome measures showed no significant differences between the two training conditions . The implication s of these findings for dissemination research and practice are discussed BACKGROUND This article reports the results of a 5-year , longitudinal evaluation of the effectiveness of Drug Abuse Resistance Education ( DARE ) , a school-based primary drug prevention curriculum design ed for introduction during the last year of elementary education . DARE is the most widely disseminated school-based prevention curriculum in the United States . METHOD Twenty-three elementary schools were r and omly assigned to receive DARE and 8 were design ated comparison schools . Students in the DARE schools received 16 weeks of protocol -driven instruction and students in the comparison schools received a drug education unit as part of the health curriculum . All students were pretested during the 6th grade prior to delivery of the programs , posttested shortly after completion , and resurveyed each subsequent year through the 10th grade . Three-stage mixed effects regression models were used to analyze these data . RESULTS No significant differences were observed between intervention and comparison schools with respect to cigarette , alcohol , or marijuana use during the 7th grade , approximately 1 year after completion of the program , or over the full 5-year measurement interval . Significant intervention effects in the hypothesized direction were observed during the 7th grade for measures of students ' general and specific attitudes toward drugs , the capability to resist peer pressure , and estimated level of drug use by peers . Over the full measurement interval , however , average trajectories of change for these outcomes were similar in the intervention and comparison conditions . CONCLUSIONS The findings of this 5-year prospect i ve study are largely consonant with the results obtained from prior short-term evaluations of the DARE curriculum , which have reported limited effects of the program upon drug use , greater efficacy with respect to attitudes , social skills , and knowledge , but a general tendency for curriculum effects to decay over time . The results of this study underscore the need for more robust prevention programming targeted specifically at risk factors , the inclusion of booster sessions to sustain positive effects , and greater attention to interrelationships between developmental processes in adolescent substance use , individual level characteristics , and social context Seven thous and one hundred twenty-four members of the Classes of 1985 and 1986 who had participated as seventh grade rs in one of several smoking prevention programs were tracked and surveyed for smoking habits at 5- and 6-year follow-up : participation exceeded 90 % in both cohorts . These data indicated that participants who received seventh- grade interventions based on the social influences model had similar smoking patterns compared to participants in other conditions . This finding supports the call for booster sessions after the initial seventh- grade intervention program . Future follow-up studies will assess whether the earlier benefits associated with the social influences model will translate into measurable differences in adult smoking patterns OBJECTIVE This study tested a CD-ROM intervention with and without a parent involvement component to reduce risk of alcohol use among an urban sample of early adolescents . METHOD Youths ( N = 514 , mean age 11.5 years at recruitment ) were assigned r and omly by community site to receive the CD-ROM intervention , the CD-ROM plus parent intervention , or no intervention . All youths completed pretest , posttest and three annual follow-up measurements . After pretesting , youths and parents received their respective interventions . RESULTS Main effects of the intervention and for measurement occasion as well as interaction effects of the intervention by measurement occasion were seen for substance use and related outcomes . Over time , youths in all 3 groups reported increased use of alcohol , tobacco and marijuana ; youths who received the interventions reported smaller increases than control youths . At 3-year follow-up , alcohol use was lower for CD-ROM plus parent intervention youths than for CD-ROM only youths , who , in turn , reported less use than controls . Cigarette use was lower for youths in either intervention group than in the control group at posttest and at 1- , 2- and 3-year follow-ups . Marijuana use was lower for youths in either intervention than for controls at 1- , 2- and 3-year follow-ups . Youths in both intervention groups outperformed control youths at posttest and at 1- and 3-year follow-ups on levels of negative and peer influence toward substance use . Finally , at the 3-year follow-up , youths in the CD-ROM plus parent intervention group reported more family involvement in their alcohol use prevention efforts than did youths in the CD-ROM group , who , in turn , reported more positive levels of family involvement than youths in the control group . CONCLUSIONS Study findings modestly support the CD-ROM intervention with and without the parent intervention to reduce alcohol use risks among urban early adolescents OBJECTIVE To evaluate the long-term efficacy of a school-based approach to drug abuse prevention . DESIGN R and omized trial involving 56 public schools that received the prevention program with annual provider training workshops and ongoing consultation , the prevention program with videotaped training and no consultation , or " treatment as usual " ( ie , controls ) . Follow-up data were collected 6 years after baseline using school , telephone , and mailed surveys . PARTICIPANTS A total of 3597 predominantly white , 12th- grade students who represented 60.41 % of the initial seventh- grade sample . INTERVENTION Consisted of 15 classes in seventh grade , 10 booster sessions in eighth grade , and five booster sessions in ninth grade , and taught general " life skills " and skills for resisting social influences to use drugs . MEASURES Six tobacco , alcohol , and marijuana use self-report scales were recorded to create nine dichotomous drug use outcome variables and eight polydrug use variables . RESULTS Significant reductions in both drug and polydrug use were found for the two groups that received the prevention program relative to controls . The strongest effects were produced for individuals who received a reasonably complete version of the intervention -- there were up to 44 % fewer drug users and 66 % fewer polydrug ( tobacco , alcohol , and marijuana ) users . CONCLUSIONS Drug abuse prevention programs conducted during junior high school can produce meaningful and durable reductions in tobacco , alcohol , and marijuana use if they ( 1 ) teach a combination of social resistance skills and general life skills , ( 2 ) are properly implemented , and ( 3 ) include at least 2 years of booster sessions This study compared two strategies for preventing cigarette smoking among high-school students . One strategy emphasized social-pressure resistance skills , while the other focused on education about health concerns which are relevant to high-school students . Additionally , the use of same-age peer leaders and the use of familiar models in media presentations were investigated . The results suggest that social-influences resistance training was efficacious in reducing transitions to higher use by those who had previously experimented with cigarettes . Health education was most effective in preventing initial experimentation among those who had not smoked prior to the beginning of the study . Neither program was effective in limiting transitions among those who had gone beyond the experimental stage of smoking , and neither had any effect on encouraging cessation . There were no differences which could be attributed to peer leaders or to familiar media models . During later adolescence , a combined health education and social skills training approach is advocated . It is suggested that while there are some gains by implementing programs during late adolescence , prevention programs targeted at younger students may be more effective generally BACKGROUND This article reports follow-up results during grade 9 for a multisite drug prevention program that curbed both marijuana and cigarette use during junior high . Based on the social influence model of prevention , the curriculum sought to motivate young people against drug use and to teach them skills for resisting pro-drug pressures . METHODS Thirty schools drawn from eight urban , rural , and suburban communities in California and Oregon were r and omly assigned to three experimental conditions , two treatment groups and one control . Students in 20 schools received 11 lessons , 8 during grade 7 and 3 in grade 8 ; in 10 of the treatment schools , older teens assisted an adult teacher in program delivery . Students were pretested prior to the program ( grade 7 ) and post-tested 24 months later ( grade 9 ) . RESULTS Earlier effects on cognitive risk factors ( perceived consequences of drug use , normative beliefs , resistance self-efficacy , and expectations of future use ) persisted through grade 9 in the teen leader schools ; in the condition under which adults taught the lessons without teens , the prior beneficial effects on beliefs largely eroded . All of the earlier effects on actual use disappeared by grade 9 , regardless of who taught the lesions . CONCLUSION Continued reinforcement of earlier lessons may be required to sustain prevention gains through the transition to high school A quasi-experimental , longitudinal study was conducted to test the effectiveness over a 1-year period of a cardiovascular risk reduction program for school-age children . The effectiveness of the program was measured with the children 's knowledge of physiology of the heart and cardiovascular risk factors , their health habits , and their physical measurements . Ninety-eight children between the ages of 9 and 12 years participated in the study . The experimental group received a series of five 40-minute sessions on physiology of the heart , smoking , hypertension , diet , and physical activity . Short-term effectiveness of the program was found for the children 's knowledge of physiology of the heart and smoking . Long-term effectiveness was found for running activity Prior investigations have linked behavioral competencies in primary school to a reduced risk of later drug involvement . In this r and omized prevention trial , we sought to quantify the potential early impact of two developmentally inspired universal preventive interventions on the risk of early-onset alcohol , inhalant , tobacco , and illegal drug use through early adolescence . Participants were recruited as they entered first grade within nine schools of an urban public school system . Approximately , 80 % of the sample was followed from first to eighth grade s. Two theory-based preventive interventions , ( 1 ) a family-school partnership ( FSP ) intervention and ( 2 ) a classroom-centered ( CC ) intervention , were developed to improve early risk behaviors in primary school . Generalized estimating equations ( GEE ) multivariate response profile regressions were used to estimate the relative profiles of drug involvement for intervention youths versus controls , i.e. youth in the st and ard educational setting . Relative to control youths , intervention youths were less likely to use tobacco , with modestly stronger evidence of protection associated with the CC intervention ( RR=0.5 ; P=0.008 ) as compared to protection associated with the FSP intervention ( RR=0.6 ; P=0.042 ) . Intervention status was not associated with risk of starting alcohol , inhalants , or marijuana use , but assignment to the CC intervention was associated with reduced risk of starting to use other illegal drugs by early adolescence , i.e. heroin , crack , and cocaine powder ( RR=0.32 , P=0.042 ) . This study adds new evidence on intervention-associated reduced risk of starting illegal drug use . In the context of ' gateway ' models , the null evidence on marijuana is intriguing and merits attention in future investigations Few studies have examined the long-term efficacy of computer-based smoking prevention and cessation programs . We analyzed the long-term impact of A Smoking Prevention Interactive Experience ( ASPIRE ) , a theoretically sound computer-based smoking prevention and cessation curriculum for high school students . Sixteen predominantly minority , inner-city high schools were r and omly assigned to receive the ASPIRE curriculum or st and ard care ( receipt of the National Cancer Institute 's Clearing the Air self-help booklet ) . A total of 1160 students , 1098 of whom were nonsmokers and 62 smokers at baseline , were included . At 18-month follow-up , among baseline nonsmokers , smoking initiation rates were significantly lower in the ASPIRE condition ( 1.9 % vs. 5.8 % , p < .05 ) . Students receiving ASPIRE also demonstrated significantly higher decisional balance against smoking and decreased temptations to smoke . Differences between groups in self-efficacy and resistance skills were not significant . There was a nonsignificant trend toward improved smoking cessation with ASPIRE , but low recruitment of smokers precluded conclusions with respect to cessation . ASPIRE demonstrated the potential for an interactive multimedia program to promote smoking prevention . Further studies are required to determine ASPIRE 's effects on cessation Objective : To investigate why urban Indian 6th grade rs may be using more tobacco than urban Indian 8th grade rs . Design : Cross-sectional survey of students conducted in the summer of 2004 , as the baseline evaluation tool for a group-r and omised tobacco prevention intervention trial ( Project MYTRI ) . Mixed-effects regression models were used to ( 1 ) examine the relationship between 15 psychosocial risk factors and current use of any tobacco , by grade ; and ( 2 ) examine differences in psychosocial risk factors , by grade . Setting : Thirty-two private ( high socioeconomic status ( SES ) ) and government ( low-mid SES ) schools in two large cities in India ( Delhi and Chennai ) . Subjects : Students in the 6th and 8th grade in these schools ( n = 11642 ) . Among these , 50.6 % resided in Delhi ( v Chennai ) , 61.4 % attended a government school ( v a private school ) , 52.9 % were enrolled in 6th grade ( v 8th ) , and 54.9 % were male ( v female ) . Main outcome measure : Current ( past 30 day ) use of any tobacco , including chewing tobacco ( for example , gutkha ) , bidis , or cigarettes . Result : Almost all psychosocial factors were significantly related to tobacco use , for students in both grade s. Some of the strongest correlates included social susceptibility to and social norms about use . Exposure to tobacco advertising was a strong correlate of tobacco use for 6th grade rs , but not for 8th grade rs . Sixth grade rs scored lower than 8th grade rs on almost all factors , indicating higher risk . Conclusions : The “ risk profile ” of 6th grade rs suggests they would be vulnerable to use and to begin using tobacco , as well as to outside influences that may encourage use OBJECTIVES Underst and ing the developmental pathways and sex differences in cigarette smoking behaviors in adolescents has the potential to positively impact substance abuse prevention and to reduce smoking-related health problems . Using data from the Unplugged school-based prevention trial , we investigated different patterns of smoking behavior development among secondary school students in the Czech Republic . METHODS Growth mixture modeling was used to examine different trajectories in cigarette smoking behaviors among male and female students ( N=1874 6th grade rs ; 50.4 % male , mean age 11.8 years at baseline ) participating in the Unplugged school-based r and omized control trial for substance use prevention . RESULTS A two-class model characterized cigarette use as a function of sex and Unplugged intervention status . More rapid cigarette use increases were observed in females ( OR=1.17 , p=0.01 in both rapid/moderate and slow smoking escalator classes ) as compared to males . Further , in both classes , more rapid increases in smoking were observed for the control group as compared to the intervention group ( OR=1.22 , p<0.01 slow escalators ; OR=1.54 , p=0.08 rapid/moderate escalators ) . There was no difference in sex distribution when comparing the two classes ( OR=1.02 , p=0.98 ) . CONCLUSIONS This study adds to a growing literature on developmental and sex differences in cigarette use among adolescents . This research supports additional multi-year prevention strategies aim ed at adolescent females and early treatment programs for adolescent smokers to prevent increasing cigarette use with age This paper presents a cost-benefit analysis of the Communities That Care ( CTC ) prevention system , a public health approach to reducing risk , enhancing protection , and reducing the prevalence of adolescent health and behavior problems community wide . The analysis is based on outcomes from a panel of students followed from Grade 5 through Grade 8 in a r and omized controlled trial involving 24 communities in 7 states . Previous analyses have shown that CTC prevented the initiation of cigarette smoking , alcohol use , and delinquency by the end of 8th grade in CTC communities compared to controls . This paper estimates long-term monetary benefits associated with significant intervention effects on cigarette smoking and delinquency as compared to the cost of conducting the intervention . Under conservative cost assumptions , the net present benefit is $ 5,250 per youth , including $ 812 from the prevention of cigarette smoking and $ 4,438 from the prevention of delinquency . The benefit-cost ratio indicates a return of $ 5.30 per $ 1.00 invested . Under less conservative but still viable cost assumptions , the benefit-cost ratio due to prevention of cigarette smoking and delinquency increases to $ 10.23 per $ 1.00 invested . Benefits from CTC ’s reduction in alcohol initiation as well as broader inclusion of quality -of-life gains would further increase CTC ’s benefit-cost ratio . Results provide evidence that CTC is a cost-beneficial preventive intervention and a good investment of public dollars , even under very conservative cost and benefit assumptions The efficacy of prevention programs is typically determined through analysis of covariance . To date , a growth curve modeling approach is not used extensively in program evaluation . However , for longitudinal data there are several advantages to using this approach as compared to methods comparing means at two time points in a piecemeal fashion . In this study , latent growth curve models were used to evaluate the effect of a program on the average level of drug use , rate of change ( growth ) of drug use , and acceleration or deceleration in the rate of change of drug use . The study relied on data from the Adolescent Alcohol Prevention Trial , a r and omized longitudinal drug use prevention program . The program consists of drug use information , resistance skills training , and normative education components . Data regarding cigarette and alcohol use were collected over a 5-year period , grade 7 to grade 11 . Students receiving the normative education program had significantly lower average levels of reported cigarette and alcohol use , lower rates of growth for reported cigarette and alcohol use , and less deceleration of reported levels of cigarette and alcohol use as compared with the control group . Growth curve analysis is a powerful and effective tool with which to model change and program efficacy This paper presents the short-term and long-term results of a r and omized smoking prevention trial . The purpose was to evaluate two smoking prevention programs , a social influence ( SI ) program and a SI program with an additional decision-making component ( SI(DM ) ) . Moreover , the contribution of boosters was assessed as well . Fifty-two schools were r and omly assigned to the SI program , the SI(DM ) program or a control group . Half of the treatment schools were r and omly assigned to the booster condition ; the other half did not receive boosters . Both programs consisted of five lessons , each lasting 45 min , and were given in weekly sessions in grade s 8 and 9 of high schools in the Netherl and s. The most successful program was the SI program with boosters which result ed in a significantly lower increase in smoking rates ( 5.6 and 9.7 % , respectively ) compared to the control group ( 12.6 and 14.9 % , respectively ) at both 12 and 18 months follow-up . The results suggest that boosters can be an effective tool for maintaining or increasing the effectiveness of smoking prevention programs . It is recommended that the SI program with the booster be implemented at the national level , since this intervention showed the greatest behavioral effects The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) was the largest school-based field trial ever sponsored by the National Institutes of Health . The trial demonstrated positive changes in the school food service and physical education program , as well as in students ' cardiovascular health behaviors . Because the CATCH intervention programs were implemented in 56 schools ( in four states ) that were typical of schools throughout the United States , their reception by schools and degree of implementation provide evidence about their feasibility for schools nationally . Extensive process evaluation data were collected from students , teachers , school food service personnel , and physical education specialists throughout the three school years of the CATCH intervention . Four of the CATCH programs — school food service , physical education , classroom curricula , and home programs — were assessed over the three school years . The process data provide information on participation , dose , fidelity , and compatibility of the CATCH programs in the intervention schools for these programs . High levels of participation , dose , fidelity , and compatibility were observed for the four programs during the 3 school years . CATCH emerges as a model of a feasible multilevel health promotion program to improve eating and exercise behaviors for elementary schools in the United States A five-year intervention study of the effectiveness of the " Know Your Body " program in reducing coronary heart disease risk factors among black students in the District of Columbia , who were in grade s 4 - 6 at baseline , was begun in 1983 . Nine schools were stratified on socioeconomic status and r and omly assigned to control and intervention groups . The " Know Your Body " curriculum focuses on nutrition , fitness , and the prevention of cigarette smoking . At baseline , 1,234 students were eligible for the screening in which the following target risk factors were measured : systolic and diastolic blood pressures , ponderosity index , triceps skinfold thickness , postexercise pulse recovery rate , serum total and high density lipoprotein ( HDL ) cholesterol , and serum thiocyanate . After two years of intervention , results indicated that the program may have had a favorable impact on the following risk factors : systolic and diastolic pressures , HDL cholesterol , ratio of total to HDL cholesterol , fitness ( postexercise pulse recovery rate ) , and smoking . Significant net changes in the favorable direction also were found for health knowledge and attitude toward smoking . Blood pressure reduction was associated with decreased ponderosity and improved fitness , and increased HDL cholesterol was associated with decreased ponderosity . These results are consistent with other evaluations of the " Know Your Body " program , suggesting that the program may be effective in reducing chronic disease risk in diverse school population A primary prevention research project is described which tests an intervention model based on cognitive and interpersonal skill enhancement . Thirty-two classrooms of sixth grade students were r and omly assigned to either Program or Control conditions , with Program classrooms receiving a twelve-session cognitive skill development curriculum aim ed at reducing rates of substance use as measured by a drug use survey . Students in Program classrooms showed greater decision-making skills , including the ability to generate alternatives and to consider consequences and risks , greater ability to utilize social networks , and greater underst and ing of group roles , behavior , and alternatives . In addition , Program students reported less use of tobacco in the past year than Control Group students , but no differences between groups were found in use of alcohol , marijuana , or other drugs except for a tendency on the part of Program students to show greater experimentation with alcohol . The effectiveness of the intervention in promoting skill development and factors influencing the impact of the intervention on substance use behavior are discussed BACKGROUND The empirical evidence of effectiveness of many school-based programs against substance abuse is rather weak . The EU-Dap study is a multicenter cluster r and omized community trial ( C RCT ) design ed to evaluate such a program . This paper presents study design and baseline characteristics of the study population . METHODS 170 schools from 9 centers from seven countries ( Austria , Belgium , Germany , Greece , Italy , Spain , Sweden ) , stratified according to average social status in the catchment area , were r and omized to either three variants of the active intervention ( basic curriculum , basic with peer involvement , and basic with parent involvement ) or to a control group . The program under evaluation is based on a comprehensive social influence approach , and was delivered during the scholar year 2004 - 2005 to a population of 12- to 14-year-old students attending junior high school . An anonymous question naire administered before and after the intervention was used to track behavioral and attitudinal changes . RESULTS All in all , we included in the study 143 schools and 7079 students , of which 3547 in the intervention groups and 3532 in the control group . At baseline , 34.9 % of students had smoked cigarettes , 24.7 % had been drunk , and 8.9 % had used cannabis at least once in life . DISCUSSION EU-Dap is the first European multicenter r and omized study to evaluate the effectiveness of a school program targeting tobacco , alcohol and drug use . The baseline assessment showed high prevalence and wide geographical variations of substance use BACKGROUND School-based drug prevention programs have been criticized on method ologic grounds because the unit of analysis is often not the unit of r and omization , thus increasing the likelihood of Type I errors . Application of multilevel analytic strategies appropriately corrects this biasing tendency . This study demonstrates the practical use of such analysis . METHODS Data from 2,370 seventh- grade students participating in a substance use prevention trial were analyzed using a multilevel strategy . We examined the effectiveness of a social pressure resistance training and a normative education ( NORM ) intervention against an information-only control group . RESULTS The NORM condition revealed 1-year program effects for cigarette and marijuana use with individuals as the unit of analysis and only marginal effects with classroom as the unit of analysis . No program effects were found using school as the analysis unit . A multilevel strategy revealed program effects for cigarettes and marijuana with both class and school as grouping levels . The effect for alcohol use was significant at the 2-year follow-up . CONCLUSIONS Interventions establishing conservative drug use norms in classrooms may be an effective strategy in reducing substance use onset among adolescents . Utilization of appropriate analytic strategies is important in the analysis and interpretation of data containing nested structures A five-year intervention study of the feasibility and effectiveness of a program aim ed at the primary prevention of chronic disease was initiated in 1980 among children in 22 elementary schools in the Bronx , New York . Schools r and omly were assigned either to the intervention program or to a control group . The intervention program consists of a curriculum focusing on nutrition , physical fitness , and cigarette smoking prevention . The study population at baseline comprised 2,283 fourth- grade rs . Subjects were eligible at baseline and at one-year follow-up for participation in a medical examination in which the following target risk factors were measured : systolic and diastolic blood pressures , plasma total and high-density lipoprotein ( HDL ) cholesterol , serum thiocyanate , ponderosity index , triceps skinfold thickness , and postexercise pulse recovery rate . After one year of intervention , systolic pressure increased less in the intervention group than among controls . Diastolic pressure decreased in both groups , but more in the intervention subjects than in controls . Total cholesterol decreased in the intervention group while increasing among controls . Significant net changes in the favorable direction also were observed for total cholesterol/HDL cholesterol ratio and for thiocyanate . These observations indicate that it is feasible to implement a school-based program aim ed at the primary prevention of chronic disease . The intervention program appears to have had a favorable effect on several target risk factors . Although the effects were relatively small , intervention programs in schools may prove to be effective in lowering chronic disease risk BACKGROUND The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) is a multistate field trial examining the effects of school environment , classroom curricula , and family intervention components in promoting the cardiovascular health of elementary school students . The purpose of this paper is to describe the CATCH tobacco use intervention and measurement , including the adoption of tobacco-free school policies . METHODS In this study , changes in school tobacco use policies and smoking experimentation among students were assessed . Smoking experimentation was measured in all CATCH schools when the students were in their fifth- grade year . A total of 6,527 subjects in 96 schools in California , Louisiana , Minnesota , and Texas answered questions about behaviors and potential correlates of smoking as part of the CATCH health behavior question naire in Spring 1994 . School tobacco use policy , an important complement to classroom- and home-based prevention efforts , was promoted as part of the CATCH intervention . The degree to which such policy was implemented was measured using surveys of school officials . RESULTS At the end of fifth grade , only 4.8 % of the subjects indicated that they had experimented with tobacco . School intervention condition was not a factor in the prediction of experimentation . Those whose best friend or sibling smoked , or who had ready access to cigarettes in the home , were more likely to have experimented with smoking . In the 3 years of the study , the percentages of tobacco-free schools went up from 49.7 to 76.8 % . Though differences in the rate of policy adoption could not be directly attributed to the CATCH intervention , the implementation of the tobacco-free schools ' policies did vary substantially from state to state . Minnesota and Texas , with stronger state laws supporting local policy , had nearly completely smoke-free schools . In spite of a statewide tobacco control initiative , California was slower to implement school policies . Louisiana , which allows local decision making regarding smoking policy , had the most difficulty establishing a policy for all districts . CONCLUSION Future studies should examine the impact of parallel policy interventions that are ongoing at both school and state levels . Tobacco-free policies appear to be a crucial part of school-based interventions and must be tailored to political and regional factors affecting a given school district BACKGROUND Tobacco use is a significant public health problem in China . Culturally specific smoking prevention programs are needed for Chinese adolescents . This study evaluated a school-based smoking prevention curriculum with a social normative approach developed in the United States for adolescents in urban Wuhan , China . METHODS As a r and omized trial , the intervention was implemented in 1998 with 7th grade students in seven schools with seven matched control schools . Multilevel logistic regression models were used to compare ever and recent ( past-month ) smoking behaviors for the control and program conditions . RESULTS At the 1-year follow-up , smoking had increased more rapidly in the control schools than in the program schools . The odds of baseline nonsmokers initiating smoking did not differ between the program and control groups ( OR=1.08 with 95 % CI=0.71 , 1.64 ) . The program prevented progression to recent smoking among boys who were baseline ever smokers . Among boys who were recent smokers at baseline , the prevention program significantly reduced risk of remaining recent smokers at follow-up ( OR=0.45 with 95 % CI=0.23 , 0.88 ) . CONCLUSIONS This social normative smoking prevention curriculum did not demonstrate a significant primary prevention effect but showed potential for secondary prevention . Culturally specific smoking prevention programs are needed for Chinese adolescents OBJECTIVE To evaluate the effectiveness of the school-based drug abuse prevention program developed in the EU-Dap study ( EUropean Drug Abuse Prevention trial ) in preventing the use of tobacco , alcohol and drugs at the post-test . METHODS Cluster R and omised Controlled Trial . Seven European countries participated in the study ; 170 schools ( 7079 pupils 12 - 14 years of age ) were r and omly assigned to one of three experimental conditions or to a control condition during the school year 2004/2005 . A pre-test survey assessing past and current substance use was conducted before the implementation of the program . The program consisted in 12-hour class-based curriculum based on a comprehensive social-influence approach . A post-test survey was carried out in all participating schools , 3 months after the end of the program . The association between program condition and change in substance use at post-test was expressed as adjusted Prevalence Odds Ratio ( POR ) , estimated by multilevel regression model . RESULTS Program effects were found for daily cigarette smoking ( POR=0.70 ; 0.52 - 0.94 ) and episodes of drunkenness in the past 30 days ( POR=0.72 ; 0.58 - 0.90 for at least one episode , POR=0.69 ; 0.48 - 0.99 for three or more episodes ) , while effects on Cannabis use in the past 30 days were of marginal statistical significance ( POR=0.77 ; 0.60 - 1.00 ) . The curriculum was successful in preventing baseline non-smokers or sporadic smokers from moving onto daily smoking , but it was not effective in helping baseline daily smokers to reduce or stop smoking . CONCLUSION School curricula based on a comprehensive social-influence model may delay progression to daily smoking and episodes of drunkenness BACKGROUND The effectiveness of school-based tobacco use prevention programs depends on proper implementation . This study examined factors associated with teachers ' implementation of a smoking prevention curriculum in a cluster r and omized trial called Project SPLASH ( Smoking Prevention Launch Among Students in Hawaii ) . METHODS A process evaluation was conducted and a cross-condition comparison used to examine whether teacher characteristics , teacher training , external facilitators and barriers , teacher attitudes , and curriculum attributes were associated with the dose of teacher implementation in the intervention and control arms of the study . Data were collected from a total of 62 middle school teachers in 20 public schools in Hawaii , during the 2000 - 2001 and 2001 - 2002 school years . Sources included teacher question naires and interviews . Chi-square test and t test revealed that implementation dose was related to teachers ' disciplinary background s and skills and student enjoyment of the curriculum . RESULTS Content analysis , within case , and cross-case analyses of qualitative data revealed that implementing the curriculum in a year long class schedule and high teacher self-efficacy supported implementation , while high perceived curriculum complexity was associated with less complete implementation . CONCLUSIONS The results have implication s for research , school health promotion practice , and the implementation of evidence -based youth tobacco use prevention curricula Smoking-prevention programs , run by both teachers , and teachers and peers , have been introduced into school curricula in many parts of the world . This paper describes a long-term follow-up of a r and omised controlled trial of a smoking education program for children conducted in Western Australia . Seven years after the first survey of 2,366 Year 7 students in 1981 , 68 per cent of initial participants were traced through public records ; 53 per cent of these responded to a new survey concerning smoking . Previous follow-up after one and two years had shown that both teacher-led and peer-led programs continued to reduce the taking up of smoking by girls to about the same degree , whereas in boys , the teacher-led program appeared to be effective after one year but neither program was effective after two years . In nonsmoking girls , both the intervention programs maintained their effects at the seven-year follow-up , with an almost 50 per cent reduction in smoking prevalence in the intervention group . Nonsmoking girls appeared to respond to cigarette advertisements . Mothers seemed to influence nonsmokers of both sexes and brothers seemed to influence smokers of both sexes . The seven-year follow-up confirmed the results seen at two years for boys , that the effects of the education program had dissipated . However , this study suggests that the smoking-prevention program had a lasting effect on preventing girls from taking up smoking This paper reports six-year follow-up data from the first large-scale r and omized trial of the social influences approach to smoking prevention . In 1979 , 22 schools were r and omly assigned to program or control conditions . Students in program schools received a social influences curriculum in six core and two maintenance sessions in grade 6 , two booster sessions in grade 7 , and one booster session in grade 8 . All students were assessed at pretest ( T1 ) , immediate posttest ( T2 ) , end of grade 6 ( T3 ) , beginning and end of grade 7 ( T4 and T5 ) , end of grade 8 ( T6 ) , and grade s 11 and 12 ( T7 and T8 ) . Ninety percent of study students were relocated and data obtained from over 80 percent of them at T8 . Program effects on experimental smoking observed in grade s 7 and 8 had completely decayed by T8 , six years after the beginning of the program . Grade 6 smoking experience and social risk were each strong predictors of T8 smoking behavior . Subjects who had left school were smoking at more than twice the rate of subjects still in high school ( grade 12 ) at T8 . We discuss implication s of the results Because preschoolers and first grade rs show signs of readiness to try smoking and because they are already learning about smoking through their environment , smoking prevention at the preschool level is appropriate . The large numbers of children seen in primary care practice s and day care facilities are indicative of the numbers that could be exposed to smoking prevention instruction through these setting s. This study assessed the future expectations of children to protect themselves from sidestream smoke after participating in a preschool smoking prevention program offered in four primary care setting s. Through this program , children and their parents read stories and complete activities concerning the human body and the health risks of smoking . Using a r and omized posttest-only case control design , the authors found that children who were exposed to the curriculum were more than twice as likely as others to report the intention to act to protect themselves from adult sidestream smoke A six-year intervention study of the feasibility and effectiveness of a program aim ed at the primary prevention of coronary heart disease ( CHD ) has been initiated among children in six school districts in Westchester County , New York . Schools r and omly were assigned either to the intervention program or to a control group . The intervention program consists of a curriculum focusing on nutrition , physical fitness , and cigarette smoking prevention . The study population at baseline comprised 1,822 fourth- grade rs . This paper presents the findings at baseline and at one-year follow-up for the following target risk factors : systolic and diastolic blood pressure , plasma total and high-density lipoprotein ( HDL ) cholesterol , serum thiocyanate , ponderosity index , triceps skinfold thickness , and postexercise pulse recovery rate . After one year of intervention , the program was found to be acceptable to school administrators , teachers , parents , and children . Small net changes in the favorable direction were observed for diastolic blood pressure and thiocyanate . Intervention programs in schools may , after sufficient duration , prove to be effective in lowering CHD risk School health educators have devoted much attention to cigarette smoking . Recent years have seen the testing of interventions to prevent smoking . To date , controlled studies have not evaluated the added value of skills methods for preventing smoking . This article describes such an evaluation with sixth- grade students from two schools . Subjects were pretested and r and omly assigned to receive conventional health education methods or to receive skills intervention . Both conditions included films , peer testimonials , discussion s , and homework . Health education condition subjects additionally participated in oral quizzes , games , and debates . Skills condition subjects additionally learned problem-solving , self-instruction , and interpersonal communication methods . At postintervention , skills condition subjects , more than health education condition subjects , had better scores on measures of smoking-related knowledge , attitudes , and intentions . In addition , reported cigarette use , vali date d by biochemical data collection , was lower in the skills condition than in the health education condition at all postintervention measurements , including a 24-month follow-up . The article discusses the strengths , limits , and implication s of the study for other smoking prevention efforts in schools Smoking prevention programs based on social influences have reduced smoking prevalence among youth . However , these effects have not been replicated consistently . It is possible that individuals and population s with different dispositional and behavioral characteristics will experience different program effects . This study explored a possible moderation of program effect by comorbidity between depression and smoking ( CoM ) . Data for this analysis were from 2,450 seventh- grade youth ( 51 % boys ) who participated in the Wuhan ( China ) Smoking Prevention Trial ( WSPT ) . WSPT was a r and omized , controlled , 14-session , middle-school-based smoking prevention trial . Baseline and 1-year follow-up surveys were administered . The moderation effect between the program and CoM was tested on 1-year change in recent smoking . The CoM indicator was defined dichotomously as monthly cigarette use and high in depression level ( among the top 20 % in the sample ) . At baseline , a total of 26 girls and 60 boys were identified to have CoM. Among boys ( but not girls ) , CoM significantly moderated the program effect on recent smoking ( p = .01 ) . The program effect among boys with CoM was 4.17 ( 95 % CI 1.47 - 11.76 ) times larger than those without CoM. Among boys with CoM , the odds ratio of recent smoking was 0.18 ( 95 % CI 0.06 - 0.55 ) for program vs. control condition . Among those without CoM , the program did not reduce the odds of recent smoking significantly ( OR = 0.74 , 95 % CI 0.37 - 1.48 ) . The study demonstrated that smoking prevention program effects can vary with individual characteristics , in this case comorbidity between depression and smoking . These findings may help explain the inconsistency in program effects across studies and population s. The findings also may contribute to the design of future programs to address the needs of defined population s and individuals with specific characteristics This r and omized controlled trial evaluated the effectiveness of a multicomponent Health Promoting Schools ( HPS ) intervention program in improving self-reported smoking outcomes among a cohort of adolescents in 22 public secondary schools in the Hunter Region of New South Wales , Australia . Pre-test surveys were completed by students in the first 2 years of secondary school , with a 2-year post-test survey . Multivariate analyses examined intervention effect for the main outcome , post-test smoking behavior , controlling for pre-test smoking status , school and other confounders . The sample comprised the cohort of 1852 students who completed both surveys . The results demonstrated that the HPS program failed to improve smoking behavior over the 2 years ( equal increase of 10 % in both groups ) . The program was successful in improving smoking knowledge , but not attitudes , in intervention versus control group ( P < 0.001 ) . Independent predictors of post-test smoking included : pre-test smoking [ odds ratio ( OR ) = 5.44 ; 95 % confidence interval ( CI ) = 3.20 - 9.28 ] , being female ( OR = 0.55 ; CI = 0.35 - 0.87 ) , having more close friends who smoked ( OR = 1.42 ; CI = 1.33 - 1.52 ) , peer group having no clear opinion about smoking ( OR = 3.23 ; CI = 1.27 - 8.27 ) , having more positive and less negative attitudes towards smoking , and being less involved in school activities . We discuss method ological issues in multicomponent community-based interventions , and highlight the strengths and limitations of this study A smoking prevention project in six European countries ( European Smoking prevention Framework Approach ) was developed , featuring activities for adolescents , schools and parents , including out-of-school activities . Consensus meetings result ed in agreement between the countries on goals , objectives and theoretical methods . Countries ' specific objectives were also included . National diversities required country-specific methods to realize the goals and objectives . The community intervention trial was used as the research design . Since interventions took place at the community level , communities or regions were allocated at r and om to the experimental or control conditions . Complete r and omization was achieved in four countries . At baseline , smoking prevalence among 23 125 adolescents at the start of the project was 5.6 % for regular smoking and 4.0 % for daily smoking . Smoking prevalence rates were higher among girls than boys in all countries as far as weekly smoking was concerned . Process evaluations revealed that the project 's ambitions were high , but were limited by various constraints including time and delays in receiving funds . Future smoking prevention projects should aim to identify the effective components within the social influence approach as well as within broader approaches and on reaching sustained effects This study developed and tested skills- and community-based approaches to prevent substance abuse among Native American youth . After completing pretest measurements , 1,396 third- through fifth- grade Native American students from 27 elementary schools in five states were divided r and omly by school into two intervention arms and one control arm . Following intervention delivery , youths in all arms completed posttest measurements and three annual follow-up measurements . Youths in schools assigned to the intervention arms learned cognitive and behavioral skills for substance abuse prevention . One intervention arm additionally engaged local community residents in efforts to prevent substance use among Native American youth . Outcome assessment batteries measured youths ' reported use of smoked and smokeless tobacco , alcohol , and marijuana . Over the course of the 3.5-year study , increased rates of tobacco , alcohol , and marijuana use were reported by youths across the three arms of the study . Though cigarette use was unaffected by intervention , follow up rates of smokeless tobacco , alcohol , and marijuana use were lower for youths who received skills intervention than for youths in the control arm . Community intervention components appeared to exert no added beneficial influence on youths ' substance use , beyond the impact of skills intervention components alone . Finally , gender differences were apparent across substances , measurements , and study arms , with girls smoking more cigarettes and boys using more smokeless tobacco , alcohol , and marijuana OBJECTIVE To test whether the Communities That Care ( CTC ) prevention system reduces adolescent alcohol , tobacco , and other drug use and delinquent behavior communitywide . DESIGN The Community Youth Development Study is the first r and omized trial of CTC . SETTING In 2003 , 24 small towns in 7 states , matched within state , were r and omly assigned to control or CTC conditions . PARTICIPANTS A panel of 4407 fifth- grade students was surveyed annually through eighth grade . Intervention A coalition of community stakeholders received training and technical assistance to install the CTC prevention system . They used epidemiological data to identify elevated risk factors and depressed protective factors in the community , and chose and implemented tested programs to address their community 's specific profile from a menu of effective programs for families , schools , and youths aged 10 to 14 years . MAIN OUTCOME MEASURES Incidence and prevalence of alcohol , tobacco , and other drug use and delinquent behavior by spring of grade 8 . RESULTS The incidences of alcohol , cigarette and smokeless tobacco initiation , and delinquent behavior were significantly lower in CTC than in control communities for students in grade s 5 through 8 . In grade 8 , the prevalences of alcohol and smokeless tobacco use in the last 30 days , binge drinking in the last 2 weeks , and the number of different delinquent behaviors committed in the last year were significantly lower for students in CTC communities . CONCLUSION Using the CTC system to reduce health-risking behaviors in adolescents can significantly reduce these behaviors communitywide OBJECTIVES This paper describes the one-year outcomes of the fourth experimental trial of Project Towards No Drug Abuse . Two theoretical content components of the program were examined to increase our underst and ing of the relative contribution of each to the effectiveness of the program . METHODS High schools in Southern California ( n=18 ) were r and omly assigned to one of three conditions : cognitive perception information curriculum , cognitive perception information+behavioral skills curriculum , or st and ard care ( control ) . The curricula were delivered to high school students ( n=2734 ) by project health educators and regular classroom teachers . Program effectiveness was assessed with both dichotomous and continuous measures of 30-day substance use at baseline and one-year follow-up . RESULTS Across all program schools , the two different curricula failed to significantly reduce dichotomous measures of substance use ( cigarette , alcohol , marijuana , and hard drugs ) at one-year follow-up . Both curricula exerted an effect only on the continuous measure of hard drug use , indicating a 42 % ( p=0.02 ) reduction in the number of times hard drugs were used in the last 30 days in the program groups relative to the control . CONCLUSIONS The lack of main effects of the program on dichotomous outcomes was contrary to previous studies . An effect on an ordinal count measure of hard drug use among both intervention conditions replicates previous work and suggests that this program effect may have been due to changes in cognitive misperception of drug use rather than behavioral skill Recent evaluations of smoking prevention programs have suggested considerable promise for curricula emphasizing resistance of social influences . The present study extends these evaluations by addressing key method ological limitations in previous work . Twenty-two matched schools were r and omized to experimental and control conditions . Grade 6 students received a 6-week core curriculum , plus additional sessions through Grade s 7 and 8 . Question naires , and saliva sample s to vali date self-reported smoking behavior , were collected at five times over the 2-year study period . Cross-sectional and longitudinal analyses examined program impact for five levels of initial smoking experience , ranging from “ never smoker ” through regular , weekly smoker . Significant program effects were documented , most clearly for those having some experience with smoking before the program began and for those with smoking peer and family models . This study provides the method ologically most rigorous test to date of social influence programs for smoking prevention and documents for the first time significant effects for those at high risk for smoking This study examined whether sixth- grade rs ' depressed mood and positive substance use expectancies predicted increases over the next two years in students ' lifetime and 30-day cigarette , alcohol , and marijuana use , and whether sixth grade rs ' positive substance use expectancies moderated the relationship between baseline depressed mood and changes over the next two years in the use of these substances . Study data came from a r and omized controlled trial of Project ALERT , a school-based substance use prevention program , in which students from 34 schools completed self-report surveys as sixth ( n=5782 ) , seventh ( n=5065 ) , and eighth grade rs ( n=4940 ) . Primary analyses were performed using Hierarchical Nonlinear Modeling . Over time , there were significant effects of baseline positive expectancies on each of the six measures of substance use . Baseline depressed mood predicted increases over time only for lifetime use of cigarettes and alcohol , and for 30-day alcohol use . Positive expectancies significantly moderated the effects of adolescent depressed mood only on lifetime marijuana use . Although depressed mood predicted substance use for half of our variables , our results suggest that positive expectancies are a more consistent predictor of adolescent substance use , and that they may moderate the effects of depressed mood on marijuana , but not cigarette or alcohol , use . Substance use prevention programs may benefit from addressing adolescents ' perceptions about the positive consequences of drug use OBJECTIVE To test whether baseline data from a r and omised clinical trial are predictive of initiation of tobacco use over a two-year follow-up interval , and to discuss results in the context of a theoretical model . DESIGN Secondary , non-experimental analyses of data collected from a prospect i ve cluster-r and omised clinical trial comparing an intervention with a control condition for reduction of tobacco incidence rates . Orthodontic offices in southern California were recruited and r and omised to an experimental or control group . Patient participants were sample d within each office , and completed a short survey , repeated two years later . SUBJECTS 13,923 patients , 11 - 18 years of age , r and omly sample d from each office . MAIN OUTCOME MEASURES The ability of baseline data to predict initiation of tobacco use over the two-year follow-up interval was tested through a series of logistic regression models . Significant predictors and their interactions were identified in fixed-effects models , and verified in a mixed-effects logistic regression model to account for cluster r and omisation . RESULTS Clinician advice against tobacco use was associated with a lower rate of tobacco use initiation among young people whose peer group considered smoking socially desirable . Rates of initiation increased with age , but this association differed by gender and by whether the adolescent had been offered tobacco within 30 days prior to the baseline assessment . People from minority groups were less likely to initiate tobacco use than whites , and young people engaging in other risk practice s were more likely to initiate tobacco use . CONCLUSIONS Findings support predictions based on learning theory that social processes are critical in the development of health-risk behaviours . Future preventive efforts should target changing the density with which young people encounter pro- and anti-tobacco prompts and consequences in the community OBJECTIVES The purpose of the study was to determine whether a universal school-based substance abuse prevention program , Take Charge of Your Life ( TCYL ) , prevents or reduces the use of tobacco , alcohol , or marijuana . METHODS Eighty-three school clusters ( representing school districts ) from six metropolitan areas were r and omized to treatment ( 41 ) or control ( 42 ) conditions . Using active consenting procedures , 19,529 seventh grade rs were enrolled in the 5-year study . Self-administered surveys were completed by the students annually . Trained Drug Abuse Resistance Education ( D.A.R.E. ) police officers presented TCYL in seventh and ninth grade s in treatment schools . Analyses were conducted with data from 17,320 students who completed a baseline survey . Intervention outcomes were measured using self-reported past-month and past-year use of tobacco , alcohol , and marijuana when students were in the 11th grade . RESULTS Main effect analyses show a negative program effect for use of alcohol and cigarettes and no effect for marijuana use . Subgroup analyses indicated that the negative effect occurred among nonusers at baseline , and mostly among white students of both genders . A positive program effect was found for students who used marijuana at baseline . Two complementary papers explore the relationship of the targeted program mediators to the use of alcohol , tobacco , and marijuana and specifically for students who were substance-free or who used substances at baseline . CONCLUSIONS The negative impact of the program on baseline nonusers of alcohol and tobacco indicate that TCYL should not be delivered as a universal prevention intervention . The finding of a beneficial effect for baseline marijuana users further supports this conclusion . The programmatic and method ological challenges faced by the Adolescent Substance Abuse Prevention Study ( ASAPS ) and lessons learned offer insights for prevention research ers who will be design ing similar r and omized field trials in the future The life-skills approach to smoking prevention was tested in this study . In total , 1024 pupils ( mean age 11.4 years , SD = 0.90 ) from Austria , Denmark , Luxembourg and Germany were recruited as an experimental group , and a sample of 834 matched pupils served as a control group . While the pupils from the control group received no specific intervention , the pupils in the experimental group participated in an intervention programme which was based on the life-skills approach and consisted of 21 sessions . The aims of the programme were to promote fundamental social competencies and coping skills . In addition , specific information on cigarette smoking was given and skills for resisting social influences to smoke were rehearsed . The programme was conducted by trained school teachers during a course of 4 months . Anonymous question naires were administrated ( 1 ) before the programme was implemented and ( 2 ) 15 months after the programme had started . Teachers as well as pupils showed a high level of satisfaction with the programme idea and the material s. With regard to the outcome variables , the programme had no differential effect on current smoking ( 4-week prevalence ) . The programme showed a weak effect ( P < 0.1 ) on lifetime smoking prevalence and experimental smoking . There was also an effect of the programme on smoking knowledge , on the social competences of the pupils as well as on the classroom climate . No effects were found on susceptibility to smoking among never-smokers , attitudes towards smoking and the perceived positive consequences of smoking . The results indicate that prevention programmes that are run for only a few months can have a positive impact on variables considered to be protective with regard to smoking uptake OBJECTIVE To determine the efficacy of a spit tobacco ( ST ) intervention design ed to promote ST cessation and discourage ST initiation among male high school baseball athletes . METHODS This study was a cluster-r and omized controlled trial . Forty-four r and omly selected high schools in rural California were r and omized within strata ( prevalence of ST use and number and size of baseball teams ) to either the intervention or the control group . Ninety-three percent of eligible baseball athletes participated , yielding 516 subjects in 22 intervention schools and 568 subjects in 22 control schools . Prevalences of sustained ST cessation and ST use initiation over 1 year were assessed by self-report . Multivariate logistic regression models for clustered responses were used to test the null hypotheses of no association between group and the two outcomes , adjusted for the stratified design and baseline imbalances between groups in significant predictors of ST use . RESULTS Prevalence of cessation was 27 % in intervention high schools and 14 % in control high schools ( odds ratio (OR)=2.29 ; 95 % confidence interval ( CI ) , 1.36 - 3.87 ) . The intervention was especially effective in promoting cessation among those who , at baseline , lacked confidence that they could quit ( OR=6.4 ; 95 % CI , 1.0 - 4.3 ) , among freshmen ( OR=15 ; 95 % CI , 0.9 - 260 ) , and among nonsmokers ( OR=3.2 ; 95 % CI , 0.9 - 11 ) . There was no significant difference between groups in the prevalence of ST initiation . CONCLUSIONS This intervention was effective in promoting ST cessation , but was ineffective in preventing initiation of ST use by nonusers A quasiexperimental study was conducted to explore the efficacy of the program Stay Away from Tobacco ( SAFT ) . Participants -from 11 classes with 381 students total in grade s 7 , 8 , 10 , and 11-were assigned by class to three groups ( intervention group T with school teachers delivering the program , intervention group R with research ers delivering the program , and comparison group C ) . Data were collected at baseline , immediately after the intervention , and 6 months after the intervention . Self-reported smoking was the outcome measure . The 30-day smoking prevalence in group C increased from 4 % at baseline to 10 % at the 6-month follow-up , whereas this rate declined from 11 % to 6 % in group T , and from 9 % to 1 % in group R. For group T , the odds ratio ( for 30-day smoking ) and the regression coefficient ( for indexed number of cigarettes smoked ) assessing interactions between intervention and time were 0.20 ( p < .001 ) and -.1605 ( p < .05 ) , respectively . The same statistics for group R were 0.09 ( p < .001 ) and -.2406 ( p < .01 ) , respectively . The predicted smoking rate declined by 19 % from baseline to 6-month follow-up in group T ( 11.5 % vs. 9.3 % ) , and the same rate declined by 26 % in group R ( 11.1 % vs. 8.2 % ) . The results from this pilot trial suggest that SAFT can reduce cigarette smoking among middle and high school students through its effect on improving these students ' refusal skills and changing their perceived mental and physical values from smoking . A full-scale evaluation is recommended BACKGROUND Antisocial personality disorder ( ASPD ) , violent and criminal behavior , and drug abuse disorders share the common antecedent of early aggressive , disruptive behavior . In the 1985 - 1986 school year teachers implemented the Good Behavior Game ( GBG ) , a classroom behavior management strategy targeting aggressive , disruptive behavior and socializing children to the student role . From first through seventh grade the developmental trajectories of 2311 students from 19 Baltimore City Public Schools were examined . We report the GBG impact on these trajectories and ASPD and violent and criminal behavior by age 19 - 21 . METHODS In five urban , poor to lower middle class predominately African-American areas , three to four schools were matched and within each set r and omly assigned to one of three conditions : ( 1 ) GBG , ( 2 ) a reading achievement program , or ( 3 ) the st and ard program . Classrooms and teachers were r and omly assigned to intervention or control . Measures at 19 - 21 included self reports and juvenile court and adult incarceration records . GBG impact was assessed via General Growth Mixture Modeling based on repeated measures of aggressive , disruptive behavior . RESULTS Three trajectories of aggressive , disruptive behavior were identified . By young adulthood , GBG significantly reduced the rates of ASPD and violent and criminal behavior among males in the persistent high aggressive , disruptive trajectory . REPLICATION : A replication was implemented with the following cohort of first- grade children using the same teachers , but with diminished mentoring and monitoring . Beneficial impact was found among persistent high males through seventh grade . By young adulthood GBG effects on ASPD and violent and criminal behavior were non-significant , but generally in the hypothesized direction The purpose of this article is to present the intermediate results for Project MYTRI , a school-based , multiple component intervention design ed to prevent and reduce many forms of tobacco use ( chewing tobacco , cigarettes , and bidis ) among youth in India . The intervention is based on effective models in the United States “ translated ” for use in this context . The intervention targets two cohorts of students who were in the 6th and 8th grade when the study started . Thirty-two schools in Delhi ( north India ) and Chennai ( south India ) were r and omized to receive the intervention ( n = 16 ) or serve as a delayed intervention control ( n = 16 ) . Students in these schools were surveyed before the intervention began and at an intermediate point , 1 year into this 2-year intervention ( n = 8,369 ) . A test of the changes in risk factors for tobacco use between the baseline and intermediate surveys revealed that , compared with the control , students in the intervention condition ( a ) had better knowledge about the health effects of tobacco ( P < 0.01 ) ; ( b ) believed that there were more negative social consequences to using tobacco ( P = 0.04 ) ; ( c ) had fewer reasons to use tobacco ( P < 0.01 ) ; ( d ) had more reasons not to use tobacco ( P = 0.03 ) ; ( e ) were less socially susceptible to chewing ( P = 0.04 ) and smoking ( P = 0.03 ) tobacco ; ( f ) perceived fewer peers and adults around them smoked ( P < 0.01 ) or chewed ( P < 0.01 ) tobacco ; ( g ) felt that tobacco use was not acceptable , especially among their peers ( P < 0.01 ) ; ( h ) were more confident in their ability to advocate for tobacco control ( P = 0.03 ) ; ( i ) were more knowledgeable about tobacco control policies ( P < 0.01 ) ; and ( j ) supported these policies , too ( P = 0.04 ) . Fewer students in the intervention condition reported having intentions to smoke tobacco in the next year ( P = 0.02 ) or chew tobacco when they reached college ( P < 0.01 ) . No changes in actual tobacco use were observed at this stage of the study . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1050–6 Five hundred and eleven fourth , fifth , and sixth grade students and their parents from six schools in northwest Arkansas participated in this study . Students were blocked on school and grade level , then assigned r and omly by class to either the intervention Keep A Clear Mind ( KACM ) program or a waiting list control . KACM students received four weekly correspondence lessons design ed to be completed at home with a parent . KACM students reported significantly less perceived peer use of alcohol , tobacco , and marijuana , as well as significantly less peer pressure susceptibility to experiment with cigarettes . Mothers in the KACM program reported significantly more recent and frequent communication with their children about refusing drugs , and significantly greater discussion s with their children regarding how to resist peer pressure to use alcohol , tobacco , and marijuana . Intervention program fathers reported significantly more communication with their children concerning how to resist peer pressure to drink alcohol and use tobacco , and significantly greater motivation to help their children avoid drug use . No significant differences were found between groups on student intentions to use drugs . These data suggest a print medium that emphasizes parent-child activities holds promise for accessing families and enhancing drug prevention communication OBJECTIVES To study if receptivity and exposure to tobacco marketing are correlated with tobacco use and psychosocial risk factors for tobacco use among a sample of urban Indian youth . METHODS Analysis of cross-sectional survey data from Project MYTRI , a group r and omized intervention trial , in Delhi and Chennai , India , collected from sixth and eighth grade rs ( n=11,642 ) , in 32 schools in 2004 . RESULTS Exposure to tobacco advertisements and receptivity to tobacco marketing were significantly related to increased tobacco use among students . CONCLUSION This association suggests the need to strengthen policy and program-based interventions in India to reduce the influence of such exposures OBJECTIVE To evaluate the effects of Project ALERT on adolescents ' lifetime and 30-day use of cigarettes , alcohol , marijuana , and inhalants . DESIGN Cluster r and omized trial . SETTING Schools from 11 states were enrolled in 2 successive cohorts from 2004 to 2008 . PARTICIPANTS All public schools in the United States that included grade s 6 through 8 and enrolled at least 100 students in sixth grade were recruited . Of the 40 schools that began the study , 34 ( 17 per condition ) completed it . Data were analyzed from 5883 unique participants . Intervention Project ALERT , a manualized classroom-based substance use prevention curriculum for the middle grade s , was taught to sixth and seventh grade rs . MAIN OUTCOME MEASURES Students were surveyed before the onset of the intervention , as sixth grade rs , and after the completion of the 2-year intervention , as seventh grade rs . Outcome measures included lifetime and 30-day use of cigarettes , alcohol , marijuana , and inhalants . RESULTS At baseline , students in the intervention condition were slightly to moderately more likely to report use for each of the 8 measures examined than were students in the control condition . For all measures except lifetime use of cigarettes , these differences were less pronounced at follow-up and therefore were in the direction of favorable program effects . These changes were statistically significant , however , for only 1 outcome measure , past 30-day use of alcohol ( reduction in the adjusted odds ratio from 2.07 at baseline to 1.32 at follow-up ; P = .006 ) . CONCLUSION Project ALERT was not effective when delivered to the sixth grade population we targeted Tobacco intervention studies that employ a community trial design require adjustment to the usual analytic methods to account for the allocation of intact social groups to study conditions and the positive intraclass correlation ( p ) that is inevitable in such a design . In the absence of valid estimates of the relevant p , investigators seeking to establish an appropriate sample size could only guess about the magnitude of the problem . We recently published estimates of p for common measures of adolescent tobacco use , but those estimates were unadjusted for potential covariates and so represented an upper limit on the magnitude of p. This report demonstrates how estimates of intraclass correlation may be substantially reduced through regression adjustment for easily measured covariates . Results show that both the p and the residual variance can be reduced , by an average of 20 and 11 % , respectively , offering greater efficiency for investigators who plan future studies and who are able to measure those covariates in their studies . Future work should seek both to replicate this work and to extend it ; for example , to cohort design s where the improvements might be even greater BACKGROUND The Czech Unplugged Study , inspired by the European Drug Addiction Prevention Trial , is a prospect i ve , school-based , r and omized controlled prevention trial design ed to reduce the risk of alcohol , tobacco , inhalant , and illegal drug use in 6th grade rs in the Czech Republic . The intervention uses the comprehensive social influence model to affect alcohol and drug using norms among primary school students . METHODS Descriptive statistics and chi-square analyses were used to assess differences between the experimental and control groups on demographic characteristics and study outcomes . Multilevel techniques were used to take the hierarchical structure of the data into account . Prevalence odds ratios using the Bonferroni correction were calculated to assess the differences between the experimental ( N = 914 ) and control ( N = 839 ) groups on each outcome 1 , 3 , 12 , 15 , and 24 months after the end of the intervention . RESULTS Multilevel analysis using the Bonferroni correction showed statistically significant intervention effects at the final follow-up for any smoking ( OR = 0.75 , 99.2 % CI 0.65 - 0.87 ) , daily smoking ( OR = 0.62 , 99.2 % CI 0.48 - 0.79 ) , heavy smoking ( OR = 0.48 , 99.2 % CI 0.28 - 0.81 ) , any cannabis use ( OR = 0.57 99.2 % CI 0.42 - 0.77 ) , frequent cannabis use ( OR = 0.57 , 99.2 % CI 0.36 - 0.89 ) , and any drug use ( OR = 0.78 , 99.2 % CI 0.65 - 0.94 ) . CONCLUSIONS This study adds new evidence on the effectiveness of the Unplugged school-based prevention program for primary school students in the Czech Republic " I do n't smoke , and you ? " is a project aim ed at secondary school students and is part of a wider project called " Free from Smoke " , implemented by the Lombardia Region and involving elementary and secondary school students . The project is a controlled non r and omized study whose aim is to direct students toward a healthy and smoke-free way of living , by also involving parents and teachers . A total of 11,610 12 year-olds of both sexes were evaluated , 6392 of whom were enrolled in the program and 5218 of whom served as controls and only completed the question naire . Three years after the start of the program , a greater increase in the prevalence of smokers was found amongst the group of controls than amongst the enrolled group ( 108,3 % vs + 93.8 % , p>0.001 ) . The percentage of students who believe that smoking even a small number of cigarettes is harmful , increased in the enrolled group ( + 0.6 % ) while it diminished in controls ( -2.1 % ) . In addition , a strong association was found between receiving a weekly allowance and smoking habits . In conclusion , positive results were obtained as regards the prevalence of smokers and the perceived risk of smoking ; however parents ' attitude towards smoking and the availability of a weekly allowance were found to have a strong influence in students ' smoking habits Eighth , ninth and tenth grade rs ( N = 281 ) from two schools in suburban New York participated in a study to test the efficacy of a 10-session comprehensive psychosocial smoking prevention program . Schools were r and omly assigned to experimental and control conditions . All students were given a pretest , posttest and three-month follow-up which assessed smoking behavior as well as knowledge and personality variables . There were significantly fewer new " smokers " in the experimental school than in the control school at both the initial posttest ( p less than .01 ) and the three-month followup ( p less than .05 ) along with significantly greater changes on some of the knowledge and personality variables . Overall , these results support the use of a smoking prevention strategy that focuses on the main psychosocial factors promoting the onset of cigarette smoking by teaching students basic coping skills OBJECTIVES We conducted a group r and omized trial of 2 South African school-based smoking prevention programs and examined possible sources and implication s of why our actual intraclass correlation coefficients ( ICCs ) were significantly higher than the ICC of 0.02 used to compute initial sample size requirements . METHODS Thirty-six South African high schools were r and omly assigned to 1 of 3 experimental groups . On 3 occasions , students completed question naires on tobacco and drug use attitudes and behaviors . We used mixed-effects models to partition individual and school-level variance components , with and without covariate adjustment . RESULTS For 30-day smoking , unadjusted ICCs ranged from 0.12 to 0.17 across the 3 time points . For lifetime smoking , ICCs ranged from 0.18 to 0.22 ; for other drug use variables , 0.02 to 0.10 ; and for psychosocial variables , 0.09 to 0.23 . Covariate adjustment substantially reduced most ICCs . CONCLUSIONS The unadjusted ICCs we observed for smoking behaviors were considerably higher than those previously reported . This effectively reduced our sample size by a factor of 17 . Future studies that anticipate significant cluster-level racial homogeneity may consider using higher-value ICCs in sample -size calculations to ensure adequate statistical power BACKGROUND The transtheoretical model ( TTM ) and computer technology are promising technologies for changing health behavior , but there is little evidence of their effectiveness among adolescents . METHOD Four thous and two hundred twenty-seven Year 9 ( ages 13 - 14 ) pupils in 26 schools were r and omly allocated to control and 4,125 in 26 schools were allocated to TTM intervention . TTM pupils received three whole class lessons and three sessions with an interactive computer program . Control pupils received no special intervention . Positive change in stage and smoking status was assessed from a question naire completed at baseline , 1 year , and 2 years . R and om effects logistic regression was used to compare the change in stage and smoking status between the arms . RESULTS Eighty-nine percent of the TTM group and 89.3 % of the control group were present at 1-year and 86.0 and 83.1 % , respectively , were present at 2-year follow-up . The adjusted odds ratio ( 95 % confidence interval ) for positive stage movement in the TTM relative to control was 1.13 ( 0.91 - 1.41 ) at 1 year and 1.25 ( 0.95 - 1.64 ) at 2 years and for regular smoking was 1.14 ( 0.93 - 1.39 ) at 1 year and 1.06 ( 0.86 - 1.31 ) at 2 years . Subgroup analysis by initial smoking status revealed no benefit for prevention or cessation . CONCLUSIONS The intervention was ineffective A two-year primary prevention program for junior high school students was evaluated . The program consisted of drug education , " alternatives , " and affective in- service training for the students ' teachers . Students in one junior high school received the intervention and students in another school served as a no-treatment control group . The students were pretested at the beginning of 7th grade and posttested at the end of 8th grade . Positive effects were found for females on several drug-related variables ; few effects were found for males . The findings are discussed with regard to the individual prevention strategies OBJECTIVE To evaluate a secondary school smoking prevention program in a small rural Norwegian municipality . DESIGN The project applied grade specific intervention strategies to all students grade s 6 - 9 and comprised a total of 32 lessons over a period of 3 years , with high student activity . A non-r and omised control group was constituted by all 6th-9th grade students in municipalities of similar characteristics in the same county . Results were recorded in annual class-based surveys . SUBJECTS The intervention group totalled 187 and the control group 364 students . MAIN OUTCOME MEASURES Prevalence of daily and occasional smoking and number of cigarettes smoked , during the intervention period . RESULTS An 80 % lower rate of daily smoking and 50 % fewer cigarettes smoked by daily smokers . Lower rates of smoking in 9th grade occurred mostly among girls . CONCLUSION The project result ed in a lower recruitment of daily smokers up to grade 9 , as well as fewer cigarettes smoked by daily smokers . The intervention was more successful among girls than boys The article presents 2-year follow-up data from a school-based tobacco use prevention project design ed to test the effectiveness of 3 primary components in social influence programs . The components either teach refusal skills , awareness of social value misperceptions , or physical consequences . Curricula were tested with a r and omized experiment involving 48 junior high schools . These data suggested that ( a ) a physical-consequences curriculum is successful at attenuating increases in adolescent smokeless tobacco use , ( b ) cigarette experimentation may be attenuated by various approaches , and ( c ) a comprehensive program with all 3 components was necessary to attenuate increases in weekly use of both forms of tobacco . These results also indicate that school-based tobacco use interventions can be effective at least 2 years postprogram , after students make their transition to high school Factors associated with changes in the smoking behaviour of approximately 6000 schoolchildren ( two cohorts aged between 10 and 12 years in 1979 ) over 12 months are described . They were measured twice as part of a r and omized controlled trial of a smoking prevention programme . Four groups were defined : ( a ) those who became smokers ( adopters ) ; ( b ) those who remained non-smokers ; ( c ) those who became non-smokers ( quitters ) , and , ( d ) those who remained smokers . Personal and social variables were ordered using a logistic regression model according to the strength of their association with adopting and quitting smoking . Factors distinguishing adopters from children who remained nonsmokers were , being a member of the older cohort , having friends who smoke , having siblings who smoke , approving of cigarette advertising and having a relatively large amount of money to spend each week . Factors distinguishing quitters from children who continued to smoke were , having siblings who do not smoke , being a member of the younger cohort , disapproving of cigarette advertising and having a relatively small amount of money to spend each week . Initial attitude scores were indicative of future smoking behaviour and where smoking behaviour changed , attitudes also changed so that the two remained congruent . The younger cohort improved their knowledge of smoking hazards over the year irrespective of their smoking behaviour . The older cohort showed significant differences in knowledge which were dependent upon smoking category , with 1980 smokers having lower knowledge scores than non-smokers and showing an apparent decrement in their previous knowledge The effectiveness of a 20 session cognitive-behavioral approach to substance abuse prevention was tested on seventh grade students ( n = 1,311 ) from 10 suburban New York junior high schools . The prevention strategy attempted to reduce intrapersonal pressure to smoke , drink excessively , or use marijuana by fostering the development of general life skills as well as teaching students tactics for resisting direct interpersonal pressure to use these substances . Additionally , this study was design ed to compare the relative effectiveness of this type of prevention program when implemented by either older peer leaders or regular classroom teachers . Results indicated that the prevention program had a significant impact on cigarette smoking , excessive drinking , and marijuana use when implemented by peer leaders . Furthermore , significant changes were also evident with respect to selected cognitive , attitudinal , and personality predisposing variables in a direction consistent with non-substance use . These results provide further support for the efficacy of a broad-spectrum smoking prevention strategy and tentative support for its applicability to the prevention of other forms of substance abuse This study reports outcome evaluation results from a segment of one of the most widely used drug education/prevention programs entitled “ Here 's Looking At You 2000 . ” HLAY 2000 was offered to the seventh and eighth grade students ( n = 463 ) by regular classroom teachers of Yadkin County Schools located in one of the rural areas in North Carolina . Six schools served as the experimental group while two r and omly selected schools served as a control group . The program was implemented during the 1990–91 school year This study evaluated the effects of a school-based intervention on growth trajectories of smoking , drinking , and antisocial behavior among early adolescents . Seven middle schools were r and omized to intervention or comparison conditions and students in two successive cohorts ( n = 1484 ) provided five waves of data from sixth to ninth grade . The Going Places Program , included classroom curricula , parent education , and school environment components . Latent growth curve analyses demonstrated significant treatment group effects , including reducing increases in friends who smoke , outcome expectations for smoking , and smoking progression , but had non-significant effects on drinking or antisocial behavior . The Going Places Program was effective in preventing increases in smoking progression , but its efficacy as a more cross-cutting problem behavior preventive intervention was not confirmed Recent studies have supported the efficacy of approaches to smoking prevention that focus primary attention on social and psychological factors implicated in initiation of adolescent cigarette smoking . This article reports first year data from a large-scale smoking prevention study conducted within three geographic regions of New York State . The sample consists of 5,954 seventh grade rs from 56 middle/junior high schools . Schools were r and omly assigned to ( 1 ) receive the Life Skills Training ( LST ) prevention program with a one-day teacher training workshop ; ( 2 ) receive the LST prevention program with teacher training provided by video tape ; or ( 3 ) serve as a comparison group . This study was design ed to further test the efficacy of this type of smoking prevention program and to compare the relative effectiveness of two different types of provider training in an effort to learn more about the potential effectiveness of this prevention strategy when implemented under " real world " conditions . Pretest and postt OBJECTIVE To test the efficacy of implementation intentions in reducing smoking uptake in a sample of adolescents . DESIGN Classes of adolescents ( aged 11 - 12 years ) were r and omly allocated to one of four conditions : implementation intention , self-efficacy , two control conditions . An implementation intention or a self-efficacy manipulation ( both formed in relation to how to refuse offers of cigarettes ) was completed by intervention condition participants at 0 , 4 , 8 , 12 , 16 , 20 , and 24 months . MAIN OUTCOME MEASURES Long-term smoking behavior ( self-report and objective ) was assessed at 48 months post-baseline . RESULTS There were no differences between the two control conditions and the self-efficacy condition . Controlling for baseline smoking , sex , attitudes to smoking , friends and family smoking , and the multilevel nature of the data , intention-to-treat analyses indicated the implementation intention manipulation significantly reduced self-reported smoking compared to the other three conditions combined . Analyses on objective ly assessed smoking ( carbon monoxide breath measure ) in a r and om sub sample of participants also indicated that the implementation intention manipulation compared to the other three conditions significantly reduced smoking . CONCLUSION Implementation intentions can reduce smoking in adolescent sample s. Implication s for using implementation intentions to reduce smoking in adolescents are discussed This paper describes the third and final evaluation of drug education conducted by the Napa Project . In the present course students were taught decision-making skills , personal goal setting , a motivational model , peer and media influences on behavior , assertiveness training , and information on the consequences of , and alternatives to , alcohol , cigarette , and marijuana use . The evaluation employed an experimental design in which seventh grade classes in two schools were matched and then r and omly assigned to experimental and control conditions . Pre- , post- , and follow-up tests covered drug knowledge ; drug attitudes ; perceived benefits and costs of substance use ; perceived peer attitudes toward , and use of , substances ; and intentions to use , current use and lifetime use of various substances . The posttest and follow-up data were analyzed using hierarchical analyses of covariance controlling for corresponding pretest scores . The course was found to have had no significant effect on girls and only a few effects at follow-up for boys BACKGROUND Knowledge about age of smoking initiation among adolescents in China is helpful for exploring cultural differences in adolescent smoking behavior and informative for global tobacco control . However , little has been documented on this issue . METHOD Adolescents ( 6,473 ) attending grade s 7 , 8 , and 9 completed the baseline survey of a longitudinal , r and omized smoking prevention trial . Data were collected in classrooms with a paper- and -pencil question naire . A survival model was used in the statistical analysis . RESULTS The hazard of smoking initiation for boys showed a pattern previously observed in the United States : very low ( < 2 % ) before 7 years of age , increasing rapidly after age 10 , and peaking at 14 - 15 years of age . The hazard for girls was below or around 1 % until 12 years of age before it increased . The hazard levels were similar for adolescents both in urban and in rural areas , but higher for those in grade 7 than in grade s 8 and 9 . CONCLUSIONS Chinese boys in Wuhan , China , experienced a hazard pattern of smoking initiation by age similar to those observed in the United States , while Chinese girls there experienced a rather low risk of smoking initiation . The hazard pattern suggests that the best time for smoking prevention is between 10 and 15 years of age . Adolescents in lower grade s are at higher risk of early smoking initiation , suggesting a potential cohort effect in adolescent smoking initiation in Wuhan , China For students to realize the benefits of behavior change curricula for disease prevention , programs must be implemented effectively . However , implementation failure is a common problem documented in the literature . In this article , teacher training is conceptualized as a behavior change process with explicit teacher motivation components included to help effect the intended behavior ( i.e. , implementation ) . Using this method , the Hutchinson Smoking Prevention Project , a r and omized controlled trial in school-based smoking prevention , conducted 65 in-service programs , training nearly 500 teachers ( Grade s 3 - 10 ) from 72 schools . Implementation was monitored by teacher self-report and classroom observations by project staff . The results were favorable . All eligible teachers received training , virtually all trained teachers implemented the research curriculum , and 89 % of observed lessons worked as intended . It is concluded that teacher training conceptualized as a behavior change process and including explicit teacher motivation components can promote effective implementation of behavior change curricula in public school classrooms We describe the results of a r and omized controlled study on the efficacy of a smoking prevention program based on behavioral methods ( Waterloo Smoking Prevention Program 1 , adapted ) . 792 children of 12 - 13 years of age from the Health District of Rozzano ( MI ) were the study base . The program was delivered directly by voluntary teachers during school classes . Two follow-up , at 18 and 36 month from the end of the program were conducted using self-administered question naire and telephonic interviews . At 36 months the proportion of non-smokers was higher in the intervention group ( 55 % vs 44 % ; OR ( adjusted for clustering ) = 1.7 ; p = .03 ) and that of regular ( at least one cigarette a week ) smokers lower ( 22 % vs 39 % ) than in the control group . We found no difference of effect between males and females students . Social pressure associated with starting to smoke ( friends , sibsters , parents smokers ) measured before intervention had no demonstrable influence on efficacy . We propose this kind of intervention for Italian students as an effective and low-cost program , even though more research is needed to maintain effectiveness of these kind of programs beyond adolescence In this article , the authors examine whether delayed substance initiation during adolescence , achieved through universal family-focused interventions conducted in middle school , can reduce problematic substance use during young adulthood . Sixth- grade students enrolled in 33 rural midwestern schools and their families were r and omly assigned to 3 experimental conditions . Self-report question naires provided data at 7 time points for the Iowa Strengthening Families Program ( ISFP ) , Preparing for the Drug Free Years ( PDFY ) , and control groups through young adulthood . Five young adult substance frequency measures ( drunkenness , alcohol-related problems , cigarettes , illicit drugs , and polysubstance use ) were modeled as distal outcomes affected by the average level and rate of increase in substance initiation across the adolescent years in latent growth curve analyses . Results show that the models fit the data and that they were robust across outcomes and interventions , with more robust effects found for ISFP . The addition of direct intervention effects on young adult outcomes was not supported , suggesting long-term effects were primarily indirect . Relative reduction rates were calculated to quantify intervention-control differences on the estimated proportion of young adults indicating problematic substance use ; they ranged from 19 % to 31 % for ISFP and from 9 % to 16 % for PDFY The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) is an elementary school cardiovascular health education field trial in progress in San Diego , California , New Orleans , Louisiana , Minneapolis , Minnesota , and Austin , Texas . Because a significant part of a child 's health behaviors are shaped within the home , CATCH is evaluating whether the effects of the school-based program are enhanced by the inclusion of a home-based program . A 7 x 7 x 10 r and omized design with 7 school-only and 7 school-plus-family intervention schools , along with 10 control schools is implemented at each site . The CATCH family intervention is implemented during Grade s 3 through 5 and consists of home-based curricula and Family Fun Nights focusing on healthier eating and increased physical activity during Grade s 3 and 4 , along with a smoking prevention curriculum in Grade 5 . CATCH is examining the effectiveness of family ( household ) involvement through changes in students ' dietary intake of fat and sodium . This paper describes the process evaluation methods used to document the extent of participation in the family program . Data reported for the third- grade Family Fun Nights held in the 28 family schools across all sites reflected an average student participation rate of 67 % . The average family member to student ratio was approximately 2:1 . Participation by all third- grade teachers and the majority of physical education specialists was observed Health promotion interventions can not work if people do not engage with them . The aim of this study was to examine whether disengagement from an adolescent smoking prevention and cessation intervention was an independent risk factor for regular smoking 1 and 2 years later . The data were taken from a cluster r and omised controlled trial , in the West Midl and s , UK , based on the transtheoretical or stages of change model . In this trial , 8,352 13 - 14-year old school pupils enrolled , and the data in this report were based on the 7,413 and 6,782 pupils present at 1 and 2 years follow-ups , respectively . The intervention group undertook three sessions using an interactive computer programme . At the end of the programme , pupils recorded their responses to it . Pupils were classed as engaged if they thought the intervention was both useful and interesting ; all others were classed as disengaged . R and om effects logistic regression related the number of times engaged to regular smoking at 1 and 2 years follow-up , adjusted for school absences and 11 potential confounders . The majority of pupils were engaged by the intervention . For participants using the intervention three times but not engaging once , the odds ratios ( 95 % confidence intervals ) for smoking at 1 and 2 years relative to the controls were 1.83 ( 1.41 - 2.39 ) and 1.70 ( 1.38 - 2.11 ) . For those engaging three times , they were 0.79 ( 0.60 - 1.03 ) and 0.96 ( 0.75 - 1.21 ) . There was no interaction with baseline intention to smoke , classified by stage of change , but there was a borderline significant interaction with baseline smoking status , with disengagement acting as a stronger risk factor among baseline never-smokers . We conclude that disengagement from interventions is a risk factor for smoking independently of experimentation with cigarettes . The best explanation is that disengagement from school , an established risk factor for smoking , generalises to disengagement from didactic school-based health promotion programmes The longitudinal study compared effects of varying amounts of tobacco instruction ( one , two , and three years ) on the knowledge , attitudes , and behavioral intentions of urban elementary students . A three-year , fourth-through-sixth grade tobacco prevention curriculum was developed based on the Centers for Disease Control and Prevention 's Guidelines for School Health Programs to Prevent Tobacco Use and Addiction . The curriculum comprised five , 45-minute lessons per year . The same trained instructor taught the curriculum all three years . Six intervention schools were taught the curriculum , and two control schools were not . A 49-item question naire was used to assess tobacco knowledge , attitudes , and behavioral intentions . The experimental group 's posttest knowledge and attitude scores were significantly higher than the control group 's posttest scores . No significant differences occurred in posttest behavioral intention scores between the control and intervention groups This analysis examined the possible synergistic effect of exposure to the National Youth Anti-Drug Media Campaign and a classroom-based drug prevention curriculum among 9th grade students participating in a r and omized trial of ALERT Plus . A total of 45 South Dakota high schools and their middle-school feeder(s ) were r and omly assigned to an ALERT condition ( basic prevention curriculum delivered in 7th and 8th grade s ) , an ALERT Plus condition ( basic curriculum with booster lessons added for 9th and 10th grade s ) , or a control condition . Marijuana use in the past month was significantly less likely among ALERT Plus students reporting at least weekly exposure to anti-drug media messages . The National Youth Anti-Drug Media Campaign may have led to reductions in marijuana use among youth who simultaneously received school-based drug prevention BACKGROUND The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) was the first multicenter school-based research study to employ the fundamentals of clinical trials including the st and ardized protocol and Manuals of Operation , a steering committee for study governance , a distributed data system , an extensive quality control system , and a Data and Safety Monitoring Board . METHOD CATCH tested the effectiveness of changes in school lunches , physical education , smoking policy , curricula , and family activities . Ninety-six elementary schools in four states were r and omized to intervention or control conditions . The baseline cohort comprised 5 , 106 ethnically diverse third grade rs followed through fifth grade . RESULTS The percentages of calories from fat and saturated fat were reduced significantly more in the intervention school lunches than among the controls . Significant increases in moderate to vigorous activity levels in existing physical education classes were made as well . Changes in self-reported dietary , physical activity , and psychosocial measures were significant . There were no significant differences in the physiological measures . Measurement error was generally low for all physiologic measures except skinfolds , indicating a high level of reliability . Across all sites , the coefficients of variation for lipids , height , and weight were less than 3 % , whereas for skinfolds , they were considerably higher , ranging from 6 to 8 % . Intraclass correlations for lipid studies were also uniformly high at 0.99 . Interobserver agreement scores for SOFIT were greater than 90 % for 9 of the 11 activities observed . Data entry error rates were low with less than five errors per 1,000 fields for all forms . CONCLUSIONS The CATCH results provided more scientific evidence on the importance of schools in the population approach to health promotion . Many of the strategies used in this complex multicenter trial in the areas of design and analysis , measurement , training , data management , and quality control protocol s might be appropriate for adoption in other studies This study examined the long-term substance use outcomes of 2 brief interventions design ed for general population families of young adolescents . Thirty-three public schools were r and omly assigned to 3 conditions : the 5-session Preparing for the Drug Free Years Program , the 7-session Iowa Strengthening Families Program , and a minimal contact control condition . The pretest involved 667 6th grade rs and their families . Assessment s included multiple measures of initiation and current use of alcohol , tobacco , and marijuana . Pretest data were collected in the 6th grade and the reported follow-up data were collected in the 10th grade . Significant intervention-control differences in initiation and current use were found for both interventions . It is concluded that brief family skills-training interventions design ed for general population s have the potential to reduce adolescent substance use and thus have important public health implication BACKGROUND Adolescents at risk for cigarette smoking are difficult to reach with conventional interventions but have substantial exposure to the mass media . This study is the first to show that smoking prevention messages presented through the mass media can have large and durable effects on higher risk adolescents . METHODS Students in two communities received media and school interventions beginning in grade s 5 - 7 ; those in matched comparison communities received school interventions . Media interventions were targeted to higher risk youths . School surveys were conducted before and after the interventions , in grade s 4 - 6 and grade s 8 - 10 . Two years after interventions ended , when participants were in grade s 10 - 12 , school and telephone surveys were conducted to assess smoking status . Survey participants ( n = 2,860 ) were classified at baseline as having higher or lower risk for becoming a smoker . RESULTS Smoking prevalence within the higher risk sample was significantly lower for those receiving media-school interventions than for those receiving school interventions only ( odds ratio = 0.71 ) . Effects on the lower risk sample were similar in magnitude but marginally significant . CONCLUSIONS Mass media and school interventions achieved lower smoking rates among higher risk youngsters 2 years following completion of the interventions . This strategy represents a uniquely effective method for communicating with a high-priority group A six-year , school-based prevention program , which modified classroom teacher practice s , offered parent training , and provided child social skills training , was evaluated for its effects on school failure , drug abuse , and delinquency among low-income urban children . Compared to a low-income control group , children in the intervention group showed enhanced school commitment and class participation . The girls in the group also evidence d lower rates of substance use initiation , while the boys exhibited increased social and school work skills The study examined the effectiveness of a psycho-social tobacco use prevention intervention with a refusal skills training component on the refusal skills of high-risk adolescents , and investigated skill acquisition as related to subject demographics , performance of health facilitators and attendance at skills training sessions . Tobacco refusal skills were assessed for a group ( n = 389 ) of high-risk , seventh- grade students participating as intervention and control subjects in Project SHOUT , a large tobacco use prevention program in the San Diego area . In addition , subject demographics , ratings of health facilitator performance and information about subjects ' attendance at skills training sessions were collected . Subjects ' responses to audiotaped peer offers of cigarettes and smokeless tobacco were coded for content and quality . Greater tobacco refusal skills among intervention subjects was hypothesized . Further health facilitator performance , attendance at training sessions and subject demographics were thought to be related to skill acquisition . High-risk intervention subjects gave significantly higher quality tobacco-refusal responses than did controls , although the differences between means were small . Results suggested that Hispanic adolescents were particularly receptive to the refusal skills training . The association between health facilitator performance and skill acquisition varied by subject ethnicity , as did the relationship between attendance at training sessions and skill acquisition Project Northl and is a community-wide research program funded by the National Institute on Alcoholism and Alcohol Abuse , for a 5-year period ( 1990 - 95 ) . The aim of the study is to prevent or delay onset of alcohol use among young adolescents , as well as to reduce use among those who are already drinkers . Twenty communities were recruited in northeastern Minnesota , an area referred to as the Northl and , Arrowhead or Iron Range region , and then were r and omly assigned to either Education or Delayed Program conditions . The 10 Education school districts have agreed to participate in 3 years of intervention programs in schools , with parents and in the community-at-large . One group of young adolescents , the Class of 1998 ( sixth grade students in the 1991 - 92 school year ) , form the study cohort . Surveys ( 1991 - 94 ) of the Class of 1998 , their parents , community leaders and alcohol merchants are the primary components of the program 's evaluation . Many conceptual and method ological questions emerged during the development of the research protocol s for Project Northl and over the past 2 years . These questions are the impetus for this article . Specifically , the focus on young adolescents and alcohol use was selected , as contrasted with older adolescents or with multiple problem behaviors . The project was design ed using a community-wide model that addresses both supply and dem and issues , rather than limited to a school-based model . Intervention strategies and evaluation methods were chosen that could address community-level as well as individual-level behavior change , which required the development and application of new technologies . The rationale for these decisions may be useful to others considering community-wide health promotion efforts Abstract Objectives : To examine whether a year long programme based on the transtheoretical model of behaviour change , incorporating three sessions using an expert system computer program and three class lessons , could reduce the prevalence of teenage smoking . Design : Cluster r and omised trial comparing the intervention to a control group exposed only to health education as part of the English national curriculum . Setting : 52 schools in the West Midl and s region . Participants : 8352 students in year 9 ( age 13 - 14 years ) at those schools . Main outcome measures : Prevalence of teenage smoking 12 months after the start of the intervention . Results : Of the 8352 students recruited , 7444 ( 89.1 % ) were followed up at 12 months . The intention to treat odds ratio for smoking in the intervention group relative to control was 1.08 ( 95 % confidence interval 0.89 to 1.33 ) . Sensitivity analysis for loss to follow up and adjustment for potential confounders did not alter these findings . Conclusions : The smoking prevention and cessation intervention based on the transtheoretical model , as delivered in this trial , is ineffective in schoolchildren aged 13 - 14 . Key messages The transtheoretical model proposes that individuals move through a series of stages in behaviour change A computer programme gave 13 and 14 year old school students tailored information about what stage they were in and what to do to move to the next stage Students given this information were no more likely to move stage , refrain from smoking , or stop smoking than those exposed to ordinary classroom health education There is no evidence that the computerised expert system based on the transtheoretical model is effective in smoking prevention and Two drug abuse prevention curricula were tested to determine their efficacy in preventing the onset of tobacco , alcohol , and marijuana use among adolescents . The first program focused on prevention through social pressure resistance training . The second featured affective education approaches to prevention . Curricula were tested on seventh grade students . Subjects were pretested just prior to the program and were post-tested at 12 and 24 months . Post-test analyses indicated that the social program delivered to seventh grade subjects was effective in delaying the onset of tobacco , alcohol , and marijuana use . No preventive effect of the affective education program was observed . By the final post-test , classrooms that had received the affective program had significantly more drug use than controls OBJECTIVES Project Northl and is an efficacy trial with the goal of preventing or reducing alcohol use among young adolescents by using a multilevel , communitywide approach . METHODS Conducted in 24 school districts and adjacent communities in northeastern Minnesota since 1991 , the intervention targets the class of 1998 ( sixth- grade students in 1991 ) and has been implemented for 3 school years ( 1991 to 1994 ) . The intervention consists of social-behavioral curricula in schools , peer leadership , parental involvement/education , and communitywide task force activities . Annual surveys of the class of 1998 measure alcohol use , tobacco use , and psychosocial factors . RESULTS At the end of 3 years , students in the intervention school districts report less onset and prevalence of alcohol use than students in the reference districts . The differences were particularly notable among those who were nonusers at baseline . CONCLUSIONS The results of Project Northl and suggest that multilevel , targeted prevention programs for young adolescents are effective in reducing alcohol use OBJECTIVE The aims of this trial , conducted 2004 - 2008 , were to examine ( 1 ) the effectiveness of Project Towards No Drug Abuse ( TND ) at the one-year follow-up when implemented on a large scale ; and ( 2 ) the relative effectiveness of two training approaches for program implementers . METHOD A total of 65 high schools from 14 school districts across the United States were r and omized to one of three conditions : regular workshop training , comprehensive implementation support , or st and ard care control . Physical education and health teachers delivered the program to students ( n=2538 ) . Program effectiveness was assessed with dichotomous measures of 30-day substance use at baseline and one-year follow-up . RESULTS When the program conditions were considered in aggregate and compared to controls , the program showed a marginally significant effect in lowering marijuana use from baseline to the one-year follow-up . Significant program effects on hard drug use were achieved for baseline non-users only . There were no differences in the effects of the two program conditions . CONCLUSION Positive outcomes may be achieved by trained teachers when they implement Project TND in real-world high school environments ; however , program effects are likely to be weaker than those achieved in efficacy trials . Training workshops may be adequate to build capacity for successful program implementation Little documentation exists regarding the functioning of formalized adolescent groups as drug abuse prevention agents . Two studies are described that were conducted at high schools whose students are at high risk for drug abuse . Twenty-one schools were r and omly assigned to one of three conditions : ( a ) st and ard care , ( b ) classroom drug abuse education only , or ( c ) classroom plus school-as-conununity . Results of the first study tndicated that the school-as-communtty component — which involved weekly meetings and periodic events at seven schools — was imple mented as planned , drug abused focused , and perceived as productive in discouraging drug abuse . In the second study , staff in the classroom plus school-as-community condition self- reported involvement in the greatest number of community activities across the school year , compared with staff from the other two conditions . These two studies support the feasibility of formalized groups of high-risk youth to promote drug-free events The purpose of this project was to develop and test culturally appropriate , low literacy , smoking cessation intervention material s design ed to increase quit rates and prevent relapse postpartum for low-income African American and Hispanic women . A quasi-experimental , pretest-posttest design was used . Four Women , Infants , and Children ( WIC ) clinic sites in south and central Los Angeles were identified , pair-matched based on ethnic mix , and r and omized to intervention ( 2 sites ) or control status ( 2 sites ) . Participants were 18 years of age or older and either current or exsmokers ( stopped smoking in the past year ) . The intervention group received the " Time for a Change : A Program for Healthy Moms and Babies " program including a 15-minute one-to-one counseling session and self-help guide , incorporating behavior-change strategies , booster postcard , and incentive contest . All material s were design ed to match the cultural , language , and literacy needs of the target population . The smoking cessation intervention had a positive impact on both quit-smoking behavior during pregnancy and relapse prevention postpartum . Almost twice as many smokers in the intervention group ( 43 % ) reported quitting smoking at 9 months , compared to the control group ( 25 % ) ( P < 0.01 ) . At 6 weeks postpartum , 25 % of the intervention baseline smokers were abstinent , compared to 12 % of the control group ( P < 0.01 ) . Although no significant differences were observed for relapse during pregnancy among exsmokers at 6 weeks postpartum , a significantly higher proportion of intervention exsmokers were still abstinent ( 79 % ) , compared to control exsmokers ( 62 % ) ( P < 0.01 ) . For the exsmokers , relapse prevention rates remained significant when adjusted for cotinine vali date d abstinence . ( ABSTRACT TRUNCATED AT 250 WORDS Students ( N = 4,466 ) attending 56 schools in New York State were involved in a 3-year study testing the effectiveness of a cognitive-behavioral approach to substance abuse prevention . In a r and omized block design , schools were assigned to receive ( a ) the prevention program with formal provider training and implementation feedback , ( b ) the prevention program with videotaped provider training and no feedback , or ( c ) no treatment . After pretest equivalence and comparability of conditions with respect to attrition were established , students who received at least 60 % of the prevention program ( N = 3,684 ) were included in analyses of program effectiveness . Significant prevention effects were found for cigarette smoking , marijuana use , and immoderate alcohol use . Prevention effects were also found for normative expectations and knowledge concerning substance use , interpersonal skills , and communication skills OBJECTIVES Although several studies have reported short-term gains for drug-use prevention programs targeted at young adolescents , few have assessed the long-term effects of such programs . Such information is essential for judging how long prevention benefits last . This paper reports results over a 6-year period for a multisite r and omized trial that achieved reductions in drug use during the junior high school years . METHODS The 11-lesson curriculum , which was tested in 30 schools in eight highly diverse West Coast communities , focused on helping 7th and 8th grade students develop the motivation and skills to resist drugs . Schools were r and omly assigned to treatment and control conditions . About 4000 students were assessed in grade 7 and six times thereafter through grade 12 . Program effects were adjusted for pretest covariates and school effects . RESULTS Once the lessons stopped , the program 's effects on drug use stopped . Effects on cognitive risk factors persisted for a longer time ( many through grade 10 ) , but were not sufficient to produce corresponding reductions in use . CONCLUSIONS It is unlikely that early prevention gains can be maintained without additional prevention efforts during high school . Future research is needed to develop and test such efforts Aims : This article details the application of Complier Average Causal Effect ( CACE ) analysis to the examination of youth outcomes from adaptive substance use prevention trials . Methods : CACE analysis is illustrated using youth-reports of tobacco-use from ages 11 to 22 , from the Adolescent Transitions Program , a family-focused r and omized encouragement trial design ed for delivery in the school setting Results : Female gender and early peer deviance predicted family engagement with active intervention components . Further , long-term reductions in youth tobacco use from age 11 to age 22 were found for families that engaged with treatment . Conclusions : CACE modeling techniques enable research ers to examine factors that predict engagement with core intervention components and to examine intervention effects specifically for youth who engaged with those components BACKGROUND This study reports the prevalence of adolescent smoking in the urban and rural areas of Wuhan , China , the capital of Hubei Province , on the Yangtze River in central China . METHODS Smoking behavior was examined by age , gender , and urbanicity as part of the Wuhan Smoking Prevention Trial . Subjects included 6994 seventh- to ninth- grade students attending 22 r and omly selected schools in urban and rural districts . Outcome measures included lifetime smoking , past-30-day smoking , established smoking ( > 100 cigarettes in lifetime ) , and susceptibility to smoking ( absence of a firm commitment not to smoke ) . RESULTS Lifetime smoking prevalence was 47 % among boys and 18 % among girls . Past-30-day smoking prevalence was 16 % among boys and 4 % among girls . Established smoking prevalence was 2 % among boys and 0 % among girls . The prevalence of susceptibility to smoking was 31 % among boys and 10 % among girls . Smoking increased significantly with age ( p<.0005 ) . Susceptibility was more prevalent in rural areas than in urban areas ( p<.05 ) , but there were no urban-rural differences in lifetime , past 30-day smoking , or established smoking . Trend analyses revealed that smoking increased with age more rapidly among boys than among girls ( p<.05 ) . Smoking was more prevalent among rural boys than among urban boys , but it was more prevalent among urban girls than among rural girls ( p<.05 ) . CONCLUSIONS Adolescent smoking is a significant public health problem in China . Boys are at particularly high risk , as are girls living in urban areas . Effective smoking prevention programs for adolescents , as well as restrictions on tobacco industry marketing and youth access to tobacco , are needed to prevent tobacco-related morbidity and mortality in China UNLABELLED BACKGROUND . There are strong theoretical reasons for including a family component with a school-based intervention aim ed at eating , activity , and smoking behaviors , but the empirical findings to date are limited and show mixed results . The overall CATCH family intervention added only knowledge and attitudinal effects , but no additional behavioral outcomes . This study provides a dose analysis of the family component of the CATCH study by assessing the effect of the level of adult participation . METHOD This secondary analysis included students who attended a CATCH family intervention school during all 3 years of the study . The extent of the adult-child interaction , the key aspect of the CATCH family intervention , was measured by the number of activity packets that an adult household member completed with the child . Multiple regression analysis was used to assess the association of adult participation with the child 's knowledge , attitudes , and behaviors related to diet and physical activity . RESULTS Statistically significant results suggested that dose effects were found for knowledge and attitudes related to diet and physical activity . These effects were more pronounced for minority and male students . CONCLUSIONS These results suggest that dose response of a family intervention has been shown in the acquisition of positive knowledge and attitudes toward health habit changes . The methodology of dose response can be applied to other health promotion projects PURPOSE The objective of the present study was to study the ability to influence young at-risk patients ' attitudes toward tobacco use through two intervention methods that were performed by dental health professionals . MATERIAL S AND METHODS Two interventions , a brief individual motivational interview and an adapted school lecture , were studied , and both were compared with a control group . Before and after interventions , a question naire was used . Patients born in 1989 and 1992 who were judged by the dental personnel as potentially at risk for dental diseases , a total of 301 individuals , were included . RESULTS Both before and after interventions , the results showed a generally negative attitude towards tobacco use . A majority of the participants were positive towards measures that were taken to control the spread of tobacco use , younger participants ( born 1992 ) to a greater extent ( 73 % ) than the older participants ( born 1989 ) ( 54 % ) . Important factors that kept the participants away from tobacco use were the harmful effects and the approaches of parents and friends . The older participants believed to a greater extent that they would try smoking as adults . No change in tobacco use was registered after intervention , although the participants reported an increased use among friends . CONCLUSIONS The two pedagogical methods that were used in the present study influenced the young people 's attitudes towards tobacco use only to a small extent . However , the period between 12 and 15 years old seems to provide a good opportunity to influence attitudes towards tobacco . The adolescents ' dem and for interactive learning and their development of attitudes and tobacco use habits in relation to family and friends provide opportunities to use new pedagogical models INTRODUCTION This paper describes the experimental design and baseline characteristics of the Hutchinson Smoking Prevention Project ( HSPP ) , a 15-year trial to determine to what extent a grade 3 - 12 school-based tobacco use prevention intervention can deter tobacco use throughout and beyond high school . DESIGN Trial design features include use of the school district as the unit of r and omization , inclusion of the school district 's entire enrollment of 3rd grade rs , long-term follow-up of the entire original cohort , and sample size and evaluation methods that account for the group-r and omization and intraclass correlation of endpoints within school districts . The theory-based intervention is teacher-led and includes grade 3 - 10 curriculum units , teacher training , grade 9 - 12 tobacco use cessation material s , and high school staff newsletters . RESULTS Baseline data were collected on the trial cohort of 8388 children and their parents and on the 40 collaborating school districts and communities . A comparison of the distribution of baseline variables between experimental conditions shows good balance . CONCLUSIONS . The HSPP trial 's experimental design will provide a rigorous test of the intervention . The balance in baseline variables between the experimental and control conditions will help provide assurance that the trial 's intervention effectiveness results , scheduled for publication in 2000 , will be unbiased BACKGROUND This paper examines whether the Massachusetts Tobacco Control Program is affecting the rates of smoking and smokeless tobacco use among Massachusetts ' youth . METHODS School survey data from the Massachusetts Prevalence Study were analyzed to estimate differences between 1993 and 1996 rates of youth cigarette and smokeless tobacco use , attitudes toward smoking , and awareness of cigarette ads and promotions of antismoking messages . RESULTS Lifetime and Current Smoking rates declined significantly among middle school males , contrasting with stable national trends . Among girls in this age group , Lifetime and Current Smoking did not change significantly . Hispanic middle school students exhibited a significant decline in Lifetime Use . There were no significant changes in Lifetime or Current Smoking rates among high school students . Lifetime use of smokeless tobacco declined among middle school students while Current Use declined among both middle and high school students . Students reported declines in awareness of cigarette ads or promotions and increases in awareness of antismoking messages . CONCLUSIONS These results provide evidence for cautious optimism regarding the impact of tobacco control , but indicate that these efforts should begin earlier and that additional research is needed to underst and and address the problems of tobacco use by girls OBJECTIVE To reduce tobacco use among adolescents . METHODS Thirty schools in New Delhi , India , were r and omly assigned to 3 conditions : school-based and family-based intervention , school-based intervention only , or control group . Students were in the seventh grade at pretest ( N = 4,776 ) . The smoking intervention included posters , booklets , classroom activities , debates , and a signature campaign . The family intervention involved home activities . The survey measured tobacco knowledge , attitudes , offers , use , and intentions . RESULTS Intervention students were significantly less likely than controls to have been offered , received , experimented with , or have intentions to use tobacco . CONCLUSION The project had a significant impact on tobacco use OBJECTIVES We evaluated the effectiveness of a parent-based add-on component to a school-based intervention to prevent cigarette smoking among African American and Latino middle school youths . METHODS Mother-adolescent dyads ( n=1386 ) were r and omly assigned to 2 groups : ( 1 ) a school-based smoking-prevention intervention or ( 2 ) the same intervention with a parent-based add-on component called Raising Smoke-Free Kids . Mothers in the experimental condition received the parent add-on component . Mothers in the control condition received information on selecting a high school . All adolescents received a version of Project Towards No Tobacco Use ( TNT ) . The primary outcome was a reduction in adolescent cigarette smoking . Follow-up data were obtained from 1096 mother-adolescent dyads at 15 months postintervention . RESULTS At follow-up , the odds of smoking cigarettes were reduced by 42 % for adolescents in the parent add-on condition versus the TNT-only condition . Mothers in the parent add-on condition were more likely than were mothers in the TNT-only condition to set rules about risk-sensitive social activities and to be perceived as trustworthy by their child . Group differences also were found in the frequency and quality of mother-adolescent communication . CONCLUSIONS Including parent add-on components in school-based smoking prevention programs can reduce smoking behavior on the part of inner-city middle school youths PURPOSE To determine whether self-concept , gender , and age are significant factors in an adolescent 's transition through stages of smoking to regular smoking . METHODS A question naire composed of 29 items ( nine questions pertaining to smoking behavior and 20 to four self-concept variables : physical , family , social , and peer self-concept ) was administered to 368 r and omly selected high school adolescents ( 188 males and 180 females ) aged 12 - 17 years during regular contact ( roll call ) time . RESULTS Overall , 40.5 % of the sample had tried tobacco ( excluding chewing tobacco ) ( 42.8 % of females and 38.3 % of males ) . Although prevalence of smoking varied according to the stage of smoking , it increased with age . With reference to self-concept , Scheffe post hoc contrasts revealed a statistically significant difference between physical self-concept and the remaining measures of self-concept ( peer , family , and social ) and at each stage of smoking . The effect for male students was less than for females . CONCLUSION Programs aim ed at prevention and intervention should incorporate strategies which are commensurate with female lifestyles and the more positive aspects that individuals might experience on quitting Reaching nonvolunteer female smokers with effective smoking cessation programs is a critical public health challenge . Smokers ( N = 2,786 ) among 15,004 female members of a health maintenance organization who completed a routine needs assessment were invited into the " UCLA Preventive Health Behavior Study , " consisting of five telephone interviews over 2 years assessing health practice s. Participants ( N = 1,396 ) were r and omized into experimental or control conditions of an unsolicited , mailed , self-help smoking cessation program . Subjects were not alerted to the link between the program and the health study . Smoking status was assessed at 1 , 6 , 12 , and 18 months . Across all subjects , point prevalence at 18 months was 18.62 , and continuous abstinence was 2.71 % . No difference was found between treatment and control groups regarding smoking status or readiness to stop smoking -- raising questions about the value of mailing cessation material s to nonvolunteers . Quit rates increased over the 18-month follow-up ; those still smoking at 18 months reported increased readiness to quit . Predictors at each follow-up point were examined multivariately How effective are peer-led programmes in preventing the uptake of smoking by children ? In 1981 , we conducted a r and omized controlled trial of a school-based educational programme for the prevention of smoking in children who were in their seventh year at school . In this article , the reported results of two years of follow-up confirm an earlier report that both teacher-led and peer-led programmes result ed in a reduction , to about the same degree , in the uptake of smoking by girls , while only the teacher-led programme appeared to be effective in boys . In girls , both the teacher-led and peer-led programmes maintained their effects over the two years of follow-up with adjusted differences in prevalence rates of the uptake of smoking relative to the control group of -6.6 % ( 95 % CL , -17.3 % , 4.0 % ) and -8.1 % ( 95 % CL , -18.9 % , 2.7 % ) , respectively , after two years . In boys , the effect of the teacher-led programme was reduced substantially by the second year with a difference in the prevalence rate of -2.8 % ( 95 % CL , -11.2 % , 5.6 % ) ; for the peer-led programme the difference in the prevalence rate was + 6.4 % ( 95 % CL , -3.6 % , 16.4 % ) . Other variables which had a significant effect on the smoking behaviour were the perceived response to cigarette advertising , parental and sibling smoking status , the perceived parental sanctions on smoking behaviour , selected peer influences and the intention to smoke . The children 's perceived responses to cigarette advertising showed the strongest and most consistent evidence of an effect on the uptake of smoking by children who initially were non-smokers . After adjustment for the effects of other variables there was an excess of 15.0 % ( 95 % CL , 2.1 % , 27.9 % ) in the prevalence rate of smoking after two years for girls who thought that they were influenced by advertising compared with those who did not . The corresponding difference for boys was 15.3 % ( 95 % CL , 4.0 % , 26.6 % ) . As smoking-prevention programmes only may delay the onset of smoking in children , it is important that legislative measures be introduced to reduce the effects of cigarette advertising OBJECTIVE To test a classroom-based intervention to reduce cardiovascular disease risk factors in elementary school children . STUDY DESIGN This was a r and omized , controlled field trial in 12 schools across North Carolina , stratified by geographic region and urban/rural setting . Subjects were 1274 third and fourth grade rs ( 48 % boys ) . The intervention , taught by regular classroom and physical education teachers , provided all children an 8-week exercise program and 8 weeks of classes on nutrition and smoking . Data were analyzed at the school level with survey regression models and at the individual level with multivariate analysis of variance and analysis of covariance models ; 95 % confidence intervals were computed . RESULTS Children in the intervention group had significantly greater knowledge ( 7.9 % more correct ) and a significant increase in self-reported physical activity than children in the control group . Trends for the intervention group were a reduction in total cholesterol level ( -5.27 mg/dl ) , an increase in aerobic power , a reduction in body fat , and smaller rise in diastolic blood pressure than control children . CONCLUSIONS This classroom-based , public health approach improved children 's cardiovascular disease risk profiles ; it is practical and fairly easy to incorporate into the school day . All children directly receive the potential benefits of the intervention without a risk of labeling . This program can improve health knowledge , habits , and health outcomes of young children at a time when health habits are being formed Sixth- grade students ( N = 56 ) were assigned r and omly to one of four experimental conditions : pretest and primary prevention ; primary prevention ; pretest ; and neither pretest nor primary prevention . In eight group sessions , primary prevention students learned facts , problem solving , decision making , self-instructions and interpersonal skills to help keep them from using tobacco . All students completed posttests and a six-month follow-up . Compared with untrained controls , trained students had greater knowledge of smoking , more perspectives on tobacco problems , better linkages between problems and solutions , more insights on the consequences of nonsmoking decisions and greater nonverbal and verbal competence in tobacco use situations . Follow-up data showed trained students with stronger commitments to tobacco abstinence , more frequent refusals of tobacco , and less smoking than controls . Midway through seventh grade , 8 % of trained students and 37.5 % of controls had smoked in the most recent month OBJECTIVES This study examined whether interventions aim ed at aggressive/disruptive classroom behavior and poor academic achievement would reduce the incidence of initiation of smoking . METHODS An epidemiologically based , universal r and omized preventive trial involved 2311 children in 2 classroom-based preventive interventions or controls . Each intervention was directed at 1 of the aforementioned 2 antecedents over first and second grade s in 19 urban schools . RESULTS Smoking initiation was reduced in both cohorts for boys assigned to the behavioral intervention . CONCLUSIONS Targeting early risk antecedents such as aggressive behavior appears to be an important smoking prevention strategy A one year r and omized controlled trial was used to evaluate the effectiveness of a smoking prevention programme design ed by health educationalists for 10 - 12 year old primary schoolchildren . The study was carried out in the Hunter Region of New South Wales , Australia , using a sample of over 6000 children which would be large enough to detect , with high probability , differences of about 5 % in smoking prevalence between the treatment and control groups . We report the results from the children surveyed in 1979 and 1980 , before and after the programme was implemented . It was found that there were no significant differences in smoking behaviour between treatment and control groups . The changes that the programme did bring about were very small compared with the overall increases in smoking prevalence which occurred during the study period . The programme 's effectiveness varied with both the age and sex of the children . It was most successful among older girls , aged 11 - 12 years , for whom smoking prevalence rates increased from 10.7 % in 1979 to 22.6 % in 1980 in the treatment group compared with 6.2 % to 26.8 % in the control group . It was least successful for younger boys , aged 10 - 11 years , for whom smoking increased from 9.4 % to 14.5 % in the treatment group compared with 10.3 % to 11.8 % in the control group . Attitudes changed in parallel with changes in smoking behaviour . Changes in knowledge differed only slightly between treatment and control groups . Inadequate implementation of the programme by some teachers may have been associated with adverse effects on the children 's behaviour , attitudes and knowledge This study analyzed quantitative data on tobacco use and dependency for 3,589 high-school students , qualitative data for 448 students , and outcome data for a r and omized trial comparing the efficacy of two cessation interventions and a control condition for 337 students . Data were collected from 1988 through 1992 in California and Illinois as part of a larger longitudinal study . Smokeless tobacco users , but not smokers , were more likely than controls to maintain cessation for 4 months : biochemically vali date d cessation at 4 months was 6.5 % versus 3.2 % for smokers and 14.3 % versus 0.0 % for smokeless tobacco users . Implication s and limitations are discussed A cognitive-developmental model postulates three predominant adolescent dispositions ( self-definition , social compliance , and affect regulation ) which may impede or facilitate transitions in stages of smoking . The purpose of the present prospect i ve study was to build on the findings supporting this model . One hundred schools were r and omly assigned to either receive or not receive a social influences smoking prevention program . A baseline survey , including smoking behavior and dispositional items , was administered in the sixth grade in 1990 , interventions were delivered in the sixth and seventh grade s , and a survey was administered following the seventh grade intervention . Principal component patterns , based on dispositional items , were very similar for grade s 6 and 7 , did not vary by gender , and the components ( rebelliousness , rejection of adult authority , personal dissatisfaction , and peer approval ) were correlated . All smoking-stage transitions were positively related to rebelliousness for boys . The relationship of the dispositional scores with smoking-stage transitions was more complex for girls . Receiving the program modified the effects of the dispositional risk scores , particularly for girls The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) is a multicenter trial design ed to test the effectiveness of school and family-based cardiovascular health promotion for preadolescents . CATCH interventions target multiple cardiovascular health behaviors such as dietary intake of fat and sodium , physical activity , and tobacco use . Evaluation includes physiological , psychosocial , behavioral , and process measures . An important aspect of the process evaluation is the assessment of environmental factors and " secular events " in both intervention and control schools that may affect outcomes independently of the CATCH interventions . With such information , CATCH investigators are able to isolate the impact of the CATCH intervention from competing ( non-CATCH ) factors as well as " track " proximal ( i.e. , immediate and short term ) changes related to the intervention that may in turn lead to " distal " ( long-term ) behavior change . The School Health Question naire , the major process evaluation tool for monitoring secular and environmental changes in the schools , is described in detail , and data describing tobacco-related environmental factors and secular events are presented The purpose of the study was to evaluate the impact of the Going Places Program and mediation of treatment effects . Seven middle schools were r and omized to intervention or comparison conditions and students ( n = 1,320 ) in two successive cohorts provided five waves of data from sixth through eighth grade . The Going Places Program included classroom curriculum , parent education , and school environment components . Latent growth curve analyses demonstrated significant treatment group effects on outcome expectancies , friends who smoke , and smoking . Friends who smoke mediated the program effect on adolescents ’ smoking progression . The protective effect of the Going Places Program on smoking progression was due in part to the prevention of increases in friends who smoke BACKGROUND Two strategies for preventing the onset of alcohol abuse , and marijuana and cigarette use were tested in junior high schools in Los Angeles and Orange Counties , California . The first strategy taught skills to refuse substance use offers . The second strategy corrected erroneous normative perceptions about prevalence and acceptability of use among peers and established conservative groups norms regarding use . METHODS Four experimental conditions were created by r and omly assigning schools to receive ( a ) neither of the experimental curricula ( placebo comparison ) , ( b ) resistance skill training alone , ( c ) normative education alone , or ( d ) both resistance skill training and normative education . Students were pretested prior to the program and post-tested 1 year following delivery of the program . RESULTS There were main effects of normative education for summary measures of alcohol ( P = 0.0011 ) , marijuana ( P = 0.0096 ) , and cigarette smoking ( P = 0.0311 ) . All individual dichotomous measures of alcohol , marijuana , and tobacco use indicated significant reductions in onset attributable to normative education . There were no significant main effects of resistance skill training . CONCLUSION These results suggest that establishing conservative norms is an effective strategy for preventing substance use The distal impact of a school based universal preventive intervention targeting disruptive behavior problems on tobacco and alcohol use from age 10 to 13 years was explored . Second grade classrooms ( children aged 7 years ) were r and omly assigned to the intervention or a control condition . Tobacco and alcohol use from age 10 to 13 years was available for 477 children ( 72 % of original sample ) . The impact of intervention on the initial level and growth in probability of substance use was explored . Results showed that intervention children had lower probabilities of tobacco use over the ages 10 - 13 years . This effect remains significant when controlling for ( male ) sex , pre-intervention levels of conduct problems , exposure to prenatal smoking or current parental smoking . For alcohol use , no effect of intervention during childhood was found . However , intervention children reported having a lower probability in alcohol use with age among those children reporting having used in the last week . The results underscore the importance of the early prevention of disruptive behavior problems substance use initiation . Implication s for prevention and research are discussed OBJECTIVE To develop a new measure of smoking initiation and progression among adolescents . METHOD This study used data from 2504 regular and alternative high school students to evaluate the psychometric properties of a new 3-item , 5-stage measure of smoking initiation and progression . RESULTS The categorization method showed good 4-week test-retest reliability ( .83 among boys and .87 among girls ) . The demographic distribution of adolescents into stages was consistent with previous research . CONCLUSION This 5-stage classification method could be a useful framework for describing variation along the smoking up-take and progression continuum A prospect i ve anti-smoking clinical trial was conducted as part of a coronary risk factor intervention study in three rural South African communities in the south-western Cape over a period of 4 years . The aim of this part of the study was to reduce smoking rates in two of the communities through application of high- and low-intensity intervention . The effect was evaluated by examining the net change in smoking habits , which was defined as the residual change in the intervention areas after allowing for change in the reference area . This paper presents the analyses of the estimated effect of the programme on the cohort aged 15 - 64 years at baseline who participated in the two surveys ( 4,087 subjects ) . The intervention programme among men in the high-intensity intervention area result ed in a reduction of 8.4 % in smoking rates and 13.0 % in the amount smoked per day . Among women in this area there was a reduction of 30.6 % in smoking rates and 20.5 % in amount smoked . Smoking and the amount smoked per day also decreased in the low-intensity intervention area , but less so than in the high-intensity intervention area . Smoking quit rates were strongly associated with initial smoking levels , with light smokers being significantly more successful quitters than heavy smokers . This study has proved that a community-based intervention programme can effectively reduce smoking The effectiveness of a fifteen session psychosocial smoking prevention strategy was tested on 902 seventh grade rs from seven junior high schools in suburban New York over 2 years . The prevention program was implemented by regular classroom teachers and consisted of a cognitive component dealing with the immediate consequences of cigarette smoking , a decision-making component , a relaxation-training component , a social skills training component , and a self-improvement component . In addition to testing the overall effectiveness of this approach , the relative efficacy of two different scheduling formats was compared and the extent to which “ booster ” sessions conducted during the year after completion of the program helped to maintain reductions in new smoking was also examined . Results indicated that the prevention program was able to reduce new cigarette smoking by 50 % at the end of the first year and by 55 % at the end of the second year for the intensive format condition . New regular cigarette smoking was reduced by 87 % in the second year for the students in the booster condition . Significant changes consistent with nonsmoking were also evident on several cognitive , attitudinal , and personality variables BACKGROUND An outcome evaluation of a high school tobacco control intervention using extracurricular activities developed by teachers and students is reported . METHODS Eligible subjects ( n = 3,028 ) had participated in a r and omized trial of an elementary school smoking prevention curriculum . Their high schools were matched in pairs ; one school in each pair was r and omly assigned to the intervention condition , the second to a " usual-care " control condition . Data were collected at the end of Grade s 9 and 10 . RESULTS For Grade 8 never smokers , regular smoking rates were significantly lower for males from intervention schools ( 9.8 vs 16.2 % , P = 0.02 ) at the end of Grade 10 . There were no significant differences among Grade 10 smoking rates for females , or for students of either gender with previous smoking experience in Grade 8 . CONCLUSIONS The extracurricular activities approach to tobacco control is practical to implement and has promise BACKGROUND This study evaluates the effects of a 3-year smoking prevention programme in secondary schools in Helsinki . The study is part of the European Smoking prevention Framework Approach ( ESFA ) , in which Denmark , Finl and , the Netherl and s , Portugal , Spain and the UK participated . METHODS A total of 27 secondary schools in Finl and participated in the programme ( n = 1821 ) . Schools were r and omised into experimental ( 13 ) and control groups ( 14 ) . The programme included 14 information lessons about smoking and refusal skills training . The 3-year smoking prevention programme was also integrated into the st and ard curriculum . The community-element of the programme included parents , parish confirmation camps and dentists . The schools in the experimental group received the prevention programme and the schools in the control group received the st and ard health education curriculum . RESULTS Among baseline never smokers ( 60.8 % ) , the programme had a significant effect on the onset of weekly smoking in the experimental group [ OR = 0.63 ( 0.45 - 0.90 ) P = 0.009 ] when compared with the control group . Being female , doing poorly at school , having parents and best friends who smoke and more pocket money to spend compared with others were associated with an increased likelihood of daily and weekly smoking onset . These predictors did not have an interaction effect with the experimental condition . CONCLUSION This study shows that a school- and community-based smoking prevention programme can prevent smoking onset among adolescents INTRODUCTION We conducted a group-r and omized trial to increase smoking cessation and decrease smoking onset and prevalence in 30 colleges and universities in the Pacific Northwest . METHODS R and om sample s of students , oversampling for freshmen , were drawn from the participating colleges ; students completed a question naire that included seven major areas of tobacco policies and behavior . Following this baseline , the colleges were r and omized to intervention or control . Three interventionists developed Campus Advisory Boards in the 15 intervention colleges and facilitated intervention activities . The freshmen cohort was resurveyed 1 and 2 years after the baseline . Two-years postr and omization , new cross-sectional sample s were drawn , and students were surveyed . RESULTS At follow-up , we found no significant overall differences between intervention and control schools when examining smoking cessation , prevalence , or onset . There was a significant decrease in prevalence in private independent colleges , a significant increase in cessation among rural schools , and a decrease in smoking onset in urban schools . DISCUSSION Intervention in this college population had mixed results . More work is needed to determine how best to reach this population of smokers This paper describes the curricula contents , and presents data to evaluate the implementation , process and immediate post-test knowledge of Project Towards No Tobacco Use ( Project TNT ) . Four different school-based tobacco use prevention curricula were developed to counteract the effects of three types of tobacco use acquisition variables typically addressed within a comprehensive social influences program : ( 1 ) peer approval for using tobacco ( normative social influence ) , ( 2 ) incorrect social informational provided about tobacco use ( information social influence ) and ( 3 ) lack of knowledge or misperceptions about physical consequences result ing from tobacco use . Three curricula were design ed to counteract the effects of single acquisition variables , whereas a fourth curriculum was design ed to counteract the effects of combined social and physical consequences-related influences . These curricula were delivered to seventh grade students by trained project health educators to maximize implementation . ' Program ' schools , those schools that received one of these curricula , were compared to ' control ' schools that provided a systematic health education delivered by school personnel . A total of five conditions were contrasted through use of a r and omized experiment involving 48 southern California junior high schools . This paper documents high levels of implementation in all program conditions . Also , favorable process ratings were obtained across the four program conditions , using multiple measures and sources of ratings ( students , health educators and classroom teachers who observed curricula delivery ) . Finally , knowledge item sets completed by the students demonstrated discriminant validity across all five conditions . Because the program conditions were discriminable , yet were quite similar in implementation and process ratings , planned future study of behavioral outcomes can be interpreted as relatively uncontaminated by delivery or credibility confounds Thirty-four schools ( n=7426 consented sixth grade rs , 71 % of the eligible population ) were r and omized to conditions to test the hypothesis that Skills for Adolescence ( SFA ) , a widely used comprehensive life skills training curriculum with a dedicated drug education unit , is more effective than st and ard care in deterring and delaying substance use through middle school . Two-year posttest ( 1-year post-intervention ) data were collected from 5691 eighth grade rs ( 77 % of those who completed the sixth- grade survey and 87 % of those who completed the seventh- grade survey ) . Lifetime and recent ( last 30 days ) use of five substances or combinations of substances was compared using mixed-model regression to control for school clustering . There were two significant treatment main effects at the end of the eighth grade : lifetime ( P=.05 ) and recent ( P<.03 ) marijuana use were lower in SFA than control schools with pretest usage and salient demographic and psychosocial variables controlled . There was also one significant Treatment x Pretest Usage interaction around binge drinking . Baseline binge drinkers in SFA schools were less likely to report recent binge drinking than students in control schools ( P<.01 ) ; there were no treatment differences among baseline nonbinge drinkers . Analyses of potential mediators of SFA treatment effects on eighth- grade binge drinking and marijuana use suggested that SFA increased self-efficacy around drug refusal skills , but did not affect behavioral intentions , perceptions of harm , or perceived peer norms . These 2-year ( 1-year post-intervention ) outcomes offer some additional support for SFA effectiveness and the general thrust of school-based , life skills-based prevention programs . The promising sixth- through eighth- grade findings for SFA , a commercially available program , provide a further step in bridging a major gap in the " research to practice " literature : theory-based interventions that have documented behavioral effects have not enjoyed large-scale implementation , while intuition-based programs that have no documented effects still enjoy wide exposure OBJECTIVES We investigated the links between working for pay and adolescent tobacco use to determine whether working for pay increases smoking risk . METHODS We performed retrospective and prospect i ve analyses using data from a cohort of 799 predominantly African American students in Baltimore , Md , who had been followed since the first grade . RESULTS At the 10th year of follow-up , when the adolescents were aged 14 to 18 years , there was a positive relationship between the time they spent working for pay and current tobacco use . This relationship was attenuated somewhat after adjustment for potential selection effects . Adolescents who spent more than 10 hours per week working for pay also tended to initiate tobacco use earlier than did their peers . Among adolescents who had not yet used tobacco , those who started to work 1 year after assessment and those who worked over 2 consecutive assessment s had an elevated risk of initiating use relative to adolescents who did not start working . CONCLUSIONS There is a strong link between working for pay and adolescent tobacco use . Policymakers should monitor the conditions under which young people work to help minimize young workers ' tobacco use and potential for initiating use This study assessed the outcomes of adapting the culturally-grounded , middle school , substance-use prevention intervention , keepin ' it REAL ( kiR ) , to target elementary school students and to address acculturation . At the beginning of 5th grade , 29 schools were r and omly assigned to conditions obtained by crossing grade of implementation ( 5th , 7th , 5th + 7th , and control/comparison ) by curriculum version [ kiR-Plus vs. kiR-Acculturation Enhanced ( AE ) ] . Students ( n = 1984 ) completed 6 assessment s through the end of 8th grade . The kiR curricula generally appear no more effective than the comparison schools ' programming . Students receiving either version of the kiR intervention in only the 5th grade report greater increases in substance use than did control students . Receiving the kiR-AE version twice ( both 5th and 7th grade s ) has benefits over receiving it once This study evaluated the effects of self-control skills intervention to prevent smoking with middle school subjects . Informed and consenting subjects were pretested , then by school were r and omly divided into three conditions : experimental , placebo , and test-only control . Experimental condition subjects received self-control skills intervention covering self-instruction , self-reinforcement , problem solving , and interpersonal communication . Placebo condition subjects received a discussion -oriented intervention employing health education methods to prevent smoking . Results at 15-month follow-up indicated that self-control and placebo condition subjects , relative to control condition subjects , improved more on measures of health knowledge and nonsmoking intentions . Self-control skills subjects had better 15-month follow-up scores than subjects in the other two conditions on measures of communication , self-instruction , self-praise , cigarette refusals , and noncompliance to smoke . Self-control condition subjects reported less weekly cigarette smoking compared with placebo and control condition subjects at final follow-up The Internet may be an effective medium for delivering smoking prevention to children . Consider This , an Internet-based program , was hypothesized to reduce expectations concerning smoking and smoking prevalence . Group-r and omized pretest-posttest controlled trials were conducted in Australia ( n = 2,077 ) and the United States ( n = 1,234 ) in schools containing Grade s 6 through 9 . Australian children using Consider This reported reduced 30-day smoking prevalence . This reduction was mediated by decreased subjective norms . The amount of program exposure was low in many classes , but program use displayed a dose-response relationship with reduced smoking prevalence . American children only reported lower expectations for smoking in the future . Intervening to prevent smoking is a challenge , and this data suggest small benefits from an Internet-based program that are unlikely to be of practical significance unless increased by improved implementation . Implementation remains the major challenge to delivering interventions via the Internet , both for health educators and research ers Data from a 2-year study describe tobacco use trends , perceptions , and prevention effects for 1,281 5th and 6th grade rs enrolled in 12 r and omly selected Washington State elementary schools . Youths were pretested , then r and omly divided by school into skills , discussion , and control groups . Preventive intervention curriculums for the skills and discussion groups included age-relevant information on smoked and smokeless tobacco use , peer testimonials , debates , games , and homework . Youths in the skills group also learned communication and problem-solving methods for h and ling difficult situations around tobacco use . Following intervention , youths were posttested , then retested semiannually for 2 years . During the 2-year study , three-quarters of all smokers and nonusers and half of all smokeless tobacco users maintained their statuses . Only 10 percent of all smokers and 3 percent of all smokeless users quit their habits . One in six reported new tobacco use , one-third of smokers began using smokeless tobacco , and two-thirds of all smokeless users began smoking during the study . Most youths at final measurement perceived smokeless tobacco as less of a health risk than smoking . Nearly one in two of all smokeless users intended to smoke , and two-thirds were actually smoking at 24-month followup . Both smoked and smokeless tobacco use rates increased in all groups , and youths in the skills intervention group consistently showed the lowest rates relative to the other groups . These findings demonstrate the potential of skills intervention methods for lowering tobacco use rates among adolescents OBJECTIVE Experimental evaluation of comprehensive community wide programme to prevent adolescent tobacco use . DESIGN Eight pairs of small Oregon communities ( population 1700 to 13 500 ) were r and omly assigned to receive a school based prevention programme or the school based programme plus a community programme . Effects were assessed through five annual surveys ( time 1–5 ) of seventh and ninth grade ( ages 12–15 years ) students . INTERVENTION The community programme included : ( a ) media advocacy , ( b ) youth anti-tobacco activities , ( c ) family communications about tobacco use , and ( d ) reduction of youth access to tobacco . MAIN OUTCOME MEASURE The prevalence of self reported smoking and smokeless tobacco use in the week before assessment . RESULTS The community programme had significant effects on the prevalence of weekly cigarette use at times 2 and 5 and the effect approached significance at time 4 . An effect on the slope of prevalence across time points was evident only when time 2 data points were eliminated from the analysis . The intervention affected the prevalence of smokeless tobacco among grade 9 boys at time 2 . There were also significant effects on the slope of alcohol use among ninth grade rs and the quadratic slope of marijuana for all students . CONCLUSION The results suggest that comprehensive community wide interventions can improve on the preventive effect of school based tobacco prevention programmes and that effective tobacco prevention may prevent other substance use OBJECTIVES This study determined the effect of provider ( nurse or teacher ) and training method ( workshop or self-preparation ) on outcomes of a social influences smoking prevention program . METHODS One hundred elementary schools were stratified by school risk score ( high risk = high smoking rate among senior students ) and assigned r and omly to conditions : ( 1 ) teacher/self-preparation , ( 2 ) teacher/workshop , ( 3 ) nurse/self-preparation , ( 4 ) nurse/workshop , and ( 5 ) control . Intervention occurred in grade s 6 to 8 . Smoking status at the end of grade 8 was the primary endpoint variable . RESULTS Intervention reduced grade 8 smoking rates in high-risk schools ( smoking rates of 26.9 % in control vs 16.0 % in intervention schools ) but not in low-risk schools . There were no significant differences in outcome as a function of training method and no significant differences in outcome between teacher-provided and nurse-provided interventions in high- and medium-risk schools . Although nurses achieved better outcomes than did teachers in low-risk schools , neither provider type achieved outcomes superior to the control condition in those schools . CONCLUSIONS Workshop training did not affect outcomes . Teachers and nurses were equally effective providers . Results suggest that programming should target high-risk schools OBJECTIVES This paper describes the 2-year follow-up of a 12-session version of an indicated drug abuse prevention program , Project Towards No Drug Abuse ( TND ) . Self-instruction programming often is used to help youth that are at high risk for dropout and drug abuse to complete their high school education . However , a health educator-led program is much more interactive . METHODS The effects of self-instruction versus health educator-led versions of this curriculum were examined . Eighteen schools were r and omly assigned by block to one of three conditions -- st and ard care ( control ) , health educator-led classroom program , and self-instruction classroom program . Subjects were followed up 1 and 2 years later . Two-year results are reported here . RESULTS The self-instruction program produced no behavioral effects relative to the st and ard care control condition . The 2-year follow-up results indicated maintenance of program effects on cigarette smoking and hard drug use in the health educator-led version . CONCLUSIONS Project TND shows maintenance of effects on some drugs 2 years after program implementation , when most youth were young adults . More work is needed to learn how to maintain effects across substances . Continued exploration of modalities of implementation may be helpful Skills intervention to prevent cigarette smoking was evaluated with 689 adolescents . At 24-month follow-up , youths who received health information and skills intervention had lower intentions to smoke and less cigarette use than youths who received health information alone and youths who received no intervention . Conclusions about the effects of skills intervention are strengthened by the common preparation and r and om assignment of intervention leaders and by process measurement data OBJECTIVE Research ers continue to try to develop effective teen tobacco use prevention and cessation programs . Three previous school clinic-based studies established the efficacy of Project EX for teen smoking cessation . This fourth study adapts Project EX to the classroom context . This paper reports the findings based on pretest and posttest surveys conducted immediately prior and post-intervention . METHODS An eight-session classroom-based curriculum was developed and tested with a r and omized controlled trial that involved a total of 1097 students in six program and six control continuation high schools . Program-specific knowledge and smoking measures were assessed at both the pretest and posttest surveys , and were used to evaluate the program 's effect on the immediate outcomes . The immediate outcomes effects were analyzed with multi-level r and om coefficients models . RESULTS Program students provided favorable process ratings of the overall program and each session . Compared with the students in the control condition , students in the program condition showed a greater change in correct knowledge responses from pretest to posttest ( beta=+5.5 % , p=0.0003 ) . Students in the program condition also experienced a greater reduction in weekly smoking ( beta=-6.9 % , p=0.038 ) , and intention for smoking in the next 12 months ( beta=-0.21 in 5-level scale , p=0.023 ) . CONCLUSIONS EX-4 immediate outcome results revealed favorable student responses to the program , increases in knowledge , and decreases in smoking relative to a st and ard care control condition PURPOSE To describe smoking initiation , and to investigate factors that predict the early initiation of smoking in schoolchildren using a longitudinal approach . METHODS A prospect i ve study of smoking habits of children from the third and fourth grade s through the eighth and ninth grade s. The initial study population was 1970 ; 79.8 % were white and 20.2 % were African-American . Children were classified as " nonsmokers , " " experimental smokers , " or " current smokers " at five time points over 6 years . Multivariate regression models examined relationships of demographic and developmental factors with smoking initiation . RESULTS Experimental smoking increased from 4 % at Grade s 3 - 4 to 42 % at Grade s 8 - 9 , and current smoking prevalence rose from 0.4 % to 9 % over the same period . The mean age of initiation of smoking was 12.3 years . Smoking initiation ( experimental smoking ) was significantly different by racial group , socioeconomic status ( SES ) , and pubertal development . White children and those of low SES were more likely to be experimental smokers , and also started earlier than African-American children and children of high SES . Once they started , white children advanced more rapidly to become current smokers . Boys had a higher prevalence of experimental smoking than girls at all time points . Children in rural areas were more likely than urban children to start smoking after age 12 years . Children who were at a higher pubertal stage than their peers were also more likely to experiment with smoking . CONCLUSIONS Race , SES , and pubertal stage are important predictors of initiation of smoking in schoolchildren . This study indicates a need for smoking prevention classes in elementary and middle school , especially in areas with large numbers of white and low-SES youth . Also , smoking cessation programs , as well as smoking prevention classes , would be useful for middle school and high school students To evaluate a multicultural smoking prevention curriculum , 16 schools were r and omized to receive the multicultural curriculum or a st and ard curriculum and program effects on 1-year smoking initiation among 1430 never smokers were assessed . Hispanic boys who received the multicultural curriculum were less likely to initiate smoking than were those who received the st and ard curriculum ; effects were insignificant among other groups . The prevention effect among Hispanic boys is encouraging , but additional research is needed to improve prevention effects among other groups We conducted a study of the effectiveness of an educational intervention design ed to modify risk factors associated with coronary heart disease among 3388 children in 37 schools in two demographically dissimilar areas ( the Bronx and Westchester County ) in and around New York City . Schools within each area were r and omly assigned to either intervention or nonintervention groups . In schools targeted for intervention , children in the fourth through eighth grade s were taught a teacher-delivered curriculum focusing on diet , physical activity , and cigarette smoking . Risk-factor levels were measured in all schools at base line and at four follow-up points . A total of 1769 of the children qualified for analysis of the intervention effect . After five years , the net mean change in plasma levels of total cholesterol was -1.7 mg per deciliter per year ( -0.04 mmol per liter ) ( 95 percent confidence interval , -2.7 to -0.7 mg per deciliter [ -0.07 to -0.02 mmol per liter ] ) in the Westchester County schools , or -8.5 mg per deciliter ( -0.22 mmol per liter ) ( 5.1 percent ) over a period of five years . In the schools in the Bronx , the net mean change was -1.0 mg per deciliter per year ( -0.03 mmol per liter ) ( 95 percent confidence interval , -2.3 to + 0.3 mg per deciliter [ -0.06 to + 0.01 mmol per -2.3 to + 0.3 mg per deciliter [ -0.06 to + 0.01 mmol per liter ] ) , or -5.0 mg per deciliter ( -0.13 mmol per liter ) ( 2.9 percent ) over a period of five years . Favorable trends in dietary intake and health knowledge were also observed , whereas the other targeted risk factors were not significantly altered . If these findings can be replicated , this will suggest that educational programs to modify coronary risk factors are feasible and may have a favorable ( albeit small ) effect on blood levels of cholesterol in children Mobilising Youth for Tobacco-Related Initiatives in India ( Project MYTRI ) is a r and omized community trial to prevent tobacco use among students in Grade s 6 through 9 in 32 private and government schools in Delhi and Chennai , India ( N = 12,484 ) . The project is a partnership between research ers and practitioners in the United States and India . This article describes the steps that were carried out to ensure that prior effective programs are appropriate and applicable to India . These steps involve ( a ) developing a conceptual behavioral intervention model , ( b ) ensuring the appropriateness of the model for urban India , ( c ) developing intervention strategies that modify factors in the model , ( d ) implementing the MYTRI program with more than 5,000 students , and ( e ) evaluating the process and outcomes of the intervention . Data to date suggest that this process has been successful , including high participation rates , teacher perceptions of appropriateness , and agreements for further implementation National survey data indicate that illicit drug use has steadily increased among American adolescents since 1992 . This upward trend underscores the need for identifying effective prevention approaches capable of reducing the use of both licit and illicit drugs . The present study examined long-term follow-up data from a large-scale r and omized prevention trial to determine the extent to which participation in a cognitive-behavioral skills-training prevention program led to less illicit drug use than for untreated controls . Data were collected by mail from 447 individuals who were contacted after the end of the 12th grade , 6.5 years after the initial pretest . Results indicated that students who received the prevention program ( Life Skills Training ) during junior high school reported less use of illicit drugs than controls . These results also support the hypothesis that illicit drug use can be prevented by targeting the use of gateway drugs such as tobacco and alcohol OBJECTIVE This study evaluated the efficacy of a version of Project EX that was adapted for implementation in the classroom context ( Project EX-4 ) . This paper reports the program outcomes based on pretest , six-month , and one-year follow-up surveys . METHODS An 8 session classroom-based curriculum was tested with a clustered r and omized controlled trial that involved a total of 1097 students in 6 program and 6 control alternative high schools . Weekly and monthly smoking was assessed at the three time points . Outcome effects were analyzed with multi-level r and om coefficients models . RESULTS Students in the program condition experienced a greater reduction in weekly smoking and monthly smoking , at 6- and -12-month follow-ups . The net change varied between -5.1 % and -7.6 % , comparing the program condition to the control condition . CONCLUSIONS The implementation of Project EX in a classroom setting produced decreases in smoking among students in the program , relative to those in the st and ard care control condition . It is likely that a classroom-based smoking prevention/cessation program can lead to lower overall smoking prevalence than a cessation program that is implemented in a school-based smoking cessation clinic format OBJECTIVES We assessed the effectiveness of a 5-year trial of a comprehensive school-based program design ed to prevent substance use , violent behaviors , and sexual activity among elementary-school students . METHODS We used a matched-pair , cluster-r and omized , controlled design , with 10 intervention schools and 10 control schools . Fifth- grade rs ( N = 1714 ) self-reported on lifetime substance use , violence , and voluntary sexual activity . Teachers of participant students reported on student ( N = 1225 ) substance use and violence . RESULTS Two-level r and om-effects count models ( with students nested within schools ) indicated that student-reported substance use ( rate ratio [ RR ] = 0.41 ; 90 % confidence interval [ CI ] = 0.25 , 0.66 ) and violence ( RR = 0.42 ; 90 % CI = 0.24 , 0.73 ) were significantly lower for students attending intervention schools . A 2-level r and om-effects binary model indicated that sexual activity was lower ( odds ratio = 0.24 ; 90 % CI = 0.08 , 0.66 ) for intervention students . Teacher reports substantiated the effects seen for student-reported data . Dose-response analyses indicated that students exposed to the program for at least 3 years had significantly lower rates of all negative behaviors . CONCLUSIONS Risk-related behaviors were substantially reduced for students who participated in the program , providing evidence that a comprehensive school-based program can have a strong beneficial effect on student behavior This paper describes development , over a five-year period , of the Hunter Region Health Promoting Schools Project in New South Wales ( NSW ) , Australia . The project implemented the principles and philosophy of the Health Promoting Schools concept and evaluated its effectiveness using a r and omized controlled trial involving 22 public secondary schools . An overview of the preliminary intervention model based on the health promoting schools philosophy and trialed in a pilot study is provided . The authors also outline barriers to , and difficulties in , implementing the philosophically based intervention model in the secondary school setting . The current intervention approach , which evolved over five years , is described in relation to the roles played by project team members and school communities . In addition , the authors outline guiding principles arising from the new approach which facilitated adoption of health promotion strategies in secondary school setting The present study provides an implementation , process , and immediate outcomes evaluation of the classroom component of Project Towards No Drug Abuse ( TND ) . This project involves development and evaluation of a school-based drug abuse prevention curriculum for continuation high school youth , who are at relatively high risk for drug abuse . Three r and omized conditions were evaluated : a st and ard care , classroom only , and classroom plus school-as-community . The latter condition was an enhanced school-based condition which involved outside-of-classroom meetings and activities . Implementation was high in both program conditions even though this was a higher risk context . Process evaluation data were favorable and did not vary between the two program conditions . Immediate outcomes data ( knowledge ) was higher in the two program conditions than in the st and ard care condition . Regarding the classroom program , addition of extra-classroom activities does not appear to alter the quality of delivery of the program The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) is a multisite intervention research study that builds on significant progress made in school health education research in the 1980s . The study has three phases : Phase I deals with study design , intervention , and measurement development , Phase II involves the main trial in 96 schools in four states , and Phase III focuses on analysis . The intervention program targets third-fifth grade students and focuses on multiple cardiovascular health behaviors , including eating habits , physical activity , and cigarette smoking . Classroom curricula , school environmental change , and family involvement programs are developed for each grade level and behavioral focus . This paper describes Phase II of CATCH with a rationale for cardiovascular health promotion with youth . The process of change that appears to be necessary for school-based health promotion and that will be tested in CATCH are presented as a framework to guide these efforts Despite the high rates of smoking-related cancers among black Americans , little is known about the type of smoking prevention program that might be effective with black youth . The current study pilot-tested a promising smoking prevention approach to determine its feasibility , acceptability , and effectiveness . A total of 608 students in nine predominantly black urban junior high schools were stratified by community and r and omly assigned to treatment and control conditions . Students in the treatment condition participated in a 12-session smoking prevention program which taught resistance skills and general life skills . Process data indicated that this prevention approach was feasible and acceptable to students , teachers , and administrators . Outcome data indicated that this program reduced the proportion of children who smoked in the past month by 56 percent , and it increased knowledge of the adverse consequences of smoking and normative expectations concerning adult and peer smoking . These results are discussed in terms of their implication s for prevention and modifications which might further strengthen the efficacy of this approach for urban black adolescents This exploratory study sought to determine if a popular school-based drug prevention program might be effective in schools that are making adequate yearly progress ( AYP ) . Thirty-four schools with grade s 6 through 8 in 11 states were r and omly assigned either to receive Project ALERT ( n = 17 ) or to a control group ( n = 17 ) ; of these , 10 intervention and nine control schools failed to make AYP . Students completed three self-report surveys . For lifetime cigarette use and 30-day alcohol use , Project ALERT was more effective in schools that made AYP . However , in these schools , Project ALERT negatively affected students ' lifetime marijuana use . This study provided some preliminary evidence that prevention programming may not work as well in poorer performing schools ; however , further exploration is needed Purpose . The Child and Adolescent Trial for Cardiovascular Health is a multi-site study of a school-based intervention design ed to reduce or prevent the development of risk factors for cardiovascular disease . The goal was to change ( or prevent ) related risk behaviors and the psychosocial variables that theoretically influence those behaviors . Design . A nested design was used in which schools served as the primary unit of analysis . Twenty-four schools participated at each of four sites ( Austin , San Diego , Minneapolis , and New Orleans ) . Each site had 10 control and 14 intervention schools . Setting and Subject . Ninety-six schools ( with more than 6000 students ) in the four sites were r and omized to three treatment conditions : control , school-based interventions , and school-plus-family interventions . The sample included approximately equal numbers of males and females and was 67.5 % white , 13.9 % African-American , 13.9 % Hispanic , and 4.7 % other . Measures . The psychosocial determinants measured included improvements in dietary knowledge , intentions , self-efficacy , usual behavior , perceived social reinforcement for healthy food choices , and perceived reinforcement and self-efficacy for physical activity . Results . The findings indicated significant improvements in all the psychosocial determinants measured ( p < .0001 ) . The results revealed a greater impact in the school-plus-family intervention schools for two determinants , usual dietary behavior and intentions to eat heart-healthy foods . Conclusions . These findings support theory-based interventions for changing selected psychosocial determinants of cardiovascular disease risk behavior among children Adolescent smoking prevalence is usually assessed via self-complete question naires . However , concern has been expressed about the validity of such self-report . One approach to increase validity involves the threat of biological validation , known as the bogus pipeline method (BPL).This study aim ed to assess the effects of BPL , using an expired air carbon monoxide monitor , and of question naire anonymity on student smoking self-report data . High school students ( n=801 ) were r and omly allocated to one of four conditions : anonymous question naire+BPL , named question naire+BPL , anonymous question naire without BPL and named question naire without BPL . Overall , 37 % of students agreed that question naires were a good way to obtain honest answers . In a logistic regression analysis , students in the BPL condition had significantly higher odds of reporting weekly smoking ( OR=1.83 95 % CI 1.27 - 2.65 ) and monthly smoking ( OR=1.66 95 % CI 1.21 - 2.28 ) but not of lifetime smoking compared with non-BPL students . Students in the named question naire condition had a significantly higher odds of reporting lifetime smoking ( OR=1.49 95 % CI 1.08 - 2.04 ) compared with anonymous students . Studies assessing current smoking patterns in adolescents should consider incorporating a BPL method Project SUCCESS is a selective and indicated substance use prevention program that targets high risk students in secondary school setting s. We evaluated the effects of Project SUCCESS on adolescents ' substance use immediately following program implementation , and again one year later . Two successive cohorts of alternative high schools were r and omly assigned to an intervention or control group , yielding seven schools per condition . Main outcomes included 30-day use of alcohol , marijuana , and illegal drugs excluding marijuana , and drinking to intoxication . We conducted exploratory analyses on 30-day cigarette use . Using Hierarchical Linear Modeling , we found that students in the control schools reported significantly less use of illegal drugs excluding marijuana than those in the intervention group at the first posttest ; however , this effect did not persist one year later . There were no other outcome effects of even a marginal nature . While results of this study do not provide evidence of Project SUCCESS ' effectiveness , students ' program exposure was low . It is possible that Project SUCCESS would perform better in schools with higher and more regular rates of attendance INTRODUCTION This study examined the distribution of psychosocial risk factors and prevalence of tobacco use among youth in urban India by gender . METHODS Data were obtained from a cross-sectional baseline survey of a group-r and omized tobacco intervention trial involving 6th and 8th grade rs from 32 schools in Delhi and Chennai ( N = 11,642 ) . Mixed-effects regression models were used to examine differences in the prevalence of tobacco use by gender , to determine how the relationship between current tobacco use and related psychosocial risk factors varied by gender , to compare the distribution of risk factors by gender , and to determine if any of these relationships varied by grade level or school type . RESULTS 14.7 % of girls and 21.1 % of boys reported ever-use of tobacco . The psychosocial risk profile for tobacco use was remarkably similar for boys and girls , though some differences were apparent . For example , exposure to advertising and beliefs about social effects of use were significant risk factors for girls but not for boys . Across the board , girls showed lower risk for all psychosocial risk factors , except for perceived prevalence of chewing and smoking , for which girls had higher risk compared with boys . DISCUSSION While the psychosocial risk profile for boys suggests a more vulnerable population for tobacco use , the closing gap in tobacco use between boys and girls indicates a need to examine possible differences in psychosocial risk factors . This study reports that there are subtle , but important , differences in risk factors between genders , having implication s for gender-specific intervention development INTRODUCTION Smoking prevention interventions have been shown to be effective in reducing smoking prevalence in the United States . Further work is needed to address smoking in China , where over one third of the world 's current smokers reside . China , with more than 60 % of the male population being smokers , also presents a unique opportunity to test cognitive processes involved in depression , social influences , and smoking . Adolescents at-risk for developing depression may process social information differently from low-risk counterparts . METHODS The Wuhan Smoking Prevention Trial was a school-based longitudinal r and omized controlled trial aim ed at preventing initiation and escalation of adolescent smoking behaviors . Thous and three hundred and ninety-one male seventh- grade students were assessed with a 200-item paper- and -pencil baseline survey , and it was readministered 1 year later following program implementation . RESULTS Friend prevalence estimates were significantly higher among 30-day smokers and among those at highest risk for depression symptoms . The program appeared to be successful in changing the perception of friend smoking prevalence only among adolescents with a comorbidity of high scores of depression symptoms and who have experimented previously with smoking . This Program x Comorbidity interaction on perceived friend smoking prevalence was significant in predicting 30-day smoking 1 year after program implementation . CONCLUSIONS This study provides evidence that those adolescents with high levels of depressive symptoms may be more sensitive to social influences associated with smoking prevalence . Individual Disposition x Social Environmental Influences may be important when developing future effective prevention programming Project EX is an eight-session teen school-based clinic tobacco use cessation program that involves the inclusion of enjoyable , motivating activities ( " games , " " talk show , " and alternative medicine-type ) to try to enhance quit rates among youth . This clinic program was tested in a three-group experimental design : clinic-only , clinic plus a school-as-community ( SAC ) component , and st and ard care control . Eighteen schools were assigned to the three conditions using a r and omized block design . A total of 335 smokers participated in the study , making this the largest controlled teen smoking cessation field trial conducted to date . Seventeen percent of the smokers enrolled in the clinics had reports of having quit smoking for at least the last 30 days at 3-month follow-up ( 5 months after the program quit day ) , compared to only 8 % of the control condition smokers over than same time period . The Project EX clinic component appears to be an effective means of tobacco use cessation among teens BACKGROUND The Good Behavior Game ( GBG ) is a classroom behavior management strategy focused on socializing children to the role of student and aim ed at reducing early aggressive , disruptive behavior , a confirmed antecedent to service use . The GBG was tested in a r and omized field trial in 19 elementary schools with two cohorts of children as they attended first and second grade s. This article reports on the impact of the GBG on service use through young adulthood . METHODS Three or four schools in each of five urban areas were matched and r and omly assigned to one of three conditions : ( 1 ) GBG , ( 2 ) an intervention aim ed at academic achievement , or ( 3 ) the st and ard program of the school system . Children were assigned to classrooms to ensure balance , and teachers and classrooms were r and omly assigned to intervention conditions . RESULTS This study provides evidence of a positive impact of a universal preventive intervention on later service use by males , although not by females , for problems with emotions , behavior , or drugs or alcohol . For both cohorts , males in GBG classrooms who had been rated as highly aggressive , disruptive by their teachers in the fall of first grade had a lower rate of school-based service use than their counterparts in control classrooms . REPLICATION : The design employed two cohorts of students . Although both first- and second- grade teachers received less training and support with the second cohorts of students than with the first cohort , the impact of GBG was similar across both cohorts This article reports adolescent substance use outcomes of universal family and school preventive interventions 5(1/2 ) years past baseline . Participants were 1677 7th grade students from schools ( N=36 ) r and omly assigned to the school-based Life Skills Training plus the Strengthening Families Program : For Parents and Youth 10 - 14 ( LST+SFP 10 - 14 ) , LST-alone , or a control condition . Self-reports were collected at baseline , 6 months later following the interventions , then yearly through the 12th grade . Measures included initiation-alcohol , cigarette , marijuana , and drunkenness , along with a Substance Initiation Index (SII)- and measures of more serious use-frequency of alcohol , cigarette , and marijuana use , drunkenness frequency , monthly poly-substance use , and advanced poly-substance use . Analyses ruled out differential attrition . For all substance initiation outcomes , one or both intervention groups showed significant , positive point-in-time differences at 12th grade and /or significant growth trajectory outcomes when compared with the control group . Although no main effects for the more serious substance use outcomes were observed , a higher-risk sub sample demonstrated significant , positive 12th grade point-in-time and /or growth trajectory outcomes for one or both intervention groups on all measures . The observed pattern of results likely reflects a combination of predispositions of the higher-risk sub sample , the timing of the interventions , and baseline differences between experimental conditions favoring the control group Purpose . This study examined whether brief intervention strategies founded on the Behavior-Image Model and addressing positive images of college and career success could be potentially efficacious in impacting multiple health habits of high-risk adolescents transitioning into adulthood . Design . Participants were stratified by grade level and drug use and individually r and omized to one of the three Plan for Success interventions , with baseline and 1 month postintervention data collection s. Setting . A large , relatively diverse suburban school in northeast Florida . Subjects . A total of 375 11th and 12th grade students participated during the spring semester 2006 . Intervention . Three interventions studied included : ( 1 ) Goal Survey , ( 2 ) Goal Survey plus Contract , or ( 3 ) Goal Survey plus Consult . Measures . Outcome measures included multiple health risk , health promotion , and personal development behaviors , as well as image and belief measures . Analysis . Repeated- measures MANOVAs and ANOVAs were used to examine intervention effects . Results . MANOVAs were significant for alcohol use , F(4,328 ) = 6.33 , p = .001 ; marijuana use , F(4,317 ) = 3.72 , p = .01 ; exercise , F(3,299 ) = 4.28 , p = .01 ; college preparation , F(2,327 ) = 6.26 , p = .001 ; and career preparation , F(2,329 ) = 6.17 , p = .001 , with most behaviors improving over time , whereas group-by-time interaction effects were found for nutrition habits , F(6,652 ) = 2.60 , p = .02 ; and career preparation , F(4,658 ) = 3.26 , p = .01 , favoring the consultation . Conclusion . Brief interventions founded on the Behavior-Image Model may have potential to improve selected health and personal development habits among older adolescents |
1,034 | 28,621,260 | The use of ALK-TKIs significantly increases the risk of developing high- grade ILD and QTc prolongation in lung cancer patients . | BACKGROUND To conduct a systematic review and meta- analysis to assess the overall incidence and risk of interstitial lung disease ( ILD ) and QTc prolongation associated with anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors ( -TKIs ) in non-small-cell lung cancer ( NSCLC ) patients . | 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 ; 533 placebo ) . Median survival for patients treated with erlotinib was 10.6 v 10.5 months for placebo ( hazard ratio , 0.99 ; 95 % CI , 0.86 to 1.16 ; P = .95 ) . There was no difference in OR or median TTP . Patients who reported never smoking ( 72 erlotinib ; 44 placebo ) experienced improved OS in the erlotinib arm ( 22.5 v 10.1 months for placebo ) , though no other prespecified factors showed an advantage in OS with erlotinib . Erlotinib and placebo arms were equivalent in adverse events ( except rash and diarrhea ) . CONCLUSION Erlotinib with concurrent carboplatin and paclitaxel did not confer a survival advantage over carboplatin and paclitaxel alone in patients with previously untreated advanced NSCLC . Never smokers treated with erlotinib and chemotherapy seemed to experience an improvement in survival and will undergo further investigation in future r and omized trials BACKGROUND ALK fusion genes occur in a subset of non-small-cell lung cancers ( NSCLCs ) . We assessed the tolerability and activity of crizotinib in patients with NSCLC who were prospect ively identified to have an ALK fusion within the first-in-man phase 1 crizotinib study . METHODS In this phase 1 study , patients with ALK-positive stage III or IV NSCLC received oral crizotinib 250 mg twice daily in 28-day cycles . Endpoints included tumour responses , duration of response , time to tumour response , progression-free survival ( PFS ) , overall survival at 6 and 12 months , and determination of the safety and tolerability and characterisation of the plasma pharmacokinetic profile of crizotinib after oral administration . Responses were analysed in evaluable patients and PFS and safety were analysed in all patients . This study is registered with Clinical Trials.gov , number NCT00585195 . FINDINGS Between Aug 27 , 2008 , and June 1 , 2011 , 149 ALK-positive patients were enrolled , 143 of whom were included in the response-evaluable population . 87 of 143 patients had an objective response ( 60·8 % , 95 % CI 52·3 - 68·9 ) , including three complete responses and 84 partial responses . Median time to first documented objective response was 7·9 weeks ( range 2·1 - 39·6 ) and median duration of response was 49·1 weeks ( 95 % CI 39·3 - 75·4 ) . The response rate seemed to be largely independent of age , sex , performance status , or line of treatment . Median PFS was 9·7 months ( 95 % CI 7·7 - 12·8 ) . Median overall survival data are not yet mature , but estimated overall survival at 6 and 12 months was 87·9 % ( 95 % CI 81·3 - 92·3 ) and 74·8 % ( 66·4 - 81·5 ) , respectively . 39 patients continued to receive crizotinib for more than 2 weeks after progression because of perceived ongoing clinical benefit from the drug ( 12 for at least 6 months from the time of their initial investigator-defined disease progression ) . Overall , 144 ( 97 % ) of 149 patients experienced treatment-related adverse events , which were mostly grade 1 or 2 . The most common adverse events were visual effects , nausea , diarrhoea , constipation , vomiting , and peripheral oedema . The most common treatment-related grade 3 or 4 adverse events were neutropenia ( n=9 ) , raised alanine aminotransferase ( n=6 ) , hypophosphataemia ( n=6 ) , and lymphopenia ( n=6 ) . INTERPRETATION Crizotinib is well tolerated with rapid , durable responses in patients with ALK-positive NSCLC . There seems to be potential for ongoing benefit after initial disease progression in this population , but a more formal definition of ongoing benefit in this context is needed BACKGROUND ALK-rearranged non-small-cell lung cancer ( NSCLC ) is sensitive to ALK tyrosine kinase inhibitors ( ALK inhibitors ) such as crizotinib , but resistance invariably develops , often with progression in the brain . Ceritinib is a more potent ALK inhibitor than crizotinib in vitro , crosses the blood-brain barrier in vivo , and shows clinical responses in patients with crizotinib-resistant disease . We aim ed to assess whole-body activity of ceritinib in both ALK inhibitor-pretreated and ALK inhibitor-naive patients with ALK-rearranged NSCLC . METHODS ASCEND-1 was an open-label , phase 1 trial that recruited patients from 20 academic hospitals or cancer centres in 11 countries in Europe , North America , and Asia-Pacific . Eligible patients were aged 18 years or older with ALK-rearranged locally advanced or metastatic cancer that had progressed despite st and ard therapy ( or for which no effective st and ard therapy existed ) , who had at least one measurable lesion at baseline . The primary objective ( to determine the maximum tolerated dose ) has been reported previously . This up date d analysis includes all patients with ALK-rearranged NSCLC given oral ceritinib at the recommended dose of 750 mg/day in the dose-escalation and expansion phases . Here we report the secondary outcomes of overall response , duration of response , and progression-free survival , analysed in all patients who received at least one 750 mg dose of ceritinib . Exploratory analyses included retrospective analysis of intracranial activity by independent neuroradiologists , in patients with untreated or locally treated neurologically stable brain metastases at baseline . Safety was assessed in all patients who received at least one dose of ceritinib . This study is no longer recruiting patients ; however , treatment and follow-up are ongoing . This study is registered with Clinical Trials.gov , number NCT01283516 . FINDINGS Between Jan 24 , 2011 , and July 31 , 2013 , 255 patients were enrolled and received at least one dose of ceritinib 750 mg/day , of whom 246 had ALK-rearranged NSCLC . At data cutoff ( April 14 , 2014 ) , median follow-up was 11·1 months ( IQR 6·7 - 15·2 ) and 147 ( 60 % ) patients had discontinued treatment , 98 ( 40 % ) as a result of disease progression . An overall response was reported in 60 ( 72 % [ 95 % CI 61 - 82 ] ) of 83 ALK inhibitor-naive patients and 92 ( 56 % [ 49 - 64 ] ) of 163 ALK inhibitor-pretreated patients . Median duration of response was 17·0 months ( 95 % CI 11·3-non-estimable [ NE ] ) in ALK inhibitor-naive patients and 8·3 months ( 6·8 - 9·7 ) in ALK inhibitor-pretreated patients . Median progression-free survival was 18·4 months ( 95 % CI 11·1-NE ) in ALK inhibitor-naive patients and 6·9 months ( 5·6 - 8·7 ) in ALK inhibitor-pretreated patients . Of 94 patients with retrospectively confirmed brain metastases and at least one post-baseline MRI or CT tumour assessment , intracranial disease control was reported in 15 ( 79 % [ 95 % CI 54 - 94 ] ) of 19 ALK inhibitor-naive patients and in 49 ( 65 % [ 54 - 76 ] ) of 75 ALK inhibitor-pretreated patients . Of these 94 patients , 11 had measurable brain lesions and no previous radiotherapy to the brain , six of whom achieved a partial intracranial response . Serious adverse events were recorded in 117 ( 48 % ) of 246 patients . The most common grade 3 - 4 laboratory abnormalities were increased alanine aminotransferase ( 73 [ 30 % ] patients ) and increased aspartate aminotransferase ( 25 [ 10 % ] ) . The most common grade 3 - 4 non-laboratory adverse events were diarrhoea and nausea , both of which occurred in 15 ( 6 % ) patients . Two on-treatment deaths during the study were deemed to be related to study drug by the investigators , one due to interstitial lung disease and one as a result of multiorgan failure that occurred in the context of infection and ischaemic hepatitis . INTERPRETATION The durable whole-body responses reported , together with the intracranial activity , support a clinical benefit for treatment with ceritinib in patients with ALK-rearranged NSCLC who have received crizotinib , or as an alternative to crizotinib . A confirmatory phase 2 clinical trial is ongoing to assess ceritinib activity in patients with ALK-rearranged NSCLC and brain or leptomeningeal metastases . FUNDING Novartis Pharmaceuticals Corporation |
1,035 | 24,487,610 | 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 . | BACKGROUND The authors conducted a systematic review to assess the efficacy and safety of fluoride toothpaste use in children younger than 6 years . | 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 this double-blind trial , the anticaries effectiveness of a test toothpaste formulated for young children with 550 ppm F was compared with that of a positive control toothpaste containing 1055 ppm fluoride . More than 3000 2-year-old children were enrolled in the study and after 3 years of toothpaste use , 2177 ( 72 per cent ) were examined . From a clinical and radiographic assessment , more than half the children were found to be caries free and only 32 ( 1.5 per cent ) had evidence of rampant caries . There appeared to be little or no difference between children who had used test or control pastes , either in caries or in plaque levels . On the basis of this clinical trial the experimental toothpaste with 550 ppm fluoride would appear to have a similar anticaries efficacy to that of the control toothpaste . Differences were seen in relation to sex of the child and to social class . Girls had lower levels of plaque than boys but more carious teeth . Children from families in higher social classes had fewer carious teeth and lower levels of plaque OBJECTIVE This paper reports the results of a community trial to assess the effects of a multi-stage dental health promotion programme in reducing Early Childhood Caries ( ECC ) . RESEARCH DESIGN Two health districts ( Primary Care Groups ) were matched for dental disease levels and socio-demographic factors . One was r and omly allocated to be the test Primary Care Group ( PCG ) , the other the control PCG . Children in the test PCG received a series of interventions to support positive dental health behaviour from the age of 8 to 32 months . Interviews were conducted with parents of children aged 21 months and clinical examinations were undertaken on a larger cohort of children aged 3 - 4 years in test and control PCGs . SETTING The interventions were gift bags containing a trainer cup , toothpaste containing 1,450 ppm F and toothbrush , and advice given to the children 's parents on attendance at design ated clinics and medical practice s and further paste and brushes posted to the children 's homes . Parents were interviewed on the telephone . Examinations took place at Children 's Centres and nursery departments attached to primary schools . OUTCOME MEASURES Severity and prevalence of ECC and general caries and proportion of parents reporting adopting dentally healthy behaviours . RESULTS In the test PCG the prevalence of ECC in children who had received the interventions was 16.6 % compared with 23.5 % of children in the control area , a reduction of 29 % ( p=0.003 ) . The mean dmft ( 1.17 ) and prevalence of general caries experience ( 28.7 % ) in the test children were also significantly lower than for children in the control PCG ( 1.72 : 39.2 % ) ( p=0.001 ) . Analysis from a community perspective , which included data from all children examined in both areas , showed the prevalence of ECC in the test and control PCGs was 21.3 % and 22.8 % respectively and the mean dmft 1.47 and 1.72 . The proportion with general caries experience remained statistically significant in favour of the test area 33.8 % vs 39.9 % ( p=0.01 ) . Parents in the test PCG were more likely to report cessation of bottle use ( 33 % vs 18 % ) , use of sugar-free drinks ( 49 % vs 24 % ) , commencement of brushing before first birthday ( 45 % vs 27 % ) and twice daily brushing ( 52 % vs 34 % ) . CONCLUSION The parents who received this multi-stage intervention were more likely to report adoption of three positive oral health behaviours ; using a trainer cup from one year of age , using safe drinks and brushing twice daily with a fluoride toothpaste . The programme failed to reduce the prevalence of ECC in the community but the prevalence of ECC and general caries experience among the children who participated was less than among children in the control PCG Background : Low-fluoride dentifrices have been suggested as alternatives to reduce dental fluorosis risk , but there is no consensus regarding their clinical effectiveness , which has been suggested to be increased when their pH is acidic . Aims : This single-blind r and omized clinical trial evaluated the caries increment during the use of a low-fluoride acidic liquid dentifrice . Methods : Four-year-old schoolchildren ( n = 1,402 ) living in a fluori date d area ( 0.6–0.8 ppm F ) were r and omly allocated to 4 groups differing according to the type of dentifrice used over a 20-month period . Group 1 ( n = 345 ) : liquid dentifrice , 1,100 ppm F , pH 4.5 . Group 2 ( n = 343 ) : liquid dentifrice , 1,100 ppm F , pH 7.0 . Group 3 ( n = 354 ) : liquid dentifrice , 550 ppm F , pH 4.5 . Group 4 ( n = 360 ) : toothpaste , 1,100 ppm F , pH 7.0 . At baseline and after 20 months , clinical examinations were conducted ( dmfs index ) and caries increment was calculated . Data were analysed by GLM procedure using classrooms ( cluster ) as unit of analysis ( p < 0.05 ) . Results : The mean ± SD ( 95 % CI ) net increments found were as follows . Group 1 : 2.06 ± 2.38 ( 1.8–2.3 ) ; group 2 : 2.08 ± 2.87 ( 1.7–2.4 ) ; group 3 : 2.05 ± 2.79 ( 1.7–2.4 ) , and group 4 : 2.08 ± 2.34 ( 1.8–2.4 ) . No significant differences were detected among the groups . Conclusion : In a population with high caries risk living in a fluori date d area , as the selected sample , and according to the present protocol , the low-fluoride acidic liquid dentifrice seems to lead to similar caries progression rates as conventional 1,100 ppm F toothpaste OBJECTIVES To determine the effect of oral health education carried out by a specially trained health visitor on the dental health of young children . DESIGN AND SETTING Children , who were recruited during their 8-month distraction-hearing test , were r and omly allocated to intervention and control groups . A home visit by the health visitor was arranged to parents in the intervention group who were given dental health advice . A second home visit , when the child was about 20 months old , focused on a completed diet record sheet and discussion s about what and when the child was eating and drinking . Children in the intervention group received a toothbrush and toothpaste containing 440 ppm fluoride at both visits while those in the control group received the level of care usually provided by health visitors in the area . The children 's teeth were examined when they were three years old and two years later as part of a census survey of 5-year-old children in the area . MAIN OUTCOME MEASURES The numbers of decayed , missing and filled tooth surfaces . RESULTS 251 children were recruited to the control group and 250 to the intervention group . At age three , they were examined ; the mean dmfs scores were 2.19 ( 95 % Confidence Interval : 1.41 - 2.97 ) in the control group ( n = 171 ) and 2.03 ( CI : 1.39 - 2.67 ) in the intervention group ( n = 181 ) . During the census survey 276 of the children in the study were examined at school . At this age the mean dmfs scores were 4.84 ( CI : 3.39 - 6.29 ) in the control group ( n = 129 ) and 3.99 ( CI : 2.54 - 5.04 ) in the intervention group ( n = 147 ) . However , the mean dmfs of the remaining 2,253 children who were examined was 5.94 ( CI : 5.55 - 6.33 ) . CONCLUSIONS No statistically significant differences in mean dmfs scores were found between the control and intervention groups of children , although , as the children grew older , the gap between them widened . However , the mean dmfs score of other 5-year-olds in the area was significantly worse than that of children in the intervention group . Asking the control parents to take part in the study and examining their children at three years may have had an effect on their dental health status and have made it more difficult to detect any differences achieved by the programme This study aim ed to evaluate the risk-benefit balance of several fluoride exposures . Fluoride exposure history of r and omly selected children was collected for calculation of exposure to fluori date d water , toothpaste , and other fluoride sources . We evaluated the risk-benefit balance of fluoride exposure by comparing dental fluorosis on maxillary central incisors , recorded at the time of the study with the use of the Thylstrup and Fejerskov Index , and deciduous caries experience , recorded at age six years , of the same group of South Australian children who were from 8 to 13 years old in 2002–03 . Population Attributable Risk for fluorosis and Population Prevented Fraction for caries were estimated . Fluorosis prevalence was found to be 11.3 % ; caries prevalence , 32.3 % ; mean dmfs , 1.57 ( SD 3.3 ) . Exposure to fluori date d water was positively associated with fluorosis , but was negatively associated with caries . Using 1000-ppm-F toothpaste ( compared with 400- to 550-ppm-F toothpaste ) and eating/licking toothpaste were associated with higher risk of fluorosis without additional benefit in caries protection . Evaluation of the risk-benefit balance of fluoride exposure provides evidence to assist in the formulation of appropriate guidelines for fluoride use Caries in China appears to be a significant problem , especially among preschool children . The effect of caries prevention in the primary teeth of preschool children through the use of fluori date d dentifrices and prevention programs has not been widely addressed . The purpose of this study was to examine the caries preventive effects of an 1100 ppm sodium fluoride dentifrice used in the context of a kindergarten-based oral health program compared to a matched placebo dentifrice in the absence of a kindergarten-based oral health program . This was a r and omized , placebo-controlled , examiner-blind , two-year caries study . A population of 1,334 preschool school children , three years of age , was recruited from 24 school kindergartens in Huairoi and Miyun counties , located approximately 60 kilometers northeast of Beijing , China . Classrooms were stratified based on mean baseline dmfs scores derived from the visual-tactile baseline examination , and r and omly assigned to one of the two dentifrice treatment groups : 0.243 % sodium fluoride ( 1100 ppm fluoride ion ) or placebo ( 0 ppm fluoride ion ) . Children attending the schools participating in the program brushed twice a day ( morning and afternoon ) at school under the supervision of classroom teachers during the school week . The children r and omized to schools receiving the placebo dentifrice were supplied with toothbrushes and dentifrice for ad libitum use at home and did not participate in the school program or supervised classroom brushing . For the primary examiner , the two-year caries increment data demonstrated evidence of anticaries efficacy for the sodium fluoride dentifrice/school program group as compared to the placebo/no school program group . In the evaluable subset , the 1100 ppm fluoride treatment group had a 20.7 % reduction in dmfs compared to the placebo treatment group , that was statistically significant ( p = 0.004 ) . The secondary examiner observed a similar overall treatment effect , as the 1100 ppm fluoride treatment group had an 22.1 % reduction in dmfs compared to the placebo treatment group that was statistically significant ( p = 0.014 ) . In contrast to the primary examiner , there was a county-by-treatment interaction for the secondary examiner 's results necessitating that the counties be examined independently . In Miyun county , the sodium fluoride/school program group had a 39.9 % reduction in caries compared to the placebo/no program group that was statistically significant ( p = 0.001 ) . In Huairou county , the sodium fluoride/school program group had a 6.8 % reduction in caries compared to the placebo/no program group that was not statistically significant ( p > 0.05 ) . These results demonstrate that fluoride in conjunction with increased dental awareness can deliver important reductions in caries in preschool children OBJECTIVES To evaluate the effect of a 2-year oral health education and caries prevention program implemented in kindergartens in China . METHODS Seven hundred and thirty-one 3-year-old children were recruited from 10 kindergartens in Miyun County , Beijing , China . The kindergartens were r and omly divided into two groups . Oral health education was provided to teachers in the test kindergartens every 3 months . Oral health education sessions were conducted for the test children monthly and for their parents semiannually . Children in the test kindergarten brushed their teeth twice daily with fluori date d toothpaste ( 1100 ppm F- ) in their kindergarten under the supervision of teachers during weekdays . No oral health education session and no supervised tooth brushing activities were carried out in the control kindergartens . A clinical examination of the study children and a question naire survey of their parents were conducted at baseline and after a 2-year program . RESULTS Five hundred and fourteen children remained in the study after 2 years . The mean caries increments of the test group ( n = 258 ) and the control group ( n = 256 ) were 2.47 and 3.56 dmfs , respectively . The reduction in dmfs increment was 30.6 % ( P = 0.009 ) . At the evaluation , a significantly higher percentage of children in the test group than in the control group reported brushing their teeth twice a day ( 87.6 % vs. 69.0 % ; P < 0.001 ) . Parents of children in the test group had better oral health knowledge and attitude than the parents of children in the control group . CONCLUSION This oral health education program was effective in establishing good oral health habits among preschool children and in increasing oral health knowledge of their parents , in conjunction with supervised daily tooth brushing with fluori date d toothpaste , which could reduce the development of new dental caries in preschool children in China |
1,036 | 28,433,640 | Conclusions : Early evidence suggests that partial gl and ablation is a safe treatment option for men with localized disease . | Purpose : Advances in prostate imaging , biopsy and ablative technologies have been accompanied by growing enthusiasm for partial gl and ablation , particularly using high‐intensity focused ultrasound , to treat prostate cancer .
Preserving noncancerous prostate tissue and minimizing damage to the neurovascular bundles and external urethral sphincter may improve functional outcomes . | 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 or greater tumors while simultaneously mitigating the detection of lower grade disease . The gold st and ard for cancer detection in primary biopsy is a combination of systematic and targeted cores PURPOSE Men with localized prostate cancer currently face a number of treatment options that treat the entire prostate . These can cause significant sexual and urinary side effects . Focal therapy offers a novel strategy that targets the cancer rather than the prostate in an attempt to preserve tissue and function . MATERIAL S AND METHODS A prospect i ve , ethics committee approved trial was conducted to determine the side effects of focal therapy using high intensity focused ultrasound . Multiparametric magnetic resonance imaging ( T2-weighted , dynamic contrast enhanced , diffusion-weighted ) and template transperineal prostate mapping biopsies were used to identify unilateral disease . Genitourinary side effects and quality of life outcomes were assessed using vali date d question naires . Posttreatment biopsies were performed at 6 months and followup was completed to 12 months . RESULTS A total of 20 men underwent high intensity focused ultrasound hemiablation . Mean age was 60.4 years ( SD 5.4 , range 50 to 70 ) with mean prostate specific antigen 7.3 ng/ml ( SD 2.8 , range 3.4 to 11.8 ) . Of the men 25 % had low risk and 75 % had intermediate risk cancer . Return of erections sufficient for penetrative sex occurred in 95 % of men ( 19 of 20 ) . In addition , 90 % of men ( 18 of 20 ) were pad-free , leak-free continent while 95 % were pad-free . Mean prostate specific antigen decreased 80 % to 1.5 ng/ml ( SD 1.3 ) at 12 months . Of the men 89 % ( 17 of 19 , 1 refused biopsy ) had no histological evidence of any cancer , and none had histological evidence of high volume or Gleason 7 or greater cancer in the treated lobe . In addition , 89 % of men achieved the trifecta status of pad-free , leak-free continence , erections sufficient for intercourse and cancer control at 12 months . CONCLUSIONS Our results appear sufficiently promising to support the further evaluation of focal therapy as a strategy to decrease some of the harms and costs associated with st and ard whole gl and treatments PURPOSE To evaluate the long-term efficacy of prostate cancer control and complication rates , in the elderly , after focal therapy with high-intensity focused ultrasound ( HIFU ) . MATERIAL S AND METHODS Between June 1997 and March 2000 , patients with localized prostate cancer were included into a focal therapy protocol . Inclusion criteria were : PSA ≤ 10 ng/mL , ≤ 3 positive biopsies with only 1 lobe involved , clinical stage ≤ T2a , Gleason score ≤ 7 ( 3 + 4 ) , negative CT scan and bone scan . Hemi-ablation of the prostate was performed with the Ablatherm ® device . Survival , complication rates and urinary continence were evaluated . Control biopsies were performed at 1 year . Treatment failure was defined as a positive biopsy or need for salvage therapy . RESULTS Twelve patients with a mean age 70 years were included . Median follow-up was 10 years . Control prostate biopsies were negative in 11/12 ( 91 % ) patients . Overall survival was 83 % ( 10/12 ) and cancer specific survival was 100 % at 10 years . Two patients died from other causes . Recurrence free survival was 90 % ( 95 % CI ; 0.71 - 1 ) at 5 years , and 38 % ( 95 % CI ; 0.04 - 0.73 ) at 10 years . Five patients had salvage therapy with repeat HIFU ( n = 1 ) or hormonal therapy ( n = 4 ) and all salvage patients were alive at 10 years . No patients developed lymph node or bone metastasis . No patients suffered from urinary incontinence . International Prostate Symptom Score was stable at 1 year . Complications included two urinary tract infections and one episode of acute urinary retention . CONCLUSIONS Hemi-prostate ablation with HIFU can be safely performed in selected elderly patients with adequate long-term cancer control and low complication rates . Results from larger prospect i ve studies using improved imaging techniques and extensive biopsy protocol s are awaited Summary Background Radical whole-gl and therapy can lead to significant genitourinary and rectal side-effects for men with localised prostate cancer . We report on whether selective focal ablation of unifocal and multifocal cancer lesions can reduce this treatment burden . Methods Men aged 45–80 years were eligible for this prospect i ve development study if they had low-risk to high-risk localised prostate cancer ( prostate specific antigen [ PSA ] ≤15 ng/mL , Gleason score ≤4 + 3 , stage ≤T2 ) , with no previous and rogen deprivation or treatment for prostate cancer , and who could safely undergo multiparametric MRI and have a general anaesthetic . Patients received focal therapy using high-intensity focused ultrasound , delivered to all known cancer lesions , with a margin of normal tissue , identified on multiparametric MRI , template prostate-mapping biopsies , or both . Primary endpoints were adverse events ( serious and otherwise ) and urinary symptoms and erectile function assessed using patient question naires . Analyses were done on a per- protocol basis . This study is registered with Clinical Trials.gov , number NCT00561314 . Findings 42 men were recruited between June 27 , 2007 , and June 30 , 2010 ; one man died from an unrelated cause ( pneumonia ) 3 months after treatment and was excluded from analyses . After treatment , one man was admitted to hospital for acute urinary retention , and another had stricture interventions requiring hospital admission . Nine men ( 22 % , 95 % CI 11–38 ) had self-resolving , mild to moderate , intermittent dysuria ( median duration 5·0 days [ IQR 2·5–18·5 ] ) . Urinary debris occurred in 14 men ( 34 % , 95 % CI 20–51 ) , with a median duration of 14·5 days ( IQR 6·0–16·5 ) . Urinary tract infection was noted in seven men ( 17 % , 95 % CI 7–32 ) . Median overall International Index of Erectile Function-15 ( IIEF-15 ) scores were similar at baseline and at 12 months ( p=0·060 ) , as were median IIEF-15 scores for intercourse satisfaction ( p=0·454 ) , sexual desire ( p=0·644 ) , and overall satisfaction ( p=0·257 ) . Significant deteriorations between baseline and 12 months were noted for IIEF-15 erectile ( p=0·042 ) and orgasmic function ( p=0·003 ) . Of 35 men with good baseline function , 31 ( 89 % , 95 % CI 73–97 ) had erections sufficient for penetration 12 months after focal therapy . Median UCLA Exp and ed Prostate Cancer Index Composite ( EPIC ) urinary incontinence scores were similar at baseline as and 12 months ( p=0·045 ) . There was an improvement in lower urinary tract symptoms , assessed by International Prostate Symptom Score ( IPSS ) , between baseline and 12 months ( p=0·026 ) , but the IPSS- quality of life score showed no difference between baseline and 12 months ( p=0·655 ) . All 38 men with no baseline urinary incontinence were leak-free and pad-free by 9 months . All 40 men pad-free at baseline were pad-free by 3 months and maintained pad-free continence at 12 months . No significant difference was reported in median Trial Outcomes Index scores between baseline and 12 months ( p=0·113 ) but significant improvement was shown in median Functional Assessment of Cancer Therapy (FACT)-Prostate ( p=0·045 ) and median FACT-General scores ( p=0·041 ) . No histological evidence of cancer was identified in 30 of 39 men biopsied at 6 months ( 77 % , 95 % CI 61–89 ) ; 36 ( 92 % , 79–98 ) were free of clinical ly significant cancer . After retreatment in four men , 39 of 41 ( 95 % , 95 % CI 83–99 ) had no evidence of disease on multiparametric MRI at 12 months . Interpretation Focal therapy of individual prostate cancer lesions , whether multifocal or unifocal , leads to a low rate of genitourinary side-effects and an encouraging rate of early absence of clinical ly significant prostate cancer . Funding Medical Research Council ( UK ) , Pelican Cancer Foundation , and St Peters Trust PURPOSE Anxiety may serve as a major barrier to participation in active surveillance . Intolerance of uncertainty , that is the tendency to perceive the potential for negative events as threatening , has been linked to cancer related worry . Accordingly we explored prospect ively the relationship of intolerance of uncertainty with anxiety along with other clinical factors among men treated with active surveillance for prostate cancer . MATERIAL S AND METHODS A total of 119 men with D'Amico low risk prostate cancer participating in active surveillance completed the HADS ( Hospital Anxiety and Depression Scale ) , MAX-PC ( Memorial Anxiety Scale for Prostate Cancer ) , IUS ( Intolerance of Uncertainty Scale ) and I-PSS ( International Prostate Symptom Score ) surveys from 2011 to 2014 . We evaluated the relationship between anxiety and IUS score after adjusting for patient characteristics , cancer information and I-PSS using bivariable and multivariable analyses . RESULTS Of the men 18 ( 15.1 % ) and 17 ( 14.3 % ) reported clinical ly significant anxiety on the generalized and prostate cancer specific scales , respectively . On bivariable analysis men with moderate/severe urinary symptoms and higher IUS scores reported more generalized and prostate cancer specific anxiety than men with mild urinary symptoms and lower IUS scores , respectively ( p ≤0.008 ) . Men with depressive symptoms ( p = 0.024 ) or a family history of prostate cancer ( p = 0.006 ) experienced greater generalized anxiety . On multivariable analysis IUS score was significantly associated with generalized and prostate cancer specific anxiety ( OR 1.22 , 95 % CI 1.09 - 1.38 and OR 1.29 , 95 % CI 1.13 - 1.49 , respectively ) while moderate/severe urinary symptoms were associated with prostate cancer specific anxiety ( OR 6.89 , 95 % CI 1.33 - 35.68 ) . CONCLUSIONS Intolerance of uncertainty and urinary symptoms may promote anxiety in men on active surveillance for prostate cancer . Patient education , management of lower urinary tract symptoms and behavioral interventions may lessen anxiety related to uncertainty intolerance and help maintain patient engagement in active surveillance Background : Focal therapy is an emerging mini-invasive treatment modality for localized prostate cancer aim ed to reduce the morbidity associated with radical therapy while maintaining optimal cancer control . We report the mid-term oncological and functional results of primary hemiablation high-intensity focused ultrasound ( HIFU ) in a prospect i ve cohort of patients . Methods : Over 8 years , hemiablation HIFU was primarily performed in 50 selected patients with biopsy-proven clinical ly localized unilateral , low – intermediate risk prostate cancer in complete concordance with the prostate cancer lesions identified by magnetic resonance imaging with precise loci matching on multimodal approach . Post-treatment follow-up included regular serial PSA measurements . Biochemical recurrence was reported using Stuttgart and Phoenix criteria . The latter was used as a threshold to offer whole-gl and biopsies . Results : Complete follow-up was available for all patients and the median follow-up was 39.5 months ( range : 6–94 ) . Mean nadir PSA value was 1.6 ng ml−1 , which represents 72 % reduction compared with initial PSA pre-treatment value ( P<0.001 ) . Median time to achieve PSA nadir was 3 months . Biochemical recurrence , according to Phoenix and Stuttgart definition , occurred in 28 and 36 % of patients , respectively . The 5-year actuarial metastases-free survival , cancer-specific survival and overall survival rates were 93 , 100 and 87 % , respectively . Out of the eight patients undergoing biopsy , six patients had a positive biopsy for cancer occurring in the untreated contralateral ( n=3 ) or treated ipsilateral lobe ( n=1 ) or bilaterally ( n=2 ) . A Clavien – Dindo grade 3b complication occurred in two patients . Complete continence ( no pads ) and erection sufficient for intercourse were documented in 94 or 80 % of patients , respectively . Conclusion : Hemiablation HIFU therapy , delivered with intention to treat , for carefully selected patients affords mid-term promising functional and oncological outcomes . The effectiveness of this technique should be now compared with whole-gl and radical therapy BACKGROUND We evaluated the efficacy and feasibility of high-intensity-focused ultrasound ( HIFU ) for localized prostate cancer . METHODS Seventy patients received HIFU using Sonablate((R ) ) 500 ( Focus Surgery , IN , USA ) . In patients whose cancer was confined to only one lobe by multi-regional biopsies , total peripheral zone and a half portion of transitional zone were ablated ( focal therapy ) . Otherwise , patients received whole organ ablation ( whole therapy ) . Scheduled biopsies were performed at 6 and 12 months after treatment . Pre- and post-HIFU serum testosterone levels were measured . Result The 2-year biochemical disease-free survival ( DFS ) rates in patients at low , intermediate and high risk were 85.9 , 50.9 and 0 % , respectively , ( P = 0.0028 ) . After 12 months , 81.6 % ( 40/49 ) of patients were biopsy negative ; 84.4 % in patients who received whole therapy , whereas 76.5 % in those with focal therapy . The 2-year biochemical DFS rates for the patients at low and intermediate risk was 90.9 and 49.9 % , respectively , in patients with whole therapy , whereas 83.3 and 53.6 % in patients with focal therapy . In patients without neoadjuvant and rogen deprivation , serum testosterone levels continuously decreased after whole therapy , whereas no changes were seen in those with focal therapy . The patients whose follow-up biopsies were positive tended to have significantly higher changes in prostate-specific antigen levels than biopsy-negative patients . CONCLUSIONS In patients with low-risk prostate cancer , HIFU monotherapy result ed in comparable immediate cancer control with other modalities . Particularly , focal therapy might offer a feasible minimally invasive therapeutic option , which maintained serum testosterone level . To our knowledge , this is the first report that whole , but not focal , therapy affects the serum testosterone level BACKGROUND There is a lack of prospect i ve studies focusing on the sexual quality of life of prostate cancer patients after conformal radiotherapy ( RT ) . OBJECTIVE To evaluate the incidence , progression , and predictive factors for erectile dysfunction ( ED ) . DESIGN , SETTING AND PARTICIPANTS Patients who responded to the sexual domain of the Exp and ed Prostate Cancer Index Composite ( EPIC ) question naire before and more than 1 yr after RT and never received an anti and rogen treatment were included ( n=123 ) . INTERVENTION RT dose was 70.2 - 72 Gy . Eleven patients used a phosphodiesterase-5 ( PDE-5 ) inhibitor . MEASUREMENTS Patients responded to the EPIC question naire before ( time A ) , at the last day ( B ) , a median time of 2 mo after ( C ) , and 16 mo after ( D ) RT . In a multivariate analysis , risk factors ( patient age , prostate volume , planning target volume , use of PDE-5 inhibitor , comorbidities ) were tested for their independent effects on ED before and after RT . RESULTS AND LIMITATIONS Sexual function and bother scores had already decreased by the end of RT ( median function and bother scores at times A/B/C/D : 41/30/32/24 and 75/50/50/50 ) . Initial function scores correlated well with late function scores ( r=0.7 ; p<0.001 ) . The ability to have an erection was reported by 81%/72%/74%/60 % ( preserved erectile ability in 70 % at time D ) , erections firm enough for sexual intercourse by 44%/33%/35%/27 % ( preserved erections sufficient for intercourse in 53 % at time D ) of patients . A higher patient age and diabetes were predictive of both a pre-existing ED and a post-RT acquired ED . Nightly erections before treatment proved prognostically favourable ( at least weekly vs. < weekly-hazard ratio of 5.9 for preserved erections sufficient for intercourse ; p=0.01 ) . Higher rates of ED can be expected with longer follow-up . CONCLUSIONS The incidence of ED progressively increases after RT . Patient age and diabetes are risk factors for both pre-treatment and RT-associated ED . Nightly erections before RT proved prognostically favourable BACKGROUND Although localised prostate cancer is multifocal in most instances , the index lesion might be responsible for disease progression . OBJECTIVE To determine the early genitourinary functional and cancer control outcomes of index lesion ablation . DESIGN , SETTING , AND PARTICIPANTS This was a single-centre prospect i ve development study in which 56 men were treated ( July 2009-January 2011 ) . The mean age was 63.9 yr ( st and ard deviation 5.8 ) and median prostate-specific antigen ( PSA ) was 7.4 ng/ml ( interquartile range [ IQR ] 5.6 - 9.5 ) . There were seven ( 12.5 % ) low-risk , 47 ( 83.9 % ) intermediate-risk , and two ( 3.6 % ) high-risk cancers . INTERVENTION Multiparametric magnetic resonance imaging ( mpMRI ) and prostate biopsies to localise disease , followed by index lesion ablation using high-intensity focused ultrasound . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary outcomes were genitourinary side effects measured using vali date d question naires . Secondary outcomes included absence of clinical ly significant disease at 12 mo . RESULTS AND LIMITATIONS The composite of leak-free , pad-free continence , and erections sufficient for penetration decreased from a baseline frequency of 40/56 ( 71.4 % ) to 33/56 ( 58.9 % ) at 12 mo . Pad-free and leak-free , pad-free continence was preserved in 48/52 ( 92.3 % ) and 46/50 ( 92.0 % ) patients , respectively . Erections sufficient for intercourse were preserved in 30/39 ( 76.9 % ) patients . The median PSA nadir decreased to 2.4 ng/ml ( IQR 1.6 - 4.1 ) . At 12 mo , 42/52 ( 80.8 % ) patients had histological absence of clinical ly significant cancer and 85.7 % ( 48/56 ) had no measurable prostate cancer ( biopsy and /or mpMRI ) . Two ( 3.6 % ) patients had clinical ly significant disease in untreated areas not detected at baseline . The main study limitation is the short follow-up duration . CONCLUSIONS Index lesion ablation had low rates of genitourinary side effects and acceptable short-term absence of clinical ly significant cancer . Comparative effectiveness trials are required to assess cancer control outcomes against radical therapy . PATIENT SUMMARY In this study we looked at whether it is possible to treat the largest and highest- grade tumour in men who have more than one known prostate tumour . We show that the side effects of targeted ablation were low , with acceptable rates of early cancer control . Larger studies with longer follow-up are needed . TRIAL REGISTRATION NCT00988130 BACKGROUND Robust data on patient-reported outcome measures comparing treatments for clinical ly localized prostate cancer are lacking . We investigated the effects of active monitoring , radical prostatectomy , and radical radiotherapy with hormones on patient-reported outcomes . METHODS We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment ( ProtecT ) trial who completed question naires before diagnosis , at 6 and 12 months after r and omization , and annually thereafter . Patients completed vali date d measures that assessed urinary , bowel , and sexual function and specific effects on quality of life , anxiety and depression , and general health . Cancer-related quality of life was assessed at 5 years . Complete 6-year data were analyzed according to the intention-to-treat principle . RESULTS The rate of question naire completion during follow-up was higher than 85 % for most measures . Of the three treatments , prostatectomy had the greatest negative effect on sexual function and urinary continence , and although there was some recovery , these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial . The negative effect of radiotherapy on sexual function was greatest at 6 months , but sexual function then recovered somewhat and was stable thereafter ; radiotherapy had little effect on urinary continence . Sexual and urinary function declined gradually in the active-monitoring group . Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat , except for the increasing frequency of bloody stools ; bowel function was unchanged in the other groups . Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months . Effects on quality of life mirrored the reported changes in function . No significant differences were observed among the groups in measures of anxiety , depression , or general health-related or cancer-related quality of life . CONCLUSIONS In this analysis of patient-reported outcomes after treatment for localized prostate cancer , patterns of severity , recovery , and decline in urinary , bowel , and sexual function and associated quality of life differed among the three groups . ( Funded by the U.K. National Institute for Health Research Health Technology Assessment Program ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) OBJECTIVE To summarize the discussion that took place at a public workshop , co-sponsored by the U.S. Food and Drug Administration , the American Urological Association , and Society of Urologic Oncology review ing the current state of the art for partial gl and ablation ( PGA ) for the management of patients with prostate cancer . The purpose of this workshop was to discuss potential indications , current available evidence , and design s for future trials to provide the evidence needed by patients and providers to decide how and when to use PGA . METHODS A workshop evaluating PGA for prostate cancer was held in New Orleans , Louisiana , in May 2015 . Invited experts representing all stakeholders and attendees discussed the regulatory development of medical products , technology available , potential indications , and design s of trials to evaluate this modality of therapy . RESULTS The panel presented the current information on the technologies available to perform PGA , the potential indications , and results of prior consensus conferences . Use of magnetic resonance imaging for patient selection , guide therapy , and follow-up was discussed . Design s of trials to assess PGA outcomes were discussed . CONCLUSION The general consensus was that currently available technologies are capable of selective ablation with reasonable accuracy , but that criteria for patient selection remain debatable , and long-term cancer control remains to be established in properly design ed and well-performed prospect i ve clinical trials . Concerns include the potential for excessive , unnecessary use in patients with low-risk cancer and , conversely , that current diagnostic techniques may underestimate the extent and aggressiveness of some cancers , leading to inadequate treatment BACKGROUND Up to a third of patients with localized prostate cancer have unilateral disease that may be suitable for partial treatment with hemiablation . OBJECTIVE To evaluate the ability of high intensity focused ultrasound ( HIFU ) to achieve local control of the tumor in patients with unilateral localized prostate cancer . DESIGN , SETTING , AND PARTICIPANTS The French Urological Association initiated a prospect i ve IDEAL multi-institutional study ( 2009 - 2015 ) , to evaluate HIFU-hemiablation as a primary treatment . INTERVENTION Multiparametric magnetic resonance imaging and biopsy were used for unilateral cancer diagnosis and control , and HIFU-hemiablation . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary : absence of clinical ly significant cancer ( CSC ) on control biopsy at 1 yr ( CSC : Gleason score ≥ 7 or cancer core length>3 mm regardless of grade or > 2 positive cores ) . Secondary : presence of any cancer on biopsy , biochemical response , radical treatment free survival , adverse events , continence ( no pad ) , erectile function ( International Index of Erectile Function-5 ≥ 16 ) , and quality of life ( European Organization for Research and Treatment of Cancer QLQ-C28 ) question naires . RESULTS AND LIMITATIONS One hundred and eleven patients were treated ( mean age : 64.8 yr [ st and ard deviation 6.2 ] ; mean prostate-specific antigen : 6.2 ng/ml [ st and ard deviation 2.6 ] ; 68 % low risk , 32 % intermediate risk ) . Of the 101 patients with control biopsy , 96 ( 95 % ) and 94 ( 93 % ) had no CSC in the treated and contralateral lobes , respectively . Mean prostate-specific antigen at 2 yr was 2.3 ng/ml ( st and ard deviation 1.7 ) . The radical treatment-free survival rate at 2 years was 89 % ( radical treatments : six radical prostatectomies , three radiotherapies , and two HIFU ) . Adverse events were Grade 3 in 13 % . At 12 mo continence and erectile functions were preserved in 97 % and 78 % . No significant decrease in quality of life score was observed at 12 mo . One limitation is the number of low-risk patients included in this study . CONCLUSIONS At 1 yr , HIFU-hemiablation was efficient with 95 % absence of clinical ly significant cancer associated with low morbidity and preservation of quality of life . Radical treatment-free survival rate was 89 % at 2 yr . PATIENT SUMMARY This report shows that high intensity focused ultrasound half-gl and treatment of unilateral prostate cancer provides promising results with high cancer control and low morbidity BACKGROUND Focal therapy ( FT ) for prostate cancer ( PCa ) seems to be part of a natural evolution in the quest to improve the management of early organ-confined disease . OBJECTIVE To assess the morbidity of the initial experience of FT in a tertiary referral center for PCa management . DESIGN , SETTING , AND PARTICIPANTS From 2009 to 2011 , a total of 1213 patients with clinical ly localized PCa were treated at our institution . Of these patients , 547 were considered to have indolent disease according to the D'Amico criteria for low-risk disease plus unilateral disease with a maximum of three positive biopsies . A total of 106 patients underwent FT using high-intensity focused ultrasonography ( HIFU ) , brachytherapy , cryotherapy , or vascular-targeted photodynamic therapy ( VTP ) . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Complications were prospect ively recorded and grade d according to the Clavien-Dindo scale . Data were prospect ively collected and retrospectively analyzed . RESULTS AND LIMITATIONS This study included 106 patients , median age 66.5 yr ( interquartile range [ IQR ] ) : 61 - 73 ) , who had a prostate hemiablation ; 50 patients ( 47 % ) had cryotherapy , 23 patients ( 22 % ) had VTP , 21 patients ( 20 % ) received HIFU , and 12 patients ( 11 % ) had brachytherapy . The median prostate-specific antigen ( PSA ) level was 6.1 ng/ml ( IQR : 5 - 8.1 ) , all the patients had a biopsy Gleason score of 6 , and the median prostate weight was 43 g ( IQR : 33 - 55 ) . The median International Prostate Symptom Score was 6 ( IQR : 3 - 10 ) , and the median International Index of Erectile Function score was 20 ( IQR : 15 - 23 ) . After treatment , the median PSA at 3 , 6 , and 12 mo was 3.1 2.9 , and 2.7 ng/ml ( IQR : 2 - 5.1 , 1.1 - 4.7 , and 1 - 4.4 ) , respectively . Thirteen percent of the patients experienced treatment-related complications . There were 11 minor medical complications ( 10 grade 1 complications and 1 grade 2 complication ) , 2 grade 3 complications , and no grade 4 or higher complications . CONCLUSIONS FT for a highly selected population with PCa is feasible and had an acceptable morbidity with < 2 % major complications |
1,037 | 26,837,498 | 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 . | Mitral regurgitation ( MR ) is one of the common complications in myocardial infa rct ion ( MI ) patients .
Almost half of the post MI patients have MR ( ischemic MR)17 which is moderate to severe ( grade II-IV ) .
Whether there is a mortality benefit of performing mitral valve repair ( MVR ) along with coronary artery bypass grafting ( CABG ) in patients with post MI moderate MR remains inconclusive . | 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 symptoms at rest and during exercise . Combined coronary artery bypass grafting and mitral valve repair have no effect on survival at short-term follow-up , and the trends that are evident will likely become more significant with time BACKGROUND Mitral regurgitation ( MR ) may complicate acute myocardial infa rct ion ( MI ) . However , it is not known whether mild MR is an independent predictor of post-MI outcome . METHODS AND RESULTS The study cohort consisted of 727 Survival and Ventricular Enlargement Study patients who underwent cardiac catheterization , including left ventriculography , up to 16 days after MI . Left ventriculograms were analyzed for diastolic and systolic volumes , global left ventricular sphericity , extent of wall motion abnormality , and endocardial curvature . The presence of MR was related to the risk of developing a cardiovascular event during 3.5 years of follow-up . MR was present in 141 patients ( 19.4 % ) . Severe ( 3 + ) MR was present in only 2 patients . Patients with MR were more likely to have a persistently occluded infa rct artery ( MR versus no MR , 27.3 % versus 15.2 % ; P=.001 ) . Although the ejection fractions were similar , MR patients had larger end-systolic and end-diastolic volumes and more spherical ventricles than patients without MR . Sphericity change from diastole to systole was also significantly reduced in MR patients . Patients with MR were more likely to experience cardiovascular mortality ( 29 % versus 12 % ; P<.001 ) , severe heart failure ( 24 % versus 16 % ; P=.0153 ) , and the combined end point of cardiovascular mortality , severe heart failure , or recurrent myocardial infa rct ion ( 47 % versus 29 % ; P<.001 ) . The presence of MR was an independent predictor of cardiovascular mortality ( relative risk , 2.00 ; 95 % CI , 1.28 to 3.04 ) . CONCLUSIONS Mild MR is an independent predictor of post-MI mortality . As such , it adds important information for risk stratification of post-MI patients OBJECTIVE Mitral incompetence is a chronic sequela of myocardial infa rct ion . It is caused by apical displacement and tethering of the mitral valve leaflets after myocardial infa rct ion , result ing in incomplete coaptation . The consensus is for mitral valve surgery in the presence of significant ischemic mitral regurgitation ( IMR ) . Previously , the only option was mitral valve replacement ( MVR ) with a mechanical or tissue valve . The suboptimal results obtained prompted the development of several methods of mitral valve repair . Today , the most commonly used repair is undersized annuloplasty . METHODS We conducted a retrospective nonr and omized study of all patients who underwent operation for coronary artery disease and IMR between 2000 and 2006 . The surgeon chose the surgical method used for the mitral valve procedure . The most commonly used procedures were restrictive mitral valve annuloplasty ( MVP ) and MVR with a mechanical prosthesis . We collected all pertinent preoperative , intraoperative , and early-postoperative data . We followed up with phone interviews of the patients and their relatives and with complete clinical and echocardiography examinations . RESULTS We carried out operations on 138 patients during the study period ( MVR , 52 patients ; MVP , 86 patients ) . The 2 groups had comparable demographic data and risk factors . The 2 groups were significantly different with respect to mean ( + /-SD ) New York Heart Association ( NYHA ) class ( MVP , 2.72 + /- 0.62 ; MVR , 2.48 + /- 0.70 ; P < .01 ) and ejection fraction ( MVP , 29.01 % + /- 11.00 % ; MVR , 35.87 % + /- 11.00 % ; P < /= .01 ) . The 30-day mortality rates for the MVR and MVP groups were significantly different ( 9.61 % and 5.81 % , respectively ; P < .01 ) . Our follow-up included 83 % of the patients and continued for up to 84 months . The 2 groups showed no significant difference in mortality by the end of follow-up ; however , the MVR patients had a better ejection fraction ( 37.79 % versus 29.86 % ) and NYHA functional class ( 1.88 + /- 0.498 versus 2.36 + /- 0.564 ; P < .01 ) . CONCLUSION Correcting chronic IMR with either repair or replacement produces a good mid-term survival rate ( approximately 75 % ) for survivors in NYHA classes I and II . In our study , mortality rates for the MVP and MVR groups were similar , even though the repair group had a lower mean ejection fraction and a higher NYHA class before and after the operation . We therefore conclude that repair is superior to replacement in treating ischemic mitral insufficiency . A prospect i ve r and omized study is needed to better compare these 2 approaches BACKGROUND Ischemic mitral regurgitation is associated with increased mortality and morbidity . For surgical patients with moderate regurgitation , the benefits of adding mitral-valve repair to coronary-artery bypass grafting ( CABG ) are uncertain . METHODS We r and omly assigned 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus mitral-valve repair ( combined procedure ) . The primary end point was the left ventricular end-systolic volume index ( LVESVI ) , a measure of left ventricular remodeling , at 1 year . This end point was assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized as the lowest LVESVI rank . RESULTS At 1 year , the mean LVESVI among surviving patients was 46.1±22.4 ml per square meter of body-surface area in the CABG-alone group and 49.6±31.5 ml per square meter in the combined-procedure group ( mean change from baseline , -9.4 and -9.3 ml per square meter , respectively ) . The rate of death was 6.7 % in the combined-procedure group and 7.3 % in the CABG-alone group ( hazard ratio with mitral-valve repair , 0.90 ; 95 % confidence interval , 0.38 to 2.12 ; P=0.81 ) . The rank-based assessment of LVESVI at 1 year ( incorporating deaths ) showed no significant between-group difference ( z score , 0.50 ; P=0.61 ) . The addition of mitral-valve repair was associated with a longer bypass time ( P<0.001 ) , a longer hospital stay after surgery ( P=0.002 ) , and more neurologic events ( P=0.03 ) . Moderate or severe mitral regurgitation was less common in the combined-procedure group than in the CABG-alone group ( 11.2 % vs. 31.0 % , P<0.001 ) . There were no significant between-group differences in major adverse cardiac or cerebrovascular events , deaths , readmissions , functional status , or quality of life at 1 year . CONCLUSIONS In patients with moderate ischemic mitral regurgitation , the addition of mitral-valve repair to CABG did not result in a higher degree of left ventricular reverse remodeling . Mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation but an increased number of untoward events . Thus , at 1 year , this trial did not show a clinical ly meaningful advantage of adding mitral-valve repair to CABG . Longer-term follow-up may determine whether the lower prevalence of mitral regurgitation translates into a net clinical benefit . ( Funded by the National Institutes of Health and the Canadian Institutes of Health Research ; Clinical Trials.gov number , NCT00806988 . ) BACKGROUND Mortality for patients with coronary artery disease and functional ischemic mitral regurgitation ( IMR ) remains high regardless of the treatment strategy . Data regarding risk factors , progression of MR , and cause of death in this subgroup are limited . METHODS A retrospective study was performed on 257 consecutive patients undergoing mitral valve repair exclusively for IMR from 1996 to 2005 . Potential preoperative and perioperative risk factors for death and postoperative echocardiographic data were recorded . RESULTS Preoperative echocardiography demonstrated 3 + to 4 + MR in 98.4 % ( 252 of 257 ) . Concomitant coronary artery bypass grafting was performed in 80.9 % ( 208 of 257 ) . Operative mortality was 10.1 % ( 26 of 257 ) . Overall survival by Kaplan-Meier analysis was 68.3 % at 3 years and 52.0 % at 5 years . Factors associated with late mortality by multivariate analysis include advanced age ( relative risk [ RR ] , 1.037 ; 95 % confidence interval [ CI ] , 1.016 to 1.059 ; p < or = 0.001 ) , preoperative dialysis ( RR , 3.504 ; 95 % CI , 1.590 to 7.720 ; p = 0.008 ) , and diabetes ( RR , 2.047 ; 95 % CI , 1.319 to 3.177 ; p = 0.001 ) . Echocardiographic data at 20 + /- 25 months were available in 57 % ( 147 of 257 ) . Their survival by Kaplan-Meier analysis was 76.4 % at 3 years and 65.1 % at 5 years with 0 to 2 + MR postoperatively ( n = 106 ) vs 61.3 % and 35.8 % with 3 + to 4 + MR ( n = 41 ; p = 0.003 ) . Cause of death was available in 72.3 % ( 60 of 83 ) of late deaths , with 42.2 % ( 35 of 83 ) attributed to cardiac causes and 30.1 % ( 25 of 83 ) noncardiac . CONCLUSIONS Mortality for IMR remains high despite surgical management and may be related to risk factors for progression of coronary artery disease . Despite repair , MR progresses in many patients and is associated with poor survival , although more detailed prospect i ve data are needed to characterize this relationship OBJECTIVES The aim of this work was to determine whether mitral valve ( MV ) annuloplasty benefits patients with moderate/severe ( 3+/4 + ) functional ischemic mitral regurgitation ( MR ) who undergo coronary artery bypass grafting ( CABG ) . BACKGROUND Mitral regurgitation is a strong predictor of poor outcomes in patients with ischemic cardiomyopathy ; whether correcting it at the time of CABG improves outcomes is less certain . METHODS From 1991 to 2003 , 390 patients with 3+/4 + ischemic MR had CABG with ( n = 290 ) or without ( n = 100 ) MV annuloplasty . Groups were propensity-matched using demographics , extent of coronary disease , regional wall motion , and quantitative electrocardiography . Survival , echocardiographic severity of MR , and New York Heart Association ( NYHA ) functional class were compared . RESULTS One- , 5- , and 10-year survival was 88 % , 75 % , and 47 % after CABG alone and 92 % , 74 % , and 39 % after CABG + MV annuloplasty ( p = 0.6 ) . Mortality was increased in patients with severe lateral wall motion abnormalities ( p = 0.05 ) , ST-segment elevation in lateral leads ( p < 0.004 ) , and higher QRS voltage sum ( p < 0.0001 ) . Patients undergoing CABG alone were more likely to have 3+/4 + postoperative MR than those undergoing CABG + MV annuloplasty ( 48 % vs. 12 % at 1 year , p < 0.0001 ) . The NYHA functional class substantially improved in both groups ( p < 0.001 ) and remained improved ; at 5 years , 23 % of patients having CABG + mitral annuloplasty and 25 % having CABG alone were in NYHA functional class III/IV . CONCLUSIONS Although CABG + MV annuloplasty reduces postoperative MR and improves early symptoms compared with CABG alone , it does not improve long-term functional status or survival in patients with severe functional ischemic MR . The MV annuloplasty in this setting , without addressing fundamental ventricular pathology , is insufficient to improve long-term clinical outcomes |
1,038 | 23,588,126 | 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 . | OBJECTIVES The aims of this study were to identify partner attributes associated with sexually transmitted infections ( STIs ) among adolescents and to summarize implication s for research and prevention . | 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 of gonorrhoea and chlamydia between black ethnic groups in Lambeth , Southwark and Lewisham Health Authority . Methods : Episodes of gonorrhoea or chlamydia recorded among attenders at 11 genitourinary clinics in south and central London from 1 January 1994 to 31 December 1995 were retrieved . Complete data on chlamydia were only available for women . Ethnic group was assigned according to census categories — white , black Caribbean , black African , black other , Asian , or other . We calculated yearly incidence rates for episodes of gonorrhoea and chlamydia in residents of Lambeth , Southwark and Lewisham Health Authority . R and om effects Poisson regression models were used to examine associations between infection rates and age , ethnic group , and material deprivation . Results : During the study period there were 1996 episodes of gonorrhoea in men and women and 1376 episodes of chlamydia in women with complete data . For both infections rates among individuals from black Caribbean and black other ethnic groups were markedly higher than among black Africans . In men , the gonorrhoea rate among black Caribbean 20–24 year olds was 2348 ( 95 % CI 1965 to 2831 ) episodes per 100 000 compared with 931 ( 95 % CI 690 to 1288 ) in black African men and 111 ( 95 % CI 100 to 124 ) per 100 000 in white men of the same age . Among women gonorrhoea rates were highest in black Caribbean 15–19 year olds ( 2612 , 95 % CI 2161 to 3190 per 100 000 ) . In contrast , rates in black African women of the same age ( 331 , 95 % CI 154 to 846 per 100 000 ) were similar to those of white women ( 222 , 95 % CI 163 to 312 ) . Chlamydia rates were also highest in black Caribbean 15–19 year old women ( 4579 , 95 % CI 3966 to 5314 per 100 000 ) , compared with 1286 ( 95 % CI 907 to 1888 ) in black African and 433 ( 95 % CI 349 to 544 ) per 100 000 white women . Controlling for material deprivation and age only attenuated differences in rates between ethnic groups slightly . Conclusions : There are marked differences in rates of gonorrhoea and chlamydia between different black ethnic groups , with higher rates in black Caribbeans than black Africans . This study supports the hypothesis that assortative sexual mixing patterns can restrict epidemics of sexually transmitted infections within ethnic groups . Differences in disease occurrence between black ethnic groups should be explored before combining data , even when numbers of episodes are small Our objective was to estimate HIV seroconversion rates among commercial sex workers ( CSWs ) between 1990 and 1991 and to identify the behavioral , demographic , and reproductive determinants of these rates . This study has a prospect i ve ( n = 240 with 15 cases ) and a cross-sectional component ( n = 271 with 34 cases ) . In November 1990 , HIV-negative female CSWs from 24 brothels in Khon Kaen city were interviewed and were followed prospect ively for up to 1 year . In March , June , and September 1991 , additional HIV-negative CSWs were enrolled and prospect ively followed . HIV seroconversion rates were calculated , and the Cox regression model was used to estimate the relative risks of HIV seroconversion from demographic , sexual practice , and reproductive factors , adjusted for the effects of the others , among 232 of the 240 without missing data . Seroprevalence rates were also calculated for the 271 participants enrolled between March and December 1991 , and relative risks of HIV seroprevalence were calculated for demographic , sexual practice , and reproductive risk factors among 184 of the 271 without missing data . The average seroprevalence was 12.5 % ( 95 % confidence interval 9.6 - 15.4 % ) . With 1,947 person-months of observation obtained from 240 participants who were uninfected at baseline and seen at least twice during the course of the study , the cumulative incidence of HIV seroconversion between November 1990 and December 1991 was 9.4 % ( 95 % confidence interval 5.4 - 13.4 % ) , and the average incidence rate of HIV seroconversion was 9.2 per 100 person-years ( 95 % confidence interval 4.6 - 13.9 per 100 person-years ) . In the multivariate analysis , later date of enrollment into the study , having < 3 months experience as a CSW , and use of injectable contraceptives were the only risk factors that remained significant , with relative risks of 2.1 ( 95 % confidence interval 1.2 - 3.7 ) for enrollment 3 months later , 3.8 ( 95 % confidence interval 1.0 - 14.4 ) for < 3 months experience as a CSW versus > 3 months experience , and 3.9 ( 95 % confidence interval 1.3 - 11.8 ) [ corrected ] for use of injectable contraceptives . In multivariate analysis of the cross-sectional data with 184 participants , of whom 21 were HIV seropositive , risk of HIV seropositivity increased significantly with current syphilis infection ( odds ratio 5.8 , 95 % confidence interval 1.1 - 31.0 ) . The results of this study will contribute to a better underst and ing of the risk factors of infection with HIV and thus allow for better targeting of group-specific interventions , particularly for CSWs and their clients . Further investigation of a possible association between injectable contraceptive use and HIV infection is needed PURPOSE To compare characteristics of sexual relationships in HIV infected and HIV uninfected female adolescents and their association with condom use . METHODS HIV infected and uninfected subjects , aged 13 - 19 years , were enrolled in a prospect i ve HIV study from 15 sites in 13 U.S. cities . Baseline data on demographic information , substance use , sexual behavior , partner information , and condom use were collected through direct and computer-assisted interviews from currently sexually active females . Univariate , multiple logistic regression , and repeated measures analyses were employed . RESULTS Data from 153 HIV infected and 90 HIV uninfected female subjects showed , on average , that current partners were 4 - 6 years older . In multivariate analysis , HIV infected subjects were older ( OR = 1.37 ; 95 % CI : 1.04 - 1.81 ) , had more lifetime partners ( OR = 2.23 ; 95 % CI : 1.03 - 4.82 ) , initiated consensual vaginal sex earlier ( OR = .74 ; 95 % CI:.58-.95 ) , perceived partner to also be HIV infected ( OR = 7.46 ; 95 % CI : 3.2 - 17.4 ) , and had less unprotected sex ( OR = .27 ; 95 % CI:.16-.45 ) . Length of relationship was associated with more unprotected sex for both HIV infected and uninfected subjects ( OR = 2.59 , 95 % CI : 1.27 - 5.27 , OR = 4.13 ; 95 % CI : 1.31 - 13.05 , respectively ) . Mean partner age difference was greater among HIV infected than for HIV uninfected ( OR = 1.06 ; 95%CI : 1.01 - 1.12 ) ; this greater age difference for HIV infected females was associated with less protection ( OR = 1.09 ; 95 % CI : 1.03 - 1.15 ) . HIV disclosure influenced condom use : without disclosure , less condom use was reported ( OR = 6.8 ; 95 % CI : 2.29 - 20.24 ) controlling for perception that partner was also HIV infected ( OR = 1.1 ; 95 % CI : 1.02 - 1.21 ) . CONCLUSIONS Because age differential influenced reported condom use , more research , particularly qualitative , is needed into the dynamics of these relationships . Prevention efforts must address partners , particularly older ones PURPOSE Among adolescent women , having older sexual partners has been associated with initial Chlamydia trachomatis ( Ct ) infection and high-risk behaviors . This study evaluates the role of older partners in the risk of three outcomes : recurrent Ct , lack of condom use , and nonadherence with partner management ( PM ) strategies . METHODS Female participants aged 14 to 18 years enrolled in a r and omized clinical trial of patient-delivered partner treatment ( PDPT ) with at least one follow-up visit were included in this secondary analysis . Patient- and partner-level data were collected at baseline , one , and four months follow-up . Generalized estimating equations ( GEE ) and logistic regression were used to examine unadjusted and adjusted associations . RESULTS The majority of the 496 women were African-American ( 63.3 % ) , aged 16 to 18 years ( 62.3 % ) , and asymptomatic for Ct ( 66.7 % ) . At baseline , all of the women had laboratory-demonstrated Ct and were treated ; they had 622 partners during the last 60 days , 21.4 % reported having more than one partner with a mean ( SD ) of 1.5 ( .78 ) partners per woman , and 46.3 % of the partners were at least three years older than the woman . Over follow-up , 16.1 % of the women experienced Ct recurrence , in 41.9 % of the partnerships a condom was not used at last sex , and 80.6 % of women reported giving PM . After adjusting for confounders , having a partner at least three years older was not associated with increased risk of Ct recurrence , lack of condom use , or nonadherence to PM strategies . CONCLUSIONS Risk of Ct recurrence , lack of condom use , and nonadherence to PM strategies was not higher among adolescent women with older partners A serosurvey was conducted in a r and om sample of 259 women and 231 men in 12 rural communities in Mwanza Region , Tanzania , using a type-specific ELISA for Herpes simplex virus type 2 ( HSV-2 ) infection . Seroprevalence rose steeply with age to approximately 75 % in women > = 25 years old and 60 % in men > = 30 . After adjusting for age and residence , HSV-2 prevalence was higher in women who were married , in a polygamous marriage , Treponema pallidum hemagglutination assay (TPHA)-positive , had more lifetime sex partners , or who had not traveled . Prevalence was higher in men who were married , had lived elsewhere , had more lifetime partners , had used condoms , or were TPHA-positive . HSV-2 infection was significantly associated with recent history of genital ulcer . The association between HSV-2 infection and lifetime sex partners was strongest in those < 25 years old in both sexes . This association supports the use of HSV-2 serology as a marker of risk behavior in this population , particularly among young people We conducted a cross-sectional study of sexually transmitted disease and HIV infections among a r and om sample of the 2364 adult population in 2000 in Bobo-Dioulasso , the second largest town in Burkina Faso . The prevalence of HIV infection was 5.2 % . Risk factor analysis was conducted among sexually active men 20 to 34 years old and women 15 to 24 years old . Factors independently associated with HIV infection among men were having been married ( adjusted odds ratio (aOR)=8.19 [ 1.70 - 39 ] ) , reporting more than two non-marital partners in the last 12 months ( aOR=6.07 [ 1.14 - 32.4 ] ) , reporting a past urban residence other than Bobo-Dioulasso ( aOR = 6.37 [ 1.96 - 20.7 ] and having a positive serology for HSV-2 infection ( aOR=12.0 [ 3.49 - 40.9 ] ) . Among women the factors were being Christian ( aOR=3.73 [ 1.20 - 11.6 ] ) , having had a first sexual partner more than 24 years old ( aOR = 4.30 [ 1.35 - 13.6 ] ) and having a positive serology for HSV-2 infection ( aOR = 4.40 [ 1.32 - 14.6 ] ) . HIV infection in Bobo-Dioulasso therefore depends on both exposure factors ( sexual behaviours ) and transmissibility cofactors ( HSV-2 ) OBJECTIVE To investigate the factors associated with positive syphilis serology results in puerperal women who were receiving care at 24 health centers accredited by Brazil 's National Program on Sexually Transmitted Diseases and AIDS . METHODS This cross-sectional study included a probabilistic r and om sample of 3047 puerperal women . The eligibility criterion was being admitted for delivery or curettage in the selected centers . After an interview to collect demographic and clinical information , a blood sample was taken and then examined with the Venereal Disease Research Laboratory ( VDRL ) slide test . With positive VDRL results , the fluorescent treponemal antibody-absorption test ( FTA-Abs ) was used for confirmation . The event considered for analysis was positivity on the VDRL test , with confirmation by the FTA-Abs . For the statistical analysis , odds ratios and 95 % confidence intervals were calculated . The model fit was assessed using the Hosmer-Lemeshow test . RESULTS The prevalence of syphilis among the women studied was 1.7 % . Multivariate analysis showed that increased risk for positive VDRL and FTA-Abs results was associated with the following characteristics : family income below one minimum wage , age < 17 years at first sexual intercourse , age < or = 14 years at first pregnancy , history of syphilis or of other sexually transmitted diseases prior to the current pregnancy , treatment for syphilis during the current pregnancy , partner having been tested for syphilis , having a positive HIV test result or having no HIV test result on record , previous preterm delivery , and stillbirth as an outcome of pregnancy . Only 43 % of the women had had six or more prenatal visits , and only 3 % had had one VDRL test during the first trimester of pregnancy and another VDRL test during the third trimester , as is recommended by Brazil 's national Ministry of Health . CONCLUSIONS This study shows that the problem of congenital syphilis is far from being solved in Brazil . It is necessary to provide adolescents with family planning services as well as guidance on sexual issues , to improve prenatal follow-up , and to research the history of sexually transmitted diseases in both the pregnant woman and her sexual partner Objectives To determine the seroprevalence of HIV and herpes simplex virus-2 ( HSV-2 ) by age and gender among young people aged 14 - 24 years in a South African town and to identify risk factors for HIV infection . Design A community-based , cross-sectional study was conducted on a r and om sample of men ( n = 723 ) and women ( n = 784 ) living in a township in the Carletonville district of South Africa . Methods Potential demographic and behavioural risk factors associated with HIV were recorded by question naire and biological tests were performed on serum and urine . Data analysis was performed using multivariate logistic regression . Results Among men and women the prevalence of HIV infection was 9.4 and 34.4 % , respectively , and of positive HSV-2 serology was 17.0 and 53.3 % , respectively . Among 24-year-old women the prevalence of HIV was 66.7 % [ 95 % confidence interval ( CI ) , 54.6–77.3 % ] . HSV-2 seropositivity was a strong independent risk factor for HIV infection with odds ratios of 5.3 ( 95 % CI , 2.7–10.3 ) for men and 8.4 ( 95 % CI , 4.9–14.2 ) for women . There was no independent effect of age at first sex or serological markers of other sexually transmitted infections on HIV infection . Conclusions HIV infection among young women increases rapidly after the onset of sexual activity and reaches extremely high levels by 24 years of age . These findings suggest that rates of HIV transmission from men to women are high and that HSV-2 plays a major role in the spread of HIV in this population |
1,039 | 30,197,721 | 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 . | Introduction High prevalence of anemia attributable to intestinal parasite infection occurs among children in developing countries .
As a result mass treatment of all children with anti-helminthic drugs particularly in school setting is being implemented .
There are few studies conducted to assess impact of deworming on anemia prevalence among school children with inconclusive finding .
Therefore we aim ed to conduct a systematic review on impact assessment of deworming on anemia prevalence or hemoglobin level of school children so that policy makers and other stalk holders could have pooled evidence on the direction to make decision . | 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 and visited by a study team 1–5 months after any trial deworming to sample faeces ( for presence of worm eggs , reliably assessed only after mid- study ) , weigh children , and interview caregivers . Separately , all 8338 centres were visited every 6 months to monitor pre-school deaths ( 100 000 visits , 25 000 deaths at age 1·0–6·0 years [ the primary outcome ] ) . This trial is registered at Clinical Trials.gov , NCT00222547 . Findings Estimated compliance with 6-monthly albendazole was 86 % . Among 2589 versus 2576 children surveyed during the second half of the study , nematode egg prevalence was 16 % versus 36 % , and most infection was light . After at least 2 years of treatment , weight at ages 3·0–6·0 years ( st and ardised to age 4·0 years , 50 % male ) was 12·72 kg albendazole versus 12·68 kg control ( difference 0·04 kg , 95 % CI −0·14 to 0·21 , p=0·66 ) . Comparing the 36 albendazole-allocated versus 36 control blocks in analyses of the primary outcome , deaths per child-care centre at ages 1·0–6·0 years during the 5-year study were 3·00 ( SE 0·07 ) albendazole versus 3·16 ( SE 0·09 ) control , difference 0·16 ( SE 0·11 , mortality ratio 0·95 , 95 % CI 0·89 to 1·02 , p=0·16 ) , suggesting absolute risks of dying between ages 1·0 and 6·0 years of roughly 2·5 % albendazole versus 2·6 % control . No specific cause of death was significantly affected . Interpretation Existing ICDS village staff can be organised to deliver simple pre-school interventions sustainably for many years at low cost , but regular deworming had little effect on mortality in this lightly infected pre-school population . Funding UK Medical Research Council , USAID , World Bank ( albendazole donated by GlaxoSmithKline ) |
1,040 | 31,868,655 | 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 . | BACKGROUND Tenofovir Disoproxil Fumarate ( TDF ) , the oral prodrug of Tenofovir ( TFV ) , is advocated in pregnancy to for prevention of mother to child transmission ( PMCT ) with failure of hepatitis B immunoglobulin and vaccination . | 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 transmission and birth defects . The secondary outcomes were the safety of TDF , the percentage of mothers with an HBV DNA level of less than 200,000 IU per milliliter at delivery , and loss or seroconversion of HBeAg or hepatitis B surface antigen at postpartum week 28 . RESULTS At delivery , 68 % of the mothers in the TDF group ( 66 of 97 women ) , as compared with 2 % in the control group ( 2 of 100 ) , had an HBV DNA level of less than 200,000 IU per milliliter ( P<0.001 ) . At postpartum week 28 , the rate of mother-to-child transmission was significantly lower in the TDF group than in the control group , both in the intention-to-treat analysis ( with transmission of virus to 5 % of the infants [ 5 of 97 ] vs. 18 % [ 18 of 100 ] , P=0.007 ) and the per- protocol analysis ( with transmission of virus to 0 vs. 7 % [ 6 of 88 ] , P=0.01 ) . The maternal and infant safety profiles were similar in the TDF group and the control group , including birth-defect rates ( 2 % [ 2 of 95 infants ] and 1 % [ 1 of 88 ] , respectively ; P=1.00 ) , although more mothers in the TDF group had an increase in the creatine kinase level . After the discontinuation of TDF , alanine aminotransferase elevations above the normal range occurred more frequently in mothers in the TDF group than in those in the control group ( 45 % [ 44 of 97 women ] vs. 30 % [ 30 of 100 ] , P=0.03 ) . The maternal HBV serologic outcomes did not differ significantly between the groups . CONCLUSIONS In a cohort of HBeAg-positive mothers with an HBV DNA level of more than 200,000 IU per milliliter during the third trimester , the rate of mother-to-child transmission was lower among those who received TDF therapy than among those who received usual care without antiviral therapy . ( Funded by Gilead Sciences ; Clinical Trials.gov number , NCT01488526 . ) ABSTRACT Tenofovir ( TFV ) is effective in preventing simian immunodeficiency virus ( SIV ) transmission in a macaque model , is available as the oral agent tenofovir disoproxil fumarate ( TDF ) , and may be useful in the prevention of mother-to-child transmission of human immunodeficiency virus ( HIV ) . We conducted a trial of TDF and TDF-emtricitabine ( FTC ) in HIV-infected pregnant women and their infants . Women received a single dose of either 600 mg TDF , 900 mg TDF , or 900 mg TDF-600 mg FTC at labor onset or prior to a cesarean section . Infants received no drug or a single dose of TDF at 4 mg/kg of body weight or of TDF at 4 mg/kg plus FTC at 3 mg/kg as soon as possible after birth . All regimens were safe and well tolerated . Maternal areas under the serum concentration-time curve ( AUC ) and concentrations at the end of sampling after 24 h ( C24 ) were similar between the two doses of TDF ; the maximum concentrations of the drugs in serum ( Cmax ) and cord blood concentrations were higher in women delivering via cesarean section than in those who delivered vaginally ( P = 0.04 and 0.046 , respectively ) . The median ratio of the TFV concentration in cord blood to that in the maternal plasma at delivery was 0.73 ( range , 0.26 to 1.95 ) . Without TDF administration , infants had a median TFV concentration of 12 ng/ml 12 h after birth . Following administration of a single dose of TDF at 4 mg/kg , infant TFV concentrations fell below the targeted level , 50 ng/ml , by 24 h postdose . In HIV-infected pregnant women and their infants , 600 mg of TDF is acceptable as a single dose during labor . Low concentrations at birth support infant dosing as soon after birth as possible . Rapidly decreasing TFV levels in infants suggest that multiple or higher doses of TDF will be necessary to maintain concentrations that are effective for viral suppression Objective : To describe the pharmacokinetics of tenofovir and emtricitabine in the third trimester of pregnant HIV-infected women and at postpartum . Design : A nonr and omized , open-label , multicentre phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe . Methods : HIV-infected pregnant women treated with the nucleotide/nucleoside analogue reverse transcriptase inhibitors ( NRTIs ) tenofovir disoproxil fumarate ( TDF 300 mg ; equivalent to 245 mg tenofovir disoproxil ) and /or emtricitabine ( FTC 200 mg ) were included in the study . Twenty-four-hour pharmacokinetic curves were recorded in the third trimester ( preferably week 33 ) and postpartum ( preferably week 4–6 ) . Collection of a cord blood sample and maternal sample at delivery was optional . Pharmacokinetic parameters were calculated using WinNonlin software version 5.3 . Statistical analysis was conducted using SPSS version 16.0 . Results : Thirty-four women were included in the analysis . Geometric mean ratios of third trimester vs. postpartum [ 90 % confidence interval ( CI ) ] were 0.77 ( 0.71–0.83 ) for TDF area under the curve ( AUC0–24 h ) ; 0.81 ( 0.68–0.96 ) for TDF Cmax and 0.79 ( 0.70–0.90 ) for TDF C24 h and 0.75 ( 0.68–0.82 ) for FTC AUC0–24 h ; and 0.87 ( 0.77–0.99 ) for FTC Cmax and 0.77 ( 0.52–1.12 ) for FTC C24 h. The viral load close to delivery was less than 200 copies/ml in all but one patient , the average gestational age at delivery was 38 weeks . All children were tested HIV-negative and no congenital abnormalities were reported . Conclusion : Although pharmacokinetic exposure of the NRTIs TDF and FTC during pregnancy is approximately 25 % lower , this was not associated with virological failure in this study and did not result in mother-to-child transmission Background : Data describing the pharmacokinetics and safety of tenofovir in neonates are lacking . Methods : The HIV Prevention Trials Network 057 protocol was a phase 1 , open-label study of the pharmacokinetics and safety of tenofovir disoproxil fumarate ( TDF ) in HIV-infected women during labor and their infants during the first week of life with 4 dosing cohorts : maternal 600 mg doses/no infant dosing ; no maternal dosing/infant 4 mg/kg doses on days 0 , 3 , and 5 ; maternal 900 mg doses/infant 6 mg/kg doses on days 0 , 3 , and 5 ; maternal 600 mg doses/infant 6 mg/kg daily for 7 doses . Pharmacokinetic sampling was performed on cohort 1 and 3 mothers and all infants . Plasma , amniotic fluid , and breast milk tenofovir concentrations were determined by liquid chromatographic – t and em mass spectrometric assay . The pharmacokinetic target was for infant tenofovir concentration throughout the first week of life to exceed 50 ng/mL , the median trough tenofovir concentration in adults receiving st and ard chronic TDF dosing . Results : One hundred twenty-two mother – infant pairs from Malawi and Brazil were studied . Tenofovir exposure in mothers receiving 600 and 900 mg exceeded that in nonpregnant adults receiving st and ard 300 mg doses . Tenofovir elimination in the infants was equivalent to that in older children and adults , and trough tenofovir plasma concentrations exceeded 50 ng/mL in 74%–97 % of infants receiving daily dosing . Conclusions : A TDF dosing regimen of 600 mg during labor and daily infant doses of 6 mg/kg maintains infant tenofovir plasma concentration above 50 ng/mL throughout the first week of life and should be used in the studies of TDF efficacy for HIV prevention of mother-to-child transmission and early infant treatment Thirty‐eight human immunodeficiency virus‐1 (HIV‐1)‐infected pregnant women were administered tenofovir disoproxil fumarate ( TDF ; 300 mg)–emtricitabine ( FTC ; 200 mg ) tablets : two at labor initiation and one daily for 7 days postpartum . Maternal , umbilical , and neonatal plasma tenofovir concentrations were measured by high‐performance liquid chromatography and analyzed using a population approach . Data were described using a two‐compartment model for the mother , an effect compartment linked to maternal circulation for cord , and a neonatal compartment disconnected after delivery . Absorption was greater for women delivering by caesarian section than for those delivering vaginally . The maternal 600 mg TDF administration before delivery produces the same concentrations as 300 mg administration in other adults . If the time elapsed between maternal administration and delivery is ≥12 h , two tablets of TDF – FTC should be readministered . Tenofovir showed good placental transfer ( 60 % ) . Administering 13 mg/kg of TDF as soon as possible after birth should produce neonatal concentrations comparable with those observed in adults BACKGROUND In China , women with chronic HBV infection and who are of childbearing age receive lamivudine at an early age . Thus , viral resistance becomes a challenge for intervention to prevent mother-to-infant transmission . We prospect ively assessed the efficacy of tenofovir in pregnant women with lamivudine-resistant HBV . METHODS Chronic HBV-infected mothers resistant to lamivudine were enrolled . Tenofovir was administrated at gestation weeks 24 or 28 . Virological and biochemical parameters were assessed . All infants received combined immunoprophylaxis and were followed for 1 year . RESULTS Of the 48 mothers enrolled , 21 started tenofovir therapy at gestation week 24 and 27 started at week 28 . Tenofovir result ed in an HBV DNA decline of 5.23 ± 1.68 log10 IU/ml at delivery . The group starting therapy at week 24 exhibited a more rapid viral inhibition ( P<0.001 ) and more significant HBV DNA load decline ( 5.89 ± 1.66 versus 4.72 ± 1.55 ; P=0.019 ) than the group starting at week 28 . At delivery , all mothers had a viral titre < 10(6 ) IU/ml , 76.2 % from the week 24 starting group displayed virus < 10(4 ) IU/ml , and 52.4 % showed undetectable virus at delivery , much higher than the week 28 starting group ( 29.6 % ) , although there was no statistically significant difference in viral levels at delivery between the two groups . Congenital abnormalities and neonatal growth were comparable to the normal population . No case of perinatal transmission was diagnosed . CONCLUSIONS This investigation clarifies the efficacy of tenofovir for reducing vertical transmission of HBV in mothers with lamivudine-resistant HBV and demonstrates that tenofovir is well-tolerated in the second and third trimesters We assessed tenofovir exposure during pregnancy and postpartum in hepatitis B virus (HBV)-infected HIV-uninfected women receiving tenofovir disoproxil fumarate ( TDF ) to prevent mother-to-child transmission of HBV . Data from 154 women who received TDF within a r and omized controlled trial were included . ABSTRACT We assessed tenofovir exposure during pregnancy and postpartum in hepatitis B virus (HBV)-infected HIV-uninfected women receiving tenofovir disoproxil fumarate ( TDF ) to prevent mother-to-child transmission of HBV . Data from 154 women who received TDF within a r and omized controlled trial were included . Individual plasma tenofovir exposures ( area under the concentration-time curve from 0 to 24 h [ AUC0–24 ] ) were estimated using a population pharmacokinetic approach . The estimated geometric mean tenofovir AUC0–24 was 20 % ( 95 % confidence interval [ 95 % CI ] , 19 to 21 % ) lower during pregnancy than during postpartum ; this modest reduction in the absence of HBV transmission suggests that no dose adjustment is needed Mother-to-child transmission is the major cause of chronic hepatitis B virus ( HBV ) infection . This double-blind trial tested the effect of tenofovir disoproxil fumarate ( TDF ) in preventing vertical transmission . Pregnant women who were HBsAg/HBeAg-positive with a HBV DNA titer ≥ 2 × 106 IU/mL were r and omly assigned to the control ( n = 60 ) and TDF-treated ( n = 60 ) groups . TDF treatment ( oral dose 300 mg/day ) was initiated at 24 weeks of gestation and continued to 4 weeks after delivery . The subjects were followed up to 28 weeks postpartum . The effects of TDF on vertical transmission , outcomes of the mothers and infants and virological changes were monitored . TDF dynamically reduced the serum HBV DNA level of the mothers , particularly during the first 4 weeks of treatment . The lower viral loads were maintained in the pregnancies until delivery . Approximately 90 % and 33.9 % of the TDF-treated mothers had viral loads ≤2000 IU/mL after delivery and at 28 weeks postpartum , respectively . No cervical transmission or adverse effects were observed in the TDF-treated individuals , whereas 13.5 % of the infants were infected with HBV in the control group . We conclude that TDF treatment initiated at 24 weeks of gestation in high-viremia , HBsAg/HBeAg-positive mothers efficiently prevents mother-to-child HBV transmission without adverse events in mothers and infants The efficacy and safety of maternal tenofovir disoproxil fumarate ( TDF ) in reducing mother‐to‐infant hepatitis B virus ( HBV ) transmissions is not clearly understood . We conducted a prospect i ve , multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)– and hepatitis B e antigen – positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication ( control group , n = 56 , HBV DNA 8.22 ± 0.39 log10 IU/mL ) or TDF 300 mg daily ( TDF group , n = 62 , HBV DNA 8.18 ± 0.47 log10 IU/mL ) from 30‐32 weeks of gestation until 1 month postpartum . Primary outcome was infant HBsAg at 6 months old . At delivery , the TDF group had lower maternal HBV DNA levels ( 4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL , P < 0.0001 ) . Of the 121/123 newborns , the TDF group had lower rates of HBV DNA positivity at birth ( 6.15 % versus 31.48 % , P = 0.0003 ) and HBsAg positivity at 6 months old ( 1.54 % versus 10.71 % , P = 0.0481 ) . Multivariate analysis revealed that the TDF group had lower risk ( odds ratio = 0.10 , P = 0.0434 ) and amniocentesis was associated with higher risk ( odds ratio 6.82 , P = 0.0220 ) of infant HBsAg positivity . The TDF group had less incidence of maternal alanine aminotransferase ( ALT ) levels above two times the upper limit of normal for ≥3 months ( 3.23 % versus 14.29 % , P = 0.0455 ) , a lesser extent of postpartum elevations of ALT ( P = 0.007 ) , and a lower rate of ALT over five times the upper limit of normal ( 1.64 % versus 14.29 % , P = 0.0135 ) at 2 months postpartum . Maternal creatinine and creatinine kinase levels , rates of congenital anomaly , premature birth , and growth parameters in infants were comparable in both groups . At 12 months , one TDF‐group child newly developed HBsAg positivity , presumably due to postnatal infection and inefficient humoral responses to vaccines . Conclusions : Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations . ( Hepatology |
1,041 | 32,390,133 | 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 . | BACKGROUND Malnutrition is common in patients with chronic kidney disease ( CKD ) on dialysis .
Oral protein-based nutritional supplements are often provided to patients whose oral intake is otherwise insufficient to meet their energy and protein needs .
Evidence for the effectiveness of oral protein-based nutritional supplements in this population is limited .
OBJECTIVES The aims of this review were to determine the benefits and harms of using oral protein-based nutritional supplements to improve the nutritional state of patients with CKD requiring dialysis . | 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 dietary recall and counselling for the prescribed diet ( protein intake of 1.2 g/kgIBW/d and energy of 35 to 45 kcal/kgIBW/d ) but no specific post-HD supplement . Patients in the supplement group received the respective supplement post-HD ( providing 500 kcal and 15 g protein ) for 1 month in addition to the monitored diet prescription . MAIN OUTCOME MEASURES ( 1 ) Nutritional status parameters , BMI and serum albumin ; ( 2 ) functional status on a 10-point Karnofsky scale ; ( 3 ) adverse metabolic effects , hyperphosphatemia at start and end of study ; and ( 4 ) subjective scoring for appetite , and acceptability of and tolerance to supplement . RESULTS Both groups showed an improvement in dry weight and BMI . In addition , the supplement group showed a significant increase in serum albumin level and functional scoring . Mild hyperphosphatemia occurred in the supplement group . An increase in baseline food intake was seen in the control group , but not in the supplemented group . No intolerance was reported to either supplement . CONCLUSION Enteral nutrient supplementation was shown to bring about a significant improvement in serum albumin level even in a short-term study . Use of an HP supplement was beneficial , acceptable , and inexpensive BACKGROUND Anorexia may be associated with decreased plasma levels of branched-chain amino acids ( BCAA ) . In malnourished elderly haemodialysis ( HD ) patients , oral BCAA supplementation may improve anorexia , result ing in improved nutritional status . METHODS Among 44 elderly ( age > 70 years ) patients on chronic HD , 28 patients with low plasma albumin concentration ( < 3.5 g/dl ) were classified as the malnourished group ; they also suffered from anorexia . The other 16 patients did not complain of anorexia and were classified as the well-nourished group . We performed a 12-month , placebo-controlled , double-blind study on the malnourished group . Fourteen patients each received daily oral BCAA supplementation ( 12 g/day ) or a placebo in r and om order in a crossover trial for 6 months . Body fat percentage , lean body mass , plasma albumin concentration , dietary protein and caloric intakes , and plasma amino acid profiles were monitored . RESULTS Lower plasma levels of BCAA and lower protein and caloric intakes were found in the malnourished group as compared to the well-nourished group . In BCAA-treated malnourished patients , anorexia and poor oral protein and caloric intakes improved within a month concomitant with the improvement in plasma BCAA levels over the values in well-nourished patients . After 6 months of BCAA supplementation , anthropometric indices showed a statistically significant increase and mean plasma albumin concentration increased from 3.31 g/dl to 3.93 g/dl . After exchanging BCAA for a placebo , spontaneous oral food intake decreased , but the favourable nutritional status persisted for the next 6 months . In 14 patients initially treated with a placebo , no significant changes in nutritional parameters were observed during the first 6 months . However , positive results were obtained by BCAA supplementation during the subsequent 6 months , and mean plasma albumin concentration increased from 3.27 g/dl to 3.81 g/dl . CONCLUSIONS Normalization of low plasma levels of BCAA by oral supplementation can reduce anorexia and significantly improve overall nutritional status in elderly malnourished HD patients INTRODUCTION Malnutrition is multifactorial and may be modified by nutritional intervention . We aim ed to assess the impact of an intervention on the nutritional status of malnourished hemodialysis patients and their acceptance of a non-industrialized nutritional supplement . METHODS 18 patients were studied , they were selected from a previous nutritional assessment where nutritional risk was defined as : subjective global assessment > 15 plus one criterion for malnutrition . The following variables were assessed : anthropometric parameters , subjective global assessment , dietary intake , six-minute walking test , quality of life ( SF-36 ) , and biochemical tests . Patients were r and omized to either Control or Intervention Groups . The Intervention Group received a dietetic supplement during dialysis containing 355 kcal , prepared from simple ingredients . After three months , subjects from the Control Group and other patients also considered at nutritional risk underwent the same intervention . The study groups were compared after three months , and all patients were analyzed before and after the intervention . RESULTS Fifteen men and three women , aged 56.4 ± 15.6 years-old , nine in each group , were studied . The Intervention Group showed an improvement in the subjective global assessment ( p = 0.04 ) . There were differences in role physical and bodily pain domains of SF-36 , with improvement in the Intervention Group and worsening in the Control Group ( p = 0.034 and p = 0.021 ) . Comparisons before and after intervention for all patients showed improvement in the subjective global assessment ( 16.18 ± 4.27 versus 14.37 ± 4.20 , p = 0.04 ) , and in the six-minute walking test ( 496.60 ± 132.59 versus 547.80 ± 132.48 m ; p = 0.036 ) . The nutritional supplement was well tolerated by all patients , and it did not cause side effects . CONCLUSIONS The nutritional intervention improved the subjective global assessment and quality of life of hemodialysis patients at short-term . A global intervention by a dietitian produced specific and nonspecific positive effects in the whole group . Nutritional supplementation was feasible , palatable , and had low cost . Its clinical impact and effectiveness need to be further assessed in a larger group of patients at long-term MATERIAL S AND METHODS The concentrations of free intracellular amino acids in granulocytes and plasma amino acids , normalized protein nitrogen appearance rate , serum insulin-like growth factors , plasma proteins , anthropometric and bioimpedance measurements were determined before and after an oral protein supplement in 19 stable patients on maintenance hemodialysis in a r and omized , double-blind placebo-controlled study with crossover after 3 months . The hemodialysis patients were well-nourished with an ideal body weight of 91 % after both protein supplementation and after placebo . RESULTS After protein supplementation ( 7.8 g/d ) the intracellular concentration of valine , isoleucine , threonine and tyrosine and the valine/glycine and tyrosine/phenylalanine ratios in the cells were significantly increased ( p < 0.05 ) . In contrast , the concentrations of plasma amino acids , serum insulin-like growth factors , and plasma proteins and body weight and anthropometric and bioimpedance measurements were unchanged . Dialysis efficiency was unchanged throughout the study . CONCLUSIONS The present study supports the conclusion that protein supplementation to well-nourished hemodialysis patients does not improve the nutritional status measured by plasma proteins , body weight , anthropometric and bioimpedance measurements . The increase in intracellular amino acid concentrations indicates better cellular nutrition and metabolic control Many long-term maintenance hemodialysis patients have symptoms of protein-energy wasting caused by malnutrition . Each session of hemodialysis removes about 10 to 12 g of amino acids and 200 to 480 kcal of energy . Patients receiving hemodialysis for chronic kidney disease may be undernourished for energy , protein consumption , or both . Non-diabetic hemodialysis patients were r and omized to three treatment groups : oral supplementation , oral supplementation plus high-concentration glucose solution ( 250 mL containing 50 % glucose ) and these two interventions plus 8.5 % amino acids solution . The post-treatment energy status of the glucose group was significantly higher than its baseline level , whereas the control group ’s status was significantly lower . The glucose group had significantly higher concentrations of asparagine , glutamine , glycine , alanine , and lysine after treatment . All treatment groups had significantly increased hemoglobin levels but significantly decreased transferrin levels after treatment compared to baseline . After treatment , the amino acid group had significantly higher albumin level compared to the glucose group ( p = 0.001 ) and significantly higher prealbumin level compared to the control group ( p = 0.017 ) . In conclusion , long-term intervention with high-concentration glucose solution at each hemodialysis session is a simple and cheap method that replenished energy stores lost during hemodialysis of non-diabetic patients Background Fatigue is a predictor of cardiovascular events in patients with end-stage renal disease ( ESRD ) undergoing hemodialysis treatment . We hypothesized that multinutritional support would improve quality of life , fatigue symptoms , and potential quantitative measures including endocrine , immune and autonomic functions in patients with ESRD undergoing hemodialysis . Methods Two hundred and two hemodialysis patients were r and omly assigned to receive active treatment ( containing vitamin B1 , vitamin B2 , niacin , vitamin B6 , vitamin B12 , folic acid , vitamin C , carnitine , coenzyme Q10 , naïve galacto-oligosaccharide , and zinc ) or placebo after each dialysis session for 12 weeks . The patients and attending physicians were blinded to the treatment , and 172 patients ( 86 in each group ) completed the study . Fatigue was evaluated via fatigue question naire at 0 , 4 , and 12 weeks . To assess human herpes virus ( HHV ) 6 and 7 reactivation , numbers of viral DNA copies were determined in saliva by polymerase chain reaction at weeks 0 and 12 . Autonomic function was determined via measurement of beat-to-beat variation by using acceleration plethysmography . Results Clinical characteristics , changes in fatigue , quality of life score , endocrine functions , and laboratory data did not differ significantly between the two groups . Several parameters of heart rate variability significantly increased after nutritional treatment compared to placebo . Nutritional drink for 12 weeks significantly suppressed HHV7 DNA copy numbers . Similarly , HHV6 DNA copy numbers tended to be decreased by treatment but without reaching statistical significance . Conclusions Nutritional supplementation may modulate immune and autonomic dysfunction in ESRD patients undergoing hemodialysis The aim of this study was to verify the clinical efficacy of a diet associated with already commercially available oral amino acid functional cluster ( AFC ) compared to the administration of a diet associated with a nitrogen protein-based supplement ( casein ) in antagonizing malnutrition in patients with Chronic renal failure ( CRF ) undergoing haemodialysis . The secondary aim was to assess the changes in protein levels during the acute phase such as the expression of inflammatory cytokines . Twenty patients in haemodialysis aged between 18 and 85 of both genders ( 13 m , 7f ) were recruited , r and omized and divided into two groups and treated for 4 months respectively with : ( 1 ) oral AFC supplement (*)8 g/die : group A , and ( 2 ) oral supplementation of a protein nitrogenous mixture compared to AFC with a casein protein source ) of 6.6 g : group P. During the initial assessment and thereafter on a monthly basis all patients underwent the following : Dietary recall 24 h ; Anthropometric : Weight , height , BMI , expected dry weight , actual weight ; Biochemical : Albumin , transferrin , Na , K , Cl , Ca , P , Mg , long-interval creatinine ( Aminotrofic ® : Errekappa Euroterapici , Milano ) pre-albumin , α1 acid glycoprotein , C reactive protein ( CRP ) , protein nitrogen appearance ( PNA ) ; Instrumental : H and grip strength evaluation , Calorimetry by means of Armb and , Bio-impedance analysis ( BIA ) , Spitzer Index ( quality of life ) , Subjective Global Assessment Generated by the patient ( PG SGA ) . Considering the nutritional parameters , no significant differences concerning dry weight emerged between the beginning ( T0 ) and the end ( T4 ) ( weight A to T0 : kg 64.41 ± 6.34 ; weight A to T4 : kg 64.51 ± 7.05 : P = NS ; weight P to T0 : kg 60.17 ± 11.94 ; weight P to T4 : kg 59.86 ± 11.43 : P = NS ) ; biochemical parameters , significant differences were observed only for two parameters : pre-albumin ( Pre-albumin A to T0 30.12 ± 7.23 ; Pre-albumin A to T4 : 28.91 ± 5.8 ; Pre-albumin P to T0 22.51 ± 6.04 ; Pre-albumin P to T4 : 26.10 ± 9.82 ) , and Transferrin ( Transferrin A to T0 171.77 ± 28.87 mg/dL , Transferrin A to T4 : 181.44 ± 38.83 mg/dL : P < 0.005 ; Transferrin P to T0 160.29 ± 27.46 mg/dL , Transferrin P to T4 : 146.57 ± 24.96 mg/dL : P < 0.005 ) , but not in other parameters . From a nutritional perspective , after 4 months of treatment an increase in protein synthesis was noted in group A compared to group P which was proved by the significant increase of transferrin . This pilot study suggests the AFC oral supplementation may represent a valid alternative to intradialytic parenteral treatment and may also allow for an improvement in blood chemical values and nutritional status Background Protein-energy wasting ( PEW ) is common in hemodialysis patients and is a powerful predictor of morbidity and mortality . Although much progress has been made in recent years in identifying the causes and pathogenesis of PEW in hemodialysis patients , actual management by nutritional interventions is not always able to correct PEW . Some investigators suggest that physical exercise may increase the anabolic effects of nutritional interventions , and therefore may have a potential to reverse PEW . The aim of this study is to investigate the effect of intra-dialytic progressive exercise training and adequate nutritional supplementation on markers of PEW , functional capacities and quality of life of adult hemodialysis patients . Methods and design Fifty end-stage renal disease patients undergoing hemodialysis , who meet the diagnostic criteria for PEW , will be r and omly allocated into an exercise or control group for 6 months . The exercise consists of a progressive submaximal individualized cycling exertion using an adapted cycle ergometer , during the three weekly dialysis sessions . Biological markers of nutrition ( albumin , prealbumin ) will be followed monthly and all patients will be assessed for body composition , walk function , muscle strength , postural stability and quality of life at baseline and during the eighth week ( t+2 ) , the sixteenth week ( t+4 ) and the twenty-fourth week ( t+6 ) of the 6-month adapted rehabilitation program . Discussion The successful completion of this current trial may give precious clues in underst and ing PEW and encourage nephrologists to extend prescription of exercise programs as well as therapeutic and as preventive interventions in this high-risk population .Trial registration The protocol for this study was registered with the France Clinical Trials Registry NCT01813851 Haemodialysis is a form of renal replacement therapy but is a catabolic process that not only filters toxins but is also known to lead to amino acid losses . Patients with chronic kidney disease often have a poor appetite and this in combination with limited dietary intake and the detrimental effects of haemodialysis can lead to the development of malnutrition . Between 20 % and 50 % of haemodialysis patients are thought to be malnourished . Malnutrition can worsen clinical outcomes and increase the risk of hospitalisation . We hypothesise that a nutritional supplement taken during haemodialysis may help to improve nutritional status . The aim of this study is to conduct a pilot r and omised controlled trial to assess the use of an intradialytic nutritional supplement on nutritional status . The objectives are to assess the feasibility of the trial including : recruitment and retention of participants ; preference of nutritional supplements ; compliance with the intervention ; ease of completion of the question naires and appropriateness of the tools used . Secondary outcomes include clinical outcomes to obtain variance in the patient population and estimates of effect size to inform the sample size for a future definitive trial . The trial is a single centre , r and omised , parallel-group , two armed external pilot with an intervention and control group . The intervention group will take a nutritional supplement each dialysis session from a choice of prescribable drink or pudding style supplements . The control group will receive st and ard care . Recruitment and feasibility elements are the primary outcomes . Recruitment will be to time ( t = 6 weeks ) . In order to collect sufficient data to inform a future sample size calculation , we will aim to recruit 30 participants to obtain 12 evaluable per arm anticipating some drop out . Secondary outcome measures include clinical variables ; h and grip strength , quality of life , weight and biochemistry completed at baseline , 1 and 2 months . Descriptive statistics will be used to analyse the baseline characteristics of the recruited participants . Means , confidence intervals and st and ard deviations will be reported for the outcome measures of h and grip strength , dietary intake , quality of life and weight . Trial registration IS RCT N37431579 Background The study was done to assess the feasibility of conducting a trial evaluating the use of an intradialytic oral nutritional supplement ( ONS ) on nutritional status . Methods The study design is a single centre , parallel group , external pilot r and omised controlled trial ( RCT ) . The setting was at a haemodialysis unit in Sheffield , UK . The aim was to recruit 30 trial participants to allow at least 12 evaluable patients per arm , but the actual study sample consisted of 10 adults with a body mass index ( BMI ) ≤22 kg/m2 , receiving thrice weekly haemodialysis . All participants received nutritional advice from a renal dietitian as per usual practice . The intervention included the provision of an intradialytic ONS . Feasibility outcomes included recruitment to time and retention of participants along with palatability of ONS . Secondary outcomes were clinical parameters to obtain variance and estimates of effect size to inform the sample size calculation for a definitive trial . Results Recruitment was undertaken for a fixed period of 6 weeks . Rates were lower than expected mainly due to in eligibility with only 7 % of screened patients ( 19/265 ) being eligible and 4 % ( 10/265 ) of these being recruited . Due to the small proportion of patients eligible for the trial , all haemodialysis patients at the specified unit were assessed for eligibility . Data completion rates were low for session question naires ( 23 % ) . Sample sizes derived from variance in secondary outcome measure of h and grip strength and adjusted for a dropout rate of 20 % indicate that 189 patients would be required for a definitive RCT , requiring 19 UK haemodialysis units to participate . Conclusions A definitive RCT is feasible with some adaptation to exclusion criteria and methodology . The exclusion criteria could be adapted to include an increase in upper limit for BMI . The use of question naires at each dialysis session may not be feasible but the inclusion of appetite and supplement consumption data collection at the main assessment s would provide similar outcome data . Quality of life assessment using SF-12 would be acceptable . Trial registration IS RCT N37431579 OBJECTIVE To evaluate differences between dietary energy intake ( DEI ) , dietary protein intake ( DPI ) , appetite , dietary patterns , and eating habits during dialysis treatment days ( DD ) and non-dialysis treatment days ( NDD ) in 1,901 adults receiving maintenance hemodialysis who were enrolled in the baseline phase of the National Institutes of Health-sponsored Hemodialysis ( HEMO ) study . DESIGN A cross-sectional analysis of participants at baseline ( before r and omization ) . SETTING Fifteen clinical centers across the United States . MEASUREMENTS DEI , DPI , and self-reported assessment of appetite , dietary patterns , and eating habits . RESULTS For the entire study cohort , total mean ( + /- SD ) DEI ( 1,566 + /- 636 kcal/day ) and weight-adjusted DEI ( 23.2 + /- 9.5 kcal/kg/day ) were significantly higher ( P < .0001 ) on NDD than on DD ( 1,488 + /- 620 kcal/day and 22.2 + /- 9.6 kcal/kg/day ) , respectively . Similarly , DPI was significantly higher ( P < .0001 ) on NDD ( 65.0 + /- 29.0 g/day and 0.96 + /- 0.43 g/kg/day ) than on DD ( 60.2 + /- 26.5 g/day and 0.90 + /- 0.41 g/kg/day ) . On DD and NDD , the mean weight-adjusted DEI for the entire cohort was less than the HEMO study st and ard of care ( SOC ) of > or = 28 kcal/kg/day , whereas on NDD , several subgroups reported dietary protein intakes that were closer to the study 's SOC . These included men , patients under 50 years of age , nonblack participants , those without diabetes , those with a normal or mild Index of Co-Existing Disease score , and those on dialysis for more than 5 years . Protein and energy intakes declined with worsening self-reported appetites in both DD and NDD after adjusting for other subgroup effects . CONCLUSION Dietary energy and protein intakes of HEMO study participants were lower on DD than on NDD , and also lower than the SOC on both days , particularly with regard to energy intake . People receiving maintenance hemodialysis should be counseled to consume adequate amounts of energy and protein daily , especially on DD . Practitioners should monitor closely those patients who report poor appetite and should intervene appropriately Protein-energy wasting ( PEW ) , defined as a loss of body protein mass and fuel reserves , is a powerful predictor of adverse outcomes in haemodialysis ( HD ) patients . Robust arguments suggest that intra-dialytic exercise , combined with oral/parenteral nutrition , enhances the effect of nutritional interventions in HD patients . This pilot r and omized controlled trial investigated the feasibility and the effects of a 6 month intra-dialytic cycling program combined to a nutritional support on PEW , physical functioning ( gait , balance , muscle strength ) and quality of life ( QoL ) in older HD patients ( mean age 69.7 ± 14.2 years).Twenty-one patients fulfilling diagnostic criteria of PEW were r and omly assigned to Nutrition-Exercise group ( GN-Ex , n = 10 ) or Nutrition group ( GN , n = 11 ) . Both groups received nutritional supplements in order to reach recommended protein and energy intake goals . In addition GN-Ex completed a cycling program . No significant difference between groups was found in the number of patients having reached remission of PEW . Likewise , no change was observed in serum-albumin , -prealbumin , C-reactive protein , body mass index , lean- and fat-tissue index , or quadriceps force . Interestingly , we found positive effects of exercise on physical function and QoL for the GN-Ex , as evidence d by a significant improvement in the 6-min walk test ( + 22 % ) , the absence of decline in balance ( unlike the GN ) , and a noteworthy increase in QoL ( + 53 % ) . Combining intra-dialytic exercise and nutrition in HD patients is feasible , and well accepted , improves physical function and QoL but it appears not to have the potential to reverse PEW BACKGROUND Resistance exercise combined with intradialytic oral nutrition ( IDON ) supplementation improves net protein balance in the acute setting in chronic hemodialysis patients . We hypothesized that combination of long-term resistance exercise and IDON would improve markers of muscle mass and strength further compared with IDON alone . METHODS Thirty-two participants ( 21 male ; mean age , 43 ± 13 years ) on chronic hemodialysis were r and omly assigned to IDON plus resistance exercise ( NS + EX ) , or IDON ( NS ) alone for 6 months . IDON consisted of a lactose-free formula consisting of protein , carbohydrate , and fat . Three sets of 12 repetitions of leg-press were completed before each dialysis session in the NS + EX arm . Primary outcome measurement was lean body mass . Muscle strength and other nutritional parameters were measured as secondary outcomes . RESULTS Of 32 participants , 22 completed the 6-month intervention . There were no statistically significant differences between the study interventions with respect to changes in lean body mass and body weight , when comparing NS + EX to NS . There were also no statistically significant differences in any of the secondary outcomes measured in the study . Body weight ( 80.3 ± 16.6 kg , 81.1 ± 17.5 kg , and 80.9 ± 18.2 kg at baseline , month 3 , and month 6 , respectively ; P = .02 ) and 1-repetition maximum ( 468 ± 148 lb , 535 ± 144 lb , and 552 ± 142 lb , respectively ; P = .001 ) increased statistically significantly during the study for all patients combined . CONCLUSION This study did not show further benefits of additional resistance exercise on long-term somatic protein accretion above and beyond nutritional supplementation alone . When both treatments groups were combined , body weight and muscle strength improved during the study A r and omized study was planned to compare the effects of whey and egg albumin protein supplements in dialysis patients . Fifty adult patients were r and omized to receive either whey protein or egg albumin as per their deficit calculated from K/DOQI recommendations . Actual intake was calculated from three-day dietary diary . Assessment of nutritional status was done by serum albumin and bioelectric impedance analysis ( BIA ) . Repeat evaluation was done after 6 months . The mean initial intake of protein in whey and egg albumin group was 0.74 ± 0.3 vs. 0.69 ± 0.2 g/kg/day , ( P = 0.5 ) and calorie intake was 20 ± 5.6 vs. 20.5 ± 5.1 kcal/kg/day , ( P = 0.8 ) , respectively . Out of 50 patients , two died within 2 months and were excluded from the study and 14 ( 28 % ) dropped out within one month because of side effects . The most common side effect in drop-outs was nausea and vomiting ( 43 % ) . Out of remaining 34 patients who completed the study , 80 % could not consume > 50 % of the recommended supplement because of side effects . The protein and calorie intake remained similar at baseline and 6 months in both the groups . The main side effects in whey group were bloating and nausea with vomiting , and in egg protein group were nausea with vomiting , bloating and anorexia . Oral protein supplements were not tolerated in dialysis patients and side effects result ed in high degree of non-compliance OBJECTIVE To determine the difference in the rate of change of serum albumin levels between protein-energy malnourished patients who receive intensive dietary counseling and patients who receive a special oral liquid nutritional supplement ( Nepro ; Ross Products , Division Abbott Laboratories , Columbus , OH ) . DESIGN Participants with serum albumin values < or = 3.5 g/dL ( bromocresol green ) or 3.2 g/dL ( bromocresol purple ) and a Mini Nutrition Assessment ( MNA ) Malnutrition score < or = 23.5 were r and omized to the supplement group ( Nepro ) or the nonsupplement group with intensive dietary counseling . PATIENTS Forty-one hemodialysis patients 18 years and older who had been on dialysis for at least 6 months . INTERVENTION Participants were r and omly assigned to supplement ( 26 ) or nonsupplement ( 14 ) groups . MAIN OUTCOME MEASURES Albumin levels . STATISTICAL ANALYSES PERFORMED Analysis of variance and chi2 tests , linear regression . RESULTS After adjustment for demographic and clinical characteristics , the rate of change in serum albumin level was significantly greater among patients r and omized to dietary counseling alone than among those who received oral supplements . These preliminary results suggest that intensive nutritional counseling may be of greater benefit than nutritional supplements alone in the management of protein-energy malnutrition in patients on hemodialysis . These preliminary findings should be confirmed by a larger full-scale trial In maintenance hemodialysis ( MHD ) patients , low protein intake is associated with protein-energy wasting , a risk factor that affects outcome . However , increased protein intake may lead to hyperphosphatemia and hyperkalemia , which are also mortality risk factors . Here , we evaluated the safety and effects of purified rice endosperm protein ( REP ) , which contains less phosphorus and potassium than soy and casein proteins , as a supplemental protein source for MHD patients . This r and omized , double-blind , placebo-controlled , crossover pilot study of REP supplementation ( 5 g/day × 4 weeks ) was carried out in 50 Japanese adult MHD patients ( 1 dropped out ) ; the primary outcome was the change in the urea kinetic-based normalized protein catabolic rate ( nPCR ) , an indicator of protein intake in MHD patients . Intention-to-treat analyses of 24 patients in the REP-first group and 25 in the placebo-first group showed that REP supplementation increased nPCR significantly by 0.07 g/kg/day ( 95 % confidence interval , 0.03–0.11 ) , whereas changes in serum phosphorus and potassium concentrations were not different from the placebo . REP supplementation did not show a significant effect on other nutritional or metabolic parameters and no specific complications . In conclusion , purified REP with efficient bioavailability may be safe and useful for dietary supplementation in MHD patients OBJECTIVE The aim of this study was to investigate the effects of high-load strength training and protein intake in patients undergoing dialysis with a focus on muscle strength , physical performance , and muscle morphology . DESIGN This was a r and omized controlled study conducted in three dialysis centers . SUBJECTS Subjects for the study included 29 patients undergoing dialysis . INTERVENTION The participants went through a control period of 16 weeks before completing 16 weeks of strength training . Before the training period , the participants were r and omly assigned to receive a protein or a nonprotein drink after every training session . MAIN OUTCOME MEASURE Muscle strength and power were tested using the good strength equipment and the leg extensor power rig . Physical performance and function were assessed using a chair st and test and the Short Form 36 question naire . Muscle fiber type size and composition were analyzed in biopsies obtained from the m. vastus lateralis . RESULTS All variables remained unchanged during the control period . After training , muscle strength and power , physical performance , and physical function increased significantly . Muscle fiber composition was changed by a relative decrease in type 2x muscle fiber number whereas muscle size at the fiber level was unchanged . There were no effects of combining the training with protein intake . CONCLUSIONS High-load strength training is associated with improvements in muscle strength and power , physical performance , and quality of life . The effects were surprisingly not associated with muscle hypertrophy , and the results did not reveal any additional benefit of combining the training with protein intake . The positive results in muscle strength and physical performance have clinical ly relevant implication s in the treatment of patients undergoing dialysis Background Low serum albumin is common and associated with protein-energy wasting , inflammation , and poor outcomes in maintenance hemodialysis ( MHD ) patients . We hypothesized that in-center ( in dialysis clinic ) provision of high-protein oral nutrition supplements ( ONS ) tailored for MHD patients combined with anti-oxidants and anti-inflammatory ingredients with or without an anti-inflammatory appetite stimulator ( pentoxifylline , PTX ) is well tolerated and can improve serum albumin concentration . Methods Between January 2008 and June 2010 , 84 adult hypoalbuminemic ( albumin < 4.0 g/dL ) MHD out patients were double-blindly r and omized to receive 16 weeks of interventions including ONS , PTX , ONS with PTX , or placebos . Nutritional and inflammatory markers were compared between the four groups . Results Out of 84 subjects ( mean ± SD ; age , 59 ± 12 years ; vintage , 34 ± 34 months ) , 32 % were Blacks , 54 % females , and 68 % diabetics . ONS , PTX , ONS plus PTX , and placebo were associated with an average change in serum albumin of + 0.21 ( P = 0.004 ) , + 0.14 ( P = 0.008 ) , + 0.18 ( P = 0.001 ) , and + 0.03 g/dL ( P = 0.59 ) , respectively . No related serious adverse events were observed . In a predetermined intention-to-treat regression analysis modeling post-trial serum albumin as a function of pre-trial albumin and the three different interventions ( ref = placebo ) , only ONS without PTX was associated with a significant albumin rise ( + 0.17 ± 0.07 g/dL , P = 0.018 ) . Conclusions In this pilot-feasibility , 2 × 2 factorial , placebo-controlled trial , daily intake of a CKD-specific high-protein ONS with anti-inflammatory and anti-oxidative ingredients for up to 16 weeks was well tolerated and associated with slight but significant increase in serum albumin levels . Larger long-term controlled trials to examine hard outcomes are indicated OBJECTIVE In end-stage renal disease ( ESRD ) patients , malnutrition is mainly addressed from a pharmacological but not educational point of view . Therefore , the objective of this study was to implement a nutritional education program ( NEP ) and to evaluate and compare its effectiveness in the treatment and prevention of malnutrition with oral supplementation (OS)-the st and ard treatment in these patients . DESIGN This study was a longitudinal , 4-month prospect i ve study . SETTING S The study was conducted from January to May 2012 in the Hemodialysis Fresenius Medical Care Clinic of Murcia . SUBJECTS One hundred twenty patients with ESRD undergoing hemodialysis were r and omly assigned to a NEP or to OS . INTERVENTION Patients assigned to the NEP group followed an educational program for 4 months that aim ed to improve general nutritional knowledge and included culinary recommendations and an elaboration of balanced menus . The OS group received a nutritional supplement during the hemodialysis procedure . MAIN OUTCOME MEASURE The main outcome measure was certain biochemical markers of nutritional and metabolic status . Nutrition knowledge was also evaluated . RESULTS After 4 months of intervention , nutritional knowledge was increased in all patients ( P < .050 ) after the NEP , which was reflected in a decrease in the prevalence of malnutrition , especially in this group . Creatinine clearance , total protein serum values , and other biochemical parameters improved significantly in both groups ( P < .050 in all cases ) , although other parameters such as C-reactive protein were impaired only in the NEP group . CONCLUSION The NEP was at least as effective as OS for preventing and even treating malnutrition in patients with chronic renal failure on hemodialysis , improving their nutritional status , which may result in a long-term decrease in the mortality and morbidity of these patients Background : Protein malnutrition and lowering serum albumin is frequent in hemodialysis patients . A special amino acid formulation has recently been used with favorable effects in elderly people but no data exist in renal patients . Aim : To assess the effects of this novel amino acid formulation in stable hemodialysis patients with reduced albumin levels . Methods : Thirty stable hemodialysis patients with serum albumin levels < 3.5 g/dL , normalized protein nitrogen appearance ( nPNA ) < 1.1 g/kg/d , and body mass index ( BMI ) > 20 kg/m2 were selected : 15 patients were r and omized to oral amino acid supplementation ( 4 g thrice a day ) for 3 months and 15 patients comparable for age , gender , and dialysis duration s formed the control group . Biochemistry and bioimpedentiometry parameters were measured at baseline and at the end of treatment . Results : No difference was observed between study group and control group at baseline . At the end of the study period , no change occurred in the studied parameters in the control group , whereas increase in serum albumin ( 3.1 ± 0.3 vs. 3.6 ± 0.2 g/dL , p < 0.001 ) and in total proteins ( 5.7 ± 0.4 vs. 6.4 ±0.7 g/dL , p < 0.001 ) occurred in the study group . Hemoglobin rose from 10.7 ± 0.9 to 11.7 ± 0.8 g/dL ( p < 0.05 ) at the same erythropoiesis-stimulating agent ( ESA ) dosage . C-Reactive protein ( CRP ) levels decreased in the study group ( 8.7 ± 7.3 vs. 3.8 ± 3.1 mg/L , p < 0.01 ) . Increase of body weight and of equilibrated protein catabolic rate ( ePCR ) was observed in the study group . Conclusions : Oral amino acids supplementation was able to improve albumin and total protein in hypoalbuminemia hemodialysis patients . This effect was associated with reduction of CRP levels that is with lowering of pro-inflammatory status and anemia improvement Background / Aim Malnutrition is highly prevalent in patients on continuous ambulatory peritoneal dialysis ( CAPD ) and is a strong predictor of increased morbidity and mortality . Therefore , the aim of this study was to evaluate the effect of oral administration of an egg albumin-based protein supplement on the nutritional status of CAPD patients . Methods In this r and omized , open label , controlled clinical trial , 28 CAPD patients were allocated to a study ( n = 13 ) or a control ( n = 15 ) group . Both groups received conventional nutritional counseling ; the study group received , additionally , an oral egg albumin-based supplement . During a 6-month follow-up , all patients had monthly clinical and biochemical evaluations and quarterly assessment s of adequacy of dialysis and nutrition . Results Serum albumin levels were not different between groups ; however , a significant increase ( baseline vs final ) was observed in the study group ( 2.64 ± 0.35 vs 3.05 ± 0.72 g/dL ) but not in the control group ( 2.66 ± 0.56 vs 2.80 ± 0.54 mg/dL ) . Calorie and protein intake increased more in the study group ( calories 1331 ± 432 vs 1872 ± 698 kcal ; proteins 1.0 ± 0.3 vs 1.7 ± 0.7 g/kg ) than in the control group ( calories 1423 ± 410 vs 1567 ± 381 kcal ; proteins 1.0 ± 0.4 vs 1.0 ± 0.3 g/kg ) . Similarly , non-protein nitrogen appearance rate ( nPNA ) increased significantly more in the study ( 1.00 ± 0.23 vs 1.18 ± 0.35 g/kg/day ) than in the control group ( 0.91 ± 0.11 vs 0.97 ± 0.14 g/kg/day ) . Triceps skinfold thickness ( TSF ) and midarm muscle area ( MAMA ) displayed a nonsignificant trend to a greater increase in the study group ( TSF 16.7 ± 8.7 vs 18.3 ± 10.7 mm ; MAMA 23.8 ± 6.2 vs 25.8 ± 5.9 cm2 ) than in controls ( TSF 16.4 ± 5.7 vs 16.9 ± 7.0 mm ; MAMA 28.7 ± 7.8 vs 30.0 ± 7.9 cm2 ) . At the end of follow-up , the frequency of patients with moderate or severe malnutrition decreased 6 % in the control group and decreased 28 % in the study group . At the final evaluation , the most important predictors of serum albumin were the oral egg albumin-based supplement administration and protein intake ( p < 0.05 ) ; secondary predictors ( p = 0.06 ) were peritoneal transport rate and MAMA . Conclusions In the study group , oral administration of the egg albumin-based supplement significantly improved serum albumin , calorie and protein intake , and nPNA , and , compared to controls , this maneuver was associated with a trend to increased anthropometric parameters and improved Subjective Global Assessment evaluation . Oral administration of the albumin supplement and protein intake were the most significant predictors of serum albumin at the end of follow-up . This oral supplement may be a safe , effective , and cheap method to improve nutritional status in peritoneal dialysis patients OBJECTIVE Protein malnutrition is both a cause and consequence of inflammation and related comorbidities for maintenance hemodialysis ( MHD ) patients . This study sought to determine if oral supplementation with soy or whey protein during dialysis treatment reduces inflammation and improves physical function and body composition in MHD patients . DESIGN The design used in the study was r and omized controlled trial , and the setting used was hemodialysis clinics in Champaign and Chicago , Illinois . SUBJECTS Patients who received treatment ≥3 days/week , were ages ≥30 years did not have congestive heart failure or chronic obstructive pulmonary disease , and were receiving dialysis treatment for ≥3 months were eligible for inclusion . INTERVENTION Patients were r and omized to oral supplementation with a whey protein , soy protein , or placebo beverage . Patients ( WHEY , n = 11 ; SOY , n = 12 ; CON , n = 15 ) consumed their assigned beverage before every dialysis session for 6 months . MAIN OUTCOME MEASURES Body composition was measured by dual-energy x-ray absorptiometry , physical function by gait speed and shuttle walk test , and markers of inflammation ( C-reactive protein and interleukin 6 ) using commercially available enzyme-linked immunosorbent assay kits before and after the 6-month intervention . Dietary intake was assessed by 24-hour dietary recalls . RESULTS Six months of whey or soy supplementation significantly reduced predialysis interleukin 6 levels ( P < .05 for both ) , whereas there was a trend for a reduction in C-reactive protein when both protein groups were combined ( P = .062 ) . Gait speed and shuttle walk test performance also significantly improved in the protein groups ( P < .05 for both ) . No changes in body composition were observed . However , alkaline phosphatase , a marker of bone turnover , was significantly reduced in the protein groups . CONCLUSIONS Intradialytic protein supplementation during a 6-month intervention reduced inflammation and improved physical function and represents an affordable intervention to improve the health of MHD patients BACKGROUND AND AIMS Poor dietary intake is commonly associated with malnutrition in the dialysis population and oral nutritional supplementation is strategized to redress dietary inadequacy . Knowledge on clinical efficacy of whey protein supplementation ( WPS ) as an option to treat malnutrition in continuous ambulatory peritoneal dialysis ( CAPD ) patients is limited . METHODS This multicenter , parallel , open-label , r and omized controlled trial investigated the clinical efficacy of WPS in 126 malnourished CAPD patients with serum albumin < 40 g/L and body mass index ( BMI ) < 24 kg/m2 . Patients r and omized to the intervention group ( IG , n = 65 ) received protein powder ( 27.4 g ) for 6 months plus dietary counseling ( DC ) while the control group ( CG , n = 61 ) received DC only . Anthropometry , biochemistry , malnutrition-inflammation-score ( MIS ) , dietary intake inclusive of dialysate calories , h and grip strength ( HGS ) and quality of life ( QOL ) were assessed at baseline and 6 months . Clinical outcomes were assessed by effect size ( Cohen 's d ) comparisons within and between groups . RESULTS Seventy-four patients ( n = 37 per group ) completed the study . Significantly more IG patients ( 59.5 % ) achieved dietary protein intake ( DPI ) adequacy of 1.2 g/kg per ideal body weight ( p < 0.001 ) compared to CG ( 16.2 % ) although difference in the adequacy of dietary energy intake between groups was non-significant ( p > 0.05 ) . A higher DPI paralleled significant increases in serum urea ( mean Δ : IG = + 2.39 ± 4.36 mmol/L , p = 0.002 , d = 0.57 vs CG = -0.39 ± 4.59 mmol/L , p > 0.05 , d = 0.07 ) and normalized protein catabolic rate , nPCR ( mean Δ : IG = + 0.11 ± 0.14 g/kg/day , p < 0.001 , d = 0.63 vs CG = + 0.001 ± 0.17 g/kg/day , p > 0.05 , d = 0.09 ) for IG compared to CG patients . Although not significant , comparison for changes in post-dialysis weight ( mean Δ : + 0.64 ± 1.16 kg vs + 0.02 ± 1.36 kg , p = 0.076 , d = 0.58 ) and mid-arm circumference ( mean Δ : + 0.29 ± 0.93 cm vs -0.12 ± 0.71 cm , p = 0.079 , d = 0.24 ) indicated trends favoring IG vs CG . Other parameters remained unaffected by treatment comparisons . CG patients had a significant decline in QOL physical component ( mean Δ = -6.62 ± 16.63 , p = 0.020 , d = 0.47 ) . Using changes in nPCR level as a marker of WPS intake within IG , ' positive responders ' achieved significant improvement in weight , BMI , skinfold measures and serum urea ( all p < 0.05 ) , while such changes within ' negative responders ' were non-significant ( all p > 0.05 ) . CONCLUSION A single macronutrient approach with WPS in malnourished CAPD patients was shown to achieve DPI adequacy and improvements in weight , BMI , skin fold measures , serum urea and nPCR level . CLINICAL TRIAL REGISTRY : www . clinical trials.gov ( NCT03367000 ) Malnutrition inflammation complex syndrome ( MICS ) occurs commonly in maintenance hemodialysis ( MHD ) patients and may correlate with increased morbidity and mortality . An optimal , comprehensive , quantitative system that assesses MICS could be a useful measure of clinical status and may be a predictor of outcome in MHD patients . We therefore attempted to develop and vali date such an instrument , comparing it with conventional measures of nutrition and inflammation , as well as prospect i ve hospitalization and mortality . Using components of the conventional Subjective Global Assessment ( SGA ) , a semiquantitative scale with three severity levels , the Dialysis Malnutrition Score ( DMS ) , a fully quantitative scoring system consisting of 7 SGA components , with total score ranging between 7 ( normal ) and 35 ( severely malnourished ) , was recently developed . To improve the DMS , we added three new elements to the 7 DMS components : body mass index , serum albumin level , and total iron-binding capacity to represent serum transferrin level . This new comprehensive Malnutrition-Inflammation Score ( MIS ) has 10 components , each with four levels of severity , from 0 ( normal ) to 3 ( very severe ) . The sum of all 10 MIS components ranges from 0 to 30 , denoting increasing degree of severity . These scores were compared with anthropometric measurements , near-infrared-measured body fat percentage , laboratory measures that included serum C-reactive protein ( CRP ) , and 12-month prospect i ve hospitalization and mortality rates . Eighty-three out patients ( 44 men , 39 women ; age , 59 + /- 15 years ) on MHD therapy for at least 3 months ( 43 + /- 33 months ) were evaluated at the beginning of this study and followed up for 1 year . The SGA , DMS , and MIS were assessed simultaneously on all patients by a trained physician . Case-mix-adjusted correlation coefficients for the MIS were significant for hospitalization days ( r = 0.45 ; P < 0.001 ) and frequency of hospitalization ( r = 0.46 ; P < 0.001 ) . Compared with the SGA and DMS , most pertinent correlation coefficients were stronger with the MIS . The MIS , but not the SGA or DMS , correlated significantly with creatinine level , hematocrit , and CRP level . During the 12-month follow-up , 9 patients died and 6 patients left the cohort . The Cox proportional hazard-calculated relative risk for death for each 10-unit increase in the MIS was 10.43 ( 95 % confidence interval , 2.28 to 47.64 ; P = 0.002 ) . The MIS was superior to its components or different subversions for predicting mortality . The MIS appears to be a comprehensive scoring system with significant associations with prospect i ve hospitalization and mortality , as well as measures of nutrition , inflammation , and anemia in MHD patients . The MIS may be superior to the conventional SGA and the DMS , as well as to individual laboratory values , as a predictor of dialysis outcome and an indicator of MICS OBJECTIVE We evaluated the impact of oral protein supplementation given during hemodialysis and peritoneal dialysis on nutritional status , number of hospitalizations , and length of stay . DESIGN We used a r and omized crossover design in which serum albumin , normalized protein catabolic rate ( nPCR ) , total hospitalizations , and length of stay were compared in patients who received protein supplements with those who did not . The study was conducted for 1 year ( November 2005 to October 2006 ) . SETTING This study was conducted at an outpatient dialysis facility . SUBJECTS Forty-nine patients were treated with hemodialysis or peritoneal dialysis for at least 3 months . RESULTS The nPCR significantly increased by month 4 of treatment from a baseline of 1.05 to 1.16 ( P = .007 ) . The control group had a significant decline in nPCR during the first 6 months , from 1.11 to 0.98 ( P = .038 ) . Improvement was evident in albumin by month 3 , from 3.49 to 3.52 ( P = .035 ) , but this was not sustained . In the second 6 months , the control group had a significant drop , from 3.35 to 3.19 ( P = .014 ) , and the difference between the protein-supplementation and control groups was significant during the second 6 months ( P = .037 ) . The nPCR also dropped significantly ( P = .024 ) for the control group in the second 6 months . When protein supplementation ended , weight dropped significantly for those with a body mass index of < 20 . Trends toward a reduction in hospitalization admissions and hospital days were seen in both crossover treatment groups . CONCLUSIONS In-center supplementation of protein generally improves serum markers of nutrition overall , and when it is discontinued , these markers decline . Larger studies are needed to confirm the trends that we observed regarding nutritional markers and reductions in hospitalizations and hospitalization days BACKGROUND Malnutrition is a common finding in hemodialysis patients and can increase oxidative stress and inflammation levels . STUDY DESIGN A r and omized , controlled , nonblinded , parallel trial . SETTING & PARTICIPANTS 92 hemodialysis patients from a single center with malnutrition according to subjective global assessment ( SGA ) score ( SGA score > 7 ) . INTERVENTION 3 treatment groups ( 23 patients each ) received 220mL of fermented vitamin E-fortified whey beverage ( 15 g of whey protein concentrate + 600IU of vitamin E ) or 220mL of fermented whey beverage ( 15 g of whey protein concentrate ) or vitamin E ( 600IU ) 3 times a week for 8 weeks . The control group ( 23 patients ) received no intervention . OUTCOME & MEASUREMENTS Primary outcomes were change in SGA score and malnutrition-inflammation score ( MIS ) from baseline to the end of the trial . RESULTS At the end of the study , 83 patients were analyzed ( 2 , 3 , 1 , and 3 patients left the study in the vitamin E-fortified whey beverage , whey beverage , vitamin E , and control groups , respectively ) . Changes in SGA scores were -3.48 ( 95 % CI , -4.90 to -2.00 ) , -3.22 ( 95 % CI , -4.13 to -2.30 ) , -1.70 ( 95 % CI , -3.20 to -0.24 ) , and 1.56 ( 95 % CI , 0.60 to 2.50 ) for the vitamin E-fortified whey beverage , whey beverage , vitamin E , and control groups , respectively ( overall P<0.001 ; P≤0.001 for each treatment group vs control ) . Changes in MISs were -3.17 ( 95 % CI , -4.40 to -1.90 ) , -1.83 ( 95 % CI , -2.50 to -1.10 ) , -2.30 ( 95 % CI , -3.50 to -1.10 ) , and 1.48 ( 95 % CI , 0.65 to 2.30 ) for the vitamin E-fortified whey beverage , whey beverage , vitamin E , and control groups , respectively ( overall P<0.001 ; P<0.001 for each treatment group vs control ) . Few adverse effects were reported in any group . LIMITATIONS Lack of blinding , small sample size , and short duration . CONCLUSIONS Whey protein in the form of a new fermented whey beverage and vitamin E supplementation may improve SGA score and MIS in the short term Decreased dietary protein intake and hemodialysis-associated protein catabolism are among several factors that predispose chronic hemodialysis ( CHD ) patients to protein calorie malnutrition . Since attempts to increase protein intake by dietary counseling are usually ineffective , intradialytic parenteral nutrition ( IDPN ) has been proposed as a potential therapeutic approach in malnourished CHD patients . In this study , we examined protein and energy homeostasis during hemodialysis in seven CHD patients at two separate hemodialysis sessions , with and without IDPN administration . Patients were studied 2 hours before , during , and 2 hours following a hemodialysis session , using a primed constant infusion of L-(1-(13)C ) leucine and L-(ring-(2)H(5 ) ) phenylalanine . Our results showed that IPDN promoted a large increase in whole-body protein synthesis and a significant decrease in whole-body proteolysis , along with a significant increase in forearm muscle protein synthesis . The net result was a change from an essentially catabolic state to a highly positive protein balance , both in whole-body and forearm muscle compartments . We conclude that the provision of calories and amino acids during hemodialysis with IDPN acutely reverses the net negative whole-body and forearm muscle protein balances , demonstrating a need for long-term clinical trials evaluating IDPN in malnourished CHD patients AIM Evidence has vali date d that the nutritional status of hospitalized patients on haemodialysis could be compromised because of admission-related and hospital-associated morbidities on the background of their kidney disease . However , nutritional status is not assessed and monitored routinely during the hospitalization period . The aim of the present study was to assess the nutritional status of hospitalized patients requiring haemodialysis with the subjective global assessment ( SGA ) tool during the hospitalization period . METHODS This is a prospect i ve cohort study conducted in an acute tertiary general hospital . Patients aged 21 - 75 years old , admitted for various illnesses and requiring haemodialysis between November 2011 and May 2012 were enrolled into this study . A trained dietician assessed patients ' nutritional status with the SGA tool , which included historical data on weight change , dietary intake , gastrointestinal symptoms , functional capacity , comorbidities and physical examination on subcutaneous fat loss , muscle wasting and presence of oedema and /or ascites . Patients were categorized under three groups : SGA-A ( well-nourished ) , SGA-B ( moderately malnourished ) and SGA-C ( severely malnourished ) . RESULTS Eighty patients ( mean ± SD age = 59 ± 10 years ; 76 % Chinese ethnicity ) were assessed . Mean ± SD body mass index ( BMI ) was 25.1 ± 6.1 kg/m2 . SGA categories were 48 % SGA-A , 46 % SGA-B , and 6 % SGA-C. Mean energy and protein intake ( P < 0.001 ) , length of hospitalization stay ( P = 0.03 ) and BMI ( P = 0.001 ) were significantly different across the three categories of nutritional status . CONCLUSIONS More than half of the hospitalized patients requiring haemodialysis were malnourished . It is important to incorporate SGA in the care of hospitalized haemodialysis patients for early detection of malnutrition and for medical nutrition therapy to optimise patients ' nutritional status for better outcomes BACKGROUND Disease-related malnutrition has been reported in 10 % to 55 % of people in hospital and the community . Dietary advice encouraging the use of energy- and nutrient-rich foods rather than oral nutritional supplements has been suggested as the initial approach for managing disease-related malnutrition . OBJECTIVES To examine evidence that dietary advice in adults with disease-related malnutrition improves survival , weight and anthropometry ; to estimate the size of any additional effect of nutritional supplements combined with dietary advice and to compare the effects of dietary advice with oral nutritional supplements . SEARCH STRATEGY Relevant publications were identified from comprehensive electronic data base search es and h and search ing . Last search : 14 February 2010 . SELECTION CRITERIA R and omised controlled trials of dietary advice with or without oral nutritional supplements in people with disease-related malnutrition in any health-care setting compared with no advice , oral nutritional supplements or dietary advice given alone . DATA COLLECTION AND ANALYSIS Two authors independently assessed trial eligibility , risk of bias and extracted data . MAIN RESULTS Forty-five studies ( 3186 participants ) met the inclusion criteria ; ( dietary advice compared with : no advice ( 1053 participants ) ; with oral nutritional supplements ( 332 participants ) ; with dietary advice and oral nutritional supplements ( 731 participants ) ; and dietary advice plus oral nutritional supplements compared with no additional intervention ( 1070 participants ) . Follow-up ranged from 18 days to 24 months . No comparison showed a significant difference between groups for mortality or morbidity . There was a significant change in weight found between groups when comparing dietary advice to no advice for interventions lasting greater than 12 months , mean difference 3.75 kg ( 95 % confidence interval 0.97 to 6.53 ) , and when all studies were combined , mean difference 1.47 kg ( 95 % confidence interval 0.32 to 2.61 ) although there was significant heterogeneity in the combined analysis ( I(2 ) = 90 % ) . Similar improvements in weight were found for the comparison of dietary advice with nutritional supplements if required versus no advice , mean difference 2.20 kg ( 95 % confidence interval 1.16 to 3.25 ) . Dietary advice compared with no advice was also associated with significantly improved mid-arm muscle circumference when all studies were combined , but with moderate heterogeneity , mean difference 0.81 mm ( 95 % confidence interval 0.31 to 1.31 ) . Dietary advice given with nutritional supplements compared with dietary advice alone result ed in improvements in : mid-arm muscle circumference , mean difference -0.89 mm ( 95 % confidence interval -1.35 to -0.43 ) ; triceps skinfold thickness , mean difference -1.22 mm ( 95 % confidence interval -2.34 to -0.09 ) ; and grip strength , mean difference -1.67 kg ( 95 % confidence interval -2.96 to -0.37 ) , although the effects on triceps skinfold thickness and grip strength were heterogeneous . Dietary advice with supplements if required result ed in a significant increase in triceps skinfold thickness compared with no advice , mean difference 0.40 mm ( 95 % confidence interval 0.10 to 0.70 ) , although these results are from a single trial with only 29 participants . AUTHORS ' CONCLUSIONS Evidence of variable quality suggests that dietary advice with or without oral nutritional supplements may improve weight , body composition and grip strength . We found no evidence of benefit of dietary advice or oral nutritional supplements given alone or in combination on survival . Studies addressing the impact of nutritional interventions on nutritional , functional and patient-centred outcomes are needed BACKGROUND Protein-energy wasting is a frequent and debilitating condition in maintenance dialysis . We r and omly tested if an energy-dense , phosphate-restricted , renal-specific oral supplement could maintain adequate nutritional intake and prevent malnutrition in maintenance haemodialysis patients with insufficient intake . METHODS Eighty-six patients were assigned to a st and ard care ( CTRL ) group or were prescribed two 125-ml packs of Renilon 7.5(R ) daily for 3 months ( SUPP ) . Dietary intake , serum ( S ) albumin , prealbumin , protein nitrogen appearance ( nPNA ) , C-reactive protein , subjective global assessment ( SGA ) and quality of life ( QOL ) were recorded at baseline and after 3 months . RESULTS While intention to treat analysis ( ITT ) did not reveal strong statistically significant changes in dietary intake between groups , per protocol ( PP ) analysis showed that the SUPP group increased protein ( P < 0.01 ) and energy ( P < 0.01 ) intakes . In contrast , protein and energy intakes further deteriorated in the CTRL group ( PP ) . Although there was no difference in serum albumin and prealbumin changes between groups , in the total population serum albumin and prealbumin changes were positively associated with the increment in protein intake ( r = 0.29 , P = 0.01 and r = 0.27 , P = 0.02 , respectively ) . The SUPP group did not increase phosphate intake , phosphataemia remained unaffected , and the use of phosphate binders remained stable or decreased . The SUPP group exhibited improved SGA and QOL ( P < 0.05 ) . CONCLUSION This study shows that providing maintenance haemodialysis patients with insufficient intake with a renal-specific oral supplement may prevent deterioration in nutritional indices and QOL without increasing the need for phosphate binders Few long-term studies have assessed whether changes in both diet and exercise can improve the health and quality of life ( QOL ) of hemodialysis ( HD ) patients . Here we examined whether 12 months of intradialytic protein supplementation and endurance exercise improves physical function , risk of cardiovascular disease ( CVD ) , and QOL in HD patients in a r and omized controlled trial ( RCT ) . A total of 138 HD patients ( average age 58 years ) were assigned for 12 months to control , intradialytic protein , or protein plus exercise groups . The protein and protein plus exercise groups consumed an oral protein supplement ( 30 grams of whey ) three days/week during dialysis . The protein plus exercise group cycled for 30 - 45 minutes during dialysis treatment . The primary outcome was change in physical function at 12 months , assessed by a shuttle walk test . Secondary outcomes included arterial stiffness , blood pressure , body composition , muscle strength , markers of nutritional status , and QOL . Assessment s were conducted at baseline , 6 and 12 months . In total , 101 patients completed the intervention . There were no significant differences between groups in shuttle walk test performance from baseline to 12 months . There were trends for improvements in some secondary measures of physical function and strength in the protein and protein plus exercise groups at six or 12 months , but these did not reach statistical significance . Thus , our trial did not demonstrate significant improvements in markers of physical function , risk of CVD or QOL after one year of intradialytic oral OPS and aerobic exercise training . More comprehensive lifestyle management may be needed to uncover robust improvements in the health and QOL of HD patients |
1,042 | 28,158,453 | The finding of clinical ly important surgically related morbidities but lower perioperative mortality with lymphadenectomy seems inconsistent . | OBJECTIVES To re-examine the evidence for recommendations for complete dissection versus sampling of ipsilateral mediastinal lymph nodes during lobectomy for cancer . | 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 . After postoperative pathological re-staging , eligible cases were followed up until 30 November 2000 . The Kaplan-Meier method was used for survival analysis . COX proportional hazards model was used for prognostic analysis . RESULTS Of the 532 patients who were enrolled in the study , 268 patients were assigned to lung resection combined with SND and 264 were assigned to lung resection combined with MLS . After surgical restaging only 471 cases were eligible for follow-up . The median survival was 59 months in the group given SND and 34 months in the group given MLS ( P=0.0000 by the log rank test ) . There was significant difference in survival in Stage I ( 5-year survival 82.16 vs. 57.49 % ) and Stage IIIA ( 26.98 vs. 6.18 % ) by the log rank test and Breslow test . There was no significant yet marginal difference in survival by log rank test ( 10-year survival 32.04 vs. 26.92 % , P=0.0523 ) but significant difference in survival by Breslow test ( 5-year survival 50.42 vs. 34.05 % , P=0.0284 ) in Stage II . Types of mediastinal lymph node dissection , pTNM stage , tumor size and number of lymph node metastasis were four factors that influenced long-term survival rate by multivariate analysis . CONCLUSIONS As compared with MLS , lobectomy ( pneumonectomy ) combined with SND can improve survival in resectable NSCLC Abstract . The value of radical systematic lymphadenectomy for treatment of early-stage bronchial carcinoma is controversial . We performed a prospect i ve r and omized study to address this question . Altogether 115 patients with peripheral non-small-cell lung cancers smaller than 2 cm in diameter were enrolled in this study . They were r and omly assigned into a lobectomy with lymph node sampling group ( sampling group , n= 56 ) or a lobectomy with radical systematic lymph node dissection group ( dissection group , n= 59 ) . Inclusion criteria were based only on preoperative clinical studies . Four tumors were larger than 2 cm postoperatively . One patient had disseminated disease , and two had intrapulmonary metastases discovered at surgery . Two patients had small-cell carcinoma . There were four with pathologic N1 disease and seven with N2 disease in the dissection group and three with N1 and eight with N2 disease in the sampling group . The numbers of local and distant recurrences were two and six , respectively , in the dissection group and two and five in the sampling group . The overall 5-year survival was 81 % in the dissection group and 84 % in the sampling group . No significant differences in the recurrence rate or survival was seen between the groups . Our results demonstrate that clinical ly evaluated peripheral non-small-cell carcinomas smaller than 2 cm in diameter do not require radical systematic mediastinal and hilar lymph node dissection OBJECTIVE To evaluate the effectiveness of lymphadenectomy in the treatment of non-small cell lung cancer ( NSCLC ) . SUMMARY BACKGROUND DATA The extent of lymphadenectomy in the treatment of NSCLC is still a matter of controversy . Although some centers perform mediastinal lymph node sampling ( LS ) with resection of only suspicious lymph nodes , others recommend a radical , systematic mediastinal lymphadenectomy ( LA ) to improve survival and to achieve a better staging . METHODS In a controlled , prospect i ve , r and omized clinical trial , the effects of LA on recurrence rates and survival were analyzed , comparing LS and LA in 169 patients with operable NSCLC . RESULTS After a median follow-up of 47 months , LA did not improve survival in the overall group of patients ( hazard ratio : 0.78 ; 95 % confidence interval : 0.47 - 1.24 ) . Although recurrences rates tended to be reduced among patients who underwent LA , these decreases were not statistically significant ( hazard ratio : 0.82 ; 95 % confidence interval : 0.54 - 1.27 ) . However , analysis of subgroups of patients according to histopathologic lymph node staging revealed that LA appears to prolong relapse-free survival ( p = 0.037 ) with a borderline effect on overall survival ( p = 0.058 ) in patients with limited lymph node involvement ( pN1 disease or pN2 disease with involvement of only one lymph node level ) ; in patients with pN0 disease , no survival benefit was observed . CONCLUSIONS Radical systematic mediastinal lymphadenectomy does not influence disease-free or overall survival in patients with NSCLC and without overt lymph node involvement . However , a small subgroup of patients with limited mediastinal lymph node metastases might benefit from a systematic lymphadenectomy The extent of lymphadenectomy in the treatment of non-small cell lung cancer is still a matter of controversy . While some centers perform mediastinal lymph node sampling with resection of only suspicious lymph nodes , others recommend a radical , systematic mediastinal lymphadenectomy ( LA ) to improve survival and achieve a better staging . Herein we report on the impact of LA on tumor staging in a controlled , prospect i ve , r and omized clinical trial comparing lymph node sampling and LA in a total of 182 patients with operable non-small cell lung cancer . Regardless of the type of lymphadenectomy performed , the percentage of patients with pathologic N1 or N2 ( sampling : n = 23 , 23.0 % ; LA : n = 22 , 26.8 % ) disease was very similar in both groups , indicating that systematic radical lymphadenectomy is not an essential prerequisite to determine the N stage of a patient . In contrast , the number of patients detected to have lymph node involvement at multiple levels was significantly increased by LA . In the lymph node sampling group only 4 of 23 patients ( 17.4 % ) with N2 disease were found to have more than one lymph node level involved , whereas LA results in the detection of excessive N2 disease in 12 of 21 patients ( 57.2 % ; p = 0.007 ) , which was associated with a shorter distant metastases-free ( p = 0.021 ) and overall survival . In conclusion , LA is not essential to determine the N stage of a patient , but results in a more detailed staging of the N2 region , which is of prognostic significance . Therefore , it might be useful to identify patients with a higher risk for tumor relapse OBJECTIVE To determine whether mediastinal lymph node dissection improves survival compared with mediastinal lymph node sampling in patients undergoing resection for N0 or nonhilar N1 , T1 , or T2 non-small cell lung cancer . METHODS Patients with non-small cell lung cancer underwent sampling of 2R , 4R , 7 , and 10R for right-sided tumors and 5 , 6 , 7 , and 10L for left-sided tumors . If all tumors were negative for malignancy , patients were r and omized to no further lymph node sampling ( mediastinal lymph node sampling ) or complete mediastinal lymph node dissection . RESULTS Of 1111 patients r and omized , 1023 ( mediastinal lymph node sampling in 498 , mediastinal lymph node dissection in 525 ) were eligible and evaluable . There were no significant differences between the 2 groups in terms of demographics , Eastern Cooperative Oncology Group status , histology , cancer location , type or extent of resection , and pathologic stage . Occult N2 disease was found in 21 patients in the mediastinal lymph node dissection group . At a median follow-up of 6.5 years , 435 patients ( 43 % ) have died : mediastinal lymph node sampling in 217 ( 44 % ) and mediastinal lymph node dissection in 218 ( 42 % ) . The median survival is 8.1 years for mediastinal lymph node sampling and 8.5 years for mediastinal lymph node dissection ( P = .25 ) . The 5-year disease-free survival was 69 % ( 95 % confidence interval , 64 - 74 ) in the mediastinal lymph node sampling group and 68 % ( 95 % confidence interval , 64 - 73 ) years in the mediastinal lymph node dissection group ( P = .92 ) . There was no difference in local ( P = .52 ) , regional ( P = .10 ) , or distant ( P = .76 ) recurrence between the 2 groups . CONCLUSIONS If systematic and thorough presection sampling of the mediastinal and hilar lymph nodes is negative , mediastinal lymph node dissection does not improve survival in patients with early stage non-small cell lung cancer , but these results are not generalizable to patients staged radiographically or those with higher stage tumors |
1,043 | 28,540,716 | Differential efficacy between dental surgery and other types of surgery seen for both drugs is unusual .
Both drugs were well tolerated in single doses | BACKGROUND This review is an up date of " Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults " last up date d in Issue 4 , 2009 .
Ketoprofen is a non-selective nonsteroidal anti-inflammatory drug ( NSAID ) used to treat acute and chronic painful conditions .
Dexketoprofen is the (S)-enantiomer , which is believed to confer analgesia .
Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose , with a consequent reduction in gastrointestinal adverse events .
This review is one of a series on oral analgesics for acute postoperative pain .
Individual review s have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions .
OBJECTIVES To assess the efficacy and safety of single dose oral ketoprofen and oral dexketoprofen compared with placebo for acute postoperative pain , using methods that permit comparison with other analgesics evaluated in the same way , and criteria of efficacy recommended by an in-depth study at the individual patient level . | 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 Abstract Objective : To evaluate in a r and omised , double-blind , placebo-controlled trial , the efficacy ( time to onset of meaningful pain relief ) of single doses of buffered ketoprofen ( 12.5 mg ) and ibuprofen ( 200 mg ) in 180 patients with postoperative pain after third molar surgery . Methods : 180 adult patients who had undergone third molar surgery under general anaesthesia participated in this study . After dosing , patients recorded their time to meaningful pain relief , pain intensity on both visual analogue scales and verbal rating scales , pain relief and the need for additional analgesia . Pain recordings were made at fixed time points over a 6-h investigation period . Result : Buffered ketoprofen ( 12.5 mg ) provided quicker meaningful pain relief than placebo ( P=0.023 ) . For secondary efficacy measures ( SPIDS4 , SPIDS6 , TOTPAR4 , TOTPAR6 ) , the buffered ketoprofen was significantly superior to both placebo ( P < 0.001 ) and ibuprofen ( 200 mg ) ( P < 0.05 ) . Similarly , the amount of time before taking an escape analgesic was significantly less in the placebo group than both the ibuprofen and buffered ketoprofen groups ( P < 0.03 ) . Conclusions : Buffered ketoprofen ( 12.5 mg ) provides effective pain control in the early postoperative period after third molar surgery . This ketoprofen preparation was also superior to ibuprofen ( 200 mg ) with respect to both reducing pain intensity and providing an earlier onset of pain relief & NA ; Ketorolac 10 and 20 mg , ketoprofen 50 mg and placebo were compared in a multiple‐dose , double‐blind , r and omized analgesic study that included 150 patients with pain after impacted third molar removal . Patients evaluated their study medication over a 48 h period . Bivariate and multivariate analysis revealed statistically significant differences between the different medications studied , evaluated by the consumption of rescue medication ( 50.4–80.4 % of the placebo group required rescue versus 17.0–47.6 % of the ketoprofen , 5.7–31.9 % of the ketorolac 10 mg and 1.8–22.5 % of the ketorolac 20 mg groups ) , the pain relief experienced by the patient ( P<0.05 ) , and the overall efficacy of the medication ( P<0.05 ) . The efficacy of ketorolac 10 mg did not differ from that of ketorolac 20 mg , and both were more efficacious than ketoprofen 50 mg , which in turn was more efficacious than the placebo . One‐third of the placebo group did not require rescue medication . The factors with the greatest influence on the use of rescue medication were the analgesic taken by the patient and the presence or not of postoperative inflammation Two-hundred-forty-eight patients undergoing abdominal surgery were admitted to a multicentric clinical trial . The patients were r and omly assigned to a single i.v . dose of ketoprofen or acetylsalicylic acid , 15 minutes after the end of operation . Ketoprofen showed a better analgesic activity with a statistically significant difference at 2 and 4 hours after administration . Two patients treated with ketoprofen reported vomiting and skin rash respectively . The results of this study confirm the efficacy of ketoprofen for the prophylaxis of postoperative pain in abdominal surgery Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data BACKGROUND This prospect i ve , r and omized study was conducted to evaluate the quality of postoperative pain relief when using dexketoprofen , ketoprofen , or paracetamol after outpatient knee arthroscopy . METHODS Without premedication , 45 ASA physical status I-II patients undergoing elective outpatient knee arthroscopy with combined sciatic-femoral nerve block , were r and omly allocated to receive either 25 mg oral dexketoprofen ( n = 15 ) , 50 mg oral ketoprofen ( n = 15 ) , or 500 mg oral paracetamol ( n = 15 ) before block placement . After completion of surgery the same pain medication was given according to st and ard protocol s , while 50 mg oral tramadol were allowed as rescue analgesic if required by the patient . After st and ard discharge criteria had been fulfilled , patients were discharged from the day-surgery unit , while a telephone follow-up was performed the day after surgery using st and ard question naires evaluating the quality of pain relief during the first 24 hours after surgery . Total consumption of rescue tramadol , maximum pain complained of after hospital discharge , as well as the visual analogue scale of pain measured at hospital discharge were assessed by an independent trained observer . RESULTS No differences in anthropometric variables , duration of surgical procedure , and fulfillment of discharge criteria were observed between the three groups . The degree of pain measured at rest at hospital discharge was similar in the three groups , while the VAS measured during motion was higher in patients receiving paracetamol ( 24 + /- 2.5 mm ) than in those patients treated with dexketoprofen ( 13 + /- 6 mm ) or ketoprofen ( 17 + /- 5 mm ) ( p = 0.016 ) . Two patients ( one in ketoprofen group and one in paracetamol group ) required rescue tramadol after hospital discharge ; however , no differences in maximum pain complained of after surgery or patient acceptance were observed between groups . CONCLUSIONS This prospect i ve , r and omized study demonstrated that in out patients receiving arthroscopic knee surgery , the use of 75 mg/day dexketoprofen was as effective and safe as 150 mg/day racemate ketoprofen , with a better pain relief during motion compared to 2 g/day paracetamol when patients were discharged from the day-surgery unit A r and omized , double-blind parallel group , placebo-controlled study was carried out in order to evaluate the analgesic and antiin-flammatory activity of ketoprofen lysine salt as granular formulation . Sixty patients undergoing extraction of an impacted third molar were treated orally with 80 mg ketoprofen lysine salt sachet or placebo t.i.d . for 3 days . The inflammation related local signs ( pain , flare , local heat and wheal ) were evaluated by scores at 1th and 3th day of observation ; to study the time-course of analgesic activity , pain intensity was evalauted by Visual Analogic-Scale ( VAS ) by Scott-Huskisson before and 0.30 minutes , 1 , 2 , 3 , 4 , 5 , 6 , 8 hours after the first administration . Ketoprofen lysine salt was significantly superior to placebo in reducing all inflmamtory signs and symptoms starting from the first day of treatment ; the analgesic effect was evident already 30 minutes after administration . Investigator 's and patient 's global evaluations of efficacy result ed favourable for ketoprofen lysine salt in 96.6 % and for placebo in 26.7 % . The three adverse events reported were limited to gastric pyrosis ( ketoprofen lysine salt , two patients ; placebo one patient ) and posed no problem to patient management . These data demonstrate the pronouced and rapid analgesic and antinflammatory activity of 80 mg ketoprofen lysine salt granular formulation in post-operative pain and inflammation associated with dental surgery 1 . A placebo-controlled , double-blind , r and omized trial was carried out to evaluate the efficacy of single doses of racemic ketoprofen 12.5 and 25 mg and paracetamol 500 and 1000 mg in patients with post-operative pain after third molar surgery over a 6 h investigation period . 2 . Outcome variables included overall pain scores ( AUC(0,360 min ) , maximum pain relief , pain relief at 1 h after dosage and the number of patients taking escape analgesics . 3 . Overall pain scores ( AUC(0,360 min ) were significantly lower for all active treatments when compared to placebo ( P < 0.01 ) . 4 . Both ketoprofen treatments and patients treated with paracetamol 1000 mg reported significantly greater pain relief ( P < 0.01 ) and a later time to taking escape analgesics ( P < 0.01 ) than patients medicated with placebo . 5 . At 1 h after dosage , pain scores were significantly less ( P < 0.01 ) after both doses of ketoprofen when compared with placebo . 6 . Single doses of ketoprofen 12.5 and 25 mg , together with paracetamol 1000 mg are effective analgesics for treating post-operative pain after third molar surgery . These treatments provide up to 4 h of pain relief after this surgical procedure & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed The objective of this single dose , double-blind study was to determine the relative analgesic efficacy of low-dose ketoprofen ( 6.25 mg , 12.5 mg , and 25 mg ) compared with ibuprofen ( 200 mg ) and placebo in 175 patients with moderate to severe postoperative pain secondary to extraction of impacted third molars . Analgesia was measured during the 6-hour period after administration based on onset of relief , hourly and summary variables , and duration of treatment effect . All active treatments were significantly more effective than placebo for many hourly measures and for the summary measures sum of pain intensity differences ( SPID ) , sum of hourly pain relief values ( TOTPAR ) , time to peak pain relief , and patient global assessment of study medication . The three ketoprofen doses were significantly more effective than placebo beginning at 30 minutes , whereas ibuprofen was significantly better than placebo beginning at 1 hour . A dose-response relationship was observed for ketoprofen , with the two higher doses providing significantly greater analgesia than the lower dose . However , a plateau effect was seen between the 12.5-mg and 25-mg dose levels . A significantly greater proportion of patients treated with each of the active treatments ( ranging from 0.83 to 0.88 ) reported onset of relief compared with placebo ( 0.20 ) . The distribution functions of onset of relief differed significantly among treatments , with ketoprofen 12.5 mg and 25 mg having a faster onset than ibuprofen 200 mg and ketoprofen 6.25 mg . The duration of effect was generally shorter for ketoprofen than for ibuprofen , and these difference were significant . This study provides evidence that at the dose levels of 12.5 mg and 25 mg , ketoprofen is an effective analgesic in providing relief of postoperative dental pain . Ketoprofen 12.5 mg and 25 mg provide significantly greater relief in the earlier time period , with a faster onset and shorter duration of effect than ibuprofen 200 mg . The two higher doses of ketoprofen provided similar analgesia , and no additional benefit was obtained by increasing the dose of ketoprofen to 25 mg . Therefore , we conclude that ketoprofen 12.5 mg is an appropriate dose for over-the-counter use This double-blind , r and omized , parallel-group study compared the analgesic efficacy and safety of single doses of (R)- ketoprofen 25 mg and 100 mg to that of acetaminophen 1,000 mg and placebo in 177 patients experiencing moderate to severe pain after surgical removal of their impacted third molars . Both (R)- ketoprofen 100 mg and acetaminophen 1,000 mg were significantly ( P < 0.05 ) more efficacious than placebo for all summary analgesic measures . Other than a more rapid analgesic onset ( 45 minutes versus 60 minutes ) for acetaminophen 1,000 mg , (R)- ketoprofen 100 mg and acetaminophen 1,000 mg were statistically equivalent to each other . The 25 mg dose of (R)- ketoprofen appeared to approach the analgesic threshold dose , being numerically but not statistically superior to placebo for all summary measures . There were no serious adverse events observed in this study , with the overall incidence of side effects being somewhat less in the (R)- ketoprofen groups than in the acetaminophen 1,000 mg group . (R)- Ketoprofen possesses analgesic activity and an acceptable side-effect profile in the oral surgery pain model BACKGROUND A combination of analgesic drugs with different pharmacologic properties may be more effective , with fewer adverse events , than either agent used alone . OBJECTIVE This study assessed whether the combination of acetaminophen and ketoprofen is more effective and better tolerated than either drug used alone in treating postoperative pain . METHODS This single-dose r and omized , double-blind , active- and placebo-controlled study was conducted at the Finnish Student Health Service , Oulu , Finl and . Patients aged 18 to 40 years with moderate or severe pain ( > or=3 on a numerical rating scale [ NRS ] of 0 - 10 ) after surgical removal of impacted third molars were r and omly assigned to receive one of the following drugs in single oral doses : ketoprofen 100 mg + acetaminophen 1000 mg , ketoprofen 100 mg , acetaminophen 1000 mg , or placebo tablets . Effectiveness was assessed by the onset of analgesia , pain intensity difference ( PID ) from baseline , sum of PID ( SPID ) , and duration of analgesic effect . Patients rated pain intensity on the NRS at rest and on dry swallowing . Onset of pain relief was measured using time to PID in > or=1 category at rest or on dry swallowing ( PID > or=1 ) . Patients recorded the occurrence of adverse events and the supplemental consumption of rescue medication ( ibuprofen ) . RESULTS The study included 76 patients , accounting for 78 cases ( 2 patients were operated on twice and were assessed as 4 individual patients ) ( 59 % women , 41 % men ; mean age , 22.8 years ; white race , 100 % ; and mean weight , 68.3 kg ) . At 1.5 hours , mean SPIDs at rest and on swallowing were significantly greater in the combination group than in the acetaminophen , ketoprofen , and placebo groups ( all , P < 0.05 ) . Mean time to onset of pain relief ( PID > or=1 ) at rest and on swallowing were significantly less in the combination group than the acetaminophen , ketoprofen , and placebo groups ( all , P < 0.05 ) . Median time to use of rescue medication was significantly longer in the combination group than in the acetaminophen group ( P = 0.006 ) and the placebo group ( P < 0.001 ) but not the ketoprofen group . At 1.5 hours after administration , maximum sedation scores were not significantly different between the study groups . The prevalences of trismus , bleeding , and edema were not significantly different between the study groups . CONCLUSIONS The results from this study suggest that the combination of ketoprofen 100 mg + acetaminophen 1000 mg provided a significantly more rapid onset of analgesia than either drug given alone in the management of pain after oral surgery in this patient population . Adverse events were not significantly different between the study groups . These results support the clinical practice of combining ketoprofen with acetaminophen for the management of acute pain OBJECTIVE The objective of this single-center , single-dose , double-blind r and omized parallel group study was to evaluate the analgesic efficacy of a new liquid formulation of ketoprofen at two dose levels ( 25 mg or 50 mg ) compared to a commercially available liquid form of dipyrone 500 mg and placebo with all treatments administered as drops to patients with severe postepisiotomy pain . METHODS The study was design ed with a sample size of 69 patients per treatment for a total of 276 patients . However , due to administrative changes at the site , the study was prematurely terminated ; thus only 108 patients ( 26 to 28 patients per treatment ) , 18 years or older , with severe postepisiotomy pain were r and omized to one of the four treatments . Treatments were assessed over a 6-hour period using st and ard scales for pain intensity and pain relief and a number of derived variables based on these data . Since the study medications were not identical in appearance , the preparation and administration of the study medication , and the observation of the patient , were carried out by two different individuals to maintain double-blind conditions . RESULTS All active treatments were significantly superior to placebo for several measures of analgesia including 4-hour and 6-hour SPID and TOTPAR scores . The global rating was assessed as " good " or " excellent " by over 75 % of the patients in the active treatment groups compared to 7.4 % of the patients in the placebo group . Reduction in pain intensity was very similar for the two-dose levels of ketoprofen and the comparator dipyrone 500 mg . CONCLUSION Ketoprofen 25 mg or 50 mg , and dipyrone 500 mg seem to be equally suited for use as pain relief medication after minor surgery , as well as episiotomy . This study did not demonstrate a need for more than 25 mg of ketoprofen in postepisiotomy pain . All treatments were well tolerated . No adverse events were reported Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale Ketoprofen ( Orudis ) is a nonsteroidal anti‐inflammatory drug that is currently approved in the United States for the management of mild to moderate pain . The objective of this trial was to determine the effectiveness of orally administered ketoprofen in the management of severe postoperative pain . This r and omized , double‐blind parallel study compared the efficacy and safety of single doses of 100 mg or 50 mg ketoprofen , the combination of 650 mg acetaminophen plus 10 mg oxycodone hydrochloride , 650 mg acetaminophen , or placebo in 240 patients with severe postoperative pain after cesarean section . Analgesia for the first dose was assessed over an 8‐hour period . Multiple doses of 100 mg or 50 mg ketoprofen and the combination at half the dose ( 325 mg acetaminophen plus 5 mg oxycodone ) were also assessed for up to 7 days . The 100 and 50 mg doses of ketoprofen and the combination were statistically superior to acetaminophen and placebo for many analgesic measures . A dose response was observed between the two doses of ketoprofen , with the 100 mg dose providing significantly greater analgesia over the lower dose . Ketoprofen , 100 mg , was at least as effective as the combination and its effects lasted longer , with the exception of hour 1 when the combination was superior . Remedication time for the group receiving 100 mg ketoprofen was significantly longer than for the other treatment groups . Significantly more patients who took repeated doses of the combination ( 84 % ) than those who took either dose of ketoprofen ( 70 % ) had adverse effects . Ketoprofen at both dose levels was shown to be effective , long‐lasting , and well tolerated , and it should be considered as a viable option for the management of moderate to severe postoperative pain Ibuprofen is a peripherally acting nonsteroidal anti-inflammatory drug indicated fo ranalgesia , antipyresis , and various arthritic conditions . A solubilized 200 mg liquigel formulation of ibuprofen has been shown to have a more rapid rate of absorption compared with ibuprofen 200 mg tablets . Ibuprofen liquigels have a kinetic profile similar to ibuprofen suspension , with both a higher Cmax and an earlier tmax than any solid tablet . The objective of this single-dose , double-blind , triple-dummy , parallel-group study was to assess the time to onset of relief and overall analgesic efficacy of liquigel ibuprofen 400 mg , ketoprofen 25 mg compared with acetaminophen 1000 mg , and placebo in 239 patients with moderate or severe pain following third molar extraction s. Treatments were compared over 6 hours using st and ard scales for pain intensity and relief and stopwatch onset of meaningful relief . All active treatments provided meaningful relief significantly faster compared with placebo . Ibuprofen provided significantly faster relief compared with acetaminophen and ketoprofen . By the end of the study ( 6 h ) , onset of meaningful relief was achieved by 36 % , 99 % , 96 % , and 88 % of the patients in the placebo , ketoprofen , ibuprofen , and acetaminophen groups , respectively . The median times to onset of relief were > 6 hours for placebo , 25.5 minutes for ketoprofen , 24.2 minutes for ibuprofen , and 29.9 minutes for acetaminophen . In addition , both ibuprofen and ketoprofen showed statistical superiority over acetaminophen at earlier time points on the time-effect curves for pain relief and pain intensity difference . Consistent results were seen with respect to the 6-hour summary efficacy variables : the three active treatments were significantly better than placebo , and ibuprofen was significantly better than both acetaminophen and ketoprofen . Liquigel ibuprofen 400 mg was shown to provide faster relief and superior overall efficacy compared with ketoprofen 25 mg , acetaminophen 1000 mg , and placebo . No serious adverse effects were reported in this single-dose study |
1,044 | 21,446,048 | 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 | The authors undertook a systematic review to design ate the role that radiotherapy ( RT ) might play in the treatment of retroperitoneal sarcomas .
Correlating with recent literature , the objective of this review was to evaluate whether there was enough evidence for the authors to develop an institutional treatment protocol concerning the use of RT in the treatment of retroperitoneal sarcoma .
Furthermore , this was a call for surgeons to talk to radiation oncologists before performing surgery .
The 2 objectives of this review were : 1 ) to determine the benefit of RT in terms of local control and /or survival in the treatment of retroperitoneal sarcomas and 2 ) to discover the optimal timing of RT in the treatment sequence . | 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 , 40 % recurred by 10 years . Radiation therapy was the only factor significant ( P = .02 ) for a reduction in the risk of local recurrence . Age < or = 50 years and high- grade tumors were significant factors ( P = .003 and .009 , respectively ) for an increased risk of distant metastasis . Incomplete gross resection was the only factor significant for an increased risk of tumor mortality ( P = .003 ) . CONCLUSION Complete surgical resection at the time of primary presentation is likely to afford the best chance for long-term survival . With long-term follow-up , it is clear that recurrence will continue to occur , and a 5-year disease-free interval is not a cure . Patients with an incomplete initial resection , age less than 50 years , and high- grade tumors are c and i date s for investigational adjuvant therapy PURPOSE Retroperitoneal sarcomas represent a formidable challenge to the treating oncologist due to their location , large size , and poor prognosis . The purpose of this study was to determine if the addition of high-dose-rate intraoperative radiation therapy ( HDR-IORT ) to surgery and external beam radiotherapy ( EBRT ) would improve the outcome in these patients . METHODS AND MATERIAL S Thirty-two patients with retroperitoneal soft tissue sarcoma were prospect ively treated according to a protocol that included maximal tumor resection , HDR-IORT , and postoperative EBRT when feasible . Twelve patients presented with primary and 20 with locally recurrent disease . The tumors were high- grade in 20 patients and low- grade in 12 patients . Complete gross resection was achieved in 30 patients . HDR-IORT was given to a dose of 12 - 15 Gy . Additional EBRT was given to 78 % of patients to a dose of 45 - 50.4 Gy . The two patients with gross residual disease received an additional I-125 permanent implant to a median peripheral dose of 140 - 160 Gy . The median follow-up was 33 months ( range 1 - 77 mo ) . RESULTS The 5-year actuarial local control rate for the whole group was 62 % . For patients with primary disease , the local control rate was 74 % compared to 54 % in patients with recurrent disease ( p = 0.4 ) . The overall 5-year distant metastasis-free survival rate was 82 % . In patients with high- grade tumors the rate was 70 % vs. 100 % in those with low- grade tumors . This difference was statistically significant , p = 0.05 . The 5-year disease-free and overall survival rates were 55 % and 45 % , respectively . The most common type of post-treatment complication was gastrointestinal obstruction ( 18 % ) followed by fistula formation ( 9 % ) , peripheral neuropathy ( 6 % ) , hydronephrosis ( 3 % ) , and wound complication ( 3 % ) . CONCLUSIONS We are encouraged by the favorable local control rate and the acceptable morbidity with this new technique applied to a challenging patient population Background : A consecutive series of 47 patients with retroperitoneal sarcoma ( RPS ) were resected and prospect ively followed Background The purpose of this study was to analyze the results of treatment of retroperitoneal soft tissue sarcomas ( RSTS ) by surgery combined with intraoperative brachytherapy ( IOBRT ) . Methods Seventy adult patients with RSTS were considered for combined treatment ( surgery plus IOBRT ) between June 1998 and February 2004 . There were 64 ( 91 % ) recurrent tumors , and 93 % of tumors exceeded 5 cm . IOBRT was performed with high-dose-rate Gammamed 12 with iridium 192 ( IOBRT time range , 20–87 minutes ; median , 56 minutes ) . Results After intraoperative re-evaluation , 24 patients ( 34 % ) were found to be ineligible for IOBRT because of multiple intraperitoneal recurrences , macroscopically nonradical resection , poor general condition , and technical aspects . Thirty-seven patients underwent IOBRT immediately after surgery during the same general anesthesia procedure . Nine patients underwent delayed IOBRT within 1 to 3 days after the primary operation . Ten ( 21.5 % ) of 46 patients underwent reoperation because of surgical complications . One patient died in the postoperative period . After IOBRT , 24 patients ( 52 % ) underwent adjuvant external beam radiotherapy ( EBRT ) to a total dose of 50 Gy . Over a median follow-up time of 20 months , the estimated 5-year overall survival and local recurrence – free survival rates in IOBRT patients were 55 % and 51 % , respectively . Application of adjuvant EBRT showed a favorable local control rate . Conclusions The scheduled combined treatment ( surgery plus IOBRT ) was possible to perform in 66 % of RSTS cases that received surgical treatment . The complication rate was high , but we consider it acceptable because of the necessity for extensive aggressive surgical treatment in regionally advanced RSTS . EBRT seems to be an indispensable part of treatment that provides better local control PURPOSE To evaluate the disease control , survival results , and tolerance of intraoperative electron beam radiotherapy ( IOERT ) as a component of treatment for retroperitoneal soft tissue sarcomas . METHODS AND MATERIAL S Between March 1981 and September 1995 , 87 patients with primary ( n = 43 ) or recurrent ( n = 44 ) retroperitoneal or intrapelvic sarcomas received IOERT as a component of treatment at the Mayo Clinic . The tumors were high grade in 54 patients ( 62 % ) and low grade in 33 ( 38 % ) . The median tumor size was 10 cm ( range 2 - 36 ) . All patients underwent maximal surgical resection with IOERT ; in 72 patients , only microscopic or no residual tumor remained . The IOERT doses ranged from 8.75 to 30 Gy ( median 15 ) . All primary tumors received external beam irradiation ( EBRT ) with a median dose of 48.6 Gy . Thirty-four of the 44 recurrent tumors received EBRT to a median dose of 45 Gy . All patients were followed prospect ively for outcome and toxicity evaluation . RESULTS The median follow-up , based on 46 patients ( 53 % ) currently alive , was 3.5 years . The overall estimated 5-year survival was 47 % . For patients with tumors > or = 10 cm , the 5-year overall survival was significantly poorer ( 28 % ) than for those with smaller lesions ( 60 % ) ( p = 0.01 ) . Neither primary vs. recurrent status nor tumor grade had a significant impact on survival . Patients with gross residual tumor had a marginally significantly poorer survival compared with patients with microscopic or no residual tumor , with a 5-year survival rate of 37 % and 52 % , respectively ( p = 0.08 ) . A total of 49 patients ( 56 % ) experienced failure , including 20 local recurrences ( 23 % ) . The median time to failure was 2.3 years . Four recurrences were within the IOERT field , 3 within the IOERT and EBRT field , and 13 within the EBRT field alone . The 3- and 5-year estimated local control rate was 77 % and 59 % , respectively . Local control was marginally significantly affected by the amount of residual tumor , with a 5-year local control rate of 41 % for those with gross residual tumor , 60 % for those with microscopic residual tumor , and 100 % for those with no residual tumor ( p = 0.09 ) . Gastrointestinal complications were recorded in 12 incidences ( Grade 3 or higher toxicity ) . These complications were believed to be secondary to surgery and /or EBRT in 10 of the 12 cases . Seven patients had fistula formation , and 3 experienced severe proctitis . Grade 3 peripheral neurologic toxicities occurred in 9 patients ( 10 % ) , but none had pain as a component of their neuropathy . CONCLUSION Retroperitoneal soft tissue sarcomas can be treated with an aggressive combined approach of EBRT , surgery , and IOERT , with acceptable toxicity . Local control in primary disease appears to be improved in this retrospective series with this approach . Distant disease control and options for recurrent disease needs further definition Introduction We report our experience of treating retroperitoneal sarcoma ( RPS ) using pre-operative external beam radiotherapy ( EBRT ) in combination with radical resectional surgery from 1990 to 2005 . Methods Twenty-eight primary and 10 recurrent tumors were identified from a prospect i ve data base . Results The resection rate was 71 % overall ; 82 % in primary ( 23/28 ) and 40 % ( 4/10 ) in recurrent cases . EBRT was administered preoperatively in 25 patients , postoperatively in 1 , and palliatively in 11 . In 33 patients a saline-filled tissue exp and er was inserted into the abdomen before radiotherapy to displace small bowel from the radiation field . 4,500–5,000 cGy was administered in fractions of 180–200 cGy over a 5-week period ; surgery followed 6–8 weeks later . Exp and er insertion was associated with minimal morbidity ; 31/37 patients received a dose of 4,000 cGy or more ( median 4,650 cGy ) . Median resected tumor diameter was 13 cm , and a median of three adjacent organs was resected per patient . Complete macroscopic resection was achieved in 25/27 patients ( 93 % ) ; R0 in 9 ( 33 % ) and R1 in 13 ( 48 % ) ( microscopic margins unclear in 5 ) . There was no postoperative mortality . Tumors were high- grade in 20 patients , low- grade in 14 and un grade d in 4 . Actuarial 5- and 10-year survival for all patients was 74 and 60 % . For operable primary tumors , the 5-year survival and disease-free rates were 90 and 80 % . In four patients with operable recurrent tumors , median disease-free interval was 91 months ( 27–160 ) . In the 11 inoperable cases , median survival after radiotherapy was 48 months ( 9–77 ) . Conclusions We conclude that a combination of pre-operative tissue exp and er placement , high-dose EBRT and radical resectional surgery can achieve acceptable morbidity , extended survival and low long-term recurrence in patients with RPS.StatisticsMedian ( interquartile range ) PURPOSE To define the optimal initial management and the best extent of surgery that would optimize margins on primary retroperitoneal sarcomas ( RPS ) . PATIENTS AND METHODS A total of 382 patients with primary RPS were analyzed . Sixty-five patients had a simple resection of the tumor , 120 patients had a complete compartmental resection ( systematic resection of noninvolved contiguous organs ) , 130 patients had a contiguously involved organ resection , 21 patients had a systematic re-excision , 38 patients had an incomplete gross resection , and eight patients had a biopsy alone . Radiotherapy and chemotherapy were administered to 121 and 145 patients , respectively . RESULTS One , 3- , and 5-year overall survival ( OS ) rates were 86 % ( 95 % CI , 0.82 to 0.89 ) , 66 % ( 95 % CI , 0.61 to 0.71 ) , and 57 % ( 95 % CI , 0.51 to 0.62 ) , respectively . Median overall survival was 6 years . In the multivariate analysis , high grade , tumor rupture , gross residual disease , and positive margins were associated with decreased OS . Low grade , no tumor rupture , negative histologic margins , a high number of patients undergoing operation per center , and compartmental resection compared with st and ard procedures were associated with decreased abdominal recurrences . Compartmental resection is a significant variable , predicting a 3.29-fold lower rate of abdominal recurrence compared with simple complete resection . CONCLUSION Complete compartmental surgery without tumor rupture should be performed when possible to achieve clear margins . This surgery should be performed in a high-volume center . The role of adjuvant treatments should be evaluated in a r and omized trial in association with this optimal surgery v 2 T p p ALIDATION oft tissue sarcomas ( STS ) are rare neoplasms of mesenchyal origin with a disease specific mortality of up to 50 % . he ability of physicians to accurately assess risk in patients ith STS is essential in providing effective treatment . As is one intuitively by an experienced physician , effective paient care requires the integration of various prognostic ariables to arrive at an appropriate treatment plan . This llows for reassurance of low risk patients and treatment of igh risk patients with adjuvant therapy . But the simple ounting of individual patient risk factors does not optiize the information available for prediction . A nomogram is a prognostic tool that may improve nd better direct care for individual patients . Based on rospectively followed adult patients with primary STS reated at Memorial Sloan-Kettering Cancer Center MSKCC ) , Kattan and colleagues developed a nomoram in 2002 that integrated these prognostic factors to redict sarcoma specific death ( Fig. 1 ) . Instead of rouping patients into stages , which can have remarkble variability of outcomes within a given stage , the omogram provides a more tailored outcome predicion . The nomogram is an ideal tool for primary STS as hey have multitude of prognostic factors that greatly etermine the survival of patients with these tumors . any of these important prognostic factors ( histology , ite , and age ) are not included in the current American oint Committee on Cancer ( AJCC ) staging system . In ddition , available systemic therapy is toxic and benefiial to only a few selected high risk patients . At the time of its development , the MSKCC Sarcoma omogram was assessed for accuracy and vali date d on the ame cohort of patients used for its development . Although he nomogram was found to be accurate by such internal alidation , it had not been vali date d by an external patient ohort and thus general applicability remained unproen . Such external validation is essential , as a |
1,045 | 22,192,712 | 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 . | The purpose of this systematic review was to summarize and critically appraise the results of 10 years of human laboratory research on pain and sex/gender . | & 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 resembles a review of the delayed onset muscle soreness and pain literature . However , the findings contradict a few other acute muscle pain investigations , in which actual muscle tissue damage was not induced by eccentric contractions . Additional research is required to identify the parameters that influence the detection of sex differences There are limited data addressing the question of sex differences in pain-related cerebral processing . This study examined whether pain-related blood oxygenation level-dependent ( BOLD ) signal change measured with functional magnetic resonance imaging ( fMRI ) demonstrated sex differences , under conditions of equivalent pain perception . Twenty-eight healthy volunteers ( 17 women , 11 men ) were subject to a fMRI scan while noxious heat stimuli were applied to the dorsum of the left foot . Significant BOLD signal modulation was observed in several nociceptive processing regions of interest ( ROIs ) in all subjects . There were no sex differences in the spatial extent of BOLD signal change for any ROI , but the signal amplitude was lower for women in most ROIs and significantly so for the primary somatosensory cortex ( S1 ) , the midanterior cingulate cortex , and the dorsolateral prefrontal cortex ( DLPFC ) . The BOLD signal response could be positive or negative , and frequently , both polarities were observed within a single ROI . In most ROIs , women show proportionately more voxels with negative signal change than men , and this difference was statistically significant for the S1 and the DLPFC . The time course of the negative signal change was very similar to that of the positive signal change , suggesting that the latter was not " driving " the former . The location of negative and positive clusters formed distinct patterns in several of the ROIs , and these patterns suggest something other than a local " steal " phenomenon as an explanation for the negative signal changes . Sex differences in baseline cerebral blood flow may contribute to the BOLD signal differences observed in this study OBJECTIVE To assess the prevalence , treatment and impact of chronic pain in Canada . METHODS A stratified r and om sample of 2012 adult Canadians ( weighted by sex , age and region according to 1996 census data ) was surveyed by telephone in 2001 to determine the prevalence of chronic pain , defined as continuous or intermittent pain for at least six months . A second sample of 340 chronic pain sufferers who were taking prescription medication for their pain was studied in detail to determine current therapeutic approaches and to assess the social and economic impact of chronic pain . RESULTS Chronic noncancer pain was reported by 29 % of the respondents , with increased frequency in women and older age groups . The average duration of pain was 10.7 years and the average intensity was 6.3 ( on a scale from 1 to 10 ) , with 80 % reporting moderate or severe pain . Anti-inflammatory agents were prescribed for 49 % of respondents and opioid analgesics were prescribed for 22 % ( two-thirds of these were codeine ) . Almost 70 % were worried about addiction potential , and one-third felt that strong analgesics should be reserved for terminal illnesses . Almost one-half were unable to attend social and family events , and the mean number of days absent from work in the past year due to chronic pain was 9.3 . INTERPRETATION Chronic noncancer pain is common in Canadian adults and has a major social and economic impact . Despite growing evidence supporting the efficacy and safety of major opioid analgesics for chronic noncancer pain , less than 10 % of chronic pain patients taking prescription medication were treated with a major opioid . Chronic pain is undertreated in Canada , and major opioid analgesics are probably underutilized in the management of moderate to severe pain as part of a multidisciplinary treatment program Pupillary response to noxious stimulation was investigated in men ( n = 11 ) and women ( n = 9 ) . Subjects experienced repeated trials of noxious electrical fingertip stimulation at four intensities , ranging from faint to barely tolerable pain . Measures included pupil dilation response ( PDR ) , pain report ( PR ) , and brain evoked potentials ( EPs ) . The PDR began at 0.33 s and peaked at 1.25 s after the stimulus . Multivariate mixed-effects analyses revealed that ( a ) the PDR increased significantly in peak amplitude as stimulus intensity increased , ( b ) EP peaks at 150 and 250 ms differed significantly in both amplitude and latency across stimulus intensity , and ( c ) PR increased significantly with increasing stimulus intensity . Men demonstrated a significantly greater EP peak amplitude and peak latency at 150 ms than did women . With sex and stimulus intensity effects partialled out , the EP peak latency at 150 ms significantly predicted PR , and EP peak amplitude at 150 ms significantly predicted the PDR peak amplitude The literature demonstrating sex differences in pain is sizable . Most explanations for these differences have focused on biologic mechanisms , and only a few studies have examined social learning . The purpose of this study was to examine the contribution of gender-role stereotypes to sex differences in pain . This study used experimental manipulation of gender-role expectations for men and women . One hundred twenty students participated in the cold pressor task . Before the pain task , participants were given 1 of 3 instructional sets : no expectation , 30-second performance expectation , or a 90-second performance expectation . Pain ratings , threshold , and tolerance were recorded . Significant sex differences in the " no expectation " condition for pain tolerance ( t = 2.32 , df = 38 , P < .05 ) and post-cold pressor pain ratings ( t = 2.6 , df = 37 , P < .05 ) were found . Women had briefer tolerance times and higher post-cold pressor ratings than men . When given gender-specific tolerance expectations , men and women did not differ in their pain tolerance , pain threshold , or pain ratings . This is the first empirical study to show that manipulation of expectations alters sex differences in laboratory pain UNLABELLED Pain-related fear and catastrophizing are important variables of consideration in an individual 's pain experience . Method ological limitations of previous studies limit strong conclusions regarding these relationships . In this follow-up study , we examined the relationships between fear of pain , pain catastrophizing , and experimental pain perception . One hundred healthy volunteers completed the Fear of Pain Question naire ( FPQ-III ) , Pain Catastrophizing Scale ( PCS ) , and Coping Strategies Question naire-Catastrophizing scale ( CSQ-CAT ) before undergoing the cold pressor test ( CPT ) . The CSQ-CAT and PCS were completed again after the CPT , with participants instructed to complete these measures based on their experience during the procedure . Measures of pain threshold , tolerance , and intensity were collected and served as dependent variables in separate regression models . Sex , pain catastrophizing , and pain-related fear were included as predictor variables . Results of regression analyses indicated that after controlling for sex , pain-related fear was a consistently stronger predictor of pain in comparison to catastrophizing . These results were consistent when separate measures ( CSQ-CAT vs PCS ) and time points ( pretask vs " in vivo " ) of catastrophizing were used . These findings largely corroborate those from our previous study and are suggestive of the absolute and relative importance of pain-related fear in the experimental pain experience . PERSPECTIVE Although pain-related fear has received less attention in the experimental literature than pain catastrophizing , results of the current study are consistent with clinical reports highlighting this variable as an important aspect of the experience of pain Animal studies have suggested that tissue injury-related increased levels of glutamate may be involved in peripheral nociceptive mechanisms in deep craniofacial tissues . Indeed , injection of glutamate ( 0.1 - 1 M , 10 microl ) into the temporom and ibular region evokes reflex jaw muscle responses through activation of peripheral excitatory amino acid receptors . It has recently been found that this glutamate-evoked reflex muscle activity is significantly greater in female than male rats . However , it is not known whether peripheral administration of glutamate , in the same concentrations that evoke jaw muscle activity in rats , causes pain in humans or activates deep craniofacial nociceptive afferents . Therefore we examined whether injection of glutamate into the masseter muscle induces pain in male and female volunteers and , since masseter afferent recordings were not feasible in humans , whether glutamate excites putative nociceptive afferents supplying the masseter muscle of male and female rats . Injection of glutamate ( 0.5 M or 1.0 M , 0.2 ml ) into the masseter muscle of both men and women caused significantly higher levels of peak pain , duration of pain , and overall pain than injection of isotonic saline ( 0.2 ml ) . In addition , glutamate-evoked peak and overall muscle pain in women was significantly greater than in men . In rats of both sexes , glutamate ( 10 microl , 0.5 M ) evoked activity in a sub population of masseter muscle afferents ( n = 36 ) that projected to the subnucleus caudalis , an important relay of noxious input from the craniofacial region . The largest responses to glutamate were recorded in muscle afferents with the slowest conduction velocities ( 2.5 - 5 m/s ) . Further , glutamate-evoked masseter muscle afferent activity was significantly greater in female than in male rats . These results indicate that glutamate injection into the masseter muscle evokes pain responses that are greater in women than men and that one possible mechanism for this difference may be a greater sensitivity to glutamate of masseter muscle afferents in females . These sex-related differences in acute experimental masseter muscle pain are particularly interesting given the higher prevalence of many chronic muscle pain conditions in women OBJECTIVES There is growing evidence to suggest that certain psychological modulators of pain sensitivity are dependent on gender . The aim of the present study was to examine further whether cognitive-affective factors ( with specific focus on situational anxiety ) shown to modulate pain report and behaviour have differential effects on men 's and women 's response to experimentally induced pain . METHOD A sample of 80 healthy university students ( 40 women , 40 men ) was assessed on subjective measures of anxiety ( situational and dispositional ) , anxiety-sensitivity and attitudes toward the experimental pain procedure prior to being exposed to a cold pressor test ( constant temperature + 1 degrees C ; + /- 1 degrees C , cut-off limit 240 s ) . RESULTS The present study produced three main findings : ( 1 ) No effect of gender was found on any of the pain measures ; however , an interactive effect of anxiety and gender was found on measures of pain tolerance with low anxiety men displaying significantly higher pain tolerance than both low and high anxiety women . ( 2 ) Men classified as low-anxious tolerated cold pressor pain significantly longer than men classified as high-anxious , while no such effect of anxiety on pain response was observed in women . ( 3 ) Gender-specific associations were observed between other psychological variables ( including anxiety-sensitivity and attitudes toward pain ) and thermal pain response . CONCLUSION Results from the present study suggest that there are important differences in the way cognitive-affective factors impact on the pain response of men and women . Further research is needed to explore potential psychosocial and physiological mechanisms that may underlie such differences Objectives Semmes-Weinstein monofilaments are too long for use in parts of the oral cavity . The present study used shortened Semmes-Weinstein monofilaments to evaluate reliability and spatial differences in the intraoral tactile detection threshold ( TDT ) and the filament-prick pain detection threshold ( FPT ) in healthy volunteers . Methods For practical purpose s , classic Semmes-Weinstein monofilaments with 20 different diameters were cut to half their length ( ie , 19 mm ) and the bending forces were measured . Eighteen men and 18 women ( age range , 20 to 33 y ) were recruited to evaluate the reliability and reproducibility of measurements using half-cut monofilaments . The TDT and the FPT were measured on the labial maxillary gingiva , on the palatal maxillary gingiva , and at the anterior tip of the tongue , using a double r and om staircase method . Results According to the forces needed to bend the half-cut filaments , they were renumbered from 2.55 to 6.86 . There were significant differences of bending force between the half-cut and original monofilaments ( P<0.001 ) , Using half-cut filaments , the following differences could be detected ; the labial maxillary gingiva had a significantly higher TDT threshold compared with the other test sites ( P<0.001 ) . By contrast , the palatal posterior maxillary gingiva had a significantly higher FPT threshold compared with the other test sites ( P<0.001 ) . Discussion s The present study illustrated that in healthy participants , half-cut Semmes-Weinstein monofilaments reliably and easily assess TDT and FPT intraorally . A combined examination of sensory and pain thresholds using these filaments contributes to the clinical examination for orofacial pain AIM There is agreement that females report greater pain in response to typical experimental pain stimuli than males . However , investigations of sex differences in the sensation of delayed onset muscle soreness ( DOMS ) have equivocal RESULTS The objective of this investigation was to examine sex differences in the pain from DOMS with an adequate sample size , quantification of stimulus intensity , and 2 measures of pain . METHODS Sixty-seven participants ( 52 % females ) completed a 2-session protocol . DOMS was induced using eccentric resistance exercises in the elbow flexors of the non-dominant arm . The intensity of the eccentric contractions was based upon concentric strength . Pain response was measured 48 hrs later . The dependent variables were pressure threshold , which was assessed using a dolorimeter , and pain intensity when the arm was moved through full active range of motion , which was assessed with a visual analog scale . RESULTS The occurrence of DOMS was confirmed by a decrease in pressure threshold after the eccentric contractions and higher pain intensity in the arm that performed the eccentric contractions than the arm that did not . Females reported lower pain intensities ( M=3.41 , SD=2.13 ) compared to males ( M=5.12 , SD=2.05 ) , but no significant sex difference was found in pressure threshold . CONCLUSION In this investigation , females reported lower muscle pain intensity than males , but showed no sex difference in pressure threshold . These and previous findings suggest that the detection of a sex difference in muscle pain depends upon the methodology of inducing DOMS and measuring sensation CONTEXT There is little information on the extent of persistent pain across cultures . Even though pain is a common reason for seeking health care , information on the frequency and impacts of persistent pain among primary care patients is inadequate . OBJECTIVE To assess the prevalence and impact of persistent pain among primary care patients . DESIGN AND SETTING Survey data were collected from representative sample s of primary care patients as part of the World Health Organization Collaborative Study of Psychological Problems in General Health Care , conducted in 15 centers in Asia , Africa , Europe , and the Americas . PARTICIPANTS Consecutive primary care attendees between the age of majority ( typically 18 years ) and 65 years were screened ( n = 25 916 ) and stratified r and om sample s interviewed ( n = 5438 ) . MAIN OUTCOME MEASURES Persistent pain , defined as pain present most of the time for a period of 6 months or more during the prior year , and psychological illness were assessed by the Composite International Diagnostic Interview . Disability was assessed by the Groningen Social Disability Schedule and by activity-limitation days in the prior month . RESULTS Across all 15 centers , 22 % of primary care patients reported persistent pain , but there was wide variation in prevalence rates across centers ( range , 5.5%-33.0 % ) . Relative to patients without persistent pain , pain sufferers were more likely to have an anxiety or depressive disorder ( adjusted odds ratio [ OR ] , 4.14 ; 95 % confidence interval [ CI ] , 3.52 - 4.86 ) , to experience significant activity limitations ( adjusted OR , 1.63 ; 95 % CI , 1.41 -1.89 ) , and to have unfavorable health perceptions ( adjusted OR , 1.26 ; 95 % CI , 1.07 - 1.49 ) . The relationship between psychological disorder and persistent pain was observed in every center , while the relationship between disability and persistent pain was inconsistent across centers . CONCLUSIONS Persistent pain was a commonly reported health problem among primary care patients and was consistently associated with psychological illness across centers . Large variation in frequency and the inconsistent relationship between persistent pain and disability across centers suggests caution in drawing conclusions about the role of culture in shaping responses to persistent pain when comparisons are based on patient sample s drawn from a limited number of health care setting s in each culture UNLABELLED Women have a higher prevalence of fibromyalgia and myofascial pain than men , but sex differences in muscle pain are inconsistently detected . We examined sex differences in ratings and effects of recalled and experimentally-induced muscle pain . In study 1 ( n = 188 ) , participants completed a question naire about recalled muscle pain . In study 2 ( n = 55 ) , participants described muscle pain from an exercise stimulus across 3 days by telephone . Muscle pain ratings , self-care behaviors for muscle pain , and effects of muscle pain on activities were measured . No significant sex differences were found except that women tended to view exercise as more effective for decreasing muscle pain than men ( F ( 1 , 187 ) = 5.43 , P = .02 , eta(2 ) = .03 ) , fewer women performed exercise for induced muscle pain than men , and women 's activity interference was significantly higher than men 's at the third day after exercise ( F ( 2 , 42 ) = 6.54 , P = .01 , eta(2 ) = .14 ) . These findings support the absence of meaningful sex differences in muscle pain ratings . However , additional investigations are needed that consider the daily activities completed by people and the prevalence and incidence of performing a wide range of self-care behaviors for pain . PERSPECTIVE These studies support that sex differences are not present in recalled and experimentally-induced muscle pain ratings . Therefore , we must be cautious about generalizing the musculoskeletal pain literature to muscle pain . Additional research is needed to interpret potential sex differences in self-care behaviors for muscle pain and activity interference from muscle pain PURPOSE To examine the influence of isometric h and grip exercise ( ISO EX ) on pain perception and blood pressure in men and women . METHODS Fifteen men and 16 women completed max and submax ISO EX consisting of squeezing a h and dynamometer with the right h and as hard as possible for the max session , and squeezing between 40 % and 50 % of max for 2 min for the submax session . Pain thresholds ( PT ) , pain ratings ( PR ) , blood pressure ( SBP and DBP ) , and heart rate ( HR ) were assessed while a noxious pressure stimulus was applied to the right forefinger for 2 min before and after ISO EX . Data were analyzed with a 2 ( gender ) x 2 ( trials ) ANOVA . RESULTS Results indicated a significant trials effect and a significant gender by trials interaction ( P < 0.05 ) for PT for the max and submax sessions . Women had lower PT before ISO EX in comparison with the men . In addition , PT for the women increased significantly after ISO EX but did not change for the men . There were significant gender and trials effects ( P < 0.05 ) for SBP for the submax session . Women had lower SBP before ISO EX , and SBP increased after ISO EX . DBP was also found to be lower ( P < 0.05 ) in women before max and submax ISO EX , with DBP increasing after submax ISO EX in men and women . PR were found to be lower after max ISO EX in men and women , whereas PR were found to be lower in women after submax ISO EX . CONCLUSION It is concluded that : 1 ) men and women differed in PT , SBP , and DBP before ISO EX ; and 2 ) analgesia after ISO EX is observed more consistently in women Abstract The present study aim ed to investigate if ( 1 ) subcutaneous injection of glutamate induces pain , sensitization and vasomotor responses in humans and ( 2 ) if sex differences exist in these responses . Thirty healthy volunteers ( men‐15 and women‐15 ) were included . Each subject received four subcutaneous injections ( 0.1 ml ; glutamate 100 , 10 , 1 mM and isotonic saline 0.9 % ) into the forehead skin in two sessions separated by one week . Assessment s of pain intensity ( VAS ) , quality , distribution ; area of pinprick hyperalgesia ; pressure pain threshold ( PPT ) at the injection site ; surface skin temperature and local blood flow were performed at predetermined time points . The highest concentration of glutamate evoked the highest pain intensity , the longest duration of pain and the largest pain area under the VAS – time curve ( P < 0.001 ) in both men and women , although responses in women were larger than in men ( P < 0.05 ) . The face‐chart pain area was the largest for the highest concentration of glutamate ( P < 0.001 ) and women drew a larger pain area than men ( P = 0.024 ) . The area of pinprick hyperalgesia was the largest for glutamate 100 mM ( P < 0.001 ) and women indicated a larger area than men ( P < 0.001 ) . Concentration‐dependent local vasomotor responses were found following the subcutaneous injection of glutamate but there was no sex difference in this effect . Glutamate 100 mM significantly reduced the PPT values ( P < 0.001 ) without sex‐related differences . The present study demonstrates for the first time that subcutaneous injection of glutamate evokes pain , vasomotor responses and pinprick hyperalgesia in human volunteers and that there are sex‐related differences in some of these responses Objective : A self-reported history of childhood physical and /or sexual abuse is frequently reported among chronic pain population s and has been associated with poorer adjustment to pain . In addition , self-reported abuse history has been related to increased pain complaints in population -based studies . One possible explanation for the association between abuse and clinical pain is that abuse victims may display enhanced sensitivity to painful stimuli , which increases the risk of developing clinical pain . However , the limited evidence addressing this issue has been mixed . The purpose of this study was to examine the association between self-reported history of childhood sexual or physical abuse and experimental pain responses in a non clinical sample of generally healthy young adults . Design : Participants were 110 ( 56 female , 54 male ) college students who completed a series of question naires assessing abuse history , recent pain , health care utilization , perceived health , and psychologic variables . Also , measures of thermal and ischemic pain threshold and tolerance were obtained in all participants . In addition , a procedure assessing temporal summation of heat pain was conducted in which intensity and unpleasantness ratings of repetitive thermal stimuli were obtained . Systolic and diastolic blood pressure and heart rate were assessed at resting and during the ischemic pain task . Results : Participants with a positive childhood abuse history were over sample d , yielding 21 out of 56 ( 37.5 % ) women with a positive history of abuse and 13 out of 54 ( 24.1 % ) PHA men . No abuse group differences emerged for thermal or ischemic pain thresholds or tolerances ( P values > 0.05 ) . However , compared to women with no childhood abuse history , women with a positive history of abuse provided significantly lower average pain unpleasantness and peak pain unpleasantness ratings and lower unpleasantness ratings of the first trial during the temporal summation procedure , whereas no abuse group differences emerged for men . Also , compared to participants with no childhood abuse history , participants of both genders with a positive history of abuse demonstrated smaller increases ( ie , less temporal summation ) in pain unpleasantness ratings across trials of thermal stimulation , and participants with a positive history of abuse showed greater decreases in pain intensity and unpleasantness after reaching their peak pain level ( ie , greater wind-down ) compared to participants with no childhood abuse history . In addition , participants with a positive history of abuse reported more sites of recent pain , poorer perceived health , greater somatization , and more negative affect . No group differences in resting cardiovascular measures or cardiovascular reactivity were observed . Conclusion : These findings indicate that a self-reported history of childhood abuse is associated with decreased sensitivity to experimentally induced pain , especially among women . However , abuse history was associated with increased pain complaints , poorer self-reported health , and greater negative affect . These data highlight the complexity of the relationship between abuse history and pain and illustrate the need for further investigation of potential pain-related correlates of abuse Reference data on cold and warmth perception at three different body areas are provided based on 24 young ( 20 - 30 years ) and 24 elderly ( 55 - 65 years ) healthy women and men . Perception thresholds ( method of limits ) , perceived intensity ( free-number magnitude estimation ) , and perceived quality ( verbal descriptors ) were assessed for cold and for warmth at thenar , the upper arm , the knee , and the foot . Interindividual comparison of perceived-intensity scales for cold and warmth was achieved by a Master Scaling procedure utilizing thenar as a reference area . Perception thresholds showed gender difference for cold at thenar , and interaction effect of age and gender for heat-pain tolerance at the upper arm . In contrast , perceived intensity of cold and warmth showed multiple effects of age , gender , and specific body area ( also for the nociceptive channels ) . For instance , at the knee , elderly women 's perceived intensity for stimulation in the nociceptive range was elevated for both cold and warmth , as compared to young women and men , and to elderly men . Conversely , at the upper arm , elderly women 's perceived intensity for the corresponding nociceptive range was lowered , as compared to young women and young men , and to elderly men . At the foot , both elderly women 's and men 's perceived intensity of cold and warmth was lowered , as compared to young women and men . Overall , the perceived quality of perceptions did not differ between groups . The present findings on age differences in perceived intensity of cold and warmth at the upper arm , knee and foot in healthy women and men provide reference data hitherto lacking for diagnostic work in patients with somatosensory dysfunctions and ongoing pain Objective To test whether muscle pain intensity caused by different intensities of unaccustomed eccentric exercise was moderately and negatively associated with resting blood pressure , and whether women reported higher pain ratings compared with men in response to such exercise . Design and SubjectsThe repeated measures design involved r and om assignment of 42 young adults ( 21 women , 7 per condition ) to complete elbow extension exercises with a weight that was 80 % , 100 % , or 120 % of their maximal voluntary concentric strength . Total work was equated by manipulating the number of repetitions performed in the 80 % ( n = 45 ) , 100 % ( n = 36 ) , and 120 % ( n = 30 ) condition groups . Setting A clinical laboratory in a large university in the southeastern U.S. Outcome Measures Pain intensity ratings averaged over 3 days and resting blood pressure measurements averaged over 6 days . Results For both sexes there was a dose – response relation between the relative intensity of the unaccustomed eccentric exercise and mean pain intensity ratings . Mean pain intensity was not significantly related to systolic or diastolic blood pressure . There was no significant sex difference in pain intensity , although men 's ratings , in contrast to expectations , tended to be higher than the women 's ratings . Conclusions The negative findings , contrary to those predicted from previous experiments in which other types of noxious stimuli have been used , suggest that sex and blood pressure associations with pain intensity are stimulus dependent STUDY DESIGN Two-group ( gender ) posttest only using a sample of convenience . OBJECTIVES Our study examined the effect of gender on selected stimulus properties , perceived pain thresholds , and maximally tolerated level of contraction of the plantar flexor muscle group . BACKGROUND There is a dearth of literature regarding gender as a factor that may influence the outcome following the application of neuromuscular electrical stimulation . Data from other disciplines suggest that males and females may not have similar tolerance to electrical stimulation . METHODS AND MEASURES Eleven women ( mean age , 28.3 years + /- 5.6 years ) and 9 men ( mean age , 33.2 years + /- 6 years ) participated in a single session of electrical stimulation . A pair of 4.5 x 4.5 cm , self-adhesive , synthetic , polymer electrodes was placed over the medial and lateral heads of the gastrocsoleus muscle group . Electrical stimulation was provided by a battery-powered pulsatile stimulator generating a symmetric biphasic waveform , 200-mu second phase duration , and pulse rate of 50 pulses per second . During testing , the subjects were seated on a specially constructed chair that incorporated a foot pedal attached to a piezoelectric force transducer to measure plantar flexion force . Stimulation amplitude was increased slowly until 4 thresholds ( sensory , motor , pain , and maximal pain ) were sequentially achieved . At each threshold , stimulus peak voltage , peak current , and phase charge used to elicit that threshold were recorded . Plantar flexion force was also recorded when stimulation was sufficient to achieve pain and maximal pain thresholds . RESULTS The peak voltage , peak current , and phase charge needed to elicit the 4 thresholds did not differ between women and men at any threshold examined ( 2-factor ANOVA ; Newman-Keuls post hoc tests ) . However , significantly higher stimulus peak voltage , peak current , and phase charge were recorded for each of the 4 thresholds ( sensory , motor , pain , and maximal pain tolerance ) for both groups . The plantar flexion force elicited by electrical stimulation was significantly lower in female subjects than in male subjects at both pain threshold and maximally tolerated stimulation levels . CONCLUSIONS Gender can influence the magnitude of electrically induced plantar flexion contraction force . We hypothesize that females may require longer conditioning periods to achieve therapeutic levels of muscle contraction The aim of the present study was to identify and characterize hemispheric lateralization for pain intensity perception . A sample of 351 healthy volunteers was tested by the immersion of the right h and for 10 s followed by the same test for the left h and ( RL group ; n = 199 ) or in a r and om sequence ( RND group ; n = 152 ) into a water bath ( 48 ° C , 15 s ) . Pain intensity was self-reported by the Visual Analogue Scale ( VAS ) . The motor hemispherical Lateralization Index ( LI ) was obtained by the Edinburgh Inventory . Gender , h and skin fold , interstimulus time and menstrual cycle data in case of female subjects were recorded . The sample , 60.7 % females and 39.3 % males , 20.4 - 0.18 ( mean - SEM ) years old , showed 92.1 % right-h and ed subjects . Left h and VAS was significantly higher than right h and VAS for RL ( 7.24 - 1.31 vs 6.74 - 1.52 ; p < 0.01 ) and RND ( 7.24 - 0.82 vs 6.73 - 1.25 ; p < 0.01 ) both for right- and left-h and ed subjects . A low but significant correlation for VAS scores and LI was found ( r = 0.14 ; p < 0.05 or r = 0.18 ; p < 0.05 , for left or right h and , respectively ) . Skin fold was statistically similar in both h and s ( p > 0.05 ) being highly correlated with each other ( r = 0.68 ; p < 0.05 ) . Pain subjective perception was not correlated to interstimulus time ( r = -0.01 ; p > 0.05 ) . Females showed significantly higher values than males for both left and right h and VAS scores . Periovulatory phase VAS value was significantly higher than luteal phase VAS only for the right h and test ( 7.57 - 0.20 vs 6.47 - 0.33 ; p < 0.01 ) . The results of the present study suggest a lateralization of pain intensity perception to the right hemisphere not correlated with the motor hemispheric lateralization Objective : The study was to assess the local pain intensity , referred pain patterns , and changes in the pressure pain thresholds of the local and referred pain areas following bilateral injections of hypertonic saline into trapezius muscles and to delineate gender differences in pain profile and the possible modulation of pressure pain thresholds . Methods : Fifteen healthy men and women each participated . Pain intensity and areas were assessed after bilateral injections . The pressure pain thresholds in the trapezius and posterolateral neck muscles ( referred pain areas ) were measured before and 7.5 and 15 minutes postinjection . Results : The time to maximal pain intensity was significantly shorter after the second injection than after the first injection . Patients exhibited a bilaterally symmetrical distribution of pain areas that included the neck to shoulder angle and the posterolateral neck . Bilateral injections significantly elevated pressure pain thresholds in the right and left posterolateral neck muscles 7.5 and 15 minutes postinjection . In men but not women , the pressure pain thresholds measured in the posterolateral neck muscles 7.5 and 15 minutes after the second injection were higher than those after the first injection and also higher than those after the second injection in women , men tolerated more pressure than women at all time points . Discussion : These findings indicate that both excitatory and inhibitory mechanisms modulate pain response characteristics in bilateral neck-shoulder pain conditions and suggest that there may be a more potent inhibitory control mechanism in men than women . This experimental model may be potentially used to detect gender differences in descending inhibition Animal and human research has shown that pain sensitivity changes during the menstrual cycle . This has sometimes been ascribed to hormonal variations . The aim of the present study was to examine how perception of pain , induced by the cold pressor test to the dominant h and , was related to gender and phases of the menstrual cycle . A repeated-meausres design was used , where twenty-two female students participated at two different phases of the menstrual cycle ( days 2–4 and days 20–24 ) . A control group of nineteen male students participated on two occasions , separated by a three week period . The cycle phase during which each woman began her participation was r and omized . Pain was induced using the cold pressor test . Pain threshold was determined as the duration of time between when the subject first reported pain and exposure to the painful stimulus . Pain tolerance was determined as the duration of time until the subject withdraw her/his h and from the test water because the pain was too intensive . The results showed that men tolerated significantly greater pain than women . Women ’s pain threshold was significantly higher during the second phase of the menstrual cycle . Systolic pressure was higher in men than women , increasing more in men in response to cold pressor testing than women . Further research , including measurments of plasma hormone levels during the menstrual cycle , is needed to clarify the role played by estrogens in pain perception The present study evaluated the reproducibility of the late exteroceptive suppression period ( ES2 ) and of pain perception . The surface electro-myogram ( EMG ) was recorded from the left masseter muscle in 12 males and 12 females ( 22 - 31 year ) . Thirteen fixed stimulus intensities from 5 to 25 mA with 2.5 mA intervals were applied at r and om to the left mental area , and stimulus-response ( S-R ) curves were built for each subject . The first stimulation intensity at which the ES2 appeared was defined the reflex threshold , while the lowest stimulus intensity the subjects scored as painful , was called the pain threshold . Using the S-R curves , the other reflex parameters ( appearance level , saturation level , slope from appearance to saturation , maximum duration of ES2 , and maximum suppression degree ) were also determined . Two measurement sessions were scheduled . Both the reflex and the pain sensation appeared at significantly lower stimulus intensity in females than males ( P < 0.05 ) . The reflex threshold , the reflex appearance and saturation level showed a significant decrease from the first to second session ( P < 0.05 ) , while the pain threshold was significantly higher during the second session ( P < 0.01 ) . By contrast , a good reproducibility was found for the maximum duration and suppression degree of ES2 . Consequently , if S-R curves would be used to study the relation between the ES2 parameters and stimulus intensity in normal subjects for their applicability in clinical conditions , maximum duration and maximum suppression degree should be focused upon , in order to avoid session and gender effects as confounding factors OBJECTIVE To establish basic epidemiological data on chronic pain ( duration > 3 months ) in a defined population . Relationships between age , gender , and social class were tested . DESIGN A survey of pain symptoms , including location , intensity , duration , and functional capacity , was conducted by means of a mail question naire . SETTING General population s in two Swedish primary health care districts . Medical care was provided in a state health system . SUBJECTS A r and om sample ( from the population register ) of 15 % of the population aged 25 - 74 ( n = 1,806 ) . The response rate was 90 % . OUTCOME MEASURES Descriptive epidemiologic data in relation to objectives of the study . RESULTS Without sex differences , 55 % ( 95 % confidence interval , 53 - 58 % ) of the population had perceived persistent pain for 3 months and 49 % for 6 months . Among individuals with chronic pain , 90 % localized their pain to the musculoskeletal system to a variable extent . Women experienced more multiple localizations of pain and had pain in the neck , shoulder , arm , and thigh to a greater extent than men . Prevalence of pain increased by age up to 50 - 59 years for both genders and then slowly decreased . The neck-shoulder area was the most common site of pain ( 30.2 % ) , followed by the lower back ( 23.2 % ) . Even in the youngest age groups more than one of four reported chronic pain . Blue-collar workers and employers ( including farmers ) reported chronic pain to a greater extent than other groups . In 13 % of the population , manifest pain problems were associated with reduced functional capacity . CONCLUSION Chronic pain symptoms are common but unevenly distributed in a general population . The results may influence planning and consultation in primary health care as well as warranting selective prevention activities OBJECTIVE To examine the effects of experimentally evoked masticatory muscle fatigue , without and with experimental muscle pain , on the short-latency jaw-stretch reflex , using a r and omised crossover design . METHODS Reflexes were evoked in both the masseter and temporalis muscles in 15 men and 13 women . The study was performed in two blocks , both containing 3 experimental conditions ( before , directly after , and 15 min after provocation ) . Provocation consisted of a fatiguing chewing test , followed by an intramuscular injection of either isotonic saline ( IS ; non-painful ) or hypertonic saline ( HS ; painful ) . RESULTS No significant effects of the experimental condition ' fatigue+IS ' were found for any of the reflex outcome variables . For each muscle , the ' fatigue+HS ' condition yielded significantly higher normalized reflex amplitudes than the other conditions . Several muscles displayed gender differences regarding both onset latency and normalized reflex amplitude . CONCLUSIONS Experimentally evoked mild-to-moderate muscle fatigue does not modulate the human jaw-stretch reflex . On the other h and , experimental muscle pain , evoked after the performance of a fatiguing chewing test , does yield a facilitation of this reflex . The gender differences found in both onset latency and peak-to-peak amplitude stress the need to take gender into consideration in future jaw reflex studies . SIGNIFICANCE The sensitivity of the human jaw-stretch reflex can be modulated by HS-induced muscle pain ; not by muscle fatigue that is provoked by intense chewing & NA ; This study examined within‐ and across‐session consistency of visual analog scale ( VAS ) pain intensity and unpleasantness ratings of contact heat stimuli in 64 subjects ( 32 male ) . Subjects participated in four sessions over 14 days , with three stimulus series per session . Two levels of painful heat ( pain‐lo : rated 40 , and pain‐hi : rated 70 on a 0–100 VAS ) were delivered in r and omized order during each series , with temperatures selected on an individual subject basis to equalize pain perception across subjects . Across‐session ratings declined by the fourth session for both pain levels ( p = 0.01 ) . Within‐session ratings declined by the third series for both pain levels ( p < 0.001 ) . While significant , changes in across‐ and within‐session ratings were of small magnitude . Comparison of coefficients of variation ( CVs ) for across‐ and within‐session ratings revealed that pain‐lo ratings were more variable than pain‐hi ratings ( p < 0.001 ) . Across‐ and within‐session CVs were highly correlated for each pain level ( pain‐lo p < 0.001 ; pain‐hi p = 0.001 ) , suggesting that variability of VAS ratings is a characteristic of individual subjects over both short and long time scales . Across‐ and within‐session CVs were significantly negatively correlated with individual ratings of the stimuli , but were not correlated with demographic or psychosocial factors . Furthermore , sex did not impact consistency of ratings , demonstrating that neither sex is more variable in ratings than the other over time . Taken together , these findings suggest that VAS ratings of painful contact heat are relatively stable over time but the variability of these ratings is significantly impacted by the perceived intensity of the stimulus The literature regarding whether or not there are diurnal differences in pain perception in men and women is equivocal . The purpose of this study was to examine the influence of time of day on experimentally induced pain threshold in men and women . A secondary purpose was to measure selected psychological and physiological responses . Pressure ( 3000 gm force ) was applied to the middle digit of the left forefinger for 2-min with the Forgione-Barber pain stimulator . Twenty-nine volunteers ( women = 14 ; men = 15 ) completed two r and omly assigned sessions between 6.00 - 8.00 in the AM and PM . Selected psychological variables ( STAI , POMS ) and physiological variables ( BP , HR , TEMP ) were assessed before application of the pressure stimulus . Data were analyzed with a 2x2 ANOVA . Results indicated that men had significantly higher ( p<.05 ) systolic blood pressure and pain thresholds than women however , there was not a significant time of day effect for pain threshold . Significant time of day effects ( p<.05 ) were found for systolic blood pressure and tympanic temperature . Heart rate , and tympanic temperature were found to be significantly higher ( p<.05 ) in women in comparison to men . It is concluded that pain threshold did not differ in the AM and PM . Furthermore , men were found to have higher pain thresholds compared to the women We examined the effects of baroreceptor stimulation on nociceptive responding in men and women with a positive or negative parental history of hypertension . The effects of three baroreceptor conditions ( stimulation , inhibition , and control ) on subjective pain and nociceptive responding were evaluated during electrocutaneous sural nerve stimulation . Pain ratings were lower in men with positive parental history relative to men with negative parental history , but this difference was not found in women . Both stimulatory and inhibitory baroreceptor conditions were associated with reduced pain reports compared to the control condition . There were no significant differences in nociceptive responding as a function of parental history of hypertension . Although this study confirms a link between hypoalgesia and risk for hypertension in men , it does not support the hypothesis that this attenuated pain perception is due to enhanced baroreceptor activity & NA ; The aim of this study was to investigate the effects of diffuse noxious inhibitory controls ( DNICs ) on the temporal summation of the nociceptive flexion reflex ( RIII reflex ) in humans . Recordings were obtained from 36 healthy adults ( 16 M , 20 F ) , and the area and temporal summation threshold ( TST ) of the RIII reflex were measured . The subjective intensity of the painful sensation was rated on an 11‐point visual analogue scale ( VAS ) . Neurophysiological and VAS measurements were recorded after activation of DNICs by means of the cold pressor test ( CPT ) , which involved immersing the h and in cold water ( 2–4 ° C ) . A slight significant lower TST was found in the females versus the males . In all the subjects , the CPT induced a significant TST increase and RIII area reduction compared with the control session . The VAS results paralleled those of the RIII reflex area and TST . During the CPT , a significant difference in the percentage TST increase emerged between females and males , being lower in the former . Similarly , we found a significantly lower percentage reduction of the RIII area in women than in men during the CPT . To summarize , activation of DNICs through the CPT significantly increased the TST of the RIII reflex in healthy subjects . This inhibitory effect was gender‐specific . Whereas other findings are based on psychophysical evaluations , the results of this experimental study provide an objective neurophysiological demonstration that DNICs attenuate temporal summation in humans and confirm the presence of significant differences in pain modulation mechanisms between men and women Experimentally induced pain often reveals sex differences , with higher pain sensitivity in females . The degree of differences has been shown to depend on the stimulation and assessment methods . Since sex differences in pain develop anywhere along the physiological and psychological components of the nociceptive system , we intended to compare the nociceptive flexion reflex ( NFR ) as a more physiological ( spinal ) aspect of pain procession to the verbal pain report of intensity and unpleasantness as the more psychological ( cortical ) aspect . Twenty female and twenty male healthy university students were investigated by use of nociceptive flexion reflex threshold ( staircase method ) after electrical stimulation of the N. suralis . Furthermore , we assessed supra-threshold reflex responses ( latency , amplitude and area ) by applying 10 stimuli 5 mA above reflex threshold . Following each stimulation , the subjects provided pain ratings of intensity and unpleasantness on a visual analogue scale . Females exhibited marked lower nociceptive flexion reflex thresholds than males , while the supra-threshold reflex response tailored to the individual reflex threshold did not show any significant differences . The verbal pain ratings , corrected for NFR threshold , were not found to differ significantly . The large sex differences in nociception that were present in NFR threshold but not in the pain ratings corroborate the hypothesis that spinal processes contribute substantially to sex differences in pain procession UNLABELLED As a method of experimental pain induction , the cold pressor test is thought to mimic the effects of chronic conditions effectively . A survey of previous studies using the cold pressor , however , revealed a lack of st and ardization and control of water temperature , question ing comparability and reliability . This study reports the influence of temperature on pain tolerance and intensity by using a commercially available circulating water bath . Twenty-six participants ( 12 men , 14 women ) underwent 4 cold pressor trials with temperature order counterbalanced across 1 degrees C , 3 degrees C , 5 degrees C , and 7 degrees C , temperatures representative of the range used in previous literature . After each cold immersion participants rated pain intensity on a visual analogue scale and the McGill Pain Question naire . Tolerance times were recorded for each trial . Significant main effects of temperature were found for tolerance time , with higher temperatures result ing in longer times , and pain intensity , with lower temperatures result ing in higher intensities . Gender differences were found , with men tolerating the stimulus for significantly longer than women . It was concluded that small differences in water temperature have a significant effect on pain intensity and tolerance time . The use of cold pressor equipment that ensures a precise constant temperature of circulating water is necessary to ensure comparable and reliable results . PERSPECTIVE The cold pressor method of experimental pain induction has been widely used in the evaluation of psychological and physiological pain treatments . This article highlights the need for clear method ologic guidelines for the technique and demonstrates that very minor changes in experimental protocol can produce significant differences & NA ; Little is known about sex differences in the temporal pattern of descending inhibitory mechanisms , such as descending noxious inhibitory control ( DNIC ) . Sex differences in temporal characteristics of DNIC were investigated by measuring pressure pain thresholds ( PPTs ) over time in the trapezius muscles ( local pain areas ) and the posterolateral neck muscles ( referred pain areas ) following repeated bilateral injection of hypertonic versus isotonic saline into both trapezius muscles . Ten females and 11 males received two consecutive bilateral injections , with 15 min interval , of either 5.8 % hypertonic saline ( 0.5 ml in each side for each bilateral injection ) or isotonic saline as a control in a r and omized manner . Following hypertonic saline injection , the maximal pain intensities of the first and second bilateral injections were significantly higher in females than in males . The PPTs in the trapezius muscles were significantly lower in females than in males . Significantly higher PPTs ( hypoalgesia ) in men than in women were shown 15 min after the first bilateral injection , and 7.5 and 15 min after the second bilateral injection in the referred pain areas . Importantly , the second bilateral injection failed to further increase the PPTs for both sexes . These results showed that there were sex differences in temporal characteristics of descending inhibition with long‐lasting hypoalgesia in men than in women . Repeated noxious muscular stimuli may inhibit further build‐up of DNIC , which may reflect a mechanism of plasticity of the descending inhibitory systems following recurrent nociceptive barrage for both sexes OBJECTIVES To describe the clinical features , antecedents and impact of chronic pain . DESIGN Telephone survey of r and omly selected household respondents . SETTING Northern Sydney Health Area , metropolitan Sydney , July to September 1998 . PARTICIPANTS 2092 English-speaking residents aged 18 years or over . MAIN OUTCOME MEASURES Age- and sex-adjusted prevalence of chronic pain ( pain experienced every day for 3 months in the previous 6 months ) , pain-related disability , and use of health services and analgesic medications . RESULTS Chronic pain affected 474/2092 respondents ( 22.1 % ; 95 % CI , 20.2%-24.0 % ) , with high levels of pain-related disability in 129/439 ( 27 % ) . Nominated causes of chronic pain were injury in 173 ( 38 % ) , most commonly sports injury ( 54 ; 13 % ) , and a health problem in 132 ( 29 % ) . Pain was work-related in 62 ( 14 % ) . A musculoskeletal condition was the leading diagnosis ( 127 ; 26 % ) . Of the 474 with chronic pain , 374 ( 78 % ) had consulted at least one health practitioner for pain in the previous 6 months , comprising medical practitioners ( consulted by 292 [ 60 % ] and including general practitioners [ 55 % ] ) , allied health professionals ( 245 ; 50 % ) , and alternative practitioners ( 99 ; 21 % ) . Current or recent use of oral analgesic medications ( often over-the-counter preparations ) was common ( 339 ; 70 % ) . Higher levels of pain-related disability were associated with greater use of medications and health services . CONCLUSIONS Our study shows that chronic pain is common and often results from injury . It highlights the importance of timely interventions to prevent progression from acute to chronic pain and the need for a coordinated approach to managing pain-related disability & NA ; The processing of noxious and non‐noxious sensations differs between chronic pain syndromes , and we believe that studies of sensory processing in the presence of pain will help to clarify the aetiology of the conditions . Here we measured in humans the threshold‐level mechanosensitivity in tonic experimental muscle pain . We found ( 1 ) that muscle pain induced by hypertonic saline reduced cutaneous threshold‐level mechanosensitivity at the site of pain and at the mirror site in the contralateral face , ( 2 ) that this effect outlasted the sensation of pain , ( 3 ) that it was more pronounced when the painful area was reported to be large , and ( 4 ) that the loss of mechanosensitivity was greater in males than females . Comparing our findings to results obtained with other pain models , all classes of nociceptors do not seem to have the same effect on cutaneous mechanosensitivity . The observed threshold‐level hypoesthesia is consistent with the hypothesis that the increased mechanical thresholds found in clinic cases of temporom and ibular disorders and cervicobrachialgia are a direct result of the activation of muscle nociceptors & NA ; This study reports chronic pain prevalence in a r and omly selected sample of the adult Australian population . Data were collected by Computer‐Assisted Telephone Interview ( CATI ) using r and omly generated telephone numbers and a two‐stage stratified sample design . Chronic pain was defined as pain experienced every day for three months in the six months prior to interview . There were 17,543 completed interviews ( response rate=70.8 % ) . Chronic pain was reported by 17.1 % of males and 20.0 % of females . For males , prevalence peaked at 27.0 % in the 65–69 year age group and for females , prevalence peaked at 31.0 % in the oldest age group ( 80–84 years ) . Having chronic pain was significantly associated with older age , female gender , lower levels of completed education , and not having private health insurance ; it was also strongly associated with receiving a disability benefit ( adjusted OR=3.89 , P<0.001 ) or unemployment benefit ( adjusted OR=1.99 , P<0.001 ) ; being unemployed for health reasons ( adjusted OR=6.41 , P<0.001 ) ; having poor self‐rated health ( adjusted OR=7.24 , P<0.001 ) ; and high levels of psychological distress ( adjusted OR=3.16 , P<0.001 ) . Eleven per cent of males and 13.5 % of females in the survey reported some degree of interference with daily activities caused by their pain . Prevalence of interference was highest in the 55–59 year age group in both males ( 17.2 % ) and females ( 19.7 % ) . Younger respondents with chronic pain were proportionately most likely to report interference due to pain , affecting 84.3 % of females and 75.9 % of males aged 20–24 years with chronic pain . Within the subgroup of respondents reporting chronic pain , the presence of interference with daily activities caused by pain was significantly associated with younger age ; female gender ; and not having private health insurance . There were strong associations between having interfering chronic pain and receiving disability benefits ( adjusted OR=3.31 , P<0.001 ) or being unemployed due to health reasons ( adjusted OR=7.94 , P<0.001 , respectively ) . The results show that chronic pain impacts upon a large proportion of the adult Australian population , including the working age population , and is strongly associated with markers of social disadvantage |
1,046 | 9,820,349 | 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 | BACKGROUND The efficacy of homeopathic remedies has remained controversial .
The homeopathic remedy most frequently studied in placebo-controlled clinical trials is Arnica montana .
OBJECTIVE To systematic ally review the clinical efficacy of homeopathic arnica . | 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 ) |
1,047 | 29,181,191 | 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 | Background To compare the efficacy and toxicity of anti-programmed cell death receptor 1 ( PD-1 ) and anti-programmed cell death lig and 1 ( PD-L1 ) versus docetaxel in previously treated patients with advanced non-small cell lung cancer ( NSCLC ) . | 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 , 0.62 ; 95 % CI , 0.47 to 0.81 ; P<0.001 ) . The expression of the PD-1 lig and ( PD-L1 ) was neither prognostic nor predictive of benefit . Treatment-related adverse events of grade 3 or 4 were reported in 7 % of the patients in the nivolumab group as compared with 55 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced , previously treated squamous-cell NSCLC , overall survival , response rate , and progression-free survival were significantly better with nivolumab than with docetaxel , regardless of PD-L1 expression level . ( Funded by Bristol-Myers Squibb ; CheckMate 017 Clinical Trials.gov number , NCT01642004 . ) BACKGROUND Outcomes are poor for patients with previously treated , advanced or metastatic non-small-cell lung cancer ( NSCLC ) . The anti-programmed death lig and 1 ( PD-L1 ) antibody atezolizumab is clinical ly active against cancer , including NSCLC , especially cancers expressing PD-L1 on tumour cells , tumour-infiltrating immune cells , or both . We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC , analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population . METHODS In this open-label , phase 2 r and omised controlled trial , patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practice s across 13 countries in Europe and North America . Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1 , measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 ( RECIST v1.1 ) , and adequate haematological and end-organ function . Patients were stratified by PD-L1 tumour-infiltrating immune cell status , histology , and previous lines of therapy , and r and omly assigned ( 1:1 ) by permuted block r and omisation ( with a block size of four ) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m(2 ) once every 3 weeks . Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells ( as percentage of PD-L1-expressing tumour cells TC3≥50 % , TC2≥5 % and < 50 % , TC1≥1 % and < 5 % , and TC0<1 % ) and tumour-infiltrating immune cells ( as percentage of tumour area : IC3≥10 % , IC2≥5 % and < 10 % , IC1≥1 % and < 5 % , and IC0<1 % ) . The primary endpoint was overall survival in the intention-to-treat population and PD-L1 subgroups at 173 deaths . Biomarkers were assessed in an exploratory analysis . We assessed safety in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01903993 . FINDINGS Patients were enrolled between Aug 5 , 2013 , and March 31 , 2014 . 144 patients were r and omly allocated to the atezolizumab group , and 143 to the docetaxel group . 142 patients received at least one dose of atezolizumab and 135 received docetaxel . Overall survival in the intention-to-treat population was 12·6 months ( 95 % CI 9·7 - 16·4 ) for atezolizumab versus 9·7 months ( 8·6 - 12·0 ) for docetaxel ( hazard ratio [ HR ] 0·73 [ 95 % CI 0·53 - 0·99 ] ; p=0·04 ) . Increasing improvement in overall survival was associated with increasing PD-L1 expression ( TC3 or IC3 HR 0·49 [ 0·22 - 1·07 ; p=0·068 ] , TC2/3 or IC2/3 HR 0·54 [ 0·33 - 0·89 ; p=0·014 ] , TC1/2/3 or IC1/2/3 HR 0·59 [ 0·40 - 0·85 ; p=0·005 ] , TC0 and IC0 HR 1·04 [ 0·62 - 1·75 ; p=0·871 ] ) . In our exploratory analysis , patients with pre-existing immunity , defined by high T-effector-interferon-γ-associated gene expression , had improved overall survival with atezolizumab . 11 ( 8 % ) patients in the atezolizumab group discontinued because of adverse events versus 30 ( 22 % ) patients in the docetaxel group . 16 ( 11 % ) patients in the atezolizumab group versus 52 ( 39 % ) patients in the docetaxel group had treatment-related grade 3 - 4 adverse events , and one ( < 1 % ) patient in the atezolizumab group versus three ( 2 % ) patients in the docetaxel group died from a treatment-related adverse event . INTERPRETATION Atezolizumab significantly improved survival compared with docetaxel in patients with previously treated NSCLC . Improvement correlated with PD-L1 immunohistochemistry expression on tumour cells and tumour-infiltrating immune cells , suggesting that PD-L1 expression is predictive for atezolizumab benefit . Atezolizumab was well tolerated , with a safety profile distinct from chemotherapy . FUNDING F Hoffmann-La Roche/Genentech Introduction : The Blueprint Programmed Death Lig and 1 ( PD‐L1 ) Immunohistochemistry ( IHC ) Assay Comparison Project is an industrial‐academic collaborative partnership to provide information on the analytical and clinical comparability of four PD‐L1 IHC assays used in clinical trials . Methods : A total of 39 NSCLC tumors were stained with four PD‐L1 IHC assays ( 22C3 , 28‐8 , SP142 , and SP263 ) , as used in the clinical trials . Three experts in interpreting their respective assays independently evaluated the percentages of tumor and immune cells staining positive at any intensity . Clinical diagnostic performance was assessed through comparisons of patient classification above and below a selected expression cutoff and by agreement using various combinations of assays and cutoffs . Results : Analytical comparison demonstrated that the percentage of PD‐L1–stained tumor cells was comparable when the 22C3 , 28‐8 , and SP263 assays were used , whereas the SP142 assay exhibited fewer stained tumor cells overall . The variability of immune cell staining across the four assays appears to be higher than for tumor cell staining . Of the 38 cases , 19 ( 50.0 % ) were classified above and five ( 13 % ) were classified below the selected cutoffs of all assays . For 14 of the 38 cases ( 37 % ) , a different PD‐L1 classification would be made depending on which assay/scoring system was used . Conclusions : The Blueprint PD‐L1 IHC Assay Comparison Project revealed that three of the four assays were closely aligned on tumor cell staining whereas the fourth showed consistently fewer tumor cells stained . All of the assays demonstrated immune cell staining , but with greater variability than with tumor cell staining . By comparing assays and cutoffs , the study indicated that despite similar analytical performance of PD‐L1 expression for three assays , interchanging assays and cutoffs would lead to “ misclassification ” of PD‐L1 status for some patients . More data are required to inform on the use of alternative staining assays upon which to read different specific therapy‐related PD‐L1 cutoffs 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 Despite recent advances in the treatment of advanced non-small-cell lung cancer , there remains a need for effective treatments for progressive disease . We assessed the efficacy of pembrolizumab for patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . METHODS We did this r and omised , open-label , phase 2/3 study at 202 academic medical centres in 24 countries . Patients with previously treated non-small-cell lung cancer with PD-L1 expression on at least 1 % of tumour cells were r and omly assigned ( 1:1:1 ) in blocks of six per stratum with an interactive voice-response system to receive pembrolizumab 2 mg/kg , pembrolizumab 10 mg/kg , or docetaxel 75 mg/m(2 ) every 3 weeks . The primary endpoints were overall survival and progression-free survival both in the total population and in patients with PD-L1 expression on at least 50 % of tumour cells . We used a threshold for significance of p<0.00825 ( one-sided ) for the analysis of overall survival and a threshold of p<0.001 for progression-free survival . This trial is registered at Clinical Trials.gov , number NCT01905657 . FINDINGS Between Aug 28 , 2013 , and Feb 27 , 2015 , we enrolled 1034 patients : 345 allocated to pembrolizumab 2 mg/kg , 346 allocated to pembrolizumab 10 mg/kg , and 343 allocated to docetaxel . By Sept 30 , 2015 , 521 patients had died . In the total population , median overall survival was 10.4 months with pembrolizumab 2 mg/kg , 12.7 months with pembrolizumab 10 mg/kg , and 8.5 months with docetaxel . Overall survival was significantly longer for pembrolizumab 2 mg/kg versus docetaxel ( hazard ratio [ HR ] 0.71 , 95 % CI 0.58 - 0.88 ; p=0.0008 ) and for pembrolizumab 10 mg/kg versus docetaxel ( 0.61 , 0.49 - 0.75 ; p<0.0001 ) . Median progression-free survival was 3.9 months with pembrolizumab 2 mg/kg , 4.0 months with pembrolizumab 10 mg/kg , and 4.0 months with docetaxel , with no significant difference for pembrolizumab 2 mg/kg versus docetaxel ( 0.88 , 0.74 - 1.05 ; p=0.07 ) or for pembrolizumab 10 mg/kg versus docetaxel ( HR 0.79 , 95 % CI 0.66 - 0.94 ; p=0.004 ) . Among patients with at least 50 % of tumour cells expressing PD-L1 , overall survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 14.9 months vs 8.2 months ; HR 0.54 , 95 % CI 0.38 - 0.77 ; p=0.0002 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 17.3 months vs 8.2 months ; 0.50 , 0.36 - 0.70 ; p<0.0001 ) . Likewise , for this patient population , progression-free survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 5.0 months vs 4.1 months ; HR 0.59 , 95 % CI 0.44 - 0.78 ; p=0.0001 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 5.2 months vs 4.1 months ; 0.59 , 0.45 - 0.78 ; p<0.0001 ) . Grade 3 - 5 treatment-related adverse events were less common with pembrolizumab than with docetaxel ( 43 [ 13 % ] of 339 patients given 2 mg/kg , 55 [ 16 % ] of 343 given 10 mg/kg , and 109 [ 35 % ] of 309 given docetaxel ) . INTERPRETATION Pembrolizumab prolongs overall survival and has a favourable benefit-to-risk profile in patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . These data establish pembrolizumab as a new treatment option for this population and vali date the use of PD-L1 selection . FUNDING Merck & BACKGROUND Nivolumab , a programmed death 1 ( PD-1 ) checkpoint inhibitor , was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma . This r and omized , open-label , phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment . METHODS A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were r and omly assigned ( in a 1:1 ratio ) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily . The primary end point was overall survival . The secondary end points included the objective response rate and safety . RESULTS The median overall survival was 25.0 months ( 95 % confidence interval [ CI ] , 21.8 to not estimable ) with nivolumab and 19.6 months ( 95 % CI , 17.6 to 23.1 ) with everolimus . The hazard ratio for death with nivolumab versus everolimus was 0.73 ( 98.5 % CI , 0.57 to 0.93 ; P=0.002 ) , which met the prespecified criterion for superiority ( P≤0.0148 ) . The objective response rate was greater with nivolumab than with everolimus ( 25 % vs. 5 % ; odds ratio , 5.98 [ 95 % CI , 3.68 to 9.72 ] ; P<0.001 ) . The median progression-free survival was 4.6 months ( 95 % CI , 3.7 to 5.4 ) with nivolumab and 4.4 months ( 95 % CI , 3.7 to 5.5 ) with everolimus ( hazard ratio , 0.88 ; 95 % CI , 0.75 to 1.03 ; P=0.11 ) . Grade 3 or 4 treatment-related adverse events occurred in 19 % of the patients receiving nivolumab and in 37 % of the patients receiving everolimus ; the most common event with nivolumab was fatigue ( in 2 % of the patients ) , and the most common event with everolimus was anemia ( in 8 % ) . CONCLUSIONS Among patients with previously treated advanced renal-cell carcinoma , overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus . ( Funded by Bristol-Myers Squibb ; CheckMate 025 Clinical Trials.gov number , NCT01668784 . ) |
1,048 | 21,369,541 | 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 . | OBJECTIVE To determine whether the nonspecific effects that occur following the use of sham interventions to treat nonspecific low back pain ( LBP ) are large enough to be considered clinical ly meaningful . | 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 subacute low-back pain were shown to benefit from massage therapy , as regulated by the College of Massage Therapists of Ontario and delivered by experienced massage therapists & NA ; Individual differences in pharmacokinetics and pharmacodynamics , the type of pain and the method of drug administration can account for the response variability to analgesics . By integrating a clinical and an experimental approach , we report here that another important source of variability is represented by individual differences in non‐specific ( placebo ) activation of endogenous opioid systems . In the first part of this study , we analyzed the effectiveness of buprenorphine , tramadol , ketorolac and metamizol in the clinical setting , where the placebo effect was completely eliminated by means of hidden infusions . We found that the hidden injections were significantly less effective and less variable compared with open injections ( in full view of the subject ) , suggesting that part of the response variability was due to non‐specific factors ( placebo ) . Since we could not administer the opioid antagonist , naloxone , to these patients , in the second part of this study , we induced experimental ischemic arm pain in healthy volunteers and found that , as occurred in clinical pain , the analgesic response to a hidden injection of the non‐opioid ketorolac was less effective and less variable than an open injection . Most importantly , we obtained the same effects by adding naloxone to an open injection of ketorolac , thus blocking the opioid‐mediated placebo component of analgesia . These findings indicate that both the psychological ( hidden injection ) and pharmacological ( naloxone ) blockade of the placebo response reduce the effectiveness of , and the response variability to , analgesic drugs . Therefore , an important source of response variability to analgesics appears to be due to differences in non‐specific activation of endogenous opioid systems OBJECTIVE The objective of the present study was to assess the degree of pain relief obtained by applying infrared ( IR ) energy to the low back in patients with chronic , intractable low back pain . METHODS Forty patients with chronic low back pain of over six years ' duration were recruited from patients attending the Rothbart Pain Management Clinic , North York , Ontario . They came from the patient lists of three physicians at the clinic , and were r and omly assigned to IR therapy or placebo treatment . One patient dropped out of the placebo group ; as a result , 21 patients received IR therapy and 18 received placebo therapy . The IR therapy was provided by two small , portable units in a sturdy waistb and powered by small , rechargeable batteries made by MSCT Infrared Wraps Inc ( Canada ) . These units met safety st and ards for Food and Drug Administration portability , and are registered with the Food and Drug Administration as a therapeutic device . The unit converted electricity to IR energy at 800 nm to 1200 nm wavelength . The treated group received IR therapy . The placebo group had identical units , but the power was not connected to the circuit-board within the IR pad . Patients attended seven weekly sessions . One baseline and six weekly sets of values were recorded . The principle measure of outcome was pain rated on the numerical rating scale ( NRS ) . The pain was assessed overall , then rotating and bending in different directions . RESULTS The mean NRS scores in the treatment group fell from 6.9 of 10 to 3 of 10 at the end of the study . The mean NRS in the placebo group fell from 7.4 of 10 to 6 of 10 . CONCLUSION The IR therapy unit used was demonstrated to be effective in reducing chronic low back pain , and no adverse effects were observed Selecting an appropriate control group or placebo for r and omised controlled trials of spinal manipulative therapy is essential to the final interpretation and usefulness of these studies . Prior to starting a r and omised controlled trial of spinal manipulative therapy for acute low back pain we wanted to ensure that the placebo selected would be considered appropriate by experts in the field thereby making the results more likely to be accepted and more likely to influence clinical practice . We developed ten placebo techniques that aim ed to mimic spinal manipulative therapy as closely as possible which , while not including the active component of spinal manipulative therapy , were still credible . This list of placebo techniques with detailed descriptions was sent to 25 experts in the field from Australia and New Zeal and including both clinicians and academics . We asked the experts to rate whether they believed each technique was appropriate for use as a placebo in a trial of spinal manipulative therapy . Sixteen ( 64 % ) of the experts responded . There were extremely low levels of agreement between the experts on which placebos were appropriate ( kappa = 0.05 , 95 % CI 0.01 to 0.10 ) . For nine of the ten placebos at least one expert considered the placebo to include the active component of spinal manipulative therapy while at least one other expert believed the same placebo was not only not active but also not credible . The results of this study demonstrate the different views of experts on what constitutes an appropriate placebo for trials of spinal manipulative therapy . Different beliefs about what is the active component of spinal manipulative therapy appear to be responsible for much of the disagreement [ The cure for the headache ] was a kind of leaf , which required to be accompanied by a charm , and if a person would repeat the charm at the same time that he used the cure , he would be made whole ; but that without the charm the leaf would be of no avail . Socrates , according to Plato ( 1 ) There is a renewed interest in placebos and the placebo effecton their reality , their ethics , their place in medicine , or not , both in and out of the clinic and academy . The U.S. National Institutes of Health recently sponsored a large conference called Science of the Placebo ( 2 ) . At least five serious books on the subject ( 3 - 7 ) plus a book of poetry ( 8) and a novel (9)each titled Placebo Effecthave been published since 1997 . In the past 10 years , the National Library of Medicine has annually listed an average of 3972 scholarly papers with the keywords placebo , placebos , or placebo effect , with a low of 3362 papers in 1992 and a high of 4814 in 2000 . During the fall of 2000 , a discussion of the effect of new drag free suits , which might give an edge to Olympic swimmers , appeared in US News and World Report : [S]wimming officials are n't convinced this is anything more than the placebo effect . Swimmers excel because they think they 've got an edge ( 10 ) . One widely reported study , which concluded that placebos were powerless ( 11 ) , or represented the Wizard of Oz ( 12 ) , occasioned a blizzard of criticism ( 13 - 26 ) and some support ( 27 ) . It 's in the papers ( 28 , 29 ) . It 's in the air . Yet the most recent serious attempt to try logically to define the placebo effect failed utterly ( 30 ) . Given the ways people have gone about it , this seems unsurprising . Arthur K. Shapiro , MD , who spent much of his career as a psychiatrist study ing the placebo effect , recently wrote : A placebo is a substance or procedure that is objective ly without specific activity for the condition being treated The placebo effect is the therapeutic effect produced by a placebo . ( 31 ) If we replace the word placebo in the second sentence with its definition from the first , we get : The placebo effect is the therapeutic effect produced by [ things ] objective ly without specific activity for the condition being treated . This makes no sense whatsoever . Indeed , it flies in the face of the obvious . The one thing of which we can be absolutely certain is that placebos do not cause placebo effects . Placebos are inert and do n't cause anything . Moreover , people frequently exp and the concept of the placebo effect very broadly to include just about every conceivable sort of beneficial biological , social , or human interaction that does n't involve some drug well-known to the pharmacopoeia . A narrower form of this expansion includes identifying natural history or regression to the mean ( as we might observe them in a r and omized , controlled trial ) as part of the placebo effect . But natural history and regression occur not only in the control group . Nothing in the theory of regression to the mean ( 31 ) hints that when people are selected for being extreme on some measure ( blood pressure or cholesterol , for example ) , they are immune to regression if they receive active treatment . Such recipients are as likely ( or unlikely ) to move toward homeostasis as are control group patients . So , regression to the mean is in no meaningful way a placebo effect . Ernst and Resch ( 32 ) took an important step in trying to clarify this situation by differentiating the true from the perceived placebo effect . But true placebo effect has n't really caught on as a viable concept . The concept of the placebo effect has been exp and ed much more broadly than this . Some attribute the effects of various alternative medical systems , such as homeopathy ( 33 ) or chiropractic ( 34 ) , to the placebo effect . Others have described studies that show the positive effects of enhanced communication , such as Egbert 's ( 35 ) , as the placebo response without the placebo ( 7 ) . No wonder things are confusing . Meaning and Medicine We suggest thinking about this issue in a new way . A group of medical students was asked to participate in a study of two new drugs , one a tranquilizer and the other a stimulant [ 36 ] . Each student was given a packet containing either one or two blue or red tablets ; the tablets were inert . The students ' responses to a question naire indicated that 1 ) the red tablets acted as stimulants while the blue ones acted as depressants and 2 ) two tablets had more effect than one . The students were not responding to the inertness of the tablets . Moreover , these responses can not be easily accounted for by natural history , regression to the mean , or physician enthusiasm [ presumably the experimenters were as enthusiastic about the reds as the blues ] . Instead , they can be explained by the meanings in the experiment : 1 ) Red means up , hot , danger , while blue means down , cool , quiet and 2 ) two means more than one . These effects of color ( 37 - 40 ) and number ( 41 , 42 ) have been widely replicated . In a British study , 835 women who regularly used analgesics for headache were r and omly assigned to one of four groups ( 43 ) . One group received aspirin labeled with a widely advertised br and name ( one of the most popular analgesics in the United Kingdom that had been widely available for many years and supported by extensive advertising ) . The other groups received the same aspirin in a plain package , placebo marked with the same widely advertised br and name , or unmarked placebo . In this study , br and ed aspirin worked better than unbr and ed aspirin , which worked better than br and ed placebo , which worked better than unbr and ed placebo . Among 435 headaches reported by br and ed placebo users , 64 % were reported as improved 1 hour after pill administration compared with only 45 % of the 410 headaches reported as improved among the unbr and ed placebo users . Aspirin relieves headaches , but so does the knowledge that the pills you are taking are good ones . In a study of the benefits of aerobic exercise , two groups participated in a 10-week exercise program . One group was told that the exercise would enhance their aerobic capacity , while the other group was told that the exercise would enhance aerobic capacity and psychological well-being . Both groups improved their aerobic capacity , but only the second group improved in psychological well-being ( actually self-esteem ) . The research ers called this strong evidence that exercise may enhance psychological well-being via a strong placebo effect ( 44 ) . In the red versus blue pill study , we can correctly ( if not very helpfully ) classify the responses of the students as placebo effects because they did indeed receive inert tablets ; it seems clear , however , that they responded not to the pills but to their colors . In the second study , the presence of the br and name enhanced the effect of both the inert and the active drug . It does n't seem reasonable to classify the br and name effect as a placebo effect because no placebos are necessarily involved . Meanwhile , calling the consequences of authoritative instruction to the exercisers a placebo effect could come only from someone who believes that words do not affect the world , someone who has never been told I love you or who has never read the review s of a rejected grant proposal . It seems reasonable to label all these effects ( except , of course , of the aspirin and the exercise ) as meaning responses , a term that seeks , among other things , to recall Dr. Herbert Benson 's relaxation response ( 45 ) . Ironically , although placebos clearly can not do anything themselves , their meaning can . We define the meaning response as the physiologic or psychological effects of meaning in the origins or treatment of illness ; meaning responses elicited after the use of inert or sham treatment can be called the placebo effect when they are desirable and the nocebo effect ( 46 ) when they are undesirable . This is obviously a complex notion with several terms that would be challenging to unpack ( desirable , effect , meaning , treatment , illness)an exercise that can not be carried out here . Note that this definition excludes several elements that are usually included in our underst and ing of the placebo effect , such as natural history , regression , experimenter or subject bias , and error in measurement or reporting . Note as well that the definition is not phrased in terms of nonspecific effects ; although many elements of the meaning response or placebo effect may seem nonspecific , they are often quite specific in principle after they are understood . Meaning Permeates Medical Treatment Insofar as medicine is meaningful , it can affect patients , and it can affect the outcome of treatment ( 47 - 49 ) . Most elements of medicine are meaningful , even if practitioners do not intend them to be so . The physician 's costume ( the white coat with stethoscope hanging out of the pocket ) ( 50 ) , manner ( enthusiastic or not ) , style ( therapeutic or experimental ) , and language ( 51 ) are all meaningful and can be shown to affect the outcome ; indeed , we argue that both diagnosis ( 52 ) and prognosis ( 53 ) can be important forms of treatment . Many studies can be cited to document aspects of the therapeutic quality of the practitioner 's manner ( 54 ) . In one , a strong message of the effect of a drug ( an inert capsule ) substantially reduced the patients ' report of the pain of m and ibular block injection compared with the pain after a weak message . Patients who received the weak message reported less pain than a group that received no placebos and no message at all ( 55 ) . In another study , 200 patients with symptoms but no abnormal physical signs were r and omly assigned to a positive or a negative consultation . In a survey of patients 2 weeks later , 64 % of patients in the positive consultation group said they were all better , while only 39 % of those who had negative consultations thought they were better ( 56 ) . Although there is strong evidence for such physician effects , little evidence shows that patient effects are very important . A mass of research in the UNLABELLED Physical dependence or withdrawal is an expected effect of prolonged opioid therapy . Oxytrex ( oxycodone + ultralow-dose naltrexone ) is an investigational drug shown here to minimize physical dependence while providing strong analgesia with twice-daily dosing . In this 719-patient , double-blind , placebo- and active-controlled Phase III clinical trial in chronic low back pain , patients were r and omized to receive placebo , oxycodone qid , or oxytrex qid or bid . Each oxytrex tablet contains 1 microg naltrexone ; oxytrex bid and qid treatments provide 2 and 4 microg naltrexone/day , respectively . Following a washout , patients with pain > or=5 on a 0 - 10 scale were dose-escalated weekly from 10 up to 80 mg/day until reaching adequate pain relief ( < or=2 ) or a tolerable level of side effects . Following titration , the dose was fixed for 12 weeks . Active treatment groups attained comparable analgesia despite significantly lower drug use ( P = .03 ) by oxytrex patients . Patients taking oxytrex bid reported 55 % less physical dependence than patients on oxycodone ( P = .01 ) by the Short Opiate Withdrawal Scale 24 h after treatment cessation . Oxytrex bid patients also reported decreased moderate-to-severe constipation ( by 44 % , P = .01 ) , somnolence ( by 33 % , P = .03 ) , and pruritus ( by 51 % , P < .001 ) . This is the first large well controlled study to show strong analgesia with minimal withdrawal symptoms and better safety compared with oxycodone . PERSPECTIVE Previous clinical data have shown ultralow-dose naltrexone enhances and prolongs oxycodone analgesia , and pre clinical data also show a suppression of opioid tolerance and dependence . A cellular mechanism of action has been demonstrated to be the prevention of aberrant G protein signaling by mu opioid receptors caused by chronic opioid administration R and omized , placebo-controlled clinical trials are recommended for evaluation of a treatment 's efficacy with the goal of separating the specific effects ( verum ) from the non-specific ones ( placebo ) . In order to be able to carry out placebo-controlled acupuncture trials , minimal/sham acupuncture procedures and a sham acupuncture needle has been used with the intention of being inert . However , clinical and experimental results suggest that sham/minimal acupuncture is not inert since it is reported that both verum acupuncture and sham/minimal acupuncture induce a significant alleviation of pain . This alleviation is as pronounced as the alleviation obtained with st and ard treatment and more obvious than the one obtained with placebo medication or by the use of waiting list controls . These results also suggest that sham acupuncture needles evoke a physiological response . In healthy individuals sham acupuncture results in activation of limbic structures , whereas a deactivation is seen in patients with pain , i.e. results from healthy individuals do not reflect what is seen in clinical conditions . Also , depending on the etiology of pain ( or any under clinical condition under investigation ) , the response to sham acupuncture is varying . The acupuncture ritual may also be seen as an emotional focused therapy allowing for psychological re-orientation . Sham needling in such context may be as powerful as verum acupuncture . We recommend that the evaluated effects of acupuncture could be compared with those of st and ard treatment , also taking the individual response into consideration , before its use or non-use is established OBJECTIVES To investigate the course of low back pain ( LBP ) in a general population over 5 years . DESIGN Prospect i ve population -based survey by postal question naires in 1991 , 1992 , and 1996 . SETTING The municipal of Ebeltoft , Denmark . SUBJECTS Two thous and people aged 30 to 50 years , representative of the Danish population . Main outcome measure Number of days with low back pain during the past year . RESULTS One thous and three hundred seventy were recruited of whom 813 ( 59 % ) were followed to 5 years . The responders could be divided into 3 groups with regard to LBP : no pain , short-term pain , and long-lasting/recurring pain . More than one third of people who experienced LBP in the previous year did so for > 30 days . Forty percent of people with LBP > 30 days at baseline remained in that group 1 and 5 years later , and 9 % with LBP > 30 days in year 0 were pain free in year 5 . People with LBP in year 0 were 4 times more likely to have LBP in year 1 , and 2 times more likely to be affected in year 5 . CONCLUSIONS Low back pain should not be considered transient and therefore neglected , since the condition rarely seems to be self-limiting but merely presents with periodic attacks and temporary remissions . On the other h and , chronicity as defined solely by the duration of symptoms should not be considered chronic Objectives of this study were to assess efficacy and effects on psychomotor performances of thiocolchicoside ( TCC ) and tizanidine ( TZ ) compared to placebo . Patients complaining of acute low back pain ( LBP ) associated with muscle spasm were enrolled in this r and omised , double-blind clinical trial , comparing the effects of oral TCC , TZ and placebo on psychomotor performances assessed by a visual analogue scale of tiredness , drowsiness , dizziness and alertness and by psychometric tests after 2 and 5 - 7 days of treatment . The efficacy assessment s , both TCC and TZ , were more effective than placebo in improving pain at rest , h and -to-floor distance , Schober test and decreased paracetamol consumption . There were significant differences among the treatment groups in favour of TCC compared to TZ in visual analog scale-parameters . TZ-induced reduction of psychomotor performances of the patients was confirmed by psychometric tests , which showed significant differences among groups . This study showed that TCC is at least as effective as TZ in the treatment of acute LBP , while it appears devoid of any sedative effect in contrast to TZ OBJECTIVE To evaluate the analgesic efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg ( tramadol/APAP ) combination tablets for treatment of chronic low back pain ( LBP ) . METHODS This 91 day , multicenter , outpatient , r and omized , double blind , placebo controlled study enrolled 338 patients with chronic LBP requiring daily medication for > or = 3 months . Patients with at least moderate pain [ pain visual analog scale ( VAS ) with scores > or = 40/100 mm ] after washout were r and omized to tramadol/APAP or placebo . After a 10 day titration , patients received 1 or 2 tablets QID . Primary outcome measure was final pain VAS score . Secondary measures included pain relief , quality of life and physical functioning , efficacy failure , and overall medication assessment s. RESULTS In total , 336 intent-to-treat patients received tramadol/APAP ( n = 167 ) or placebo ( n = 169 ) . Mean baseline pain VAS score was 67.8 . Intent-to-treat analysis showed significantly better mean final pain VAS scores ( 47.4 vs 62.9 ; p < 0.001 ) and mean final pain relief scores ( 1.8 vs 0.7 ; p < 0.001 ) for tramadol/APAP than for placebo . Rol and Disability Question naire scores and physical-related subcategories of the McGill Pain Question naire and the Medical Outcome Study Short Form-36 Health Survey were significantly better for tramadol/APAP patients . More patients rated tramadol/APAP as " very good " or " good " than placebo ( 63.6 vs 25.2 % ; p < 0.001 ) . Kaplan-Meier estimates of cumulative discontinuation rates due to efficacy failures were 22.9 % ( tramadol/APAP ) vs 54.7 % ( placebo ; p < 0.001 ) . The most common treatment related adverse events with tramadol/APAP were nausea ( 12.0 % ) , dizziness ( 10.8 % ) , and constipation ( 10.2 % ) . Average daily dose of tramadol/APAP was 4.2 tablets ( tramadol 158 mg/APAP 1369 mg ) . CONCLUSION Tramadol 37.5 mg/APAP 325 mg combination tablets show efficacy in pain reduction , in measures of physical functioning and quality of life , and in overall medication assessment s , with a tolerability profile comparable with other opioids used for the treatment of chronic LBP & NA ; To assess the efficacy of nortriptyline , a tricyclic antidepressant , as an analgesic in chronic back pain without depression , we conducted a r and omized , double‐blind , placebo‐controlled , 8‐week trial in 78 men recruited from primary care and general orthopedic setting s , who had chronic low back pain ( pain at T‐6 or below on a daily basis for 6 months or longer ) . Of these 57 completed the trial ; of the 21 who did not complete , four were withdrawn because of adverse effects . The intervention consisted of inert placebo or nortriptyline titrated to within the therapeutic range for treating major depression ( 50–150 ng/ml ) . The main outcome endpoints were pain ( Descriptor Differential Scale ) , disability ( Sickness Impact Profile ) , health‐related quality of life ( Quality of Well‐Being Scale ) , mood ( Beck Depression Inventory , Spielberger State Anxiety Inventory , Hamilton Anxiety/Depression Rating Scales ) , and physician rated outcome ( Clinical Global Impression ) . Reduction in pain intensity scores was significantly greater for participants r and omized to nortriptyline ( difference in mean change 1.68 , 95 % −0.001 , CI −3.36 , P=0.050 ) , with a reduction of pain by 22 % compared to 9 % on placebo . Reduction in disability marginally favored nortriptyline ( P=0.055 ) , but health‐related quality of life , mood , and physician ratings of overall outcome did not differ significantly between treatments . Subgroup analyses of study completers supported the intent‐to‐treat analysis . Also , completers with radicular pain on nortriptyline ( n=5 ) had significantly ( P<0.05 ) better analgesia and overall outcome than did those on placebo ( n=6 ) . The results suggest noradrenergic mechanisms are relevant to analgesia in back pain . This modest reduction in pain intensity suggests that physicians should carefully weigh the risks and benefits of nortriptyline in chronic back pain without depression Thirty-seven patients with chronic back pain were entered into a r and omised , 3-way , double-blind , cross-over comparison of naproxen sodium 550 mg twice daily , diflunisal 500 mg twice daily , and placebo . Each treatment was given for 14 days after a preadmission wash-out week during which only paracetamol was allowed . Patients were assessed on admission and at the end of each treatment with respect to global pain , night pain , pain on movement , and pain on st and ing . Both visual analogue scales and simple descriptive scales were used to measure pain . Side effects were elicited by a nonleading question . Both methods of pain measurement gave similar results and were highly correlated . Naproxen sodium was superior to placebo in relieving global pain and depending on the method of measurement , in relieving night pain and pain on movement . Diflunisal showed no significant differences from placebo . Side effects were similar on all 3 treatments . The final preference of the patients was significantly in favour of the active treatments OBJECTIVE To assess the efficacy and safety of oral adenosine triphosphate ( ATP ) in subacute low back pain . METHODS This was a r and omized , double-blind , parallel group , placebo controlled clinical trial . The patients were given either ATP 90 mg once daily ( n=81 ) or placebo ( n=80 ) for one month . The patients were assessed 3 times during the study period , at days 0 , 7 , and 30 . The primary outcome measure was the Rol and -Morris Disability Question naire ( RDQ ) at day 30 . Secondary measures of efficacy included visual analog scale ( VAS ) pain , overall assessment s of efficacy by both patient and investigator , and number of dextropropoxyphene and acetaminophen combination tablets used as rescue analgesic . RESULTS Regarding the RDQ , the mean values dropped from 10.3 + /-2.8 at baseline to 7.5 + /-3.8 ( day 7 ) and 5.2 + /-5.2 ( day 30 ) in the ATP group , and from 11.0 + /- 3.5 to 9.1 + /- 4.2 ( day 7 ) and 6.1 + /- 4.3 ( day 30 ) in the placebo group . The difference between the 2 groups was statistically significant at day 7 ( p= 0.02 ) but not at day 30 ( p=0.2 ) . In other words , the mean changes from baseline were 2.8 + /- 3.1 and 2.0 + /- 2.6 at day 7 ( p=0.06 ) , and 5.1 + /- 3.9 and 5.0 + /- 4.2 at day 30 ( p=0.78 ) in the ATP group and the placebo group , respectively . There were no statistically significant differences in the VAS pain and overall assessment s of efficacy between groups at any time point during the study . Conversely , there was a significant difference in the use of the rescue analgesic between groups , in favor of ATP ( p=0.04 ) . Oral ATP was well tolerated . CONCLUSION Oral ATP might have an early acting effect in subacute low back pain & NA ; Response expectancies have been proposed as the major determinant of placebo effects . Here we report that different expectations produce different analgesic effects which in turn can be harnessed in clinical practice . Thoracotomized patients were treated with buprenorphine on request for 3 consecutive days , together with a basal intravenous infusion of saline solution . However , the symbolic meaning of this basal infusion was changed in three different groups of patients . The first group was told nothing about any analgesic effect ( natural history ) . The second group was told that the basal infusion was either a powerful painkiller or a placebo ( classic double‐blind administration ) . The third group was told that the basal infusion was a potent painkiller ( deceptive administration ) . Therefore , whereas the analgesic treatment was exactly the same in the three groups , the verbal instructions about the basal infusion differed . The placebo effect of the saline basal infusion was measured by recording the doses of buprenorphine requested over the three‐days treatment . We found that the double‐blind group showed a reduction of buprenorphine requests compared to the natural history group . However , this reduction was even larger in the deceptive administration group . Overall , after 3 days of placebo infusion , the first group received 11.55 mg of buprenorphine , the second group 9.15 mg , and the third group 7.65 mg . Despite these dose differences , analgesia was the same in the three groups . These results indicate that different verbal instructions about certain and uncertain expectations of analgesia produce different placebo analgesic effects , which in turn trigger a dramatic change of behaviour leading to a significant reduction of opioid intake The purpose of this double-blind study was to ascertain the effects of helium-neon ( He-Ne ) laser irradiation on skin resistance and pain in patients with trigger points in the neck or low back . This study entailed a partial replication of a previous study by Snyder-Mackler and associates that determined the use of the He-Ne laser increased skin resistance overlying a trigger point . Twenty-four patients were r and omly assigned to either a treatment or a control group and received three 20-second applications of laser irradiation or placebo " stimulation , " respectively . Pretreatment and posttreatment skin resistance and pain measurements ( via visual analog scale ) were taken during each session . Results indicated a statistically significant increase in skin resistance ( p less than .001 ) and a decrease in pain ( p less than .005 ) following laser treatment . There was not a significant correlation between skin resistance and pain across subjects . These data substantiate the previous findings of Snyder-Mackler and associates and demonstrate a reduction in pain . Helium-neon laser treatment , therefore , may be an effective adjunct to conventional physical therapy of these patients Patients ( 112 ) with acute low-back pain of recent onset were recruited to this double-blind , r and omized , placebo-controlled parallel group study in general practice to evaluate the efficacy and tolerability of the muscle relaxant , tizanidine . They were treated for 7 days with tizanidine ( 4 mg three times daily ) or matching placebo . Aspirin tablets ( 300 mg ) were taken as required as ‘ rescue ’ medication . Symptoms were assessed by the patient and doctor before treatment , and after 3 and 7 days . Patients recorded pain and aspirin consumption in a daily diary . Both treatments were effective . In patients who had taken no medication prior to entry , aspirin consumption was almost halved in the first 3 days of taking tizanidine compared with placebo ( P = 0.037 ) . Results for pain at rest , pain at night , restriction of movement and pain on movement suggest that tizanidine may give greater improvement , earlier . No serious drug-related adverse events or abnormal biochemistry or haematology were observed in either group . Drowsiness occurred in 22 % of patients taking tizanidine although , in patients with severe acute low-back pain , sedation , analgesia and bed rest might be beneficial and desired . Considerably more patients given aspirin/placebo had gastro-intestinal side-effects ( P = 0.018 ) . In conclusion , tizanidine may reduce the need for analgesics and be useful in the treatment of acute low-back pain BACKGROUND Tramadol and acetaminophen ( APAP ) have both shown efficacy in the treatment of lower back pain . The combination of these 2 agents has demonstrated synergistic analgesic action in animal models at specific ratios . OBJECTIVE This study assessed the long-term ( 3-month ) efficacy and safety of tramadol 37.5 mg/APAP 325 mg combination tablets in the treatment of chronic lower back pain . METHODS Patients with at least moderate lower back pain ( pain visual analog [ PVA ] score > /=40 mm on a 100-mm scale ) were r and omized to receive up to 8 tablets of tramadol/APAP per day or placebo for 91 days . Medication was titrated from 1 to 4 tablets/d by day 10 . The primary efficacy measure was PVA score at the final visit . Secondary measures included scores on the Pain Relief Rating Scale ( PRRS ) , Short-Form McGill Pain Question naire ( SF-MPQ ) , Rol and Disability Question naire ( RDQ ) , and 36-Item Short-Form Health Survey ( SF-36 ) ; the incidence of discontinuation due to insufficient pain relief ( Kaplan-Meier analysis ) ; and overall assessment s of medication by the patients and investigators . RESULTS Three hundred eighteen patients ( 161 tramadol/APAP , 157 placebo ) were included in the intent-to-treat population , defined as all patients who took > /=1 dose of study medication and had > /=1 postr and omization efficacy measurement . The mean age of the study population was 53.9 years , 63.2 % were female , 90.3 % were white , and the mean baseline PVA score was 70.0 mm . There were no significant differences between groups at baseline . Tramadol/APAP significantly improved final PVA scores ( P = 0.015 ) and final PRRS scores ( P < 0.001 ) compared with placebo . Tramadol/APAP also significantly improved RDQ scores ( P < /= 0.027 ) and scores on many subcategories of the SF-MPQ , including total score ( P = 0.021 ) . The tramadol/APAP group had significant improvements on the role-physical ( P = 0.005 ) , bodily pain ( P = 0.046 ) , role-emotional ( P = 0.001 ) , mental health ( P = 0.026 ) , reported health transition ( P = 0.038 ) , and mental component summary ( P = 0.008 ) subscales of the SF-36 . The cumulative incidence of discontinuation due to insufficient pain relief was 22.1 % for tramadol/APAP and 41.0 % for placebo ( P < 0.001 ) . Treatment-emergent adverse events in the tramadol/APAP group included nausea ( 13.0 % ) , somnolence ( 12.4 % ) , and constipation ( 11.2 % ) . CONCLUSIONS In this study , tramadol 37.5 mg/APAP 325 mg combination tablets were effective and had a favorable safety profile in the treatment of chronic lower back pain BACKGROUND This study evaluated the safety and efficacy of tramadol ER 300 mg and 200 mg versus placebo once daily in the treatment of chronic low back pain , using an open-label run-in followed by , without washout , a r and omized controlled study design . METHODS Adults with scores > or = 40 on a pain intensity visual analog scale ( VAS ; 0 = no pain ; 100 = extreme pain ) received open-label tramadol ER , initiated at 100 mg once daily and titrated to 300 mg once daily during a three-week open-label run-in . Patients completing run-in were r and omized to receive tramadol ER 300 mg , 200 mg , or placebo once daily for 12 weeks . RESULTS Of 619 patients enrolled , 233 ( 38 percent ) withdrew from the run-in , primarily because of adverse event ( n = 128 ) or lack of efficacy ( n = 41 ) . A total of 386 patients were then r and omized to receive either 300 mg ( n = 128 ) , 200 mg ( n = 129 ) , or placebo ( n = 129 ) . Following r and omization , mean scores for pain intensity VAS since the previous visit , averaged over the 12-week study period , increased more in the placebo group ( 12.2 mm ) than in the tramadol ER 300-mg ( 5.2 mm , p = 0.009 ) and 200-mg ( 7.8 mm , p = 0.052 ) groups . Secondary efficacy scores for current pain intensity VAS , patient global assessment , Rol and Disability Index , and overall sleep quality improved significantly ( p < or = 0.029 each ) in the tramadol ER groups compared with placebo . The most common adverse events during the double-blind period were nausea , constipation , headache , dizziness , insomnia , and diarrhea . CONCLUSIONS In patients who tolerated and obtained pain relief from tramadol ER , continuation of tramadol ER treatment for 12 weeks maintained pain relief more effectively than placebo . Adverse events were similar to those previously reported for tramadol ER The efficacy and safety of baclofen ( 30–80 mg daily ) for the treatment of acute low-back syndrome were evaluated in a 14-day , double-blind , r and omized study of 200 patients ( 100 baclofen , 100 placebo ) . Patients with initially severe or extremely severe symptoms ( as opposed to moderate symptoms ) benefitted most from treatment with baclofen . The incidence of adverse effects was significantly higher in the baclofen group ; however , most were mild to moderate and disappeared in all but two patients who required a reduction in dosage , without reduced drug efficacy . Baclofen was shown to be effective , safe , and well-tolerated for the treatment of patients with acute low-back syndrome UNLABELLED This r and omized , double-blind , placebo- and active-controlled , parallel-group study was design ed to demonstrate the superiority of oxycodone in combination with naloxone in a prolonged release ( PR ) formulation over placebo with respect to analgesic efficacy . The active control group was included for sensitivity and safety analyses , and furthermore to compare the analgesic efficacy and bowel function of oxycodone PR/naloxone PR with oxycodone PR alone . The analgesic efficacy was measured as the time from the initial dose of study medication to multiple pain events ( ie , inadequate analgesia ) in patients with moderate to severe chronic low back pain . The full analysis population consisted of 463 patients . The times to recurrent pain events were significantly longer in the oxycodone PR/naloxone PR group compared with placebo ( P < .0001-.0003 ) ; oxycodone PR/naloxone PR reduced the risk of pain events by 42 % ( P < .0001 ; full analysis population ) . The appearance of pain events was comparable for oxycodone PR/naloxone PR versus oxycodone PR , confirming that the addition of naloxone PR to oxycodone PR in a combination tablet did not negatively affect analgesic efficacy of the opioid . Furthermore , oxycodone PR/naloxone PR offers benefits in terms of an improvement in bowel function . In a therapeutic area of great unmet need , therefore , the combination tablet of oxycodone PR/naloxone PR offers patients effective analgesia while improving opioid-induced bowel dysfunction . Taken together with the observation that the safety profile of oxycodone PR/naloxone PR is consistent with that expected from other opioid analgesics except opioid-induced constipation , these findings indicate that the addition of naloxone to oxycodone in a PR combination tablet offers improved tolerability . Oxycodone PR/naloxone PR is therefore a promising new treatment approach for the management of chronic pain . PERSPECTIVE This study evaluated the analgesic efficacy and safety of the combination of oxycodone PR/naloxone PR in chronic nonmalignant pain . Opioids are often reduced in dosage or even discontinued as a result of impaired bowel function , leading to insufficient pain treatment . Not only does oxycodone PR/naloxone PR demonstrate analgesic efficacy comparable with oxycodone PR , but it also improves opioid-induced bowel dysfunction , and may therefore improve the acceptability of long-term opioid treatment for chronic pain Twenty-seven investigators participated in a double-blind , parallel placebo-controlled trial of piroxicam involving 278 patients with acute low back pain . Therapy commenced within 48 hours of the injury and continued for 7 days . The drug was given in the recommended regimen of 40 mg once daily for the first 2 days and 20 mg once daily thereafter . After 3 days of therapy , piroxicam patients showed a statistically greater amount of pain relief in the lying ( P<0.001 ) , sitting ( P<0.01 ) , and st and ing ( P<0.01 ) positions , but after 7 days the difference between treatments was no longer significant . After 1 week 's therapy , however , the requirement for additional analgesic was significantly lower in the piroxicam group ( P<0.05 ) , and more piroxicam than placebo patients ( 42 versus 28 ) had returned to work ( P<0.05 ) . Toleration was excellent in most patients , with only 13 % of the piroxicam and 17 % of the placebo group reporting adverse effects of mainly mild or moderate severity . The profile of the adverse effects was similar for both treatments . Piroxicam can provide effective relief of acute low-back pain with good toleration ; it should be considered for use in the initial treatment of this condition We evaluated etoricoxib , a novel COX-2-specific inhibitor , in 319 patients with chronic low back pain ( LBP ) in this double-blind , placebo-controlled trial . Patients were r and omized to a 60 mg dose ( n = 103 ) or 90 mg dose ( n = 107 ) of etoricoxib , or placebo ( n = 109 ) , daily for 12 weeks . The primary endpoint was low back pain intensity scale ( Visual Analog Scale of 0- to 100-mm ) time-weighted average change from baseline over 4 weeks . Other endpoints included evaluation over 3 months of low back pain intensity scale , Rol and -Morris Disability Question naire ( RMDQ ) , low back pain bothersomeness scale , patient- and investigator-global assessment s , Patient Health Survey ( MOS SF-12 ) , rescue acetaminophen use , and discontinuation due to lack of efficacy . Etoricoxib provided significant improvement from baseline versus placebo in pain intensity ( 4 weeks : 12.9 mm and 10.3 mm for 60-mg and 90-mg doses , P < .001 for each ; 12 weeks : 10.5 mm and 7.5 mm for 60-mg and 90-mg doses , P = .001 and .018 , respectively ) . Etoricoxib at either dose led to significant improvement in other endpoints , including RMDQ scores , bothersomeness scores and global assessment s. Etoricoxib given once daily provided significant relief of symptoms , and disability associated with chronic LBP that was observed 1 week after initiating therapy , was maximal at 4 weeks , and was maintained over 3 months Abstract OBJECTIVES : To define the spectrum of chronic noncancer pain treated with opioid medications in 2 primary care setting s , and the prevalence of psychiatric comorbidity in this patient population . We also sought to determine the proportion of patients who manifested prescription opioid abuse behaviors and the factors associated with these behaviors . DESIGN : A retrospective cohort study . SETTING : A VA primary care clinic and an urban hospital-based primary care center ( PCC ) located in the northeastern United States . PATIENTS : A r and om sample of VA patients ( n=50 ) and all PCC patients ( n=48 ) with chronic noncancer pain who received 6 or more months of opioid prescriptions during a 1-year period ( April 1 , 1997 through March 31 , 1998 ) and were not on methadone maintenance . MEASUREMENTS : Information regarding patients ’ type of chronic pain disorder , demographic , medical , and psychiatric status , and the presence of prescription opioid abuse behaviors was obtained by medical record review . MAIN RESULTS : Low back pain was the most common disorder accounting for 44 % and 25 % of all chronic pain diagnoses in the VA and PCC sample s , respectively , followed by injury-related ( 10 % and 13 % ) , diabetic neuropathy ( 8 % and 10 % ) , degenerative joint disease ( 16 % and 13 % ) , spinal stenosis ( 10 % and 4 % ) , headache ( 4 % and 13 % ) and other chronic pain disorders ( 8 % and 22 % ) . The median duration of pain was 10 years ( range 3 to 50 years ) in the VA and 13 years in the PCC sample ( range 1 to 49 years ) . Among VA and PCC patients , the lifetime prevalence rates of psychiatric comorbidities were : depressive disorder ( 44 % and 54 % ) , anxiety disorder ( 20 % and 21 % ) , alcohol abuse/dependence ( 46 % and 31 % ) , and narcotic abuse/dependence ( 18 % and 38 % ) . Prescription opioid abusive behaviors were recorded for 24 % of VA and 31 % of PCC patients . A lifetime history of a substance use disorder ( adjusted odds ratio [ OR ] , 3.8 ; 95 % confidence interval [ CI ] , 1.4 to 10.8 ) and age ( adjusted OR , 0.94 ; 95 % CI , 0.89 to 0.99 ) were independent predictors of prescription opioid abuse behavior . CONCLUSIONS : A broad spectrum of chronic noncancer pain disorders are treated with opioid medications in primary care setting s. The lifetime prevalence of psychiatric comorbidity was substantial in our study population . A significant minority of patients manifested prescription opioid abusive behaviors , and a lifetime history of a substance use disorder and decreasing age were associated with prescription opioid abuse behavior . Prospect i ve studies are needed to determine the potential benefits as well as risks associated with opioid use for chronic noncancer pain in primary care UNLABELLED Clinical trials of the efficacy of antidepressant drugs in patients with chronic low back pain have had mixed results , possibly because of the different mechanisms of action of the drugs that have been studied . Because bupropion has a mechanism of action that differs from other antidepressants and has shown efficacy in neuropathic pain , a r and omized , placebo-controlled , 2-period crossover trial was conducted to evaluate its efficacy in subjects with chronic low back pain . The primary efficacy variable was mean daily diary pain intensity ratings , and secondary pain intensity and relief outcomes included weekly pain intensity ratings , the McGill Pain Question naire ( MPQ ) Present Pain Intensity scale , pain relief ratings , and satisfaction with pain relief ratings . Adverse events were also assessed throughout the trial . Analyses were performed of an intention-to-treat sample of 44 patients , only 3 of whom met criteria for neuropathic low back pain . Daily and weekly pain intensity ratings , the MPQ Present Pain Intensity scale , and pain relief ratings were not significantly different following treatment with bupropion sustained release ( SR ) vs. placebo . These results suggest that bupropion SR was not significantly better than placebo in the treatment of patients with non-neuropathic chronic low back pain . PERSPECTIVE Antidepressant medications that have both noradrenergic and serotonergic effects appear to have greater efficacy in patients with chronic low back pain than those with only serotonergic activity . We studied bupropion because it inhibits the reuptake of both norepinephrine and dopamine , but found no evidence of efficacy in patients with non-neuropathic chronic low back pain ABSTRACT Objective : Determine the efficacy and tolerability of oxymorphone extended release ( OPANA ER† ) in opioid-naive patients with moderate to severe chronic low back pain ( CLBP ) . Design and methods : Patients ≥ 18 years of age were titrated with oxymorphone ER ( 5- to 10‑mg increments every 12 h , every 3–7 days ) to a well-tolerated , stabilized dose . Patients were then r and omized to continue their oxymorphone ER dose or receive placebo every 12 h for 12 weeks . Oxymorphone immediate release was available every 4–6 h , as needed , for the first 4 days and twice daily thereafter . Results : Sixty-three percent of patients ( 205/325 ) were titrated to a stabilized dose of oxymorphone ER , most ( 203/205 ) within 1 month . During titration , 18 % discontinued from adverse events ( AEs ) and 1 % from lack of efficacy . For patients completing titration , average pain intensity decreased from 69.4 mm at screening to 22.7 mm ( p < 0.0001 ) . After r and omization , 68 % of oxymorphone ER and 47 % of placebo patients completed 12 weeks of double-blind treatment . Approximately 8 % of patients in each group discontinued because of AEs . Placebo patients discontinued significantly sooner from lack of efficacy than those receiving oxymorphone ER ( p < 0.0001 ) . Pain intensity increased significantly more in the placebo group ( least squares [ LS ] mean change 26.9 ± 2.4 [ median 28.0 ] ) than in the oxymorphone ER group ( LS mean change 10.0 ± 2.4 [ median 2.0 ] ; p < 0.0001 ) . Oxymorphone ER was generally well tolerated without unexpected AEs . Although limitations of a r and omized withdrawal study include the potential for unblinding and opioid withdrawal in placebo patients , opioid withdrawal was limited to two patients in the placebo group and one in the oxymorphone ER group . Conclusions : Stabilized doses of oxymorphone ER were generally safe and effective over a 12‑week double-blind treatment period in opioid-naive patients with CLBP BACKGROUND The adult lifetime incidence for low back pain is 75 % to 85 % in the United States . Investigating appropriate care has proven difficult , since , in general , acute pain subsides spontaneously and chronic pain is resistant to intervention . Subacute back pain has been rarely studied . OBJECTIVE To compare the relative efficacy of chiropractic adjustments with muscle relaxants and placebo/sham for subacute low back pain . DESIGN A r and omized , double-blind clinical trial . METHODS Subjects ( N = 192 ) experiencing low back pain of 2 to 6 weeks ' duration were r and omly allocated to 3 groups with interventions applied over 2 weeks . Interventions were either chiropractic adjustments with placebo medicine , muscle relaxants with sham adjustments , or placebo medicine with sham adjustments . Visual Analog Scale for Pain , Oswestry Disability Question naire , and Modified Zung Depression Scale were assessed at baseline , 2 weeks , and 4 weeks . Schober 's flexibility test , acetaminophen usage , and Global Impression of Severity Scale ( GIS ) , a physician 's clinical impression used as a secondary outcome , were assessed at baseline and 2 weeks . RESULTS Baseline values , except GIS , were similar for all groups . When all subjects completing the protocol were combined ( N = 146 ) , the data revealed pain , disability , depression , and GIS decreased significantly ( P < .0001 ) ; lumbar flexibility did not change . Statistical differences across groups were seen for pain , a primary outcome , ( chiropractic group improved more than control group ) and GIS ( chiropractic group improved more than other groups ) . No significant differences were seen for disability , depression , flexibility , or acetaminophen usage across groups . CONCLUSION Chiropractic was more beneficial than placebo in reducing pain and more beneficial than either placebo or muscle relaxants in reducing GIS The efficacy of an NSAID ( tenoxicam ) in the treatment of acute low back pain ( LBP ) was assessed in a double blind controlled study by using an objective functional evaluation . Seventy-three patients consulting for acute LBP were r and omized into two groups : Group I was treated with tenoxicam for 14 days and Group II was given a placebo . Trunk function was measured with a computerized isoinertial dynamometric trunk testing device ( Isostation B200 ) . Isometric and dynamic torques , range of motion and movement velocities were measured before treatment and after 14 days . Clinical evaluation was realized by the patient on a pain visual analogue scale ( VAS ) on days 1 , 8 and 15 and by the investigator on a five-point scale on days 8 and 15 . The functional evaluation showed significant differences in favour of the tenoxicam treatment for velocity and extension isometric torque . VAS and investigator evaluations showed a significant difference in favour of tenoxicam on day 8 but no difference on day 15 . This study shows that the use of tenoxicam in acute LBP is of interest . Tenoxicam has an effect on pain during the first part of the treatment and may help to restore full function even if the symptoms have disappeared OBJECTIVE To evaluate the efficacy and safety of tramadol in the treatment of chronic low back pain . METHODS A 3 phase trial : ( 1 ) a washout/screening phase ; ( 2 ) a 3 week , open label , run-in phase ; and ( 3 ) a 4 week , r and omized , placebo controlled , double blind treatment phase . Three hundred eighty out patients between 21 and 79 years with chronic low back pain with no or a distant history of back surgery enrolled in the open label phase and were treated with tramadol up to 400 mg/day . At the end of the open label phase , patients who tolerated tramadol and perceived benefit from it were r and omized to continue treatment with tramadol or to convert to placebo in the double blind phase . Reasons for discontinuing from the open label phase included adverse events , 78 patients ( 20.5 % ) ; drug ineffective , 23 patients ( 6.1 % ) ; and other reasons , 25 patients ( 6.6 % ) . Two hundred fifty-four patients entered the double blind phase , during which the daily dose was maintained within the range 200 - 400 mg tramadol or equivalent amount of placebo . The primary outcome measure in the double blind phase was the time to discontinuation due to inadequate pain relief . RESULTS The distribution of time to therapeutic failure was significantly ( p < or = 0.0001 ) different in the tramadol group compared to placebo . Kaplan-Meier estimate of the cumulative discontinuation rate due to therapeutic failure was 20.7 % in the tramadol group and 51.3 % in the placebo group . There were significantly lower ( p < or = 0.0001 ) mean pain visual analog scores ( 10 cm scale ) among tramadol patients ( 3.5 cm ) compared to placebo patients ( 5.1 cm ) at the final visit of the double blind phase . Tramadol patients scored significantly better on the McGill Pain Question naire ( p = 0.0007 ) and the Rol and Disability Question naire ( p = 0.0001 ) . Five of 127 tramadol treated patients and 6/127 placebo treated patients discontinued treatment during the double blind phase due to an adverse event . Commonly reported adverse events with tramadol included nausea , dizziness , somnolence , and headache . CONCLUSION Among patients who tolerated it well , tramadol was effective for the treatment of chronic low back pain Two daily doses of oral Harpagophytum extract WS 1531 ( 600 and 1200 , respectively , containing 50 and 100 mg of the marker harpagoside ) were compared with placebo over 4 weeks in a r and omized , double-blind study in 197 patients with chronic susceptibility to back pain and current exacerbations that were producing pain worse than 5 on a 0 - 10 visual analogue scale . The principal outcome measure , based on pilot studies , was the number of patients who were pain free without the permitted rescue medication ( tramadol ) for 5 days out of the last week . The treatment and placebo groups were well matched in physical characteristics , in the severity of pain , duration , nature and accompaniments of their pain , the Arhus low back pain index and in laboratory indices of organ system function . A total of 183 patients completed the study . The numbers of pain-free patients were three , six and 10 in the placebo group ( P ) , the Harpagophytum 600 group ( H600 ) and the Harpagophytum 1200 group ( H1200 ) respectively ( P = 0.027 , one-tailed Cochrane-Armitage test ) . The majority of responders ' were patients who had suffered less than 42 days of pain , and subgroup analyses suggested that the effect was confined to patients with more severe and radiating pain accompanied by neurological deficit . However , subsidiary analyses , concentrating on the current pain component of the Arhus index , painted a slightly different picture , with the benefits seeming , if anything , to be greatest in the H600 group and in patients without more severe pain , radiation or neurological deficit . Patients with more pain tended to use more tramadol , but even severe and unbearable pain would not guarantee that tramadol would be used at all , and certainly not to the maximum permitted dose . There was no evidence for Harpagophytum-related side-effects , except possibly for mild and infrequent gastrointestinal symptoms Chronic low back pain is a common problem that has been noted in several studies to exist as a component of masked depression . To determine the usefulness of imipramine in the treatment of chronic low back pain , either by a direct action or indirectly via resolution of a depressive equivalent , 50 consecutive patients were entered into a controlled trail that employed serum imipramine and desipramine levels and Beck depression question naires . Forty-one patients completed the study , and 48 were used in the statistical analysis . Imipramine had a statistically significant effect over placebo in most , but not all , of the clinical parameters that were measured . A linear relationship between serum drug levels and reported symptoms was not noted . Only 10 of the 50 patients entered into the study were judged clinical ly depressed and , of these , 7 were depressed according to st and ard criteria . There was no statistically significant difference noted in either the initial or the change in Beck depression scores between those on imipramine and those on placebo . However , among those on the active drug , the patients with a greater symptomatic response had a simultaneous change in the total Beck depression scores ( toward less depression ) that approached statistical significance when compared with those with a less symptomatic response . Although the results are not conclusive , imipramine may possibly be useful in the treatment of chronic low back pain , especially so when it exists as a component of masked depression A 6-week placebo-controlled trial evaluated the efficacy of trazodone hydrochloride for the relief of chronic low back pain . Forty-two subjects ( 22 trazodone , 20 placebo ) with a 20.3-year average history of back pain were titrated to an average dose of trazodone 201 mg or placebo 238 mg and evaluated daily on a Visual Analogue Scale of pain intensity , at 2-week intervals on an observer rating of pain behavior while walking , and before and after the trial on the Beck Depression Inventory , the Sickness Impact Profile , and a solid state microcomputer ( Vitalog ) that measured physical activity . Trazodone blood levels and urine toxicology screens were also obtained . There were no significant differences between groups in treatment effect . The results of this study require confirmation by longer trials with larger , less chronic , more homogeneous sample s at higher doses with follow-up assessment OBJECTIVE To assess the effectiveness of low-intensity laser therapy in the treatment of musculoskeletal low back pain . DESIGN A double-masked , placebo-controlled , r and omized clinical trial . SETTING A physical medicine and rehabilitation clinic . PARTICIPANTS Sixty-three ambulatory men and women between the ages of 18 and 70yrs with symptomatic nonradiating low back pain of more than 30 days ' duration and normal neurologic examination results . INTERVENTION Subjects were bloc r and omized into two groups with a computer-generated schedule . All underwent irradiation for 90 seconds at eight symmetric points along the lumbosacral spine three times a week for 4 weeks by a masked therapist . The sole difference between the groups was that the probes of a 1.06 microm neodymium : yttrium-aluminum-garnet laser emitted 542mW/cm2 for the treated subjects and were inactive for the control subjects . MAIN OUTCOME MEASURES Subject 's perception of benefit , level of function as assessed by the Oswestry Disability Question naire , and lumbar mobility . RESULTS The treated group had a time-dependent improvement in two of the three outcome measures : perception of benefit and level of function . These results were most marked at the midpoint evaluation ( p < .005 , p < .01 ) and end of treatment ( p < .017 , p < .001 ) but tended to lessen at the 1-month follow-up ( p < .10 , p < .004 ) . Lumbar mobility did not differ between the groups at any time . All tests were two- sample t tests with unequal variances . CONCLUSIONS Treatment with low-intensity 1.06 microm laser irradiation produced a moderate reduction in pain and improvement in function in patients with musculoskeletal low back pain . Benefits , however , were limited and decreased with time . Further research is warranted Abstract R and omised controlled trials ( RCTs ) alone are unlikely to provide reliable estimates of the incidence of rare events because of their limited size . Cohort , case control , and other observational studies have large numbers but are vulnerable to various kinds of bias . Wanting to estimate the risk of death from bleeding or perforated gastroduodenal ulcers with chronic usage of non‐steroidal anti‐inflammatory drugs ( NSAIDs ) with greater precision , we developed a model to quantify the frequency of rare adverse events which follow a biological progression . The model combined data from both RCTs and observational studies . We search ed systematic ally for any report of chronic ( ≥2 months ) use of NSAIDs which gave information on gastroduodenal ulcer , bleed or perforation , death due to these complications , or progression from one level of harm to the next . Fifteen RCTs ( 19 364 patients exposed to NSAIDs for 2–60 months ) , three cohort studies ( 215 076 patients redeeming a NSAID prescription over a 3–12 month period ) , six case‐control studies ( 2957 cases ) and 20 case series ( 7406 ) , and case reports ( 4447 ) were analysed . In RCTs the incidence of bleeding or perforation in 6822 patients exposed to NSAIDs was 0.69 % ; two deaths occurred . Of 11 040 patients with bleeding or perforation with or without NSAID exposure across all reports , 6–16 % ( average 12 % ) died ; the risk was lowest in RCTs and highest in case reports . Death from bleeding or perforation in all controls not exposed to NSAIDs occurred in 18 out of 849 489 ( 0.002 % ) . From these numbers we calculated the number‐needed‐to‐treat for one patient to die due to gastroduodenal complications with chronic ( ≥2 months ) NSAIDs as 1/((0.69 × {6–16 % , average 12%})−0.002%))=909–2500 ( average 1220 ) . On average 1 in 1200 patients taking NSAIDs for at least 2 months will die from gastroduodenal complications who would not have died had they not taken NSAIDs . This extrapolates to about 2000 deaths each year in the UK Background : Chronic low back pain ( LBP ) is a growing health problem . Non‐steroidal anti‐inflammatory drugs ( NSAIDs ) are used to treat this condition , but have not demonstrated efficacy beyond 2 weeks , and no studies have shown that NSAIDs produce durable improvements in disability . Methods : To evaluate the efficacy and durability of effect of etoricoxib for chronic LBP , a r and omized , double blind , placebo‐controlled trial was conducted at 46 centres . Three hundred and twenty‐five patients with chronic LBP requiring treatment with an NSAID or paracetamol were r and omized 1:1:1 to etoricoxib 60 mg ( n=109 ) , 90 mg ( n=106 ) , or placebo ( n=110 ) , daily for 3 months . Pre‐specified endpoints over 3 months included LBP intensity scale ( visual analog scale 0–100 mm ) time‐weighted average change from baseline , the Rol and –Morris Disability Question naire ( RMDQ ) , the LBP bothersomeness scale , patient and investigator global assessment s , and measures of quality of life . Results : Both etoricoxib groups experienced significant reductions in LBP intensity at 4 weeks versus placebo [ −15.15 mm and −13.03 mm for 60 and 90 mg , respectively , probability (p)<0.001 for each ] , which was maintained over 3 months . Treatment result ed in significant improvement from baseline compared to placebo in RMDQ scores ( etoricoxib 60 mg , −2.82 and 90 mg , −2.38 , p<0.001 for each ) over 12 weeks and most other efficacy endpoints . There were no significant differences between treatments in incidence of adverse events ( AEs ) or discontinuations due to AEs . Conclusion : Etoricoxib provided significant relief of symptoms and disability associated with chronic LBP detected at 1 week , confirmed at 4 weeks , and maintained over 3 months . Reductions in chronic LBP severity corresponded to improvements in physical functioning and quality of life . All treatments were generally well tolerated OBJECTIVE To assess efficacy and safety of diclofenac-K 12.5 mg tablets in the treatment of acute low back pain ( low back pain ) . MATERIAL / METHOD A multiple dose , double-blind , double-dummy , r and omized , placebo-controlled , parallel group trial compared diclofenac-K ( 12.5 mg ; n = 124 ) with ibuprofen ( 200 mg ; n = 122 ) and placebo ( n = 126 ) in patients with moderate-to-severe acute low back pain . The treatment consisted of an initial dose of 2 tablets followed by 1 or 2 tablets every 4 - 6 hours as needed ( maximum 6 tablets/day ) for 7 days . The primary efficacy outcome for the initial dose was TOTPAR-3 , the summed total pain relief over the first 3 hours . Secondary initial dose outcomes included TOTPAR-6 , summed pain intensity differences SPID-3 and SPID-6 , time to rescue medication or remedicate , and the End of First Dose global efficacy assessment . The primary efficacy outcome for the flexible multiple dosing regimen was the End of Study global efficacy assessment . Secondary outcomes for multiple dosing included time to rescue medication over the entire study , the End of Day global efficacy assessment s ( daily over Days 1 - 7 ) , pain intensity differences on the VAS measured at Visit 2 and 3 , and change in Eifel algofunctional index . Safety/tolerability was assessed by recording adverse events . RESULTS Diclofenac-K 12.5 mg demonstrated superiority vs placebo on the primary efficacy parameter and almost all secondary initial dose outcomes . With respect to the initial dose , diclofenac-K 12.5 mg was also significantly superior to ibuprofen 200 mg on SPID-3 . Ibuprofen 200 mg was superior to placebo only on the End of First Dose global efficacy assessment . The flexible multiple dosing regimens of diclofenac-K and ibuprofen were both significantly superior to placebo on the End of Study global efficacy assessment , time to rescue medication over the entire study period , the End of Day global efficacy assessment on Days 1 - 2 , pain intensity difference on the VAS at Visit 3 and the Eifel algofunctional index at Visit 3 ( also at Visit 2 in diclofenac-K 12.5 mg group ) . Both active treatments were as well tolerated as placebo . CONCLUSIONS The flexible multiple dosing regimen of diclofenac-K 12.5 mg ( initial dose of 2 tablets followed by 1 - 2 tablets every 4 - 6 hours , max . 75 mg/day ) is an effective and safe treatment of acute low back pain Abstract Objectives : To investigate the cl aim that 90 % of episodes of low back pain that present to general practice have resolved within one month . Design : Prospect i ve study of all adults consulting in general practice because of low back pain over 12 months with follow up at 1 week , 3 months , and 12 months after consultation . Setting : Two general practice s in south Manchester . Subjects : 490 subjects ( 203 men , 287 women ) aged 18 - 75 years . Main outcome measures : Proportion of patients who have ceased to consult with low back pain after 3 months ; proportion of patients who are free of pain and back related disability at 3 and 12 months . Results : Annual cumulative consultation rate among adults in the practice s was 6.4 % . Of the 463 patients who consulted with a new episode of low back pain , 275 ( 59 % ) had only a single consultation , and 150 ( 32 % ) had repeat consultations confined to the 3 months after initial consultation . However , of those interviewed at 3 and 12 months follow up , only 39/188 ( 21 % ) and 42/170 ( 25 % ) respectively had completely recovered in terms of pain and disability . Conclusions : The results are consistent with the interpretation that 90 % of patients with low back pain in primary care will have stopped consulting with symptoms within three months . However most will still be experiencing low back pain and related disability one year after consultation . Key messages It is widely believed that 90 % of episodes of low back pain seen in general practice resolve within one month In a large population based study we examined the outcome of episodes of low back pain in general practice with respect to both consultation behaviour and self reported pain and disability While 90 % of subjects consulting general practice with low back pain ceased to consult about the symptoms within three months , most still had substantial low back pain and related disability Only 25 % of the patients who consulted about low back pain had fully recovered 12 months later Since most consulters continue to have long term low back pain and disability , effective early treatment could reduce the burden of these symptoms and their social , economic , and medical The use of colchicine for the treatment of low-back pain has been controversial ; however , recent studies have shown its effectiveness when used intravenously . Studies using oral colchicine alone are lacking . The purpose of this study is to evaluate in a prospect i ve , double-blind fashion the use of oral colchicine in the treatment of low back pain . Group I patients ( 15 ) were treated with a placebo capsule , and Group II ( 12 ) patients were treated with a colchicine capsule prescribed in a “ burst dose ” regimen . Patients were evaluated at 1 , 2 , 4 , 6 , and 12 weeks with a mean followup of 12 weeks . Parameters studied included patient characteristics , compliance , the McCoy pain drawings , pain analogue scales , the Million scale and objective tests . In terms of therapeutic response , the study shows no statistically significant difference between oral colchicine and placebo . The colchicine group did have an increased number of side effects Study Design A prospect i ve cohort study of patients seen in primary care for low back pain . Objectives A new measure of back pain outcomes is used to describe the status of back problems at various intervals after visits to primary care physicians and to identify subsets of patients with worse prognoses . Summary of Background Data Most previous studies of the prognosis of back pain in primary care have failed to provide clinical ly useful information . Methods Baseline data were collected from 219 patients making an initial visit for an episode of low back pain to a primary care clinic . A measure of how patients reported they would feel if they had their current back symptoms for the rest of their lives ( “ Symptoms Satisfaction ” ) was used to distinguish good from poor outcomes . Patient outcomes were assessed 1 , 3 , 7 , and 52 weeks after the index visit . Results Only 67 % of patients reported good outcomes after 7 weeks , and only 71 % were satisfied with their condition 1 year later . After controlling for the effects of other variables measured during the initial physician visit , only younger age , depression , and pain below the knee were significant predictors of poor outcome at 7 weeks , and only pain below the knee and depression were significant predictors at 1 year . Conclusions The proportion of primary care patients with back pain who have poor outcomes appears to be higher than generally recognized . Ways of improving how primary care responds to patients with persisting pain should be investigated BACKGROUND Valdecoxib , a cyclooxygenase (COX)-2 specific inhibitor , is indicated for relief of the signs and symptoms of rheumatoid arthritis , osteoarthritis , and primary dysmenorrhea . Therapeutic doses of COX-2 specific inhibitors are as effective as nonspecific nonsteroidal anti-inflammatory drugs in reducing inflammatory pain while sparing the gastrointestinal and platelet toxicity associated with nonspecific COX-1 inhibition . OBJECTIVE The aim of this study was to assess the analgesic efficacy and tolerability of valdecoxib 40 mg/d compared with placebo in the treatment of chronic low back pain . METHODS This 4-week , prospect i ve , r and omized , double-blind placebo-controlled , parallel-group study was conducted at 37 centers across the United States and 5 centers in Canada . Patients aged > or = 18 years with chronic low back pain in flare were enrolled . Patients were r and omized to receive valdecoxib 40-mg/d or placebo tablets , once daily for 4 weeks . Patients rated low back pain intensity on a visual analog scale and completed the Rol and -Morris Disability Question naire and the modified Brief Pain Inventory-Short Form ( mBPI-SF ) at each visit . RESULTS Two hundred ninety-three patients were enrolled . The valdecoxib group comprised 148 patients ( 81 women , 67 men ; mean [ SD ] age , 48.6 [ 13.3 ] years ; mean [ SD ] body weight , 86.6 [ 20.9 ] kg ) , and the placebo group included 145 patients ( 85 women , 60 men ; mean [ SD ] age , 48.7 [ 12.6 ] years ; mean [ SD ] body weight , 85.6 [ 19.9 ] kg ) . Of the enrolled patients , 249 completed the study : 134 patients ( 91 % ) who received valdecoxib and 115 patients ( 79 % ) who received placebo . No statistically significant differences in patient baseline characteristics were noted between treatment groups , except in response to 1 mBPI-SF question ; patients in the valdecoxib group reported significantly greater interference in relations with other people due to pain than did those in the placebo group ( P = 0.048 ) . Changes from baseline in low back pain intensity were significantly greater in valdecoxib-treated patients at each assessment ( all , P < 0.001 vs placebo ) . Pain scores on the mBPI-SF indicated significantly greater pain relief with valdecoxib at each assessment ( all , P < or = 0.014 vs placebo ) . Improvements in mean Rol and -Morris Disability Question naire score with valdecoxib were significantly greater than with placebo at each assessment ( all , P < or = 0.003 ) . Although the overall incidence of adverse events ( AEs ) was significantly higher among patients receiving valdecoxib than those receiving placebo ( 35.1 % vs 24.1 % , respectively ; P = 0.042 ) , no significant differences were found between groups for the incidence of any individual AE . Most AEs ( 89 % [ 77/87 total events ] ) were mild or moderate in severity . CONCLUSIONS In this study of patients with chronic low back pain , valdecoxib 40 mg/d provided rapid relief ( within 1 week ) and consistent relief ( over 4 weeks ) . In addition , significant improvement in function and decreased disability were found with valdecoxib compared with placebo Low back pain ( LBP ) is a very common problem in primary care and a major cause of disability . There is no evidence for the efficacy of therapeutic modalities such as ultrasound in LBP In a r and omized , single blind placebo controlled clinical trial , we aim ed to evaluate the effect of continuous ultrasound ( US ) in patients with non specific LBP Of the fifty eight patients recruited , 10 patients ( 8 women and 2 men ) r and omly allocated to ultrasound ( n=5 ) or placebo controlled ( n=5 ) groups . The patients were treated by either US or sham-US for ten sessions , three days per week , every other day . The outcome measures were Functional Rating Index ( FRI ) , Hmax/Mmax ratio and range of motion ( ROM ) , which were measured at baseline , after 5 treatment sessions and at the end of treatment . To analyze the data , The Mann Whitney U test and Wilcoxon Signed Rank test were used . After treatment , both US and placebo groups showed statistically significant decrease in FRI scores indicating improvement in functional ability ( p = 0.042 and p = 0.043 , respectively ) . The mean changes of FRI during the second five treatment sessions and after the end of treatment was significantly better in the US group than in the placebo group ( p = 0.016 and p = 0.032 , respectively ) . Before and after treatment , the mean H reflex latency and Hmax/Mmax ratio , right and left side were similar in the groups ( p > 0.05 ) , and no significant changes were observed in the treatment groups ( p > 0.05 ) . After treatment , the extension and lateral flexion range of motion significantly increased in the US group ( p = 0.04 ) , but the back movements in the placebo group did not show significant changes ( p > 0.05 ) . The present study supports the significant effect of US on LBP , and suggests that US may improve the functional ability of patients with non specific low back pain Background Placebo treatments should be believable to ensure expectation of benefit , yet not provide a true treatment effect . One obstacle to conducting clinical trials with osteopathic manipulative treatment ( OMT ) is choosing an appropriate placebo . Various placebo treatments have been used in OMT clinical trials . The purpose of this study was to determine expectations of 3 treatments ( HVLA , placebo light touch , placebo sub-therapeutic ultrasound ) commonly used in OMT clinical research trials . Methods A r and omized , cross-over design was utilized . Subjects were recruited from the Family Medicine Clinic , Texas College of Osteopathic Medicine . Participants watched a video with 2 minute demonstrations of a High Velocity Low Amplitude ( HVLA ) , placebo light touch ( LT ) , and placebo sub-therapeutic ultrasound ( ULTRA ) treatment for low back pain . The order of presentations was r and omized to control for order effect bias . Subjects indicated the extent of their agreement ( using a 4 point Likert scale ) with 4 statements that were presented after each treatment was viewed : 1)I believe this treatment would allow me to get better quicker ; 2)I believe this treatment would decrease my low back pain ; 3)I believe this treatment would make me more able to do the things I want to do ; 4)This seems like a logical way to treat low back pain . Repeated measures analysis of variance was performed , and a partial Eta squared was calculated for each statement . Effect sizes ( Cohen 's d ) were calculated where appropriate . Results Thirty of 40 eligible subjects participated . Twenty-two ( 73 % ) were female , 16 ( 53 % ) were Caucasian , and 11 ( 37 % ) had completed college . The mean age was 43 ( SD = 15 . ) . Repeated measures ANOVA revealed no significant differences for statements 2 and 4 . For both statements 1 ( p = 0.025 ) and 3 ( p = 0.039 ) , post hoc analysis revealed a difference between HVLA and LT . The partial Eta squared ( ηp2 ) was 0.105 , 0.072 , 0.107 , and 0.024 for each statement , respectively . Conclusion There is a difference in treatment expectation between HVLA and LT for statements 1 and 3 . Participants responded more positively after viewing the HVLA treatment than the LT treatment . This suggests that sub-therapeutic ultrasound is the better placebo because the expectations were similar to those for HVLA |
1,049 | 21,972,275 | 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 . | BACKGROUND Long duration of untreated psychosis ( DUP ) is common and associated with poor outcomes .
Strategies to enhance early detection of first-episode psychosis have been advocated .
AIMS To evaluate initiatives for early detection of psychosis . | 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 |
1,050 | 19,059,756 | 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 . | This systematic review compares the safety and efficacy of varicose vein treatments , including conservative therapy , sclerotherapy , phlebectomy , endovenous laser therapy , radiofrequency ablation , and surgery involving saphenous ligation and stripping .
Ligation with stripping plus phlebectomy is generally regarded as the " gold st and ard " for treating primary long saphenous veins . | 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 ( interquartile range [ IQR ] 35 - 58 ) years , and a surgery group with 62 patients , median age 49 ( IQR 35 - 61 ) years . Patients were assessed prior to and at 1 , 6 , and 12 weeks following the procedure using the Short Form 36 ( SF-36 ) , the Aberdeen Varicose Veins Question naire ( AVVQ ) , and the Venous Clinical Severity Score ( VCSS ) . Follow-up at 1 , 6 , and 12 weeks was 100 % , 77 % , and 70 % following EVLT and 100 % , 85 % , and 47 % following surgery . SF-36 scores were significantly better in the EVLT group at 1 week ( Physical Functioning , Role Physical , Bodily Pain , Vitality , and Social Functioning domains ) and at 6 weeks ( Physical Functioning and Role Physical ) . At 12 weeks , no significant differences were evident between the groups . AVVQ scores were significantly better in the EVLT group at 6 and 12 weeks . VCSS scores were significantly improved in both groups at 12 weeks . EVLT and surgery provide similar QoL improvements in patients with varicose veins . EVLT , however , removes the QoL limitations experienced by patients in the early postoperative period BACKGROUND Endovenous laser ( EVL ) ablation of the great saphenous vein ( GSV ) is thought to minimize postoperative morbidity and reduce work loss compared with high ligation and stripping ( HL/S ) . However , the procedures have not previously been compared in a r and omized trial with parallel groups where both treatments were performed in tumescent anesthesia on an out-patient basis . METHODS Patients with varicose veins due to GSV insufficiency were r and omized to either EVL ( 980 nm ) or HL/S in tumescent anesthesia . Miniphlebectomies were also performed . Patients were examined preoperatively and at 12 days , and 1 , 3 , and 6 months postoperatively . Sick leave , time to normal physical activity , pain score , use of analgesics , Aberdeen score , Medical Outcomes Study Short Form-36 quality -of-life score , Venous Clinical Severity Score ( VCSS ) , and complication rates were investigated . The total cost of the procedures , including lost wages and equipment , was calculated . Cost calculations were based on the st and ard fee for HL/S with the addition of laser equipment and the st and ard salary and productivity level in Denmark . RESULTS A follow-up of 6 months was achieved in 121 patients ( 137 legs ) . The groups were well matched for patient and GSV characteristics . Two HL/S procedures failed , and three GSVs recanalized in the EVL group . The groups experienced similar improvement in quality -of-life scores and VCSS score at 3 months . Only one patient in the HL/S group had a major complication , a wound infection that was treated successfully with antibiotics . The HL/S and EVL groups did not differ in mean time to resume normal physical activity ( 7.7 vs 6.9 calendar days ) and work ( 7.6 vs 7.0 calendar days ) . Postoperative pain and bruising was higher in the HL/S group , but no difference in the use of analgesics was recorded . The total cost of the procedures , including lost wages , was euro 3084 ( $ 3948 US ) in the HL/S and euro 3396 ( $ 4347 US ) in the EVL group . CONCLUSIONS This study suggests that the short-term efficacy and safety of EVL and HL/S are similar . Except for slightly increased postoperative pain and bruising in the HL/S group , no differences were found between the two treatment modalities . The treatments were equally safe and efficient in eliminating GSV reflux , alleviating symptoms and signs of GSV varicosities , and improving quality of life . Long-term outcomes , particularly with respect to recurrence rates , shall be investigated in future studies , including the continuation of the present The study compared , by a prospect i ve , r and omized method , 6 treatment options : A : Sclero therapy ; B : High-dose sclerotherapy ; C : Multiple ligations ; D : Stab avulsion ; E : Foam-sclero therapy ; F : Surgery ( ligation ) followed by sclerotherapy . Results were analyzed 10 years after inclusion and initial treatment . Endpoints of the study were variations in ambulatory venous pressure ( AVP ) , refilling time ( RT ) , presence of duplex-reflux , and number of recurrent or new incompetent venous sites . The number of patients , limbs , and treated venous segments were comparable in the 6 treatment groups , also comparable for age and sex distribution . The occur rence of new varicose veins at 5 years varied from 34 % for group F ( surgery + sclero ) and ligation ( C ) to 44 % for the foam + sclero group ( E ) and 48 % for group A ( dose 1 sclero ) . At 10 years the occurrence of new veins varied from 37 % in F to 56 % in A. At inclusion AVP was comparable in the different groups . At 10 years the decrease in AVP and the increase in RT ( indicating decrease in reflux ) , was generally comparable in the different groups . Also at 10 years the number of new points of major incompetence was comparable in all treatment groups . These results indicate that , when correctly performed , all treatments may be similarly effective . " St and ard , " low-dose sclerotherapy appears to be less effective than high-dose sclero and foam-sclerotherapy which may obtain , in selected subjects , results comparable to surgery In a controlled clinical investigation 516 patients with previously untreated saphenous varices were divided into three treatment groups according to a stratified group comparative design . The patients in treatment group 1 underwent a radical operation under full anaesthesia ; the patients in group 2 were treated by means of minor operations followed by injection/compression therapy ; the patients in group 3 were treated by means of injection/compression therapy alone . The results were evaluated both objective ly and subjectively 3 months and 3 years after treatment , the follow‐up being 100 per cent and 98.1 per cent complete at those times . With regard to the period of disability among those patients with jobs outside the home ( 63.8 per cent ) , there was a statistically significant difference between the three groups , the median period of disability being 14.2 , 7.6 and 0 days respectively . In all three treatment groups the results were worse after 3 years than after 3 months , but the difference was significantly less following radical operation than after combined treatment , and significantly less following combined treatment than after injection/compression therapy alone . The patients were r and omized and treated by the author and the results of treatment were evaluated by the author and partly controlled by another investigator We evaluated the 3-year outcome of a series of patients with primary varicose veins who were r and omized to radiofrequency endovenous obliteration vs. stripping of the long saphenous vein ( LSV ) . Twenty-eight patients were included in the study : 15 were r and omized to the radiofrequency endovenous obliteration procedure and 13 to LSV stripping . At 3-year follow-up , five patients ( 33.3 % ) of the endovenous group had recurrent or residual varices and in three of them a reflux in the thigh veins was detected . None of the primarily occluded LSV segments was recanalized . In the stripping group , three patients ( 23.1 % , p = 0.68 ) showed varicosities at clinical and duplex examinations . In one patient , a patent duplicate LSV trunk was detected . In the remaining two patients , no reflux in the thigh region was detected . According to the present results , radiofrequency endovenous obliteration of the LSV is associated with somewhat poorer short-term results compared with the stripping operation PURPOSE To study intermediate clinical outcomes , rates of recurrent varicosities and neovascularisation , ultrasound changes of the GSV , and the quality of life changes in patients from EVOLVeS trial . METHODS Forty five patients were re-examined 1 year and 65 two years after treatment . Follow-up visits included clinical examination with CEAP classification and calculation of venous clinical severity score ( VCSS ) , ultrasound examination , and a quality of life question naire . RESULTS The clinical course of the disease ( CEAP , VCSS ) was similar in the two treatment groups . 51 % of the GSV trunks occluded by RFO underwent progressive shrinkage with the external diameter decreased from 6.3 SD 1.4 mm at 72 h after treatment to 2.9 SD 1.5 mm at 2 years . An additional 41 % of the GSV became undetectable by ultrasound at 2-year follow up . In two patients we observed re-opening of an initially closed GSV lumen . Neovascularisation was found in one RFO case and in four S and L cases . Cumulative rates of recurrent varicose veins at combined 1 and 2 years follow-up were 14 % for RFO and 21 % for S and L ( NS ) . The difference in global QOL score in favour of RFO re-appeared at 1 year and remained significant at 2 years after treatment . CONCLUSION The 2-year clinical results of radiofrequency obliteration are at least equal to those after high ligation and stripping of the GSV . In the vast majority of RFO patients the GSV remained permanently closed , and underwent progressive shrinkage to eventual sonographic disappearance . Recurrence and neovascularisation rates were similar in the two groups although limited patient numbers prevent reliable statistical analysis . Improved quality of life scores persisted through the 2-year observations in the RFO group compared to the S and L group |
1,051 | 25,518,953 | 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 . | Purpose To assess the benefits and harms of levosimendan for low cardiac output syndrome in critically ill patients . | 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 required inotropic support . The trial was conducted at 75 centers in 9 countries and patients were r and omized between March 2003 and December 2004 . INTERVENTIONS Intravenous levosimendan ( n = 664 ) or intravenous dobutamine ( n = 663 ) . MAIN OUTCOME MEASURE All-cause mortality at 180 days . RESULTS All-cause mortality at 180 days occurred in 173 ( 26 % ) patients in the levosimendan group and 185 ( 28 % ) patients in the dobutamine group ( hazard ratio , 0.91 ; 95 % confidence interval , 0.74 - 1.13 ; P = .40 ) . The levosimendan group had greater decreases in B-type natriuretic peptide level at 24 hours that persisted through 5 days compared with the dobutamine group ( P<.001 for all time points ) . There were no statistical differences between treatment groups for the other secondary end points ( all-cause mortality at 31 days , number of days alive and out of the hospital , patient global assessment , patient assessment of dyspnea at 24 hours , and cardiovascular mortality at 180 days ) . There was a higher incidence of cardiac failure in the dobutamine group . There were higher incidences of atrial fibrillation , hypokalemia , and headache in the levosimendan group . CONCLUSION Despite an initial reduction in plasma B-type natriuretic peptide level in patients in the levosimendan group compared with patients in the dobutamine group , levosimendan did not significantly reduce all-cause mortality at 180 days or affect any secondary clinical outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00348504 BACKGROUND : Patients with poor left ventricular function often require inotropic drug support immediately after cardiopulmonary bypass . Levosimendan improves cardiac function by a novel mechanism of action compared to currently available drugs . We hypothesized that , in patients with severely compromised ventricular function , the use of levosimendan would be associated with better postoperative cardiac function than with inotropic drugs that increase myocardial oxygen consumption . METHODS : Thirty patients with a preoperative ejection fraction ≤30 % scheduled for elective cardiac surgery with cardiopulmonary bypass were r and omized to two different inotropic protocol s : milrinone 0.5 mg · kg−1 · min−1 or levosimendan 0.1 mg · kg−1 · min−1 , started immediately after the release of the aortic crossclamp . The treatment was masked to the observers . All patients received dobutamine 5 mg · kg−1 · min−1 . RESULTS : Stroke volume was similar between groups initially after surgery , but it declined 12 h after surgery in the milrinone group but not in the levosimendan group ( P < 0.05 between groups ) despite similar filling pressures . Total dose , duration of inotropic drug administration and norepinephrine dose were lower in the levosimendan group than in the milrinone group ( P < 0.05 ) . The duration of tracheal intubation was shorter in the former group compared with the milrinone group ( P = 0008 ) . Three patients in the milrinone group but none in the levosimendan group died within 30 days of surgery . CONCLUSION : In cardiac surgery patients with a low preoperative ejection fraction , stroke volume was better maintained with the combination of dobutamine with levosimendan than with the combination of dobutamine with milrinone Abstract : The role of repeated infusions of Levosimendan ( LEVO ) in patients with chronic advanced heart failure is still unclear . Thirty-three patients with chronic heart failure presenting clinical deterioration were r and omized 2:1 to receive monthly infusions of LEVO ( n = 22 ) or Furosemide ( Controls , n = 11 ) . At the first drug 's administration , noninvasive hemodynamic evaluation was performed ; before and after each infusion , we assessed NYHA class , systolic and diastolic function , functional mitral regurgitation , and brain natriuretic peptide ( BNP ) levels . Noninvasive hemodynamic in the LEVO group showed vasodilation and decrease in thoracic conductance ( index of pulmonary congestion ) , whereas in Controls , only a reduced thoracic conductance was observed . In the LEVO group , systolic and diastolic function , ventricular volumes , severity of mitral regurgitation , and BNP levels improved over time from baseline and persisted 4 weeks after the last infusion ( P < 0.01 ) . In Controls , no change developed over time in cardiac function and BNP levels . In LEVO-treated patients , 1-year mortality tended to be lower than in those treated with Furosemide . In conclusion , serial LEVO infusions in advanced heart failure improved ventricular performance and favorably modulated neurohormonal activation . Multicenter r and omized studies are warranted to test the effect of LEVO on long-term outcome BACKGROUND Levosimendan , a novel calcium sensitiser , improves myocardial contractility without causing an increase in myocardial oxygen dem and . We compared the effects of levosimendan and dobutamine on haemodynamic performance and clinical outcome in patients with low-output heart failure . METHODS Patients were recruited into a multicentre , r and omised , double-blind , double-dummy , parallel-group trial . Under continuous haemodynamic monitoring , an initial loading dose of levosimendan of 24 microg/kg was infused over 10 min , followed by a continuous infusion of 0.1 microg kg(-1 ) min(-1 ) for 24 h. Dobutamine was infused for 24 h at an initial dose of 5 microg kg(-1 ) min(-1 ) without a loading dose . The infusion rate was doubled if the response was inadequate at 2h . The primary endpoint was the proportion of patients with haemodynamic improvement ( defined as an increase of 30 % or more in cardiac output and a decrease of 25 % or more in pulmonary-capillary wedge pressure ) at 24 h. Analyses were by intention to treat . FINDINGS 103 patients were assigned levosimendan and 100 dobutamine . The primary haemodynamic endpoint was achieved in 29 ( 28 % ) levosimendan-group patients and 15 ( 15 % ) in the dobutamine group ( hazard ratio 1.9 [ 95 % CI 1.1 - 3.3 ] ; p=0.022 ) . At 180 days , 27 ( 26 % ) levosimendan-group patients had died , compared with 38 ( 38 % ) in the dobutamine group ( 0.57 [ 0.34 - 0.95 ] ; p=0.029 ) . INTERPRETATION In patients with severe , low-output heart failure , levosimendan improved haemodynamic performance more effectively than dobutamine . This benefit was accompanied by lower mortality in the levosimendan group than in the dobutamine group for up to 180 days INTRODUCTION AND OBJECTIVES Levosimendan is an inotropic agent that is effective in the treatment of heart failure . However , experience with levosimendan in patients with reduced cardiac output following cardiopulmonary bypass is limited . The objective of this study was to compare the short-term hemodynamic effects of levosimendan with those of dobutamine in managing low cardiac output after cardiac surgery . METHODS Forty-one patients who had low cardiac output after cardiopulmonary bypass were r and omly assigned to dobutamine ( n=20 ) , 24-hour infusion of 7.5 microg/kg per min , or levosimendan ( n=21 ) , at a loading dose of 12 microg/kg followed by 24-hour infusion of 0.2 microg/kg per min . The following parameters were determined during a 48-hour observation period : arterial , central venous , pulmonary arterial and pulmonary capillary wedge pressure , cardiac index , heart rate , stroke volume , and systemic and pulmonary vascular resistance . RESULTS Although both dobutamine and levosimendan improved the cardiac index , the increase was significantly greater with levosimendan ( 2.4 [ 0.2 ] l/min per m2 vs 2.9 [ 0.3 ] l/min per m2 , respectively , at 24 h ; P<.05 ) . Moreover , levosimendan significantly reduced systemic and pulmonary vascular resistance , and significantly decreased systemic arterial , pulmonary arterial , pulmonary capillary wedge , and central venous pressure . CONCLUSIONS Both dobutamine and levosimendan are effective in managing postoperative low cardiac output . However , levosimendan induces non-specific systemic , venous and pulmonary vasodilation which can result in hypotension as a adverse event . In these patients , it is advisable to omit or reduce the loading dose Objective : To investigate whether levosimendan diminishes the incidence of heart failure after cardiac surgery . Design : Prospect i ve , r and omized , placebo-controlled clinical study . Setting : Cardiac surgery operating room and postanesthesia care unit in a university hospital . Patients : Two hundred patients assigned to undergo heart valve or combined heart valve and coronary artery bypass grafting surgery . Interventions : Patients were r and omized to receive a 24-hr infusion of placebo or levosimendan administered as a 24 & mgr;g/kg bolus over 30-mins and thereafter at a dose of 0.2 & mgr;g/kg/min . Measurements and Main Results : Heart failure was defined as cardiac index < 2.0 L/min/m2 or failure to wean from cardiopulmonary bypass necessitating inotrope administration for at least 2 hrs postoperatively . Heart failure was less frequent in the levosimendan compared to the placebo group : 15 patients ( 15 % ) in the levosimendan and 59 patients ( 58 % ) in the placebo group experienced heart failure postoperatively ( risk ratio 0.26 ; 95 % confidence interval 0.16–0.43 ; p < .001 ) . Accordingly , a rescue inotrope ( adrenaline ) was needed less frequently in the levosimendan compared to the placebo group ( risk ratio 0.11 ; 95 % confidence interval 0.01–0.89 ) , p = .005 . Intra-aortic balloon pump was utilized in one patient ( 1 % ) in the levosimendan and in nine patients ( 9 % ) in the placebo group ( risk ratio 0.11 ; 95 % confidence interval 0.01–0.87 ) , p = .018 . The hospital and the 6-month mortality were comparable between groups . There were no significant differences in major organ failures postoperatively . Eighty-three patients were hypotensive and needed noradrenaline in the levosimendan compared to 52 patients in the placebo group , p < .001 . The cardiac enzymes ( creatine kinase MB isoenzyme mass ) indicating myocardial damage were lower in the levosimendan group on the first postoperative day , p = .011 . Conclusions : In the present study , levosimendan infusion reduced the incidence of heart failure in cardiac surgery patients but was associated with arterial hypotension and increased requirement of vasopressor agents postoperatively . Improved mortality or morbidity was not demonstrated Aims The aim of this study is to compare the effects of a 24 h intravenous infusion of levosimendan and a 48 h infusion of dobutamine on invasive haemodynamics in patients with acutely decompensated chronic NYHA class III – IV heart failure . All patients were receiving optimal oral therapy including a β-blocker . Methods and results This was a multinational , r and omized , double-blind , phase IV study in 60 patients ; follow-up was 1 month . There was a significant increase in cardiac index and a significant decrease in pulmonary capillary wedge pressure ( PCWP ) at 24 and 48 h for both dobutamine and levosimendan . The improvement in cardiac index with levosimendan was not significantly different from dobutamine at 24 h ( P = 0.07 ) , but became significant at 48 h ( 0.44 ± 0.56 vs. 0.66 ± 0.63 L/min/m2 ; P = 0.04 ) . At 24 h , the reduction in the mean change in PCWP from baseline was similar for levosimendan and dobutamine , however , at 48 h the difference was more marked for levosimendan ( −3.6 ± 7.6 vs. −8.3 ± 6.7 mmHg ; P = 0.02 ) . No difference was observed between the groups for change in NYHA class , β-blocker use , hospitalizations , treatment discontinuations or rescue medication use . Reduction in B-type natriuretic peptide ( BNP ) was significantly greater with levosimendan at 48 h ( P = 0.03 ) . According to physician 's assessment , the improvement in fatigue ( P = 0.01 ) and dyspnoea ( P = 0.04 ) was in favour of dobutamine treatment , and hypotension was significantly more frequent with levosimendan ( P = 0.007 ) . No increase in atrial fibrillation or ventricular tachycardia was seen in either group . Conclusion A 24 h levosimendan infusion achieved haemodynamic and neurohormonal improvement that was at least comparable at 24 h and superior at 48 h to a 48 h dobutamine infusion Background Levosimendan is a promising new inodilator agent but its effectiveness in peripartum cardiomyopathy ( PPCM ) has not been tested in a clinical trial . The authors sought to evaluate the effect of levosimendan therapy and to determine the predictors of clinical outcome in patients with PPCM . Methods and results The authors prospect ively r and omized 24 consecutive women with PPCM . Twelve patients ( control group ) were r and omized to conventional heart failure therapy and 12 patients ( levosimendan group ) were r and omized to levosimendan in addition to the conventional therapy . Mean follow-up period was 20.9 ± 9 months ( ranged 12–38 months ) . The two groups did not differ in baseline demographic and echocardiographic characteristics . Eleven patients ( 45.8 % ) recovered completely ( 6 in control group and 5 in levosimendan group , p > 0.05 ) , 6 died ( 25 % ) ( 3 in control group and 3 in levosimendan group ) , and 7 ( 29.1 % ) were left with persistent left ventricular dysfunction ( PLVD ) ( 3 in control group and 4 in levosimendan group , p > 0.05 ) . There were significant differences in baseline characteristics between deceased patients and survivors including left ventricular end-diastolic diameter ( 7.1 ± 0.6 vs. 6.4 ± 0.5 cm , p = 0.031 ) , left ventricular end-systolic diameter ( LVESD ) ( 6.4 ± 0.8 vs. 5.5 ± 0.6 cm , p = 0.027 ) , left ventricular ejection fraction ( LVEF ) ( 19.7 vs. 27.4 % , p = 0.025 ) , and left atrial diameter ( 4.9 ± 0.3 vs. 4.3 ± 0.4 cm , p = 0.011 ) . Conclusions Addition of levosimendan to conventional therapy did not improve outcome in patients with PPCM . In patients with PLVD or patients who died , LVEF , LVESD and left atrial diameter were worse than those with complete resolution BACKGROUND Long-term impact of levosimendan on renal function remains undefined . Prospect ively , we evaluated effects of levosimendan on renal function in patients with advanced chronic heart failure awaiting cardiac transplantation . METHODS AND RESULTS Of 40 patients , 20 were r and omized to receive levosimendan ( 10-minute bolus 12 microg/kg , followed by 0.1 microg/kg/min for 24 hours ; LS Group ) , and 20 received no levosimendan ( Controls ) . The groups did not differ in age , heart failure etiology , left ventricular ejection fraction , and plasma brain natriuretic peptide . Patients were followed for 3 months . At baseline , the groups did not differ in serum creatinine ( 1.92 + /- 0.13 mg/dL in LS Group versus 1.91 + /- 0.12 mg/dL in Controls , P = .81 ) and creatinine clearance ( 43.7 + /- 2.9 mL/min versus 43.9 + /- 2.8 mL/min , P = .84 ) . At 3 months , we found a decrease in serum creatinine and an increase in creatinine clearance in LS Group , but not in Controls , leading to a significant intergroup difference in serum creatinine ( 1.60 + /- 0.26 mg/dL in LS Group versus 1.90 + /- 0.14 mg/dL in Controls , P = .005 ) and creatinine clearance ( 53.6 + /- 8.6 mL/min versus 44.0 + /- 3.3 mL/min , P = .005 ) . An improvement in creatinine > or = 0.5 mg/dL occurred in 50 % patients from LS Group compared with 10 % of Controls ( P = .005 ) . CONCLUSIONS Levosimendan improves long-term renal function in advanced chronic heart failure patients awaiting cardiac transplantation BACKGROUND Levosimendan is a compound with vasodilatory and inotropic properties . Experimental data suggest effective reversal of stunning and cardioprotective properties . METHODS This prospect i ve , r and omized , placebo-controlled , double-blind study included 60 patients with 3-vessel coronary disease and left ventricular ejection fraction ( LVEF ) of less than 0.50 . Levosimendan administration ( 12 microg/kg bolus , followed by an infusion of 0.2 microg/kg/min ) was started immediately after induction anesthesia . Predefined strict hemodynamic criteria were used to assess the success of weaning . If weaning was not successful , CPB was reinstituted and an epinephrine infusion was started . If the second weaning attempt failed , intraaortic balloon pumping ( IABP ) was instituted . RESULTS The groups had comparable demographics . The mean ( st and ard deviation ) preoperative LVEF was 0.36 ( 0.8 ) in both groups . The baseline cardiac index was 1.8 ( 0.3 ) L/min/m(2 ) in the levosimendan group and 1.9 ( 0.4 ) L/min/m(2 ) in the placebo group . The mean duration of CPB to primary weaning attempt was 104 ( 25 ) minutes in the levosimendan and 109 ( 22 ) minutes in the placebo group . Primary weaning was successful in 22 patients ( 73 % ) in the levosimendan group and in 10 ( 33 % ) in the placebo group ( p = 0.002 ) . The odds ratio for failure in primary weaning was 0.182 ( 95 % confidence interval , 0.060 to 0.552 ) . Four patients in the placebo group failed the second weaning and underwent IABP compared with none in the levosimendan group ( p = 0.112 ) . CONCLUSIONS Levosimendan significantly enhanced primary weaning from CPB compared with placebo in patients undergoing 3-vessel on-pump coronary artery bypass grafting . The need for additional inotropic or mechanical therapy was decreased Severe heart failure represents a major source of morbidity and mortality . Poor right ventricular function is an independent prognostic marker for mortality in patients with chronic heart failure . In this study , levosimendan ( L ) and dobutamine ( D ) in patients with severe chronic biventricular failure were compared . Forty consecutive patients , who were judged for inotropic therapy by their primary physicians , with acutely decompensated systolic heart failure and having moderate-to-severe right ventricular dysfunction with right ventricular fractional area change of ≤24%m were r and omized to L and D in a 2:1 fashion . Echocardiographic parameters including tricuspid annular motion and clinical issues were considered . Mean age and sex distribution were not different between the two groups . After the infusion , ejection fraction improved and systolic pulmonary artery pressure decreased significantly in both arms . Longitudinal systolic function of tricuspid annulus improved significantly better in patients with L compared to patients with D ( 15 % ± 12 % vs. 2 % ± 6 % improvement , P < 0.001 ) . Furthermore , L improved both 24-h urine output and creatinine , whereas D showed only a small , but significant improvement in urine output without any improvement in the creatinine levels . Levosimendan seems to offer more beneficial effects compared to dobutamine in a specific group of patients with biventricular failure BACKGROUND In advanced chronic heart failure ( CHF ) 20 % of patients do not tolerate beta-blockers and 50 % do not reach target doses . AIM To test whether levosimendan or prostagl and in E1 ( PGE1 ) can facilitate uptitration of beta-blockers in advanced CHF . METHODS AND RESULTS Seventy-five advanced CHF patients ( LVEF<35 % , NYHA class IIIb or IV ) intolerant to beta-blocker uptitration to target doses ( 10 mg bisoprolol/day ) were r and omised to a monthly 24 h infusion with levosimendan ( n=39 ) or a chronic infusion with PGE1 ( n=36 ) for 3 months . Bisoprolol was uptitrated following predefined criteria . At 12 weeks , bisoprolol dose increased from 4 mg to 10 mg in both groups . Heart failure worsening occurred in 29 levosimendan patients ( 74 % ) versus 16 PGE1 patients ( 44 % , p=0.008 ) . Uptitration was impossible in 9 levosimendan patients ( 23 % ) versus 2 PGE1 patients ( 6 % , p=0.03 ) . The combined endpoint of death or urgent heart transplantation or implantation of a ventricular assist device was reached by 12 levosimendan patients ( 31 % ) versus 4 PGE1 patients ( 11 % , p=0.04 ) . After 1 year , LVEF increased from 23+/-7 % to 28+/-11 % ( p=0.0004 ) , and BNP decreased from 994+/-806 to 659+/-564 pg/ml ( p=0.03 ) . CONCLUSION Levosimendan and PGE1 facilitate uptitration of beta-blockers in previously intolerant CHF patients . PGE1 treatment allowed uptitration in more patients and result ed in a better clinical outcome compared to levosimendan . This approach increased LVEF and decreased BNP after 1 year Positive inotropes used for the treatment of heart failure have been arrhythmogenic . Levosimendan is a novel calcium sensitizer with vasodilating properties and a complex mechanism of action . Its effect on ventricular arrhythmias and 24-hour Holter electrocardiographically derived prognostic autonomic nervous system-related markers , because it occurs in parallel with changes in cardiac function and neurohormonal response , has not been systematic ally assessed . Forty-five patients ( mean age 65 + /- 1.3 years ) with heart failure refractory to conventional therapy and a mean ejection fraction of 23 + /- 1.2 % , r and omized to levosimendan or placebo , were studied . After Holter electrocardiographic recording , 1 drug was infused for 24 hours ( levosimendan at a dose of 0.1 mug/kg/min ) . During this period , another Holter recording was performed to assess changes in ventricular arrhythmogenesis , 24-hour heart rate variability indexes , QTc , QT variability , and QT/RR slope . Clinical evaluation , echocardiography , and B-type natriuretic peptide measurements were performed at baseline and after treatment . After levosimendan , clinical and echocardiographic improvement was observed , associated with beneficial neurohormonal modulation ( mean B-type natriuretic peptide level after levosimendan 668 + /- 108 vs 1,009 + /- 122 pg/ml at baseline , p < 0.05 ) . Episodes of nonsustained ventricular tachycardia increased with levosimendan ( 21.9 + /- 9.6 vs 3.0 + /- 1.2 , p < 0.05 ) . Levosimendan and placebo exerted a neutral effect on all autonomic markers assessed . In conclusion , levosimendan at low doses increases nonsustained ventricular arrhythmias , without affecting Holter-derived , prognostically significant autonomic markers . At the same time , it is associated with improvements in cardiac function and neurohormonal response . These findings may have important clinical and prognostic implication BACKGROUND This study evaluated the efficacy and safety of levosimendan , a positive inotropic drug with vasodilator effects , given intravenously to patients with acutely decompensated heart failure ( ADHF ) . METHODS We performed 2 sequential trials , the first to develop a new measure of efficacy in 100 patients , and the second to use this measure to evaluate levosimendan in an additional 600 patients . Patients admitted with ADHF received placebo or intravenous levosimendan for 24 h in addition to st and ard treatment . The primary endpoint was a composite that evaluated changes in clinical status during the first 5 days after r and omization . RESULTS In the 600-patient trial , more levosimendan than placebo patients ( 58 vs. 44 ) were improved at all 3 pre-specified time points ( 6 h , 24 h , and 5 days ) , whereas fewer levosimendan patients ( 58 vs. 82 ) experienced clinical worsening ( p = 0.015 for the difference between the groups ) . These differences were apparent , despite more frequent intensification of adjunctive therapy in the placebo group ( 79 vs. 45 patients ) . Improvements in patient self- assessment and declines in B-type natriuretic peptide levels with levosimendan persisted for 5 days and were associated with reduced length of stay ( p = 0.009 ) . Similar findings were present in the 100-patient pilot trial . Levosimendan was associated with more frequent hypotension and cardiac arrhythmias during the infusion period and a numerically higher risk of death across the 2 trials ( 49 of 350 on a regimen of levosimendan vs. 40 of 350 on a regimen of placebo at 90 days , p = 0.29 ) . CONCLUSIONS In patients with ADHF , intravenous levosimendan provided rapid and durable symptomatic relief . As dosed in this trial , levosimendan was associated with an increased risk of adverse cardiovascular events . ( Evaluation of Intravenous Levosimendan Efficacy in the Short Term Treatment of Decompensated Chronic Heart Failure ; NCT00048425 ) To investigate the effects of levosimendan , a positive inotropic agent , on the new heart failure markers immunoglobulin free light chains kappa and lambda ( FLC-κ and FLC-λ ) in decompensated chronic heart failure ( HF ) , 59 patients with New York Heart Association ( NYHA ) class III – IV HF were enrolled . Patients were r and omized into levosimendan ( n = 31 ) and st and ard HF treatment ( n = 29 ) groups . Serum FLC-κ and FLC-λ , brain natriuretic peptide ( BNP ) , and ejection fraction ( EF ) were measured before treatment and on the 5th day of treatment initiation . Forty-two percent of subjects were females ( n = 25 ) and overall mean age was 64.1 ± 10.7 years . FLC-κ ( P < 0.05 ) and FLC-λ ( P < 0.05 ) were significantly decreased in the levosimendan group compared to baseline , but no difference in either marker in the st and ard treatment group was observed . Pre- and post-treatment FLC-κ/FLC-λ ratios in both groups were similar , whereas FLC-κ and FLC-λ levels and the FLC-κ/FLC-λ ratio showed no significant correlation with NYHA class , brain natriuretic peptide ( BNP ) and ejection fraction ( EF ) levels ; and BNP and EF changes after the treatment . Symptomatic improvement in the levosimendan group according to the NYHA class was significantly better than in the st and ard treatment group ( P = 0.044 ) . While 55.2 % of patients in the levosimendan group showed a 1-degree shift to lower NYHA classes , 10.3 % showed a 2-degree decrease . In conclusion , levosimendan caused short-term hemodynamic and symptomatic improvements , with a more pronounced decrease in FLC levels in patients with advanced decompensated HF OBJECTIVES The purpose of this study was to compare the hemodynamic profiles and the postoperative insulin requirements in 2 groups of type 2 diabetic patients with depressed myocardial function who underwent elective surgery for coronary artery disease and who received levosimendan or milrinone for postcardiopulmonary bypass low-output syndrome . DESIGN R and omized controlled trial . SETTING The Chest Diseases Hospital , Safat , Kuwait . PARTICIPANTS Type 2 diabetic patients undergoing elective surgery for coronary artery disease . INTERVENTIONS Fourteen patients and 16 patients received levosimendan and milrinone infusions , respectively , for treatment of the low-output syndrome . MEASUREMENTS AND MAIN RESULTS The hemodynamic , mixed venous oxygen saturation , oxygen extraction ratios , arterial lactate concentrations , and postoperative insulin infusion rates were serially documented for the first 48 hours after the diagnosis . The cardiac index and mixed venous oxygen saturation were significantly higher in the levosimendan group . The pulmonary capillary wedge pressure , systemic vascular resistance , and oxygen extraction ratios were significantly higher in the milrinone treatment group . The insulin requirements were similar for both of the treatment groups . CONCLUSIONS Levosimendan was more efficient than milrinone for treating the hemodynamic manifestations of the postcardiopulmonary bypass low-output syndrome . However , all the values in the milrinone treatment group were normalized . In this small population , both treatment groups had similar postoperative insulin requirements BACKGROUND Levosimendan ( LS ) improves cardiac contractility without increasing myocardial oxygen dem and . We administrated LS on a monthly intermittent 24-hour protocol and evaluated the clinical effect after 6 months in a r and omized , open , prospect i ve study . METHODS AND RESULTS Fifty patients ( age 45 - 65 years ) with LV systolic dysfunction and New York Heart Association ( NYHA ) III or IV were r and omized in 2 groups . LS group ( n = 25 ) was compared with a control group ( n = 25 ) matched for sex , age , and NYHA class . LS was given monthly on a 24-hour intravenous protocol for 6 months . Patients were evaluated by specific activity question naire ( SAQ ) and echocardiography ( ECHO ) before and 3 to 5 days after last drug administration , whereas 24-hour Holter recording was performed before and during last drug administration . Patients in LS and control group had same baseline SAQ , ECHO , and Holter parameters . At the end of the study , a larger proportion of patients in the levosimendan group reported improvement in symptoms ( dyspnea and fatigue ) ( 65 % versus 20 % in controls , P < .01 ) . After 6 months , the LS group had a significant increase in LV ejection fraction versus controls ( 28 + /- 7 versus 21 + /- 4 % , P = .003 ) , LV shortening fraction ( 15 + /- 3 versus 11 + /- 3 % , P = .006 ) and a decrease in mitral regurgitation ( 1.5 + /- 0.8 versus 2.7 + /- 0.6 , P = .0001 ) . There was no increase in supraventricular or ventricular beats or supraventricular tachycardia and VT episodes in LS group , compared with controls . Two patients from the LS group died in the 6-month follow-up period , compared with 8 patients in the control group ( 8 % versus 32 % , P < .05 ) . CONCLUSIONS A 6-month intermittent LS treatment in patients with decompensated advanced heart failure improved symptoms and LV systolic function Levosimendan , a new drug that sensitizes troponin-C to calcium and selectively inhibits phosphodiesterase III , was administered to 24 patients with ischemic heart disease and ejection fraction below 40 % . In a placebo-controlled , crossover , double-blind study , each patient received two intravenous doses of levosimendan on 2 consecutive study days . The doses were 0.25 mg ( n = 6 ) , 0.5 mg ( n = 11 ) , 1 mg ( n = 12 ) , 2 mg ( n = 12 ) , and 4 mg ( n = 5 ) . After 0.25 mg and 0.5 mg , cardiac output increased by 0.49 - 0.67 L/min ( p < 0.05 ) due to an increase in stroke volume of 6 - 11 ml . After 2 and 4 mg , cardiac output increased by 0.61 - 0.88 L/min due to an increase in heart rate of 6 - 12 beats/min . The baseline filling pressures , i.e. , right atrial pressure ( RAP ) and pulmonary capillary wedge pressure ( PCWP ) , were within the normal range . RAP decreased significantly ( p < 0.05 ) after 2 and 4 mg and PCWP after 0.5 , 1 , 2 , and 4 mg . The most profound decreases were observed 10 min after infusion of 4 mg , from 5.0 to 3.2 mm Hg in RAP and from 9.8 to 6.0 mm Hg in PCWP . Total peripheral resistance decreased significantly only after 2 and 4 mg , by 13 and 21 % , respectively . However , there were no statistically significant changes in pulmonary vascular resistance . It is concluded that levosimendan has a hemodynamically favorable action after 0.25 and 0.5 mg but that decreases in filling pressures probably prevented the increase in stroke volume and caused a reflex increase in heart rate after 2 and 4 mg OBJECTIVE To test the hypothesis that levosimendan is more effective than intra-aortic balloon pump ( IABP ) support in cardiac surgical patients with low left ventricular ejection fraction to decrease cardiac troponin I levels ( primary endpoint ) and improve hemodynamics . DESIGN Prospect i ve r and omized trial . SETTING Tertiary cardiothoracic referral center . PARTICIPANTS Ninety patients with coronary artery disease and left ventricular ejection fraction < 35 % who underwent surgery with cardiopulmonary bypass . INTERVENTION Patients were assigned r and omly to 1 of 3 groups . Group A received a prophylactic IABP one day before surgery . Group B received a prophylactic IABP one day before surgery and a levosimendan infusion at a dose of 0.1 μg/kg/min with an initial bolus ( 12 μg/kg for 10 minutes ) after anesthesia induction . Group C received a levosimendan infusion at a dose of 0.1 μg/kg/min with an initial bolus ( 12 μg/kg for 10 minutes ) after anesthesia induction . Hemodynamic and biochemical data and rate of complications were analyzed . MEASUREMENTS AND MAIN RESULTS The cardiac troponin I level in group C 6 hours after surgery was lower than in group A ( p = 0.048 ) . The cardiac index in group A was significantly lower than in groups B and C. The intensive care unit stay was significantly shorter in group C than in groups A and B ( p = 0.001 ) . The need for inotropic support , the rate of complications , and mortality among groups did not differ . CONCLUSIONS The infusion of levosimendan after anesthesia induction in cardiac surgical patients contributes to lower cardiac troponin I levels and improved hemodynamics compared with a preoperative IABP OBJECTIVES We sought to define the therapeutic dose range of levosimendan in patients with New York Heart Association class II-IV heart failure of ischemic origin . BACKGROUND Levosimendan is a calcium sensitizer for treatment of acute decompensated heart failure . METHODS A double-blind , placebo-controlled , r and omized , multicenter , parallel-group study included 151 adult patients . Levosimendan was given as a 10-min intravenous bolus of 3 , 6 , 12 , 24 or 36 microg/kg , followed by a 24-h infusion of 0.05 , 0.1 , 0.2 , 0.4 or 0.6 microg/kg/min , respectively . Dobutamine , for comparative purpose s , was given as an open-label infusion ( 6 microg/kg/min ) . The primary efficacy variable was the proportion of patients achieving in each treatment group at least one of the following : 1 ) a > or = 15 % increase in stroke volume ( SV ) at 23 h to 24 h ; 2 ) a > or = 25 % decrease in pulmonary capillary wedge pressure ( PCWP ) ( and > or = 4 mm Hg ) at 23 h to 24 h ; 3 ) a > or = 40 % increase in cardiac output ( CO ) ( with change in heart rate [ HR ] < 20 % ) ; 4 ) a > or = 50 % decrease in PCWP during two consecutive measurements . RESULTS The response rate to levosimendan ranged from 50 % at the lowest dose to 88 % at the highest dose ( compared with placebo 14 % , dobutamine 70 % ) . A dose-response relationship was demonstrated for levosimendan on increases in CO and SV , and reductions in PCWP during the infusion ( for all , p < or = 0.001 ) . Headache ( 9 % ) , nausea ( 5 % ) and hypotension ( 5 % ) were the most frequently reported adverse events at higher dosages . CONCLUSIONS Dosing of levosimendan with a 10-min bolus of 6 to 24 microg/kg followed by an infusion of 0.05 to 0.2 microg/kg/min is well tolerated and leads to favorable hemodynamic effects BACKGROUND Levosimendan is a novel inotropic agent that enhances cardiac contractility without increasing cellular calcium intake , so that it is not supposed to cause intracellular calcium overload and related arrhythmias . In patients with heart failure , prolonged QRS duration is associated with increased risk of mortality and sudden cardiac death . Structural changes in the left ventricle may lead to asynchronous contraction , causing conduction delay and a prolonged QRS on the surface electrocardiogram . OBJECTIVE We aim ed to compare the acute effects of levosimendan and dobutamine on QRS duration in patients with severe heart failure and sinus rhythm . METHODS Sixty consecutive patients with ischemic heart failure were enrolled for the study and r and omized into two groups for levosimendan ( n=37 ) or dobutamine ( n=23 ) infusions . 67.2 % were male ; mean age was 66.4 ± 9.2 years for all patients . Baseline QRS duration s in levosimendan and dobutamine groups were , 120.44 ± 23.82 ms vs 116.59 ± 13.80 ms respectively . Baseline ejection fractions were both depressed ( 23.15 ± 8.3 % vs 24.56 ± 7.5 % ) . RESULTS In the levosimendan group , QRS duration shortened from baseline value to 116.47 ± 24.56 msec ( p=0.006 ) , whereas dobutamine group showed no significant change ( p=0.605 ) . Both drugs caused an increase in ejection fraction , but only the levosimendan group showed significance ( 27.95 ± 8.9 % p=0.003 vs 26.67 ± 7.6 % , p=0.315 ) . CONCLUSION We suggest that the administration of levosimendan , not dobutamine , shortens QRS duration on the surface ECG , possibly by means of providing collective contraction in the left ventricle muscle fibers . The molecular basis of this effect remains to be clarified BACKGROUND Septic shock is the leading causes of death in intensive care units . In addition to generous fluid administration , inotropic agents are commonly used to improve cardiac output . The effects of inotropic agents on regional blood flow remains unknown . OBJECTIVE The aim of this study was to assess the effects of levosimendan vs dobutamine added to dopamine on liver functions assessed using noninvasive liver function monitoring ( LiMON ) in patients with septic shock . DESIGN Prospect i ve analysis . MEASUREMENTS AND RESULTS We analyzed 30 patients with septic shock who were treated in an intensive care unit . Indocyanine green plasma disappearance rate ( ICG-PDR ) was conducted concurrently using the LiMON system . A dose of 0.3 mg/kg ICG was given through a cubital fossa vein as a bolus . RESULTS Statistical analysis showed that the variation of hemodynamic variables was different between groups . In our results , the increase in systolic blood pressure , diastolic blood pressure , and mean arterial pressure was significantly higher in levosimendan group than in dobutamine group ( P < .05 ) . There was a decrease in before- and after-infusion ICG-PDR values in dobutamine group ( 20.38 ± 4.83 vs 20.34 ± 5.30 ) , and no statistical difference was detected ( P = .649 ) . There was an increase in before- and after-infusion ICG-PDR values in levosimendan group ( 18.70 ± 2.59 vs 21.65 ± 3.20 ) , and a statistical difference was detected ( P = .001 ) . There was statistical difference between groups ( P = .000 ) . CONCLUSION These results suggest that levosimendan added to dopamine improves systemic hemodynamics and increases splanchnic perfusion assessed using the user-friendly noninvasive bedside system LiMON in patients with septic shock compared with dobutamine OBJECTIVE The effect of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery was investigated . DESIGN A prospect i ve , double-blinded , r and omized clinical trial . SETTING Tertiary teaching and research hospital . PARTICIPANTS Of a total of 147 patients , 128 patients completed the study . In the levosimendan group ( n = 64 ) , levosimendan was administered in addition to st and ard inotropic support ; whereas , in the control group ( n = 64 ) , only st and ard inotropic support was given . INTERVENTIONS In the levosimendan group , a loading dose of levosimendan ( 6 μg/kg ) was administered after removal of the aortic cross-clamp , followed by an infusion ( 0.1 μg/kg/min ) in addition to st and ard inotropic therapy for 24 hours . In the control group , only st and ard inotropic therapy was administered . Preoperative characteristics , serum creatinine ( sCr ) levels , and estimated glomerular filtration rate ( eGFR ) were determined preoperatively , on postoperative days 1 , 3 , and 10 . Independent risk factors for renal replacement therapy ( RRT ) requirement were investigated with stepwise multivariate logistic regression analysis . MEASUREMENTS AND MAIN RESULTS The primary endpoint was the effect of levosimendan on postoperative renal clearance ( sCr and eGFR ) . The secondary endpoint was the effect of levosimendan on clinical outcomes ( length of intensive care unit and hospital stays , need for RRT ) . Preoperative characteristics and eGFR were similar between the groups ( p>0.05 ) . On postoperative days 1 and 3 , sCr values were lower and eGFR values were higher in the levosimendan group in comparison with the control group ( p = 0.0001 , p = 0.009 , respectively ) . Six patients ( 9.4 % ) in the levosimendan group and 10 patients ( 15.6 % ) in the control group required RRT therapy ( p = 0.284 ) . Independent risk factors for need of RRT include preoperative sCr value between 1.2 to 2.09 mg/dL and ≥2.1 mg/dL ( p < 0.05 ) . CONCLUSIONS Perioperative treatment with levosimendan in addition to st and ard inotropic therapy in patients with a low ejection fraction undergoing mitral valve surgery improved immediate postoperative renal function and reduced need for RRT BACKGROUND Levosimendan is a new calcium sensitizer with positive inotropic properties . Cardiac power output ( CPO ) has been shown to be instrumental in the diagnosis of cardiogenic shock ( CS ) and is an important determinant of outcomes . AIMS To evaluate the haemodynamic effects of levosimendan compared to dobutamine in acute myocardial infa rct ion ( AMI ) patients revascularised by primary percutaneous coronary intervention ( PCI ) , who developed CS . METHODS AND RESULTS Twenty two consecutive AMI patients revascularised by PCI , who developed CS , were r and omly assigned to levosimendan ( 24 microg kg(-1 ) bolus plus 24-h continuous infusion 0,1 microg kg(-1 ) min(-1 ) ) or dobutamine ( initial dose 5 microg kg(-1 ) min(-1 ) , with a maximum dose adjustment in order to reach the desired haemodynamic effect ) . Evaluations were performed from baseline to 30 h. The primary end-point was an increase > or = 30 % in CPO , after 24 h of therapy . The baseline clinical and haemodynamic characteristics were similar in both groups . Levosimendan had a consistently better effect on CPO than dobutamine , while the decrease in PCWP was similar . CONCLUSION The primary objective of our study was achieved better by the end of the 24 h infusion of levosimendan than by dobutamine A single levosimendan administration has recently been shown to result in clinical and hemodynamic improvement in patients with decompensated heart failure ( HF ) , but without survival benefits . In this study , the effects of levosimendan and dobutamine on plasma levels of proinflammatory and proapoptotic mediators in decompensated HF were compared and correlated with the concomitant effects on cardiac function and prognosis . Sixty-nine patients were r and omized to received 24-hour intravenous infusions of levosimendan ( n = 23 ) , dobutamine ( n = 23 ) , or placebo ( n = 23 ) . Echocardiographic , hemodynamic , and biochemical assessment s were performed at baseline , immediately after treatment , and 48 hours later . Patients were subsequently followed for 4 months for disease progression . End-systolic wall stress , the left ventricular ejection fraction , pulmonary capillary wedge pressure , and cardiac index were significantly improved in the levosimendan group but remained practically unaffected in the other groups . Plasma N-terminal-pro-B-type natriuretic peptide , tumor necrosis factor-alpha , and soluble Fas lig and levels were significantly decreased only in the levosimendan group ( from 1,900 + /- 223 to 1,378 + /- 170 pg/ml , 13.4 + /- 1.0 to 12.3 + /- 1.2 pg/ml , and 68.2 + /- 3.7 to 59.8 + /- 3.6 pg/ml , respectively ; p < 0.05 for all ) ; interleukin-6 was also borderline reduced ( p = 0.051 ) . Levosimendan-induced reduction in end-systolic wall stress was significantly correlated with respective decreases in N-terminal-pro-B-type natriuretic peptide ( r = 0.671 , p < 0.01 ) , tumor necrosis factor-alpha ( r = 0.586 , p < 0.01 ) , soluble Fas ( r = 0.441 , p < 0.05 ) , and soluble Fas lig and ( r = 0.614 , p < 0.01 ) . Event-free survival was significantly longer in the levosimendan group ( p < 0.05 ) . In conclusion , the superiority of levosimendan over dobutamine in improving central hemodynamics and left ventricular performance in decompensated HF seems to be related to its anti-inflammatory and antiapoptotic effects AIMS Inotrope treatment is often necessary in refractory to optimal management end stage heart failure , when signs of end-organ hypoperfusion appear . The effect of specific inotropes on patient outcome remains controversial . The aim of the study was to compare the effect of levosimendan versus dobutamine , alone or in combination with levosimendan , on the outcome of end-stage heart failure patients , requiring inotropic therapy . METHODS AND RESULTS We studied 63 patients in NYHA class IV , refractory to optimal medical therapy , recently hospitalized for cardiac decompensation and stabilized by an intravenous inotrope . They were r and omly assigned to intermittent infusions of either a ) dobutamine , 10mg/kg/min , versus b ) levosimendan , 0.3mg/kg/min , versus c ) dobutamine , 10mg/kg/min+levosimendan 0.2 mg/kg/min , each administered weekly , for 6h , over a 6-month period . All patients received amiodarone , 400 mg/day , to suppress the proarrhythmic effects of the inotropes . Baseline characteristics of the 3 groups were similar . At 6 months , survival free from death or urgent left ventricular device implantation was 80 % in the levosimendan , 48 % in the dobutamine ( P=0.037 versus levosimendan ) , and 43 % in the levosimendan+dobutamine ( P=0.009 versus levosimendan ) group . At 3months , NYHA class improved significantly in all 3 groups , whereas pulmonary capillary wedge pressure decreased ( 27 ± 4 to 19 ± 8 mmHg , P=0.008 ) and cardiac index increased ( 1.5 ± 0.3 to 2.1 ± 0.3 l/min/m(2 ) , P=0.002 ) significantly only in patients assigned to levosimendan . CONCLUSIONS In patients with refractory end-stage heart failure , intermittent administration of levosimendan conferred survival and hemodynamic benefits in comparison to a regimen of intermittent infusions of dobutamine , alone or in combination with levosimendan Objective : Cardiogenic shock is the leading cause of death in patients hospitalized for acute myocardial infa rct ion . The objectives were to investigate the effects of levosimendan , a novel inodilator , compared with the phosphodiesterase-III inhibitor enoximone in refractory cardiogenic shock complicating acute myocardial infa rct ion , on top of current therapy . Design : Prospect i ve , r and omized , controlled single-center clinical trial . Setting : Medical and coronary intensive care unit in a university hospital . Patients : Thirty-two patients with refractory cardiogenic shock for at least 2 hrs requiring additional therapy . Interventions : Infusion of either levosimendan ( 12 & mgr;g/kg over 10 min , followed by 0.1 & mgr;g/kg/min over 50 min , and of 0.2 & mgr;g/kg/min for the next 23 hrs ) or enoximone ( fractional loading dose of 0.5 mg/kg , followed by 2–10 & mgr;g/kg/min continuously ) after initiation of current therapy , always including revascularization , intra-aortic balloon pump counterpulsation , and inotropes . Measurements and main results : Survival rate at 30 days was significantly higher in the levosimendan-treated group ( 69 % , 11 of 16 ) compared with the enoximone group ( 37 % , 6 of 16 , p = 0.023 ) . Invasive hemodynamic parameters during the first 48 hrs were comparable in both groups . Levosimendan induced a trend toward higher cardiac index , cardiac power index , left ventricular stroke work index , and mixed venous oxygen saturation . In addition , lower cumulative values for catecholamines at 72 hrs and for clinical signs of inflammation were seen in the levosimendan-treated patients . Multiple organ failure leading to death occurred exclusively in the enoximone group ( 4 of 16 patients ) . Conclusions : In severe and refractory cardiogenic shock complicating acute myocardial infa rct ion , levosimendan , added to current therapy , may contribute to improved survival compared with enoximone AIMS To determine the duration of haemodynamic and neurohormonal action of a 24-h infusion of levosimendan in heart failure . METHODS AND RESULTS This was a double-blind , parallel group study in patients with New York Heart Association class II to IV heart failure . Twenty-two patients , with left ventricular ejection fraction < 35 % and pulmonary capillary wedge pressure ( PCWP ) above 12 mmHg , were r and omised to receive either levosimendan ( 12 microg/kg followed by a continuous infusion of 0.1 - 0.2 microg/min ) or placebo . Invasively measured cardiac output ( CO ) increased from 4.3 l/min to 5.4 l/min in the levosimendan group at 6 h. PCWP decreased from 20 mmHg to 15 mmHg in response to levosimendan . Echocardiographically measured maximal effect on PCWP occurred after 6 h , whereas CO reached its highest value at 24 h. The estimated duration of the decrease in PCWP was 7 - 9 days , and in CO was 12 - 13 days . Plasma NT-proANP and NT-proBNP levels reached their lowest values at days 3 and 2 , and the treatment effect was estimated to last 16 and 12 days , respectively . The long-acting haemodynamic responses reflect levels of the active metabolites OR-1896 and OR-1855 , maximal metabolite levels occurred at day 3 . CONCLUSIONS Levosimendan infusion achieved a rapid improvement in haemodynamic parameters in patients with congestive heart failure with maximal effects occurring 1 - 3 days after starting the infusion , effects were sustained for up to at least a week The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes |
1,052 | 30,049,604 | 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 | BACKGROUND Currently , there is no consensus on which treatments should be a part of st and ard deceased-donor management to improve graft quality and transplantation outcomes .
The objective of this systematic review was to evaluate the effects of treatments of the deceased , solid-organ donor on graft function and survival after transplantation . | 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(-1 ) h(-1 ) infusion ) ( n = 20 ) , methylprednisolone ( 1000 mg bolus ) ( n = 19 ) , both drugs ( n = 20 ) , or placebo ( n = 21 ) following initial haemodynamic assessment . After hormone or placebo administration , cardiac output-guided optimization was initiated , using vasopressin as a pressor and weaning norepinephrine and inotropes . Treatment was administered for 5.9 + /- 1.3 h until retrieval or end- assessment . Cardiac index increased significantly ( P < 0.001 ) but administration of T3 and methylprednisolone alone or in combination did not affect this change or the heart retrieval rate . Thirty-five per cent ( 14/40 ) of initially marginal or dysfunctional hearts were suitable for transplant at end- assessment . At end- assessment , 50 % of donor hearts fulfilled criteria for transplant suitability . CONCLUSION Cardiac output-directed donor optimization improves donor circulatory status and has potential to increase the retrieval rate of donor hearts . Tri-iodothyronine and methylprednisolone therapy do not appear to acutely affect cardiovascular function or yield The cadaveric renal graft is exposed to ischaemic injury during preservation and to oxidative damage during reperfusion . Both these mechanisms are known to cause cell damage , which may impair graft function . Reperfusion injury ( RPI ) is mediated by reactive oxygen species ( ROS ) . Ascorbic acid ( AA ) is a potent physiological extracellular scavenger of ROS . We perfused 31 renal grafts immediately before implantation with a solution of Euro-Collins containing 0.5 mg/ml of AA to diminish RPI . From every donor , the contralateral kidney served as a control . The control grafts were perfused with the same perfusion as those of the AA group , only without the AA substitution . We assessed the effect of AA by recording serum creatinine , creatinine clearance , initial graft function and early rejections . The incidence of delayed graft function ( DGF ) was 32 % in the AA group , and 29 % in the control group . Other parameters were also similar in both groups , except for the length of DGF , which showed a trend towards a shorter duration in the AA group . The pre-operative systemic AA concentration was significantly ( P=0.01 ) lower in the haemodialysis patients than in those on peritoneal dialysis . In conclusion , this clinical study could not demonstrate significant benefits of AA in renal transplantation BACKGROUND AND OBJECTIVES Delayed graft function ( DGF ) is associated with adverse long-term outcomes after deceased-donor kidney ( DDK ) transplantation . Ischemia-reperfusion injury plays a crucial role in the development of DGF . On the basis of promising animal data , this study evaluated any potential benefits of erythropoietin-alfa ( EPO-α ) given intra-arterially at the time of reperfusion of renal allograft on the degree of allograft function , as well as tubular cell injury measured by urinary biomarkers in the early post-transplant period . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A prospect i ve , r and omized , double-blind , placebo-controlled clinical trial was conducted to evaluate the influence of EPO-α administered intraoperatively on the outcomes of DDK transplantations performed at the study center between March 2007 and July 2009 . RESULTS Seventy-two patients were r and omly assigned to EPO-α ( n=36 ) or placebo ( n=36 ) . The incidences of DGF , slow graft function , and immediate graft function did not significantly differ between the treatment and control groups ( 41.7 % versus 47.2 % , 25.0 % versus 36.1 % , and 33.3 % versus 16.7 % , respectively ; P=0.24 ) . The groups had similar levels of urinary biomarkers , including neutrophil gelatinase-associated lipocalin and IL-18 at multiple times points soon after transplantation ; urinary output during the first 3 postoperative days ; 1-month renal function ; and BP readings , hemoglobin , and adverse effects during the first month . CONCLUSIONS This study did not show any clinical ly demonstrable beneficial effects of high-dose EPO-α given intra-arterially during the early reperfusion phase in DDK transplant recipients in terms of reducing the incidence of DGF or improving short-term allograft function Background . Brain stem death can elicit a potentially manipulable cardiotoxic proinflammatory cytokine response . We investigated the prevalence of this response , the impact of donor management with tri-iodothyronine ( T3 ) and methylprednisolone ( MP ) administration , and the relationship of biomarkers to organ function and transplant suitability . Methods . In a prospect i ve r and omized double-blinded factorially design ed study of T3 and MP therapy , we measured serum levels of interleukin-1 and -6 ( IL-1 and IL-6 ) , tumor necrosis factor-alpha ( TNF-&agr ; ) , C-reactive protein , and procalcitonin ( PCT ) levels in 79 potential heart or lung donors . Measurements were performed before and after 4 hr of algorithm-based donor management to optimize cardiorespiratory function and ±hormone treatment . Donors were assigned to receive T3 , MP , both drugs , or placebo . Results . Initial IL-1 was elevated in 16 % donors , IL-6 in 100 % , TNF-&agr ; in 28 % , CRP in 98 % , and PCT in 87 % . Overall biomarker concentrations did not change between initial and later measurements and neither T3 nor MP effected any change . Both PCT ( P = 0.02 ) and TNF-&agr ; ( P = 0.044 ) levels were higher in donor hearts with marginal hemodynamics at initial assessment . Higher PCT levels were related to worse cardiac index and right and left ventricular ejection fractions and a PCT level more than 2 ng·mL−1 may attenuate any improvement in cardiac index gained by donor management . No differences were observed between initially marginal and nonmarginal donor lungs . A PCT level less than or equal to 2 ng·mL−1 but not other biomarkers predicted transplant suitability following management . Conclusions . There is high prevalence of a proinflammatory environment in the organ donor that is not affected by tri-iodothyronine or MP therapy . High PCT and TNF-&agr ; levels are associated with donor heart dysfunction Background Given the persistent shortage of organs for transplantation , new donor management strategies to improve both organ utilization and quality of procured organs are needed . Current management protocol s for the care of the deceased donor before organ procurement are based on physiological rationale , experiential reasoning , and retrospective studies without rigorous testing . Although many factors contribute to the lack of controlled clinical trials in donor management , a major factor is the unique challenges posed by research in the brain-dead organ donor . Methods and Results This article describes the study design and the challenges faced during implementation of the Beta-agonists for Oxygenation in Lung Donors ( BOLD ) study , a r and omized , placebo-controlled clinical trial of nebulized albuterol vs. placebo in 500 organ donors . The study design and implementation are described with emphasis on aspects of the study that are unique to research in brain-dead organ donors . Conclusions Experience gained during the design and implementation of the BOLD study should be useful for investigators planning future clinical trials in the brain-dead donor population and for intensivists who are involved in the care of the brain-dead organ donor Verapamil has proven effective in preventing acute renal failure in animal models if given prior to the insult and hence possibly has a role in the preservation of cadaveric renal tissue for transplantation . Twenty renal donors were r and omly assigned to treatment ( receiving verapamil 20 mg intravenously ) and control groups . Recipients were monitored for renal failure by urine output and serum creatinines on days 1 and 7 and dialysis requirement to one week . Early urine outputs and serum creatinines ( day 1 ) were significantly better in the treated than control group ( p greater than 0.01 , 0.05 respectively ) . We conclude therefore that verapamil may prevent post-transplant acute renal failure , but its optimal dosage and route of administration remain to be determined Introduction Circulatory failure during brain death organ donor resuscitation is a problem that compromises recovery of organs . Combined administration of steroid , thyroxine and vasopressin has been proposed to optimize the management of brain deceased donors before recovery of organs . However the single administration of hydrocortisone has not been rigorously evaluated in any trial . Methods In this prospect i ve multicenter cluster study , 259 subjects were included . Administration of low-dose steroids composed the steroid group ( n = 102 ) . Results Although there were more patients in the steroid group who received norepinephrine before brain death ( 80 % vs. 66 % : P = 0.03 ) , mean dose of vasopressor administered after brain death was significantly lower than in the control group ( 1.18 ± 0.92 mg/H vs. 1.49 ± 1.29 mg/H : P = 0.03 ) , duration of vasopressor support use was shorter ( 874 min vs. 1160 min : P < 0.0001 ) and norepinephrine weaning before aortic clamping was more frequent ( 33.8 % vs. 9.5 % : P < 0.0001 ) . Using a survival approach , probability of norepinephrine weaning was significantly different between the two groups ( P < 0.0001 ) with a probability of weaning 4.67 times higher in the steroid group than in the control group ( 95 % CI : 2.30 – 9.49 ) . Conclusions Despite no observed benefits of the steroid administration on primary function recovery of transplanted grafts , administration of glucocorticoids should be a part of the resuscitation management of deceased donors with hemodynamic instability IMPORTANCE The shortage of organs available for transplant has led to the use of exp and ed criteria donors ( ECDs ) to extend the donor pool . These donors are older and have more comorbidities and efforts to optimize the quality of their organs are needed . OBJECTIVE To determine the impact of meeting a st and ardized set of critical care end points , or donor management goals ( DMGs ) , on the number of organs transplanted per donor in ECDs . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve interventional study from February 2010 to July 2013 of all ECDs managed by the 8 organ procurement organizations in the southwestern United States ( United Network for Organ Sharing Region 5 ) . INTERVENTIONS Implementation of 9 DMGs as a checklist to guide the management of every ECD . The DMGs represented normal cardiovascular , pulmonary , renal , and endocrine end points . Meeting the DMG bundle was defined a priori as achieving any 7 of the 9 end points and was recorded at the time of referral to the organ procurement organization , at the time of authorization for donation , 12 to 18 hours later , and prior to organ recovery . MAIN OUTCOMES AND MEASURES The primary outcome measure was 3 or more organs transplanted per donor and binary logistic regression was used to identify independent predictors with P < .05 . RESULTS There were 671 ECDs with a mean ( SD ) number of 2.1 ( 1.3 ) organs transplanted per donor . Ten percent of the ECDs had met the DMG bundle at referral , 15 % at the time of authorization , 33 % at 12 to 18 hours , and 45 % prior to recovery . Forty-three percent had 3 or more organs transplanted per donor . Independent predictors of 3 or more organs transplanted per donor were older age ( odds ratio [ OR ] = 0.95 per year [ 95 % CI , 0.93 - 0.97 ] ) , increased creatinine level ( OR = 0.73 per mg/dL [ 95 % CI , 0.63 - 0.85 ] ) , DMGs met prior to organ recovery ( OR = 1.90 [ 95 % CI , 1.35 - 2.68 ] ) , and a change in the number of DMGs achieved from referral to organ recovery ( OR = 1.11 per additional DMG [ 95 % CI , 1.00 - 1.23 ] ) . CONCLUSIONS AND RELEVANCE Meeting DMGs prior to organ recovery with ECDs is associated with achieving 3 or more organs transplanted per donor . An increase in the number of critical care end points achieved throughout the care of a potential donor by both donor hospital and organ procurement organization is also associated with an increase in organ yield Ischemic preconditioning ( IPC ) has the potential to decrease graft injury and morbidity after liver transplantation . We prospect ively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers r and omized 1:1 to st and ard ( STD ) recovery ( N = 28 ) or IPC ( N = 34 ) . Safety was assessed by measurement of heart rate , blood pressure , and visual inspection of abdominal organs during recovery , and efficacy by recipient aminotransferases ( aspartate aminotransferase [ AST ] and alanine aminotransferase [ ALT ] , both measured in U/L ) , total bilirubin , and international normalized ratio of prothrombin time ( INR ) after transplantation . IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion . Recipient median AST , median ALT , and mean INR , in STD vs. IPC were as follows : day 1 AST 696 vs. 841 U/L ; day 3 AST 183 vs. 183 U/L ; day 1 ALT 444 vs. 764 U/L ; day 3 ALT 421 vs. 463 U/L ; day 1 INR 1.7 + /- .4 vs. 2.0 + /- .8 ; and day 3 INR 1.3 + /- .2 vs. 1.4 + /- .3 ; all P > .05 . No instances of nonfunction occurred . The 6-month graft and patient survival STD vs. IPC were 82 vs. 91 % and median hospital stay was 10 vs. 8 days ; both P > .05 . In conclusion , deceased donor livers tolerated 5 minutes of hilar clamping well , but IPC did not decrease graft injury . Further trials with longer periods of preconditioning such as 10 minutes are needed Brain death is associated with altered cardiac function and low concentrations of circulating triiodothryronine (T3).However , the effects of T3 administration on hemodynamic status and cardiac function in potential heart donors remain controversial . Thirty-seven braindead patients were r and omly and blindly allocated to receive an intravenous bolus of either 0.2 micro gram/kg T3 ( n = 19 ) or saline placebo ( n = 18 ) . Measurements included conventional hemodynamic and echocardiographic variables of cardiac volume conditions and systolic function of the left ventricle ( fractional area change [ FAC ] , velocity of myocardial fiber shortening ) using a transesophageal probe , arterial and mixed venous blood gas parameters , and serum thyroid hormone concentrations . The mean concentration of T3 was 1.86 + /- 1.55 pmol/L , and only six patients ( 16 % ) had normal values of T3 in control conditions . There was no significant correlation between T3 concentration and FAC ( R = 0.17 , not significant ) . All patients receiving T3 had normalized serum T3 concentration ( 7.55 + /- 2.56 pmol/L ) in contrast to patients receiving saline ( 1.48 + /- 1.26 pmol/L ) . No significant differences in hemodynamic and echocardiographic parameters were observed between the placebo and T3 groups . Indeed , FAC remained unchanged after T3 ( 44 % + /- 17 % vs 46 % + /- 22 % ) or placebo ( 47 % + /- 18 % vs 50 % + /- 14 % ) administration . In 20 patients with impaired left ventricular function ( FAC < 50 % ) , FAC remained unchanged after T3 ( n = 10 ; 34 % + /- 12 % vs 30 % + /- 10 % ) or placebo ( n = 10 ; 38 % + /- 12 % vs 35 % + /- 13 % ) administration . In 17 patients in whom organ harvesting was delayed , transesophageal echocardiography was performed 6 h later and no significant changes in FAC were noted in the T3 group ( n = 8 ; 49 % + /- 17 % vs 44 % + /- 17 % ) and the placebo group ( n = 9 ; 51 % + /- 18 % vs 47 % + /- 18 % ) . In conclusion , T3 administration did not improve hemodynamic status and myocardial function in brain-dead patients , suggesting that the euthyroid sick syndrome is not the main determinant of myocardial dysfunction in these patients . ( Anesth Analg 1996;83:41 - 7 Abstract Background Critical shortages of organs for transplantation jeopardize many lives . Observational data suggest that better fluid management for deceased organ donors could increase organ recovery . We conducted the first large multicenter r and omized trial in brain-dead donors to determine whether protocol ized fluid therapy increases the number of organs transplanted . Methods We r and omly assigned donors to either protocol ized or usual care in eight organ procurement organizations . A “ protocol -guided fluid therapy ” algorithm targeting the cardiac index , mean arterial pressure and pulse pressure variation was used . Our primary outcome was the number of organs transplanted per donor , and our primary analysis was intention to treat . Secondary analyses included : ( 1 ) modified intention to treat where only subjects able to receive the intervention were included and ( 2 ) 12-month survival in transplant recipients . The study was stopped early . Results We enrolled 556 donors : 279 protocol ized care and 277 usual care . Groups had similar characteristics at baseline . The study protocol could be implemented in 76 % of subjects r and omized to the intervention . There was no significant difference in mean number of organs transplanted per donor : 3.39 organs per donor ( 95 % CI 3.14–3.63 ) with protocol ized care compared to 3.29 usual care ( 95 % CI 3.04–3.54 ; mean difference , 0.1 , 95 % CI −0.25 to 0.45 ; p = 0.56 ) . In modified intention-to-treat analysis the mean number of organs increased ( 3.52 organs per donor , 95 % CI 3.23–3.8 ) , but not statistically significantly ( mean difference , 0.23 , 95 % CI −0.15 to 0.61 ; p = 0.23 ) . Among the 1,430 recipients of organs from study subjects with data available , 56 deaths ( 7.8 % ) occurred in the protocol ized care arm and 56 ( 7.9 % ) in the usual care arm in the first year ( hazard ratio : 0.97 , p = 0.86 ) . Conclusions In brain-dead organ donors , protocol -guided fluid therapy compared to usual care may not increase the number of organs transplanted per donor BACKGROUND Lung transplantation activity is frustrated by donor lung availability . We sought to examine the effect of active donor management and hormone administration on pulmonary function and yield in cadaveric heart-beating potential lung donors . METHODS We studied 182 potential lung donors ( arterial oxygen tension [PaO2]/fractional inspired oxygen [ FIO2 ] ratio > or = 230 ) . From this group , 60 patients ( 120 lungs ) were allocated , within a r and omized trial , to receive methylprednisolone ( 1 g ) , triiodothyronine ( 0.8 microg/kg bolus and 0.113 microg/kg/h infusion ) , both methylprednisolone and triiodothyronine , or placebo as soon as feasible after consent and initial assessment . Trial donors underwent protocol -guided optimization of ventilation and hemodynamics , lung water assessment , and bronchoscopy . Function was assessed by PaO2/FIO2 ratio , extravascular lung water index ( EVLWI ) , and pulmonary vascular resistance ( PVR ) . A nontrial group of 122 donors ( 244 lungs ) received similar management without bronchoscopy , pulmonary artery flotation catheter monitoring , or lung water assessment . RESULTS Within the trial , management commenced within a median of 2 hours ( interquartile range , 0.5 to 3.5 hours ) of consent and continued for an average of 6.9 + /- 1.2 hours . The PaO2/FIO2 ratio deteriorated ( p = 0.028 ) from 397 + /- 78 ( 95 % CL , 376 to 417 ) to 359 + /- 126 ( 95 % CL , 328 to 390 ) and EVLWI from 9.7 + /- 4.5 mL/kg ( 95 % CL , 8.6 to 10.9 mL/kg ) to 10.8 + /- 5.2 mL/kg ( 95 % CL , 9.4 to 12.2 mL/kg ; p = 0.009 ) . PVR remained unchanged ( p = 0.28 ) . At end management , 48 of 120 trial lungs ( 40 % ) were transplanted versus 66 of 244 nontrial lungs ( 27 % ; p = 0.016 ) . Neither methylprednisolone and triiodothyronine nor T3 increased lung yield or affected PaO2/FIO2 or EVLWI ; however , methylprednisolone attenuated the increase in EVLWI ( p = 0.009 ) . CONCLUSIONS Early active management of lung donors increases yield . Steroid administration reduces progressive lung water accumulation Background . Pharmacological preconditioning is one of the tools used to diminish preservation injury . We investigated the influence of sevoflurane preconditioning of liver grafts on postoperative graft function . Methods . Consecutive 60 deceased brain donors were r and omized into sevoflurane group or control group . In sevoflurane group donors were treated with endexpiratory 2,0 volume% of sevoflurane during procurement . Primary endpoint was postoperative liver injury . Secondary endpoint was incidence of early allograft dysfunction ( EAD ) . Results . The groups were not different in median DRI , donor age , graft steatosis , and MELD score . Peak AST and ALT levels were lower in sevoflurane group than in control group : 792 and 1861 ( P = 0 , 038 ) for AST and 606 and 1191 for ALT ( P = 0 , 117 ) . Incidence of EAD was 16,7 % in sevoflurane group and 50 % in control group ( Fisher test , P = 0 , 013 ) . In subgroups without steatosis preconditioning with sevoflurane did not have influence on incidence of EAD . In subgroups with mild and moderate steatosis incidence of EAD was lower in recipients of liver grafts treated with sevoflurane . Conclusions . Preconditioning with sevoflurane during organ procurement improves graft function by lowering incidence of early allograft dysfunction , particularly in recipients of steatotic liver grafts BACKGROUND Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function . Therapeutic hypothermia is recommended by international guidelines , but the supporting evidence is limited , and the target temperature associated with the best outcome is unknown . Our objective was to compare two target temperatures , both intended to prevent fever . METHODS In an international trial , we r and omly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33 ° C or 36 ° C . The primary outcome was all-cause mortality through the end of the trial . Secondary outcomes included a composite of poor neurologic function or death at 180 days , as evaluated with the Cerebral Performance Category ( CPC ) scale and the modified Rankin scale . RESULTS In total , 939 patients were included in the primary analysis . At the end of the trial , 50 % of the patients in the 33 ° C group ( 235 of 473 patients ) had died , as compared with 48 % of the patients in the 36 ° C group ( 225 of 466 patients ) ( hazard ratio with a temperature of 33 ° C , 1.06 ; 95 % confidence interval [ CI ] , 0.89 to 1.28 ; P=0.51 ) . At the 180-day follow-up , 54 % of the patients in the 33 ° C group had died or had poor neurologic function according to the CPC , as compared with 52 % of patients in the 36 ° C group ( risk ratio , 1.02 ; 95 % CI , 0.88 to 1.16 ; P=0.78 ) . In the analysis using the modified Rankin scale , the comparable rate was 52 % in both groups ( risk ratio , 1.01 ; 95 % CI , 0.89 to 1.14 ; P=0.87 ) . The results of analyses adjusted for known prognostic factors were similar . CONCLUSIONS In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause , hypothermia at a targeted temperature of 33 ° C did not confer a benefit as compared with a targeted temperature of 36 ° C . ( Funded by the Swedish Heart-Lung Foundation and others ; TTM Clinical Trials.gov number , NCT01020916 . ) OBJECTIVES We determined the outcome of cardiac allografts from multiorgan donors enrolled in a r and omized trial of donor pre-treatment with dopamine . BACKGROUND Treatment of the brain-dead donor with low-dose dopamine improves immediate graft function after kidney transplantation . METHODS A cohort study of 93 heart transplants from 21 European centers was undertaken between March 2004 and August 2007 . We assessed post-transplant left ventricular function ( LVF ) , requirement of a left ventricular assist device ( LVAD ) or biventricular assist device ( BVAD ) , need for hemofiltration , acute rejection , and survival of recipients of a dopamine-treated versus untreated graft . RESULTS Donor dopamine was associated with improved survival 3 years after transplantation ( 87.0 % vs. 67.8 % , p = 0.03 ) . Fewer recipients of a pre-treated graft required hemofiltration after transplant ( 21.7 % vs. 40.4 % , p = 0.05 ) . Impaired LVF ( 15.2 % vs. 21.3 % , p = 0.59 ) , requirement of a LVAD ( 4.4 % vs. 10.6 % , p = 0.44 ) , and biopsy-proven acute rejection ( 19.6 % vs. 14.9 % , p = 0.59 ) were not statistically different between groups . Post-transplant impaired LVF ( hazard ratio [ HR ] : 4.95 ; 95 % confidence interval [ CI ] : 2.08 to 11.79 ; p < 0.001 ) , requirement of LVAD ( HR : 6.65 ; 95 % CI : 2.40 to 18.45 ; p < 0.001 ) , and hemofiltration ( HR : 2.83 ; 95 % CI : 1.20 to 6.69 ; p = 0.02 ) were predictive of death . The survival benefit remained ( HR : 0.33 ; 95 % CI : 0.12 to 0.89 ; p = 0.03 ) after adjustment for various risks affecting mortality , including pre-transplant LVAD/BVAD , inotropic support , and impaired kidney function . CONCLUSIONS Treatment of brain-dead donors with dopamine of 4 μg/kg/min will not harm cardiac allografts but appears to improve the clinical course of the heart allograft recipient . ( Prospect i ve R and omized Trial to Evaluate the Efficacy of Donor Preconditioning With Dopamine on Initial Graft Function After Kidney Transplantation ; NCT00115115 ) BACKGROUND To test the effectiveness of a simpler surgical technique for cadaveric liver procurement for liver transplantation , a prospect i ve r and omized study was carried out between August 1994 and December 1995 , to compare aortic perfusion only ( APO ) for flush-preservation of the liver with the conventional combined aortic and portal perfusion ( APP ) technique . METHODS Forty multiple organ donors were enrolled with 20 in each arm of the trial . Donor parameters ( age , bodyweight , liver function tests ) , surgeons performing the operations , the involvement of other procurement teams and the total ischaemic times were similar in the two groups . The liver recipients had a wide range of native liver pathology but were of similar age , sex and bodyweight in the two groups . RESULTS The mean procurement operation times for the APO and APP groups were 126.7+/-38.6 and 137.8+/-55.9 min , respectively ( P = ns ) . The perfusion took longer to complete in the APO group ( 10.2+/-1.7 vs 7.2+/-1.4 min ( APP ) , P < 0.001 ) . The liver temperature fell to its lowest level ( 12.5+/-3.4 degrees C ( APO ) vs 11+/-3 degrees C ( APP ) , P = ns ) in a similar time ( 11.9+/-3.8 min ( APO ) vs 9.3+/-3.4 mins ( APP ) , P = ns ) . There was no graft primary non-function or graft arterial injury in either group . There was no significant difference between the APO and APP initial graft outcomes . The 3-month patient survival rate was identical in the two groups ( 95 % ) ; 81 % of renal grafts from the APO donors functioned well from the time of transplantation as did 76 % of those from APP donors . CONCLUSIONS It is concluded that the APO procurement technique produces equivalent results to those achieved with the APP method . The simplicity of the APO technique makes it the preferred technique The effect of ischemic preconditioning ( IPC ) in orthotopic liver transplantation ( OLT ) has not yet been clarified . We performed a pilot study to evaluate the effects of IPC in OLT by comparing the outcomes of recipients of grafts from deceased donors r and omly assigned to receive ( IPC+ group , n = 23 ) or not ( IPC- group , n = 24 ) IPC ( 10-min ischemia + 15-min reperfusion ) . In 10 cases in the IPC+ group and in 12 in the IPC- group , the expression of inducible nitric oxide synthase ( iNOS ) , neutrophil infiltration , and hepatocellular apoptosis were tested by immunohistochemistry in prereperfusion and postreperfusion biopsies . Median aspartate aminotransferase ( AST ) levels were lower in the IPC+ group vs. the IPC- group on postoperative days 1 and 2 ( 398 vs. 1,234 U/L , P = 0.002 ; and 283 vs. 685 U/L , P = 0.009 ) . Alanine aminotransferases were lower in the IPC+ vs. the IPC- group on postoperative days 1 , 2 , and 3 ( 333 vs. 934 U/L , P = 0.016 ; 492 vs. 1,040 U/L , P = 0.008 ; and 386 vs. 735 U/L , P = 0.022 ) . Bilirubin levels and prothrombin activity throughout the first 3 postoperative weeks , incidence of graft nonfunction and graft and patient survival rates were similar between groups . Prereperfusion and postreperfusion immunohistochemical parameters did not differ between groups . iNOS was higher postreperfusion vs. prereperfusion in the IPC- group ( P = 0.008 ) . Neutrophil infiltration was higher postreperfusion vs. prereperfusion in both groups ( IPC+ , P = 0.007 ; IPC- , P = 0.003 ) . Prereperfusion and postreperfusion apoptosis was minimal in both groups . In conclusion , IPC reduced ischemia/reperfusion injury through a decrease of hepatocellular necrosis , but it showed no clinical benefits During a prospect i ve study , 13 patients received renal transplants from cadaveric donors whose hearts beat up to the time of their death . These donors were pretreated with cyclophosphamide-methylprednisolone ( group A ) or methylprednisolone-procarbazine hydrochloride ( group B ) . After a minimum follow-up of 12 months , all grafts in group A but only one graft in group B survived . On the basis of this small experience , the combination of cyclophosphamide and methylprednisolone seems to be superior to that of methylprednisolone and procarbazine hydrochloride in reducing allograft immunogenicity . In order to achieve longer survival of the graft in the recipient , pretreatment with procarbazine hydrochloride has been discontinued . Pretreatment of the potential cadaveric allograft donor with cyclophosphamide and methylprednisolone is being continued at our institution BACKGROUND Hydroxyethylstarch used as a plasma-volume exp and er in brain-dead kidney donors has been suggested to induce osmotic-nephrosis-like lesions . We have studied its effect on kidney-transplant function . METHODS 52 patients who had received hydroxyethylstarch of iodinated contrast-media before brain death were excluded . 69 other brain-dead patients were prospect ively included over 18 months and r and omised into two groups . In the hydroxyethylstarch-gelatin group , patients received hydroxyethylstarch up to 33 mL/kg for colloid plasma-volume expansion , and afterwards received modified fluid gelatin . In the gelatin-only group , patients received only modified fluid gelatin as colloid plasma-volume exp and er . Multiple organs were procured in 29 cases , which included the kidneys in 27 cases ( hydroxyethylstarch-gelatin 15 , gelatin-only 12 ) . FINDINGS There were no significant differences in the characteristics of patients between the two groups of kidney donors or of recipients ( except for a small imbalance in sex in the recipients ) . During the first 8 days after transplantation , nine of 27 ( 33 % ) patients required extrarenal haemodialysis or haemodiafiltration in the hydroxyethylstarch-gelatin group compared with one of 20 ( 5 % ) in the gelatin-only group ( p = 0.029 ) . Serum creatinine concentrations were significantly lower in the gelatin-only group than in the other group ( p = 0.009 ) . 10 days after transplantation , mean ( SD ) serum creatinine was , respectively , 145 ( 70 ) and 312 ( 259 ) mumol/L. INTERPRETATION These data suggest that hydroxyethylstarch used as a plasma-volume exp and er in brain-dead donors impairs immediate renal function in kidney-transplant recipients BACKGROUND Diabetes insipidus is common among brain-dead donors and may lead to decreased graft function . The use of desmopressin to limit the consequences of diabetes insipidus is controversial . We assessed the effects of desmopressin administered to brain-dead donors on early and long-term graft function in kidney recipients . METHODS In a r and omised controlled study , 97 brain-dead donors received desmopressin as 1 microg bolus every 2 h when diuresis was more than 300 mL/h ( desmopressin group n=49 ) or no desmopressin ( control group n=48 ) . In 175 kidney recipients ( controls n=89 , desmopressin group n=86 ) we measured serum concentrations of creatinine and haemodialysis requirements to assess early renal function in the first 15 days after transplantation . We assessed long-term results of transplantation ( median time 45 months ) for a homogeneous subgroup of 95 recipients ( 48 in the desmopressin group ) . FINDINGS We found no significant differences between the two groups of brain-dead donors , except for final diuresis , which was lower in the desmopressin group than among controls . Haemodialysis requirement in controls and the desmopressin group ( 20 vs 23 % , p=0.63 ) and serum creatinine concentrations ( decrease from 903 micromol/L to 206 micromol/L vs 814 micromol/L to 193 micromol/L , p=0.14 ) did not differ significantly in the first 15 days after transplantation . Long-term graft survival was similar in the two groups ( 88 vs 87 % ) . INTERPRETATION Desmopressin can be given to brain-dead donors to limit the harmful effects of diabetes insipidus without any substantial effects to graft function in recipients While animal studies show that ischemic preconditioning ( IPC ) is beneficial in liver transplantation ( LT ) , evidence from few smaller clinical trials is conflicting . From October 2003 to July 2006 , 101 deceased donors ( DD ) were r and omized to 10 min IPC ( n = 50 ) or No IPC ( n = 51 ) . Primary objective was efficacy of IPC to decrease reperfusion ( RP ) injury . Both groups had similar donor risk index ( DRI ) ( 1.54 vs. 1.57 ) . Aminotransferases on days 1 and 2 were significantly greater ( p < 0.05 ) in IPC recipients . In multivariate analyses , IPC had an independent effect only on day 2 aspartate transferase . Prothrombin time , bilirubin and histological injury were similar in both groups . IPC had no significant effect on plasma TNF‐α , IL‐6 and IL‐10 in the donor and TNF‐α and IL‐6 in the recipient . In contrast , IPC recipients had a significant rise in systemic IL‐10 levels after RP ( p < 0.05 ) and had fewer moderate/severe rejections within 30 days ( p = 0.09 ) . Hospital stay was similar in both groups . One‐year patient and graft survival in IPC versus No IPC were 88 % versus 78 % ( p = 0.1 ) and 86 versus 76 % ( p = 0.25 ) , respectively . IPC increases RP injury after DDLT , an ‘ IPC paradox ’ . Other potential benefits of IPC are limited . IPC may be more effective in combination with other preconditioning regimens Our objective was to evaluate the impact of hydroxyethyl starch ( HES ) use in organ donors after neurologic determination of death ( DNDD ) on recipient renal graft outcomes . The following data elements were prospect ively collected for every DNDD managed by a single organ procurement organization from June 2011 to July 2013 : demographics ; critical care endpoints ; treatments , including the use of HES ; graft cold ischemia time ( CIT ) ; and the occurrence of recipient delayed graft function ( DGF , dialysis in the first week after transplantation ) . Logistic regression was performed to identify independent predictors of DGF with a p‐value < 0.05 . The results were then adjusted for each donor 's calculated propensity to receive HES . Nine hundred eighty‐six kidneys were transplanted from 529 donors . Forty‐two percent received HES ( 1217 ± 528 mL ) and 35 % developed DGF . Kidneys from DNDDs who received HES had a higher crude rate of DGF ( 41 % vs. 31 % , p < 0.001 ) . After accounting for the propensity to receive HES , independent predictors of DGF were age ( OR 1.02 [ 1.01–1.04 ] per year ) , CIT ( OR 1.04[1.02–1.06 ] per hour ) , creatinine ( OR 1.5 [ 1.32–1.72 ] per mg/dL ) and HES use ( OR 1.41 [ 1.02–1.95 ] ) . HES use during donor management was independently associated with a 41 % increase in the risk of DGF in kidney transplant recipients Brain death is associated with neuroendocrine changes , in particular with a significant reduction of plasma-free triiodothyronine ( T3 ) that results in impaired aerobic metabolism . Myocardial energy stores are reduced and tissue lactate increased . Cardiac function deteriorates . Similar metabolic changes are seen in patients undergoing open-heart surgery on cardiopulmonary bypass , including those undergoing heart transplantation . Therapy with T3 leads to a reversal of these metabolic changes , result ing in improved cardiac function . One hundred and sixteen consecutive potential donors have been so treated , as have 70 of the recipients . Immediate posttransplant cardiac function was good in all but 3 , and these hearts recovered to normal within a maximum of 24 hr of mechanical support . In 2 small r and omized trials in patients undergoing myocardial revascularization on cardiopulmonary bypass , postoperative T3 therapy was associated with a reduced need for inotropic support and diuretic therapy in the first study and improved cardiac output in the second study BACKGROUND As diabetes insipidus in brain-dead organ donors leads to hypovolaemia , hyponatraemia , and hypotension , desmopressin is recommended for treatment of diabetes insipidus . As its effect on early renal allograft function remains unclear , we conducted a study to evaluate the effect of desmopressin on renal-graft survival . METHODS We report the results of a prospect i ve study in 41 brain-dead organ donors ( mean age 45 + /- 12 years ) with diabetes insipidus , who were treated either with adequate fluid substitution and bolus application of desmopressin ( desmopressin group ; n = 22 ) or with volume substitution along ( control group ; n = 19 ) . Donors as well as recipients of both groups were well matched with respect to age , sex , dopamine dosage , serum electrolytes , cold ischaemic time , HLA match , number of prior transplantations , and current cytotoxic antibodies . Early renal allograft function was evaluated in 71 recipients ( mean age 48 + /- 4 years within 3 days after transplantation . RESULTS Overall , primary non-function was observed in 26 ( 36.6 % ) of 71 recipients . The rate of primary non-function was significantly higher in the desmopressin group compared to the control group ( desmopressin group 48.6 % ; control group 23.5 % ; P = 0.28 ) . CONCLUSION The use of desmopressin during organ procurement is associated with a higher rate of primary non-function of renal allografts The aim of the study was to evaluate safety and efficacy of IP in LT , particularly in marginal grafts . From 2007 to 2008 , 75 LT donors were r and omized to receive IP ( IP+ ) or not ( IP– ) . Considering the graft quality , we divided the main groups in two subgroups ( marg+/marg– ) . IP was performed by 10‐min inflow occlusion ( Pringle maneuver utilizing a toruniquet ) . Donor variables considered were gender , age , AST/ALT , ischemia time and steatosis . Recipient variables were gender , age , indication to LT and MELD/CHILD/UNOS score . AST/ALT levels , INR , bilirubin , lactic acid , bile output on postoperative days 1 , 3 and 7 were evaluated . Histological analysis was performed evaluating necrosis/steatosis , hepatocyte swelling , PMN infiltration and councilman bodies . Thirty patients received IP+ liver . No differences were seen between groups considering recipient and donor variables . Liver function and AST/ALT levels showed no significant differences between the main two groups . Marginal IP+ showed lower AST levels on day1 compared with untreated marginal livers ( 936.35 vs. 1268.23 ; p = 0.026 ) . IP+ livers showed a significant reduction of moderate‐severe hepatocyte swelling ( 33.3 % vs. 65.9 % ; p = 0.043 ) . IP+ patients had a significant reduction of positive early microbiological investigations ( 36.7 % vs. 57.1 % ; p = 0.042 ) . In our experience IP was safe also in marginal donors , showing a protective role against IRI Objective : Many organ procurement organizations have implemented critical care end points as donor management goals in efforts to increase organs transplanted per donor after neurologic determination of death . Although retrospective studies have demonstrated an association between meeting donor management goals and organ yield , prospect i ve studies are lacking . Design : In June 2008 , nine donor management goals were prospect ively implemented as a checklist and every donor after neurologic determination of death was managed to meet them . The donor management goals represented normal cardiovascular , pulmonary , renal , and endocrine end points . Data were collected for 7 months . Donor management goals “ met ” was defined a priori as achieving any seven of the nine donor management goals , and this was recorded at the time of consent , 12–18 hrs later , and prior to organ recovery . The primary outcome measure was ≥4 organs transplanted per donor , and binary logistic regression was used to identify independent predictors of this outcome with a p < .05 . Setting : All eight organ procurement organizations in the five Southwestern United States ( United Network for Organ Sharing Region 5 ) . Subjects : All st and ard criteria donors after neurologic determination of deaths . Intervention : Prospect i ve implementation of a donor management goal checklist . Measurements and Main Results : There were 380 st and ard criteria donors with 3.6±1.7 organs transplanted per donor . Fifteen percent had donor management goals met at the time of consent , 33 % at 12–18 hrs , and 38 % prior to organ recovery . Forty-eight percent had ≥4 organs transplanted per donor . Donors with ≥4 organs transplanted per donor had significantly more individual donor management goals met at all three time points . Independent predictors of ≥4 organs transplanted per donor were age ( odds ratio = 0.95 per year ) , final creatinine ( odds ratio = 0.75 per 1-unit increase ) , donor management goals “ met ” at consent ( odds ratio = 2.03 ) , donor management goals “ met ” prior to organ recovery ( odds ratio = 2.34 ) , and a change in the number of donor management goals achieved from consent to 12–18 hrs later ( odds ratio = 1.13 per additional donor management goal ) . Conclusions : Meeting donor management goals prior to consent and prior to organ recovery were both associated with achieving ≥4 organs transplanted per donor . However , only 15 % of donors have donor management goals met at the time of consent . The donor hospital management of patients with catastrophic brain injuries , before the intent to donate organs is known , affects outcomes and should remain a priority in the intensive care unit Brain‐dead organ donors are often dehydrated and have serum electrolyte disorders . This study was design ed to analyse the haemodynamic condition and serum electrolyte balance of liver donors . Two different fluid management plans for the harvesting operation were studied . Sixteen consecutive organ donors were included . They were r and omly infused either with a combination of colloid ( hydroxy ethyl starch ) and electrolyte solution ( group COL ) or with crystalloid fluid alone ( group CR ) . Arterial pressures , heart rate , central venous pressure and oesophageal temperature were monitored and serum electrolytes were analysed before the beginning of the operation and during harvesting . The amount of fluid needed in the COL group was signific and y less ( P<0.01 ) than in the CR group . There were no statistical differences between the groups in the haemodynamic parameters during the study period . The oesophageal temperature was maintained in both groups . All donors were initially hypernatraemic , but the serum sodium values returned towards normal during surgery in both groups . Immediate function was seen in all livers . In conclusion , the haemodynamic stability is maintained with a smaller infused volume if hydroxyethyl starch is combined with crystalloid fluids . The formation of interstitial oedema will be less when colloids are used , but its significance in organ donation needs further evaluation To assess the immediate and long‐term effects of ischemic preconditioning ( IPC ) in deceased donor . liver transplantation ( LT ) , we design ed a prospect i ve , r and omized controlled trial involving 60 donors : control group ( CTL , n = 30 ) or study group ( IPC , n = 30 ) . IPC was induced by 10‐min hiliar clamping immediately before recovery of organs . Clinical data and blood and liver sample s were obtained in the donor and in the recipient for measurements . IPC significantly improved biochemical markers of liver cell function such as uric acid , hyaluronic acid and Hypoxia‐Induced Factor‐1alpha ( HIF‐1α ) levels . Moreover , the degree of apoptosis was significantly lower in the IPC group . On clinical basis , IPC significantly improved the serum aspartate aminotransferase ( AST ) levels and reduced the need for reoperation in the postoperative period . Moreover , the incidence of primary nonfunction ( PNF ) was lower in the IPC group , but did not achieve statistical significance . We conclude that 10‐min IPC protects against I/R injury in deceased donor LT Background Multiple factors have been implicated in the process of ischemia-reperfusion injury ( IRI ) in organ transplantation . Among these factors , oxidative damage seems to initiate the injury . & agr;-lipoic acid ( ALA ) is a potent antioxidant that is used in patients with diabetic polyneuropathy . The aim of the present study was to determine the effect of ALA in patients undergoing simultaneous kidney-pancreas transplant by evaluating the functional recovery of the graft and biochemical markers of IRI . Methods Twenty-six patients were included in the following groups : ( i ) untreated control ; ( ii ) donor and recipient ( DR ) ALA-treated , in which ALA was administered both to the deceased donor and to the recipients ; and ( iii ) recipient ALA-treated group . The expression of inflammatory genes , as observed in biopsies taken at the end of surgery , as well as the serum cytokines , secretory leukocyte protease inhibitor , regenerating islet-derived protein 3&bgr;/pancreatitis-associated protein , amylase , lipase , glucose , and creatinine levels were quantified as markers of organ function . Results The DR group showed high levels of TGF&bgr ; and low levels of C3 and TNF&agr ; in the kidneys , whereas high levels of C3 and heme oxygenase were identified in pancreas biopsies . Decreases in serum IL-8 , IL-6 , secretory leukocyte protease inhibitor , and regenerating islet-derived protein 3 & bgr;/pancreatitis-associated protein were observed after surgery in the DR group . Serum lipase and amylase were lower in the DR group than in the control and recipient groups . Early kidney dysfunction and clinical pancreatitis were higher in the control group than in either treatment group . Conclusions These results show that ALA preconditioning is capable of reducing inflammatory markers while decreasing early kidney dysfunction and clinical posttransplant pancreatitis BACKGROUND Despite efforts to increase organ donation , there remain critical shortages in organ donors and organs procured per donor . Our trial is a large-scale , multicentre , r and omised controlled trial in brain-dead donors , to compare protocol ised care ( using minimally invasive haemodynamic monitoring ) with usual care . We describe the study design and discuss unique aspects of doing research in this population . METHODS Our study will r and omise brain-dead patients to protocol ised or usual care . The primary end point is the number of organs transplanted per donor . Secondary end points include number of transplantable organs per donor , recipient 6-month hospital-free survival time , and the relationship between the level of interleukin-6 and the number and usability of organs transplanted . The primary analysis will be an intention-to-treat analysis ; secondary analyses include modified intention-to-treat and as-treated analyses . The study will also compare the ratio of observed to expected number of organs transplanted per donor , by treatment arm , as a secondary end point . Preplanned subgroup analyses include restriction to extended criteria donors , and donors older or younger than 65 years . RESULTS AND CONCLUSIONS Several unique challenges for study design and execution can be seen in our trial , and it should generate results that will inform and influence the fields of organ donation and transplantation Objective We compared hemodynamic values , oxygen utilization , and adenine nucleotide concentration in the extracted organs of brain-dead donors treated with triiodothyronine vs. st and ard support treatment . Design Prospect i ve , r and omized , double-blind controlled study . Patients We recruited 52 consecutive adult cadaveric organ donors . Inclusion criteria were diagnosis of brain-death , transplantation suitability [ 1 ] , and family consent for donation ; exclusion criterion was preexisting thyroid disease . Interventions The treatment group ( n=29 ) received an intravenous bolus of 1 µg/kg triiodothyronine followed by continuous perfusion at 0.06 µg/kg per hour , and controls ( n=23 ) received 0.9 % ClNa delivered over 270 min . Hemodynamics , tonometry , thyroid hormones , and serum lactate were measured every 90 min from brain death to extraction procedure . Biopsies were processed to determine adenine nucleotides concentration . Results Hemodynamic measurements did not differ significantly in the two groups , and the inotrope dose could not be diminished after treatment . Thyrotropin levels increased from brain death to extraction procedure in controls . Thyrotropin measured 90 and 180 min after the beginning of the perfusion was significantly lower in the treatment group than controls . The Pco2 gap increased in both groups from brain death to the extraction procedure . The lactate level of the treatment group was lower than in controls . Biopsy specimens were obtained in 19 controls and in 20 donors of the treatment group ; the adenine nucleotides concentration did not show any significant difference . Conclusions Triiodothyronine did not add any benefit over the st and ard management of the organ donor nor did it affect the adenine nucleotides concentration of any biopsied organs Objective : Although a significant number of patients with severe brain injury develop acute lung injury , only intracranial risk factors have previously been studied . We investigated the role of extracranial predisposing factors , including hemodynamic and ventilatory management , as independent predictors of acute lung injury in brain-injured patients . Design : Prospect i ve multicenter observational study . Setting : Four European intensive care units in university-affiliated hospitals . Patients : Eighty-six severely brain-injured patients enrolled in 13 months . Interventions : None . Measurements and Main Results : All patients with severe brain injury ( Glasgow Coma Scale score < 9 ) were studied for 8 days from admission . Ventilatory pattern , respiratory system compliance , blood gas analysis , and hemodynamic profile were recorded and entered in a stepwise regression model . Length of stay in the intensive care unit , ventilator-free days , and mortality were collected . Eighteen patients ( 22 % ) developed acute lung injury on day 2.8 ± 1 . They were initially ventilated with significantly higher tidal volume per predicted body weight ( 9.5 ± 1 vs. 10.4 ± 1.1 ) , respiratory rate , and minute ventilation and more often required vasoactive drugs ( p < .05 ) . In addition to a lower Pao2/Fio2 ( odds ratio 0.98 , 95 % confidence interval 0.98–0.99 ) , the use of high tidal volume ( odds ratio 5.4 , 95 % confidence interval 1.54–19.24 ) and relatively high respiratory rate ( odds ratio 1.8 , 95 % confidence interval 1.13–2.86 ) were independent predictors of acute lung injury ( p < .01 ) . After the onset of acute lung injury , patients remained ventilated with similar tidal volumes to maintain mild hypocapnia and had a longer length of stay in the intensive care unit and fewer ventilator-free days ( p < .05 ) . Conclusions : In addition to a lower Pao2/Fio2 , the use of high tidal volume and high respiratory rate are independent predictors of acute lung injury in patients with severe brain injury . In this patient population , alternative ventilator strategies should be considered to protect the lung and guarantee a tight CO2 control Fifty cadaveric kidney donors were r and omly allocated to two groups . Group 1 received 5 grams of intravenously administered methylprednisolone two to four hours prior to organ harvesting after the pronouncement of brain death . Group 2 , which served as the control group , received no pretreatment . Of 100 kidneys harvested , 16 were discarded for various reasons , and 84 were transplanted and were available for evaluation , 40 from the pretreatment group and 44 from the control group . The transplant centers using these kidneys were unaware of the status of the kidney they received , that is , whether it was from a pretreated or a control group . The two groups of kidneys , pretreated and control , did not differ according to the length of warm or cold ischemia time or presence of preformed cytotoxic antibodies . The difference in graft failure between the two groups at three months was insignificant , even when the two groups were compared according to the method of preservation used Aspartate transaminase , a liver specific enzyme released into serum following acute liver injury , is used in experimental organ preservation studies as a measure of liver IR injury . Whether post-operative serum transaminases are a good indicator of IR injury and subsequent graft and patient survival in human liver transplantation remains controversial . A single centre prospect ively collected liver transplant data base was analysed for the period 1988 - 2012 . All patients were followed up for 5 years or until graft failure . Transaminase levels on the 1st , 3rd and 7th post-operative days were correlated with the patient demographics , operative outcomes , post-operative complications and both graft and patient survival via a binary logistic regression analysis . Graft and patient survival at 3 months was 80.3 % and 87.5 % . AST levels on the 3rd ( P = 0.005 ) and 7th ( P = 0.001 ) post-operative days correlated with early graft loss . Patients were grouped by their AST level ( day 3 ) : < 107iU , 107 - 1213iU , 1213 - 2744iU and > 2744iU. The incidence of graft loss at 3 months was 10 % , 12 % . 27 % and 59 % and 1-year patient mortality was 12 % , 14 % , 27 % and 62 % . Day 3 AST levels correlate with patient and graft outcome post-liver transplantation and would be a suitable surrogate endpoint for clinical trials in liver transplantation Donor lung utilization rates are persistently low primarily due to donor lung dysfunction . We hypothesized that a treatment that enhances the resolution of pulmonary edema by stimulating the rate of alveolar fluid clearance would improve donor oxygenation and increase donor lung utilization . We conducted a r and omized , blinded , placebo‐controlled trial of aerosolized albuterol ( 5 mg q4h ) versus saline placebo during active donor management in 506 organ donors . The primary outcome was change in oxygenation arterial partial pressure of oxygen/fraction of inspired oxygen [ PaO2/FiO2 ] from enrollment to organ procurement . The albuterol ( n = 260 ) and placebo ( n = 246 ) groups were well matched for age , gender , ethnicity , smoking , and cause of brain death . The change in PaO2/FiO2 from enrollment to organ procurement did not differ between treatment groups ( p = 0.54 ) nor did donor lung utilization ( albuterol 29 % vs. placebo 32 % , p = 0.44 ) . Donors in the albuterol versus placebo groups were more likely to have the study drug dose reduced ( 13 % vs. 1 % , p < 0.001 ) or stopped ( 8 % vs. 0 % , p < 0.001 ) for tachycardia . In summary , treatment with high dose inhaled albuterol during the donor management period did not improve donor oxygenation or increase donor lung utilization but did cause tachycardia . High dose aerosolized albuterol should not be used in donors to enhance the resolution of pulmonary edema Context Catecholamines and inflammatory mediators , with elevated levels after brain death , are associated with reduced function and survival of transplanted organs . Enteral nutrition reduces tissue damage and may benefit organs . Objective To evaluate the effects of immunomodulating enteral nutrition in organ donors . Design Prospect i ve , r and omized , open-label study . Setting Intensive care unit . Patients Thirty-six brain-dead organ donors . Interventions Donors were r and omized to receive enteral nutrition containing omega-3 polyunsaturated fatty acid , antioxidants , and glutamine or st and ard care ( fasting ) . Donors received hormonal replacement therapy of corticosteroid , levothyroxine , dextrose , and insulin . Main Outcome Measures Gastrointestinal assimilation ( measured by 13carbon-labeled uracil breath analysis ) , quantity of organs recovered , resting energy expenditure , urine level of urea nitrogen , and serum levels of albumin , prealbumin , interleukin 6 , tumor necrosis factor-α , and C-reactive protein were evaluated . Results Thirteen patients ( 36 % ) assimilated 13C-labeled uracil . Resting energy expenditure was significantly higher than predicted between 10 and 14 hours after baseline in 33 donors ( P = .007 ) . Other measures were not conclusively different between fed and fasting groups . No adverse events occurred that were related to the enteral feeding . Conclusions About 30 % of donors metabolized 13C-labeled uracil , although no difference in oxidation rate was found between fasting and fed donors . Corticosteroid administration lowers plasma levels of interleukin 6 and most likely contributes to greater than predicted resting energy expenditure . Thus energy needs may not be met during fasting if hormones are given . Consequences of this possible energy deficit warrant further study SUMMARY In a r and omized study we have been unable to demonstrate any beneficial effect of cadaver donor pretreatment with 5 g of methylprednisolone and 7 g of cyclophosphamide on graft function or survival in 22 recipients of pretreated kidneys compared with 30 recipients of nonpretreated kidneys Brain death is associated with increased inflammatory cytokines levels and poor graft quality to transplant . We aim ed to evaluate the impact of Ascorbic Acid ( AA ) on the inflammatory status of Brain-Dead Donors ( BDDs ) . Forty BDDs were r and omly divided into two groups . Donor treatment ( n=20 ) consisted of 100 mg/kg AA infusion 6 hours before donor operation and subsequent infusion of 100 mg/kg/p6h until organ removal . Blood sample s were taken at three times , 6 hours before donor surgery ( TP(1 ) ) , immediately after laparotomy ( TP(2 ) ) , and before organ removal ( TP(3 ) ) . Gene expression level and serum concentration of IL-6 and TNF-α cytokines were assessed by real-time PCR and ELISA methods . To investigate transplanted liver function , serum values of Aspartate Aminotransferase ( AST ) , Alanine Aminotransferase ( ALT ) , and Billirubin-Total were evaluated on the 1(st ) , 3(rd ) , and 10(th ) postoperative days . We found a significant reduction in IL-6 mRNA expression ratio of TP(3 ) to TP(1 ) following AA application among BDDs . Despite the considerable decrease in treated donors regarding IL-6 mRNA expression ratio of TP(2 ) to TP(1 ) , TP(3 ) to TP(2 ) , and also TNF-α variations in these periods , the results were not significant . Regarding serum concentration of these cytokines , particularly IL-6 , there was a decrease between TP(2 ) and TP(3 ) following AA application in the treated donors . Furthermore , a significant reduction was found in serum AST and ALT levels in the recipients of treated group on the 3(rd ) day compared to the 1(st ) day after transplantation . It seems that AA beneficially affects the inflammatory status of BDDs , result ing in improved primary allograft function Lung transplantation is limited by a shortage of suitable lung donors . Fluid loading is widely used to increase blood pressure during donor maintenance . In a prospect i ve study , we investigated the effect of fluid loading with lactated Ringers solution on pulmonary function in 26 brain-dead adult organ donors . In all patients , the initial central venous pressure ( CVP ) was < 6 mmHg . In 13 patients , a CVP of 8–10 mmHg was achieved and maintained for 90 min by an infusion of lactated Ringers solution . This result ed in a significant increase ( P<0.05 ) in the alveolar arterial oxygen gradient . In 13 patients , the CVP was maintained at 4–6 mmHg for 90 min by , if necessary , an infusion of lactated Ringers solution . In these patients , no significant change in the alveolar arterial oxygen gradient occurred . Pulmonary gas exchange has been shown to be a reliable means of evaluating donor lung function . We conclude that crystalloid fluid loading to a CVP of 8–10 mmHg may be deleterious to lung function and should be avoided in potential lung donors UNLABELLED Administration of catecholamines can lead to myocyte damage . Dopamine treatment is often used in potential cardiac donors to attain hemodynamic stability . Donor hearts exposed to dopamine are rejected or selected for transplantation without clearly defined criteria . A prospect i ve study was undertaken to analyze the clinical relevance of dopamine-induced myocardial lesions in 25 hearts ( 21 male , 4 female ; 15 - 40 years , mean : 26 + /- 7 ) that were later used for transplantation . Donors were divided into those who had received dopamine and those who had not . Dopamine doses ranged from 2 - 12.5 micrograms/kg/min ( mean : 6.3 + /- 3 ) . Time of administration was 3 - 26 hours ( mean : 16 + /- 8) . Use of dopamine was unrelated to donor electrocardiographic findings , intra- or postoperative death , or difficulty coming off by-pass . Postoperatively , filling pressures were similar in both groups of patients at 2 and 10 days postoperatively . Left ventricular ejection fraction was similar in the two groups . Dopamine requirements were significantly higher in the dopamine-treated hearts ( P = 0.05 ) . Histologic findings at first biopsy revealed infiltration and cell damage in a similar proportion of patients in both groups . IN CONCLUSION donor hearts exposed to dopamine can be accepted for transplantation if doses ranging from 2 - 12.5 micrograms/kg/min have been administered up to 24 hours In recent years , an increasing number of suboptimal grafts has been used to reduce the gap between the supply and dem and of organs for liver transplantation ( LT ) . In this r and omized prospect i ve study , we tested the impact of donor harvesting technique on the posttransplantation outcome of suboptimal donor livers . A modified double perfusion ( MDP ) technique ( aortic and portal cooling with tourniquet clamping of splenomesenteric vein inflow ) was compared with the single aortic perfusion ( SAP ) technique . Between February and November 2005 , 35 suboptimal grafts were r and omly assigned to either technique ( 18 MDP livers and 17 SAP livers ) . Donor and recipient variables were comparable in the 2 study groups . The SAP group had significantly higher blood transaminases and bilirubin levels after LT . The prevalence of graft primary dysfunction ( PDF ) was also significantly higher ( P=0.01 ) in the SAP group ( 35 % ) than in the MDP group ( 5 % ) . In 5 cases , all in the SAP group ( P=0.02 ) , early re-LT ( < 30 days ) was needed . The 6-month patient and graft survival rates were significantly higher in the MDP ( 100 % in both cases ) than in the SAP group ( 68 % and 58 % , respectively ) . The study was stopped in November 2005 , when the interim analysis revealed such markedly significant differences between the two groups . In conclusion , the present study showed a very low prevalence of PDF , death , and re-LT after transplantation with suboptimal liver when a MDP technique was used to harvest the donor graft In a prospect i ve study , we documented the hemodynamic effects of conventional donor maintenance in 24 brain-dead organ donors . Patients were then r and omized to receive either saline or a low dose arginine vasopressin ( AVP ) infusion . In the AVP group ( n = 11 ) , plasma hyperosmolality decreased ( P < 0.05 ) , blood pressure increased ( P < 0.01 ) , inotrope use decreased ( P < 0.01 ) , and cardiac output was maintained . In the control group ( n = 13 ) , plasma hyperosmolality increased ( NS ) ; no significant change in blood pressure , cardiac output , or inotrope infusion rate occurred . Myocardial ATP levels were higher in the AVP than the control group ( NS ) . Early organ function was similar in the 2 groups . We conclude that the use of a low dose AVP infusion enables inotrope use to be reduced and recommend consideration be given to the use of a low dose AVP infusion in potential thoracic organ donors The aim of the study was to evaluate the influence of reduced vascular resistance following calcium channel blocker verapamil administration on kidney function at 3 months after transplantation . A group of 48 kidneys received 100 microg verapamil by injection directly into renal artery before starting perfusion . The control group included 48 paired kidneys without verapamil addition . Calcium channel blocker therapy with verapamil greatly decreased renal vascular resistance but it did not affect graft function . Administration of calcium channel blockers improved kidney function in the early period after transplantation . A better-functioning graft seems to be based more on metabolic than hemodynamic effects BACKGROUND Prostagl and ins have been shown to protect against a variety of liver insults , including ischemia-reperfusion injury . Decreased graft injury and improved survival have been demonstrated in animal studies of liver transplantation after donor pretreatment with prostagl and in before organ retrieval . This potential clinical application has not been examined in human subjects . PATIENTS AND METHODS One hundred and six liver donors were r and omly assigned to receive either prostagl and in I2 ( epoprostenol , 500 microg intravenous bolus ) immediately before cold perfusion or no drug as control . Donor and recipient characteristics were recorded , and liver function tests were monitored after transplant to assess the effect of epoprostenol on graft injury . RESULTS Donor pretreatment with epoprostenol significantly improved the rapidity and homogeneity of graft reperfusion . Epoprostenol pretreatment also significantly reduced peak values of transaminases after transplantation : serum glutamic-pyruvic transaminase , control ( 851+/-121 international units [IU]/L ) and epoprostenol ( 463+/-78 IU/L ) ; serum glutamic-oxalaacetic transaminase , control ( 870+/-127 IU/L ) and epoprostenol ( 463+/-78 IU/L ) ; serum glutamate dehydrogenase , control ( 458+/-95 IU/L ) and epoprostenol ( 170+/-30 IU/L ) ; P<0.01 for all , by t test . Serum levels of bilirubin and alkaline phospatase were not significantly altered by donor pretreatment with epoprostenol . CONCLUSIONS Reduction of ischemia-reperfusion injury by administration of epoprostenol before graft retrieval may have important applications in liver transplantation . Further studies are required to establish the mechanism of this effect and to define its precise role in clinical practice Kidneys from donors after cardiac death ( DCD ) are at risk for inferior outcomes , possibly due to microthrombi and additional warm ischemia . We describe an organ procurement organization‐wide trial utilizing thrombolytic tissue plasminogen activator ( tPA ) during machine pulsatile perfusion ( MPP ) . A kidney from each recovered kidney pair was prospect ively r and omized to receive tPA ( 50 mg Alteplase ) or no tPA ( control ) in the MPP perfusate . From 2011 to 2013 , 24 kidneys were placed with enrolled recipients from 19 DCD kidney donors . There were no significant differences for absolute values of flow or resistance while undergoing MPP between the groups , nor rates of achieving discrete flow and resistance targets . While there was a trend toward lower creatinine and higher glomerular filtration rates in the tPA group at 3 , 6 , 9 , and 12 months , these differences were not significant . Delayed graft function ( DGF ) rates were 41.7 % in the tPA group vs. 58.4 % in the control group ( OR 0.51 , 95%CI 0.10–2.59 , p = 0.68 ) . Death‐censored graft survival was similar between the groups . In this pilot study , encouraging trends are seen in kidney allograft function independent of MPP parameters following DCD kidney transplantation for those kidneys receiving thrombolytic tPA and MPP , compared with st and ard MPP BACKGROUND / AIMS The efficacy of ischemic preconditioning ( IPC ) in preventing reperfusion injury in human liver transplants is still question ed . Phosphoinositide-3-kinase ( PI3 K ) is essential for IPC development in rodent livers . This work investigates whether PI3K-dependent signals might account for the inconsistent responses to IPC of transplanted human livers . METHODS Forty livers from deceased donors were r and omized to receive or not IPC before recovery . PI3 K activation was evaluated in biopsies obtained immediately before IPC and 2 h after reperfusion by measuring the phosphorylation of the PI3 K downstream kinase PKB/Akt and the levels of the PI3 K antagonist phosphatase tensin-homologue deleted from chromosome 10 ( PTEN ) . RESULTS IPC increased PKB/Akt phosphorylation ( p = 0.01 ) and decreased PTEN levels ( p = 0.03 ) in grafts , but did not significantly ameliorate post-transplant reperfusion injury . By calculating T(2h)/T(0 ) PKB/Akt phosphorylation ratios , 10/19 ( 53 % ) of the preconditioned grafts had ratios above the control threshold ( IPC-responsive ) , while the remaining nine grafts showed ratios comparable to controls ( IPC-non-responsive ) . T(2h)/T(0 ) PTEN ratios were also decreased ( p < or = 0.03 ) only in IPC-responsive grafts . The patients receiving IPC-responsive organs had ameliorated ( p < or = 0.05 ) post-transplant aminotransferase and bilirubin levels , while prothrombin activity was unchanged . CONCLUSIONS Impaired PI3 K signaling might account for the variability in the responses to IPC of human grafts from deceased donors Background & Aims Brain death-associated inflammatory response contributes to increased risk of impaired early liver allograft function , which might be counterbalanced by steroid pretreatment of the organ donor . The aim of this r and omized controlled trial was to eluci date whether steroid pretreatment of liver donors improves early liver allograft function , prevents rejection and prolongs survival . Methods A placebo-controlled blinded r and omized clinical trial was performed in three different centers in Austria and Hungary between 2006 and 2008 . Ninety deceased organ donors received either 1000 mg of methylprednisolone or placebo 6 h before recovery of organs . The primary end point was the concentration slope of transaminases within the first week . The secondary end point included survival and biopsy-confirmed acute rejection ( BCAR ) within 3 years after transplantation . Results Of the 90 r and omized donors , 83 recipients were eligible for study . The trajectories of ALT and AST were not different between treatments ( p = 0.40 and p = 0.13 , respectively ) . Eight subjects died in the steroid and 13 in the placebo group within 3 years after engraftment ( RR = 0.63 95 % CI [ 0.29 , 1.36 ] , p = 0.31 ) . Eleven recipients experienced biopsy-confirmed rejection ( BCAR ) in the steroid and 11 in the placebo group ( RR = 1.02 95 % CI [ 0.50 , 2.10 ] , p = 1.00 ) . No effect modification could be identified in the predefined strata of donor age , sex , cold ischemic time , and cause of donor death . Conclusions Steroid pretreatment of organ donors did not improve outcomes after liver transplantation |
1,053 | 30,340,537 | Conclusions Our study suggested that additional use of bisphosphonate was well-tolerated and more favorable in KTRs to improve BMD | Background Mineral bone disease constitutes a common complication of post-kidney transplantation , leading to great disability .
As there is no consensus on the optimal treatment for post-kidney transplant recipients ( KTRs ) , we aim ed to evaluate the efficacy and safety of bisphosphonate and its combined therapies . | 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 BACKGROUND We aim ed to investigate different treatment drugs for the prevention of post-transplant bone loss . METHODS Sixty adult male recent renal transplant recipients were enrolled into the study . Patients were r and omized into 4 groups : group I received daily alfacalcidol 0.5 microg PO ; group II received oral alendronate 5 mg/day ; group III received intranasal salmon calcitonin 200 IU every other day ; and group IV was considered a control group . Every patient was supplemented with daily 500 mg oral calcium carbonate . Parameters of bone metabolism were measured before and at 12 months after starting treatment . Bone mineral density ( BMD ) was measured by ( DEXA ) at lumber spine , femoral neck , and forearm before and after treatment period . RESULTS BMD was increased at lumber spine by 2.1 % , 0.8 % , 1.7 % , by 1.8 % , 0.6 % , 1.6 % at femoral neck , and by 3.2 % , 1.9 % , 2.6 % at forearm in groups I , II , and III , respectively , while it decreased by 3.2 % , 3.8 % , and 1.8 % at the same sites , respectively , in control group ( P= < 0.05 ) . iPTH level decreased significantly in group I , while the decrease was insignificant in other groups ( P= 0.003 ) . All other parameters were not statistically significant between treatment groups . Apart from transient hypocalcaemia in 3 patients in group II , and 2 patients in group III , no other significant adverse effects were noted . CONCLUSION This study proves that early bone loss that occurs during the first 12 months after renal transplantation could be prevented by alfacalcidol , calcitonin , or alendronate . Among the treatment groups , alfacalcidol significantly improved the hyperparathyroidism . All treatment drugs are safe and tolerable Daily bisphosphonate is effective in preventing and treating corticosteroid-induced osteoporosis in renal transplant recipients , although it frequently has gastrointestinal side effects . The aim was to assess efficacy and side effect profile of weekly oral risedronate . Eighty-four renal transplant patients , receiving either cyclosporin A or tacrolimus and steroids were prospect ively included . The study group ( 39 patients ) received 35 mg risedronate weekly , vitamin D and calcium , while control group ( 45 patients ) only vitamin D and calcium . At baseline , 6 and 12 months , creatinine , calcium , phosphorus , alkaline phosphatase and iPTH were determined . Fractures and bone mineral densities were assessed by X-rays and dual-energy X-ray absorptiometry , respectively . Pain was assessed by clinical interview . Mineral bone density score increased significantly in risedronate group after 1 year . There were no differences in the incidence of fractures , although , anamnestic pain assessment revealed that 3 % of treatment group reported to have bone pain compared with 18 % in nontreatment group ( P < 0.05 ) . Follow-up calcium , phosphorus , alkaline phosphatases , and iPTH levels showed no differences from basal measures . Risedronate was well tolerated with no major side effects . Weekly oral risedronate in renal transplanted patients reduces bone mineral loss and bone pain and has an excellent side effect profile BACKGROUND Bisphosphonates can prevent bone mineral density loss after renal transplantation , but their effect on trabecular mineralization and bone morphology , two key factors of bone stability , remains unknown . METHODS In a 6-month , r and omized , placebo-controlled study , 20 kidney transplant recipients received either 4 mg zoledronic acid or placebo twice within 3 months after engraftment . At transplantation and after 6 months , mean trabecular calcium concentration and trabecular morphometry were measured in bone biopsies . Bone mineral density ( BMD ) of the femoral neck and the lumbar spine were evaluated by dual-energy x-ray absorptiometry , and serum biochemical markers of bone metabolism were determined monthly . RESULTS Trabecular calcium content increased significantly in the zoledronic acid group , but remained unchanged in the placebo group . BMD at femoral neck showed no change in the zoledronic acid group , but decreased in the placebo group . BMD of the lumbar spine was increased in the zoledronic acid group without change in the placebo group . High-turnover bone disease resolved similarly in both groups , as evidence d by a significant decrease of eroded bone surface , osteoclast and osteoblast surface . Serologic markers of bone formation and resorption were significantly lower in zoledronic acid-treated patients throughout the study . Kidney transplant function was stable after zoledronic acid therapy . CONCLUSIONS Our results show that administration of zoledronic acid improves the calcium content of cancellous bone after kidney transplantation . The beneficial effect of bisphosphonate therapy is further evidence d by an increase of lumbar spine BMD , and stabilization of femur BMD BACKGROUND Osteopenia and osteoporosis are frequent complications after kidney transplantation . Data for the treatment of low bone mass after kidney transplantation are not available . METHODS To test the efficacy of antiresorptive treatment , 46 patients with osteopenia or osteoporosis after kidney transplantation ( bone mineral density < or = 1.5 SD below normal ) were r and omly assigned to three groups cyclically treated as follows : group 1 with daily oral clodronate ( 800 mg ) and group 2 with daily intranasal calcitonin ( 200 IU ) for 2 weeks every 3 months . These two groups were compared with a control group ( group 3 ) . Every patient was supplemented with 500 mg of calcium per day . Bone mineral density ( BMD ) was measured by dual energy x-ray absorptiometry ( DEXA ) at the lumbar spine and femoral neck before and after the 12-month treatment period . RESULTS BMD at the lumbar spine was increased by 4.6 % in the clodronate group ( n=15 , P=0.005 ) , by 3.2 % in the calcitonin group ( n=16 , P=0.034 ) , and by 1.8 % in the control group ( n=15 , P=0.265 ) . However , the differences in BMD changes among the groups were not statistically significant . During therapy , serum calcium decreased slightly in all groups by 4.6 % ; however , parathyroid hormone values increased significantly in the treatment groups by 116 % . Therapy was well tolerated without impact on graft function . CONCLUSIONS Cyclical therapy with clodronate or calcitonin appears to induce a gain in BMD at the lumbar spine in patients with low bone mass after kidney transplantation . This treatment had no adverse impact on graft function but may aggravate preexisting secondary hyperparathyroidism Background . Treatment with oral risedronate to prevent bone mineral density ( BMD ) loss in renal transplant recipients has been shown to be effective . There is no agreement on the optimum moment of introduction or how long it should be continued . The aim was to evaluate the effectiveness of risedronate at doses of 35 mg/week in renal transplant recipients who underwent treatment immediately after transplant . Methods . A r and omized clinical trial was performed on 101 renal transplant patients . The study group ( 52 patients ) received 35 mg risedronate weekly , vitamin D , and calcium , whereas the control group ( 49 patients ) received only vitamin D and calcium . At baseline , 3 , 6 , and 12 months , basic biochemistry and mineral bone metabolic parameters were determined . Vertebra and hip fracture assessment was performed by means of x-ray and DEXA ; an intention-to-treat analysis was performed . Results . Patients in control group showed a significant worsening of BMD ( P<0.05 ) 12 months into the study . At all follow-up points , lumbar BMD of the study group was significantly greater ( P<0.05 ) , whereas femoral BMD of those treated with risedronate was only significant at 6-month follow-up ( P<0.05 ) . There was a trend of more vascular calcifications and fractures in the control group , but this was not statistically significant . Conclusion . Weekly oral administration of risedronate immediately after renal transplantation contributes to an improved BMD , particularly in the femoral neck at 6-month follow-up , without major side effects . Long-term follow-up is needed to establish whether oral risedronate has an influence on vascular calcifications and bone fractures Renal transplant recipients are at risk of developing bone abnormalities that result in bone loss and bone fractures . These are related to underlying renal osteodystrophy , hypophosphatemia , and immunosuppressive treatment regimen . Although bisphosphonates are useful in ameliorating bone mineral loss after transplantation , it is not known whether their use in renal transplant patients leads to excessive suppression of bone turnover and increased incidence of adynamic bone disease . A r and omized , prospect i ve , controlled , clinical trial was conducted using the bisphosphonate pamidronate intravenously in patients with new renal transplants . Treatment subjects ( PAM ) received pamidronate with vitamin D and calcium at baseline and at months 1 , 2 , 3 , and 6 . Control ( CON ) subjects received vitamin D and calcium only . During months 6 to 12 , the subjects were observed without pamidronate treatment . Biochemical parameters of bone turnover were obtained monthly and , bone mineral density ( BMD ) was obtained at baseline and months 6 and 12 . Bone biopsies for mineralized bone histology were obtained at baseline and at 6 mo in a subgroup of subjects who underwent scheduled living donor transplantation . PAM preserved bone mass at 6 and 12 mo as measured by bone densitometry and histomorphometry . CON had decreased vertebral BMD at 6 and 12 mo ( 4.8 + /- 0.08 and 6.1 + /- 0.09 % , respectively ) . Biochemical parameters of bone turnover were similar in both groups at 6 and 12 mo . Bone histology revealed low turnover bone disease in 50 % of the patients at baseline . At 6 mo , all of PAM had adynamic bone disease , whereas 50 % of CON continued to have or developed decreased bone turnover . Pamidronate preserved vertebral BMD during treatment and 6 mo after cessation of treatment . Pamidronate treatment was associated with development of adynamic bone histology . Whether an improved BMD with adynamic bone histology is useful in maintaining long-term bone health in renal transplant recipients requires further study BACKGROUND Fracture rate after renal transplantation is substantially increased , is a source of morbidity and mortality , and correlates with osteopenia . The rate of bone loss after transplantation is time dependent . While we recorded marked bone loss during the first year after renal transplantation , bone loss in long-term recipients ( > 24 months ) was found to be similar to expected age-related decline . We have previously shown that treatment with pamidronate at the time of transplantation protected the skeleton over a 1-year study period . METHODS We have reexamined patients who participated in our original study , all of whom had been r and omized to receive either placebo or pamidronate ( 0.5 mg/kg ) at the time of transplantation and 1 month later . We now report 4-year data from 17 of the 26 original cohort . All patients received immunosuppression , comprising prednisolone , cyclosporine , and azathioprine . RESULTS We found that without prophylaxis bone loss at 4 years was substantial and significant at the femoral neck ( mean loss was -12.3 % ) but was not significant at the lumbar spine ( mean loss was -4.64 % ) . Patients who received two doses of pamidronate experienced no statistically significant bone loss at either the femoral neck or the lumbar spine . Patient characteristics of the placebo and treatment groups were similar with the exception of serum parathyroid hormone concentrations , which remained higher at 4 years in the pamidronate-treated patients ( 15.8 + /- 3.7 pmol/L vs. 9.8 + /- 1.8 pmol/L , P < 0.05 ) . CONCLUSION Without prophylaxis , most patients who continue to receive low dose glucocorticoids as part of maintenance immunosuppression manifest a substantial deficit in bone mineral density ( BMD ) at the femoral neck . In contrast , two doses of pamidronate given at the time of transplantation and 1 month later protected the skeleton from significant bone loss over the 4 years after transplantation Persistent hyperparathyroidism ( HPT ) after kidney transplantation ( KTx ) is associated with hypercalcemia , hypophosphatemia and abnormally high levels of parathyroid hormone ( PTH ) . In this r and omized trial , cinacalcet was compared to placebo for the treatment of hypercalcemia in adult patients with persistent HPT after KTx . Subjects were r and omized 1:1 to cinacalcet or placebo with r and omization stratified by baseline corrected total serum calcium levels ( ≤11.2 mg/dL [ 2.80 mmol/L ] or > 11.2 mg/dL [ 2.80 mmol/L ] ) . The primary end point was achievement of a mean corrected total serum calcium value < 10.2 mg/dL ( 2.55 mmol/L ) during the efficacy period . The two key secondary end points were percent change in bone mineral density ( BMD ) at the femoral neck and absolute change in phosphorus ; 78.9 % cinacalcet‐ versus 3.5 % placebo‐treated subjects achieved the primary end point with a difference of 75.4 % ( 95 % confidence interval [ CI ] : 63.8 , 87.1 ) , p < 0.001 . There was no statistical difference in the percent change in BMD at the femoral neck between cinacalcet and placebo groups , p = 0.266 . The difference in the change in phosphorus between the two arms was 0.45 mg/dL ( 95 % CI : 0.26 , 0.64 ) , p < 0.001 ( nominal ) . No new safety signals were detected . In conclusion , hypercalcemia and hypophosphatemia were effectively corrected after treatment with cinacalcet in patients with persistent HPT after KTx Fractures are common in chronic kidney disease ( CKD ) . The optimal methods by which to assess fracture risk are unknown , in part , due to a lack of prospect i ve studies . We determined if bone mineral density ( BMD ) by dual-energy X-ray absorptiometry ( DXA ) , and /or high-resolution peripheral quantitative computed tomography ( HRpQCT ) could predict fractures in men and women ≥18 years old with stages 3 to 5 CKD . BMD was measured by DXA ( at the total hip , lumbar spine , ultradistal , and 1/3 radius ) and by HRpQCT ( at the radius ) , and subjects were followed for 2 years for incident morphometric spine fractures and low-trauma clinical fractures . The mean age of the subjects was 62 years with equal numbers having stages 3 , 4 , and 5 CKD . Over 2 years there were 51 fractures in 35 subjects . BMD by DXA at baseline was significantly lower at all sites among those with incident fractures versus those without . For example , the mean BMD at the total hip in those with incident fractures was 0.77 g/cm2 ( 95 % confidence interval [ CI ] , 0.73 to 0.80 ) and in those without fracture was 0.95 g/cm2 ( 95 % CI , 0.92 to 0.98 ) . Almost all baseline HRpQCT measures were lower in those with incident fracture versus those without . For example , volumetric BMD in those with incident fractures was 232 mg HA/cm3 ( 95 % CI , 213 to 251 ) and in those without fracture was 317.6 mg HA/cm3 ( 95 % CI , 306 to 329.1 ) . Bone loss occurred in all subjects , but was significantly greater among those with incident fractures . Our data demonstrate that low BMD ( by DXA and HRpQCT ) and a greater annualized percent decrease in BMD are risk factors for subsequent fracture in men and women with predialysis CKD Summary This study evaluates the efficacy of low doses of pamidronate after renal transplantation to prevent bone loss in osteopenic patients . Results show that pamidronate is safe and significantly reduced spinal bone loss when administered immediately after renal transplantation . Introduction The purpose of this work is to evaluate the efficacy of two intravenous infusions of pamidronate in the immediate post-transplant period in a renal transplant ( RT ) population . Methods In this 12-month , r and omized , double-blind , multicenter trial , 39 kidney recipients with diagnosed osteopenia received two doses of 30 mg of disodium pamidronate ( n = 24 ) or placebo ( n = 15 ) , at surgery and 3 months post-RT . All patients received calcium and vitamin D. Bone density of the lumbar spine and total femur was measured by dual-energy X-ray absorptiometry ( DXA ) and X-rays were performed at RT , 6 and 12 months post-RT . Biochemical and hormonal determinations were performed before and after treatment . Results Pamidronate significantly reduced spinal bone loss , but no significant benefit was found for the incidence of fractures . Elevated baseline intact parathyroid hormone ( iPTH ) and bone remodeling markers returned to normal levels 3 months post-RT . However , normal procollagen type I N propeptide ( PINP ) concentrations were only maintained in the pamidronate group . After RT , a comparable graft function was observed in both groups according to creatinine values , 25-hydroxyvitamin-D ( 25-OH-D ) levels were improved , and serum calcium levels normalized after a transient fall during the first 3 months . Conclusion A low dose of pamidronate prevents bone loss in osteopenic patients when administered immediately after RT INTRODUCTION Steroid-induced osteoporosis is a major problem after organ transplantation . There is considerable evidence that bisphosphonates are effective in decreasing osteoporosis . AIM This prospect i ve study was carried out to see the effects of bisphosphonates on bone mineral density ( BMD ) after successful renal transplantation . MATERIAL AND METHODS Fifty consecutive patients of successful renal transplantation were r and omized into two groups . Group A ( n = 27 ) received 35 mg/wk of Alendronate for 6 months after transplantation . Group B ( n = 23 ) did not receive Alendronate and served as a control . Both groups underwent a pretransplant baseline dual-energy X-ray absorptiometry ( DEXA ) scan of their hips and lumber spines . Both groups received oral calcium and vitamin D supplement . Both groups were matched for the regimen and dose of immunosuppressive drugs . BMD was measured at 3 months and 6 months after transplantation . RESULTS Both groups showed a decline in BMD in early months posttransplantation . However , the 6-month DEXA scans showed a significant rise in BMD in group A as compared to group B. CONCLUSION Bisphosphonates appear to have a beneficial effect on steroid-induced bone loss Very rapid bone loss , osteopenia , and osteoporosis have been documented in the first 6 to 12 mo after renal transplantation . Investigated was the effect of treatment with active vitamin D on the prevention of posttransplantation bone loss . Forty adult men who were recent renal transplant recipients were enrolled onto the study . Patients were r and omized into two groups : group 1 received daily alfacalcidol 0.5 micro g by mouth , and group 2 ( control ) received placebo . Every patient in both groups received daily 500-mg calcium carbonate supplements . Parameters of bone metabolism and bone mineral density measured at three sites were assessed before and after the study period . Bone mineral density was increased by 2.1 % , 1.8 % , and 3.2 % at lumbar spine , femoral neck , and forearm , respectively , in group 1 , whereas it decreased by 3.2 % , 3.8 % , and 1.8 % at the same sites in the control group ( P < 0.05 ) . Serum intact parathyroid hormone level decreased significantly in group 1 compared with the control group ( P = 0.003 ) . Early bone loss that occurs during the first 1 yr after renal transplantation could be prevented by alfacalcidol . Use of alfacalcidol early after transplantation is safe and well tolerated BACKGROUND We recently showed that two doses of 4 mg of zoledronic acid ( ZOL ) ameliorated the bone loss and improved bone histology within the first six months after kidney transplantation . The aim of the present study was to evaluate whether this early short-term intervention exhibited a sustained bone-sparing effect . METHODS A homogenous group of 20 de novo renal transplant recipients were equally r and omized to two infusions of 4 mg of ZOL or placebo at two weeks and three months after engraftment . Patients were followed up for three years by sequential determination of bone densitometry and specific biochemical markers . RESULTS From month six to three years after transplantation , both treatment groups exhibited an improvement of bone mineralization . Femoral neck bone mineral density z-scores increased statistically significantly from -1.3 ( 2.6 ) to -0.2 ( 3.6 ) in the placebo group and from -1.6 ( 2.9 ) to -1.2 ( 1.9 ) in the ZOL group ( median , range ) . Biochemical parameters of osteoblast activity such as osteocalcin and bone-specific alkaline phosphatase did not increase significantly in both groups . Osteoprotegerin , a marker of osteoclast inhibition , was significantly elevated over the first six months in the ZOL group , but decreased to similar levels , as in the placebo group , over the next two and a half years . Other markers of osteoclast activity such as c-telopeptide of type 1 collagen , calcitonin , and intact parathyroid hormone were not different between six months and three years in either group . CONCLUSION The early bone-sparing effect of short-term ZOL therapy confers no sustained benefit versus placebo at three year post-transplantation Background . Reduced bone mineral density ( BMD ) is common in long-term renal transplant recipients and results in a high incidence of fractures . The optimal therapy for these patients is not known . Methods . Baseline BMD determinations were obtained in 211 long-term adult renal transplant recipients . One hundred and seventeen patients with a reduced BMD ( T score ≤ −1 ) were r and omly assigned to treatment with alendronate and calcium ( n=60 ) versus calcitriol and calcium ( n=57 ) . Of these , 46 and 51 patients , respectively , completed 1 year of treatment . Forty-nine patients who were not eligible or did not consent to the trial were followed prospect ively . Results . Reduced baseline BMD ( T score ≤ −1 ) was present in 159 ( 78.7 % ) of patients at the lumbar spine or femur . There was no significant loss of BMD in the prospect ively followed patients during 2.7 years . The average lumbar BMD increased from 0.984±0.149 to 1.025±0.143 g/cm2 ( P < 0.001 ) with alendronate and from 1.014±0.15 to 1.034±0.146 g/cm2 ( P = 0.002 ) with calcitriol . BMD at the femur increased from 0.809±0.092 to 0.836±0.107 g/cm2 ( P < 0.001 ) with alendronate and from 0.830±0.144 to 0.857±0.125 g/cm2 ( P = 0.023 ) with calcitriol . Conclusions . One year of treatment with alendronate or calcitriol , both with calcium supplementation , result ed in significant increases in BMD at the lumbar spine and femur , with a trend toward alendronate being more effective at the spine ( P = 0.082 ) . Further studies are needed to determine whether BMDs continue to increase after 1 year and whether there is any additional benefit to combining vitamin D and alendronate . Larger studies are needed to determine whether treatment decreases fracture rates UNLABELLED Bone loss is a common complication among renal transplant patients . Some studies have shown that alendronate may be effective to treat bone loss in these patients . In this study , we have reported our experience with administration of alendronate to treat bone loss in renal transplanted patients . METHODS The 46 kidney transplant recipients with bone loss were r and omly divided into 2 groups : group I was treated with calcium and calcitriol , and group II with calcium , calcitriol , and alendronate . We examined bone mineral density ( BMD ) and biochemical indicators of both groups . All patients received cyclosporine and prednisone treatment . RESULTS There was no significant difference in age , body mass index , gender , immunosuppression , time since transplantation , 25(OH)D(3 ) , or intact parathyroid hormone levels at study commencement . The BMD of the femoral neck was significantly increased ( P < .05 ) , and the serum type I collagen-cross-linked N telopeptide ( NTx ) dramatically ( P < .05 ) decreased in posttransplantation group II recipients treated with calcium , calcitriol , and alendronate . There were also significant differences in BMD and serum NTx between recipients treated with versus without alendronate ( P < .05 ) . CONCLUSION At least in the short term , alendronate is a effective inhibitor for the treatment of bone loss in renal transplantation patients We sought to compare the treatment modalities of alendronate , alfacalcidol , and alendronate combined with alfacalcidol in renal transplant recipients with low bone mineral density . Sixty-four kidney graft recipients ( 22 women , 42 men ) were recruited to this study . Of these 64 patients , 9 served as the control group with T scores more than -1 . The remaining 55 patients r and omly assigned to treatment had T scores less than -1 and were assigned to 3 groups : group 1 received alfacalcidol ( 0.5 microg/d ) ; group 2 , alendronate ( 10 mg/d ) ; and group 3 , alendronate ( 10 mg/d ) + alfacalcidol ( 0.5 microg/d per os ) . Twenty-five patients were allocated to alfacalcidol , 13 patients to alendronate , and 17 patients to alendronate + alfacalcidol treatment . Bone mineral densities of the lumbar spine and femoral neck were measured before and 12 months after treatment . The groups were compared for risk factors of osteoporosis , biochemistry , and bone mineral density . Kruskal-Wallis , one-way ANOVA , and Student t tests were used . With the alendronate + alfacalcidol group , bone mineral density at the lumbar spine significantly increased by 7.9 % ( P = .006 ) with a significant improvement in T score ( P = .003 ) . Bone mineral density at the femoral neck significantly increased by 8 % in the alendronate + alfacalcidol group ( P = .01 ) with a significant improvement in T score ( P = .02 ) . The use of a combination of alendronate and alfacalcidol seemed to be safe and more effective than the separate use of the 2 agents to improve bone mass in renal transplant recipients |
1,054 | 30,946,319 | 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 . | Background : Whether bridging strategies[intravenous thrombolysis ( IVT ) + mechanical thrombectomy ( MT ) ] are superior to mechanical thrombectomy alone for large vessel occlusion(LVO ) is still uncertain .
A systematic review and meta- analysis was conducted to investigate and evaluate comparative efficacy and safety of bridging strategies vs direct MT in patients with LVO . | 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 = 0.53 ) . Rates of symptomatic intracranial hemorrhage [ 13.8 % ( 19/138 ) vs. 13.0 % ( 18/138 ) , P = 1.00 ] and mortality [ 25.4 % ( 35/138 ) vs. 23.9 % ( 33/138 ) , P = 0.88 ] within 90 days were also not significantly different . Patients in the DEVT group had a lower rate of asymptomatic intracranial hemorrhage [ 28.3 % ( 39/138 ) vs. 44.9 % ( 62/138 ) , P = 0.01 ] and a higher rate of successful reperfusion [ 92.0 % ( 127/138 ) vs. 81.9 % ( 113/138 ) , P = 0.02 ] . CONCLUSIONS Our results suggest that , in Chinese patients with anterior circulation LVO stroke , direct endovascular mechanical thrombectomy initiated within an intravenous thrombolysis time window carries similar effectiveness to that of bridging therapy and a decreased asymptomatic intracranial hemorrhage risk . DEVT may be an alternative for bridging therapy . Future r and omized controlled trials are warranted BACKGROUND Whether intravenous thrombolysis ( IVT ) before mechanical thrombectomy ( MT ) provides additional benefits remains controversial . We aim ed to compare clinical and radiologic outcomes between IVT+MT and MT alone groups . METHODS We retrospectively review ed the clinical and radiological features of patients from the prospect ively collected data base who sustained anterior circulation stroke due to large vessel occlusion ( LVO ) and were treated with MT within 8 hours of symptom onset . We compared rates of successful reperfusion , functional independence and mortality at 90 days , and symptomatic intracranial hemorrhage ( sICH ) as clinical endpoints between the 2 groups . RESULTS The 81 patients included in this study included 38 ( 46.9 % ) in the MT alone group ( mean age , 72.6 ± 14.1 years ; 17 males [ 44.7 % ] ) and 43 in the IVT+MT group ( mean age , 68.9 ± 12.8 years ; 29 males [ 67.4 % ] ) . There were no significant differences in patient baseline characteristics between the 2 groups except for a male predominance in the IVT+MT group . The mean interval from onset to groin puncture ( 221.6 ± 110.5 minutes vs. 204.7 ± 63.7 minutes ; P = 0.472 ) and the rate of successful reperfusion rate ( thrombolysis in cerebral infa rct ion 2b/3 , 60.5 % vs. 58.1 % ; P = 0.827 ) did not differ significantly between the MT and IVT+MT groups . The rate of favorable functional outcome , as determined by a modified Rankin Scale score 0 - 2 ( 36.8 % vs. 51.2 % ; P = 0.263 ) and mortality at 90 days ( 18.4 % vs. 9.3 % ; P = 0.332 ) , and the rate of sICH ( 5.3 % vs. 4.6 % ; P = 1.000 ) were also not significantly different between the 2 groups . CONCLUSIONS This study suggests that previous IVT might not facilitate successful reperfusion and favorable functional outcomes in patients with anterior circulation stroke treated with MT . MT alone can be a safe and effective treatment modality in patients who are ineligible for IVT for various reasons Recent clinical trials demonstrated that mechanical thrombectomy ( MT ) using second-generation endovascular devices has beneficial effects in acute ischemic stroke ( AIS ) due to large vessel occlusion ( LVO ) . However , it remains controversial if intravenous thrombolysis ( IVT ) prior to MT is superior compared to direct mechanical thrombectomy ( DMT ) . The aims of this study were to compare short and long-term outcomes between IVT + MT and DMT patients . We prospect ively recruited AIS patients with LVO in the anterior or posterior circulation eligible for MT with and without prior IVT . Modified Rankin Scale ( mRS ) and mortality were assessed at baseline , at discharge , 90-days and 1-year after stroke . Favorable outcome was defined as a mRS score ≤2 . Of the 66 patients included , 33 ( 50 % ) were in IVT + MT group and 33 ( 50 % ) were in DMT group . Except for a higher prevalence of patients using anticoagulants at admission in DMT group , baseline characteristics did not differ in the two groups . Procedural characteristics were similar in IVT + MT and DMT group . Rate of favorable outcome was significantly higher in IVT + MT patients than DMT ones both 90-days ( 51.5 vs. 18.2 % ; p = 0.004 ) and 1-year ( 51.5 vs. 15.2 % ; p = 0.002 ) after stroke . DMT patients were six times more likely to die during the 1-year follow-up compared to IVT + MT patients . This study suggests that bridging therapy may improve short and long-term outcomes in patients eligible for endovascular treatment . Further studies with larger patient numbers and r and omized design are needed to confirm our findings BACKGROUND Among patients with a proximal vessel occlusion in the anterior circulation , 60 to 80 % of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment . We evaluated rapid endovascular treatment in addition to st and ard care in patients with acute ischemic stroke with a small infa rct core , a proximal intracranial arterial occlusion , and moderate-to-good collateral circulation . METHODS We r and omly assigned participants to receive st and ard care ( control group ) or st and ard care plus endovascular treatment with the use of available thrombectomy devices ( intervention group ) . Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset . Patients with a large infa rct core or poor collateral circulation on computed tomography ( CT ) and CT angiography were excluded . Workflow times were measured against predetermined targets . The primary outcome was the score on the modified Rankin scale ( range , 0 [ no symptoms ] to 6 [ death ] ) at 90 days . A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care ( shift analysis ) . RESULTS The trial was stopped early because of efficacy . At 22 centers worldwide , 316 participants were enrolled , of whom 238 received intravenous alteplase ( 120 in the intervention group and 118 in the control group ) . In the intervention group , the median time from study CT of the head to first reperfusion was 84 minutes . The rate of functional independence ( 90-day modified Rankin score of 0 to 2 ) was increased with the intervention ( 53.0 % , vs. 29.3 % in the control group ; P<0.001 ) . The primary outcome favored the intervention ( common odds ratio , 2.6 ; 95 % confidence interval , 1.7 to 3.8 ; P<0.001 ) , and the intervention was associated with reduced mortality ( 10.4 % , vs. 19.0 % in the control group ; P=0.04 ) . Symptomatic intracerebral hemorrhage occurred in 3.6 % of participants in intervention group and 2.7 % of participants in control group ( P=0.75 ) . CONCLUSIONS Among patients with acute ischemic stroke with a proximal vessel occlusion , a small infa rct core , and moderate-to-good collateral circulation , rapid endovascular treatment improved functional outcomes and reduced mortality . ( Funded by Covidien and others ; ESCAPE Clinical Trials.gov number , NCT01778335 . ) Background and Purpose : Endovascular thrombectomy ( EVT ) improves the functional outcome when added to best medical therapy , including alteplase , in patients with acute ischaemic stroke secondary to large vessel occlusion ( LVO ) in the anterior circulation . However , the evidence for EVT in alteplase-ineligible patients is less compelling . It is also uncertain whether alteplase is necessary in patients with successful recanalization by EVT , as the treatment effect of EVT may be so powerful that bridging alteplase may not add to efficacy and may compromise safety by increasing bleeding risks . We aim ed to survey the proportion of patients suitable for EVT who are alteplase-ineligible and to compare the safety and effectiveness of st and ard care of acute large artery ischaemic stroke by EVT plus thrombolysis with that of EVT alone in a tertiary hospital clinical stroke service . Methods : We performed a retrospective analysis of acute ischaemic stroke patients treated with EVT at our centre between October 2013 and April 2016 , based on a registry with prospect i ve and consecutive patient collection . Individual patient records were retrieved for review . Significant early neurological improvement was defined as a NIHSS score of 0–1 , or a decrease from baseline of ≤8 , at 24 h after stroke onset . Results : Fifty patients with acute ischaemic stroke secondary to LVO in the anterior circulation received EVT in this period , of whom 21 ( 42 % ) received concurrent alteplase and 29 ( 58 % ) EVT alone . The 2 groups had similar baseline characteristics and similar outcomes . Significant neurological improvement at 24 h occurred in 47.6 % of the patients with EVT and bridging alteplase and in 51.7 % of the patients with EVT alone ( p = 0.774 ) . Mortality during acute hospitalization was 20 % for the bridging alteplase group versus 7.1 % for EVT alone ( p = 0.184 ) . Intracranial haemorrhage rates were 14.3 % for bridging alteplase versus 20.7 % for EVT alone ( p = 0.716 ) . Local complications , groin haematoma ( 23.8 vs. 10.3 % ) and groin pseudoaneurysms ( 4.8 vs. 0 % ) ( p = 0.170 ) , were not significantly different . Conclusion : Our study highlights the relatively large proportion of patients suitable for EVT who have a contraindication to alteplase and raises the hypothesis that adding alteplase to successful EVT may not be necessary to optimize functional outcome . The results are consistent with observational data from other endovascular centres and support a r and omised controlled trial of EVT versus EVT with bridging alteplase Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background and Purpose — Five r and omized controlled trials have consistently shown that mechanical thrombectomy ( MT ) in addition to best medical treatment ( ±intravenous tissue-type plasminogen activator ) improves outcome after acute ischemic stroke in patients with large artery anterior circulation stroke . Whether direct MT is equally effective as combined intravenous thrombolysis with MT ( ie , bridging thrombolysis ) remains unclear . Methods — We retrospectively compared clinical and radiological outcomes in 167 bridging patients with 255 patients receiving direct MT because of large artery anterior circulation stroke . We matched all patients from the direct MT group who would have qualified for intravenous tissue-type plasminogen activator with controls from the bridging group , using multivariate and propensity score analyses . Functional independence was defined as modified Rankin Scale score of 0 to 2 . Results — From February 2009 to August 2014 , 40 patients from the direct MT group would have qualified for bridging thrombolysis but were treated with MT only . Clinical and radiological characteristics did not differ from the bridging cohort , except for higher rates of hypercholesterolemia ( P=0.019 ) , coronary heart disease ( P=0.039 ) , and shorter intervals from symptom onset to endovascular intervention ( P=0.01 ) in the direct MT group . Functional independence , mortality , and intracerebral hemorrhage rates did not differ ( P>0.1 ) . After multivariate matching analysis outcome in both groups did not differ , except for lower rates of asymptomatic intracerebral hemorrhage ( P=0.023 ) and lower mortality ( P=0.007 ) in the direct MT group . Conclusions — In patients with large anterior circulation stroke , direct mechanical intervention seems to be equally effective as bridging thrombolysis . A r and omized trial comparing direct MT with bridging therapy is warranted BACKGROUND Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear . METHODS In this study , we r and omly assigned patients within 8 hours after the onset of large-vessel , anterior-circulation strokes to undergo mechanical embolectomy ( Merci Retriever or Penumbra System ) or receive st and ard care . All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain . R and omization was stratified according to whether the patient had a favorable penumbral pattern ( substantial salvageable tissue and small infa rct core ) or a nonpenumbral pattern ( large core or small or absent penumbra ) . We assessed outcomes using the 90-day modified Rankin scale , ranging from 0 ( no symptoms ) to 6 ( dead ) . RESULTS Among 118 eligible patients , the mean age was 65.5 years , the mean time to enrollment was 5.5 hours , and 58 % had a favorable penumbral pattern . Revascularization in the embolectomy group was achieved in 67 % of the patients . Ninety-day mortality was 21 % , and the rate of symptomatic intracranial hemorrhage was 4 % ; neither rate differed across groups . Among all patients , mean scores on the modified Rankin scale did not differ between embolectomy and st and ard care ( 3.9 vs. 3.9 , P=0.99 ) . Embolectomy was not superior to st and ard care in patients with either a favorable penumbral pattern ( mean score , 3.9 vs. 3.4 ; P=0.23 ) or a nonpenumbral pattern ( mean score , 4.0 vs. 4.4 ; P=0.32 ) . In the primary analysis of scores on the 90-day modified Rankin scale , there was no interaction between the pretreatment imaging pattern and treatment assignment ( P=0.14 ) . CONCLUSIONS A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke , nor was embolectomy shown to be superior to st and ard care . ( Funded by the National Institute of Neurological Disorders and Stroke ; MR RESCUE Clinical Trials.gov number , NCT00389467 . ) Background and Purpose — Whether intravenous thrombolysis adds a further benefit when given before endovascular thrombectomy ( EVT ) is unknown . Furthermore , intravenous thrombolysis delays time to groin puncture , mainly among drip and ship patients . Methods — Using region-wide registry data , we selected cases that received direct EVT or combined intravenous thrombolysis+EVT for anterior circulation strokes between January 2011 and October 2015 . Treatment effect was estimated by stratification on a propensity score . The average odds ratios for the association of treatment with good outcome and death at 3 months and symptomatic bleedings at 24 hours were calculated with the Mantel – Haenszel test statistic . Results — We included 599 direct EVT patients and 567 patients with combined treatment . Stratification through propensity score achieved balance of baseline characteristics across treatment groups . There was no association between treatment modality and good outcome ( odds ratio , 0.97 ; 95 % confidence interval , 0.74–1.27 ) , death ( odds ratio , 1.07 ; 95 % confidence interval , 0.74–1.54 ) , or symptomatic bleedings ( odds ratio , 0.56 ; 95 % confidence interval , 0.25–1.27 ) . Conclusions — This observational study suggests that outcomes after direct EVT or combined intravenous thrombolysis+EVT are not different . If confirmed by a r and omized controlled trial , it may have a significant impact on organization of stroke systems of care Background No r and omized trial has investigated the effect of mechanical thrombectomy ( MT ) alone in patients with acute stroke . There are conflicting results as to whether prior intravenous thrombolysis ( IVT ) facilitates subsequent MT , and data in patients treated with MT alone owing to contraindications to IVT are limited . Objective To compare consecutive patients treated with MT alone or with preceding IVT in a large tertiary neurointerventional center , with special emphasis on contraindications to IVT . Methods Retrospective analysis of 283 consecutive patients with acute ischemic stroke treated with MT in a tertiary neurovascular center over 14 months . Data on characteristics of periprocedural times , recanalization rate , complications , and long-term functional outcome were collected prospect ively . Results Information on prior IVT and functional outcome was available in 250 patients . Mean ( SD ) follow-up period was 5.7 ( 5.1 ) months and 105 ( 42 % ) patients received both IVT and MT . No significant differences were found in successful recanalization rates ( Thrombolysis in Cerebral Infa rct ion ( TICI ) 2b/3 , 73.8 % vs 73.1 , p=0.952 ) , complication rates , and long-term favorable outcome ( modified Rankin Scale 0–2 , 35.2 % vs 40 % , p=0.444 ) between patients receiving MT plus IVT and those receiving MT alone . A favorable outcome in patients directly treated with MT alone who were eligible for IVT was achieved in 48.2 % . Thrombectomy was safe and result ed in a favorable outcome in 32 % of patients with absolute contraindications to IVT . Conclusions Preceding use of IVT was not an independent predictor of favorable outcome in patients with acute stroke treated with MT and complication rates did not differ whether or not IVT was used . MT is safe and achieved a favorable outcome in one-third of patients with stroke ineligible for IVT BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator ( t-PA ) for patients with moderate-to-severe acute ischemic stroke , but whether a combined approach is more effective than intravenous t-PA alone is uncertain . METHODS We r and omly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone , in a 2:1 ratio . The primary outcome measure was a modified Rankin scale score of 2 or less ( indicating functional independence ) at 90 days ( scores range from 0 to 6 , with higher scores indicating greater disability ) . RESULTS The study was stopped early because of futility after 656 participants had undergone r and omization ( 434 patients to endovascular therapy and 222 to intravenous t-PA alone ) . The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment ( 40.8 % with endovascular therapy and 38.7 % with intravenous t-PA ; absolute adjusted difference , 1.5 percentage points ; 95 % confidence interval [ CI ] , -6.1 to 9.1 , with adjustment for the National Institutes of Health Stroke Scale [ NIHSS ] score [ 8 - 19 , indicating moderately severe stroke , or ≥20 , indicating severe stroke ] ) , nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher ( 6.8 percentage points ; 95 % CI , -4.4 to 18.1 ) and those with a score of 19 or lower ( -1.0 percentage point ; 95 % CI , -10.8 to 8.8 ) . Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days ( 19.1 % and 21.6 % , respectively ; P=0.52 ) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA ( 6.2 % and 5.9 % , respectively ; P=0.83 ) . CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA , as compared with intravenous t-PA alone . ( Funded by the National Institutes of Health and others ; Clinical Trials.gov number , NCT00359424 . ) Background Bridging treatment with intravenous thrombolysis ( IVT ) before endovascular thrombectomy ( EVT ) in acute ischemic stroke is applied under the assumption of benefits for patients with large vessel occlusion ( LVO ) . However , the benefit of this additional step has not yet been proven . Purpose To compare procedural parameters ( procedural time , number of attempts ) , complications , and clinical outcome in patients receiving EVT vs. patients with bridging treatment . Material and Methods In this prospect i ve study all patients had acute anterior cerebral circulation occlusion and were treated with EVT . All patients were selected for treatment based on clinical criteria , multimodal computed tomography ( CT ) imaging . Eighty-four patients were treated with bridging IVT followed by EVT ; 62 patients were treated with EVT only . Results Bridging therapy did not influence endovascular procedure time ( P = 0.71 ) or number of attempts needed ( P = 0.63 ) . Bleeding from any site was more common in the bridging group ( 27 , 32 % ) vs. the EVT group ( 12 , 19 % ) ( P = 0.09 ) . Functional independence modified Rankin Scale after 90 days was slightly higher in the bridging group ( 44 % ) vs. the EVT group ( 42 % ) ( P = 0.14 ) . Mortality did not differ significantly at 90 days : 17 % in the bridging group vs. 21 % in EVT alone ( P = 0.57 ) . Both treatment methods showed high recanalization rates : 94 % in the bridging group and 89 % for EVT alone . Conclusion Bridging treatment in LVO did not show benefits or elevated risks of complications in comparison to EVT only . The bridging group did not show significantly better neurological outcome or significant impact on procedural parameters vs. EVT alone Objective and design Whether combining intravenous thrombolysis ( IVT ) and mechanical thrombectomy ( MT ) is superior to mechanical thrombectomy alone for large vessel occlusion acute ischemic stroke is still uncertain . Our aim was to compare the safety and the efficacy of these two therapeutic strategies . Material s Patients with acute ischemic stroke secondary to anterior circulation large vessel occlusion . Methods A retrospective analysis was conducted . IVT was performed with full dose recombinant tissue plasminogen activator . MT alone was performed only if intravenous thrombolysis was contraindicated . Primary outcomes were successful reperfusion , 3-month functional independence , symptomatic intracranial hemorrhage ( sICH ) , and 3-month mortality . Results 325 patients were analyzed : 193 treated with combined IVT and MT , 132 with MT alone . The combined treatment group showed higher systolic blood pressure ( 140 [ 80–230 ] vs 150 [ 90–220 ] ; p = 0.036 ) , rate of good collaterals ( 55.9 % vs 67 % ; p = 0.03 ) , use of aspiration devices ( 68.2 % vs 79.3 % ; p = 0.003 ) and shorter onset-to-reperfusion time ( 300 [ 90–845 ] vs 288 [ 141–435 ] ; p = 0.008 ) . No differences were found in the efficacy and safety outcomes except for mortality which was lower in the combined treatment group ( 36.4 % vs 25.4 % ; p = 0.02 ) . However , after multivariable analysis combined treatment was not associated with lower mortality ( OR 1.47 ; 95 % CI 0.73–2.96 ; p = 0.3 ) . Conclusions Our study suggests that mechanical thrombectomy alone is effective and safe in patients with contraindications to intravenous thrombolysis . Preceding use of IVT in eligible patients was not associated with increased harm or benefit . R and omized controlled trials are needed to clarify whether intravenous thrombolysis before mechanical thrombectomy is associated with additional benefit Importance Mechanical thrombectomy ( MT ) improves clinical outcomes in patients with acute ischemic stroke ( AIS ) caused by a large vessel occlusion . However , it is not known whether intravenous thrombolysis ( IVT ) is of added benefit in patients undergoing MT . Objective To examine whether treatment with IVT before MT with a stent retriever is beneficial in patients undergoing MT . Design , Setting , and Participants This post hoc analysis used data from 291 patients treated with MT included in 2 large , multicenter , prospect i ve clinical trials that evaluated MT for AIS ( Solitaire With the Intention for Thrombectomy performed from January 1 , 2010 , through December 31 , 2011 , and Solitaire Flow Restoration Thrombectomy for Acute Revascularization from January 1 , 2010 , through December 31 , 2012 ) . An independent core laboratory scored the radiologic outcomes in each trial . Interventions Patients were treated with IVT with tissue plasminogen activator followed by MT ( IVT and MT group ) with the use of a stent retriever or MT with a stent retriever alone ( MT group ) . Main Outcomes and Measures Successful reperfusion , functional independence ( modified Rankin Scale score of 0 - 2 ) and mortality at 90 days , symptomatic intracranial hemorrhage , emboli to new territory , and vasospasm were compared . Results Of 291 patients included in the analysis , 160 ( 55.0 % ) underwent IVT and MT ( mean [ SD ] age , 67 [ 13 ] years ; 97 female [ 60.6 % ] ) , and 131 ( 45.0 % ) underwent MT alone ( mean [ SD ] age , 69 [ 12 ] years ; 71 [ 55.7 % ] female ) . Median Alberta Stroke Program Early CT Score at baseline was lower in the IVT and MT group ( 8 vs 9 , P = .04 ) . There was no statistically significant difference in the duration from symptom onset to groin puncture ( 254 minutes for the IVT and MT group vs 262 minutes for the MT group , P = .10 ) . The number of passes , rate of successful reperfusion , functional independence at 90 days , mortality at 90 days , and emboli to new territory were also similar among groups . Symptomatic intracranial hemorrhage ( 1 % vs 4 % ) and parenchymal hemorrhages type 1 ( 1 % vs 3 % ) or type 2 ( 1 % vs 2 % ) did not differ significantly ( P = .25 ) . Vasospasm occurred more often in patients who received IVT and MT vs MT alone ( 27 % vs 14 % , P = .006 ) . In multivariate analysis , no statistically significant association was observed between IVT and MT vs MT alone for any of the outcomes . Conclusions and Relevance The results indicate that treatment of patients experiencing AIS due to a large vessel occlusion with IVT before MT does not appear to provide a clinical benefit over MT alone . A r and omized clinical trial seems warranted . Trial Registration clinical trials.gov Identifiers : NCT01054560 and |
1,055 | 31,022,301 | 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 . | BACKGROUND Multiparametric magnetic resonance imaging ( MRI ) , with or without MRI-targeted biopsy , is an alternative test to systematic transrectal ultrasonography-guided biopsy in men suspected of having prostate cancer .
At present , evidence on which test to use is insufficient to inform detailed evidence -based decision-making .
OBJECTIVES To determine the diagnostic accuracy of the index tests MRI only , MRI-targeted biopsy , the MRI pathway ( MRI with or without MRI-targeted biopsy ) and systematic biopsy as compared to template-guided biopsy as the reference st and ard in detecting clinical ly significant prostate cancer as the target condition , defined as International Society of Urological Pathology ( ISUP ) grade 2 or higher .
Secondary target conditions were the detection of grade 1 and grade 3 or higher- grade prostate cancer , and a potential change in the number of biopsy procedures . | 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 alone . The risk models demonstrate a benefit in making a decision about which patient needs a biopsy and concurrently help avoid unnecessary biopsies BACKGROUND Multiparametric magnetic resonance imaging ( MP-MRI ) may improve the detection of clinical ly significant prostate cancer ( PCa ) . OBJECTIVE To compare MP-MRI transrectal ultrasound (TRUS)-fusion targeted biopsy with routine TRUS-guided r and om biopsy for overall and clinical ly significant PCa detection among patients with suspected PCa based on prostate-specific antigen ( PSA ) values . DESIGN , SETTING , AND PARTICIPANTS This institutional review board-approved , single-center , prospect i ve , r and omized controlled trial ( April 2011 to December 2014 ) included 130 biopsy-naive patients referred for prostate biopsy based on PSA values ( PSA < 20 ng/ml or free-to-total PSA ratio ≤0.15 and PSA < 10 ng/ml ) . Patients were r and omized 1:1 to the MP-MRI or control group . Patients in the MP-MRI group underwent prebiopsy MP-MRI followed by 10- to 12-core TRUS-guided r and om biopsy and cognitive MRI/TRUS fusion targeted biopsy . The control group underwent TRUS-guided r and om biopsy alone . INTERVENTION MP-MRI 3-T phased-array surface coil . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was the number of patients with biopsy-proven PCa in the MP-MRI and control groups . Secondary outcome measures included the number of positive prostate biopsies and the proportion of clinical ly significant PCa in the MP-MRI and control groups . Between-group analyses were performed . RESULTS AND LIMITATIONS Overall , 53 and 60 patients were evaluable in the MP-MRI and control groups , respectively . The overall PCa detection rate and the clinical ly significant cancer detection rate were similar between the MP-MRI and control groups , respectively ( 64 % [ 34 of 53 ] vs 57 % [ 34 of 60 ] ; 7.5 % difference [ 95 % confidence interval ( CI ) , -10 to 25 ] , p=0.5 , and 55 % [ 29 of 53 ] vs 45 % [ 27 of 60 ] ; 9.7 % difference [ 95 % CI , -8.5 to 27 ] , p=0.8 ) . The PCa detection rate was higher than assumed during the planning of this single-center trial . CONCLUSIONS MP-MRI/TRUS-fusion targeted biopsy did not improve PCa detection rate compared with TRUS-guided biopsy alone in patients with suspected PCa based on PSA values . PATIENT SUMMARY In this r and omized clinical trial , additional prostate magnetic resonance imaging ( MRI ) before prostate biopsy appeared to offer similar diagnostic accuracy compared with routine transrectal ultrasound-guided r and om biopsy in the diagnosis of prostate cancer . Similar numbers of cancers were detected with and without MRI . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01357512 & NA ; The detection rate for clinical ly significant prostate cancer ( PCa ) of transperineal ( TP ) versus transrectal ( TR ) multiparametric ( mp ) magnetic resonance imaging (MRI)/transrectal ultrasound‐guided ( TRUS ) fusion targeted biopsy has been prospect ively evaluated in 200 men su bmi tted to repeat TP saturation prostate biopsy . mpMRI/TRUS TP cognitive targeted biopsy found a greater percentage of clinical ly significant PCa of the anterior zone compared to the mpMRI/TRUS TR fusion approach ( 93.3 vs. 25 % ) . Introduction : To evaluate the detection rate for clinical ly significant prostate cancer ( PCa ) of transperineal ( TP ) versus transrectal ( TR ) multiparametric ( mp ) magnetic resonance imaging (MRI)/transrectal ultrasound‐guided ( TRUS ) fusion targeted biopsy . Patients and Methods : From January 2015 to January 2016 , a total of 200 men ( median age , 61 years ) with negative digital rectal examination findings underwent repeat saturation TP prostate biopsy ( SPBx ; median 30 cores ) for increasing or persistent elevated prostate‐specific antigen values . Ten day before SPBx , all patients underwent 3.0 T pelvic mpMRI ( Achieva 3 T ; Philips Healthcare Best , Netherl and s ) . In the presence of mpMRI lesions suggestive of cancer ( Prostate Imaging — Reporting and Data System [ PI‐RADS ] score 4/5 ) , targeted mpMRI/TRUS TR fusion guided biopsies ( 4 cores ) and TP cognitive biopsies ( 4 cores ) were added to SPBx . Results : Median prostate‐specific antigen was 8.6 ng/mL , and mpMRI revealed a suspicious lesion in 95 ( 47.5 % ) of 200 cases . Overall , in 60 ( 30 % ) of 200 men , a clinical ly significant PCa was found , and in all cases , mpMRI was positive . SPBx , TR fusion , and mpMRI/TRUS TP cognitive targeted biopsy diagnosed 59 ( 98.3 % ) , 40 ( 78.3 % ) , and 56 ( 93.3 % ) clinical ly significant PCa , respectively . TR fusion versus TP targeted biopsy missed 12 versus 1 ( P = .001 ) cancers of the anterior zone and 8 versus 3 ( P = .12 ) cancers of the peripheric gl and , respectively ; moreover , PCa diagnosed by TR fusion versus TP targeted biopsy had a mpMRI lesion diameter and percentage of positive cores equal to 13 versus 10 mm and 33 % versus 58 % ( P = .001 ) , respectively . Conclusion : mpMRI/TRUS TP cognitive targeted biopsy found a greater percentage of clinical ly significant PCa of the anterior zone compared to the mpMRI/TRUS TR fusion approach ( 93.3 % vs. 25 % ; P = .0001 ) 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 or greater tumors while simultaneously mitigating the detection of lower grade disease . The gold st and ard for cancer detection in primary biopsy is a combination of systematic and targeted cores PURPOSE We clarified the diagnostic ability of multiparametric magnetic resonance imaging to reveal anterior cancer missed by transrectal 12-core prostate biopsy based on the results of 3-dimensional 26-core prostate biopsy , which is a combination of transrectal 12-core and transperineal 14-core biopsies . MATERIAL S AND METHODS The study population consisted of 324 patients who prospect ively underwent prebiopsy multiparametric magnetic resonance imaging and then 3-dimensional 26-core prostate biopsy at a single institution . We defined transrectal 12-core negative cancer as cancer detected by transperineal 14-core but not transrectal 12-core prostate biopsy . We focused on cancer in the anterior region . Any findings suspicious for malignancy in the region anterior to the urethra on multiparametric magnetic resonance imaging were defined as an anterior lesion on imaging . Significant cancer was defined as a biopsy Gleason score of 4 + 3 or greater , a greater than 20 % positive core and /or a maximum cancer length of 5 mm or greater . Associations between an anterior lesion on imaging and transrectal 12-core negative cancer were investigated . RESULTS The overall cancer detection rate on 3-dimensional 26-core prostate biopsy was 39 % ( 128 of 324 cases ) , of which 28 % ( 36 of 128 ) were transrectal 12-core negative cancers . An anterior lesion on prebiopsy multiparametric magnetic resonance imaging was identified in 20 % of men overall ( 65 of 324 ) . Of men with and without an anterior lesion on imaging 40 % ( 26 of 65 ) and 3.8 % ( 10 of 259 ) , respectively , had transrectal 12-core negative cancer . Significant transrectal 12-core negative cancer was observed in 0.4 % ( 1 of 259 men ) without an anterior lesion on imaging . Prebiopsy multiparametric magnetic resonance imaging revealed an anterior lesion in 92 % of cases ( 11 of 12 ) of significant transrectal 12-core negative cancer . CONCLUSIONS Prebiopsy multiparametric magnetic resonance imaging has the potential to efficiently select men who could advantageously undergo anterior samplings , in addition to transrectal 12-core prostate biopsy Abstract Objectives To measure the performance characteristics of combined T2-weighted ( T2W ) and diffusion-weighted ( DW ) magnetic resonance imaging ( MRI ) suspicion scoring prior to MR-transrectal ultrasound ( TRUS ) fusion template transperineal ( TTP ) re-biopsy . Methods Thirty-nine patients referred for prostate re-biopsy , with prior MRI examinations , were retrospectively included . The MR images , including T2W and DW-MRI , had been independently evaluated prospect ively by two radiologists using a structured scoring system . An MR-TRUS fusion TTP re-biopsy was used for MR target and non-targeted biopsy cores . Targeting performance and correlation with disease status were evaluated on a per-patient and per-region basis . Results The cancer yield was 41 % ( 16/39 patients ) . MR targeting accurately detected the disease in 12/16 ( 75 % ) cancerous patients and missed the disease in 4/16 ( 25 % ) patients , all with Gleason 3 + 3 disease . There was a significant relationship ( P < 0.01 ) between MR suspicion score and the significance of cancer . Reader 1 had significantly higher sensitivity in the transition zone ( TZ ; 0.84 ) compared with the peripheral zone ( PZ ; 0.32 ) ( P = 0.04 ) . Inter-reader agreement was moderate for the PZ and substantial for the TZ . Conclusions MRI targeting is beneficial in the setting of TTP MR-TRUS fusion re-biopsy and MR suspicion score relates to prostate cancer clinical significance . A T2W and DW-MRI structured scoring system results in good inter-reader agreement in this setting .Key Points• Pre-biopsy MRI aids the detection of high significance cancer during prostate re-biopsy . • MRI suspicion level correlates with the clinical significance of prostate cancer detected . • T2W and DW-MRI structured scoring of pre-biopsy MRI permits good inter-reader agreement PURPOSE Multiparametric magnetic resonance imaging appears to improve prostate cancer detection but prospect i ve studies are lacking . We determined the accuracy of multiparametric magnetic resonance imaging for detecting significant prostate cancer before diagnostic biopsy in men with abnormal prostate specific antigen/digital rectal examination . MATERIAL S AND METHODS In this single center , prospect i ve study men older than 40 years with abnormal prostate specific antigen/digital rectal examination and no previous multiparametric magnetic resonance imaging underwent T2-weighted , diffusion-weighted and dynamic contrast enhanced imaging without an endorectal coil . Imaging was allocated alternately to 1.5/3.0 Tesla . Imaging was double reported independently using PI-RADS ( Prostate Imaging Reporting and Data System ) by specialist radiologists . Transperineal grid directed 30-core biopsy was performed with additional magnetic resonance imaging directed cores for regions of interest outside template locations . Four significant cancer definitions were tested . Chi-square and logistic regression analysis was done . Men undergoing prostatectomy were analyzed . RESULTS Of the 165 men who enrolled in the study 150 were analyzed . Median age was 62.4 years , median prostate specific antigen was 5.6 ng/ml , 29 % of patients had an abnormal digital rectal examination and 88 % underwent initial biopsy . Multiparametric magnetic resonance imaging was positive ( PI-RADS 3 to 5 ) in 66 % of patients , 61 % had prostate cancer and 30 % to 41 % had significant prostate cancer ( definitions 1 to 4 ) . For significant cancer sensitivity was 93 % to 96 % , specificity was 47 % to 53 % , and negative and positive predictive values were 92 % to 96 % and 43 % to 57 % , respectively ( definitions 1 to 4 ) . Radical prostatectomy results in 48 men were similar . Aggregate PI-RADS ( 4 to 20 ) performed similarly to overall PI-RADS ( 1 to 5 ) . Negative and positive predictive values ( 100 % and 71 % , respectively ) were similar in men at higher risk , defined as prostate specific antigen greater than 10 ng/ml with abnormal digital rectal examination . On multivariate analysis PI-RADS score was associated with significant prostate cancer ( p < 0.001 ) but magnet strength was not . Adding PI-RADS to the multivariate model improved the AUC from 0.810 to 0.913 ( 95 % CI 0.038 - 0.166 , p = 0.002 ) . Radiologist agreement was substantial ( weighted κ = 0.626 ) . CONCLUSIONS Multiparametric magnetic resonance imaging reported by expert radiologists achieved an excellent negative predictive value and a moderate positive predictive value for significant prostate cancer at 1.5 and 3.0 Tesla BACKGROUND The debate on the optimal number of prostate biopsy core sample s that should be taken as an initial strategy is open . OBJECTIVE To prospect ively evaluate the diagnostic yield of a 21-core biopsy protocol as an initial strategy for prostate cancer ( PCa ) detection . DESIGN , SETTING , AND PARTICIPANTS During 10 yr , 2753 consecutive patients underwent a 21-core biopsy scheme for their first set of biopsy specimens . INTERVENTION All patients underwent a st and ardized 21-core protocol with cores mapped for location . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The PCa detection rate of each biopsy scheme ( 6 , 12 , or 21 cores ) was compared using a McNemar test . Predictive factors of the diagnostic yield achieved by a 21-core scheme were studied using logistic regression analyses . RESULTS AND LIMITATIONS PCa detection rates using 6 sextant biopsies , 12 cores , and 21 cores were 32.5 % , 40.4 % , and 43.3 % , respectively . The 12-core procedure improved the cancer detection rate by 19.4 % ( p=0.004 ) , and the 21-biopsy scheme improved the rate by 6.7 % overall ( p<0.001 ) . The six far lateral cores were the most efficient in terms of detection rate . The diagnostic yield of the 21-core protocol was > 10 % in prostates with volume > 70 ml , in men with a prostate-specific antigen level<4 ng/ml , with a prostate-specific antigen density ( PSAD ) < 0.20 ng/ml per gram . A PSAD < 0.20 ng/ml per gram was the strongest independent predictive factor of the diagnostic yield offered by the 21-core scheme ( p<0.001 ) . The 21-core protocol significantly increased the rate of PCa eligible for active surveillance ( 62.5 % vs 48.4 % ; p=0.036 ) than those detected by a 12-core scheme without statistically increasing the rate of insignificant PCa ( p=0.503 ) . CONCLUSIONS A 21-core biopsy scheme improves significantly the PCa detection rate compared with a 12-core protocol . We identified a cut-off PSAD ( 0.20 ng/ml per gram ) below which an extended 21-core scheme might be systematic ally proposed to significantly improve the overall detection rate without increasing the rate of detected insignificant PCa OBJECTIVE The primary objective of the PICTURE study is to assess the negative predictive value of multi-parametric MRI ( mp-MRI ) and Prostate HistoScanning ™ ( PHS ) in ruling-out clinical ly significant prostate cancer . PATIENTS AND METHODS PICTURE is a prospect i ve diagnostic validating cohort study conforming to level 1 evidence . PICTURE will assess the diagnostic performance of multi-parametric Magnetic Resonance Imaging ( mp-MRI ) and Prostate HistoScanning ™ ( PHS ) ultrasound . PICTURE will involve validating both index tests against a reference test , transperineal Template Prostate Mapping ( TPM ) biopsies , which can be applied in all men under evaluation . Men will be blinded to the index test results and both index tests will be reported prospect ively prior to the biopsies being taken to ensure reporter blinding . Paired analysis of each of the index tests to the reference test will be done at patient level . Those men with an imaging lesion will undergo targeted biopsies to assess the clinical utility of sampling only suspicious areas . The study is powered to assess the negative predictive value of these imaging modalities in ruling-out clinical ly significant prostate cancer . DISCUSSION The PICTURE study aims to assess the performance characteristics of two imaging modalities ( mp-MRI and Prostate HistoScanning ) for their utility in the prostate cancer pathway . PICTURE aims to identify if either imaging test may be useful for ruling out clinical ly significant disease in men under investigation , and also to examine if either imaging modality is useful for the detection of disease . Recruitment is underway and expected to complete in 2014 PURPOSE We compared the accuracy of visual targeted biopsies vs computerized transrectal ultrasound-magnetic resonance imaging registration using a rigid ( Esaote ® , nondeformable ) or elastic ( Koelis ® , deformable ) approach . MATERIAL S AND METHODS A total of 391 consecutive patients with suspected localized prostate cancer were prospect ively included in analysis . All patients underwent prostate magnetic resonance imaging , followed by 10 to 12-core r and om prostate biopsies . When magnetic resonance imaging detected suspicious findings , targeted biopsy was performed , including visual , rigid system and elastic system targeted biopsies in the first 127 patients , the next 131 and the last 133 , respectively . Cancer detection rates were assessed by conditional logistic regression . Targeted biopsies alone and r and om biopsies were further compared for the amount of tissue sample d and microfocal cancer detection , the latter defined as a single core with 5 mm or less of Gleason 6 cancer . RESULTS Patient characteristics and r and om biopsy detection rates were similar among the groups . Magnetic resonance imaging detected at least 1 suspicious area in 54 ( 42 % ) , 78 ( 59 % ) and 82 patients ( 62 % ) in groups 1 , 2 and 3 , respectively . The cancer detection rates of rigid and elastic system targeted biopsies were significantly higher than the r and om biopsy rate ( p = 0.0065 and 0.0016 , respectively ) . Visual targeted biopsy did not perform better than r and om biopsy ( p = 0.66 ) . Rigid and elastic system targeted biopsies allowed for decreasing the number of cores and the detection of microfocal cancer , while increasing the detection of high grade cancer . CONCLUSIONS When performed with computerized magnetic resonance imaging-transrectal ultrasound image registration , targeted biopsy alone improved cancer detection over r and om biopsies , decreased the detection rate of microfocal cancer and increased the detection rate of cancer with a Gleason score of greater than 6 IMPORTANCE Targeted magnetic resonance (MR)/ultrasound fusion prostate biopsy has been shown to detect prostate cancer . The implication s of targeted biopsy alone vs st and ard extended-sextant biopsy or the 2 modalities combined are not well understood . OBJECTIVE To assess targeted vs st and ard biopsy and the 2 approaches combined for the diagnosis of intermediate- to high-risk prostate cancer . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 1003 men undergoing both targeted and st and ard biopsy concurrently from 2007 through 2014 at the National Cancer Institute in the United States . Patients were referred for elevated level of prostate-specific antigen ( PSA ) or abnormal digital rectal examination results , often with prior negative biopsy results . Risk categorization was compared among targeted and st and ard biopsy and , when available , whole-gl and pathology after prostatectomy as the " gold st and ard . " INTERVENTIONS Patients underwent multiparametric prostate magnetic resonance imaging to identify regions of prostate cancer suspicion followed by targeted MR/ultrasound fusion biopsy and concurrent st and ard biopsy . MAIN OUTCOMES AND MEASURES The primary objective was to compare targeted and st and ard biopsy approaches for detection of high-risk prostate cancer ( Gleason score ≥ 4 + 3 ) ; secondary end points focused on detection of low-risk prostate cancer ( Gleason score 3 + 3 or low-volume 3 + 4 ) and the biopsy ability to predict whole-gl and pathology at prostatectomy . RESULTS Targeted MR/ultrasound fusion biopsy diagnosed 461 prostate cancer cases , and st and ard biopsy diagnosed 469 cases . There was exact agreement between targeted and st and ard biopsy in 690 men ( 69 % ) undergoing biopsy . Targeted biopsy diagnosed 30 % more high-risk cancers vs st and ard biopsy ( 173 vs 122 cases , P < .001 ) and 17 % fewer low-risk cancers ( 213 vs 258 cases , P < .001 ) . When st and ard biopsy cores were combined with the targeted approach , an additional 103 cases ( 22 % ) of mostly low-risk prostate cancer were diagnosed ( 83 % low risk , 12 % intermediate risk , and 5 % high risk ) . The predictive ability of targeted biopsy for differentiating low-risk from intermediate- and high-risk disease in 170 men with whole-gl and pathology after prostatectomy was greater than that of st and ard biopsy or the 2 approaches combined ( area under the curve , 0.73 , 0.59 , and 0.67 , respectively ; P < .05 for all comparisons ) . CONCLUSIONS AND RELEVANCE Among men undergoing biopsy for suspected prostate cancer , targeted MR/ultrasound fusion biopsy , compared with st and ard extended-sextant ultrasound-guided biopsy , was associated with increased detection of high-risk prostate cancer and decreased detection of low-risk prostate cancer . Future studies will be needed to assess the ultimate clinical implication s of targeted biopsy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00102544 BACKGROUND An approach based on multiparametric magnetic resonance imaging ( mpMRI ) might increase the detection rate ( DR ) of clinical ly significant prostate cancer ( csPCa ) . OBJECTIVE To compare an mpMRI-based pathway with the st and ard approach for the detection of prostate cancer ( PCa ) and csPCa . DESIGN , SETTING , AND PARTICIPANTS Between November 2014 and April 2016 , 212 biopsy-naïve patients with suspected PCa ( prostate specific antigen level ≤15 ng/ml and negative digital rectal examination results ) were included in this r and omized clinical trial . Patients were r and omized into a prebiopsy mpMRI group ( arm A , n=107 ) or a st and ard biopsy ( SB ) group ( arm B , n=105 ) . INTERVENTION In arm A , patients with mpMRI evidence of lesions suspected for PCa underwent mpMRI/transrectal ultrasound fusion software-guided targeted biopsy ( TB ) ( n=81 ) . The remaining patients in arm A ( n=26 ) with negative mpMRI results and patients in arm B underwent 12-core SB . OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was comparison of the DR of PCa and csPCa between the two arms of the study ; the secondary end point was comparison of the DR between TB and SB . RESULTS AND LIMITATIONS The overall DRs were higher in arm A versus arm B for PCa ( 50.5 % vs 29.5 % , respectively ; p=0.002 ) and csPCa ( 43.9 % vs 18.1 % , respectively ; p<0.001 ) . Concerning the biopsy approach , that is , TB in arm A , SB in arm A , and SB in arm B , the overall DRs were significantly different for PCa ( 60.5 % vs 19.2 % vs 29.5 % , respectively ; p<0.001 ) and for csPCa ( 56.8 % vs 3.8 % vs 18.1 % , respectively ; p<0.001 ) . The reproducibility of the study could have been affected by the single-center nature . CONCLUSIONS A diagnostic pathway based on mpMRI had a higher DR than the st and ard pathway in both PCa and csPCa . PATIENT SUMMARY In this r and omized trial , a pathway for the diagnosis of prostate cancer based on multiparametric magnetic resonance imaging ( mpMRI ) was compared with the st and ard pathway based on r and om biopsy . The mpMRI-based pathway had better performance than the st and ard pathway Introduction . To compare , in the same cohort of men , the detection of clinical ly significant disease in st and ard ( STD ) cores versus multiparametric magnetic resonance imaging ( mpMRI ) targeted ( TAR ) cores . Material and Methods . A prospect i ve study was conducted on 129 biopsy naïve men with clinical suspicion of prostate cancer . These patients underwent prebiopsy mpMRI with STD systematic biopsies and TAR biopsies when lesions were found . The agreement between the TAR and the STD protocol s was measured using Cohen 's kappa coefficient . Results . Cancer detection rate of MRI-targeted biopsy was 62.7 % . TAR protocol demonstrated higher detection rate of clinical ly significant disease compared to STD protocol . The proportion of cores positive for clinical ly significant cancer in TAR cores was 28.9 % versus 9.8 % for STD cores ( P < 0.001 ) . The proportion of men with clinical ly significant cancer and the proportion of men with Gleason score 7 were higher with the TAR protocol than with the STD protocol ( P = 0.003 ; P = 0.0008 , resp . ) . Conclusion . mpMRI improved clinical ly significant prostate cancer detection rate compared to STD protocol alone with less tissue sampling and higher Gleason score . Further development in imaging as well as multicentre studies using the START recommendation is needed to eluci date the role of mpMRI targeted biopsy in the management of prostate cancer Introduction We aim to present transperineal template-guided prostate biopsy ( template biopsy ) outcomes at a tertiary referral centre . Furthermore , to identify the detection rate of prostate cancer in those with a previous negative transrectal ultrasound guided prostate biopsy and the up grade rate of those on active surveillance for Gleason 3 + 3 = 6 prostate adenocarcinoma . Material and methods We conducted a prospect i ve study of 200 consecutive men who underwent template biopsy over a 22-month period in a tertiary referral centre , using a st and ard 24 region template prostate biopsy technique . Indications and histology results , as well as complications , were recorded . Results Median age was 67 years and median PSA was 10 ng/mL. Overall detection rate was 47 % . 39.5 % of cases with previous negative transrectal biopsies were found to have prostate adenocarcinoma . 47.5 % of cases on active surveillance for Gleason 3 + 3 = 6 prostate adenocarcinoma were up grade d. The most frequent complication was acute urinary retention at a rate of 12.5 % , however , the use of a single prophylactic dose of tamsulosin was found to be beneficial , with 13 cases needed to treat to prevent one episode . Conclusions Template biopsies are safe and efficacious with an overall detection rate of 47 % in the present series . Due to the high detection rate , one must consider template biopsy following one negative transrectal biopsy where there is persistent clinical suspicion . Furthermore , those considering active surveillance for Gleason 3 + 3 = 6 disease should be offered template biopsy to confirm the grade of their disease PURPOSE The identification of clinical ly insignificant prostate cancer could help avoid overtreatment . Current criteria for insignificant prostate cancer use a tumor volume threshold of less than 0.5 ml for the index tumor . In this study we reassess this tumor volume threshold for clinical ly insignificant prostate cancer using an independent data set . MATERIAL S AND METHODS The rate of insignificant prostate cancer was calculated by modeling lifetime risk estimates of prostate cancer diagnosis in screened and nonscreened participants in a r and omized prostate cancer screening trial . Using lifetime risk estimates 50.8 % of screen detected prostate cancer was calculated to be clinical ly insignificant and the 49.2 % largest tumor volume of 325 prostatectomy specimens was used to determine the threshold tumor volume for insignificant prostate cancer . Because stage and grade represent the strongest determinants of cancer aggressiveness , we also calculated the tumor volume threshold for insignificant cancer after the selection of patients with organ confined prostate cancer without Gleason pattern 4/5 . The analyses were performed for total tumor volume and for index tumor volume . RESULTS The minimum threshold tumor volume of the index tumor and total tumor was 0.55 and 0.70 ml , respectively . After accounting for tumor stage and grade we obtained a threshold volume for the index tumor and total tumor of 1.3 and 2.5 ml , respectively . CONCLUSIONS We confirmed the original value of the index tumor volume threshold of 0.5 ml for insignificant prostate cancer , and we demonstrated that clinical ly insignificant prostate cancer may include index Gleason score 6 , pT2 tumors with volumes up to at least 1.3 ml . These results suggest a reconsideration of current methods and nomograms used for pretreatment risk assessment Objective : This study is a prospect i ve evaluation of a volume-based , computer-assisted method for transperineal optimized prostate ( TOP ) biopsy . The TOP algorithm automates core planning for systematic prostate biopsies using the 3-dimensional organ contour and an alterable volume for tumors to be excluded . Subjects and Methods : MRI-transrectal ultrasound fusion biopsy with MRI-targeted biopsies ( TBs ) and systematic -TOP biopsies were performed on 172 men between October 2013 and March 2014 . Systematic biopsies were placed according to TOP for detection of tumor volumes > 0.5 mL with a minimum of 80 % organ coverage in prostates up to 50 mL ( 70 % in larger organs ) . Results : Median 24 TOP cores and 3 MRI-TBs have been placed . Prostate cancer ( PCa ) was detected in 112 of 172 ( 65 % ) of men ; TOP detected 109 ( 97 % ) and TB 62 ( 55 % ) . Significant cancer ( Gleason score ≥7 ) was detected in 75 ( 44 % ) of men and of these TOP detected 73 of 75 ( 97 % ) and TB 51 of 75 ( 68 % ) . Overall , systematic -TOP sampling significantly outperformed TB for the detection of both , all PCa as well as significant PCa ( p < 0.0001 , p = 0.0005 ) . Conclusion : The TOP method is innovative by integrating the individual prostate volume and PCa volume detection thresholds . In the present cohort , it diagnosed more significant tumors than TB alone . However , at the same time , more low-risk tumors are detected OBJECTIVES To assess whether the proportion of men with clinical ly significant prostate cancer ( PCa ) is higher among men r and omized to multiparametric magnetic resonance imaging (mp-MRI)/biopsy vs. those r and omized to transrectal ultrasound (TRUS)-guided biopsy . METHODS In total , 1,140 patients with symptoms highly suggestive of PCa were enrolled and divided in 2 groups of 570 patients to follow 2 different diagnostic algorithms . Group A underwent a TRUS-guided r and om biopsy . Group B underwent an mp-MRI and a TRUS-guided targeted+r and om biopsy . The accuracy of mp-MRI in the diagnosis of PCa was calculated using prostatectomy as the st and ard of reference . RESULTS In group A , PCa was detected in 215 patients . The remaining 355 patients underwent an mp-MRI : the findings were positive in 208 and unremarkable in 147 patients . After the second r and om+targeted biopsy , PCa was detected in 186 of the 208 patients . In group B , 440 patients had positive findings on mp-MRI , and PCa was detected in 417 at first biopsy ; 130 group B patients had unremarkable findings on both mp-MRI and biopsy . In the 130 group B patients with unremarkable findings on mp-MRI and biopsy , a PCa Gleason score of 6 or precancerous lesions were detected after saturation biopsy . mp-MRI showed an accuracy of 97 % for the diagnosis of PCa . CONCLUSIONS The proportion of men with clinical ly significant PCa is higher among those r and omized to mp-MRI/biopsy vs. those r and omized to TRUS-guided biopsy ; moreover , mp-MRI is a very reliable tool to identify patients to schedule in active surveillance Background Multiparametric magnetic resonance imaging ( mpMRI ) can improve detection of clinical ly significant prostate cancer ( csPCa ) . Purpose To compare mpMRI score subgroups to systematic transrectal ultrasound-guided biopsies ( TRUSbx ) and prostate-specific antigen (PSA)-based findings for detection of csPCa in men undergoing repeat biopsies . Material and Methods MpMRI was performed prior to re-biopsy in 289 prospect ively enrolled patients . All underwent repeat TRUSbx followed by targeted biopsies ( MRITB ) of any mpMRI-identified lesion . MpMRI suspicion grade , PSA level , and density ( PSAd ) were compared with biopsy results and further matched to the radical prostatectomy ( RP ) specimen if available . Results PCa was detected in 128/289 ( 44 % ) patients with median age , PSA , and prior negative TRUSbx of 64 ( interquartile range [ IQR ] = 59–67 ) , 12.0 ng/mL ( IQR = 8.3–19.1 ) , and 2 ( IQR = 1–3 ) , respectively . TRUSbx detected PCa in 108/289 ( 37 % ) patients , of which 49 ( 45 % ) had insignificant cancer . MRITB was performed in 271/289 ( 94 % ) patients and detected PCa in 96 ( 35 % ) with 78 ( 81 % ) having csPCa . MpMRI scores showed a high association between suspicion level and biopsy results on both lesion and patient level ( P < 0.001 ) . MpMRI was better than PSA and PSAd ( P < 0.001 ) to identify patients with missed csPCa . In total , 64/128 ( 50 % ) patients underwent RP ; 60/64 had csPCa . MpMRI was significantly better in predicting csPCa on RP compared with TRUSbx ( P = 0.019 ) as MRITB and TRUSbx correctly identified 47/60 ( 78 % ) and 35/60 ( 58 % ) patients , respectively . Conclusion MpMRI improves detection of missed csPCa and suspicion scores correlate well with biopsy and RP results on both patient and lesion level PURPOSE Most prostate cancer active surveillance protocol s recommend a confirmatory biopsy within 3 to 6 months of diagnosis . Transperineal template guided biopsy is an approach to improve the detection of high grade prostate cancer . However , to our knowledge the optimal technique is unknown . We evaluated the relative performance of 2 transperineal template guided biopsy approaches . MATERIAL S AND METHODS Institutional review board approved prospect i ve data bases at Virginia Mason and University of Michigan were used . Men eligible for active surveillance based on initial 12-core biopsy demonstrating NCCN ® guideline low risk prostate cancer were included in study . All men underwent confirmatory transperineal template guided biopsy between 2005 and 2014 , and within 6 months of diagnosis . The biopsy technique was based on a 24-core template with 12 anterior and 12 posterior cores or a template based on gl and volume with an average of 1 core per cc . Outcome comparisons were made by the chi-square and Fisher exact tests , the Welch t-test and linear regression . RESULTS Of the 135 men 46 underwent 24-core biopsy and 89 underwent volume based biopsy ( median 62 cores ) . No statistically significant difference was noted in the prevalence of upgrading ( 35 % vs 29 % , p = 0.64 ) or complications ( 9 % vs 16 % , p = 0.38 ) between the 24-core and volume based groups . The difference in the probability of upgrading by volume based biopsy adjusted for age , prostate specific antigen , prostate volume , clinical stage and number of prior biopsies was -4 % ( 95 % CI -24 to 14 % , p = 0.63 ) . CONCLUSIONS A significant difference was not detected in upgrading or morbidity between a 24-core template and a more exhaustive volume based template . A less invasive 24-core transperineal template guided biopsy strategy may suffice to accurately identify men who are appropriate for active surveillance Introduction : The aim of the study was to compare the prostate cancer ( PCa ) detection rate of systematic transrectal ultrasound-guided biopsies ( TRUS-bx ) and multiparametric-MRI targeted biopsies ( mp-MRI-bx ) in a repeat biopsy setting and evaluate the clinical significance following an “ MRI-targeted-only ” approach . Material s and Methods : Patients with prior negative biopsies underwent prostatic multiparametric-MRI that was scored using the Prostate Imaging Reporting and Data System ( PI-RADS ) classification . All underwent both repeated TRUS-bx and mp-MRI-bx using image fusion of any PI-RADS ≥3 lesion . Biopsy results from TRUS-bx , mp-MRI-bx , and the combination were compared . Results : PCa was detected in 89 out of 206 ( 43 % ) patients . Of these , 64 ( 31 % ) and 74 ( 36 % ) patients were detected using mp-MRI-bx and TRUS-bx , respectively . Overall , mp-MRI-bx detected fewer patients with low- grade ( Gleason score [ GS ] 3 + 3 ) cancers ( 14/64 vs. 41/74 ) and more patients with intermediate/high- grade cancers ( GS ≥3 + 4 ) ( 50/64 vs. 33/74 ) using fewer biopsy cores compared with TRUS-bx ( p < 0.001 ) . Using an “ MRI-targeted-only ” approach in men with PI-RADS ≥3 lesions reduced the number of men requiring repeated biopsies by 50 % , decreased low- grade cancer diagnoses by 66 % , and increased intermediate/high- grade cancer diagnoses by 52 % . Conclusions : MRI-targeted biopsies have a high detection rate for significant PCa in patients with prior negative transrectal ultrasound-guided biopsies and preferentially detect intermediate/high- grade compared with low- grade tumors PURPOSE Diagnosis and precise risk stratification of prostate cancer is essential for individualized treatment decisions . Magnetic resonance imaging/transrectal ultrasound fusion has shown encouraging results for detecting clinical ly significant prostate cancer . We critically evaluated magnetic resonance imaging targeted , transrectal ultrasound guided transperineal fusion biopsy in routine clinical practice . MATERIAL S AND METHODS Included in this prospect i ve study were 347 consecutive patients with findings suspicious for prostate cancer . Median age was 65 years ( range 42 to 84 ) and mean prostate specific antigen was 9.85 ng/ml ( range 0.5 to 104 ) . Of the men 49 % previously underwent transrectal ultrasound guided biopsies , which were negative , and 51 % underwent primary biopsy . In all patients 3 Tesla multiparametric magnetic resonance imaging was done . Systematic stereotactic prostate biopsies plus magnetic resonance imaging targeted , transrectal ultrasound guided biopsies were performed in those with abnormalities on magnetic resonance imaging . Imaging data and biopsy results were analyzed . A self- design ed question naire was sent to all men on further clinical history and biopsy adverse effects . RESULTS Of 347 patients biopsy sample s of 200 ( 58 % ) showed prostate cancer and 73.5 % of biopsy proven prostate cancer were clinical ly relevant according to National Comprehensive Cancer Network ( NCCN ) criteria . On multiparametric magnetic resonance imaging 104 men had findings highly suspicious for prostate cancer . The tumor detection rate was 82.6 % ( 86 of 104 men ) with a Gleason score of 7 or greater in 72 % . Overall targeted cores detected significantly more cancer than systematic biopsies ( 30 % vs 8.2 % ) . Of 94 patients without cancer suspicious lesions on magnetic resonance imaging 11 ( 11.7 % ) were diagnosed with intermediate risk disease . Regarding adverse effects , 152 of 300 patients ( 50.6 % ) reported mild hematuria , 26 % had temporary erectile dysfunction and 2.6 % needed short-term catheterization after biopsy . Nonseptic febrile urinary tract infections developed in 3 patients ( 1 % ) . CONCLUSIONS Magnetic resonance imaging targeted , transrectal ultrasound guided transperineal fusion biopsy provides high detection of clinical ly significant tumors . Since multiparametric magnetic resonance imaging still has some limitations , systematic biopsies should currently not be omitted . The morbidity of the transperineal saturation approach is reasonable and mainly self-limiting BACKGROUND Prostate biopsy guided by computer-assisted fusion of magnetic resonance imaging ( MRI ) and transrectal ultrasound ( TRUS ) images ( MRI group ) has not yet been compared with 12-core r and om biopsy ( RB ; control group ) in a r and omized controlled trial ( RCT ) . OBJECTIVE To compare the rate of detection of clinical ly significant prostate cancer ( csPCa ) between the two groups . DESIGN , SETTING , AND PARTICIPANTS This RCT included 175 biopsy-naïve patients with suspicion for prostate cancer , r and omized to an MRI group ( n=86 ) and a control group ( n=89 ) between September 2011 and June 2013 . INTERVENTION In the MRI group , two-core targeted biopsy ( TB ) guided by computer-assisted fusion of MRI/TRUS images of MRI-suspicious lesions was followed by 12-core RB . In the control group , both two-core TB for abnormal digital rectal examination ( DRE ) and /or TRUS-suspicious lesions and 12-core RB were performed . In patients with normal MRI or DRE/TRUS , only 12-core RB was performed . OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS The detection rates for any cancer and csPCa were compared between the two groups and between TB and RB . RESULTS AND LIMITATIONS Detection rates for any cancer ( MRI group 51/86 , 59 % ; control group 48/89 , 54 % ; p=0.4 ) and csPCa ( 38/86 , 44 % vs 44/89 , 49 % ; p=0.5 ) did not significantly differ between the groups . Detection of csPCa was comparable between two-core MRI/TRUS-TB ( 33/86 , 38 % ) and 12-core RB in the control group ( 44/89 , 49 % ; p=0.2 ) . In a subset analysis of patients with normal DRE , csPCa detection was similar between two-core MRI/TRUS-TB ( 14/66 , 21 % ) and 12-core RB in the control group ( 15/60 , 25 % ; p=0.7 ) . Among biopsy-proven csPCas in MRI group , 87 % ( 33/38 ) were detected by MRI/TRUS-TB . The definition of csPCa was only based on biopsy outcomes . CONCLUSION Overall csPCa detection was similar between the MRI and control groups . Two-core MRI/TRUS-TB was comparable to 12-core RB for csPCa detection . PATIENT SUMMARY Our r and omized controlled trial revealed a similar rate of prostate cancer detection between targeted biopsy guided by magnetic resonance imaging ( MRI ) and transrectal ultrasound ( TRUS ) and 12-core r and om biopsy . The traditional 12-core r and om biopsy may be replaced by two-core MRI/TRUS targeted biopsy for detection of clinical ly significant prostate cancer BACKGROUND The current diagnosis of prostate cancer ( PCa ) uses transrectal ultrasound-guided biopsy ( TRUSGB ) . TRUSGB leads to sampling errors causing delayed diagnosis , overdetection of indolent PCa , and misclassification . Advances in multiparametric magnetic resonance imaging ( mpMRI ) suggest that imaging and selective magnetic resonance (MR)-guided biopsy ( MRGB ) may be superior to TRUSGB . OBJECTIVE To compare the diagnostic efficacy of the magnetic resonance imaging ( MRI ) pathway with TRUSGB . DESIGN , SETTING , AND PARTICIPANTS A total of 223 consecutive biopsy-naive men referred to a urologist with elevated prostate-specific antigen participated in a single-institution , prospect i ve , investigator-blinded , diagnostic study from July 2012 through January 2013 . INTERVENTION All participants had mpMRI and TRUSGB . Men with equivocal or suspicious lesions on mpMRI also underwent MRGB . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was PCa detection . Secondary outcomes were histopathologic details of biopsy and radical prostatectomy specimens , adverse events , and MRI reader performance . Sensitivity , specificity , negative predictive values ( NPVs ) , and positive predictive values were estimated and basic statistics presented by number ( percentage ) or median ( interquartile range ) . RESULTS AND LIMITATIONS Of 223 men , 142 ( 63.7 % ) had PCa . TRUSGB detected 126 cases of PCa in 223 men ( 56.5 % ) including 47 ( 37.3 % ) classed as low risk . MRGB detected 99 cases of PCa in 142 men ( 69.7 % ) with equivocal or suspicious mpMRI , of which 6 ( 6.1 % ) were low risk . The MRGB pathway reduced the need for biopsy by 51 % , decreased the diagnosis of low-risk PCa by 89.4 % , and increased the detection of intermediate/high-risk PCa by 17.7 % . The estimated NPVs of TRUSGB and MRGB for intermediate/high-risk disease were 71.9 % and 96.9 % , respectively . The main limitation is the lack of long follow-up . CONCLUSIONS We found that mpMRI/MRGB reduces the detection of low-risk PCa and reduces the number of men requiring biopsy while improving the overall rate of detection of intermediate/high-risk PCa . PATIENT SUMMARY We compared the results of st and ard prostate biopsies with a magnetic resonance ( MR ) image-based targeted biopsy diagnostic pathway in men with elevated prostate-specific antigen . Our results suggest patient benefits of the MR pathway . Follow-up of negative investigations is required BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects PURPOSE Definitions of prostate cancer risk are limited since accurate attribution of the cancer grade and burden is not possible due to the r and om and systematic errors associated with transrectal ultrasound guided biopsy . Transperineal prostate mapping biopsy may have a role in accurate risk stratification . We defined the transperineal prostate mapping biopsy characteristics of clinical ly significant disease . MATERIAL S AND METHODS A 3-dimensional model of each gl and and individual cancer was reconstructed using 107 radical whole mount specimens . We performed 500 transperineal prostate mapping simulations per case by varying needle targeting errors to calculate sensitivity , specificity , and negative and positive predictive value to detect lesions 0.2 ml or greater , or 0.5 ml or greater . Definitions of clinical ly significant cancer based on a combination of Gleason grade and cancer burden ( cancer core length ) were derived . RESULTS Mean±SD patient age was 61±6.4 years ( range 44 to 74 ) and mean prostate specific antigen was 9.7±5.9 ng/ml ( range 0.8 to 36.2 ) . We reconstructed 665 foci . The total cancer core length from all positive biopsies for a particular lesion that detected more than 95 % of lesions 0.5 ml or greater and 0.2 ml or greater was 10 mm or greater and 6 mm or greater , respectively . The maximum cancer core length that detected more than 95 % of lesions 0.5 ml or greater and 0.2 ml or greater was 6 mm or greater and 4 mm or greater , respectively . We combined these cancer burden thresholds with dominant and nondominant Gleason pattern 4 to derive 2 definitions of clinical ly significant disease . CONCLUSIONS Transperineal prostate mapping may provide an effective method to risk stratify men with localized prostate cancer . The definitions that we present require prospect i ve validation Background : To compare prostate cancer detection rates between transrectal ultrasound ( TRUS ) prostate biopsy and transperineal template prostate biopsy ( TPTPB ) in biopsy naïve men . TRUS biopsy is still regarded as gold st and ard for prostate cancer diagnosis . TPTPB has been shown to improve prostate cancer detection in men with rising PSA and previous negative TRUS biopsies . We carried out a prospect i ve study performing both biopsies in the same group of men with a benign feeling digital rectal examination ( DRE ) , PSA < 20 ng ml−1 and no previous prostate biopsies . Methods : A total of 50 patients with mean age of 67 years ( range : 54–84 ) , mean prostate volume 58 cc ( range : 19–165 ) and mean PSA 8 ng l−1 ( range : 4–18 ) underwent st and ard 12-core TRUS biopsy followed immediately by 36-core TPTPB under general anaesthetic . We determined the prostate cancer detection rate between the two diagnostic modalities . Results : In total , 20/50 ( 40 % ) had benign pathology . Of 30/50 ( 60 % ) diagnosed with prostate cancer , 16 ( 32 % ) had positive results in both TRUS and TPTPB , whereas 14 ( 28 % ) had negative TRUS but positive TPTPB . No cancers were detected solely by TRUS biopsy . TRUS biopsy detected cancer in 32 % versus 60 % with TPTPB . In total , 19/30(63 % ) cancers detected by TPTPB had Gleason score ⩾7 . 2 ( 4 % ) experienced urosepsis , 7 ( 14 % ) temporary urinary retention , 16 ( 32 % ) mild haematuria and 19 ( 38 % ) haematospermia . Conclusions : TPTPB is associated with significantly higher prostate cancer detection rate than TRUS biopsies in biopsy naïve men with a benign feeling DRE and PSA < 20 ng ml−1 . PSA appears to be better biomarker than previously thought INTRODUCTION This study evaluates the clinical benefit of magnetic resonance-transrectal ultrasound ( MR-TRUS ) fusion biopsy over systematic biopsy between first-time and repeat prostate biopsy patients with prior atypical small acinar proliferation ( ASAP ) . MATERIAL S 100 patients were enrolled in a single-centre prospect i ve cohort study : 50 for first biopsy , 50 for repeat biopsy with prior ASAP . Multiparameteric magnetic resonance imaging ( MP-MRI ) and st and ard 12-core ultrasound biopsy ( Std-Bx ) were performed on all patients . Targeted biopsy using MRI-TRUS fusion ( Fn-Bx ) was performed f suspicious lesions were identified on the pre-biopsy MP-MRI . Classification of clinical ly significant disease was assessed independently for the Std-Bx vs. Fn-Bx cores to compare the two approaches . RESULTS Adenocarcinoma was detected in 49/100 patients ( 26 first biopsy , 23 ASAP biopsy ) , with 25 having significant disease ( 17 first , 8 ASAP ) . Fn-Bx demonstrated significantly higher per-core cancer detection rates , cancer involvement , and Gleason scores for first-time and ASAP patients . However , Fn-Bx was significantly more likely to detect significant cancer missed on Std-Bx for ASAP patients than first-time biopsy patients . The addition of Fn-Bx to Std-Bx for ASAP patients had a 166.7 % relative risk reduction for missing Gleason ≥ 3 + 4 disease ( number needed to image with MP-MRI=10 patients ) compared to 6.3 % for first biopsy ( number to image=50 patients ) . Negative predictive value of MP-MRI for negative biopsy was 79 % for first-time and 100 % for ASAP patients , with median followup of 32.1 ± 15.5 months . CONCLUSIONS MR-TRUS Fn-Bx has a greater clinical impact for repeat biopsy patients with prior ASAP than biopsy-naïve patients by detecting more significant cancers that are missed on Std-Bx PURPOSE We have previously demonstrated that transperineal template prostate biopsy ( TPTPB ) has a significantly higher cancer detection rate compared to transrectal ultrasound guided ( TRUS ) biopsy in biopsy naive men with a PSA < 20 ng/mL. We , therefore , performed a prospect i ve study to determine whether TPTPB is still superior to TRUS biopsy in the detection of prostate cancer in men with persistently elevated PSA after one previous negative set of TRUS biopsies . MATERIAL S AND METHODS 42 patients with a background of one previous negative set of TRUS biopsy , persistently elevated PSA ( but < 20 ng/mL ) and benign feeling digital rectal examination ( DRE ) underwent simultaneous st and ard 12-core TRUS biopsy and 36-core TPTPB under general anaesthesia . We determined the prostate cancer detection rate between the two diagnostic modalities . RESULTS Mean age was 65 years ( range : 50 - 75 ) , mean prostate volume was 59 cc ( range : 21 - 152 ) , mean PSA is 8.3 ng/L ( range : 4.4 - 19 ) , mean time difference between the study and the previous TRUS biopsy was 33 months ( range : 1 - 150 ) with mean PSA velocity of 0.7 ng/mL/year ( range : 0 - 8 ) . Out of the 42 patients , 22 ( 52 % ) had benign pathology . Of the 20 patients ( 48 % ) diagnosed with prostate cancer , 4 ( 10 % ) had positive results in both TRUS biopsy and TPTPB , 1 ( 2 % ) had positive result in TRUS biopsy with negative TPTPB , while 15 ( 36 % ) had negative TRUS biopsy with positive TPTPB . Hence , TRUS biopsy detected cancer in 5/42 ( 12 % ) patients versus ( 19/42 ) 45 % detected by TPTPB ( P < 0.01 ) . 13/19 ( 68 % ) of cancers detected by TPTPB had Gleason score ≥7 . A total of 82/141 ( 58 % ) of positive cores was found in the anterior zone . One patient ( 2 % ) experienced urosepsis , 2 ( 5 % ) temporary urinary retention , 14 ( 34 % ) mild haematuria and 13 ( 32 % ) haematospermia . CONCLUSION TPTPB still shows a significantly higher prostate cancer detection rate compared to TRUS biopsy ( 12 % versus 45 % , P < 0.01 ) in men with a previous set of negative TRUS biopsy , persistently elevated PSA ( but < 20 ng/mL ) and benign feeling prostate on DRE BACKGROUND Approximately 670,000 people in the UK have dementia . Previous literature suggests that physical exercise could slow dementia symptom progression . OBJECTIVES To estimate the clinical effectiveness and cost-effectiveness of a bespoke exercise programme , in addition to usual care , on the cognitive impairment ( primary outcome ) , function and health-related quality of life ( HRQoL ) of people with mild to moderate dementia ( MMD ) and carer burden and HRQoL. DESIGN Intervention development , systematic review , multicentred , r and omised controlled trial ( RCT ) with a parallel economic evaluation and qualitative study . SETTING 15 English regions . PARTICIPANTS People with MMD living in the community . INTERVENTION A 4-month moderate- to high-intensity , structured exercise programme design ed specifically for people with MMD , with support to continue unsupervised physical activity thereafter . Exercises were individually prescribed and progressed , and participants were supervised in groups . The comparator was usual practice . MAIN OUTCOME MEASURES The primary outcome was the Alzheimer 's Disease Assessment Scale - Cognitive Subscale ( ADAS-Cog ) . The secondary outcomes were function [ as measured using the Bristol Activities of Daily Living Scale ( BADLS ) ] , generic HRQoL [ as measured using the EuroQol-5 Dimensions , three-level version ( EQ-5D-3L ) ] , dementia-related QoL [ as measured using the Quality of Life in Alzheimer 's Disease ( QoL-AD ) scale ] , behavioural symptoms [ as measured using the Neuropsychiatric Inventory ( NPI ) ] , falls and fractures , physical fitness ( as measured using the 6-minute walk test ) and muscle strength . Carer outcomes were HRQoL ( Quality of Life in Alzheimer 's Disease ) ( as measured using the EQ-5D-3L ) and carer burden ( as measured using the Zarit Burden Interview ) . The economic evaluation was expressed in terms of incremental cost per quality -adjusted life-year ( QALY ) gained from a NHS and Personal Social Services perspective . We measured health and social care use with the Client Services Receipt Inventory . Participants were followed up for 12 months . RESULTS Between February 2013 and June 2015 , 494 participants were r and omised with an intentional unequal allocation ratio : 165 to usual care and 329 to the intervention . The mean age of participants was 77 years [ st and ard deviation ( SD ) 7.9 years ] , 39 % ( 193/494 ) were female and the mean baseline ADAS-Cog score was 21.5 ( SD 9.0 ) . Participants in the intervention arm achieved high compliance rates , with 65 % ( 214/329 ) attending between 75 % and 100 % of sessions . Outcome data were obtained for 85 % ( 418/494 ) of participants at 12 months , at which point a small , statistically significant negative treatment effect was found in the primary outcome , ADAS-Cog ( patient reported ) , with a mean difference of -1.4 [ 95 % confidence interval ( CI ) -2.62 to -0.17 ] . There were no treatment effects for any of the other secondary outcome measures for participants or carers : for the BADLS there was a mean difference of -0.6 ( 95 % CI -2.05 to 0.78 ) , for the EQ-5D-3L a mean difference of -0.002 ( 95 % CI -0.04 to 0.04 ) , for the QoL-AD scale a mean difference of 0.7 ( 95 % CI -0.21 to 1.65 ) and for the NPI a mean difference of -2.1 ( 95 % CI -4.83 to 0.65 ) . Four serious adverse events were reported . The exercise intervention was dominated in health economic terms . LIMITATIONS In the absence of definitive guidance and rationale , we used a mixed exercise programme . Neither intervention providers nor participants could be masked to treatment allocation . CONCLUSIONS This is a large well-conducted RCT , with good compliance to exercise and research procedures . A structured exercise programme did not produce any clinical ly meaningful benefit in function or HRQoL in people with dementia or on carer burden . FUTURE WORK Future work should concentrate on approaches other than exercise to influence cognitive impairment in dementia . TRIAL REGISTRATION Current Controlled Trials IS RCT N32612072 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full programme and will be published in full in Health Technology Assessment Vol . 22 , No. 28 . See the NIHR Journals Library website for further project information . Additional funding was provided by the Oxford NIHR Biomedical Research Centre and the Oxford NIHR Collaboration for Leadership in Applied Health Research and Care PURPOSE We evaluated the usefulness of pre-biopsy multiparametric magnetic resonance imaging and clinical variables to decrease initial prostate biopsies . MATERIAL S AND METHODS We prospect ively evaluated 351 consecutive men with prostate specific antigen between 2.5 and 20 ng/ml , and /or digital rectal examination suspicious for clinical ly localized disease . All men underwent pre-biopsy multiparametric magnetic resonance imaging and initial 14 to 29-core biopsy , including anterior sampling . Three definitions of significant cancer were defined based on Gleason score and cancer volume ( percent positive core and /or maximum cancer length ) . The overall cohort was divided into men at low risk-prostate specific antigen less than 10 ng/ml and normal digital rectal examination , and high risk-prostate specific antigen 10 ng/ml or greater and /or abnormal digital rectal examination . We evaluated the frequency of significant cancer according to magnetic resonance imaging and risk categories . Clinical variables as significant cancer predictors were analyzed using logistic regression . The sensitivity , specificity , and positive and negative predictive values of magnetic resonance imaging were calculated with or without clinical variables for significant cancer . RESULTS The frequency of significant cancer in men with negative vs positive magnetic resonance imaging was 9 % to 13 % vs 43 % to 50 % in the low risk group and 47 % to 51 % vs 68 % to 71 % in the high risk group . In men at low risk with negative magnetic resonance imaging prostate volume was the only significant predictor of significant cancer . In the low risk group the negative predictive value for significant cancer of a combination of positive magnetic resonance imaging and lower prostate volume ( less than 33 ml ) was 93.7 % to 97.5 % . CONCLUSIONS Pre-biopsy multiparametric magnetic resonance imaging along with prostate volume decreases the number of initial prostate biopsies by discriminating between significant cancer and other cancer in men with prostate specific antigen less than 10 ng/ml and normal digital rectal examination CONTEXT The Prostate Imaging-Reporting and Data System ( PI-RADS ) v2 analysis system for multiparametric magnetic resonance imaging ( mpMRI ) detection of prostate cancer ( PCa ) is based on PI-RADS v1 , accumulated scientific evidence , and expert consensus opinion . OBJECTIVE To summarize the accuracy , strengths and weaknesses of PI-RADS v2 , discuss pathway implication s of its use and outline opportunities for improvements and future developments . EVIDENCE ACQUISITION For this consensus expert opinion from the PI-RADS steering committee , clinical studies , systematic review s , and professional guidelines for mpMRI PCa detection were evaluated . We focused on the performance characteristics of PI-RADS v2 , comparing data to systems based on clinicoradiologic Likert scales and non-PI-RADS v2 imaging only . Evidence selection s were based on high- quality , prospect i ve , histologically verified data , with minimal patient selection and verifications biases . EVIDENCE SYNTHESIS It has been shown that the test performance of PI-RADS v2 in research and clinical practice retains higher accuracy over systematic transrectal ultrasound ( TRUS ) biopsies for PCa diagnosis . PI-RADS v2 fails to detect all cancers but does detect the majority of tumors capable of causing patient harm , which should not be missed . Test performance depends on the definition and prevalence of clinical ly significant disease . Good performance can be attained in practice when the quality of the diagnostic process can be assured , together with joint working of robustly trained radiologists and urologists , conducting biopsy procedures within multidisciplinary teams . CONCLUSIONS It has been shown that the test performance of PI-RADS v2 in research and clinical practice is improved , retaining higher accuracy over systematic TRUS biopsies for PCa diagnosis . PATIENT SUMMARY Multiparametric magnetic resonance imaging ( MRI ) and MRI-directed biopsies using the Prostate Imaging-Reporting and Data System improves the detection of prostate cancers likely to cause harm , and at the same time decreases the detection of disease that does not lead to harms if left untreated . The keys to success are high- quality imaging , reporting , and biopsies by radiologists and urologists working together in multidisciplinary teams BACKGROUND More specific diagnostic for prostate cancer is needed to decrease overdetection and number of diagnostic procedures . OBJECTIVE To assess the performance of combining a blood-based biomarker panel and magnetic resonance imaging (MRI)-targeted biopsies for prostate cancer detection . DESIGN , SETTING , AND PARTICIPANTS We used a prospect i ve , multicenter , paired diagnostic study design . A total of 532 men aged 45 - 74 yr referred for prostate cancer workup were included during 2016 - 2017 . INTERVENTION Participants underwent blood sampling for analysis of the Stockholm3 test including protein biomarkers , genetic polymorphisms , and clinical variables ; 1.5 T MRI ; systematic prostate biopsies ; and MRI-targeted biopsies to lesions with Prostate Imaging Reporting and Data System version 2 ≥3 . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The main outcome was numbers of detected prostate cancer characterized by grade group ( GG ) and the number of performed biopsies using relative sensitivity ( RS ) . RESULTS AND LIMITATIONS Median prostate-specific antigen was 6.3 ng/ml , and mean age was 63.9 yr . Targeted and systematic biopsies detected 170 and 162 GG ≥2 tumors , respectively ( RS 1.05 ; 95 % confidence interval [ CI ] 0.96 - 1.14 ) . Compared with performing systematic biopsies on all men , performing targeted and systematic biopsies only on men with > 10 % risk of GG ≥2 cancer , as predicted by the Stockholm3 test , required 62 % ( 95 % CI 58 - 66 ) of the biopsy procedures and detected 58 % ( 95 % CI 48 - 70 ) of GG 1 disease , with increased sensitivity for GG ≥2 detection ( RS 1.10 ; 95 % CI 1.02 - 1.17 ) . Performing only targeted biopsies in men with elevated Stockholm3 test altered these results only slightly . Compared with performing systematic and targeted biopsies on all men , performing this only for men with an elevated Stockholm3 test decreased detection of GG ≥2 cancer slightly ( RS 0.92 ; 95 % CI 0.88 - 0.95 ) . Limitations include lacking knowledge of true disease prevalence . CONCLUSIONS These findings provide evidence that strategies combining the blood-based Stockholm3 test and MRI-targeted biopsies can be used to inform biopsy decision making . PATIENT SUMMARY In this study , 532 men coming for prostate cancer workup underwent blood sampling , and both traditional and magnetic resonance imaging/fusion-guided prostate biopsies . We report that performing targeted biopsies only in men with an elevated risk as assessed by the Stockholm3 test saved biopsies , decreased overdetection , and maintained the number of detected high- grade cancers Purpose : We evaluated the detection of clinical ly significant prostate cancer using magnetic resonance imaging targeted biopsies and compared visual estimation to image fusion targeting in patients requiring repeat prostate biopsies . Material s and Methods : The prospect i ve , ethics committee approved PICTURE trial ( Clinical Trials.gov NCT01492270 ) enrolled 249 consecutive patients from January 11 , 2012 to January 29 , 2014 . Men underwent multiparametric magnetic resonance imaging and were blinded to the results . All underwent transperineal template prostate mapping biopsies . In 200 men with a lesion this was preceded by visual estimation and image fusion targeted biopsies . As the primary study end point clinical ly significant prostate cancer was defined as Gleason 4 + 3 or greater and /or any grade of cancer with a length of 6 mm or greater . Other definitions of clinical ly significant prostate cancer were also evaluated . Results : Mean ± SD patient age was 62.6 ± 7 years , median prostate specific antigen was 7.17 ng/ml ( IQR 5.25–10.09 ) , mean primary lesion size was 0.37 ± 1.52 cc with a mean of 4.3 ± 2.3 targeted cores per lesion on visual estimation and image fusion combined , and a mean of 48.7 ± 12.3 transperineal template prostate mapping biopsy cores . Transperineal template prostate mapping biopsies detected 97 clinical ly significant prostate cancers ( 48.5 % ) and 85 insignificant cancers ( 42.5 % ) . Overall multiparametric magnetic resonance imaging targeted biopsies detected 81 clinical ly significant prostate cancers ( 40.5 % ) and 63 insignificant cancers ( 31.5 % ) . In the 18 cases ( 9 % ) of clinical ly significant prostate cancer on magnetic resonance imaging targeted biopsies were benign or clinical ly insignificant on transperineal template prostate mapping biopsy . Clinical ly significant prostate cancer was detected in 34 cases ( 17 % ) on transperineal template prostate mapping biopsy but not on magnetic resonance imaging targeted biopsies and approximately half was present in nontargeted areas . Clinical ly significant prostate cancer was found on visual estimation and image fusion in 53 ( 31.3 % ) and 48 ( 28.4 % ) of the 169 patients ( McNemar test p = 0.5322 ) . Visual estimation missed 23 clinical ly significant prostate cancers ( 13.6 % ) detected by image fusion . Image fusion missed 18 clinical ly significant prostate cancers ( 10.8 % ) detected by visual estimation . Conclusions : Magnetic resonance imaging targeted biopsies are accurate for detecting clinical ly significant prostate cancer and reducing the over diagnosis of insignificant cancers . To maximize detection visual estimation as well as image fusion targeted biopsies are required BACKGROUND The Rotterdam European R and omized Study of Screening for Prostate Cancer risk calculators ( ERSPC-RCs ) help to avoid unnecessary transrectal ultrasound-guided systematic biopsies ( TRUS-Bx ) . Multivariable risk stratification could also avoid unnecessary biopsies following multiparametric magnetic resonance imaging ( mpMRI ) . OBJECTIVE To construct MRI-ERSPC-RCs for the prediction of any- and high- grade ( Gleason score ≥3 + 4 ) prostate cancer ( PCa ) in 12-core TRUS-Bx±MRI-targeted biopsy ( MRI-TBx ) by adding Prostate Imaging Reporting and Data System ( PI-RADS ) and age as parameters to the ERSPC-RC3 ( biopsy-naïve men ) and ERSPC-RC4 ( previously biopsied men ) . DESIGN , SETTING , AND PARTICIPANTS A total of 961 men received mpMRI and 12-core TRUS-Bx±MRI-TBx ( in case of PI-RADS ≥3 ) in five institutions . Data of 504 biopsy-naïve and 457 previously biopsied men were used to adjust the ERSPC-RC3 and ERSPC-RC4 . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Logistic regression models were constructed . The areas under the curve ( AUCs ) of the original ERSPC-RCs and MRI-ERSPC-RCs ( including PI-RADS and age ) for any- and high- grade PCa were compared . Decision curve analysis was performed to assess the clinical utility of the MRI-ERSPC-RCs . RESULTS AND LIMITATIONS MRI-ERSPC-RC3 had a significantly higher AUC for high- grade PCa compared with the ERSPC-RC3 : 0.84 ( 95 % confidence interval [ CI ] 0.81 - 0.88 ) versus 0.76 ( 95 % CI 0.71 - 0.80 , p<0.01 ) . Similarly , MRI-ERSPC-RC4 had a higher AUC for high- grade PCa compared with the ERSPC-RC4 : 0.85 ( 95 % CI 0.81 - 0.89 ) versus 0.74 ( 95 % CI 0.69 - 0.79 , p<0.01 ) . Unlike for the MRI-ERSPC-RC3 , decision curve analysis showed clear net benefit of the MRI-ERSPC-RC4 at a high- grade PCa risk threshold of ≥5 % . Using a ≥10 % high- grade PCa risk threshold to biopsy for the MRI-ERSPC-RC4 , 36 % biopsies are saved , missing low- and high- grade PCa , respectively , in 15 % and 4 % of men who are not biopsied . CONCLUSIONS We adjusted the ERSPC-RCs for the prediction of any- and high- grade PCa in 12-core TRUS-Bx±MRI-TBx . Although the ability of the MRI-ERSPC-RC3 for biopsy-naïve men to avoid biopsies remains question able , application of the MRI-ERSPC-RC4 in previously biopsied men in our cohort would have avoided 36 % of biopsies , missing high- grade PCa in 4 % of men who would not have received a biopsy . PATIENT SUMMARY We have constructed magnetic resonance imaging-based Rotterdam European R and omized study of Screening for Prostate Cancer ( MRI-ERSPC ) risk calculators for prostate cancer prediction in transrectal ultrasound-guided biopsy and MRI-targeted biopsy by incorporating age and Prostate Imaging Reporting and Data System score into the original ERSPC risk calculators . The MRI-ERSPC risk calculator for previously biopsied men could be used to avoid one-third of biopsies following MRI BACKGROUND Whether multiparametric MRI improves the detection of clinical ly significant prostate cancer and avoids the need for systematic biopsy in biopsy-naive patients remains controversial . We aim ed to investigate whether using this approach before biopsy would improve detection of clinical ly significant prostate cancer in biopsy-naive patients . METHODS In this prospect i ve , multicentre , paired diagnostic study , done at 16 centres in France , we enrolled patients aged 18 - 75 years with prostate-specific antigen concentrations of 20 ng/mL or less , and with stage T2c or lower prostate cancer . Eligible patients had been referred for prostate multiparametric MRI before a first set of prostate biopsies , with a planned interval of less than 3 months between MRI and biopsies . An operator masked to multiparametric MRI results did a systematic biopsy by obtaining 12 systematic cores and up to two cores targeting hypoechoic lesions . In the same patient , another operator targeted up to two lesions seen on MRI with a Likert score of 3 or higher ( three cores per lesion ) using targeted biopsy based on multiparametric MRI findings . Patients with negative multiparametric MRI ( Likert score ≤2 ) had systematic biopsy only . The primary outcome was the detection of clinical ly significant prostate cancer of International Society of Urological Pathology grade group 2 or higher ( csPCa-A ) , analysed in all patients who received both systematic and targeted biopsies and whose results from both were available for pathological central review , including patients who had protocol deviations . This study is registered with Clinical Trials.gov , number NCT02485379 , and is closed to new participants . FINDINGS Between July 15 , 2015 , and Aug 11 , 2016 , we enrolled 275 patients . 24 ( 9 % ) were excluded from the analysis . 53 ( 21 % ) of 251 analysed patients had negative ( Likert ≤2 ) multiparametric MRI . csPCa-A was detected in 94 ( 37 % ) of 251 patients . 13 ( 14 % ) of these 94 patients were diagnosed by systematic biopsy only , 19 ( 20 % ) by targeted biopsy only , and 62 ( 66 % ) by both techniques . Detection of csPCa-A by systematic biopsy ( 29·9 % , 95 % CI 24·3 - 36·0 ) and targeted biopsy ( 32·3 % , 26·5 - 38·4 ) did not differ significantly ( p=0·38 ) . csPCa-A would have been missed in 5·2 % ( 95 % CI 2·8 - 8·7 ) of patients had systematic biopsy not been done , and in 7·6 % ( 4·6 - 11·6 ) of patients had targeted biopsy not been done . Four grade 3 post-biopsy adverse events were reported ( 3 cases of prostatitis , and 1 case of urinary retention with haematuria ) . INTERPRETATION There was no difference between systematic biopsy and targeted biopsy in the detection of ISUP grade group 2 or higher prostate cancer ; however , this detection was improved by combining both techniques and both techniques showed substantial added value . Thus , obtaining a multiparametric MRI before biopsy in biopsy-naive patients can improve the detection of clinical ly significant prostate cancer but does not seem to avoid the need for systematic biopsy . FUNDING French National Cancer Institute BACKGROUND There is growing interest to implement multiparametric magnetic resonance imaging ( mpMRI ) and MR-guided biopsy ( MRGB ) for biopsy-naïve men with suspected prostate cancer . OBJECTIVE Primary objective was to compare and evaluate an MRI pathway and a transrectal ultrasound-guided biopsy ( TRUSGB ) pathway in biopsy-naïve men with prostate-specific antigen levels of ≥3ng/ml . DESIGN , SETTING , AND POPULATION A prospect i ve , multicenter , powered , comparative effectiveness study included 626 biopsy-naïve patients ( from February 2015 to February 2018 ) . INTERVENTION All patients underwent prebiopsy mpMRI followed by systematic TRUSGB . Men with suspicious lesions on mpMRI also underwent MRGB prior to TRUSGB . MRGB was performed using the in-bore approach . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Clinical ly significant prostate cancer ( csPCa ) was defined as grade group ≥2 ( Gleason score ≥3 + 4 ) in any core . The main secondary objectives were the number of men who could avoid biopsy after nonsuspicious mpMRI , the number of biopsy cores taken , and oncologic follow-up . Differences in proportions were tested using McNemar 's test with adjusted Wald confidence intervals for differences of proportions with matched pairs . RESULTS AND LIMITATIONS The MRI pathway detected csPCa in 159/626 ( 25 % ) patients and insignificant prostate cancer ( insignPCa ) in 88/626 patients ( 14 % ) . TRUSGB detected csPCa in 146/626 patients ( 23 % ) and insignPCa in 155/626 patients ( 25 % ) . Relative sensitivity of the MRI pathway versus the TRUSGB pathway was 1.09 for csPCa ( p=0.17 ) and 0.57 for insignPCa ( p<0.0001 ) . The total number of biopsy cores reduced from 7512 to 849 ( -89 % ) . The MRI pathway enabled biopsy avoidance in 309/626 ( 49 % ) patients due to nonsuspicious mpMRI . Immediate TRUSGB detected csPCa in only 3 % ( 10/309 ) of these patients , increasing to 4 % ( 13/309 ) with 1-yr follow-up . At the same time , TRUSGB would overdetect insignPCa in 20 % ( 63/309 ) . " Focal saturation " by four additional perilesional cores to MRGB improved the detection of csPCa in 21/317 ( 7 % ) patients . Compared with the literature , our proportion of nonsuspicious mpMRI cases is significantly higher ( 27 - 36 % vs 49 % ) and that of equivocal cases is lower ( 15 - 28 % vs 6 % ) . This is probably due to the high- quality st and ard in this study . Therefore , a limitation is the duplication of these results in less experienced centers . CONCLUSIONS In biopsy-naïve men , the MRI pathway compared with the TRUSGB pathway results in an identical detection rate of csPCa , with significantly fewer insignPCa cases . In this high- quality st and ard study , almost half of men have nonsuspicious MRI , which is higher compared with other studies . Not performing TRUS biopsy is at the cost of missing csPCa only in 4 % . PATIENT SUMMARY We compared magnetic resonance imaging ( MRI ) with MRI-guided biopsy against st and ard transrectal ultrasound biopsy for the diagnosis of prostate cancer in biopsy-naïve men . Our results show that patients can benefit from MRI because biopsy may be omitted in half of men , and fewer indolent cancers are detected , without compromising the detection of harmful disease . Men also need fewer needles to make a diagnosis Background Multiparametric magnetic resonance imaging ( MRI ) , with or without targeted biopsy , is an alternative to st and ard transrectal ultrasonography – guided biopsy for prostate‐cancer detection in men with a raised prostate‐specific antigen level who have not undergone biopsy . However , comparative evidence is limited . Methods In a multicenter , r and omized , noninferiority trial , we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI , with or without targeted biopsy , or st and ard transrectal ultrasonography – guided biopsy . Men in the MRI‐targeted biopsy group underwent a targeted biopsy ( without st and ard biopsy cores ) if the MRI was suggestive of prostate cancer ; men whose MRI results were not suggestive of prostate cancer were not offered biopsy . St and ard biopsy was a 10‐to‐12–core , transrectal ultrasonography – guided biopsy . The primary outcome was the proportion of men who received a diagnosis of clinical ly significant cancer . Secondary outcomes included the proportion of men who received a diagnosis of clinical ly insignificant cancer . Results A total of 500 men underwent r and omization . In the MRI‐targeted biopsy group , 71 of 252 men ( 28 % ) had MRI results that were not suggestive of prostate cancer , so they did not undergo biopsy . Clinical ly significant cancer was detected in 95 men ( 38 % ) in the MRI‐targeted biopsy group , as compared with 64 of 248 ( 26 % ) in the st and ard‐biopsy group ( adjusted difference , 12 percentage points ; 95 % confidence interval [ CI ] , 4 to 20 ; P=0.005 ) . MRI , with or without targeted biopsy , was noninferior to st and ard biopsy , and the 95 % confidence interval indicated the superiority of this strategy over st and ard biopsy . Fewer men in the MRI‐targeted biopsy group than in the st and ard‐biopsy group received a diagnosis of clinical ly insignificant cancer ( adjusted difference , ‐13 percentage points ; 95 % CI , ‐19 to ‐7 ; P<0.001 ) . Conclusions The use of risk assessment with MRI before biopsy and MRI‐targeted biopsy was superior to st and ard transrectal ultrasonography – guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously . ( Funded by the National Institute for Health Research and the European Association of Urology Research Foundation ; PRECISION Clinical Trials.gov number , NCT02380027 . OBJECTIVE To prove the feasibility and evaluate the initial clinical results of targeted prostate biopsies using the Urostation novel platform using magnetic resonance imaging (MRI)/transrectal ultrasound ( TRUS ) registration to help steer the biopsy needle to suspicious areas . METHODS We prospect ively included 30 patients for suspicion of prostate cancer from November 2011 to August 2012 . All patients were previously evaluated by a multiparametric MRI , interpreted by a single radiologist who attributed a Prostate Imaging-Reporting and Data System ( PI-RADS ) score to each lesion . A conventional 12-core r and omized biopsy protocol was performed and 2 additional targeted biopsies were performed on suspicious area(s ) . The results of r and omized and targeted biopsies were compared . RESULTS Among the 30 patients , suspicious area(s ) were found on MRI in 20 cases ( 67 % ) . Median procedure time was 23 minutes . Targeting success rate ( biopsy visualized inside the target ) was 83 % , with at least 1 biopsy reaching the target in all cases . Prostate cancer was detected in 14 cases ( 47 % ) , including 11 cases with an abnormal MRI . Targeted biopsies detected cancer in all 11 cases and all but 1 were clinical ly significant . R and omized biopsies detected 10 of these 11 cases , and 3 more cases that MRI considered normal . Sensitivity to detect a significant cancer was 91 % in both modalities . CONCLUSION This initial clinical study showed encouraging results for targeted MRI-guided prostate biopsies using MRI-TRUS fusion . Although further studies are needed to determine the role of prostate MRI before biopsy and the relevance of targeted biopsies , the Urostation is an MRI-TRUS fusion device that has good accuracy for targeting suspicious areas on MRI Background Transrectal ultrasound-guided prostate biopsies are prone to detection errors . Multi-parametric MRI ( MP-MRI ) may improve the diagnostic pathway . Methods PROMIS is a prospect i ve validating paired-cohort study that meets criteria for level 1 evidence in diagnostic test evaluation . PROMIS will investigate whether multi-parametric (MP)-MRI can discriminate between men with and without clinical ly-significant prostate cancer who are at risk prior to first biopsy . Up to 714 men will have MP-MRI ( index ) , 10–12 core TRUS-biopsy ( st and ard ) and 5 mm transperineal template mapping ( TPM ) biopsies ( reference ) . The conduct and reporting of each test will be blinded to the others . Results PROMIS will measure and compare sensitivity , specificity , and positive and negative predictive values of both MP-MRI and TRUS-biopsy against TPM biopsies . The MP-MRI results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of clinical ly-significant cancers . For the primary outcome , significant cancer on TPM is defined as Gleason grade > /= 4 + 3 and /or maximum cancer core length of ≥ 6 mm . PROMIS will also assess inter-observer variability among radiologists among other secondary outcomes . Cost-effectiveness of MP-MRI prior to biopsy will also be evaluated . Conclusions PROMIS will determine whether MP-MRI of the prostate prior to first biopsy improves the detection accuracy of clinical ly-significant cancer PURPOSE To evaluate the differences in prostate cancer detection rate and biopsy effectiveness between magnetic resonance imaging ( MRI ) target biopsy ( TB ) and transperineal st and ard biopsy ( SB ) in biopsy-naïve patients . MATERIAL AND METHODS Between October 2014 and April 2016 , 60 men with a mean age of 64.1±6.7 ( SD ) years ( range : 53 - 82 years ) were prospect ively enrolled . All patients underwent a prostate MRI study , evaluated by two radiologists , before undergoing the biopsy . A transperineal 12-core SB was carried out before TB , without the information from the MRI . The detection rate for all tumors and for clinical ly significant tumors ( CS ) was recorded . Sampling variables such as the proportion of cores positive for CS cancer ( PCP-CS ) and the maximum cancer core length ( MCCL ) were also calculated . The ability of MRI to predict the presence of a CS tumor at biopsy was studied using a sector analysis . Patients with negative biopsies were followed during a minimum of 12 months . RESULTS The detection rate for SB and TB was 53.3 % ( 32/60 ) and 46.7 % ( 28/60 ) respectively for all tumors ( P=0.289 ) and 45 % ( 27/60 ) in both techniques for CS tumors . TB obtained a larger PCP-CS ( P<0.001 ) and MCCL ( P=0.018 ) . The sensitivity , specificity , positive predictive value , negative predictive value and cancer prevalence was 83.3 % , 92.9 % , 83.3 % , 92.9 % and 30 % for peripheral zone sectors and 43.8 % , 97.1 % , 70.0 % , 91.8 % and 13,3 % for transitional zone sectors . The proportion of patients that showed an increase of PSA faster than 0.75ng/mL/year after a negative biopsy was 26.1 % . CONCLUSION Detection rate of prostate cancer did not show significant differences between a TB and a SB technique in biopsy-naïve patients . However , targeted prostate biopsies demonstrated a better sampling effectiveness thus reducing the cores needed to diagnose clinical ly significant tumors BACKGROUND Prostate cancer prediction tools provide quantitative guidance for doctor-patient decision-making regarding biopsy . The widely used online Prostate Cancer Prevention Trial Risk Calculator ( PCPTRC ) utilized data from the 1990s based on six-core biopsies and out date d grading systems . OBJECTIVE We prospect ively gathered data from men undergoing prostate biopsy in multiple diverse North American and European institutions participating in the Prostate Biopsy Collaborative Group ( PBCG ) in order to build a state-of-the-art risk prediction tool . DESIGN , SETTING , AND PARTICIPANTS We obtained data from 15 611 men undergoing 16 369 prostate biopsies during 2006 - 2017 at eight North American institutions for model-building and three European institutions for validation . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We used multinomial logistic regression to estimate the risks of high- grade prostate cancer ( Gleason score ≥7 ) on biopsy based on clinical characteristics , including age , prostate-specific antigen , digital rectal exam , African ancestry , first-degree family history , and prior negative biopsy . We compared the PBCG model to the PCPTRC using internal cross-validation and external validation on the European cohorts . RESULTS AND LIMITATIONS Cross-validation on the North American cohorts ( 5992 biopsies ) yielded the PBCG model area under the receiver operating characteristic curve ( AUC ) as 75.5 % ( 95 % confidence interval : 74.2 - 76.8 ) , a small improvement over the AUC of 72.3 % ( 70.9 - 73.7 ) for the PCPTRC ( p<0.0001 ) . However , calibration and clinical net benefit were far superior for the PBCG model . Using a risk threshold of 10 % , clinical use of the PBCG model would lead to the equivalent of 25 fewer biopsies per 1000 patients without missing any high- grade cancers . Results were similar on external validation on 10 377 European biopsies . CONCLUSIONS The PBCG model should be used in place of the PCPTRC for prediction of prostate biopsy outcome . PATIENT SUMMARY A contemporary risk tool for outcomes on prostate biopsy based on the routine clinical risk factors is now available for informed decision-making BACKGROUND Multiparametric magnetic resonance imaging ( mpMRI ) may have a role in detecting clinical ly significant prostate cancer in men with raised serum prostate-specific antigen levels . Variations in technique and the interpretation of images have contributed to inconsistency in its reported performance characteristics . OBJECTIVE Our aim was to make recommendations on a st and ardised method for the conduct , interpretation , and reporting of prostate mpMRI for prostate cancer detection and localisation . DESIGN , SETTING , AND PARTICIPANTS A consensus meeting of 16 European prostate cancer experts was held that followed the UCLA-R AND Appropriateness Method and facilitated by an independent chair . MEASUREMENT Before the meeting , 520 items were scored for " appropriateness " by panel members , discussed face to face , and rescored . RESULTS AND LIMITATIONS Agreement was reached in 67 % of 260 items related to imaging sequence parameters . T2-weighted , dynamic contrast-enhanced , and diffusion-weighted MRI were the key sequences incorporated into the minimum requirements . Consensus was also reached on 54 % of 260 items related to image interpretation and reporting , including features of malignancy on individual sequences . A 5-point scale was agreed on for communicating the probability of malignancy , with a minimum of 16 prostatic regions of interest , to include a pictorial representation of suspicious foci . Limitations relate to consensus methodology . Dominant personalities are known to affect the opinions of the group and were countered by a neutral chairperson . CONCLUSIONS Consensus was reached on a number of areas related to the conduct , interpretation , and reporting of mpMRI for the detection , localisation , and characterisation of prostate cancer . Before optimal dissemination of this technology , these outcomes will require formal validation in prospect i ve trials |
1,056 | 27,592,496 | Definitive trials are needed to demonstrate that CBT is an empirically vali date d treatment for use with people who have ASDs | The aims of this study were to undertake a meta-analytic and systematic appraisal of the literature investigating the effectiveness of cognitive behavioural therapy ( CBT ) when used with individuals who have autistic spectrum disorders ( ASDs ) for either a ) affective disorders , or b ) the symptoms of ASDs . | 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 predictors of outcome , after controlling for baseline covariates . RESULTS Higher CBT competence was associated with better clinical outcomes whereas CBT adherence was not . Also , CBT competence was inversely correlated with years of clinical experience and trended ( not significantly , though ) down as the study progressed . CBT adherence was inversely correlated with therapist tenure in the study . CONCLUSIONS Therapist competence was related to improved clinical outcomes when CBT for anxiety disorders was delivered by novice clinicians with technology assistance . The results highlight the value of the initial training for novice therapists as well as booster training to limit declines in therapist adherence Impaired social functioning is a hallmark feature of autism spectrum disorder ( ASD ) , often requiring treatment throughout the life span . PEERS ® ( Program for the Education and Enrichment of Relational Skills ) is a parent‐assisted social skills training for teens with ASD . Although PEERS ® has an established evidence base in improving the social skills of adolescents and young adults with ASD in North America , the efficacy of this treatment has yet to be established in cross‐cultural validation trials . The objective of this study is to examine the feasibility and treatment efficacy of a Korean version of PEERS ® for enhancing social skills through a r and omized controlled trial ( RCT ) .The English version of the PEERS ® Treatment Manual ( Laugeson & Frankel , 2010 ) was translated into Korean and review ed by 21 child mental health professionals . Items identified as culturally sensitive were surveyed by 447 middle school students , and material was modified accordingly . Participants included 47 teens between 12 and 18 years of age with a diagnosis of ASD and a verbal intelligence quotient ( IQ ) ≥ 65 . Eligible teens were r and omly assigned to a treatment group ( TG ) or delayed treatment control group ( CG ) . Primary outcome measures included question naires and direct observations quantifying social ability and problems directly related to ASD . Secondary outcome measures included scales for depressive symptoms , anxiety , and other behavioral problems . Rating scales for parental depressive symptoms and anxiety were examined to detect changes in parental psychosocial functioning throughout the PEERS ® treatment . Independent sample s t‐tests revealed no significant differences at baseline across the TG and CG conditions with regard to age ( 14.04 ± 1.64 and 13.54 ± 1.50 years ) , IQ ( 99.39 ± 18.09 & 100.67 ± 16.97 ) , parental education , socioeconomic status , or ASD symptoms ( p < 0.05 ) , respectively . Results for treatment outcome suggest that the TG showed significant improvement in communication and social interaction domain scores on the Autism Diagnostic Observation Schedule , interpersonal relationship and play/leisure time on the subdomain scores of the Korean version of the Vinel and Adaptive Behavior Scale ( p 's < 0.01 ) , social skills knowledge total scores on the Test of Adolescent Social Skills Knowledge — Revised ( p < 0.01 ) , and decreased depressive symptoms on the Child Depression Inventory following treatment ( p < 0.05 ) . Analyses of parental outcome reveal a significant decrease in maternal state anxiety in the TG after controlling for potential confounding variables ( p < 0.05 ) . Despite cultural and linguistic differences , the PEERS ® social skills intervention appears to be efficacious for teens with ASD in Korea with modest cultural adjustment . In an RCT , participants receiving the PEERS ® treatment showed significant improvement in social skills knowledge , interpersonal skills , and play/leisure skills , as well as a decrease in depressive symptoms and ASD symptoms . This study represents one of only a few cross‐cultural validation trials of an established evidence ‐based treatment for adolescents with ASD . Autism Res 2014 , 7 : 145–161 . © 2014 International Society for Autism Research , Wiley Periodicals , Introduction A number of studies have established that children , adolescents and adults with Asperger syndrome ( AS ) and high functioning autism ( HFA ) have significant problems with anxiety . Cognitive behavioural therapy ( CBT ) is an effective treatment for anxiety in a variety of clinical population s. There is a growing interest in exploring the effectiveness of CBT for people with AS who have mental health problems , but currently there are no known clinical trials involving adults with AS or HFA . Studies with children who have AS have reported some success . The current study aims to examine whether modified group CBT for clinical ly significant anxiety in an AS population is likely to be efficacious . Methods and analysis This study is a r and omised , single-blind crossover trial . At least 36 individuals will be recruited and r and omised into a treatment arm or a waiting-list control arm . During treatment , individuals will receive 3 sessions of individual CBT , followed by 21 sessions of group CBT . Primary outcome measures focus on anxiety . Secondary outcome measures focus on everyday social and psychiatric functioning , additional measures of anxiety and fear , depression , health-related quality of life and treatment cost . Assessment s will be administered at pregroup and postgroup and at follow-up by research ers who are blinded to group allocation . The trial aims to find out whether or not psychological treatments for anxiety can be adapted and used to successfully treat the anxiety experienced by people with AS . Furthermore , we aim to determine whether this intervention represents good value for money . Ethics and dissemination The trial received a favourable ethical opinion from a National Health Service ( NHS ) Research Ethics Committee . All participants provided written informed consent . Findings will be shared with all trial participants , and the general public , as well as the scientific community . Trial Registration IS RCT N 30265294 ( DOI : 10.1186/IS RCT N30265294 ) , UKCRN 8370 Anxiety is common among adolescents with autism spectrum disorders ( ASD ) and may amplify the core social disability , thus necessitating combined treatment approaches . This pilot , r and omized controlled trial evaluated the feasibility and preliminary outcomes of the Multimodal Anxiety and Social Skills Intervention ( MASSI ) program in a sample of 30 adolescents with ASD and anxiety symptoms of moderate or greater severity . The treatment was acceptable to families , subject adherence was high , and therapist fidelity was high . A 16 % improvement in ASD social impairment ( within-group effect size = 1.18 ) was observed on a parent-reported scale . Although anxiety symptoms declined by 26 % , the change was not statistically significant . These findings suggest MASSI is a feasible treatment program and further evaluation is warranted This study tested the efficacy of a new social skills intervention , SocialSkillsGRoupINtervention-High Functioning Autism ( S.S.GRIN-HFA ) , design ed to improve social behaviors in children with high functioning autism spectrum disorders . Fifty-five children were r and omly assigned to S.S.GRIN-HFA treatment ( n = 27 ) or control ( i.e. , traditional S.S.GRIN intervention ; n = 28 ) . Examination of the direction and magnitude of change in functioning revealed that children who participated in S.S.GRIN-HFA exhibited significantly greater mastery of social skill concepts compared to children in the control group . Parents of S.S.GRIN-HFA group participants reported an improved sense of social self-efficacy , whereas parents of control participants reported a decline . The advantages of a specialized intervention such as S.S.GRIN-HFA , design ed specifically for children with high functioning autism spectrum disorders , are discussed OBJECTIVE To examine the efficacy of a modular cognitive-behavioral therapy ( CBT ) protocol relative to treatment as usual ( TAU ) among children with high-functioning autism spectrum disorders ( ASD ) and clinical ly significant anxiety . METHOD A total of 45 children ( 7 - 11 years of age ) with high-functioning ASD and clinical ly significant anxiety were r and omized to receive 16 sessions of weekly CBT or TAU for an equivalent duration . After screening , assessment s were conducted at baseline , post-treatment , and 3-month follow-up . Raters were blind to treatment condition . RESULTS Youth receiving CBT showed substantial improvement relative to TAU on primary anxiety outcomes . Of 24 children r and omized to the CBT arm , 18 ( 75 % ) were treatment responders , versus only 3 of 21 children ( 14 % ) in the TAU arm . Gains were generally maintained at 3-month follow-up for CBT responders . CONCLUSIONS Relative to usual care , CBT adapted for anxious youth with high-functioning ASD demonstrates large effects in reducing anxiety symptoms . This study contributes to the growing literature supporting adapted CBT approaches for treating anxiety in youth with ASD Research shows that depression and anxiety disorders are the most common psychiatric concern in autism spectrum disorders ( ASD ) . Mindfulness-based therapy ( MBT ) has been found effective in reducing anxiety and depression symptoms , however research in autism is limited . Therefore , we examined the effects of a modified MBT protocol ( MBT-AS ) in high-functioning adults with ASD . 42 participants were r and omized into a 9-week MBT-AS training or a wait-list control group . Results showed a significant reduction in depression , anxiety and rumination in the intervention group , as opposed to the control group . Furthermore , positive affect increased in the intervention group , but not in the control group . Concluding , the present study is the first controlled trial to demonstrate that adults with ASD can benefit from MBT-AS BACKGROUND High rates of anxiety disorders , particularly obsessive compulsive disorder ( OCD ) are reported in people with Autism spectrum disorders ( ASD ) . Group cognitive behavioral treatment ( CBT ) has been found effective for anxiety in young people with ASD but not been OCD specific . One uncontrolled pilot study of individual CBT for OCD for adults with ASD showed good treatment efficacy . METHODS Forty-six adolescents and adults ( mean age 26.9 years , 35 Males ) with ASD and comorbid OCD were r and omized to CBT for OCD or anxiety management ( AM ) , a plausible control treatment . Treatments were matched in duration ( mean of 17.4 sessions CBT ; 14.4 sessions AM ) , the Yale-Brown Obsessive Compulsive Severity Scale ( YBOCS ) as primary outcome measure and evaluations blind to treatment group . Treatment response was defined as > 25 % reduction in YBOCS total severity scores . RESULTS Both treatments produced a significant reduction in OCD symptoms , within-group effect sizes of 1.01 CBT group and 0.6 for the AM group . There were no statistically significant differences between the two groups at end of treatment , although more responders in the CBT group ( 45 versus 20 % ) . Effect sizes for self-rated improvement were small ( 0.33 CBT group ; -0.05 AM group ) . Mild symptom severity was associated with improvement in the AM but not the CBT group . Family/carer factors were important for both groups , in that increased family accommodation was associated with poorer outcome . CONCLUSIONS Evidence -based psychological interventions , both AM and CBT , were effective in treating comorbid OCD in young people and adults with ASD CONTEXT To our knowledge , there is no published information on the epidemiology of autism spectrum disorders ( ASDs ) in adults . If the prevalence of autism is increasing , rates in older adults would be expected to be lower than rates among younger adults . OBJECTIVE To estimate the prevalence and characteristics of adults with ASD living in the community in Engl and . DESIGN A stratified , multiphase r and om sample was used in the third national survey of psychiatric morbidity in adults in Engl and in 2007 . Survey data were weighted to take account of study design and nonresponse so that the results were representative of the household population . SETTING General community ( ie , private households ) in Engl and . PARTICIPANTS Adults ( people 16 years or older ) . MAIN OUTCOME MEASURES Autism Diagnostic Observation Schedule , Module 4 in phase 2 vali date d against the Autism Diagnostic Interview-Revised and Diagnostic Interview for Social and Communication Disorders in phase 3 . A 20-item subset of the Autism-Spectrum Quotient self-completion question naire was used in phase 1 to select respondents for phase 2 . Respondents also provided information on sociodemographics and their use of mental health services . RESULTS Of 7461 adult participants who provided a complete phase 1 interview , 618 completed phase 2 diagnostic assessment s. The weighted prevalence of ASD in adults was estimated to be 9.8 per 1000 ( 95 % confidence interval , 3.0 - 16.5 ) . Prevalence was not related to the respondent 's age . Rates were higher in men , those without educational qualifications , and those living in rented social ( government-financed ) housing . There was no evidence of increased use of services for mental health problems . CONCLUSIONS Conducting epidemiologic research on ASD in adults is feasible . The prevalence of ASD in this population is similar to that found in children . The lack of an association with age is consistent with there having been no increase in prevalence and with its causes being temporally constant . Adults with ASD living in the community are socially disadvantaged and tend to be unrecognized Although adults with autism spectrum disorder are an increasingly identified patient population , few treatment options are available . This preliminary r and omized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range : cognitive behavioural therapy and recreational activity . Both interventions comprised 36 weekly 3-h sessions led by two therapists in groups of 6–8 patients . A total of 68 psychiatric patients with autism spectrum disorders participated in the study . Outcome measures were Quality of Life Inventory , Sense of Coherence Scale , Rosenberg Self-Esteem Scale and an exploratory analysis on measures of psychiatric health . Participants in both treatment conditions reported an increased quality of life at post-treatment ( d = 0.39 , p < 0.001 ) , with no difference between interventions . No amelioration of psychiatric symptoms was observed . The dropout rate was lower with cognitive behavioural therapy than with recreational activity , and participants in cognitive behavioural therapy rated themselves as more generally improved , as well as more improved regarding expression of needs and underst and ing of difficulties . Both interventions appear to be promising treatment options for adults with autism spectrum disorder . The interventions ’ similar efficacy may be due to the common elements , structure and group setting . Cognitive behavioural therapy may be additionally beneficial in terms of increasing specific skills and minimizing dropout The purpose of this pilot study was to evaluate whether a modified version of the Coping Cat program could be effective in reducing anxiety in children with autism spectrum disorder ( ASD ) . Twenty-two children ( ages 8–14 ; IQ ≥ 70 ) with ASD and clinical ly significant anxiety were r and omly assigned to 16 sessions of the Coping Cat program ( cognitive-behavioral therapy ; CBT ) or a 16-week waitlist . Children in the CBT condition evidence d significantly larger reductions in anxiety than those in the waitlist . Treatment gains were largely maintained at two-month follow-up . Results provide preliminary evidence that a modified version of the Coping Cat program may be a feasible and effective program for reducing clinical ly significant levels of anxiety in children with high-functioning ASD Limited perspective taking or “ Theory of Mind ” ( ToM ) abilities are a core deficit of autism , and many interventions are aim ed to improve ToM abilities . In this study , we investigated the effectiveness of a ToM treatment for children with autism spectrum disorders ( ASD ) and , for the first time , the moderating roles of social interaction style ( SIS ) and disruptive behavior ( DB ) , to determine which children are most likely to respond to this intervention . The trial protocol is registered at www.trialregister.nl , trial number 2327 and published before the data collection was finished ( www.trialsjournal.com ) . Children with autism aged 7–12 years ( n = 97 ) were r and omized over a waitlist control or a treatment condition . Outcome measures included ToM and emotion underst and ing , parent and teacher question naires on children 's social skills , ToM‐related social behavior , and autistic traits . Six‐month follow‐up parent reported data were collected for the treatment group . The treatment had a positive effect on ToM underst and ing , parent‐reported ToM behavior , and autistic traits , but not on parent or teacher‐reported social behavior . Passive SIS was associated with diminished treatment effects on autistic traits , but DB was unrelated to outcomes . The ToM intervention improved conceptual social underst and ing and ToM‐related behavior of children with ASD . However , broader application of learned skills to other domains of functioning was limited . Individual differences with regard to treatment response are discussed . Autism Res 2015 , 8 : 738–748 . © 2015 International Society for Autism Research , Wiley Periodicals , This study aim ed to evaluate the Program for the Education and Enrichment of Relational Skills ( PEERS : Laugeson et al. in J Autism Dev Disord 39(4):596–606 , 2009 ) . PEERS focuses on improving friendship quality and social skills among adolescents with higher-functioning ASD . 58 participants aged 11–16 years-old were r and omly assigned to either an immediate treatment or waitlist comparison group . Results revealed , in comparison to the waitlist group , that the experimental treatment group significantly improved their knowledge of PEERS concepts and friendship skills , increased in their amount of get-togethers , and decreased in their levels of social anxiety , core autistic symptoms , and problem behaviors from pre-to post-PEERS . This study provides the first independent replication and extension of the empirically-supported PEERS social skills intervention for adolescents with ASD BACKGROUND Group-based psychotherapy in Autism Spectrum Disorder ( ASD ) has predominantly been studied in the United States by small studies in school-aged children without long-term follow-up . We report results of a large , confirmatory , multicentre r and omized-controlled phase-III trial in children and adolescents study ing the ASD specific , manualized group-based cognitive behavioural SOSTA-FRA approach . METHODS High-functioning ASD individuals aged 8 - 19 years old were r and omized to 12 sessions SOSTA-FRA or treatment as usual . Primary outcomes were change in total raw score of the parent-rated Social Responsiveness Scale ( pSRS ) between baseline ( T2 ) and end of intervention ( T4 ) , and between T2 and 3 months after end of intervention ( T5 ) . TRIAL REGISTRATION IS RCT N94863788 . RESULTS Between 20/5/2010 and 14/2/2013 , n = 320 ASD patients were screened , n = 228 patients were r and omized , and N = 209 analysed . Mean pSRS difference between groups at T4 was -6.5 ( 95 % CI -11.6 to - 1.4 ; p = .013 ) , and at T5 -6.4 ( -11.5 to -1.3 , p = .015 ) . Pre-treatment SRS and IQ were positively associated with stronger improvement at T4 and T5 . CONCLUSIONS Short-term ASD-specific add-on group-based psychotherapy has shown postintervention efficacy with regard to parent-rated social responsiveness predominantly in male high-functioning children and adolescents with ASD . Future studies should implement blinded st and ardized observational measures of peer-related social interaction High-functioning autism ( HFA ) is characterized by persistent impairment in social interaction despite the absence of mental retardation . Although an increasing number of group-based programs for the improvement of social skills have been described , r and omized controlled trials are needed to evaluate their efficacy . To compare the effect of a Social Skills Training Group-based Program ( SST-GP ) and a Leisure Activities Group-based Program ( LA-GP ) on the perception of facial emotions and quality of life ( QoL ) in young people with HFA . Eligible patients were children and adolescents with HFA . Participants were r and omized to the SST or LA group . The primary outcome was defined as an improvement of 2 points in error rates for facial emotion labeling ( DANVA2 ) from baseline . After the 6-month training period , the SST Group made fewer errors in labeling anger on adult faces , whereas error rates in the LA Group remained stable . Progress in the ability to recognize anger in the SST Group was due to better recognition of low intensity stimuli on adult faces . QoL increased in the SST Group in the dimension of school environment , as a marker of the transfer of skills acquired in the treatment setting to their use in the community . The SST-GP had higher efficacy than the LA-GP . Data justify replication using larger sample Clinical ly elevated anxiety is a common , impairing feature of autism spectrum disorders ( ASD ) . A modular CBT program design ed for preteens with ASD , Behavioral Interventions for Anxiety in Children with Autism ( BIACA ; Wood et al. , 2009 ) was enhanced and modified to address the developmental needs of early adolescents with ASD and clinical anxiety . Thirty-three adolescents ( 11 - 15 years old ) were r and omly assigned to 16 sessions of CBT or an equivalent waitlist period . The CBT model emphasized exposure , challenging irrational beliefs , and behavioral supports provided by caregivers , as well as numerous ASD-specific treatment elements . Independent evaluators , parents , and adolescents rated symptom severity at baseline and posttreatment/postwaitlist . In intent-to-treat analyses , the CBT group outperformed the waitlist group on independent evaluators ' ratings of anxiety severity on the Pediatric Anxiety Rating Scale ( PARS ) and 79 % of the CBT group met Clinical Global Impressions-Improvement scale criteria for positive treatment response at posttreatment , as compared to only 28.6 % of the waitlist group . Group differences were not found for diagnostic remission or question naire measures of anxiety . However , parent-report data indicated that there was a positive treatment effect of CBT on autism symptom severity . The CBT manual under investigation , enhanced for early adolescents with ASD , yielded meaningful treatment effects on the primary outcome measure ( PARS ) , although additional developmental modifications to the manual are likely warranted . Future studies examining this protocol relative to an active control are needed BACKGROUND Children with autism spectrum disorders often present with comorbid anxiety disorders that cause significant functional impairment . This study tested a modular cognitive behavioral therapy ( CBT ) program for children with this profile . A st and ard CBT program was augmented with multiple treatment components design ed to accommo date or remediate the social and adaptive skill deficits of children with ASD that could pose barriers to anxiety reduction . METHOD Forty children ( 7 - 11 years old ) were r and omly assigned to 16 sessions of CBT or a 3-month waitlist ( 36 completed treatment or waitlist ) . Therapists worked with individual families . The CBT model emphasized behavioral experimentation , parent-training , and school consultation . Independent evaluators blind to treatment condition conducted structured diagnostic interviews and parents and children completed anxiety symptom checklists at baseline and posttreatment/postwaitlist . RESULTS In intent-to-treat analyses , 78.5 % of the CBT group met Clinical Global Impressions-Improvement scale criteria for positive treatment response at posttreatment , as compared to only 8.7 % of the waitlist group . CBT also outperformed the waitlist on diagnostic outcomes and parent reports of child anxiety , but not children 's self-reports . Treatment gains were maintained at 3-month follow-up . CONCLUSIONS The CBT manual employed in this study is one of the first adaptations of an evidence -based treatment for children with autism spectrum disorders . Remission of anxiety disorders appears to be an achievable goal among high-functioning children with autism This study compared cognitive behavioral therapy ( CBT ) and treatment-as-usual ( TAU ) in terms of effects on observed social communication-related autism symptom severity during unstructured play time at school for children with autism spectrum disorders ( ASD ) . Thirteen children with ASD ( 7–11 years old ) were r and omly assigned to 32 sessions of CBT or community-based psychosocial treatment ( TAU ) for 16 weeks . The CBT program is based on the memory retrieval competition model and emphasizes the development of perspective-taking through guided behavioral experimentation supplemented with reflective Socratic discussion and supported by parent training and school consultation to promote generalization of social communication and emotion regulation skills . Trained observers blind to treatment condition observed each child during recess on two separate days at baseline and again at posttreatment , using a structured behavioral observation system that generates frequency scores for observed social communication-related autism symptoms . CBT outperformed TAU at posttreatment on the frequency of self-isolation , the proportion of time spent with peers , the frequency of positive or appropriate interaction with peers , and the frequency of positive or appropriate peer responses to the target child ( d effect size range 1.34–1.62 ) . On average , children in CBT were engaged in positive or appropriate social interaction with peers in 68.6 % of observed intervals at posttreatment , compared to 25 % of intervals for children in TAU . Further investigation of this intervention modality with larger sample s and follow-up assessment s is warranted BACKGROUND The aim of the study was to evaluate the effectiveness of a brief CBT intervention for anxiety with children diagnosed with Asperger syndrome ( AS ) . A second interest was to evaluate whether more intensive parent involvement would increase the child 's ability to manage anxiety outside of the clinic setting . METHODS Seventy-one children aged ten to twelve years were recruited to participate in the anxiety programme . All children were diagnosed with AS and the presence of anxiety symptoms was accepted on parent report via brief interview . Children were r and omly assigned to one of three conditions : intervention for child only , intervention for child and parent , wait-list control . RESULTS The two intervention groups demonstrated significant decreases in parent-reported anxiety symptoms at follow-up and a significant increase in the child 's ability to generate positive strategies in an anxiety-provoking situation . There were a number of significant differences between the two interventions to suggest parent involvement as beneficial . CONCLUSIONS The sample of children with AS in this study presented with a profile of anxiety similar to a sample of clinical ly diagnosed anxious children . The intervention was endorsed by parents as a useful programme for children diagnosed with Asperger syndrome and exhibiting anxiety symptoms , and active parent involvement enhanced the usefulness of the programme . Limitations of the study and future research are discussed Youth with autism spectrum disorders frequently experience significant symptoms of anxiety . Empirically supported psychosocial interventions exist , yet access is limited , especially for families in rural areas . Telehealth ( i.e. videoconferencing ) has potential to reduce barriers to access to care ; however , little is known about the feasibility or efficacy of directly intervening with youth with autism spectrum disorders through this modality . This study details the pilot testing of a telehealth version of an empirically supported intervention targeting anxiety in youth with autism spectrum disorders . The primary focus of this study is on feasibility , with evaluation of outcomes as a starting point for future r and omized trials . In all , 33 families of youth with autism spectrum disorders and significant anxiety symptoms participated in this study ( Telehealth Facing Your Fears ( FYF ) Intervention : n = 17 ; Wait-list control : n = 16 ) . Youth of all functioning levels were included . Acceptability was strong ; however , the usability of the technology was problematic for some families and impeded some sessions significantly . Fidelity of the telehealth version to the critical elements of the original , in vivo version was excellent . More work is needed to improve delivery of exposure practice s and parent coaching . Preliminary efficacy analyses are promising , with improvements observed in youth anxiety over time ( relative to a comparison group waiting for live intervention ) and parent sense of competence ( within group ) . Clearly , stronger design s are necessary to evaluate efficacy sufficiently ; however , this study does provide support for further investigation of clinic-to-home videoconferencing as a direct intervention tool for youth with autism spectrum disorders and their parents OBJECTIVE This study evaluated the efficacy of a targeted social skills training group in school-aged children with autism spectrum disorder ( ASD ) . The intervention , Seaver-NETT ( Nonverbal communication , Emotion recognition , and Theory of mind Training ) , is a 12-session cognitive-behavioral intervention ( CBI ) for verbal , school-aged children targeting ASD-specific social behavioral impairments . METHOD Sixty-nine children with ASD , 8 to 11 years of age , with verbal IQs greater than 70 , participated in a r and omized comparative trial to examine the efficacy of NETT relative to a facilitated play group . Treatment outcomes included caregiver reports of social behavior and neuropsychological assessment s of social cognition conducted by blinded raters . Outcomes were collected at baseline , endpoint , and 3 months posttreatment . RESULTS Significant improvements were found on social behavior outcomes such as nonverbal communication , empathic responding , and social relations in the NETT condition relative to the active control at endpoint . Verbal IQ moderated the interaction effect on social behavior , with higher verbal IQ associated with improvements in the CBI condition . No significant improvements were found on social cognitive outcomes . No significant group differences were found at 3-month follow-up conducted with approximately half the sample ( n = 34 ) . CONCLUSION These data indicate that targeted CBI social skills groups such as NETT improve social communication deficits in verbal , school-aged children with ASD . The moderating effects of high verbal IQ suggest a need to consider participant and treatment characteristics associated with outcomes in future studies . Clinical trial registration information-Neural and Behavioral Outcomes of Social Skills Groups in Children With Autism Spectrum Disorder ; https:// clinical trials.gov ; NCT01190917 This RCT examined the efficacy of a manualized social intervention for children with HFASDs . Participants were r and omly assigned to treatment or wait-list conditions . Treatment included instruction and therapeutic activities targeting social skills , face-emotion recognition , interest expansion , and interpretation of non-literal language . A response-cost program was applied to reduce problem behaviors and foster skills acquisition . Significant treatment effects were found for five of seven primary outcome measures ( parent ratings and direct child measures ) . Secondary measures based on staff ratings ( treatment group only ) corroborated gains reported by parents . High levels of parent , child and staff satisfaction were reported , along with high levels of treatment fidelity . St and ardized effect size estimates were primarily in the medium and large ranges and favored the treatment group The purpose of the study described was to evaluate the effectiveness of a cognitive behavioural intervention for anger management with children diagnosed with Asperger syndrome . Forty-five children and their parents were r and omly assigned to either intervention or wait-list control conditions . Children in the intervention participated in six 2-h weekly sessions while parents participated in a larger parent group . Parent reports indicated a significant decrease in episodes of anger following intervention and a significant increase in their own confidence in managing anger in their child . Qualitative information gathered from parents and teachers indicated some generalization of strategies learned in the clinic setting to both home and school setting s. Limitations of the study and suggestions for future research are also discussed We compared the effects of a 16-week Cognitive-Behavioral Therapy ( CBT ) program and a Social Recreational ( SR ) program on anxiety in children with Autism Spectrum Disorders ( ASD ) . Seventy children ( 9–16 years old ) were r and omly assigned to either of the programs ( nCBT = 36 ; nSR = 34 ) . Measures on child ’s anxiety using the Spence Child Anxiety Scale — Child ( SCAS-C ) and the Clinical Global Impression — Severity scale ( CGI-S ) were administered at pre- , post-treatment , and follow-ups ( 3- and 6-month ) . Children in both programs showed significantly lower levels of generalized anxiety and total anxiety symptoms at 6-month follow-up on SCAS-C. Clinician ratings on the CGI-S demonstrated an increase in the percentage of participants rated as “ Normal ” and “ Borderline ” for both programs . Findings from the present study suggest factors such as regular sessions in a structured setting , consistent therapists , social exposure and the use of autism-friendly strategies are important components of an effective framework in the management of anxiety in children and adolescents with ASD OBJECTIVE The research on the association between the working alliance and therapist competence/adherence and outcome from cognitive behavioral therapy ( CBT ) is limited and characterized by inconclusive findings . This study investigates the working alliance and competence/adherence as predictors of outcome of CBT for social anxiety disorder ( SAD ) and panic disorder ( PD ) . METHOD Eighty-two clinical ly referred patients ( 58.5 % female ; age : M = 33.6 years , SD = 10.3 ) with PD ( n = 31 ) or SAD ( n = 51 ) were treated with 12 sessions of manualized CBT by 22 clinicians with limited CBT experience in a r and omized controlled effectiveness trial . Independent assessors rated the CBT competence/adherence of the therapists using a revised version of the Cognitive Therapy Adherence and Competence Scale , and the patients rated the quality of the working alliance using the Working Alliance Inventory-short form in therapy sessions 3 and 8 . The outcome was assessed by independent assessors as well as by patients self-report . A total of 20.7 % of the patients ( 27.5 % SAD , 9.7 % PD ) dropped out during treatment . The association between the alliance , competence/adherence , outcome and dropout was investigated using multiple regression analyses . RESULTS Higher therapist ' competence/adherence early in the therapy was associated with a better outcome among PD patients , lower competence/adherence was associated with dropout among SAD patients . Higher rating of the alliance late in the therapy was associated with a better outcome , whereas lower alliance rating late in the therapy was associated with dropout . CONCLUSION The findings indicate that the therapist competence/adherence and the working alliance have independent contributions to the outcome from CBT for anxiety disorders , but in different phases of the treatment |
1,057 | 32,138,657 | 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 . | Catecholamines are the first-line vasopressors used in patients with septic shock .
However , the search for novel drug c and i date s is still of great importance due to the development of adrenergic hyposensitivity accompanied by a decrease in catecholamine activity .
Terlipressin ( TP ) is a synthetic vasopressin analogue used in the management of patients with septic shock .
In the current study , we aim ed to compare the effects of TP and catecholamine infusion in treating septic shock patients . | 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 each set of measurement . The terlipressin-induced increase in urine output was associated with a significantly increased creatinine clearance ( p<0.05 ) . Reduction of the high-dose norepinephrine was observed in all patients ( p<0.05 ) . Conclusions Our findings showed that , in patients with norepinephrine-treated septic shock , terlipressin increased GMP , urine output and creatinine clearance by an increase in mean arterial pressure Objectives : Sepsis induces microvascular alterations that may play an important role in the development of organ dysfunction . However , the relationship of these alterations to systemic variables and outcome is still not well defined . We investigated which factors may influence microcirculatory alterations in patients with severe sepsis and whether these are independently associated with mortality . Design : Analysis of prospect ively collected data from previously published studies by our group . Setting : A 36-bed , medicosurgical university hospital Department of Intensive Care . Patients : A total of 252 patients with severe sepsis in whom the sublingual microcirculation was visualized using orthogonal polarization spectral or sidestream darkfield imaging techniques . Measurements and Main Results : Microcirculatory measurements were obtained either early , within 24h of the onset of severe sepsis ( n = 204 ) , or later , after 48h ( n = 48 ) . When multiple measurements were obtained , only the first was considered . Although global hemodynamic variables were relatively preserved ( mean arterial pressure 70 [ 65–77 ] mm Hg , cardiac index 3.3 [ 2.7–4.0 ] L/min.m2 , and SvO2 68.3 [62.8–74.7]% ) , microvascular variables were markedly altered ( proportion of perfused small vessels 65 [50–74]% , microvascular flow index 2.15 [ 1.80–2.60 ] , and heterogeneity of proportion of perfused small vessels 35 [20–50]% ) . Among microcirculatory variables , proportion of perfused small vessels was the strongest predictor of outcome ( receiver operating characteristic curve area 0.818 [ 0.766–0.871 ] , p < 0.001 ) . Survival rates decreased markedly with severity of alterations in the proportion of perfused small vessels ( 70 % and 75 % in the two upper proportion of perfused small vessel quartiles compared with 3 % and 44 % in the two lower quartiles , p < 0.0001 ) . Multivariable analysis identified proportion of perfused small vessels and sequential organ failure assessment score as independent predictors of outcome . Microcirculatory alterations were less severe in the later than in the earlier ( proportion of perfused small vessels , 74 [57–82]% vs. 63 [48–71]% , p = 0.004 ) phase of sepsis . In multivariable analysis focused on the early period of sepsis , proportion of perfused small vessels and lactate were independent predictors of outcome . Conclusions : Microcirculatory alterations are stronger predictors of outcome than global hemodynamic variables This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence Purpose To compare the effects of first-line therapy with low-dose arginine vasopressin ( AVP ) or terlipressin ( TP ) on mesenteric blood flow , plasma AVP levels , organ function and mortality in ovine septic shock . Methods Twenty-four adult ewes were anesthetized and instrumented for chronic hemodynamic monitoring . A flow-probe was placed around the superior mesenteric artery , and feces were extracted from the cecum . Following baseline measurements , feces were injected into the peritoneal cavity . When mean arterial pressure ( MAP ) decreased to less than 60 mmHg , animals were r and omly assigned to receive AVP ( 0.5 mU kg−1 min−1 ) , TP ( 1 μg kg−1 h−1 ) or saline ( n = 8 each ) . A norepinephrine infusion was titrated to maintain MAP at 70 ± 5 mmHg in all groups . Results Cardiovascular pressures , cardiac output , mesenteric blood flow , and lung tissue concentrations of 3-nitrotyrosine and hemoxygenase-1 were similar among groups throughout the study period . TP infusion result ed in lower plasma AVP concentrations , reduced positive net fluid balance , increased central venous oxygen saturation and slightly prolonged survival compared to control and AVP-treated animals . However , TP treatment was associated with higher liver transaminases and lactate dehydrogenase versus control animals after 12 h. Conclusions This study provides evidence that the effects of low-dose TP differ from those of AVP , not only as TP has a longer half life , but also because of different mechanisms of action . Although low-dose TP infusion may be superior to sole norepinephrine or AVP therapy in septic shock , the safety of this therapeutic approach should be determined in more detail OBJECTIVE To compare , in patients with hyperdynamic septic shock , the effects of norepinephrine or terlipressin on hemodynamic variables and renal function . DESIGN Prospect i ve , r and omized , open-label study . SETTING Intensive care unit of a university , tertiary , and referral center . PATIENTS Twenty adult patients with hyperdynamic septic shock , after fluid resuscitation . INTERVENTIONS Patients were r and omized to receive norepinephrine or terlipressin . Global hemodynamic variables , oxygen consumption , urine flow , creatinine clearance , and arterial blood lactate levels were measured . MEASUREMENTS AND MAIN RESULTS Mean arterial pressure , systemic vascular resistance , pulmonary vascular resistance , and left and right ventricular stroke work were significantly increased with both drugs . With terlipressin , but not with norepinephrine , a significant decrease in heart rate ( from 113 + /- 17 to 104 + /- 11 beats.min(-1 ) , p < .01 ) and cardiac index ( from 5.1 + /- 1.7 to 4.2 + /- 1.6 L.min(-1).m(-2 ) ) was observed , with no change in stroke volume . Oxygen delivery index ( from 784 + /- 131 to 701 + /- 92 mL.min(-1).m(-2 ) ) and consumption index ( from 244 + /- 69 to 210 + /- 54 mL.min(-1).m(-2 ) ) were significantly decreased with terlipressin , but not with norepinephrine . Blood lactate concentrations were significantly decreased with both drugs . Urine flow and creatinine clearance were increased with both drugs . CONCLUSIONS In patients with hyperdynamic septic shock , both norepinephrine and terlipressin were effective to raise mean arterial blood pressure . With terlipressin , but not norepinephrine , the improvement in blood pressure was achieved at the expense of cardiac index and oxygen consumption , which were significantly decreased . Renal function was improved with both drugs . In further studies , alternative strategies to maintain cardiac index should be explored , such as a synergy between low-dose terlipressin and dobutamine BACKGROUND Terlipressin bolus infusion may reduce cardiac output and global oxygen supply . The present study was design ed to determine whether dobutamine may counterbalance the terlipressin-induced depression in mixed-venous oxygen saturation ( Svo ) in patients with catecholamine-dependent septic shock . METHODS Prospect i ve , r and omized , controlled study performed in a university hospital intensive care unit . Septic shock patients requiring a continuous infusion of norepinephrine ( 0.9 microg kg(-1 ) min(-1 ) ) to maintain mean arterial pressure ( MAP ) at 70 ( sd 5 ) mm Hg were r and omly allocated to be treated either with ( i ) sole norepinephrine infusion ( control , n=20 ) , ( ii ) a single dose of terlipressin 1 mg ( n=19 ) , or ( iii ) a single dose of terlipressin 1 mg followed by dobutamine infusion titrated to reverse the anticipated reduction in Svo2 ( n=20 ) . Systemic , pulmonary , and regional haemodynamic variables were obtained at baseline and after 2 and 4 h. Laboratory surrogate markers of organ (dys)function were tested at baseline and after 12 and 24 h. RESULTS Terlipressin ( with and without dobutamine ) infusion preserved MAP at 70 ( 5 ) mm Hg , while allowing to reduce norepinephrine requirements to 0.17 ( 0.2 ) and 0.2 ( 0.2 ) microg kg(-1 ) min(-1 ) , respectively [ vs1.4 ( 0.3 ) microg kg(-1 ) min(-1 ) in controls at 4 h ; each P<0.001 ] . The terlipressin-linked decrease in Svo2 was reversed by dobutamine at a mean dose of 20 ( 8) microg kg(-1 ) min(-1 ) [ Svo2 at 4 h : 59 (11)% vs 69 (12)% , P=0.028 ] . CONCLUSIONS In human catecholamine-dependent septic shock , terlipressin ( with and without concomitant dobutamine infusion ) increases MAP and markedly reduces norepinephrine requirements . Although no adverse events were noticed in the present study , potential benefits of increasing Svo2 after terlipressin bolus infusion need to be weighted against the risk of cardiovascular complications result ing from high-dose dobutamine To determine the effects on hemodynamics , laboratory parameters , and renal function of terlipressin used in septic-shock patients with hypotension not responsive to high-dose norepinephrine ( > 2.0 μg · kg−1 · min−1 ) and dopamine ( 25 μg · kg−1 · min−1 ) , a prospect i ve , open-label study was carried out in 17 patients . Patients received one or two boluses of 1 mg of terlipressin . In all patients terlipressin induced a significant increase in mean arterial pressure ( MAP ) , systemic vascular resistance , pulmonary vascular resistance , and left and right ventricular stroke work . The increase in MAP was accompanied by a significant decrease in heart rate and cardiac index , but stroke volume remained unchanged . Oxygen delivery and consumption were significantly decreased . Blood lactate concentrations significantly decreased over the study period . Bilirubin , aspartate aminotransferase ( AST ) , and alanine aminotransferase ( ALT ) were significantly increased . Thrombocytes were significantly decreased . No change in prothrombin time was observed . Renal function , assessed by urine flow and creatinine clearance , was significantly improved . Pulmonary function assessed by Pao2/Fio2 ratio was not affected . A significant reduction in norepinephrine and dopamine infusion rates was observed in all patients . Eight patients died during their ICU stay from late multiple organ failure . Within the limitations of the present study ( open-label design , small group of patients ) , it can be concluded that in septic shock patients with hypotension nonresponsive to fluid resuscitation and high-dose vasopressors , terlipressin can be effective to restore MAP . Cardiac index should be closely monitored because it was significantly decreased by terlipressin . Renal function was significantly improved . Mesenteric circulation was not evaluated , but hepatic function was altered during the study period . Further studies are required to determine whether terlipressin is safe in terms of outcome in septic shock patients OBJECTIVE To approach the effect of different vasopressor on hemodynamics , volume responsiveness , fluid volume balance , renal function and prognosis in patients with acute respiratory distress syndrome ( ARDS ) complicated with septic shock . METHODS A prospect i ve single-blind r and omized controlled trial was conducted . ARDS patients with septic shock admitted to the Department of Critical Care Medicine of Jiangxi Provincial People 's Hospital from January 1st , 2015 to May 1st , 2016 were enrolled . The patients satisfied ARDS Berlin diagnostic criteria , over 15 years old , needing vasopressor after fluid resuscitation were enrolled . The patients were divided into norepinephrine group ( NE group ) and terlipressin group ( TP group ) by r and omise number table derived by computer . Patients in TP group were given terlipressin ( 0.01 - 0.04 U/min ) with an intravenous pump , while those of NE group were given norepinephrine ( > 1 μg/min ) with an intravenous pump , and the target mean arterial pressure ( MAP ) was maintained at 65 - 75 mmHg ( 1 mmHg = 0.133 kPa ) . Hemodynamics and extravascular lung water index ( EVLWI ) were monitored by pulse indicator continuous cardiac output ( PiCCO ) . The volume responsiveness of patient was evaluated by passive leg raising ( PLR ) test , and cardiac index ( CI ) change ( ΔCI ≥ 10 % ) served as positive volume responsiveness . The differences in hemodynamics , EVLWI , oxygenation index ( OI ) , lactate clearance rate ( LCR ) , rate of positive volume responsiveness , urinary output , fluid volume balance , renal function , and prognostic indicators were compared between the two groups . RESULTS Fifty-seven patients with ARDS complicated with septic shock were enrolled , with 26 patients in NE group , and 31 patients in TP group , the baseline data in both groups was balanced with comparability . Compare with NE group , 48-hour and 72-hour heart rate ( HR ) in TP group was significantly slowed ( bpm : 82.1±6.8 vs. 87.6±7.4 , 81.3±6.1 vs. 85.6±8.3 , both P < 0.05 ) , 72-hour central venous pressure ( CVP ) was significantly decreased ( mmHg : 9.4±2.6 vs. 10.9±3.0 , P < 0.05 ) , but no significant difference was found in HR , MAP , CVP , CI , EVLWI , OI and LCR at other time points between the two groups . 48-hour and 72-hour positive volume responsiveness rate in TP group were significantly increased as compared with those of NE group ( 74.2 % vs. 46.2 % , 64.5 % vs. 38.5 % , both P < 0.05 ) , urinary output on the 2nd day ( mL/24 h : 2 342.8±704.1 vs. 1 944.6±684.3 ) and fluid volume balance ( mL : -319.7±54.8 vs. -169.6±27.2 ) were significantly decreased ( both P < 0.05 ) . There was no significant difference in positive volume responsiveness rate , urine output , fluid volume balance , and the level of serum creatinine at other time points between the two groups . There was no statistically significant difference in the following features between TP group and NE group : duration of mechanical ventilation ( days : 8.41±2.97 vs. 9.67±3.56 ) , length of intensive care unit ( ICU ) stay ( days : 12.84±4.47 vs. 14.77±5.01 ) , total length of hospital stay ( days : 19.34±7.37 vs. 21.07±8.41 ) , and 28-day mortality ( 29.0 % vs. 30.8 % , all P > 0.05 ) . CONCLUSIONS Compared with norepinephrine , terlipressin for ARDS patients with septic shock is more conducive to restrict fluid load , improve the renal perfusion and increase urine output . However , in both groups there was no significant difference in the efficiency of stabilizing hemodynamics , shortening the duration of mechanical ventilation , reducing ICU or hospital days and decreasing 28-day mortality BACKGROUND / AIMS Norepinephrine , but also dopamine and epinephrine are recommended as first line vasopressors in the treatment of septic shock . In some patients , septic shock deteriorates and becomes to be resistant to catecholamines . In this situation , addition of vasopressin or terlipressin can be advantageous . The aim of our pilot study was to evaluate the impact of terlipressin on open label norepinephrine requirements and mortality . METHODOLOGY In a r and omized , controlled , single centre study we assigned patients with late advanced septic shock refractory to catecholamines ( norepinephrine > 0.6µg/kg/min for more than 24h ) to receive either continuously terlipressin 4mg/24h for 72 hours in addition to open label norepinephrine ( TERLI group ) or to continue therapy only with catecholamines ( CON group ) . All vasopressor infusions were titrated to maintain a target blood pressure . RESULTS We enrolled 30 patients , of whom 13 were assigned to terlipressin and in 17 we continued in catecholamine therapy . There was no significant difference in norepinephrine consumption between the groups . Open label norepinephrine infusion rates decreased significantly in the TERLI group as compared with initial consumption , but the decrease we observed only in 7 ( 54 % ) patients . There was no significant difference between groups in the rate of death at day 28 ( 77 % in TERLI group and 94 % in CON group ; p=0.18 ) or at day 90 ( 91 % vs. 94 % ; p=0.85 ) . CONCLUSIONS Continuous terlipressin infusion was not effective in reducing norepinephrine consumption or in the mortality of patients , if administered in late phase of catecholamine refractory septic shock BACKGROUND & AIMS The choice of vasopressor for treating cirrhosis with septic shock is unclear . While noradrenaline in general is the preferred vasopressor , terlipressin improves microcirculation in addition to vasopressor action in non-cirrhotics . We compared the efficacy and safety of noradrenaline and terlipressin in cirrhotics with septic shock . PATIENTS AND METHODS Cirrhotics with septic shock underwent open label r and omization to receive either terlipressin ( n=42 ) or noradrenaline ( n=42 ) infusion at a titrated dose . The primary outcome was mean arterial pressure ( MAP ) > 65 mm Hg at 48 h. RESULTS Baseline characteristics were comparable between the terlipressin and noradrenaline groups . SBP and pneumonia were major sources of sepsis . A higher proportion of patients on terlipressin were able to achieve MAP > 65 mm of Hg ( 92.9 % vs 69.1 % P=.005 ) at 48 h. Subsequent discontinuation of vasopressor after hemodynamic stability was better with terlipressin ( 33.3 % vs 11.9 % , P<.05 ) . Terlipressin compared to noradrenaline prevented variceal bleed ( 0 % vs 9.5 % , P=.01 ) and improved survival at 48 h ( 95.2 % vs 71.4 % , P=.003 ) . Percentage lactate clearance ( LC ) is an independent predictor of survival [ P=.0001 , HR=3.9 ( 95 % CI : 1.85 - 8.22 ) ] after achieving the target MAP.Therapy related adverse effect were comparable in both the arms ( 40.5 % vs 21.4 % , P=.06 ) , mostly minor ( Grade II-88 % ) and reversible . CONCLUSIONS Terlipressin is as effective as noradrenaline as a vasopressor in cirrhotics with septic shock and can serve as a useful drug . Terlipressin additionally provides early survival benefit and reduces the risk of variceal bleed . Lactate clearance is a better predictor of outcome even after achieving target MAP , suggesting the role of microcirculation in septic shock Purpose Recent clinical data suggest that terlipressin , a vasopressin analogue , may be more beneficial in septic shock patients than catecholamines . However , terlipressin ’s effect on mortality is unknown . We set out to ascertain the efficacy and safety of continuous terlipressin infusion compared with norepinephrine ( NE ) in patients with septic shock . Methods In this multicentre , r and omised , double-blinded trial , patients with septic shock recruited from 21 intensive care units in 11 provinces of China were r and omised ( 1:1 ) to receive either terlipressin ( 20–160 µg/h with maximum infusion rate of 4 mg/day ) or NE ( 4–30 µg/min ) before open-label vasopressors . The primary endpoint was mortality 28 days after the start of infusion . Primary efficacy endpoint analysis and safety analysis were performed on the data from a modified intention-to-treat population . Results Between 1 January 2013 and 28 February 2016 , 617 patients were r and omised ( 312 to the terlipressin group , 305 to the NE group ) . The modified intention-to-treat population comprised 526 ( 85.3 % ) patients ( 260 in the terlipressin group and 266 in the NE group ) . There was no significant difference in 28-day mortality rate between the terlipressin group ( 40 % ) and the NE group ( 38 % ) ( odds ratio 0.93 [ 95 % CI 0.55–1.56 ] ; p = 0.80 ) . Change in SOFA score on day 7 was similar between the two groups : − 7 ( IQR − 11 to 3 ) in the terlipressin group and − 6 ( IQR − 10 to 5 ) in the NE group . There was no difference between the groups in the number of days alive and free of vasopressors . Overall , serious adverse events were more common in the terlipressin group than in the NE group ( 30 % vs 12 % ; p < 0.001 ) . Conclusions In this multicentre , r and omised , double-blinded trial , we observed no difference in mortality between terlipressin and NE infusion in patients with septic shock . Patients in the terlipressin group had a higher number of serious adverse events . Trial registration This trial is registered at Clinical Trials.gov : ID NCT01697410 |
1,058 | 17,054,128 | 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 | BACKGROUND Malaria contributes to maternal illness and anaemia in pregnancy , especially in first-time mothers , and can harm the mother and the baby .
Drugs given routinely to prevent or mitigate the effects of malaria during pregnancy are often recommended .
OBJECTIVES To assess drugs given to prevent malaria infection and its consequences in pregnant women living in malarial areas .
This includes prophylaxis and intermittent preventive treatment ( IPT ) . | 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 weekly chloroquine ( CQ ) chemoprophylaxis in preventing these adverse consequences . To our knowledge , there are no published trials evaluating IPT in West Africa . METHODS We undertook a r and omized controlled trial of weekly CQ chemoprophylaxis , 2-dose IPT with CQ , and 2-dose IPT with SP ; 1163 women were enrolled . RESULTS In multivariate analyses , when compared with weekly CQ , IPT/SP was associated with a reduction in third-trimester anemia ( adjusted odds ratio [ AOR ] , 0.49 ; P<.001 ) , placental parasitemia ( AOR , 0.69 ; P=.04 ) , and low birth weight ( < 2500 g ) ( AOR , 0.69 ; P=.04 ) . The prevalence of placental infection remained unexpectedly high , even in the IPT/SP group ( 24.5 % ) , possibly because of the intensity of seasonal transmission . There were no significant differences in stillbirths , spontaneous abortions , or neonatal deaths among the 3 groups . CONCLUSIONS In Mali , IPT with SP appears more efficacious than weekly chloroquine chemoprophylaxis in preventing malaria during pregnancy . These data support World Health Organization recommendations to administer at least 2 doses of IPT during pregnancy . In intensely seasonal transmission setting s in Mali , > 2 doses may be required to prevent placental reinfection prior to delivery To define an effective and deliverable antimalarial regimen for use during pregnancy , pregnant women at highest risk of malaria ( those in their first or second pregnancy ) in an area of Malawi with high transmission of chloroquine (CQ)-resistant Plasmodium falciparum were placed on CQ and /or sulfadoxine-pyrimethamine ( SP ) . Of 38 pregnant women who received CQ treatment followed by weekly CQ prophylaxis ( CQ/CQ ) for at least 45 days prior to delivery , 32 % had placental malaria infection , compared with 26 % of 50 pregnant women who received a treatment dose of SP followed by weekly CQ prophylaxis ( SP/CQ ) , and only 9 % of 71 pregnant women who received a two-dose SP regimen ( SP/SP ; given once during the second trimester and repeated at the beginning of the third trimester ) ( P = 0.006 , by chi-square test ) . During the peak transmission season from April to July , 47 % of the women who received CQ/CQ had placental malaria infection at delivery , as compared with 37 % of the women who received SP/CQ , and 10 % of women who received SP/SP ( P = 0.004 , by chi-square test ) . Among women in their first or second pregnancy , two treatment doses of SP were highly effective in decreasing the proportion of women with placental malaria infection at delivery A r and omized , double blind , placebo-controlled community based trial of Maloprim ( pyrimethamine 12.5 mg+dapsone 100 mg ) administered to primigravid pregnant women by Traditional Birth Attendants was carried out in a rural area of The Gambia , West Africa . Placental histology showed less malaria infection in women who received chemoprophylaxis than in those who received placebo . The birth weight of children born to women who received chemoprophylaxis was increased by an average of 153 g. Within the treatment groups , there were no significant differences in the birthweights of babies born to women who had histological evidence of malaria infection of the placenta compared to those who had no malaria infection . This study confirms the beneficial effect of malaria prophylaxis for primigravid pregnant women but questions the mechanism by which malaria affects foetal development The safety of daily application of N , N-diethyl-m-toluamide ( DEET ) ( 1.7 g of DEET/day ) in the second and third trimesters of pregnancy was assessed as part of a double-blind , r and omized , therapeutic trial of insect repellents for the prevention of malaria in pregnancy ( n = 897 ) . No adverse neurologic , gastrointestinal , or dermatologic effects were observed for women who applied a median total dose of 214.2 g of DEET per pregnancy ( range = 0 - 345.1 g ) . DEET crossed the placenta and was detected in 8 % ( 95 % confidence interval = 2.6 - 18.2 ) of cord blood sample s from a r and omly selected subgroup of DEET users ( n = 50 ) . No adverse effects on survival , growth , or development at birth , or at one year , were found . This is the first study to document the safety of DEET applied regularly in the second and third trimesters of pregnancy . The results suggest that the risk of DEET accumulating in the fetus is low and that DEET is safe to use in later pregnancy A prospect i ve comparison of the antimalarial efficacy of bed nets was conducted with 341 pregnant women living in a mesoendemic malarious area of the Thai-Burmese border . Women in 3 adjacent study sites were allocated at r and om to receive either a single size permethrin-impregnated bed net ( PIB ) , a non-impregnated bed net ( NIB ) , or to a control group who used either their own family size non-impregnated bed net ( FNIB ) or no net . In one study site , but not the other 2 , PIB significantly reduced parasite densities and , together with FNIB , reduced the incidence of malaria in pregnancy from 56 % to 33 % ( relative risk = 1.67 , confidence interval = 1.07 - 2.61 , P = 0.03 , allowing for parity ) . Anaemia proved a more sensitive marker of bed net antimalarial efficacy than parasite rates . The incidence of anaemia ( haematocrit < 30 % ) at all study sites was significantly lower at delivery in the PIB ( 27 % ) and FNIB groups ( 21 % ) than in the NIB group ( 41 % ) or those using no net ( 56 % ) . This suggests that a significant proportion of the malaria in pregnancy in this mesoendemic area was sub-patent . Both patent Plasmodium falciparum parasitaemia and anaemia were associated with a reduction in birth weight . Infant mortality was high ( 16 % ) and strongly associated with prematurity , low birth weight and maternal anaemia . PIB were well tolerated and had no apparent adverse effect on the pregnancy or infant development . Although the overall effect of bed nets on patent parasitaemia was marginal , they were associated with a significant reduction in maternal malaria-associated anaemia . ( ABSTRACT TRUNCATED AT 250 WORDS A trial of malaria chemoprophylaxis given by traditional birth attendants was undertaken in a rural area of The Gambia where access to antenatal clinics is difficult . Women received one or more doses of Maloprim or placebo from a traditional birth attendant during 1049 of 1208 pregnancies ( 87 % ) recorded in 16 villages over a 3-year period . Primigravidae who received Maloprim had a lower parasite rate and a significantly higher mean packed cell volume than primigravidae who received placebo , and their babies were significantly heavier ( 6 % low birth weight vs 22 % ) . In multigravidae chemoprophylaxis reduced malaria parasitaemia but it had no beneficial effect on haemoglobin level and much less effect on birth weight than was observed in primigravidae . However , the mean birth weight of babies born to gr and emultigravidae who received chemoprophylaxis was significantly higher than that of babies born to gr and emultigravidae who did not Despite international recommendations to use malaria treatment and prevention in pregnant women in malaria-endemic areas , few studies have evaluated the efficacy of available antimalarial regimens . This issue is of particular concern in the face of spreading chloroquine (CQ)-resistance of Plasmodium falciparum in malarious areas of sub-Saharan Africa . In a prospect i ve trial in rural Malawian pregnant women , we examined three regimens using CQ ( including the existing national policy regimen ) and one regimen using mefloquine ( MQ ) . The efficacy of the regimens was determined by comparing rates of clearance of initial parasitemia ; prevention of breakthrough infection ; and parasitemia at delivery in maternal peripheral blood , placental blood , and in infant umbilical cord blood . Among 1,528 parasitemic women at enrollment , 281 ( 18.4 % ) had persistent infections ; and among 1,852 initially aparasitemic women , 320 ( 17.3 % ) had breakthrough parasitemia on one or more follow-up visits . Compared with women on MQ , women on a CQ regimen were at significantly greater risk of persistent and breakthrough infection ( odds ratios [ OR ] = 30.9 and 11.1 , respectively , P < 10(-6 ) ) . Other significant risk factors for persistent and breakthrough infections in a multivariate model included first pregnancy ; enrollment in the rainy or postrainy season ; maternal age < or = 25 years ; seropositivity to the human immunodeficiency virus ( HIV ) ( persistent infections only ) ; and no use of antimalarial prophylaxis before enrollment ( breakthrough infections only ) . At delivery , compared with women on MQ , women on a CQ regimen were at significantly greater risk of peripheral , placental , or umbilical cord blood parasitemia ( OR = 8.7 , 7.4 , and 4.1 , respectively , P < 10(-6 ) ) . Additional risk factors for parasitemia at delivery in multivariate models included first pregnancy ; delivery in the rainy or postrainy season ; HIV-seropositivity ; and maternal age < or = 25 years ( risk for peripheral and placental blood parasitemia only ) . Maternal anemia ( hematocrit < 30 % ) at enrollment or at delivery was not associated with persistent or breakthrough parasitemia or parasitemia at deliver in these multivariate models . While factors leading to increased malaria parasite exposure ( high transmission seasons ) and lowered or altered host immune response ( low pregnancy number , young age , and HIV infection ) are important risk factors for malaria in pregnant women , the use of an ineffective intervention ( CQ in a setting with CQ-resistant parasites ) was the most important determinant of P. falciparum parasitemia in these pregnant women . Strategies to reduce the impact of malaria in pregnant women must use efficacious interventions and may need to consider targeting the intervention to the most susceptible women during the seasons of high malaria exposure 73 pregnant women in Malawi were given weekly antimalarial chemoprophylaxis under observation and were monitored for Plasmodium falciparum parasitaemia and placental infection . 3 of 19 women ( 16 % ) who were parasitaemic at the time they began chemoprophylaxis were infected with chloroquine-resistant P. falciparum . After clearance of initial infections , 25 % of the 73 women became parasitaemic while taking prophylaxis and 56 % had evidence of active or past placental infection at the time of delivery . None of the women who were parasitaemic at the time of enrollment , and only 11 % of those who had breakthrough parasitaemias while taking prophylaxis , had a history of fever and signs or symptoms that they recognized as malaria . Although the density of P. falciparum infection and rates of placental infection appeared to be lower among women taking regular chloroquine prophylaxis , this drug did not prevent P. falciparum infection among pregnant women A double-blind , placebo-controlled study of mefloquine antimalarial prophylaxis in pregnancy ( > 20 weeks of gestation ) was conducted in 339 Karen women living in an area of multidrug-resistant malaria transmission on the Thai-Burmese border . Mefloquine gave > or = 86 % ( 95 % confidence interval [ CI ] , 59%-94 % ) protection against Plasmodium falciparum and complete protection against Plasmodium vivax infections . Mefloquine prophylaxis was well tolerated ; use of an initial loading dose ( 10 mg/kg ) was associated with transient dizziness , but there were no other significant adverse effects on the mother , the pregnancy , or infant survival or development ( followed for 2 years ) . Falciparum malaria was associated with maternal anemia and a mean reduction in birth weight in gravidae I , II , and III of 225 g ( 95 % CI , 26 - 423 ) . Maternal anemia at delivery ( hematocrit < 30 % ) was associated with increased infant mortality : 26 % versus 15 % ( relative risk , 1.9 ; 95 % CI , 1.1 - 3.2 ) . Mefloquine is safe and effective for antimalarial prophylaxis in the second half of pregnancy The control of malaria in pregnant African women , one of several child survival strategies applied through antenatal care , has been particularly challenging . Prevention and control recommendations for typical areas of high Plasmodium falciparum transmission have promoted the use of antimalarial chemoprophylaxis to prevent placental infection . Persistently low program coverage coupled with diminishing intervention effectiveness have forced a re-evaluation of the relative importance of malaria in pregnancy . The Mangochi Malaria Research Project ( MMRP ) , a prospect i ve evaluation of malaria prevention in pregnant women in rural Malawi conducted during 1987 - 1990 , contributed to establishing new criteria for policy and program development for malaria prevention in pregnancy . The principle findings of the MMRP include : 1 ) population s at risk of the adverse consequences of malaria in pregnancy include women with low parity , women infected with human immunodeficiency virus , pregnancy during the high malaria transmission season , and the use of a malaria drug that is suboptimally efficacious ; 2 ) the estimated maximum benefits of an antimalarial intervention that clears placental and umbilical cord parasitemia are a 5 - 12 % reduction of low birth weight ( LBW ) , an approximately 35 % reduction in the risk of LBW for risks that are actually preventable once a woman has become pregnant ( e.g. , risks such as infectious disease or poor nutrition during gestation ) , and a 3 - 5 % reduction in the rate of infant mortality ; 3 ) the intervention must be capable of rendering the woman malaria parasite free , including clearance of parasites from the placental vascular space and umbilical cord blood ; 4 ) other diseases adversely affect pregnancy outcome and , while the control of malaria in pregnancy may not warrant independent programming , if coupled with prevention programs to provide a range of antenatal services , the incremental costs of malaria control may prove to be highly cost-effective ; and 5 ) the choice of a regimen must balance intervention efficacy with safety , availability , affordability , and simplicity of delivery , and several antimalarials may meet these criteria . The Malawi Ministry of Health has modified its malaria prevention in pregnancy recommendations and now faces the challenge of effective programming to improve child survival A r and omized , double-blind , placebo-controlled trial , which compared the effects of three interventions ( weekly chloroquine prophylaxis , daily iron and weekly folic-acid supplementation , and case management of malaria ) on congenital malaria , maternal haemoglobin ( Hb ) and foetal outcome , was conducted among primigravidae resident in Hoima district , Ug and a. Among 473 babies examined at birth or within 7 days of birth , 198 ( 42 % ) were parasitaemic , the level of parasitaemia in an infant being strongly correlated with those of placental ( P < 0.01 ) and maternal , peripheral parasitaemia ( P < 0.01 ) . However , 33 ( 17 % ) of the parasitaemic babies were born to mothers who had placental but not peripheral parasitaemia , 22 ( 11 % ) to mothers who had peripheral but not placental parasitaemia , and 12 ( 6 % ) to mothers with neither peripheral nor placental parasitaemia . Overall , 163 babies were each examined for malarial parasites at birth and 1 month later . Of the 76 ( 47 % ) found to have parasitaemia at birth , 37 ( 23 % ) appeared aparasitaemic at the 1-month follow-up but 28 ( 17 % ) were still parasitaemic at that time . Among the babies born to the mothers who only received case management of malaria during pregnancy , parasitaemia at birth was associated with infant anaemia at birth ( i.e. < 140 g Hb/litre ; P = 0.03 ) . Infants found to be parasitaemic at the 1-month follow-up had lower mean concentrations of Hb at that time than their aparasitaemic counterparts ( P= 0.03 ) . Parasitaemia at birth was not significantly associated with low birthweight , in any of three intervention groups . The intervention given to the mother had no significant effect on the parasitaemia of her baby , either at birth or at the age of 1 month . Congenital malaria per se may have little influence on birthweight but may have an impact on infant anaemia . In conclusion , congenital parasitaemia was not associated with birthweight , but was related to anaemia at birth in infants born to women who had only received active case management during their pregnancies Maternal mortality has recently received attention as a neglected public health problem in many developing countries where mortality rates are estimated to be 8 - 200 times those in developed countries . Most maternal mortality estimates in sub-Saharan Africa have used retrospective methods because of the lack of large population -based studies . The Mangochi Malaria Research Project , a trial of antimalarial chemoprophylaxis in pregnant women , provided an opportunity to examine prospect ively mortality among the study women . Among 4,053 monitored pregnant women , 27 women were known to have died during pregnancy , labor , delivery and the one-year follow-up period . Three women died during the antenatal period and 12 died within six weeks of delivery for an estimated maternal mortality rate of 370 per 100,000 pregnant women ; this rate was consistent with rates reported from retrospective surveys in Malawi . Twelve women died between three and 10 months after delivery , and the mortality rate in this nonmaternal period was estimated to be 341 per 100,000 . Mortality rates in the maternal and nonmaternal periods were surprisingly similar . Human immunodeficiency virus type-1 ( HIV-1 ) infection and anemia were strongly associated with death in the nonmaternal period . Mortality among infants of mothers who died was 3.7 times higher than the rate of death among infants born to mothers who survived . This study highlights that for rural Malawian women , pregnancy and delivery are risky periods , that the death of the mother adversely affects the survival of her children , and that HIV and anemia are important contributors to nonmaternal mortality in reproductive-age women . Strategies to reduce mortality among women of child-bearing age in sub-Saharan Africa must focus on decreasing the complications of pregnancy and delivery , and address important preventable causes of death , such as anemia and HIV infection To evaluate the efficacy of pyrimethamine on the blood stage ( suppressive prophylaxis ) and liver stage ( causal prophylaxis ) of Plasmodium falciparum in pregnant women , in vivo and in vitro field studies were conducted in Ilorin , Nigeria , from Jan 1 to June 30 , 1988 . For pregnant women with P falciparum infections who received 25 mg of pyrimethamine weekly for suppressive prophylaxis , 67 % ( 59/88 ) of in vivo and 60 % ( 6/10 ) of in vitro tests showed pyrimethamine resistance . A second group of parasitaemic and parasite-free pregnant women was enrolled to evaluate the efficacy of pyrimethamine as a primary tissue schizonticide ; after receiving a curative dose of chloroquine ( 25 mg/kg ) , half the women were given 25 mg of pyrimethamine weekly and half received no prophylaxis . Parasitologic failure rates did not differ between the pyrimethamine-treated ( 8/34 ) and the control ( 11/37 ) groups during the 16-week follow-up . Thus , pyrimethamine is not effective for suppressive or causal prophylaxis in pregnant women in Ilorin Malaria infection due to Plasmodium falciparum has been widely recognized as associated with important adverse consequences in pregnant women , particularly in areas of high transmission . Although strategies using antimalarial drugs for prevention had been recommended , even by the late 1980s , few studies had been carried out to examine the efficacy of these prevention efforts . The objectives of the Mangochi Malaria Research Project investigation were to determine the comparative efficacy of regimens containing chloroquine ( CQ ) or mefloquine ( MQ ) antimalarial treatment and chemoprophylaxis in an area of CQ-resistant P. falciparum on the following outcomes : 1 ) the frequency of placental malaria infection ; 2 ) the frequency of low birth weight ; 3 ) the frequency of prematurity or intrauterine growth retardation ; 4 ) the frequency of maternal fever illness and severe anemia ; and 5 ) the likelihood of infant acquisition of malaria infection . Although the investigation was not design ed to evaluate the role of antimalarial chemoprophylaxis and treatment on infant mortality reduction , because babies born to study women were scheduled to be followed for up to two years of life , the study allowed for an examination of mortality and morbidity in this population . The sample size was insufficient to provide more than descriptive analysis of mortality and morbidity in the fetal , perinatal , neonatal , postneonatal , and infant time intervals . The study design allowed for the evaluation of two additional aspects of maternal and infant health : other determinants of the above-listed outcomes in addition to malaria prevention ( e.g. , maternal age , gravidity , socioeconomic status , infection with human immunodeficiency virus or syphilis ) and reported cause-specific mortality in the fetal-to-infant intervals . The study design included 22 months of enrollment of pregnant women at their first antenatal clinic visit from four clinic sites in Mangochi District , Malawi , with assignment to one of four antimalarial regimens and prospect i ve follow-up through pregnancy , at delivery , and during infancy . All drug dosing was performed under supervision by the study team , making this an evaluation of intervention efficacy ( excluding the role of patient compliance ) The distribution of birth weights among the infants of 172 Gambian primigravidae who had received chemoprophylaxis with Maloprim ( pyrimethamine+dapsone ) during pregnancy was compared with that of the infants of 149 primigravidae who had received placebo . Administration of chemoprophylaxis led to a reduction in the prevalence of low birth weight babies and to an increase in the median birth weight . However , these changes were not accompanied by a comparable increase in the prevalence of high birth weight babies . The perinatal mortality rate was lower , although not significantly so , among the babies of women who had received chemoprophylaxis . Thus , no evidence was found to support the view that administration of chemoprophylaxis might increase the risks of delivery by causing cephalo/pelvic disproportion The widespread problem of low and non-compliance to antimalarial chemoprophylaxis during pregnancy dem and s that attention be focused on alternative approaches to programming , product acceptability and dem and for preventive services . This study describes the testing of three interventions to determine their effect on use of chloroquine ( currently the most widely used drug for chemoprophylaxis ) during pregnancy . The strategies evolved from community-based formative research undertaken to learn about the local concept of malaria and issues surrounding malaria prevention and treatment during pregnancy . The result ing interventions were tested in four clinics , and included a change in the health education message given during antenatal sessions , distribution of a sugar-coated chloroquine tablet , and an intervention combining the two strategies . The results showed a 45 % increase in chloroquine use when the health education message was changed , and a 64 % increase when the product was changed . High use levels were maintained with the combined intervention ; an additive effect was seen . The study shows that improving the product was the most important factor in increasing the use of the program , and that changing the health education message can also make an impact on use The effects of weekly chloroquine prophylaxis , daily iron-weekly folic acid supplementation or passive case management on maternal haemoglobin and parasitaemia and on birthweight were examined in primigravidae in a r and omized , double-blind placebo-controlled intervention trial in 1996 - 98 in Hoima District , western Ug and a. Iron-folic acid supplementation significantly increased mean birthweight as compared to case management ( P = 0.03 ) . Low birthweight ( < 2.5 kg ) occurred in 2 % of babies of women receiving chloroquine prophylaxis for > or = 8 weeks and in 9 % in the case management group ( RR = 0.36 , 95 % CI 0.13 - 1.00 , P = 0.009 ) . Parasitaemia at enrolment significantly correlated with low birthweight in the case management group as compared to the intervention groups ( P = 0.02 ) . Women in the case management group who were parasitaemia and had haemoglobin levels < 100 g/L at delivery had babies with lower mean birthweight as compared to babies in the other groups ( P = 0.04 ) . Low haemoglobin level at enrolment , irrespective of parasitaemia status , was a predictor of low birthweight in the case management group only ( P = 0.04 ) . Chloroquine prophylaxis and iron-folic acid supplementation significantly increased maternal haemoglobin levels during pregnancy as compared to case management ( P = 0.01 and 0.007 , respectively ) and the increase correlated to the duration of the intervention OBJECTIVE To determine baseline data among pregnant women consenting to participate in a r and omised trial of alternative strategies of malaria chemoprophylaxis in Kigoma urban district , western Tanzania . DESIGN Cross-sectional study . SETTING The study was conducted in an urban MCH clinic in Kigoma town in western Tanzania . SUBJECTS All consenting pregnant women who fulfilled entry criteria were recruited into the study . BASELINE STUDIES : Baseline data were collected prior to r and omisation of women to antimalarial prophylactic regimens . Baseline measurements included examination for blood depleting parasitic infections ( stool and urine examinations ) , haemoglobin levels , haematocrit , sickling test , and blood slide for malaria parasites . RESULTS A total of 728 pregnant women consented to participate in the interview and of these 705 participated in baseline studies constituting a participation rate of 96.8 % . The age of participating women ranged from 14 to 45 years with a mean age of 23.7 years ( st and ard deviation [ SD ] = 5.4 ) while the mean number of pregnancies ranged from 1 to 13 with a mean of 3.2 ( SD = 2.2 ) . The prevalence of malaria parasitaemia among the pregnant women examined was 9.4 % ( N = 705 ) while the prevalence of anaemia ( defined as Hb < 8.5 gdl-1 ) was 12.4 % ( N = 579 ) . No significant difference was observed in prevalence proportions of malaria parasitaemia in relation to age , parity , marital status and use of mosquito bednets . However the prevalence of anaemia among women in the age group 31 - 45 years was significantly lower than that observed among women in the age group 14 - 20 years ( 2.9 % versus 18.9 % ; crude odds ratio [ OR ] = 0.13 ; 95 % confidence interval [ CI ] , 0.02 - 0.55 ) . Sickle cell disease ( HbAS ) was found in 2.3 % ( N = 564 ) of the pregnant women examined . CONCLUSION It is concluded that the prevalence of malaria parasitaemia and anaemia was very high in this population suggesting the need for interventions directed at controlling these major causes of maternal morbidity and mortality in Tanzania A r and omized prophylactic drug trial was conducted in a malaria holoendemic area , in the Muheza District of Tanzania . Of 327 pregnant women , 124 received proguanil ( PROG ) , 113 chloroquine ( CQ ) , 90 the proguanil and chloroquine combination ( CQ+PROG ) . Prophylaxis was supervised . Chemosuppressive efficacy was measured through the incidence of malaria breakthrough parasitaemias and clinical episodes . Groups were comparable by age , parity , residential area , and enrollment gestational age . Compliance and drug bio-availability was good . The median breakthrough time of the first parasitaemia episode for primigravidae ( PG ) and multigravidae ( MG ) was significantly shorter for the CQ group ( PG = 56 , MG = 78 days ) than in the PROG ( PG = 97 , MG = 112 days ) and the CQ+PROG ( PG = 138 , MG = 140 days ) groups . 56 % of the CQ group experienced 2 or more clinical episodes compared to 19 % ( PROG ) and 10 % ( CQ+PROG ) . PROG and CQ+PROG did not differ significantly . Parasite densities and in vitro tests suggested that CQ selected for more and highly resistant strain(s ) . Proguanil is suitable for prophylaxis . However , proguanil resistance should be monitored as well as controlled drug distribution and usage . Malaria control strategies other than chemoprophylaxis should be investigated The problems of Plasmodium falciparum infection in pregnant women have been described in numerous sub-Saharan African countries , but the frequency of parasitemia at the first antenatal visit and risk factors for infection have not been fully investigated . During a prospect i ve antimalarial treatment and prophylaxis trial in pregnant women in Malawi ( three groups receiving a chloroquine regimen and one group receiving a mefloquine regimen ) , we examined women at their first antenatal clinic visit to evaluate these issues and to verify that subjects in the study treatment/prevention arms were similar . Among 4,127 women with enrollment blood smear results , 1,836 ( 44.5 % ) were parasitemic . The highest infection rates and densities were observed in primigravidas ( 66 % infected , geometric mean parasite density [ GMPD ] = 1,588 parasites/mm3 of whole blood ) , followed by second pregnancies ( 46 % infected , GMPD = 615 parasites/mm3 ) and subsequent pregnancies ( 29 % infected , GMPD = 238 parasites/mm3 ) , ( P < 10(-6 ) for both infection prevalence and density , by chi-square test for trend ) . Significant risk factors for parasitemia at first antenatal clinic visit in a multivariate model included low gravidity , high transmission season , no use of prophylaxis before first antenatal clinic visit , young age ( < 20 years ) , human immunodeficiency virus ( HIV ) infection , low hematocrit , short stature , and second trimester ( compared with third trimester ) . Women in the different treatment arms of the study were generally similar in many characteristics ; statistically significant differences , where present , were small . Targeting malaria control efforts to women in their first or second pregnancy and during the high transmission season will be an important strategy to reach most parasitemic women and minimize re source expenditure . Women infected with HIV had a 55 % increased risk of parasitemia at their first antenatal clinic visit and may represent an additional important risk group whose numbers may be increasing and who may benefit from identification and management for malaria |
1,059 | 20,963,527 | 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 . | Background Carpal tunnel syndrome ( CTS ) is the most commonly diagnosed compression neuropathy of the upper extremity .
Current AAOS recommendations are to obtain a confirmatory electrodiagnostic test in patients for whom surgery is being considered .
Ultrasound has emerged as an alternative confirmatory test for CTS ; however , its potential role is limited by lack of adequate data for sensitivity and specificity relative to electrodiagnostic testing .
Questions / purpose sIn this meta- analysis we determined the sensitivity and specificity of ultrasound in the diagnosis of CTS . | 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+/-1.42 mm2 by EF in control group . The differences between study group and control group according to both TM and EF were significant ( t-test p=0.0079 , p=0.0460 , respectively ) . In study group , CSAs were larger than 10.5 mm2 in 18 ( 30.51 % ) and 16 ( 27.12 % ) wrists according to TM and EF findings , respectively , and in only one wrist ( 3.33 % ) in control group by both TM and EF . The differences of ultrasonographic CTS numbers between study group and control group were significant ( p=0.0024 by TM , p=0.0086 by EF ) . We confirmed the usefulness of quantitative US assessment in the diagnosis of CTS in the patients with negative EDT findings . If EDT findings are inadequate to confirm the CTS in the patients with clinical CTS , US studies may be helpful to diagnose AIM The aim of study was to assess the usefulness of ultrasonographic measurements of the median nerve in the diagnosis of carpal tunnel syndrome . MATERIAL S AND METHODS Eighty-six patients with carpal tunnel syndrome confirmed by electromyography and 45 asymptomatic controls were included in the study and underwent high-resolution ultrasonography of the wrists . The cross-sectional area and flattening ratio at the level of the pisiform bone of the proximal carpal tunnel were measured . Data from the patient group and control group were compared to determine the statistical significance . The accuracy of the ultrasonographic diagnostic criteria for carpal tunnel syndrome was evaluated using receiver-operating characteristic ( ROC ) analysis . RESULTS One hundred and forty-eight wrists of 86 patients with carpal tunnel syndrome and 76 wrists of 45 control patients were examined . All measurements showed significant differences between patients and controls . Increased cross-sectional area of the median nerve was the most predictive measurement of carpal tunnel syndrome . Using the ROC curve , a cut-off value of > 10.5 mm2 at the level of pisiform bone provided a diagnostic sensitivity of 89 % and specificity of 94.7 % CONCLUSION The ultrasonographic measurement of the median nerve cross-sectional area is a sensitive , specific and useful non-invasive method for the diagnosis of carpal tunnel syndrome PURPOSE To prospect ively evaluate accuracy of sonography for diagnosis of carpal tunnel syndrome ( CTS ) in patients clinical ly suspected of having the disease in one or both h and s. MATERIAL S AND METHODS A prospect i ve cohort of 133 patients suspected of having CTS were referred to a teaching hospital between October 2001 and June 2002 for electrodiagnostic study . One hundred twenty patients ( 98 women , 22 men ; mean age , 49 years ; range , 19 - 83 years ) underwent sonography within 1 week after electrodiagnostic study . Radiologist was blinded to electrodiagnostic study results . Seventy-five patients had bilateral symptoms ; 23 patients , right-h and symptoms ; and 22 patients , left-h and symptoms ( total , 195 symptomatic h and s ) . Cross-sectional area of median nerve was measured at three levels : immediately proximal to carpal tunnel inlet , at carpal tunnel inlet , and at carpal tunnel outlet . Flexor retinaculum was used as a l and mark to margins of carpal tunnel . Optimal threshold levels ( determined with classification and regression tree analysis ) for areas proximal to and at tunnel inlet and at tunnel outlet were used to discriminate between patients with and patients without disease . Sensitivity , specificity , and false-positive and false-negative rates were derived on the basis of final diagnosis , which was determined with clinical history and electrodiagnostic study results as reference st and ard . RESULTS For right h and s , sonography had sensitivity of 94 % ( 66 of 70 ) ; specificity , 65 % ( 17 of 26 ) ; false-positive rate , 12 % ( nine of 75 ) ; and false-negative rate , 19 % ( four of 21 ) ( cutoff , 0.09 cm(2 ) proximal to tunnel inlet and 0.12 cm(2 ) at tunnel outlet ) . For left h and s , sensitivity was 83 % ( 53 of 64 ) ; specificity , 73 % ( 24 of 33 ) ; false-positive rate , 15 % ( nine of 62 ) ; and false-negative rate , 31 % ( 11 of 35 ) ( cutoff , 0.10 cm(2 ) proximal to tunnel inlet ) . CONCLUSION Sonography is comparable to electrodiagnostic study in diagnosis of CTS and should be considered as initial test of choice for patients suspected of having CTS OBJECTIVE To determine the diagnostic value of sonography in patients with suspected carpal tunnel syndrome ( CTS ) . METHODS We conducted a prospect i ve study of 110 wrists in 74 consecutive patients with suspected CTS who had been referred to a tertiary care center . We determined the largest cross-sectional area of the median nerve at the carpal tunnel . Because of the lack of a universally accepted reference st and ard , we first examined the association of sonography with nerve conduction . Then , we compared sonography with a reference st and ard based on the combination of nerve conduction studies and signs and symptoms . Sonography and reference st and ard tests were performed independently and interpreted under blinded conditions . Based on a fitted receiver operating characteristic curve , we estimated likelihood ratios ( LRs ) and posttest probabilities for different cutoffs . RESULTS There was a high concordance between sonography and nerve conduction . Based on the combined reference st and ard , a cutoff of 10 mm(2 ) result ed in approximately equal sensitivity and specificity , but only moderate LRs . A cutoff of < 8 mm(2 ) had satisfactory power to rule out CTS : the fitted-negative LR was 0.13 . Conversely , a cutoff of > or = 12 mm(2 ) had excellent power to rule in CTS , with a fitted-positive LR of 19.9 . For nerves > or = 12 mm(2 ) and a pretest probability of 70 % expected in patients with suspected CTS in tertiary care , we found a posttest probability of CTS of 98 % . CONCLUSION Depending on setting and purpose , different cutoff values for the largest cross-sectional area may be used to accurately rule in or rule out CTS . Using sonography as a first-line test may cost-effectively reduce the number of nerve conduction studies in patients with suspected CTS . A large-scale , r and omized controlled trial is required to determine the effects of sonography on clinical outcomes , the number of nerve conduction studies performed , and the total cost |
1,060 | 26,535,266 | 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 . | Background : When to allow an athlete to return to unrestricted sporting activity after anterior cruciate ligament ( ACL ) reconstruction remains controversial .
Purpose : To report the results of functional performance testing reported in the literature for individuals at differing time points following ACL reconstruction and to examine differences between graft types . | 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 15 minute neuromuscular warm-up programme ( targeting core stability , balance , and proper knee alignment ) to be carried out twice a week throughout the season . Main outcome measures The primary outcome was rate of anterior cruciate ligament injury ; secondary outcomes were rates of severe knee injury ( > 4 weeks ’ absence ) and any acute knee injury . Results Seven players ( 0.28 % ) in the intervention group , and 14 ( 0.67 % ) in the control group had an anterior cruciate ligament injury . By Cox regression analysis according to intention to treat , a 64 % reduction in the rate of anterior cruciate ligament injury was seen in the intervention group ( rate ratio 0.36 , 95 % confidence interval 0.15 to 0.85 ) . The absolute rate difference was −0.07 ( 95 % confidence interval −0.13 to 0.001 ) per 1000 playing hours in favour of the intervention group . No significant rate reductions were seen for secondary outcomes . Conclusions A neuromuscular warm-up programme significantly reduced the rate of anterior cruciate ligament injury in adolescent female football players . However , the absolute rate difference did not reach statistical significance , possibly owing to the small number of events . Trial registration Clinical trials NCT00894595 Background : Previous studies have found significant predictors for functional outcome after anterior cruciate ligament ( ACL ) reconstruction ; however , studies examining predictors for functional outcome in nonoperatively treated individuals are lacking . Hypothesis : Single-legged hop tests predict self-reported knee function ( International Knee Documentation Committee [ IKDC ] 2000 ) in nonoperatively treated ACL-injured individuals 1 year after baseline testing . Study Design : Cohort study ( prognosis ) ; Level of evidence , 2 . Methods : Ninety-one nonoperatively treated patients with an ACL injury were tested using 4 single-legged hop tests on average 74 ± 30 days after injury in a prospect i ve cohort study . Eighty-one patients ( 89 % ) completed the IKDC 2000 1 year later . Patients with an IKDC 2000 score equal to or higher than the age- and gender-specific 15th percentile score from previously published data on an uninjured population were classified as having self-reported function within normal ranges . Logistic regression analyses were performed to identify predictors of self-reported knee function . The area under the curve ( AUC ) from receiver operating characteristic curves was used as a measure of discriminative accuracy . Optimal limb symmetry index ( LSI ) cutoff for the best single-legged hop test was defined as the LSI with the highest product of sensitivity and specificity . Results : Single hop for distance symmetry indexes predicted self-reported knee function at the 1-year follow-up ( P = .036 ) . Combinations of any 2 hop tests ( AUC = 0.64 - 0.71 ) did not give a higher discriminative accuracy than the single hop alone ( AUC = 0.71 ) . A cutoff of 88 % ( LSI ) for the single hop revealed a sensitivity of 71.4 % and a specificity of 71.7 % . Conclusion : The single hop for distance ( LSI ) significantly predicted self-reported knee function after 1 year in nonoperatively treated ACL-injured patients . Combinations of 2 single-legged hop tests did not lead to higher discriminative accuracy than the single hop alone 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 PURPOSE To investigate the influence of harvesting semitendinosus and gracilis tendons on the rotational muscle strength of the limb after anterior cruciate ligament ( ACL ) reconstruction . TYPE OF STUDY Prospect i ve study . METHODS We performed a prospect i ve study of 62 consecutive ( 34 male , 28 female ) patients with ACL reconstructions using the semitendinosus and gracilis tendons . The mean age at surgery was 20.8 years . The semitendinosus tendon was harvested in 32 patients ( ST group ) , and semitendinosus and gracilis tendons in 30 patients ( STG group ) . The peak isokinetic torques for extension , flexion , internal rotation , and external rotation were measured before and 12 months after ACL reconstruction using the Cybex 6000B system ( Cybex Division of Lumex , Ronkonkoma , NY ) . The rotational torque was measured at 30 degrees/sec and 120 degrees/sec . RESULTS Before reconstruction , the mean isokinetic peak torque of the involved limb was decreased in extension and internal rotation . The mean isokinetic peak torque of the involved limb in extension recovered 12 months after ACL reconstruction ; however , the weakness in internal rotation persisted . The preoperative weakness of the involved limb in extension and internal rotation recovered in the male patients , but not in the female patients after postoperative rehabilitation . The peak torque of the involved limb in internal rotation was decreased in the STG group , but not in the ST group . CONCLUSIONS The internal rotational torque was influenced by harvesting the semitendinosus and gracilis tendons after ACL reconstruction , especially in female patients and patients from whom the gracilis tendon was harvested . Semitendinosus and gracilis tendons are important for the internal rotation of the limb and it was difficult to compensate for this function . Thus , we recommend harvesting the semitendinosus tendon only if tendon quality is sufficient to further minimize harvesting morbidity Fifty-nine people , 31 healthy subjects with no previous knee injuries and 28 who had undergone an intra-articular anterior cruciate ligament reconstruction 6 - 12 months prior to testing took part in the study . The subjects were r and omly tested bilaterally on a Cybex 6000 isokinetic testing device ( ITD ) and on an ordinary leg extension bench ( LEB ) . Strength and endurance were tested with both methods . The linear relationships for paired strength and endurance differences between ITD and LEB were found to be acceptable for the operated group . The LEB alone explained 57 % and 38 % of the ITD outcome for strength and endurance , respectively . The agreement between observed and predicted ITD values based on the LEB measurements was found satisfactory with a positive st and ardized agreement index . This indicates that the LEB can be used as a helpful tool in evaluation of quadriceps muscle strength deficits Functional dynamic tests are increasingly used in rehabilitation after injuries of the lower extremities . In these tests quantitative measures ( e.g. time , height , distance ) are mainly used as parameters , whereas the quality of the neuromuscular performance is poorly evaluated . In the present study the neuromuscular performance of leg muscles in different motor tasks was investigated 10 - 16 months after ACL-reconstruction . In 39 subjects with arthroscopically assisted ACL-reconstruction and 20 controls , isometric knee extensor strength , thigh circumference , knee stability , subjective knee function and the neuromuscular performance ( by kinematic data and EMG ) during three dynamic tests ( stair descending , one-legged drop jump , one-legged cyclic hops ) were measured . During the strength measurements a superimposed twitch technique was used for the detection of neuromuscular inhibition . The results demonstrate a significantly reduced Lysholm-Score and a distinct strength deficit , but no neuromuscular inhibition and no differences in knee stability in the operated leg . Besides reduced motor abilities of the injured leg , significant differences of the neuromuscular performance could be detected . It was evident that different test conditions revealed different persisting changes of the neuromuscular performance , which could not be detected by kinematic parameters alone OBJECTIVE It was hypothesized that testing of ambulatory function and more dem and ing activities were more appropriate predictors of dynamic knee function before and after reconstruction of the anterior cruciate ligament than conventional measures of functional evaluation . It was assumed that assessment of dynamic plantar pressure distribution would represent a practical tool for guidance of the rehabilitation process after anterior cruciate ligament reconstruction . DESIGN In a prospect i ve study , 10 patients with isolated anterior cruciate deficiency were examined before and after replacement of the anterior cruciate ( 6 , 12 , 24 weeks ) in a st and ardized technique . BACKGROUND Today , functional assessment following anterior cruciate ligament reconstruction relies on clinical examination supplemented by instrumented testing of knee laxity and on isokinetic evaluation of muscle performance . Gait analysis has not been used as a quantitative measure of rehabilitation progress after surgery . METHODS All patients were subjected to the same physiotherapy protocol . The clinical results were documented using the International Knee Documentation Committee ( IKDC ) protocol and the degree of knee laxity by an instrumented anterior drawer test . Muscular performance was evaluated by isokinetic testing . Dynamic pedography ( EMED-SF 4 ) was performed to compare the non-injured and the operated leg during level walking and while descending stairs . RESULTS Gait performance six weeks after surgery tended to be inferior to preoperative and late postoperative values . While the slight increase of maximum knee extensor torque in the operated leg and the improvement of the IKDC score during the rehabilitation period were not statistically significant , a significantly decreased gait asymmetry could be observed 12 weeks after surgery . The descending stairs test revealed functional deficits better than level walking . The latter test exhibited a strong correlation with the preoperative IKDC level and the maximum knee extensor deficit at 60 degrees /s . CONCLUSIONS Dynamic pedography during level walking and while descending stairs is a valuable tool for monitoring the rehabilitation process after anterior cruciate ligament reconstruction . RELEVANCE Due to the better resolution of functional deficits compared with indirect measures of function ( isokinetic testing ) assessment of the plantar pressure distribution may provide a more individualized adaptation for the rehabilitation program The purpose of this study was to evaluate prospect ively the results of anterior cruciate ligament ( ACL ) reconstruction with doubled hamstring tendon graft in a selected group of 18 rugby players . The graft was fixed with a transcondylar screw ( Transfix ) on the femur , and with an absorbable interference screw and a metallic staple on the tibia . All the patients followed the same rehabilitation program . Return to sports activities was allowed after 6 months . Follow-up was 2 years in all cases . The athletic level of the patients was rated according to the Tegner scoring system . Clinical results were evaluated using the International Knee Documentation Committee ( IKDC ) scoring system . Furthermore , an instrumented evaluation of the anterior laxity with a KT–1000 arthrometer , and an isokinetic evaluation were performed 6 and 24 months after surgery . The Tegner mean score at follow-up ( 8.2 ) was similar to that prior to injury ( 8.3 ) . IKDC overall results were normal in ten cases ( 55.6 % ) , nearly normal in six cases ( 33.3 % ) , and abnormal in two cases ( 11.1 % ) . Side-to-side difference of anterior laxity measured with KT–1000 at 6 and 24 months did not show an impairment of knee stability with time . Isokinetic evaluation showed a significant improvement on peak torque both in extension and flexion on comparison between 6- and 24-month measurements . The results reported in this study showed that the use of doubled hamstring tendon graft for ACL reconstruction in athletes that were at risk for high-energy traumas to the knees , such as rugby players , gave normal or nearly normal results in about 90 % of the cases . Recovery of muscle strength was almost complete 2 years after surgery , and there was no impairment of knee stability with time Background and Purpose The purpose of this study was to determine the effect of a 6-month neuromuscular training ( NT ) program versus a traditional strength training ( ST ) program following anterior cruciate ligament ( ACL ) reconstruction . Subjects Seventy-four subjects with ACL reconstruction participated in the study . Methods The study was a r and omized , single-blinded , controlled trial . The NT and ST groups were tested preoperatively and at 3 and 6 months . The main outcome measure was the Cincinnati Knee Score . Secondary outcome measures were visual analog scales ( VASs ) for pain and function , the 36-Item Short-Form Health Survey ( SF-36 ) , hop tests , isokinetic muscle strength , proprioception , and static and dynamic balance tests . Results The NT group demonstrated significantly improved Cincinnati Knee Scores and VAS scores for global knee function compared with the ST group at the 6-month follow-up . There were no significant differences between the groups for the other outcome measures ( ie , hop , balance , proprioception , and muscle strength tests ) . Discussion and Conclusion The results of this study suggest that exercises included in the NT program should be part of the rehabilitation program following ACL reconstruction The aim of the study was to compare the results after arthroscopic anterior cruciate ligament ( ACL ) reconstruction using central -third , bone-patellar tendon-bone ( BPTB Group ) ( n = 45 ) and four-str and semitendinosus/gracilis ( ST/G Group ) ( n = 78 ) autografts in male patients . The type of study is non-r and omised , prospect i ve consecutive series . A consecutive series of 126 male patients , all with unilateral ACL ruptures , was included in the study . In both groups , interference screw fixation of the graft was used at both ends and 123/126 ( 97 % ) of the patients returned for the follow-up examination after a period of 25 ( 23–33 ) months . The pre-operative assessment s in both groups were similar in terms of the Tegner activity level , the Lysholm knee scoring scale , KT-1000 measurements , one-leg-hop test and knee-walking test . A significant reduction in knee laxity as measured with the KT-1000 arthrometer , compared with the pre-operative assessment s , was found in both groups ( P < 0.001 ) . No significant differences in the post-operative knee-laxity measurements were found between the groups . Both groups had a significantly improved functional outcome at follow-up in terms of the Lysholm knee scoring scale , Tegner activity level and one-leg-hop test . The BPTB Group had a significantly higher Tegner activity level at follow-up , compared with the ST/G Group ( P = 0.02 ) . Moreover , the patients in the BPTB Group were significantly more likely to have a Tegner activity level of 6 or above ( P = 0.03 ) . Otherwise , no significant differences were found between the two study groups at the 2-year follow-up . Two years after an ACL reconstruction , the two groups displayed no significant differences in terms of functional outcome and knee laxity . However , more patients in the BPTB Group returned to a higher Tegner activity level than that in the ST/G Group Abstract In a prospect i ve study 60 patients were r and omized to brace and no-brace groups after bone-tendon-bone anterior cruciate ligament reconstruction . The brace group wore a rehabilitation orthosis for 12 weeks postoperatively , while the no-brace group was mobilized immediately , and crutches were discarded 2 weeks postoperatively . The groups were comparable with respect to age , gender , time from injury to surgery , knee score ( Lysholm ) , activity level ( Tegner ) , degree of laxity and isokinetic muscle torque . Although compared with the preoperative situation patients in both groups had significantly improved , there were no differences between the groups 1 and 2 years postoperatively in terms of functional outcome ( Lysholm and Tegner scores ) , stability of the knee or isokinetic muscle torque The purpose of this study was to examine the effects of 8-week retraining programs , with either two or three training sessions per week , on measures of functional performance and muscular power in athletes with anterior cruciate ligament reconstruction ( ACLR ) . Sixteen male athletes were r and omly assigned to two groups after ACLR : a functional training group ( FTG , n = 8) training 2 intense sessions per week ( 4hrs/week ) , and a control group ( CG , n = 8) training 3 sessions per week with moderate intensity ( 6hrs/week ) . The two groups were assessed at four and six months post-ACLR and the effects of retraining were measured using the following assessment s : the functional and the muscular power tests , and the agility T-test . After retraining , the FTG had improved more than the CG in the operated leg in the single leg hop test ( + 34.64 % vs. + 10.92 % ; large effect ) , the five jump test ( + 8.87 % vs. + 5.03 % ; medium effect ) , and single leg triple jump ( + 32.15 % vs. + 16.05 % ; medium effect ) . For the agility T-test , the FTG had larger improvements ( + 17.26 % vs. + 13.03 % , medium effect ) as compared to the CG . For the bilateral power tests , no significant training effects were shown for the two groups in the squat jump ( SJ ) , the counter movement jump ( CMJ ) and the free arms CMJ ( Arm CMJ ) . On the other h and , the unilateral CMJ test with the injured and the uninjured legs showed a significant increase for the FTG with respect to CG ( p < 0.05 ) . The present study introduces a new training modality in rehabilitation after ACLR that results in good recovery of the operated limb along with the contra-lateral leg . This may allow the athletes to reach good functional and strength performance with only two physical training sessions per week , better preparing them for a return to sport activity at 6 months post- ACLR and eventually sparing time for a possible progressive introduction of the sport specific technical training . Key pointsFunctional training ( plyometrics , neuromuscular , proprioceptive and agility exercises ) in athletes during 4th to 6th months post-ACLR further improved functional outcomes , compared to a conventional rehabilitation program . The former program was more time-efficient compared to the latter one as indicated by the weekly training duration ( 4hrs/week vs. 6hrs/week).This study provides evidence of the functional training in knee rehabilitation and provides important information that is highly relevant to clinicians , physiotherapists , coaches and trainers who are in charge of the injured athletes during the later phase of the rehabilitation after ACLR Objective To examine the effect of a comprehensive warm-up programme design ed to reduce the risk of injuries in female youth football . Design Cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 125 football clubs from the south , east , and middle of Norway ( 65 clusters in the intervention group ; 60 in the control group ) followed for one league season ( eight months ) . Participants 1892 female players aged 13 - 17 ( 1055 players in the intervention group ; 837 players in the control group ) . Intervention A comprehensive warm-up programme to improve strength , awareness , and neuromuscular control during static and dynamic movements . Main outcome measure Injuries to the lower extremity ( foot , ankle , lower leg , knee , thigh , groin , and hip ) . Results During one season , 264 players had relevant injuries : 121 players in the intervention group and 143 in the control group ( rate ratio 0.71 , 95 % confidence interval 0.49 to 1.03 ) . In the intervention group there was a significantly lower risk of injuries overall ( 0.68 , 0.48 to 0.98 ) , overuse injuries ( 0.47 , 0.26 to 0.85 ) , and severe injuries ( 0.55 , 0.36 to 0.83 ) . Conclusion Though the primary outcome of reduction in lower extremity injury did not reach significance , the risk of severe injuries , overuse injuries , and injuries overall was reduced . This indicates that a structured warm-up programme can prevent injuries in young female football players . Trial registration IS RCT N10306290 STUDY DESIGN R and omized clinical trial . OBJECTIVES Determine effective interventions for improving readiness to return to sports postoperatively in patients with complete , unilateral , anterior cruciate ligament ( ACL ) rupture who do not compensate well after the injury ( noncopers ) . Specifically , we compared the effects of 2 preoperative interventions on quadriceps strength and functional outcomes . BACKGROUND The percentage of athletes who return to sports after ACL reconstruction varies considerably , possibly due to differential responses after acute ACL rupture and different management . Prognostic data for noncopers following ACL reconstruction is absent in the literature . METHODS Forty noncopers were r and omly assigned to receive either progressive quadriceps strength-training exercises ( STR group ) or perturbation training in conjunction with strength-training exercises ( PERT group ) for 10 preoperative rehabilitation sessions . Postoperative rehabilitation was similar between groups . Data on quadriceps strength indices [ ( involved limb/uninvolved limb force ) x 100 ] , 4 hop score indices , and 2 self-report question naires were collected preoperatively and 3 , 6 , and 12 months postoperatively . Mann-Whitney U tests were used to compare functional differences between the groups . Chi-square tests were used to compare frequencies of passing functional criteria and reasons for differences in performance between groups postoperatively . RESULTS Functional outcomes were not different between groups , except a greater number of patients in the PERT group achieved global rating scores ( current knee function expressed as a percentage of overall knee function prior to injury ) necessary to pass return-to-sports criteria 6 and 12 months after surgery . Mean scores for each functional outcome met return-to-sports criteria 6 and 12 months postoperatively . Frequency counts of individual data , however , indicated that 5 % of noncopers passed RTS criteria at 3 , 48 % at 6 , and 78 % at 12 months after surgery . CONCLUSION Functional outcomes suggest that a subgroup of noncopers require additional supervised rehabilitation to pass stringent criteria to return to sports . LEVEL OF EVIDENCE Therapy , level 2b . Note : If watching the first video , we recommend downloading and referring to the accompanying PowerPoint slides for any text that is not readable The purpose of the present investigation was to evaluate physical outcome after anterior cruciate ligament ( ACL ) reconstruction with early versus late initiation of open kinetic chain ( OKC ) exercises for the quadriceps in patients operated on either patellar tendon or hamstring grafts . Sixty-eight patients , 36 males and 32 females , with either patellar tendon graft ( 34 patients ) or hamstring graft ( 34 patients ) were enrolled in this study . All patients were r and omly allocated to either early ( the 4th postoperative week ) or late ( the 12th postoperative week ) start of OKC exercises for the quadriceps , result ing in four subgroups : patellar tendon reconstruction , early start ( P4 ) or late start ( P12 ) of OKC quadriceps exercises , hamstring tendon reconstruction , early start ( H4 ) or late start ( H12 ) of quadriceps OKC exercises . Prior to surgery and 3 , 5 and 7 months later , assessment s of range of motion ( goniometer ) , anterior knee laxity ( KT-1000 ) , postural sway ( KAT 2000 ) , thigh muscle torques ( Kin – Com dynamometer ) and anterior knee pain ( anterior knee pain score ) were evaluated . No significant group differences were found in terms of range of motion 3 , 5 and 7 months postoperatively . The H4 group showed a significantly higher mean difference of laxity over time of 1.0 mm ( CI : 0.18–1.86 ) than the P4 group ( P = 0.04 ) . Within the same type of surgery , the H4 against the H12 , the mean difference over time was 1.2 mm ( 0.37–2.1 ) higher in the H4 group than in the H12 group ( P = 0.01 ) . There were no significant group differences in terms of postural sway or anterior knee pain at the different test occasions . Significant differences in trends ( changes over time ) were found when comparing the four groups , for both quadriceps muscle torques ( P < 0.001 ) and hamstring muscle torques ( P < 0.001 ) . All groups , except the P4 group , reached preoperative values of quadriceps muscle torques at the 7 months follow-up . In the H4 and the H12 groups , significantly lower hamstring muscle torques at the 7 months follow-up compared with preoperative values were found . In conclusion , early start of OKC quadriceps exercises after hamstring ACL reconstruction result ed in significantly increased anterior knee laxity in comparison with both late start and with early and late start after bone – patellar tendon – bone ACL reconstruction . Furthermore , the early introduction of OKC exercises for quadriceps did not influence quadriceps muscle torques neither in patients operated on patellar tendon nor hamstring tendon grafts . On the contrary , it appears as if the choice of graft affected the strength of the specific muscle more than the type of exercises performed . Our results could not determine the appropriate time for starting OKC quadriceps exercises for patients who have undergone ACL reconstruction with hamstring tendon graft . Future studies of long-term results of anterior knee laxity and functional outcome are needed UNLABELLED The patellar and semitendinosus tendon autograft are the two most common techniques that orthopedic surgeons use to reconstruct the anterior cruciate ligament ( ACL ) . It has not been established , however , whether either of these techniques provides a greater functional advantage to the patient . PURPOSE To identify patients ' functional capabilities after reconstruction of the ACL with a patellar or semitendinosus tendon autograft . METHODS Forty male soccer players volunteered for the study and were assigned to three homogeneous groups : individuals who had patellar tendon reconstruction ( N = 15 ) , individuals who had semitendinosus tendon reconstruction ( N = 15 ) , and a control group ( N = 10 ) . All patients had undergone surgery 2 yr before this study and received the same rehabilitation training . The testing procedures included measurement of thigh circumference , maximal isometric strength of quadriceps and hamstrings , two- and one-legged jump , squat and gait analysis . Kinetic , kinematic , and electromyographic data were collected . RESULTS The patellar tendon group exhibited lower ( P < 0.05 ) coactivation of the agonist and antagonist muscles around the knee joint during the squat movement and lower stabilization- and l and ing degrees during the jumps . Furthermore , the patellar tendon group had a shorter stance phase and reached the first vertical maximum later with the impaired leg while walking ( 720.2 + /- 15.6 ms vs 740.3 + /- 14.3 ms , and 24.3 + /- 0.64 % vs 22.9 + /- 0.74 % of stance phase ) , which was not observed in the semitendinosus tendon and control groups . CONCLUSION Functional performance is compromised in patients who undergo a patellar tendon graft compared with a semitendinosus graft , possibly due to an altered activation of the quadriceps and hamstring muscles OBJECTIVE To evaluate functional hop performance in subjects with an anterior cruciate ligament ( ACL ) reconstruction with a bone-patellar tendon-bone graft during 12 , 18 , 26 , 39 , and 52 weeks . DESIGN A longitudinal comparative study . SETTING University research laboratory . PARTICIPANTS Patients ( N=19 ) were evaluated at 12 , 18 , 26 , 39 , and 52 weeks after ACL reconstruction surgery . INTERVENTION Testing on 5 separate occasions . MAIN OUTCOME MEASURES The Cincinnati Knee Rating System and analog scales , the 6-meter timed hop , crossover hop , stair hop , and vertical hop , and limb symmetry indices . RESULTS The uninjured and injured legs and test order were r and omized . There was a significant test occasion main effect for both the Cincinnati and analog scores ( P=.001 ) . Subjective rating scores improved over the 5 testing occasions . For all 4 hop tests , test occasion and limb main effects were significant ( P=.001 ) . Paired t test comparisons at each testing occasion indicated a significant difference between the reconstructed and uninjured limb ( P<.05 ) . Furthermore , significant test occasion main effects were noted for limb symmetry indices for the 4 hop tests ( P=.001 ) . Using a score of greater than or equal to 85 % as a criterion for normative limb symmetry , normative scores were recorded in the 6-m timed hop at the week 18 test occasion , the stair hop and vertical hop at the week 26 test occasion , and the crossover hop at the week 39 test occasion . CONCLUSIONS These hop tests showed different levels of imposed dem and s on the knee that could be used to assess functional recovery and readiness to resume sport Objective : To determine whether the psychological characteristics of athletes who have undergone an anterior cruciate ligament ( ACL ) reconstruction change during rehabilitation are related to returning to competitive sport . Design : Prospect i ve longitudinal study . Method : 87 athletes completed the Emotional Response of Athletes to Injury Question naire ( ERAIQ ) and the ACL Return to Sport after Injury scale ( ACL-RSI ) at 3 , 6 and 12 months following ACL reconstruction surgery . Physical outcome measures were also taken at each time point . Results : At 12 months 44 ( 51 % ) participants had returned to competitive sport and 43 ( 49 % ) participants had not returned . There were no differences in physical recovery or scores on the ERAIQ between the two groups . Participants who had returned to competitive sport at 12 months , however , scored significantly higher on the ACL-RSI scale ( reflecting a more positive psychological response about sport participation ) at both 6 and 12 months than participants who had not returned to competitive sport . Conclusions : During rehabilitation there are significant psychological differences regarding sport resumption between athletes who do , and do not , resume competitive sport 12 months following ACL reconstruction . These differences occur as early as 6 months postoperatively and highlight the importance of addressing all aspects of an athlete ’s recovery in order to help facilitate the athlete returning to sport The purpose of this prospect i ve and r and omized study was to compare rehabilitation with early range of motion ( ROM ) training vs immobilization following anterior cruciate ligament ( ACL ) reconstruction . Fifty patients , undergoing an ACL reconstruction with a bone-patellar tendon-bone graft , were postoperatively allocated r and omly to either a plaster cast or a brace for 5 weeks . The brace group had ROM exercises from postoperative day 7 . The commencement of ROM exercises was postponed 4 weeks for the plaster group compared to the brace group , but progressed subsequently with equal speed . There was no difference between the groups in the ROM of flexion or extension 20 weeks after the ACL reconstruction and later . Twenty-four months after surgery , the muscle strength deficit in the hamstring muscles ( isokinetic measurements ; percent difference , injured vs uninjured ) was significantly larger in the brace group ( mean + /- SD : 5.9 + /- 7.8 % , P < 0.01 ) than in the plaster group ( - 0.9 + /- 11.8 % , NS ) ( brace vs plaster group , P < 0.05 ) . Furthermore , there was also a tendency in the brace group to a larger strength deficit in the quadriceps muscle ( brace : 11.1 + /- 13.2 % , P < 0.001 ; plaster : 3.8 + /- 12.9 % , NS ) ( brace vs plaster group , P= 0.07 ) . There was no difference between the groups in the total sagittal knee laxity , as measured with an arthrometer , or in the subjective knee function or activity level ( Lysholm score together with the Tegner activity level ) between the groups . It is concluded that the postoperative treatment with early range of motion training after ACL reconstruction gave as good ROM , knee stability , subjective knee function and activity level as the treatment with immobilization . It is hypothesized that the larger strength deficit observed after rehabilitation with early range of motion training is secondary to the more intensive training and physical therapist involvement that was dem and ed in order to achieve full ROM following immobilization The aim of the study is to compare the results after arthroscopic anterior cruciate ligament ( ACL ) reconstruction using central -third , bone-patellar tendon-bone ( BTB group ) ( n=28 ) and four-str and semitendinosus/gracilis ( ST/G group ) ( n=31 ) autografts in female patients . The type of study was non-r and omised prospect i ve consecutive series . A consecutive series of 61 female patients , all with unilateral ACL ruptures , was included in the study . In both groups , interference screw fixation of the graft was used at both ends , and 59/61 ( 97 % ) of the patients returned for the follow-up examination after a period of 26 ( 23–31 ) months . The pre-operative assessment s in both groups were similar in terms of the Lysholm score , KT−1000 measurements , one-leg-hop test , and knee-walking test . At the 2-year follow-up , the knee-walking test was significantly worse in the BTB group than in the ST/G group ( P=0.003 ) . Furthermore , the knee-walking test was significantly worse at follow-up than pre-operatively in the BTB group ( P<0.005 ) . The corresponding finding was not made in the ST/G group . A reduction in knee laxity compared with the pre-operative assessment s was found in both groups . No significant difference in the post-operative knee laxity measurement was found between the groups . A significant increase in activity level and subjective scores was found in both groups compared with pre-operative values , without any significant differences between the groups . Two years after ACL reconstruction , the groups displayed no significant differences in terms of functional outcome and knee laxity . However , the use of ST/G autografts rendered significantly less discomfort during the knee-walking test than the use of BTB autografts OBJECTIVE To determine the effectiveness of coach-led neuromuscular warm-up on reducing lower extremity ( LE ) injuries in female athletes in a mixed-ethnicity , predominantly low-income , urban population . DESIGN Cluster r and omized controlled trial . SETTING Chicago public high schools . PARTICIPANTS Of 258 coaches invited to participate , 95 ( 36.8 % ) enrolled ( 1558 athletes ) . Ninety coaches and 1492 athletes completed the study . INTERVENTIONS We r and omized schools to intervention and control groups . We trained intervention coaches to implement a 20-minute neuromuscular warm-up . Control coaches used their usual warm-up . MAIN OUTCOME MEASURES Coach compliance was tracked by self-report and direct observation . Coaches reported weekly athlete exposures ( AEs ) and LE injuries causing a missed practice or game . Research assistants interviewed injured athletes . Injury rates were compared between the control and intervention groups using χ(2 ) and Fisher exact tests . Significance was set at P < .05 . Poisson regression analysis adjusted for clustering and covariates in an athlete subset reporting personal information ( n = 855 ; 57.3 % ) . RESULTS There were 28 023 intervention AEs and 22 925 control AEs . Intervention coaches used prescribed warm-up in 1425 of 1773 practice s ( 80.4 % ) . Intervention athletes had lower rates per 1000 AEs of gradual-onset LE injuries ( 0.43 vs 1.22 , P < .01 ) , acute-onset noncontact LE injuries ( 0.71 vs 1.61 , P < .01 ) , noncontact ankle sprains ( 0.25 vs 0.74 , P = .01 ) , and LE injuries treated surgically ( 0 vs 0.17 , P = .04 ) . Regression analysis showed significant incidence rate ratios for acute-onset noncontact LE injuries ( 0.33 ; 95 % CI , 0.17 - 0.61 ) , noncontact ankle sprains ( 0.38 ; 95 % CI , 0.15 - 0.98 ) , noncontact knee sprains ( 0.30 ; 95 % CI , 0.10 - 0.86 ) , and noncontact anterior cruciate ligament injuries ( 0.20 ; 95 % CI , 0.04 - 0.95 ) . CONCLUSION Coach-led neuromuscular warm-up reduces noncontact LE injuries in female high school soccer and basketball athletes from a mixed-ethnicity , predominantly low-income , urban population . TRIAL REGISTRATION CLINICAL TRIALS.ORG IDENTIFIER : NCT01092286 BACKGROUND The aim of the study was to compare the results after arthroscopic anterior cruciate ligament ( ACL ) reconstruction using central -third bone-patellar tendon-bone ( BTB ) autografts and triple/quadruple semitendinosus ( ST ) autografts . HYPOTHESIS In the long-term , ACL reconstruction using BTB autografts will render more donor-site problems than ST autografts . STUDY DESIGN R and omized controlled trial ; Level of evidence , 1 . METHODS A r and omized series of 71 patients ( 22 women and 49 men ) with a unilateral ACL rupture who underwent reconstructive surgery were included in the study . The BTB graft was used in 34 patients ( BTB group ) and the ST-tendon graft was used in 37 patients ( ST group ) . The patients were examined a median of 86 months ( range , 68 to 114 months ) after the reconstruction . RESULTS Sixty-eight of 71 patients ( 96 % ) were examined at follow-up . The clinical assessment s at follow-up revealed no significant differences between the BTB group and the ST group in terms of the Lysholm score , Tegner activity level , International Knee Documentation Committee evaluation system , 1-legged hop test , KT-1000 arthrometer laxity measurements , manual Lachman test , and range of motion . A significant improvement was seen in both groups compared with the preoperative values in terms of most clinical assessment s. Donor-site morbidity in the form of knee-walking ability , kneeling ability , and area of disturbed anterior knee sensitivity revealed no significant differences between the groups . CONCLUSION Seven years after ACL reconstruction , the subjective and objective outcomes were similar after using the central -third BTB autograft and triple/quadruple ST autograft . Furthermore , no difference in terms of donor-site morbidity was found between the 2 groups Health care reform will quite possibly change the delivery of physical therapy by dem and ing physical therapists to be more accountable for providing appropriate , yet cost-effective treatment . The purpose of this study was to retrospectively compare the results after anterior cruciate ligament ( ACL ) reconstruction between two groups of patients with different numbers and frequencies of physical therapy visits postoperatively . Two r and om sample s of 100 patients from a total of 1,345 patients identified as undergoing ACL reconstruction from 1990 through 1993 were included . Group A patients attended physical therapy regularly and participated in a home exercise program , while patients in Group B attended limited physical therapy visits and also performed a prescribed home exercise program . Both groups followed the same postoperative rehabilitation program for early range of motion , early weight bearing , and muscle control . The outcome variables measured 1 , 6 , and 12 months postoperatively included the number of structured visits to physical therapy , range of motion , isokinetic strength testing , and subjective rating . Group A averaged 20 visits in the first 6 months while Group B averaged seven visits . The results revealed no significant difference for flexion , isokinetic strength , or subjective rating . There was a significant difference for hyperextension ( Group A , 2 degrees ; Group B , 6 degrees ) . The results of this investigation indicated that by following a structured physical therapy program postoperatively , it is possible for patients to achieve a successful outcome with a limited number of routine physical therapy visits Abstract The purpose of this study was to determine : ( 1 ) the sensitivity to changes over time for the IKDC form , the Lysholm score , and the Cincinnati knee score , ( 2 ) the relationship between the IKDC form , the Lysholm score and the Cincinnati knee score , ( 3 ) the criterion validity of each grade d variable included in the IKDC form , and ( 4 ) if a functional knee test should be included as a grade d variable and part of the final result of the IKDC form . We included in this prospect i ve study 120 subjects who underwent ACL reconstruction with follow-up times of 3 and 6 months , and 1 and 2 years after surgery . Outcome measurements were the grade d variables of the IKDC form ( IKDC1–4 and IKDC-final ) , the Lysholm score , the Cincinnati knee score , a visual analogue scale for patient ’s satisfaction , knee joint laxity measurement ( KT-1000 knee arthrometer ) , and two functional knee tests ( the triple jump and stairs hopple tests ) . The IKDC1 , IKDC2 , IKDC-final , and the Lysholm score were not sensitive to changes over time . The Cincinnati knee score was highly sensitive to changes over time and showed significantly improved outcome between each follow-up . IKDC1–4 showed high criterion validity , indicating that the IKDC1–4 is a good means of documenting clinical examination at one follow-up , but not of detecting changes over time . The functional knee tests were significant outcome measurements after ACL reconstruction , and should be reported separately One hundred twenty-one patients were prospect ively studied to determine whether the different remaining patellar tendon widths after central 10-mm bone- patellar tendon-bone graft harvest influenced the rate and level of quadriceps strength achieved during reha bilitation . Size of the patellar tendon width , measured at the same location in each patient , ranged from 24 to 35 mm . For this study , patients were grouped according to their remaining tendon size into small ( 14 to 17 mm ; mean , 15.8 ) , medium ( 18 to 20 mm ; mean , 19.2 ) , and large ( 21 to 25 mm ; mean , 22.5 ) widths . Postopera tively , the patient 's isokinetic quadriceps scores were determined at 6 weeks , 3 months , 6 months , and 1 year . At 6 weeks , the small- and medium-width tendon groups were significantly weaker than the large-width tendon group . At 3 months , only the small-width tendon group continued to be significantly weaker than the large- width tendon group . At and beyond 6 months , no sta tistically significant differences were seen between re maining patellar tendon width groups and their isokinetic quadriceps scores . A constant-sized autog enous patellar tendon graft may be harvested for an terior cruciate ligament reconstruction without compro mising ultimate postoperative quadriceps strength recovery PURPOSE The aim of this study was to compare the results after arthroscopic anterior cruciate ligament ( ACL ) reconstruction using central -third , bone-patellar tendon-bone ( BPTB group ) , 3-str and semitendinosus ( ST group ) , or 4-str and semitendinosus/gracilis ( ST/G group ) autografts . TYPE OF STUDY Prospect i ve r and omized trial . METHODS A r and omized series of 134 patients , all with unilateral ACL rupture was included in the study . In all 3 groups , interference screw fixation of the graft was used at both ends and 125 of 134 ( 93 % ) of the patients returned for the follow-up examination after 26 months ( range , 20 to 43 months ) . The preoperative assessment s in all 3 groups were similar in terms of gender , Tegner activity level , Lysholm score , KT-1000 measurements , 1-leg hop test , and the knee-walking test . RESULTS At follow-up , the knee-walking test was significantly worse in the BPTB group than in the ST group ( P = .0004 ) and ST/G group ( P < .0001 ) . Furthermore , the knee-walking test was significantly worse at follow-up than preoperatively in the BPTB group ( P < .0001 ) . The corresponding findings were not made in the other 2 groups . A significant reduction in knee laxity and an increase in activity level compared with the preoperative assessment s were found in all 3 groups , without any significant differences between the groups . CONCLUSIONS Two years after ACL reconstruction , the use of ST and ST/G autografts rendered significantly less discomfort during the knee-walking test than the use of BPTB autografts . However , in terms of functional outcome and knee laxity , the groups displayed no significant differences . LEVEL OF EVIDENCE Level BACKGROUND The choice of graft for anterior cruciate ligament reconstruction is a matter of debate , with patellar and hamstring tendons being the two most popular autologous graft options . The objective of this study was to determine in a prospect i ve , r and omized clinical trial whether two grafts ( bone-patellar tendon-bone or doubled hamstring tendons ) fixed with modern devices affect the two-year minimum clinical and radiographic outcomes of anterior cruciate ligament reconstruction . METHODS One hundred and twenty patients with a chronic unilateral rupture of the anterior cruciate ligament underwent arthroscopically assisted reconstruction with use of either autologous bone-patellar tendon-bone or doubled hamstring tendon grafts , in a strictly alternating manner . Both groups were comparable with regard to demographic data , preoperative activity level , mechanism of injury , interval between the injury and the operation , and the amount of knee laxity present preoperatively . The same well-proven surgical technique and aggressive controlled rehabilitation was used . An independent observer , who was blinded with regard to the involved leg and the type of graft , performed the outcome assessment with use of a visual analog scale , the new International Knee Documentation Committee form , the Knee Injury and Osteoarthritis Outcome Score , the Functional Knee Score for Anterior Knee Pain , and an arthrometric and an isokinetic dynamometric evaluation . Radiographs were also made . RESULTS At the two-year follow-up evaluation , no differences were found in terms of the visual analog score , the Knee Injury and Osteoarthritis Outcome Score , the new International Knee Documentation Committee subjective and objective evaluation scores , the KT-1000 side-to-side laxity measurements , the Functional Knee Score for Anterior Knee Pain , muscle strength recovery , or return to sports activities . In the bone-patellar tendon-bone group , we found a higher prevalence of postoperative kneeling discomfort ( p < 0.01 ) and an increased area of decreased skin sensitivity ( p < 0.001 ) . In the hamstring tendon group , we recorded a higher prevalence of femoral tunnel widening ( p < 0.01 ) . In this group , a correlation was also found between medial meniscectomy and an increased prevalence of pivot-shift glide ( p = 0.035 ) . CONCLUSIONS We believe that , with use of accurate and proven surgical and rehabilitation techniques , both grafts are an equivalent option for anterior cruciate ligament reconstruction PURPOSE The goal of this study was to evaluate strength and functional capacity before and after anterior cruciate ligament ( ACL ) reconstruction to determine the influences of preoperative strength deficit , graft type , and gender , as well as their clinical relevance in predicting postsurgical recovery and determining the postoperative rehabilitation program . METHODS This was a retrospective review of prospect ively collected uniform data from a group of 191 patients undergoing ACL reconstruction . We assessed functional capabilities and strength of the quadriceps and hamstring at 60 degrees/s and 180 degrees/s by use of a Cybex II dynamometer ( Lumex , Ronkonkoma , NY ) before and 6 , 9 , and 12 months after surgery . RESULTS There was a preoperative quadriceps strength deficit and a decreased limb symmetry index in patients with an ACL deficiency . This strength deficit increased postoperatively , with the highest measured deficit occurring at 6 months postoperatively and a clear improvement from 6 to 12 months . Functional assessment showed identical development . There was a statistically significant relation between an increased quadriceps strength deficit preoperatively and poor early postoperative functional performance . For the bone-patellar tendon-bone ( BPTB ) group , there was an increased quadriceps strength deficit compared with the semitendinosus and gracilis tendon ( STG ) group , and the STG group had an increased hamstring strength deficit on postoperative testing . The postoperative hamstring strength deficit is significantly increased in female patients . CONCLUSIONS All of these data suggest that quadriceps strength deficit is related to the ACL injury and is increased by ACL reconstruction . Even 1 year after ACL reconstruction , a quadriceps strength deficit of almost 20 % persists . Flexion strength is within the normal range before and after surgery . These results are influenced by graft choice , with a higher quadriceps strength deficit for BPTB grafts . STG grafts induce a higher hamstring strength deficit compared with BPTB grafts . Functional assessment is improved at 9 and 12 months postoperatively compared with preoperatively regardless of graft type . However , an increased preoperative quadriceps strength deficit results in a lower limb symmetry index at 6 and 9 months postoperatively . LEVEL OF EVIDENCE Level IV , therapeutic case series This study compares the early functional outcomes of anterior cruciate ligament ( ACL ) reconstruction using a one-incision endoscopic technique versus a two-incision arthroscopically assisted technique . Thirty patients with chronic ACL-deficient knees were r and omly assigned to either group 1 ( one-incision technique ; 15 patients ) or group 2 ( two-incision technique ; 15 patients ) . Middle third ipsilateral patellar tendon was used in all reconstructions . All patients followed the same home-based accelerated rehabilitation protocol . The International Knee Documentation Committee scoring system was used to assess pre- and postoperative knee function . The mean length of follow-up was 17 months for group 1 and 15 months for group 2 . Three patients were lost to follow-up in group 2 . Patients in group 1 achieved a mean one-leg hop value of 89 % of the uninjured side while group 2 patients averaged 92 % . The mean side-to-side difference in anterior tibial translation was 2 mm in both groups at manual maximum translation . The mean isokinetic quadriceps strength at 300 degrees/second of the operated side 1 year after surgery was 83 % of normal for group 1 versus 73 % for group 2 . Both groups achieved maximum range of motion within 3 months . There was no statistically significant difference between the outcomes of the one- and two-incision techniques for ACL reconstruction . All patients in both groups had improved stability and function of their operative knees compared with their preoperative condition Abstract . Rehabilitation after anterior cruciate ligament ( ACL ) reconstruction has focused over the past decade on closed kinetic chain ( CKC ) exercises due to presumably less strain on the graft than with isokinetic open kinetic chain exercises ( OKC ) ; however , recent reports suggest that there are only minor differences in ACL strain values between some CKC and OKC exercises . We studied anterior knee laxity , thigh muscle torque , and return to preinjury sports level in 44 patients with unilateral ACL ; group 1 carried out quadriceps strengthening only with CKC while group 2 trained with CKC plus OKC exercises starting from week 6 after surgery . Anterior knee laxity was determined with a KT-1000 arthrometer ; isokinetic concentric and eccentric quadriceps and hamstring muscle torque were studied with a Kin-Com dynamometer before and 6 months after surgery . At an average of 31 months after surgery the patients answered a question naire regarding their current knee function and physical activity/sports to determine the extent and timing of their recovery . No significant differences in anterior knee laxity were noted between the groups 6 months postsurgery . Patients in group 2 increased their quadriceps torque significantly more than those in group 1 , but no differences were found in hamstring torque between the groups . A significantly higher number of patients in group 2 ( n=12 ) than in group 1 ( n=5 ) returned to sports at the same level as before the injury ( P<0.05 ) . Patients from group 2 who returned to sports at the same level did so 2 months earlier than those in group 1 . Thus the addition of OKC quadriceps training after ACL reconstruction results in a significantly better improvement in quadriceps torque without reducing knee joint stability at 6 months and also leads to a significantly higher number of athletes returning to their previous activity earlier and at the same level as before injury PURPOSE / BACKGROUND The decision to return an athlete to sports following anterior cruciate ligament reconstruction can be controversial . The purpose s of this study are 1 ) to describe a functional test ( Vail Sport Test ™ ) that includes the evaluation of muscle strength , endurance , power , and movement quality in those patients attempting to return to sports following ACL reconstruction and 2 ) to assess the reliability of the Vail Sport Test ™ . METHODS A prospect i ve cohort study design . A total of 30 ( 12 F , 18 M ) subjects ( 18.1±5.3 yrs ) volunteered for the study . All subjects were post-operative ACL reconstruction ( 5.2±1.9 months ) and were in the process of returning to sports . Each subject completed the Vail Sport Test ™ and was videotaped from the anterior and lateral view . The videotape was then viewed and grade d at two different points in time ( 48 hours apart ) by three licensed physical therapists . Intraclass correlations ( ICCs ) were calculated to determine intra- and inter-rater reliability . RESULTS Intra-rater reliability was excellent with a range of .95 to 1.0 . Reliability values between grade rs were .97 ( ICC(2),k ) and 1.55 ( SEM ) . CONCLUSIONS The results of this study suggest that the Vail Sport Test ™ has excellent reliability when the same grade rs scored the test using video on repeated occasions . In addition , the test was reliable between different grade rs . LEVEL OF EVIDENCE Level 2b OBJECTIVE To study muscle strength and functional performance in patients with anterior cruciate ligament ( ACL ) injury with or without surgical reconstruction 2 to 5 years after injury . Good muscle function is important in preventing early-onset osteoarthritis ( OA ) , but the role of reconstructive surgery in restoring muscle function is unclear . METHODS Of 121 patients with ACL injury included in a r and omized controlled trial on training and surgical reconstruction versus training only ( the Knee , Anterior cruciate ligament , NON-surgical versus surgical treatment [ KANON ] study , IS RCT N : 84752559 ) , 54 ( mean age at followup 30 years , range 20 - 39 , 28 % women ) were assessed a mean + /- SD of 3 + /- 0.9 years after injury with reliable , valid , and responsive test batteries for strength ( knee extension , knee flexion , leg press ) and hop performance ( vertical jump , one-leg hop , side hop ) . The Limb Symmetry Index ( LSI ; injured leg divided by uninjured and multiplied by 100 ) value and absolute values were used for comparisons between groups ( analysis of variance ) . An LSI > or=90 % was considered normal . RESULTS There were no differences between the surgical and nonsurgical treatment groups in muscle strength or functional performance . Between 44 % and 89 % of subjects had normal muscle function in the single tests , and between 44 % and 56 % had normal function in the test batteries . CONCLUSION The lack of differences between patients treated with training and surgical reconstruction or training only indicates that reconstructive surgery is not a prerequisite for restoring muscle function . Abnormal muscle function , found in approximately one-third or more of the patients , may be a predictor of future knee OA Background Bracing after anterior cruciate ligament reconstruction is expensive and is not proven to prevent injuries or influence outcomes . Purpose To determine whether postoperative functional knee bracing influences outcomes . Study Design Prospect i ve , r and omized , multicenter clinical trial . Methods One hundred volunteers from the 3 US service academies with acute anterior cruciate ligament tears were r and omized into braced or nonbraced groups . Only those subjects with anterior cruciate ligament tears treated surgically within the first 8 weeks of injury were included . Patients with chondral injuries , significant meniscal tears , or multiple knee ligament injuries were excluded . Surgical procedures and the postoperative physical therapy protocol s were identical for both groups . The braced group was instructed to wear an off-the-shelf functional knee brace for all cutting , pivoting , or jumping activities for the first year after surgery . Results Ninety-five subjects were available with a minimum 2-year follow-up . There were no statistically significant differences between groups in knee stability , functional testing with the single-legged hop test , International Knee Documentation Committee scores , Lysholm scores , knee range of motion , or isokinetic strength testing . Two braced subjects had reinjuries , and 3 nonbraced subjects had reinjuries . Conclusions In this young , active population , postoperative bracing does not appear to change the clinical outcomes after anterior cruciate ligament reconstruction Background Bone-patellar tendon-bone graft has been the most commonly used graft material in anterior cruciate reconstructions , but there has been increasing use of hamstring tendon grafts . However , no existing clinical studies show adequate support for the choice of one graft over the other . Hypothesis Hamstring tendons are equally as good as patellar tendon in anterior cruciate ligament reconstructions . Study Design Prospect i ve r and omized clinical trial . Methods Ninety-nine patients with laxity caused by a torn anterior cruciate ligament underwent arthroscopically assisted reconstruction with graft r and omization according to their birth year . Grafts were either bone-patellar tendon-bone with metal interference screw fixation or double-looped hamstring tendons with metal plate fixation . There were no significant differences between the two groups preoperatively or at operation . St and ard rehabilitation included immediate postoperative mobilization without a knee brace , protected weightbearing for 2 weeks , and return to full activity at 6 to 12 months . Results Forty-three patients in the patellar tendon group and 46 patients in the hamstring tendon group were available for clinical evaluation at a minimum of 21 months after surgery . No statistically significant differences were seen with respect to clinical and instrumented laxity testing , International Knee Documentation Committee Score ratings , isokinetic muscle torque measurements , and Kujala patellofemoral , Lysholm , and Tegner scores . Conclusion Equal results were seen for patellar and hamstring tendon autograft anterior cruciate ligament reconstructions at 2 years after surgery . Both techniques seem to improve patients ' performance Background : There have been no long-term follow-up studies comparing a predominantly home-based rehabilitation program with a st and ard physical therapy program after anterior cruciate ligament ( ACL ) reconstruction . Demonstrating the long-term success of such a cost-effective program would be beneficial to guide future rehabilitation practice . Purpose : To determine whether there were any differences in long-term outcome between recreational athletes who performed a physical therapy-supervised rehabilitation program and those who performed a primarily home-based rehabilitation program in the first 3 months after ACL reconstruction . Study Design : R and omized clinical trial ; Level of evidence , 1 . Methods : Patients were r and omized before ACL reconstruction surgery to either the physical therapy-supervised ( 17 physical therapy sessions ) or home-based ( 4 physical therapy sessions ) program . Eighty-eight of the original 129 patients returned 2 to 4 years after surgery to assess their long-term clinical outcomes . Primary outcome was the ACL quality of life question naire ( ACL QOL ) . Secondary outcomes were bilateral difference in knee extension and flexion range of motion , sagittal plane knee laxity , relative quadriceps and hamstring strength , and objective International Knee Documentation Committee score . Unpaired t tests and a chi-square test were used for the comparisons . Results : The home-based group had a significantly higher mean ACL QOL score ( 80.0 ± 16.2 ) than the physical therapy-supervised group ( 69.9 ± 22.0 ) a mean of 38 months after surgery ( P = .02 , 95 % confidence interval [ CI ] : 1.7 , 18.4 ) . The mean change in ACL QOL score from before surgery to follow-up was not significantly different between the groups ( physical therapy = 40.0 , home = 45.8 , P = .26 , 95 % CI : −15.8 , 4.4 ) . There were no significant differences in the secondary outcome measures . Conclusion : This long-term study upholds the short-term findings of the original r and omized clinical trial by demonstrating that patients who participate in a predominantly home-based rehabilitation program in the first 3 months after ACL reconstruction have similar 2- to 4-year outcomes compared with those patients who participate in a more clinical ly supervised program ACL-reconstruction with patellar tendon autograft is a st and ard procedure which can be performed arthroscopically with a femoral half tunnel drilled from the joint or using the two-tunnel technique with medial miniarthrotomy and additional femoral approach . The arthroscopic procedure with single incision was hypothesized to improve proprioception and to provide earlier rehabilitation . Twenty-nine patients with chronic ACL-deficiency were included in the prospect i ve study . Fifteen patients were operated endoscopically , 14 patients using the two-tunnel technique . Proprioception , Lysholm and Tegner scores as well as stability ( KT-1000 ) were assessed preoperatively , 3 and 6 months postoperatively as well as after 3.9 + /- 0.4 years . A significant deficit of proprioception was assessed in both groups preoperatively . Six months postoperatively , both groups showed a restitution of proprioception near full extension and full flexion of the knee . In the mid-range position , the proprioception could not be restored . At the final examination after 3.9 years , the deficit documented in the mid-range position still persisted . There were no differences in proprioception , clinical results and stability between the arthroscopic and the open technique Purpose The aim of our study was to review the clinical and radiological outcome of patients who had undergone anterior cruciate ligament ( ACL ) reconstruction in comparison to a group of non-operatively treated patients . Methods In a retrospective study we compared ACL reconstruction using a bone-patellar tendon-bone graft with a non-operatively treated group of patients 17–20 years later . Fifty-four patients that met the inclusion criteria , with arthroscopically proven ACL rupture , were treated between 1989 and 1991 . Thirty-three patients underwent ACL reconstruction , forming group one . Eighteen non-reconstructed patients continued with rehabilitation and modification of activities ( group two ) . The International Knee Documentation Committee ( IKDC ) subjective and objective evaluation forms and the Lysholm and Tegner scale were used to assess the knees at follow-up . Radiographic assessment was performed using the IKDC grading scale . Results Follow-up results showed that 83 % of reconstructed patients had stable knees and normal or nearly normal IKDC grade . Patients in the non-reconstructed group had unstable knees with 84 % having abnormal or severe laxity . The subjective IKDC score was significantly in favour of group one : 83.15 compared to 64.6 in group two . The Lysholm and Tegner score was also significantly better in group one . Conservatively treated patients all had unstable knees and worse scores . The rate of osteoarthritis showed more severe changes in non-reconstructed patients with additional meniscus injury . Conclusions We can conclude that 94 % of patients who underwent ACL reconstruction had stable knees after 15–20 years and there was a significantly lower percentage of osteoarthritis in comparison to conservatively treated patients Background Among female athletes it has not been established whether a neuromuscular and proprioceptive sports-specific training program will consistently reduce the incidence of anterior cruciate ligament injuries . Purpose To determine whether a neuromuscular and proprioceptive performance program was effective in decreasing the incidence of anterior cruciate ligament injury within a select population of competitive female youth soccer players . Study Design Cohort study ; Level of evidence , 2 . Methods In 2000 , 1041 female subjects from 52 teams received a sports-specific training intervention in a prospect i ve non-r and omized trial . The control group consisted of the remaining 1905 female soccer players from 95 teams participating in the same league who were age and skill matched . In the 2001 season , 844 female athletes from 45 teams were enrolled in the study , with 1913 female athletes ( from 112 teams ) serving as the age- and skill-matched controls . All subjects were female soccer players between the ages of 14 and 18 and participated in either their traditional warm-up or a sports-specific training intervention before athletic activity over a 2-year period . The intervention consisted of education , stretching , strengthening , plyometrics , and sports-specific agility drills design ed to replace the traditional warm-up . Results During the 2000 season , there was an 88 % decrease in anterior cruciate ligament injury in the enrolled subjects compared to the control group . In year 2 , during the 2001 season , there was a 74 % reduction in anterior cruciate ligament tears in the intervention group compared to the age- and skill-matched controls . Conclusion Using a neuromuscular training program may have a direct benefit in decreasing the number of anterior cruciate ligament injuries in female soccer players PURPOSE The purpose of this study was to determine , first , if there is measurable deficit in proprioception in an anterior cruciate ligament (ACL)-deficient knee , either compared to the contralateral knee or external controls ; second , if this deficit , if present , improves after ACL reconstruction ; and third , if improvement occurs , what the time course of improvement is . TYPE OF STUDY Prospect i ve cohort study . METHODS Patients undergoing ACL reconstruction at the University of Chicago , demonstrating a full and painless range of motion and no other knee ligament injury or history of previous knee surgery , were eligible . Twenty-six patients , with an average age of 25 years ( range , 16 to 48 ) were enrolled . Average time from injury to reconstruction was 8 weeks . The patients ' contralateral knee served as an internal control , and 26 age-matched and gender-matched healthy volunteers were enrolled as an external control group . ACL reconstructions were performed using a single-incision technique with either bone-patellar tendon-bone or quadrupled hamstring autograft . They were allowed immediate weightbearing as tolerated and participated in a st and ardized rehabilitation program , with the goal of returning to sport at approximately 6 months . Proprioception testing was carried out using an electrogoniometer , in a seated position . Joint position sense ( JPS ) and threshold to detection of passive motion ( TDPM ) were measured preoperatively and at 3 and 6 weeks and 3 and 6 months postoperatively . RESULTS Mean KT-2000 values 6 months postoperatively were 1.38 mm ( + /-2 ) . Modified Lysholm score improved significantly ( P < .01 ) . Calculated r values were 0.65 for JPS and 0.96 for TDPM . No significant differences in postoperative proprioception were found between hamstring and patellar tendon grafts or among patients with meniscus injury , meniscus repair , or chondral injury . Preoperatively , the mean TDPM in both the injured and contralateral knees was significantly higher ( worse ) than in the external control knees ( P = .008 ; P = .016 ) . Evaluation of changes in proprioception from preoperative to 6 months postoperative showed significant improvement in both injured and contralateral knees ( P = .04 ; P = .01 ) . At 6-month follow-up , there was no significant difference from controls . CONCLUSIONS TDPM was a more reliable method than JPS for testing proprioception before and after ACL reconstruction in this study . Bilateral deficits in knee joint proprioception ( TDPM ) were documented after unilateral ACL injury . Reconstruction of a mechanical restraint ( ACL graft ) was believed to have a significantly positive impact on early and progressive improvement in proprioception We evaluated extensor mechanism function in 10 pa tients after they had arthroscopically assisted ACL reconstruction using the central third of the patellar tendon . The patients were r and omly selected 12 to 24 months after reconstruction . All had rehabilitation where range of motion was initiated within the 1 st postoperative week . All patients stated that they were satisfied and considered their knee to be stable . The KT-1000 maximum measurements ( 30 to 40 pounds ) averaged an increase of 1.7 mm when compared with the opposite knee . Subjective complaints , such as an terior knee pain , grating , and weakness , were common and only 3 of 10 patients returned to all of their preinjury sports . Persistent radiographic abnormalities were common . Physical examination and functional testing also re vealed persistent dysfunction of the extensor mecha nism in patients with radiographic abnormalities . Isoki netic testing at 60 deg/sec showed an average quad riceps deficit of 18 % compared to the normal extremity . Axial computed tomography scans revealed significant decrease in quadriceps cross-sectional area . Magnetic resonance imaging and computed tomography con firmed persistent defects at the harvest site ; there was significant anterior knee scar formation in these pa tients . Despite achieving ligamentous stability , patients still experienced permanent weakness , functional deficits , patellar chondrosis , and pain after ACL reconstruction using the central one-third of the patellar tendon PURPOSE To analyze the long-term evaluation of clinical , functional , and magnetic resonance imaging ( MRI ) results after implant-free press-fit anterior cruciate ligament ( ACL ) reconstruction with bone-patella tendon ( BPT ) versus quadrupled hamstring tendon ( HT ) grafts . METHODS Sixty-two ACL-insufficient patients were included in a prospect i ve , r and omized study ( 31 BPT and 31 HT ) . Both surgical procedures were performed without any implants by a press-fit technique by the senior author . The femoral tunnel was drilled through the anteromedial portal for anatomic placement . At 8.8 years after reconstruction , 53 patients ( 28 BPT and 25 HT ) were examined by different clinical and functional tests . Bilateral MRI scans were performed and interpreted by an independent radiologist . RESULTS On follow-up , the score on the International Knee Documentation Committee evaluation form was significantly better in the HT group . The clinical examination including range of motion , KT-1000 test ( MEDmetric , San Diego , CA ) , and pivot-shift test showed no significant differences . On isokinetic testing , the mean quadriceps strength was close to normal ( 96 % ) in both groups , but the hamstring strength was lower in the HT group ( 100.3%/95.1 % ) . Kneeling ( 1.5/1.1 , P = .002 ) , knee walking ( 1.72/1.14 , P = .002 ) , and single-leg hop test ( 95.8%/99.1 % , P = .057 ) were better in the HT group . The MRI findings about the mean degree of cartilage lesion ( International Cartilage Repair Society protocol ) of the operated ( 2.1/2.1 ) and nonoperated ( 1.4/1.8 ) knee showed no significant differences . No significant difference was found in the grade of medial or lateral meniscal lesion or the number of patients having meniscal lesions when the operated and nonoperated knees were compared . Tunnel measurements , Caton-Deschamps Index , and the sagittal ACL angle were similar . CONCLUSIONS The implant-free press-fit technique for anterior cruciate ligament reconstruction by use of bone-patellar tendon and hamstring grafts with anatomic graft placement is an innovative technique to preserve the cartilage and meniscal status without significant differences between the operated and nonoperated knees in the long term . Significantly less anterior knee pain was noted in the hamstring group , when testing for kneeling and knee walking . LEVEL OF EVIDENCE Level II , prospect i ve comparative study BACKGROUND Aggressive early rehabilitation is recommended after reconstruction of the anterior cruciate ligament ( ACL ) using a patellar tendon-bone graft . However , rehabilitation after reconstruction of ACL using the multistr and ed hamstring is controversial . In this study , we compared the clinical results of 3-day immobilization after reconstruction of ACL using the multistr and ed hamstring , with those of 2-week immobilization prospect ively . METHODS A total of 30 consecutive patients with ruptured ACL underwent single-socket ACL reconstruction . 10 male and 5 female patients ( mean age of 29.2+/-10.0 years ) were prospect ively r and omized for a 3-day immobilization period , and 6 male and 9 female patients ( mean age of 27.3+/-10.9 years ) were r and omized for a 2-week immobilization period . We measured the anterior laxity with a KT-2000 arthrometer , joint position sense , and thigh muscle strength at 3 , 6 and 12 months after surgery . RESULTS AND CONCLUSIONS There were no statistically significant differences between the two groups . We concluded that the post-operative 3-day immobilization period is preferable to the longer 2-week period in our rehabilitation program from the viewpoint of psychological load to the patients and the duration of hospitalization after ACL reconstruction using multistr and ed hamstring tendons A prospect i ve , r and omized study comparing arthroscopic and open anterior cruciate ligament ( ACL ) reconstructions was undertaken . Neither the patients nor the physical therapists were made aware of which technique was used . The central one third of the patellar tendon with proximal and distal bone plugs was utilized as the graft material to reconstruct the ACL in all cases . Rehabilitation was identical for each group . The following variables were compared : postoperative pain score , operating time , estimated blood loss ( EBL ) , quantity of analgesics used , complications , range of motion at 1 , 3 , and 6 months , a 6-month evaluation consisting of Lachman 's , anterior drawer , and pivot shift tests , amount of thigh atrophy , and Cybex II tests . Statistical significance was achieved ( P < .05 ) in only three parameters . The 1-month postoperative range of motion , the 6-month postoperative thigh atrophy , and the Cybex II test ( knee extension at 60 degrees/sec ) were statistically different favoring the arthroscopic method Background Athletes who return to sport participation after anterior cruciate ligament reconstruction ( ACLR ) have a higher risk of a second anterior cruciate ligament injury ( either reinjury or contralateral injury ) compared with non — anterior cruciate ligament— injured athletes . Hypotheses Prospect i ve measures of neuromuscular control and postural stability after ACLR will predict relative increased risk for a second anterior cruciate ligament injury . Study Design Cohort study ( prognosis ) ; Level of evidence , 2 . Methods Fifty-six athletes underwent a prospect i ve biomechanical screening after ACLR using 3-dimensional motion analysis during a drop vertical jump maneuver and postural stability assessment before return to pivoting and cutting sports . After the initial test session , each subject was followed for 12 months for occurrence of a second anterior cruciate ligament injury . Lower extremity joint kinematics , kinetics , and postural stability were assessed and analyzed . Analysis of variance and logistic regression were used to identify predictors of a second anterior cruciate ligament injury . Results Thirteen athletes suffered a subsequent second anterior cruciate ligament injury . Transverse plane hip kinetics and frontal plane knee kinematics during l and ing , sagittal plane knee moments at l and ing , and deficits in postural stability predicted a second injury in this population ( C statistic = 0.94 ) with excellent sensitivity ( 0.92 ) and specificity ( 0.88 ) . Specific predictive parameters included an increase in total frontal plane ( valgus ) movement , greater asymmetry in internal knee extensor moment at initial contact , and a deficit in single-leg postural stability of the involved limb , as measured by the Biodex stability system . Hip rotation moment independently predicted second anterior cruciate ligament injury ( C = 0.81 ) with high sensitivity ( 0.77 ) and specificity ( 0.81 ) . Conclusion Altered neuromuscular control of the hip and knee during a dynamic l and ing task and postural stability deficits after ACLR are predictors of a second anterior cruciate ligament injury after an athlete is released to return to sport Background Despite a lack of evidence for their effectiveness , functional knee braces are commonly prescribed to patients after anterior cruciate ligament ( ACL ) reconstruction . Purpose This trial was conducted to compare postoperative outcomes in patients using an ACL functional knee brace and patients using a neoprene knee sleeve . Hypothesis Patients using a brace will have superior outcomes than those using a sleeve . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods One hundred fifty patients were r and omized to receive a brace ( n = 76 ) or neoprene sleeve ( n = 74 ) at their 6-week postoperative visit after primary ACL reconstruction with hamstring autograft . Patients were assessed preoperatively , then 6 weeks and 6 , 12 , and 24 months postoperatively . Outcome measures included disease-specific quality of life ( Anterior Cruciate Ligament– Quality of Life [ ACL-QOL ] Question naire ) , anterior tibial translation ( KT-1000 arthrometer side-to-side difference ) , the single-limb forward hop test ( limb symmetry index ) , and Tegner Activity Scale . Outcomes at 1 and 2 years were compared after adjusting for baseline scores . Subjective ratings of how patients felt while using the brace/sleeve were also collected for descriptive purpose s using a question naire . Four a priori directional subgroup hypotheses were evaluated using tests for interactions . Results There were no significant differences between brace ( n = 62 ) and sleeve ( n = 65 ) groups for any of the outcomes at 1- and 2-year follow-ups . Adjusted mean differences at 2 years were as follows : −0.94 ( 95 % confidence interval [ CI ] , −7.52 to 5.64 ) for the ACL-QOL Question naire , −0.10 mm ( 95 % CI , −0.99 to 0.81 ) for KT-1000 arthrometer side-to-side difference , −0.87 % ( 95 % CI , −8.89 to 7.12 ) for hop limb symmetry index , and −0.05 ( 95 % CI , −0.72 to 0.62 ) for the Tegner Activity Scale . Subjective ratings of confidence in the knee provided by the brace/sleeve were higher for the brace group than the sleeve group . Subgroup findings were minimal . Adverse events were few and similar between groups . Conclusions A functional knee brace does not result in superior outcomes compared with a neoprene sleeve after ACL reconstruction . Current evidence does not support the recommendation of using an ACL functional knee brace after ACL reconstruction |
1,061 | 18,930,961 | 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 . | BACKGROUND Non-uniform reporting of relevant relationships and metrics hampers critical appraisal of the clinical utility of C-reactive protein ( CRP ) measurement for prediction of later coronary events .
METHODS We evaluated the predictive performance of CRP in the Northwick Park Heart Study ( NPHS-II ) and the Edinburgh Artery Study ( EAS ) comparing discrimination by area under the ROC curve ( AUC ) , calibration and reclassification . | 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 . RESULTS The long-term stability of C-reactive protein values ( within-person correlation coefficient , 0.59 ; 95 percent confidence interval , 0.52 to 0.66 ) was similar to that of both blood pressure and total serum cholesterol . After adjustment for base-line values for established risk factors , the odds ratio for coronary heart disease was 1.45 ( 95 percent confidence interval , 1.25 to 1.68 ) in a comparison of participants in the top third of the group with respect to base-line C-reactive protein values with those in the bottom third , and similar overall findings were observed in an up date d meta- analysis involving a total of 7068 patients with coronary heart disease . By comparison , the odds ratios in the Reykjavik Study for coronary heart disease were somewhat weaker for the erythrocyte sedimentation rate ( 1.30 ; 95 percent confidence interval , 1.13 to 1.51 ) and the von Willebr and factor concentration ( 1.11 ; 95 percent confidence interval , 0.97 to 1.27 ) but generally stronger for established risk factors , such as an increased total cholesterol concentration ( 2.35 ; 95 percent confidence interval , 2.03 to 2.74 ) and cigarette smoking ( 1.87 ; 95 percent confidence interval , 1.62 to 2.16 ) . CONCLUSIONS C-reactive protein is a relatively moderate predictor of coronary heart disease . Recommendations regarding its use in predicting the likelihood of coronary heart disease may need to be review ed CONTEXT Although it has been hypothesized that hypertension is in part an inflammatory disorder , clinical data linking inflammation with incident hypertension are scarce . OBJECTIVE To examine whether C-reactive protein levels , a marker of systemic inflammation , are associated with incident hypertension . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve cohort study that began in 1992 of 20 525 female US health professionals aged 45 years or older who provided baseline blood sample s with initially normal levels of blood pressure ( BP ) ( systolic BP < 140 mm Hg and diastolic BP < 90 mm Hg , and no history of hypertension or antihypertensive medications ) and then followed up for a median of 7.8 years for the development of incident hypertension . Plasma C-reactive protein levels were measured and baseline coronary risk factors were collected . MAIN OUTCOME MEASURE Incident hypertension , defined as either a new physician diagnosis , the initiation of antihypertensive treatment , or self-reported systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg . RESULTS During follow-up , 5365 women developed incident hypertension . In crude models , the relative risks ( RRs ) and 95 % confidence intervals ( CIs ) of developing hypertension from the lowest ( referent ) to the highest levels of baseline C-reactive protein were 1.00 , 1.25 ( 95 % CI , 1.14 - 1.40 ) , 1.51 ( 95 % CI , 1.35 - 1.68 ) , 1.90 ( 95 % CI , 1.72 - 2.11 ) , and 2.50 ( 95 % CI , 2.27 - 2.75 ) ( linear trend P<.001 ) . In fully adjusted models for coronary risk factors , the RRs and 95 % CIs were 1.00 , 1.07 ( 95 % CI , 0.95 - 1.20 ) , 1.17 ( 95 % CI , 1.04 - 1.31 ) , 1.30 ( 95 % CI , 1.17 - 1.45 ) , and 1.52 ( 95 % CI , 1.36 - 1.69 ) ( linear trend P<.001 ) . C-reactive protein was significantly associated with an increased risk of developing hypertension in all prespecified subgroups evaluated , including those with very low levels of baseline BP , as well as those with no traditional coronary risk factors . Similar results were found when treating C-reactive protein as a continuous variable and controlling for baseline BP . CONCLUSION C-reactive protein levels are associated with future development of hypertension , which suggests that hypertension is in part an inflammatory disorder Alcohol dehydrogenase 1C ( ADH1C or ADH3 ) genotype reportedly modifies the association between alcohol consumption and coronary heart disease ( CHD ) risk , as well as influencing plasma high-density lipoprotein ( HDL ) levels [ Hines LM , Stampfer MJ , Ma J , et al. Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infa rct ion . N Engl J Med 2001;344:549 - 55 ] . This relationship has been examined in a sample of middle-aged ( 50 - 61 years ) men ( total of 2773 with 220 CHD events ) , participating in the prospect i ve Second Northwick Park Heart Study ( NPHS II ) . Alcohol consumption was assessed by question naire as the number of units consumed in the previous week . Drinkers experienced lower CHD risk than abstainers [ hazard ratio ( HR ) 0.73 ( 95 % confidence intervals ( CI ) 0.53 , 0.99 ; p=0.04 ) ] and had significantly higher HDL and apolipoprotein (apo)AI concentrations ( both p<0.0001 ) and a lower fibrinogen ( p=0.02 ) . Overall , there was no effect of ADHC1 gamma1>gamma2 genotype on plasma levels of HDL , apoAI or fibrinogen or on CHD risk . To consider whether the effect of alcohol consumption on risk was modulated by genotype , the men were divided into abstainers , modest drinkers ( 1 - 3 units/week ) and those who consumed more than 3 units/week . Significant alcohol : genotype interaction on CHD risk was observed ( p=0.02 ) , with gamma2 homozygotes , who were modest drinkers , displaying 78 % CHD risk reduction compared to gamma1 homozygotes ( HR=0.22 , 95 % CI 0.05 - 0.94 ) . There was , however , no association between genotype and apoAI , HDL or fibrinogen and this was not altered when alcohol intake was considered . These findings confirm that the cardiovascular benefit of modest alcohol consumption . ADH1C genotype modifies the relationship between alcohol consumption and CHD risk but at lower levels than previously reported |
1,062 | 28,854,961 | The safety and feasibility of administering different types of stem cell therapies in stroke seem to be reasonably proven . | Stem cells have demonstrated encouraging potential as reparative therapy for patients suffering from post-stroke disability .
Reperfusion interventions in the acute phase of stroke have shown significant benefit but are limited by a narrow window of opportunity in which they are beneficial .
Thereafter , rehabilitation is the only intervention available .
The current review summarises the current evidence for use of stem cell therapies in stroke from early-phase clinical trials . | 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 . Satisfactory clinical improvement occurred in 6/20 ( 30 % ) patients at 90 days . Eight patients ( 40 % ) showed a good clinical outcome . Infusion of intra-arterial autologous BMMCs appears to be safe in patients with moderate to severe acute middle cerebral artery strokes . No cases of intrahospital mortality were seen in this pilot trial . Larger prospect i ve r and omized trials are warranted to assess the efficacy of this treatment approach PURPOSE Bone marrow stem cells ( BMSC ) were transplanted into the perilesional area in five patients bearing sequels of stroke , to evaluate the safety of the procedure and tolerance to the transplanted cells . METHODS Cells were obtained from bone marrow sample s taken from the same patient and stereotactically implanted into the targets , determined using a combination of images , and trans-operative recording of multiunit activity . The cells were implanted in several points along tracts in the perilesional region . RESULTS No important adverse events derived from surgery or transplant were observed during the one year follow-up period , or detected using a combination of tests and functional measurements applied pre- and post-surgically . In contrast , some improvements were observed regarding the neurological condition of the patients , but the small number of patients in the study does not allow any conclusive statement . CONCLUSIONS Our results demonstrate that BMSC can be safely transplanted into the brain of patients , with excellent tolerance and without complications , using the methods described here Stem cell therapy is an emerging therapeutic modality in the treatment of stroke . We assessed the safety and feasibility of the cotransplantation of neural stem/progenitor cells ( NSPCs ) and mesenchymal stromal cells ( MSCs ) in patients with ischemic stroke . Eight patients were enrolled in this study . All patients had a hemisphere with infa rct lesions located on one side of the territories of the cerebral middle or anterior arteries as revealed with cranial magnetic resonance imaging ( MRI ) . The patients received one of the following two types of treatment : the first treatment involved four intravenous injections of MSCs at 0.5 × 106/kg body weight ; the second treatment involved one intravenous injection of MSCs at 0.5 × 106/kg weight followed by three injections of MSCs at 5 × 106/patient and NSPCs at 6 × 106/patient through the cerebellomedullary cistern . The patients ' clinical statuses were evaluated with the National Institutes of Health Stroke Scale ( NIHSS ) , the modified Rankin Scale ( mRS ) , and the Barthel index ( BI ) . Six patients were given four cell transplantations . The most common side effect of stem cell transplantation in these six cases was low fever that usually lasted 2–4 days after each therapy . One patient exhibited minor dizziness . All side effects appeared within the first 2–24 h of cell transplantation , and they resolved without special treatment . There was no evidence of neurological deterioration or neurological infection . Most importantly , no tumorigenesis was found at a 2-year follow-up . The neurological functions , disability levels , and daily living abilities of the patients in this study were improved . While these observations support the use of the combination transplantation of NSPCs and MSCs as a safe and feasible method of improving neurological function , further studies that include larger sample s , longer follow-ups , and control groups are still needed . This manuscript is published as part of the International Association of Neurorestoratology ( IANR ) special issue of Cell Transplantation The goal of this clinical trial was to assess the feasibility and safety of transplanting autologous bone marrow mononuclear cells into patients suffering severe embolic stroke . Major inclusion criteria included patients with cerebral embolism , age 20–75 years , National Institute of Health Stroke Scale ( NIHSS ) score displaying improvement of ≤5 points during the first 7 days after stroke , and NIHSS score of ≥10 on day 7 after stroke . Bone marrow aspiration ( 25 or 50 mL ; N = 6 patients in each case ) was performed 7–10 days poststroke , and bone marrow mononuclear cells were administrated intravenously . Mean total transplanted cell numbers were 2.5 × 108 and 3.4 × 108 cells in the lower and higher dose groups , respectively . No apparent adverse effects of administering bone marrow cells were observed . Compared with the lower dose , patients receiving the higher dose of bone marrow cells displayed a trend toward improved neurologic outcomes . Compared with 1 month after treatment , patients receiving cell therapy displayed a trend toward improved cerebral blood flow and metabolic rate of oxygen consumption 6 months after treatment . In comparison with historical controls , patients receiving cell therapy had significantly better neurologic outcomes . Our results indicated that intravenous transplantation of autologous bone marrow mononuclear cells is safe and feasible . Positive results and trends favoring neurologic recovery and improvement in cerebral blood flow and metabolism by cell therapy underscore the relevance of larger scale r and omized controlled trials using this approach Article abstract Transplantation of cultured neuronal cells is safe in animal models and improves motor and cognitive deficits in rats with stroke . The authors studied the safety and feasibility of human neuronal cellular transplantation in patients with basal ganglia stroke and fixed motor deficits , including 12 patients ( aged 44 to 75 years ) with an infa rct 6 months to 6 years previously ( stable for at least 2 months ) . Serial evaluations ( 12 to 18 months ) showed no adverse cell-related serologic or imaging-defined effects . The total European Stroke Scale score improved in six patients ( 3 to 10 points ) , with a mean improvement 2.9 points in all patients ( p = 0.046 ) . Six of 11 PET scans at 6 months showed improved fluorodeoxyglucose uptake at the implant site . Neuronal transplantation is feasible in patients with motor infa rct ion Mesenchymal stem cell ( MSC ) transplantation improves recovery from ischemic stroke in animals . We examined the feasibility , efficacy , and safety of cell therapy using culture‐exp and ed autologous MSCs in patients with ischemic stroke . We prospect ively and r and omly allocated 30 patients with cerebral infa rcts within the middle cerebral arterial territory and with severe neurological deficits into one of two treatment groups : the MSC group ( n = 5 ) received intravenous infusion of 1 × 108 autologous MSCs , whereas the control group ( n = 25 ) did not receive MSCs . Changes in neurological deficits and improvements in function were compared between the groups for 1 year after symptom onset . Neuroimaging was performed serially in five patients from each group . Outcomes improved in MSC‐treated patients compared with the control patients : the Barthel index ( p = 0.011 , 0.017 , and 0.115 at 3 , 6 , and 12 months , respectively ) and modified Rankin score ( p = 0.076 , 0.171 , and 0.286 at 3 , 6 , and 12 months , respectively ) of the MSC group improved consistently during the follow‐up period . Serial evaluations showed no adverse cell‐related , serological , or imaging‐defined effects . In patients with severe cerebral infa rcts , the intravenous infusion of autologous MSCs appears to be a feasible and safe therapy that may improve functional recovery . Ann Neurol Transplantation of human mesenchymal stem cells has been shown to reduce infa rct size and improve functional outcome in animal models of stroke . Here , we report a study design ed to assess feasibility and safety of transplantation of autologous human mesenchymal stem cells exp and ed in autologous human serum in stroke patients . We report an unblinded study on 12 patients with ischaemic grey matter , white matter and mixed lesions , in contrast to a prior study on autologous mesenchymal stem cells exp and ed in foetal calf serum that focused on grey matter lesions . Cells cultured in human serum exp and ed more rapidly than in foetal calf serum , reducing cell preparation time and risk of transmissible disorders such as bovine spongiform encephalomyelitis . Autologous mesenchymal stem cells were delivered intravenously 36 - 133 days post-stroke . All patients had magnetic resonance angiography to identify vascular lesions , and magnetic resonance imaging prior to cell infusion and at intervals up to 1 year after . Magnetic resonance perfusion-imaging and 3D-tractography were carried out in some patients . Neurological status was scored using the National Institutes of Health Stroke Scale and modified Rankin scores . We did not observe any central nervous system tumours , abnormal cell growths or neurological deterioration , and there was no evidence for venous thromboembolism , systemic malignancy or systemic infection in any of the patients following stem cell infusion . The median daily rate of National Institutes of Health Stroke Scale change was 0.36 during the first week post-infusion , compared with a median daily rate of change of 0.04 from the first day of testing to immediately before infusion . Daily rates of change in National Institutes of Health Stroke Scale scores during longer post-infusion intervals that more closely matched the interval between initial scoring and cell infusion also showed an increase following cell infusion . Mean lesion volume as assessed by magnetic resonance imaging was reduced by > 20 % at 1 week post-cell infusion . While we would emphasize that the current study was unblinded , did not assess overall function or relative functional importance of different types of deficits , and does not exclude placebo effects or a contribution of recovery as a result of the natural history of stroke , our observations provide evidence supporting the feasibility and safety of delivery of a relatively large dose of autologous mesenchymal human stem cells , cultured in autologous human serum , into human subjects with stroke and support the need for additional blinded , placebo-controlled studies on autologous mesenchymal human stem cell infusion in stroke Stem cell-based therapy shows great potential in stroke patients . Intra-artery infusion exhibits greater biological distribution compared to intravenous delivery . In addition , umbilical cord mesenchymal stem cells ( UCMSCs ) have several advantages compared with other types of stem cells . The aim of this study was to evaluate the safety and efficacy of UCMSCs delivered by a catheter to a near lesion site for treatment of an infa rct ion in the middle cerebral artery territory . Four patients with stroke ( three with ischemic and one with hemorrhagic stroke ) in the middle cerebral artery territory were recruited in this study . One single dose of 2 × 107 UCMSCs was infused within 20 min via catheterization in the M1 segment of the middle cerebral artery . The safety and efficacy of this approach were assessed during the in-hospital and 6-month follow-up evaluation . The cell delivery was successfully performed in all of the patients , and no major accidents ( stroke or death ) were observed . Moreover , no fever or rash was reported . After cellular therapy , two of the three ischemic stroke patients demonstrated improved muscle strength . The improvement of the modified Rankin scale was observed in two patients , both of whom suffered from ischemic stroke at 90 and 180 days after the stem cell therapy . The hemorrhagic stroke patient failed to demonstrate improved muscle strength and did not amend his daily activities . Intra-artery delivery of UCMSCs via catheterization was a feasible and safe approach and may improve the neurological function of ischemic stroke patients with the middle cerebral artery territory infa rcts Background & objectives : Bone marrow mononuclear cell therapy has emerged as one of the option for the treatment of Stroke . Several pre clinical studies have shown that the treatment with mononuclear cell ( MNCs ) can reduce the infa rct size and improve the functional outcome . We evaluated the feasibility , safety and clinical outcome of administering bone marrow mononuclear cell ( MNCs ) intravenously to patients with subacute ischaemic stroke . Methods : In a non-r and omized phase-I clinical study , 11 consecutive , eligible and consenting patients , aged 30 - 70 yr with ischaemic stroke involving anterior circulation within 7 to 30 days of onset of stroke were included . Bone marrow was aspirated from iliac crest and the harvested mononuclear cells were infused into antecubital vein . Outcomes measured for safety included immediate reactions after cell infusion and evidence of tumour formation at one year in whole body PET scan . Patients were followed at week 1 , 4 - 6 , 24 and 52 to determine clinical progress using National Institute of Health Stroke Scale ( NIHSS ) , Barthel Index ( BI ) , modified Rankin Scale ( mRS ) , MRI , EEG and PET . Feasibility outcomes included target-dose feasibility . Favourable clinical outcome was defined as mRS score of 2 or less or BI score of 75 to 100 at six months after stem cell therapy . Results : Between September 2006 and April 2007 , 11 patients were infused with bone-marrow mononuclear cells ( mean 80 million with CD-34 + mean 0.92 million ) . Protocol was target-dose feasible in 9 patients ( 82 % ) . FDG-PET scan at 24 and 52 wk in nine patients did not reveal evidence of tumour formation . Seven patients had favourable clinical outcome . Interpretation & conclusions : Intravenous bone marrow mononuclear cell therapy appears feasible and safe in patients with subacute ischaemic stroke . Further , a r and omized controlled trial to examine its efficacy is being conducted Cell-based treatments have been considered a promising therapy for neurological diseases . However , currently there are no clinical ly available methods to monitor whether the transplanted cells reach and remain in the brain . In this study we investigated the feasibility of detecting the distribution and homing of autologous bone-marrow mononuclear cells ( BMMCs ) labeled with Technetium-99 m ( (99m)Tc ) in a cell-based therapy clinical study for chronic ischemic stroke . Six male patients ( ages 24 - 65 years ) with ischemic cerebral infa rcts within the middle cerebral artery ( MCA ) between 59 and 82 days were included . Cell dose ranged from 1.25x10(8 ) to 5x10(8 ) . Approximately 2x10(7 ) cells were labeled with (99m)Tc and intra-arterially delivered together with the unlabeled cells via a catheter navigated to the MCA . None of the patients showed any complications on the 120-day follow-up . Whole body scintigraphies indicated cell homing in the brain of all patients at 2 h , while the remaining uptake was mainly distributed to liver , lungs , spleen , kidneys and bladder . Moreover , quantification of uptake in Single-Photon Emission Computed Tomography ( SPECT ) at 2 h showed preferential accumulation of radioactivity in the hemisphere affected by the ischemic infa rct in all patients . However , at 24 h homing could only distinguished in the brains of 2 patients , while in all patients uptake was still seen in the other organs . Taken together , these results indicate that labeling of BMMCs with (99m)Tc is a safe and feasible technique that allows monitoring the migration and engraftment of intra-arterially transplanted cells for at least 24 BACKGROUND The alarming disability burden and a high prevalence rate of stroke in India has encouraged the research ers to develop regenerative therapies to reduce clinical deficits . This study evaluates safety , feasibility and efficacy of autologous mononuclear and mesenchymal cell transplantation in stroke patients evaluated on clinical scores and functional imaging ( fMRI and DTI ) . METHODS Forty ( n=40 ) stroke patients were recruited with the inclusion criteria as : 3 months to 2 years of index event , power of h and muscles of at least 2 ; Brunnstrom stage : 2 - 5 ; conscious and comprehendible . Fugl Meyer ( FM ) , modified Barthel Index ( mBI ) , Medical Research Council ( MRC ) grade for strength , Ashworth tone scale and functional imaging was used for assessment s at baseline , 8 weeks and 24 weeks . 50 - 60 million cells in 250 ml saline were infused intravenously over 2 - 3 h. RESULTS The safety test profile was normal with no mortality or cell related adverse reactions in stem cell patients . Among outcome parameters , only modified Barthel Index ( mBI ) showed statistical significant improvement ( p<0.05 ) in the stem cell group . An increased number of cluster activation in Brodmann areas BA 4 , BA 6 was observed post stem cell infusion indicating neural plasticity . CONCLUSION Autologous intravenous stem cell therapy is safe and feasible . Stem cells act as " scaffolds " for neural transplantation and may aid in repair mechanisms in stroke OBJECT No definitive treatment exists to restore lost brain function following a stroke . Transplantation of cultured neuronal cells has been shown to be safe and effective in animal models of stroke and safe in a Phase 1 human trial . In the present study the authors tested the usefulness of human neuron transplantation followed by participation in a 2-month stroke rehabilitation program compared with rehabilitation alone in patients with substantial fixed motor deficits associated with a basal ganglia stroke . METHODS Human neuronal cells ( LBS-Neurons ; Layton BioScience , Inc. ) were delivered frozen and then thawed and formulated on the morning of surgery . The entry criteria in this r and omized , observer-blinded trial of 18 patients included age between 18 and 75 years , completed stroke duration of 1 to 6 years , presence of a fixed motor deficit that was stable for at least 2 months , and no contraindications to stereotactic surgery . Patients were r and omized at two centers to receive either 5 or 10 million implanted cells in 25 sites ( seven patients per group ) followed by participation in a stroke rehabilitation program , or to serve as a nonsurgical control group ( rehabilitation only ; four patients ) . The surgical techniques used were the same at both centers . All patients underwent extensive pre- and postoperative motor testing and imaging . Patients received cyclosporine A for 1 week before and 6 months after surgery . The primary efficacy measure was a change in the European Stroke Scale ( ESS ) motor score at 6 months . Secondary outcomes included Fugl-Meyer , Action Research Arm Test , and Stroke Impact Scale scores , as well as the results of other motor tests . Nine strokes were ischemic in origin and nine were hemorrhagic . All 14 patients who underwent surgery ( ages 40 - 70 years ) underwent uncomplicated surgeries . Serial evaluations ( maximum duration 24 months ) demonstrated no cell-related adverse serological or imaging-defined effects . One patient suffered a single seizure , another had a syncopal event , and in another there was burr-hole drainage of an asymptomatic chronic subdural hematoma . Four of seven patients who received 5 million cells ( mean improvement 6.9 points ) and two of seven who received 10 million cells had improved ESS scores at 6 months ; however , there was no significant change in the ESS motor score in patients who received cell implants ( p = 0.756 ) compared with control or baseline values ( p = 0.06 ) . Compared with baseline , wrist movement and h and movement scores recorded on the Fugl-Meyer Stroke Assessment instrument were not improved ( p = 0.06 ) . The Action Research Arm Test gross h and -movement scores improved compared with control ( p = 0.017 ) and baseline ( p = 0.001 ) values . On the Stroke Impact Scale , the 6-month daily activities score changed compared with baseline ( p = 0.045 ) but not control ( p = 0.056 ) scores , and the Everyday Memory test score improved in comparison with baseline ( p = 0.004 ) values . CONCLUSIONS Human neuronal cells can be produced in culture and implanted stereotactically into the brains of patients with motor deficits due to stroke . Although a measurable improvement was noted in some patients and this translated into improved activities of daily living in some patients as well , this study did not find evidence of a significant benefit in motor function as determined by the primary outcome measure . This experimental trial indicates the safety and feasibility of neuron transplantation for patients with motor stroke Cell suspension consisting of cells from immature nervous and hemopoietic tissues was subarachnoidally transplanted to 10 patients with brain stroke consequences . Clinical effect of different degree was attained in all patients . Six months after cell therapy functional activity significantly increased in contrast to clinical ly comparable control group . No serious complications of cell therapy were observed . Presumably , cell therapy is a more or less safe method of treatment , which can be effectively used in the treatment of brain stroke consequences Background : Cell transplantation is safe in animal models and enhances recovery from stroke in rats . Methods : We studied the safety and feasibility of fetal porcine transplantation in 5 patients with basal ganglia infa rcts and stable neurological deficits . To prevent rejection , cells were pretreated with an anti-MHC1 antibody and no immunosuppressive drugs were given to the patients . Results : The first 3 patients had no adverse cell , procedure , or imaging-defined effects . The fourth patient had temporary worsening of motor deficits 3 weeks after transplantation , and the fifth patient developed seizures 1 week after transplantation . MRI in both patients demonstrated areas of enhancement remote from the transplant site , which resolved on subsequent imaging . Two patients showed improvement in speech , language , and /or motor impairments over several months and persisted at 4 years . The study was terminated by the FDA after the inclusion of 5 patients . Conclusion : This is the first report on the transplantation of nontumor cells in ischemic stroke patients In our previous study , intracerebral implantation of peripheral blood stem cells ( PBSCs ) improved functional outcome in rats with chronic cerebral infa rct ion . Based on this finding , a r and omized , single blind controlled study was conducted in 30 patients [ PBSC group ( n = 15 ) and control group ( n = 15 ) ] with middle cerebral artery infa rct ion confirmed on a T2-weighted MRI 6 months to 5 years after a stroke . Only subjects with neurological deficits of intermediate severity based on the National Institute of Health Stroke Scale ( NIHSS ; range : 9–20 ) that had been stable for at least 3 months were enrolled . Those in the PBSC group received subcutaneous G-CSF injections ( 15 μg/kg/day ) for 5 consecutive days , and then stereotaxic implantation of 3–8 × 106 CD34 + immunosorted PBSCs . All 30 patients completed the 12-month follow-up . No serious adverse events were noted during study period . Improvements in stroke scales ( NIHSS , ESS , and EMS ) and functional outcomes ( mRS ) from baseline to the end of the 12-month follow-up period were significantly greater in the PBSC than the control group . The fiber numbers asymmetry ( FNA ) scores based on diffusion tensor image ( DTI ) tractography were reduced in every PBSC-treated subject , but not in the control group . Reduction in the FNA scores correlated well with the improvement in NIHSS . Furthermore , a positive motor-evoked potential ( MEP ) response by transcranial magnetic stimulation ( TMS ) appeared in 9 of the 15 subjects in the PBSC group . This phase II study demonstrated that implantation of autologous CD34 + PBSC was safe , feasible , and effective in improving functional outcome We previously evaluated the short-term follow-up preliminary data of mesenchymal stem cells ( MSCs ) transplantation in patients with ischemic stroke . The present study was conducted to evaluate the long-term safety and efficacy of i.v . MSCs transplantation in a larger population . To accomplish this , we performed an open-label , observer-blinded clinical trial of 85 patients with severe middle cerebral artery territory infa rct . Patients were r and omly allocated to one of two groups , those who received i.v . autologous ex vivo cultured MSCs ( MSC group ) or those who did not ( control group ) , and followed for up to 5 years . Mortality of any cause , long-term side effects , and new-onset comorbidities were monitored . Of the 52 patients who were finally included in this study , 16 were the MSC group and 36 were the control group . Four ( 25 % ) patients in the MSC group and 21 ( 58.3 % ) in the control group died during the follow-up period , and the cumulative surviving portion at 260 weeks was 0.72 in the MSC group and 0.34 in the control group ( log-rank ; p = .058 ) . Significant side effects were not observed following MSC treatment . The occurrence of comorbidities including seizures and recurrent vascular episodes did not differ between groups . When compared with the control group , the follow-up modified Rankin Scale ( mRS ) score was decreased , whereas the number of patients with a mRS of 0 - 3 increased in the MSC group ( p = .046 ) . Clinical improvement in the MSC group was associated with serum levels of stromal cell-derived factor-1 and the degree of involvement of the subventricular region of the lateral ventricle . Intravenous autologous MSCs transplantation was safe for stroke patients during long-term follow-up . This therapy may improve recovery after stroke depending on the specific characteristics of the patients BACKGROUND CTX0E03 is an immortalised human neural stem-cell line from which a drug product ( CTX-DP ) was developed for allogeneic therapy . Dose-dependent improvement in sensorimotor function in rats implanted with CTX-DP 4 weeks after middle cerebral artery occlusion stroke prompted investigation of the safety and tolerability of this treatment in stroke patients . METHODS We did an open-label , single-site , dose-escalation study . Men aged 60 years or older with stable disability ( National Institutes of Health Stroke Scale [ NIHSS ] score ≥6 and modified Rankin Scale score 2 - 4 ) 6 - 60 months after ischaemic stroke were implanted with single doses of 2 million , 5 million , 10 million , or 20 million cells by stereotactic ipsilateral putamen injection . Clinical and brain imaging data were collected over 2 years . The primary endpoint was safety ( adverse events and neurological change ) . This trial is registered with Clinical Trials.gov , number NCT01151124 . FINDINGS 13 men were recruited between September , 2010 , and January , 2013 , of whom 11 ( mean age 69 years , range 60 - 82 ) received CTX-DP . Median NIHSS score before implantation was 7 ( IQR 6 - 8 ) and the mean time from stroke was 29 ( SD 14 ) months . Three men had subcortical infa rcts only and seven had right-hemisphere infa rcts . No immunological or cell-related adverse events were seen . Other adverse events were related to the procedure or comorbidities . Hyperintensity around the injection tracts on T2-weighted fluid-attenuation inversion recovery MRI was seen in five patients . At 2 years , improvement in NIHSS score ranged from 0 to 5 ( median 2 ) points . INTERPRETATION Single intracerebral doses of CTX-DP up to 20 million cells induced no adverse events and were associated with improved neurological function . Our observations support further investigation of CTX-DP in stroke patients . FUNDING ReNeuron Limited |
1,063 | 24,205,038 | 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 | BACKGROUND The U.S. Food and Drug Administration has the authority to regulate tobacco product constituents , including menthol , if the scientific evidence indicates harm .
Few studies , however , have evaluated the health effects of menthol cigarette use .
OBJECTIVE To investigate associations of cigarette smoking and menthol cigarette use with all-cause , cancer and cardiovascular risk in U.S. adults . | 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 , guidelines recommend that clinical laboratories compute and report estimated GFR by using estimating equations , such as equations derived from the Modification of Diet in Renal Disease ( MDRD ) Study ( 13 , 510 ) . The original MDRD Study equation was developed by using 1628 patients with predominantly nondiabetic kidney disease . It was based on 6 variables : age ; sex ; ethnicity ; and serum levels of creatinine , urea , and albumin ( 11 ) . Subsequently , a 4-variable equation consisting of age , sex , ethnicity , and serum creatinine levels was proposed to simplify clinical use ( 3 , 12 ) . This equation is now widely accepted , and many clinical laboratories are using it to report GFR estimates . Extensive evaluation of the MDRD Study equation shows good performance in population s with lower levels of GFR but variable performance in those with higher levels ( 1332 ) . Variability among clinical laboratories in calibration of serum creatinine assays ( 33 , 34 ) introduces error in GFR estimates , especially at high levels of GFR ( 35 ) , and may account in part for the poorer performance in this range ( 13 , 14 , 16 , 1821 , 27 , 30 ) . The National Kidney Disease Education Program ( NKDEP ) has initiated a creatinine st and ardization program to improve and normalize serum creatinine results used in estimating equations ( 36 ) . The MDRD Study equation has now been reexpressed for use with a st and ardized serum creatinine assay ( 37 ) , allowing GFR estimates to be reported in clinical practice by using st and ardized serum creatinine and overcoming this limitation to the current use of GFR estimating equations . The purpose of this report is to describe the performance of the reexpressed 4-variable MDRD Study equation and compare it with the performance of the reexpressed 6-variable MDRD equation and the CockcroftGault equation ( 38 ) , with particular attention to the level of GFR . This information should facilitate implementation of reporting and interpreting estimated GFR in clinical practice . Methods Laboratory Methods Urinary clearances of 125I-iothalamate after subcutaneous infusion were determined at clinical centers participating in the MDRD Study . Serum and urine 125I-iothalamate were assayed in a central laboratory . All serum creatinine values reported in this study are traceable to primary reference material at the National Institute of St and ards and Technology ( NIST ) , with assigned values based on isotope-dilution mass spectrometry . The serum creatinine sample s from the MDRD Study were originally assayed from 1988 to 1994 in a central laboratory with the Beckman Synchron CX3 ( Global Medical Instrumentation , Inc. , Ramsey , Minnesota ) by using a kinetic alkaline picrate method . Sample s were reassayed in 2004 with the same instrument . The Beckman assay was calibrated to the Roche/Hitachi P module Creatinase Plus enzymatic assay ( Roche Diagnostics , Basel , Switzerl and ) , traceable to an isotope-dilution mass spectrometry assay at NIST ( 37 , 39 ) . On the basis of these results , the 4-variable and 6-variable MDRD Study equations were reexpressed for use with st and ardized serum creatinine assay . The CockcroftGault equation was not reexpressed because the original serum creatinine sample s were not available for calibration to st and ardized serum creatinine assay . Derivation and Validation of the MDRD Study Equation The MDRD Study was a multicenter , r and omized clinical trial of the effects of reduced dietary protein intake and strict blood pressure control on the progression of chronic kidney disease ( 40 ) . The derivation of the MDRD Study equation has been described previously ( 11 ) . Briefly , the equation was developed from data from 1628 patients enrolled during the baseline period . The GFR was computed as urinary clearance of 125I-iothalamate . Creatinine clearance was computed from creatinine excretion in a 24-hour urine collection and a single measurement of serum creatinine . Glomerular filtration rate and creatinine clearance were expressed per 1.73 m2 of body surface area . Ethnicity was assigned by study personnel , without explicit criteria , probably by examination of skin color . The MDRD Study equation was developed by using multiple linear regression to determine a set of variables that jointly estimated GFR in a r and om sample of 1070 patients ( development data set ) . The regressions were performed on log-transformed data to reduce variability in differences between estimated and measured GFR at higher levels . Several equations were developed , and the performance of these equations was compared in the remaining sample of 558 patients ( validation data set ) . To improve the accuracy of the final equations , the regression coefficients derived from the development data set were up date d on the basis of data from all 1628 patients ( 11 ) . Estimation of GFR Glomerular filtration rate was estimated by using the following 4 equations : the reexpressed 4-variable MDRD Study equation ( GFR= 175st and ardized Scr 1.154age0.2031.212 [ if black]0.742 [ if female ] ) , the reexpressed 6-variable MDRD Study equation ( GFR= 161.5st and ardized Scr 0.999age0.176SUN0.17albumin0.3181.18 [ if black]0.762 [ if female ] ) , the CockcroftGault equation adjusted for body surface area ( Ccr= [140age]weight0.85 [ if female]1.73/72 st and ardized ScrBSA ) , and the CockcroftGault equation adjusted for body surface area and corrected for the bias in the MDRD Study sample ( Ccr= 0.8[140age]weight0.85 [ if female]1.73/72 st and ardized ScrBSA ) . In these equations , GFR and creatinine clearance ( Ccr ) are expressed as mL/min per 1.73 m2 , serum creatinine and urea nitrogen ( SUN ) are expressed as mg/dL , albumin is expressed as g/dL , weight is expressed as kg , age is expressed as years , and body surface area ( BSA ) is expressed as m2 . Correction for bias improves performance of the CockcroftGault equation because it adjusts for systematic differences between studies , such as differences in the measures of kidney function ( GFR in the MDRD Study and creatinine clearance in the study by Cockcroft and Gault ) , the serum creatinine assays , and the study sample s. Hence , the bias correction for the CockcroftGault equation provided here reexpresses that equation for the estimation of GFR for use with st and ardized creatinine in study sample s similar to that in the MDRD Study . Measures of Performance Measures of performance include bias ( median difference of measured minus estimated GFR and measured GFR ) and percentage bias ( percentage of bias divided by measured GFR ) , precision ( interquartile range of the difference between estimated and measured GFR , and percentage of variance in log-measured GFR explained by the regression model [ R2 values ] ) , and accuracy ( percentage of estimates within 30 % of the measured values ) . In the overall data set , bias is expected to be close to 0 for equations derived in the MDRD Study data base , including the 4-variable and 6-variable equations and the CockcroftGault equation adjusted for bias . The bootstrap method ( based on percentiles , with 2000 bootstrap sample s ) was used to estimate 95 % CIs for interquartile ranges and R2 values . Confidence intervals for the percentage of estimates within 30 % of measured values were computed by using the normal approximation to the binomial or exact binomial probabilities , as appropriate . We also computed sensitivity , specificity , positive and negative predictive value of estimated GFR less than 60 mL/min per 1.73 m2 , and receiver-operating characteristic ( ROC ) curves by using measured GFR less than 60 mL/min per 1.73 m2 as the criterion st and ard . Areas under the ROC curves were compared by using the method of DeLong and colleagues ( 41 ) . R , version 2 ( Free Software Foundation , Inc. , Boston , Massachusetts ) , and SAS , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) , were used for statistical analysis . We used the lowess function in R to plot smoothed functions in the figures . Role of the Funding Source The study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) as part of a cooperative agreement that gives the NIDDK substantial involvement in the design of the study and in the collection , analysis , and interpretation of the data . The NIDDK was not required to approve publication of the finished manuscript . The institutional review boards of all participating institutions approved the study . Results Clinical characteristics |
1,064 | 26,758,211 | Conclusions Although there is some evidence for an effect of acustimulation on nausea and vomiting or hyperemesis in pregnancy , results are not conclusive . | Background Nausea and vomiting in pregnancy ( NVP ) and hyperemesis gravidarum ( HG ) have a significant impact on quality of life .
Medication to relieve symptoms of NVP and HG are available but pregnant women and their caregivers have been concerned about the teratogenic effect , side effects and poor efficacy .
The aim of this review was to investigate if there is any clinical evidence for the efficacy of acustimulation in the treatment of NVP or HG . | 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 nausea , vomiting , or both before their prenatal clinic/office visit where they were recruited . After being accepted for the study , the women were r and omly assigned to treatment or placebo groups . INTERVENTION Treatment group 1 applied SeaB and s with acupressure buttons to both wrists for 4 days and removed the Sea-B and s for 3 subsequent days . Placebo group 2 applied the Sea-B and s without acupressure buttons to both wrists on the same time schedule as group 1 . MAIN OUTCOME MEASURE Self-report daily diaries of the number of times per day that participants experienced nausea , the severity of nausea , the number of vomiting episodes per day , and the severity of vomiting . RESULTS Mann-Whitney U procedures revealed that the treatment group had significantly less frequency and severity of nausea and vomiting of pregnancy while wearing the Sea-B and s than did the placebo group . The treatment group also had significantly less frequency and severity of nausea and vomiting of pregnancy while wearing the SeaB and s than when not wearing the Sea-B and s. CONCLUSIONS Sea-B and s with acupressure buttons are a noninvasive , inexpensive , safe , and effective treatment for the nausea and vomiting of pregnancy BACKGROUND A problem acupuncture research has to face is the concept of a control group . If , in control groups , non-acupoint needling is done , physiological acupuncture effects are implied . Therefore the effects shown in this group are often close to those shown in the acupuncture group . In other trials , control groups have received obviously different treatments , such as transcutaneous electrical nervous stimulation or TENS-laser treatment ; it is not clear if the effects of acupuncture are due only to the psychological effects of the treatment . METHODS We developed a placebo acupuncture needle , with which it should be possible to simulate an acupuncture procedure without penetrating the skin . In a cross-over experiment with 60 volunteers we tested whether needling with the placebo needle feels any different from real acupuncture . FINDINGS Of 60 volunteers , 54 felt a penetration with acupuncture ( mean visual analogue scale [ VAS ] 13.4 ; SD 10.58 ) and 47 felt it with placebo ( VAS 8.86 ; SD 10.55 ) , 34 felt a dull pain sensation ( DEQI ) with acupuncture and 13 with placebo . None of the volunteers suspected that the needle may not have penetrated the skin . INTERPRETATION The placebo needle is sufficiently credible to be used in investigations of the effects of acupuncture OBJECTIVE To explore a more effective therapy for treatment of hyperemesis gravidarum . METHODS Ninety cases were r and omly divided into an acupuncture group , a western medicine group and a Chinese medicine group , 30 cases in each group . They were treated with same supplement of water and electrolyte , with acupuncture at Dazhu ( BL 11 ) , Shangjuxu ( ST 37 ) , Neiguan ( PC 6 ) , Gongsun ( SP 4 ) , etc . added in the acupuncture group , with oral administration of Luminal 30 mg thrice each day added in the western medicine group and with oral administration of Chinese herbal decoction according to syndrome differentiation of TCM added in the Chinese medicine group . The therapeutic effect , ketone bodies , carbon dioxide combining power ( CO2-CP ) and electrolyte imbalance situation in all the groups were observed . RESULTS After treatment for 7 days , the total effective rate of 96.7 % in the acupuncture group was better than 46.7 % in the western medicine group and 60.0 % in the Chinese medicine group ( both P < 0.01 ) . There were significant improvements in ketone bodies in the acupuncture group compared with those before treatment and those in the western medicine group ( both P < 0.05 ) , and improvements in CO2-CP and electrolyte imbalance in all the groups were following the recovery of disease . CONCLUSION Acupuncture has rapid and obvious therapeutic effect on hyperemesis gravidarum without adverse reactions AIM This paper is a report of a study to examine the effect of Nei-Guan point acupressure on nausea , vomiting and ketonuria levels in women diagnosed with hyperemesis gravidarum . BACKGROUND Previous studies have shown that acupressure application on the Nei-Guan point is effective in relieving nausea and vomiting associated with pregnancy and surgery . However , no findings have been supported by physiological data . METHOD A r and omized control group pretest-post-test design was implemented from 1 April 2003 to 30 April 2004 using three groups : a Nei-Guan point acupressure group , a placebo group and a control group which received only conventional intravenous treatment . The participants were 66 women admitted to two general hospitals in Korea with hyperemesis gravidarum . RESULTS The degree of nausea and vomiting was statistically significantly lower in the Nei-Guan point acupressure group in comparison with the placebo and control groups . Ketonuria levels were reduced over time and , on days three and four of hospitalization , levels in the treatment group were statistically significantly lower than in the placebo or control groups ( P < 0.05 ) . CONCLUSION Nei-Guan point acupressure is a useful treatment for relieving symptoms experienced by women with hyperemesis gravidarum OBJECTIVES The sham control is widely used in acupuncture research , and its adequacy may be assessed by exploring the ' credibility ' of the intervention . We aim ed to examine the credibility of the study intervention , to quantify the size of the placebo response and effect of time in reducing nausea in early pregnancy . DESIGN Five hundred and ninety-three women with nausea or vomiting in early pregnancy volunteered to participate in a r and omised controlled trial , conducted at the Women 's and Children 's Hospital , South Australia . OUTCOME MEASURES Women completed the Rhodes Index of Nausea and Vomiting and the Credibility Rating Scale . RESULTS The credibility of the acupuncture and sham acupuncture interventions were not different . The relative change in nausea at the end of the first week of the study was estimated to be 28 % attributed to a time effect and 7 % to the placebo response . At the end of the third week , there was a further small increase in time effect ( 32 % ) and the placebo response ( 17 % ) . CONCLUSION Sham acupuncture is a credible control and allows assessment of the size of the placebo response AIM Several reports have suggested the use of acupuncture as a useful treatment for hyperemesis gravidarum ( HG ) , in particular the effects on nausea intensity was underlined . The aim of this study was to compare the efficacy of acupuncture sessions plus acupressure with a metoclopramide/vitamin B12 treatment . METHODS In this study we r and omized 88 pregnant patients suffering from HG to receive either acupuncture sessions plus acupressure ( acupuncture group ) or metoclopramide infusion ( metoclopramide group ) supplemented by vitamin B12 complex . Somatic symptoms and the ability to achieve the daily routine activity ( functioning ) were evaluated . Acupuncture sessions were performed at the hospital twice a week for 2 weeks according to the traditional Chinese medicine criteria . Acupression was applied for 6 - 8 h/day . In the metoclopramide group , patients received at hospital metoclopramide infusion ( 20 mg/500 mL saline for 60 min ) twice a week for 2 weeks . An oral supplementation with vitamin B12 complex ( 30 mg/day ) was also prescribed . RESULTS Both treatments reduced vomiting episodes and then nausea intensity with a consequent improvement in the rate of food intake . The effect of acupuncture seems to be progressive , increasing at the end of treatment whereas pharmacological approach has a prompt effect in responders remaining stable thereafter . Moreover , acupuncture was significantly more effective than drugs in improving functioning . CONCLUSIONS In our study for the first time acupuncture , applied accordingly to Chinese formula , was compared to drugs demonstrating the same effect of both treatments on HG symptoms . Interestingly , functioning was significantly improved just by acupuncture . Even if the effect of acupuncture on HG discomfort remains to be confirmed , the reports on the effect of acupuncture on psychosocial variables could represent a further advantage of acupuncture application and provide an incentive to widen the base of the research A prospect i ve study was design ed to test the efficacy of pressure at the P6 ( Neiguan ) acupuncture point , in preventing morning sickness . Three groups of patients in early pregnancy recorded the severity and frequency of sickness over a period of 4 consecutive days following daily pressure at P6 point , pressure at a point near the right elbow and with no treatment . Troublesome sickness was significantly less in both the genuine ( 23/119 ) and dummy ( 41/112 ) pressure groups as compared with the control series ( 67/119 ) . When the data are adversely ‘ weighted ’ to compensate for the lower incidence of fully completed returns in the active treatment groups , only the P6 group show a significant reduction in sickness . No side effects occurred in either group and while anticipation of benefit may offer a partial explanation for the findings , pressure at the Neiguan point appears to have a specific therapeutic effect |
1,065 | 27,286,988 | 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 | Background Exercise training ( ExT ) prompts multiple beneficial adaptations associated with vascular health , such as increases in skeletal muscle capillarization and vascular dilator function and decreases in arterial stiffness .
However , whether ExT performed in hypoxic conditions induces enhanced effects is unclear . | 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 17–25 years , body mass index > 27.5 kg/m2 ) were recruited for a 4-week residential camp of weight loss with low caloric intake , and trained at 60–70 % maximal heart rate of aerobics and 40–50 % of maximal strength of training . They were r and omly assigned to either a normobaric hypoxia ( HT , FiO2 = 16.4–14.5 % ) or normoxia training group ( NT , FiO2 = 21 % ) , and subjects in HT and NT groups experienced weekly 16-h normoxia and 6-h hypoxia or 22-h normoxia training , respectively . Body composition , resting blood pressure ( BP ) and brachial-ankle pulse wave velocity ( baPWV ) were determined before and after the intervention . Results Weight loss was found in HT ( −6.9 kg or −7.0 % , p < 0.01 ) and NT groups ( −4.3 kg or −4.2 % , p < 0.01 ) significantly , and the former lost more weight than the latter ( p < 0.01 ) . Hypoxia training improved systolic BP ( −7.6 % ) and mean BP ( −7.1 % ) significantly ( p < 0.05 ) despite having no effect on baPWV . Conclusion Four weeks of normobaric hypoxia residential training with low caloric diet has an additive improvement on weight loss . It seems that normobaric hypoxia training might be a promising method to treat obesity Abstract This r and omized trial evaluated the impact of different exercise training modalities on the function and size of conduit arteries in healthy volunteers . Young ( 27 ± 5 years ) healthy male subjects were r and omized to undertake 6 months of either endurance training ( ET ; n = 10 ) or resistance training ( RT ; n = 13 ) . High-resolution ultrasound was used to determine brachial , femoral and carotid artery diameter and wall thickness ( IMT ) and femoral and brachial flow-mediated dilatation ( FMD ) and glyceryl trinitrate (GTN)-mediated dilatation . Improvements in peak oxygen uptake occurred with ET ( from 3.6 ± 0.7 to 3.8 ± 0.6 l min(-1 ) , P = 0.024 ) but not RT . Upper body muscular strength increased following RT ( from 57.8 ± 17.7 to 69.0 ± 19.5 kg , P < 0.001 ) , but not ET . Both groups exhibited increases in lean body mass ( ET , 1.4 ± 1.8 kg and RT , 2.3 ± 1.3 kg , P < 0.05 ) . Resistance training increased brachial artery resting diameter ( from 3.8 ± 0.5 to 4.1 ± 0.4 mm , P < 0.05 ) , peak FMD diameter ( + 0.2 ± 0.2 mm , P < 0.05 ) and GTN-mediated diameter ( + 0.3 ± 0.3 mm , P < 0.01 ) , as well as brachial FMD ( from 5.1 ± 2.2 to 7.0 ± 3.9 % , P < 0.05 ) . No improvements in any brachial parameters were observed following ET . Conversely , ET increased femoral artery resting diameter ( from 6.2 ± 0.7 to 6.4 ± 0.6 mm , P < 0.05 ) , peak FMD diameter ( + 0.4 ± 0.4 mm , P < 0.05 ) and GTN-induced diameter ( + 0.3 ± 0.3 mm , P < 0.05 ) , as well as femoral FMD-to-GTN ratio ( from 0.6 ± 0.3 to 1.1 ± 0.8 , P < 0.05 ) . Resistance training did not induce changes in femoral artery parameters . Carotid artery IMT decreased in response to both forms of training . These findings indicate that 6 months of supervised exercise training induced changes in brachial and femoral artery size and function and decreased carotid artery IMT . These impacts of both RT and ET would be expected to translate to decreased cardiovascular risk AIM Our aim was to investigate the acute and 24-hour ( h ) effects of high-intensity interval training ( HIIT ) and moderate continuous training ( MCT ) on arterial pulse wave reflection , an established marker of arterial stiffness and cardiovascular risk . METHODS In a r and omized cross-over design , 21 young healthy male participants performed a HIIT or a MCT on separate visits . Before and 5 ( t5 ) , 20 ( t20 ) , 35 ( t35 ) , and 50 ( t50 ) minutes after the acute exercise bouts , the crude augmentation index ( AIx ) and the AIx at a set heart rate ( AIx@75 ) were analysed by applanation tonometry . Starting 1 h post-exercise , both indices were captured over 24-h with an oscillometric monitoring device . RESULTS AIx did not change significantly after MCT but declined progressively after HIIT , reaching significantly lower values compared to MCT at t35 ( P = 0.045 ) and t50 ( P = 0.008 ) . AIx@75 increased after both acute exercise types but was higher after HIIT at t5 ( P < 0.001 ) , t20 ( P < 0.001 ) and t35 ( P = 0.009 ) compared to MCT . The 24-h follow-up revealed a significant decline in AIx@75 after HIIT ( P = 0.007 ) but not after MCT ( P = 0.813 ) . CONCLUSIONS Exercise intensity affects pulse wave reflection , with different time courses for AIx and AIx@75 post-exercise . Although initially higher after HIIT , AIx@75 declines in the 24-h recovery period indicating more favourable effects on pulse wave reflection compared to MCT . This may result in substantial positive chronic training effects on arterial stiffness in health and cardiovascular disease 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 . Hypoxic preconditioning prevents cerebrovascular/cardiovascular disorders by increasing resistance to acute ischemic stress , but severe hypoxic exposure disturbs vascular hemodynamics . This study compared how various exercise regimens with/without hypoxia affect hemodynamics and oxygenation in cardiac , muscle , and cerebral tissues during severe hypoxic exposure . Sixty sedentary males were r and omly divided into five groups . Each group ( n = 12 ) received one of five interventions : 1 ) normoxic ( 21 % O(2 ) ) resting control , 2 ) hypoxic ( 15 % O(2 ) ) resting control , 3 ) normoxic exercise ( 50 % maximum work rate under 21 % O(2 ) ; N-E group ) , 4 ) hypoxic-relative exercise ( 50 % maximal heart rate reserve under 15 % O(2 ) ; H-RE group ) , or 5 ) hypoxic-absolute exercise ( 50 % maximum work rate under 15 % O(2 ) ; H-AE group ) for 30 min/day , 5 days/wk , for 4 wk . A recently developed noninvasive bioreactance device was used to measure cardiac hemodynamics , and near-infrared spectroscopy was used to assess perfusion and oxygenation in the vastus lateralis (VL)/gastrocnemius ( GN ) muscles and frontal cerebral lobe ( FC ) . Our results demonstrated that the H-AE group had a larger improvement in aerobic capacity compared with the N-E group . Both H-RE and H-AE ameliorated the suppression of cardiac stroke volume and the GN hyperemic response ( Delta total Hb/min ) and reoxygenation rate by acute 12 % O(2 ) exposure . Simultaneously , the two hypoxic interventions enhanced perfusion ( Delta total Hb ) and O(2 ) extraction [ Delta deoxyHb ] of the VL muscle during the 12 % O(2 ) exercise . Although acute 12 % O(2 ) exercise decreased oxygenation ( Delta O(2)Hb ) of the FC , none of the 4-wk interventions influenced the cerebral perfusion and oxygenation during normoxic/hypoxic exercise tests . Therefore , we conclude that moderate hypoxic exercise training improves cardiopulmonary fitness and increases resistance to disturbance of cardiac hemodynamics by severe hypoxia , concurrence with enhancing O(2 ) delivery/utilization in skeletal muscles but not cerebral tissues Blood flow to dynamically contracting myocytes is regulated to match O(2 ) delivery to metabolic dem and . The red blood cell ( RBC ) itself functions as an O(2 ) sensor , contributing to the control of O(2 ) delivery by releasing the vasodilators ATP and S-nitrosohaemoglobin with the offloading of O(2 ) from the haemoglobin molecule . Whether RBC number is sensed remains unknown . To investigate the role of RBC number , in isolation and in combination with alterations in blood oxygenation , on muscle and systemic perfusion , we measured local and central haemodynamics during one-legged knee-extensor exercise ( approximately 50 % peak power ) in 10 healthy males under conditions of normocythaemia ( control ) , anaemia , anaemia + plasma volume expansion ( PVX ) , anaemia + PVX + hypoxia , polycythaemia , polycythaemia + hyperoxia and polycythaemia + hypoxia , which changed either RBC count alone or both RBC count and oxyhaemoglobin . Leg blood flow ( LBF ) , cardiac output ( Q ) and vascular conductance did not change with either anaemia or polycythaemia alone . However , LBF increased with anaemia + PVX ( 28 + /- 4 % ) and anaemia + PVX + hypoxia ( 46 + /- 6 % ) and decreased with polycythaemia + hyperoxia ( 18 + /- 5 % ) . LBF and Q with anaemia + PVX + hypoxia ( 8.0 + /- 0.5 and 15.8 + /- 0.7 l min(-1 ) , respectively ) equalled those during maximal knee-extensor exercise . Collectively , LBF and vascular conductance were intimately related to leg arterial-venous ( a-v ) O(2 ) difference ( r(2)= 0.89 - 0.93 ; P < 0.001 ) , suggesting a pivotal role of blood O(2 ) gradients in muscle microcirculatory control . The systemic circulation accommo date d to the changes in muscle perfusion . Our results indicate that , when coping with severe haematological challenges , local regulation of skeletal muscle blood flow and O(2 ) delivery primarily senses alterations in the oxygenation state of haemoglobin and , to a lesser extent , alterations in the number of RBCs and haemoglobin molecules This study was undertaken to test the hypothesis that endurance training in hypoxia is superior to training of the same intensity in normoxia . To avoid adaptation to hypoxia , the subjects lived under normoxic conditions when not training . A secondary objective of this study was to compare the effect of high- vs. moderate-intensity training on aerobic performance variables . Thirty-three men without prior endurance training underwent a cycle ergometer training of 6 weeks , 5 d/week , 30 minutes/d . The subjects were assigned to 4 groups , N-high , N-low , H-high and H-low based on the training criteria normoxia ( N ; corresponding to a training altitude of 600 m ) , vs. hypoxia ( H ; training altitude 3850 m ) and intensity ( high ; corresponding to 80 % and low : corresponding to 67 % of VO2max ) . VO2max measured in normoxia increased between 8.5 to 11.1 % , independent of training altitude or intensity . VO2max measured in hypoxia increased between 2.9 and 7.2 % . Hypoxia training result ed in significantly larger increases than normoxia training . Maximal power that subjects could maintain over a thirty-minute period ( measured in normoxia or hypoxia ) increased from 12.3 - 26.8 % independent of training altitude . However , subjects training at high intensity increased performance more than subjects training at a low intensity . Muscle volume of the knee-extensors as measured by magnetic resonance imaging increased significantly in the H-high group only ( + 5.0 % ) . Mitochondrial volume density measured by EM-morphometry in biopsy sample s of m. vastus lat . increased significantly in all groups with the highest increase seen in the H-high group ( + 59 % ) . Capillary length density increased significantly in the H-high group only ( + 17.2 % ) . The main finding of this study is that in previously untrained people , training in hypoxia while living at low altitude increases performance in normoxia to the same extent as training in normoxia , but leads to larger increases of aerobic performance variables when measured under hypoxic conditions . Training intensity had no effect on the gain of VO2max . On the level of skeletal muscle tissue , the combination of hypoxia with high training intensity constitutes the most effective stimulus for increasing muscle oxidative capacity Six healthy subjects performed endurance training of the same duration with legs and arms consecutively . Performance and muscle structure were measured before and after training in lower and upper limbs . Training induced similar increases in maximal oxygen consumption ( 6 + /- 1 vs. 7 + /- 2 mL min-1 kg-1 : legs vs. arms , P > 0.05 ) and mitochondrial volume in leg and arm muscles ( 42 + /- 12 vs. 31 + /- 11 % : legs vs. arms , P > 0.05 ) . The gain in mitochondrial volume after training was achieved solely by increasing the fraction of mitochondria ( + 40 + /- 11 % , P < 0.05 ) in the same muscle volume ( + 2 + /- 2 % , P > 0.05 ) in the legs . In contrast , increased muscle volume ( + 14 + /- 3 % , P < 0.05 ) , in addition to a tendency for an increase in mitochondrial fraction ( + 16 + /- 11 % , P > 0.05 ) , occurred in the arms after training . Thus , similar improvements in muscle oxidative capacity in upper and lower limbs were brought about by different mechanisms . It is suggested that due to infrequent use and a lack of load-bearing function , arm muscle volume is underdeveloped in untrained , sedentary or detrained/injured subjects and that the mode of endurance training used in this study is sufficient to enlarge arm muscle volume as well as aerobic capacity |
1,066 | 23,846,738 | 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 . | BACKGROUND The rate of operative deliveries ( both caesarean sections , vacuum extraction s and forceps ) , continues to rise throughout the world .
These are associated with significant maternal and neonatal morbidity .
The most common reasons for operative births in nulliparous women are labour dystocia ( failure to progress ) , and non-reassuring fetal status .
Epidural analgesia has been shown to slow the progress of labour , as well as increase the rate of instrumental deliveries .
However , it is unclear whether the use of oxytocin in women with epidural analgesia results in a reduction in operative deliveries , and thereby reduces both maternal and fetal morbidity .
OBJECTIVES To determine whether augmentation of women using epidural analgesia with oxytocin will decrease the incidence of operative deliveries and thereby reduce fetal and maternal morbidity . | 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 ) . Patients who were undergoing active management of labor were diagnosed as being in labor on the basis of having painful palpable contractions accompanied by 80 % cervical effacement , underwent early amniotomy , and were treated with high-dose oxytocin for failure to progress adequately in labor . RESULTS The cesarean section rate in the active management of labor group was lower than that of controls but not significantly so ( active management , 7.5 % ; controls , 11.7 % ; p = 0.36 ) . The length of labor in the active management group was shortened by 1.7 hours ( from 11.4 to 9.7 hours , p = 0.001 ) . Fifty-five percent of patients received epidural analgesics ; a reduction in length of labor persisted despite the use of epidural analgesics ( active management 11.2 hours vs control 13.3 hours , p = 0.001 ) . A significantly greater proportion of active management patients were delivered by 12 hours compared with controls ( 75 % vs 58 % , p = 0.01 ) ; this difference also persisted despite the use of epidural analgesics ( 66 % vs 51 % , p = 0.03 ) . CONCLUSIONS Patients undergoing active management had shortened labors and were more likely to be delivered within 12 hours , differences that persisted despite the use of epidural analgesics . There was a trend toward a reduced rate of cesarean section Uterine activity was measured in 60 women whose first labour was progressing slowly in the active phase . The mean level of active contraction area ( uterine activity integral , UAI ) before oxytocin augmentation was 898 ( SD 458 ) kPas/15 min . UAI increased significantly with time , even in women not given oxytocin . UAI increased logarithmically with increasing oxytocin infusion rate . Levels of uterine activity before and after oxytocin infusion are correlated positively such that the higher the initial level of UAI the higher the UAI in response to oxytocin . However , the regression line approaches the line of identity such that even with high doses of oxytocin UAI would not be likely to exceed 2500 kPas/15 min . There is a positive correlation between uterine activity and cervical dilatation rate in unstimulated labour ; however , this is less evident following oxytocin infusion . Increases in uterine activity below 1200 kPas/15 min result from both higher frequency and active pressure , whereas above 1200 kPas/15 min any increase is due mainly to a rise in frequency The obstetric outcome following the elective use of oxytocin infusion was determined in a r and omised , double-blind placebo-controlled trial . 93 nulliparous women in a London hospital , who had requested epidural analgesia in labour ( < /= 6 cm . ) , were given an infusion of oxytocin ( n = 46 ) or placebo ( n = 47 ) . The initial epidural dose was 15 ml of 0.125 % bupivacaine , followed by an infusion at 10 ml per h , with 15 ml top-ups if required . When oxytocin was used electively there was a reduction in the length of the first stage of labour from 696 min to 578 min , ( P < 0.05 ) even though more than half of the control group ( 53 % ) required oxytocin augmentation . There was no significant difference between the number of operative deliveries ( 34 [ 74 % ] vs 35 [ 74 % ] ) . The rotational delivery rate was less in the study group ( 2 [ 4 % ] vs 5 [ 11 % ] ) , though this did not reach significance . There were no adverse effects on the fetus , as judged by cord pH measurement , Apgar score , admission to the special care baby unit and neonatal jaundice . The prophylactic use of oxytocin in nulliparous women with epidurals reduces the length of the first stage of labour and appears to be safe . It does not reduce the operative delivery rate |
1,067 | 25,980,984 | 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 . | BACKGROUND Self-management ( SM ) support for patients with chronic obstructive pulmonary disease ( COPD ) is variable in its coverage , content , method and timing of delivery .
There is insufficient evidence for which SM interventions are the most effective and cost-effective . | 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 carried out at study entry and after14 weeks : ( 1 ) pulmonary function studies ; ( 2 ) 6-minutes walking test 6MWT ; ( 3 ) quality of life ; and ( 4 ) BODE index . Results The following patients completed the study : 35 patients ( 87.5 % ) from the active group ( mean age , 63.7 ± 11.9 years ; mean forced expiratory volume in one second ( FEV1 ) , 41.9 ± 2.6 % of the predicted value ) ; and 36 patients ( 88 % ) from the control group ( mean age , 65.9 ± 10.3 years ; mean FEV1 , 43.33 ± 3.6 % of the predicted value ) . We found no changes in pulmonary function parameters in the active group and the control one at 14weeks . On the other h and , there were significant changes within the components of the SGRQ ( 12.3 for the score total ) for the patients of the active group but not for the patients of the control one ( only 1.5 for the score total ) , we observed also a significant increase in the distance of the 6-MWT in the patients of the active group but not for the patients of the control one , and finally a decrease of two points ( from 6 to 4 ) was noted in the score of the active group ’s BODE index without any change in the control group ’s one . Conclusion An outpatient-based of 14-week rehabilitation program significantly improved the quality of life and exercise tolerance without any change in the pulmonary function in patients with moderate COPD , and there was also a large decrease in the risk of death in rehabilitated patients as measured using the BODE index Background Chronic obstructive pulmonary disease ( COPD ) is a common cause of morbidity and mortality affecting a large number of individuals in both developed and developing countries and it represents a significant financial burden for patients , families and society . Pulmonary rehabilitation ( PR ) is a multidisciplinary program that integrates components of exercise training , education , nutritional support , psychological support and self-care , result ing in an improvement in dyspnea , fatigue and quality of life . Despite its proven effectiveness and the strong scientific recommendations for its routine use in the care of COPD , PR is generally underutilized and strategies for increasing access to PR are needed . Home-based self-monitored pulmonary rehabilitation is an alternative to outpatient rehabilitation . In the present study , patients with mild , moderate and severe COPD su bmi tted to either an outpatient or at-home PR program for 12 weeks were analyzed . Methods Patients who fulfilled the inclusion criteria were r and omized into three distinct groups : an outpatient group who performed all activities at the clinic , a home-based group who performed the activities at home and a control group . PR consisted of a combination of aerobic exercises and strengthening of upper and lower limbs 3 times a week for 12 weeks . Results There was a significant difference in the distance covered on the six-minute walk test ( p < 0.05 ) and BODE index ( p < 0.001 ) in the outpatient and at-home groups after participating in the rehabilitation program compared to baseline . Conclusion A home-based self-monitoring pulmonary rehabilitation program is as effective as outpatient pulmonary rehabilitation and is a valid alternative for the management of patients with COPD .RiassuntoRazionaleLa broncopneumopatia cronica ostruttiva ( BPCO ) è una causa frequente di morbilità e mortalità che colpisce un’ampia quota di popolazione sia nel mondo industrializzato che nei Paesi in via di sviluppo e rappresenta un peso economico di rilievo per pazienti , familiari e collettività . La riabilitazione respiratoria ( PR ) è un programma multidisciplinare che inegra componenti di riallenamento all’esercizio fisico , educazionale , supporto nutrizionale , supporto psicologico ed autoaiuto , che porta ad un miglioramento della dispnea , della affaticabilità e della qualità della vita . Nonostante la provata efficacia e le forti raccom and azioni delle società scientifiche al suo impiego routinario nel trattamento della BPCO , la PR è generalmente sottoutilizzata e si rendono perciò necessarie strategie per aumentarne l’utilizzo . La PR effettuata a domicilio ed auto-monitorata dal paziente stesso è un’alternativa alla classica riabilitazione ambulatoriale . In questo studio sono stati valuati pazienti con BPCO di grado lieve , moderato e grave sottoposti a un programma di PR ambulatoriale o domiciliare . MetodiI pazienti eligibili allo studio sono stati r and omizzati in tre gruppi : un gruppo ambulatoriale che effettuava tutte le attività in ospedale , un gruppo domiciliare che effettuava il programma a domicilio ed un gruppo di controllo . Il programma di PR consisteva in una combinazione di esercizi aerobici e di rafforzamento della muscolatura degli arti superiori e inferiori per 3 volte la settimana per 12 settimane . RisultatiSia nel gruppo che ha partecipato al PR ambulatoriale che in quello domiciliare si sono rilevate differenze significative rispetto alle misure di base nella distanza coperta con il test del cammino di 6 minuti ( p < 0.05 ) che nell’indice BODE ( p < 0.001 ) . Conclusion iUn programma di riabilitazione respiratoria automonitorato eseguito a domicilio ha efficacia sovrapponibile ad un programma ambulatoriale e può perciò essere considerato una valida alternativa nella gestione del paziente con BPCO BACKGROUND There has been limited study of yoga training as a complementary exercise strategy to manage the symptom of dyspnea in patients with chronic obstructive pulmonary disease ( COPD ) . PURPOSE The primary purpose of this pilot study was to evaluate a yoga program for its safety , feasibility , and efficacy for decreasing dyspnea intensity ( DI ) and dyspnea-related distress ( DD ) in older adults with COPD . METHODS Clinical ly stable patients with COPD ( n = 29 ; age 69.9 + /- 9.5 ; forced expiratory volume in 1 second ( FEV(1 ) ) 47.7 + /- 15.6 % predicted ; female = 21 ) were r and omized to a 12-week yoga program specifically design ed for people with COPD or usual-care control ( UC ) . The twice-weekly yoga program included asanas ( yoga postures ) and visama vritti pranayama ( timed breathing ) . Safety measure outcomes included heart rate , oxygen saturation , dyspnea , and pain . Feasibility was measured by patient-reported enjoyment , difficulty , and adherence to yoga sessions . At baseline and at 12 weeks , DI and DD were measured during incremental cycle ergometry and a 6-minute walk ( 6MW ) test . Secondary efficacy outcomes included physical performance , psychologic well-being , and health-related quality of life ( HRQoL ) . RESULTS Yoga training was safe and feasible for patients with COPD . While yoga training had only small effects on DI after the 6MW test ( effect size [ ES ] , 0.20 ; p = 0.60 ) , there were greater reductions in DD in the yoga group compared to UC ( ES , 0.67 ; p = 0.08 ) . Yoga training also improved 6MW distance ( + 71.7 + /- 21.8 feet versus -27.6 + /- 36.2 feet ; ES = 0.78 , p = 0.04 ) and self-reported functional performance ( ES = 0.79 , p = 0.04 ) compared to UC . There were small positive changes in muscle strength and HRQoL. CONCLUSIONS Elderly patients with COPD participated safely in a 12-week yoga program especially design ed for patients with this chronic illness . After the program , the subjects tolerated more activity with less DD and improved their functional performance . These findings need to be confirmed in a larger , more sufficiently powered efficacy study This study poses two questions : 1 ) is there an abnormality in isokinetic skeletal muscle strength and endurance in mild chronic obstructive pulmonary disease ( COPD ) ? and 2 ) what is the effect of a r and omized , controlled , 12 week hospital outpatient weight training programme in terms of skeletal muscle function and exercise tolerance ? Upper and lower limb isokinetic maximum and sustained muscle function were compared in 43 COPD patients ( age 49+/-11 yrs ) , mean forced expiratory volume in one second ( FEV1 ) 77+/-23 % pred and 52 healthy , sedentary subjects ( age 51 ( 10 ) yrs ) , mean FEV1 109+/-16 % pred . The 43 COPD patients were r and omly allocated into training ( n=26 ) and control ( n=17 ) groups . Isokinetic and isotonic muscle function , whole body endurance , maximal exercise capacity and lung function were measured . The COPD patients had reduced isokinetic muscle function ( with the exception of sustained upper limb strength ) as compared with healthy sedentary subjects . Muscle function improved after weight training in the COPD patients . Whole body endurance during treadmill walking also improved with no change in maximal oxygen consumption . A deficit in skeletal muscle function can be identified in patients with mild chronic obstructive pulmonary disease which can not be explained by factors such as hypoxaemia and malnutrition . Intervention with weight training is effective in countering this deficit which the authors conclude is probably due to muscle deconditioning Background Dyspnea ( SOB ) , dyspnea-related anxiety ( DA ) , and exercise performance have been shown to improve after exercise training in patients with Chronic Obstructive Pulmonary Disease ( COPD ) . However , there are no published descriptions of the changes in dyspnea intensity or dyspnea-related anxiety during or across the exercise training sessions . Objectives To describe and compare the differences in the patterns of change in SOB , DA , and exercise performance during 12 exercise training sessions with and without nurse coaching . Methods Forty-five dyspnea-limited patients with COPD were r and omly assigned to nurse-monitored ( ME ) or nurse-coached exercise ( CE ) . SOB and DA were rated on a 200 mm VAS every 2 minutes during each of 12 treadmill training sessions . Results Warm-up , peak , cool-down , mean SOB , and peak SOB/stage remained constant over the exercise sessions , with increasing exercise performance for both groups over the 12 sessions ( p < .001 ) . There was a significant difference in the pattern of mean SOB over time between the ME and CE group ( p < . 05 ) . Mean , peak DA , and peak DA/stage showed a rapid decrease within the first 4 sessions ( p < . 05 ) with no significant differences between the groups . Warm-up and cool-down DA remained constant . There were large intra- and inter-subject variations in the rating of dyspnea and dyspnea-related anxiety within and across sessions . Conclusions As theoretically proposed , both groups significantly decreased their DA over the training sessions . This decrease was early in the sessions and was not accompanied by a decrease in the SOB . In contrast , subjects maintained a nearly constant mean and peak SOB with increasing exercise performance , suggesting that people may have a dyspnea threshold above which they are unable to tolerate greater dyspnea . Description of the changes in dyspnea and the affective response during training need to be exp and ed , while study ing the type and timing of strategies to enhance the improvement in dyspnea and dyspnea-related anxiety Background : Chronic obstructive pulmonary disease ( COPD ) is characterised by both an accelerated decline in lung function and periods of acute deterioration in symptoms termed exacerbations . The aim of this study was to investigate whether these are related . Methods : Over 4 years , peak expiratory flow ( PEF ) and symptoms were measured at home daily by 109 patients with COPD ( 81 men ; median ( IQR ) age 68.1 ( 63–74 ) years ; arterial oxygen tension ( Pao2 ) 9.00 ( 8.3–9.5 ) kPa , forced expiratory volume in 1 second ( FEV1 ) 1.00 ( 0.7–1.3 ) l , forced vital capacity ( FVC ) 2.51 ( 1.9–3.0 ) l ) ; of these , 32 ( 29 men ) recorded daily FEV1 . Exacerbations were identified from symptoms and the effect of frequent or infrequent exacerbations ( > or < 2.92 per year ) on lung function decline was examined using cross sectional , r and om effects models . Results : The 109 patients experienced 757 exacerbations . Patients with frequent exacerbations had a significantly faster decline in FEV1 and peak expiratory flow ( PEF ) of –40.1 ml/year ( n=16 ) and –2.9 l/min/year ( n=46 ) than infrequent exacerbators in whom FEV1 changed by –32.1 ml/year ( n=16 ) and PEF by –0.7 l/min/year ( n=63 ) . Frequent exacerbators also had a greater decline in FEV1 if allowance was made for smoking status . Patients with frequent exacerbations were more often admitted to hospital with longer length of stay . Frequent exacerbations were a consistent feature within a patient , with their number positively correlated ( between years 1 and 2 , 2 and 3 , 3 and 4 ) . Conclusions : These results suggest that the frequency of exacerbations contributes to long term decline in lung function of patients with moderate to severe COPD Most pulmonary rehabilitation ( PR ) programs do not currently incorporate IMT in their PR programs for COPD patients . The aim of the present study was to assess the influence of adding IMT to the patients already involved in a rehabilitation program . Thirty-four patients with significant COPD were recruited for the study . All patients participated in a general exercise reconditioning ( GER ) program for 12 weeks . The patients were then r and omized to receive IMT or sham IMT , in addition to GER for the next 6 months . Following three months of GER training there was a significant increase in the 6-min walk test ( 6MWT ) ( from mean+/-SEM 254+/-38 to 322+/-42 m , p<0.01 ) , and small but non-significant decreases in the perception of dyspnea ( POD ) , and in the St. George Respiratory Question naire score ( SGRQ ) . Following the addition of IMT to the GER program there was a significant increase in the PI(max ) in the GER+IMT group ( from 66+/-4.7 to 78+/-4.5 cm H(2)O , p<0.01 ) . This was accompanied by a significant improvement in the POD and a further significant improvement in the SGRQ score . IMT provides additional benefits to patients undergoing PR program and is worthwhile even in patients who have already undergone a GER program PURPOSE The primary goal of pulmonary rehabilitation ( PR ) is for patients to achieve and maintain their maximum level of independence and functioning in the community . Traditional PR uses a predominantly aerobic/endurance approach to rehabilitation with little or no inclusion of exercises to increase strength . Few studies have investigated the impact of resistance training on PR despite growing evidence supporting its efficacy to improve physical function ( functional fitness ) in both healthy individuals and those with chronic disease . The purpose of this study was to investigate the effect of single-set resistance training on strength and functional fitness outcomes in PR patients . METHODS Twenty PR patients , 60 to 81 years old , were r and omly assigned to an 8-week endurance-based PR program ( ET ) or an ET plus resistance training program ( RT ) . RESULTS Strength increased in RT ( P < .05 ) and decreased in ET for both upper and lower body . Functional fitness improved ( P < .05 ) in 5 of 7 tests for RT compared with 2 tests for ET . CONCLUSIONS Single set RT can elicit significant improvements in both strength and functional fitness , which is not obtained by traditional PR alone . Our results are comparable to other studies with similar outcomes using multiple-set RT protocol s. These findings may have important implication s for program design , application , and adherence in PR OBJECTIVE The benefits of a domiciliary program of pulmonary rehabilitation for patients with severe to very severe chronic obstructive pulmonary disease ( COPD ) are uncertain . We aim ed to assess the short- and medium-term efficacy of such a program in this clinical setting . PATIENTS AND METHODS Patients with severe COPD ( stages III-IV , classification of the Global Initiative for Chronic Obstructive Lung Disease ) and incapacitating dyspnea ( scores 3 - 5 , Medical Research Council [ MRC ] scale ) were r and omized to a control or domiciliary rehabilitation group . The 9-week supervised pulmonary rehabilitation program included educational sessions , respiratory physiotherapy , and muscle training in weekly sessions in the patient 's home . We assessed the following variables at baseline , 9 weeks , and 6 months : lung function , exercise tolerance ( 3-minute walk test ) , dyspnea ( MRC score ) , and health-related quality of life with the Chronic Respiratory Question naire ( CRQ ) . RESULTS Thirty-eight patients with a mean ( SD ) age of 68 ( 6 ) years were enrolled . The mean MRC score was 4 ( 0.8 ) and mean forced expiratory volume in 1 second was 29 % of reference . Twenty-nine patients completed the study ( 6 months ) . Distance covered on the walk test increased significantly in the rehabilitation group ( P=.001 ) and the difference was maintained at 6 months . Dyspnea also improved significantly with rehabilitation ( P<.05 ) , but the reduction was not evident at 6 months . Statistically significant improvements in symptoms related to 2 CRQ domains were detected between baseline and 9 weeks : dyspnea ( 3.1 [ 0.8 ] vs 3.6 [ 0.7 ] ; P=.02 ) and fatigue ( 3.7 [ 0.8 ] vs 4.2 [ 0.9 ] ; P=.002 ) . A clinical ly relevant but not statistically significant change in mastery over disease was detected ( from 4.3 to 4.9 ) . All improvements were maintained at 6 months . CONCLUSIONS Home-based pulmonary rehabilitation for patients with severe to very severe COPD and severe functional incapacity leads to improvements in exercise tolerance and health-related quality of life that are maintained at 6 months BACKGROUND Previous research indicates a high prevalence of untreated anxiety and depression in patients with chronic obstructive pulmonary disease ( COPD ) . The current study examined the effect of cognitive behavioral therapy ( CBT ) in groups for co-morbid , clinical ly significant anxiety and depression in COPD out patients of both sexes . METHODS In a r and omized , controlled trial , CBT ( n = 25 ) was compared with enhanced st and ard care ( n = 26 ) . Participants in both conditions were followed up at 2 and 8 months from baseline . Main outcome measures comprised the Beck Anxiety Inventory and the Beck Depression Inventory-II . Measures of health status and sleep were included as secondary outcomes . The effects of sex and age were also investigated . RESULTS CBT result ed in improvement in symptoms of anxiety and depression , with effect sizes of 1.1 and 0.9 at post-treatment , respectively . The improvement was maintained at the 8-month follow-up , with effect sizes of 1.4 and 0.9 . In the control group , there was no significant change . Compared to men , women had higher symptom levels throughout the whole study period . Younger patients had more anxiety and depression , age had also differential effects in the two groups on change in depressive symptoms . Changes in sleep and health status were small in both groups . CONCLUSIONS The findings indicate that CBT may provide rapid symptom relief for COPD patients with clinical ly significant anxiety and depression , and underline the need for integrating mental health care into the overall medical regimen for COPD BACKGROUND Self-management interventions improve various outcomes for many chronic diseases . The definite place of self-management in the care of chronic obstructive pulmonary disease ( COPD ) has not been established . We evaluated the effect of a continuum of self-management , specific to COPD , on the use of hospital services and health status among patients with moderate to severe disease . METHODS A multicenter , r and omized clinical trial was carried out in 7 hospitals from February 1998 to July 1999 . All patients had advanced COPD with at least 1 hospitalization for exacerbation in the previous year . Patients were assigned to a self-management program or to usual care . The intervention consisted of a comprehensive patient education program administered through weekly visits by trained health professionals over a 2-month period with monthly telephone follow-up . Over 12 months , data were collected regarding the primary outcome and number of hospitalizations ; secondary outcomes included emergency visits and patient health status . RESULTS Hospital admissions for exacerbation of COPD were reduced by 39.8 % in the intervention group compared with the usual care group ( P = .01 ) , and admissions for other health problems were reduced by 57.1 % ( P = .01 ) . Emergency department visits were reduced by 41.0 % ( P = .02 ) and unscheduled physician visits by 58.9 % ( P = .003 ) . Greater improvements in the impact subscale and total quality -of-life scores were observed in the intervention group at 4 months , although some of the benefits were maintained only for the impact score at 12 months . CONCLUSIONS A continuum of self-management for COPD patients provided by a trained health professional can significantly reduce the utilization of health care services and improve health status . This approach of care can be implemented within normal practice BACKGROUND Chronic obstructive pulmonary disease ( COPD ) affects 14 to 20 million Americans and is associated with increased prevalence of affective disorders , contributing significantly to disability . This study compared cognitive behavioral therapy ( CBT ) group treatment for anxiety and depression with COPD education for COPD patients with moderate-to-severe anxiety and /or depressive symptoms . METHOD A r and omized controlled trial ( RCT ) was conducted between 11 July 2002 and 30 April 2005 at the Michael E. DeBakey VA Medical Center , Houston , TX . Participants were 238 patients treated for COPD the year before , with forced expiratory value in 1 second (FEV)1/forced vital capacity (FVC)<70 % and FEV1<70 % predicted , and symptoms of moderate anxiety and /or moderate depression , who were being treated by a primary care provider or pulmonologist . Participants attended eight sessions of CBT or COPD education . Assessment s were at baseline , at 4 and 8 weeks , and 4 , 8 and 12 months . Primary outcomes were disease-specific and generic quality of life ( QoL ) [ Chronic Respiratory Question naire ( CRQ ) and Medical Outcomes Survey Short Form-36 ( SF-36 ) respectively ] . Secondary outcomes were anxiety [ Beck Anxiety Inventory ( BAI ) ] , depressive symptoms [ Beck Depression Inventory-II ( BDI-II ) ] , 6-minute walk distance ( 6MWD ) and use of health services . RESULTS Both treatments significantly improved QoL , anxiety and depression ( p<0.005 ) over 8 weeks ; the rate of change did not differ between groups . Improvements were maintained with no significant change during follow-up . Ratios of post- to pretreatment use of health services were equal to 1 for both groups . CONCLUSIONS CBT group treatment and COPD education can achieve sustainable improvements in QoL for COPD patients experiencing moderate-to-severe symptoms of depression or anxiety STUDY OBJECTIVES To determine whether long-term treatment with exercise therapy results in more favorable , disease-specific , health-related quality of life ( HRQL ) compared with short-term treatment with exercise therapy ; and to determine whether there are gender differences in disease-specific HRQL among individuals r and omized into the two treatment groups . DESIGN R and omized clinical trial . SETTING Center-based exercise therapy unit at a university . PARTICIPANTS One hundred forty patients with COPD ; 118 completed trial . INTERVENTIONS Short-term exercise therapy ( 3 months ) ; long-term exercise therapy ( 18 months ) . MEASUREMENTS Chronic Disease Respiratory Question naire ( CRQ ) . RESULTS After 3 months of treatment , there were significant improvements in all CRQ scores for men and women ( p < 0.01 ) , and for the total sample ( p < 0.01 ) . At 18 months , individuals r and omized into the long-term group had significantly more favorable scores than the short-term group for dyspnea ( p = 0.03 ) , fatigue ( p < 0.01 ) , emotional function ( p = 0.04 ) , and mastery ( p = 0.04 ) . However , these effects were moderated by gender . That is , men in the long-term group reported significantly more favorable scores than men in the short-term group for dyspnea ( 0.04 ) , fatigue ( p < 0.001 ) , emotional function ( p = 0.02 ) , and mastery ( p = 0.02 ) . At the 18-month assessment , there were no differences between long-term and short-term exercise therapy for women on any of the subscales of the CRQ . CONCLUSIONS Taken collectively , the CRQ data demonstrate that long-term exercise therapy has little added benefit for women over short-term exercise therapy ; however , men derive significant benefits from extended training Aims : The main objective of this study was to investigate whether a comprehensive self-management programme , including self-treatment guidelines for exacerbations and a fitness programme , is an efficient treatment option for chronic obstructive pulmonary disease ( COPD ) patients . Method : We r and omly allocated 248 COPD patients to either self-management ( 127 ) or usual care ( 121 ) . Data on preference-based utilities ( EuroQol-5D ) , health-related quality of life ( HRQoL ) , health-care re source use and productivity losses associated with exacerbations were prospect ively collected . Quality -adjusted life years ( QALYs ) were calculated . The economic analysis took the societal perspective and the observation period was one year . Results : As we observed that the groups were equally effective in terms of QALYs and HRQoL ( SGRQ ) , we described a cost minimization analysis only . The self-management programme-specific costs amounted to 6642 per patient . In the base-case cost analysis , the incremental cost difference amounted to 838 per patient per year in favour of usual care . When only direct medical costs were included , the incremental annual cost of self-managementrelative to usual care was 179 per person per year . If time costs for the fitness programme were set to zero , the costs for self-management diminished to 542 . Sensitivity analysis showed that these results were robust to changes in the underlying assumptions . Conclusion : We conclude that the COPE self-management programme is not an efficient treatment option for moderate to severe COPD patients who rate their HRQoL relatively high . The programme was twice as expensive as usual care and had no measurable beneficial effects on QALYs or Background : Conventional pulmonary rehabilitation programs improve exercise tolerance but have no effect on pulmonary function in patients with chronic obstructive pulmonary disease ( COPD ) . The role of controlled breathing using respiratory biofeedback during rehabilitation of patients with COPD remains unclear . Objectives : To compare the effects of a conventional 4-week pulmonary rehabilitation program with those of rehabilitation plus controlled breathing interventions . Methods : A r and omized controlled trial was performed . Pulmonary function ( FEV1 ) , exercise capacity ( 6-min walking distance , 6MWD ) , health-related quality of life ( chronic respiratory question naire , CRQ ) and cardiac autonomic function ( rMSSD ) were evaluated . Results : Forty COPD patients ( mean ± SD age 66.1 ± 6.4 , FEV1 45.9 ± 17.4 % predicted ) were r and omized to rehabilitation ( n = 20 ) or rehabilitation plus controlled breathing ( n = 20 ) . There were no statistically significant differences between the two groups regarding the change in FEV1 ( mean difference –0.8 % predicted , 95 % CI –4.4 to 2.9 % predicted , p = 0.33 ) , 6MWD ( mean difference 12.2 m , 95 % CI –37.4 to 12.2 m , p = 0.16 ) , CRQ ( mean difference in total score 0.2 , 95 % CI –0.1 to 0.4 , p = 0.11 ) and rMSSD ( mean difference 2.2 ms , 95 % CI –20.8 to 25.1 ms , p = 0.51 ) . Conclusions : In patients with COPD undergoing a pulmonary rehabilitation program , controlled breathing using respiratory biofeedback has no effect on exercise capacity , pulmonary function , quality of life or cardiac autonomic function Objective To determine the feasibility and efficacy of a six-month , cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease ( COPD ) following pulmonary rehabilitation . Methods Participants who completed a two-week run-in were r and omly assigned to either MOBILE-Coached ( n = 9 ) or MOBILE-Self-Monitored ( n = 8) . All participants met with a nurse to develop an individualized exercise plan , were issued a pedometer and exercise booklet , and instructed to continue to log their daily exercise and symptoms . MOBILE-Coached also received weekly reinforcement text messages on their cell phones ; reports of worsening symptoms were automatically flagged for follow-up . Usability and satisfaction were assessed . Participants completed incremental cycle and six minute walk ( 6MW ) tests , wore an activity monitor for 14 days , and reported their health-related quality of life ( HRQL ) at baseline , three , and six months . Results The sample had a mean age of 68 ±11 and forced expiratory volume in one second 18 % predicted . Participants reported that logging their exercise and symptoms ( FEV1 ) of 40 ± was easy and that keeping track of their exercise helped them remain active . There were no differences between groups over time in maximal workload , 6MW distance , or HRQL ( p > 0.05 ) ; however , MOBILE-Self-Monitored increased total steps/day whereas MOBILE-Coached logged fewer steps over six months ( p = 0.04 ) . Conclusions We showed that it is feasible to deliver a cell phone-based exercise persistence intervention to patients with COPD post-rehabilitation and that the addition of coaching appeared to be no better than self-monitoring . The latter finding needs to be interpreted with caution since this was a purely exploratory study . Trial registration Clinical Trials.gov ( NCT00373932 ) PURPOSE This study examined the effects of inspiratory muscle training ( IMT ) with high-intensity inspiratory pressure loads on respiratory muscle performance and exertional dyspnea . METHODS This was a r and omized single-blind clinical trial . Twenty-seven patients with chronic obstructive pulmonary disease ( 18 men , 9 women ) with severe to very severe airflow obstruction and severely limited functional performance were assigned r and omly to an IMT group ( n = 12 ) or an educational control group ( n = 15 ) . The IMT group trained with a threshold loaded device for 30 minutes a day for 16 weeks using interval training techniques . Training was initiated with inspiratory pressure loads equal to 30 % of maximal inspiratory pressure ( Plmax ) and increased as tolerated to 60 % of Plmax . Dependent variables were measured before and after 4 months of IMT : inspiratory muscle strength ( Plmax ) , respiratory muscle endurance ( discontinuous incremental threshold loading test [ DC-ITL ] ) , dyspnea ( Chronic Respiratory Disease Question naire [ CRQ ] ) , and the Borg Category-Ratio Scale ratings of perceived breathing difficulty ( RPBD ) at equal loads during the DC-ITL . RESULTS In the IMT group , Plmax increased from 64 + /- 15 to 75 + /- 17 cm H2O ( P < .05 ) , performance on the DC-ITL test increased from a maximal load of 37 + /- 12 to 53 + /- 13 cm H2O ( P < .05 ) , RPBD decreased from 5.5 + /- 2.5 to 3.8 + /- 2.6 for equal loads on the DC-ITL ( P < .05 ) and the CRQ Dyspnea Scale improved from 18.1 + /- 5.1 to 22.4 + /- 5.2 ( P < .05 ) . CONCLUSIONS Inspiratory muscle training at high-intensity loads significantly improved inspiratory muscle strength , respiratory muscle endurance , and respiratory symptoms during daily activities and respiratory exertion Objectives : To study the effect of unsupported upper limb and lower limb exercise training and their combined influence on the exercise performance and health-related quality of life in COPD patients . Material s and Methods : Thirty patients were r and omly assigned to one of the three groups , through block r and omization . Of the three groups , group A received upper limb training , group B received lower limb training , and group C received both upper and lower limb training . Patients in group A , B , and C underwent exercise training five times a week for four weeks . The outcome measures used in the study were unsupported upper limb endurance test ( UULEX ) , Six-Minute Walk Test ( 6-MWT ) , and a Chronic Respiratory Question naire . Statistical analysis was performed with analysis of variance , Wilcoxon scale , and a Kruskal Wallis one way ANOVA test , and a P value of .05 was used in the study . Conclusion : The combined upper limb and lower limb training group showed a significant improvement in the exercise performance and health-related quality of life In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials 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 QUESTIONS Does an eight-week program of walk training improve endurance walking capacity in people with COPD compared to cycle training ? Does walk training improve peak walking capacity , cycle capacity , and quality of life compared to cycle training ? Is the endurance shuttle walk test ( ESWT ) responsive to change in walking capacity elicited by exercise training ? DESIGN R and omised trial with concealed allocation , assessor blinding , and intention-to-treat analysis . PARTICIPANTS 36 people with stable COPD recruited with four dropouts . INTERVENTION Participants were r and omised into either a walk or cycle training group . Both groups trained indoors for 30 to 45 minutes per session , three times weekly over eight weeks at Concord Hospital . Training intensities were based on baseline peak exercise tests and progressed as able . OUTCOME MEASURES The primary outcome was endurance walking capacity measured by the ESWT . Secondary outcomes included peak walking capacity , peak and endurance cycle capacity , and health-related quality of life . Measures were taken at baseline ( Week 0 ) and following training ( Week 8) . RESULTS The walk training group increased their endurance walking time by 279 seconds ( 95 % CI 70 to 483 ) more than the cycle training group . No significant differences between the groups were found for any other outcome . CONCLUSION Ground walk training increased endurance walking capacity more than cycle training and was similar to cycle training in improving peak walking capacity , peak and endurance cycle capacity and quality of life . This study provides evidence for ground walking as a mode of exercise training in pulmonary rehabilitation programs This study tested the hypothesis that severity of respiratory disability may affect the outcome of pulmonary rehabilitation . In this r and omized , controlled study , 126 patients with chronic obstructive pulmonary disease ( COPD ) were stratified for dyspnoea using the Medical Research Council ( MRC ) dyspnoea score into MRC3/4 ( Moderate ) ( n=66 ) and MRC 5 ( Severe ) dyspnoeic ( n=60 ) groups . The patients were r and omly assigned to an eight week programme of either exercise plus education ( Exercise group ) or education ( Control group ) . Education and exercise programmes for the moderately dyspnoeic patients were carried out in a hospital outpatient setting . Severely dyspnoeic patients were all treated at home . Those in the Exercise group received an individualized training programme . There was a significant improvement in shuttle walking distance in the moderate dyspnoeic group , who received exercise training ; baseline ( mean+/-SEM ) 191+/-22 m , post-rehabilitation 279+/-22 m ( p<0.001 ) . There was no improvement in exercise performance in the severely dyspnoeic patients receiving exercise . Neither group of control patients improved . Health status , assessed by the Total Chronic Respiratory Disease Question naire score , increased in the moderately dyspnoeic patients receiving exercise from 80+/-18 to 95+/-17 ( p<0.0001 ) after rehabilitation . Much smaller changes were seen in the other three groups . Improvement in exercise performance and health status in patients with chronic obstructive pulmonary disease after an exercise programme depends on the initial degree of dyspnoea OBJECTIVE To determine the feasibility of a r and omized controlled trial of the effect of a tai chi program on quality of life and exercise capacity in patients with COPD . METHODS We r and omized 10 patients with moderate to severe COPD to 12 weeks of tai chi plus usual care ( n = 5 ) or usual care alone ( n = 5 ) . The tai chi training consisted of a 1-hour class , twice weekly , that emphasized gentle movement , relaxation , meditation , and breathing techniques . Exploratory outcomes included disease-specific symptoms and quality -of-life , exercise capacity , pulmonary function tests , mood , and self-efficacy . We also conducted qualitative interviews to capture patient narratives regarding their experience with tai chi . RESULTS The patients were willing to be r and omized . Among 4 of the 5 patients in the intervention group , adherence to the study protocol was excellent . The cohort 's baseline mean ± SD age , percent-of-predicted FEV₁ , and ratio of FEV₁ to forced vital capacity were 66 ± 6 y , 50 ± 12 % , and 0.63 ± 0.14 , respectively . At 12 weeks there was significant improvement in Chronic Respiratory Question naire score among the tai chi participants ( 1.4 ± 1.1 ) , compared to the usual-care group ( -0.1 ± 0.4 ) ( P = .03 ) . There were nonsignificant trends toward improvement in 6-min walk distance ( 55 ± 47 vs -13 ± 64 m , P = .09 ) , Center for Epidemiologic Studies Depression Scale ( -9.0 ± 9.1 vs -2.8 ± 4.3 , P = .20 ) , and University of California , San Diego Shortness of Breath score ( -7.8 ± 3.5 vs -1.2 ± 11 , P = .40 ) . There were no significant changes in either group 's peak oxygen uptake . CONCLUSIONS A r and omized controlled trial of tai chi is feasible in patients with moderate to severe COPD . Tai chi exercise as an adjunct to st and ard care warrants further investigation AIM We assessed the long-term benefits of inspiratory muscle training ( IMT ) on inspiratory muscle strength , exercise capacity , the perception of dyspnea , quality of life , primary care use , and hospitalizations in patients with significant COPD . PATIENTS Forty-two consecutive COPD patients with FEV(1 ) < 50 % of predicted were r and omized into a group that received IMT for 1 year , and a control group that received training with a very low load . RESULTS There was a statistically significant increase in inspiratory muscle strength ( at the end of the third month of training ) as assessed by maximal inspiratory pressure ( from 71 + /- 4.9 to 90 + /- 5.1 cm H(2)O [ + /- SEM ] , p < 0.005 ) and 6-min walk distance ( at the end of the third month of training ; from 256 + /- 41 to 312 + /- 54 m ; p < 0.005 ) , a decrease in the mean Borg score during breathing against resistance ( at the end of the ninth month of training ) , improvement in the health-related quality -of-life scores ( at the end of the sixth month of training ) in the training group but not in the control group . At the end of the training year , these changes were maintained ; in addition , a decrease in primary health-care use and hospitalization days was observed . CONCLUSIONS Our study shows that during IMT in patients with significant COPD , there is an increase in exercise capacity , improvement in quality of life , and decrease in dyspnea . Our study also provides evidence that long-term IMT can decrease the use of health services and hospitalization days STUDY OBJECTIVES The purpose of this study was to compare the effects of endurance training only to endurance plus strength ( combined ) training in a r and omized trial of patients with COPD . METHODS Twenty-four patients completed the study : 11 patients in the combined training group ( FEV(1 ) 45 + /- 5 % predicted ) , and 13 patients in the endurance training group ( FEV(1 ) 40 + /- 4 % predicted ) [ mean + /- SE ] . Muscle strength , quality of life , exercise performance , and quadriceps fatigability were measured before and after rehabilitation . RESULTS Combined training led to significant improvements in quadriceps ( 23.6 % ) , hamstring ( 26.7 ) , pectoralis major ( 17.5 % ) , and latissimus dorsi ( 20 % ) muscle strength . Endurance training alone did not produce significant improvements in muscle strength : quadriceps ( 1.1 % decrease ) , hamstring ( 12.2 % increase ) , pectoralis major ( 7.8 % increase ) , and latissimus dorsi ( 2.8 % decrease ) . The increase in strength after training was significantly greater in the combined group compared to the endurance group for the quadriceps and latissimus dorsi muscles but not for the hamstring and pectoralis major muscles . Six-minute walk distance , endurance exercise time , and quality of life ( as measured by the Chronic Respiratory Question naire ) significantly increased in both groups after rehabilitation with no significant differences in the extent of improvement between groups . The extent of improvement in quadriceps fatigability after training ( assessed by quadriceps twitch force before and after exercise ) was not significantly different between groups . CONCLUSION Strength training can lead to significant improvement in muscle strength in elderly patients with COPD . However , this improvement in muscle strength does not translate into additional improvement in quality of life , exercise performance or quadriceps fatigability compared to that achieved by endurance exercise alone The aim of this study was to examine the effect of high intensity physical group training in water and on l and for patients with COPD with regard to physical capacity and health related quality of life ( HRQoL ) . A controlled , semi-r and omised study was conducted where 30 patients were r and omised to training either in water or on l and . Thirteen patients constituted a control group . Forty-three out patients , with moderate to severe COPD ( 27w/16 m ) , from two local hospitals in northern Sweden , were included in the study . High intensity physical group training in water ( water group ) or on l and ( l and group ) was performed for 12weeks , three times per week , 45min per session . The control group received no intervention . Pre- and post-intervention , all patients performed incremental and endurance shuttle walking tests ( ISWT and ESWT ) , cycle ergometer tests and responded question naires about HRQoL ( St. Georges Respiratory Question naire -- SGRQ and SF-36 ) . The patients trained with a mean heart rate of 80 - 90 % of peak heart rate . Both training groups increased the distance walked , i.e. l and group in ISWT ( 25 m ) and water group in ESWT ( 179 m ) . The water group increased the distance in ESWT significantly more that both the l and and the control groups . Both training groups increased the time cycled ( 40 - 85s ) and work load ( 10 - 20W ) in the cycle ergometer test . The control group deteriorated in HRQoL according to total score in SGRQ while the training groups remained constant . The water group improved their activity score in SGRQ and their physical health score in SF-36 and those improvements were significant as compared to the l and and the control groups . In conclusion , high intensity physical group training in water is of benefit for patients with COPD . It was in some areas found to be even more effective regarding improvements in physical capacity and experienced physical health compared to the same kind of training on l and It was postulated that home hospitalisation ( HH ) of selected chronic obstructive pulmonary disease ( COPD ) exacerbations admitted at the emergency room ( ER ) could facilitate a better outcome than conventional hospitalisation . To this end , 222 COPD patients ( 3.2 % female ; 71±10 yrs ( mean±sd ) ) were r and omly assigned to HH ( n=121 ) or conventional care ( n=101 ) . During HH , integrated care was delivered by a specialised nurse with the patient 's free-phone access to the nurse ensured for an 8‐week follow-up period . Mortality ( HH : 4.1 % ; controls : 6.9 % ) and hospital readmissions ( HH : 0.24±0.57 ; controls : 0.38±0.70 ) were similar in both groups . However , at the end of the follow-up period , HH patients showed : 1 ) a lower rate of ER visits ( 0.13±0.43 versus 0.31±0.62 ) ; and 2 ) a noticeable improvement of quality of life ( Δ St George 's Respiratory Question naire ( SGRQ ) , −6.9 versus −2.4 ) . Furthermore , a higher percentage of patients had a better knowledge of the disease ( 58 % versus 27 % ) , a better self-management of their condition ( 81 % versus 48 % ) , and the patient 's satisfaction was greater . The average overall direct cost per HH patient was 62 % of the costs of conventional care , essentially due to fewer days of inpatient hospitalisation ( 1.7±2.3 versus 4.2±4.1 days ) . A comprehensive home care intervention in selected chronic obstructive pulmonary disease exacerbations appears as cost effective . The home hospitalisation intervention generates better outcomes at lower costs than conventional care AIM In this study , the effects of a 12-week hospital-based outpatient pulmonary rehabilitation program ( HRP ) are compared with those of a 12-week home-care rehabilitation program ( HCRP ) in COPD patients . A control group received no rehabilitation therapy . METHODS After r and omization and stratification , effects on lung function , exercise performance ( 4-min walking test and cycle ergometer test ) , dyspnea , and leg effort during exercise , and well-being were assessed in 45 COPD patients with moderate to severe airflow limitation ( mean [ SD ] FEV1 percent predicted , 42.8 [ 8.4 ] ) . RESULTS After HRP and HCRP , at 3 to 6 months after the start of the study , equal improvements were detected in exercise capacity and in Borg dyspnea and leg effort scores at similar work levels during the cycle test . However , whereas after HRP at longer term values tended to return to baseline outcome , after HCRP a further ongoing significant improvement in exercise capacity was observed , while Borg dyspnea scores remained significantly improved over 18 months . Improvements in cycle workload and dyspnea score were significantly better maintained after HCRP as compared with HRP . Lung function , arterial oxygen saturation , and heart frequency during exercise did not change . A significant improvement in well-being was maintained over 18 months in both rehabilitation groups . CONCLUSION Beneficial effects are achieved both after a HRP and a HCRP in COPD patients with moderate to severe airflow limitation . Yet we recommend to initiate HCRPs as improvements are maintained longer and are even further strengthened in this setting We examined the feasibility of home-based walking training to maintain the benefits of a short-term exercise training in patients with severe chronic obstructive pulmonary disease ( COPD ) . After initial recovery from an exacerbation , 46 patients were r and omized into a training and a control group , and 30 patients completed the programme ( mean + /- SD FEV1 , 36 + /- 7 % predicted ) . The training group performed a 10-day walking training programme in the hospital , followed by a 6-month programme of supervised walking training at home , integrated into daily activities . The control group did not have exercise training in the hospital or at home . Until 6 months after discharge , lung function , exercise performance and symptom scores were assessed . Six-minute walking distance in the training group improved from day 1 to day 10 ( P<0.001 ) and this effect was maintained over 6 months ( P<0.001 ) . On average , daily walking distance at home was 2308 m and walking was reported on 157 days . Quality of life ( QoL ) scores changed significantly over 6 months ( P<0.001 ) . The control group showed no significant changes in exercise performance or QoL scores throughout the whole study period . Therefore , ( i ) significant improvements in exercise performance and Chronic Respiratory Disease Question naire ( CRQ ) scores could be achieved after recovery from an exacerbation and ( ii ) these improvements were maintained after discharge , when supported by a home-based walking training This r and omized , controlled study investigated the physiological effects of a specially design ed 12 week programme of isolated conditioning of peripheral skeletal muscle groups . The programme required minimal infrastructure in order to allow continued rehabilitation at home after familiarization within hospital . Forty eight patients , aged 40 - 72 yrs with chronic obstructive pulmonary disease ( COPD ) ( mean ( SD ) forced expiratory volume in one second ( FEV1 ) 61 (27)% of predicted normal ) were r and omly allocated into training ( n = 32 ) and control ( n = 16 ) groups . Physiological assessment s were performed before and after the 12 week study period , and included peripheral muscle endurance and strength , whole body endurance , maximal exercise capacity ( maximum oxygen consumption ( V'O2,max ) ) and lung function . The training group showed significant improvement in a variety of measures of upper and lower peripheral muscle performance , with no additional breathlessness . Whole body endurance measured by free arm treadmill walking increased by 6,372 ( 3,932 - 8,812 ) 3 ( p < 0.001 ) . Symptom-limited maximal V'O2 was unchanged . However , the training group showed a reduction in ventilatory equivalents for oxygen and carbon dioxide , both at peak exercise and at equivalent work rate ( Wmax ) . In summary , low intensity isolated peripheral muscle conditioning is well-tolerated , simple and easy to perform at home . The various physiological benefits should enable patients across the range of severity of chronic obstructive pulmonary disease to improve daily functioning Cognitive impairment is highly prevalent in chronic obstructive pulmonary disease ( COPD ) complicated by chronic hypoxemia , but the effect of cognitive training in patients with COPD has not been studied . The aim of the present study was to verify whether cognitive training can preserve cognitive abilities of patients with hypoxemic COPD . Our series consisted of 105 COPD patients with at rest ( n = 36 ) or effort ( n = 69 ) hypoxemia and free from concurrent dementing diseases . Neuropsychologic assessment included a screening test , the Mini Mental State Examination ( MMSE ) , and a st and ardized confirmatory battery of neuropsychological tests , the Mental Deterioration Battery ( MDB ) . After baseline assessment , patients were r and omized to receive st and ardized multidimensional care ( st and ardization of pharmacological therapy , health education , selection of inhalers according to patient 's ability , respiratory rehabilitation , nutritional counseling , oxygen therapy , and control visits ) with ( n = 53 ) or without ( n = 52 ) cognitive training aim ed at stimulating attention , learning , and logical-deductive thinking . Cognitive performance was reassessed after 1.5 , 4 , and 6 months . The analysis of variance for repeated measures ( ANOVA ) having the group membership ( study vs. control ) as grouping factor was used to assess changes in cognitive performance . Both intervention and control groups showed no significant changes in cognitive performance except for a trend toward improvement in verbal fluency and verbal memory , but cognitive intervention had no significant effect . In conclusion , cognitive training seems ineffective in COPD . However , a multidimensional st and ardized therapeutic approach , as it was indistinctly provided to all patients , could help to slow or prevent cognitive decline Chronic obstructive pulmonary disease ( COPD ) is disabling , with symptoms such as chronic cough , phlegm , wheezing , shortness of breath and increased infections of the respiratory passage . The aim was to examine the effects of a structured educational intervention programme at a nurse-led primary health care clinic ( PHCC ) on quality of life ( QoL ) , knowledge about COPD and smoking cessation in patients with COPD . This study had an experimental design in which 52 patients with COPD from a Swedish primary care setting were r and omized into two groups ( intervention or control ) . Both groups received st and ard care but patients in the intervention group were also offered two visits to a nurse specialized in COPD care . The purpose of the visits was to increase the patients ' self-care ability and their knowledge about COPD . The study was approved by the local Research Ethics Committee . Data were collected using two question naires , one pertaining to knowledge about COPD and smoking habits and St. George 's Respiratory Question naire , addressing how QoL was affected by the patients ' respiratory symptoms . The intervention and control groups answered both question naires on their first and last visits to the PHCC . A statistically significant increase was noted in the intervention group on QoL , the number of patients who stopped smoking and patients ' knowledge about COPD at the follow-up , 3 - 5 months after intervention . However , a confounding factor may have been that one of the research ers ( Eva Osterlund Efr aims son ) , as a nurse in the PHCC , performed the intervention . This implies that patients were in a dependent relationship which may have affected the responses in a favourable direction . Our findings show that conventional care alone did not have an effect on patients ' QoL and smoking habits . Instead , the evidence suggests that a structured programme with self-care education is needed to motivate patients for life-style changes STUDY OBJECTIVE To determine whether exercise training with coaching is more effective than exercise training alone in reducing dyspnea and the anxiety and distress associated with it and improving exercise performance , self-efficacy for walking , and dyspnea with activities of daily living . DESIGN R and omized clinical trial of 51 dyspnea-limited patients with COPD assigned to monitored ( n = 27 ) or coached ( n = 24 ) exercise groups . SETTING Outpatient area of university teaching hospital . INTERVENTION Both groups completed 12 supervised treadmill training sessions ( phase 1 ) over 4 weeks followed by 8 weeks of home walking ( phase 2 ) . The CE group also received coaching during training . MEASUREMENTS Perceived work of breathing , dyspnea intensity , distress associated with dyspnea , and anxiety associated with dyspnea were rated on a visual analog scale during incremental treadmill testing and after 6-min walks before and after phase 1 . Dyspnea with activities of daily living , self-efficacy for walking , state anxiety , and 6-min walks were measured before and after both phases . RESULTS Dyspnea and the associated distress and anxiety improved significantly for both groups relative to work performed and in relation to ventilation ( p < 0.05 ) . There were no significant differences between groups in any outcomes . The phase 1 improvement in laboratory dyspnea was accompanied by improvements in dyspnea with activities of daily living ( p < 0.01 ) and self-efficacy for home walking ( p < 0.01 ) that were sustained during the home phase . CONCLUSIONS Coaching with exercise training was no more effective than exercise training alone in improving exercise performance , dyspnea , and the anxiety and distress associated with it , dyspnea with activities , and self-efficacy for walking Objectives : To determine the effects of a nurse led intermediate care programme in patients who have been hospitalised with an acute exacerbation of chronic obstructive pulmonary disease ( AE COPD ) . Design : R and omised controlled trial . Setting : Community and hospital care in west London . Participants : 122 patients with COPD . Intervention : A care package incorporating initial pulmonary rehabilitation and self-management education , provision of a written , personalised COPD action plan , monthly telephone calls and 3 monthly home visits by a specialist nurse for a period of 2 years . Main outcome measure : Hospital readmission rate . Secondary outcomes : Unscheduled primary care consultations and quality of life . Results : There were no differences in hospital admission rates or in exacerbation rates between the two groups . Self-management of exacerbations was significantly different and the intervention group were more likely to be treated with oral steroids alone or oral steroids and antibiotics , and the initiators of treatment for exacerbations were statistically more likely to be the patients themselves . 12 patients in the control group died during the 2 year period , eight as a result of COPD , compared with six patients in the intervention group , of whom one died from COPD . This is a significant difference . When the numbers were adjusted to reflect the numbers still alive at 2 years , in the intervention group patients reported a total of 171 unscheduled contacts with their general practitioner ( GP ) and in the control group , 280 contacts . The number needed to treat was 0.558—ie , for every one COPD patient receiving the intervention and self-management advice , there were 1.79 fewer unscheduled contacts with the GP . Conclusions : An intermediate care package incorporating pulmonary rehabilitation , self-management education and the receipt of a written COPD action plan , together with regular nurse contact , is associated with a reduced need for unscheduled primary care consultations and a reduction in deaths due to COPD but did not affect the hospital readmission rate Chronic obstructive pulmonary disease ( COPD ) is associated with increased whole body protein breakdown and low- grade systemic inflammation . We aim ed to determine if physical training of patients with COPD induces anti-inflammatory effects and decreases whole-body protein breakdown . Nineteen subjects with severe ( FEV(1)=31+/-1 ) COPD were r and omized into a training group ( n=9 ) and a control group ( n=10 ) . Twenty healthy subjects were studied for baseline comparison . The " COPD training " group participated in an outpatient rehabilitation program consisting of endurance training ( walking at 85 % of VO(2max ) ) twice weekly for 7 weeks plus daily home-based training . Maximum walking distance increased by almost 70 % in the training group after 7 weeks of training . At baseline , the concentrations of C-reactive protein ( CRP ) and IL-18 in plasma were increased in subjects with COPD compared with healthy subjects ( P<0.05 ) and leucine rate of appearance ( R(a ) ) was approximately 15 % greater ( P<0.05 ) in subjects with COPD . Training had no effect on the plasma concentration of inflammatory markers but decreased leucine R(a ) in subjects with COPD by approximately 10 % ( P<0.05 ) . In conclusion , 7 weeks of physical training markedly improved endurance in patients with COPD and accelerated whole-body protein breakdown in patients with COPD was attenuated by physical training independent of changes in inflammatory markers R and omly assigned 119 adults with chronic obstructive pulmonary disease to an 8-week comprehensive rehabilitation program or to an 8-week education control program . Comprehensive pulmonary rehabilitation included education , physical and respiratory therapy instruction , psychosocial support , and supervised exercise training ; education control included biweekly classroom instruction and discussion s on respiratory therapy , medical aspects of lung disease , clinical pharmacology , and diet , but no exercise training . Both groups received extensive physiological and psychosocial evaluation before and after the intervention . Six months after enrollment , patients r and omly assigned to the rehabilitation program showed significant increases in exercise endurance , whereas patients r and omly assigned to control program showed nonsignificant increases . Improvement in self-efficacy was correlated with improvements in exercise endurance PURPOSE To compare the impact of a library of pulmonary rehabilitation videotapes versus an older videotape and usual care on quality of life and ability to perform activities of daily living in persons with chronic obstructive pulmonary disease . METHODS Two hundred fourteen patients diagnosed with chronic obstructive pulmonary disease , emphysema , or chronic bronchitis were recruited and r and omized to receive customized videotapes , st and ard videotapes , or usual care . Outcome measures included the Fatigue Impact Scale , Seattle Obstructive Lung Disease Question naire , and the SF-36(R ) Health Survey . RESULTS Differences in coping skills and emotional functioning on the Seattle Obstructive Lung Disease Question naire were found among the 174 subjects who completed the study . The customized videotape group improved by 8.6 and 4.8 points , respectively , whereas the score of the other groups decreased by less than 1 point for the coping skills , and the scores of the st and ard video and the control groups decreased by 3.0 and 2.1 points , respectively , for emotional functioning ( P < .05 , all comparisons ) . The scores using the Fatigue Impact Scale also improved for the customized videotape group , whereas the scores of the others remained unchanged . Videotape users demonstrated better conversion to and retention of exercise habits , with over 80 % of customized videotape subjects who reported exercise habits at baseline continuing the habits as compared with 40 % in the usual care group . Sedentary subjects at baseline were more likely to begin and maintain exercise if r and omized to videotapes . CONCLUSIONS These findings demonstrate increased quality of life , lower fatigue , and better compliance with a prescribed exercise regimen among subjects using the customized videotapes . There was a significant improvement in emotional functioning and coping skills among customized videotape subjects OBJECTIVE Patients with chronic obstructive pulmonary disease ( COPD ) and a history of frequent exacerbations are a target population of particular interest from both a clinical and an economic st and point . The objective of this study was to evaluate the effectiveness of a program design ed specifically to manage patients in this subgroup . PATIENTS AND METHODS This was a 1-year r and omized controlled trial design ed to compare the effectiveness of a specific program ( SP ) with that of conventional management ( CM ) in a group of patients with a high frequency of exacerbations ( 3 or more per year ) . Within-group and between-group comparisons were carried out for a number of variables related to the patients medical care , dyspnea , health-related quality of life ( HRQL ) , inhalation technique , and pulmonary function . RESULTS A total of 26 patients were enrolled in the study ( all men ) . The mean ( SD ) age was 73 ( 8) years , and mean forced expiratory volume in 1 second ( FEV1 ) expressed as a percentage of the reference value was 43 % ( 15 % ) . Exacerbations requiring hospital care ( emergency department visits and /or admission ) decreased in both groups : by 24.4 % ( P not significant ) in the CM group and 44.1 % ( P=.061 ) in the SP group . Hospital admissions decreased 73.3 % in the SP group and increased 22 % in the CM group ( P < .001 ) . While length of hospital stay decreased 77.3 % in the SP group , this figure almost doubled in the CM group ( P=.014 ) . Dyspnea , HRQL , and inhalation technique improved in both groups . FEV1 fell by 46 mL/year in the CM group and increased 10 mL/year in the SP group ( P not significant ) . CONCLUSIONS The use of a simple program to manage selected patients with a history of frequent exacerbations produces a significant reduction in the number of hospital admissions , an improvement in HRQL , and may improve prognosis We have developed a rehabilitation programme at home and have investigated its effects on quality of life ( QOL ) , lung function , and exercise tolerance in patients with chronic obstructive pulmonary disease ( COPD ) . We studied 43 patients with severe airflow obstruction : forced expiratory volume in one second ( FEV1 ) 1.3 + /- 0.4 l ( mean + /- SD ) , FEV1/inspiratory vital capacity ( IVC ) 37 + /- 7.9 % . After stratification , 28 patients were r and omly allocated in a home rehabilitation programme for 12 weeks . Fifteen patients in a control group received no rehabilitation . The rehabilitation group received physiotherapy by the local physiotherapist , and supervision by a nurse and a general practitioner . Quality of life was assessed by the four dimensions of the Chronic Respiratory Question naire ( CRQ ) . We found a highly significant improvement in the rehabilitation group compared to the control group for the dimensions dyspnoea , emotion , and mastery . Lung function showed no changes in the rehabilitation group . The exercise tolerance improved significantly in the rehabilitation group compared to the control group . The improvement in quality of life was not correlated with the improvement in exercise tolerance . Rehabilitation of COPD patients at home may improve quality of life ; this improvement is not correlated with an improvement in lung function and exercise tolerance To evaluate the role of ventilatory muscle endurance training ( VMET ) in the rehabilitation of out patients with chronic obstructive pulmonary disease , we carried out a prospect i ve r and om allocation trial of VMET versus IPPB . Data were obtained from 15 men allocated to VMET and from 17 men assigned to IPPB . The mean age of our experimental cohort was 61 + /- SEM 1 yr , and the FEV1 was 1.2 + /- 0.1 L. Prior to and after 6 wk of daily therapy , the following data were obtained on each subject : ( 1 ) vital statistics , ( 2 ) st and ard pulmonary function tests , ( 3 ) activities of daily living ( ADL ) , ( 4 ) maximal sustainable ventilatory capacity ( MSVC ) , ( 5 ) psychologic status ( PS ) , and ( 6 ) exercise tolerance ( ET ) . Prior to therapy , the VMET and IPPB groups showed no significant differences with respect to these parameters . After therapy , VMET subjects exhibited a greater increase ( p less than 0.05 ) in MSVC than did IPPB subjects . However , VMET and IPPB groups did not differ with respect to improvements noted in ADL , PS , and ET . These results from our controlled study raise the possibility that some aspect of the experimental protocol , other than VMET , accounted for the improvements noted in ADL , PS , and ET UNLABELLED The most common symptoms in chronic obstructive pulmonary disease ( COPD ) patients are breathlessness and exercise limitation . Although both general and inspiratory muscle training have shown clinical benefits , the effects of specific expiratory muscle training remain controversial . OBJECTIVE To investigate the effects of expiratory training on lung function , exercise tolerance , symptoms and health-related quality of life in severe COPD patients . METHODS Sixteen patients ( FEV(1 ) , 28+/-8 % pred . ) were r and omised to either expiratory muscle or sham training groups , both completing a 5-week programme ( 30 min sessions breathing through an expiratory threshold valve 3 times per week ) ( 50 % of their maximal expiratory pressure ( MEP ) vs. placebo , respectively ) . Lung function , exercise capacity ( bicycle ergometry and walking test ) , and clinical outcomes ( dyspnoea and quality of life ( St. George Respiratory Question naire ( SGRQ ) ) were evaluated both at baseline and following the training period . RESULTS Although lung function remained roughly unchanged after training , exercise capacity , symptoms and quality of life significantly improved . The improvement in both walking distance and the SGRQ score significantly correlated with changes in MEP . CONCLUSION Our results confirm that a short outpatient programme of expiratory training can improve symptoms and quality of life in severe COPD patients . These effects could be partially explained by changes in expiratory muscle strength Hospital admissions due to chronic obstructive pulmonary disease ( COPD ) exacerbations have a major impact on the disease evolution and costs . The current authors postulated that a simple and well-st and ardised , low-intensity integrated care intervention can be effective to prevent such hospitalisations . Therefore , 155 exacerbated COPD patients ( 17 % females ) were recruited after hospital discharge from centres in Barcelona ( Spain ) and Leuven ( Belgium ) . They were r and omly assigned to either integrated care ( IC ; n = 65 ; age mean±sd 70±9 yrs ; forced expiratory volume in one second ( FEV1 ) 1.1±0.5 L , 43 % predicted ) or usual care ( UC ; n = 90 ; age 72±9 yrs ; FEV1 1.1±0.05 L , 41 % pred ) . The IC intervention consisted of an individually tailored care plan upon discharge shared with the primary care team , as well as accessibility to a specialised nurse case manager through a web-based call centre . After 12 months ’ follow-up , IC showed a lower hospitalisation rate ( 1.5±2.6 versus 2.1±3.1 ) and a higher percentage of patients without re-admissions ( 49 versus 31 % ) than UC without differences in mortality ( 19 versus 16 % , respectively ) . In conclusion , this trial demonstrates that a st and ardised integrated care intervention , based on shared care arrangements among different levels of the system with support of information technologies , effectively prevents hospitalisations for exacerbations in chronic obstructive pulmonary disease patients CONTEXT There is emerging evidence that disease management with self-management education provided by a case manager might benefit COPD patients . OBJECTIVE To determine whether disease management with self-management education is more cost-effective than usual care among previously hospitalized COPD patients . DESIGN Economic analysis in conjunction with a multicenter r and omized clinical trial comparing patients conducting self-management with those receiving usual care over a 1-year follow-up period . SETTING Respiratory referral centers . PATIENTS One hundred ninety-one COPD patients who required hospitalization in the year preceding enrollment were recruited from seven respiratory outpatient clinics . INTERVENTION In addition to usual care , patients in the intervention group received st and ardized education on COPD self-management program called " Living Well with COPD " with ongoing supervision by a case manager . MAIN OUTCOME MEASURES From the perspective of the health-care payer , we compared costs between the two groups and estimated the program cost per hospitalization prevented ( incremental cost-effectiveness ratio of the program ) . We repeated these estimates for several alternate scenarios of patient caseload . RESULTS The additional cost of the self-management program as compared to usual care , $ 3,778 ( 2004 Canadian dollars ) per patient , exceeded the savings of $ 3,338 per patient based on the study design with a caseload of 14 patients per case manager . However , through a highly plausible sensitivity analysis , it was showed that if case managers followed up 50 patients per year , the self-management intervention would be cost saving relative to usual care ( cost saving of $ 2,149 per patient ; 95 % confidence interval , $ 38 to $ 4,258 ) . With more realistic potential caseloads of 50 to 70 patients per case manager , estimated program costs would be $ 1,326 and $ 1,016 per prevented hospitalization , respectively . CONCLUSION The program of self-management in COPD holds promise for positive economic benefits with increased patient caseload and rising costs of hospitalization OBJECTIVES To evaluate hospital readmission rates and mortality at 6-month follow-up in selected elderly patients with acute exacerbation of chronic obstructive pulmonary disease ( COPD ) . DESIGN Prospect i ve r and omized , controlled , single-blind trial with 6-month follow-up . SETTING San Giovanni Battista Hospital of Torino . PARTICIPANTS One hundred four elderly patients admitted to the hospital for acute exacerbation of COPD were r and omly assigned to a general medical ward ( GMW , n=52 ) or to a geriatric home hospitalization service ( GHHS , n=52 ) . MEASUREMENTS Measurements of baseline sociodemographic information ; clinical data ; functional , cognitive , and nutritional status ; depression ; and quality of life were obtained . RESULTS There was a lower incidence of hospital readmissions for GHHS patients than for GMW patients at 6-month follow-up ( 42 % vs 87 % , P<.001 ) . Cumulative mortality at 6 months was 20.2 % in the total sample , without significant differences between the two study groups . Patients managed in the GHHS had a longer mean length of stay than those cared for in the GMW ( 15.5+/-9.5 vs 11.0+/-7.9 days , P=.010 ) . Only GHHS patients experienced improvements in depression and quality -of-life scores . On a cost per patient per day basis , GHHS costs were lower than costs in GMW ( $ 101.4+/-61.3 vs $ 151.7+/-96.4 , P=.002 ) . CONCLUSION Physician-led substitutive hospital-at-home care as an alternative to inpatient care for elderly patients with acute exacerbations of COPD is associated with a substantial reduction in the risk of hospital readmission at 6 months , lower healthcare costs , and better quality of life Objective To determine whether supported self management in chronic obstructive pulmonary disease ( COPD ) can reduce hospital readmissions in the United Kingdom . Design R and omised controlled trial . Setting Community based intervention in the west of Scotl and . Participants Patients admitted to hospital with acute exacerbation of COPD . Intervention Participants in the intervention group were trained to detect and treat exacerbations promptly , with ongoing support for 12 months . Main outcome measures The primary outcome was hospital readmissions and deaths due to COPD assessed by record linkage of Scottish Morbidity Records ; health related quality of life measures were secondary outcomes . Results 464 patients were r and omised , stratified by age , sex , per cent predicted forced expiratory volume in 1 second , recent pulmonary rehabilitation attendance , smoking status , deprivation category of area of residence , and previous COPD admissions . No difference was found in COPD admissions or death ( 111/232 ( 48 % ) v 108/232 ( 47 % ) ; hazard ratio 1.05 , 95 % confidence interval 0.80 to 1.38 ) . Return of health related quality of life question naires was poor ( n=265 ; 57 % ) , so that no useful conclusions could be made from these data . Pre-planned subgroup analysis showed no differential benefit in the primary outcome relating to disease severity or demographic variables . In an exploratory analysis , 42 % ( 75/150 ) of patients in the intervention group were classified as successful self managers at study exit , from review of appropriateness of use of self management therapy . Predictors of successful self management on stepwise regression were younger age ( P=0.012 ) and living with others ( P=0.010 ) . COPD readmissions/deaths were reduced in successful self managers compared with unsuccessful self managers ( 20/75 ( 27 % ) v 51/105 ( 49 % ) ; hazard ratio 0.44 , 0.25 to 0.76 ; P=0.003 ) . Conclusion Supported self management had no effect on time to first readmission or death with COPD . Exploratory subgroup analysis identified a minority of participants who learnt to self manage ; this group had a significantly reduced risk of COPD readmission , were younger , and were more likely to be living with others . Trial registration Clinical trials NCT 00706303 Objective To assess the long term effects of two different modes of disease management ( comprehensive self management and routine monitoring ) on quality of life ( primary objective ) , frequency and patients ’ management of exacerbations , and self efficacy ( secondary objectives ) in patients with chronic obstructive pulmonary disease ( COPD ) in general practice . Design 24 month , multicentre , investigator blinded , three arm , pragmatic , r and omised controlled trial . Setting 15 general practice s in the eastern part of the Netherl and s. Participants Patients with COPD confirmed by spirometry and treated in general practice . Patients with very severe COPD or treated by a respiratory physician were excluded . Interventions A comprehensive self management programme as an adjunct to usual care , consisting of four tailored sessions with ongoing telephone support by a practice nurse ; routine monitoring as an adjunct to usual care , consisting of 2 - 4 structured consultations a year with a practice nurse ; or usual care alone ( contacts with the general practitioner at the patients ’ own initiative ) . Outcome measures The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory question naire total score . Secondary outcomes were chronic respiratory question naire domain scores , frequency and patients ’ management of exacerbations measured with the Nijmegen telephonic exacerbation assessment system , and self efficacy measured with the COPD self-efficacy scale . Results 165 patients were allocated to self management ( n=55 ) , routine monitoring ( n=55 ) , or usual care alone ( n=55 ) . At 24 months , adjusted treatment differences between the three groups in mean chronic respiratory question naire total score were not significant . Secondary outcomes did not differ , except for exacerbation management . Compared with usual care , more exacerbations in the self management group were managed with bronchodilators ( odds ratio 2.81 , 95 % confidence interval 1.16 to 6.82 ) and with prednisolone , antibiotics , or both ( 3.98 , 1.10 to 15.58 ) . Conclusions Comprehensive self management or routine monitoring did not show long term benefits in terms of quality of life or self efficacy over usual care alone in COPD patients in general practice . Patients in the self management group seemed to be more capable of appropriately managing exacerbations than did those in the usual care group . Trial registration Clinical trials NCT00128765 The aim of the present study was to investigate the effects of an interval-based high-intensity inspiratory muscle training ( H-IMT ) programme on inspiratory muscle function , exercise capacity , dyspnoea and health-related quality of life ( QoL ) in subjects with chronic obstructive pulmonary disease . A double-blind r and omised controlled trial was performed . Sixteen subjects ( 11 males , mean forced expiratory volume in one second ( FEV1 ) 37.4±12.5 % ) underwent H-IMT performed at the highest tolerable inspiratory threshold load ( increasing to 101 % of baseline maximum inspiratory pressure ) . Seventeen subjects ( 11 males , mean FEV1 36.5±11.5 % ) underwent sham inspiratory muscle training ( S-IMT ) at 10 % of maximum inspiratory pressure . Training took place three times a week for 8 weeks and was fully supervised . Pre- and post-training measurements of lung function , maximum inspiratory pressure , maximum threshold pressure , exercise capacity , dyspnoea and QoL ( Chronic Respiratory Disease Question naire ; CRDQ ) were obtained . H-IMT increased maximum inspiratory pressure by 29 % , maximum threshold pressure by 56 % , 6-min walk distance by 27 m , and improved dyspnoea and fatigue ( CRDQ ) by 1.4 and 0.9 points per item , respectively . These changes were significantly greater than any seen following S-IMT . In conclusion , high-intensity inspiratory muscle training improves inspiratory muscle function in subjects with moderate-to-severe chronic obstructive pulmonary disease , yielding meaningful reductions in dyspnoea and fatigue OBJECTIVE To determine whether a mucus clearance device ( MCD ) ( Flutter ; Axcan Sc and ipharm , USA ) could consistently improve the bronchodilator response and exercise performance in patients with chronic obstructive pulmonary disease ( COPD ) when used in an ambulatory setting over a one-week period . SUBJECTS Fifteen patients with severe COPD ( mean age 71+/-10 years ) were studied . METHODS A r and omized crossover design compared an MCD with a sham MCD ( SMCD ) , in which each were tested for one week . At the beginning and end of each study week , forced expiratory volume in 1 s ( FEV1 ) and forced vital capacity ( FVC ) were measured before and after MCD or SMCD . A bronchodilator aerosol ( ipratropium bromide and salbutamol sulphate ) was then given , and FEV1 and FVC were remeasured 30 min , 60 min and 120 min later . A 6 min walk test ( 6MWT ) was also performed . RESULTS FEV1 improved significantly ( P<0.05 ) after bronchodilator administration with both the SMCD and MCD . The improvement was always greater with MCD use than with SMCD . At the baseline measure , 120 min postbronchodilator administration , the mean FEV1 improved by 24+/-24 % with SMCD use and 60+/-28 % with MCD use ( P<0.05 ) . After one week of use , the corresponding values at 120 min were 19+/-24 % and 43+/-26 % ( P<0.05 ) . Similar findings were obtained for FVC . 6MWT distances increased by 29+/-12 m ( P<0.05 ) after one week of MCD use , whereas it decreased slightly ( by 16+/-18 m ) after SMCD . The decline in saturation with the 6MWT was smaller with MCD use than with SMCD use . After one week , the decline in saturation with MCD use was similar to baseline levels , although patients were walking farther . After one week , dyspnea was lower on walking with MCD use than with SMCD use . CONCLUSION Patients with COPD had an increased response to bronchodilator therapy after use of the MCD compared with SMCD use . The increase persisted after one week of use , and was associated with improved exercise performance as measured by the 6MWT Background : Chronic obstructive pulmonary disease ( COPD ) is a chronic disease with a high prevalence and rapidly increasing incidence rates . The effect of self-treatment of COPD exacerbations on the severity of exacerbations during a 1-year period was examined and a cost-effectiveness analysis was performed . Methods : Patients were r and omly allocated to four 2-hour self-management sessions , with or without training in self-treatment of exacerbations . Patients in the self-treatment group received an action plan with the possibility to initiate a course of prednisolone ( with or without antibiotics ) . During follow-up , all participants kept a daily symptom diary . These provided the data to calculate the frequency of exacerbations , the number of exacerbation days and mean daily severity scores . Results : Data were analysed for 142 r and omised patients ( self-treatment : n = 70 ; control : n = 72 ) . The frequency of exacerbations was identical in both study groups ( mean ( SD ) 3.5 ( 2.7 ) ) . Patients in the self-treatment group reported fewer exacerbation days ( median 31 ( interquartile range ( IQR ) 8.9–67.5 ) in the self-treatment group vs 40 ( IQR 13.3–88.2 ) in the control group ; p = 0.064 ) ; the difference was significant in the group of patients with a high number of exacerbation days per year ( > 137 ( 90th percentile of the whole study population ) ; p = 0.028 ) . The mean severity score of an exacerbation day was equal in both groups . No between-group differences were found in health-related quality of life . Cost-effectiveness analyses showed that applying self-treatment saved € 154 per patient , with a trend towards a lower probability for hospital admissions ( 0.20/patient/year in the self-treatment group vs 0.33/patient/year in the control group ; p = 0.388 ) and a significant reduction of health care contacts ( 5.37/patient/year in the self-treatment group vs 6.51/patient/year in the control group ; p = 0.043 ) . Conclusion : Self-treatment of exacerbations incorporated in a self-management programme leads to fewer exacerbation days and lower costs STUDY OBJECTIVE To determine if distractive auditory stimuli ( DAS ) in the form of music would promote adherence to a walking regimen following completion of a pulmonary rehabilitation program ( PRP ) and , thereby , maintenance of gains achieved during the program . DESIGN Experimental , r and omized , two-group design with testing at baseline , 4 weeks , and 8 weeks . SETTING Outpatient . PATIENTS Twenty-four patients ( 4 men and 20 women ) with moderate-to-severe COPD ( FEV(1 ) 41.3 + /- 13 % predicted [ mean + /- SD ] ) . INTERVENTION Experimental group subjects ( n = 12 ) were instructed to walk at their own pace for 20 to 45 min , two to five times a week , using DAS with a portable audiocassette player . The control group ( n = 12 ) received the same instructions , but no DAS . MEASUREMENTS AND RESULTS Primary outcome measures were perceived dyspnea during activities of daily living ( ADL ) and 6-min walk ( 6MW ) distance . Secondary outcome measures were anxiety , depressive symptoms , health-related quality of life ( QoL ) , global QoL , and breathlessness and fatigue at completion of the 6MW . In addition , all subjects recorded the distance and time walked using self-report ( pedometers and daily logs ) . There was a significant decrease in perceived dyspnea during ADL ( p = 0.0004 ) and a significant increase in 6MW distance ( p = 0.0004 ) over time in the DAS group compared to the control group . DAS subjects increased 6MW distance 445 + /- 264 feet ( mean + /- SD ) from baseline to 8 weeks , whereas control subjects decreased 6MW distance to 169 + /- 154 feet . No significant differences were noted for the remaining variables . The cumulative distance walked by the DAS group was 19.1 + /- 16.7 miles compared to 15.4 + /- 8.0 miles for the control group , a 24 % difference ( p = 0.49 ) . Despite this difference , self-report exercise log data were similar for the two groups . CONCLUSION Subjects who used DAS while walking had improved functional performance and decreased perceptions of dyspnea , whereas control subjects could not maintain post-PRP gains . DAS is a simple , cost-effective strategy that may have the potential to augment the effectiveness of post-PRP maintenance training OBJECTIVES To have a group of COPD patients undergo a simple program of home-based exercise training , using the shuttle walking test ( SWT ) to st and ardize the intensity of training . METHODS Sixty patients participated , r and omly distributed into two groups ( rehabilitation and control ) of 30 patients each . The following evaluations were carried out at baseline and at 12 weeks : ( 1 ) pulmonary function studies ; ( 2 ) SWT ; ( 3 ) submaximal intensity resistance test ; ( 4 ) cycle ergometer test ; ( 5 ) quality of life ; and ( 6 ) dyspnea . The rehabilitation group underwent a lower-extremity training program . Walking was selected as the type of exercise . The intensity of training was set at 70 % of the maximum speed attained on the SWT . Divided sessions were held , lasting 1 h , 6 days/wk , at home , with a checkup every 2 weeks . The duration of the program was 12 weeks . RESULTS The following patients completed the study : 20 patients ( 66.6 % ) from the rehabilitation group ( mean [ + /- SD ] ) age , 64.3 + /- 8.3 years ; mean FEV(1 ) , 41.7 + /- 15.6 % of predicted ) ; and 17 patients ( 56.6 % ) from the control group ( mean age , 63.1 + /- 6.9 years ; mean FEV(1 ) , 40 + /- 16.4 % of predicted ) . We found no changes in pulmonary function or effort parameters ( SWT or cycle ergometer ) in the rehabilitation group at 12 weeks . A twofold increase ( 1,274 + /- 980 to 2,651 + /- 2,056 m ; p < 0.001 ) was achieved in the submaximal intensity resistance test , with less dyspnea at the conclusion of the test ( p = 0.05 ) . Significant improvement also was achieved in basal dyspnea and , both statistically and clinical ly , in the quality of life . Significant changes were not achieved in the control group patients . CONCLUSIONS A simple home-based program of exercise training achieved improvement in exercise tolerance , posteffort dyspnea , basal dyspnea , and quality of life in COPD patients The effects of two 8-week programmes of exercise reconditioning on the time constants ( tau ) of the pulmonary gas exchange , ventilatory and heart rate responses to moderate intensity exercise in patients with chronic obstructive pulmonary disease ( COPD ) were studied . Thirty-five subjects ( mean+/-SD 64+/-5 yrs ; forced expiratory volume in one second ( FEV1 ) 1.09+/-0.17 L ; 41+/-6.2 % predicted ) were r and omly assigned either to supervised ( s ) training on a treadmill , 4 days x week(-1 ) ( group S ; n=21 ) or self-monitored ( SM ) walking 3 or 4 km in 1 h 4 days x week(-l ) ( group SM ; n=20 ) . The different levels of supervision result ed in a different estimated intensity of training ( 35+/-10 W in the SM group and 70+/-22 W in the S group ) . The kinetics were evaluated with a constant-load exercise test on a cycle-ergometer at a work rate corresponding to 80 % the highest oxygen consumption ( V'O2 ) that can be achieved without blood lactic acidosis ( V'O2,LAT ) or 50 % of V'O2,max , if maximum oxygen consumption V'O2,LAT was not found . Mean endurance time at a work rate equivalent to 70 % of the pretraining V'O2,max increased by 493+/-281 s in the S group and 254+/-283 s in the SM group ( p<0.001 ) . Mean tauV'O2 decreased from 83+/-17 s to 67+/-11 s ( p<0.0001 ) in the S group and from 84+/-12 to 79+/-16 ( p=0.04 ) in the SM group . Mean tau for carbon dioxide output minute ventilation and heart rate were also speeded after training , again more markedly in the S group . In the S group there was a significant correlation between the decrease in tauV'O2 and the increase in endurance time ( r=-0.56 , SEM=0.21 ) . It is concluded that training speeds the kinetic response of oxygen consumption , carbon dioxide production , minute ventilation and heart rate to moderate exercise and that the effect is greater after supervised , more intense training BACKGROUND The study aim ed to evaluate the effect of upper extremity resistance training for patients with COPD on dyspnea during activity of daily living ( ADL ) , arm function , arm exercise capacity , muscle strength , and health-related quality of life ( HRQL ) . METHODS Patients were r and omly assigned to an intervention or control group . The intervention group underwent arm resistance training . The control group performed a sham . Both groups exercised three times a week for 6 weeks . Dyspnea during ADL and HRQL were measured using the Chronic Respiratory Disease Question naire ( CRDQ ) . Arm function and exercise capacity were measured using the 6-min pegboard and ring test ( 6PBRT ) and the unsupported upper limb exercise test ( UULEX ) , respectively . Muscle strength for the biceps , triceps , and anterior and middle deltoids was obtained using an isometric dynamometer . RESULTS Thirty-six patients with COPD ( 66 ± 9 years ) participated in the study . Compared with the control group , the magnitude of change in the intervention group was greater for the 6PBRT ( P = .03 ) , UULEX ( P = .01 ) , elbow flexion force ( P = .01 ) , elbow extension force ( P = .02 ) , shoulder flexion force ( P = .029 ) , and shoulder abduction force ( P = .01 ) . There was no between-group difference in dyspnea during ADL , HRQL , or symptoms during the 6PBRT or UULEX ( all P values > .08 ) . CONCLUSIONS Resistance-based arm training improved arm function , arm exercise capacity , and muscle strength in patients with COPD . No improvement in dyspnea during ADL , HRQL , or symptoms was demonstrated STUDY OBJECTIVE We report on the incremental costs associated with improvements in health-related quality of life ( HRQL ) following 6 months of respiratory rehabilitation compared with conventional community care . DESIGN Prospect i ve r and omized controlled trial of rehabilitation . SETTING A respiratory rehabilitation unit . PARTICIPANTS Eighty-four subjects who completed the rehabilitation trial . INTERVENTION Two months of inpatient rehabilitation followed by 4 months of outpatient supervision . MEASUREMENTS AND RESULTS All costs ( hospitalization , medical care , medications , home care , assistive devices , transportation ) were included . Simultaneous allocation was used to determine capital and direct and indirect hospitalization costs . The incremental cost of achieving improvements beyond the minimal clinical ly important difference in dyspnea , emotional function , and mastery was $ 11,597 ( Canadian ) . More than 90 % of this cost was attributable to the inpatient phase of the program . Of the nonphysician health-care professionals , nursing was identified as the largest cost center , followed by physical therapy and occupational therapy . The number of subjects needed to be treated ( NNT ) to improve one subject was 4.1 for dyspnea , 4.4 for fatigue , 3.3 for emotion , and 2.5 for mastery . CONCLUSION Cost estimates of various approaches to rehabilitation should be combined with valid , reliable , and responsive measures of outcome to enable cost-effectiveness measures to be reported . Comparison studies with the same method are necessary to determine whether the improvements in HRQL that follow inpatient rehabilitation are cheap or expensive . Such information will be important in identifying the extent to which alternative approaches to rehabilitation can influence re source allocation . A consideration of cost-effectiveness from the perspective of NNT may be useful in the evaluation of health-care programs The aim of the present study was to assess the long-term impact on hospitalisation of a self-management programme for chronic obstructive pulmonary disease ( COPD ) patients . A multicentre , r and omised clinical trial was carried out involving 191 COPD patients from seven hospitals . Patients who had one or more hospitalisations in the year preceding study enrolment were assigned to a self-management programme “ Living Well with COPD TM ” or to st and ard care . Hospitalisations from all causes were the primary outcome and were documented from the provincial hospitalisation data base ; emergency visits were recorded from the provincial health insurance data base . Most patients were elderly , not highly educated , had advanced COPD ( reflected by a mean forced expiratory volume in one second of 1 L ) , and almost half reported a dyspnoea score of 5/5 ( modified Medical Research Council ) . At 2 years , there was a statistically significant and clinical ly relevant reduction in all-cause hospitalisations of 26.9 % and in all-cause emergency visits of 21.1 % in the intervention group as compared to the st and ard-care group . After adjustment for the self-management intervention effect , the predictive factors for reduced hospitalisations included younger age , sex ( female ) , higher education , increased health status and exercise capacity . In conclusion , in this study , patients with chronic obstructive pulmonary disease who received educational intervention with supervision and support based on disease-specific self-management maintained a significant reduction in hospitalisations after a 2-year period OBJECTIVE To compare the effects of twice- versus once-weekly supervised pulmonary rehabilitation on exercise capacity and quality of life in patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN Prospect i ve , r and omized , parallel-group study . SETTING Hospital outpatient physiotherapy department . PARTICIPANTS Patients with COPD . INTERVENTION Group 1 ( n=46 ) received 1 supervised exercise session a week and 2 unsupervised sessions ; group 2 ( n= 45 ) received 2 supervised exercise sessions a week and 1 unsupervised session for 6 weeks . Patients were assessed at baseline and at 6 weeks , 2 months , and 6 months . MAIN OUTCOME MEASURES Incremental ( ISWT ) and endurance ( ESWT ) shuttle walk tests and Chronic Respiratory Disease Question naire ( CRDQ ) . RESULTS Sixty-six of 91 patients ( group 1 , n=34 ; group 2 , n=32 ) completed the 6-week program . There was no significant difference in key outcome measures between the 2 groups ( ISWT , 13.50 m ; 95 % confidence interval [ CI ] , -10.06 to 37.15 m ; ESWT , 72.64s ; 95 % CI , -96.01 to 241.29s ; CRDQ total score , 2.54 ; 95 % CI , -3.16 to 8.24 ) . The results of the ESWTs suggest there may be an interaction between baseline exercise capacity and benefit of pulmonary rehabilitation , with more disabled patients achieving greater benefit if they are supervised twice weekly . Irrespective of group , allocation benefits after pulmonary rehabilitation had almost dissipated by 6 months . CONCLUSIONS There was no difference in the effectiveness of twice- versus once-weekly supervised pulmonary rehabilitation . This study highlights the need for development of strategies that will maintain the improvement achieved by the initial pulmonary rehabilitation program The effect of inspiratory muscle training ( IMT ) on exercise capacity in patients with chronic airflow limitation ( CAL ) has been debated . The present study was planned to further investigate the effects of IMT on exercise performance . Twenty patients ( aged 62+/-1 yrs ; forced expiratory volume in one second/forced vital capacity ( FEV1/FVC ) 36+/-2 % ) were trained 30 min daily for 6 days a week during 10 weeks , with either 30 % ( Group 1 ) or 10 % ( Group 2 ) of peak maximal inspiratory pressure ( PI , max ) as a training load . Exercise performance was evaluated by the distance walked in 6 min ( 6MWD ) and by changes in oxygen consumption ( V'O2 ) and minute ventilation ( V'E ) during a progressive exercise test . Changes in PI , max and dyspnoea were also measured . Results showed a significant increment in peak PI , max in both groups , whereas dyspnoea and 6MWD improved only in Group 1 ( p<0.05 and p<0.01 , respectively ) . No increment in maximal workload or in peak V'O2 was observed in either group . Patients in Group 1 , however , showed a reduction in V'E and V'O2 for the same exercise . A correlation between changes in V'E and V'O2 during a workload of 75 kpm x min(-1 ) was observed in Group 1 ( r=0.92 ; p<0.001 ) . We conclude that inspiratory muscle training using a load of 30 % peak maximal inspiratory pressure , improves dyspnoea , increases walking capacity and reduces the metabolic cost of exercise Background : The data on cost savings with disease management ( DM ) in chronic obstructive pulmonary disease ( COPD ) is limited . A multicomponent DM program in COPD has recently shown in a large r and omized controlled trial to reduce hospitalizations and emergency department visits compared to usual care ( UC ) . The objectives of this study were to determine the cost of implementing the DM program and its impact on healthcare re source utilization costs compared to UC in high-risk COPD patients . Material s and Methods : This study was a post-hoc economic analysis of a multicenter r and omized , adjudicator-blinded , controlled , 1-year trial comparing DM and UC at 5 Midwest region Department of Veterans Affairs ( VA ) medical centers . Health-care costs ( hospitalizations , ED visits , respiratory medications , and the cost of the DM intervention ) were compared in the COPD DM intervention and UC groups . Results : The composite outcome for all hospitalizations or ED visits were 27 % lower in the DM group ( 123.8 mean events per 100 patient-years ) compared to the UC group ( 170.5 mean events per 100 patient-years ) ( rate ratio 0.73 ; 0.56–0.90 ; p < 0.003 ) . The cost of the DM intervention was $ 241,620 or $ 650 per patient . The total mean ± SD per patient cost that included the cost of DM in the DM group was 4491 ± 4678 compared to $ 5084 ± 5060 representing a $ 593 per patient cost savings for the DM program . Conclusions : The DM intervention program in this study was unique for producing an average cost savings of $ 593 per patient after paying for the cost of DM intervention A pilot study was set up to assess the long-term effects of once weekly versus once monthly follow-up of pulmonary rehabilitation after a comprehensive home rehabilitation program on physical performance in patients with chronic obstructive pulmonary disease ( COPD ) during an 18-mo period . Thirty-six patients with a mean FEV1 of 1.3 + /- 0.4 L ( 43 % pred ) were included in the study . Groups A and B ( n = 23 ) visited the physical therapist twice weekly for 3 mo . Thereafter , 11 patients ( Group A ) had a follow-up of pulmonary rehabilitation once a week , and 12 patients ( Group B ) had a follow-up once a month . Thirteen patients received no rehabilitation at all ( Group C ) . Long-term home rehabilitation does not appear to improve exercise tolerance ; however , on the other h and , there is a deterioration in vital capacity ( p < 0.01 ) , walking distance ( p < 0.01 ) , and maximal work load ( p < 0.05 ) , as shown in the control group . A small improvement in exertional dyspnea ( p < 0.01 ) after 18 mo and inspiratory muscle function ( p < 0.05 ) after 12 mo was shown only in Group A. Because of the insufficient number of patients enrolled in this pilot study , no clear benefit on physical performance of long-term home rehabilitation with either weekly or monthly supervision could be demonstrated In patients with chronic obstructive pulmonary disease ( COPD ) the intensity of aerobic training is limited by dyspnea . Improving strength of the inspiratory muscles could enhance aerobic exercise training by reducing exercise-related dyspnea . We examined effects of home-based inspiratory muscle training ( IMT ) and cycle ergometry training ( CET ) in 53 patients with moderate to severe COPD ( FEV(1)% pred , 50 + /- 17 [ mean + /- SD ] ) . Patients were r and omly assigned to 4 mo of training in one of four groups : IMT , CET , CET + IMT , or health education ( ED ) . Patients were encouraged to train to the limits of their dyspnea . Inspiratory muscle strength and endurance increased in IMT and CET + IMT groups compared with CET and ED groups ( p < 0 . 01 ) . Peak oxygen uptake increased and heart rate , minute ventilation , dyspnea , and leg fatigue decreased at submaximal work rates in the CET and CET + IMT groups compared with the IMT and ED groups ( p < 0 . 01 ) . There were no differences between the CET and CET + IMT groups . Home-based CET produced a physiological training effect and reduced exercise-related symptoms while IMT increased respiratory muscle strength and endurance . The combination of CET and IMT did not produce additional benefits in exercise performance and exercise-related symptoms . This is the first study to demonstrate a physiological training effect with home-based exercise training Little is known about effects of community-based physiotherapeutic exercise programmes incorporated in COPD self-management programmes . In a r and omised trial , the effect of such a programme ( COPE-active ) on exercise capacity and various secondary outcomes including daily activity as a marker of behaviour change was evaluated . All patients attended four 2-h self-management sessions . In addition the intervention group participated in the COPE-active programme offered by physiotherapists of private practice s , consisting of a 6-month " compulsory " period ( 3 sessions/week ) and subsequently a 5-month " optional " period ( 2 sessions/week ) . Because COPE-active was intended to change behaviour with regard to exercise , one session/week in both periods consisted of unsupervised home-based exercise training . Of 153 patients , 74 intervention and 68 control patients completed the one-year follow-up . Statistically significant between-group differences in incremental shuttle walk test-distance ( 35.1 m ; 95 % CI ( 8.4 ; 61.8 ) ) and daily activity ( 1190 steps/day ; 95 % CI ( 256 ; 2125 ) ) were found in favour of the intervention group . Over the 12-month period a significant difference of the chronic respiratory question naire ( CRQ ) dyspnoea-score ( 0.33 points ; 95 % CI ( 0.01 ; 0.64 ) ) and a non-significant difference of the endurance shuttle walk test ( 135 m ( 95 % CI ( -29 ; 298 ) ) was found . No differences were found in the other CRQ-components , anxiety and depression scores and percentage of fat free mass . This study demonstrates that a community-based reactivation programme improves exercise capacity in patients with moderately to severe COPD . Even more important , the programme improves actual daily activity after one-year which indicates behaviour change with regard to daily exercise . Registered trail number : IS RCT N81447311 The purpose of this study was to analyze the effects of a home exercise program on physical work capacity and dyspnea during activities of daily living in patients with severe chronic obstructive pulmonary disease . Twenty patients with severe respiratory impairment were assigned in a stratified , r and om manner to an Exercise Group ( n = 10 ) or a Control Group ( n = 10 ) . Patients in the Exercise Group performed the supervised home exercise program of daily mobility , strengthening , and endurance exercises . Patients in the Control Group were visited regularly by a physical therapist but did not follow the exercise program . Six patients were eliminated from the study , either because of death ( n = 1 ) or noncompliance with experimental conditions ( n = 5 ) , leaving each group with seven patients . The results of a progressive bicycle ergometer test after 18 weeks showed a significant between-group difference in physical work capacity . The physical work capacity of patients in the Exercise Group had improved 3 % and had deteriorated 28 % for patients in the Control Group ( p less than .05 ) . The symptom-limited multistage step test and the Chronic Respiratory Disease Question naire showed no difference in the patients ' physical work capacity or dyspnea during ADL . Although not conclusive , this study yielded some evidence for the beneficial effects of home exercise training on patients with severe chronic obstructive pulmonary disease BACKGROUND Respiratory muscle endurance training ( hyperpnea training ) has been shown to have beneficial effects in patients with COPD . STUDY OBJECTIVES The purpose of this study was to determine whether hyperpnea training , when added to an endurance exercise training program , would lead to additional benefits compared with endurance training alone in patients with COPD . SETTING AND PARTICIPANTS Patients with COPD entering an 8-week outpatient pulmonary rehabilitation program . Fifteen patients ( mean [ + /- SE ] FEV1 , 45 + /- 6 % predicted ) were r and omized to combined therapy , and 14 patients ( mean FEV1 , 44 + /- 4 % predicted ) were r and omized to endurance training . METHODS Peak exercise capacity , exercise endurance time during constant workload cycle exercise , 6-min walk distance , quality of life as measured by the chronic respiratory question naire , respiratory muscle strength and endurance , and quadriceps fatigability were measured before and after endurance or combined training . RESULTS After rehabilitation , peak exercise capacity , exercise endurance time , 6-min walk distance , and quality of life all increased in both groups , but there was no significant difference in the extent of improvement between groups . Mean respiratory muscle endurance increased to a significantly greater extent in the combined therapy group ( 17.5 + /- 2.7 vs 8.5 + /- 2.5 min , respectively ; p = 0.02 ) . Respiratory muscle strength was significantly increased , and quadriceps fatigability was significantly reduced after rehabilitation in the combined therapy group but not in the endurance training group , but the difference between groups did not reach statistical significance . CONCLUSION The endurance of the respiratory muscles can be improved by specific training beyond that achieved by endurance training alone in patients with COPD . However , this improvement did not translate into additional improvement in quality of life or exercise performance PURPOSE Pulmonary rehabilitation programs are effective in patients with severe chronic obstructive pulmonary disease ( COPD ) in the short term , but their long-term effects are not known . We investigated the short- and long-term effects of a 6-month outpatient rehabilitation program in patients with severe COPD . SUBJECTS AND METHODS One hundred patients were r and omly assigned to receive either an exercise training program that included cycling , walking , and strength training ( n = 50 ) or usual medical care ( n = 50 ) . Thirty-four patients in the training group were evaluated after 6 months ( end of training ) , and 26 were evaluated after 18 months of follow-up . In the control group , 28 patients were evaluated at 6 months and 23 after 18 months . We measured pulmonary function , 6-minute walking distance , maximal exercise capacity , peripheral and respiratory muscle strength , and quality of life ( on a 20 to 140-point scale ) , and estimated the cost-effectiveness of the program . RESULTS At 6 months , the training group showed improvement in 6-minute walking distance [ mean difference ( training - control ) of 52 m ; 95 % confidence interval ( CI ) , 15 to 89 m ] , maximal work load ( 12 W ; 95 % CI , 6 to 19 W ) , maximal oxygen uptake ( 0.26 liters/min ; 95 % CI , 0.07 to 0.45 liters/min ) , quadriceps force ( 18 Nm ; 95 % CI , 7 to 29 Nm ) , inspiratory muscle force ( 11 cm H(2)O ; 95 % CI , 3 to 20 cm H(2)O ) , and quality of life ( 14 points ; 95 % CI , 6 to 21 points ; all P < 0.05 ) . At 18 months all these differences persisted ( P < 0.05 ) , except for inspiratory muscle strength . For 6-minute walking distance and quality of life , the differences between the training group and controls at 18 months exceeded the minimal clinical ly-important difference . CONCLUSION Among patients who completed the 6-month program , outpatient training result ed in significant and clinical ly relevant changes in 6-minute walking distance , maximal exercise performance , peripheral and respiratory muscle strength , and quality of life . Most of these effects persisted 18 months after starting the program BACKGROUND Current guidelines on pulmonary rehabilitation ( PR ) recommend upper extremity exercise training ( UEET ) in patients with COPD . However , the literature still questions the effectiveness of systematic UEET in this population . We studied the effects of 15 sessions of unsupported UEET on functional exercise capacity , the ability to perform activities of daily living ( ADL ) , and symptoms perceived during activities involving arms in patients with COPD . METHODS We conducted a r and omized trial that consisted of 3 weeks of inpatient PR , comparing the short-term effects of unsupported UEET plus PR ( intervention group ) to those of PR alone ( control group ) . A change in the 6-min ring test ( 6MRT ) was the primary outcome ; the ADL field test ( four shuttle stations ) , the dyspnea score as assessed by the Medical Research Council scale , the London Chest Activity of Daily Living scale ( LCADL ) , and the distance walked in 6 min served as secondary outcomes of the study . At the 6-month follow-up , we repeated the 6MRT and the LCADL . RESULTS Fifty patients with COPD were r and omly assigned to the two groups and completed the study . At the end of the study period , patients in the intervention group improved in the 6MRT and ADL field test compared with those patients in the control group ( p = 0.018 and p = 0.010 , respectively ) with reduced perception of fatigue ( p < or= 0.006 ) . At the 6-month follow-up , 6MRT ( p = 0.001 ) and LCADL ( p = 0.039 ) scores were still significantly better in the intervention group compared with the control group . CONCLUSIONS Our trial corroborates the effectiveness of unsupported UEET in specifically improving functional exercise capacity of patients with COPD . Moreover , it also provides evidence that this training modality may ameliorate and maintain the patients ' autonomy over and above st and ard PR . TRIAL REGISTRATION Clinical Trials.gov Identifier : NCT00825032 This study reports the costs associated with rehabilitation among participants in the National Emphysema Treatment Trial ( NETT ) , and evaluates factors associated with adherence to rehabilitation . Pulmonary rehabilitation is recommended for moderate-to-severe COPD and required by the Centers for Medicare and Medicaid Services ( CMS ) prior to lung volume reduction surgery ( LVRS ) . Between January 1998 and July 2002 , 1,218 subjects with emphysema and severe airflow limitation ( FEV1 ≤ 45 % predicted ) were r and omized . Primary outcome measures were design ated as mortality and maximal exercise capacity 2 years after r and omization . Pre-r and omization , estimated mean total cost per patient of rehabilitation was $ 2,218 ( SD $ 314 ; 2006 dollars ) for the medical group and $ 2,187 ( SD $ 304 ) for the surgical group . Post-r and omization , mean cost per patient in the medical and surgical groups was $ 766 and $ 962 respectively . Among patients who attended ≥ 1 post-r and omization rehabilitation session , LVRS patients , patients with an FEV1 ≥ 20 % predicted , and higher education were significantly more likely to complete rehabilitation . Patients with depressive and anxiety symptoms , and those who live > 36 miles compared to < 6 miles away were less likely to be adherent . Patients who underwent LVRS completed more exercise sessions than those in the medical group and were more likely to be adherent with post-r and omization rehabilitation . A better underst and ing of patient factors such as socioeconomic status , depression , anxiety and transportation issues may improve adherence to pulmonary rehabilitation This study aim ed to investigate the effects of weekly singings classes on pulmonary function parameters and quality of life ( QoL ) of COPD patients . Forty-three patients were r and omized to weekly classes of singing practice , or h and craft work . They performed spirometry and completed maximal respiratory pressure measurements , evaluations of dyspnea , and the Saint George ’s Respiratory Question naire , before and after 24 training classes . A functional evaluation , immediately after 10 minutes of singing practice , was also performed at the end of the study . Fifteen subjects completed the study in each group . In comparison to controls the singing group exhibited transitory elevations on the dyspnea Borg scale ( p = 0.02 ) , and inspiratory capacity ( p = 0.01 ) , and decreases of expiratory reserve volume ( p = 0.03 ) , just after a short session of singing . There was a significant difference on changes of maximal expiratory pressures in the comparison between groups at the end of training . While the control group showed deterioration of maximal expiratory pressure , the singing group exhibited a small improvement ( p = 0.05 ) . Both groups showed significant improvements of QoL in within group comparisons . We have concluded that singing classes are a well tolerated activity for selected subjects with COPD . Regular practice of singing may improve QoL , and preserve the maximal expiratory pressure of these patients This study examined whether cognitive behavioural therapy ( CBT ) could prevent the development or worsening of panic-spectrum psychopathology and anxiety symptoms in chronic obstructive pulmonary disease ( COPD ) . 41 patients with COPD , who had undergone pulmonary rehabilitation , were r and omised to either a four-session CBT intervention condition ( n = 21 ) or a routine care condition ( n = 20 ) . Assessment s were at baseline , post-intervention , and at 6- , 12- and 18-month follow-ups . Primary outcomes were the rates of panic attacks , panic disorder and anxiety symptoms . Secondary outcomes were depressive symptoms , catastrophic cognitions about breathing difficulties , disease-specific quality of life and hospital admission rates . There were no significant differences between the groups on outcome measures at baseline . By the 18-month follow-up assessment , 12 ( 60 % ) routine care group participants had experienced at least one panic attack in the previous 6 months , with two ( 17 % ) of these being diagnosed with panic disorder , while no CBT group participants experienced any panic attacks during the follow-up phase . There were also significant reductions in anxiety symptoms and catastrophic cognitions in the CBT group at all three follow-ups and a lower number of hospital admissions between the 6- and 12-month follow-ups . The study provides evidence that a brief , specifically targeted CBT intervention can treat panic attacks in COPD patients and prevent the development and worsening of panic-spectrum psychopathology and anxiety symptoms BACKGROUND Chronic obstructive pulmomary disease ( COPD ) is associated with substantial mortality , morbidity , and costs to the health care system . With the increasing interest in outreach care programmes it is important to evaluate their impact upon patients and health services , for conditions such as COPD . AIM To determine the effectiveness of an outreach respiratory nurse in a shared care approach , with collaboration between general practitioners and hospital services , in the management of patients with severe COPD . METHODS Patients with severe COPD attending The Queen Elizabeth Hospital , Adelaide participated in a r and omised controlled trial of a home based nursing intervention ( HBNI ) over 12 months with outcome measures including mortality rate , hospital service utilisation , FEV1 and health related quality of life ( HRQL ) using a modified Dartmouth Primary Care Co-operative Quality of Life question naire . RESULTS There were 48 subjects in each study arm , with no differences in mortality rate ( eight deaths in the HBNI group and seven in the control group ) , hospital admissions , length of stay , number of outpatient and Emergency Service visits . The study had inadequate follow-up of FEV1 and HRQL within the control group . Within the HBNI group , a small improvement in HRQL ( in three of ten indices measured ) was demonstrated , despite a deterioration in FEV1 ( 11 % reduction , p=0.04 ) compared to baseline . Quality of life of HBNI subjects ' carers did not change . CONCLUSION An increased level of care given by an outreach respiratory nurse in a shared care approach for patients with severe COPD produced small improvements in HRQL but did not result in the prevention of deaths or reduced health care utilisation STUDY OBJECTIVES To compare the effectiveness of two forms of exercise training in pulmonary rehabilitation . DESIGN A prospect i ve , r and omized , unblinded , 8-week trial . SETTING A hospital-based outpatient pulmonary rehabilitation program . PATIENTS Forty patients ( 20 patients in each group ) with COPD who were referred for pulmonary rehabilitation . INTERVENTIONS We compared the short-term effectiveness of a high-intensity , lower-extremity endurance program with a low-intensity , multicomponent calisthenics program for the rehabilitation of patients with COPD . The high-intensity group trained predominately on the stationary bicycle and treadmill , with a goal of exercising at > or = 80 % of maximal level determined from incremental testing for 30 min per session . The low-intensity group performed predominately classroom exercises for approximately 30 min per session . For both groups , twice-weekly sessions were held for 8 weeks . The primary outcome measure was health status , measured using the Chronic Respiratory Disease Question naire . Other outcomes included peak oxygen consumption on incremental treadmill exercise testing , exertional dyspnea , treadmill endurance time , the number of sit-to-st and repetitions and arm lifts in 1 min , overall dyspnea , and question naire-rated functional status . MEASUREMENTS AND RESULTS Both groups showed significant postrehabilitation improvement in exercise variables , exertional and overall dyspnea , functional performance , and health status . Patients in the high-intensity group showed greater increases in treadmill endurance and greater reductions in exertional dyspnea , whereas those in the low-intensity group showed greater increases in arm-endurance testing . Both groups had similar improvements in overall dyspnea , functional performance , and health status . CONCLUSIONS Despite differences in exercise performance , both high-intensity , lower-extremity endurance training and low-intensity calisthenics led to similar short-term improvements in question naire-rated dyspnea , functional performance , and health status BACKGROUND Dyspnea is a common complaint during daily activities in patients with advanced COPD . The mechanisms underlying dyspnea and the appropriate treatment strategies to relieve it are still not totally understood . We hypothesized that the perception of dyspnea ( POD ) may be modified by the accumulative effect of bronchodilator therapy , exercise , and inspiratory muscle training ( IMT ) . METHODS Spirometry , submaximal exercise performance , inspiratory muscle strength and endurance , and the POD were assessed before and following three consecutive 6-week periods of therapy with a long-acting bronchodilator ( LABD ) , the LABD plus exercise , and the LABD plus exercise plus IMT in 30 patients with moderate-to-severe COPD . RESULTS There was a small , statistically insignificant , increase in FEV(1 ) in the study group ( mean [ + /- SEM ] increase , 1.42+/-0.3 to 1.49+/-0.4 L ) following the LABD therapy period , and no additional increase following the two other periods of therapy . There was a significant increase ( p<0.05 ) in the 6-min walk distance following the therapy period with the LABD plus exercise ( mean increase , 252+/-41 to 294+/-47 m ) and an additional small increase following the therapy period with the LABD plus exercise plus IMT period ( mean increase , 252+/-41 to 302+/-49 m ) . The decrease in the POD was small and statistically not significant following the therapy periods with the LABD and the LABD plus exercise . The major and statistically significant decrease in the POD was noted following the therapy period with the LABD plus exercise plus IMT . CONCLUSIONS In patients with moderate-to-severe COPD , following sequential periods of therapy with the LABD , the LABD plus exercise , and the LABD plus exercise plus IMT , there is a cumulative benefit in the POD . The most significant improvement was associated with IMT and not with the LABD and exercise training . The FEV(1 ) was moderately increased following the therapy period with the LABD , and the addition of exercise has most affected the 6-min walk distance Underst and ing of what constitutes a training load adequate to induce training effects in patients with chronic obstructive pulmonary disease ( COPD ) is still evolving . The present study investigated whether interval training ( IT ) is effective in terms of inducing measurable improvements in physiological response and compared its effects on exercise tolerance ( ET ) and quality of life to those of continuous training ( CT ) . Thirty-six COPD patients , with a forced expiratory volume in one second of 45±4 % of the predicted value ( mean±sem ) , were r and omly assigned to CT ( exercise at 50 % of baseline peak work-rate ) or IT ( work for 30 s at 100 % of peak work-rate alternating with 30‐s rest intervals ) groups that cycled 40 min·day−1 and 2 days·week−1 for 12 weeks . After training , both groups showed significantly improved ET ( IT , 57±6 to 71±8 W ; CT , 57±5 to 70±6 W ) and total quality -of-life score of the Chronic Respiratory Disease Question naire ( IT , 77±3 to 88±2 ; CT , 78±3 to 93±2 ) . At identical levels of exercise , minute ventilation was significantly reduced ( IT , 35.8±2.5 to 31.7±2.5 L·min−1 ; CT , 36.4±2.7 to 32.5±2.7 L·min−1 ) . The magnitude of improvement in these variables was not significantly different among groups . The present data exp and on the principles of exercise prescription for chronic obstructive pulmonary disease patients by demonstrating that interval training elicits substantial training effects , which are similar in magnitude to those produced by continuous training at half the exercise intensity but double the exercise time The effects of two 8 week programmes of reconditioning in chronic obstructive pulmonary disease ( COPD ) patients were studied . Forty one subjects ( mean+/-SD ) 644.5 ) yrs ; forced expiratory volume in one second ( FEV1 ) 1.09+/-0.16 L ; 40.6+/-6.2 % predicted were r and omly assigned either to supervised training on a treadmill , 4 days x week(-1 ) ( group S ; n=21 ) or walking 3 or 4 km in 1 h 4 days x week(-1 ) , self-monitored with a pedometer , with weekly visits to encourage adherence ( group SM ; n=20 ) . Patients were evaluated with the chronic respiratory diseases question naire ( CRQ ) and two exercise tests on a treadmill : incremental ( IT ) and constant ( CT ) , above lactic threshold or 70 % of maximal oxygen uptake ( VO2 , max ) with arterial blood lactate determinations . Estimated mean work rate of training was 69+/-27 W and 25+/-5 W respectively for groups S and SM . Both types of training produced similar changes in the four dimensions of the CRQ . In group S reconditioning yielded significant ( p<0.05 ) increases in VO2 , max and increases in duration , with decreased lactate accumulation , ventilation , CO2 output ( VCO2 ) , heart rate ( HR ) and diastolic blood pressure ( DBP ) at the end of CT . They also adopted a deeper slower pattern of breathing during exercise . The SM group showed significant ( p<0.05 ) increases in duration , lower HR and DBP at the end of CT . Significantly ( p<0.05 ) different effects between S and SM programmes were changes in VO2 , max 100+/-101 mL x min(-1 ) versus 5+/-101 mL x min(-1 ) ) , duration of the CT ( 8.1+/-4.4 min versus 3.9+/-4.7 min ) , VCO2 ( -94+/-153 mL x min(-1 ) versus 48+/-252 mL x min(-1 ) ) , lactate accumulation ( -1.3+/-2.2 mmol x L(-1 ) versus 0+/-1.2 mmol x L(-1 ) and respiratory rate at the end of CT ( 4.3+/-3.4 min(-1 ) versus -1+/-4.2 min(-1 ) ) . Supervised , intense training yields physiological improvements in severe chronic obstructive pulmonary disease patients not induced by self-monitored training . The self-monitored , less intense training , increases submaximal exercise endurance , although to a lesser degree Background People with chronic obstructive pulmonary disease ( COPD ) continue to experience dyspnea with activities of daily living ( ADL ) despite optimal medical management . Information and communication technologies may facilitate collaborative symptom management and could potentially increase the reach of such interventions to those who are unable to attend face-to-face pulmonary rehabilitation or self-management programs . Objective The purpose of this r and omized study was to test the efficacy of two 6-month dyspnea self-management programs , Internet-based ( eDSMP ) and face-to-face ( fDSMP ) , on dyspnea with ADL in people living with COPD . Methods We r and omly assigned 50 participants with moderate to severe COPD who were current Internet users to either the eDSMP ( n = 26 ) or fDSMP ( n = 24 ) group . The content of the two programs was similar , focusing on education , skills training , and ongoing support for dyspnea self-management , including independent exercise . The only difference was the mode ( Internet/personal digital assistant [ PDA ] or face-to-face ) in which the education sessions , reinforcement contacts , and peer interactions took place . Participants returned to one of two academic clinical sites for evaluation at 3 and 6 months . The primary outcome of dyspnea with ADL was measured with the Chronic Respiratory Question naire . Secondary outcomes of exercise behavior , exercise performance , COPD exacerbations , and mediators , such as self-efficacy and social support , were also measured . A satisfaction survey was administered and a semistructured exit interview was conducted at the final visit . Results The study was stopped early due to multiple technical challenges with the eDSMP , but follow-up was completed on all enrolled participants . Data were available for 39 participants who completed the study ( female : 44 % ; age : 69.5 ± 8.5 years ; percent predicted forced expiratory volume in 1 s : 49.6 ± 17.0 % ) . The fDSMP and eDSMP showed similar clinical ly meaningful changes in dyspnea with ADL from baseline to 3 months ( fDSMP : + 3.3 points ; eDSMP : + 3.5 points ) and sustained these improvements at 6 months ( fDSMP : + 4.0 points ; eDSMP : + 2.5 points ; time effects P < .001 ; group by time P = .51 ) . Self-reported endurance exercise time ( P = .001 ) , physical functioning ( P = .04 ) , and self-efficacy for managing dyspnea ( P = .02 ) also showed positive improvements over time in both groups with no significant differences with respect to program modality . Participants who completed the study reported favorable satisfaction with the programs . Conclusions Although there were numerous technical challenges with the eDSMP , both dyspnea self-management programs were effective in reducing dyspnea with ADL in the short term . Our findings will need to be confirmed in a larger r and omized trial with more mature Web and personal digital assistant tools , use of a control group , and longer follow-up . Trial registration clinical trials.gov NCT00102401 , The effects of endurance training on exercise capacity and health-related quality of life ( HRQL ) in chronic obstructive pulmonary disease ( COPD ) patients have been studied thoroughly , while resistance training has been rarely evaluated . This study investigated the effects of resistance training in comparison with endurance training in patients with moderate to severe COPD and peripheral muscle weakness ( isometric knee extension peak torque < 75 % predicted ) . Forty-eight patients ( age 64±8 yrs , forced expiratory volume in one second 38±17 % pred ) were r and omly assigned to resistance training ( RT , n=24 ) or endurance training ( ET , n=24 ) . The former consisted of dynamic strengthening exercises . The latter consisted of walking , cycling and arm cranking . Respiratory and peripheral muscle force , exercise capacity , and HRQL were re-evaluated in all patients who completed the 12-week rehabilitation ( RT n=14 , ET n=16 ) . Statistically significant increases in knee extension peak torque ( RT 20±21 % , ET 42±21 % ) , maximal knee flexion force ( RT 31±39 % , ET 28±37 % ) , elbow flexion force ( RT 24±19 % , ET 33±25 % ) , 6-min walking distance ( 6MWD ) ( RT 79±74 m , ET 95±57 m ) , maximum workload ( RT 15±16 Watt , ET 14±13 Watt ) and HRQL ( RT 16±25 points , ET 16±15 points ) were observed . No significant differences in changes in HRQL and 6MWD were seen between the two treatments . Resistance training and endurance training have similar effects on peripheral muscle force , exercise capacity and health-related quality of life in chronic obstructive pulmonary disease patients with peripheral muscle weakness The purpose of this study was to investigate the effects on activities of daily living , quality of life , and exercise tolerance of a comprehensive out-patient rehabilitation programme for patients with moderate-to-severe chronic obstructive pulmonary disease . In this r and omized and controlled trial , the main outcome measures were Activities of Daily Living ( ADL ) score , York Quality of Life Question naire ( YQLQ ) score , Chronic Respiratory Disease Question naire ( CRDQ ) score , 6 min walking distance ( 6MWD ) , forced expiratory volume in one second ( FEV1 ) , and forced vital capacity ( FVC ) . The rehabilitation programme included physical training , occupational therapy , education , and smoking cessation therapy , and lasted for 12 weeks . The patients were evaluated at entry , halfway through , and at the end of the programme . Follow-up was at 24 weeks . Forty seven patients were recruited , and 16 in each group completed the trial . There were significant differences in the improvements in ADL and CRDQ between the control and the treatment groups at 12 and 24 weeks , and at 24 weeks , respectively . At 6 , 12 and 24 weeks , improvements in the 6MWD were 21.6 versus 79.8 , 36.1 versus 113.1 and 21.4 versus 96.2 for control and treatment groups , respectively ( p<0.004 ) . A correlation matrix showed only ADL and 6MWD to be significantly correlated ; the matrix was also used to vali date the translated question naires . The programme required 124 staff-hours in total . An inexpensive , comprehensive out-patient rehabilitation programme can produce long-term improvement in activities of daily living , quality of life , and exercise tolerance in patients with moderate-to-severe chronic obstructive pulmonary disease Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease ( COPD ) . Men with COPD have high prevalence of low testosterone levels , which may contribute to muscle weakness . We determined effects of testosterone supplementation ( 100 mg of testosterone enanthate injected weekly ) with or without resistance training ( 45 minutes three times weekly ) on body composition and muscle function in 47 men with COPD ( mean FEV(1 ) = 40 % predicted ) and low testosterone levels ( mean = 320 ng/dl ) . Subjects were r and omized to 10 weeks of placebo injections + no training , testosterone injections + no training , placebo injections + resistance training , or testosterone injections + resistance training . Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration ( to the middle of the normal range for young men ) . The lean body mass ( by dual-energy X-ray absorptiometry ) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training ( p < 0.001 ) . Increase in one-repetition maximum leg press strength averaged 17.2 % with testosterone alone , 17.4 % with resistance training alone , and 26.8 % with testosterone + resistance training ( p < 0.001 ) . Interventions were well tolerated with no abnormalities in safety measures . Further studies are required to determine long-term benefits of adding testosterone supplementation and resistance training to rehabilitative programs for carefully screened men with COPD and low testosterone levels The aim of this study was to assess the effects of a comprehensive self-management intervention on health-related quality of life ( HRQoL ) , symptoms and walking distance in patients with stable moderately severe chronic obstructive pulmonary disease ( COPD ) . This study was part of the overall COPD study of the Dept of Pulmonary Medicine , Enschede , which consisted of an inhaled corticosteroid ( ICS ) trial and a self-management trial . After the ICS trial , all patients were r and omised again to a self-management and a control group . The self-management intervention consisted of askill-oriented patient education programme and a near-home fitness programme , on top of usual care . The control group received usual care by the treating chest physician . HRQoL was measured by the St George ’s Respiratory Question naire ( SGRQ ) and walking distance by the 6‐min walking test . Patients recorded their symptoms in diaries and grade d their health status from 1–10 in a weekly report . Altogether , 248 COPD patients were r and omly allocated to either an intervention ( 127 ) or control ( 121 ) group . No differences in the SGRQ scores within and between both groups were observed over 1 yr . Similarly , no differences in symptom scores and 6‐min walking distance were found within and between groups . The intervention group reported more exacerbations than the control group . The majority ( 69 % ) of the exacerbations in the intervention group were self-treated at home . This study failed to show positive effects of a self-management programme among moderately severe chronic obstructive pulmonary disease patients OBJECTIVE This pilot study investigated whether a home exercise video programme could improve exercise tolerance and breathlessness in patients with moderate to severe chronic obstructive pulmonary disease . METHODS Twenty subjects completed the study after being r and omized to intervention or control . The intervention group ( n=10 ) , watched a 19-min video on the benefits of exercise for patients with chronic obstructive pulmonary disease and were given a 30-min exercise video , an illustrated exercise diary and an educational booklet about chronic obstructive pulmonary disease , for use at home . They were advised to follow the exercise video programme 4 times a week for 6 weeks . The control group ( n=10 ) received the chronic obstructive pulmonary disease educational booklet only . Exercise tolerance was measured using the Incremental Shuttle Walk Test and breathlessness by the self-reported Chronic Respiratory Question naire . RESULTS The median change in the Incremental Shuttle Walk Test and breathlessness score significantly improved in the intervention group compared with the control ( + 45 m vs -15 m , p=0.013 and + 0.5 vs -0.1 Chronic Respiratory Question naire units , p=0.042 ) . The other findings for the self-reported Chronic Respiratory Question naire showed significant improvements in the intervention group for emotion ( p<0.001 ) and fatigue ( p=0.012 ) , but not mastery ( p=0.253 ) . CONCLUSION This pilot study suggests that participation in a home exercise video programme may benefit people with chronic obstructive pulmonary disease Background In patients with COPD progressive dyspnoea leads to a sedentary lifestyle . To date , no studies exist investigating the effects of Nordic Walking in patients with COPD . Therefore , the aim was to determine the feasibility of Nordic Walking in COPD patients at different disease stages . Furthermore we aim ed to determine the short- and long-term effects of Nordic Walking on COPD patients ' daily physical activity pattern as well as on patients exercise capacity . Methods Sixty COPD patients were r and omised to either Nordic Walking or to a control group . Patients of the Nordic Walking group ( n = 30 ; age : 62 ± 9 years ; FEV1 : 48 ± 19 % predicted ) underwent a three-month outdoor Nordic Walking exercise program consisting of one hour walking at 75 % of their initial maximum heart rate three times per week , whereas controls had no exercise intervention . Primary endpoint : daily physical activities ( measured by a vali date d tri-axial accelerometer ) ; secondary endpoint : functional exercise capacity ( measured by the six-minute walking distance ; 6MWD ) . Assessment time points in both groups : baseline , after three , six and nine months . Results After three month training period , in the Nordic Walking group time spent walking and st and ing as well as intensity of walking increased ( Δ walking time : + 14.9 ± 1.9 min/day ; Δ st and ing time : + 129 ± 26 min/day ; Δ movement intensity : + 0.40 ± 0.14 m/s2 ) while time spent sitting decreased ( Δ sitting time : -128 ± 15 min/day ) compared to baseline ( all : p < 0.01 ) as well as compared to controls ( all : p < 0.01 ) . Furthermore , 6MWD significantly increased compared to baseline ( Δ 6MWD : + 79 ± 28 meters ) as well as compared to controls ( both : p < 0.01 ) . These significant improvements were sustained six and nine months after baseline . In contrast , controls showed unchanged daily physical activities and 6MWD compared to baseline for all time points . Conclusions Nordic Walking is a feasible , simple and effective physical training modality in COPD . In addition , Nordic Walking has proven to positively impact the daily physical activity pattern of COPD patients under short- and long-term observation . Clinical trial registration Nordic Walking improves daily physical activities in COPD : a r and omised controlled trial - IS RCT Self-management strategies improve a variety of health-related outcomes for patients with chronic obstructive pulmonary disease ( COPD ) . These strategies , however , are primarily design ed to improve chronic disease management and have not focused on early detection and early treatment of exacerbations . In COPD , the majority of exacerbations go unreported and treatment is frequently delayed , result ing in worsened outcomes . Therefore , a r and omised clinical trial was design ed to determine whether integration of self-management education with proactive remote disease monitoring would improve health-related outcomes . A total of 40 Global Initiative for Chronic Obstructive Lung Disease stage 3 or 4 COPD patients were r and omised to receive proactive integrated care ( PIC ) or usual care ( UC ) over a 3-month period . The primary and secondary outcomes were change in quality of life , measured by the St George ’s Respiratory Question naire ( SGRQ ) , and change in healthcare costs . PIC dramatically improved SGRQ by 10.3 units , compared to 0.6 units in the UC group . Healthcare costs declined in the PIC group by US$ 1,401 , compared with an increase of US$ 1,709 in the UC group , but this was not statistically significant . PIC uncovered nine exacerbations , seven of which were unreported . Therefore , proactive integrated care has the potential to improve outcomes in chronic obstructive pulmonary disease patients through effects of self-management , as well as early detection and treatment of exacerbations The study aim ed to estimate the cost-effectiveness of interdisciplinary community-based chronic obstructive pulmonary disease ( COPD ) management in patients with COPD . We conducted a cost-effectiveness analysis alongside a 2-yr r and omised controlled trial , in which 199 patients with less advanced airflow obstruction and impaired exercise capacity were assigned to the INTERCOM programme or usual care . The INTERCOM programme consisted of exercise training , education , nutritional therapy and smoking cessation counselling offered by community-based physiotherapists and dieticians and hospital-based respiratory nurses . All-cause re source use during 2 yrs was obtained by self-report and from hospital and pharmacy records . Health outcomes were the St George 's Respiratory Question naire ( SGRQ ) , exacerbations and quality -adjusted life years ( QALYs ) . The INTERCOM group had 30 % ( 95 % CI 3–56 % ) more patients with a clinical ly relevant improvement in SGRQ total score , 0.08 ( 95 % CI -0.01–0.18 ) more QALYs per patient , but a higher mean number of exacerbations , 0.84 ( 95 % CI -0.07–1.78 ) . Mean total 2-yr costs were € 2,751 ( 95 % CI -€632–€6,372 ) higher for INTERCOM than for usual care , which result ed in an incremental cost-effectiveness ratio of € 9,078 per additional patient with a relevant improvement in SGRQ or € 32,425 per QALY . INTERCOM significantly improved disease-specific quality of life , but did not affect exacerbation rate . The cost per QALY ratio was moderate , but within the range of that generally considered to be acceptable The aim of this study was to determine if weekly , supervised , outpatient-based exercise plus unsupervised home exercise following an 8-week pulmonary rehabilitation programme would maintain functional exercise capacity and quality of life at 12 months better than st and ard care of unsupervised home exercise training . Chronic obstructive pulmonary disease ( COPD ) subjects completed an 8-week pulmonary rehabilitation programme , were r and omised to an intervention group ( IG ) of weekly , supervised , exercise plus home exercise or to a control group ( CG ) of unsupervised home exercise and followed for 12 months . Outcome measurements at baseline ( after pulmonary rehabilitation ) , and 3 , 6 and 12 months included the 6-min walk test and St George 's Respiratory Question naire ( SGRQ ) . 59 subjects with moderate COPD ( Global Initiative for Chronic Obstructive Lung Disease stage II ) were recruited and 48 subjects completed the study . 12-month mean difference showed no significant change from baseline in 6-min walk distance ( IG -11 m , 95 % CI -21–10 m ; CG -6 m , 95 % CI -34–11 m ) or total SGRQ score ( IG 3 , 95 % CI -0.8–7 ; CG -3 , 95 % CI -7–3 ) . 12 months following pulmonary rehabilitation both weekly , supervised , outpatient-based exercise plus unsupervised home exercise and st and ard care of unsupervised home exercise successfully maintained 6-min walk distance and quality of life in subjects with moderate COPD STUDY OBJECTIVE To assess the effect of pulmonary rehabilitation ( PR ) on psychosocial morbidity , functional exercise capacity , and health-related quality of life ( HRQL ) in patients with severe COPD . DESIGN A prospect i ve , r and omized , controlled trial with blinding of outcome assessment and data analysis . SETTING A tertiary-care respiratory service . PATIENTS Forty patients ( mean age , 65 + /- 8 years [ + /- SD ] ) with severe chronic flow limitation ( FEV(1 ) , 35 + /- 13 % ) without respiratory failure ( Pao(2 ) , 72 + /- 9 mm Hg ; Paco(2 ) , 42 + /- 5 mm Hg ) were r and omized either to a control group or to a PR group ( PRG ) . INTERVENTIONS Sixteen weeks of PR that included breathing retraining and exercise . MEASUREMENTS At baseline and 16 weeks , we evaluated psychosocial morbidity using two question naires ( the Millon Behavior Health Inventory [ MBHI ] and the Revised Symptom Checklist [ SCL-90-R ] ) and measured 6-min walk distance ( 6WMD ) and HRQL using the Chronic Respiratory Question naire ( CRQ ) . RESULTS We found differences in favor of the PRG in the following MBHI domains : introversive , forceful , and sensitive personality styles ( all p < /= 0.05 ) and chronic tension ( p < /= 0.01 ) . Results of the depression , hostility , global severity , positive symptom distress index ( all p < /= 0.01 ) , somatization , anxiety , psychoticism , and positive symptom ( all p < /= 0.05 ) domains of the SCL-90-R favored the PRG . We also found statistically and clinical ly significant differences between groups in 6MWD ( 85 m ; p < 0.01 ) and in two domains of the CRQ : dyspnea ( 1.0 ; p < 0.01 ) and mastery ( 0.6 ; p < 0.05 ) . The other two domains of CRQ showed strong trends in favor of PRG : 0.7 for both fatigue and emotional function ( minimal important difference , 0.5 ) . CONCLUSIONS PR may decrease psychosocial morbidity in COPD patients even when no specific psychological intervention is performed . Findings from this study also confirm the positive impact of PR on functional exercise capacity and HRQL Background Despite optimal pharmacological therapy and pulmonary rehabilitation , patients with COPD continue to be breathless . There is a need to develop additional strategies to alleviate symptoms . Learning to sing requires control of breathing and posture and might have benefits that translate into daily life . Methods To test this hypothesis we performed a r and omised controlled trial , comparing a six week course of twice weekly singing classes to usual care , in 28 COPD patients . The experience of singing was assessed in a qualitative fashion , through interviews with a psychologist . In addition , we surveyed patients with chronic respiratory conditions who participated in a series of open singing workshops . Results In the RCT , the physical component score of the SF36 improved in the singers ( n = 15 ) compared to the controls ( n = 13 ) ; + 7.5(14.6 ) vs. -3.8(8.4 ) p = 0.02 . Singers also had a significant fall in HAD anxiety score ; -1.1(2.7 ) vs. + 0.8(1.7 ) p = 0.03 . Singing did not improve single breath counting , breath hold time or shuttle walk distance . In the qualitative element , 8 patients from the singing group were interviewed . Positive effects on physical sensation , general well-being , community/social support and achievement/efficacy emerged as common themes . 150 participants in open workshops completed a question naire . 96 % rated the workshops as " very enjoyable " and 98 % thought the workshop had taught them something about breathing in a different way . 81 % of attendees felt a " marked physical difference " after the workshop . ConclusionS inging classes can improve quality of life measures and anxiety and are viewed as a very positive experience by patients with respiratory disease ; no adverse consequences of participation were observed . Trial Registration Current Controlled Trials - IS RCT N17544114 OBJECTIVES This study aims to compare the impact of two different sources of re source use , self-report versus care provider registration s , on cost and cost utility . METHODS Data were gathered for a cost-effectiveness study performed alongside a 2-year r and omized controlled trial evaluating the effect of an INTERdisciplinary COMmunity-based management program ( INTERCOM ) for patients with chronic obstructive pulmonary disease ( COPD ) . The program was offered by physiotherapists , dieticians and respiratory nurses . During the 2-year period , patients reported all re source use in a cost booklet . In addition , data on hospital admissions and outpatient visits , visits to the physiotherapist , dietician or respiratory nurse , diet nutrition , and outpatient medication were obtained from administrative records . The cost per quality -adjusted life-year ( QALY ) was calculated in two ways , using data from the cost booklet or registration s. RESULTS In total , 175 patients were included in the study . Agreement between self-report and registration s was almost perfect for hospitalizations ( rho = 0.93 ) and physiotherapist visits ( rho = 0.86 ) , but above 0.55 , moderate , for all other types of care . The total cost difference between the registration s and the cost booklet was 464 euros with the highest difference for hospitalizations 386 euro . Based on the cost booklet the cost difference between the treatment group and usual care was 2,444 euros ( 95 percent confidence interval [ CI ] , -819 to 5,950 ) , which result ed in a cost-utility of 29,100 euro/QALY . For the registration s , the results were 2,498 euros ( 95 percent CI , -88 to 6,084 ) and 29,390 euro/QALY , respectively . CONCLUSIONS This study showed that the use of self-reported data or data from registration s effected within-group costs , but not between-group costs or the cost utility Seventy five patients with chronic respiratory disability were r and omised to a group visited by a respiratory health worker ( 42 ) or control group ( 33 ) . The first group was visited monthly by a respiratory nurse , who gave education and support . The effect of the intervention was assessed in terms of quality of life ( by question naires ) , the number and duration of admissions to hospital , and the number of deaths . The question naires on quality of life showed no changes in either group during the study , but nearly all of the group visited by a respiratory health worker said that they valued the visits and wished them to continue . Their knowledge about their condition also improved compared with that of the controls . The duration of stay in hospital for respiratory reasons in the group visited by a respiratory health worker was longer than that of control patients . This was explained by their being scored as more ill than the controls on admission . Fewer patients died in the group visited by a respiratory health worker than in the control group ( p = 0.11 ) . The patients in the group visited by respiratory health workers may have survived longer because they sought help rather than dying at home . If confirmed this could have implication s for the cost of their care Pursed lips breathing ( PLB ) training is often used in the management of patients with chronic obstructive lung disease ( COLD ) . Previous clinical studies have demonstrated that PLB improves arterial oxygen saturation ( SaO2 ) and CO2 removal as well as relieving dyspnea . Twelve hypoxemic subjects with stable COLD were r and omly assigned to either the pursed lips ( P ) or control group consisting of general relaxation ( R ) . The SaO2 was monitored via ear oximetry , and respiratory rate and tidal volume were monitored using a strain gage transducer and the minute volume was calculated . The PLB was taught by an experienced instructor using the ear oximeter as a monitoring display with a goal toward increasing SaO2 . The subject was taught general relaxation ( Rlx ) with the aid of pleasant music . We compared PLB and Rlx treatments using an A-B-A crossover study design . In both groups , PLB significantly improved SaO2 over baseline ( p less than 0.001 ) whereas Rlx did not . We conclude that patients can learn to increase their SaO2 by PLB using ear oximetry adjunctively PURPOSE A diminished mechanical efficiency ( work/O2 consumed ) accompanies chronic obstructive pulmonary disease ( COPD ) , and increased mechanical efficiency has been attained by maximal strength training ( MST ) with an emphasis on the maximal rate of force mobilization in the concentric phase in healthy subjects . This study combined these observations and evaluated the impact of short-term MST on patients with COPD . METHODS Twelve patients with COPD ( FEV1 = 1.1 + /- 0.1 ) were pretested and then r and omly assigned to either an MST group ( N = 6 ) or a normal activity control group ( N = 6 ) . Within each MST training session ( three times per week for 8 wk ) , patients performed four sets of seated leg presses with a focus on the rate of force development at an intensity that only allowed the performance of five repetitions . RESULTS Patients who performed MST significantly improved their rate of force development ( 105 + /- 22.8 % ) , mechanical efficiency ( 32 + /- 7 % ) , and FEV1 ( 21.5 + /- 6.8 % ) , whereas these variables were unchanged in the controls . Neither group changed either peak oxygen consumption ( VO2peak ) or body mass . CONCLUSION In combination with the observed improvement in FEV1 , these data certainly support the therapeutic role for MST in the treatment of COPD Cycle ergometer training plays an important role in the rehabilitation of patients with chronic obstructive pulmonary disease ( COPD ) , but the usefulness of specific inspiratory muscle training as part of pulmonary rehabilitation remains uncertain . To determine whether inspiratory muscle training could intensify the known beneficial effects of cycle ergometer training on exercise performance in these patients , we compared the effect of an 8 week inspiratory muscle training combined with cycle ergometer training with that of an 8 week cycle ergometer training alone on inspiratory muscle performance and general exercise capacity . Patients were r and omly assigned to the two training groups ; 21 patients received additional inspiratory muscle training ( Group 1 ) and 21 did not ( Group 2 ) . Maximal sniff assessed oesophageal and transdiaphragmatic pressures served as parameters for global inspiratory muscle strength and diaphragmatic strength , respectively . The duration for which the patient could breathe against a constant inspiratory pressure load was used as an index of inspiratory muscle endurance . Exercise capacity was determined by an incremental symptom-limited cycle ergometer test . After the training period , inspiratory muscle performance improved significantly in the patients with inspiratory muscle training , but not in those without . Both training regimens increased maximal power output and oxygen uptake , but this improvement was significantly greater in the patients with inspiratory muscle training than in those without . ( ABSTRACT TRUNCATED AT 250 WORDS Background : The effectiveness of pulmonary rehabilitation in advanced COPD is well established , but few data are available in less advanced disease . Methods : In a 2 year r and omised controlled trial , 199 patients with an average moderate airflow obstruction but impaired exercise capacity ( mean ( SD ) forced expiratory volume in 1 s ( FEV1 ) 60 (16)% , peak work load ( Wmax ) < 70 % ) were r and omised to the INTERdisciplinary COMmunity-based COPD management programme ( INTERCOM ) or usual care . Intervention consisted of 4 months multidisciplinary rehabilitation followed by a 20-month maintenance phase . Outcomes ( 4 , 12 , 24 months ) : health-related quality of life ( St George ’s Respiratory Question naire ( SGRQ ) ) , exacerbation frequency , MRC dyspnoea score , cycle endurance time ( CET ) , 6-minute walking distance ( 6MWD ) , skeletal muscle strength and patients ’ and caregivers ’ perceived effectiveness . Results : Between-group comparison after 4 months revealed the following mean ( SE ) significant differences in favour of INTERCOM : SGRQ total score 4.06 ( 1.39 ) , p = 0.004 ; activity and impact subscores , p<0.01 ; MRC score 0.33 ( 0.13 ) , p = 0.01 ; Wmax 6.0 ( 2.3 ) Watt , p = 0.02 ; CET 221 ( 104 ) s , p = 0.04 ; 6MWD 13 ( 6 ) m , p = 0.02 ; h and grip force 4.3 ( 1.5 ) lb , p<0.01 ; and fat-free mass index 0.34 ( 0.13 ) kg/m2 , p = 0.01 . Between-group differences over 2 years were as follows : SGRQ 2.60 ( 1.3 ) , p = 0.04 ; MRC score 0.21 ( 0.10 ) , p = 0.048 ; CET 253 ( 104 ) s , p = 0.0156 ; 6MWD 18 ( 8) m , p = 0.0155 . Exacerbation frequency was not different ( RR 1.29 ( 95 % CI 0.89 to 1.87 ) ) . Patients ’ and caregivers ’ perceived effectiveness significantly favoured the INTERCOM programme ( p<0.01 ) . Conclusions : This study shows that a multidisciplinary community-based disease management programme is also effective in patients with COPD with exercise impairment but less advanced airflow obstruction . Trial registration number : The purpose of this study was to examine the effects of two postrehabilitation programmes on functional exercise tolerance and health-related quality of life in patients with chronic obstructive pulmonary disease ( COPD ) . Subjects with COPD ( n=109 ) were r and omised to receive either enhanced follow-up ( EF ) or conventional follow-up ( CF ) . Subjects in the EF group attended a monthly support group and received a telephone call from a staff member at the midpoint ( 2 weeks ) between their visits . Both groups had scheduled appointments with a physical therapist and physician at 3‐monthly intervals after discharge . Longitudinal data were recorded in 85 subjects ( 37 EF and 48 CF ) . Over the course of the study , there was no difference in distance walked in 6 min between the two groups but a significant difference for time and a group-time interaction . There was no difference in total chronic respiratory disease question naire score between groups at baseline or at any time interval despite a significant difference with time . There was a clear deterioration in functional exercise capacity and health-related quality of life after completion of respiratory rehabilitation but no difference between the groups Inspiratory muscle training may have beneficial effects in certain patients with chronic obstructive pulmonary disease ( COPD ) . Because of the lack of a home training device , normocapnic hyperpnea has rarely been used as a training mode for patients with COPD , and is generally considered unsuitable to large-scale application . To study the effects of hyperpnea training , we r and omized 30 patients with COPD and ventilatory limitation to respiratory muscle training ( RMT ; n = 15 ) with a new portable device or to breathing exercises with an incentive spirometer ( controls ; n = 15 ) . Both groups trained twice daily for 15 min for 5 d per week for 8 wk . Training-induced changes were significantly greater in the RMT than in the control group for the following variables : respiratory muscle endurance measured through sustained ventilation ( + 825 + /- 170 s [ mean + /- SEM ] versus -27 + /- 61 s , p < 0.001 ) , inspiratory muscle endurance measured through incremental inspiratory threshold loading ( + 58 + /- 10 g versus + 21.7 + /- 9.5 g , p = 0.016 ) , maximal expiratory pressure ( + 20 + /- 7 cm H(2)O versus -6 + /- 6 cm H(2)O , p = 0.009 ) , 6-min walking distance ( + 58 + /- 11 m versus + 11 + /- 11 m , p = 0.002 ) , V O(2peak ) ( + 2.5 + /- 0.6 ml/kg/min versus -0.3 + /- 0.9 ml/kg/min , p = 0.015 ) , and the SF-12 physical component score ( + 9.9 + /- 2.7 versus + 1.8 + /- 2.4 , p = 0.03 ) . Changes in dyspnea , maximal inspiratory pressure , treadmill endurance , and the SF-12 mental component score did not differ significantly between the RMT and control groups . In conclusion , home-based respiratory muscle endurance training with the new device used in this study is feasible and has beneficial effects in subjects with COPD and ventilatory limitation BACKGROUND Previous studies have used electrical neuromuscular stimulation as a physical training method in patients with severe COPD . We introduce the use of the more tolerable magnetic stimulation for the same purpose , investigating the effectiveness of an eight-week protocol . METHODS Eighteen patients with severe COPD were r and omly assigned to a magnetic stimulation training protocol , n=10 , FEV(1)=30 % ( SD : 7 ) or to parallel clinical monitoring , control group , n=8 , FEV(1)=35 % ( SD : 8) . During eight weeks , patients were stimulated for 15min on each quadriceps femoris , three times per week . Quadriceps muscle strength and endurance measurements , quality -of-life question naires ( SF36 , SGRQ ) and a six-minute walking test were all carried out before and after the training period in the stimulated and control subjects . RESULTS All patients completed the training with increasing intensity of stimulation , displaying a significant improvement in voluntary quadriceps strength ( 17.5 % of the baseline value ) and exercise capacity , with a mean increase of 23 m in the six-minute walking test . The question naire scores showed greater increases in quality -of-life scores in the trained subjects compared to the controls , particularly in the physical function areas : mean increments in SF36 in " physical function " : + 26 , " role limitations due to physical problems " : + 40 and " vitality " : + 17.5 , while + 13 , -4 and + 1 , respectively in controls . Saint George 's " Activity " score improved by 19.6 points , for 11.5 in controls . CONCLUSIONS In COPD patients who are limited due to dyspnoea , magnetic neuromuscular stimulation of the quadriceps constitutes a feasible training method for the lower limbs , with positive effects on the muscle function , effort capacity and perception areas BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is an illness that affects patients on multiple levels , both physically and psychologically . While there is a growing body of evidence for the efficacy of self-management among patients with COPD , little evidence is available on the optimal content and methods for delivering self-management support . AIMS The purpose of this study was to address gaps in the literature on self-management support by examining patients ' responses to questions about goals , needs , and expectations regarding self-management using qualitative methods in a broadly representative sample of patients with moderate to severe COPD . By focusing on patients ' perceptions of their needs , we hoped to guide development of cognitive-behavioural interventions for self-management support . METHODS Patients > 45 years of age with a physician diagnosis of COPD were recruited as part of a larger r and omised controlled trial design ed to determine the effectiveness of a lifestyle behavioural intervention to increase physical activity . In-depth interviews were conducted at baseline data collection using 10 st and ardised open-ended questions tailored to examine factors relevant to self-management support including concerns , fears , learning needs , barriers , facilitators , and goals . All interviews were audio recorded and analysed using qualitative methods . Responses were coded by three raters into thematic categories . RESULTS A sample of 47 interviews with patients of mean age 68.4 years , 53 % male , 87 % white were used in the analysis . The distribution of spirometric impairment based on percent predicted forced expiratory volume in 1 second ( FEV1 ) was moderate ( 57.5 % ) , severe ( 31.9 % ) , and very severe ( 10.6 % ) . In response to questions targeting needs and goals for care , three main themes ( loss , fear , and desire for improved care ) and seven associated sub-themes were identified . Because of breathlessness and fatigue as well as symptoms from conditions other than COPD , patients reported the loss of ability to participate in pleasurable and necessary activities of daily living and the desire to recover at least some of their functioning . They expressed problems with social isolation and uncertainty about their prognosis , as well as the hope to improve . In addition , fearful experiences associated with uncontrolled breathlessness and a wish for greater underst and ing and knowledge about treatment were major concerns . CONCLUSIONS These qualitative results suggest that the content of self-management support for patients with COPD should focus on addressing patients ' fears associated with the uncertainty , progression , and suffering of their disease , their expectations about overcoming or replacing losses , their needs for improved health literacy and their desire for improved care . These responses indicate areas where cognitive-behavioural intervention should focus in order to enhance patient self-efficacy , motivation , and behavioural change for improved self-management & NA ; The purpose of this study was to compare the effects of a strength training‐enhanced program and a traditional pulmonary rehabilitation ( PR ) program on functional fitness ( FF ) in older patients with chronic obstructive pulmonary disease ( COPD ) , using the Senior Fitness Test . Twenty patients were recruited from an outpatient PR program . After completing baseline measures , including muscular strength and the Senior Fitness Test , patients were r and omly assigned to the strength training program ( TR+ST , n = 10 ) or traditional PR program ( TR , n = 10 ) . Patients completed 16 exercise sessions that were conducted twice a week for 8–10 weeks , after which patients repeated outcome measurements . Independent t tests were conducted to determine whether groups differed between measures . Both the TR+ST and TR groups improved on all FF measures . Moderate effect sizes were found for two of the FF measures when the groups were compared . The addition of strength training to PR may have a favorable impact on FF in older patients with COPD OBJECTIVE To determine the safety and usefulness of a home-based pulmonary rehabilitation program for patients with very severe chronic obstructive pulmonary disease ( COPD ) who receive long-term treatment with oxygen . METHODS A r and omized prospect i ve study that included 50 patients with very severe COPD undergoing long-term treatment with oxygen . At the start of the program and after 12 months , the following evaluations were performed : pulmonary function tests , submaximal exercise capability , and quality of life . The rehabilitation program lasted for 1 year , with periodic home visits by a physiotherapist and included respiratory reeducation training of the respiratory muscles and muscular training . RESULTS Forty-two patients completed the study ( 27 in the rehabilitation group and 15 in the control group ) . There were no initial differences between the 2 groups . No complications arising from the performance of the exercises were observed . The rehabilitation group showed a clinical ly significant increase in the distance covered in the 6-minute walk test ( 313 ± 72 m vs 392 ± 82 m , P = .0001 ) and a clinical ly significant reduction in the St George 's Respiratory Question naire score ( 55.3 ± 15.0 vs 40.5 ± 13.8 , P = .0001 ) . No significant changes were found in any of the parameters studied in the control group . CONCLUSION A home-based pulmonary rehabilitation program for patients with very severe COPD under long-term oxygen treatment is safe and useful , as it achieves an improvement in exercise tolerance , reduces dyspnea after effort , and improves quality of life without causing any complication arising from the performance of the exercises Disability and exertional dyspnea associated with chronic obstructive pulmonary disease has led to the development of rehabilitation programmes that aim to increase exercise tolerance and relief of dyspnea . To evaluate whether aerobic training ( training groups P1 and P4 ) , strength training ( P2 and P5 ) or a combination of both ( P4 and P6 ) is useful , 69 patients ( 44 m/25 f ) with moderate to severe COPD were r and omised to a three week inpatient training program . The training consisted of three weekly twenty minute exercise sessions without ( P1 - P3 ) or with supplemental oxygen ( P4 - P6 ) on a calibrated ergocycle ( 70 % W(max ) ) or three weekly sessions of 20 - 25 repetitions of 2 - 4 training series ( 40 % W(max ) ) or a combination of both . In general , the programme failed to demonstrate significant changes in lung function and arterial blood gases . Evaluation of exercise capacity via the six-minute-walking test ( 6MT ) yielded a significant increase of the walking distance in all groups except P2 ( 60 - 83 m ) , The time to finish a test-set of daily activities ( TAF ) was reduced in all groups ( 5 - 58 sec ) and reached significance in P1 , P3 , P5 and P6 . After the 6MT , exertional dyspnea improved in all groups except P4 and was significant in P1 and P3 ; after the TAF , dyspnea again was reduced in all groups with a significant change in P2 and P5 . These data support the hypotheses that a short term inpatient training programme is suitable to improve exercise-capacity and dyspnea . Patients with advanced disease ( P4 - P6 ) show greater benefits with strength training ( alone or in combination with aerobic training ) while for patients with moderate disease ( P1 - P3 ) aerobic training is favourable . These changes may translate into improved performance of daily activities and general well-being PURPOSE To compare the effects of short-term ( 3 months ) and long-term ( 18 months ) involvement in an exercise program on self-reported disability and physical function in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS A total of 140 patients with COPD were studied in a r and omized , single-blinded clinical trial . Self-reported disability and physical function were assessed using a 21-item question naire , a 6-minute walk , timed stair climb , and an overhead task . RESULTS At the completion of the trial , participants in the long-term intervention reported 12 % less disability than those in the short-term intervention ( adjusted mean with 95 % confidence interval , 1.53 ( 1.43 - 1.63 ) versus 1.71 ( 1.61 to 1.81 ) units , respectively ; P=.016 ) , walked 6 % farther during 6-minutes ( 1,815.0 [ 1,750.4 - 1,879.6 ] vs 1,711.5 [ 1,640.7 - 1,782.3 ] feet , respectively ) , climbed steps 11 % faster ( 11.6 [ 11.0 - 12.2 ] vs 12.9 [ 12.3 - 13.5 ] seconds , respectively ) , and completed an overhead task 8 % faster ( 46.8 [ 44.4 - 49.2 ] vs 50.4 [ 47.8 - 53.0 ] seconds , respectively ) than those in the short-term intervention . CONCLUSION An 18 month exercise program results in greater improvements in self-reported disability and physical function in patients with COPD when compared with a 3-month exercise program . As such , long-term exercise should be recommended for all patients with COPD PURPOSE The objective of this study was to compare the effectiveness of a short-term pulmonary rehabilitation program with brief advice given to patients with severe ventilatory impairment due to chronic obstructive pulmonary disease ( COPD ) . METHODS One hundred three patients with severe COPD , defined as having forced expiratory volume in 1 second < 40 % predicted , were r and omly assigned to rehabilitation or to brief advice . Fifty-four patients attended a rehabilitation program twice a week for 6 weeks . Forty-nine patients attended a single session during which they were given printed educational material s and verbal advice and guidance about exercise . Subjects were reassessed at 3 months . RESULTS The shuttle walking distance increased significantly in the rehabilitation group by 43 meters . The increase of 23 meters in the brief advice group was significantly less than in the rehabilitation group . Improvements in quality of life in the rehabilitation group were small and not clinical ly significant . CONCLUSIONS In these patients with severe COPD , a short outpatient rehabilitation program of low intensity achieved small but significant improvement in shuttle walking distance , compared with brief advice . The improvements in quality of life were modest and did not reach statistical significance , although in some instances the confidence limits include differences that approach clinical significance . The relatively small effect may be due to the low intensity of the program or to the severity of the subjects ' ventilatory impairment Eighteen COPD patients enrolled in a comprehensive , multidisciplinary pulmonary rehabilitation program were r and omly assigned to perform either : 1 ) walking , or 2 ) ventilatory muscle exercise training ( VMT ) using a prototype , portable device for isocapnic hyperventilation training . Both groups performed exercise training at home . Twelve patients completed the study and follow-up evaluation ( five VMT , seven walkers ) . Pulmonary function did not change in either group . For the VMT patients , there were modest increases in ventilatory muscle endurance and exercise performance . VO2max and VEmax increased significantly . For the walkers , only walking endurance time increased significantly . These results indicate that isocapnic hyperventilation exercise training can be performed successfully by COPD patients in an unsupervised home setting and can lead to improvement in both ventilatory muscle endurance and exercise performance . Walking exercise training did not improve ventilatory muscle endurance Study objectives The aims of this study were to establish whether pulmonary rehabilitation ( PR ) improves domestic function and daily activity levels in COPD and whether individually targeted exercise is more effective than general exercise . Design Prospect i ve r and omized , controlled trial . Setting Outpatient PR program in secondary care . Participants One-hundred eighty patients ( mean [ ±SD ] age , 68.3 ± 8.6 years ; FEV 1 , 0.95 ± 0.4 L ; FEV 1 /FVC ratio , 0.51 ± 0.15 ; 111 male patients ; 69 female patients ) with stable COPD . One hundred twenty-one patients completed the study . Interventions Patients were r and omized to a conventional 7-week general exercise program ( [ GEP ] n=90 ) or an individually targeted exercise program ( [ ITEP ] n=90 ) . Measurement and results Daily activity was measured using ambulatory activity monitors ( Z80 –32k V1 Int ; Gaehwiler Electronics ; Hombrechtikon , Switzerl and ) . These were lightweight devices , which contained a uniaxial accelerometer . Domestic function was assessed by the Canadian Occupational Performance Measure ( COPM ) . Exercise performance was assessed by the incremental shuttle walk test ( ISWT ) and the endurance shuttle walk test and health status by the chronic respiratory question naire – self-reported . Activity monitor counts increased by 29.18 % ( 95 % confidence interval [ CI ] , 3.19 to 55.17 ; p=0.03 ) for the GEP and 40.63 % ( 95 % CI , 7.42 to 73.83 ; p=0.02 ) for the ITEP . Mean COPM performance scores increased by 1.71 ( 95 % CI , 1.37 to 2.05 ; p=0.0001 ) for the GEP and 1.46 ( 95 % CI , 1.05 to 1.87 ; p=0.0001 ) for the ITEP . Mean COPM satisfaction scores increased by 2.27 ( 95 % CI , 1.74 to 2.81 ; p=0.0001 ) for the GEP and 2.04 ( 95 % CI , 1.56 to 2.52 ; p=0.0001 ) for the ITEP . ISWT scores increased by 81.72 m ( range , 63.83 to 99.62 ) for the GEP and by 85.52 m ( range , 67.62 to 103.42 ) for the ITEP . No statistically significant difference was found between the general exercise group and the individually targeted exercise group for any outcome measure . Conclusions Pulmonary rehabilitation improves domestic function and physical activity . This study also demonstrates that general exercise training is as effective as individually targeted training We design ed a r and omized controlled study to evaluate the benefit of upper-limb exercise training , alone and in combination with walking training , in patients with severe CAO . In an outpatient department supervised by a physiotherapist , we evaluated 28 patients with severe stable CAO ( FEV1 , 32 percent of predicted ) . Patients were r and omly allocated to either a control ( eight ) , upper-limb ( six ) , lower-limb ( seven ) , or combined ( seven ) exercise group . The upper-limb group trained with a circuit of upper-limb exercises , the lower-limb group by walking , and the combined group with both . Exercise was for one hour three times per week for eight weeks . Assessment before and after training included pulmonary function , mouth pressures , respiratory muscle endurance , maximal bicycle exercise test , maximal and submaximal arm ergometer , six-minute walking distance , and a scale of well-being ( B and ura scale ) . Twenty-six patients completed the program . There was a significant improvement ( Wilcoxon rank sum test ) in the following : six-minute walking distance in the lower-limb ( p less than 0.005 ) and combined ( p less than 0.003 ) groups ; arm ergometer in the upper-limb ( p less than 0.005 ) and combined ( p less than 0.04 ) groups ; and the scale of well-being in the combined ( p less than 0.005 ) group . There was no significant change in any other parameter measured . We conclude that exercise training improves exercise performance in severe CAO , that the training is specific for the muscle group trained , and that upper-limb exercises should be included in training programs for these patients In most chronic obstructive pulmonary disease ( COPD ) patients , dyspnoea and functional exercise capacity may improve as a result of inspiratory muscle training ( IMT ) . However , the long-term benefits of IMT have been investigated to a much lesser extent . The present study investigated the short-term and long-term benefits of IMT on inspiratory muscle performance ( strength and endurance ) , exercise capacity and the perception of dyspnoea . Thirty-eight patients with significant COPD had 3 months of basic IMT and were then r and omised into a group that received maintenance IMT for the next year , and a group that got training with very low load . Following the basic training there was a statistically significant increase in inspiratory muscle performance , 6-min walk test ( 6MWT ) , and a decrease in the dyspnoea . During the second stage of the study , the training group continued to maintain the improvement in all parameters , while there was already deterioration in the inspiratory muscle performance , exercise capacity and dyspnoea in the low intensity group during the 6–12 month period . The present study concludes that , in patients with significant chronic obstructive pulmonary disease , inspiratory muscle training results in improvement in performance , exercise capacity and in the sensation of dyspnoea . The benefits of 12‐weeks of inspiratory muscle training decline gradually over 1 yr of follow-up if maintenance training is not performed While pulmonary rehabilitation is well established in the therapy for COPD ( chronic obstructive pulmonary disease ) , the effectiveness of isolated patient education programmes still remains unclear . The aim of this study was to evaluate the effectiveness of a COPD outpatient education programme ( ATEM ) . In a prospect i ve r and omised design , 50 patients ( 38 intervention , 12 control ) with mild to very severe COPD have been examined with respect to a variety of follow-up parameters . At the end of the follow-up period of 12 months , the data of 11 patients of the control group ( st and ard therapy ) and 30 patients of the intervention group ( additional participation in the education programme ) were analysed . At entry , the two groups showed a good comparability . Over the follow-up period only the education group showed a favourable course . The BODE index ( BMI , Obstruction , Dyspnea , Exercise capacity ) showed a significant improvement of 17 % for the education group , while the score for the patients of the control group was seen to deteriorate by about 39 % . The advantages of the intervention group were also apparent for the markers of morbidity , namely hospitalisation and the need for antibiotics . In conclusion , participation in the education programme ATEM seems to be able to improve exercise capacity and well being , as measured with the BODE index , as well as important markers of morbidity in patients with mild to very severe COPD The purpose of this study was to examine the effects of a home-based pulmonary rehabilitation program on lung function , dyspnea , exercise tolerance , and quality of life in 23 Koreans with moderate to severe chronic lung disease . The outcome measures were forced expiratory volume in 1s ( FEV1 , % predicted ) , Borg score , 6 min walking distance ( 6MWD ) , and chronic respiratory disease question naire ( CRDQ ) . Experimental group ( n=15 ) performed the 8-week home-based pulmonary rehabilitation program , composed of inspiratory muscle training , upper and lower extremity exercise , relaxation , and telephone visit . Patients in control group ( n=8 ) were only given educational advice . The experimental group showed a lower level of exertional dyspnea , more exercise tolerance , and greater improvement in health-related quality of life than the control group ( p<0.05 ) . Lung function was not statistically different . This study yielded evidence for the beneficial effects of home-based pulmonary rehabilitation program BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is an important clinical disease , and its global prevalence and mortality rates are high . It is meaningful to investigate the efficacy of integrative respiratory rehabilitation training in quality of life and respiratory physiology of COPD patients in stable phase . OBJECTIVE To observe the efficacy of integrative respiratory rehabilitation training in exercise ability and quality of life of COPD patients in stable phase . DESIGN , SETTING , PARTICIPANTS AND INTERVENTIONS Eighty out patients and in patients with COPD from Department of Respiratory Medicine , Taihe Hospital , Yunyang Medical College were r and omly divided into 4 groups , with 20 patients in each group . The patients in group A only received drug therapy , the patients in group B received traditional qigong training , the patients in group C received modern rehabilitation training , and the patients in group D received integrative respiratory rehabilitation training . MAIN OUTCOME MEASURES Chronic respiratory question naire ( CRQ ) , 6-minute walking distance and Borg score in each group were examined before and after one- , three- , and six-month and one-year treatment . RESULTS The 6-minute walking distance , Borg score and CRQ score in group A had no significant changes after treatment ( P>0.05 ) . After one-month treatment , there were no significant differences in 6-minute walking distance and Borg score in groups B , C and D as compared with those before treatment ( P<0.05 ) . After three-month treatment , 6-minute walking distance and Borg score were improved in groups B , C and D ( P<0.05 ) . After six-month and one-year treatment , 6-minute walking distance , Borg score and CRQ score in groups B , C and D were improved as compared with those before treatment ( P<0.05 ) , and there were significant differences between group D and any of groups A , B and C ( P<0.05 ) . CONCLUSION Modern rehabilitation training , traditional qigong training and integrative respiratory rehabilitation training programs all can improve the quality of life and exercise ability of COPD patients , and integrative respiratory rehabilitation training program is better than modern rehabilitation training and traditional qigong training programs . The efficacy of respiratory rehabilitation training is time-dependent , and need long-time adherence to the therapy OBJECTIVE To investigate the effects of a diaphragmatic breathing training program ( DBTP ) on thoracoabdominal motion and functional capacity in patients with chronic obstructive pulmonary disease . DESIGN A prospect i ve , r and omized controlled trial . SETTING Academic medical center . PARTICIPANTS Subjects ( N=30 ; forced expiratory volume in 1s , 42%±13 % predicted ) were r and omly allocated to either a training group ( TG ) or a control group ( CG ) . INTERVENTIONS Subjects in the TG completed a 4-week supervised DBTP ( 3 individualized weekly sessions ) , while those in the CG received their usual care . MAIN OUTCOME MEASURES Effectiveness was assessed by amplitude of the rib cage to abdominal motion ratio ( RC/ABD ratio ) ( primary outcome ) and diaphragmatic mobility ( secondary outcome ) . The RC/ABD ratio was measured using respiratory inductive plethysmography during voluntary diaphragmatic breathing and natural breathing . Diaphragmatic mobility was measured by ultrasonography . A 6-minute walk test and health-related quality of life were also evaluated . RESULTS Immediately after the 4-week DBTP , the TG showed a greater abdominal motion during natural breathing quantified by a reduction in the RC/ABD ratio when compared with the CG ( F=8.66 ; P<.001 ) . Abdominal motion during voluntary diaphragmatic breathing after the intervention was also greater in the TG than in the CG ( F=4.11 ; P<.05 ) . The TG showed greater diaphragmatic mobility after the 4-week DBTP than did the CG ( F=15.08 ; P<.001 ) . An improvement in the 6-minute walk test and in health-related quality of life was also observed in the TG . CONCLUSIONS DBTP for patients with chronic obstructive pulmonary disease induced increased diaphragm participation during natural breathing , result ing in an improvement in functional capacity Background : The optimal frequency of delivering a pulmonary rehabilitation program ( PR ) is not yet a well established issue . It is still unclear whether repeated PR at established intervals will result in effective maintenance or further improvement in the patient ’s health status . Objectives : To investigate whether more frequently repeated PR in patients with COPD ( 1 ) leads to similar short and long-term physiological gains , and ( 2 ) decreases the burden due to hospitalization . Methods : Thirty-five disabled COPD patients ( FEV1 below 50 % predicted , MRC score 3 ) in a stable state were studied in a r and omized controlled trial . After completing an initial inpatient PR program , they were r and omly assigned to either group 1 ( performing a second and a third PR after 6 and 12 months ) or group 2 ( performing only a second PR after 12 months ) . Results : Lung functions , exercise capacity ( by means of a timed walk test – 6MWT ) , peak-effort dyspnea ( D ) and leg fatigue ( F ) , and health-related quality of life by means of SGRQ were assessed prior to ( T1 , T3 , T5 ) and after ( T2 , T4 , T6 ) each PR program : the same measures were taken on an outpatient basis at T3 in group 2 . The number of hospital admissions ( HA ) and days spent in the hospital ( DH ) were also recorded over the year . The two groups did not differ in any parameter at baseline . 6MWD , D , F and SGRQ improved to the same level ( p = 0.05 ) after each PR in both groups . However , the baseline level of D , F and SGRQ symptoms and impact scores progressively improved over time in group 1 but not in group 2 . After 12 months , a larger amount of patients in Group 1 , as compared to Group 2 , reported H10 DH/year ( p < 0.0001 ) . Conclusions : In severe and disabled COPD , a more frequently repeated inpatient PR may lead to some additional physiological and clinical benefits over 1 year The effect of a stress management program on morbidity and psychosocial and physical function in patients with chronic lung disease was assessed . Adults attending either a VA pulmonary clinic or university hospital pulmonary rehabilitation clinic who met criteria for obstructive or restrictive pulmonary disease were r and omly assigned to receive the intervention or to a control group . The intervention was provided by a nurse and included one to three teaching sessions , reading material , audiotapes , and telephone follow-up . The program focused on stress management techniques such as cognitive restructuring , progressive relaxation , breathing exercises , and visual imagery . The 45 experimental subjects were similar to the 49 controls with respect to baseline characteristics . Experimental and control subjects had similar rates of mortality , hospital days , bed-disability days , restricted-activity days , and physician visits during the 12-month follow-up . There were no differences between the two groups in physical or psychosocial function at six months or in levels of stressful life changes , social supports , and self-esteem at six and 12 months . Intervention recipients had better function at 12 months , suggesting a possible benefit of the intervention PURPOSE Pulmonary rehabilitation programs often show beneficial effects in patients with chronic obstructive pulmonary disease ( COPD ) . These programs are usually hospital-based . This study assesses the feasibility and application of a 12-week Home-Care Rehabilitation Program ( HCRP ) , carried out by general practitioners , physiotherapists , and home-care nurses . METHODS Effects of the HCRP are assessed in 15 COPD patients with moderate to severe airflow limitation ( inspiratory vital capacity [ IVC ] : mean , 75.4 [ SD , 13.7 ] percent predicted , mean FEV1 : 45.5 [ 6.9 ] percent predicted ) and are compared with a stratified and r and omized control group ( n = 15 ) . RESULTS All participating disciplines judged the program to be useful and feasible . Patient compliance with the rehabilitation exercises was high . No major problems concerning the rehabilitation program were reported . After the HCRP , 4-minute walking distance improved significantly from 274 m [ 61 ] to 301 m [ 72 ] and maximal work load ( W max ) , as measured during an incremental cycle test , increased from 75.3 W [ 24 ] to 85.3 W [ 28 ] . At equal work levels ( W submax ) during the cycle test both Borg dyspnea and leg effort scores decreased significantly after the HCRP ( 6.7 [ 1.3 ] versus 4.9 [ 1.7 ] and 4.2 [ 2.0 ] versus 1.7 [ 2.5 ] , respectively ) . Changes in walking distance , dyspnea , and leg effort scores at W submax were significantly different between the two groups . IVC and FEV1 did not change significantly . In the control group , no significant changes in any parameter were observed . CONCLUSION It was possible to design and perform successfully a home-care rehabilitation program , providing both objective and subjective improvements in a group of patients with COPD . A home-care rehabilitation program appears to be a valuable component in the management of COPD patients with a moderate to severe airflow limitation OBJECTIVES Autonomic modulation is adversely impacted in patients with chronic obstructive pulmonary disease ( COPD ) . The purpose of the present investigation is to assess the effects of a 6-week aerobic exercise training program on autonomic modulation of heart rate in patients with COPD . METHODS Forty patients of both sexes with moderate-to-severe COPD were r and omly allocated to aerobic exercise training ( PT , n=20 ) or to usual care ( Control , n=20 ) . The training program consisted of lower and upper limb stretching and 30 min of treadmill exercise , 3 times per week for a 6-week period . Physiological data during symptom-limited exercise testing and the six-minute walk test ( 6MWT ) were assessed . In addition , R-R intervals were obtained at rest and during the 6MWT . Heart rate variability was analyzed by time ( rMSSD and SDNN index ) and frequency domains ( high frequency -- HF , low frequency -- LF and HF/LF ratio ) . RESULTS Peak oxygen consumption significantly improved in the training group only ( p<0.05 ) . Moreover , the training group demonstrated significant improvements ( p<0.05 ) in blood lactate , minute ventilation , dyspnea at peak exercise , sympathetic activity , and parasympathetic activity at rest and during submaximal exercise . Lastly , a positive and significant correlation was found between change in 6MWT distance and rMSSD index ( r=0.65 and p=0.001 ) . CONCLUSIONS Neural control of heart rate , in addition to other clinical ly valuable measures , is positively altered in moderate-severe COPD patients following 6 weeks of aerobic exercise training . The improvement in submaximal performance after exercise training was associated with parasympathetic activity CONTEXT The initial gain from a Pulmonary Rehabilitation Program ( PRP ) among patients with chronic obstructive pulmonary disease ( COPD ) begins to fade away 6 months after the completion of a rehabilitation program . One possible reason may be due to the poor compliance of the patients to the existing forms of home exercise program ( e.g. , walking , weight training activities , etc . ) . OBJECTIVES This study tested the efficacy of health qigong ( HQG ) , a traditional Chinese exercise , as an adjunct home exercise program in optimizing the gains obtained from PRP until 6 months after discharge . DESIGN This was a r and omized controlled trial ( RCT ) on a mind-body exercise intervention . PARTICIPANTS Eighty ( 80 ) patients with COPD receiving conventional PRP pulmonary rehabilitation program were r and omized to the HQG intervention group ( n = 40 ) and control group ( n = 40 ) . OUTCOME MEASURES Assessment s were undertaken by blinded assessors at baseline , discharge from training , and follow-up ( FU ) at 3 and 6 months . Primary outcomes involved functional capacity scales and secondary outcomes involved quality -of-life scales . RESULTS Intention-to-treat analysis identified trends of improvement in all outcome measures in the HQG group , whereas lesser improvement and trends of deteriorations were identified in the control group . Ancillary analysis using a per- protocol method , however , identified significantly better improvements in functional capacity measures among the HQG at the 6-month FU . CONCLUSIONS This RCT provided some evidence to support the positive effect of HQG as an adjunct home exercise for rehabilitation among people with COPD and to support further related research OBJECTIVE AND BACKGROUND COPD is a progressive disorder characterized by periodic exacerbations . While comprehensive self-management programmes decrease health-care re source utilization , the essential components are unclear . We performed a study of written action plans in the management of COPD . METHODOLOGY A r and omized , controlled , prospect i ve parallel-group study compared written action plans to usual practice . SUBJECTS Recruited from general practice s , received an educational intervention with or without an action plan , which usually emphasized prompt treatment with antibiotics and corticosteroids . Subjects were followed up 3-monthly for a year . RESULTS One hundred and thirty-nine participants , mean FEV(1 ) 45 + /- 16 % predicted , were recruited , 81 % completing the study . Both groups had a decline in lung function and physical activity , but increase in quality of life over the study period . Exacerbations were common . The intervention group was significantly more likely to have treatment with antibiotics ( chi(2 ) = 3.86 ; d.f . = 1 ; P = 0.05 ) or short course oral corticosteroids ( chi(2 ) = 14.25 ; d.f . = 1 ; P < 0.001 ) . No differences were found between the number of general practitioner consultations , attendances at emergency departments or hospitalizations . CONCLUSIONS The use of a written action plan in COPD increased appropriate therapeutic interventions for exacerbations , but this effect was not associated with a decrease in the use of health-care re sources RATIONALE The effect of disease management for chronic obstructive pulmonary disease ( COPD ) is not well established . OBJECTIVES To determine whether a simplified disease management program reduces hospital admissions and emergency department ( ED ) visits due to COPD . METHODS We performed a r and omized , adjudicator-blinded , controlled , 1-year trial at five Veterans Affairs medical centers of 743 patients with severe COPD and one or more of the following during the previous year : hospital admission or ED visit for COPD , chronic home oxygen use , or course of systemic corticosteroids for COPD . Control group patients received usual care . Intervention group patients received a single 1- to 1.5-hour education session , an action plan for self-treatment of exacerbations , and monthly follow-up calls from a case manager . MEASUREMENTS AND MAIN RESULTS We determined the combined number of COPD -related hospitalizations and ED visits per patient . Secondary outcomes included hospitalizations and ED visits for all causes , respiratory medication use , mortality , and change in Saint George 's Respiratory Question naire . After 1 year , the mean cumulative frequency of COPD -related hospitalizations and ED visits was 0.82 per patient in usual care and 0.48 per patient in disease management ( difference , 0.34 ; 95 % confidence interval , 0.15 - 0.52 ; P < 0.001 ) . Disease management reduced hospitalizations for cardiac or pulmonary conditions other than COPD by 49 % , hospitalizations for all causes by 28 % , and ED visits for all causes by 27 % ( P < 0.05 for all ) . CONCLUSIONS A relatively simple disease management program reduced hospitalizations and ED visits for COPD . Clinical trial registered with www . clinical trials.gov ( NCT00126776 ) BACKGROUND : The effects of different exercise training programs on the level of physical activity in daily life in patients with COPD remain to be investigated . OBJECTIVE : In patients with COPD we compared the effects of 2 exercise/training regimens ( a high-intensity whole-body endurance- and -strength program , and a low-intensity calisthenics- and -breathing-exercises program ) on physical activity in daily life , exercise capacity , muscle force , health-related quality of life , and functional status . METHODS : We r and omized 40 patients with COPD to perform either endurance- and -strength training ( no. = 20 , mean ± SD FEV1 40 ± 13 % of predicted ) at 60–75 % of maximum capacity , or calisthenics- and -breathing-exercises training ( no. = 20 , mean ± SD FEV1 39 ± 14 % of predicted ) . Both groups underwent 3 sessions per week for 12 weeks . Before and after the training programs the patients underwent activity monitoring with motion sensors , incremental cycle-ergometry , 6-min walk test , and peripheral-muscle-force test , and responded to question naires on health-related quality of life and functional status ( activities of daily living , pulmonary functional status , and dyspnea ) . RESULTS : Time spent active and energy expenditure in daily life were not significantly altered in either group . Exercise capacity and muscle force significantly improved only in the endurance- and -strength group . Health-related quality of life and functional status improved significantly in both groups . CONCLUSIONS : Neither training program significantly improved time spent active or energy expenditure in daily life . The training regimens similarly improved quality of life and functional status . Exercise capacity and muscle force significantly improved only in the high-intensity endurance- and -strength group This study tested the effect of two methods of training , one individualized at the heart rate corresponding to the gas exchange threshold ( GET ) and the other at the heart rate corresponding to 50 % of maximal heart rate reserve , on maximal and submaximal cardiorespiratory response in 24 patients with chronic airway limitation ( CAL ) . The patients were r and omly assigned to either the individualized training group ( IT ; n = 12 ) or the st and ardized training group ( ST ; n = 12 ) . The training programme consisted of 4 weeks of stationary bicycle exercise , 5 days.week-1 . Before reconditioning began , the target level based on heart rate was not significantly different between groups ( 109 + /- 4 versus 110 + /- 3 beats.min-1 , in IT and ST , respectively ) . Post-training , a significant increase in symptom-limited oxygen uptake ( V'O2.sl ) and maximal O2 pulse was found in IT , whereas ST exhibited no significant change . In each group , GET was statistically increased in much the same way as V'O2,sl , with a higher increase in IT ( p < 0.01 ) than ST ( p < 0.05 ) . Nevertheless , IT exhibited a concomitant and gradual decrease in minute ventilation ( V'E ) , carbon dioxide production ( V'CO2 ) , and venous lactate concentration ( [ La ] ) , whereas ST presented no significant change in these parameters ( intergroup p < 0.01 ) . Breathing pattern was also altered after IT , at the same metabolic level and at the same ventilation level ( intergroup p < 0.05 ) . Cardiac responses were modified in the two groups . At the same metabolic level , a significantly lower cardiac frequency was found both for IT and ST ( intragroup p < 0.05 after training ) . In contrast , the increase in O2 pulse was only significantly higher in It after training . These data show the greater efficiency of an individualized training protocol based on determination of gas exchange threshold as compared to a st and ardized protocol , in improving exercise performance , when applied to a patient group . Despite an apparently similar target training level , the individualized method clearly optimized the physiological training effects in patients with chronic airway limitation and , more particularly , decreased their ventilatory requirement The purpose of this study was to evaluate whether strength training is a useful addition to aerobic training in patients with chronic obstructive pulmonary disease ( COPD ) . Forty-five patients with moderate to severe COPD were r and omized to 12 wk of aerobic training alone ( AERO ) or combined with strength training ( AERO + ST ) . The AERO regimen consisted of three weekly 30-min exercise sessions on a calibrated ergocycle , and the ST regimen included three series of eight to 10 repetitions of four weight lifting exercises . Measurements of peripheral muscle strength , thigh muscle cross-sectional area ( MCSA ) by computed tomographic scanning , maximal exercise capacity , 6-min walking distance ( 6MWD ) , and quality of life with the chronic respiratory question naire were obtained at baseline and after training . Thirty-six patients completed the program and constituted the study group . The strength of the quadriceps femoris increased significantly in both groups ( p < 0.05 ) , but the improvement was greater in the AERO + ST group ( 20 + /- 12 % versus 8 + /- 10 % [ mean + /- SD ] in the AERO group , p < 0.005 ) . The thigh MCSA and strength of the pectoralis major muscle increased in the AERO + ST group by 8 + /- 13 % and 15 + /- 9 % , respectively ( p < 0.001 ) , but not in the AERO group ( 3 + /- 6 % and 2 + /- 10 % , respectively , p > 0.05 ) . These changes were significantly different in the two study groups ( p < 0.01 ) . The increase in strength of the latissimus dorsi muscle after training was modest and of similar magnitude for both groups . The changes in peak exercise work rate , 6MWD , and quality of life were comparable in the two groups . In conclusion , the addition of strength training to aerobic training in patients with COPD is associated with significantly greater increases in muscle strength and mass , but does not provide additional improvement in exercise capacity or quality of life Objective : To undertake a cost-utility analysis ( CUA ) of a pharmacy-led self-management programme for Chronic Obstructive Pulmonary Disease ( COPD ) . Setting : A single outpatient COPD clinic at the Mater Hospital , Belfast , Northern Irel and between . Method : CUA alongside a r and omised control trial . The economic analysis used data from 127 COPD patients aged over 45 years , with an FEV1 of 30–80 % of the predicted normal value . Participants received either a pharmacy-led education and self-management programme , or usual care . One year costs were estimated from the perspective of the National Health Service and Personal Social Services and quality -adjusted life years ( QALYs ) were calculated based on responses to the EQ-5D at baseline , 6 and 12 months . Main outcome measure : Cost per QALY gained . Results : The mean differences in costs and effects between the self-management and education programme and usual care were −£671.59 ( 95 CI% : −£1,584.73 to −£68.14 ) and 0.065 ( 95 % CI ; 0.000–0.128 ) . Thus the intervention was the dominant strategy as it was both less costly and more effective than usual care . The probability of the intervention being cost-effective was 95 % at a threshold of £ 20,000/QALY gained . Sensitivity analyses indicated that conclusions were robust to variations in most of the key parameters . Conclusion : The self-management and education programme was found to be highly cost-effective compared to usual care . Further research is required to establish what aspects of self-management and education programmes have the greatest impact on cost-effectiveness Objective To determine the effectiveness of an intervention to enhance self management support for patients with chronic conditions in UK primary care . Design Pragmatic , two arm , cluster r and omised controlled trial . Setting General practice s , serving a population in northwest Engl and with high levels of deprivation . Participants 5599 patients with a diagnosis of diabetes ( n=2546 ) , chronic obstructive pulmonary disease ( n=1634 ) , and irritable bowel syndrome ( n=1419 ) from 43 practice s ( 19 intervention and 22 control practice s ) . Intervention Practice level training in a whole systems approach to self management support . Practice s were trained to use a range of re sources : a tool to assess the support needs of patients , guidebooks on self management , and a web based directory of local self management re sources . Training facilitators were employed by the health management organisation . Main outcome measures Primary outcomes were shared decision making , self efficacy , and generic health related quality of life measured at 12 months . Secondary outcomes were general health , social or role limitations , energy and vitality , psychological wellbeing , self care activity , and enablement . Results We r and omised 44 practice s and recruited 5599 patients , representing 43 % of the eligible population on the practice lists . 4533 patients ( 81.0 % ) completed the six month follow-up and 4076 ( 72.8 % ) the 12 month follow-up . No statistically significant differences were found between patients attending trained practice s and those attending control practice s on any of the primary or secondary outcomes . All effect size estimates were well below the prespecified threshold of clinical ly important difference . Conclusions An intervention to enhance self management support in routine primary care did not add noticeable value to existing care for long term conditions . The active components required for effective self management support need to be better understood , both within primary care and in patients ’ everyday lives . Trial registration Current Controlled Trials IS RCT N90940049 The aim of this study was to evaluate the short-term benefits of a pulmonary rehabilitation program in chronic obstructive pulmonary disease ( COPD ) patients . The study was a r and omized controlled trial that included 54 mild and moderate COPD patients . Patients were assigned to either an 8-week-long pulmonary rehabilitation program , which consisted of exercise plus education ( rehabilitation group ) , or were controls . All the patients were evaluated at baseline at the completion of the 8th week of the program and one month after the completion of the pulmonary rehabilitation program using five instruments : arterial blood gas analysis , postbronchodilator pulmonary function test , 6-minute walk test ( 6MWT ) , Saint George Respiratory Question naire ( SGRQ ) , and the dyspnea visual analog scale ( VAS ) There were no statistically significant differences in the pulmonary functions and pulmonary gas analysis between baseline , discharge ( 8th week ) , and the 12th-week visit in both groups ( p > 0.05 ) . Rehabilitation result ed in significant improvements in both the VAS and the 6MWT at the 8th week , but by the 12th week all of these improvements had deteriorated . All of the SGRQ domains improved both at the 8th and the 12th week , with a significant difference between the groups ( p < 0.05 ) . We conclude that rehabilitation result ed in improvements in exercise capacity , health status , and dyspnea . All of these benefits , however , tend to deteriorate in the first month after rehabilitation . Therefore , it is strongly recommended that all patients with COPD be kept motivated in order to continue with rehabilitation and maintain the benefits gained BACKGROUND AND OBJECTIVE In COPD , hospital admissions and readmissions account for the majority of health-care costs . The aim of this prospect i ve r and omized controlled study was to determine if early pulmonary rehabilitation , commenced as an inpatient and continued after discharge , reduced acute health-care utilization . METHODS Consecutive COPD patients ( n = 397 ) , admitted with an exacerbation , were screened : 228 satisfied the eligibility criteria , of whom 97 consented to r and omization to rehabilitation or usual care . Both intention-to-treat and per- protocol analyses are reported with adherence being defined a priori as participation in at least 75 % of rehabilitation sessions . RESULTS The participants were elderly with severe impairment of pulmonary function , poor health-related quality of life and high COPD -related morbidity . The rehabilitation group demonstrated a 23 % ( 95 % CI : 11 - 36 % ) risk of readmission at 3 months , with attendees having a 16 % ( 95 % CI : 0 - 32 % ) risk compared with 32 % ( 95 % CI : 19 - 45 % ) for usual care . These differences were not significant . There were a total of 79 COPD -related readmission days ( 1.7 per patient , 95 % CI : 0.6 - 2.7 , P = 0.19 ) in the rehabilitation group , compared with 25 ( 1.3 per patient , 95 % CI : 0 - 3.1 , P = 0.17 ) for the attendees and 209 ( 4.2 per patient , 95 % CI : 1.7 - 6.7 ) for usual care . The BMI , airflow obstruction , dyspnoea and exercise capacity index showed a non-significant trend to greater improvement among attendees compared with those receiving usual care ( 5.5 ( 2.3 ) and 5.6 ( 2.7 ) at baseline , improving to 3.7 ( 1.9 ) and 4.5 ( 2.5 ) , respectively , at 3 months ) . No adverse effects were identified . CONCLUSIONS Early inpatient-outpatient rehabilitation for COPD patients admitted with an exacerbation was feasible and safe , and was associated with a non-significant trend towards reduced acute health-care utilization BACKGROUND There are several reports showing that expiratory muscle strength and endurance can be impaired in patients with COPD . This muscle weakness may have clinical ly relevant implication s. Expiratory muscle training tended to improve cough and to reduce the sensation of respiratory effort during exercise in patients other than those with COPD . METHODS Twenty-six patients with COPD ( FEV(1 ) 38 % predicted ) were recruited for the study . The patients were r and omized into two groups : group 1 , 13 patients were assigned to receive specific expiratory muscle training ( SEMT ) daily , six times a week , each session consisting of 1/2 h of training , for 3 months ; and group 2 , 13 patients were assigned to be a control group and received training with very low load . Spirometry , respiratory muscle strength and endurance , 6-min walk test , Mahler baseline dyspnea index ( before ) , and the transitional dyspnea index ( after ) were measured before and after training . RESULTS The training-induced changes were significantly greater in the SEMT group than in the control group for the following variables : expiratory muscle strength ( from 86 + /- 4.1 to 104 + /- 4.9 cm H(2)O , p < 0.005 ; mean difference from the control group , 24 % ; 95 % confidence interval , 18 to 32 % ) , expiratory muscle endurance ( from 57 + /- 2.9 % to 76 + /- 4.0 % , p < 0.001 ; mean difference from the control group , 29 % ; 95 % confidence interval , 21 to 39 % ) , and in the distance walked in 6 min ( from 262 + /- 38 to 312 + /- 47 m , p < 0.05 ; mean difference from the control group , 14 % ; 95 % confidence interval , 9 to 20 % ) . There was also a small but not significant increase ( from 5.1 + /- 0.9 to 5.6 + /- 0.7 , p = 0.14 ) in the dyspnea index . CONCLUSIONS The expiratory muscles can be specifically trained with improvement of both strength and endurance in patients with COPD . This improvement is associated with increase in exercise performance and no significant change in the sensation of dyspnea in daily activities To evaluate the effect of outpatient pulmonary rehabilitation ( OPR ) on dyspnea , we measured this symptom using a visual analogue scale during grade d treadmill exercise testing and with baseline and transitional dyspnea indices ( TDI ) . The latter measure overall dyspnea in three spheres : functional impairment , magnitude of task , and magnitude of effort . Twenty patients with COPD referred for OPR were r and omly assigned to either a treatment group ( T , n = 10 ) , with dyspnea evaluated at baseline then shortly following a 6-week OPR program , or a control group ( C , n = 10 ) , with dyspnea evaluated at baseline then following a 6-week waiting period . No significant change in maximal exercise performance from baseline to repeated testing was observed in either group . Dyspnea at maximum treadmill workload ( Dmax ) , which did not significantly change in C , decreased from 74.4 + /- 18.9 percent at baseline to 50.5 + /- 23.2 percent post-OPR in T ( p = 0.006 ) . The Dmax related to minute ventilation ( Dmax/VEmax ) and oxygen consumption ( Dmax/VO2max ) also significantly decreased following OPR . The reduction in exertional dyspnea was apparent by the second minute of exercise . Additionally , TDI focal scores were significantly higher in T than C ( 2.3 + /- 1.06 vs 0.2 + /- 1.75 units , p = 0.006 ) , indicating decreased overall dyspnea following OPR . These results point to significant improvements in both exertional and clinical ly assessed dyspnea following OPR PURPOSE The effects of a long-term treatment of autogenic drainage ( AD ) and the active cycle of breathing techniques ( ACBT ) were evaluated in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS Thirty clinical ly stable male COPD patients were r and omly assigned to AD or the ACBT treatment for a 20-day treatment period . Patients were assessed through pulmonary function tests , arterial blood gases , a 6-minute walking test , and a modified Borg Scale before , and immediately after the walking test . RESULTS Autogenic drainage improved forced vital capacity , forced expiratory volume in 1 second , peak expiratory flow rate , forced expiratory volume from 25 to 75 % , chronic hypercapnia , arterial oxygenation , exercise performance , and dyspnea perception during exercise . The ACBT increased forced vital capacity , peak expiratory flow rate , arterial oxygenation and exercise performance . Peak expiratory flow rate increased in AD more than in ACBT . In AD treatment , the increase in oxygen saturation was significantly higher than in ACBT treatment . Chronic hypercapnia improved significantly in AD treatment than in ACBT . No differences were found in other lung function parameters . CONCLUSIONS Autogenic drainage is as effective as the ACBT in cleaning secretions and improving lung functions . These techniques can be used in stable COPD patients according to the patients ' and the physiotherapists ' preferences OBJECTIVE To determine the feasibility of distractive auditory stimuli ( DAS ) used during an upper extremity training ( UET ) program on perceived dyspnea , functional performance , and health-related quality of life . In addition , to determine the appropriate music tempo used during the UET . DESIGN Experimental , r and omized , 3-group design with testing at baseline and 4 weeks . SETTING Outpatient . PATIENTS Thirty patients ( 13 male and 17 female ) with moderate to severe chronic obstructive pulmonary disease ( FEV1 41.27 % + /- 18 % predicted ) . INTERVENTION Moderate DAS group ( n = 10 ) and slow DAS group ( n = 10 ) subjects were instructed to perform UET for up to 15 minutes 3 to 5 times a week using DAS ( walkman , audiocassettes ) . The control group ( n = 10 ) received the same instructions , but no DAS . MEASURES AND RESULTS Primary outcome measures were perceived dyspnea , functional performance using the 6-minute peg and ring board ( 6MRPB ) count and health-related quality of life . In addition , all subjects recorded the time of UET performance using self-report ( daily logs ) . A significant increase was seen in 6MRPB count ( P = .002 ) between groups . Moderate DAS subjects increased 6MPRB count 46 + /- 21 rings and slow DAS subjects increased 46 + /- 20 rings from baseline to 4 weeks whereas control subjects increased only 5 + /- 4 rings . No significant differences were noted for the remaining variables . CONCLUSION Subjects who used DAS ( music ) while performing UET improved functional performance whereas controls failed to continue improvement . The DAS is a feasible adjunct to UET that may have the potential to augment the effectiveness of pulmonary rehabilitation training OBJECTIVE AND BACKGROUND The role of COPD self-management plans in improving health outcomes remains unclear . The objective of this study was to assess whether self-management plans administered in primary care have beneficial effects on quality of life , self-care behaviour and health outcomes in the long term for patients with COPD . MATERIAL , PATIENTS AND METHODS The study was a prospect i ve , unblinded , r and omized controlled trial of usual care vs. usual care plus structured education on the use of a written self-management plan and patient-initiated short courses of antibiotics and oral corticosteroids . The study was conducted in general practice , in Christchurch , New Zeal and . Participants were 159 patients with COPD r and omized by general practice site into control or intervention groups . The primary outcome measure was change in St. George 's Respiratory Question naire . Secondary variables were frequency of hospital and primary -care attendance , frequency of use of courses of antibiotics and oral corticosteroids over 12 months , and change in Hospital Anxiety and Depression Scale . Self-management knowledge was assessed using a structured interview , the COPD Self-Management Interview . RESULTS Self-management plans and structured education were associated with higher levels of self-management knowledge at 12 months , but had no effect on change in St. George 's Respiratory Question naire , health utilization , mental health or self-reported outcomes of patients with COPD managed in general practice . CONCLUSIONS Self-management knowledge was higher in the intervention group but there was no difference in quality of life or health outcomes due to self-management plans Disability associated with chronic obstructive pulmonary disease has led to the development of rehabilitation programmes that aim to increase exercise tolerance and improve quality of life . Many reports of the benefits of rehabilitation have been from uncontrolled trials and unsupervised programmes . In view of the commitment asked of patients , their families , and health-care professionals , rehabilitation should be justified by a demonstration of sustained improvement over conventional treatment . We undertook a prospect i ve r and omised controlled trial of respiratory rehabilitation in 89 subjects ( 44 men , 45 women ) aged 66 ( SD 7 ) years with severe but stable chronic obstructive pulmonary disease who received rehabilitation or conventional community care . The treatment group were rehabilitated as in patients for 8 weeks and supervised as out patients for 16 weeks . Primary outcome measures of exercise tolerance and quality of life were made at baseline and repeated at 12 , 18 , and 24 weeks . The difference between baseline and last follow-up was significant for 6 min walk distance ( 37.9 m [ 95 % CI 10.8 - 65.0 ] , p = 0.0067 ) and submaximal cycle time ( 4.7 min [ 2.1 - 7.3 ] ) . There were also significant differences in question naire assessment of dyspnoea ( p = 0.0061 ) , emotional function ( p = 0.0150 ) , mastery ( p = 0.0002 ) , and dyspnoea index ( p = 0.0053 ) . Improvements in exercise tolerance and quality of life can be achieved and sustained for 6 months in patients undergoing respiratory rehabilitation compared with those receiving conventional care BACKGROUND --Pulmonary rehabilitation has been shown to have short term subjective and objective benefits for patients with chronic obstructive pulmonary disease ( COPD ) . However , appropriately controlled studies have not previously been performed , nor have the benefits of different types of continuation programme for rehabilitation been investigated . Both these problems have been addressed in a single study of the long term effects of once monthly physiotherapy versus once weekly physiotherapy at home after a comprehensive home rehabilitation programme on quality of life and exercise tolerance in patients with COPD . METHODS --Thirty six patients with severe airways obstruction ( mean SD ) forced expiratory volume in one second ( FEV1 ) 1.3(0.4 ) 1 , FEV1/inspiratory vital capacity ( IVC ) 37.2(7.9)% ) were studied . Twenty three patients followed a rehabilitation programme at home for 18 months consisting of physiotherapy and supervision by a nurse and general practitioner . During the first three months all 23 patients visited the physiotherapist twice a week for a 0.5 hour session . Thereafter , 11 patients ( group A ) received a session of physiotherapy once weekly while 12 patients ( group B ) received a session of physiotherapy once a month . The control group C ( 13 patients ) received no rehabilitation at all . Quality of life was assessed by the Chronic Respiratory Question naire , exercise tolerance by the six minute walking distance , and lung function by FEV1 and IVC . Outcome measures were assessed at baseline and at three , six , 12 , and 18 months . RESULTS --Long term improvements in quality of life were found in patients in groups A and B , but not in those in group C compared with baseline , but these only reached significance in group B at all time points . Patients in group B had a higher quality of life than those in group C only at three and 12 months . There was a decrease in both six minute walking distance ( at 12 and 18 months ) and IVC ( at three , 12 , and 18 months ) in patients in group C compared with the baseline measurement . Between groups analysis showed no differences for six minute walking distance , FEV1 , and IVC . CONCLUSIONS --This study is the first to show that rehabilitation at home for three months followed by once monthly physiotherapy sessions improves quality of life over 18 months . The change in quality of life was not associated with a change in exercise tolerance The purpose of this study was to compare the performance of measures of health-related quality of life in a r and omized controlled trial of respiratory rehabilitation versus conventional community care for patients with chronic airflow limitation . The study included 89 stable patients with moderate to severe chronic airflow limitation with measurement of health status at 12 , 18 , and 24 weeks . Outcomes included two disease-specific ( the Oxygen Cost Diagram and the Chronic Respiratory Question naire [ CRQ ] ) measures , a generic health profile ( the Sickness Impact Profile [ SIP ] ) , and two utility measures ( the St and ard Gamble and the Quality of Well-Being index [ QWB ] ) . Of the measures , only the four domains of the CRQ ( dyspnea , fatigue , mastery , and emotional function ) showed statistically significant differences ( P < or = 0.05 ) between treatment and control groups . Correlation between change in the CRQ and change in other relevant measures , including the 6-minute walk test and global ratings of change in dyspnea , fatigue , and emotional function were generally weak to moderate ( from 0.19 to 0.51 ) . All correlations between change in the QWB , SIP , and St and ard Gamble and other measures were very weak or weak ( up to 0.30 ) . Correlation between change in the three generic measures were all very weak ( < 0.15 ) . The results suggest that unless investigators include responsive and valid disease-specific measures of health-related quality of life in controlled trials in chronic diseases , they risk misleading conclusions about the effect of treatments on health status OBJECTIVES To evaluate the effects of a care protocol used by community nurses to support nursing home staff in the care of patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN Matched , r and omized case-control trial . SETTING Forty-five nursing homes of the New Territories South ( NTS ) cluster of Hong Kong . PARTICIPANTS Eighty-nine older people ( > or = 65 , present resident of a nursing home in the NTS region , main diagnosis of COPD , at least one hospital admission in previous 6 months ) discharged to the nursing homes from the geriatric units of two hospitals . INTERVENTION Using a care protocol , community nurses followed up older patients in the experimental group for 6 months after their discharge from the hospitals to the nursing homes . MEASUREMENTS Data on functional , respiratory , and psychological parameters were collected at entry to study and 6 months later with st and ard measures . Data on hospital service utilization , nursing home staff , and patient satisfaction were also collected at 6 months . RESULTS Experimental group participants had significant ( P = .008 ) improvements in psychological well-being . Nursing home staff and experimental group patients were highly satisfied with the use of the protocol . There was no significant difference between the two groups in functional and respiratory outcomes or hospital service utilization . CONCLUSION Psychological well-being as an important factor in rehabilitation in chronic illness has been much neglected in the literature . Supporting nursing home staff in the care of COPD patients through community nursing visits can enhance older residents ' psychological well-being . Psychological aspects of care should be emphasized and incorporated into the delivery of regular nursing home care BACKGROUND AND OBJECTIVE Pulmonary rehabilitation is known to have beneficial effects in COPD patients . This study aim ed to assess the applicability and efficacy of a pulmonary rehabilitation programme in a community hospital lacking specialist pulmonary rehabilitation services . METHODS This r and omized , controlled , prospect i ve study included a total of 78 patients . Question naires were used to collect data on sociodemographic characteristics , respiratory function tests , the Modified Medical Research Council dyspnoea scale , 6MWD , the Short Form-36 ( SF-36 ) quality of life scale , the Hospital Anxiety and Depression Scale ( HADS ) and the St George 's Respiratory Question naire ( SGRQ ) . The experimental group underwent a pulmonary rehabilitation programme while the control group did not participate . The first , second and third month measurements for all parameters were compared between the two groups . RESULTS No significant differences in pulmonary function tests or dyspnoea scale ( P > 0.05 ) were observed between the two groups . Significant differences were observed in the 6MWD measurements at the third month ( P < 0.05 ) , as well as in the SF-36 quality of life scale , SGRQ and HADS measurements at the second and third months ( P < 0.01 ) . CONCLUSIONS Short-term pulmonary rehabilitation had a positive impact on exercise capacity and quality of life of patients with COPD , irrespective of FEV(1 ) . This study demonstrated the efficacy of a pulmonary rehabilitation programme in a secondary care hospital not staffed by a specialist pulmonary rehabilitation group Purpose This paper evaluates the effectiveness of a 3-month Tai chi Qigong ( TCQ ) program in promoting the psychosocial functional health of clients with chronic obstructive pulmonary disease ( COPD ) in Hong Kong . Methods This study employed a single-blind , r and omized controlled trial . Two hundred and six COPD clients were r and omly assigned into three groups , namely , TCQ group , exercise group , and control group . Subjects in the TCQ group received a TCQ program , consisting of two 60-min sessions each week for 3 months . Subjects in the exercise group were taught to practice breathing techniques combined with walking as an exercise . Subjects in the control group received their usual care . Data collection s were performed at baseline , on the sixth week and on the third month . The primary outcomes were health-related quality of life using St. George Respiratory Question naire-Hong Kong Chinese version and perceived social support using the Multidimensional Scale of Perceived Social Support-Chinese version . Results The TCQ group showed greater improvements in the symptom ( F4 , 404 = 3.351 , P = 0.010 ) and activity domains ( F4 , 404 = 2.611 , P = 0.035 ) . No differences were detected in perceived social support among the three groups . Conclusions Tai chi Qigong promoted health outcomes with respect to clients ’ perception of their respiratory symptoms . Moreover , TCQ decreased disturbances to their physical activities BACKGROUND AND PURPOSE Previous studies have provided little information about the comparative efficacy of treatment with pressure threshold and targeted resistive inspiratory muscle training devices . This study compared the efficacy of these two types of inspiratory muscle training ( IMT ) devices on inspiratory muscle function , exercise capacity , and quality of life in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS Forty two patients with moderate to severe COPD were r and omly assigned to either a control group , a group receiving pressure threshold inspiratory muscle training , or a group receiving targeted resistive inspiratory muscle training . The training intensity was 50 % of patients ' maximal inspiratory pressure ( MIP ) . Home-based training comprised two 15-minute sessions a day , 5 days a week for 8 weeks . Inspiratory muscle function measurement included MIP and inspiratory muscle endurance . RESULTS Thirty patients completed the program , 10 from each group . Twelve patients were excluded because of changes in pharmacological regimen or admission to the hospital ( n = 5 ) , study withdrawal ( n = 4 ) , or poor compliance with the training program ( n = 3 ) . After training , a significant increase in endurance time was found for the threshold group and targeted resistive group ( 4.4 + /- 3.2 min and 3.0 + /- 2.9 min , respectively , both p < 0.05 vs control ) , with no significant difference between the 2 training groups . The 6-minute walking distance also increased significantly in both training groups ( p < 0.05 ) . CONCLUSIONS Targeted resistive IMT with a controlled training load has a similar efficacy to the more popularly used pressure threshold IMT and can be incorporated in the treatment of COPD patients . The targeted resistance device offers a less expensive and easily used treatment choice UNLABELLED An integrated care intervention including education , coordination among levels of care , and improved accessibility , reduced hospital readmissions in chronic obstructive pulmonary disease ( COPD ) after 1 year . This study analyses the effectiveness of this intervention in terms of clinical and functional status , quality of life , lifestyle , and self-management , under the hypothesis that changes in these factors could explain the observed reduction in readmissions . A total of 113 exacerbated COPD patients ( 14 % female , mean ( SD ) age 73(8 ) years , FEV(1 ) 1.2(0.5 ) l ) were recruited after hospital discharge in Barcelona , Spain , and r and omly assigned ( 1:2 ) to integrated care ( IC ) ( n=44 ) or usual care ( UC ) ( n=69 ) . The intervention consisted of an individually tailored care plan at discharge shared with the primary care team and access to a specialized case manager nurse through a web-based call centre . After 1 year of intervention , subjects in the intervention group improved body mass index by 1.34 kg/m(2 ) . Additionally , they scored better in self-management items : COPD knowledge 81 % vs. 44 % , exacerbation identification 85 % vs. 22 % , exacerbation early treatment 90 % vs. 66 % , inhaler adherence 71 vs. 37 % , and inhaler correctness 86 vs. 24 % . There were no differences in the evolution of dyspnea , lung function , quality of life scores , lifestyle factors , or medical treatment . CONCLUSIONS This IC trial improved disease knowledge , and treatment adherence , after 1 year of intervention , suggesting that these factors may play a role in the prevention of severe COPD exacerbations triggering hospital admissions BACKGROUND Chronic obstructive pulmonary disease ( COPD ) patients have lower levels of physical activity compared to age-matched controls , and they limit physical activities requiring normal exertion . Our purpose was to compare the effectiveness of a traditional exercise therapy ( TET ) program with a behavioral lifestyle activity program ( LAP ) in promoting physical activity . METHODS Moderate physical activity ( kcal/week ) was assessed in 176 COPD patients using the Community Health Activities Model for Seniors question naire . Patients were r and omized to either a three month TET program that meet thrice weekly or a LAP . The LAP was design ed to teach behavioral skills that encouraged the daily accumulation of self-selected physical activities of at least moderate intensity . Interventionist contact was similar ( 36 h ) between the two groups . Patients were assessed at baseline and 3 , 6 and 12 months . RESULTS Compared to baseline values , self-reported moderate physical activity increased three months post-r and omization with no significant difference ( p = 0.99 ) found between the TET ( 2501 + /- 197 kcal/week ) and the LAP ( 2498 + /- 211 kcal/week ) . At 6 and 12 months post-r and omization , there were no significant differences ( p = 0.37 and 0.69 , respectively ) in self-reported levels of moderate physical activity between the TET ( 2210 + /- 187 and 2213 + /- 218 kcal/week , respectively ) and the LAP ( 2456 + /- 198 and 2342 + /- 232 kcal/week , respectively ) . CONCLUSION Although there was no difference between treatment groups , the TET and the LAP were both effective at in increasing moderate levels of physical activity at 3 months and maintaining moderate physical activity levels 12 months post-r and omization . This clinical trial is registered with Clinical Trials.gov . Its identifier is NCT00328484 BACKGROUND : A key component in the management of chronic obstructive pulmonary disease ( COPD ) patients is pulmonary rehabilitation ( PR ) , the corner stone of which is exercise training . AIM : This study aims to evaluate the effect of a two-months , home-based PR program with outpatient supervision every two weeks , on exercise tolerance and health-related quality of life ( HRQL ) using Arabic-translated st and ardized generic and specific question naires in COPD patients recently recovered from acute exacerbation , DESIGN : R and omized clinical trial . SETTING AND SUBJECTS : A total of 39 COPD patients who recovered from acute exacerbation were r and omly allocated either a two-month home-based PR program in addition to st and ard medical therapy or st and ard medical therapy alone in the period between July 2008 and March 2009 . METHODS : Pulmonary function tests ( PFTs ) , six-minute walk distance ( 6-MWD ) test , Arabic-translated chronic respiratory disease question naire-self administered st and ardized format ( CRQ-SAS ) and quality of life scale Short Form ( SF-36 ) were compared between 25 patients with moderate to severe COPD who underwent a two-month PR program ( group 1 ) and 14 COPD patients who did not ( group 2 ) . RESULTS : Group 1 showed significant improvement in the 6-MWD , and HRQL scores at two months compared with the usual care patients in group 2 ( P less than 0.05 ) . Improvement in both CRQ-SAS and SF-36 scores were statistically significant and comparable in group 1 . CONCLUSION : The supervised , post discharge , two-month home-based PR program is an effective non pharmacological intervention in the management of stable patients with COPD . The 6-MWD is a simple , inexpensive and safe test to assess physical and functional capabilities among COPD patients . HRQL can be measured in patients with COPD either by disease-specific tools that have been specifically design ed for use in patients with respiratory system disorders or by generic HRQL tools that can be used across population s with a variety of medical conditions . The Arabic-translated CRQ-SAS is a new tool for assessment of Arabic-speaking patients with chronic respiratory diseases Twenty-eight patients with stable chronic obstructive pulmonary disease ( COPD ) undertook a training program with a simple respiratory apparatus for 15 min three times daily for 6 weeks . Fourteen patients were allocated to an inspiratory resistance training program and 14 to a control group . In all subjects the median FEV1 was 0.72 and the median FEV1/FVC was 39 % . There was no difference in FEV1 or FEV1/FVC between the control and the test groups . In both groups of patients FEV1 FVC and the corresponding values during inspiration , FIV1 and FIVC , as well as MVV , were found unchanged following the training period . Inspiratory resistance tolerance increased in both groups but no significant difference in the improvement could be observed between the two groups . Both groups also showed a similar increase , 23 ( 76 - 10 ) % , in stair-climbing ability . There was no correlation between increases in inspiratory load tolerance and stair-climbing ability . It is suggested that both inspiratory load tolerance and work ability can be improved in COPD patients , but that inspiratory resistance training does not contribute to these improvements The aims were to explore the effects and health economic consequences of patient education in patients with COPD in a 12-month follow-up . Sixty-two patients with mild-to-moderate chronic obstructive pulmonary disease ( COPD ) were at our outpatient clinic r and omly allocated to an intervention group or a control group . The intervention group participated in a 4-h schooling , followed by one-to-two individual nurse and physiotherapist consultations . Self-management was emphasized following a stepwise treatment plan . Effectiveness was expressed in terms of proportions in need of general practitioner ( GP ) consultations , patient satisfaction and utilization of rescue medication . Doctor visits , days off work , dispensed pharmaceuticals , hospital admissions , travel costs , educational and time costs were recorded . The control and intervention groups induced mean total costs of NOK 19900 and 10600 per patient , respectively . The results were robustto realistic changes in the assumptions upon which they were based . For every NOK put into patient education , there was a saving of 4.8 . The NNE to make one patient independent of their GP was 1.7 ( 95 % CI : 1.3 - -2.8 ) and associated with a concomitant saving of NOK 15 800 . The corresponding NNE to make one person satisfied with their GP was 4.5 ( 95 % CI : 2.9 - -10 ) and NOK 41900 , respectively . A reduced need of 100 DDD of rescue medication was associated with a concomitant saving of NOK5600 . We conclude that patient education of patients with COPD in a 12-month follow-up improved patient outcomes and reduced costs Thixotropy conditioning of inspiratory muscles at lower lung volumes decreases functional residual capacity ( FRC ) of following breath cycles with increases in inspiratory capacity . It remains uncertain whether this conditioning would improve exercise tolerance in chronic obstructive pulmonary disease ( COPD ) . Sixteen male stable COPD patients with mild to severe airway obstruction participated . Before the study , all patients completed the 6-min walk test at least twice . The 6-min walk distance ( 6MWD ) was measured after single inspiratory muscle training ( IMT ) maneuver or without intervention ( control ) in a r and omized cross-over fashion . The 6MWD was also measured after thixotropy conditioning of inspiratory muscles at the maximal expiratory position or without intervention ( control ) . There were no significant differences in the 6MWD after the IMT maneuver ( 493.2+/-83.7 m , P>0.05 ) versus without intervention ( 495.7+/-85.9 m ) . The 6MWD after thixotropy conditioning ( 526.2+/-96.3 m , P=0.030 ) was significantly higher than the 6MWD without intervention ( 504.3+/-94.1 m ) . The 95 % confidence interval of the difference was from 2.6 to 41.2 m . Percentage predicted FRC correlated positively with differences in the 6MWD between control and after the thixotropy conditioning maneuver ( r=0.78 , P=0.007 ) , whereas percentage predicted forced expiratory volume in 1s or the BODE index did not correlate with differences in the 6MWD ( P>0.05 ) . Thixotropy conditioning increases self-paced walking distance in patients with COPD . Patients with higher resting FRC benefited more from the conditioning with greater walking distance Several studies of chronic obstructive pulmonary disease ( COPD ) have shown that pulmonary rehabilitation , consisting of at least three training sessions a week , improves exercise performance and health status . This study investigates feasibility , effect and economic aspects of a rehabilitation programme consisting of two sessions a week for 8 weeks . Twenty-four patients with moderate COPD were r and omized to rehabilitation and 21 to placebo . Patients were assigned to an 8-week programme of exercise plus education ( Exercise group ) or conventional community care ( Placebo group ) . The rehabilitation program was carried out in a hospital outpatient setting and consisted of 16 h exercise and 13.5 h of education . The exercise group received physiotherapy and education twice a week . Seven patients did not complete the programme . The characteristics of the 38 COPD - patients at baseline were the following : ( mean + /- SD ) forced expiratory volume in 1 sec ( FEV1 ) 1.1+/-0.4 1 ( 47 % of predicted ) , 6-min walking distance ( 6MWD ) 413+/-75 m , score of St. George 's Respiratory Question naire ( SGRQ ) 44+/-21 . Health-status , assessed by SGRQ and The Psychological General Well-being ( PGWB ) Index , did not improve . Rehabilitation result ed in an insignificant improvement in the 6MWD [ 29 m ( 95 % confidence interval : -8 -66 m ) ] . We conclude that a rehabilitation program consisting of exercise and education twice a week for 8 weeks had no effect on exercise performance and well being in patients with moderate COPD Acute effects of music and relaxation have not been evaluated in hospitalized subjects with chronic obstructive pulmonary disease ( COPD ) . This study aims to evaluate the acute effects of music and progressive muscle relaxation ( PMR ) in hospitalized COPD subjects after a recent episode of exacerbation . A R and omized controlled study was performed of pre-test post-test design after recruiting 82 COPD subjects from K.M.C hospitals . All patients were admitted for acute exacerbation and were medically stabilized . After being screened for the inclusion and exclusion criteria , 72 subjects were selected for the study . Demographic and baseline data was taken on the day subjects were screened . Music group listened to a self selected music of 60 - 80 beats per minute for 30 minutes . PMR group practice d relaxation through a pre-recorded audio of instructions of 16 muscle groups . Outcome variables were Spielberger ’s state anxiety inventory ( SSAI ) , Spielberger ’s trait anxiety inventory ( STAI ) , dyspnea , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , pulse rate ( PR ) and respiratory rate ( RR ) . There was statistically significant main effect across the sessions for state anxiety ( F = 62.621 , p = 0.000 ) , trait anxiety ( F = 19.528 , p = 0.000 ) , dyspnea ( F = 122.227 , p = 0.000 ) , SBP ( F = 63.885 , p = 0.000 ) , PR ( F = 115.780 , p = 0.000 ) and RR ( F = 202.977 , p = 0.000 ) . There was statistically significant interaction effect between the two groups for state anxiety ( F = 6.024 , p = 0.003 ) , trait anxiety ( F = 8.222 , p = 0.000 ) , dyspnea ( F = 10.659 , p = 0.000 ) , SBP ( F = 12.889 , p = 0.000 ) , PR ( F = 4.746 , p = 0.008 ) and RR ( F = 12.078 , p = 0.000 ) . There were greater changes observed after the second session in both groups however , change in DBP was not significant in either group . Music and PMR are effective in reducing anxiety and dyspnoea along with physiologic measures such as SBP , PR and RR in two sessions in COPD patients hospitalized with exacerbation . However , reductions in the music group were greater compared to the PMR group Background : Malnutrition in chronic obstructive pulmonary disease ( COPD ) is associated with a poor prognosis , yet evidence to support the role of dietary counselling and food fortification is lacking . A study was undertaken to assess the impact of dietary counselling and food fortification on outcome in out patients with COPD who are at risk of malnutrition . Methods : A r and omised controlled unblinded trial was performed in 59 out patients with COPD ( 6 months intervention and 6 months follow-up ) . The intervention group received dietary counselling and advice on food fortification and the controls received a dietary advice leaflet . Outcome measures were nutritional status , respiratory and skeletal muscle strength , respiratory function , perceived dyspnoea , activities of daily living ( ADL ) and quality of life . Results : The intervention group consumed more energy ( difference 194 kcal/day ; p = 0.02 ) and protein ( difference 11.8 g/day ; p<0.001 ) than controls . The intervention group gained weight during the intervention period and maintained weight during follow-up ; the controls lost weight throughout the study . Significant differences were observed between the groups in St George ’s Respiratory Question naire total score ( difference 10.1 ; p = 0.02 ) , Short Form-36 health change score ( difference 19.2 ; p = 0.029 ) and Medical Research Council dyspnoea score ( difference 1.0 ; p = 0.03 ) ; the difference in ADL score approached statistical significance ( difference 1.5 ; p = 0.06 ) . No differences were observed between groups in respiratory function or skeletal and respiratory muscle strength . Improvements in some variables persisted for 6 months beyond the intervention period . Conclusion : Dietary counselling and food fortification result ed in weight gain and improvements in outcome in nutritionally at-risk out patients with COPD , both during and beyond the intervention period BACKGROUND Impaired exercise tolerance is frequently observed in patients with COPD . Respiratory muscle endurance training ( RMET ) by means of normocapnic hyperpnea can be used to improve respiratory muscle function and probably exercise capacity . RMET is not applied on a large scale because complicated equipment is needed to maintain carbon dioxide homeostasis during hyperpnea , which can also be done by enlarging the dead space of the ventilatory system by breathing through a tube . Therefore , tube breathing might be a new , inexpensive method for home-based RMET . The aim of this study was to assess whether home-based RMET by means of tube breathing improves endurance exercise performance in patients with COPD . METHODS We r and omized 36 patients with moderate-to-severe COPD to RMET by paced tube breathing ( n = 18 ) or sham training ( control , n = 18 ) . Both groups trained twice daily for 15 min , 7 days per week , for 5 weeks . RESULTS Patients receiving RMET showed significant improvements in endurance exercise capacity ( constant-load exercise on cycle ergometry ; 18 min vs 28 min , p < 0.001 ) , in perception of dyspnea ( Borg score ; 8.4 vs 5.4 , p < 0.001 ) , and respiratory muscle endurance capacity ( sustainable inspiratory pressure ; 25 cm H(2)O vs 31 cm H(2)O , p = 0.005 ) . Quality of life ( chronic respiratory disease question naire ) also improved ( 78.7 to 86.6 , p = 0.001 ) . The control group showed no significant changes . CONCLUSION Home-based RMET by means of tube breathing leads to a significant improvement of endurance exercise capacity , a reduction in perception of dyspnea , and an improvement in quality of life in patients with moderate-to-severe COPD OBJECTIVE To evaluate whether multidisciplinary pulmonary rehabilitation programme ( PRP ) provides additional benefit over tiotropium therapy in managing chronic obstructive pulmonary disease ( COPD ) in primary care . DESIGN A r and omized controlled trial to analyse the difference in outcomes of COPD patients receiving tiotropium plus PRP vs. tiotropium treatment alone . SETTING Two primary care teaching clinics affiliated with a university which serves a population of 600,000 . PARTICIPANTS Fifty primary care COPD patients . METHODS Fifty subjects underwent spirometry and their status of COPD was confirmed by using the Vitalograph Gold St and ard . They were then assessed by the 6-min walking distance ( 6MWD ) , Peak Visual Analogue Scale ( Peak VAS ) and Chronic Respiratory Disease Question naire ( CRQ ) . All subjects were given tiotropium to optimize their treatment . After a 6-week period , half were r and omized to the intervention group ( i.e. receiving PRP ) , whereas the rest were r and omized to control group which received only medication . Spirometry , 6MWD , Peak VAS and CRQ were performed in both groups at 6 weeks , 12 weeks and 3 months . OUTCOMES Spirometry , 6MWD , Peak VAS and CRQ . RESULTS Significant improvement ( P < 0.05 ) was seen in 6MWD , symptoms of dyspnoea measured by Peak VAS and CRQ . The improvement was sustained at 3-month follow-up . However , no additional significant improvement was seen in the intervention group when compared with control . CONCLUSION Tiotropium therapy has improved health outcomes in COPD patients in primary care setting s. A 6 weekly PRP did not give any additional benefits in patients already given tiotropium OBJECTIVE Pulmonary rehabilitation has been shown to be of benefit to clinical ly stable patients with chronic obstructive pulmonary disease ( COPD ) . This study examined the effect of pulmonary rehabilitation on some physiologic variables in COPD patients recovering from an episode of acute respiratory failure . DESIGN A prospect i ve , r and omized study . SETTING A respiratory intensive care unit ( RICU ) . PATIENTS Eighty COPD patients recovering from an episode of acute respiratory failure were r and omized in a 3:1 fashion to receive stepwise pulmonary rehabilitation ( group A , n=60 patients ) or st and ard medical therapy ( group B , n=20 patients ) . MAIN OUTCOME MEASURES Improvements in exercise tolerance , sense of breathlessness , respiratory muscle function , and pulmonary function test values were measured , respectively , by exercise capacity ( 6-minute walking distance [ 6MWD ] ) , dyspnea score ( Visual Analog Scale [ VAS ] ) , maximal inspiratory pressure ( MIP ) , forced expiratory volume in 1 second ( FEV1 ) , and forced vital capacity ( FVC ) . INTERVENTIONS Group A received pulmonary rehabilitation that consisted of passive mobilization ( step I ) , early deambulation ( step II ) , respiratory and lower skeletal muscle training ( step III ) , and if the patients were able , complete lower extremity training on a treadmill ( step IV ) . Group B received st and ard medical therapy plus a basic deambulation program . RESULTS Sixty-one of 80 patients were mechanically ventilated at admission to the unit and most of them were bedridden . Twelve of the 60 group A patients and 4 of the 20 group B patients died during their RICU stay , and 9 patients required invasive mechanical ventilation at home after their discharge . The total length of RICU stay was 38+/-14 days for patients in group A versus 33.2+/-11 days for those in group B. Most patients from both groups regained the ability to walk , either unaided or aided . At discharge , 6 MWD results were significantly improved ( p < .001 ) in Group A only . MIP improved in Group A only ( p < .05 ) , while VAS scores improved in both groups , but the improvement was more marked in group A ( p < .001 ) than in group B ( p < .05 ) . CONCLUSIONS COPD patients who were admitted to a RICU in critical condition after an episode of acute respiratory failure and who , in most cases , required mechanical ventilation benefited from comprehensive early pulmonary rehabilitation , compared with patients who received st and ard medical therapy and progressive ambulation Background Exacerbations of chronic obstructive pulmonary disease ( COPD ) are characterised by increased dyspnoea , reduced quality of life and muscle weakness . Re-exacerbation and hospital admission are common . Pulmonary rehabilitation ( PR ) administered after hospital admission for an exacerbation can improve quality of life and exercise capacity . Objective To determine whether outpatient post-exacerbation PR ( PEPR ) could reduce subsequent hospital admission episodes . Methods Patients admitted to hospital for an exacerbation of COPD were r and omised to receive either usual follow-up care ( UC ) or PEPR after discharge . Hospital admission and emergency department attendances for COPD exacerbations were recorded over a 3-month period and analysed on an intention-to-treat basis . Secondary outcomes included exercise capacity and quadriceps strength . Results 60 patients underwent concealed r and omisation at the time of their hospital discharge ( UC : n=30 , mean ( SD ) age 65 ( 10 ) years , forced expiratory volume in 1 s ( FEV1 ) 52 (22)% predicted ; PEPR : n=30 , 67(10 ) years , 52 (20)% predicted ) . The proportion of patients re-admitted to hospital with an exacerbation was 33 % in the UC group compared with 7 % in those receiving PEPR ( OR 0.15 , 95 % CI 0.03 to 0.72 , p=0.02 ) . The proportion of patients that experienced an exacerbation result ing in an unplanned hospital attendance ( either admission or review and discharge from the emergency department ) was 57 % in the UC group and 27 % in those receiving PEPR ( OR 0.28 , 95 % CI 0.10 to 0.82 , p=0.02 ) . Conclusions Post-exacerbation rehabilitation in COPD can reduce re-exacerbation events that require admission or hospital attendance over a 3-month period . Clinical Trials Registration Number NCT00557115 OBJECTIVE To observe the effect of pulmonary rehabilitation with respiratory physiology as guide in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS Sixty patients of severe and very severe COPD as categorized by global proposed diagnostic criteria for COPD ( GOLD , 2006 ) were enrolled for study . They were r and omly divided into three groups , and with 20 patients in each group . The patients in group A were given pulmonary rehabilitation guided by respiratory physiology thrice a day , 15 minutes each time for 8 weeks . The patients in group B were given pulmonary rehabilitation with pursed lip respiration thrice a day , 15 minutes per time for 8 weeks . The patients in group C were given no pulmonary rehabilitation . Six minute-walk-distance ( 6MWD ) , medical research council ( MRC ) dyspnea scale , activities of daily living ( ADL ) , maximal expiratory pressure ( MEP ) , maximal inspiratory pressure ( MIP ) , and quality of life ( QOL ) were determined before and after respective pulmonary rehabilitation course . RESULTS ( 1 ) There were 3 , 5 , 5 patients in group A , group B , group C dropped off in the course of rehabilitation respectively . ( 2 ) The patients ' MRC grade after pulmonary rehabilitation in group A and group B decreased compared with that before pulmonary rehabilitation ( both P<0.01 ) , but the difference was not significant between two groups ( P>0.05 ) . ( 3 ) 6MWD , ADL , MEP , MIP of patients in group A and group B increased after pulmonary rehabilitation compared with that before pulmonary rehabilitation , and 6MWD , ADL , MEP , MIP of patients in group A were increased after pulmonary rehabilitation more than those in group B ( P<0.05 or P<0.01 ) . (4)The patients ' body status , shortness of breath , social activity , home chores in group A and group B , and uneasiness in group A after pulmonary rehabilitation were improved more than those before pulmonary rehabilitation ( P<0.05 or P<0.01 ) , but the difference in state of mind , headache , appetite was not markedly different before and after pulmonary rehabilitation in two groups ( all P>0.05 ) . The difference in QOL was not marked between group A and group B after pulmonary rehabilitation ( all P>0.05 ) . CONCLUSION ( 1 ) The pulmonary rehabilitation with pursed lip respiration and the pulmonary rehabilitation with the guide of respiratory physiology ameliorates dyspnea , improves ADL , QOL , exercise tolerance , function of respiratory muscle in the severe and very severe COPD patients remarkably . ( 2 ) The effect of the pulmonary rehabilitation with the guide of respiratory physiology is better than that of the pulmonary rehabilitation with pursed lip respiration , and it can be considered as a more effective pulmonary rehabilitation method for the patients with severe and very severe COPD BACKGROUND Patients with chronic pulmonary disease have been shown to benefit from pulmonary rehabilitation programs . Published work has often been from specialized teaching centers and has involved inpatient stay . We assessed an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic lung disease , using the St. George 's Respiratory Question naire ( SGRQ ) ( which measures health-related quality of life ) as the primary outcome measure . METHODS We undertook a r and omized , prospect i ve , parallel-group controlled study of an outpatient rehabilitation program in 65 patients with COPD ( 44 men and 21 women ; mean age , 69.5 years [ SD , 9.2 years ] ; FEV(1 ) , 41 % predicted [ SD , 18.5 % ] ) . The active group ( n = 36 ) took part in a 6-week program of education ( 2 h weekly ) and exercise ( 1 h weekly ) . The control group ( n = 29 ) were review ed routinely as medical out patients . The SGRQ was administered under supervision by a blinded observer at study entry , 12 weeks , and 24 weeks . RESULTS The SGRQ in the active group was 59.9 ( SE , 2.0 ) at study entry ( n = 36 ) , 47.4 ( SE , 2.3 ) at 12 weeks ( n = 32 ) , and 50.6 ( SE , 2.5 ) at 24 weeks ( n = 24 ) . The SGRQ in the control group was 59.3 ( SE , 2.5 ) at study entry and did not change significantly over 24 weeks . There was a difference of 10.4 points ( confidence interval [ CI ] , 3.6 to 17.3 ) between the two groups at 12 weeks ( p < 0.001 ) and of 8.1 points ( CI , 1.4 to 14.9 ) at 24 weeks ( p = 0.02 ) in favor of the active group . CONCLUSIONS A 6-week outpatient-based program significantly improved quality of life in patients with moderate-to-severe COPD . Benefit was still evident after 24 weeks We hypothesized that the use of an Action Plan might assist self-management for patients with chronic obstructive pulmonary disease ( COPD ) . A pilot process and r and omized , controlled study were undertaken to evaluate an Action Plan that provided advice on management of usual care and exacerbations , together with a booklet on self-management . Fifty six subjects with COPD recruited through general practitioners ( GPs ) completed the 6 month study , 27 in the control group and 29 in the intervention group . The control group received usual care from their GP , and the intervention group received a booklet and Action Plan from their practice nurse plus a supply of prednisone and antibiotic from their GP . The two groups were demographically similar with a mean age of 68 yrs . The re sources were well received by GPs , practice nurses and intervention group subjects . After 6 months , there were no differences in quality of life scores or pulmonary function . There were significant changes in self-management behaviour in the intervention group compared to controls . In response to deteriorating symptoms , 34 versus 7 % ( p=0.014 ) initiated prednisone treatment and 44 versus 7 % ( p=0.002 ) initiated antibiotics . Subjects in the intervention group readily adopted self-management skills but did not show any difference in quality of life or lung function parameters . A larger , prospect i ve , controlled , clinical trial of this approach is warranted This study investigated the effects of heavy resistance training in elderly males with chronic obstructive pulmonary disease ( COPD ) . 18 Home-dwelling male patients ( age range : 65 - 80 years ) , with a mean forced expiratory volume in the first second ( FEV1 ) of 46 + /- 3.4 % of predicted value , were recruited . Baseline and post-training assessment s included : Cross-sectional area ( CSA ) of quadriceps assessed by MRI , isometric and isokinetic knee extension strength , isometric trunk strength , leg extension power , normal and maximal gait-speed on a 30 m track , stair climbing time , number of chair st and s in 30 s , lung function ( FEV1 ) and self-reported health . Subjects were r and omized to a resistance training group ( RE , n = 9 ) or a control group conducting breathing exercises ( CON , n = 9 ) . RE performed heavy progressive resistance training twice a week for 12 weeks . 6 RE and 7 CON completed the study . In RE the following improved ( P < 0.05 ) : Quadriceps CSA : 4 % , isometric knee extension strength : 14 % , isokinetic knee extension strength at 60 degrees /s . : 18 % , leg extension power : 19 % , maximal gait speed : 14 % , stair climbing time : 17 % , isometric trunk flexion : 5 % and self-reported health . In CON no changes were found . In conclusion , 12 weeks of heavy resistance training twice a week result ed in significant improvements in muscle size , knee extension strength , leg extension power , functional performance and self-reported health in elderly male COPD patients Many patients with chronic obstructive pulmonary disease ( COPD ) report greater limitation for activities involving the upper extremities than the lower extremities . Exercise training has generally emphasized lower-extremity exercise . We design ed and evaluated two simple , practical , and widely applicable upper-extremity training programs in 45 patients with COPD participating concurrently in a comprehensive , multidisciplinary pulmonary rehabilitation program . Patients were r and omly assigned to one of the following three groups : ( 1 ) gravity-resistance ( GR ) upper-extremity training ; ( 2 ) modified proprioceptive neuromuscular facilitation ( PNF ) upper-extremity training ; or ( 3 ) no upper-extremity training ( control ) . Patients were evaluated before and after at least six weeks of uninterrupted training . Twenty-eight patients completed the study . Compared to controls , both GR and PNF patients demonstrated improved performance on tests specific to the training performed ( upper-extremity performance test , maximal level and endurance on isokinetic arm cycle ) . There were no significant changes on isotonic arm cycle , ventilatory muscle endurance , or simulated activities of daily-living tests . Ratings of perceived breathlessness and fatigue decreased significantly in all groups for several tests . We conclude that specific upper-extremity training may be beneficial in the rehabilitation of patients with COPD and warrants further investigation PURPOSE The purpose of this study was to compare the effects of interval training ( IT ) and continuous steady-pace training ( CT ) in patients with COPD . METHODS Patients ( n = 21 ) ( mean forced expiratory volume in 1 second ( [ FEV1 ] = 44.6 % ± 13.9 % ) were r and omized to IT , and 20 patients ( mean FEV1 = 41.7 % ± 12.6 % ) to CT . Outcome measures included 6-minute walk distance , maximal work capacity , endurance exercise time during constant workload exercise at 60 % to 70 % of maximal work capacity , and quality of life including fatigue and dyspnea . Participants exercised 3 times per week for 8 weeks , and total work was the same for both training regimens . RESULTS Significant improvement in mean score was observed in each variable within each of the 2 groups : 6-minute walk distance ( IT = 158 ± 178 ft , CT = 106 ± 165 ft ) ; maximal work capacity ( IT = 10.0 ± 13.0 W , CT = 11.5 ± 13.1 W ) ; endurance exercise time ( IT = 15.0 ± 12.5 minutes , CT = 18.7 ± 10.6 minutes ) ; and quality of life domains , fatigue ( IT = 3.1 ± 3.0 , CT = 2.8 ± 4.7 ) , and dyspnea ( IT = 4.4 ± 5.3 , CT = 5.4 ± 5.1 ) . There was no significant difference in the extent of improvement between the 2 training regimens for any of the outcome variables . CONCLUSION Compared with CT , IT was well tolerated and produced similar improvements in exercise performance and quality of life Background : The British Thoracic Society ( BTS ) guidelines have not been examined collectively for their impact on chronic obstructive pulmonary disease ( COPD ) . Whether intensive outpatient follow up of COPD patients after acute admission , using these guidelines , improved quality of life compared to the “ usual practice ” of primary care follow up was investigated . Methods : Altogether 103 patients with a new diagnosis of COPD were admitted and screened over a four year period . Seventy patients were excluded because of another dominant medical condition or a m and atory requirement for intervention . Patients were r and omised to regular primary care ( control group , n = 15 ) or chest clinic follow up ( intervention group , n = 10 ) . Spirometry , oxygen saturation , St George ’s Respiratory Question naire ( SGRQ ) , and Short Form 36 question naire were measured at baseline and six months . The intervention group was review ed at least four times in the six month period and received spirometry , ambulatory oxygen assessment , smoking cessation advice , nebuliser assessment , a steroid trial , advice about nutrition/exercise , and introduction to a patient support group . Results : There was no significant difference between baseline measurements in the two groups . There was a significant mean ( SD ) improvement in the SGRQ symptom score from baseline to six months in the intervention group [ 20.98 ( 20.36 ) ] compared with the controls [ 0.23 ( 12.55 ) ] ( p = 0.004 ) . At six months the SGRQ symptom score , impact score , and total score was significantly better in the intervention than the control group ( p = 0.01 , 0.02 , and 0.02 ) . Conclusion : Aggressive implementation of BTS guidelines after initial hospitalisation may improve respiratory health specific quality of life scores in patients with COPD . Larger studies are needed to confirm this finding Objective : To test the effects of pulmonary rehabilitation on fatigue , functional status and health perceptions in patients with chronic obstructive pulmonary disease . Design : R and omized controlled trial . Setting : Pulmonary outpatient department . Subjects : Thirty patients r and omly assigned to a rehabilitation ( 3 men , 9 women , mean age 66 ( ±2 ) years ) or a control group ( 10 men , 4 women , mean age 64 ( ±2 ) years ) . Interventions : The patients in the rehabilitation group participated in a multidisciplinary rehabilitation programme comprising exercise training twice weekly , for a 12-week period , nutritional and self-care advice , and education about disease and energy conservation strategies . Main measures : Fatigue , functional limitations due to fatigue , functional performance and satisfaction , six-minute walking distance , h and grip strength and health perception were assessed at baseline and after 12 weeks . Results : At baseline there were no significant differences between the groups , except for gender . The six-minute walking distance was 312.6 ( ±79.3 ) m for the rehabilitation group and 360.3 ( ±84.7 ) m for the control group . After 12 weeks , the rehabilitation group improved their walking distance by 40.6 ( ±27.2 ) m ( P<0.05 ) . The rehabilitation group improved in performance ( from 4.8 ( ±2.0 ) to 6.0 ( ±1.5 ) scores , P<0.01 ) and satisfaction ( from 4.6 ( ±2.2 ) to 6.0 ( ±2.1 ) scores , P<0.001 ) with regard to own selected daily activities . No statistically significant differences were seen between the changes within the rehabilitation group and changes within the control group at the 12-week follow-up . Conclusions : Although the pulmonary rehabilitation programme had an immediate effect , it was not sustained The chronic obstructive pulmonary diseases are major causes of disability and death [ 1 - 3 ] . Health statistics underestimate the prevalence of these diseases because of difficulties in definition and recognition and because of misclassification [ 4 ] . Although st and ard medical therapy can alleviate symptoms , many patients with these diseases must cope with the distressing symptom of breathlessness that results from a chronic , irreversible , and disabling disease . These patients may use services in physician offices , emergency departments , hospitals , and intensive care units , in part because of a lack of underst and ing and inability to cope with frightening and disabling symptoms . Since a comprehensive care program for patients with chronic obstructive pulmonary disease was first described [ 5 ] , pulmonary rehabilitation has become an established way to enhance st and ard therapy to control symptoms , optimize functional capacity , and reduce the medical and economic burdens of patients with disabling chronic lung diseases [ 6 - 12 ] . Comprehensive programs usually include education , instruction in respiratory and chest physiotherapy techniques , psychosocial support , and exercise training [ 13 ] . The primary goal of rehabilitation is to restore the patient to the highest possible level of independent function . This is accomplished by helping patients to become more knowledgeable about their disease , more actively involved in their own health care , more independent in performing daily activities , and less dependent on others , including health professionals . Previous studies have shown important benefits of pulmonary rehabilitation , including increased exercise tolerance and quality of life and a decreased number of symptoms and use of health care services [ 7 ] . However , many of these findings are based on small numbers of patients and on observational , nonr and omized studies . We compared the effects of comprehensive pulmonary rehabilitation on both physiologic and psychosocial outcomes with the effects of education alone . Our study featured r and om assignment and long-term , 6-year follow-up . Methods Patients For 18 months , 352 patients with chronic obstructive pulmonary disease were screened for the study ; 128 met entry criteria and were r and omly assigned to either the comprehensive pulmonary rehabilitation program or an education program ( control group ) . Patients were recruited through mechanisms similar to those used in regular clinical pulmonary rehabilitation , including written and personal contact with physicians and direct advertisement to the general public for persons with breathlessness . Nine patients who initially agreed to participate ( 6 in the rehabilitation group and 3 in the education group ) but who withdrew from the study before completing 2 weeks of the interventions were considered to be pretreatment drop-outs . Reasons for dropping out included concurrent illness ( four patients ) , a too-large time commitment ( 2 patients ) , and no clear explanation ( 3 patients ) . Patients who dropped out and those who remained in the study did not differ . The remaining 119 patients comprised 32 women and 87 men . The following were the inclusion criteria : 1 . Clinical diagnosis of mild to severe chronic obstructive pulmonary disease that was confirmed by history , physical examination , spirometry , measurement of arterial blood gases , and chest roentgenograms . Patients with diagnoses of emphysema , chronic bronchitis , or asthmatic bronchitis were accepted . Patients with primarily acute , reversible airway disease ( asthma ) but no chronic airflow obstruction were excluded . 2 . Stable condition while the patient was receiving an acceptable medical regimen and was under the care of a primary care provider . Patients without a primary care physician who presented for evaluation were referred for appropriate evaluation and treatment before they enrolled in the study . 3 . No other significant disabling lung disease , serious heart problems , or other medical condition that would interfere with the patient 's participation . Current smokers were not excluded if they showed a commitment to quitting smoking before enrollment . Smoking cessation counseling was incorporated into the rehabilitation program for patients assigned to that group . Experimental Design All eligible patients were r and omly assigned to participate in either the comprehensive pulmonary rehabilitation program ( n = 57 ) or the education program ( n = 62 ) . The r and omization scheme was fixed before the trial with a block size of 8 . Assignment was determined by a table of r and om numbers and was indicated on cards placed in sequentially numbered envelopes that were kept in a central office separate from the study site . Clinical personnel were unaware of the r and omization scheme . After a patient agreed to enroll and signed the consent form approved by the University of California , San Diego , Human Subjects Committee , the central office was contacted by telephone and the next numbered envelope was opened . Interventions Pulmonary Rehabilitation Program The comprehensive rehabilitation program included two phases . Phase I ( core program ) consisted of twelve 4-hour sessions given over 8 weeks . Each session included two periods of classroom or group support and supervised exercise training . The rehabilitation program included four main components : 1 . Education . Groups of three to six patients were taught by experienced pulmonary rehabilitation staff and selected guest speakers . Topics included the following : How Normal Lungs Work , What Is Chronic Obstructive Pulmonary Disease ? , Medications , Nutrition , Oxygen Therapy , Coping with Stress , Energy-saving Techniques , Self-Care Tips , Travel , Pollution and Environmental Hazards , When To Call Your Doctor , Smoking Cessation Techniques , Planning a Daily Schedule , and Breathing Techniques . 2 . Physical and respiratory care instruction . Patients received individual instruction in respiratory care and chest physiotherapy techniques such as postural drainage , pursed lip and diaphragmatic breathing , oxygen therapy , and proper use of respiratory therapy equipment . 3 . Psychosocial support . Patients and staff met in weekly group sessions facilitated by a psychiatrist . Spouses or partners of the patients were encouraged to attend . Sessions focused on difficulties commonly faced by patients , such as depression , anxiety , fear , and family or social problems . Relaxation techniques were introduced to help patients better cope with the emotional stress of dyspnea . 4 . Supervised exercise training . After the baseline exercise test , each patient received an individualized exercise prescription based on the maximum , symptom-limited level [ 14 ] . Patients with severe hypoxemia ( Pao2 < 55 mm Hg at rest or < 50 mm Hg with exercise ) were trained using supplemental oxygen . The primary exercise-training modality was walking . Training emphasized steady-state exercise consisting of continuous walking at the highest tolerated symptom-limited level for as long as 30 minutes . Patients were initially trained to walk on a motor-driven treadmill under supervision . The staff then instructed patients in translating the target treadmill speed to a pace for free walking . Patients were asked to walk at home at least twice daily and to keep a training log of time , distance , pace ( steps per minute ) , and perceived symptoms of breathlessness and muscle fatigue . Patients were also instructed and trained in upper-extremity exercise using an isokinetic upper-body ergometer during supervised sessions and a progressive program of arm lifts with weights for home training [ 15 ] . Patients were asked to do upper-extremity training daily and to keep a daily log . Phase II of the rehabilitation program involved monthly follow-up visits for 1 year . These visits provided reinforcement after the core phase of the program . These sessions included a supervised period of exercise , group sessions to discuss progress and problems , and the introduction of maintenance techniques . Education Control Program The goal of the education program was to conduct a series of health education classes that would provide information similar to that provided in the rehabilitation program , but in a shorter and less intensive program without the behavioral components , individualized instruction , and supervised exercise training . Patients in the education group attended four 2-hour sessions scheduled biweekly for 8 weeks . Each group consisted of approximately 10 to 15 patients . At the beginning of each session , a videotape describing some aspect of chronic obstructive pulmonary disease management was presented [ Pulmonary Self-Care Series , Encyclopedia Britannica , Vision Multimedia Communications , Inc. , Winter Park , Florida ] . The four-part videotape series included the following programs : 1 ) Learning To Live with a Breathing Problem ; 2 ) Building Your Strength and Endurance ; 3 ) You Can Do It : Clearing Your Airways ; and 4 ) Learning To Breathe Better . Patients also completed life events [ 16 ] , social support [ 17 ] , health locus of control [ 18 ] , and sense of coherence [ 19 ] question naires and a semistructured smoking interview . The patients then participated in a group discussion about either the material covered in the videotape or the question naires . The final hour of the session included a lecture followed by a question and answer period presented by professionals in the fields of pulmonary medicine , pharmacology , respiratory therapy , and nutrition . Assessment Each patient had physiologic and psychosocial function evaluation before intervention ( baseline ) , immediately after the program ended ( 2 months ) , and at regular intervals for 72 months . Physiologic measures , including laboratory pulmonary function and maximal treadmill exercise tests , were done 2 , 12 , 24 , 48 , and 72 months after the program began . Psychosocial measures and endurance exercise tests were done more frequently at 2 , 6 , 12 , 18 , 24 , 36 , 48 , 60 , and 72 months . Laboratory tests of The present study was aim ed at evaluating the effects of a specific inspiratory muscle training protocol on the structure of inspiratory muscles in patients with chronic obstructive pulmonary disease . Fourteen patients ( males , FEV1 , 24 + /- 7 % predicted ) were r and omized to either inspiratory muscle or sham training groups . Supervised breathing using a threshold inspiratory device was performed 30 minutes per day , five times a week , for 5 consecutive weeks . The inspiratory training group was subjected to inspiratory loading equivalent to 40 to 50 % of their maximal inspiratory pressure . Biopsies from external intercostal muscles and vastus lateralis ( control muscle ) were taken before and after the training period . Muscle sample s were processed for morphometric analyses using monoclonal antibodies against myosin heavy chain isoforms I and II . Increases in both the strength and endurance of the inspiratory muscles were observed in the inspiratory training group . This improvement was associated with increases in the proportion of type I fibers ( by approximately 38 % , p < 0.05 ) and in the size of type II fibers ( by approximately 21 % , p < 0.05 ) in the external intercostal muscles . No changes were observed in the control muscle . The study demonstrates that inspiratory training induces a specific functional improvement of the inspiratory muscles and adaptive changes in the structure of external intercostal muscles PURPOSE : Breathing pattern retraining is frequently used for exertional dyspnea relief in adults with moderate to severe chronic obstructive pulmonary disease . However , there is contradictory evidence to support its use . The study objective was to compare 2 programs of prolonging expiratory time ( pursed-lips breathing and expiratory muscle training ) on dyspnea and functional performance . METHODS : A r and omized , controlled design was used for the pilot study . Subjects recruited from the outpatient pulmonary clinic of a university-affiliated Veteran Affairs healthcare center were r and omized to : 1 ) pursed-lips breathing , 2 ) expiratory muscle training , or 3 ) control . Changes over time in dyspnea [ modified Borg after 6-minute walk distance ( 6MWD ) and Shortness of Breath Question naire ] and functional performance ( Human Activity Profile and physical function scale of Short Form 36-item Health Survey ) were assessed with a multilevel modeling procedure . Weekly laboratory visits for training were accompanied by structured verbal , written , and audiovisual instruction . RESULTS : Forty subjects with chronic obstructive pulmonary disease [ age = 65 ± 9 ( mean ± st and ard deviation ) years , forced expiratory volume 1 second/forced vital capacity % = 46 ± 10 , forced expiratory volume 1 second % predicted = 39 ± 13 , body mass index = 26 ± 6 kg/m2 , inspiratory muscle strength = 69 ± 22 cm H2O , and expiratory muscle strength ( PEmax ) = 102 ± 29 cm H2O ] were enrolled . No significant Group × Time difference was present for PEmax ( P = .93 ) . Significant reductions for the modified Borg scale after 6MWD ( P = .05 ) and physical function ( P = .02 ) from baseline to 12 weeks were only present for pursed-lips breathing . CONCLUSION : Pursed-lips breathing provided sustained improvement in exertional dyspnea and physical function In order to study the efficiency of individual training programs at the ventilatory threshold level , twenty COPD patients were r and omized into two groups and studied over a two-month period . At the start , during , and at the end of the study all subjects performed incremental exercise tests . The trained group ( 59.60 SEM + /- 2.75 years ) walked four times a week at the heart rate corresponding to the metabolic level of ventilatory threshold . The other group served as controls ( 58.2 + /- 1.80 years ) . A marked increase in the symptom-limited oxygen consumption ( + /- 25 % ) ( p < 0.01 ) , the maximal ventilation ( + 20 % ) ( p < 0.01 ) , and the ventilatory threshold ( + 19 % ) ( p < 0.05 ) was found in the trained group . No modification was recorded in the control group . The ventilatory pattern at submaximal intensities expressed in percentage of the initial oxygen consumption showed significant differences between groups , the trained-group ventilation decreased at 50 % and 75 % VO2 sl ( p < 0.05 ) . The breathing frequency also decreased at 50 % and 75 % VO2 sl ( p > 0.05 ) . Moreover , we observed an increase in the oxygen pulse at 50 % VO2 sl ( p < 0.05 ) . In conclusion , this study demonstrates that individualized training at the ventilatory threshold level increases exercise tolerance and produces better ventilatory comfort in COPD patients BACKGROUND AND OBJECTIVE Skeletal muscle dysfunction contributes to exercise limitation in patients with chronic obstructive pulmonary disease ( COPD ) . Strength training increases muscle strength and muscle mass , but there is an ongoing debate on the additional effect concerning the exercise capacity . The purpose of this study was to compare the effects of three different exercise modalities in patients with COPD including endurance training ( ET ) , progressive strength training ( ST ) and the combination of strength training and endurance training ( CT ) . DESIGN A prospect i ve r and omized trial . METHODS Thirty-six patients with COPD were r and omly allocated either to ET , ST , or CT . Muscle strength , cardiopulmonary exercise testing , lung function testing and quality of life were assessed before and after a 12-week training period . RESULTS Exercise capacity ( Wmax ) increased significantly in all three training groups with increase of peak oxygen uptake ( VO2peak ) in all three groups , reaching statistical significance in the ET group and the CT group . Muscle strength ( leg press , bench press , bench pull ) improved in all three training groups , with a higher improvement in the ST ( + 39.3 % , + 20.9 % , + 20.3 % ) and the CT group ( + 43.3 % , + 18.1 % , + 21.6 % ) compared to the ET group ( + 20.4 % , + 6.4 % , + 12.1 % ) . CONCLUSIONS Progressive strength training alone increases not only muscle strength and quality of life , but also exercise capacity in patients with COPD , which may have implication s in prescription of training modality . CLINICAL TRIALS.GOV IDENTIFIER : NCT01091623 Background Chronic obstructive pulmonary disease ( COPD ) treatment goals are often not achieved despite the availability of many effective treatments . Furthermore , clinical pharmacist interventions to improve clinical and humanistic outcomes in COPD patients have not yet been explored and few r and omized controlled trials have been reported to evaluate the impact of pharmaceutical care on health outcomes in patients with COPD . Objective The aim of the present study was to evaluate the impact of pharmaceutical care intervention , with a strong focus on self-management , on a range of clinical and humanistic outcomes in patients with COPD . Setting Outpatient COPD Clinic at the Royal Medical Services Hospital . Method In a r and omised , controlled , prospect i ve clinical trial , a total of 133 COPD patients were r and omly assigned to intervention or control group . A structured education about COPD and management of its symptoms was delivered by the clinical pharmacist for patients in the intervention group . Patients were followed up at 6 months during a scheduled visit . Effectiveness of the intervention was assessed in terms of improvement in health-related quality of life , medication adherence , disease knowledge and healthcare utilization . Data collected at baseline and at the 6 month assessment was coded and entered into SPSS ® software version 17 for statistical analysis . A P value of < 0.05 was considered statistically significant . Main outcome measure The primary outcome measure was health-related quality of life improvement . All other data collected including healthcare utilization , COPD knowledge and medication adherence formed secondary outcome measures . Results A total of 66 patients were r and omized to the intervention group and 67 patients were r and omized to the control group . Although the current study failed to illustrate significant improvement in health-related quality of life parameters , the results indicated significant improvements in COPD knowledge ( P < 0.001 ) , medication adherence ( P < 0.05 ) , medication beliefs ( P < 0.01 ) and significant reduction in hospital admission rates ( P < 0.05 ) in intervention patients when compared with control group patients at the end of the study . Conclusion The enhanced patient outcomes as a result of the pharmaceutical care programme in the present study demonstrate the value of an enhanced clinical pharmacy service in achieving the desired health outcomes for patients with COPD OBJECTIVE To study the effects of a lifestyle physical activity counseling program with feedback of a pedometer during pulmonary rehabilitation . METHODS Twenty-one chronic obstructive pulmonary disease ( COPD ) patients were r and omized to an experimental group that followed a regular rehabilitation program plus the counseling intervention or to a control group that only followed rehabilitation . The primary outcome was daily physical activity assessed by pedometers . Secondary outcomes were physical fitness , health-related quality of life , activities of daily living , depression and self-efficacy . RESULTS The experimental group showed an increase of 1,430 steps/day ( + 69 % from baseline ) , whereas the control group showed an increase of 455 steps/day ( + 19 % ) ( p = 0.11 for group x time interaction ) . The secondary outcomes showed no differences . CONCLUSION AND PRACTICE IMPLICATION S This study showed that the use of the pedometer , in combination with exercise counseling and the stimulation of lifestyle physical activity , is a feasible addition to pulmonary rehabilitation which may improve outcome and maintenance of rehabilitation results Pulmonary rehabilitation ( PR ) programmes produce initial improvements in exercise tolerance and health status in patients with chronic obstructive pulmonary disease ( COPD ) . However , there is limited data on the longer term effects of PR . This study has examined whether the initial benefits gained in exercise tolerance and health status may be maintained after a 1-year follow-up programme . Sixty-six patients with COPD were assessed with the MRC Dyspnoea Scale and found to be moderately disabled due to dyspnoea ( MRC Grade s 3 and 4 ) . These patients were then r and omised to an 8 week outpatient programme of either exercise training and education ( Exercise group ) or to education alone ( Control group ) . Exercise performance was assessed with the shuttle walking test and health status assessed with two disease-specific measures , the St Georges Respiratory Question naire and the Chronic Respiratory Disease Question naire . After PR , all patients were invited to attend monthly follow-up sessions for 1 year . Fifty-six patients were available for follow-up immediately after the programme and were assessed at 6 months and 1 year . This study has shown that the patients in the Exercise group maintained improvements in exercise capacity and health status up to 6 months after an 8 week programme . At 1 year there was a significant difference between the Exercise and Control groups in terms of exercise tolerance due to a considerable decline experienced by the Control group . However , neither group had maintained improvements in health status at 1 year . Further study is required to assess whether benefit may be sustained for a longer period using alternative follow-up strategies BACKGROUND Although the benefits of comprehensive pulmonary rehabilitation have been demonstrated in patients with COPD , the effects of exercise sessions within self-management programs remain unclear . We hypothesized that 8 supervised exercise sessions incorporated in a 1-month self-management education program in COPD patients would be effective to improve health outcomes and to reduce direct medical costs after one year , compared to usual care . METHODS In this r and omized controlled trial , 38 moderate-to-severe COPD patients were assigned either to an intervention group or to a usual care group . The hospital-based intervention program provided a combination of 8 sessions of supervised exercise with 8 self-management education sessions over a 1-month period . The primary end-point was the 6-min walking distance ( 6MWD ) , with secondary outcomes being health-related quality of life (HRQoL)--using the St. George 's Respiratory Question naire ( SGRQ ) and Nottingham Health Profile ( NHP ) , maximal exercise capacity and healthcare utilization . Data were collected before and one year after the program . RESULTS After 12 months , we found statistically significant between-group differences in favor of the intervention group in 6MWD ( + 50.5 m ( 95%CI , 2 to 99 ) , in two domains of NHP ( energy , -19.8 ( -38 to -1 ) ; emotional reaction , -10.4 ( -20 to 0 ) ) ; in SGRQ-symptoms ( -14.0 ( -23 to -5 ) ) , and in cost of COPD medication ( -480.7 € ( CI , -891 to -70 ) per patient per year ) . CONCLUSION The present hospital-based intervention combining supervised exercise with self-management education provides significant improvements in patient 's exercise tolerance and HRQoL , and significant decrease of COPD medication costs , compared to usual care OBJECTIVE To investigate the effects of breathing exercise on chronic obstructive pulmonary disease ( COPD ) . PATIENTS AND METHODS 324 patients stable COPD were r and omly assigned to either the breathing exercise group ( Group I ) or control group consisting of placebo ( Group II ) . The maximum respiratory pressure ( 320 cases ) and transdiaphragmatic pressure ( 129 cases ) were monitored via RMS-I and Type-2 pressure measurements . The breathing exercises were taught and checked by experienced specialists periodically . Comparison was made between Group I and Group II using maximum inspiratory pressure ( MIP ) , maximum expiratory pressure ( MEP ) , diaphragmatic pressure ( Pdi ) and maximum transdiaphragmatic pressure ( Pdimax ) after 1 to 20 months . RESULTS In Group I MIP increased by 30.42 % , MEP 32.10 % , Pdi 30.94 % and Pdimax 65.59 % ( P < 0.001 ) . No significant changes were observed in Group II given the placebo . The MIP , MEP , Pdi and Pdimax were 6.95 % , 2.92 % , 14.63 and 9.05 % respectively ( P > 0.05 ) . CONCLUSIONS Breathing exercise has a potent and long lasting effect on respiratory muscle contraction . The methods mentioned above can be used as st and ard quantitative index for contractile properties of respiratory muscle OBJECTIVE To examine the short- and long-term effects of an outpatient pulmonary rehabilitation program for COPD patients on dyspnea , exercise , health-related quality of life , and hospitalization rate . SETTING Secondary -care respiratory clinic in Barcelona . METHODS We conducted a r and omized controlled trial with blinding of outcome assessment and follow-up at 3 , 6 , 9 , 12 , 18 , and 24 months . Sixty patients with moderate to severe COPD ( age 65 + /- 7 years ; FEV(1 ) 35 + /- 14 % ) were recruited . Thirty patients r and omized to rehabilitation received 3 months of outpatient breathing retraining and chest physiotherapy , 3 months of daily supervised exercise , and 6 months of weekly supervised breathing exercises . Thirty patients r and omized to the control group received st and ard care . RESULTS We found significant differences between groups in perception of dyspnea ( p < 0.0001 ) , in 6-min walking test distance ( p < 0.0001 ) , and in day-to-day dyspnea , fatigue , and emotional function measured by the Chronic Respiratory Question naire ( p < 0 . 01 ) . The improvements were evident at the third month and continued with somewhat diminished magnitude in the second year of follow-up . The PR group experienced a significant ( p < 0.0001 ) reduction in exacerbations , but not the number of hospitalizations . The number of patients needed to treat to achieve significant benefit in health-related quality of life for a 2-year period was approximately three . CONCLUSION Outpatient rehabilitation programs can achieve worthwhile benefits that persist for a period of 2 years Background : When choosing a specific inhalation device for a chronic obstructive pulmonary disease ( COPD ) patient , the internal airflow resistance and the ability of the patient to overcome it and to create an optimal inspiratory flow are essential . Objectives : The purpose of the present study was to investigate : ( 1 ) the peak inspiratory flow ( PIF ) that a patient with COPD can generate while breathing through two dry powder inhalers and ( 2 ) whether in patients with low PIF specific inspiratory muscle training ( SIMT ) will increase the PIF and exceed the minimal PIF that is considered necessary to guarantee optimal lung deposition of the drug . Methods : Inspiratory muscle strength and PIFs were measured in 60 patients with COPD . Then 28 patients with severe COPD and low PIF were r and omized to receive SIMT or to a control group . Results : With the Turbuhaler , 12 patients ( 20 % ) could not generate the optimal flow of 60 l/min . PIF correlated very well with maximal inspiratory mouth pressure ( PImax ) for the Diskus and the Turbuhaler , as well as for both males and females ( p < 0.001 ) . Following the training period , there was a statistically significant increase in the PImax in the training group . This increase was associated with a significant increase in the PIF . All patients overcame the minimal threshold PIF following the training . Conclusions : Some patients with severe COPD are not able to generate adequate flow to secure optimal lung deposition of the inhalation with the Turbuhaler . SIMT improves inspiratory muscle strength as well as PIF . Following 8 weeks of training , the optimal PIF enabling adequate lung deposition of the drug was attained in all the trained patients OBJECTIVE To assess the effect of psychotherapy on the anxiety and depression levels of patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN A blind , r and omized , controlled trial . SETTING Outpatient university pulmonary rehabilitation program in Brazil . PARTICIPANTS Thirty patients with COPD ( mean age , 60.33y ; 22 men ) attending a pulmonary rehabilitation program were r and omized into 2 groups : experimental group ( G1 ) and control group ( G2 ) . Both groups underwent a 12-week treatment program . INTERVENTIONS Group 1 ( n=14 ) participated in 24 sessions of physical exercise , 24 sessions of physiotherapy , 12 psychologic sessions , and 3 educational sessions . Group 2 did not participate in psychotherapy sessions . MAIN OUTCOME MEASURES All patients were evaluated at baseline and at completion of the pulmonary rehabilitation program by using 3 instruments : the Beck Anxiety Inventory ( BAI ) , Beck Depression Inventory ( BDI ) , and 6-minute walk distance ( 6MWD ) . RESULTS Both groups showed statistically significant improvements on the 6MWD ( G1 , P<.001 ; G2 , P=.03 ) . Only G1 had a significant reduction in anxiety and depression levels ( G1 : BAI , P<.001 ; BDI , P<.001 ; G2 : BAI , P=.156 ; BDI , P=.142 ) . Statistically significant differences existed between G1 and G2 for BAI ( P<.001 ) and BDI ( P=.02 ) . CONCLUSIONS Including psychotherapy in a pulmonary rehabilitation program for COPD reduced patients ' anxiety and depression levels but did not modify 6MWD performance STUDY OBJECTIVES To investigate the response to interval exercise ( IE ) training by looking at changes in morphologic and biochemical characteristics of the vastus lateralis muscle , and to compare these changes to those incurred after constant-load exercise ( CLE ) training . DESIGN R and omized , controlled , parallel , two-group study ( IE vs CLE training ) . SETTING Multidisciplinary , outpatient , hospital-based , pulmonary rehabilitation program . PATIENTS Nineteen patients with stable advanced COPD ( mean + /- SEM FEV1 , 40 + /- 4 % predicted ) . INTERVENTIONS Patients ( n = 10 ) assigned to IE training exercised at a mean intensity of 124 + /- 15 % of baseline peak exercise capacity ( peak work rate [ Wpeak ] ) with 30-s work periods interspersed with 30-s rest periods for 45 min/d . Patients ( n = 9 ) allocated to CLE training exercised at a mean intensity of 75 + /- 5 % Wpeak for 30 min/d . Patients exercised 3 d/wk for 10 weeks . MEASUREMENTS AND RESULTS Needle biopsies of the right vastus lateralis muscle were performed before and after rehabilitation . After IE training , the cross-sectional areas of type I and IIa fibers were significantly increased ( type I before , 3,972 + /- 455 microm2 ; after , 4,934 + /- 467 microm2 [ p = 0.004 ] ; type IIa before , 3,695 + /- 372 microm2 ; after , 4,486 + /- 346 microm2 [ p = 0.008 ] ) , whereas the capillary-to-fiber ratio was significantly enlarged ( from 1.13 + /- 0.08 to 1.24 + /- 0.07 [ p = 0.013 ] ) . Citrate synthase activity increased ( from 14.3 + /- 1.4 to 20.5 + /- 4.2 micromol/min/g ) , albeit not significantly ( p = 0.097 ) . There was also a significant improvement in Wpeak ( by 19 + /- 5 % ; p = 0.04 ) and in lactate threshold ( by 17 + /- 5 % ; p = 0.02 ) . The magnitude of changes in all the above variables was not significantly different compared to that incurred after CLE training . During training sessions , however , ratings of dyspnea and leg discomfort , expressed as fraction of values achieved at baseline Wpeak , were significantly lower ( p < 0.05 ) for IE training ( 73 + /- 9 % and 60 + /- 8 % , respectively ) compared to CLE training ( 83 + /- 10 % and 87 + /- 13 % , respectively ) . CONCLUSIONS High-intensity IE training is equally effective to moderately intense CLE training in inducing peripheral muscle adaptations ; however , IE is associated with fewer training symptoms Background An individualised action plan ( AP ) is a potentially effective method of helping patients with chronic obstructive pulmonary disease ( COPD ) to recognise and anticipate early exacerbation symptoms . This multicentre r and omised controlled trial evaluates the hypothesis that individualised APs reduce exacerbation recovery time . Methods Two hundred and thirty-three patients with COPD ( age 65±10 years , forced expiratory volume in 1 s 56±21 % predicted ) were r and omised to receive either an individualised AP ( n=111 ) or care as usual ( n=122 ) . The AP provides individualised treatment prescriptions ( pharmaceutical and non-pharmaceutical ) related to a colour-coded symptom status to enhance an adequate response to periods of symptom deterioration ( reinforced at 1 and 4 months ) . Exacerbation onset was defined using the Anthonisen symptom diary card algorithm . Every 3 days the Clinical COPD Question naire ( CCQ ) was assessed to evaluate the longitudinal course of health status . The primary outcome was health status recovery in the event of an exacerbation . Results During the 6-month follow-up period there was no difference in exacerbation rates and healthcare utilisation between the two groups . Cox-adjusted survival analysis including frailty showed enhanced health status recovery ( HR 1.58 ; 95 % CI 0.96 to 2.60 ) and reduced length of the exacerbation ( HR 1.30 ; 95 % CI 0.92 to 1.84 ) . The mean difference in symptom recovery time was −3.68 days ( 95 % CI −7.32 to −0.04 ) . Mixed model repeated measure analysis showed that an AP decreased the impact of exacerbations on health status both in the prodromal and early post-onset periods . Between-group differences in CCQ scores were above the minimal clinical ly relevant difference of 0.4 points ( 3.0±0.7 vs 3.4±0.9 ; p≤0.01 ) . Conclusion This study shows that an individualised AP , including ongoing support by a case manager , decreases the impact of exacerbations on health status and tends to accelerate recovery . APs can be considered a key component of self-management programmes in patients with COPD BACKGROUND Patients with severe chronic obstructive pulmonary disease ( COPD ) may develop dyspnea with minimal arm activity , thoracoabdominal dyssynchrony with unsupported arm exercise ( UAEX ) and increased oxygen uptake ( VO2 ) , and minute ventilation ( VE ) with simple unsupported arm elevation ( UAE ) and UAEX . We investigated whether unsupported arm training , as the only form of exercise , could decrease the VO2 and VE cost ( percentage increase from resting baseline ) associated with unsupported arm elevation and exercise , respectively . METHODS Twenty-six patients with severe COPD were r and omized to 21 - 24 sessions of unsupported arm ( ARMT ) or low-intensity resistive breathing ( RBT ) training as the only form of exercise . Patients were studied before and after training using a metabolic cart and esophageal and gastric pressures to evaluate metabolic and respiratory muscle function . RESULTS After ARMT , the VO2 ( 58 % vs 38 % increase , P < 0.05 ) and VE ( 41 % v. 21 % increase , P < 0.05 ) cost for UAEX at exercise isotime decreased and endurance time increased . Similarly the VO2 ( 25 % vs 18 % increase , P < 0.05 ) cost decreased and VE no longer increased in response to 2 minutes of UAE after ARMT . The RBT group showed no such change . No improvement in ventilatory load or respiratory muscle function could be identified to explain the physiologic changes observed . After ARMT , mean inspiratory flow ( VT/TL ) , a measure of central respiratory drive , was reduced during UAEX and the expected increase during UAE did not occur . CONCLUSION We conclude that arm training reduces the VO2 and VE cost of UAE and UAEX , possibly through improved synchronization and coordination of accessory muscle action during unsupported arm activity The effect of patient education on steroid inhaler compliance and rescue medication utilization in patients with asthma or chronic obstructive pulmonary disease ( COPD ) has not been previously investigated in a single study . We r and omized 78 asthmatics and 62 patients with COPD after ordinary outpatient management . Intervention consisted of two 2-h group sessions and 1 to 2 individual sessions by a trained nurse and physiotherapist . A self-management plan was developed . We registered for 12 mo medication dispensed from pharmacies according to the Anatomical Therapeutic Chemical ( ATC ) classification index . Steroid inhaler compliance ( SIC ) was defined as ( dispensed/prescribed ) x 100 and being compliant as SIC > 75 % . Among asthmatics 32 % and 57 % were compliant ( p = 0.04 ) with a median ( 25th/75th percentiles ) SIC of 55 % ( 27/96 ) and 82 % ( 44/127 ) ( p = 0.08 ) in the control and intervention groups , respectively . Patient education did not seem to change SIC in the COPD group . Uneducated patients with COPD were dispensed double the amount of short-acting inhaled beta(2)-agonists compared with the educated group ( p = 0.03 ) . We conclude that patient education can change medication habits by reducing the amount of short-acting inhaled beta(2)-agonists being dispensed among patients with COPD . Educated asthmatics showed improved steroid inhaler compliance compared with the uneducated patients , whereas this seemed unaffected by education in the COPD group The effects of additional target-flow inspiratory muscle training ( TF-IMT ) on the performance of the inspiratory muscles , on general exercise capacity , and on psychologic parameters during a pulmonary rehabilitation program ( PR ) were studied in 40 patients with COPD selected for ventilatory limitation during exercise . The mean age of the patients was 59 years , and the mean FEV1 was approximately 50 percent of predicted . All patients participated in a ten-week PR program . They were r and omized to receive either additional TF-IMT ( PR + IMT ) or not ( PR ) . The TF-IMT was performed by means of a target-flow resistive device ; the generated mouth pressure and the duration of inspiration and of the respiratory cycle were imposed . After the training period , maximal inspiratory mouth pressure and EMG-fatigability of the diaphragm were significantly better in the PR + IMT group than in the PR group . Maximal work load and psychologic symptoms increased to the same extent in both groups . The 12-minute walking distance also increased in both groups , but it increased significantly more in the PR + IMT group than in the PR group . We believe that additional TF-IMT during PR in a selected group of patients with COPD who have ventilatory limitation has an extra beneficial effect on the performance of the inspiratory muscles and on exercise performance OBJECTIVE To evaluate the effectiveness of a Tai chi Qigong ( TCQ ) program in enhancing respiratory functions and activity tolerance in clients with chronic obstructive pulmonary disease ( COPD ) . DESIGN A single-blind , r and omized controlled trial . SETTING Five general outpatient clinics in Hong Kong . INTERVENTION In total , 206 COPD clients were r and omly assigned into one of the three groups , namely , TCQ , exercise , and control group . Subjects in the TCQ group received a TCQ program consisting of two 60-min sessions each week for three months . Subjects in the exercise group were taught to practice breathing techniques combined with walking as an exercise . Subjects in the control group were instructed to maintain their usual activities . Data collection was performed at baseline and at the 6-week and 3-month marks . OUTCOMES Lung functions , 6-min walk test , and COPD exacerbation rate . RESULTS Results of repeated measures of analysis of covariance demonstrated that there were significant interaction effects between time and group in forced vital capacity ( p=.002 , η(2)=.06 ) , forced expiratory volume in 1s ( p<.001 , η(2)=.02 ) , walking distance ( p<.001 ) , and exacerbation rate ( p=.006 , η(2)=.06 ) at 3 months . Improvements were noted in the TCQ group . No changes were observed in the exercise group , while a decline in lung functions was noticed in the control group . CONCLUSION Tai chi Qigong was able to improve respiratory functions and activity tolerance level in COPD clients . The breathing and walking exercise helped maintain lung functions and slow down disease progression The aims were to explore the effects and health economic consequences of patient education in patients with COPD in a 12-month follow-up . Sixty-two patients with mild to moderate Chronic Obstructive Pulmonary Disease ( COPD ) were at our out-patient clinic r and omly allocated to an intervention group or a control group . The intervention group participated in a 4h group patient education , followed by one to two individual nurse- and physiotherapist-sessions . Self-management was emphasised following a stepwise treatment plan . Effectiveness was expressed in terms of number of general practitioner ( GP ) consultations , proportions in need of GP consultations , utilisation of rescue medication and patient satisfaction . Costs related to doctor visits , days off work , dispensed pharmaceuticals , hospital admissions , travel costs , educational and time costs were recorded . Patient education reduced the need for GP visits with 85 % ( from 3.4 to 0.5 , P<0.001 ) and kept a greater proportion independent of their GP during the 12-month follow-up , compared with no education ( 73 % versus 15 % , respectively ) . Patient education reduced the need for reliever medication from 290 to 125 Defined Daily Dosages ( DDD ) , and improved patient satisfaction with overall h and ling of their disease at GP . The control and intervention groups induced mean total costs of NOK 19,900 and 10,600 per patient , respectively . For every NOK put into patient education , there was a saving of 4.8 . The Number Needed to Educate ( NNE ) to make one person satisfied with their GP was 4.5 and associated with a concomitant saving of NOK 41,900 . Patient education of patients with COPD improved patient outcomes and reduced costs in a 12-month follow-up PURPOSE Pulmonary rehabilitation is essential for managing chronic obstructive pulmonary disease ( COPD ) . Housebound COPD patients are frequently excluded from this treatment because they are unable to access outpatient pulmonary rehabilitation programs because of the severity of their disease . This r and omized controlled trial assesses the effects of a 12-week home-based pulmonary rehabilitation program for 60 housebound COPD patients older than 60 years . METHODS Intervention patients received an individually tailored supervised walking and arm exercise program as well as individual multidisciplinary education sessions on COPD and its management . Outcomes were assessed using the 6-minute walk test , St George 's respiratory question naire , and Borg score of perceived breathlessness . Healthcare utilization was assessed using hospital admission rates with exacerbation of COPD and average length of stay at readmission . RESULTS Complete data for 23 patients in each group were available for analysis . There was no significant difference between groups on baseline measures . Compared with the control group , intervention patients demonstrated a significant improvement in 6-minute walk test ( P = .023 ) , Borg score of perceived breathlessness ( P = .024 ) , St George 's respiratory question naire total score ( P = .020 ) , and impact subscore ( P = .024 ) . At 6 months , the intervention group had a significantly shorter average length of stay at readmission to hospital with exacerbation ( P = .035 ) . CONCLUSION A 12-week home-based pulmonary rehabilitation is effective in improving exercise tolerance , perception of breathlessness , and quality of life for housebound COPD patients . To manage COPD in the community more effectively , health services should focus on exp and ing home-based pulmonary rehabilitation The clinical role of inspiratory muscle training ( IMT ) in chronic obstructive pulmonary disease ( COPD ) has not been established , because data on its clinical effect is scarce and controversial . To further investigate these aspects we studied 20 COPD patients ( FEV1 37 + /- 3 % P ) who were r and omly and double blindly trained for 30 minutes a day during 10 weeks using a threshold inspiratory trainer with either 30 % ( group 1 ) or 10 % ( group 2 ) of PIMax as a training load . The training load was crossed after each patient completed 10 weeks of training . Effects were assessed through changes in PIMax , dyspnea through the transition dyspnea index ( ITD ) and the respiratory effort with Borg 's score . Walking capacity was measured with the six minutes walking distance test ( 6WD ) and depression symptoms with Beck 's score . Daily life activities were also assessed . Results showed that after 10 weeks of IMT , PIMax increased in both groups ( p < 0.05 ) , dyspnea improved in group 1 as compared to group 2 ( p < 0.04 ) , 6WD increased significantly in patients of group 1 , who also complained of less dyspnea ( p < 0.05 ) . Depression scores fell significantly in group 2 . Daily activities improved more in group 1 . After the crossover patients in group 1 disclosed a significant deterioration in PIMax whereas group 2 disclosed significant improvements in PIMax , dyspnea and 6WD . We conclude that IMT using a threshold device with 30 % PIMax is a useful procedure for the treatment of severe COPD patients BACKGROUND Long-term exercise training is capable of improving exercise performance and quality of life in patients with severe COPD . In the present study we examined the effects of an 18-month home-based training on the rate of hospital admissions and bronchodilator use as primary end-points . Secondary end-points were exercise capacity and quality of life . METHODS The study comprised 26 patients with severe COPD ( 20m/6f ; mean + /- SD FEV1 , 37 + /- 6 % pred ) who were recruited in a previous trial and r and omised into a training ( n = 14 ) and a control group ( n = 12 ) . After initial recovery from an exacerbation the training group had performed a 10-day walking training in the hospital . This was followed by 18 months of individually defined , supervised training at home that was integrated into the patients ' daily activities . The control group had no exercise programme , neither in hospital nor at home . RESULTS During the 18-month period patients of the training group showed a lower number of hospital admissions ( total , n = 3 vs n = 14 , p = 0.026 ; disease-related , n = 3 vs n = 12 , p = 0.050 ) and used less short-acting beta 2-agonists ( mean [ 95 % CI ] , 2.4 [ 1.4 - 3.4 ] vs 5.7 [ 4.2 - 7.2 ] puffs per day ; p < 0.001 ) than the control group . Furthermore , the improvements in 6-min treadmill distance and quality of life ( CRQ ) achieved in the hospital were fully maintained in the training group , whereas the control group did not show significant improvements at any time but a tendency toward deterioration . CONCLUSIONS Our data indicate that an individually defined , home-based , long-term walking programme initiated by a short hospital-based training can reduce disease-related medical consumption , in addition to sustained benefits in exercise performance and quality of life The principals of rehabilitation medicine are to prevent muscle atrophy and improve mobility . Exacerbations of chronic obstructive pulmonary disease ( COPD ) are associated with muscle atrophy and yet many patients do not undergo pulmonary rehabilitation until they have been in stable health for some time . We investigated the outcome of a supervised home exercise programme initiated immediately after hospitalisation for an exacerbation of COPD . Thirty-one patients were r and omised into an exercise group ( n=16 , FEV(1 ) 0.94+/-0.34 L ) and a control group ( n=15 , FEV(1 ) 1.08+/-0.33 L ) . The exercise group received a twice-weekly supervised exercise programme , in their homes , for 6 weeks . Spirometry , exercise capacity , isometric muscle strength , dyspnea level , quality of life at baseline and 6 weeks as well as subsequent exacerbations were quantified . At 6 weeks , the exercise group , improved the shuttle walk test ( 198 m+/-95 - 304+/-136 m ) and increased 3 min step test capacity ( 119+/-40 - 163+/-26s ) ( both P<0.001 ) . Knee extensor muscle strength and quality of life scores also increased . Neither exercise capacity nor muscle strength altered in the control group . Follow-up at 3 months showed that three of the control group and none of the exercise group had experienced subsequent exacerbations ( P=0.06 ) . Early rehabilitation via a home from hospital programme improved exercise tolerance , muscle strength , dyspnea scores , quality of life in COPD patients and reduced the number of subsequent exacerbations BACKGROUND AND OBJECTIVE Acute exacerbations of chronic obstructive pulmonary disease ( AE COPD ) incur heavy utilization of health-care re sources for patients who require hospitalization . We evaluated whether an early outpatient pulmonary rehabilitation programme ( PRP ) after hospitalization for AE COPD could reduce acute health-care utilization over the succeeding year . METHODS Sixty patients admitted with AE COPD were r and omized to either PRP or usual care ( UC ) . The PRP group received 8weeks of outpatient rehabilitation programme 2 - 3weeks after discharge from hospital . Lung function , 6min walk test and dyspnoea score were assessed at baseline , 3 , 6 , 9 and 12months , while St George 's respiratory question naire and cardiopulmonary exercise test were assessed at baseline , 3 , 6 and 12months . RESULTS The PRP and UC groups demonstrated a 53.3 % and 43.3 % risk of readmissions at 12months ( incident risk ratio 0.97 ( 95 % CI : 0.57 - 1.60 ) , P=0.90 ) . The mean readmission rates were 1.00±1.20 and 1.03±1.87 ( P=0.47 ) for the PRP versus UC groups respectively . The rates of AE COPD and emergency department visits were similar between the two groups . The St George 's respiratory question naire total score was lower in the PRP group ( 40.15±19.10 vs 46.91±18.21 , P=0.01 and 42.3±20.06 vs 51.44±18.98 P=0.01 at 3 and 6months respectively ) . There were no statistically significant differences in the FEV(1 ) % predicted , dyspnoea score , 6min walk test and maximal oxygen consumption during exercise test between PRP and UC at different time points . CONCLUSIONS An early rehabilitation programme following AE COPD led to improvement in quality of life up to 6months , but did not reduce health-care utilization at 1year BACKGROUND / PURPOSE This study assessed how positive expiratory pressure ( PEP ) affected pulmonary function , functional capacity , and subjective cough difficulty in individuals with chronic obstructive pulmonary diseases ( COPD ) . METHODS This was a prospect i ve , r and omized , controlled study . Subjects were recruited from an outpatient department at a university hospital . Thirty-two patients with COPD were allocated to either PEP + FET ( forced expiratory technique ) group ( n = 16 ) or FET only group ( n = 16 ) . Subjects in PEP + FET and FET groups were in a clinical ly stable condition before and during the study . Subjects in the PEP + FET group received PEP breathing using a mouth adjunct to FET , and the FET group was administered FET for 4 weeks only . Patients received weekly follow-up during the study period . Pulmonary function , 6-minute walk tests , and subjective cough difficulty scores were measured before and after the 4-week interventions . RESULTS Subjects in the PEP + FET group had a significantly increased diffusing capacity ( DLCO ) compared to preintervention ( p < 0.05 ) and after intervention in the FET group ( p < 0.05 ) . DLCO significantly increased in the PEP + FET group from 18.0 + /- 7.3 to 20.1 + /- 7.2 mL/min/mmHg . The 6-minute walking distance ( 6MWD ) also increased significantly from 516.8 + /- 94.1 to 570.6 + /- 60.4 m in the PEP + FET group ( p < 0.001 ) after intervention , compared to that for the FET group ( p < 0.05 ) . Additionally , the PEP + FET group had significantly lower cough difficulty scores compared to those at baseline and in the FET group . CONCLUSION Four-week PEP therapy as an adjunct to FET further enhanced DLCO and 6MWD , and reduced cough difficulty compared to FET only in COPD patients with mucus hypersecretion OBJECTIVE Pulmonary rehabilitation in patients with COPD has been shown to be beneficial but the optimal setting is not known . In the present study , the efficacy of a short-term community-based exercise programme was compared with a st and ard hospital outpatient programme . Additionally , the usefulness of community or home programmes in maintaining improvements in the longer term was studied . METHODOLOGY Forty-three patients with moderate to severe COPD were r and omized to one of the following three groups : a 3-month hospital programme then a 9 month home programme ( Hospital/Home ) ; a 3-month hospital programme then a 9-month community programme ( Hospital/Community ) ; or a 12-month community programme ( Community/Community ) . The initial 3-month programme was analysed by comparing the Hospital group ( Hospital/Home plus Hospital/Community ) with the Community group ( Community/Community ) . Six-minute walking distance ( 6MWD ) , quality of life ( Guyatt chronic respiratory disease question naire , CRQ ) and lung function were measured at 0 , 3 , 6 and 12 months and results were analysed using the Wilcoxon rank sum test . RESULTS At 3 months , there was a significant improvement from baseline in 6MWD in the Hospital group ( 81.3 + /- 18.3 m , P < 0.05 , anova ) but not the Community group ( 14.4 + /- 28.5 m , not significant ) . The difference between the groups was not significant ( P = 0.058 ) . At 3 months , there was a significant improvement in quality of life in the Hospital group ( CRQ + 16.3 + /- 3.1 , P < 0.01 , anova ) and in the Community group ( CRQ + 10.2 + /- 4.9 , P < 0.05 , anova ) but the difference between the groups was not significant . Following the initial 3-month programme , the dropout rate was high overall ( 73 % by 12 months ) , and therefore data from the maintenance programme could not be analysed . CONCLUSIONS A 3-month community-based exercise programme for patients with COPD did not improve 6MWD . The long-term retention rates in the programmes were poor AIM Education is a key issue for the long-term management of chronic obstructive pulmonary disease in older patients . We tested the hypothesis that integrated care focusing on patient information needs for self-management can improve patient information needs and health outcomes . METHODS Patients with chronic obstructive pulmonary disease ( n=102 ) were r and omized into integrated care ( group I ) and usual care ( group U ) groups . Group I underwent a program of educational sessions for 6months ( integrated education period ) , and then repeatedly received an individually tailored education according to the Lung Information Needs Question naire score . Both groups were followed up monthly for 6months . RESULTS A total of 85 patients ( mean age : 71.7years ) were followed up for 12months . The total Lung Information Needs Question naire score was significantly better in group I than in group U at 12months ( P<0.03 ) . Activities of daily living scores were significantly improved in group I at 6months ( P<0.03 ) . The dyspnea score and the BODE index ( body mass index , dyspnea , airflow obstruction and exercise capacity ) were significantly improved in group I at 12months ( P<0.01 and P<0.02 , respectively ) . During the integrated education period , the frequency of hospitalization was significantly lower in group I than in group U ( P=0.033 ) . CONCLUSION Integrated education for older patients with chronic obstructive pulmonary disease effectively improved patients ' information needs , activities of daily living , dyspnea score , BODE index and reduced hospitalizations during the observed period . Geriatr Gerontol Int 2011 ; 11 : 422 - 430 Clinical experience suggests that exercise is beneficial for recovery after an acute exacerbation in patients with severe chronic obstructive pulmonary disease ( COPD ) . The aim of this study was to quantify the clinical benefit of exercise in these patients . Twenty-nine in patients were r and omly assigned to a training group ( n = 15 , FEV1 34 % pred ) or a control group ( n = 14 , FEV1 38 % pred ) . On ten consecutive days , patients in the training group performed a 6-min treadmill walking test and , in addition , five walking sessions per day at > or = 75 % of the respective treadmill walking distance . Patients in the control group performed only treadmill walking tests on days 1 , 5 , and 10 . To directly compare the possible benefit of exercise training all patients had an exercise test on day 11 at the same work load as on day 1 . In the training group , 6-min walking distance increased from 237 to 420 m , in the control group from 230 to 255 m over the 10 day period which was significantly different ( P < 0.0001 ) . Minute ventilation and oxygen uptake increased significantly ( P < 0.05 ) in the training but not in the control group . When comparing exercise tests on days 1 and 11 , minute ventilation , oxygen uptake , PaCO2 , lactic acid concentration , and Borg scale were significantly reduced to achieve the same work load ( P < 0.01 ) only in the training group . Intrathoracic gas volume and residual volume decreased , and FEV1 and vital capacity increased in the training ( P < 0.05 ) but not in the control group . Our data demonstrate that exercise training significantly improves the exercise capacity in patients with severe COPD after an acute exacerbation of their disease Background : Pulmonary rehabilitation is successful in improving exercise capacity and quality of life in patients with chronic obstructive pulmonary disease ( COPD ) . However , training effects diminish over time . Objectives : We evaluated the effects of simple , daily , structured , self-monitored , home-based exercise training for patients with moderate COPD after a 3-week outpatient rehabilitation . Methods : We conducted a r and omized , controlled , observer-blind trial . Twenty patients were recruited . Ten patients performed home-based exercise training ( mean age 67 years , 95 % confidence interval [ CI ] 63–72 ; FEV1 58.6 % , 95 % CI 53.8–63.4 ) , and 10 patients served as controls ( mean age 72 years , 95 % CI 69–77 ; FEV1 62.5 % , 95 % CI 57.7–67.3 ) . At baseline , and after 3 and 6 months , we assessed exercise capacity ( 6-min walk test , 6MWT , primary endpoint ) , health-related quality of life ( Chronic Respiratory Question naire , CRQ ) and lung function . An intention-to-treat analysis was performed using two-way ANOVA models for comparison of time trends between r and om groups . Results : The training group had better results than the control group in 6MWT ( p = 0.033 ) , in CRQ total ( p = 0.027 ) , CRQ dyspnea ( p = 0.014 ) and CRQ fatigue ( p = 0.016 ) . Improvement in FEV1 was also better in the intervention group than in the control group ( p = 0.007 ) . Conclusions : We demonstrated that training effects obtained from an outpatient rehabilitation program can be maintained by home-based exercise training in patients with moderate COPD OBJECTIVE To determine the importance of a breathing out into water exercise during subtotal immersion for emphysematous patients . DESIGN Results of a respiratory function test and arterial blood gas analysis were examined to compare the programs of breathing exercise with and without the breathing out into water exercise . The breathing exercises in a pool filled with 38 degrees C water were performed 30 min/day , 5 days/wk , for 2 mo in 17 patients with stable chronic emphysema . Patients were r and omly assigned to breathing exercise programs including subtotal water immersion with the nose and mouth either immersed ( 9 patients ) or out of the water ( 8 patients ) during exhalation . RESULTS The ratio of % forced expired volume in 1 sec to forced vital capacity and % forced vital capacity at rest were significantly increased in the program with the breathing out into water exercise , but they did not change in the program without the breathing out into water exercise . A significant increase in peak flow was observed in the former program , although it did not change in the latter program . The maximal expiratory flow at 25 % did not change in either program . Pao2 was significantly increased and Paco2 was significantly decreased in the former program , although a trend for a decrease in Paco2 was observed in the latter program . CONCLUSIONS These results suggest that the breathing out into water exercise enhances the effects of a breathing exercise during immersion and is useful in rehabilitation for chronic pulmonary emphysema The BODE index is frequently used to assess functional capacity in patients with COPD . The aim of this study was to investigate the effectiveness of interval-load training ( ILT ) to improve the BODE index in comparison to the commonly implemented constant-load training ( CLT ) . Forty-two patients with COPD [ FEV(1 ) : ( mean+/-SEM ) 42+/-3 % predicted ] were r and omly allocated to either ILT ( n=21 ) or CLT ( n=21 ) . The training program consisted of cycling exercise 3 days/week for 10 weeks . Patients assigned to ILT exercised at a mean intensity of 126+/-4 % of baseline peak work rate ( Wpeak ) with 30-s work periods alternated with 30-s rest periods for 45 min per day , whereas patients allocated to CLT exercised at a mean intensity of 76+/-5 % of baseline Wpeak for 30 min per day . The BODE index and its components : body mass index , FEV(1 ) , MMRC dyspnea score and the 6-min walk test ( 6-MWT ) as well as cycling Wpeak were assessed before and after both exercise training regimes . Both ILT and CLT significantly ( p<0.001 ) decreased the BODE index ( from 4.8+/-0.5 to 4.0+/-0.5 units and from 4.4+/-0.5 to 3.8+/-0.5 units , respectively ) . In addition , both ILT and CLT significantly decreased the MMRC dyspnea score by 0.4+/-0.1 units and increased the 6-MWT ( by 52+/-16 and 44+/-12 m , respectively ) as well as cycling Wpeak ( by 14+/-2 and 10+/-2W , respectively ) . The magnitude of these changes was not significantly different between ILT and CLT . Consequently , ILT is equally effective to CLT in terms of improving the BODE index in patients with COPD and as such it may constitute an alternative rehabilitative modality in COPD The aim of this study was to compare the effects of interval training ( 3-min intervals ) with continuous training on peak exercise capacity ( W peak ) , physiological response , functional capacity , dyspnoea , mental health and health-related quality of life ( HRQoL ) in patients with moderate or severe COPD . Sixty patients exercised twice weekly for 16 weeks after r and omisation to interval- or continuous training . Target intensity was 80 % of baseline W peak in the interval group ( I-group ) and 65 % in the continuous group ( C-group ) . Patients were tested by spirometry , ergometer cycle test , cardiopulmonary test and a 12 min walk test . Dyspnoea was measured by the dyspnoea scale from Chronic Obstructive Disease Question naire ( CRDQ ) , mental health by Hospital Anxiety and Depression scale ( HAD ) and HRQoL by the Medical Outcomes Survey Short Form 36 ( SF-36 ) . After training , W peak , peak oxygen uptake ( VO(2 ) peak ) and exhaled carbon dioxide ( VCO(2 ) peak ) increased significantly in both groups , no significant differences between the groups . Minute ventilation ( V(E ) peak ) increased only in the C-group . At identical work rates ( isotime ) VO(2 ) , VCO(2 ) and V(E ) were significantly more decreased in the I-group than in the C-group ( p<0.05 ) . Functional capacity , dyspnoea , mental health , and HRQoL improved significantly in both groups , no difference between the groups . Interval training and continuous training were equally potent in improving peak exercise capacity , functional exercise capacity , dyspnoea , mental health and HRQoL in patients with moderate or severe COPD . At isotime , the physiological response to training differed between the groups , in favour of the interval training This study determined the effect of a high vs low resistive inspiratory muscle interval training protocol on inspiratory muscle strength ( PImax ) , incremental inspiratory threshold loading ( Pitl ) , inspiratory muscle endurance ( IE ) , and 12-minute distance test ( 12 MD ) in severely impaired patients with COPD . We used a double-blind , two-group , repeated-measure design . Group 1 ( n = 12 ) received supervised high resistive loading at approximately 52 percent PImax and group 2 ( n = 8) received supervised low resistive loading at approximately 22 percent PImax . All subjects trained three times weekly ( progressing from 5 min per session in week 1 to 18 min per session in week 12 ) for 12 weeks . After three practice sessions , measures of PImax , Pitl , IE , and 12 MD were taken at baseline , at 4-week intervals , and within 72 h of completing the protocol . Group 1 showed significant improvement in all four dependent variables while group 2 improved in Pitl , IE , and 12 MD . The results suggest there is no significant difference between high and low resistive interval training in more severely impaired patients with COPD BACKGROUND Respiratory muscle weakness may contribute to dyspnea and exercise limitation in patients with significant COPD . In an attempt to reduce the severity of breathlessness and to improve exercise tolerance , inspiratory muscle training has been applied in many COPD patients . On the other h and , there is a paucity of data related to expiratory muscle performance and training in COPD . METHODS Thirty-two patients with significant COPD ( ie , mean FEV(1 ) , 37 % of predicted ) were recruited for the study . The patients were r and omized into four groups : eight patients were assigned to receive specific expiratory muscle training ( SEMT ) ; eight patients received specific inspiratory muscle training ( SIMT ) ; eight patients received SEMT and SIMT ( ie , the SEMT + SIMT group ) ; and eight patients who were assigned to a control group received training with very low load . All patients trained daily , six times a week , with each session consisting of one half hour of training , for 3 months . Spirometry , respiratory muscle strength and endurance , 6-min walk test distance , the perception of dyspnea , and the Mahler baseline dyspnea index ( BDI ) were measured before and following training . RESULTS Training caused a statistically significant specific increase in the expiratory muscle strength and endurance ( in the SEMT and SEMT + SIMT groups ) and in the inspiratory muscle strength and endurance ( in the SIMT and SEMT + SIMT groups ) . There was significant increase in the distance walked in 6 min in the SEMT , SIMT , and SEMT + SIMT groups . However , the increase in the SIMT and SEMT + SIMT groups was significantly greater than that in the SEMT group . There was a statistically significant increase in the BDI , and a decrease in the mean Borg score during breathing against resistance in the SIMT and SEMT + SIMT groups , with no changes in the SEMT and control groups . CONCLUSIONS The inspiratory and expiratory muscles can be specifically trained with improvement of both muscle strength and endurance . The improvement in the inspiratory muscle performance is associated with an increase in the 6-min walk test distance and the sensation of dyspnea . There is no additional benefit gained by combining SIMT with SEMT , compared to using SIMT alone QUESTIONS Does a 12-week , predominantly home-based program of progressive resistance exercises reduce impairments , activity limitations , and participation restrictions in people with chronic obstructive pulmonary disease ? Are any gains maintained 12 weeks after the cessation of the program ? DESIGN R and omised controlled trial with concealed allocation , assessor blinding , and intention-to-treat analysis . PARTICIPANTS 54 people with moderately severe chronic obstructive pulmonary disease not undergoing pulmonary rehabilitation . INTERVENTION The experimental group performed six progressive resistance exercises three times per week ( once a week hospital-based , twice a week home-based ) for 12 weeks . Exercise intensity was three sets of 8 to 12 repetition maximum progressed against elasticised b and s of increasing resistance . The control group received no intervention . OUTCOME MEASURES Primary outcomes were strength ( knee extensor , hip abductor , shoulder horizontal flexor , shoulder flexor ) measured using h and -held dynamometry , and walking capacity measured by the 6-minute Walk Test performed before and after intervention and again at 12 weeks after the cessation of intervention . RESULTS The experimental group increased their knee extensor strength by 4.9 kg ( 95 % CI 1.1 to 8.7 ) more than the control group by Week 12 . However , this gain was not maintained at Week 24 . No difference between the groups was found for any of the other primary outcomes . CONCLUSIONS A predominantly home-based progressive resistance exercise program led to modest improvements in knee extensor strength in people with chronic obstructive pulmonary disease . However , 44 % of the experimental group were unable to complete the exercise program , highlighting the need to underst and factors influencing adherence to exercise in this population We conducted a r and omized clinical trial to evaluate a limited pulmonary rehabilitation program focused on coping strategies for shortness of breath but without exercise training . Eighty-nine patients with COPD were r and omly assigned to either 6-week treatment or general health education control groups . Treatment consisted of instruction and practice in techniques of progressive muscle relaxation , breathing retraining , pacing , self-talk , and panic control . Tests of 6-min walk distance , quality of well-being , and psychological function as well as six dyspnea measures were administered at baseline , posttreatment , and 6 months after the intervention . Baseline pulmonary function tests also were obtained . At the end of the 6-week treatment , there were no significant differences between the treatment and control groups on any outcome measure . At the 6-month follow-up , a significant group difference was seen on only one variable , Mahler 's transition dyspnea index . The results of this evaluation suggest that a treatment program of dyspnea management strategies , without structured exercise training or other components of a comprehensive pulmonary rehabilitation program , is not sufficient to produce significant improvement in dyspnea , exercise tolerance , health-related quality of well-being , anxiety , or depression PURPOSE Many patients with chronic obstructive pulmonary disease ( COPD ) report dyspnea and fatigue when performing upper limb activities . Unsupported upper limb training has been shown to improve upper limb endurance , but its effects on symptoms and quality of life have not been examined . The aim of this study was to compare the effects of upper limb and lower limb training with lower limb training alone on exercise capacity , symptoms , and quality of life with COPD . METHODS For this study , 38 patients with moderate to severe COPD were r and omly allocated to unsupported upper limb endurance training or to a control group that completed a sham training task . All the patients underwent lower limb endurance training . The 6-minute walk test , the Incremental Unsupported Upper Limb Exercise Test , and the Chronic Respiratory Disease Question naire ( CRQ ) were completed before training and then 6 weeks afterward . Both patients and assessors were blinded to group allocation . RESULTS All the patients reported symptoms associated with upper limb activities on the initial CRQ . Both groups showed significant improvements in all domains of the CRQ and in the 6-minute walk test after training . Only the upper limb training group showed improvement in upper limb endurance time ( 57 + /- 75 vs 2 + /- 58 seconds ; P = .02 ) . There were no significant differences between the groups for 6-minute walk test or any domain of the CRQ . CONCLUSIONS Unsupported upper limb training for patients COPD improves upper limb exercise capacity , but has no additional effect on symptoms or quality of life , as compared with leg training alone . This type of upper limb training may not adequately address the complex interaction between respiratory mechanics and upper limb function PURPOSE The purpose of this study was twofold : ( 1 ) to determine whether exercise training adds to the benefit of a dyspnea self-management ( DM ) program ; and ( 2 ) to determine if there is a " dose response " to supervised exercise training ( 0 , 4 , or 24 sessions ) in dyspnea , exercise performance , and health-related quality of life . METHODS Subjects with chronic obstructive pulmonary disease ( n = 103 , 46 men , 57 women ; age 66 + /- 8 years ; forced expiratory volume in 1 second 44.8 + /- 14 % predicted ) were r and omized to DM , DM-exposure , or DM-training . Dyspnea self-management included individualized education about dyspnea management strategies , a home-walking prescription , and daily logs . Outcomes were measured at baseline and 2 months as part of a 1-year longitudinal r and omized clinical trial . Outcomes included dyspnea during laboratory exercise and with activities of daily living ( Chronic Respiratory Question naire [ CRQ ] ) , Shortness of Breath Question naire , Baseline/Transitional Dyspnea Index ) , exercise performance ( incremental treadmill tests ( ITTs ) and endurance treadmill tests ( ETTs ) , 6-minute walk ( 6MW ) , and health-related quality of life ( SF-36 ) . RESULTS The DM-training group had significantly greater improvements than the DM-exposure and the DM groups in dyspnea at isotime during ITT ( P = .006 ) ; exercise performance during ITT ( P = .005 ) , ETT ( P = .003 ) , and 6MW ( P = .01 ) ; SF-36 Vitality ( P = .031 ) ; and CRQ mastery ( P = .007 ) . There was a dose-dependent improvement in CRQ dyspnea scores ( P < .05 ) with significant improvements only in the DM-training and DM-exposure groups . CONCLUSION Exercise training substantially improved the impact of a dyspnea self-management program with a home walking prescription ( DM ) . This impact tended to be dependent on the " dose " of exercise The inspiratory pressure load is an important variable in inspiratory muscle training ( IMT ) , but previous studies with chronic obstructive pulmonary disease ( COPD ) patients have not controlled for this variable . We compared the effects of two months of IMT with a pressure threshold breathing device at inspiratory pressure loads equal to either 15 or 30 % of each patient 's maximal inspiratory pressure ( Plmax ) . This study was double blind and patients were r and omly assigned to the treatment groups , 12 in the 15 % group and ten in the 30 % group . Dependent variables were measured at baseline , and after one and two months of IMT . Patients who exercised with the 30 % load improved the following : Plmax by a mean of -12 + /- 9 cm H2O ( p less than 0.01 ) , endurance time while breathing against an inspiratory pressure load equal to 66 % of Plmax by 5 + /- 9 min ( p less than 0.01 ) , and 12-min distance walk ( 12MD ) by 199 + /- 90 feet ( p less than 0.01 ) . Patients who exercised with the 15 % load demonstrated no improvements in Plmax , endurance time , and 12MD . There were no changes in patients ' report of functional impairment ( Sickness Impact Profile ) , mood ( Profile of Mood States ) , health status ( Health Perceptions Question naire ) , and pulmonary symptoms ( respiratory symptom log ) . We conclude that the 30 % load was more effective than the 15 % load in this sample OBJECTIVE To compare two training programs in rehabilitation for patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) . METHODS Of the 54 patients who entered the study , 41 completed the rehabilitation program . Thirty-two COPD patients were r and omly assigned to either the anaerobic threshold group ( AT , n = 15 ) or the high-intensity group ( HI , n = 17 ) . Another group was the control group ( NT , n = 9 ) . Bicycle exercise training was conducted for 2 days each week for a period of 12 weeks . The HI group received the highest level of intensity that could be tolerated . The AT group received a training intensity corresponding to the anaerobic threshold . Main assessment s included lung function test , cardiopulmonary exercise testing , the St George 's Respiratory Question naire and the Borg dyspnea scale before and after the rehabilitation program . The data of the baseline clinical characteristics of groups were presented as ( -x ) + /- s. Comparison within two means were analysed through one- sample t test or paired t test . One-way analysis of variance was used to compare multiple means . The rates were analysis ed by Fish exact probabilities . The Wilcoxon rank sum test was used for comparisons within the groups and the Mann-Whitney u test for intergroup comparisons . RESULTS Both the AT and HI groups showed significant improvement in Vo(2peak)% pre after rehabilitation , with the former increasing from ( 61 + /- 11)% to ( 69 + /- 14)% , and the latter increasing from ( 72 + /- 12)% to ( 79 + /- 13)% . The degree of improvement of both groups ( AT and HI ) were ( 14 + /- 17)% and ( 12 + /- 13)% , the difference being not significant ( z = -0.180 , P > 0.05 ) . At 56 W work rate , the minute ventilation decreased from ( 36 + /- 4 ) L/min to ( 33 + /- 5 ) L/min ( t = 6.167 , P < 0.01 ) , the breathing frequency decreased from ( 32 + /- 1 ) beats/min to ( 31 + /- 3 ) beats/min ( t = 2.876 , P < 0.05 ) , and the tidal volume increased from ( 1.2 + /- 0.3 ) L to ( 1.3 + /- 0.3 ) L ( t = 2.587 , P < 0.05 ) in the HI group . After rehabilitation the heart rates [ ( 109 + /- 39 , 110 + /- 25 ) beats/min ] were significantly lower than those of the baseline [ ( 116 + /- 39 , 114 + /- 42 ) beats/min ] respectively in the AT and the HI groups . Oxygen pulse increased significantly from baseline ( 9.6 + /- 3.7 , 8.5 + /- 4.3 ) ml/beat to ( 10.4 + /- 4.0 , 9.0 + /- 3.2 ) ml/beat . This level of exertional dyspnea ( DeltaBorg/DeltaVo(2 ) ) was significantly improved from ( 8.6 + /- 3.2 , 6.5 + /- 2.6 ) to ( 7.4 + /- 2.5 , 5.6 + /- 2.4 ) in both the HI and the AT group ( both P < 0.05 ) . The between-group difference for the change in DeltaBorg/DeltaVo(2 ) , however , was not significant ( z = -0.378 , P > 0.05 ) . CONCLUSIONS Both the HI and the AT groups had significant improvements in exercise capacity and dyspnea after pulmonary rehabilitation . The degree of improvement in both groups was similar . But the HI group showed significant improvement in the anaerobic threshold and decrease in ventilatory requirement Paz-Díaz H , Montes de Oca M , López JM , Celli BR : Pulmonary rehabilitation improves depression , anxiety , dyspnea and health status in patients with COPD . Am J Phys Med Rehabil 2007;86:30–36 . Objective : To determine the impact of an 8-wk program of comprehensive pulmonary rehabilitation on depression , anxiety , dyspnea , and health-related quality of life in patients with chronic obstructive pulmonary disease ( COPD ) . Design : We studied 24 patients with severe COPD r and omized either to pulmonary rehabilitation ( PR ) , ( n = 10 ; FEV1 30 ± 9 % ) or control ( C ; n = 14 ; FEV1 34 ± 11 % ) . The PR program included disease education , energy conservation techniques , relaxation , and exercise including 20-min arm elevation with dumbbells and 20-min leg exercise sessions three times a week for 8 wks . At baseline and after completion of the program , all patients were evaluated using the Beck Depression Inventory , State Trait Anxiety Inventory ( STAI ) , Modified Medical Research Council Scale ( MRC ) , and St. George ’s Respiratory Question naire ( SGRQ ) . Results : After PR , there was a significant improvement in the severity of depression ( P < 0.01 ) , a decrease in symptoms ( P < 0.05 ) , an increase in daily living activities ( P < 0.05 ) , and a decrease in the total score of the SGRQ ( P < 0.01 ) . Dyspnea measured by the MRC scale was significantly better in the PR group ( P < 0.01 ) . Conclusions : The present study shows that in patients with severe COPD , pulmonary rehabilitation induces important changes on depression and anxiety independent of changes in dyspnea and health-related quality -of-life STUDY OBJECTIVES To study the short-term and long-term effects of combining activity training or lectures to exercise training on quality of life , functional status , and exercise tolerance . DESIGN R and omized clinical trial . SETTING Outpatient pulmonary rehabilitation center . PARTICIPANTS Forty-three out patients with COPD . INTERVENTIONS Patients were r and omized to one of three treatment groups : exercise training alone , exercise training plus activity training , and exercise training plus a lecture series . The mean treatment period was 10 weeks . MEASUREMENT The Chronic Respiratory Disease Question naire , the modified version of the Pulmonary Functional Status and Dyspnea Question naire , and the COPD Self-Efficacy Scale were administered at baseline , and 6 , 12 , 18 , and 24 weeks from the beginning of the rehabilitation program . The 6-min walk test was used to measure exercise tolerance . RESULTS Benefits of activity training combined with exercise included less dyspnea ( p < or = 0.04 ) and fatigue ( p < or = 0.01 ) , and increased activity involvement ( p < or = 0.02 ) and total functional status ( p < or = 0.02 ) in the short term compared to comparison treatment groups for comparatively older participants . Compared to the lecture series adjunct , the activity training adjunct result ed in significantly higher gains in total quality of life ( p = 0.04 ) maintained at 24 weeks . Significantly worse emotional function and functional status result ed from the lecture series adjunct in the oldest participants ( p < or = 0.03 ) . Treatment groups did not differ significantly on exercise tolerance or self-efficacy . CONCLUSIONS Evidence for additional benefits of activity-specific training combined with exercise was found . A behavioral method emphasizing structured controlled breathing and supervised physical activity was statistically significantly more effective than didactic instruction in facilitating additional gains and meeting participants ' learning needs BACKGROUND The partition and chronological sequence of the different training items and modalities necessary for an effective training of patients with chronic obstructive pulmonary disease ( COPD ) remains a subject of debate . We investigated the combination of effective components of pulmonary rehabilitation in the setting s outpatient lung sports group , home-based training and training in a gym . METHODS Subjects were r and omized to a 12-month training program and a no training group . PATIENTS AND MAIN RESULTS The training group ( n = 10 , mean age : 62.5 years , FEV1 53.4 % predicted ) reached an average increase in peakVO2 of 10 % ( p = 0.01 ) from 1.30 + /- 0.41 L/minute to 1.44 + /- 0.38 L/minute , in peak work rate of 14 % ( p = 0.007 ) from 82 + /- 39 W to 93 + /- 43 W and in the six-minute walking distance of 79 meters ( p = 0.003 ) , whereas in the control group ( n = 9 , mean age : 63.2 years , FEV1 53.7 % predicted ) no significant changes were observed . The quality of life obtained by use of the SF36- question naire and SGRQ also significantly improved in the training group , but not in the control group . CONCLUSION This outpatient rehabilitation program is effective and appropriate for long-term rehabilitation of patients with COPD OBJECTIVES The development of a probabilistic Markov model with a time horizon of 1 year to compare the cost-effectiveness of three bronchodilators : 1 ) the new long-acting anticholinergic tiotropium ; 2 ) the short-acting anticholinergic ipratropium ; and 3 ) the long-acting beta 2-agonist salmeterol , for the treatment of patients with chronic obstructive pulmonary disease ( COPD ) in different countries . In this article we compare The Netherl and s and Canada . METHODS The Markov model was structured along disease severity states and exacerbations . Transition probabilities between disease states and exacerbation probabilities were derived from patient-level data from six r and omized controlled trials assessing the efficacy and safety of tiotropium . Re source utilization during exacerbations and maintenance treatment for The Netherl and s were derived from two clinical trials , whereas for Canada these data were obtained from a countrywide observational study that used similar inclusion criteria as the trials . Second-order Monte Carlo simulations were undertaken in which values were r and omly drawn from distributions of these parameters . Outcomes of the model are yearly treatment costs , exacerbations , and quality -adjusted life months . RESULTS The mean difference in the number of exacerbations was 0.17 ( 95 % uncertainty interval : -0.02 - 0.37 ) in favor of tiotropium when compared with salmeterol and the difference between salmeterol and ipratropium was 0.12 ( -0.17 - 0.44 ) in favor of salmeterol . The number of quality -adjusted life months did not substantially differ between treatment groups and varied from 8.42 ( SE 0.41 ) in the tiotropium group to 8.17 ( 0.46 ) in the salmeterol group and 8.11 ( 0.50 ) in the ipratropium group . In The Netherl and s , costs in the tiotropium group were 42 Euros ( -484 - 353 ) lower than in the salmeterol group , whereas costs in the salmeterol group were 128 Euros ( -795 - 457 ) lower than in the ipratropium group . In Canada , costs were consistently lower than in The Netherl and s and nearly the same in all treatment groups . Differences between the two countries were primarily a result of a higher length of hospital stay in case of an exacerbation in The Netherl and s. The cost-effectiveness acceptability frontier of exacerbations showed that tiotropium was associated with the maximum expected net benefit for all values of the ceiling ratio above 0 Euros ( The Netherl and s ) and 10 Euros ( Canada ) in the base case analysis . CONCLUSIONS This probabilistic model-based economic evaluation demonstrates how clinical trial data can be combined and integrated with country-specific information about re source utilization and unit cost to assess the cost-effectiveness of bronchodilators in COPD patients . Quality -adjusted life months did not substantially differ between treatment groups . In terms of exacerbations , tiotropium was associated with maximum expected net benefit for plausible values of the ceiling ratio . In sensitivity analyses , this outcome was most sensitive to changes in exacerbation rates OBJECTIVE Compare unsupported ( UAEx ) vs supported ( SAEx ) arm exercise in training of patients with severe chronic airflow obstruction ( CAO ) . DESIGN R and omized trial of UAEx vs SAEx training added to a 10-week outpatient program of lower extremity ( LE ) exercise training , respiratory muscle training , breathing retraining , psychological support , and teaching . SETTING The Lahey Clinic Medical Center , a tertiary referral center . PATIENTS Forty patients with CAO entered the rehabilitation program with 32 completing training and testing . INTERVENTIONS All underwent progressive bicycle ergometer and treadmill training and respiratory muscle training using a threshold inspiratory pressure trainer . Patients were r and omized to progressive SAEx training ( arm cycle ergometer , n = 17 ) or UAEx training ( raising weighted dowel , n = 18 ) . MAIN OUTCOME MEASURES AND RESULTS There was no significant difference in disease severity or exercise capacity between the two groups . Twelve-min walk test , bicycle ergometer power output , and respiratory muscle function improved with no significant difference in improvement between the two groups . Both groups showed similar improvements in arm ergometer testing while those trained with UAEx showed greater improvement in dowel testing ( UAEx > SAEx , p = 0.002 ) . In 17 patients VO2isotime ( time at which patient performed pre-training and post-training tests ) was measured during dowel testing . Only those trained with UAEx showed decreases in VO2isotime ( UAEx trained , p = 0.02 ; SAEx , p = 0.18 ) . VO2 during the last minute of a 2-min period of simple arm elevation was also measured in 17 patients . Only those trained with UAEx showed decreases in VO2 ( UAEx , p = 0.02 ; SAEx , p = 0.20 ) . CONCLUSION We confirm that a pulmonary rehabilitation program incorporating exercise training improves LE and respiratory muscle function . Arm exercise training improved arm activity with greater increases in unsupported arm activity seen in those trained with unsupported arm training . Metabolic cost of UAEx decreased only in those trained with UAEx . As UAEx is typical of activities of daily living in patients with CAO , the changes seen with UAEx training may be of greater clinical significance . Arm training should be incorporated in exercise training and a simple program of UAEx appears the optimal format STUDY OBJECTIVE To examine the effects of targeted inspiratory muscle training on respiratory muscle function , clinical ratings of dyspnea , and perception of resistive loads in symptomatic patients with chronic obstructive pulmonary disease . DESIGN R and omized , placebo-controlled trial with an 8-week treatment period . SETTING Outpatient pulmonary clinic and pulmonary function laboratory . PARTICIPANTS We studied 19 patients with moderate to severe chronic obstructive pulmonary disease , assigning 10 patients to an experimental group and 9 to a control group . INTERVENTIONS Patients in both groups trained for 15 minutes twice each day using a device that provided breath-to-breath visual feedback of training intensity . Patients in the experimental group trained at six increasing levels of inspiratory resistance , whereas the patients in the control group trained at a constant , nominal level of resistance . MEASUREMENTS AND RESULTS Although there was no statistically discernible difference in the effects of targeted muscle training on the mean difference in maximal inspiratory pressures between the two groups ( 9.83 cm H2O ; 95 % CI , -7.37 to 27.03 ) , patients in the experimental group did show a significant increase in inspiratory muscle strength ( 15.03 cm H2O ; P = 0.01 ) . Experimental subjects also had decreased dyspnea after 8 weeks of training compared with control subjects ( P = 0.003 ) . Improvements in physiologic values and in dyspnea ratings were correlated . The perception of added resistive loads was not affected by inspiratory muscle training . CONCLUSIONS Targeted inspiratory muscle training may enhance respiratory muscle function and reduce dyspnea in symptomatic patients with moderate to severe chronic obstructive pulmonary disease The aim of this study was to explore the effects of guided imagery relaxation in people with chronic obstructive pulmonary disease ( COPD ) using a r and omized controlled design . Half of 26 participants were allocated to the treatment group in which six practice sessions on guided imagery were conducted , while the control group was instructed to take rest quietly during the six sessions . At the seventh session , physiological changes : partial percentage of oxygen saturation ; heart rate ; upper thoracic surface electromyography ; skin conductance ; and peripheral skin temperature were recorded during a 30-minute session with a sampling frequency of one minute . Repeated measures analysis of variance was used to explore the changes of the parameters between the groups . Mann-Whitney U test was used to compare the change of perceived dyspnoea between the groups . Results showed there was a statistically significant ( p < 0.05 ) increase in partial percentage of oxygen saturation in the treatment group , but no significant effects on the other physiological parameters . Further study exploring the psychological effects of guided imagery is suggested Introduction : Acute exacerbations of chronic obstructive pulmonary disease ( COPD ) are a frequent reason for admission to hospital and are responsible for the majority of the direct economic costs of treating COPD . Aims : To test whether an individualized care plan for patients experiencing acute exacerbations of COPD result in reduced health care utilization and improved quality of life for patients . Methods : Ninety-two patients with confirmed COPD were selected by general practitioners or district nurses , and r and omly assigned to care plan or usual care groups . The care plan was developed in collaboration with general practitioners , secondary care specialists , specialist nurses , ambulance service providers and the after hours clinic . Patients were followed for 12 months , and the primary end-points were frequency of use of primary care services and hospital admissions . Results : There was no significant reduction in hospital admissions or improvement in quality of life in the group of patients who used the care plan compared to controls . The care plan group called out the ambulance service more frequently [ 2.8 ( 1.3 , 4.3 ) versus 1.1 ( 0.7 , 1.5 ) calls per 12 months ; P = 0.03 ] , and there was a trend towards greater use of oral prednisone [ 2.3 ( 1.4 , 3.2 ) versus 1.3 ( 0.8 , 1.8 ) courses per 12 months ; P = 0.06 ] . Conclusion : In contrast to asthma , the provision of individualized self-management plans , whose content was enhanced to provide guidance to carers and health care professionals , did not reduce health care utilization or improve overall quality of life during acute exacerbations of COPD . Other strategies are required The purpose of this study was to evaluate whether strength or recreational activities are a useful addition to aerobic training in patients with chronic obstructive pulmonary disease ( COPD ) . Thirty-three patients with moderate to severe COPD were r and omly assigned to 12 weeks of aerobic combined with strength training ( AERO+ST ) or combined with recreational activities ( AERO+RA ) . The AERO regimen consisted of three weekly 20-min walking exercise sessions ; the ST regimen included three series of 10 repetitions of four exercises ; and the RA regimen consisted of training using exercise balls to perform smoothly for instrumental activity of daily living . Baseline and after-training measurements of peripheral muscular strength and endurance , cardio respiratory fitness , and 6-min walking distance were obtained , whereas quality of life was assessed with the Short Form 36 question naire . Change in grip strength showed a significant difference between the AERO+ST group ( 8.3±6.7 % ) and the control group ( −1.3±10.5 % ) , and AERO+RA group ( −4.7±5.6 % ) ( P<0.05 ) . A significant increase was found in percentage change in peak & OV0312;o2 between the AERO+ST group ( 5.1±11.8 % ) and the control group ( −9.2±8.6 % ) ( P<0.05 ) . In the health-related quality of life scores , there was a significant difference in mean percentage change in physical functioning between the AERO+ST group ( 7.9±24.4 % ) and the control group ( −14.8±19.1 % ) ( P<0.05 ) . A significant difference was found in mean percentage change in social functioning between the AERO+RA group ( 9.4±20.0 % ) and the control group ( −14.9±23.2 % ) ( P<0.05 ) . A significant difference in mean percentage change in mental health was also found between the AERO+RA group ( 12.2±12.4 % ) and the control group ( −5.0±7.8 % ) ( P<0.05 ) . It is preferable to introduce various forms of exercise that use different muscles involving the whole body , such as recreational activities , as they are an appropriate approach to stimulating physical activity and to improving functional fitness gradually while improving health-related quality of life , though it is necessary to practice exercises for maintenance and improvement in patients with COPD . Die vorliegende Studie soll ermitteln , ob Krafttraining oder Freizeitaktivitäten das Aerobictraining von Patienten mit chronisch-obstruktiver Lungenerkrankung ( COPD ) sinnvoll ergänzen . Insgesamt wurden 33 Patienten mit moderater bis schlimmer COPD einem 12-wöchigen Aerobictraining mit Krafttraining ( AERO+ST ) oder einem 12-wöchigen Aerobictraining mit Freizeitaktivitäten ( AERO+RA ) r and omisiert zugeordnet . Das AERO-Programm umfasste drei 20-minütige Gehübungen pro Woche , das ST-Programm dreimal je 10 Wiederholungen mit vier Übungen und das RA-Programm ein Training mit Gymnastikbällen , die wichtige Aktivitäten i m Alltagsleben erleichtern sollten . Messungen wie periphere Muskelkraft und Ausdauer , kardiorespiratorische Fitness und 6-minütiges Gehen gegenüber Baseline und nach dem Training wurden erhalten , und die Lebensqualität wurde mittels Fragebogen SF-36 beurteilt . Veränderungen bei der Griffstärke wiesen einen signifikanten Unterschied zwischen der AERO+ST Gruppe ( 8,3±6,7 % ) und der Kontrollgruppe ( −1,3±10,5 % ) und der AERO+RA Gruppe ( −4,7±5,6 % ) auf ( P<0,05 ) . Ebenfalls beobachtet wurde ein signifikanter Anstieg bei der prozentualen Veränderung von & OV0312;o2 maximal zwischen der AERO+ST Gruppe ( 5,1±11,8 % ) und der Kontrollgruppe ( −9,2±8,6 % ) ( P<0,05 ) . Bei den gesundheitsbezogenen Lebensqualitäts-Scores best and ein signifikanter Unterschied in der durchschnittlichen prozentualen Veränderung bei der körperlichen Funktion zwischen der AERO+ST Gruppe ( 7,9±24,4 % ) und der Kontrollgruppe ( −14,8±19,1 % ) ( P<0,05 ) . Ein signifikanter Unterschied wurde bei der durchschnittlichen prozentualen Veränderung bei der gesellschaftlichen Funktionsfähigkeit zwischen der AERO+RA Gruppe ( 9,4±20,0 % ) und der Kontrollgruppe ( −14,9±23,2 % ) beobachtet ( P<0,05 ) . Außerdem beobachtet wurde ein signifikanter Unterschied in der durchschnittlichen prozentualen Veränderung in der seelischen Gesundheit zwischen der AERO+RA Gruppe ( 12,2±12,4 % ) und der Kontrollgruppe ( −5,0±7,8 % ) ( P<0,05 ) . Verschiedene Übungsformen wie Freizeitaktivitäten , die verschiedene Körpermuskeln trainieren , sind als angemessener Stimulus der körperlichen Betätigung und zur allmählichen Verbesserung der funktionellen Fitness vorzuziehen , während sie gleichzeitig die gesundheitsrelevante Lebensqualität verbessern , obwohl Übungen zur Erhaltung und Verbesserung von Patienten mit COPD notwendig sind . El objetivo de este estudio fue evaluar si los ejercicios de desarrollo de fuerza o las actividades recreativas result an de utilidad , además de los ejercicios aeróbicos , en pacientes afectos de enfermedad pulmonar obstructiva crónica ( EPOC ) . Se distribuyeron de manera aleatoria a 33 pacientes afectos de EPOC de moderada a grave para participar en un programa de 12 semanas de ejercicios aeróbicos combinados ya fuese con ejercicios de desarrollo de fuerza ( AERO+EF ) o con actividades recreativas ( AERO+AR ) . El régimen de ejercicios aeróbicos ( AERO ) consistió en 3 sesiones semanales de caminatas de 20 minutos de duración cada una ; el régimen EF consistió en 3 series de 10 repeticiones de 4 tipos de ejercicios ; y el régimen AR consistió en un programa con pelotas para ejercicios , para realizar actividades instrumentales de la vida cotidiana . Al inicio del estudio y una vez terminado el régimen de ejercicios se obtuvieron datos sobre la fuerza muscular periférica , la resistencia , la aptitud cardiorrespiratoria , y tras una caminata de 6 minutos . Para evaluar la calidad de vida se utilizó el cuestionario reducido de 36 preguntas ( Short Form 36 ) . Los cambios en la fuerza de agarre mostraron una diferencia significativa entre el grupo que recibió AERO+EF ( 8,3±6,7 % ) y el grupo de referencia ( −1,3±10,5 % ) , y el grupo que recibió AERO+AR ( −4,7±5,6 % ) ( P<0,05 ) . Se apreció un aumento importante en los cambios en los valores porcentuales máximos del & OV0312;o2 entre el grupo que realizó AERO+EF ( 5,1±11,8 % ) y el grupo de referencia ( −9,2±8,6 % ) ( P<0,05 ) . En cuanto a las puntuaciones sobre la calidad de vida relacionada al estado de salud , se apreció una diferencia importante en cuanto a la media de los cambios de los porcentajes del funcionamiento social entre el grupo que realizó AERO+AR ( 9,4±20,0 % ) y el grupo de referencia ( −14,9±23,2 % ) ( P<0,05 ) . Además se observó una diferencia significativa en la media de los cambios de los porcentajes relacionados con la salud mental entre el grupo que realizó AERO+AR ( 12,2±12,4 % ) y el grupo de referencia ( −5,0±7,8 % ) ( P<0,05 ) . Result a preferible la introducción de varios tipos de ejercicio físico , en los que haya que utilizar diferentes músculos de todo el cuerpo , tales como actividades recreativas , como una manera apropiada de promover la actividad física y mejorar la aptitud funcional de manera gradual a la vez que se mejora la calidad de vida relacionada con el estado de salud , aunque en los pacientes con EPOC la práctica de ejercicios es vital para mejorar y mantener la salud . Cette étude avait pour objet d'évaluer dans quelle mesure les activités fortifiantes ou de loisir constituent une addition utile aux exercices aérobic chez les patients souffrant de maladie pulmonaire obstructive chronique ( MPCO ) . Trente-trois patients souffrant de MPCO modérée à sévère ont été affectées de manière aléatoire à un programme de 12 semaines d'exercices d'aérobic combinés avec des activités fortifiantes ( AERO+ST ) ou des activités de loisirs ( AERO+RA ) . Le programme AERO comportait trois séances hebdomadaires de 20 minutes d'exercices de marche , le programme ST consistait en trois séries de 10 répétitions de quatre exercices , et le programme RA se composait d'exercice de formation utilisant des ballons , destinés à faciliter les activités d'utilisation d'instruments au quotidien . Des mesures de référence et après exercice de la force musculaire périphérique et de l'endurance et des capacités cardio-respiratoires après un exercice de marche de 6 minutes ont été effectuées , t and is que la qualité de vie a été évaluée grâce à un rapide question naire en 36 points . L'évolution de la force de préhension témoigne d'une différence significative entre le groupe AERO+ST ( 8,3±6,7 % ) et le groupe de contrôle ( −1,3±10,5 % ) , et le groupe AERO+RA ( −4,7±5,6 % ) ( P<0,05 ) . Une augmentation significative a été observée dans le changement du pourcentage de pic de & OV0312;o2 entre le groupe AERO+ST ( 5,1±11,8 % ) et le groupe de contrôle ( −9,2±8,6 % ) ( P<0,05 ) . En ce qui concerne les scores de qualité de vie associés à la santé , une différence significative a été constatée dans l'évolution du pourcentage moyen de fonctionnalité physique entre le groupe AERO+ST ( 7,9±24,4 % ) et le groupe de contrôle ( −14,8±19,1 % ) ( P<0,05 ) . Une différence significative a été observée dans l'évolution du pourcentage moyen de fonctionnalité sociale entre le groupe AERO+RA ( 9,4±20,0 % ) et le groupe de contrôle ( −14,9±23,2 % ) ( P<0,05 ) . En outre , une différence significative a été constatée dans l'évolution du pourcentage moyen de santé mentale entre le groupe AERO+RA ( 12,2±12,4 % ) et le groupe de contrôle ( −5,0±7,8 % ) ( P<0,05 ) . Il est préférable d'introduire diverses formes d'exercice faisant entrer en jeu différents muscles de l'ensemble du corps , en utilisant des activités de loisir comme méthode appropriée pour stimuler l'activité physique et accroître graduellement la forme fonctionnelle tout en améliorant la qualité de vie associée à la santé , bien qu'il soit également nécessaire de pratiquer des exercices d'entretien et d'amélioration chez les patients souffrant de MPCO Abstract Background : Long-acting inhaled medications are an important component of the treatment of patients with chronic obstructive pulmonary disease ( COPD ) , yet few studies have examined the determinants of medication adherence among this patient population . Objective : We sought to identify factors associated with adherence to long-acting beta-agonists ( LABA ) and inhaled corticosteroids ( ICS ) among patients with COPD . Methods : We performed secondary analysis of baseline data collected in a r and omized trial of 376 Veterans with spirometrically confirmed COPD . We used electronic pharmacy records to assess adherence , defined as a medication possession ratio of ≥0.80 . We investigated the following exposures : patient characteristics , disease severity , medication regimen complexity , health behaviors , confidence in self-management , and perceptions of provider skill . We performed multivariable logistic regression , clustered by provider , to estimate associations . Results : Of the 167 patients prescribed LABA , 54 % ( n = 90 ) were adherent to therapy while only 40 % ( n = 74 ) of 184 the patients prescribed ICS were adherent . Higher adherence to LABA and ICS was associated with patient perception of their provider as being an “ expert ” in diagnosing and managing lung disease [ For LABA : OR = 21.70 ( 95 % CI 6.79 , 69.37 ) ; For ICS OR = 7.93 ( 95 % CI 1.71 , 36.67 ) ] . Factors associated with adherence to LABA , but not ICS , included : age , education , race , COPD severity , smoking status , and confidence in self-management . Conclusions : Adherence to long-acting inhaled medications among patients with COPD is poor , and determinants of adherence likely differ by medication class . Patient perception of clinician expertise in lung disease was the factor most highly associated with adherence to long-acting therapies Exercise rehabilitation is recommended increasingly for patients with chronic obstructive pulmonary disease ( COPD ) . This study examined the effect of exercise and education on 79 older adults ( M age = 66.6 + /- 6.5 years ; 53 % female ) with COPD , r and omly assigned to 10 weeks of ( a ) exercise , education , and stress management ( EXESM ; n = 29 ) ; ( b ) education and stress management ( ESM ; n = 25 ) ; or ( c ) waiting list ( WL ; n = 25 ) . EXESM included 37 sessions of exercise , 16 educational lectures , and 10 weekly stress management classes . ESM included only the 16 lectures and 10 stress management classes . Before and after the intervention , assessment s were conducted of physiological functioning ( pulmonary function , exercise endurance ) , psychological well-being ( depression , anxiety , quality of life ) , and cognitive functioning ( attention , motor speed , mental efficiency , verbal processing ) . Repeated measures multivariate analysis of variance indicated that EXESM participants experienced changes not observed among ESM and WL participants , including improved endurance , reduced anxiety , and improved cognitive performance ( verbal fluency ) AIM This paper reports a study to determine whether a nurse-initiated telephone follow-up programme could increase patients ' self-efficacy in managing dyspnoea and decrease health care service use . BACKGROUND Chronic obstructive pulmonary disease is a worldwide health problem and has been labelled a burdensome disease . Because of the fear of activity-induced dyspnoea , patients with chronic obstructive pulmonary disease lack the confidence to perform daily activities . Studies of cardiac and diabetic patients have shown that telephone follow-up care is an effective approach to increasing self-efficacy . However , little such research has been done with patients with chronic obstructive pulmonary disease . METHODS This was a r and omized controlled study . A total of 60 participants ( 30 telephone follow-up , 30 control ) with chronic obstructive pulmonary disease were recruited from an acute care hospital in Hong Kong . The Chinese Self-Efficacy Scale was used to assess self-efficacy . Measures of health care use were numbers of visits to an accident and emergency department , hospitalizations , and unscheduled visits by physicians . FINDINGS The self-efficacy scores ( U = 272.5 , P = 0.009 ) of patients who were followed up by telephone improved significantly compared with those of patients in the control group . Multiple regression analyses showed that telephone follow-up ( Beta = 0.33 , CI : 0.19 - 0.48 , P = 0.001 ) , the pulmonary rehabilitation programme ( Beta = 0.44 , CI : 0.16 - 0.72 , P = 0.003 ) , smoking ( Beta = 0.34 , CI : 0.09 - 0.57 , P = 0.009 ) , and health care use ( Beta = -0.27 , CI : -0.47-(-0.07 ) , P = 0.008 ) were significant factors in predicting patient self-efficacy . CONCLUSIONS Nurse-initiated telephone follow-up care was effective in increasing self-efficacy in managing dyspnoea . The study needs to be replicated in other setting to strengthen its external validity The oxygen cost of eccentric exercise is lower than that of concentric exercise at similar work-loads . In this study , the response to eccentric cycle exercise training ( EET ) in addition to general exercise training ( GET ) on exercise performance and quality of life was investigated in 24 patients with severe chronic obstructive pulmonary disease ( COPD ) . All patients had a normal resting PaO2 and an arterial oxygen saturation ( SaO2 ) below 90 % at Wmax , achieved during a maximal incremental concentric cycle exercise test . The patients participated in a comprehensive inpatient pulmonary rehabilitation programme of 10 weeks . They were r and omly assigned either to GET ( GET group : mean FEV1 38 % predicted ) or to GET and additional EET ( GET/EET group : FEV1 45 % predicted ) . During EET , the patients were able to cycle eccentrically for 15 min continuously at a mean of 160 ( 69 % ) of Wmax whereas the Borg dyspnoea score did not exceed 3.0 and SaO2 did not fall below 90 % . Parameters of cardiocirculatory fitness and gas exchange improved in the GET/EET group but no further improvement in exercise capacity occurred compared to GET . It is concluded that eccentric cycle exercise is a safe and attractive training modality for patients with severe COPD and can be performed at a high intensity without the patient becoming out of breath or needing supplemental oxygen OBJECTIVE To evaluate the impact of pharmaceutical care on selected clinical and economic outcomes in patients with hypertension or chronic obstructive pulmonary disease ( COPD ) in ambulatory care setting s. DESIGN Clinic patients with hypertension or COPD were r and omly assigned to a treatment group ( pharmaceutical care ) or a control group ( traditional pharmacy care ) over a six-month period . Clinical pharmacists and pharmacy residents conducted the protocol s. There were 133 evaluable patients ( 63 treatment and 70 control ) in the hypertension study arm and 98 evaluable patients ( 43 treatment and 55 control ) in the COPD study arm . SETTING 10 Departments of Veterans Affairs medical centers and 1 academic medical center . INTERVENTIONS Patient-centered pharmaceutical care model ( employing st and ardized care ) implemented by clinical pharmacy residents . MAIN OUTCOME MEASURES Patient knowledge , medication compliance , and health re source use . RESULTS The hypertension treatment group had a significantly greater reduction in systolic blood pressure from visit 1 to visit 5 than did the control group . In the COPD study arm , trends were positive in the treatment group for patients ratings of symptom interference with activities and dyspnea measures . There was a significant difference between the hypertension treatment and control group for compliance . There were no significant changes in compliance scores in the COPD study arm . Mean number of hospitalizations and other health care provider visits was higher for the hypertension control group . For patients with COPD , hospitalizations increased in the control group , and the number of other health care provider visits was higher in the control group . CONCLUSION Pharmacists ' participation in a pharmaceutical care program result ed in disease state improvement in ambulatory patients with hypertension and COPD OBJECTIVES To evaluate the effectiveness of an intensive community nurse (CN)-supported discharge program in preventing hospital readmissions of older patients with chronic lung disease ( CLD ) . DESIGN R and omized , controlled trial . SETTING Two acute hospitals in the same health region in Hong Kong . PARTICIPANTS One hundred fifty-seven hospitalized patients aged 60 and older with a primary diagnosis of CLD and at least one hospital admission in the previous 6 months . INTERVENTION CNs made home visits within 7 days of discharge , then weekly for 4 weeks and monthly until 6 months . CNs coordinated closely with a geriatric or respiratory specialist in hospital . Subjects had telephone access to CNs during normal working hours from Monday to Saturday . MEASUREMENTS The primary outcome was the rate of unplanned readmission within 6 months . The secondary outcomes were the rate of unplanned readmission within 28 days , number of unplanned readmissions , hospital bed days , accident and emergency room attendance , functional and psychosocial status , and caregiver burden . RESULTS One hundred forty hospitalized patients completed the trial . Intervention group subjects had a higher rate of unplanned readmission within 6 months than control group subjects ( 76 % vs 62 % , P=.080 , chi2 test ) . There was no significant group difference in any of the secondary outcomes except that intervention group subjects did better on social h and icap scores . CONCLUSION There was no evidence that an intensive CN-supported discharge program can prevent hospital readmissions in older patients with CLD PURPOSE To evaluate the differences in the long-term outcomes of dyspnea , exercise performance , health-related quality of life , and health re source utilization following a dyspnea self-management program with 3 different " doses " of supervised exercise . PATIENTS AND METHODS In a prospect i ve , r and omized , single-blind , 1-year trial , patients with stable chronic obstructive pulmonary disease ( N = 103 ; age 66 + /- 8 , females 57 ; FEV1 44.8 % + /- 14 % predicted ) were r and omly assigned to either : ( 1 ) Dyspnea self-management program ( DM ) ; ( 2 ) DM plus 4 supervised exercise sessions ( DM-exposure ) ; or ( 3 ) DM plus 24 supervised exercise sessions ( DM-training ) . The dyspnea self-management program included individualized education and demonstration of dyspnea self-management strategies , an individualized home walking prescription , and biweekly nurse telephone calls . Outcomes were measured at baseline and every 2 months for 1 year . RESULTS The DM-training group had significantly greater improvements in dyspnea during incremental treadmill test and in exercise performance on the incremental and endurance treadmill tests at 6 and 12 months compared with the other 2 groups . Dyspnea with activities of daily living and self-reported physical functioning significantly improved for all groups over time . The dose-response relationship between supervised exercise and improvement in dyspnea present at 2 months was not sustained over the year . CONCLUSION Consistent with previous findings from evaluation studies of pulmonary rehabilitation programs , the greater number of supervised exercise training sessions improved laboratory dyspnea and performance more than the other two doses of exercise . In the long term , the improvement in dyspnea with activities of daily living and physical functioning was similar for all 3 groups OBJECTIVES To determine whether pulmonary rehabilitation carried out in a community setting is more effective than that carried out in a st and ard hospital setting and which is more cost-effective ; also whether telephone follow-up is both cost-effective and useful in prolonging the beneficial effects of a pulmonary rehabilitation programme . DESIGN A r and omised trial . Participants were r and omised in 2 x 2 factorial fashion to hospital or community rehabilitation and telephone or st and ard follow-up with review . SETTING Hospitals or community sites in Sheffield . The community venues were selected to be close to public transport routes and have good parking and level access . The two hospital venues were the physiotherapy gym and a staff gym within the grounds of the hospital . PARTICIPANTS Patients with chronic obstructive pulmonary disease diagnosed by respiratory physicians according to Global Initiative for Chronic Obstructive Lung Disease guidelines . INTERVENTIONS Participants were r and omised to one of four groups : hospital rehabilitation with no telephone follow-up ; hospital rehabilitation with telephone follow-up ; community rehabilitation with no telephone follow-up ; or community rehabilitation with telephone follow-up . All were blinded to the telephone intervention arm until 1 month post rehabilitation , when only the assessment team and research participants were unblinded . MAIN OUTCOME MEASURES The primary outcome measure was the difference in improvement in endurance shuttle walking test ( ESWT ) between hospital and community pulmonary rehabilitation groups post rehabilitation , and the difference in ESWT during 18 months ' follow-up between those receiving telephone encouragement and those receiving st and ard care . A secondary measure was health-related quality of life . RESULTS A total of 240 participants had evaluable data . Of these , 129 were r and omised to hospital rehabilitation ( 64 with telephone follow-up and 65 with no telephone follow-up ) and 111 to community rehabilitation ( 55 with telephone follow-up and 56 with no telephone follow-up ) . For the primary outcome measure , there were 162 patients with data for analysis : hospital rehabilitation with no telephone follow-up ( n = 38 ) ; hospital rehabilitation with telephone follow-up ( n = 48 ) ; community rehabilitation with no telephone follow-up ( n = 43 ) ; and community rehabilitation with telephone follow-up ( n = 33 ) . For the acute phase post-rehabilitation outcomes , before patients had the opportunity for telephone follow-up , we compared outcomes between the 76 patients in the community rehabilitation group and the 86 patients in the hospital rehabilitation group . Patients in the hospital rehabilitation group increased the distance they could walk at the post-rehabilitation follow-up by 283 m ( SD 360 m ) , an increase relative to baseline of 109 % ( SD 137 % ) . Patients in the community rehabilitation group increased the distance they could walk at the post-rehabilitation follow-up by 216 m ( SD 340 m ) , an increase relative to baseline of 91 % ( SD 133 % ) . There was no statistically significant difference between the groups [ 17.8 % ( 95 % CI -24.3 to 59.9 , p = 0.405 ) ] . For longer term outcomes at 6 , 12 and 18 months post rehabilitation there was no evidence of a rehabilitation group effect . After allowing for the initial post-rehabilitation baseline distance walked , time ( follow-up visit ) and the factorial design ( telephone follow-up group ) , the average difference in the post-rehabilitation follow-up distance walked on the ESWT between the hospital and community rehabilitation groups was 1.5 m ( 95 % CI -82.1 to 97.2 , p = 0.971 ) , and between the telephone and no-telephone groups it was 56.9 m ( 95 % CI -25.2 to 139 , p = 0.174 ) . There was no difference between hospital or community groups in terms of acute effect or persistence of effect . Health economic analysis favoured neither hospital nor community setting s , nor did it clearly favour telephone follow-up or routine care . CONCLUSIONS Pulmonary rehabilitation delivered in a community setting has similar efficacy to that produced in a more traditional hospital-based setting , both setting s producing significant improvements in terms of exercise capacity and quality of life acutely and after long-term follow-up . Health economic analysis showed that neither hospital nor community programmes were greatly favoured . The choice of model will depend on local factors of convenience , existing availability of re sources and incremental costs . Staff characteristics may be important in gaining optimal outcome , and care should be taken in staff recruitment and training . TRIAL REGISTRATION Current Controlled Trials IS RCT N86821773 BACKGROUND Pulmonary rehabilitation is recommended for the treatment of COPD in international guidelines . However , patient education as an important part of pulmonary rehabilitation has not been addressed sufficiently to show its benefit . The aim of this study was to find out whether education improves the effectiveness of rehabilitation with regard to quality of life ( QoL ) and morbidity in the year following rehabilitation . METHODS COPD patients of multidisciplinary pulmonary inpatient rehabilitation programme participated in this prospect i ve , r and omised and controlled trial . To the education group we offered a programme of patient education ( 4 x 1.5 hours ) and an individual action plan on how to cope with exacerbations . Pulmonary function tests and QoL as measured by the Saint George Respiratory Question naire ( SGRQ ) were tested at baseline and at follow-up after 1 year . PATIENTS AND MAIN RESULTS 90 patients were r and omly assigned to the multidisciplinary rehabilitation programme with the usual care ( control group , CG ) and 94 patients received additional patient education ( education group , EG ) . In both groups the total number of hospital admissions was diminished after 1 year ( CG : 24.7 % to 11.5 % , p = 0.02 ; EG : 30.8 % to 9.9 % , p = 0,001 ) . Only the EG needed less intensive care ( 11.8 days to 2.2 , p = 0.02 ) , received less home emergency medical service ( 18.3 to 5.5 % , p = 0.01 ) and had less emergency hospital admissions ( 19.6 % to 8.7 % , p = 0.03 ) . One year after rehabilitation , patients of the EG had a higher chance of improved quality of life ( OR = 2.5 ; CI 1.07 - 5.84 ) , and they could maintain a longer duration of weekly exercise training ( more than 1 hour/week : EG n = 58 , CG n = 34 , p < 0.01 ) . CONCLUSION Patient education for COPD has been shown to improve the effectiveness of an inpatient rehabilitation programme regarding quality of life . It also reduces morbidity and supports a change of lifestyle . Therefore , education should be an essential component of rehabilitation in COPD BACKGROUND A steady increase in chronic obstructive pulmonary disease ( COPD ) admissions was addressed by enhancing primary care to provide intensive chronic disease management . AIM To compare the effect of a disease management programme , including a COPD management guideline , a patient-specific care plan and collaboration between patients , general practitioners , practice nurses , hospital physicians and nurse specialists with conventional care , on hospital admissions and quality of life . METHODS One hundred and thirty-five patients with a clinical diagnosis of moderate to severe COPD were identified from hospital admission data and general practice records . General practice s were r and omized to either conventional care ( CON ) , or the intervention ( INT ) . Pre- and post- study assessment included spirometry , Shuttle Walk Test , Short Form-36 , and the Chronic Respiratory Question naire ( CRQ ) . Admission data were compared for 12 months prior to and during the trial . RESULTS For respiratory conditions , mean hospital bed days per patient per year for the INT group were reduced from 2.8 to 1.1 , whereas those for the CON group increased from 3.5 to 4.0 ( group difference , P = 0.030 ) The INT group also showed an improvement for two dimensions of the CRQ , fatigue ( P = 0.010 ) and mastery ( P = 0.007 ) . CONCLUSIONS A chronic disease management programme for COPD patients that incorporated a variety of interventions , including pulmonary rehabilitation and implemented by primary care , reduced admissions and hospital bed days . Key elements were patient participation and information sharing among healthcare providers The effect of patient education in patients with asthma and Chronic Obstructive Pulmonary Disease ( COPD ) on health-related quality of life ( HRQoL ) is not previously investigated using the St. George 's Respiratory Question naire ( SGRQ ) . We r and omly allocated at our out-patient clinic 78 asthmatics and 62 patients with COPD to either a control or an intervention group . Intervention consisted of two 2-h group sessions and one to two individual sessions each by a nurse and a physiotherapist . A self-management plan was developed . Baseline quality of life assessment showed comparable scores independent of treatment groups among asthmatics and patients with COPD , but statistically significantly better scores ( p < 0.05 ) for the educated asthma group after 12 mo compared with the control group . This aligned with the 12-mo SGRQ assessment , which revealed better symptoms , activity , impact , and total scores by 11 ( p < 0.02 ) , 15 ( p < 0.01 ) , 19 ( p < 0.001 ) , and 16 ( p < 0.001 ) units , respectively . Patient education among asthmatics increased the FEV1 by a mean value of 6.1 % ( SD , 12 ) compared with the control group ( p < 0.05 ) . Education among patients with COPD did not indicate a significant increase in HRQoL as measured by the SGRQ or increased FEV1 . We conclude that patient education increased HRQoL and FEV1 among asthmatics , but not among patients with COPD Twenty patients with stable COPD ( mean age 67.8 yr ; mean FEV1 1.08 1 ) , all limited by ventilation at maximum exercise , were r and omly allocated after a four week control period , to an eight week programme of either inspiratory resistive training ( IRT ) , with a P Flex device , or conventional breathing retraining ( BR ) . Exercise performance was evaluated every four weeks , using a 12-min walking test , an incremental progressive exercise on a cycle ergometer and a cycle endurance test . Inspiratory muscle endurance was measured as the highest tolerated resistance for 10 min on a P Flex device . IRT produced a significant ( p less than 0.05 ) increase in the highest tolerated resistance , but IRT and BR failed to improve lung function or exercise performance . The present study shows that in COPD patients with ventilatory limitation on exercise an IRT programme may fail to improve exercise performance , in spite of an efficient training effect on the endurance of the inspiratory muscles BACKGROUND Improving a patient 's ability to self-monitor and manage changes in chronic obstructive pulmonary disease ( COPD ) symptoms may improve outcomes . OBJECTIVE To determine the efficacy of a comprehensive care management program ( CCMP ) in reducing the risk for COPD hospitalization . DESIGN A r and omized , controlled trial comparing CCMP with guideline -based usual care . ( Clinical Trials.gov registration number : NCT00395083 ) SETTING : 20 Veterans Affairs hospital-based outpatient clinics . PARTICIPANTS Patients hospitalized for COPD in the past year . INTERVENTION The CCMP included COPD education during 4 individual sessions and 1 group session , an action plan for identification and treatment of exacerbations , and scheduled proactive telephone calls for case management . Patients in both the intervention and usual care groups received a COPD informational booklet ; their primary care providers received a copy of COPD guidelines and were advised to manage their patients according to these guidelines . Patients were r and omly assigned , stratifying by site based on r and om , permuted blocks of variable size . MEASUREMENTS The primary outcome was time to first COPD hospitalization . Staff blinded to study group performed telephone-based assessment of COPD exacerbations and hospitalizations , and all hospitalizations were blindly adjudicated . Secondary outcomes included non- COPD health care use , all-cause mortality , health-related quality of life , patient satisfaction , disease knowledge , and self-efficacy . RESULTS Of the eligible patients , 209 were r and omly assigned to the intervention group and 217 to the usual care group . Citing serious safety concerns , the data monitoring committee terminated the intervention before the trial 's planned completion after 426 ( 44 % ) of the planned total of 960 patients were enrolled . Mean follow-up was 250 days . When the study was stopped , the 1-year cumulative incidence of COPD -related hospitalization was 27 % in the intervention group and 24 % in the usual care group ( hazard ratio , 1.13 [ 95 % CI , 0.70 to 1.80 ] ; P= 0.62 ) . There were 28 deaths from all causes in the intervention group versus 10 in the usual care group ( hazard ratio , 3.00 [ CI , 1.46 to 6.17 ] ; P= 0.003 ) . Cause could be assigned in 27 ( 71 % ) deaths . Deaths due to COPD accounted for the largest difference : 10 in the intervention group versus 3 in the usual care group ( hazard ratio , 3.60 [ CI , 0.99 to 13.08 ] ; P= 0.053 ) . LIMITATIONS Available data could not fully explain the excess mortality in the intervention group . Ability to assess the quality of the educational sessions provided by the case managers was limited . CONCLUSION A CCMP in patients with severe COPD had not decreased COPD -related hospitalizations when the trial was stopped prematurely . The CCMP was associated with unanticipated excess mortality , results that differ markedly from similar previous trials . A data monitoring committee should be considered in the design of clinical trials involving behavioral interventions The effect of patient education on morbidity in asthmatics and COPD patients has not previously been investigated in a single study . We r and omized 78 asthmatics and 62 COPD patients after ordinary outpatient management . Intervention consisted of educational group sessions and individual sessions administered by a trained nurse and physiotherapist . A self-management plan was developed . The utilization of health re sources and absenteeism from work was self-reported monthly . During the 12-month follow-up , approximately two ( P= 0.001 ) and three ( P= 0.001 ) times as many uneducated asthmatics and COPD patients , respectively , visited their general practitioner ( GP ) compared with educated . The mean reduction in GP consultations for the educated were 73 % ( P<0.001 ) and 85 % ( P<0.0001 ) for the asthma and COPD group , respectively , compared with uneducated . Fifty percent of uneducated asthmatics reported absenteeism from work compared with 24 % of the educated ( P = 0.06 ) . The mean reduction in days offwork for the educated was 69 % ( P = 0.03 ) , compared with uneducated . A positive correlation was observed between St George 's Respiratory Question naire total score and number of GP visits for both the asthma and COPD group ( P < 0.001 ) . We conclude that patient education in asthmatics and COPD patients reduced the need for GP visits and kept a greater proportion of patients independent of their GP . Patient education among asthmatics also reduced the number of days off work and appeared to increase the proportion of patients not reporting absenteeism from work at all . Increasing number of GP visits was correlated with decreased health-related quality of life as measured by the SGRQ for both the asthmatics and the COPD patients To examine the efficacy of targeted inspiratory muscle training ( IMT ) , 25 patients with moderate COPD were r and omly assigned to one of three groups . Eight patients received IMT along with general exercise reconditioning , GER+IMT ; nine patients received general exercise reconditioning , GER ; eight patients received sham breathing exercises , CONTROL . All groups used a spring-loaded inspiratory muscle trainer ; however , the GER and CONTROL groups breathed through these devices at only 15 % of their maximal inspiratory pressure . The GER+IMT group increased the load on these devices until at 6 wk the load was equal to 80 % of their maximal inspiratory pressure . All patients exercised three times per week for a 12-wk period in supervised sessions . Analysis of covariance revealed no significant differences in spirometric measurements , maximal inspiratory pressure , or maximal oxygen consumption among any of the three groups after the intervention ( p > 0.05 ) . Twelve-minute walk distance was significantly greater in the GER+IMT and GER groups than in the CONTROL group ( p = 0.03 ) . After the intervention , there was a trend ( p = 0.08 ) for treadmill time to be greater for the GER+IMT and GER groups than for the CONTROL group . Dyspnea ratings at different exercise intensities were not found to be significantly different among the three groups after the intervention . These results demonstrate that GER+IMT and GER alone are equally effective in improving exercise performance in patients with COPD . Additionally , the combination of GER and IMT does not appear to provide any clinical ly significant improvements in exercise performance or perceptions of dyspnea during exercise when compared with GER alone We compared , in a controlled clinical trial , the effect of specific inspiratory muscle training combined with general exercise reconditioning , for six months , with that of general exercise reconditioning alone on inspiratory muscle strength , endurance , and exercise performance in patients with COPD . Thirty-six patients were recruited into three groups ; 12 patients received specific inspiratory muscle training combined with general exercise reconditioning , 12 patients underwent general exercise reconditioning alone , and the remaining 12 patients received no training . Specific inspiratory muscle training , for six months , improved the inspiratory muscle strength and endurance in patients with COPD . This training combined with general exercise reconditioning also provided improvement in exercise tolerance , and this improvement was significantly greater than that of general exercise reconditioning alone OBJECTIVE To investigate whether a 12-week pedometer-based exercise counseling strategy is feasible and effectively enhances daily physical activity in outclinic Chronic Obstructive Pulmonary Disease ( COPD ) patients who do not participate in a rehabilitation program in a controlled way . METHODS 35 outclinic COPD patients ( 21 males , mean age 62 years , GOLD I-III , mean FEV(1)% predicted 64.7 ) were r and omized for a 12-week individual pedometer-based exercise counseling program promoting daily physical activities or usual care . Daily physical activity ( DigiWalker SW-200 ) , physical fitness , health-related quality of life , self-efficacy , fatigue , depression and motivation to be physically active were assessed before and after the intervention . RESULTS After the intervention , COPD patients in the exercise counseling group showed a significant increase in their mean number of steps/day ( from 7087 to 7872 ) , whereas the usual care group showed a decrease ( from 7539 to 6172 ) . Significant differences favoring the exercise counseling group were demonstrated in arm strength , leg strength , health-related quality of life and intrinsic motivation to be physically active . CONCLUSION Our study shows that a 12-week pedometer-based exercise counseling strategy is feasible and effectively enhances daily physical activity , physical fitness , health-related quality of life and intrinsic motivation in outclinic COPD patients who do not participate in a rehabilitation program . PRACTICE IMPLICATION S The feasibility of our exercise counseling strategy is good and patients were motivated to participate The effect of inspiratory resistive breathing training using a simple apparatus was tested in 27 optimally medicated consecutive out patients with severe chronic airflow limitation , r and omly assigned to a test and a control group . Patients trained in their homes for up to 10 min thrice daily and increments in resistance were made , if possible , every fortnight . The control group used the same apparatus , but without inspiratory resistance . Three months from the start of training , the following statistically significant differences between the 2 groups were observed : a marked decrease in dyspnea in the trained group , a 60 % versus 22 % rise in endurance time on a cycle ergometer at 2/3 of maximal work load , a fall in functional residual capacity , and a fall in respiratory frequency both at rest and during exercise OBJECTIVE Chronic obstructive pulmonary disease ( COPD ) is a major health problem with high societal costs . The Global Initiative for Chronic Lung Disease ( GOLD ) has identified a need for health economics data for COPD . For chronic diseases , such as COPD , where the natural history of disease is lifetime , a modeling approach for economic evaluation may be more realistic than prospect i ve , piggy-backed clinical trials or specific COPD cohort studies . Simulation models can be used to extrapolate clinical data beyond the limited time frame of clinical trials , to analyze subgroups of patients or to explore uncertainty regarding the results by using sensitivity analysis techniques . Our purpose has been to develop a flexible computer simulation model for COPD that will represent disease progression and GOLD recommendations , useful for economic evaluations of new medicines to meet the needs of various payer requirements for reimbursement and re source allocation . METHODS This article describes a two-dimensional Markov model , which uses data from multiple sources about disease progression , exacerbation frequency and duration , mortality , costs , burden of illness , and the relationships between those variables . The model is evaluated using stochastic uncertainty analysis , it allows comparison of treatments affecting different disease mechanisms , and it uses primary data vali date d against published sources . RESULTS We have evaluated two hypothetical interventions treating different features of the disease ( lung function decline and acute exacerbations ) . These analyses show that reducing lung function decline must be a long-term strategy compared to reducing the number of exacerbations . It was necessary to have a long term like 30 years , with 10,000 patients and 20 % increase in price , or 20 years with equal prices to show cost-effectiveness with statistical significance for a treatment that reduces lung function decline . CONCLUSIONS Our study shows the value of modeling as a tool for evaluating different scenarios and for combining several sources of data , to provide estimates that would otherwise be unavailable . Clinical trials of this size and duration would be unrealistic This study was design ed to determine whether inspiratory resistive training could improve the exercise performance of patients with severe chronic airflow limitation who had already received optimum conventional therapy with bronchodilators and physiotherapy . Eighteen patients were studied . Ten patients were trained with an inspiratory resistance device for six weeks and eight patients used a placebo device . Psychological factors , likely to influence exercise capacity , were taken into account . Although there was no significant increase in maximum inspiratory pressure in the ten trained subjects , inspiratory muscle endurance was improved . Exercise performance , as assessed by progressive cycle exercise , stair climbing , 12 minute walking distance and treadmill walking did not change significantly in either group . It was concluded that inspiratory muscle training , using a currently available technique , produced no additional improvement in exercise capacity beyond that achieved by conventional bronchodilator and rehabilitation therapy This study assessed the impact of a r and omized trial of nursing-based case management for patients with chronic obstructive pulmonary disease , their caregivers , and nursing and medical staff . Sixty-six patients were matched by FEV on admission to hospital , and r and omized into an intervention or control group . Intervention group patients reported significantly less anxiety at 1 month postdischarge ; however , this effect was not sustained . There was little difference between groups in terms of unplanned readmissions , depression , symptoms , support , and subjective well being . Interviews with patients and caregivers found that the case management improved access to re sources and staff-patient communication . Interviews with nursing and medical staff found that case management improved communication between staff and enhanced patient care.(1 PURPOSE : The success of long-term exercise training ( ExT ) programs resides in the integration between exercise prescription and patient compliance with home training . One of the crucial issues for the patients is the underst and ing of appropriate exercise intensity . We compared 2 methods of home ExT , based on walking . METHODS : Forty-seven patients with chronic obstructive pulmonary disease were recruited and underwent respiratory function , exercise capacity evaluation with a 6-minute walk test , and treadmill tests . Physical activity was monitored by a multisensor Armb and ( SenseWear , Body Media , Pittsburgh , PA ) . Patients were r and omly assigned to 2 different home training methods and assessed again after 6 and 12 months ; group A1 : speed walking paced by a metronome , and group A2 : walking a known distance in a fixed time . RESULTS : Thirty-six patients completed the study . All subjects showed a significant improvement in the 6-minute walk test after 1 year but the improvement was higher in A1 than in A2 ( P < .05 ) . Physical activity levels were significantly higher at T12 versus baseline only in group A1 ( P < .05 ) . CONCLUSIONS : The use of a metronome to maintain the rate of walking during home ExT seems to be beneficial , allowing patients to achieve and sustain the optimal exercise intensity , and result ing in greater improvement compared to simply using a fixed time interval exercise PURPOSE To compare the effects on exercise capacity and health related quality of life ( HRQoL ) of two exercise programmes ; one programme including endurance training and one including only resistance training and callisthenics . A second purpose was to find out whether the severity of chronic obstructive pulmonary disease ( COPD ) affected the training response and whether the interventions had a long-term effect . METHODS Sixty-three patients were stratified according to severity of COPD and r and omised to two training groups . Group A had a mixed programme including endurance training . Group B had resistance training and callisthenics . All trained twice weekly for 8 weeks . A symptom-limited ergometer test , 12-min walking test , dynamic spirometry , blood gas analysis at rest and HRQoL were measured before and after the training period . Follow-up tests were conducted at 6 and 12 months after training . RESULTS Forty-two patients fulfilled the trial . In group A ( n=20 ) peak exercise capacity increased by 7W ( P<0.001 ) and 12-min walking distance ( 12MWD ) by 50 m ( P<0.01 ) , whereas group B ( n=22 ) did not change in any of these variables . HRQoL did not change significantly in either group . Training response was similar in patients with moderate and severe disease . One year post-training 12MWD had returned to pre-training level in group A , and below pre-training level in group B ( P<0.05 ) . CONCLUSIONS Exercise capacity in patients with severe and moderate COPD improved by intensive endurance training , two sessions a week for 8 weeks . The improvement was however small and HRQoL did not improve . Severity of illness did not affect response to training . The results indicated that the effects of a short endurance training intervention slowed down decline in baseline functional exercise capacity for 1 year STUDY OBJECTIVES Whereas pulmonary rehabilitation reduces symptoms and improves the quality of life of patients with COPD and is recommended in management guidelines , few patients have access to rehabilitation services . The purpose of this study was to investigate the effectiveness of increasing access to selected components of pulmonary rehabilitation by providing nurse-assisted home care that was composed of patient education , efforts to improve patient self-management skills , and enhanced follow-up . DESIGN We conducted a 6-month , r and omized , controlled trial . SETTING Primary care clinics associated with an urban academic health system . PATIENTS Patients were > or = 45 years of age with a physician diagnosis of COPD , and had a > or = 20-pack-year smoking history , had experienced at least one respiratory symptom during the past 12 months , and had airflow obstruction ( ie , FEV1/FVC ratio , < 70 % ; FEV1 , < 80 % ) . INTERVENTIONS Four nurses were trained in the use of the Global Initiative for Chronic Obstructive Lung Disease guidelines , and two of the four nurses received additional training in collaborative management . Patients were r and omly assigned to usual care ( UC ) , nurse-assisted medical management ( MM ) , or nurse-assisted collaborative management ( CM ) . MEASUREMENTS The main outcome measures were of generic ( Medical Outcome Study 36-item short form [ SF-36 ] , illness intrusiveness ) and disease-specific ( St. George 's respiratory question naire [ SGRQ ] ) quality of life and self-reported health-care utilization . RESULTS Overall , 151 patients ( UC group , 51 patients ; MM group , 49 patients ; and CM group , 51 patients ) completed the study , their average age was 69 years , and 56.9 % were women . The average change in the SF-36 general health domain for the MM group vs the UC group was 1.1 ( 95 % confidence interval [ CI ] , -7.9 to 11.2 ) , and for the CM group vs the UC group the average change was 2.5 ( 95 % CI , -7.0 to 12.3 ) . The corresponding changes in SGRQ total domain were -2.9 ( 95 % CI , -9.8 to 4.1 ) and -2.6 ( 95 % CI , -9.5 to 4.3 ) . There was no change in the number of self-reported emergency department visits or hospitalizations , but the utilization of these services was infrequent . CONCLUSION The findings of our investigation and those from the published literature suggest that interventions to enhance patient education , self-management skills , and follow-up among patients with COPD do not result in clinical ly meaningful improvements in health status or self-reported health-care utilization . Moreover , future studies of disease management programs for patients with COPD need to evaluate interventions that address associated comorbidities , exercise , and social support OBJECTIVE To evaluate the effects of pharmaceutical care on selected humanistic outcomes in patients with hypertension or chronic obstructive pulmonary disease ( COPD ) . DESIGN Clinic patients with hypertension or COPD were r and omly assigned to a treatment group ( pharmaceutical care ) or a control group ( traditional pharmacy care ) over a six-month period . Clinical pharmacists and pharmacy residents conducted the protocol s. There were 133 evaluable patients ( 63 treatment , 70 control ) in the hypertension study arm and 98 evaluable patients ( 43 treatment , 55 control ) in the COPD study arm . The Pharmaceutical Care Question naire evaluated patient satisfaction with care . Tests specific to the disease states assessed disease and disease management knowledge . Quality of life ( QOL ) was evaluated using the Health Status Question naire 2.0 ( HSQ 2.0 ) in the COPD arm ; in the hypertension arm , the Hypertension/Lipid TyPE Specification Form 5.1 was used . SETTING Ambulatory care centers of 10 Department of Veterans Affairs ( DVA ) medical centers and 1 university medical center . INTERVENTIONS Patient-centered pharmaceutical care model ( employing st and ardized care ) implemented by clinical pharmacy residents . MAIN OUTCOME MEASURES Satisfaction with pharmaceutical care , disease and disease management knowledge , and QOL . RESULTS Statistically significant differences in most satisfaction items were found , with treatment patients expressing greater satisfaction . Treatment groups in both arms strongly agreed that pharmacists helped them with confidence in use of their medication and underst and ing of their illness , gave complete explanations about their medications , made them feel that their care was a priority , and followed up on their questions and concerns . In the hypertension arm , treatment patients demonstrated significant increases in knowledge scores . Trends in QOL were positive for both hypertension groups , with a significant decrease found in number of treatment patients reporting problems with sexual function . In the COPD arm , improvement trends were significantly stronger for treatment patients . CONCLUSION Although patients were not dissatisfied with traditional pharmacy care , they were more satisfied overall with the pharmaceutical care model Prior studies demonstrate the ability of upper extremity training to increase arm strength and endurance when incorporated into a pulmonary rehabilitation program . However , patients with severe chronic obstructive pulmonary disease ( COPD ) may have transportation or mobility problems that make it difficult to travel to a rehabilitation site to obtain this training . This pilot study was design ed to determine whether a home-based , upper-arm exercise program could increase arm strength and endurance , and decrease perceptions of breathlessness and fatigue during five activities of daily living . Twenty patients with severe COPD ( FEV1 0.80 + /- 0.42 ) were r and omized to an experimental ( n = 10 ) or control group ( n = 10 ) . The experimental-group training included three upper arm exercises five times a week for 8 weeks , with training level incremented during weekly home visits . Control-group subjects were contacted weekly to equalize attention from health care providers . During the upper-extremity endurance test for number of rings moved , no significant differences between groups were seen for interaction or treatment . However , there was a significant interaction between treatment and time for perceived fatigue ( p = 0.0012 ) , with the experimental group perceiving less fatigue during upper arm work than did the control group . No change was seen in perceived breathlessness . Findings of this study suggest that a home-based , upper-arm exercise program can reduce perceptions of fatigue for patients with severe COPD during activities involving upper arm work . Testing in a larger sample is indicated to determine whether this training can also improve ability to perform unsupported arm work 51 male patients with mild degree chronic airway obstruction underwent detailed evaluation of pulmonary function tests , blood gas analysis and exercise tolerance test before and after a short-term therapy . The patients were r and omly assigned to medical therapy alone or to medical and rehabilitative therapy . 23 patients treated with medical and rehabilitative therapy showed a significant decrease of respiratory rate and PaCO2 and a significant increase of TV , FEV 1.0 , FEV 0.75 x 40 , PaO2 , SaO2 and exercise tolerance after a month of therapy . 28 patients treated with medical therapy alone showed a significant increase of VC and FEV 0.75 x 40 . These data suggest that rehabilitative therapy is a valid adjunct to medical therapy in the short-term treatment of chronic airway obstruction AIM To verify the outcome of different physical therapy interventions in activities of daily living of individuals with chronic obstructive pulmonary disease ( COPD ) . METHODS Twenty-two COPD individuals were r and omly divided into three groups : the Lower Limb Training Group ( LLTG , n=8 ) performed treadmill exercise , Upper Limb Training Group ( ULTG , n=8 ) performed upper limb ( UL ) training , and Control Group ( CG , n=6 ) underwent bronchial hygiene therapy for 6 weeks , three times per week . The following were simulated in the activities of the daily living test : blackboard erasing , weight lifting exercise , stair climbing and treadmill walking . The duration of these tasks was 5 min of blackboard erasing and weight lifting , and 6 min of stair climbing and treadmill walking . RESULTS Intragroup analysis presented a significant post-treatment ventilatory dem and ( V(E)/MVV ) decrease for the LLTG during basal conditions and walking , and significant decrease during blackboard erasing and walking for the ULTG , with similar metabolic dem and ( VO(2)/VO(2)max ) for both groups . Dyspnoea decreased significantly in the LLTG during post-treatment walking and increased for CG . The number of stairs climbed decreased significantly for the CG and increased for LLTG and ULTG post treatment , along with the walked distance for LLTG . The intergroup analysis presented significant differences in post-treatment dyspnoea with greater values observed for the CG during walking . CONCLUSION The different protocol s utilized promoted benefits towards physical exercise tolerance , particularly in the ULTG that presented better performance in sustained UL tasks , which may suggest better conditioning and coordination of the muscles involved in UL elevation AIM The aim was to investigate the impact of a disease and medicine management programme , focusing on self-management in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS One hundred and seventy-three patients ( mean age 67 years ; 54 % female ) were recruited ; 86 patients were r and omly assigned to an intervention group and 87 to a usual care ( control ) group . Intervention patients received education on disease state , medications and breathing techniques . Patients were given booklets and a customized action plan ( antibiotic and oral steroid to be initiated promptly by patients for exacerbations ) . Patients were followed up at 6 and 12 months during a scheduled visit . The St George 's Respiratory Question naire ( SGRQ ) , COPD Knowledge and Morisky adherence question naires were administered to all patients at baseline , 6 and 12 months . Outcome measures included hospital admissions , emergency department ( ED ) visits , health-related quality of life ( HRQoL ) and medication adherence . RESULTS Over the 12-month period in the intervention group , ED visits decreased by 50 % ( P= 0.02 ) and hospitalization by approximately 60 % ( P= 0.01 ) . On the SGRQ , differences reached statistical significance on the symptom ( -7.5 ; P= 0.04 ) and impact ( -7.4 ; P= 0.03 ) subscales but not on the physical activity subscale . There was a significant difference between the intervention and usual care groups regarding knowledge scores ( 75.0 vs. 59.3 ; P= 0.001 ) and good adherence to medication ( 77.8 % vs. 60.0 % , P= 0.019 ) . There was no significant difference regarding smoking between study groups . CONCLUSIONS The clinical pharmacy-led management programme can improve adherence , reduce the need for hospital care in patients with COPD and improve aspects of their |
1,068 | 26,012,875 | 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 | Introduction In the occupational environment , there are a considerable number of stressors that can affect physical performance in job tasks .
Whole-body vibration ( WBV ) , which arises from vehicle transit , is one such stressor that has been demonstrated to alter human function in several ways .
This study identifies the known physical changes to human function which result from WBV , to comment on changes which may translate to performance in physically dem and ing occupational tasks . | 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 mechanisms explaining the disruption in performance at lower frequencies are discussed Summary The question as to whether shock-type whole-body vibration causes increasingly acute strain was investigated . R and om vibrations were superimposed with shocks differing in amplitude and in number per unit of time in a systematic manner . The weighted root mean square ( rms ) acceleration was kept constant in all over the varied experiments . A total of 17 men were exposed to vibration from an electrohydraulic simulator . The following strain criteria were used : biodynamic behavior of the trunk and the head , electrical activity of the muscles of the back and the neck , subjective sensation , skin temperature in the lumbar area and visual and tracking performance . It was found that increasing shock amplitude and , in some experiments , also increasing numbers of shocks led to increasingly acute effects that varied , depending on the kind of shock used . New methods should be developed for the assessment of transient vibration that are better than the existing st and ards Objective : The influence of backrest support and h and grip contractions on acute metabolic , respiratory , and cardiovascular responses were evaluated in 13 healthy men during exposure to whole-body vibration ( WBV ) . Methods : Following assessment of aerobic fitness during arm cranking , subjects were exposed to frequencies 3 , 4.5 , and 6 Hz with 0.9 gr.m.s acceleration magnitude on a vibrating base in r and omized order , on separate days . Each exposure included 6 min baseline without WBV , 8 min of WBV exposure either ‘ with ‘ or ‘ without ’ backrest , 4 min recovery , followed by 8 min of WBV with opposite backrest condition , and 4 min recovery . During the final minute of WBV , subjects performed right h and maximal rhythmic h and grip contractions for one minute . During baseline and before completion of WBV session ‘ with ’ and ‘ without ’ backrest , cardiac output was estimated indirectly by carbon dioxide rebreathing . Results : At 3 and 4.5 , and 3 and 6 Hz , absolute and relative oxygen uptake demonstrated significantly greater responses during sitting ‘ without ’ backrest than ‘ with ’ backrest ( P<0.01 ) . At 3 and 4.5 Hz , heart rate and oxygen pulse responses were significantly greater during WBV combined with h and grip contractions than during WBV alone ( P<0.01 ) , demonstrating physical work during WBV will enhance greater metabolic responses . Stroke volume was the lowest at 4.5 Hz ( P<0.01 ) . Influence of aerobic fitness was evident only in absolute oxygen uptake , oxygen pulse , and ventilation volume ( P<0.01 ) . Conclusions : This study demonstrates that subjects exposed to physical work during WBV will experience greater metabolic responses compared to WBV alone , and the physiological responses during WBV resemble to that of a light physical work . Despite low metabolic rates during WBV , the effect of aerobic fitness suggests the importance of physical activity in occupations exposed to WBV 1 . Thresholds for the perception of postural sway induced by gentle perturbations were determined for five normal st and ing subjects . In this context we underst and ' perception ' to mean ' able to give a subjective report ' . The thresholds for the perception of movements that were equivalent to sway in velocity and amplitude were determined when the available sensory input was limited to only one , or a pair , of the vestibular , visual , and proprioceptive systems . To examine vestibular inputs alone , vision was excluded and the whole body was moved with the ankles in a fixed position . To examine visual inputs alone , the body was kept stationary and a ' room ' was moved around the subjects to simulate the relative visual-field movement that occurs during st and ing . To limit the available sensory input to proprioception from the legs , subjects were held stationary and balanced a load that was equivalent to their own body using their ankles . In this situation , perturbations were applied to the ' equivalent body ' and these could only be perceived from the result ing ankle movements . Thresholds for perceiving ankle movements were also determined in the same posture , but with the leg muscles bearing no load . 2 . The thresholds for the perception of sway during st and ing were very small , typically 0.003 rad at a velocity of 0.001 rad s-1 , and even smaller movements were perceived as the mean velocity of the sway increased up to 0.003 rad s-1 . No difference was found between the thresholds for perceiving forward sway and backward sway . Eye closure during st and ing did not affect the threshold for perceiving sway . 3 . When sensory input was limited to proprioception from the legs , the thresholds for the perception of passive ankle movements were equivalent to the thresholds for the perception of sway during st and ing with all sensory inputs available . When the leg muscles were relaxed , the thresholds for perceiving ankle movements increased approximately twofold . 4 . The visual thresholds for perceiving movement were higher than the proprioceptive thresholds at slower velocities of movement , but there was no difference at higher velocities . 5 . Both the proprioceptive and visual thresholds were sufficiently small to allow perception of the sway that was recorded when the subjects stood normally in a relaxed manner . In contrast , the vestibular thresholds were an order of magnitude greater than the visual or proprioceptive thresholds and above the largest sway movements that were recorded during normal st and ing . ( ABSTRACT TRUNCATED AT 400 WORDS OBJECTIVES To examine the changes in torque output result ing from fatigue , as well as changes in electromyographic measures of trunk muscles during isometric axial rotation and to compare these changes between directions of axial rotation . DESIGN Subjects performed fatiguing right and left isometric axial rotation of the trunk at 80 % of maximum voluntary contraction while st and ing upright . SETTING A rehabilitation center . PARTICIPANTS Twenty-three men with no history of back pain . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Surface electromyographic signals were recorded from 6 trunk muscles bilaterally . The primary torque in the transverse plane and the coupling torques in sagittal and coronal planes were also measured . RESULTS During the fatiguing axial rotation contraction , coupling torques of both sagittal and coronal planes were slightly decreased and no difference was found between directions of axial rotation . Decreasing median frequency and an increase in electromyographic amplitude were also found in trunk muscles with different degrees of changes in individual muscles . There were significant differences ( P<.05 ) between right and left axial rotation exertions in median frequency slope of external oblique , internal oblique , latissimus dorsi , and iliocostalis lumborum muscles , but no such difference was found in median frequency slope of rectus abdominis and multifidus muscles . This could be attributed to different functional roles among the muscles . Similar differences ( P<.05 ) between right and left axial rotation in median frequency slope were also detected in the electromyographic amplitude slope of the trunk muscles . Coefficient of variation of the torque output and electromyographic activation in most of the trunk muscles increased during the fatigue process . CONCLUSION The changing coupling torque , different fatigue rate , and activation changes of trunk muscles , as well as the increase in variability during fatiguing axial rotation exertion , could affect the internal loading and stability of the spine ; this needs to be further quantified in future studies |
1,069 | 17,886,288 | 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 . | This study is a systematic review and meta- analysis of studies using nucleic acid-based techniques to detect Mycobacterium avium paratuberculosis ( MAP ) in patients with Crohn 's disease ( CD ) compared with controls . | 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 |
1,070 | 28,641,044 | 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 . | Abstract Although the effects of short versus long inter-set rest intervals in resistance training on measures of muscle hypertrophy have been investigated in several studies , the findings are equivocal and the practical implication s remain unclear . | 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 biceps curl 1RM for G2 . After the 1RM tests , both groups performed three sets to concentric failure with 75 % of 1RM in combination with different RIs ( 2 min or self-suggested ) on separate days and the exercises performance was evaluated by the number of repetitions . The results demonstrated no significant differences in the number of repetitions between 2 min and self-suggested RIs that presented similar reductions with the sets progression . It was also shown that the self-suggested RI spent less time recovering than the 2 min RI group on average . This suggests that for individuals with previous experience , the self-suggested RI can be an effective option when using workloads commonly prescribed aim ing hypertrophy . Also , the self-suggested RI can reduce the total training session duration , which can be a more time-effective strategy 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 Ratamess , NA , Chiarello , CM , Sacco , AJ , Hoffman , JR , Faigenbaum , AD , Ross , RE , and Kang , J. The effects of rest interval length on acute bench press performance : the influence of gender and muscle strength . J Strength Cond Res 26(7 ) : 1817–1826 , 2012 . The purpose of this study was to investigate the effects of rest interval ( RI ) length on bench press performance in subjects with disparity in maximum strength . Two cohorts of subjects performed 3 bench press protocol s in r and om order consisting of 3 sets of up to 10 repetitions with 75 % of 1-repetition maximum ( 1RM ) using either 1- , 2- , or 3-minute RIs between sets . In the first cohort , 22 men and women were studied to investigate gender influence . In the second cohort , 23 men were tested for 1RM bench press strength and placed into a low 1RM ( mean = 80.7 ± 7.5 kg ) or high 1RM ( mean = 140.6 ± 11.9 kg ) experimental group . The number of successful repetitions completed , average power , and velocity for each set were recorded . Women performed significantly more repetitions than men with 1-minute ( 26.9 ± 4.4 vs. 21.1 ± 3.5 ) , 2-minute ( 29.0 ± 2.0 vs. 24.0 ± 4.5 ) , and 3-minute ( 29.7 ± 1.8 vs. 25.8 ± 5.1 ) RIs . The magnitude of decline in average velocity and power was significantly higher in men than in women . Total number of repetitions performed was significantly greater in the low 1RM group than in the high 1RM group at 1-minute ( 21.6 ± 5.0 vs. 18.1 ± 2.0 ) and 2-minute RIs ( 24.2 ± 5.4 vs. 21.3 ± 2.8 ) . Significant negative correlations were observed between 1RM bench press and total number of repetitions completed for 1- and 2-minute RIs ( r = −0.558 and −0.490 , respectively ) . These data indicate that maximal strength plays a role in bench press performance with varying RIs and suggest that shorter RIs may suffice in women to attain a specific volume We aim ed to determine if any mechanistic differences exist between a single set ( 1SET ) and multiple sets ( i.e. 3 sets ; 3SET ) of resistance exercise by utilizing a primed constant infusion of [ring-13C6]phenylalanine to determine myofibrillar protein synthesis ( MPS ) and Western blot analysis to examine anabolic signalling molecule phosphorylation following an acute bout of resistance exercise . Eight resistance-trained men ( 24+/-5 years , BMI = 25+/-4 kg m2 ) were r and omly assigned to perform unilateral leg extension exercise at 70 % concentric one repetition maximum ( 1RM ) until volitional fatigue for 1SET or 3SET . Biopsies from the vastus lateralis were taken in the fasted state ( Fast ) and fed state ( Fed ; 20 g of whey protein isolate ) at rest , 5 h Fed , 24 h Fast and 29 h Fed post-exercise . Fed-state MPS was transiently elevated above rest at 5 h for 1SET ( 2.3-fold ) and returned to resting levels by 29 h post-exercise . However , the exercise induced increase in MPS following 3SET was superior in amplitude and duration as compared to 1SET at both 5 h ( 3.1-fold above rest ) and 29 h post-exercise ( 2.3-fold above rest ) . Phosphorylation of 70 kDa S6 protein kinase ( p70S6 K ) demonstrated a coordinated increase with MPS at 5 h and 29 h post-exercise such that the extent of p70S6 K phosphorylation was related to the MPS response ( r=0.338 , P=0.033 ) . Phosphorylation of 90 kDa ribosomal S6 protein kinase ( p90RSK ) and ribosomal protein S6 ( rps6 ) was similar for 1SET and 3SET at 24 h Fast and 29 h Fed , respectively . However , 3SET induced a greater activation of eukaryotic translation initiation factor 2B ( eIF2B ) and rpS6 at 5 h Fed . These data suggest that 3SET of resistance exercise is more anabolic than 1SET and may lead to greater increases in myofibrillar protein accretion over time |
1,071 | 30,200,307 | We also confirmed that RCTs are valuable tools for assessing the effectiveness , acceptability , safety , privacy , appropriateness , satisfaction , performance , usefulness and adherence . | Background : The application of Health Information Technologies ( HITs ) can be an effective way to advance medical research and health services provision .
The two-fold objective of this work is to : ( i ) identify and review state-of-the-art HITs that facilitate the aims of evidence -based medicine and ( ii ) propose a methodology for HIT assessment .
Conclusions : To improve health service delivery , RCTs apply and exhibit formalization by providing measurable outputs . | 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 ) . However , an important study limitation is that post-intervention interviewers were not blinded to the study conditions . The program also effectively reduced depression and dysfunctional thinking ( between-group Cohen´s d = 0.84 for depression and d = 0.63 for dysfunctional thinking ) . Moreover , the iCBT intervention appears to have a long-term impact for participants ’ functioning , as the treatment gains were maintained six months later . Conclusions Internet-delivered interventions display a high potential to quickly and widely disseminate effective evidence -based programs around the world . This study provides support for guided iCBT as a promising treatment approach in Romania . Trial Registration Clinical Trials.gov Background Applying mobile phones in healthcare is increasingly prioritized to strengthen healthcare systems . Antenatal care has the potential to reduce maternal morbidity and improve newborns ’ survival but this benefit may not be realized in sub-Saharan Africa where the attendance and quality of care is declining . We evaluated the association between a mobile phone intervention and antenatal care in a re source -limited setting . We aim ed to assess antenatal care in a comprehensive way taking into consideration utilisation of antenatal care as well as content and timing of interventions during pregnancy . Methods This study was an open label pragmatic cluster-r and omised controlled trial with primary healthcare facilities in Zanzibar as the unit of r and omisation . 2550 pregnant women ( 1311 interventions and 1239 controls ) who attended antenatal care at selected primary healthcare facilities were included at their first antenatal care visit and followed until 42 days after delivery . 24 primary health care facilities in six districts were r and omized to either mobile phone intervention or st and ard care . The intervention consisted of a mobile phone text-message and voucher component . Primary outcome measure was four or more antenatal care visits during pregnancy . Secondary outcome measures were tetanus vaccination , preventive treatment for malaria , gestational age at last antenatal care visit , and antepartum referral . Results The mobile phone intervention was associated with an increase in antenatal care attendance . In the intervention group 44 % of the women received four or more antenatal care visits versus 31 % in the control group ( OR , 2.39 ; 95 % CI , 1.03 - 5.55 ) . There was a trend towards improved timing and quality of antenatal care services across all secondary outcome measures although not statistically significant . Conclusions The wired mothers ’ mobile phone intervention significantly increased the proportion of women receiving the recommended four antenatal care visits during pregnancy and there was a trend towards improved quality of care with more women receiving preventive health services , more women attending antenatal care late in pregnancy and more women with antepartum complications identified and referred . Mobile phone applications may contribute towards improved maternal and newborn health and should be considered by policy makers in re source -limited setting s . Trial registration Clinical Trials.gov , NCT01821222 Background One in 25 Ug and an adolescents is HIV positive . Purpose The aim of this study is to examine the impact of an Internet-based HIV prevention program on Information-Motivation-Behavioral skills ( IMB ) Model-related constructs . Methods Three hundred and sixty-six sexually experienced and inexperienced students 13–18 + years old in Mbarara , Ug and a , were r and omly assigned to the five-lesson CyberSenga program or the treatment-as-usual control group . Half of the intervention participants were further r and omized to a booster session . Assessment s were collected at 3 and 6 months post-baseline . Results Participants ’ HIV-related information improved over time at a greater rate for the intervention groups compared to the control group . Motivation for condom use changed to a greater degree over time for the intervention group — especially those in the intervention + booster group — compared to the control group . Behavioral skills for condom use , and motivation and behavioral skills for abstinence were statistically similar over time for both groups . Conclusions CyberSenga improves HIV preventive information and motivation to use condoms Background Brief interventions via the internet have been shown to reduce university students ’ alcohol intake . This study tested two smartphone applications ( apps ) targeting drinking choices on party occasions , with the goal of reducing problematic alcohol intake among Swedish university students . Methods Students were recruited via e-mails sent to student union members at two universities . Those who gave informed consent , had a smartphone , and showed risky alcohol consumption according to the Alcohol Use Disorders Identification Test ( AUDIT ) were r and omized into three groups . Group 1 had access to the Swedish government alcohol monopoly ’s app , Promillekoll , offering real-time estimated blood alcohol concentration ( eBAC ) calculation ; Group 2 had access to a web-based app , PartyPlanner , developed by the research group , offering real-time eBAC calculation with planning and follow-up functions ; and Group 3 participants were controls . Follow-up was conducted at 7 weeks . Results Among 28574 students offered participation , 4823 agreed to join ; 415 were excluded due to incomplete data , and 1932 fulfilled eligibility criteria for r and omization . Attrition was 22.7–39.3 percent , higher among heavier drinkers and highest in Group 2 . Self-reported app use was higher in Group 1 ( 74 % ) compared to Group 2 ( 41 % ) . Per- protocol analyses revealed only one significant time-by-group interaction , where Group 1 participants increased the frequency of their drinking occasions compared to controls ( p = 0.001 ) . Secondary analyses by gender showed a significant difference among men in Group 1 for frequency of drinking occasions per week ( p = 0.001 ) , but not among women . Among all participants , 29 percent showed high-risk drinking , over the recommended weekly drinking levels of 9 ( women ) and 14 ( men ) st and ard glasses . Conclusions Smartphone apps can make brief interventions available to large numbers of university students . The apps studied using eBAC calculation did not , however , seem to affect alcohol consumption among university students and one app may have led to a negative effect among men . Future research should : 1 ) explore ways to increase user retention , 2 ) include apps facilitating technical manipulation for evaluation of added components , 3 ) explore the effects of adapting app content to possible gender differences , and 4 ) offer additional interventions to high-risk users . Trial registration clinical trials.gov : NCT01958398 Background Males experience a shorter life expectancy and higher rates of chronic diseases compared to their female counterparts . To improve health outcomes among males , interventions specifically developed for males that target their health behaviors are needed . Information technology (IT)-based interventions may be a promising intervention approach in this population group , however , little is known about how to maximize engagement and retention in Web-based programs . Objective The current study sought to explore attributes hypothesized to influence user engagement among a sub sample of participants from the ManUp study , a r and omized controlled trial testing the efficacy of an interactive Web-based intervention for promoting physical activity and nutrition among middle-aged males . Methods Semistructured interviews were conducted and audiotaped with 20 of the ManUp participants . Interview questions were based on a conceptual model of engagement and centered on why participants took part in the study , what they liked and did not like about the intervention they received , and how they think the intervention could be improved . Interview recordings were transcribed and coded into themes . Results There were five themes that were identified in the study . These themes were : ( 1 ) users ’ motives , ( 2 ) users ’ desired outcomes , ( 3 ) users ’ positive experiences , ( 4 ) users ’ negative emotions , and ( 5 ) attributes desired by user . Conclusions There is little research in the field that has explored user experiences in human-computer interactions and how such experiences may relate to engagement , especially among males . Although not conclusive , the current study provides some insight into what personal attributes of middle-aged males ( such as their key motives and goals for participating ) and attributes of the intervention material s ( such as usability , control , and interactivity ) may impact on user engagement in this group . These findings will be helpful for informing the design and implementation of future health behavior interventions for males . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN12611000081910 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?ACTRN=12611000081910 ( Archived by WebCite at http://www.webcitation.org/6M4lBlvCA ) Background By adding new levels of experience , mobile Augmented Reality ( mAR ) can significantly increase the attractiveness of mobile learning applications in medical education . Objective To compare the impact of the heightened realism of a self-developed mAR blended learning environment ( mARble ) on learners to textbook material , especially for ethically sensitive subjects such as forensic medicine , while taking into account basic psychological aspects ( usability and higher level of emotional involvement ) as well as learning outcomes ( increased learning efficiency ) . Methods A pre study was conducted based on a convenience sample of 10 third-year medical students . The initial emotional status was captured using the “ Profile of Mood States ” question naire ( POMS , German variation ) ; previous knowledge about forensic medicine was determined using a 10-item single-choice ( SC ) test . During the 30-minute learning period , the students were r and omized into two groups : the first group consisted of pairs of students , each equipped with one iPhone with a preinstalled copy of mARble , while the second group was provided with textbook material . Subsequently , both groups were asked to once again complete the POMS question naire and SC test to measure changes in emotional state and knowledge gain . Usability as well as pragmatic and hedonic qualities of the learning material was captured using AttrakDiff2 question naires . Data evaluation was conducted anonymously . Descriptive statistics for the score in total and the subgroups were calculated before and after the intervention . The scores of both groups were tested against each other using paired and unpaired signed-rank tests . An item analysis was performed for the SC test to objectify difficulty and selectivity . Results Statistically significant , the mARble group ( 6/10 ) showed greater knowledge gain than the control group ( 4/10 ) ( Wilcoxon z=2.232 , P=.03 ) . The item analysis of the SC test showed a difficulty of P=0.768 ( s=0.09 ) and a selectivity of RPB=0.2 . For mARble , fatigue ( z=2.214 , P=.03 ) and numbness ( z=2.07 , P=.04 ) decreased with statistical significance when comparing pre- and post-tests . Vigor rose slightly , while irritability did not increase significantly . Changes in the control group were insignificant . Regarding hedonic quality ( identification , stimulation , attractiveness ) , there were significant differences between mARble ( mean 1.179 , CI −0.440 to 0.440 ) and the book chapter ( mean −0.982 , CI −0.959 to 0.959 ) ; the pragmatic quality mean only differed slightly . Conclusions The mARble group performed considerably better regarding learning efficiency ; there are hints for activating components of the mAR concept that may serve to fascinate the participants and possibly boost interest in the topic for the remainder of the class . While the small sample size reduces our study ’s conclusiveness , its design seems appropriate for determining the effects of interactive eLearning material with respect to emotions , learning efficiency , and hedonic and pragmatic qualities using a larger group . Trial Registration German Clinical Trial Register ( DRKS ) , DRKS-ID : DRKS00004685 ; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004685 Background Depressive disorders and symptoms affect more than one-third of primary care patients , many of whom do not receive or do not complete treatment . Internet-based social support from peers could sustain depression treatment engagement and adherence . We do not know whether primary care patients will accept referral to such websites nor do we know which methods of referral would be most effective . Objective We conducted a r and omized clinical trial to determine whether ( 1 ) a simple generic referral card ( control ) , ( 2 ) a patient-oriented brochure that provided examples of online postings and experience ( internal motivation ) , or ( 3 ) a physician letter of recommendation ( external motivation ) would generate the greatest participation in a primary care Internet depression treatment support portal focused around an Internet support group ( ISG ) . Methods We used 3 offline methods to identify potential participants who had not used an ISG in the past 6 months . Eligibility was determined in part by a brief structured psychiatric interview based on the Patient Health Question naire-9 ( PHQ-9 ) . After consent and enrollment , participants were r and omly assigned to 1 of 3 groups ( control , internal motivation , or external motivation ) . We constructed a portal to connect primary care patients to both fact-based information and an established ISG ( Psycho-Babble ) . The ISG allowed participants to view messages and then decide if they actually wished to register there . Participation in the portal and the ISG was assessed via automated activity tracking . Results Fifty participants were assigned to the 3 groups : a motivation-neutral control group ( n=18 ) , an internal motivation group ( n=19 ) , and an external motivation group ( n=13 ) . Of these participants , 31 ( 62 % ) visited the portal ; 27 ( 54 % ) visited the ISG itself . The internal motivation group showed significantly greater participation than the control group on several measures . The external motivation group spent significantly less time logged onto the portal than the control group . The internal motivation group showed significantly greater participation than the external motivation group on several measures . Conclusions Referral of primary care patients with depressive disorders and symptoms to an ISG is feasible even if they have never previously used one . This may best be accomplished by enhancing their internal motivation . Trial Registration Clinical trials.gov : NCT00886730 ; http:// clinical trials.gov/show/NCT00886730 ( Archived by WebCite at http://www.webcitation.org/6F4981fDN Aim Achieving target recruitment in r and omized controlled trials ( RCTs ) is challenging . This paper compares our experience of recruiting for an RCT with the predictions made in our proposal . Methods Participating UK primary care practice s search ed their computer data bases to identify patients ( 12 years and over ) with asthma who may be poorly controlled . Postal invitations were sent to all patients identified . Respondees were prescreened by phone , to assess their asthma control and establish their mobile phone suitability . Potentially eligible patients were booked for a trial recruitment visit . Results We recruited 288 patients ( 2.4 % of those invited ) across 32 practice s , with a total list size of 311,926 patients . This compares to our predicted recruitment of 312 patients from a population of 72,000 patients in six to eight practice s. In addition to the recognized problem of poor response rates , the major challenges were insufficiently discriminating computer search es and incompatibilities between mobile phone h and sets , networks and the asthma application . Conclusion Our data have implication s for clinicians , managers , and research ers in primary care . Research ers in this area may wish to consider our data when design ing their recruitment strategies . Improved coding of asthma morbidity data in clinical practice would ease identification of poorly controlled patients , both for clinical interventions and recruitment to trials . If telehealth is to become mainstream , there needs to be st and ardization of applications , operating platforms , and network capabilities Diaries are frequently used to evaluate therapy . Forgetfulness , however , can lead to missed entries . With paper diaries , these missing entries can be backfilled , compromising the reasons for using a diary . Electronic diaries are a potential means of mitigating this limitation . The pilot study was conducted to evaluate use of a mobile phone diary . Twelve subjects with mild persistent asthma were r and omly assigned to mobile or paper diary for 2 weeks and then crossed over to use the other diary type for next 2 weeks . Of the 12 subjects , 7 preferred the mobile diary . However , the mean prevalence of missing data was greater when using the mobile ( 18 % ± 9 % ) compared to paper diary ( 9 % ± 4 % ; P = 0.05 ) . In conclusion , the mobile diary was preferred by slightly more subjects . The greater prevalence of missing data when using this diary most likely results from the inability to backfill missing entries . Trial Registration : Clintrials.gov NCT00367263 ( http:// clinical trials.gov/ct2/show/NCT00367263 ) OBJECTIVE Nocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control , especially in young children with type 1 diabetes . We conducted an in-home r and omized trial to assess the efficacy and safety of a continuous glucose monitor – based overnight predictive low-glucose suspend ( PLGS ) system . RESEARCH DESIGN AND METHODS In two age-groups of children with type 1 diabetes ( 11–14 and 4–10 years of age ) , a 42-night trial for each child was conducted wherein each night was assigned r and omly to either having the PLGS system active ( intervention night ) or inactive ( control night ) . The primary outcome was percent time < 70 mg/dL overnight . RESULTS Median time at < 70 mg/dL was reduced by 54 % from 10.1 % on control nights to 4.6 % on intervention nights ( P < 0.001 ) in 11–14-year-olds ( n = 45 ) and by 50 % from 6.2 % to 3.1 % ( P < 0.001 ) in 4–10-year-olds ( n = 36 ) . Mean overnight glucose was lower on control versus intervention nights in both age-groups ( 144 ± 18 vs. 152 ± 19 mg/dL [ P < 0.001 ] and 153 ± 14 vs. 160 ± 16 mg/dL [ P = 0.004 ] , respectively ) . Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL ( P < 0.001 ) in the 11–14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL ( P = 0.11 ) in the 4–10-year-olds , respectively . No differences were found between intervention and control in either age-group in morning blood ketosis . CONCLUSIONS In 4–14-year-olds , use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis , although overnight mean glucose is slightly higher Objectives To compare the costs and cost-effectiveness of managing patients with uncontrolled blood pressure ( BP ) using telemonitoring versus usual care from the perspective of the National Health Service ( NHS ) . Design Within trial post hoc economic evaluation of data from a pragmatic r and omised controlled trial using an intention-to-treat approach . Setting 20 socioeconomically diverse general practice s in Lothian , Scotl and . Participants 401 primary care patients aged 29–95 with uncontrolled daytime ambulatory blood pressure ( ABP ) ( ≥135/85 , but < 210/135 mm Hg ) . Intervention Participants were central ly r and omised to 6 months of a telemonitoring service comprising of self-monitoring of BP transmitted to a secure website for review by the attending nurse/doctor and patient , with optional automated patient decision-support by text/email ( n=200 ) or usual care ( n-201 ) . R and omisation was undertaken with minimisation for age , sex , family practice , use of three or more hypertension drugs and self-monitoring history . Main outcome measures Mean difference in total NHS costs between trial arms and blinded assessment of mean cost per 1 mm Hg systolic BP point reduced . Results Home telemonitoring of BP costs significantly more than usual care ( mean difference per patient £ 115.32 ( 95 % CI £ 83.49 to £ 146.63 ; p<0.001 ) ) . Increased costs were due to telemonitoring service costs , patient training and additional general practitioner and nurse consultations . The mean cost of systolic BP reduction was £ 25.56/mm Hg ( 95 % CI £ 16.06 to £ 46.89 ) per patient . Conclusions Over the 6-month trial period , supported telemonitoring was more effective at reducing BP than usual care but also more expensive . If clinical gains are maintained , these additional costs would be very likely to be compensated for by reductions in the cost of future cardiovascular events . Longer-term modelling of costs and outcomes is required to fully examine the cost-effectiveness implication s. Trial registration International St and ard R and omised Controlled Trials , number IS RCT N72614272 Objective : There is limited evidence on whether growing mobile phone availability in sub-Saharan Africa can be used to promote high adherence to antiretroviral therapy ( ART ) . This study tested the efficacy of short message service ( SMS ) reminders on adherence to ART among patients attending a rural clinic in Kenya . Design : A r and omized controlled trial of four SMS reminder interventions with 48 weeks of follow-up . Methods : Four hundred and thirty-one adult patients who had initiated ART within 3 months were enrolled and r and omly assigned to a control group or one of the four intervention groups . Participants in the intervention groups received SMS reminders that were either short or long and sent at a daily or weekly frequency . Adherence was measured using the medication event monitoring system . The primary outcome was whether adherence exceeded 90 % during each 12-week period of analysis and the 48-week study period . The secondary outcome was whether there were treatment interruptions lasting at least 48 h. Results : In intention-to-treat analysis , 53 % of participants receiving weekly SMS reminders achieved adherence of at least 90 % during the 48 weeks of the study , compared with 40 % of participants in the control group ( P = 0.03 ) . Participants in groups receiving weekly reminders were also significantly less likely to experience treatment interruptions exceeding 48 h during the 48-week follow-up period than participants in the control group ( 81 vs. 90 % , P = 0.03 ) . Conclusion : These results suggest that SMS reminders may be an important tool to achieve optimal treatment response in re source -limited setting Objectives To evaluate the impact of a mobile phone-based , remote monitoring , advanced symptom management system ( ASyMS © ) on the incidence , severity and distress of six chemotherapy-related symptoms ( nausea , vomiting , fatigue , mucositis , h and –foot syndrome and diarrhoea ) in patients with lung , breast or colorectal cancer . Design A two group ( intervention and control ) by five time points ( baseline , pre-cycle 2 , pre-cycle 3 , pre-cycle 4 and pre-cycle 5 ) r and omised controlled trial . Setting Seven clinical sites in the UK ; five specialist cancer centres and two local district hospitals . Participants One hundred and twelve people with breast , lung or colorectal cancer receiving outpatient chemotherapy . Interventions A mobile phone-based , remote monitoring , advanced symptom management system (ASyMS © ).Main outcome measures Chemotherapy-related morbidity of six common chemotherapy-related symptoms ( nausea , vomiting , fatigue , mucositis , h and –foot syndrome and diarrhoea ) . Results There were significantly higher reports of fatigue in the control group compared to the intervention group ( odds ratio = 2.29 , 95%CI = 1.04 to 5.05 , P = 0.040 ) and reports of h and –foot syndrome were on average lower in the control group ( odds ratio control/intervention = 0.39 , 95%CI = 0.17 to 0.92 , P = 0.031 ) . Conclusion The study demonstrates that ASyMS © can support the management of symptoms in patients with lung , breast and colorectal cancer receiving chemotherapy OBJECTIVES To evaluate the effectiveness of computer-assisted decision support in reducing potentially inappropriate prescribing to older adults . DESIGN R and omized , controlled trial . SETTING An academic emergency department ( ED ) in Indianapolis , Indiana , where computerized physician order entry was used to write all medication prescriptions . PARTICIPANTS Sixty-three emergency physicians were r and omized to the intervention ( 32 physicians ) or control ( 31 physicians ) group . INTERVENTION Decision support that advised against use of nine potentially inappropriate medications and recommended safer substitute therapies . MEASUREMENTS The primary outcome was the proportion of ED visits by seniors that result ed in one or more prescriptions for an inappropriate medication . The main secondary outcomes were the proportions of medications prescribed that were inappropriate and intervention physicians ' reasons for rejecting the decision support . RESULTS The average age of the patients was 74 , two-thirds were female , and just over half were African American . Decision support was provided 114 times to intervention physicians , who accepted 49 ( 43 % ) of the recommendations . Intervention physicians prescribed one or more inappropriate medications during 2.6 % of ED visits by seniors , compared with 3.9 % of visits managed by control physicians ( P=.02 ; odds ratio=0.55 , 95 % confidence interval=0.34 - 0.89 ) . The proportion of all prescribed medications that were inappropriate significantly decreased from 5.4 % to 3.4 % . The most common reason for rejecting decision support was that the patient had no prior problems with the medication . CONCLUSION Computerized physician order entry with decision support significantly reduced prescribing of potentially inappropriate medications for seniors . This approach might be used in other efforts to improve ED care . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00297869 Background This paper reports the results of a pilot r and omized controlled trial comparing the delivery modality ( mobile phone/tablet or fixed computer ) of a cognitive behavioural therapy intervention for the treatment of depression . The aim was to establish whether a previously vali date d computerized program ( The Sadness Program ) remained efficacious when delivered via a mobile application . Method 35 participants were recruited with Major Depression ( 80 % female ) and r and omly allocated to access the program using a mobile app ( on either a mobile phone or iPad ) or a computer . Participants completed 6 lessons , weekly homework assignments , and received weekly email contact from a clinical psychologist or psychiatrist until completion of lesson 2 . After lesson 2 email contact was only provided in response to participant request , or in response to a deterioration in psychological distress scores . The primary outcome measure was the Patient Health Question naire 9 ( PHQ-9 ) . Of the 35 participants recruited , 68.6 % completed 6 lessons and 65.7 % completed the 3-months follow up . Attrition was h and led using mixed-model repeated- measures ANOVA . Results Both the Mobile and Computer Groups were associated with statistically significantly benefits in the PHQ-9 at post-test . At 3 months follow up , the reduction seen for both groups remained significant . Conclusions These results provide evidence to indicate that delivering a CBT program using a mobile application , can result in clinical ly significant improvements in outcomes for patients with depression . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN Background Involving stakeholders and consumers throughout the content and study design ensures interventions are engaging and relevant for end-users . The aim of this paper is to present the content development process for a mHealth ( mobile phone and internet-based ) cardiac rehabilitation ( CR ) exercise intervention . Methods An innovative mHealth intervention was developed with patient input using the following steps : conceptualization , formative research , pre-testing , and pilot testing . Conceptualization , including theoretical and technical aspects , was undertaken by experts . For the formative component , focus groups and interviews with cardiac patients were conducted to discuss their perceptions of a mHealth CR program . A general inductive thematic approach identified common themes . A preliminary library of text and video messages were then developed . Participants were recruited from CR education sessions to pre-test and provide feedback on the content using an online survey . Common responses were extracted and compiled . An iterative process was used to refine content prior to pilot testing and conduct of a r and omized controlled trial . Results 38 CR patients and 3 CR nurses participated in the formative research and 20 CR patients participated in the content pre-testing . Participants perceived the mHealth program as an effective approach to inform and motivate patients to exercise . For the qualitative study , 100 % ( n = 41 ) of participants thought it to be a good idea , and 11 % of participants felt it might not be useful for them , but would be for others . Of the 20 participants who completed the online survey , 17 out of 20 ( 85 % ) stated they would sign up to a program where they could receive information by video messages on a website , and 12 out of 20 ( 60 % ) showed interest in a texting program . Some older CR patients viewed technology as a potential barrier as they were unfamiliar with text messaging or did not have mobile phones . Steps to instruct participants to receive texts and view the website were written into the study protocol . Suggestions to improve videos and wording of texts were fed back to the content development team and refined . Conclusions Most participants thought a mHealth exercise program was an effective way to deliver exercise-based CR . The results were used to develop an innovative multimedia exercise intervention . A r and omized controlled trial is currently underway . Trial registration Background Using two-way mobile phone text messages to improve adherence to antiretroviral medication enhances communication between patients and health workers . We describe the implication s of participants ’ responses to text messages in the Cameroon Mobile Phone SMS ( CAMPS ) trial . Findings This is a cross-sectional analysis of data from the intervention arm of the CAMPS trial . CAMPS was a r and omized controlled trial of motivational text messaging versus usual care to improve adherence to antiretroviral medication among people living with HIV in Yaounde , Cameroon ( n = 200 ) over a 6 month period . Participants in the intervention arm ( n = 101 ) were given a contact phone number , but were not required to respond to their reminder messages . If they did , their responses were noted and reported as counts and percentages . We received 99 phone calls and 55 text messages ( 154 responses ) from 48 participants during the study period . The median number of responses was 1 ( first quartile [ Q1 ] : 1 ; third quartile [ Q3 ] : 3 ) . Half ( n = 79 , 51.1 % ) of them were expressions of gratitude . The rest included requests for logistical ( n = 21 , 13.6 % ) , medical ( n = 20 , 12.9 % ) and financial ( n = 11 , 7.1 % ) support . Conclusion Initiating two-way mobile communication opens more channels for people living with HIV to express unmet needs . Research ers , policy makers and clinicians should be ready to respond to the needs expressed by patients who respond to text messages . Trial registration Pan-African Clinical Trials Registry : PACTR201011000261458 Clinical trials.gov : Context Computerized drug alerts for psychotropic drugs are expected to reduce fall-related injuries in older adults . However , physicians over-ride most alerts because they believe the benefit of the drugs exceeds the risk . Objective To determine whether computerized prescribing decision support with patient-specific risk estimates would increase physician response to psychotropic drug alerts and reduce injury risk in older people . Design Cluster r and omized controlled trial of 81 family physicians and 5628 of their patients aged 65 and older who were prescribed psychotropic medication . Intervention Intervention physicians received information about patient-specific risk of injury computed at the time of each visit using statistical models of non-modifiable risk factors and psychotropic drug doses . Risk thermometers presented changes in absolute and relative risk with each change in drug treatment . Control physicians received commercial drug alerts . Main outcome measures Injury risk at the end of follow-up based on psychotropic drug doses and non-modifiable risk factors . Electronic health records and provincial insurance administrative data were used to measure outcomes . Results Mean patient age was 75.2 years . Baseline risk of injury was 3.94 per 100 patients per year . Intermediate-acting benzodiazepines ( 56.2 % ) were the most common psychotropic drug . Intervention physicians review ed therapy in 83.3 % of visits and modified therapy in 24.6 % . The intervention reduced the risk of injury by 1.7 injuries per 1000 patients ( 95 % CI 0.2/1000 to 3.2/1000 ; p=0.02 ) . The effect of the intervention was greater for patients with higher baseline risks of injury ( p<0.03 ) . Conclusion Patient-specific risk estimates provide an effective method of reducing the risk of injury for high-risk older people . Trial registration number clinical trials.gov Identifier : NCT00818285 Background Over 75 % of mental health problems begin in adolescence and primary care has been identified as the target setting for mental health intervention by the World Health Organisation . The mobiletype program is a mental health assessment and management mobile phone application which monitors mood , stress , coping strategies , activities , eating , sleeping , exercise patterns , and alcohol and cannabis use at least daily , and transmits this information to general practitioners ( GPs ) via a secure website in summary format for medical review . Methods We conducted a r and omised controlled trial in primary care to examine the mental health benefits of the mobiletype program . Patients aged 14 to 24 years were recruited from rural and metropolitan general practice s. GPs identified and referred eligible participants ( those with mild or more mental health concerns ) who were r and omly assigned to either the intervention group ( where mood , stress , and daily activities were monitored ) or the attention comparison group ( where only daily activities were monitored ) . Both groups self-monitored for 2 to 4 weeks and review ed the monitoring data with their GP . GPs , participants , and research ers were blind to group allocation at r and omisation . Participants completed pre- , post- , and 6-week post-test measures of the Depression , Anxiety , Stress Scale and an Emotional Self Awareness ( ESA ) Scale . Results Of the 163 participants assessed for eligibility , 118 were r and omised and 114 participants were included in analyses ( intervention group n = 68 , comparison group n = 46 ) . Mixed model analyses revealed a significant group by time interaction on ESA with a medium size of effect suggesting that the mobiletype program significantly increases ESA compared to an attention comparison . There was no significant group by time interaction for depression , anxiety , or stress , but a medium to large significant main effect for time for each of these mental health measures . Post-hoc analyses suggested that participation in the RCT lead to enhanced GP mental health care at pre-test and improved mental health outcomes . Conclusions Monitoring mental health symptoms appears to increase ESA and implementing a mental health program in primary care and providing frequent reminders , clinical re sources , and support to GPs substantially improved mental health outcomes for the sample as a whole . Trial Registration Clinical Trials.gov NCT00794222 Electronically delivered health promotion programs that are aim ed primarily at educated , health-literate individuals have proliferated , raising concerns that such trends could exacerbate health disparities in the United States and elsewhere . The efficacy of a culturally and linguistically adapted virtual advisor that provides tailored physical activity advice and support was tested in low-income older adults . Forty inactive adults ( 92.5 % Latino ) 55 years of age and older were r and omized to a 4-month virtual advisor walking intervention or a waitlist control . Four-month increases in reported minutes of walking/week were greater in the virtual advisor arm ( mean increase = 253.5 ± 248.7 minutes/week ) relative to the control ( mean increase = 26.8 ± 67.0 minutes/week ; p = .0008 ) . Walking increases in the virtual advisor arm were substantiated via objective ly measured daily steps ( slope analysis p = .002 ) . All but one intervention participant continued some interaction with the virtual advisor in the 20-week post study period ( mean number of post study sessions = 14.0 ± 20.5 ) . The results indicate that a virtual advisor delivering culturally and linguistically adapted physical activity advice led to meaningful 4-month increases in walking relative to control among underserved older adults . This interactive technology , which requires minimal language and computer literacy , may help reduce health disparities by ensuring that all groups benefit from e-health opportunities OBJECTIVE To assess the impact of a web-based intervention supplemented with text messages to reduce cancer risk linked with smoking , unhealthy diet , alcohol consumption , obesity , sedentary lifestyle and sun exposure . METHODS A total of 2001 voluntary adolescents from Spain and Mexico were recruited between 2009 and 2012 and r and omly assigned to : one control group and two experimental groups , which received exclusively the online intervention ( experimental group 1 ) or the intervention supplemented with encouraging text messages ( experimental group 2 ) . The educational intervention was based on both : successful psychosocial models ( i.e. A.S.E. and Transtheoretical model ) and the school curriculum . RESULTS After a 9-month follow-up , the prevalence of students who did not eat fruit was reduced significantly in all groups : experimental group 1 ( -62.6 % ) , experimental group 2 ( -71.5 % ) and even the control group ( -66.8 % ) . Being overweight was only reduced in the experimental group 2 ( -19.6 % ) . The total cancer behavioral risk score , which ranged from 0 to 100 points ( highest risk ) , was significantly reduced in the experimental group 1 ( -3.5 points ) and in the experimental group 2 ( -5.3 points ) . The text-supplemented online intervention increased the probability of improving the post-test total cancer behavioral risk ( OR=1.62 ) . CONCLUSION The web-based intervention supplemented with text messages had a positive global impact , but it lead to only minimal changes in risky behaviors . This intervention appears useful in controlling overweight adolescents . CLINICAL TRIAL REGISTRATION NUMBER IS RCT N27988779 ABSTRACT Little is known about how online social networking can help enhance weight loss . To examine the types of online social support utilized in a behavioral weight loss intervention and relationship of posting and weight loss . A sub- analysis of the content and number of posts to Twitter among participants ( n = 47 ) r and omized to a mobile , social network arm as part of a 6-month trial among overweight adults , examining weight loss , use of Twitter , and type of social support ( informational , tangible assistance , esteem , network , and emotional support ) . A number of Twitter posts were related to % weight loss at 6 months ( p < 0.001 ) . Initial reported weight loss predicted engagement with Twitter ( p < 0.01 ) but prior Twitter use or initial Twitter engagement did not . Most Twitter posts ( total posts n = 2,630 ) were Informational support ( n = 1,981 ; 75 % ) , with the predominant subtype of Teaching ( n = 1,632 ; 62 % ) , mainly in the form of a status up date ( n = 1,319 ) . Engagement with Twitter was related to weight loss and participants mainly used Twitter to provide Information support to one another through status up date Background Mobile phones are increasingly used in health systems in developing countries and innovative technical solutions have great potential to overcome barriers of access to reproductive and child health care . However , despite widespread support for the use of mobile health technologies , evidence for its role in health care is sparse . Objective We aim ed to evaluate the association between a mobile phone intervention and perinatal mortality in a re source -limited setting . Methods This study was a pragmatic , cluster-r and omized , controlled trial with primary health care facilities in Zanzibar as the unit of r and omization . At their first antenatal care visit , 2550 pregnant women ( 1311 interventions and 1239 controls ) who attended antenatal care at selected primary health care facilities were included in this study and followed until 42 days after delivery . Twenty-four primary health care facilities in six districts were r and omized to either mobile phone intervention or st and ard care . The intervention consisted of a mobile phone text message and voucher component . Secondary outcome measures included stillbirth , perinatal mortality , and death of a child within 42 days after birth as a proxy of neonatal mortality . Results Within the first 42 days of life , 2482 children were born alive , 54 were stillborn , and 36 died . The overall perinatal mortality rate in the study was 27 per 1000 total births . The rate was lower in the intervention clusters , 19 per 1000 births , than in the control clusters , 36 per 1000 births . The intervention was associated with a significant reduction in perinatal mortality with an odds ratio ( OR ) of 0.50 ( 95 % CI 0.27 - 0.93 ) . Other secondary outcomes showed an insignificant reduction in stillbirth ( OR 0.65 , 95 % CI 0.34 - 1.24 ) and an insignificant reduction in death within the first 42 days of life ( OR 0.79 , 95 % CI 0.36 - 1.74 ) . Conclusions Mobile phone applications may contribute to improved health of the newborn and should be considered by policy makers in re source -limited setting s. Trial Registration Clinical Trials.gov NCT01821222 ; http://www . clinical trials.gov/ct2/show/NCT01821222 ( Archived by WebCite at http://www.webcitation.org/6NqxnxYn0 ) BACKGROUND An artificial pancreas ( AP ) that can be worn at home from dinner to waking up in the morning might be safe and efficient for first routine use in patients with type 1 diabetes . We assessed the effect on glucose control with use of an AP during the evening and night plus patient-managed sensor-augmented pump therapy ( SAP ) during the day , versus 24 h use of patient-managed SAP only , in free-living conditions . METHODS In a crossover study done in medical centres in France , Italy , and the Netherl and s , patients aged 18 - 69 years with type 1 diabetes who used insulin pumps for continuous subcutaneous insulin infusion were r and omly assigned to 2 months of AP use from dinner to waking up plus SAP use during the day versus 2 months of SAP use only under free-living conditions . R and omisation was achieved with a computer-generated allocation sequence with r and om block sizes of two , four , or six , masked to the investigator . Patients and investigators were not masked to the type of intervention . The AP consisted of a continuous glucose monitor ( CGM ) and insulin pump connected to a modified smartphone with a model predictive control algorithm . The primary endpoint was the percentage of time spent in the target glucose concentration range ( 3·9 - 10·0 mmol/L ) from 2000 to 0800 h. CGM data for weeks 3 - 8 of the interventions were analysed on a modified intention-to-treat basis including patients who completed at least 6 weeks of each intervention period . The 2 month study period also allowed us to asses HbA1c as one of the secondary outcomes . This trial is registered with Clinical Trials.gov , number NCT02153190 . FINDINGS During 2000 - 0800 h , the mean time spent in the target range was higher with AP than with SAP use : 66·7 % versus 58·1 % ( paired difference 8·6 % [ 95 % CI 5·8 to 11·4 ] , p<0·0001 ) , through a reduction in both mean time spent in hyperglycaemia ( glucose concentration > 10·0 mmol/L ; 31·6 % vs 38·5 % ; -6·9 % [ -9·8 % to -3·9 ] , p<0·0001 ) and in hypoglycaemia ( glucose concentration < 3·9 mmol/L ; 1·7 % vs 3·0 % ; -1·6 % [ -2·3 to -1·0 ] , p<0·0001 ) . Decrease in mean HbA1c during the AP period was significantly greater than during the control period ( -0·3 % vs -0·2 % ; paired difference -0·2 [ 95 % CI -0·4 to -0·0 ] , p=0·047 ) , taking a period effect into account ( p=0·0034 ) . No serious adverse events occurred during this study , and none of the mild-to-moderate adverse events was related to the study intervention . INTERPRETATION Our results support the use of AP at home as a safe and beneficial option for patients with type 1 diabetes . The HbA1c results are encouraging but preliminary . FUNDING European Commission BACKGROUND Severe health anxiety is a common condition associated with functional disability , making it a costly disorder from a societal perspective . Internet-based cognitive behaviour therapy ( ICBT ) is a promising treatment but no previous study has assessed the cost-effectiveness or long-term outcome of ICBT for severe health anxiety . The aim of this study was to investigate the cost-effectiveness and 1-year treatment effects of ICBT for severe health anxiety . METHOD Cost-effectiveness and 1-year follow-up data were obtained from a r and omized controlled trial ( RCT ) comparing ICBT ( n = 40 ) to an attention control condition ( CC , n = 41 ) . The primary outcome measure was the Health Anxiety Inventory ( HAI ) . A societal perspective was taken and incremental cost-effectiveness ratios ( ICERs ) were calculated using bootstrap sampling . RESULTS The main ICER was -£1244 , indicating the societal economic gain for each additional case of remission when administering ICBT . Baseline to 1-year follow-up effect sizes on the primary outcome measure were large ( d = 1.71 - 1.95 ) . CONCLUSIONS ICBT is a cost-effective treatment for severe health anxiety that can produce substantial and enduring effects BACKGROUND Quality of life ( QoL ) is an important outcome in the treatment of schizophrenia . Cognitive deficits have an impact on functional outcomes . Cognitive remediation therapy is emerging as a psychological intervention that targets cognitive impairment , but the effect of computer-assisted cognitive remediation on neuropsychology and social functioning and wellbeing remains unclear . The aim of the current study is to investigate the neurocognitive outcomes of computer-assisted cognitive remediation ( CACR ) therapy in a sample of schizophrenia patients , and to measure the quality of life and self-esteem as secondary outcomes . METHODS Sixty-seven people with schizophrenia were r and omly assigned to computer-assisted cognitive remediation or an active control condition . The main outcomes were neuropsychological measures and secondary outcomes ( self-esteem and quality of life ) . Measurements were recorded at baseline and post-treatment . RESULTS The CACR therapy group improved in speed of processing , working memory and reasoning and problem-solving cognitive domains . QoL and self-esteem measures also showed significant improvements over time in this group . CONCLUSIONS Computer-assisted cognitive remediation therapy for people with schizophrenia achieved improvements in neuropsychological performance and in QoL and self-esteem measurements OBJECTIVES The objective was to assess the efficiency and safety of an interactive computer kiosk module for the management of uncomplicated urinary tract infections ( UTI ) in emergency departments ( EDs ) . METHODS This was a prospect i ve unblinded r and omized trial . Women age 18 to 64 years seeking care for suspected UTI in three urban EDs were referred to a computer kiosk after triage . The kiosk evaluated women for uncomplicated UTI ( based on patient report of at least one irritable voiding symptom within 7 days and absence of complicating features ) , and eligible patients were r and omized to expedited management or usual ED care . Expedited management consisted of a brief clinician encounter to confirm computer kiosk responses and selection of one of four st and ard antibiotic regimens . Study outcomes included urine culture results , duration of ED visit , time to illness resolution , return visits , and satisfaction with care . RESULTS Seventeen percent ( n = 103 ) of 624 participants with suspected UTI fulfilled uncomplicated criteria and were r and omized . Sixty-nine percent of these women had a positive urine culture . Compared with the control group , the computer-expedited management group had lower median visit duration ( 89 minutes , interquartile range [ IQR ] = 65 to 150 minutes vs. 146 minutes , IQR = 105 to 216 minutes ) for a decrease of 57 minutes ( 95 % confidence interval [ CI ] = 27 to 87 , p = 0.004 ) . They had similar time to illness resolution , number of return visits , and satisfaction with care . CONCLUSIONS An interactive computer kiosk accurately , efficiently , and safely expedited the management of women with uncomplicated UTI in a busy , urban ED . Exp and ing the use of this technology to other conditions could help to improve ED patient flow Background Accurate immunosuppression is of critical importance in preventing rejection , while avoiding toxicity following lung transplantation . The mainstay immunosuppressants are calcineurin inhibitors , which require regular monitoring due to interactions with other medications and diet . Adherence to immunosuppression and patient knowledge is vital and can be improved through patient education . Education using tablet-computers was investigated . Objective To compare tablet-PC education and conventional education in improving immunosuppression trough levels in target range 6 months after a single education . Secondary parameters were ratio of immunosuppression level measurements divided by per protocol recommended measurements , time and patient satisfaction regarding education . Design Single-centre , open labelled r and omised controlled trial . Participants Patients > 6 months after lung-transplantation with < 50 % of calcineurin inhibitor trough levels in target range . Intervention Tablet-pc education versus personal , nurse-led education . Measurements Calcineurin inhibitor levels in target range 6 months after education , level variability , interval adherence , knowledge and adherence was studied . As outcome parameter , renal function was measured and adverse events registered . Results Sixty-four patients were 1:1 r and omised for either intervention . Levels of immunosuppression 6 months after education were equal ( tablet-PC 58 % vs. conventional 48 % , p = 0.27 ) , both groups improved in achieving a CNI trough level within target range by either education method ( delta tablet-PC 29 % vs. conventional 20 % ) . In all patients , level variability decreased ( −20.4 % ) , whereas interval adherence remained unchanged . Knowledge about immunosuppression improved by 7 % and compliance tests demonstrated universal improvements with no significant difference between groups . Conclusion Education is a simple , effective tool in improving adherence to immunosuppression . Tablet-PC education was non-inferior to conventional education . Trial Registration Clinical Trials.gov NCT01398488 http:// clinical trials.gov/ct2/show/NCT01398488?term=gottlieb+tablet+pc+education&rank=1 Background Computer-delivered psychological treatments have great potential , particularly for individuals who can not access traditional approaches . Little is known about the acceptability of computer-delivered treatment , especially among those with comorbid mental health and substance use problems . Objective The objective of our study was to assess the acceptability of a clinician-assisted computer-based ( CAC ) psychological treatment ( delivered on DVD in a clinic- setting ) for comorbid depression and alcohol or cannabis use problems relative to a therapist-delivered equivalent and a brief intervention control . Methods We compared treatment acceptability , in terms of treatment dropout/participation and therapeutic alliance , of therapist-delivered versus CAC psychological treatment . We r and omly assigned 97 participants with current depression and problematic alcohol/cannabis use to three conditions : brief intervention ( BI , one individual session delivered face to face ) , therapist-delivered ( one initial face-to-face session plus 9 individual sessions delivered by a therapist ) , and CAC interventions ( one initial face-to-face session plus 9 individual CAC sessions ) . R and omization occurred following baseline and provision of the initial session , and therapeutic alliance ratings were obtained from participants following completion of the initial session , and at sessions 5 and 10 among the therapist-delivered and CAC conditions . Results Treatment retention and attendance rates were equal between therapist-delivered and CAC conditions , with 51 % ( 34/67 ) completing all 10 treatment sessions . No significant differences existed between participants in therapist-delivered and CAC conditions at any point in therapy on the majority of therapeutic alliance subscales . However , relative to therapist-delivered treatment , the subscale of Client Initiative was rated significantly higher among participants allocated to the BI ( F2,54 = 4.86 , P = .01 ) and CAC participants after session 5 ( F1,29 = 9.24 , P = .005 ) , and this domain was related to better alcohol outcomes . Linear regression modeled therapeutic alliance over all sessions , with treatment allocation , retention , other demographic factors , and baseline symptoms exhibiting no predictive value . Conclusions Participants in a trial of CAC versus therapist-delivered treatment were equally able to engage , bond , and commit to treatment , despite comorbidity typically being associated with increased treatment dropout , problematic engagement , and complexities in treatment planning . The extent to which a client feels that they are directing therapy ( Client initiative ) may be an important component of change in BI and CAC intervention , especially for hazardous alcohol use . Trial Registration Australian New Zeal and Clinical Trials Registry ACTRN12607000437460 ; http://www.anzctr.org.au/trial_view.aspx?ID=82228 ( Archived by WebCite at http://www.webcitation.org/5ubuRsULu OBJECTIVE Numerous mobile health ( mHealth ) interventions are being developed to aid in management of complex chronic medical conditions . However , the acceptance of mHealth programs by low-income , bilingual population s has not yet been evaluated . The Trial to Examine Text-based mHealth for Emergency department patients with Diabetes ( TExT-MED ) program is a text message-based mHealth program design ed specifically for re source -poor patients with diabetes . We conducted a prospect i ve proof-of-concept trial to assess satisfaction and preliminary effectiveness of the TExT-MED program . RESEARCH DESIGN AND METHODS A consecutive sample of adult patients in the emergency department with diabetes and a text message-capable mobile phone was enrolled in the TExT-MED program . Participants received three text messages daily for 3 weeks in English or Spanish in the following domains : educational/motivational , medication reminders , healthy living challenges , diabetes trivia , and links to free diabetes management tools . RESULTS Twenty-three patients with diabetes ( median hemoglobin A1c , 8.9 % ) were enrolled in TExT-MED . In the week before TExT-MED , 56.5 % of subjects reported eating fruits/vegetables daily versus 83 % after , 43.5 % reported exercising before versus 74 % after , and 74 % reported performing foot checks before versus 85 % after . Self-efficacy , measured by the Diabetes Empowerment Scale-Short Form , improved from 3.9 to 4.2 . Scores on the Morisky Medication Adherence Scale improved more dramatically from 3.5 to 4.75 . Ninety percent of participants indicated they would like to continue the program , and 100 % would recommend the program to family or friends . CONCLUSIONS This pilot trial of the TExT-MED program demonstrated increased healthy behaviors , improved diabetes self-efficacy and medication adherence , and received excellent satisfaction scores in re source -poor , inner city patients with diabetes BACKGROUND The obesity epidemic has spread to young adults , leading to significant public health implication s later in adulthood . Intervention in early adulthood may be an effective public health strategy for reducing the long-term health impact of the epidemic . Few weight loss trials have been conducted in young adults . It is unclear what weight loss strategies are beneficial in this population . PURPOSE To describe the design and rationale of the NHLBI-sponsored Cell Phone Intervention for You ( CITY ) study , which is a single center , r and omized three-arm trial that compares the impact on weight loss of 1 ) a behavioral intervention that is delivered almost entirely via cell phone technology ( Cell Phone group ) ; and 2 ) a behavioral intervention delivered mainly through monthly personal coaching calls enhanced by self-monitoring via cell phone ( Personal Coaching group ) , each compared to 3 ) a usual care , advice-only control condition . METHODS A total of 365 community-dwelling overweight/obese adults aged 18 - 35 years were r and omized to receive one of these three interventions for 24 months in parallel group design . Study personnel assessing outcomes were blinded to group assignment . The primary outcome is weight change at 24 [ corrected ] months . We hypothesize that each active intervention will cause more weight loss than the usual care condition . Study completion is anticipated in 2014 . CONCLUSIONS If effective , implementation of the CITY interventions could mitigate the alarming rates of obesity in young adults through promotion of weight loss . Clinical Trial.gov : NCT01092364 BACKGROUND Colorectal cancer ( CRC ) screening reduces mortality yet remains underutilized . Low health literacy may contribute to this underutilization by interfering with patients ' ability to underst and and receive preventive health services . PURPOSE To determine if a web-based multimedia CRC screening patient decision aid , developed for a mixed-literacy audience , could increase CRC screening . DESIGN RCT . Patients aged 50 - 74 years and overdue for CRC screening were r and omized to the web-based decision aid or a control program seen immediately before a scheduled primary care appointment . SETTING / PARTICIPANTS A large community-based , university-affiliated internal medicine practice serving a socioeconomically disadvantaged population . MAIN OUTCOME MEASURES Patients completed surveys to determine their ability to state a screening test preference and their readiness to receive screening . Charts were abstract ed by masked observers to determine if screening tests were ordered and completed . RESULTS Between November 2007 and September 2008 , a total of 264 patients enrolled in the study . Data collection was completed in 2009 , and data analysis was completed in 2010 . A majority of participants ( mean age=57.8 years ) were female ( 67 % ) , African-American ( 74 % ) , had annual household incomes of < $ 20,000 ( 76 % ) , and had limited health literacy ( 56 % ) . When compared to control participants , more decision-aid participants had a CRC screening preference ( 84 % vs 55 % , p<0.0001 ) and an increase in readiness to receive screening ( 52 % vs 20 % , p=0.0001 ) . More decision-aid participants had CRC screening tests ordered ( 30 % vs 21 % ) and completed ( 19 % vs 14 % ) , but no statistically significant differences were seen ( AOR=1.6 , 95 % CI=0.97 , 2.8 , and AOR=1.7 , 95 % CI=0.88 , 3.2 , respectively ) . Similar results were found across literacy levels . CONCLUSIONS The web-based decision aid increased patients ' ability to form a test preference and their intent to receive screening , regardless of literacy level . Further study should examine ways the decision aid can be combined with additional system changes to increase CRC screening Context Domestic violence is difficult to recognize , and screening is often difficult to implement . Contribution This r and omized trial found that when a computer-generated report detailing patients ' responses to questions about intimate partner violence and control was attached to medical charts , family practitioners asked about it and detected it more often . Caution The trial was conducted at a single family practice clinic in Canada . Implication Computer-assisted screening for intimate partner violence and control led to improved detection in a busy ambulatory care setting . The Editors Intimate partner violence ( IPV ) is physical or sexual violence or threats of violence made by one partner to another , often accompanied by controlling behaviors ( 1 ) . Intimate partner violence is a prevalent and serious health risk for women ( 14 ) . Despite frequent health care visits ( 58 ) , many women refrain from disclosing their experience of IPV to clinicians because of feelings of shame ( 912 ) . Direct inquiry by physicians facilitates disclosure ( 1315 ) , but physicians often fail to inquire about IPV risk owing to lack of time , more pressing acute medical problems , discomfort , fear of offending the patient , and lack of familiarity with re sources ( 1621 ) . The result is missed opportunities for intervening and preventing harm . Computer screening may help to overcome some of the barriers to discussing risk for IPV . Studies in hospital emergency departments reported higher frequency of patient disclosure and of physician detection of IPV when interactive computer screening was used , compared with patients receiving st and ard medical care ( 2224 ) . Computer-assisted screening may be particularly useful in primary care setting s , where physicians focus on comprehensive care , including psychosocial risks , and where women experiencing IPV seek ongoing care from their trusted physicians ( 25 ) . Universal screening for IPV is under debate ( 2628 ) . On the basis of inconclusive systematic review s ( 2931 ) , however , some medical associations ( including the American Medical Association and American Academy of Family Physicians ) recommend routine screening for IPV among adult women ( 3235 ) . These recommendations are based on available evidence about the burden of IPV , the benefits of provider referral for help , and the low risk associated with asking ( 36 ) . Several qualitative studies of abused women report that IPV risk assessment by concerned health care providers reduces their feelings of isolation and improves their sense of self-worth , knowledge about re sources , and willingness to seek help ( 3739 ) . Longitudinal studies show that use of tailored counseling services reduces partners ' controlling behavior or physical violence and , in pregnant women , postnatal depression ( 40 , 41 ) . In addition , access to employment and social support reduces revictimization ( 42 ) . Primary care physicians can be pivotal in detecting IPV and offering support and referrals in a timely manner to at-risk women who might otherwise remain silent and delay seeking help ( 43 , 44 ) . Assessment of the partner 's controlling behavior is important because such acts precede physical violence ( 45 ) or have negative consequences ( 46 ) . We tested the effectiveness of computer-assisted screening for identifying patients at risk for intimate partner violence or control ( IPVC ) in a Canadian family practice clinic . We hypothesized that computer-assisted screening of female patients would create opportunities for women to discuss IPVC with their providers and would increase the frequency of IPVC detection compared with st and ard medical care . Methods Study Site The study was conducted at a multiphysician , hospital-affiliated , academic family practice clinic in inner-city Toronto , Ontario , Canada , between March and September 2005 . The clinic had a multidisciplinary clinical team providing care to diverse patients ( 50000 annual visits ) . The clinic nurse manager , a social worker , and a physician collaborated on development of the trial protocol , modifications of the computer survey , and pilot testing . Relevant university and hospital ethical approvals were obtained from the research ethics boards of St. Michael 's Hospital and University of Toronto . Intervention The study intervention was a computer program that administered a previously vali date d survey ( 22 , 23 , 25 ) to patients and generated risk reports for physicians and recommendation sheets for patients at the time of their clinic visit ( Appendix Figure ) . We modified the program , called Promote Health , for a Canadian family practice context . Our modified version included 79 questions on IPVC and alcohol , tobacco , and street drug use ; risk for sexually transmitted infection ; road and home safety ; depression ; cardiovascular risks ; and some sociodemographic factors . Embedding questions about women 's risk for IPVC ( physical or sexual violence , threat of violence , and control by partner ) allowed us to conceal the study focus from physician and patient participants . The survey was written on a fifth- grade reading level . Appendix Figure . Example of a physician report printed by Promote Health . The section on IPVC included questions on partner 's controlling behavior , physical and sexual violence , and threat of violence . These questions were derived from vali date d scales of the Abuse Assessment Screen ( 47 , 48 ) and Partner Violence Screen ( 49 ) , along with items from Improving the Health Care Response to Domestic Violence : A Re source Manual For Health Care Providers ( 50 ) . The survey section on depression included questions derived from vali date d scales of the Center for Epidemiologic Studies Depression scale , Hamilton Rating Scale for Depression , and the Geriatric Depression Scale ( 5153 ) . The questions were modified after cognitive interviewing with patients in earlier work by Rhodes and colleagues ( 22 ) . Any yes response to IPVC-related questions was reported on the 1-page risk report and labeled Possible Partner Abuseassess for victimization for physician review . Relevant community referrals were printed at the end of the risk report . Participants and Procedures All physicians initially received study information , and those willing to participate provided written consent . Training was provided during clinical team meetings and at the time of consent . Physician participants were blinded to the study 's primary purpose throughout the trial by emphasizing all health risks included in the multirisk computer survey and by using a nonspecific study title . Female patients were eligible to participate if they were at least 18 years of age , were in a current or recent intimate relationship ( within the last 12 months ) , and were able to read and write English . At registration , the clinic receptionist gave letters of invitation to the patients who were then approached by a recruiter . Eligible consenting patients received further details in a separate room , unaccompanied by friends or family . Women were blinded to the study 's primary purpose by using the same strategies we used for physician participants . Women who provided informed consent were then r and omly assigned to the intervention ( computer survey ) or control ( usual care ) group , with an allocation ratio of 1:1 . We used a r and om-number sampling scheme stratified by participating physicians ( 54 ) . Before recruitment , the r and omization assignment was computer-generated by an off-site biostatistician using varying block sizes of 2 and 4 . These patient assignments were sealed in opaque envelopes that were marked on the outside with a physician number and sequence number ( 55 ) . The envelopes were opened by the recruiter after patients ' written consent . Women assigned to the computer group completed the computer survey by using a touch screen . The computer-generated risk reports were attached to the women 's medical chart . These women also received a computer-generated recommendation sheet about their reported health risks with the contact numbers of appropriate community agencies . Women assigned to the control group continued to receive usual care with no screening before the consultation . The visits of participating women were audiotaped . After their visit , women completed a pencil- and -paper exit survey and received brochures on cancer screening , cardiac and mental health , and domestic assault , at which time the research staff disclosed the purpose of the study to patients . No one withdrew consent at that stage . The purpose of the exit survey was to collect information about IPVC risk from women in either group , so that those who reported having risk for IPVC or experiencing symptoms of depression could immediately be provided assistance in the form of emotional support , recommendation to see an on-site nurse counselor , and contact numbers for community-based counselors and crisis help lines . Questions about IPVC in the exit survey were identical to those in the computer survey . The exit survey also gathered information on demographic characteristics and measures of self-perceived health , symptoms of depression , and acceptance of computer-assisted screening by using the Computerized Lifestyle Assessment Scale ( CLAS ) ( 56 , 57 ) , which assessed patient perceptions about the benefits of screening and the quality of the subsequent medical visit , concerns about privacy , and concerns about interference in the interaction with the physician . Outcomes and Data Collection The primary outcomes of the trial were whether the patient or physician raised the possibility of the patient being at risk for IPVC ( discussion opportunity ) and , for cases in which an opportunity occurred , whether the risk was detected when the woman identified that risk as being present and recent ( IPVC detection ) . The trial 's secondary outcomes were provider assessment of patient safety and provision of appropriate referrals and advice for follow-up , and patient acceptance of the computerized screening . Using an iterative qualitative approach , 2 coders BACKGROUND Missed scheduled HIV appointments lead to increased mortality , resistance to antiretroviral therapy , and suboptimum virological response . We aim ed to assess whether reminders sent to carers by text message , mobile phone call , or concomitant text message and mobile phone call increase attendance at medical appointments for HIV care in a population of children infected with or exposed to HIV in Cameroon . We also aim ed to ascertain the most cost-effective method of mobile-phone-based reminder . METHODS MORE CARE was a multicentre , single-blind , factorial , r and omised controlled trial in urban , semi-urban , and rural setting s in Cameroon . Carers of children who were infected with or had been exposed to HIV were r and omly assigned electronically in blocks of four and allocated ( 1:1:1:1 ) sequentially to receive a text message and a call , a text message only , a call only , or no reminder ( control ) . Investigators were masked to group assignment . Text messages were sent and calls made 2 or 3 days before a scheduled follow-up appointment . The primary outcomes were efficacy ( the proportion of patients attending a previously scheduled appointment ) and efficiency ( attendance/ [ measures of staff working time × cost of the reminders ] ) , as a measure of cost-effectiveness . The primary analysis was by intention to treat . This study is registered with the Pan African Clinical Trials Register , number PACTR201304000528276 . FINDINGS The study took place between Jan 28 and May 24 , 2013 . We r and omly assigned 242 adult-child ( carer-patient ) pairs into four groups : text message plus call ( n=61 ) , call ( n=60 ) , text message ( n=60 ) , and control ( n=61 ) . 54 participants ( 89 % ) in the text message plus call group , 51 ( 85 % ) in the call group , 45 ( 75 % ) in the text message group , and 31 ( 51 % ) in the control group attended their scheduled appointment . Compared with control , the odds ratios for improvement in the primary efficacy outcome were 7·5 ( 95 % CI 2·9 - 19·0 ; p<0·0001 ) for text message plus call , 5·5 ( 2·3 - 13·1 ; p=0·0002 ) for call , and 2·9 ( 1·3 - 6·3 ; p=0·012 ) for text message . No significant differences were seen in comparisons of the three intervention groups with each other , and there was no synergism between text messages and calls . For the primary efficiency outcome , the mean difference for text message versus text message plus call was 1·5 ( 95 % CI 0·7 to 2·4 ; p=0·002 ) , for call versus text message plus call was 1·2 ( 0·7 to 1·6 ; p<0·0001 ) , and for call versus text message was 0·4 ( -1·3 to 0·6 ; p=0·47 ) . INTERPRETATION Mobile-phone-based reminders of scheduled HIV appointments for carers of paediatric patients in low-re source setting s can increase attendance . The most effective method of reminder was text message plus phone call , but text messaging alone was the most efficient ( ie , cost-effective ) method . FUNDING No external funding THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard Background Mobile health ( mHealth ) interventions hold great promise for helping smokers quit since these programs can have wide reach and facilitate access to comprehensive , interactive , and adaptive treatment content . However , the feasibility , acceptability , and effectiveness of these programs remain largely untested . Objective To assess feasibility and acceptability of the My Mobile Advice Program ( MyMAP ) smoking cessation program and estimate its effects on smoking cessation and medication adherence to inform future research planning . Methods Sixty-six smokers ready to quit were recruited from a large regional health care system and r and omized to one of two mHealth programs : ( 1 ) st and ard self-help including psychoeducational material s and guidance how to quit smoking or ( 2 ) an adaptive and interactive program consisting of the same st and ard mHealth self-help content as controls received plus a ) real-time , adaptively tailored advice for managing nicotine withdrawal symptoms and medication side-effects and b ) asynchronous secure messaging with a cessation counselor . Participants in both arms were also prescribed a 12-week course of varenicline . Follow-up assessment s were conducted at 2 weeks post-target quit date ( TQD ) , 3 months post-TQD , and 5 months post-TQD . Indices of program feasibility and acceptability included acceptability ratings , utilization metrics including use of each MyMAP program component ( self-help content , secure messaging , and adaptively tailored advice ) , and open-ended feedback from participants . Smoking abstinence and medication adherence were also assessed to estimate effects on these treatment outcomes . Results Utilization data indicated the MyMAP program was actively used , with higher mean program log-ins by experimental than control participants ( 10.6 vs 2.7 , P<.001 ) . The majority of experimental respondents thought the MyMAP program could help other people quit smoking ( 22/24 , 92 % ) and consistently take their stop-smoking medication ( 17/22 , 97 % ) and would recommend the program to others ( 20/23 , 87 % ) . They also rated the program as convenient , responsive to their needs , and easy to use . Abstinence rates at 5-month follow-up were 36 % in the experimental arm versus 24 % among controls ( odds ratio 1.79 [ 0.61 - 5.19 ] , P=.42 ) . Experimental participants used their varenicline an average of 46 days versus 39 among controls ( P=.49 ) . More than two-thirds ( 22/33 , 67 % ) of experimental participants and three-quarters ( 25/33 , 76 % ) of controls prematurely discontinued their varenicline use ( P=.29 ) . Conclusions The MyMAP intervention was found to be feasible and acceptable . Since the study was not powered for statistical significance , no conclusions can be drawn about the program ’s effects on smoking abstinence or medication adherence , but the overall study results suggest further evaluation in a larger r and omized trial is warranted . Clinical Trial Clinical Trials.gov NCT02136498 ; https:// clinical trials.gov/ct2/show/NCT02136498 ( Archived by WebCite at http://www.webcitation.org/6jT3UMFLj We all want good evidence available when making medical decisions . Evidence , however , comes in a variety of forms and purpose s , and what may be good for one purpose may not be good for another . The term “ evidence -based medicine ” ( EBM ) has become almost a cliche in recent years , being used as a synonym for “ good ” or “ scientific , ” both to support and refute the value of complementary medicine practice s.1 But EBM takes a narrow view of what constitutes “ good ” evidence , and it excludes important qualitative and observational information about the use and benefits of complementary medicine . The key idea of EBM is a “ hierarchy of evidence ” ( figure 1 ) . In this hierarchy , information from systematic review s of r and omized controlled trials is the “ best ” evidence , followed by individual r and omized controlled trials , then by nonr and omized trials , observational studies , and finally case-series.2 When the evidence of what type of medicine works and what type does not is synthesized , the type of emphasis is at the top of the pyramid , and the evidence that is considered inferior is at the lower levels . Clinical experiments that isolate a causal and additive link between a specific intervention and a specific clinical outcome are seen as the “ gold st and ard ” in this evidence model . Figure 1 The traditional hierarchy of evidence is narrow As most clinicians know , the reasons that patients recover from illness are complex and synergistic , and many can not simply be isolated in controlled environments . The best evidence under these circumstances may be observational data from clinical practice that can estimate the likelihood of a patient 's recovery in a realistic context .3 In addition , patient 's illnesses are complex physical , psychological , and social experiences that can not be reduced to single , objective measures .4 In some cases , the most valuable information for a clinical decision is a highly subjective judgment about life quality . This personal experience of illness might be captured only through qualitative research , not using question naires or results of blood tests.5 The “ best ” evidence under these circumstances may be the meaning that patients give to their illness and recovery . At other times , the “ best ” evidence comes from laboratory studies . The discovery that St John 's wort can reduce blood levels of immunosuppressive drugs , for example , is the most crucial evidence when making decisions about its use in patients taking immunosuppressive medications.6 Findings of controlled trials often do not reveal such drug interactions . Arranging types of evidence in a “ hierarchy ” obscures the fact that sometimes the best evidence is not objective , not additive , and not clinical .7 In the place of an evidence hierarchy , I suggest we build an “ evidence house ” with “ rooms ” for different types of information and purpose s ( figure 2 ) . The rooms on the left side of the house contain types of information that seek out causal attributions and mechanisms of action . One such room is for laboratory research , which forms a foundation of underst and ing of mechanisms and causal links on which controlled clinical research can build . In the case of homeopathy or prayer , for example , r and omized controlled trial data seem to point us in an illogical direction , eg , that pills with no active ingredients have specific effects.8 Other rooms on the left side of the house are for r and omized controlled trials and systematic review s , which attempt to verify the suspected links between specific interventions and specific outcomes . Figure 2 The evidence house affords greater accessibility to important information If confined to the left side of the evidence house , however , physicians will never obtain information about the relevance of medicine for patients , what happens in the actual world of clinical practice , or the generalizability of an intervention in our health care delivery system . Information about relevance and utility of practice , both proven and unproven , is available in rooms on the right side of the house . The evidence house has something for everyone . Regulatory agencies and those interested in the approval of new treatments are most interested in the rooms on the left side . They want data from r and omized controlled trials and systematic review s rather than findings from observational research , yet the need for alternative approaches to treatment is evident.9 Other stakeholders in the health care system are more interested in information from the right side of the house . Health care practitioners often want to know the anticipated effects of an intervention in the clinical practice setting . Those paying for care are generally more interested in health services research . Patients are intensely interested in stories and detailed descriptions of cases similar to their own.10 If re sources are disproportionately invested in certain rooms of the house to the neglect of others , it is not possible to obtain the evidence needed for full public participation in clinical decisions . A livable house should not have an elaborate kitchen and no bathroom . Each has different functions and all need to be high quality . Complementary and alternative medicine helps us think about who will live in the evidence house and how it should be constructed . The public is the architect , driving the interest in complementary medicine . They seek holistic and preventive care , safer treatments for chronic illness , and more participation in health care decisions.11 As patient advocates , physicians must help them find a seat at the research table , so it is possible to build an evidence house where everyone can live Background Previous interventions have shown promising results using theory-based podcasts to deliver a behavioral weight-loss intervention . Objective The objective of our study was to examine whether a combination of podcasting , mobile support communication , and mobile diet monitoring can assist people in weight loss . Methods In this 6-month , minimal contact intervention , overweight ( n = 96 , body mass index 32.6 kg/m2 ) adults were recruited through television advertisements and email listservs and r and omly assigned to Podcast-only or Podcast+Mobile groups . Both groups received 2 podcasts per week for 3 months and 2 minipodcasts per week for months 3–6 . In addition to the podcasts , the Podcast+Mobile group was also instructed to use a diet and physical activity monitoring application ( app ) on their mobile device and to interact with study counselors and other participants on Twitter . Results Weight loss did not differ by group at 6 months : mean –2.7 % ( SD 5.6 % ) Podcast+Mobile , n = 47 ; mean –2.7 % ( SD 5.1 % ) Podcast , n = 49 ; P = .98 . Days/week of reported diet monitoring did not differ between Podcast+Mobile ( mean 2.3 , SD 1.9 days/week ) and Podcast groups ( mean 1.9 , SD 1.7 days/week ; P = .28 ) but method of monitoring did differ . Podcast+Mobile participants were 3.5 times more likely than the Podcast group to use an app to monitor diet ( P = .01 ) , whereas the majority of Podcast participants reported using the Web ( 14/41 , 34 % ) or paper ( 12/41 , 29 % ) . There were more downloads per episode in the Podcast+Mobile group ( 1.4/person ) than in the Podcast group ( 1.1/person ; P < .001 ) . The number of podcasts participants reported downloading over the 6-month period was significantly moderately correlated with weight loss in both the Podcast+Mobile ( r = –.46 , P = .001 ) and the Podcast ( r = –.53 , P < .001 ) groups . Podcast+Mobile participants felt more user control at 3 months ( P = .02 ) , but not at 6 months , and there was a trend ( P = .06 ) toward greater elaboration among Podcast+Mobile participants . There were significant differences in reported source of social support between groups . More Podcast participants relied on friends ( 11/40 , 28 % vs 4/40 , 10 % ; P = .045 ) whereas Podcast+Mobile participants relied on online sources ( 10/40 , 25 % vs 0/40 ; P = .001 ) . Conclusions Results confirm and extend previous findings showing a minimally intensive weight-loss intervention can be delivered via podcast , but prompting and mobile communication via Twitter and monitoring app without feedback did not enhance weight loss . Trial Registration Clinical trials.gov NCT01139255 ; http:// clinical trials.gov/ct2/show/NCT01139255 ( Archived by WebCite at http://www.webcitation.org/625OjhiDy BACKGROUND To improve the documentation and treatment of tobacco use in primary care , we developed and implemented a 3-part electronic health record enhancement : (1)smoking status icons , ( 2 ) tobacco treatment reminders , and ( 3 ) a Tobacco Smart Form that facilitated the ordering of medication and fax and e-mail counseling referrals . METHODS We performed a cluster-r and omized controlled trial of the enhancement in 26 primary care practice s between December 19 , 2006 , and September 30 , 2007 . The primary outcome was the proportion of documented smokers who made contact with a smoking cessation counselor . Secondary outcomes included coded smoking status documentation and medication prescribing . RESULTS During the 9-month study period , 132 630 patients made 315 962 visits to study practice s. Coded documentation of smoking status increased from 37 % of patients to 54 % ( + 17 % ) in intervention practice s and from 35 % of patients to 46 % ( + 11 % ) in control practice s ( P < .001 for the difference in differences ) . Among the 9589 patients who were documented smokers at the start of the study , more patients in the intervention practice s were recorded as nonsmokers by the end of the study ( 5.3 % vs 1.9 % in control practice s ; P < .001 ) . Among 12 207 documented smokers , more patients in the intervention practice s made contact with a cessation counselor ( 3.9 % vs 0.3 % in control practice s ; P < .001 ) . Smokers in the intervention practice s were no more likely to be prescribed smoking cessation medication ( 2 % vs 2 % in control practice s ; P = .40 ) . CONCLUSION This electronic health record-based intervention improved smoking status documentation and increased counseling assistance to smokers but not the prescription of cessation medication BACKGROUND Decreases in smoking prevalence from recent decades have slowed , and national goals to reduce tobacco use remain unmet . Healthcare providers , including those in physician and dental teams , have access to evidence -based guidelines to help patients quit smoking . Translation of those guidelines into practice , however , remains low . Approaches that involve screening for drug use , brief intervention , and referral to treatment ( SBIRT ) are a promising , practical solution . PURPOSE This study examined whether dentists and dental hygienists would assess interest in quitting , deliver a brief tobacco intervention , and refer to a tobacco quitline more frequently as reported by patients if given computer-assisted guidance in an electronic patient record versus a control group providing usual care . DESIGN A blocked , group-r and omized trial was conducted from November 2010 to April 2011 . R and omization was conducted at the clinic level . Patients nested within clinics represented the lowest-level unit of observation . SETTING / PARTICIPANTS Participants were patients in HealthPartners dental clinics . INTERVENTION Intervention clinics were given a computer-assisted tool that suggested scripts for patient discussion s. Usual care clinics provided care without the tool . MAIN OUTCOME MEASURES Primary outcomes were post-appointment patient reports of the provider assessing interest in quitting , delivering a brief intervention , and referring them to a quitline . RESULTS Patient telephone surveys ( 72 % response rate ) indicated that providers assessed interest in quitting ( control 70 % vs intervention 87 % , p=0.0006 ) ; discussed specific strategies for quitting ( control 26 % vs intervention 47 % , p=0.003 ) ; and referred the patient to a tobacco quitline ( control 17 % vs intervention 37 % , p=0.007 ) more frequently with the support of a computer-assisted tool integrated into the electronic health record . CONCLUSIONS Clinical decision support embedded in electronic health records can effectively help providers deliver tobacco interventions . These results build on evidence in medical setting s supporting this approach to improve provider-delivered tobacco cessation . TRIAL REGISTRATION This study is registered at Clinical Trials.govNCT01584882 Objective To determine if an intervention consisting of telemonitoring and supervision by usual primary care clinicians of home self measured blood pressure and optional patient decision support leads to clinical ly important reductions in daytime systolic and diastolic ambulatory blood pressure in patients with uncontrolled blood pressure . Design Multicentre r and omised controlled trial . Setting 20 primary care practice s in south east Scotl and . Participants 401 people aged 29 - 95 years with uncontrolled blood pressure ( mean daytime ambulatory measurement ≥135/85 mm Hg but ≤210/135 mm Hg ) . Intervention Self measurement and transmission of blood pressure readings to a secure website for review by the attending nurse or doctor and participant , with optional automated patient decision support by text or email for six months . Main outcome measures Blinded assessment of mean daytime systolic ambulatory blood pressure six months after r and omisation . Results 200 participants were r and omised to the intervention and 201 to usual care ; primary outcome data were available for 90 % of participants ( 182 and 177 , respectively ) . The mean difference in daytime systolic ambulatory blood pressure adjusted for baseline and minimisation factors between intervention and usual care was 4.3 mm Hg ( 95 % confidence interval 2.0 to 6.5 ; P=0.0002 ) and for daytime diastolic ambulatory blood pressure was 2.3 mm Hg ( 0.9 to 3.6 ; P=0.001 ) , with higher values in the usual care group . The intervention was associated with a mean increase of one general practitioner ( 95 % confidence interval 0.5 to 1.6 ; P=0.0002 ) and 0.6 ( 0.1 to 1.0 ; P=0.01 ) practice nurse consultations during the course of the study . Conclusions Supported self monitoring by telemonitoring is an effective method for achieving clinical ly important reductions in blood pressure in patients with uncontrolled hypertension in primary care setting s. However , it was associated with increase in use of National Health Service re sources . Further research is required to determine if the reduction in blood pressure is maintained in the longer term and if the intervention is cost effective . Trial registration Current Controlled Trials IS RCT N72614272 BACKGROUND Hypochondriasis , characterised by severe health anxiety , is a common condition associated with functional disability . Cognitive-behavioural therapy ( CBT ) is an effective but not widely disseminated treatment for hypochondriasis . Internet-based CBT , including guidance in the form of minimal therapist contact via email , could be a more accessible treatment , but no study has investigated internet-based CBT for hypochondriasis . AIMS To investigate the efficacy of internet-based CBT for hypochondriasis . METHOD A r and omised controlled superiority trial with masked assessment comparing internet-based CBT ( n = 40 ) over 12 weeks with an attention control condition ( n = 41 ) for people with hypochondriasis . The primary outcome measure was the Health Anxiety Inventory . This trial is registrated with Clinical Trials.gov ( NCT00828152 ) . RESULTS Participants receiving internet-based CBT made large and superior improvements compared with the control group on measures of health anxiety ( between-group Cohen 's d range 1.52 - 1.62 ) . CONCLUSIONS Internet-based CBT is an efficacious treatment for hypochondriasis that has the potential to increase accessibility and availability of CBT for hypochodriasis INTRODUCTION We hypothesized that fruit/vegetable intake and eating behaviors mediate the relationship between experimental condition and weight loss in a r and omized trial evaluating a text-message based weight loss program . METHODS Overweight/obese individuals from San Diego , CA ( N = 52 with complete data ) were r and omly assigned in 2007 into one of two groups for four months : 1 ) the intervention group that received 2 - 5 weight management text-messages p/day ; 2 ) the usual-care comparison group . Three 24-hour recalls assessed fruit/vegetable intake change and the eating behavior inventory ( EBI ) measured change in eating behaviors . Regression path models tested intervention mediation . RESULTS Direct effects of the intervention were found for change in body weight ( b = -3.84 , R(2 ) = 0.074 ) , fruit/vegetable intake ( b = 2.00 , R(2 ) = 0.083 ) , and EBI scores ( b = 7.15 , R(2 ) = 0.229 ) ( ps < 0.05 ) . The treatment group to weight change path was not statistically significant ( b = -0.673 , R(2 ) = 0.208 ) when fruit/vegetable intake change and EBI score change were specified as intervention mediators in the model . The total indirect effect was 3.17 lb indicating that the indirect paths explained 82.6 % of the total effect on weight change . DISCUSSION Fruit/vegetable intake and eating behaviors mediated the intervention 's effect on weight change . The findings suggest that sending text-messages that promote healthy eating strategies result ed in moderate short-term weight loss |
1,072 | 31,137,728 | 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 . | Breast density , a measure of dense fibrogl and ular tissue relative to non-dense fatty tissue , is confirmed as an independent risk factor of breast cancer .
Although there has been an increasing interest in the quantitative assessment of breast density , no research has investigated the optimal technical approach of breast MRI in this aspect .
Therefore , we performed a systematic review and meta- analysis to analyze the current studies on quantitative assessment of breast density using MRI and to determine the most appropriate technical/operational protocol . | 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 95 % confidence intervals for MRI-measured breast density at ages 25–29 years across quartiles of fat intake using linear mixed-effect regression . Results : Comparing women in the extreme quartiles of adolescent fat intakes , percent dense breast volume ( % DBV ) was positively associated with saturated fat ( mean = 16.4 % vs. 21.5 % ; Ptrend < 0.001 ) . Conversely , % DBV was inversely associated with monounsaturated fat ( 25.0 % vs. 15.8 % ; Ptrend < 0.001 ) and the ratio of polyunsaturated fat to saturated fat ( P/S ratio ; 19.1 % vs. 14.3 % ; Ptrend < 0.001 ) . When examining intake by pubertal stages , % DBV was inversely associated with intake of polyunsaturated fat ( 20.8 % vs. 16.4 % ; Ptrend = 0.04 ) , long-chain omega-3 fat ( 17.8 % vs. 15.8 % ; Ptrend < 0.001 ) , and P/S ratio ( 22.5 % vs. 16.1 % ; Ptrend < 0.001 ) before menarche , but not after . These associations observed with % DBV were consistently observed with absolute dense breast volume but not with absolute nondense breast volume . Conclusions : In our study , adolescent intakes of higher saturated fat and lower mono- and polyunsaturated fat are associated with higher breast density measured approximately 15 years later . Impact : The fat subtype composition in adolescent diet may be important in early breast cancer prevention . Cancer Epidemiol Biomarkers Prev ; 25(6 ) ; 918–26 . © 2016 AACR Objectives The purpose s of this study were to introduce and assess an automated user-independent quantitative volumetric ( AUQV ) breast density ( BD ) measurement system on the basis of magnetic resonance imaging ( MRI ) using the Dixon technique as well as to compare it with qualitative and quantitative mammographic ( MG ) BD measurements . Material s and Methods Forty-three women with normal mammogram results ( Breast Imaging Reporting and Data System 1 ) were included in this institutional review board – approved prospect i ve study . All participants were subjected to BD assessment with MRI using the following sequence with the Dixon technique ( echo time/echo time , 6 milliseconds/2.45 milliseconds/2.67 milliseconds ; 1-mm isotropic ; 3 minutes 38 seconds ) . To test the reproducibility , a second MRI after patient repositioning was performed . The AUQV magnetic resonance ( MR ) BD measurement system automatically calculated percentage ( % ) BD . The qualitative BD assessment was performed using the American College of Radiology Breast Imaging Reporting and Data System BD categories . Quantitative BD was estimated semiautomatically using the thresholding technique Cumulus4 . Appropriate statistical tests were used to assess the agreement between the AUQV MR measurements and to compare them with qualitative and quantitative MG BD estimations . Results The AUQV MR BD measurements were successfully performed in all 43 women . There was a nearly perfect agreement of AUQV MR BD measurements between the 2 MR examinations for % BD ( P < 0.001 ; intraclass correlation coefficient , 0.998 ) with no significant differences ( P = 0.384 ) . The AUQV MR BD measurements were significantly lower than quantitative and qualitative MG BD assessment ( P < 0.001 ) . Conclusions The AUQV MR BD measurement system allows a fully automated , user-independent , robust , reproducible , as well as radiation- and compression-free volumetric quantitative BD assessment through different levels of BD . The AUQV MR BD measurements were significantly lower than the currently used qualitative and quantitative MG-based approaches , implying that the current assessment might overestimate breast density with MG |
1,073 | 23,857,562 | AUTHORS ' CONCLUSIONS Once daily treatment with LMWH is as effective and safe as twice daily treatment with LMWH | BACKGROUND In the initial treatment of venous thromboembolism ( VTE ) low molecular weight heparin ( LMWH ) is administered once or twice daily .
A once daily treatment regimen is more convenient for the patient and may optimise home treatment .
However , it is not clear whether a once daily treatment regimen is as safe and effective as a twice daily treatment regimen .
This is the second up date of a review first published in 2003 .
OBJECTIVES To compare the efficacy and safety of once daily versus twice daily administration of LMWH . | 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 ) amidolytic assay to obtain a target concentration from 0.5 to 1 IU/ml . AntiXa and antithrombin activities were also measured retrospectively on frozen plasma from all patients . The two regimens were comparable in terms of hemorrhagic complications ( 4 in group A and 3 in group B ) . Bilateral ascending phlebography was performed before inclusion and at the end of LMWH treatment . Treatment efficacy , based on Marder 's score , did not differ between the two groups ( p = 0.3 ) . Dosage adjustment to between 0.5 to 1 IU anti-Xa/ml does not therefore appear to improve the efficacy or safety of LMWH treatment . However , correlations between the change in Marder 's score and both anti-Xa ( p < 0.001 ) and antithrombin activity ( p < 0.001 ) were observed , suggesting a relationship between the degree of FXa or thrombin inhibition and antithrombotic activity BACKGROUND An intravenous course of st and ard ( unfractionated ) heparin with the dose adjusted to prolong the activated partial-thromboplastin time to a desired length is the st and ard initial in-hospital treatment for patients with deep-vein thrombosis , but fixed-dose subcutaneous low-molecular-weight heparin appears to be as effective and safe . Because the latter treatment can be given on an outpatient basis , we compared the two treatments in symptomatic out patients with proximal-vein thrombosis but no signs of pulmonary embolism . METHODS We r and omly assigned patients to adjusted-dose intravenous st and ard heparin administered in the hospital ( 198 patients ) or fixed-dose subcutaneous low-molecular-weight heparin administered at home , when feasible ( 202 patients ) . We compared the treatments with respect to recurrent venous thromboembolism , major bleeding , quality of life , and costs . RESULTS Seventeen of the 198 patients who received st and ard heparin ( 8.6 percent ) and 14 of the 202 patients who received low-molecular-weight heparin ( 6.9 percent ) had recurrent thromboembolism ( difference , 1.7 percentage points ; 95 percent confidence interval , -3.6 to 6.9 ) . Major bleeding occurred in four patients assigned to st and ard heparin ( 2.0 percent ) and one patient assigned to low-molecular-weight heparin ( 0.5 percent ; difference , 1.5 percentage points ; 95 percent confidence interval , -0.7 to 2.7 ) . Quality of life improved in both groups . Physical activity and social functioning were better in the patients assigned to low-molecular-weight heparin . Among the patients in that group , 35 percent were never admitted to the hospital at all , and 40 percent were discharged early . This treatment was associated with a mean reduction in hospital days of 67 percent , ranging from 29 percent to 86 percent in the various study centers . CONCLUSIONS In patients with proximal-vein thrombosis , treatment with low-molecular-weight heparin at home is feasible , effective , and safe In view of the potential of low-molecular-weight heparins ( LMWH ) to simplify initial therapy and allow outpatient treatment of proximal deep-vein thrombosis , we undertook a r and omised comparison of fixed-dose subcutaneous LMWH with adjusted-dose intravenous st and ard heparin in the initial treatment of this disorder . Our main objectives were to compare the efficacy of these regimens for 6 months of follow-up and to assess the risk of clinical ly important bleeding . Of 170 consecutive symptomatic patients with venographically proven proximal deep-venous thrombosis , 85 received st and ard heparin ( to achieve an activated partial thromboplastin time of 1.5 to 2.0 times the pretreatment value ) and 85 LMWH ( adjusted only for body weight ) for 10 days . Oral coumarin was started on day 7 and continued for at least 3 months . The frequency of recurrent venous thromboembolism diagnosed objective ly did not differ significantly between the st and ard-heparin and LMWH groups ( 12 [ 14 % ] vs 6 [ 7 % ] ; difference 7 % [ 95 % confidence interval -3 % to 15 % ] ; p = 0.13 ) . Clinical ly important bleeding was infrequent in both groups ( 3.5 % for st and ard heparin vs 1.1 % for LMWH ; p greater than 0.2 ) . We conclude that fixed-dose subcutaneous LMWH is at least as effective and safe as intravenous adjusted-dose heparin in the initial treatment of symptomatic proximal-vein thrombosis . Since there is no need for laboratory monitoring with the LMWH regimen , patients with venous thrombosis can be treated at home UNLABELLED We assessed the time course of lung perfusion after 3 mo of anticoagulant therapy for acute pulmonary embolism ( APE ) on the basis of perfusion lung scan ( PLS ) findings for 157 patients included in the Tinzaparin ou Heparin St and ard : Evaluation dans l'Embolie Pulmonaire Study ( THESEE ) , a multicenter , r and omized , nonmasked trial comparing st and ard , continuous , adjusted-dose intravenous heparin with once-daily , subcutaneous , low-molecular-weight heparin in patients with APE . METHODS We calculated the percentage-of-vascular-obstruction score ( PVOs ) on PLSs on the day of diagnosis of APE ( PVOsD1 ) , on day 8 ( PVOsD8 ) , and after 3 mo ( PVOsM3 ) and the mean relative changes in PVOs on day 8 versus the day of diagnosis and after 3 mo versus the day of diagnosis . RESULTS Mean PVOsD1 + /- SD was 49 % + /- 20 % , PVOsD8 was 29 % + /- 18 % , and PVOsM3 was 19 % + /- 18 % . PVOsD1 was at least 50 % in 49 % of patients . Reperfusion did not correlate with age , importance of initial obstruction , or clinical severity of disease at inclusion in THESEE . Relative change after 3 mo versus at diagnosis was lower in the 87 patients with associated prior cardiopulmonary disease than in those without . In the 43 patients with a history of thromboembolic disease , neither mean PVOsD1 nor the time course of PVOs was different from those in patients without a history of thromboembolic disease . Residual defects after 3 mo were observed in 104 patients ( 66 % ) , including 13 with a PVOs of at least 50 % . CONCLUSION These results emphasize the need for a control PLS at completion of anticoagulant therapy for APE , even in patients with full resolution of symptoms Context Are selective inhibitors of factor Xa as good as low-molecular-weight heparin in treating deep venous thrombosis ? Contribution In this large , multicenter , double-blind trial , patients with symptomatic deep venous thrombosis were r and omly assigned to receive either fondaparinux ( a selective inhibitor of factor Xa ) or enoxaparin given subcutaneously for at least 5 days plus an oral vitamin K antagonist for 3 months . In both groups , about 1 % of the patients experienced major bleeding during initial treatment and about 4 % had recurrent thromboembolic events within 3 months . Implication s Fondaparinux and enoxaparin have similar safety and efficacy for initial treatment of symptomatic deep venous thrombosis . The Editors Low-molecular-weight heparin ( LMWH ) therapy has exp and ed the options for initial management of patients presenting with deep venous thrombosis ( 1 , 2 ) . Low-molecular-weight heparin treatment is simple and consists of once- or twice-daily subcutaneous injection of a dose adjusted only for body weight . Treating suitable patients at home , often with self-injection , is effective and safe and has become st and ard practice in many setting s ( 2 - 4 ) . Clinical ly relevant aspects of LMWH treatment of venous thromboembolism remain uncertain , which may influence usage and recurrence or bleeding . First , LMWHs differ among themselves . Second , data on whether once- or twice-daily LMWH may be superior are conflicting ( 5 , 6 ) , suggesting that a once-daily regimen of enoxaparin may be less effective in patients with higher body mass index and patients with cancer ( 7 ) . Third , since LMWHs are eliminated in the urine and plasma levels are higher in patients with even modest renal insufficiency ( 8) , some clinicians administer lower dosages when the patient 's creatinine clearance is less than 0.84 mL/s ( 9 ) , despite few outcome data to guide such alterations . Finally , in addition to the clinical and economic circumstances , practical issues surround drug administration , including the patient 's capacity to administer the desired dosage from a fixed-volume syringe or multidose vial ; these issues can affect the feasibility of early discharge and home treatment . Fondaparinux is a synthetic and selective inhibitor of factor Xa that has proven efficacy and safety for preventing venous thromboembolism in orthopedic surgery . Although laboratory observations and theory suggested that such a compound might not be effective for treating established thrombosis ( 10 ) , a dose-ranging study of deep venous thrombosis treatment found that a once-daily subcutaneous injection of fondaparinux , 7.5 mg , may be effective and safe across a broad range of body weights ( 50 kg and 100 kg ) ( 11 ) . Pharmacokinetic analyses suggested that daily doses of 5 mg and 10 mg are appropriate for patients less than and more than that weight range , respectively . Moreover , the predictable and sustained anticoagulant effect of fondaparinux for 24 hours allows once-daily injection , and since fondaparinux does not cross-react with heparin-induced antibodies , platelet count monitoring may no longer be needed ( 12 ) . This may further simplify treatment . Therefore , we design ed this r and omized , double-blind study of 2205 symptomatic patients to determine whether the efficacy and safety of a once-daily subcutaneous fixed-dose regimen of fondaparinux are similar to those of the st and ard therapy of a twice-daily , subcutaneous , body weightadjusted regimen of enoxaparin . Early discharge was encouraged in both treatment groups . The large sample size allowed outcome assessment in patients with a broad range of body weights and renal function . Methods Patients Consecutive patients ( > 18 years of age ) who presented with acute symptomatic deep venous thrombosis involving the popliteal , femoral , or iliac veins or the trifurcation of the calf veins and who required antithrombotic therapy were eligible for the study . Diagnostic criteria for deep venous thrombosis were a noncompressible vein found on ultrasonography or an intraluminal filling defect found on venography ( 11 , 13 ) . Patients were ineligible for the study if they had symptomatic pulmonary embolism ; received therapeutic doses of anticoagulants or oral anticoagulant therapy for more than 24 hours ; required thrombolysis , thrombectomy , or a vena cava filter ; had contraindication to anticoagulant therapy ( for example , active bleeding , thrombocytopenia [ platelet count < 100 109 cells/L ] ) ; had elevated serum creatinine levels ( > 177 mol/L [ > 2 mg/dL ] ) ; had contraindication to contrast medium ; had uncontrolled hypertension ( systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg ) ; were pregnant ; or had a life expectancy of less than 3 months . After giving informed consent , patients were r and omly assigned by a computerized interactive voice response system that recorded information about patients before treatment assignment . R and omization was stratified by center in balanced blocks of 4 patients . The respective institutional review boards approved the study protocol , and an independent data safety monitoring board monitored the study . We assessed 5141 patients for eligibility : 2205 patients were r and omly assigned to study groups , 2416 patients were excluded , and 520 patients declined to participate ( Figure ) . The most common reasons for exclusion were the use of therapeutic anticoagulation for more than 24 hours , thrombolytic therapy , or vena cava filter ( 580 patients ) ; contraindication to anticoagulant therapy ( 395 patients ) ; symptomatic pulmonary embolism ( 387 patients ) ; and a life expectancy of less than 3 months ( 228 patients ) . Figure . Flow of patients through the study . Treatment Regimens The patients allocated to fondaparinux ( Arixtra , NV Organon , Oss , the Netherl and s , and Sanofi-Synthlabo , Paris , France ) received a once-daily subcutaneous injection of 5.0 mg if they weighed less than 50 kg , 7.5 mg if they weighed between 50 and 100 kg , or 10.0 mg if they weighed more than 100 kg . They also received twice-daily subcutaneous injections of placebo that appeared identical to enoxaparin . The patients allocated to enoxaparin ( Lovenox , Clexane , Aventis Pharmaceuticals , Bridgewater , New Jersey ) received a twice-daily subcutaneous dose of 1 mg/kg of body weight and a once-daily subcutaneous injection of placebo that appeared identical to fondaparinux . Although home treatment with the study drug was allowed , the treating physician made this decision and the drug had to be administered by a home care service . In both groups , vitamin K antagonist therapy was started as soon as possible but within 72 hours of initiation of fondaparinux or enoxaparin therapy . The investigator chose the type of vitamin K antagonist therapy according to local hospital practice . The same type of vitamin K antagonist was recommended for all patients in a particular center . During initial treatment , prothrombin times were measured at least every other day and the dose of vitamin K antagonist was adjusted to maintain the international normalized ratio between 2.0 and 3.0 . Double-blind , initial treatment was continued for at least 5 days and until the international normalized ratio was greater than 2.0 for 2 consecutive days . Treatment with vitamin K antagonists was continued for 3 months , and the international normalized ratio was determined at least once per month . Surveillance and Follow-up All patients were contacted daily during initial treatment and at 1 and 3 months . At each contact , patients were evaluated for symptomatic recurrence of deep venous thrombosis or pulmonary embolism and bleeding and were informed about the symptoms and signs of these conditions . They were instructed to report to the study center on an emergency basis if any of these conditions occurred . If recurrent deep venous thrombosis or pulmonary embolism was suspected , the protocol required objective testing for confirmation . Outcome Assessment The primary efficacy outcome was the incidence of symptomatic recurrent venous thromboembolism during the 3-month study period . Symptomatic recurrent venous thromboembolism was defined as objective ly documented recurrent deep venous thrombosis or pulmonary embolism or death in which pulmonary embolism was a contributing cause or could not be excluded . Without objective test results to adequately confirm or exclude recurrent venous thromboembolism , this diagnosis was accepted if the physician managed the patient with therapeutic doses of LMWH for more than 2 days , thrombolysis , a vena cava filter , or thrombectomy ( 3 , 13 ) . The criteria for the objective diagnosis of recurrent deep venous thrombosis were a new noncompressible venous segment or a substantial increase ( 4 mm ) in diameter of the thrombus during full compression in a previously abnormal segment on ultrasonography ( 14 , 15 ) or a new intraluminal filling defect found on venography . The criteria for the objective diagnosis of pulmonary embolism were an intraluminal filling defect on spiral computed tomography or pulmonary angiography , cut-off of a vessel of more than 2.5 mm in diameter on pulmonary angiography , perfusion defect of at least 75 % of a segment with corresponding normal ventilation ( high-probability lung scan ) , nondiagnostic lung scan associated with new deep venous thrombosis documented by ultrasonography or venography , or pulmonary embolism confirmed by autopsy . The main safety outcomes were major bleeding during the initial treatment period and 3-month mortality . Bleeding was defined as major if it was clinical ly overt and associated with a decrease in the hemoglobin level of 20 g/L or more , led to transfusion of 2 or more units of red blood cells or whole blood cells , was retroperitoneal or intracranial , occurred in a critical organ , or contributed to death . Bleeding episodes that were clinical ly relevant but not major ( for example , epistaxis that required intervention or spontaneous macroscopic hematuria ) were an additional safety outcome . The cause of BACKGROUND Heparins substantially reduce the risk of thromboembolic complications after total hip or knee replacement . However , they can be given only by injection and have several other drawbacks . We did a multicentre , r and omised , double-blind study to examine the dose-response relation of subcutaneous melagatran , a direct thrombin inhibitor , followed by oral ximelagatran as thromboprophylaxis after total hip or knee replacement . We aim ed to compare the efficacy and safety with that of dalteparin . METHODS Of 1900 patients , 1495 were assigned to four dose categories of subcutaneous melagatran from just before surgery ( 1.00 mg , 1.50 mg , 2.25 mg , or 3.00 mg twice daily ) followed from the day after surgery by oral ximelagatran ( 8 mg , 12 mg , 18 mg , or 24 mg twice daily ) . 381 patients were assigned subcutaneous dalteparin 5000 IU once daily , from the evening before surgery . Bilateral venography was done at 7 - 10 days , and clinical ly suspected venous thromboembolism ( VTE ) was confirmed radiologically . The primary endpoint was the rate of deep-vein thrombosis and pulmonary embolism ( PE ) . Analyses were by intention to treat . FINDINGS 1876 patients underwent total replacement of hip ( n=1270 ) or knee ( n=606 ) ; evaluable venograms were obtained in 1473 ( 79 % ) . Four patients without evaluable venograms had PE . Overall , a significant dose-dependent decrease in VTE was seen with melagatran/ximelagatran ( lowest to highest group : 111 [ 37.8 % ] , 70 [ 24.1 % ] , 71 [ 23.7 % ] , and 43 [ 15.1 % ] ; p=0.0001 ) ; there were also significant relations for both total hip and total knee replacement individually . The frequency of VTE was significantly lower with the highest dose of melagatran/ximelagatran than with dalteparin ( 15.1 % vs 28.2 % , p<0.0001 ) . There were no reoperations due to bleeding and no critical organ bleeding . Excessive surgical bleeding was uncommon but more frequent in the highest dose group . INTERPRETATION This sequential therapy was effective and safe in patients undergoing major joint replacement surgery . The findings should be confirmed in a large phase III trial BACKGROUND A low-molecular-weight heparin , enoxaparin sodium , has been shown to be effective and safe in preventing deep vein thrombosis both in general surgery and in high-risk orthopedic surgery . We conducted a controlled , r and omized trial with enoxaparin in the treatment of established deep vein thrombosis . METHODS In a multicenter trial , we compared fixed-dose subcutaneous enoxaparin , given twice daily , with adjusted-dose intravenous unfractionated heparin ( UFH ) given by continuous intravenous infusion for the initial 10 days of treatment of patients with proximal vein thrombosis . The primary efficacy outcome was the change of the size of the thrombus assessed by repeated venograms between day 0 and day 10 . The primary analysis of safety was based on the incidence of major bleeding during 10 days of treatment . RESULTS There were 67 patients in each group . Venographic assessment of clot size evolution between day 0 and day 10 showed a statistically significant superiority ( P < .002 ) of enoxaparin over the reference treatment with UFH . Moreover , the incidence of overall recurrent thromboembolic events during 10 days of treatment was significantly higher ( P < .002 ) in the UFH group ( seven of 67 ) than in the enoxaparin group ( one of 67 ) . There were no serious bleeding complications in either group . CONCLUSIONS Enoxaparin is at least as effective and safe as UFH under the conditions of this study . Moreover , it is more comfortable for patients and less time-consuming for nurses and laboratories . Thus , our study confirmed , with the use of enoxaparin , other observations that low-molecular-weight heparin provides a real therapeutic advance in the treatment of deep vein thrombosis In a prospect i ve study all positive phlebographies within the well-defined population of the city of Malmö , Sweden , during 1987 were studied in order to determine the incidence of deep venous thrombosis ( DVT ) . Epidemiological data were analysed for the detection of patient groups at increased risk of DVT . The incidence was found to be equal for both sexes , i.e. 1.6 per 1000 inhabitants a year . Risk factors were found to be in accordance with earlier studies . The median age for men was 66 years , compared to 72 years for women . At diagnosis of DVT , 19 % of subjects had a known malignancy and within 1 year 5 % ( 19 cases ) developed a new malignancy . Of the men , 29 % had postoperative or post-traumatic ( fracture ) DVT , compared to 46 % of the women . Fewer patients with DVT than expected ( 39 % ) belonged to blood group 0 ( 31 % ) ( P less than 0.005 ) . Pulmonary embolism ( PE ) was clinical ly suspected in only 5 % of cases , and diagnosis was verified scintigraphically in 2 % of cases . None of these died of PE , but of 6 patients who were found to have PE at autopsy , four died about 4 weeks after the DVT was diagnosed BACKGROUND Low-molecular-weight heparin appears to be at least as effective and safe as st and ard , unfractionated heparin for the treatment of deep-vein thrombosis , but only limited data are available on the use of low-molecular-weight heparin to treat acute symptomatic pulmonary embolism . METHODS We r and omly assigned 612 patients with symptomatic pulmonary embolism who did not require thrombolytic therapy or embolectomy to either subcutaneous low-molecular-weight heparin ( tinzaparin ) given once daily in a fixed dose or adjusted-dose , intravenous unfractionated heparin . Oral anticoagulant therapy was begun between the first and the third day and was given for at least three months . We compared the treatments at day 8 and day 90 with respect to a combined end point of recurrent thromboembolism , major bleeding , and death . RESULTS In the first eight days of treatment , 9 of 308 patients assigned to receive unfractionated heparin ( 2.9 percent ) reached at least one of the end points , as compared , with 9 of 304 patients assigned to low-molecular-weight heparin ( 3.0 percent ; absolute difference , 0.1 percentage point ; 95 percent confidence interval , -2.7 to 2.6 ) . By day 90 , 22 patients assigned to unfractionated heparin ( 7.1 percent ) and 18 patients assigned to low-molecular-weight heparin ( 5.9 percent ) had reached at least one end point ( P=0.54 ; absolute difference , 1.2 percentage points ; 95 percent confidence interval , -2.7 to 5.1 ) . The risk of major bleeding was similar in the two treatment groups throughout the study . CONCLUSIONS Under the conditions of this study , initial subcutaneous therapy with the low-molecular-weight heparin tinzaparin appeared to be as effective and safe as intravenous unfractionated heparin in patients with acute pulmonary embolism UNLABELLED A total of 164 patients were recruited from a r and omized trial comparing a low molecular weight heparin , dalteparin , given subcutaneously once daily with a continuous intravenous infusion of unfractionated heparin in the initial treatment of acute deep vein thrombosis . The primary objective of this follow-up study was to investigate whether there were any differences between the two treatment groups with respect to Marder score changes 6 months after the initial diagnosis using repeated venography . The secondary objectives were to analyse whether certain haemostatic and acute phase parameters or patient characteristics influenced the venographic outcome . RESULTS Complete lysis of the thrombus was observed in 38.4 % of the patients and a partial lysis in another 54.3 % assessed by venography 6 months after the acute event . Extension of the thrombus was seen in 7.3 % of the patients . There were no significant differences in the change in mean Marder score before treatment and at the 6 month follow-up between the two treatment groups , irrespective of thrombus localisation . In a regression model , male gender , low levels of orosomucoid and increased levels of d-dimer in plasma on day 5 were independently associated ( p < 0.05 ) with an enhanced absolute resolution of the thrombus at 6 months . No differences in symptoms and signs in the thrombotic leg at follow-up , comparing the treatment given , or thrombus extension at diagnosis and 6 months later , were demonstrated . CONCLUSION Dalteparin given once daily subcutaneously was as effective as continuous intravenous infusion of unfractionated heparin in the initial treatment of deep vein thrombosis assessed by Marder score evaluation 6 months after the acute event BACKGROUND Low-molecular-weight heparins are frequently used to treat venous thromboembolism , but optimal dosing regimens and clinical outcomes need further definition . METHODS In this multicenter , open-label study with blinded adjudication of end points , we r and omly assigned patients with acute deep-vein thrombosis to one of three treatment regimens : intravenous administration of unfractionated heparin ; subcutaneous administration of a low-molecular-weight heparin , reviparin , twice a day for one week ; or subcutaneous administration of reviparin once a day for four weeks . The primary end point was evidence of regression of the thrombus on venography on day 21 ; secondary end points were recurrent venous thromboembolism , major bleeding within 90 days after enrollment , and death . RESULTS Of the patients receiving unfractionated heparin , 40.2 percent ( 129 of 321 ) had thrombus regression , as compared with 53.4 percent ( 175 of 328 ) of patients receiving reviparin twice daily and 53.5 percent ( 167 of 312 ) of the patients receiving reviparin once daily . With regard to thrombus regression , reviparin administered twice daily was significantly more effective than unfractionated heparin ( relative likelihood of thrombus regression , 1.28 ; 97.5 percent confidence interval , 1.08 to 1.52 ) , as was reviparin administered once daily ( relative likelihood , 1.29 ; 97.5 percent confidence interval , 1.08 to 1.53 ) . Mortality and the frequency of episodes of major bleeding were similar in the three groups . CONCLUSIONS In acute deep-vein thrombosis , reviparin regimens are more effective than unfractionated heparin in reducing the size of the thrombus . Reviparin is also more effective than unfractionated heparin for the prevention of recurrent thromboembolism and equally safe Two hundred and four consecutive patients with venographically confirmed deep vein thrombosis ( DVT ) were r and omised either to a low molecular weight heparin , Fragmin , administered subcutaneously ( s.c . ) once daily as a fixed dose of 200 IU anti-factor Xa/kg or to continuous intravenous infusion of unfractionated heparin ( UFH ) . The UFH dose was adjusted to maintain the activated partial thromboplastin time between 1.5 and 3.0 times the upper limit of the reference value at each centre . Fragmin or UFH was given for a minimum of 5 days until anticoagulation with warfarin , given from day 1 , was established ( i.e. an Internation Normalised Ratio , of 2.0 - 3.0 ) . A second venogram was obtained after Fragmin or UFH treatment . There were no significant differences in the change in mean Marder score before and after treatment between the two treatment groups , irrespective of thrombus localisation . No major bleeding events , symptomatic pulmonary embolism , symptomatic thrombosis progression or death occurred during hospitalisation . Eight documented venous thromboembolic events occurred before the follow-up visit 6 months after r and omisation : 5 in patients treated with Fragmin and 3 in those treated with UFH . Six of these events occurred after cessation of warfarin treatment . In conclusion Fragmin given s.c . once daily in a fixed dose adjusted for body weight , is no less effective or safe than a continuous infusion of UFH in the initial treatment of acute DVT Low-molecular-weight and unfractionated heparins are frequently used to treat venous thromboembolism , but it is not known whether they are equally effective in inhibiting in vivo generation of thrombin . In this multicenter trial , 1048 patients were r and omized to intravenous unfractionated heparin ( group A ) , twice daily low-molecular-weight heparin ( reviparin ) for 1 week ( group B ) , or once daily reviparin for 4 weeks ( group C ) . All patients received vitamin K antagonists . Blood sample s withdrawn at the baseline and at weeks 1 and 3 were analyzed using markers of in vivo thrombin generation and other coagulation parameters . During the first 3 weeks symptomatic recurrent deep vein thrombosis-pulmonary embolism ( DVT/PE ) occurred in 17 ( 4.5 % ) of 375 patients in group A compared with 4 ( 1.0 % ) of 388 patients in group B , and 9 ( 2.4 % ) of 374 patients in group C. Forty percent of patients in group A , 53.4 % in group B , and 53.5 % in group C showed 30 % or greater reduction in thrombus size assessed by venography . Patients in group B had significantly greater reduction in D-dimer , prothrombin fragments 1 and 2 ( F1 + 2 ) , endogenous thrombin potential ( ETP ) , and thrombin-antithrombin ( TAT ) complexes compared to groups A and C. Greater release of tissue factor pathway inhibitor ( TFPI ) and reduction in levels of thrombin activatable fibrinolysis inhibitor ( TAFI ) and fibrinogen were significantly more pronounced in group C patients . Reviparin administered twice daily plus vitamin K antagonist is more effective in inhibiting in vivo thrombin generation compared to intravenous unfractionated heparin plus vitamin K antagonist , and reviparin once daily produced significantly higher TFPI release and greater reduction in TAFI and fibrinogen levels Method : We used a previously described economic model created in the context of the UK National Health Service and applied it to St. Thomas ’ Hospital , London . A clinical review to determine the number of medical admissions that would require thromboprophylaxis at St. Thomas ’ Hospital , based on the inclusion criteria of a medical thromboprophylaxis trial ( MEDENOX ) , was conducted . Costs and effectiveness were determined , based on the provision of thromboprophylaxis to 2000 medical patients . Results : Comparing treatment with low-molecular-weight heparin ( enoxaparin , 40 mg once daily ) , unfractionated heparin ( 5000 IU twice daily ) , or no prophylaxis , the highest cost of thromboprophylaxis was associated with unfractionated heparin ( £ 199,000=€306,000 ) , compared with enoxaparin ( £ 198,000=€305,000 ) or no prophylaxis ( £ 176,000=€271,000 ) . The model suggested that enoxaparin thromboprophylaxis would result in fewer thromboembolic-related events . Using sensitivity analysis , incorporating certain St. Thomas’-specific costs showed enoxaparin compared with unfractionated heparin or no thromboprophylaxis was cost saving . The cost savings of £ 65,000 ( = € 100,000 ) and £ 31,000 ( = € 48,000 ) respectively are based on maximum uptake of thromboprophylaxis . Conclusions : The grade d implementation of enoxaparin thromboprophylaxis over a four-year period would require funding redistribution . The funding Health Authority would save overall but St. Thomas ’ would require an increase in drug expenditure across the clinical directorates of £ 35,000 (= € 54,000 ) after 4 years OBJECTIVE To compare oral anticoagulant treatment ( fluindione ) started on either the 1st or the 10th day of a low-molecular-weight heparin ( enoxaparin ) treatment for deep vein thrombosis confirmed by venography . DESIGN An open , multicenter , r and omized study in two parallel treatment groups . INTERVENTIONS All patients received enoxaparin , 1 mg/kg s.c . twice daily , and oral fluindione , 20 mg once daily , either beginning on day 1 or on day 10 of the enoxaparin treatment . Enoxaparin was discontinued once the international normalized ratio under fluindione was stable between 2.0 and 3.0 over 2 days . Fluindione treatment was maintained during a 3-month follow-up period . OUTCOME MEASUREMENTS Specific examinations ( venography and /or V/Q lung scanning and /or angiography ) were performed only in the event of a clinical ly suspected recurrence of venous thromboembolism during the 3-month follow-up period . All cases were blindly assessed by an independent Reading Committee . RESULTS A clinical ly suspected venous thromboembolism was confirmed by objective tests in 1 of 223 patients ( group of delayed introduction of fluindione ; n = 111 ) . Equivalence was demonstrated between the two treatment schedules ( p < 0.0001 ) for a maximal difference of 10 % ( 90 % confidence interval : -2.42 to 0.58 ) . The mean duration of hospitalization was significantly reduced ( p = 0.0001 ) in the group with early introduction of fluindione . The incidence of hemorrhage was comparable between the two treatment groups . CONCLUSION Early and delayed introduction of oral anticoagulant treatment in association with subcutaneous enoxaparin in patients with deep vein thrombosis was shown to be equivalent in preventing the recurrence of venous thromboembolism . In patients with early introduction of oral anticoagulant , hospitalization was significantly reduced In order to avoid selective biases and to minimize r and om errors , inference about the effects of treatment on serious endpoints needs to be based not on one , or a few , of the available trial results , but on a systematic overview of the totality of the evidence from all the relevant unconfounded r and omized trials . But , only where coverage of all , or nearly all , r and omized patients in all relevant trials ( or a reasonably unbiased sample of such trials ) can be assured , is a systematic overview of trials reasonably trustworthy , for then any selective biases are likely to be small in comparison with any moderate effects of treatment . Checks for the existence of such biases can best be conducted if reasonably detailed data are available from each trial . Future trials should take into account the results of any relevant overviews in their design , and should plan to obtain sufficient numbers of events to contribute substantially to such overviews . In many cases , this implies the need for r and omized trials that are much larger than is currently st and ard BACKGROUND The mechanism for the efficacy of once- or twice-daily subcutaneous injections of low-molecular-weight heparins ( LMWHs ) for the treatment of venous thromboembolism has been difficult to explain . The confusion exists because the observation from experimental studies that the antithrombin activity of LMWHs is necessary for their antithrombotic effect is inconsistent with the reported short half-life of the antithrombin activity of LMWHs . Previous pharmacokinetic studies were performed with lower doses of LMWHs than have been used in contemporary trials , and antithrombin activity was assessed with the barely sensitive chromogenic assay . METHODS AND RESULTS We performed a pharmacokinetic study to compare the relative half-lives of prophylactic and therapeutic doses of LMWHs assessing antithrombin activity with both the chromogenic and a more sensitive assay ( plasma thrombin neutralization assay ) . An eight-way cross-over r and omized study in healthy volunteers was performed . Enoxaparin ( 20 and 40 mg and 1 and 2 mg/kg ) and nadroparin ( 7500 and 10,000 ICU and 225 and 450 ICU/kg ) were administered subcutaneously . The maximal peak activity for aPTT ratio was 1.7 . A dose-dependent peak activity was found for both antifactor Xa and antithrombin activities . Disappearance time of these activities after the highest dose of both LMWHs was longer than 16 hours . Overall mean antifactor Xa activity half-life was 4.6 hours . Overall mean antithrombin activity half-life was longer than 4 hours . CONCLUSIONS Our results provide an explanation for the effectiveness of LMWHs administered either once or twice daily . High and sustained plasma antithrombin activity is achieved when LMWHs are administered in therapeutic doses used in contemporary trials with only a moderate prolongation of the aPTT A low molecular weight heparin ( Fragmin , Kabi-Vitrum ) with a mean molecular weight of 4,000 - 5,000 D has been investigated in healthy volunteers and in patients with DVT . We found a T 1/2 of 4 hours and a high bioavailability after subcutaneous injection in volunteers . In a r and omised study , patients with phlebographically verified DVT , 120 U(anti-FXa)/kg Fragmin injected twice daily was found to be as effective as 240 U/kg , 12 h st and ard heparin as continuous infusion in preventing DVT progress . No major bleedings were seen in the Fragmin group . We conclude that Fragmin administered subcutaneously twice daily results in adequate anticoagulation and is safe and practical in the treatment of DVT BACKGROUND Multiple clinical trials have been performed to compare st and ard heparin with low molecular weight heparin in the therapy of deep vein thrombosis , but little is known about the time course of the markers of hemostatic system during the treatment with these two heparin regimens . METHODS Twenty patients with proximal deep vein thrombosis confirmed by duplex ultrasound and phlebography were r and omly assigned to either unfractionated heparin ( UH ) given as an intravenous bolus of 80 U/kg followed by a constant infusion of 18 U/kg/h , or nadroparin 185 AXa IU/kg once daily subcutaneously . Oral anticoagulants were started at day 4 . Markers of hemostatic activation ( F1 + 2 , FPA , TAT , D-dimer ) were measured daily for 4 days . Primary endpoints were the time course of these markers ; secondary endpoints consisted in the evaluation of thromboembolic and hemorrhagic complications by clinical outcome and Marder score . RESULTS Treatment with UH result ed in a rapid achievement of therapeutic heparin levels . UH reduced markers of fibrin formation and fibrinolysis more rapidly than nadroparin ( p < 0.05 ) . Within the nadroparin group activation of prothrombotic markers four hours after the subcutaneous injection ( peak level ) was significantly lower when compared with the time prior to injection ( trough level ) . Secondary endpoints showed no significant difference between the two groups . CONCLUSION Continuous intravenous perfusion of UH administered on a basis of a weight-adjusted nomogram controlled markers of the hemostatic system more rapidly than once-daily subcutaneously administered weight-adjusted nadroparin In a prospect i ve , r and omized , open study 119 consecutive patients with phlebographically verified deep venous thrombosis ( DVT ) of the leg ( 36 % distal and 64 % proximal ) were treated either with a low molecular weight heparin ( Fragmin , Kabi-Vitrum ) subcutaneously ( 120 anti-FXa U/kg ) twice daily or st and ard heparin ( SH ) as continuous intravenous infusion ( 480 IU kg-1 day-1 ) . The Fragmin doses were adjusted to achieve an anti-FXa activity of 0.2 - 0.4 U/ml before injection and not greater than 1.5 U/ml 4 h after the morning injection . The SH dose was modified to prolong the APTT 2 - 3 times . Repeat phlebography after 5 - 7 days showed improvement in 34/45 patients ( 76 % ) in the Fragmin group and in 30/49 patients ( 61 % ) in the SH group and progress in 2/45 ( 4 % ) and 3/49 ( 6 % ) , respectively . The mean Marder scores decreased from 18.7 + /- 12.1 to 15.7 + /- 12.7 in the Fragmin group and from 16.9 + /- 12.0 to 14.4 + /- 11.8 in the SH group ( ns ) . Two patients in the SH group and none in the Fragmin group had major bleedings . After 22 + /- 7 months follow up 6 rethromboses had occurred in the SH group and 4 in the Fragmin group . Postthrombotic signs and symptoms were similar in both groups . We conclude that two daily sc Fragmin doses seem as effective and safe as continuous SH in the treatment of DVT of the leg In this study , 294 patients with acute proximal DVT ( deep venous thrombosis ) were r and omly assigned to receive intravenous st and ard heparin in the hospital ( 98 patients ) or low-molecular-weight heparin ( LMWH ) ( nadroparin 0.1 mL [ equivalent to 100 AXa IU ] per kg of body weight subcutaneously twice daily ) administered primarily at home ( out patients ) or alternatively in hospital ( 97 patients ) or subcutaneous calcium heparin ( SCHep ) ( 99 patients , 0.5 mL bid ) administered directly at home . The study design allowed out patients taking LMWH heparin to go home immediately and hospitalized patients taking LMWH to be discharged early . Patients treated with st and ard heparin or LMWH received the oral anticoagulant starting on the second day , and heparin was discontinued when the therapeutic range ( INR 2 - 3 ) had been reached . Anticoagulant treatment was maintained for 3 months . Patients treated with SCHep were injected twice daily for 3 months without oral anticoagulants . Patients were evaluated for inclusion and follow-up with color duplex scanning . Venography was not used . In case of suspected pulmonary embolism ( PE ) a ventilatory-perfusional lung scan was performed . Endpoints of the study were recurrent or extension of DVT , bleeding , the number of days spent in hospital , and costs of treatments . Of the 325 patients included , 294 completed the study . Dropouts totaled 31 ( 10.5 % ) ; six of the 325 included patients ( 1.8 % ) died from the related , neoplastic illness . Recurrence or extension of DVT was observed in 6.1 % of patients in the LMWH group , in 6.2 % in the st and ard heparin group , and in 7.1 % in the SCHep group . Most recurrences ( 11/17 ) were in the first month in all groups . Bleedings were all minor , mostly during hospital stay . Hospital stay in patients treated with LMWH was 1.2 ± 1.4 days in comparison with 5.4 ± 1.2 in those treated with st and ard heparin . There was no hospital stay in the SCHep group . Average treatment costs in 3 months in the st and ard heparin group ( US $ 2,760 ) were considered to be 100 % ; in comparison costs in the LMWH group was 28 % of the st and ard heparin and 8 % in the SCHep group . This study indicated that LMWH and SCHep can be used safely and effectively to treat patients with proximal DVT at home at a lower cost BACKGROUND Elective hip-replacement surgery carries significant risk of venous thromboembolism , despite use of thromboprophylaxis . We aim ed to see whether the pentasaccharide fondaparinux , the first drug of a new class of synthetic antithrombotic agents , could reduce this risk to a greater extent than other available treatments . METHODS In a double-blind study , we r and omly assigned 2275 consecutive patients aged 18 years or older who were undergoing elective hip-replacement surgery to receive postoperative subcutaneous injections of either 2.5 mg fondaparinux once daily or 30 mg enoxaparin twice daily . The primary efficacy outcome was venous thromboembolism to day 11 . The main safety outcomes were bleeding and death . Patients were followed up for 6 weeks . FINDINGS We assessed venous thromboembolism to day 11 in 1584 ( 70 % ) of 2275 patients . By day 11 , venous thromboembolisms were recorded in 48 ( 6 % ) of 787 patients on fondaparinux and in 66 ( 8 % ) of 797 patients on enoxaparin . The relative reduction in risk was 26.3 % ( 95 % CI -10.8 to 52.8 , p=0.099 ) . The two groups did not differ in the number of patients who died or in the number who had clinical ly relevant bleeding . INTERPRETATION In patients undergoing elective hip-replacement surgery , 2.5 mg fondaparinux once daily was not significantly more effective than 30 mg enoxaparin twice daily in reducing risk of venous thromboembolism . However , the lower risk recorded with fondaparinux than enoxaparin was clinical ly important , with no increase in clinical ly relevant bleeding A total of 1290 patients ( Pts ) undergoing general surgery were enrolled in a r and omized , multicentre double-blind study in order to investigate the efficacy and safety of two different doses of a low molecular weight heparin ( LMWH ) ( Logiparin ) for the prevention of deep vein thrombosis . Patients were r and omized to either 5,000 IU unfractionated heparin twice daily , 2,500 anti-Xa or 3,500 anti-Xa units of Logiparin once daily . Each treatment was given subcutaneously two hours before surgery and continued for seven to ten days . All coagulation tests were performed blindly in a core laboratory . Blood sample s were collected before surgery and then 3 hours after injection on Day 3 and 5 after surgery . Anti-Xa amidolytic activities were significantly higher in the two LMW Heparin groups than in the unfractionated heparin group ( mean peak levels + /- s.e.m . on Day 3 : 0.097 + /- 0.004 ; 0.152 + /- 0.004 and 0.034 + /- 0.003 IU respectively ) . As expected a significant correlation was observed between anti-Xa activity and the dose of LMW Heparin injected . The correlation coefficient was higher when the doses were expressed in anti-Xa units/kg body weight . However , the body weight accounts for only 16 % of the interindividual variability of anti-Xa activity . Therefore , there is no clear evidence to suggest that weight-adjusted doses should be recommended when this LMW Heparin is used as prophylactic treatment in general surgery . A weak negative correlation was found between anti-Xa activity and thrombosis as demonstrated by a positive radiolabelled fibrinogen uptake test and confirmed by positive phlebography . No significant correlation was demonstrated between anti-Xa activity and the occurrence of postoperative bleeding The effect of LMW heparin ( Kabi 2165 , Fragmin ) was compared with placebo for the prevention of DVT in 103 patients with acute ischemic stroke using a prospect i ve , double-blind , r and omized trial design . Treatment was started within 72 hours , and LMW heparin was administered subcutaneously once daily according to body weight classes , which corresponded to about 55 to 65 Factor-Xa inhibitory U/kg , for 14 days , or until discharge from the hospital , if earlier . All patients underwent thrombosis surveillance with unilateral venography of the paretic limb . Evaluation of venography could be performed in 42 of 52 patients r and omized to LMW heparin and in 50 of 51 patients r and omized to placebo . The frequency of DVT was 15 of 42 patients or 36 % ( 95 % confidence interval 22 to 52 % ) in the LMW heparin group and 17 of 50 patients or 34 % ( 21 to 49 % ) in the placebo group . The frequency of proximal thrombi was 5 of 42 ( 12 % ) and 8 of 50 ( 16 % ) , respectively . There was one fatal pulmonary embolism in the placebo group . The mortality rate ( 28 days follow-up ) was 5 of 52 in the LMW heparin group and 1 of 51 in the placebo group ( p = 0.24 ) . None of the deaths was related to treatment . No major hemorrhagic complications were observed . The mean Factor Xa inhibitory activity levels at peak concentration were 0.34 U/ml on day 2 and 0.42 U/ml on day 12 ( p = 0.02 ) . We conclude that LMW heparin in the dose range studied did not provide efficient prophylaxis against DVT in patients with acute ischemic stroke In an open , r and omised controlled study , 101 patients with phlebographically diagnosed deep vein thrombosis of the leg , not extending into more than two thirds of the femoral vein , were r and omised to receive Fragmin ( a low molecular weight heparin ) administered subcutaneously either once or twice daily in doses of 200 U(anti-FXa)/kg/24h or 100 U(anti-FXa)/kg/12h respectively . Prior to Fragmin unfractionated heparin had been administered by continuous iv infusion for not longer than 24h . Warfarin was administered from the first treatment day . Fragmin was administered for at least 5 days or until the prothrombin complex had been within the therapeutic range for at least 2 days . Patients were kept in bed for the first day but thereafter were ambulant . Phlebography was repeated at 5 - 7 days . Comparison of the phlebograms revealed a similar improvement ( reduction in Marder score ) in both groups . There were 5 cases of bleeding : 1 major and 3 minor in the twice daily group and 1 minor bleed in the once daily group . There were no cases of clinical pulmonary embolism . It is concluded that Fragmin , administered as a single daily subcutaneous injection , is effective in the treatment of deep vein thromboses , and offers the advantages of reduced costs , despite higher price of the drug , including reduced nursing time BACKGROUND In most countries , heparin is used in the initial treatment of patients with deep-vein thrombosis . Well- design ed studies establishing the efficacy of heparin therapy are lacking , however . Treatment with acenocoumarol alone , according to the hypothesis that high dosages of oral anticoagulants obviate the need for heparin , is considered an effective alternative in some countries . METHODS In a r and omized , double-blind study we compared the efficacy and safety of continuous intravenous heparin plus acenocoumarol with the efficacy and safety of acenocoumarol alone in the initial treatment of out patients with proximal-vein thrombosis . The principal study end point was a confirmed symptomatic extension or recurrence of venous thromboembolism during six months of follow-up . In addition , we assessed asymptomatic extension or pulmonary embolism by repeating venography and lung scanning after the first week of treatment . The incidence of major bleeding was determined during three months of follow-up . RESULTS The study was terminated early by the Data Safety and Monitoring Committee because of an excess of symptomatic events in the group that received acenocoumarol alone ( in 12 of 60 patients [ 20 percent ] , as compared with 4 of 60 patients [ 6.7 percent ] in the combined-therapy group by intention-to-treat analysis ; P = 0.058 ) . Asymptomatic extension of venous thrombosis was observed in 39.6 percent of the patients in the acenocoumarol group and in 8.2 percent of patients treated with heparin plus acenocoumarol ( P < 0.001 ) . Major bleeding complications were infrequent and comparable in the two groups . CONCLUSIONS Patients with proximal-vein thrombosis require initial treatment with full-dose heparin , which can safely be combined with acenocoumarol therapy Venous thromboembolism may be efficiently treated by once-a-day ( o.d . ) administration of a high dose of low molecular weight heparin ( LMWH ) instead of administration of the same total dose in two injections a day ( b.i.d . ) . To reduce the volume of the subcutaneous ( s.c . ) injection , a more concentrated form of the drug is advisable . This study was design ed to compare the bioavailability of 2 formulations of nadroparin containing 10,250 and 20,500 anti-Xa IU x ml(-1 ) respectively . This was an open , r and omized , cross-over study where 12 healthy volunteers ( age 18 - 35 ) were enrolled . They received either 90 anti-Xa IU x kg(-1 ) b.i.d . of the 10,250 IU preparation ( treatment A ) , or 180 anti-Xa IU x kg(-1 ) o.d . of the 20,500 IU preparation ( treatment B ) for 10 days . On day 1 , the subjects were sample d between 0 and 12 h ( treatment A ) or between 0 and 24 h ( treatment B ) . On day 10 , they were sample d between 0 and 12 h and between 12 and 24 h ( treatment A ) or between 0 and 24 h ( treatment B ) . Anti-Xa and anti-IIa activities were determined by specific chromogenic assays . The main result of the study was that the bioavailability of the anti-Xa activity of the 2 nadroparin formulations was equivalent , as shown by the comparison of the AUC(0 - 12 h ) plus AUC(12 - 24 h ) ( treatment A ) and the AUC(0 - 24 h ) ( treatment B ) , calculated on day 10 . This study also allowed a number of interesting observations to be made . 1 ) Between day 1 and day 10 , there was an accumulation of the anti-Xa activity for treatment A but not for treatment B ( accumulation factors : 1.6 and 1.1 respectively ) ; 2 ) On day 10 , the AUC(0 - 12 h ) were slightly but significantly lower than the AUC(12 - 24 h ) suggesting a circadian effect for anti-Xa and anti-IIa activities ; 3 ) the clearance of the anti-Xa activity was comparable at the 2-dose regimens , while that of the anti-IIa activity was lower in treatment B than in treatment A , indicating a significant dose effect for the pharmacodynamics of the longer heparin chains ; 4 ) On average , the clearance of the anti-IIa activity was twice as high as that of the anti-Xa activity ; 5 ) For treatment B , significant APTT prolongations were noticed at Tmax ( prolongation factor : 1.7 + /- 0.25 ) , in relation with the anti-IIa activity ( 0.3 + /- 0.1 IU x ml(-1 ) ) Venous thromboembolic disease causes significant morbidity and mortality in both hospitalized and nonhospitalized patients . The mean annual incidence in the United States is 48 per 100 000 for deep venous thrombosis and 23 per 100 000 for pulmonary embolism , according to an epidemiologic study conducted in Massachusetts ( 1 ) . A similar study in Sweden showed an annual incidence of 160 new cases of deep venous thrombosis per 100 000 inhabitants ( 2 ) . Five to 10 days of unfractionated heparin is a common recommended initial treatment for deep venous thrombosis . This treatment maintains the activated partial thromboplastin time above 1.5 times its control value ( 3 , 4 ) , as calibrated by protamine titration or an antifactor Xa assay . Another recommended initial treatment is 5 to 10 days of weight-adjusted low-molecular-weight heparin followed by at least 3 months of oral anticoagulant therapy ( 3 - 7 ) . Low-molecular-weight heparins are now frequently being used in place of unfractionated heparin for both prevention and treatment of venous thromboembolism ( 3 , 8) . R and omized trials and meta-analyses have shown subcutaneously administered low-molecular-weight heparins to have antithrombotic efficacy equal to ( 9 - 12 ) or greater than ( 13 - 16 ) that of continuously infused unfractionated heparin in the initial treatment of deep venous thrombosis and equal to that of unfractionated heparin in the treatment of pulmonary embolism ( 17 , 18 ) . However , many of these studies enrolled small numbers of patients ( 9 - 13 , 15 , 16 ) , used primarily venographic plethysmographic or scintigraphic end points ( 9 - 11 , 13 , 16 ) , and sometimes excluded patients with pulmonary embolism ( 11 , 15 ) . Most trials of twice-daily low-molecular-weight heparin adjusted treatment regimens according to patient weight without laboratory monitoring . However , several studies suggest that once-daily weight-adjusted dosage of a low-molecular-weight heparin is as effective in the treatment of proximal deep venous thrombosis as adjusted dosages of intravenous unfractionated heparin ( 14 , 19 ) or twice-daily low-molecular-weight heparin ( 20 ) . Since low-molecular-weight heparins differ in their physicochemical and pharmacologic characteristics , study results that apply to one can not be extended to another ( 21 , 22 ) . We conducted the present study to determine whether enoxaparin administered subcutaneously once or twice per day is as effective as continuously infused unfractionated heparin in the treatment of patients with acute , symptomatic venous thromboembolic disease . Methods Study Description This parallel-group , r and omized , partially blinded , international , multicenter clinical trial compared continuously infused unfractionated heparin ( adjusted to maintain activated partial thromboplastin time within a defined range ) with two weight-adjusted dosages of enoxaparin administered subcutaneously once or twice daily . The study was conducted in 74 hospitals in 16 countries , including the United States , several European countries , Australia , and Israel , and was approved by the institutional review board or ethics committees at each location . Written informed consent was obtained from each patient . Four committees participated in this study : an Advisory Committee ; an Outcome Adjudication Committee , which provided blinded outcome assignments for incidence of recurrent venous thromboembolic disease , major or minor hemorrhage , immune thrombocytopenia , and cause of death ; an independent Safety Committee ; and a Vascular Imaging Committee , which review ed all baseline venograms and all vascular imaging studies in a blinded manner to determine whether deep venous thrombosis was present at baseline and whether objective evidence of recurrence existed . Patient Characteristics Patients were required to be at least 18 years of age and willing to remain hospitalized during r and omized therapy . The primary inclusion criteria were symptomatic lower-extremity deep venous thrombosis confirmed by venography or ultrasonography ( if venography was inconclusive ) , symptomatic pulmonary embolism confirmed by high-probability ventilationperfusion scanning , or positive pulmonary angiography with confirmation of lower-extremity deep venous thrombosis . All eligible patients underwent baseline lung scanning or angiography . Exclusion criteria were more than 24 hours of previous treatment with heparin or warfarin ; need for thrombolytic therapy ; known hemorrhagic risk , including active hemorrhage , active intestinal ulcerative disease , known angiodysplasia , or eye , spinal , or central nervous system surgery within the previous month ; renal insufficiency ( serum creatinine concentration>180 mol/L [ 2.03 mg/dL ] ) ; severe hepatic insufficiency ; allergy to heparin , protamine , porcine products ( both heparin and enoxaparin are derived from pork intestinal mucosa ) , iodine , or contrast media ; history of heparin-associated thrombocytopenia or heparin- or warfarin-associated skin necrosis ; treatment with other investigational therapeutic agents within the previous 4 weeks ; inferior vena cava interruption ; or known pregnancy or lactation . Treatments Within each center , consecutive eligible patients were r and omly assigned sequentially to one of three treatment groups . R and omization was done without stratification in blocks of six , according to ascending r and omization number . The numbers were affixed to sealed treatment kits that contained study medication and were provided by the study sponsor . Patients assigned to enoxaparin received a weight-adjusted subcutaneous dose . Two blinded regimens were tested : 1.0 mg/kg of body weight twice daily or 1.5 mg/kg once daily . Several clinical trials have shown the twice-daily regimen to be effective and safe ( 16 , 23 , 24 ) . The once-daily dosage was chosen on the basis of results of pharmacokinetic studies that showed it to have a suitable pharmacokinetic profile in healthy volunteers and to be well tolerated in the treatment of patients with venous thromboembolism ( 25 , 26 ) . In these previous studies , therapeutic antifactor Xa levels were present for up to 18 hours in both volunteers and patients , and measurable levels were present for up to 24 hours . A total of three injections , study drug and placebo , were given each day to maintain blinding for volume of solutions and frequency of administration . Patients assigned to the nonblinded unfractionated heparin group received an intravenous bolus dose and infusion on the basis of an approved institution-specific nomogram . In most cases , administration was as follows : Six hours after the initial bolus , the activated partial thromboplastin time was measured and the dose was adjusted to maintain the specified value , which was between 55 and 80 seconds in most centers ( 4 - 7 ) . Activated partial thromboplastin time was measured at least daily during unfractionated heparin treatment . Enoxaparin and heparin treatments were continued for at least 5 days , and warfarin was started within 72 hours of initial study drug administration . Forty-three patients received phenprocoumon in place of warfarin sodium . Prothrombin time was measured daily , and patients could be discharged from the hospital after the international normalized ratio was found to be between 2.0 and 3.0 on 2 consecutive days . Oral anticoagulation was continued for at least 3 months . Study Assessment s Observers who were aware of treatment assignment assessed patients daily and monthly during the 3-month follow-up for worsening or recurrence of deep venous thrombosis or pulmonary embolism , hemorrhage , adverse events , changes in concomitant medications and adequacy of warfarin use , and warfarin adherence . For patients receiving unfractionated heparin , adherence was defined as an activated partial thromboplastin time within or above the therapeutic range on the second day of treatment . For patients receiving enoxaparin , adherence was defined as at least 10 doses of study medication given with no dosing errors . Adherence to warfarin therapy was defined as having at least one international normalized ratio value greater than or equal to 2.0 between day 4 and the last dose of study treatment during the initial treatment period . These definitions of treatment adherence were established before the analysis of the study outcomes . Efficacy Analysis The efficacy analysis was performed on two study sample s : all treated patients , who received at least one dose of study medication , and evaluable patients , which excluded all patients who met at least one of the criteria for nonevaluability . These criteria were no confirmed deep venous thrombosis at baseline , insufficient study therapy , placement of an inferior vena cava filter , two r and om assignments , and no 3-month follow-up . Insufficient study therapy was defined as one or more missed enoxaparin doses among at least eight consecutive enoxaparin doses or less than 4 consecutive days of heparin infusion . The definition of insufficient study therapy was established before analysis of study outcomes . These two study sample s were analyzed to strengthen the conclusion of equivalence among the treatment groups . The homogeneity of the results of the two analyses is considered to be more supportive of the conclusion of equivalence than the results of either analysis alone . Primary clinical end points were recurrent deep venous thrombosis or pulmonary embolism within 3 months of r and omization . Patients with symptoms of recurrent thrombosis underwent confirmatory testing with venography , ultrasonography , or both . Patients presenting with signs or symptoms of pulmonary embolism underwent lung perfusion scanning , pulmonary angiography , or both . Clinical symptoms and supportive findings on objective tests ; extension of existing thrombi or new thrombi for venography , angiography , or ultrasonography ; or high-probability defect patterns on perfusion scans were required to confirm recurrent thrombosis . Prespecified subgroup analyses were performed on the basis of patient Objective : Guidelines recommend low-dose unfractionated heparin ( UFH ) and low-molecular-weight heparin for the prophylaxis of venous thromboembolism ( VTE ) in acutely ill medical patients . We report the findings of an open-label , active-controlled , multicenter study in acutely ill medical patients comparing certoparin and UFH . Research design and methods : Open-label , active-controlled , multicenter study . Patients received certoparin 3000 IU daily or UFH 7500 IU twice daily . Main outcome measures : The primary endpoint was a composite of symptomatic or asymptomatic proximal or distal deep vein thrombosis , symptomatic pulmonary embolism , or VTE-related death . Results : 172 patients were r and omized to UFH and 163 to certoparin for 8.5 ± 2.1 days . The incidence of the primary endpoint was 18.0 % in patients receiving UFH and 10.7 % with certoparin [ absolute difference -7.3 ; 95 % confidence interval ( CI ) -16.9 to 2.3 ; p = 0.1353 ] . The incidence during follow-up was 2.6 % in the UFH and 2.0 % in the certoparin group ( absolute difference -0.6 ; 95%CI -4.0 to 2.8 ; p = 0.7150 ) . Major bleeding events occurred in three patients with UFH and one patient with certoparin . Conclusions : In acutely ill medical patients of at least 40 years of age , thromboprophylaxis with certoparin 3000 IU daily is effective and safe in comparison with 7500 IU twice daily UFH Possible correlation of the effects of pharmacotherapy on the inhibition of the in-vivo generation of thrombin and on the prevention of thrombus extension in patients with deep vein thrombosis ( DVT ) could help to define patients at higher risk . Patients with symptomatic deep vein thrombosis confirmed by phlebography were r and omised to intravenous unfractionated heparin ( UFH ) , or a subcutaneous low-molecular-weight heparin ( reviparin ) twice daily for one week , or a subcutaneous reviparin once daily for four weeks . The patients were treated with oral anticoagulants for at least 3 months . Main endpoints were regression of thrombus on phlebography on Day 21 and recurrent symptomatic venous thromboembolism up to 3 months . Coagulation parameters , markers of in-vivo thrombin generation , and TFPI-release were determined at r and omisation , weeks 1 and 3 . Four hundred sixty six responders ( reduction of at least 30 per cent in Marder score ) and 419 non-responders ( Marder score unchanged or changed less than + /-30 % ) showed no significantly different baseline characteristics . The non-responder group had a higher median Marder score at baseline and after one and three weeks of treatment , and had significantly higher fibrinogen levels , TAT complexes and F1 + 2 values than responders . There were no significant differences in coagulation parameters between non-responders and patients with asymptomatic + symptomatic VTE with the exception of higher TAT complexes at baseline . Significant differences in Marder score and coagulation parameters at baseline were found between responders and nonresponders . Non-responders have a higher risk tosuffer recurrent VTE and may need intensified treatment BACKGROUND Recent clinical trials of venous thromboembolism treatment suggest inadequate initial heparin therapy predisposes patients to late recurrence of thromboembolism . However , a recent review article was unable to demonstrate a relationship between initial heparin therapy and late recurrence . OBJECTIVE To evaluate the relationship between initial heparin treatment and long-term clinical outcome in 3 consecutive , r and omized , double-blind trials that used similar study design s and patient population s and objective documentation of recurrent venous thromboembolism . METHODS The trials were performed sequentially and compared the use of continuous intravenous with subcutaneous heparin , continuous intravenous heparin for 10 or 5 days , and continuous intravenous heparin with once-daily subcutaneous low-molecular-weight heparin . All patients were followed up for 3 months to assess the a priori hypothesis that inadequate initial heparin therapy could lead to recurrent venous thromboembolism during long-term therapy with warfarin sodium . RESULTS The following were the observed rates of recurrent venous thromboembolism : continuous intravenous heparin , 3 ( 5.2 % ) of 58 patients vs subcutaneous heparin , 11 ( 19.3 % ) of 57 patients ; continuous intravenous heparin for 10 days , 7 ( 7.0 % ) of 100 patients or for 5 days , 7 ( 7.1 % ) of 99 patients ; and continuous intravenous heparin , 15 ( 6.9 % ) of 219 patients vs low-molecular-weight heparin , 6 ( 2.8 % ) of 213 patients . Pooled analysis of the patients treated with continuous intravenous heparin showed that of the total 32 patients with recurrent venous thromboembolism , in 6 patients thromboembolism occurred early ( < 10 days ) and 26 patients thromboembolism occurred late . Of these patients , the majority ( 20/32 [ 62.5 % ] ) had therapeutic prothrombin time or international normalized ratio values before or at the time of the recurrent thromboembolic event . CONCLUSION Our findings demonstrate that the initial heparin treatment affects the long-term outcome . This conclusion applies when these data are analyzed for each individual study by treatment group , observed difference in outcome , and pooled analysis The aim of the study was to compare the efficacy and safety of once-daily subcutaneous injection of dalteparin , a low molecular weight heparin , with that of intravenous unfractionated heparin in the treatment of deep venous thrombosis ( DVT ) . Patients were included if they had deep venous thrombosis distal to inguinal ligament and were r and omised either before , if it was considered necessary , or after phlebographic verification of the diagnosis . There was no pre- inclusion treatment with unfractionated heparin . One hundred and twenty patients received dalteparin , administered subcutaneously once-daily at a fixed dose of 200 IU anti-factor Xa/kg , and 133 patients received a continuous intravenous infusion of unfractionated heparin ( UFH ) . Oral anticoagulation was started on the first or second day , and initial treatment with dalteparin or UFH discontinued when the prothrombin time was in the therapeutic range ( 2 < INR < 3 ) on two consecutive days . Control phlebograms were taken within 4 days , thereafter . There were no significant differences between the two initial treatment groups in improvements in Marder score . Two major bleeding events occurred in the UFH group versus none in the dalteparin group . One patient in each group experienced clinical ly significant pulmonary embolism . During a mean follow-up period of 6.9 + /- 1.5 months , recurrent DVT occurred in four patients in the dalteparin group and in two of the UFH group . These results confirm those of a previous study on dalteparin in the initial treatment of DVT , and suggest that dalteparin administered once-daily at a fixed dose of 200 UI/kg is as effective and well-tolerated as UFH in patients with DVT below the inguinal ligament . The present study also demonstrates that dalteparin can be started as soon as the diagnosis of DVT is suspected and without pre-treatment with UFH . Given that the administration of once-daily subcutaneous injections needs not require a patient to be hospitalised , studies to investigate the possibility of using dalteparin for the initial treatment of DVT in the outpatient setting are warranted Venous thromboembolism remains an important cause of maternal mortality . In a r and omised open study , 44 pregnant women with confirmed previous or current thromboembolism were r and omised to receive either low-molecular-weight heparin , dalteparin ( N = 21 ) once daily subcutaneously or unfractionated sodium heparin ( UF heparin , N = 23 ) twice daily subcutaneously for thromboprophylaxis during pregnancy and puerperium . Bone mineral density ( BMD ) in the lumbosacral spine was measured with dual X-ray absorptiometry ( DEXA ) 1 , 6 , 16 , 52 weeks and , if possible , 3 years after delivery . BMD values were also compared with those of healthy , delivered women ( N = 19 ) . Mean BMD of the lumbar spine was significantly lower in the unfractionated heparin group compared with the dalteparin and with the control groups ( repeated measures ANOVA p = 0.02 ) . BMD in the dalteparin group did not differ from BMD of healthy delivered women . Multiple logistic regression analysis revealed that therapy was the only independent factor influencing BMD at weeks 16 and 52 . Therefore we recommend use of dalteparin instead of UF heparin for long-term thromboprophylaxis during and after pregnancy Conventional anticoagulation for symptomatic pulmonary embolism consists of continuous intravenous unfractionated heparin as a " bridge " to oral anticoagulation . This strategy requires 5 days or more of intravenous heparin while oral vitamin K antagonists gradually achieve a therapeutic effect . Oral vitamin K antagonists require frequent blood testing to optimize dosing , and their interactions with other medications and foods make regulation difficult . Therefore we tested a different approach to therapy : long-term enoxaparin monotherapy . We r and omized 60 symptomatic pulmonary embolism patients in a 2:1 ratio to 90 days of enoxaparin as monotherapy without warfarin ( N=40 ) or to intravenous unfractionated heparin as a " bridge " to warfarin , target INR 2.0 - 3.0 ( N=20 ) . Enoxaparin patients received 1 mg/kg twice daily for 14 days during the acute phase followed by r and omized assignment during the chronic phase to 1.0 mg/kg vs. 1.5 mg/kg once daily . In an intention-to-treat analysis , 3 of the 40 enoxaparin patients developed recurrent venous thromboembolism compared with 0 of 20 st and ard therapy patients ( p = 0.54 ) . One of the 40 enoxaparin patients had a major hemorrhagic complication compared with 2 of the 20 st and ard therapy patients ( p = 0.26 ) . Median hospital length of stay was shorter with enoxaparin compared to st and ard therapy ( 4 vs. 6 days ) ( p = 0.001 ) . Following our study we can conclude that extended 3-month treatment with enoxaparin as monotherapy for symptomatic , acute pulmonary embolism is feasible and warrants further study in a large clinical trial Low molecular weight heparin ( LMWH ) is currently prescribed for the treatment of deep vein thrombosis at the dose of 100 IU antiXa/kg twice daily or at a dose of 175 IU antiXa/kg once daily with a similar efficacy . We decided to study the chrono-pharmacology of curative dose of LMWH once daily administrated according to the one previously described with unfractionated heparin ( UFH ) . Ten healthy volunteers participated in an open three-period crossover study according to three 24 h cycles , separated by a wash-out interval lasting 7 days : one control cycle without injection , two cycles with subcutaneous injection of 200 IU antiXa/kg of Dalteparin ( Fragmin ) at 8 a.m. or at 8 p.m. Parameters of heparin activity were analysed as maximal values and area under the curve . Activated partial thromboplastin time ( APTT ) , thrombin time ( TT ) , prothrombin time ( PT ) and tissue factor pathway inhibitor ( TFPI ) were higher after 8 p.m. injection than after 8 a.m. injection ( p < 0.05 ) while no chrono-pharmacological variation of anti factor Xa ( AXa ) activity was observed . Thus the biological anticoagulant effect of 200 IU antiXa/kg of Dalteparin seems to be higher after an evening injection than after a morning injection . A chrono-therapeutic approach with LMWH , as prescribed once daily , deserves further investigation since our results suggest that a preferential injection time may optimise the clinical efficacy of these LMWH BACKGROUND Clinical trials have been performed to compare with st and ard heparin a once or a twice daily regimen of low-molecular-weight heparin but no direct comparison has been done between these two low-molecular-weight heparin regimens in terms of efficacy and safety with a long-term clinical evaluation . METHODS Patients with proximal deep vein thrombosis , confirmed by venography were r and omly assigned to either nadroparin ( 10,250 AXa IU/ml ) twice daily or nadroparin ( 20,500 AXa IU/ml ) once daily for at least 5 days . Regimens were adjusted to bodyweight . Oral anticoagulants were started on day 1 or 2 and continued for 3 months . Patients were followed up for 3 months . The composite outcome of venous thromboembolism and death possibly related to pulmonary embolism was the primary measure of efficacy . Major bleeding was the principal measure of safety . The study was design ed to show equivalence between the two regimens . RESULTS Recurrent thromboembolic events or death possibly related to pulmonary embolism were reported in 13 patients in the once daily group ( 4.1 % ) and in 24 patients of the twice daily group ( 7.2 % ) : ( absolute difference 3.1 % in favor of the once daily regimen ; 95 % confidence interval -6.6 % , + 0.5 % ) . Major bleeding episodes during nadroparin treatment occurred in 4 ( 1.3 % ) and 4 patients ( 1.2 % ) in the once and twice daily groups , respectively . CONCLUSIONS A nadroparin regimen of one injection per day is at least as effective and safe as the same total daily dose divided over two injections for the treatment of acute deep vein thrombosis Low-molecular-weight heparins have been extensively investigated in the treatment of deep venous thrombosis but limited data are available concerning their use in pulmonary embolism . In an open , pilot , r and omized study , we compare the safety and efficacy of Fragmin , a low-molecular-weight heparin with those of unfractionated heparin in 60 patients with non massive pulmonary embolism ( Miller Index < 20 ) . Thirty one patients received unfractionated heparin intravenously and 29 received a fixed dose of 120 Anti-Xa IU/kg of Fragmin administered subcutaneously twice a day for 10 days . There was no pulmonary embolism recurrence nor major bleeding in either group during the treatment period . The decrease in pulmonary vascular obstruction on perfusion lung scan between day 0 and day 10 was 17 + /- 13 % in the Fragmin group and 16 + /- 13 % in the heparin group ( NS ) . These results indicate that Fragmin may be a safe and effective treatment of submassive pulmonary embolism We have performed a prospect i ve , r and omized , controlled trial comparing continuous intravenous unfractionated heparin with twice-daily subcutaneous ( s.c . ) high-dose low-molecular-weight ( LMW ) heparin in the initial treatment of 50 patients with acute proximal deep vein thrombosis . In this article we analyze the relationship between the dosage of the heparins , the anticoagulant effects on aPTT , and thrombin and factor Xa inhibition to the improvement of the Marder score after a 10-day treatment period . Improvement of the Marder score was observed in about 70 % of patients without regard to administration of unfractionated or LMW heparin . Patients in both treatment categories were divided into two groups , namely , those who showed an improvement of the Marder score and those who did not . In the group of patients with unfractionated heparin and regression of thrombus size the mean dosage was 33,000 U/day , whereas the mean dosage was 37,000 U/day in the patients with status idem of the Marder score after the 10-day treatment period . Thrombin clotting time values were in contrast to the dosage . Patients with regression of thrombosis showed higher thrombin clotting time values compared with those with status idem . These results were also seen with aPTT and the Heptest coagulation assay , but the differences between the two groups were less pronounced . No differences between these two groups of patients were seen or detected with the S2222 chromogenic anti-factor Xa method . Patients receiving 2 x 12,000 IU s.c./day LMW heparin did not show these differences , the dosage being adjusted by the anti-Xa levels , ranging from 0.6 to 1.0 U/mL 4 hours after the s.c . injection . The groups of patients categorized as to improvement or not of the Marder score did not show differences in the daily dose . The anti-Xa activity was higher in patients with regression of thrombosis compared with patients without regression . The other coagulation parameters did not show any relation to the clinical outcome of thrombus regression . The relationship between the change of the Marder score at day 10 and the anticoagulant effect on the different coagulation systems correlated weakly for patients receiving unfractionated heparin . The highest correlation was found for the improvement of Marder score and thrombin inhibition in the heparin group with r = 0.42 . For LMW heparin no correlation could be detected . Heptest coagulation values were in the same range for patients receiving unfractionated and LMW heparin . In contrast to the chromogenic anti-Xa assay , aPTT , thrombin clotting time , and prothrombin time values differed substantially in the two treatment regimens . Treatment of recent deep vein thrombosis with unfractionated heparin profits from laboratory monitoring , whereas monitoring of the anticoagulant effect during the treatment with s.c . LMW heparin does not influence the outcome on thrombus regression We evaluated whether a postoperative regimen with melagatran followed by oral ximelagatran , two new direct thrombin inhibitors , was an optimal regimen for thromboprophylaxis in major orthopaedic surgery . In a double-blind study , 2788 patients undergoing total hip or knee replacement were r and omly assigned to receive for 8 to 11 days either 3 mg of subcutaneous melagatran started 4 - 12 h postoperatively , followed by 24 mg of oral ximelagatran twice-daily or 40 mg of subcutaneous enoxaparin once-daily , started 12 h preoperatively . Ximelagatran was to be initiated within the first two postoperative days . The primary efficacy endpoint was venous thromboembolism ( deep-vein thrombosis detected by m and atory venography , pulmonary embolism or unexplained death ) . The main safety endpoint was bleeding . Venous thromboembolism occurred in 355/1146 ( 31.0 % ) and 306/1122 ( 27.3 % ) patients in the ximelagatran and enoxaparin group , respectively , a difference in risk of 3.7 % in favour of enoxaparin ( p = 0.053 ) . Bleeding was comparable between the two groups OBJECTIVES To compare the efficacy and safety of the low molecular weight heparin ( LMWH ) dalteparin with unfractionated heparin ( UFH ) in the acute treatment of DVT patients who had not previously received UFH . DESIGN An open r and omized multicentre trial with blinded analysis of venograms . SETTING Seven hospitals in Sweden , Finl and and the USA . SUBJECTS A total of 330 patients , of 20 years or older , with suspected DVT , verified using venography . INTERVENTIONS Fixed-dose dalteparin ( 200 IU kg-1 ) given as a once-daily subcutaneous injection , or aPTT adjusted i.v . UFH infusion for 6 to 10 days . MAIN OUTCOME MEASURES Change in Marder score in patients with confirmed DVT and two evaluable venograms ; PE , bleeding events and follow-up . RESULTS Marder scores improved in 51 % ( 95 % CI 42 - 60 % ) of 92 patients treated with dalteparin and in 62 % ( 95 % CI 53 - 70 % ) of 98 patients treated with UFH ( P = 0.152 ) . One dalteparin-treated patient had a PE confirmed by V/Q scan ; another had progressive thrombosis with swelling in the affected limb . Bleeding complications occurred in six patients in each group . One patient treated with dalteparin and five treated with UFH died during the 6-month follow-up period as a result of underlying malignancy or heart disease . The 6-month recurrence rate was low with both treatments ( dalteparin , 3/97 ; UFH , 2/103 ) . CONCLUSIONS Fixed-dose subcutaneous dalteparin given once daily from the start of treatment is of equivalent efficacy and safety to conventional UFH therapy in the routine management of DVT Tissue injury during hip surgery results in the activation of the haemostatic system . The aim of this study was to detect markers of haemostatic activity , i.e. prothrombin fragment 1 and 2 ( F1 + 2 ) , thrombin-antithrombin ( TAT ) complexes , fibrin degradation products ( FbDP ) , and soluble fibrin monomers ( SF ) , preoperatively , and on days 1 , 7 and 35 in plasma of patients undergoing total hip arthroplasty . The study was part of a multicentre study in which the patients were r and omized to receive a subcutaneous injection of low molecular weight heparin ( LMWH , dalteparin , Fragmin ) once daily for 5 weeks or placebo following a 1-week LMWH treatment ( once daily ) . Bilateral phlebography was performed between days 33 and 35 or before if patients had clinical symptoms of deep vein thrombosis . A lung scan was performed in patients with clinical symptoms of pulmonary embolism . Levels of the markers were significantly increased on day 35 in the patients receiving LMWH for 7 days compared to patients receiving LMWH for 35 days . In patients receiving LMWH for 5 weeks , levels of FbDP and SF were significantly higher during the entire study period , but TAT and F1 + 2 were normalized on day 35 . The markers were increased two to five times on the 1st postoperative day in patients with diagnosed venous thromboembolism Fifty patients presenting with acute deep-vein thrombosis were r and omized in a prospect i ve , controlled study to determine the safety and efficacy of a treatment with low-molecular-weight ( LMW ) heparin compared with unfractionated heparin . LMW heparin ( n = 24 ) was administered twice daily subcutaneously at a dose of 2 X 150 anti-Xa units/kg body weight , and unfractionated heparin ( n = 26 ) was given intravenously by continuous infusion at a dose of 450 anti-Xa units/kg body weight daily for 10 days . Doses were adjusted to maintain peak anti-Xa levels between 0.5 and 1.0 anti-Xa units per milliliter . One patient in the unfractionated heparin group and 2 patients in the LMW heparin group suffered from bleeding complications . Two patients on LMW heparin and on unfractionated heparin had high evidence of pulmonary embolism based on defects on ventilation-perfusion scintigraphy . Control phlebography and duplex sonography demonstrated a significant improvement during both treatment regimens . Reperfusion of the deep-vein system was 70 % with LMW heparin and 75 % with unfractionated heparin . The anti-Xa levels were significantly higher in the LMW heparin group , and activated partial thromboplastin and thrombin clotting times were significantly higher in the group receiving unfractionated heparin . Thrombin-antithrombin III complexes and D-dimer concentration decreased during the treatment , but did not differ between the two regimens . At the end of the treatment period with LMW heparin , protein C and antithrombin III were significantly higher |
1,074 | 21,735,410 | 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 | BACKGROUND Intra-aortic balloon pump counterpulsation ( IABP ) is currently the most commonly used mechanical assist device for patients with cardiogenic shock due to acute myocardial infa rct ion .
Although there is only limited evidence by r and omised controlled trials , the current guidelines of the American Heart Association/American College of Cardiology and the European Society of Cardiology strongly recommend the use of the intra-aortic balloon counterpulsation in patients with infa rct ion-related cardiogenic shock on the basis of pathophysiological considerations as also non-r and omised trials and registry data .
OBJECTIVES To determine the effect of IABP versus non-IABP or other assist devices guideline compliant st and ard therapy , in terms of efficacy and safety , on mortality and morbidity in patients with acute myocardial infa rct ion complicated by cardiogenic shock . | 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 |
1,075 | 27,132,058 | 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 . | BACKGROUND About 10 % of reproductive-aged women suffer from endometriosis , a costly chronic disease causing pelvic pain and subfertility .
Laparoscopy is the gold st and ard diagnostic test for endometriosis , but is expensive and carries surgical risks .
Currently , there are no non-invasive or minimally invasive tests available in clinical practice to accurately diagnose endometriosis .
Although other review s have assessed the ability of blood tests to diagnose endometriosis , this is the first review to use Cochrane methods , providing an up date on the rapidly exp and ing literature in this field .
OBJECTIVES To evaluate blood biomarkers as replacement tests for diagnostic surgery and as triage tests to inform decisions on surgery for endometriosis .
Specific objectives include:1 .
To provide summary estimates of the diagnostic accuracy of blood biomarkers for the diagnosis of peritoneal , ovarian and deep infiltrating pelvic endometriosis , compared to surgical diagnosis as a reference st and ard.2 .
To assess the diagnostic utility of biomarkers that could differentiate ovarian endometrioma from other ovarian masses . | 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 sample s obtained from 89 women without endometriosis and 165 women with endometriosis ( histologically confirmed ) undergoing laparoscopies for infertility with or without pelvic pain . Data were analyzed using least squares support vector machines and were divided r and omly ( 100 times ) into a training data set ( 70 % ) and a test data set ( 30 % ) . RESULTS : Minimal-to-mild endometriosis was best predicted ( sensitivity 75 % , 95 % confidence interval [ CI ] 63–89 ; specificity 86 % , 95 % CI 71–94 ; positive predictive value 83.6 % , negative predictive value 78.3 % ) using a model based on five peptide and protein peaks ( range 4.898–14.698 m/z ) in menstrual phase sample s. Moderate-to-severe endometriosis was best predicted ( sensitivity 98 % , 95 % CI 84–100 ; specificity 81 % , 95 % CI 67–92 ; positive predictive value 74.4 % , negative predictive value 98.6 % ) using a model based on five other peptide and protein peaks ( range 2.189–7.457 m/z ) in luteal phase sample s. The peak with the highest intensity ( 2.189 m/z ) was identified as a fibrinogen & bgr;-chain peptide . Ultrasonography-negative endometriosis was best predicted ( sensitivity 88 % , 95 % CI 73–100 ; specificity 84 % , 95 % CI 71–96 ) using a model based on five peptide peaks ( range 2.058–42.065 m/z ) in menstrual phase sample s. CONCLUSION : A noninvasive test using proteomic analysis of plasma sample s obtained during the menstrual phase enabled the diagnosis of endometriosis undetectable by ultrasonography with high sensitivity and specificity . LEVEL OF EVIDENCE : Background : We investigated possible biomarkers for endometriosis ( EM ) using the ClinProt technique and proteomics methods . Methods : We enrolled 50 patients with EM , 34 with benign ovarian neoplasms and 40 healthy volunteers in this study . Serum proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry ( MS ) combined with weak cationic exchange ( WCX ) magnetic beads . Possible biomarkers were analyzed by a r and om and repeat pattern model-validation method that we design ed , and ClinProtools software , results were refined using online liquid chromatography-t and em MS . Results : We found a cluster of 5 peptides ( 4210 , 5264 , 2660 , 5635 , and 5904 Da ) , using 3 peptides ( 4210 , 5904 , 2660 Da ) to discriminate EM patients from healthy volunteers , with 96.67 % sensitivity and 100 % specificity . We selected 4210 and 5904 m/z , which differed most between patients with EM and controls , and identified them as fragments of ATP1B4 , and the fibrinogen alpha ( FGA ) isoform 1/2 of the FGA chain precursor , respectively . Conclusions : ClinProt can identify EM biomarkers , which – most notably – distinguish even early-stage or minimal disease . We found 5 stable peaks at 4210 , 5264 , 2660 , 5635 , and 5904 Da as potential EM biomarkers , the strongest of which were associated with ATP1B4 ( 4210 Da ) and FGA ( 5904 Da ) ; this indicates that ATP1B4 and FGA are associated with EM pathogenesis STUDY QUESTION Can plasma microRNAs be used as a non-invasive diagnostic test for the detection of endometriosis ? SUMMARY ANSWER Plasma miR-17 - 5p , miR-20a and miR-22 are down-regulated in women with endometriosis compared with those without endometriosis in mainl and China . WHAT IS KNOWN ALREADY There is currently a pressing need to develop a non-invasive diagnostic test for endometriosis . Altered circulating microRNA profiles have already been linked to various disease states . STUDY DESIGN , SIZE , AND DURATION This was a prospect i ve laboratory study in a tertiary-referral university hospital in Beijing , PR China , between January 2012 and May 2012 . Twenty-three women with histologically proven endometriosis and 23 endometriosis-free controls were enrolled in this study . PARTICIPANTS / MATERIAL S , SETTING , AND METHODS Laparoscopic inspection of the abdominopelvic cavity was performed for each patient , and peripheral blood sample s were collected before laparoscopy . Microarray-based microRNA expression profiling was used to identify differentially expressed microRNAs in plasma sample s between women with and without endometriosis , and quantification of selected microRNAs was performed using quantitative RT-PCR . MAIN RESULTS AND THE ROLE OF CHANCE Twenty-seven microRNAs were differentially expressed between women with and without endometriosis , of which six microRNAs ( miR-15b-5p , miR-17 - 5p , miR-20a , miR-21 , miR-22 and miR-26a ) were selected for validation . MiR-17 - 5p , miR-20a and miR-22 were significantly down-regulated in women with endometriosis compared with controls ( P = 0.011 , 0.0020 and 0.0002 , respectively ) , yielding an area under the receiver operator characteristics curve of 0.74 [ 95 % confidence interval ( CI ) : 0.58 - 0.90 ] , 0.79 ( 95 % CI : 0.65 - 0.93 ) and 0.85 ( 95 % CI : 0.71 - 0.98 ) in discriminating endometriosis from controls , respectively . LIMITATIONS AND REASONS FOR CAUTION Our sample size was small and all cases were rAFS stage III-IV , which may limit generalization of plasma microRNAs for early diagnosis of endometriosis . Moreover , only six microRNAs were selected for validation . WIDER IMPLICATION S OF THE FINDINGS Plasma microRNAs provide a promising opportunity for detection of endometriosis Pelvic endometriosis is an immune-related chronic inflammatory disease , characterized by ectopic implants of endometrium in the peritoneal cavity and associated with increased secretion of proinflammatory cytokines and neoangiogenesis . Leptin , the adipocyte-derived hormone , has been shown to have a role in food intake , basal metabolism , and reproductive function . Leptin levels are dynamically regulated , being elevated by inflammatory mediators and reduced by starvation . Leptin itself can influence the proinflammatory immune responses of CD4 + T lymphocytes , and reports have also shown this hormone to be an angiogenic factor in vitro and in vivo . We investigated whether leptin concentrations in serum and peritoneal fluid ( PF ) differed between 13 patients with different stages of endometriosis and 15 age- and body mass index-matched controls . We found a statistically significant ( P < 0.05 ) increase in leptin levels in serum ( 30.3 + /- 14.8 ng/mL ) and PF ( 35.9 + /- 17.4 ng/mL ) of patients with endometriosis , compared with our control population ( serum , 15.6 + /- 8.4 ; PF , 17.5 + /- 7.2 ng/mL ) . Regression equations , relating leptin to body mass index , were also significantly different in endometriosis patients , compared with controls . Higher levels of leptin were observed in the earlier stages of endometriosis than advanced-stage disease . These data suggest that the proinflammatory and neoangiogenic actions of leptin may contribute to the pathogenesis of endometriosis STUDY QUESTION Can prostagl and in E(2 ) ( PGE(2 ) ) in menstrual and peritoneal fluid ( PF ) promote bacterial growth in women with endometriosis ? SUMMARY ANSWER PGE(2 ) promotes bacterial growth in women with endometriosis . WHAT IS KNOWN ALREADY Menstrual blood of women with endometriosis is highly contaminated with Escherichia coli ( E. coli ) compared with that of non-endometriotic women : E. coli-derived lipopolysaccharide ( LPS ) promotes the growth of endometriosis . STUDY DESIGN , SIZE AND DURATION Case-controlled biological research with a prospect i ve collection of body fluids and endometrial tissues from women with and without endometriosis with retrospective evaluation . PARTICIPANTS / MATERIAL S , SETTING AND METHODS PF and sera were collected from 58 women with endometriosis and 28 women without endometriosis in an academic research laboratory . Menstrual blood was collected from a proportion of these women . Macrophages ( Mφ ) from PF and stromal cells from eutopic endometria were isolated in primary culture . The exogenous effect of PGE(2 ) on the replication of E. coli was examined in a bacterial culture system . Levels of PGE(2 ) in different body fluids and in the culture media of Mφ and stromal cells were measured by ELISA . The effect of PGE(2 ) on the growth of peripheral blood lymphocytes ( PBLs ) was examined . MAIN RESULTS AND THE ROLE OF CHANCE The PGE(2 ) level was 2 - 3 times higher in the menstrual fluid ( MF ) than in either sera or in PF . A significantly higher level of PGE(2 ) was found in the MF and PF of women with endometriosis than in control women ( P < 0.05 for each ) . Exogenous treatment with PGE(2 ) dose dependently increased E. coli colony formation when compared with non-treated bacteria . PGE(2)-enriched MF was able to stimulate the growth of E. coli in a dilution-dependent manner ; this effect was more significantly enhanced in women with endometriosis than in control women ( P < 0.05 ) . PGE(2 ) levels in the culture media of LPS-treated Mφ/stromal cells were significantly higher in women with endometriosis than in non-endometriosis ( P < 0.05 for each ) . Direct application of PGE(2 ) and culture media derived from endometrial Mφ or stromal cells significantly suppressed phytohemagglutinin-stimulated growth of PBLs . LIMITATIONS AND REASONS FOR CAUTION Further studies are needed to examine the association between PGE(2)-stimulated growth of E. coli and endotoxin level and to investigate the possible occurrence of sub- clinical infection within vaginal cavity . WIDER IMPLICATION S OF THE FINDINGS Our findings may provide some new insights to underst and the physiopathology or pathogenesis of the mysterious disease endometriosis and may hold new therapeutic potential . STUDY FUNDING /COMPETING INTEREST(S ) This work was supported by grants-in-aid for Scientific Research from the Ministry of Education , Sports , Culture , Science and Technology of Japan . There is no conflict of interest related to this study . TRIAL REGISTRATION NUMBER Not applicable BACKGROUND In order to test our hypothesis that endometriosis is associated with abnormal expression of telomerase and telomere lengthening in endometrium , we assessed endometrial expression of the human telomerase enzyme and telomere length ( TL ) . METHODS This prospect i ve pilot study , included 29 women with symptomatic , surgically diagnosed endometriosis ( Group 1 ) and 27 healthy , fertile , symptom-free women without endometriosis ( Group 2 , confirmed by laparoscopy ) . Seventeen women in Group 1 and 15 women in Group 2 had endometrial biopsies taken on Day 21 + /- 2 of the cycle . A further 12 women in each group were biopsied on Day 26 + /- 2 . Telomerase and estrogen receptor beta ( ERbeta ) expression was evaluated by immunohistochemistry . Mean TL was determined by quantitative PCR . RESULTS The endometria of fertile healthy women showed either weak or no telomerase immunoreactivity throughout the luteal phase . Immunostaining for telomerase was significantly increased during the implantation window and the premenstrual endometria of women with endometriosis ( P < 0.0001 ) . This was associated with a loss of stromal and vascular ERbeta immunostaining ( P < 0.05 ) . The mean TL were significantly longer in endometria of women with endometriosis during the implantation window ( P = 0.005 ) , indicating the biological relevance of our novel finding of telomerase in benign endometrium . There was positive correlation of the circulating estradiol with peripheral blood TL in women . CONCLUSIONS We speculate that aberrant endometrial expression of telomerase mediates alterations in cell fate that enhance proliferation , contributing to the pathogenesis of endometriosis Background Low concentrations of nitric oxide ( NO ) are necessary for the biology and physiology of spermatozoa , but high levels of NO are toxic and have negative effects on sperm functions . Although several studies have considered the relationship between infertility and semen NO concentrations , no study on the effects of asthenospermia treatments such as oral zinc supplementation on concentrations of NO , which are important in fertility , has been reported . Studies have shown that oral zinc supplementation develops sperm count , motility and the physical characteristics of sperm in animals and in some groups of infertile men . The present study was conducted to study the effect of zinc supplementation on the quantitative and qualitative characteristics of semen , along with enzymes of the NO pathway in the seminal plasma of asthenospermic patients . Methods Semen sample s were obtained from 60 fertile and 60 asthenozoospermic infertile men of matched age . The subfertile group was treated with zinc sulfate ; each participant took two capsules ( 220 mg per capsule ) per day for 3 months . Semen sample s were obtained ( before and after zinc sulfate supplementation ) . After liquefaction of the seminal fluid at room temperature , routine semen analyses were performed . The stable metabolites of NO ( nitrite ) in seminal plasma were measured by nitrophenol assay . Arginase activity and NO synthase activity were measured spectrophotometrically . Results Peroxynitrite levels , arginase activity , NO synthase activity and various sperm parameters were compared among fertile controls and infertile patients ( before and after treatment with zinc sulfate ) . Peroxynitrite levels and NO synthase activity were significantly higher in the infertile patients compared to the fertile group . Conversely , arginase activity was significantly higher in the fertile group than the infertile patients . Peroxynitrite levels , arginase activity and NO synthase activity of the infertile patient were restored to normal values after treatment with zinc sulfate . Volume of semen , progressive sperm motility percentage and total normal sperm count were increased after zinc supplementation . Conclusions Treatment of asthenospermic patients with zinc supplementation leads to restored peroxynitrite levels , arginase activity and NO synthase activity to normal values and gives a statistically significant improvement of semen parameters compared with controls . Trial registration Clinical Trials.gov identifier : ObjetiveThrombospondin-1 serum levels is correlate with pelvic pain in patients with ovarian endometriosis . Patients Thrombospondin-1 serum levels were prospect ively analysed in 51 patients ( group A asymptomatic patients or patients presenting mild dysmenorrhea and 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 thrombospondin-1 serum levels and pelvic pain . Results From 56 patients , five cases were ultimateley excluded , because the histological diagnosis was other than cystic ovarian endometriosis ( 2 teratomas and 3 haemorragic cysts ) . The mean thrombospondin-1 serum levels in group A was 256,69 pg/ml_+37,07 and in group B was 291,41 pg/ml + 35,59 . Conclusion Pain symptoms in ovarian endometriosis is not correlated with thrombospondin-1 serum levels OBJECTIVE To compare high-sensitivity C-reactive protein ( hs-CRP ) with CRP as a soluble serum marker for the diagnosis of women with endometriosis . DESIGN Prospect i ve nonr and omized controlled trial ( Canadian Task Force classification II-1 ) . SETTING University hospital . PATIENT(S ) Eighty-two women were laparoscopically evaluated . No endometriosis was diagnosed in 34 women ( the non-E group ) . Endometriosis was confirmed by histology in 48 women ( the E group ) . Eighty-two women did not undergo laparoscopic evaluation ( the unknown-E group ) . Afterward , the women were staged according to the revised American Society for Reproductive Medicine criteria ( r-ASRM ) . INTERVENTION(S ) CRP and hs-CRP were measured initially before laparoscopy . MAIN OUTCOME MEASURE(S ) The hs-CRP and CRP levels and the correlation of those parameters with the stage of the disease . RESULT ( S ) There was a trend toward higher CRP levels and higher hs-CRP levels in the E group , while the lowest levels of both markers were found in the non-E group . There was a significantly lower hs-CRP level in the non-E group in comparison with the CRP level in this group . No differences between the different stages of the disease were found with either marker . CONCLUSION ( S ) Measurement of the two markers did not appear to be advantageous for the diagnosis of endometriosis independent of the stage of the disease . Nevertheless , a very low hs-CRP level might serve as a marker for an absence of endometriosis OBJECTIVE To evaluate soluble Fas lig and concentrations in serum and peritoneal fluid from women with endometriosis and from fertile controls without endometriosis , and to study levels of soluble Fas lig and in conditioned media of cultured endometrial stromal cells . DESIGN Prospect i ve , experimental trial . SETTING Two academic IVF centers . PATIENT(S ) Twenty-nine fertile women without endometriosis and 57 infertile women with endometriosis ( 32 with stage I or II disease and 25 with stage III or IV disease ) . MAIN OUTCOME MEASURE(S ) Enzyme-linked immunosorbent assay was used to measure soluble Fas lig and concentrations in paired sample s of serum and peritoneal fluid from women with and without endometriosis . Concentrations were also measured in conditioned media of cultured endometrial stromal cells at basal conditions and after stimulation with interleukin-8 ( 0.001 - 10 ng/mL ) and tumor necrosis factor-alpha ( 1 - 10 ng/mL ) . RESULT ( S ) Compared with fertile controls and women with early-stage of endometriosis , women with moderate to severe endometriosis had elevated serum ( 87.2 + /- 6.4 , 88.2 + /- 6.9 , and 162.3 + /- 7.8 pg/mL , respectively ) and peritoneal fluid ( 81.0 + /- 6.0 , 80.5 + /- 6.8 , and 166.2 + /- 10.3 pg/mL , respectively ) concentrations of soluble Fas lig and . Serum levels of soluble Fas lig and positively correlated with levels in peritoneal fluid . Comparison of patients in the same menstrual cycle in each group revealed that increased levels of soluble Fas lig and in patients with advanced endometriosis were not attributable to the difference in cycle phases . Soluble Fas lig and was not detected in conditioned media of endometrial stromal cells under baseline conditions or after stimulation . CONCLUSION ( S ) Serum and peritoneal fluid of women with moderate to severe endometriosis contain elevated concentrations of soluble Fas lig and compared to women with minimal or mild endometriosis and women without endometriosis . These findings suggest a role for apoptotic dysregulation in the pathophysiology of endometriosis Background In women with pelvic mass , cancer antigen 125 ( CA125 ) had not achieved satisfactory sensitivity and specificity in the detection of ovarian cancer , particularly in patients with underlying endometriosis . The aim of this study was to determine the diagnostic potential of human epididymal protein 4 ( HE4 ) , the combination of HE4+CA125 , and the Risk of Ovarian Malignancy Algorithm ( ROMA ) for patients with pelvic mass , particularly in differentiating endometriosis from carcinoma . Methods A prospect i ve cross-sectional study was conducted at the Clinic for Gynecology and Obstetrics , Clinical Center of Serbia . Serum sample s were obtained preoperatively from 108 women undergoing surgery for pelvic mass ; 29 of them had ovarian carcinoma , and 79 had a nonmalignant ovarian disease ( 39 with benign tumor , 20 with endometriosis , 20 healthy controls ) . Sera were analyzed for the levels of HE4 and CA125 and were then compared with the final pathologic results . The diagnostic performance of HE4 and CA125 was estimated using receiver operating characteristic curve and area under the receiver operating characteristic curve . Results The level of HE4 and CA125 was significantly higher among the patients with malignant tumors , compared with patients with nonmalignant disease . At the predefined specificity of 95 % , HE4 and CA125 showed sensitivity of 65.5 % and 58.6 % , respectively , whereas the combination of HE4+CA125 reached 68.9 % at the same specificity . Importantly , the level of HE4 did not differ significantly between the patients with endometriosis and with other nonmalignant diseases ( which was not the case with CA125 ) . Risk of Ovarian Malignancy Algorithm classified 96 % of benign premenopausal cases as at low risk for ovarian cancer . Conclusions HE4 showed satisfactory capability of distinguishing endometriosis from ovarian cancer , which CA125 lacked . The Risk of Ovarian Malignancy Algorithm score proved to be useful in excluding malignant diagnosis in premenopausal women Objective To investigate the level of cytokines and immune cells in the peripheral blood ( PB ) and peritoneal fluid ( PF ) of different stages of endometriosis . Methods A prospect i ve study was conducted to include 97 women with ( n 60 ) and without ( n 37 ) histopathologically confirmed endometriosis . Based on rASRM classification , stage I/II and stage III/IV were categorized as early- and late-staged endometriosis . Prior to surgery , 10 ml of blood was withdrawn from antecubital vein and serum was obtained . Aliquots were made and stored at −70 ° C until assayed for cytokines . PF was aspirated from the pouch of Douglas . Peripheral and PF sample s were analyzed by ELISA in terms of IL-2 , IL-4 , IL-10 and IFN-γ . Determinations of T helper , T suppressor , NK , and B cells were assessed by using cluster determinant-3 ( CD-3 ) , CD4 , CD8 , CD25 , CD28 , CD45 , CD16 , CD23 and antibodies against early T cell activation antigens such as CD45RA/CD45RO , CD-69 and late activation antigens such as HLA-DR . A multiparameter flow cytometry was applied to detect the cell activation antigen expression . Results In terms of cytokine levels in PB and PF ’s of control group and early- and late-staged endometriosis cases , no significant difference was depicted in the cytokine levels ( p > 0.05 ) . Levels of immune cells did not differ between three groups ( p > 0.05 ) . Conclusions The result of this study did not show any significant difference in PB and PF cytokine and lymphocyte subgroups between normal and early- and late-staged endometriosis In group of 16 patients with internal endometriosis verified by histopathological investigations following immunological indices in peripheral blood were estimated : 1 ) number of leucocytes and neutrophils , 2 ) neutrophil adherence to fibres , 3 ) phagocytic activity of neutrophil using the latex granules , 4 ) concentration of immunological complexes in serum . The results were compared with those in control group ( 20 healthy women ) . In patients with internal endometriosis compared to control group the increase of the number of leucocytes and neutrophils and decrease of phagocytic activity of neutrophils were observed Endometriosis is clinical ly associated with pelvic pain and infertility , with implantation failure strongly suggested as an underlying cause for the observed infertility . Eutopic endometrium of women with endometriosis provides a unique experimental paradigm for investigation into molecular mechanisms of reproductive dysfunction and an opportunity to identify specific markers for this disease . We applied paralleled gene expression profiling using high-density oligonucleotide microarrays to investigate differentially regulated genes in endometrium from women with vs. without endometriosis . Fifteen endometrial biopsy sample s ( obtained during the window of implantation from eight subjects with and seven subjects without endometriosis ) were processed for expression profiling on Affymetrix Hu95A microarrays . Data analysis was conducted with GeneChip Analysis Suite , version 4.01 , and GeneSpring version 4.0.4 . Nonparametric testing was applied , using a P value of 0.05 , to assess statistical significance . Of the 12,686 genes analyzed , 91 genes were significantly increased more than 2-fold in their expression , and 115 genes were decreased more than 2-fold . Unsupervised clustering demonstrated down-regulation of several known cell adhesion molecules , endometrial epithelial secreted proteins , and proteins not previously known to be involved in the pathogenesis of endometriosis , as well as up-regulated genes . Selected dysregulated genes were r and omly chosen and vali date d with RT-PCR and /or Northern/dot-blot analyses , and confirmed up-regulation of collagen alpha2 type I , 2.6-fold ; bile salt export pump , 2.0-fold ; and down-regulation of N-acetylglucosamine-6-O-sulfotransferase ( important in synthesis of L-selectin lig and s ) , 1.7-fold ; glycodelin , 51.5-fold ; integrin alpha2 , 1.8-fold ; and B61 ( Ephrin A1 ) , 4.5-fold . Two-way overlapping layer analysis used to compare endometrial genes in the window of implantation from women with and without endometriosis further identified three unique groups of target genes , which differ with respect to the implantation window and the presence of disease . Group 1 target genes are up-regulated during the normal window of implantation but significantly decreased in women with endometriosis : IL-15 , proline-rich protein , B61 , Dickkopf-1 , glycodelin , N-acetylglucosamine-6-O-sulfotransferase , G0S2 protein , and purine nucleoside phosphorylase . Group 2 genes are normally down-regulated during the window of implantation but are significantly increased with endometriosis : semaphorin E , neuronal olfactomedin-related endoplasmic reticulum localized protein mRNA and Sam68-like phosphotyrosine protein alpha . Group 3 consists of a single gene , neuronal pentraxin II , normally down-regulated during the window of implantation and further decreased in endometrium from women with endometriosis . The data support dysregulation of select genes leading to an inhospitable environment for implantation , including genes involved in embryonic attachment , embryo toxicity , immune dysfunction , and apoptotic responses , as well as genes likely contributing to the pathogenesis of endometriosis , including aromatase , progesterone receptor , angiogenic factors , and others . Identification and validation of selected genes and their functions will contribute to uncovering previously unknown mechanism(s ) underlying implantation failure in women with endometriosis and infertility , mechanisms underlying the pathogenesis of endometriosis and providing potential new targets for diagnostic screening and intervention OBJECTIVE To determine whether the surgical diagnosis of endometriosis can be predicted using symptoms , signs , and ultrasound findings . DESIGN Prospect i ve study ( study sample ) ; retrospective record review ( test sample ) . SETTING Hospital of Desio ( study sample ) and Mangiagalli Hospital ( test sample ) , Italy . PATIENT(S ) Ninety women scheduled to undergo laparoscopy or laparotomy ( study sample ) ; 120 women who underwent laparoscopy ( test sample ) . INTERVENTION The study sample group was interviewed before surgery about infertility and dysmenorrhea , dyspareunia , and noncyclic pelvic pain and each member had a pelvic examination and a transvaginal ultrasound . At surgery , endometriosis was noted . For the test sample , the same information was abstract ed from medical records after laparoscopy . MAIN OUTCOME MEASURE(S ) The ability of symptoms , signs , and ultrasound to predict endometriosis at surgery . A classification tree was developed with the study sample and evaluated with the test sample . RESULT ( S ) Ovarian endometriosis , but not nonovarian endometriosis , could be reliably predicted with noninvasive tools . Ultrasound and examination best predicted ovarian endometriosis , correctly classifying 100 % of cases with no false positive diagnoses in the study sample . Similar results were found in the test sample . CONCLUSION ( S ) Noninvasive tools may be used to identify women with ovarian , but not nonovarian endometriosis , with excellent agreement with surgical diagnosis OBJECTIVE We analyzed selected well-known and less well-known serum markers that have been proposed for diagnosis and severity assessment of endometriosis , in a case-control study . STUDY DESIGN This prospect i ve study was carried out in a Clinical Department of Gynecology in Iasi , Romania . Study participants included endometriosis patients , and controls in whom laparoscopy had excluded endometriosis . Each case and control was investigated for serum levels of CA125 , TNF , IL-1 , IL-6 and IL-8 . The data were correlated with clinical symptoms and revised American Fertility Society ( rAFS ) score and stage , and interpreted by Mann-Whitney U-test and ANOVA regression analysis . RESULTS Over the course of 1 year , 24 cases of endometriosis and 24 controls of matched age were selected . The rAFS stages were : stage I , 12.5 % ; stage II , 16.7 % ; stage III , 58.3 % ; and stage IV , 12.5 % . CA125 levels were over the cut-off of 35 IU/l in 54 % of patients ( versus 8 % of controls ) , averaging 67.5 ( CI95 : ±17.5 ) . The sensitivity and specificity were 54 % and 91 % , respectively , with a p value of < 0.001 ( statistically significant ) . For IL-6 , 71 % of cases and 87 % of controls were above the cut-off of 2 pg/ml , with an average of 11.83 ± 7 . The sensitivity and specificity were 71 % and 12 % , respectively , but the difference was not statistically significant , p = 0.071 . Other tested serum markers had no discrimination value . A correlation with severity of endometriosis was seen for CA125 ( p = 0.03 ) but not for IL-6 , by ANOVA . CONCLUSION CA125 correlated with endometriosis screening and severity , indicating its superiority as a marker for further , larger studies BACKGROUND This study aim ed to calculate costs and health-related quality of life of women with endometriosis-associated symptoms treated in referral centres . METHODS A prospect i ve , multi-centre , question naire-based survey measured costs and quality of life in ambulatory care and in 12 tertiary care centres in 10 countries . The study enrolled women with a diagnosis of endometriosis and with at least one centre-specific contact related to endometriosis-associated symptoms in 2008 . The main outcome measures were health care costs , costs of productivity loss , total costs and quality -adjusted life years . Predictors of costs were identified using regression analysis . RESULTS Data analysis of 909 women demonstrated that the average annual total cost per woman was € 9579 ( 95 % confidence interval € 8559-€10 599 ) . Costs of productivity loss of € 6298 per woman were double the health care costs of € 3113 per woman . Health care costs were mainly due to surgery ( 29 % ) , monitoring tests ( 19 % ) and hospitalization ( 18 % ) and physician visits ( 16 % ) . Endometriosis-associated symptoms generated 0.809 quality -adjusted life years per woman . Decreased quality of life was the most important predictor of direct health care and total costs . Costs were greater with increasing severity of endometriosis , presence of pelvic pain , presence of infertility and a higher number of years since diagnosis . CONCLUSIONS Our study invited women to report re source use based on endometriosis-associated symptoms only , rather than drawing on a control population of women without endometriosis . Our study showed that the economic burden associated with endometriosis treated in referral centres is high and is similar to other chronic diseases ( diabetes , Crohn 's disease , rheumatoid arthritis ) . It arises predominantly from productivity loss , and is predicted by decreased quality of life Adhesion molecules regulate the interaction of cells with the extracellular matrix and /or other cells . The intercellular adhesion molecule-1 ( ICAM-1 ; CD54 ) is a member of the immunoglobulin superfamily and expressed by several cell types , including leukocytes and endothelial cells . A circulating form of the usually membrane-bound molecule was identified and characterized in normal human serum and in sera from patients with endometriosis . In the present study , we established the serum-soluble ICAM-1 ( sICAM-1 ) levels in patients with endometriosis . We also studied the effect of danazol and leuprorelin acetate depot on the levels of sICAM-1 . Thirty-eight women , 18 - 45 years of age , with regular menses and documented pelvic endometriosis were recruited from a University Hospital setting . Twenty-two women with endometriosis were r and omly divided into two groups . Danazol ( 600 mg ) were given every day for 6 months , and 3.75 mg of leuprorelin acetate depot every 28 days for 6 months . Serum sICAM-1 concentrations were measured before , during and after treatment , and its quantitative determination was performed by an ELISA technique using a specific immunoassay . We found that ( 1 ) sICAM-1 levels were higher in women with endometriosis in comparison to healthy subjects ; ( 2 ) the 6 month treatment with danazol or leuprorelin acetate depot increased sICAM-1 levels ( P<0.001 ) ; ( 3 ) 3 months after termination of both treatments , sICAM-1 levels were unchanged . Although the mechanism leading to the increase of sICAM-1 needs to be further clarified , any benefits of medical treatment of endometriosis such as danazol or leuprorelin appear to be independent of changes in ICAM-1 serum levels OBJECTIVE To evaluate whether distinct patterns of serum proteins in symptomatic women are of value to predict endometriosis before laparoscopy . DESIGN Prospect i ve exploratory cohort study . SETTING Tertiary care center . PATIENT(S ) A total of 91 consecutive symptomatic patients suffering from dysmenorrhea , dyspareunia , chronic pelvic pain , or unexplained infertility . INTERVENTION(S ) Collection of serum sample s and a st and ardized protocol for patients ' history before laparoscopic diagnosis . MAIN OUTCOME MEASURE(S ) Protein expression was analyzed by mass spectrometric analysis according to surface-enhanced laser desorption/ionization time-of-flight mass spectrometry ( SELDI-TOF MS ) st and ards . The analysis of data was performed using a genetic algorithm ( ClinProTools 2.0 software ) and a rule-based decision-tree algorithm ( XLminer software ) . RESULT ( S ) A total of 90 out of 91 sample s were eligible for analysis . At laparoscopy , 51 of 90 patients ( 56.7 % ) exhibited endometriosis and 39 of 90 ( 43.3 % ) were disease free . Analyzing the serum sample s , the software revealed a unique selection of mass peaks between 2,000 and 20,000 Da , which allowed for discrimination between patients suffering from endometriosis and control subjects . Overall recognition capacity was 70.8 % , exhibiting a sensitivity of 81.3 % ( 95 % confidence interval [ CI ] 66.5 - 92.5 ) and a specificity of 60.3 % ( 95 % CI 46.1 - 74.2 ] ) using the genetic algorithm , and a sensitivity of 78.4 % and a specificity of 59.0 % using the rule-based decision-tree algorithm . CONCLUSION ( S ) These findings provide direct evidence that screening for serum protein patterns using SELDI-TOF MS before laparoscopy might be of discriminative value in the prediction of disease and partly confirms recently published data . However , in this prospect i ve setting , we found both low sensitivity and low specificity , which disqualifies the screening for serum protein patterns by SELDI-TOF MS as a " quick fix " diagnostic test The sensitivity and specificity of CA125 , as a sole serum marker of endometriosis , are not high enough for routine clinical assessment . To explore new markers for the diagnosis of endometriosis , serum autoantibodies in endometriotic patients were investigated employing a fibroblast cell line , two-dimensional ( 2D ) gel electrophoresis and Western blotting . Proteins reacting with serum autoantibodies by Western blotting were identified using MASCOT analysis . ELISAs were then prepared using recombinant proteins and titers of serum autoantibodies were determined in the endometriotic patients , disease controls , and healthy subjects . Among the autoantibodies identified , anti-syntaxin 5 ( STX5 ) autoantibody levels were significantly elevated in endometriotic patients . Sensitivity ( 53.6 % ) and accuracy ( 72.2 % ) of the serum anti-STX5 autoantibody assay were better than those of serum CA125 levels ( 36.2 % and 62.9 % , respectively ) for diagnosis . The sensitivity of anti-STX5 autoantibody was remarkably high in Stage II ( 80.0 % ) compared with that of CA125 ( 40.0 % ) . A combination assay of anti-STX5 autoantibody with CA125 improved the overall sensitivity to 69.6 % . We conclude that serum anti-STX5 autoantibody , which was discovered by a proteomic approach , is a potential new serum marker for the diagnosis of endometriosis . This initial study now requires validation by further clinical evaluation As the best-known tumor marker for ovarian carcinoma , CA 125 has also been commonly used to monitor patients with common benign gynecologic diseases such as endometriosis and leiomyoma . Both of these benign tumors are known to be at risk of developing into cancer . During the screening of an asymptomatic population with multiple tumor markers , including alpha-fetoprotein ( AFP ) , carcinoembryonic antigen ( CEA ) , prostate-specific antigen ( PSA ) , CA 125 , CA 19 - 9 , CA 15 - 3 , chromogranin A ( CgA ) , and squamous cell carcinoma antigen ( SCC ) , we have detected elevated tumor markers in 142 individuals ; 19 of them were diagnosed with endometriosis or leiomyoma or both . In addition to the detection of elevation of CA 125 in these benign tumors , elevated CA 19 - 9 or CgA was also found in these patients with endometriosis or leiomyoma . Many patients only had elevated CA 19 - 9 or CgA ; the elevation of CA 125 was not detected . It appears that instead of monitoring only CA 125 , as is traditionally done , multiple tumor markers , including CA 19 - 9 , CgA , and CA 125 , should be measured simultaneously in women with clinical disorders associated with the ovary or uterus in order to detect gynecologic benign tumors and in order to prevent further development of cancer OBJECTIVE To determine serum levels of TNF-alpha ( tumor necrosis factor alpha ) as a prediction of endometriosis . DESIGN Prospect i ve clinical case control study . SETTING Department of Obstetrics and Gynaecology and Department of Pathology , Jessenius Faculty Hospital , Kollarova 2 , Martin , Slovakia . METHODS The serum TNF-alpha was determined in women who underwent laparoscopy or laparotomy due to pelvic pain , infertility , dysmenorea or pelvic tumor . Endometriosis was confirmed histologically and classified by rAFS . RESULTS On the basis of entering criteria 65 women were enrolled in this study . In 61 cases serum level of TNF-alpha was evaluated . The average serum level of TNF-alpha in the endometriotic group was 73.847 pg/ml ( n=30 ) and without endometriosis was 21.089 pg/ml ( n=31 ) . We have found a significant statistical difference between the above mentioned groups in the medium levels of TNF-alpha ( p<0.0001 ) . We did not find statistical significance between TNF-alpha levels and in the group of women with endometriosis in relation to the stage of the disease ( I.-II . , III.-IV . , adenomyosis ) . At a cut-off level of TNF-alpha 30 pg/ml there was a 63.33 % sensitivity , 77.42 % specificity , a positive prediction value 73.07 % , and 68.57 % of negative predictive value . CONCLUSION TNF-alpha serum levels are good diagnostic markers of endometriosis in the spectrum of noninvasive methods PURPOSE OF INVESTIGATION By the comparison between most used tumor marker trend ( cancer antigen 125 : CA 125 and human epididymal secretory protein E4 : HE4 ) before and after laparoscopic surgery , the aim of the present study was to assess HE4 usefulness in ovarian benign cyst and endometrioma diagnosis . MATERIAL S AND METHODS Thirty-eight patients were enrolled in this prospect i ve study : 25 women underwent unilateral endometriosis ovarian cyst excision , 13 underwent benign ovarian cyst incision , and 26 were healthy controls . CA 125 and HE4 serum levels were estimated before surgery ( in the early proliferative phase of the cycle ) and one month after surgery . RESULTS A statistically significant decrease of CA 125 serum level was found after an endometrioma surgical excision but no decreases in HE4 serum level . CONCLUSION In patients with endometrioma , no alteration was found in HE4 serum levels before and after surgery , while CA125 serum levels decreased after surgery . HE4 may better distinguish a malign cyst from benign one , but it is not useful in the diagnosis of low risk endometrioma OBJECTIVE To identify molecular biomarkers for endometriosis in peripheral blood lymphocytes by using DNA microarrays . DESIGN Case-control . SETTING Multicenter academic research programs . PATIENT(S ) Premenopausal women with or without endometriosis , determined by obstetrics and gynecology specialists during surgery . Microarray analysis included six endometriosis patients and five controls ; 15 endometriosis patients and 15 controls were analyzed by using real-time reverse-transcription polymerase chain reaction ( RT-PCR ) . Patients with all disease stages were included . INTERVENTION(S ) Peripheral blood sample s were collected by venipuncture . MAIN OUTCOME MEASURE(S ) The expression levels of mRNAs in blood lymphocytes from endometriosis patients and controls were compared with those of a st and ard total RNA . Gene expression data were vali date d by real-time RT-PCR analysis . RESULT ( S ) A gene selection program identified genes that were differentially expressed in sample s from endometriosis patients . To vali date the gene expression data , the nine most discriminatory genes were analyzed by real-time RT-PCR . Two of the nine genes identified , IL2RG and LOXL1 , were shown to be significantly differentially expressed . CONCLUSION ( S ) This is the first report of genes that are differentially expressed in peripheral blood lymphocytes of patients with endometriosis , which may provide important clues regarding the pathogenesis of this disease . Moreover , they could be considered potential targets for noninvasive diagnostic assays for endometriosis and need to be vali date d in a larger population OBJECTIVE To determine Müllerian inhibiting substance ( MIS ) levels in follicular fluid ( FF ) and sera of IVF patients . DESIGN Prospect i ve study . SETTING Fertility center . PATIENT(S ) Sixty-six patients : 20 with tubal factor infertility , 17 with polycystic ovary syndrome ( PCOS ) , and 29 with endometriosis . INTERVENTION(S ) All patients underwent ovarian stimulation with hMG and /or FSH , as well as oocyte retrieval for IVF . MAIN OUTCOME MEASURE(S ) Follicular fluid and serum MIS levels and oocyte fertilization rates . RESULT ( S ) Levels of MIS in FF and sera of PCOS patients were significantly higher than those in tubal factor patients : 7.01 + /- 1.52 versus 1.65 + /- 0.23 ng/mL ( mean + /- SE ) and 2.97 + /- 0.52 versus 0.92 + /- 0.19 ng/mL , respectively . In endometriosis patients , follicular fluid and serum MIS levels were not significantly different from those in tubal factor patients . In PCOS patients , the percentage of immature oocytes retrieved ( 17.9 % + /- 5.0 % ) was significantly higher compared with tubal factor ( 1.5 % + /- 1.0 % ) and endometriosis ( 9.2 % + /- 2.3 % ) patients . The percentage of oocytes fertilize was significantly lower in PCOS patients ( 30.2 % + /- 5.3 % ) compared with tubal factor ( 62.2 % + /- 5.5 % ) and endometriosis ( 37.5 % + /- 5.7 % ) patients . CONCLUSION ( S ) Women with PCOS had higher serum and follicular fluid MIS levels , a higher percentage of immature oocytes , and lower fertilization rates than women with endometriosis or pelvic adhesions OBJECTIVE To investigate the hypothesis that soluble intercellular adhesions molecule-1 ( sICAM-1 ) may be used as a new serum marker of endometriosis . DESIGN Prospect i ve cohort study . SETTING An academic department specializing in gynecologic laparoscopy . PATIENT(S ) Consecutive series of 120 women of reproductive age who underwent laparoscopy for benign gynecologic conditions . INTERVENTION(S ) Data were collected on baseline clinical characteristics , and surgical and histologic diagnosis . MAIN OUTCOME MEASURE(S ) Serum concentration of both CA125 and sICAM-1 . RESULT ( S ) Endometriosis was documented in 71 women ( stage I to II in 24 cases and stage III to IV in 47 cases ) . Serum levels of sICAM-1 were only slightly but not significantly increased in women with endometriosis compared with women without the disease . However , serum concentration of sICAM-1 in the 21 women who were found to have deep peritoneal endometriosis was significantly enhanced when compared with both women without the disease and those with other forms of endometriosis . The sensitivity and specificity of sICAM-1 in detecting deep peritoneal endometriosis were 0.19 and 0.97 , respectively ; whereas those of CA125 were 0.14 and 0.92 , respectively . When both parameters were used concomitantly , the sensitivity and specificity were 0.28 and 0.92 , respectively . CONCLUSION ( S ) Although the present study tends to support a role of sICAM-1 in the development of endometriosis , serum concentrations of this molecule do not seem to be an effective indicator for the diagnosis of either the early or advanced stage of endometriosis . However , an integrated clinical and laboratory approach using both CA125 and sICAM-1 may be helpful in specifically identifying women with deep peritoneal endometriosis BACKGROUND To estimate the value of CA-125 for the diagnosis of endometriosis in women with dysmenorrhea , as well as its significance in monitoring therapy and follow-up . METHODS One hundred and fifty-seven women undergoing laparoscopy for dysmenorrhea were prospect ively studied for serum CA-125 concentration . For those with advanced endometriosis receiving danazol treatment after conservative surgery , CA-125 was also determined every month during medication and once every 12 months after treatment . RESULTS The sensitivity and specificity of serum CA-125 for the diagnosis of endometriosis were 61.1 % and 87.5 % respectively . Elevated CA-125 ( > 35 U/ml ) was noted in 65/75 cases ( 86.70 % ) with advanced endometriosis , but in only 15/56 patients ( 26.8 % ) with minimal and mild endometriosis . Although there were significantly higher CA-125 levels in unmarried women , and a negative correlation ( r=-0.1970 , p=0.0284 ) between CA-125 and parity , there was no statistical difference in incidence of endometriosis by the status of marriage or parity . Ten women with advanced endometriosis were found with persistent endometriosis by laparoscopy during danazol treatment , even though they tested with normal CA-125 levels ( < 35 U/ml ) at that time . Fifteen patients had elevated CA-125 levels before and one year after therapy , and were confirmed with recurrence of endometriosis by laparoscopy . Nine women with elevated CA-125 levels before treatment , were found without recurrence of endometriosis and had normal CA-125 levels one year after therapy . CONCLUSION For endometriosis , CA-125 is a valuable adjuvant in the follow-up of recurrence in patients with advanced endometriosis and initially elevated CA-125 levels . It is not an effective screening tool for patients with dysmenorrhea , or for monitoring therapy . There was no significant correlation between the development of endometriosis and reproductive factors The circulating concentration of endometrial protein PP14 varied during the menstrual cycle in patients with endometriosis . The highest levels were found on days 1 to 4 of the cycle ( 176 + /- 123 micrograms/L ; mean + /- SD ) , and the lowest on days 5 to 20 ( 44.1 + /- 29.7 micrograms/L ) . Rising levels were observed on days 21 to 30 ( 58.3 + /- 62.6 micrograms/L ) . On days 5 to 20 ( i.e. , during period of the lowest levels ) patients with advanced endometriosis had higher PP14 levels ( 63.9 + /- 39.0 micrograms/L ) than those with mild endometriosis ( 29.3 + /- 18.2 micrograms/L ; p less than 0.01 ) . Patients with mild endometriosis had slightly higher serum PP14 levels than apparently healthy control subjects ( p less than 0.05 ) , but overlapping of values between the two groups is remarkable . Conservative surgical elimination of endometriosis significantly decreased the serum PP14 levels . Treatment with danazol ( 600 mg/day ) , or with medroxyprogesterone acetate ( 100 mg/day ) after laparoscopy also result ed in significant decreases in the serum PP14 concentration . After 6 months of treatment , conservative surgery in combination with danazol or with medroxyprogesterone acetate , yielded more pronounced declines in serum PP14 level than conservative surgery plus placebo . No significant difference was observed between the effects of danazol and medroxyprogesterone acetate . We conclude that endometriosis tissue contributes to the circulating PP14 level , and the decline in PP14 level during danazol and medroxyprogesterone acetate treatments reflects regression of intrauterine and ectopic endometrial tissues OBJECTIVE To measure the levels of antigamete antibodies in serum and peritoneal fluid of women with endometriosis and /or infertility . DESIGN Antibody activity against human sperm and porcine oocytes was analyzed in selected subgroups of women . SETTING Clinic of reproduction . PATIENT(S ) Women with endometriosis and /or infertility . INTERVENTION(S ) No treatment was implemented before peritoneal fluid and blood sample collection . MAIN OUTCOME MEASURE(S ) Quantitative ELISA . RESULT ( S ) Four groups of women ( n = 98 ) were analyzed for the presence of antizona and antisperm antibodies : infertile with endometriosis ( n = 30 ) , idiopathic infertility ( n = 28 ) , fertile with endometriosis ( n = 20 ) , and healthy fertile controls ( n = 20 ) . Antibodies were analyzed simultaneously in serum and peritoneal fluid . No statistically significant differences in antibody levels were detected in serum sample s among the analyzed groups . The median values for antizona and antisperm antibodies in peritoneal fluid were significantly higher in women with idiopathic infertility than in the control group . In women with unexplained infertility , a high degree of correlation ( Spearman ) was found between the presence of antizona antibodies in peritoneal fluid and serum ( r = 0.579 ) . A positive predictive value of 80 % was calculated for the presence of antizona antibodies ( > 5 ng/oocyte ) in the peritoneal fluid of patients with infertility . CONCLUSION ( S ) Antizona antibodies locally produced in the peritoneal fluid have diagnostic value for infertility status ; however , they can not be treated as a marker or prognostic factor for minimal endometriosis and /or its treatment OBJECTIVE To obtain histologic confirmation of lesions suspected of endometriosis at laparoscopy . DESIGN Prospect i ve clinical study . SETTING Patients in an academic hospital . PATIENT(S ) Women of reproductive age who complained of chronic pelvic pain . INTERVENTION(S ) A total of 122 biopsies were obtained from 54 patients undergoing laparoscopy , after exclusion of other potential causes of pelvic pain . MAIN OUTCOME MEASURE(S ) Lack of consistency between laparoscopic and histologic diagnosis of endometriosis , in particular for minimal/mild stages . RESULTS Endometriosis was confirmed by histology in 54 % of the excised lesions . Diagnosis was more often confirmed among classic lesions than for all atypical lesions considered together . The histologic diagnosis of fibrosis was the most common among those biopsies , which lacked the presence of endometriosis . The revised American Fertility Association ( AFS ) scores before and after histologic confirmation differed significantly . In particular , 20 patients in either revised AFS class I or II were down- grade d to stage 0 . No single anatomical site turned out to be particularly prone to misdiagnosis at laparoscopy , in comparison to the other sites . CONCLUSION ( S ) These results confirm the need of histologic confirmation to obtain a diagnosis of endometriosis . However , the clinical impact of such findings remains a matter of debate BACKGROUND Recent studies have proposed the measurement of CA 19 - 9 and IL-6 as an alternative to CA 125 as markers for endometriosis . This study was performed in order to verify the clinical value of serum CA 125 , CA 19 - 9 and IL-6 levels , either by themselves or combined , in the detection of the disease . METHODS In a prospect i ve cohort study , serum concentrations of CA 125 , CA 19 - 9 and IL-6 were measured in a consecutive series of 80 women of reproductive age who underwent laparoscopy for benign gynaecological pathologies . RESULTS Endometriosis was documented in 45 women ( stage I-II in 14 cases and stage III-IV in 31 cases ) . Patients with endometriosis had significantly higher levels of CA 125 than controls [ 23.4 IU/ml ( 13.3 - 37.6 ) versus 11.4 IU/ml ( 9.1 - 18.5 ) , P < 0.001 ) ] . Conversely , women with and without the disease were shown to have similar levels of both IL-6 pg/ml [ 0.6 ( undetectable-1.4 ) versus 1.0 pg/ml ( 0.4 - 1.9 ) , P = 0.09 ] and CA 19 - 9 [ 9.8 IU/ml ( 4.5 - 20.8 ) versus 7.4 IU/ml ( 2.8 - 11.5 ) , P = 0.11 ] . The area under the receiver operating characteristics curve result ed in a statistically significant difference from the null hypothesis only for CA 125 ( P < 0.001 ) . Sensitivity and specificity of CA 125 were 27 and 97 % respectively and were higher than those related to CA 19 - 9 and IL-6 . Concomitant use of the three dosages led to a sensitivity and a specificity of 42 and 71 % respectively . CONCLUSIONS The concomitant dosage of CA 125 , CA 19 - 9 and IL-6 does not add significant information in respect to the CA 125 test alone in diagnosing either early or advanced stages of endometriosis OBJECTIVE To investigate the effects of danazol and leuprorelin acetate on CA-125 levels during treatment for endometriosis . PATIENTS AND METHODS Fifty women with laparoscopically diagnosed and treated endometriosis , and 50 women without pelvic disease as a control group . Following surgical treatment , 35 women with endometriosis were divided into two groups . The first group ( 20 women ) received 200 mg danazol three times daily for 6 months ; the second group ( 15 women ) received 3.75 mg leuprorelin acetate depot every 28 days for 6 months . Serum CA-125 levels were measured before medical treatment , during the last 15 days of the 6-month treatment course , and 3 months after treatment . RESULTS Serum CA-125 levels were significantly higher in women with endometriosis than in women in the control group . Before treatment , CA-125 levels in patients with stage III/IV endometriosis were significantly higher than those in stage I/II endometriosis . Six months of danazol or leuprorelin acetate depot treatment decreased serum CA-125 levels . Three months after stopping danazol , CA-125 levels remained significantly lower than pretreatment levels . On the other h and , 3 months after stopping leuprorelin acetate , CA-125 levels returned to pretreatment levels . CONCLUSIONS ( a ) Danazol and leuprorelin acetate are equally effective in the treatment of endometriosis . ( b ) Moreover , the results support the view that the determination of CA-125 levels may assist in evaluating progress of endometriosis treatment OBJECTIVES To evaluate a clinical examination during menstruation and plasma CA-125 concentrations to diagnose deep endometriosis . DESIGN Prospect i ve study in 61 women scheduled for a laparoscopy , a retrospective study in 140 women with deep endometriosis , and a clinical validation study in 16 women with painful pelvic nodularities during menstruation . SETTING University Hospital Gasthuisberg , a tertiary referral center . RESULTS In the retrospective study , deep endometriosis was detected by routine clinical examination in only 36 % of women . Lesions infiltrating deeper than 15 mm were detected in 50 % . In the prospect i ve study pelvic nodularities were detected by routine clinical examination in 4 women but were detected in 22 by clinical examination during menstruation . The latter was highly reliable to diagnose deep endometriosis , cystic ovarian endometriosis , and cul-de-sac obliteration . CA-125 concentrations were higher during menstruation and correlated with deep endometriosis and with deep and cystic ovarian endometriosis . Nodularities at clinical examination or follicular phase CA-125 concentrations > 35 U/mL are useful to decide that a bowel preparation should be given , achieving a sensitivity of 87 % and a specificity of 83 % . In the clinical validation study , deep endometriosis was found in 14 of 16 women . CONCLUSION Clinical examination during menstruation can diagnose reliably deep endometriosis , cystic ovarian endometriosis , or cul-de-sac adhesions . This test , preferentially combined with a follicular phase CA-125 assay , should be used to decide whether a preparation for bowel surgery should be given OBJECTIVE To assess the role of transvaginal ultrasonography combined with CA-125 plasma levels in the diagnosis of endometrioma . DESIGN Prospect i ve study with pathological confirmation of the diagnosis . SETTING Department of Obstetrics and Gynecology of the University of Cagliari , Italy . PATIENTS One hundred one consecutive premenopausal nonpregnant women su bmi tted to laparoscopy or laparotomy , from November 1993 to October 1994 , because of the presence of an adnexal mass . INTERVENTIONS Within 2 days before surgery all patients underwent transvaginal ultrasonography and evaluation of CA-125 plasma levels . The ultrasonographic impression and the CA-125 value were then compared with the histopathological diagnosis . MAIN OUTCOME MEASURE The overall agreement between the test result and the actual outcome was calculated using the kappa index for the transvaginal ultrasonography used alone and for the combination of transvaginal ultrasonography and CA-125 values , for each chosen cutoff and range . RESULTS Transvaginal ultrasonography has a strong agreement between test and surgery ( kappa value 0.76 ) whereas the combined use of the two methods is associated with a lower kappa index , ranging from 0.40 to 0.69 . CONCLUSION Transvaginal ultrasonography used alone has a better predictive capacity in differentiating endometrioma from other adnexal masses than combined methods Background . The suitable parameter in PF as well as in serum that may predict the activity of endometriosis is not well described . Therefore , we tried to examine the peritoneal fluid ( PF ) and serum concentrations of hepatocyte growth factor ( HGF ) in different revised American Society of Reproductive Medicine ( r‐ASRM ) staging and morphologic appearances of endometriosis in an attempt to determine whether HGF can be clinical ly useful to predict the activity of pelvic endometriosis OBJECTIVE To study the relationship between aromatase expression in endometriotic tissues and clinical and laboratory findings . DESIGN Prospect i ve basic and clinical research . SETTING University hospital . PATIENT(S ) Sixty-two women with endometriosis , and 12 without endometriosis . INTERVENTION(S ) Conservative surgery , or hysterectomy and adnexectomy , along with an immunohistochemical study of aromatase in endometriotic and nonendometriotic tissues . MAIN OUTCOME MEASURE(S ) Symptoms of the disease , ultrasound and surgical findings , values of tumor markers , steroids and immunoglobulins , and recurrences after surgery . RESULT ( S ) We observed positive immunohistochemical expression for aromatase in endometriotic tissues from 38 patients ( 61.3 % ) . Aromatase expression was negative in the rest of the tissues studied and in the 12 cases without endometriosis . Aromatase-positive patients had a higher number of endometriomas , more bilaterality , and more moderate-to-severe chronic pelvic pain . Also , infertility and associated leiomyomas were more frequent in these patients , though without significant differences . There were no differences in recurrence of the disease 1 year later . Estradiol and PRL levels were significantly higher , and IgG values lower , than in aromatase-negative patients . High values of blood sedimentation rate were more frequent in aromatase-negative patients . CONCLUSION ( S ) Molecular alterations such as the presence of aromatase in endometriotic tissues could be involved in the development or maintenance of endometriosis . Our findings suggest major severity , activity , and chronic pelvic pain in patients with aromatase in endometriotic tissue In a 3-year prospect i ve study of 643 consecutive laparoscopies for infertility , pelvic pain , or infertility and pain , the pelvic area , the depth of infiltration , and the volume of endometriotic lesions were evaluated . The incidence , area , and volume of subtle lesions decreased with age , whereas for typical lesions these parameters and the depth of infiltration increased with age . Deeply infiltrating endometriosis was strongly associated with pelvic pain , women with pain having larger and deeper lesions . Because deep endometriosis has little emphasis in the revised American Fertility Society classification and after analyzing the diagnoses made in each class , considerations for a simplifying revision with inclusion of deep lesions are suggested . In conclusion , suggestive evidence is presented to support the concept that endometriosis is a progressive disorder , and it is demonstrated that deep endometriosis is strongly associated with pelvic pain OBJECTIVE To investigate the biochemical parameters of the erythrocyte response to diamide-induced oxidative stress , alone or as adjuncts to serum values of CA-125 and human epididymal secretory protein E4 ( HE4 ) , in the diagnosis and study of endometriosis . SETTING University of Padova . DESIGN Prospect i ve study . PATIENT(S ) Forty-five patients of reproductive age undergoing laparoscopy . INTERVENTION(S ) All women were studied for endometriotic foci during laparoscopic surgery . Forty-one had laparoscopically and histologically confirmed endometriosis , and four did not . Twenty women with confirmed endometriosis were reassessed 1 - 4 months later . MAIN OUTCOME MEASURE(S ) CA-125 and HE4 and two new parameters evaluated in erythrocytes after diamide-induced stress , that is , b and 3 tyrosine phosphorylation ( Tyr-P ) level and decrease in total glutathione content ( ΔGSH ) , were assessed in all patients . RESULT ( S ) In association with serum CA-125 levels but not with HE4 , diamide-related erythrocyte b and 3 Tyr-P and ΔGSH were significantly higher in patients with endometriosis and were able to discriminate with high sensitivity and specificity between patients before and after surgery . CONCLUSION ( S ) Endometriosis is associated with an increase in systemic oxidative stress , affecting the antioxidative defenses of circulating erythrocytes . All related implication s , including evaluation of other oxidative stress-related changes , warrant further study OBJECTIVE To investigate the expression and role of oxidative stress markers in the serum and follicular fluid of patients with endometriosis . MATERIAL S AND METHODS A prospect i ve case-control study was conducted in 42 patients who underwent in vitro fertilization-embryo transfer ( IVF-ET ) . They were divided into Group I : patients with endometriosis ( n = 20 ) and Group II : patients with tubal factor infertility ( n = 22 ) . All patients underwent a long gonadotropin-releasing hormone ( GnRH ) agonist protocol for pituitary downregulation followed by controlled ovarian hyperstimulation . Level of reactive oxygen species ( ROS ) , superoxide dismutase ( SOD ) , and vitamin E ( VE ) were measured by enzyme-linked immunosorbent assay ( ELISA ) . The results of IVF-ET between the two groups were compared . RESULTS The ROS levels in both serum and follicular fluid of the study group were significantly higher than in the control group . The serum levels of SOD and VE in the study group were significantly lower than those in the control group , but there was no difference in follicular fluid levels of SOD and VE between the two groups . Furthermore , the mature oocyte and fertilization rates in the study group were significantly lower than those of the control group . However , the levels of ROS , SOD , and VE in serum and follicular fluid were not significantly correlated with outcome following IVF-ET . CONCLUSION Patients with endometriosis have increased oxidative stress , as well as lower mature oocyte rates and fertilization rates . Nevertheless , there is no evidence that the oxidative stress status is directly related to the outcome of IVF treatment BACKGROUND The objective of this prospect i ve controlled trial was to investigate the ability of a group of serum and peritoneal fluid ( PF ) markers to predict , non-surgically , endometriosis . METHODS AND RESULTS Serum and PF sample s were obtained from 130 women while undergoing laparoscopy for pain , infertility , tubal ligation or sterilization reversal . Concentrations of six cytokines [ interleukin (IL)-1beta , IL-6 , IL-8 , IL-12 , IL-13 and tumour necrosis factor (TNF)-alpha ] were measured in serum and PF , and reactive oxygen species ( ROS ) in PF , and levels were compared among women who were allocated to groups according to their post-surgical diagnosis . Fifty-six patients were diagnosed with endometriosis , eight with idiopathic infertility , 27 underwent tubal ligation or reanastomosis ( control group ) and 39 were excluded due to bloody PF . Only serum IL-6 and PF TNF-alpha could be used to discriminate between patients with and without endometriosis with a high degree of sensitivity and specificity ( P < 0.001 ) . A threshold of 15 pg/ml PF TNF-alpha provided 100 % sensitivity and 89 % specificity ( positive likelihood ratio of 9.1 and negative likelihood ratio of 0 ) . A threshold of 2 pg/ml for serum IL-6 provided a sensitivity of 90 % and specificity of 67 % ( positive likelihood ratio of 2.7 and negative likelihood ratio of 0.14 ) . CONCLUSIONS By measuring serum IL-6 and PF TNF-alpha , it was possible to discriminate between patients with endometriosis and those without . Before these markers can be used as a non-surgical diagnostic tool , these data should be verified in a larger study Objective To evaluate the role of serum level of VEGF-A in comparison to CA-125 in diagnosis and follow-up of patients with advanced endometriosis after conservative laparoscopic surgery . Methods A prospect i ve r and omized case – control study was performed on patients referred for laparoscopy complaining of unexplained primary infertility with or without chronic pelvic pain . Thirty patients with advanced endometriosis ; stage III – IV were included ( study group ) , another 30 women without endometriosis or any other medical conditions were settled as a control group . Pre-operative blood sample s were collected from study and control cases . Post-operative blood sample s were collected from 25 treated patients in the follicular phase of the third menstrual cycle ; 5 cases were drop-outs . Serum level of cancer antigen-125 ( CA-125 ) and vascular endothelial growth factor ( VEGF-A ) were assayed by using enzyme linked immunosorbent assay ( ELISA ) kit . Results There was a statistically significant difference in serum CA-125 and VEGF-A level in patients with advanced endometriosis before conservative laparoscopic surgery and those without endometriosis ( p < 0.001 ) and after conservative laparoscopic surgery ( p < 0.001 ) . High sensitivity ( 93.3 % ) , specificity ( 96.7 % ) and accuracy ( 95.0 % ) of VEGF-A assay than in CA-125 distinguishing between patients with endometriosis from those without endometriosis ; CA-125 has 70.0 % sensitivity , 90.0 % specificity and 85.0 % accuracy . Percentage of decrease of VEGF-A level after operation was higher than that of CA-125 ( 45.9 vs. 25.8 % ) p < 0.001 , respectively . Conclusion The use of VEGF-A for diagnosis of advanced endometriosis at cut-off 680 pg/ml and for follow-up is better than CA-125 OBJECTIVE To evaluate serum and peritoneal concentrations of amyloid protein A in women with endometriosis and to compare them with those of women without endometriosis . STUDY DESIGN A prospect i ve study evaluated 76 women suspected of having pelvic endometriosis . Fifty-seven women ( group A ) were confirmed by videolaparoscopy and had their serum and peritoneal amyloid A concentrations measured by ELISA . The average levels from group A were compared to those obtained in group B. Group B was composed of 13 women without endometriosis , su bmi tted to elective laparoscopy for tubal ligation . RESULTS Peritoneal amyloid A concentrations in group A ( 310.3 + /- 97.8 ng/mL ) were higher than those of group B ( 53.4 + /- 58.2 ng/mL ) ; p = 0.0 . However , serum concentrations in groups A ( 14.01 + /- 32.3 ng/mL ) and B ( 9.5 + /- 15.9 ng/mL ) did not differ significantly ; p = 0.35 . CONCLUSION The peritoneal amyloid A protein concentration in pelvic endometriosis was higher when compared to normal controls , corroborating the inflammatory nature of the disease . This finding suggests that the procedure of evaluating the peritoneal amyloid A concentration in endometriosis merits further investigation Objective : To examine variations in CA 125 levels during the three phases of the menstrual cycle in women with and without endometriosis . Methods : One hundred infertile women were studied prospect ively . CA 125 levels were measured during menses and during the follicular and luteal phases before diagnostic laparoscopy . Subjects were divided into four groups : no evidence of endometriosis ( 35 women ) , stage I endometriosis ( 30 women ) , stage II endometriosis ( 21 women ) , and stages III and IV endometriosis ( 14 women ) . Results : In the endometriosis groups , there was a significant difference in the mean CA 125 levels drawn at menses and those drawn in the follicular phase . In patients with severe endometriosis , there was also a difference in the mean CA 125 levels drawn at menses and in the luteal phase . This finding led to the development of a screening test based on the ratio of CA 125 levels at menses to levels in the follicular phase . The test based on this ratio ( with a cutoff of 1.5 ) had a sensitivity of 62.5 % and specificity of 75 % , compared with a sensitivity of 26.8 % and specificity of 100 % for the test based on a single CA 125 level drawn at menses ( with a cutoff of 35 U/mL ) . Conclusions : CA 125 levels during menses are elevated compared with those during the follicular phase in patients with endometriosis . Screening tests based on the relationship of multiple CA 125 levels taken throughout the menstrual cycle were more sensitive for detection of endometriosis than tests based on a single CA 125 level . ( Obstet Gynecol 1993;81:99 - 103 The purpose of this prospect i ve study was to compare the accuracy of computed tomography ( CT ) and transvaginal ultrasonography in the differential diagnosis of persistent cystic ovarian lesions . The c and i date s for this study were 161 premenopausal non-pregnant women with an adnexal mass . After a 3-month follow-up , 83 masses persisted and were examined by both techniques before surgery . We also evaluated the CA-125 plasma levels . The CT and ultrasonographic diagnoses were then compared with the histopathological diagnosis . The overall agreement between the test results and the actual outcome was calculated by means of the kappa statistic . Transvaginal ultrasonography has a closer accuracy in the diagnosis of serous cysts and serous cystadenoma , ovarian carcinoma and endometrioma ( value of kappa : 0.78 , 0.73 and 0.80 , respectively ) than CT , even if the latter is associated with clinical and biochemical parameters such as patient 's age and CA-125 plasma levels . Only in the diagnosis of cystic teratoma , is transvaginal ultrasonography less accurate than CT . In conclusion , in premenopausal women , transvaginal ultrasonography remains a cost-effective method in the diagnosis of most cystic ovarian lesions CA-125 , a high-molecular-weight glycoprotein antigen , has been identified as a possible marker for endometriosis , with discrepant results . CA-72 , another glycoprotein antigen , is expressed by a variety of adenocarcinomas , including endometrial carcinoma . This controlled , prospect i ve study evaluated serum CA-125 and CA-72 levels in 35 consecutive patients with endometriosis of varying stages and in patients without endometriosis . Serum CA-125 and CA-72 were measured with immunoradiologic methods prior to diagnostic laparoscopy for infertility evaluation . Endometriosis , scored by American Fertility Society guidelines , was identified in 19 patients , and 16 patients had normal pelvic findings . CA-125 and CA-72 levels were not different between patients with no pelvic disease ( controls ) and women with stage I-IV endometriosis . The positive predictive value of CA-125 was 0 % ; the negative predictive value was 47 % . The positive predictive value of CA-72 was 5 % ; the negative predictive value was 53 % . CA-72 and CA-125 are not helpful in the routine workup of the infertile woman to determine the likelihood that she has pelvic endometriosis CONTEXT AND OBJECTIVE One of the diagnostic markers of endometriosis is CA-125 , and elevated levels of this are caused by high concentrations in the ectopic endometrium . The objective of this study was to correlate CA-125 levels in serum and peritoneal fluid from women with and without pelvic endometriosis . DESIGN AND SETTING This was a prospect i ve , cross-sectional , controlled study of consecutive patients undergoing laparoscopy for infertility , pelvic pain or tubal ligation , during early follicular phase , at the university hospital of Faculdade de Medicina de Ribeirão Preto . METHODS Fifty-two patients were divided into two groups : endometriosis group , consisting of 35 patients with biopsy-confirmed pelvic endometriosis , and control group , consisting of 17 patients without endometriosis . CA-125 levels in serum sample s and peritoneal fluid were determined by chemiluminescence . RESULTS CA-125 levels in serum and peritoneal fluid were higher in patients with advanced pelvic endometriosis ( means of 39.1 + /- 45.8 U/ml versus 10.5 + /- 5.9 U/ml in serum , p < 0.005 ; 1,469.4 + /- 1,350.4 U/ml versus 888.7 + /- 784.3 U/ml in peritoneal fluid , p < 0.05 ) , and showed a positive correlation between each other ( correlation coefficient ( r ) = 0.4880 ) . Women with more advanced degrees of endometriosis showed higher CA-125 levels in both serum and peritoneal fluid ( p = 0.0001 ) . CONCLUSION There is a positive correlation between serum and peritoneal fluid values of CA-125 in women with and without endometriosis , and their levels are higher in peritoneal fluid . Advanced endometriosis is related to higher levels in both serum and peritoneal fluid OBJECTIVE To evaluate serum and peritoneal fluid concentrations of interferon-gamma-inducible protein-10 ( CXCL10 ) , a chemokine involved in local immune function , in women with endometriosis . DESIGN Prospect i ve study . SETTING Division of Obstetrics and Gynecology , University of Siena . PATIENT(S ) A total of 147 women were divided in two groups : women with ( n = 77 ) and without ( n = 70 ) endometriosis . INTERVENTION(S ) Serum and peritoneal fluid were collected from all patients undergoing laparoscopy . MAIN OUTCOME MEASURE(S ) CXCL10 concentrations were measured by a specific ELISA . RESULT ( S ) Serum CXCL10 concentrations in women with endometriosis were significantly lower than in those without endometriosis . No statistically significant difference between women with early endometriosis and those with advanced endometriosis was found . CXCL10 concentrations in peritoneal fluid of women with advanced endometriosis were significantly lower than in that of women with an early stage of , or without , endometriosis . CONCLUSION ( S ) The decreased concentrations of CXCL10 in serum and peritoneal fluid of women with endometriosis indicate an impaired immune activity in women with endometriosis The purpose of the present prospect i ve multi‐center study is to investigate the relationship between laparoscopic diagnosis of endometriosis and results of a serum antiendometrial antibody ( AEA ) assay Endometriosis is a common gynecologic syndrome of unknown etiology and pathogenesis . Growth factors and inflammatory mediators produced by peritoneal leukocytes have recently been postulated to participate in the pathogenesis of endometriosis . Angiogenic factors released from peritoneal macrophages may also play a role in the development of this disease . In the present study , we investigate the soluble levels of vascular endothelial growth factor ( VEGF ) , epidermal growth factor-receptor ( EGF-R ) , granulocyte/macrophage-colony stimulating factor ( GM-CSF ) , Insulin-like growth factor-1 ( IGF-1 ) and interferon-gamma ( IFN-gamma ) in the serum of 28 women with and 20 without endometriosis . We also compared these levels before , during and after treatment with danazol and leuprorelin acetate depot , the two therapeutic regiments of choice concerning this disease . We found that only sVEGF levels were higher in women with endometriosis in comparison to controls ( P < 0.001 ) while sEGF-R is not present . GM-CSF , IGF-1 and IFN-gamma soluble levels are not affected in either healthy or endometriotic subjects . The 6-month treatment with danazol decreased sVEGF levels ( P < 0.02 ) and increased sEGF-R levels ( P < 0.001 ) . These observations support the view that VEGF may be associated with the disease process and that danazol may bring sVEGF levels to a normal threshold . However , future studies will be focused on the anti-angiogenic control of the action of VEGF in patients with endometriosis Abstract Endometriosis compromises the quality of life of countless women worldwide and is a leading cause of disability . Clinical symptoms of endometriosis can be very heterogeneous leading to a long interval between onset of symptoms and surgical diagnosis . A noninvasive , rapid diagnostic test is urgently needed . In this prospect i ve study , we evaluated the usefulness of Cytokeratin-19 ( CK19 ) as a biomarker for the diagnosis of endometriosis through urine and serum ELISA . 76 reproductive-aged women undergoing laparoscopy for benign conditions were included to this study and divided into two groups by the presence ( n = 44 ) or absence ( n = 32 ) of endometriosis . There was no statistically significant correlation between the concentration of CK19 in urine ( p = 0.51 ) or in serum ( p = 0.77 ) and the diagnosis of endometriosis . Assigning the sample s to the proliferative or secretory cycle stage did not sufficiently lower the p values . In this study , the promising data reported in the recent literature about CK19 serving as a sufficient biomarker for endometriosis could not be verified when tested in a larger sample size . Further studies are warranted to explore the usefulness of CK19 in the diagnosis of endometriosis OBJECTIVE To determine whether interleukin-8 ( IL-8 ) serum levels are correlated with pelvic pain in patients with ovarian endometriomas . DESIGN Prospect i ve study . SETTING Tertiary-care university hospital . PATIENT(S ) Interleukin-8 serum levels were prospect ively analyzed in 51 patients ( group A , asymptomatic patients or patients with mild dysmenorrhea ; 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 between IL-8 serum levels and pelvic pain . INTERVENTION(S ) Interleukin-8 serum levels determination . MAIN OUTCOME MEASURE(S ) Interleukin-8 serum levels and pelvic pain . RESULT ( S ) From 56 patients , five cases were ultimately excluded because the histologic diagnosis was not cystic ovarian endometriosis ( 2 teratomas and 3 haemorragic cysts ) . The mean ( + /-SD ) IL-8 serum levels in group A were 6.41 + /- 12.17 pg/mL and in group B were 6.52 + /- 8.73 pg/mL. CONCLUSION ( S ) Pain symptoms in ovarian endometriosis is not correlated with IL-8 serum levels OBJECTIVE To assess whether complement components iC3b , C3c , C4 , and SC5b-9 may be involved in the pathogenesis of endometriosis . DESIGN Prospect i ve , experimental trial . SETTING Medical university . PATIENT(S ) 112 women infertile women undergoing laparoscopy . INTERVENTION(S ) Venipuncture and laparoscopic peritoneal fluid collection . MAIN OUTCOME MEASURE(S ) Peritoneal fluid and serum iC3b , C3c , C4 , and SC5b-9 levels were measured by the enzyme-linked immunosorbent assay ( ELISA ) method . RESULT ( S ) Higher levels of C3c , C4 , and SC5b-9 complement components were found in the serum compared with the peritoneal fluid , but the levels of iC3b were higher in the peritoneal fluid . We observed higher concentrations of C3c , C4 , and SC5b-9 in the peritoneal fluid and serum of women with endometriosis compared with healthy women . However , the levels of iC3b in both peritoneal fluid and serum were statistically significantly lower than in the control group . CONCLUSION ( S ) The impairment of the mechanisms involved in the regulation of activation of complement system may be an important factor in the pathogenesis of endometriosis and endometriosis-associated infertility OBJECTIVE To measure autoantibodies that recognize oxidatively modified proteins in the sera of women with surgically proven endometriosis . DESIGN Prospect i ve study . SETTING Tertiary care academic medical center . PATIENT(S ) Women undergoing surgery for endometriosis or tubal ligation . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Serum and peritoneal fluid autoantibody titers to malondialdehyde-modified low-density lipoprotein , oxidized low-density lipoprotein , and lipid peroxide-modified rabbit serum albumin determined by ELISA . Correlation of autoantibody titers with revised American Fertility Society staging classification , symptoms , and morphologic type of endometriosis . RESULT ( S ) Mean ( + /-SEM ) serum autoantibody titers ( in optical density units ) to the three antigens were as follows : [ 1 ] lipid peroxide-modified rabbit serum albumin , 0.49 + /- 0.12 units in the patients with endometriosis and 0.2 + /- 0.02 units in the controls ; [ 2 ] oxidized low-density lipoprotein , 0.22 + /- 0.005 units in the patients with endometriosis and 0.18 + /- 0.006 units in the controls ; and [ 3 ] malondialdehyde-modified low-density lipoprotein , 0.21 + /- 0.005 units in the patients with endometriosis and 0.16 + /- 0.003 units in the controls . There was no correlation between autoantibody titers and revised American Fertility Society stage , symptoms , or morphologic type of endometriosis . Peritoneal fluid did not contain autoantibodies to any of the three antigens . CONCLUSION ( S ) Autoantibodies to markers of oxidative stress were significantly increased in women with endometriosis . These findings strongly support our data demonstrating that women with endometriosis have enhanced oxidative stress Activated B cells have recently been shown to produce soluble CD23 from their membranes . The serum-soluble CD23 concentration in 21 patients with pelvic pain diagnosed as having endometriosis and confirmed by histology , and in 18 patients without pelvic pain , who had a normal pelvis during laparoscopic sterilization , was studied by chemiluminescent enzyme-linked immunosorbent assay . The endometriosis patients were r and omized to 3 months of either danazol or leuprolide acetate injection . Serum was taken before and after 3 months of therapy . The serum-soluble CD23 concentration was significantly elevated in patients with endometriosis when compared with the controls ( P < 0.0001 ) . There was no correlation between soluble CD23 concentrations and the severity of endometriosis ( r = 0.48 , P > 0.05 ) . The serum concentration of soluble CD23 decreased significantly on treatment with danazol but not leuprolide acetate ( P < 0.05 ) . We conclude that the elevation of soluble CD23 in patients with endometriosis suggests that there is activation of B cells , which respond to danazol but not leuprolide acetate injection BACKGROUND At present , the only way to conclusively diagnose endometriosis is laparoscopic inspection , preferably with histological confirmation . This contributes to the delay in the diagnosis of endometriosis which is 6 - 11 years . So far non-invasive diagnostic approaches such as ultrasound ( US ) , MRI or blood tests do not have sufficient diagnostic power . Our aim was to develop and vali date a non-invasive diagnostic test with a high sensitivity ( 80 % or more ) for symptomatic endometriosis patients , without US evidence of endometriosis , since this is the group most in need of a non-invasive test . METHODS A total of 28 inflammatory and non-inflammatory plasma biomarkers were measured in 353 EDTA plasma sample s collected at surgery from 121 controls without endometriosis at laparoscopy and from 232 women with endometriosis ( minimal-mild n = 148 ; moderate-severe n = 84 ) , including 175 women without preoperative US evidence of endometriosis . Surgery was done during menstrual ( n = 83 ) , follicular ( n = 135 ) and luteal ( n = 135 ) phases of the menstrual cycle . For analysis , the data were r and omly divided into an independent training ( n = 235 ) and a test ( n = 118 ) data set . Statistical analysis was done using univariate and multivariate ( logistic regression and least squares support vector machines ( LS-SVM ) approaches in training- and test data set separately to vali date our findings . RESULTS In the training set , two models of four biomarkers ( Model 1 : annexin V , VEGF , CA-125 and glycodelin ; Model 2 : annexin V , VEGF , CA-125 and sICAM-1 ) analysed in plasma , obtained during the menstrual phase , could predict US-negative endometriosis with a high sensitivity ( 81 - 90 % ) and an acceptable specificity ( 68 - 81 % ) . The same two models predicted US-negative endometriosis in the independent validation test set with a high sensitivity ( 82 % ) and an acceptable specificity ( 63 - 75 % ) . CONCLUSIONS In plasma sample s obtained during menstruation , multivariate analysis of four biomarkers ( annexin V , VEGF , CA-125 and sICAM-1/or glycodelin ) enabled the diagnosis of endometriosis undetectable by US with a sensitivity of 81 - 90 % and a specificity of 63 - 81 % in independent training- and test data set . The next step is to apply these models for preoperative prediction of endometriosis in an independent set of patients with infertility and /or pain without US evidence of endometriosis , scheduled for laparoscopy STUDY QUESTION Is there any combined effect between inflammation and stress reaction on Toll-like receptor 4 (TLR4)-mediated growth of endometriotic cells ? SUMMARY ANSWER A combined effect of local inflammation and stress reaction in the pelvic environment may be involved in TLR4-mediated growth of endometriotic stromal cells . WHAT IS KNOWN ALREADY In endometriosis , higher endotoxin levels in the menstrual fluid ( MF ) and peritoneal fluid ( PF ) and higher tissue concentrations of human heat shock protein 70 ( HSP70 ) in the eutopic and ectopic endometria promote TLR4-mediated growth of endometriotic cells . STUDY DESIGN , SIZE AND DURATION This is a case-controlled research study with prospect i ve collection and retrospective evaluation of sera , MF , PF and endometrial tissues from 43 women with and 20 women without endometriosis . PARTICIPANTS / MATERIAL S , SETTING , METHODS PF was collected from 43 women with endometriosis and 20 control women during laparoscopy . Sera and endometrial biopsy specimens were collected from a proportion of these women . MF was collected from a separate population of 20 women with endometriosis and 15 control women . HSP70 concentrations in sera , MF , PF and in culture media were measured by ELISA . Gene expression of HSP70 by endometrial cells in response to lipopolysaccharide ( LPS ) was examined by qRT-PCR . The individual and combined effects of LPS and HSP70 on the secretion of interleukin-6 ( IL-6 ) and tumor necrosis factor α ( TNFα ) by PF-derived macrophages ( M[Symbol : see text ] ) were examined by ELISA , while their effects on endometrial cell proliferation were examined by bromodeoxyuridine and [(3)H]-thymidine incorporation assay . MAIN RESULTS AND THE ROLE OF CHANCE Concentrations of HSP70 were maximal in MF , intermediate in PF and the lowest in sera . In MF and PF , HSP70 levels were higher in women with endometriosis than in controls . LPS stimulated gene expression and secretion of HSP70 by eutopic endometrial stromal cells ( ESCs ) and this effect was abrogated after pretreatment of cells with an anti-TLR4 antibody . This effect was significantly higher for ESCs derived from women with endometriosis than for ESCs from control women . Exogenous treatment with either HSP70 or LPS significantly stimulated the production of IL-6 and TNFα by M[Symbol : see text ] and promoted the proliferation of ESCs , and a significant additive effect between LPS and HSP70 was observed . While individual treatment with either polymyxin B , an LPS antagonist , or anti-HSP70 antibody was unable to suppress the combined effects of LPS and HSP70 on cytokine secretion or ESC proliferation , pretreatment of cells with the anti-TLR4 antibody was able to significantly suppress their combined effects . LIMITATIONS , REASONS FOR CAUTION S Further studies are needed to examine the mutual role between other secondary inflammatory mediators and endogenous stress proteins in promoting pelvic inflammation and growth of endometriotic stromal cells . WIDER IMPLICATION S OF THE FINDINGS Our findings suggest that endotoxin and HSP70 are mutually involved in a stress reaction and in inflammation . A combined effect between local inflammation and a stress reaction in pelvic environment may be involved in TLR4-mediated growth of endometriotic cells . Since endometriosis is a multi-factorial disease , it is difficult to explain uniformly its growth regulation by a single factor . Our findings may provide some new insights in underst and ing the physiopathology or pathogenesis of endometriosis and may hold new therapeutic potential . STUDY FUNDING /COMPETING INTEREST(S ) This work was supported by Grants-in-Aid for Scientific Research ( grant no. 16591671 and 18591837 ) from the Ministry of Education , Sports , Culture , Science and Technology of Japan ( to K.N.K. ) . There is no conflict of interest related to this study . TRIAL REGISTRATION NUMBER Not applicable Cytokines , and specifically interleukin 6 ( IL-6 ) and interleukin 8 ( IL-8 ) , have been associated with the pathogenesis of endometriosis . We studied serum concentrations of IL-6 and IL-8 in patients with deep infiltrating endometriosis ( DIE ) or ovarian endometriomas ( OE ) , but no other forms of associated endometriosis disease type . We carried out a case-control study including 19 patients with OE alone ( OE group ) , 14 patients with DIE alone ( DIE group ) and 24 healthy patients without endometriosis ( C group ) . Serum concentrations of IL-6 and IL-8 were measured in the three groups of patients . Serum levels of both IL-6 and IL-8 were significantly higher in the OE group . A high positive correlation was found between serum IL-6 and IL-8 levels in the OE group but not in the DIE and C groups . Serum IL-8 alone achieved the highest predictive value of the presence of OE ( adjusted OR : 1.44 ; sensitivity : 78.2 % ; specificity : 76.2 % ) . The combination of IL-6 and IL-8 levels did not significantly improve the discrimination between subjects with OE and those with DIE over that of IL-8 . OE but not DIE are associated with increased serum levels of IL-6 and IL-8 , and thus these may become useful tools for discriminating OE alone from DIE OBJECTIVE To investigate the diagnostic potentials of the serum levels of nine different biomarkers in endometriosis . STUDY DESIGN In this case-controlled , prospect i ve clinical study , 80 women underwent laparoscopy or laparotomy with a preliminary diagnosis of chronic pelvic pain , severe secondary dysmenorrhea , infertility , pelvic endometriosis or pelvic mass . The 60 women with confirmed pelvic endometriosis constituted the endometriosis group , and the other 20 women without endometriosis constituted the control group . Preoperative blood sample s were obtained for serum biomarker measurements . Serum levels of nine different serum biomarkers including α-enolase , macrophage migration inhibitory factor , leptin , interleukin-8 , anti-endometrial antibody , phosphoinositide dependent protein kinase 1 , CA125 , syntaxin-5 , and laminin-1 were measured concurrently and compared between the control and endometriosis groups , and among control group and endometriosis subgroups including stage I , stage II , stage III and stage IV endometriosis . RESULTS The serum levels of α-enolase , macrophage migration inhibitory factor , leptin , interleukin-8 and antiendometrial antibodies showed a statistically significant difference neither between control and endometriosis groups nor among control group and endometriosis subgroups . The serum levels of CA125 , syntaxin-5 and laminin-1 showed a statistically significant difference both between the control and endometriosis groups ( p<0.01 ) and among control group and endometriosis subgroups ( p<0.01 ) . Serum levels of laminin-1 in stage II and IV endometriosis ; syntaxin-5 in stage I and II endometriosis ; and CA125 in stage III and IV endometriosis were found to have the different levels compared to control group . CONCLUSIONS These findings show that the concurrent measurement of CA125 , syntaxin-5 and laminin-1 might be a useful non-invasive test in strengthening the diagnosis of endometriosis and in predicting its severity Preoperative blood sample s and intraoperative tissue specimens were obtained from 101 patients with endometriosis and 78 patients without endometriosis referred for benign gynecologic operations to investigate the clinical value of serum and tissue CA 19 - 9 levels in the diagnostic evaluation of endometriosis as compared to CA 125 . Our prospect i ve cohort study showed that serum CA 19 - 9 is a valuable marker in the diagnosis of endometriosis , and it may be used to predict the patients with severe endometriosis when used with CA 125 |
1,076 | 25,196,408 | 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 | When compared with men of other racial or ethnic groups , African American men are more likely to experience adverse health conditions .
The systematic review objectives were to ( i ) determine the current evidence base concerning African American men 's response to lifestyle behavioural interventions design ed to promote weight loss , increase physical activity , and /or improve healthy eating and ( ii ) determine the next steps for research in these areas . | 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 , 18 , and 36 months of 2.9 ( P<0.001 ) , 2.0 ( P<0.001 ) , and 1.3 ( P=0.02 ) mmHg in sodium reduction vs usual care were associated with an overall 18 % lower incidence of hypertension ( P=0.048 ) ; were relatively unchanged by adjustment for ethnicity , gender , age , and baseline blood pressure , BMI , and sodium excretion ; and were observed in both black and white men and women . From these beneficial but modest results with highly motivated and extensively counselled individuals , sodium reduction sufficient to favourably influence the population blood pressure distribution will be difficult to achieve without food supply changes Recommendations for control of high blood pressure ( BP ) emphasize lifestyle modification , including weight loss , reduced sodium intake , increased physical activity , and limited alcohol consumption . The Dietary Approaches to Stop Hypertension ( DASH ) dietary pattern also lowers BP . The PREMIER r and omized trial tested multicomponent lifestyle interventions on BP in demographic and clinical subgroups . Participants with above-optimal BP through stage 1 hypertension were r and omized to an Advice Only group or one of two behavioural interventions that implement established recommendations ( Est ) or established recommendations plus DASH diet ( Est plus DASH ) . The primary outcome was change in systolic BP at 6 months . The study population was 810 individuals with an average age of 50 years , 62 % women , 34 % African American ( AA ) , 95 % overweight/obese , and 38 % hypertensive . Participants in all the three groups made lifestyle changes . Mean net reductions in systolic ( S ) BP in the Est intervention were 1.2 mmHg in AA women , 6.0 in AA men , 4.5 in non-AA women , and 4.2 in non-AA men . The mean effects of the Est Plus DASH intervention were 2.1 , 4.6 , 4.2 , and 5.7 mmHg in the four race – sex subgroups , respectively . BP changes were consistently greater in hypertensives than in nonhypertensives , although interaction tests were nonsignificant . The Est intervention caused statistically significant BP reductions in individuals over and under age 50 . The Est Plus DASH intervention lowered BP in both age groups , and significantly more so in older individuals . In conclusion , diverse groups of people can adopt multiple lifestyle changes that can lead to improved BP control and reduced CVD risk OBJECTIVE This study was design ed to compare the initial efficacy of Motivational Interviewing ( MI ) , Online Transtheoretical Model (TTM)-tailored communications and a brief Health Risk Intervention ( HRI ) on four health risk factors ( inactivity , BMI , stress and smoking ) in a worksite sample . METHOD A r and omized clinical trial assigned employees to one of three recruitment strategies and one of the three treatments . The treatment protocol included an HRI session for everyone and in addition either a recommended three TTM online sessions or three MI in person or telephone sessions over 6 months . At the initial post-treatment assessment at 6 months , groups were compared on the percentage who had progressed from at risk to taking effective action on each of the four risks . RESULTS Compared to the HRI only group , the MI and TTM groups had significantly more participants in the Action stage for exercise and effective stress management and significantly fewer risk behaviors at 6 months . MI and TTM group outcomes were not different . CONCLUSION This was the first study to demonstrate that MI and online TTM could produce significant multiple behavior changes . Future research will examine the long-term impacts of each treatment , their cost effectiveness , effects on productivity and quality of life and process variables mediating outcomes BACKGROUND Fruit and vegetable ( FV ) intake in black men are far below national recommendations . METHODS Urban , primarily immigrant , black men ( n=490 ) from the New York City metropolitan area participating in the Cancer Awareness and Prevention ( CAP ) Trial ( 2005 - 2007 ) were r and omly assigned to one of two intervention groups : 1 ) FV Education ( FVE ) or 2 ) Prostate Education ( PE ) . Both interventions entailed a mailed brochure plus two tailored telephone education ( TTE ) calls . Outcomes , measured at baseline and at eight months , included knowledge of FV recommendations , perceived benefits , stage of readiness to adopt recommendations and self-reported FV consumption . RESULTS At follow-up , the FVE group consumed an average of 1.2 more FV servings per day than the PE group ( P<0.001 ; adjusted for baseline ) . The FVE group also demonstrated increases in knowledge about recommended FV amounts ( P<0.01 ) and appropriate serving sizes ( P<0.05 ) , and in the percent of participants moving from a lower to a higher stage of readiness to adopt FV recommendations ( P<0.05 ) . The FVE group did not demonstrate increases in knowledge related to the importance of eating a colorful variety or in the ability to name potential health benefits . CONCLUSIONS TTE can be a practical and moderately effective intervention for raising awareness of FV recommendations and for promoting FV consumption in urban and primarily immigrant black men A Dietary Intervention Study of Hypertension ( DISH ) was undertaken to determine whether patients whose high blood pressure had been controlled pharmacologically for a period of more than 5 years could maintain that control with sodium restriction or weight reduction instead of drugs . Four hundred ninety-six patients , classified by degree of overweight , were r and omly assigned into one of seven groups . Included were those who would be withdrawn from antihypertensive medication and receive intervention for either sodium restriction or weight reduction . After 8 weeks of intervention , an average reduction of 24-hour urinary sodium output from a baseline of 158 mEq to 106 mEq ( p less than .001 ) and from 130 mEq to 96 mEq ( p less than .01 ) was achieved for the overweight and nonoverweight groups , respectively . That decline was still maintained at 56 weeks . Dietary estimates , obtained by analysis of 3-day food records , underestimated urinary output by an average of 12 % , with blacks more likely to underestimate than whites , and the overweight more likely to underestimate than the nonoverweight . An average 10-lb weight loss was achieved , with no difference between men and women . Weight declined for 32 weeks , then leveled off and was maintained up to 56 weeks , indicating that sodium intake modification can be accomplished faster than weight reduction . Modest sodium restriction and weight reduction are feasible and achievable in a free-living population and have a positive effect on control of hypertension Phase I of the Trials of Hypertension Prevention was a multicenter , r and omized trial of the feasibility and efficacy of seven nonpharmacologic interventions , including sodium reduction , in lowering blood pressure in 30- to 54-year-old individuals with a diastolic blood pressure of 80 to 89 mm Hg . Six centers tested an intervention design ed to reduce dietary sodium to 80 mmol ( 1800 mg)/24 h with a total of 327 active intervention and 417 control subjects . The intervention consisted of eight group and two one-to-one meetings during the first 3 months , followed by less-intensive counseling and support for the duration of the study . The mean net decrease in sodium excretion was 43.9 mmol/24 h at 18 months . Women had lower sodium intake at baseline and were therefore more likely to decrease to less than 80 mmol/24 h. Black subjects were less likely to decrease to less than 80 mmol/d , independent of sex or baseline sodium excretion . The mean ( 95 % confidence interval ) net decrease associated with treatment was -2.1 ( -3.3 , -0.8 ) mm Hg for systolic blood pressure and -1.2 ( -2.0 , -0.3 ) mm Hg for diastolic blood pressure at 18 months ( both P < .01 ) . Multivariate analyses indicated a larger systolic blood pressure effect in women ( -4.44 versus -1.23 mm Hg in men ) , adjusted for age , race , baseline blood pressure , and baseline 24-hour urinary sodium excretion ( P = .02 ) . Dose-response analyses indicated an adjusted decrease of -1.4 mm Hg for systolic blood pressure and -0.9 mm Hg for diastolic blood pressure for a decrease of 100 mmol/24 h in 18-month sodium excretion . These results support the utility of sodium reduction as a population strategy for hypertension prevention and raise questions about possible differences in dose response associated with gender and initial level of sodium intake CONTEXT Behavioral weight loss interventions achieve short-term success , but re-gain is common . OBJECTIVE To compare 2 weight loss maintenance interventions with a self-directed control group . DESIGN , SETTING , AND PARTICIPANTS Two-phase trial in which 1032 overweight or obese adults ( 38 % African American , 63 % women ) with hypertension , dyslipidemia , or both who had lost at least 4 kg during a 6-month weight loss program ( phase 1 ) were r and omized to a weight-loss maintenance intervention ( phase 2 ) . Enrollment at 4 academic centers occurred August 2003-July 2004 and r and omization , February-December 2004 . Data collection was completed in June 2007 . INTERVENTIONS After the phase 1 weight-loss program , participants were r and omized to one of the following groups for 30 months : monthly personal contact , unlimited access to an interactive technology-based intervention , or self-directed control . Main Outcome Changes in weight from r and omization . RESULTS Mean entry weight was 96.7 kg . During the initial 6-month program , mean weight loss was 8.5 kg . After r and omization , weight regain occurred . Participants in the personal-contact group regained less weight ( 4.0 kg ) than those in the self-directed group ( 5.5 kg ; mean difference at 30 months , -1.5 kg ; 95 % confidence interval [ CI ] , -2.4 to -0.6 kg ; P = .001 ) . At 30 months , weight regain did not differ between the interactive technology-based ( 5.2 kg ) and self-directed groups ( 5.5 kg ; mean difference -0.3 kg ; 95 % CI , -1.2 to 0.6 kg ; P = .51 ) ; however , weight regain was lower in the interactive technology-based than in the self-directed group at 18 months ( mean difference , -1.1 kg ; 95 % CI , -1.9 to -0.4 kg ; P = .003 ) and at 24 months ( mean difference , -0.9 kg ; 95 % CI , -1.7 to -0.02 kg ; P = .04 ) . At 30 months , the difference between the personal-contact and interactive technology-based group was -1.2 kg ( 95 % CI -2.1 to -0.3 ; P = .008 ) . Effects did not differ significantly by sex , race , age , and body mass index subgroups . Overall , 71 % of study participants remained below entry weight . CONCLUSIONS The majority of individuals who successfully completed an initial behavioral weight loss program maintained a weight below their initial level . Monthly brief personal contact provided modest benefit in sustaining weight loss , whereas an interactive technology-based intervention provided early but transient benefit . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00054925 This report provides a further analysis of the first year weight losses in the Look AHEAD ( Action for Health in Diabetes ) study and identifies factors associated with success . Participants were a total of 5,145 men and women with type 2 diabetes who were recruited at 16 sites and r and omly assigned to an intensive lifestyle intervention ( ILI ) or a control condition , Diabetes Support and Education ( DSE ) . During year 1 , participants in ILI received comprehensive diet and physical activity counseling in a total of 42 group and individual sessions , compared with three educational sessions for DSE participants . As reported previously , at the end of the year , ILI participants lost 8.6 % of initial weight , compared to 0.7 % for DSE ( P < 0.001 ) . Within the ILI group , all racial/ethnic groups achieved clinical ly significant weight losses ( > 5.5 % ) , although there were significant differences among groups . For the year , ILI participants attended an average of 35.4 treatment sessions and reported exercising a mean of 136.6 min/week and consuming a total of 360.9 meal replacement products . Greater self-reported physical activity was the strongest correlate of weight loss , followed by treatment attendance and consumption of meal replacements . The use of orlistat , during the second half of the year , increased weight loss only marginally in those ILI participants who had lost < 5 % of initial weight during the first 6 months and chose to take the medication thereafter as a toolbox option . The lifestyle intervention was clinical ly effective in all subsets of an ethnically and demographically diverse population Health information tailored to meet individuals ' unique needs has been shown to be more effective than generic information in promoting risk-reducing behavior changes . To explore mechanisms underlying tailoring 's effectiveness , this study r and omly assigned 198 overweight adults to receive weight-loss material s that were ( a ) tailored to the individual , ( b ) in an American Heart Association ( AHA ) brochure , or ( c ) AHA-content formatted to look like tailored material s. Participants who received tailored material s had more positive thoughts about the material s , positive personal connections to the material s , positive self- assessment thoughts , and positive thoughts indicating behavioral intention than those who received either of the untailored material s. The tailoring of health information can significantly improve the chances the information will be thoughtfully considered and can stimulate prebehavioral changes such as self- assessment and intention BACKGROUND The prevalence of hypertension and its cardiovascular complications is higher in African Americans than in whites . Interventions to control blood pressure in this population are particularly important . Regular exercise lowers blood pressure in patients with mild-to-moderate hypertension , but its effects in patients with severe hypertension have not been studied . We examined the effects of moderately intense exercise on blood pressure and left ventricular hypertrophy in African-American men with severe hypertension . METHODS We r and omly assigned 46 men 35 to 76 years of age to exercise plus antihypertensive medication ( 23 men ) or antihypertensive medication alone ( 23 men ) . A total of 18 men in the exercise group completed 16 weeks of exercise , and 14 completed 32 weeks of exercise , which was performed three times per week at 60 to 80 percent of the maximal heart rate . RESULTS After 16 weeks , mean ( + /- SD ) diastolic blood pressure had decreased from 88 + /- 7 to 83 + /- 8 mm Hg in the patients who exercised , whereas it had increased slightly , from 88 + /- 6 to 90 + /- 7 mm Hg , in those who did not exercise ( P = 0.002 ) . Diastolic blood pressure remained significantly lower after 32 weeks of exercise , even with substantial reductions in the dose of antihypertensive medication . In addition , the thickness of the interventricular septum ( P = 0.03 ) , the left ventricular mass ( P = 0.02 ) , and the mass index ( P = 0.04 ) had decreased significantly after 16 weeks in the patients who exercised , whereas there was no significant change in the nonexercisers . CONCLUSIONS Regular exercise reduced blood pressure and left ventricular hypertrophy in African-American men with severe hypertension BACKGROUND To improve methods for long-term weight management , the Weight Loss Maintenance ( WLM ) trial , a four-center r and omized trial , was conducted to compare alternative strategies for maintaining weight loss over a 30-month period . This paper describes methods and results for the initial 6-month weight-loss program ( Phase I ) . METHODS Eligible adults were aged > or = 25 , overweight or obese ( BMI = 25 - 45 kg/m2 ) , and on medications for hypertension and /or dyslipidemia . Anthropomorphic , demographic , and psychosocial measures were collected at baseline and 6 months . Participants ( n=1685 ) attended 20 weekly group sessions to encourage calorie restriction , moderate-intensity physical activity , and the DASH ( dietary approaches to stop hypertension ) dietary pattern . Weight-loss predictors with missing data were replaced by multiple imputation . RESULTS Participants were 44 % African American and 67 % women ; 79 % were obese ( BMI > or = 30 ) , 87 % were taking anti-hypertensive medications , and 38 % were taking antidyslipidemia medications . Participants attended an average of 72 % of 20 group sessions . They self-reported 117 minutes of moderate-intensity physical activity per week , kept 3.7 daily food records per week , and consumed 2.9 servings of fruits and vegetables per day . The Phase-I follow-up rate was 92 % . Mean ( SD ) weight change was -5.8 kg ( 4.4 ) , and 69 % lost at least 4 kg . All race-gender subgroups lost substantial weight : African-American men ( -5.4 kg + /- 7.7 ) ; African-American women ( -4.1 kg + /- 2.9 ) ; non-African-American men ( -8.5 kg + /- 12.9 ) ; and non-African-American women ( -5.8 kg + /- 6.1 ) . Behavioral measures ( e.g. , diet records and physical activity ) accounted for most of the weight-loss variation , although the association between behavioral measures and weight loss differed by race and gender groups . CONCLUSIONS The WLM behavioral intervention successfully achieved clinical ly significant short-term weight loss in a diverse population of high-risk patients Effective weight management interventions could reduce race-sex disparities in cardiovascular disease ( CVD ) , yet little is known about factors associated with successful weight loss maintenance in race-sex subgroups . In the Weight Loss Maintenance trial ( WLM ) , overweight/obese ( BMI 25 - 45 kg/m(2 ) ) adults who lost ≥4 kg in a 6-month behavioral weight loss intervention ( phase I ) were r and omized into one of three 30-month maintenance interventions ( phase II ) . To investigate predictors in subgroups , r and omized groups were combined for this analysis . Of 1,685 phase I participants , 1,032 ( 61 % ) entered phase II , including 12 % black men ( BM ) , 26 % black women ( BW ) , 25 % white men ( WM ) , and 37 % white women ( WW ) . Weight change over the 36-month study ranged from -2.3 % ( 95 % confidence interval = -3.1 to -1.5 % ) in BW to -4.5 % ( 95 % confidence interval = -5.7 to -4.0 % ) in WM , the result of differential weight loss during phase I. Within race , men lost significantly more weight than women , but within sex group , weight loss did not differ significantly between races . Although participants regained weight during phase II , regain did not differ by race-sex group , and mean weight at the end of the study was significantly lower than phase I entry weight for each subgroup . In regression models , phase I weight loss predicted overall 36-month weight loss in all race-sex groups . Healthy dietary pattern at entry , improvement in dietary pattern , or both were predictive in three of four race-sex groups . Few other variables other than initial weight loss and dietary pattern were predictive . Future research should identify additional modifiable influences on long-term maintenance after a modest weight loss OBJECTIVE To evaluate a cardiovascular nutrition education package design ed for African-American adults with a wide range of literacy skills . DESIGN Comparison of a self-help group and a full-instruction group ; each group received nutrition counseling and clinical monitoring every 4 months . SUBJECTS Three hundred thirty African-American adults , aged 40 to 70 years , with elevated cholesterol level or high blood pressure were r and omly assigned to the self-help or full-instruction group ; 255 completed the 12-month follow-up . INTERVENTIONS Counseling to reduce intake of dietary fat , cholesterol , and sodium was based on Cardiovascular Dietary Education System ( CARDES ) material s , which included food-picture cards , a nutrition guide ( self-help and full-instruction group ) , a video and audiotape series , and 4 classes ( full-instruction group only ) . MAIN OUTCOME MEASURES Changes in lipid levels and blood pressure after 12 months . STATISTICAL ANALYSES PERFORMED Primary analyses consisted of repeated- measures analysis of variance to examine effects of time and r and omization group on outcomes . RESULTS Total cholesterol and low-density lipoprotein cholesterol level decreased by 7 % to 8 % in the self-help and full-instruction groups of men and women ( P < .01 ) . The ratio of total cholesterol to high-density lipoprotein cholesterol ( HDL-C ) decreased in both groups of women and in the men in the full-instruction group ( P < .01 ) . In full-instruction and self-help participants with elevated blood pressure at baseline , systolic blood pressure decreased by 7 to 11 mm Hg and diastolic blood pressure decreased by 4 to 7 mm Hg ( P < .01 ) . Outcomes did not differ by literacy scores but were positively related to the reported initial frequency of using CARDES material s. APPLICATIONS/ CONCLUSIONS These results suggest that periodic nutrition counseling based on CARDES material s used for home study can enhance management of lipid levels and blood pressure in African-American out patients |
1,077 | 32,290,590 | 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 . | Pregnancy is a period of complex bio-psychological changes , during which the development of an attachment bond to the fetus takes on a central role .
Depressive symptoms are common during this period .
Both symptoms of depression and low levels of prenatal attachment are related to negative outcomes in caregivers and infants . | 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 . SETTING A county in central Sweden . PARTICIPANTS Low risk pregnant women from 34 to 42 weeks gestation , N=456 , 299 multiparous and 157 primiparous women . MEASUREMENTS The revised version of the Prenatal Attachment Inventory ( PAI-R ) and assessment of the perception of foetal movements per 24h in the current gestational week . FINDINGS A total of 81 per cent of the eligible women completed the question naire . The overall sample of women found that the majority ( 96 % ) felt their baby move mostly in the evening . More than half of the respondents ( 55 % ) stated that they perceived frequent foetal movement on two occasions during a 24h period , while almost a fifth ( 18 % ) never or only once reported frequent foetal movement in a 24h period . Just over a quarter ( 26 % ) of respondents perceived frequent movement at least three times during a 24h period . Perceiving frequent foetal movements on three or more occasions during a 24h period , was associated with higher scores of prenatal attachment in all the three subscales . KEY CONCLUSION Perceiving frequent foetal movements at least during three occasions per 24h periods in late pregnancy was associated with prenatal attachment . IMPLICATION S FOR PRACTICE encouraging women to focus on foetal movements may positively affect prenatal attachment , especially among multiparous women > 35 years Purpose This prospect i ve study investigated associations between prenatal attachment of adult first-time mothers to the unborn child , perinatal factors and levels of depression before and up to 18 months after delivery . Method Primiparas ( N = 161 ) without specific risk factors answered the following question naires during the last term of pregnancy ( t1 ) : Edinburgh Postnatal Depression Scale ( EPDS ) , Maternal Antenatal Attachment Scale ( MAAS ) , question naire on the schema of the unborn child , and a question naire about the pregnancy . Perinatal data were taken from the patients ’ files . The EPDS was answered 3 weeks ( t2 , N = 157 ) , 6 months ( t3 , N = 159 ) , and 18 months ( t4 , N = 132 ) postpartum . Results During pregnancy , 16.9 % of the women indicated mild depressive symptoms , and 7.5 % , medium to severe symptoms of depression . Mild symptoms of depression were found in 25.5 % at t2 , 10.1 % at t3 , and 12.2 % at t4 ; medium to severe symptoms were reported by 7.6 , 1.9 and 5.6 % , respectively . Women with low control during delivery ( emergency Caesarean ) showed a tendency for higher levels ( p = 0.067 ) of depression at t3 than women with elective Caesarean did . The quality of prenatal attachment to the unborn child correlated negatively with depressive symptoms at t1–t4 . Conclusions The closer the prenatal attachment of a mother to her unborn child , the less symptoms of depression she reports during the last term of pregnancy and postpartum . Therefore , promoting good mother – child attachment during pregnancy might influence the level of postpartum depression Maternal-foetal attachment represents the earliest and most basic form of human intimacy , and has both theoretical and clinical significance . Utilizing a previously published self-report question naire to assess antenatal attachment , the present paper explores its correlates using 238 women in the third trimester of pregnancy . Extrapolating from studies of maternal-infant attachment , it was hypothesized that depression and a lack of social support would be detrimental to the development of maternal antenatal attachment . The findings confirmed these hypothesized effects . In particular , the subgroup of women having low attachment was characterized by high levels of depression and anxiety , low levels of social support ( outside the partner relationship ) and high levels of control , domination and criticism within the partner relationship . Antenatal attachment may be predictive for future maternal-infant attachment . The findings suggest that negative mood states and lack of social support during pregnancy may warrant greater attention than has previously been accorded them OBJECTIVE : To estimate the prevalence of major and minor depression , panic disorder , and suicidal ideation during pregnancy while also identifying factors independently associated with antenatal depressive disorders . METHODS : In this prospect i ve study , participants were 1,888 women receiving ongoing prenatal care at a university obstetric clinic from January 2004 through January 2009 . Prevalence of psychiatric disorders was measured using the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) criteria based on the Patient Health Question naire . Multiple logistic regression identified factors associated with probable major depressive disorder and any depressive disorder . RESULTS : Antenatal depressive disorders were present in 9.9 % with 5.1 % ( 97 ) meeting criteria for probable major depression and 4.8 % ( 90 ) meeting criteria for probable minor depression . Panic disorder was present in 3.2 % ( 61 ) , and current suicidal ideation was reported by 2.6 % ( 49 ) . Among patients with probable major depression , 29.5 % ( 28 ) reported current suicidal ideation . Psychosocial stress ( odds ratio [ OR ] , 1.29 ; 95 % confidence interval [ CI ] , 1.21–1.36 ) , domestic violence ( OR 3.45 ; 95 % CI 1.46–8.12 ) , chronic medical conditions ( OR 3.05 ; 95 % CI 1.63–5.69 ) , and race ( Asian : OR 5.81 ; 95 % CI 2.55–13.23 ; or African American : OR 2.98 ; 95 % CI 1.24–7.18 ) each significantly increased the odds of probable antepartum major depressive disorder , whereas older age ( OR 0.92 ; 95 % CI 0.88–0.97 ) decreased the odds . Factors associated with odds of any depression were similar overall except that Hispanic ethnicity ( OR 2.50 ; 95 % CI 1.09–5.72 ) also independently increased the odds of any depression . CONCLUSION : Antenatal major and minor depressive disorders are common and significantly associated with clinical ly relevant and identifiable risk factors . By underst and ing the high point prevalence and associated factors , clinicians can potentially improve the diagnosis and treatment rates of serious depressive disorders in pregnant women . LEVEL OF EVIDENCE : BACKGROUND Depression is familial . Evidence shows that untreated postnatal depression is associated with adverse outcomes for the child . Few studies have traced prospect ively the course of maternal depression through pregnancy , the postnatal period and the following 16 years in relation to adolescent offspring depression . METHOD The sample was recruited from two general practice antenatal clinics . Of 151 mother-child dyads followed from pregnancy to 16 years , information on the course of maternal depression and on depression in adolescent offspring was available for 127 ( 84 % ) . RESULTS Two-thirds ( 82/125 ) of the women had been depressed during the 17-year time period , with the majority ( 54/82 ) experiencing more than one episode . A third of the women were depressed in pregnancy ( 41/124 ) . Over half of these women ( 23/41 ) had consulted a doctor about their mental health prior to being pregnant and almost 90 % ( 35/39 ) had further episodes during the child 's lifetime . 14 % ( 18/127 ) of the adolescent offspring were diagnosed with a depressive disorder at 16 years . Every depressed adolescent had been exposed to maternal depression . The risk of depression for the 16-year-olds exposed to antenatal depression was 4.7 times greater than for offspring not so exposed . The effect of antenatal depression was mediated by repeated exposure . LIMITATIONS The number of study participants is small and limited to an inner-city population . Only depression spectrum diagnoses in the adolescent offspring have been considered . CONCLUSIONS Detection of depression in pregnancy identifies mothers at risk of further depressive episodes and a group of children who are at risk of depression in adolescence Extant research has demonstrated that compared to adults with insecure attachment styles , more securely attached parents tend to be more responsive , sensitive , and involved parents , result ing in improved outcomes for their children . Less studied is the influence of a mother 's attachment style on her attachment to her unborn child during pregnancy and the consequent developmental outcomes of the child during early childhood . Thus , the aim of this prospect i ve longitudinal study was to examine the relationship between maternal – fetal attachment ( MFA ) during pregnancy and infant and toddler outcomes and the role of mothers ' attachment style on early childhood developmental outcomes in an economically disadvantaged sample of women and their children . Gamma regression modeling demonstrated that an avoidant maternal attachment style ( b = .98 , 95 % CI [ .97 , .98 ] , p < 0.001 ) and post-partum depressive symptomatology ( b = .97 , 95 % CI [ .96–.99 ] , p = 0.03 ) were significant predictors of early childhood development . Women demonstrating higher avoidant attachment styles and greater depressive symptomatology were more likely to have children demonstrating early childhood developmental delays than those women with less avoidant attachment styles and less depressive symptomatology . Furthermore , women reporting higher MFA during pregnancy had more secure attachment styles , and their children had more optimal early childhood development than those women reporting lower MFA and less secure attachment styles . Findings have implication s for enhancing early intervention programs aim ed at improving maternal and childhood outcomes . An earlier identification of disruptions in attachment may be beneficial in tailoring interventions focused on the mother – child dyad Adverse effects of perinatal depression on the mother – child interaction are well documented ; however , the influence of maternal – fetal bonding during pregnancy on postpartum bonding has not been clearly identified . The subject of this study was to investigate prospect ively the influence of maternal – fetal bonding and perinatal symptoms of anxiety and depression on postpartum mother – infant bonding . Data from 80 women were analyzed for associations of symptoms of depression and anxiety as well as maternal bonding during pregnancy to maternal bonding in the postpartum period using the Edinburgh Postnatal Depression Scale ( EPDS ) , the State – Trait Anxiety Inventory ( STAI ) , the Pregnancy Related Anxiety Question naire ( PRAQ-R ) , the Maternal – Fetal Attachment Scale ( MFAS ) and the Postpartum Bonding Question naire ( PBQ-16 ) . Maternal education , MFAS , PRAQ-R , EPDS and STAI-T significantly correlated with the PBQ-16 . In the final regression model , MFAS and EPDS postpartum remained significant predictors of postpartum bonding and explained 20.8 % of the variance . The results support the hypothesized negative relationship between maternal – fetal bonding and postpartum maternal bonding impairment as well as the role of postpartum depressive symptoms . Early identification of bonding impairment during pregnancy and postpartum depression in mothers plays an important role for the prevention of potential bonding impairment in the early postpartum period OBJECTIVE To examine the effects of paternal depression during children 's first year on their wellbeing at 4 - 5 years of age using a large , representative sample of Australian families . DESIGN , SETTING AND PARTICIPANTS Prospect i ve study of Australian families from 2004 to 2008 . Two-biological-parent families ( n = 2620 ) from the Longitudinal Study of Australian Children were included if depression measures were available for both parents in 2004 , behavioural and developmental measures were available for children in 2008 , and the families had not separated by 2008 . MAIN OUTCOME MEASURE Child scores on the Strengths and Difficulties Question naire and on a set of Derived Outcome Indices , measured when the child was 4 - 5 years old . Logistic regression modelling was used to investigate how early paternal depression in 2004 influenced child outcomes 4 years later . RESULTS Early paternal depression was a significant predictor of a range of poorer child outcomes ( odds ratio [ OR ] for behavioural difficulties , 3.34 [ 95 % CI , 3.06 - 3.65 ] ; OR for a low development and wellbeing score , 2.70 [ 95 % CI , 2.44 - 2.98 ] ) . These effects remained significant after controlling for both early maternal depression and later paternal depression ( adjusted OR for behavioural difficulties , 1.93 [ 95 % CI , 1.75 - 2.14 ] ; OR for a low development and wellbeing score , 1.65 [ 95 % CI , 1.48 - 1.85 ] ) . CONCLUSIONS Depression in fathers during the first year of a child 's life can have a detrimental impact on their child 's behaviour , and social and emotional development at the point of school entry , in addition to and uniquely compared with depression in mothers . Early intervention to identify and address the mental health needs of fathers is required for the benefit of fathers , children and families BACKGROUND Although maternal perinatal mental illnesses commonly present to and are primarily treated in general practice , few population -based estimates of this burden exist , and the most affected socioeconomic groups of pregnant women remain unclear . AIM To provide estimates of maternal depression , anxiety and serious mental illness ( SMI ) in UK general practice and quantify impacts of socioeconomic deprivation . DESIGN AND SETTING Cross-sectional analysis of prospect ively recorded general practice records from a UK-wide data base . METHOD A pregnancy ending in live birth was r and omly selected for every woman of childbearing age , 1994 - 2009 . Prevalence and diagnostic overlap of mental illnesses were calculated using a combination of medical diagnoses and psychotropic drug prescriptions . Socioeconomic deprivation was assessed using multivariate logistic regression , adjusting for calendar period and pregnancy history . RESULTS Among 116 457 women , 5.1 % presented with antenatal depression and 13.3 % with postnatal depression . Equivalent figures for anxiety were 2.6 % and 3.7 % and for SMI 1/1000 and 2/1000 women . Socioeconomic deprivation increased the risk of all mental illnesses , although this was more marked in older women . Those age 35 - 45 years in the most deprived group had 2.63 times the odds of antenatal depression ( 95 % confidence interval [ CI ] = 2.22 to 3.13 ) compared with the least deprived ; in women aged 15 - 25 years the increased odds associated with deprivation was more modest ( odds ratio = 1.35 , 95 % CI = 1.07 to 1.70 ) . Similar patterns were found for anxiety and SMI . CONCLUSION Strong socioeconomic inequalities in perinatal mental illness persist with increasing maternal age . Targeting detection and effective interventions to high-risk women may reduce inequity and avoid substantial psychiatric morbidity OBJECTIVE to estimate the prevalence of poorer prenatal attachment and its association with psycho-affective factors in pregnant women during the third trimester . DESIGN AND SETTING cross-sectional study in Temuco , La Araucanía Region , Chile . MEASUREMENTS data were collected by structured interview with closed questions for the sociodemographic characterisation of the sample and measurement of six aspects : prenatal attachment , perceived stress , depression , perception of relationship with partner , subjective family support , and obstetric information regarding current and previous pregnancies . PARTICIPANTS 244 pregnant women selected by stratified r and om sampling in all centres ( n=5 ) of the public health system in Temuco , Chile , with proportional allocation . FINDINGS the prevalence of poorer prenatal attachment was 24.3 % ( 95 % confidence interval 19 - 30 % ) , and this was found to be associated with discontent with the pregnancy , unwanted pregnancy , higher levels of perceived stress , depression and low family support . Religious activity and work were found to modulate the association between poorer prenatal attachment and psycho-affective aspects . The percentage of unplanned pregnancies was high in this study ( 61.35 ) , and although this does not have a direct influence on poorer prenatal attachment , it is associated with discontent with the pregnancy and unwanted pregnancy . KEY CONCLUSIONS AND IMPLICATION S FOR PRACTICE the high proportion of poorer prenatal attachment during the third trimester of pregnancy associated with potentially detectable psychosocial factors means that early diagnosis and timely intervention during prenatal care are an essential challenge for midwives in their work . Any progress that can be made during pregnancy will favour the development of the bonding experience after birth , and thus the balanced development of the child Scarce data exists regarding the prevalence of antenatal depression in hospitalized pregnant women , and its effect on perinatal outcome . We aim ed to estimate the risk of maternal depression among women hospitalized in a high-risk pregnancy department , and to evaluate its potential association with adverse perinatal outcome . A depression screening self- question naire-based prospect i ve study was performed , in which hospitalized pregnant women who screened positive for depression were compared to those who screened negative . The Edinburgh Postnatal Depression Scale ( EPDS ) was used for antenatal depression screening . Pregnancy course and perinatal outcome were compared between the groups . A multivariate logistic regression model was constructed to control for clinical ly relevant confounders . During the study period , 279 women met the inclusion criteria . Among them , 28.3 % ( n = 79 ) screened positive for depression ( ≥ 10 points on the EPDS ) . In the univariate analysis , a significantly higher incidence of preterm delivery ( < 37 weeks ) , low birthweight ( < 2500 g ) , low Apgar scores ( at 1 and 5 min ) , and neonatal intensive care unit ( NICU ) admissions were noted among the screen positive group . In the multivariate regression model , controlled for maternal age , ethnicity , gestational diabetes mellitus , preeclampsia , past preterm delivery , and gestational age upon admission , maternal antenatal depression during hospitalization was noted as an independent risk factor for preterm delivery ( adjusted OR 3.32 , 95%CI 1.16–9.52 , p = 0.026 ) . Maternal antenatal depression during hospitalization is very common and appears to play a significant and independent role in the prediction of preterm delivery BACKGROUND Anxiety and depression are common during pregnancy and associated with adverse outcomes for the mother and infant if left untreated . Despite the need to improve treatment accessibility and uptake in this population , no studies have investigated internet-delivered cognitive behavioural therapy ( iCBT ) for antenatal anxiety and depression . In a r and omised controlled trial , we examined the efficacy and acceptability of a brief , unguided iCBT intervention - the MUMentum Pregnancy program - in pregnant women with anxiety and /or depression . METHODS Participants meeting clinical threshold on vali date d self-report measures of generalised anxiety and /or depression were recruited online and r and omised to iCBT ( n = 43 ) or a treatment as usual ( TAU ) control ( n = 44 ) . Outcomes were assessed at baseline , post-treatment and four-week follow-up ; and included anxiety , depression , psychological distress , antenatal bonding , quality of life , and treatment acceptability . RESULTS Of the 36 women who started iCBT , 26 completed all three lessons of treatment ( 76 % adherence rate ) . iCBT produced moderate to large effect size reductions for anxiety on the GAD-7 ( Hedges ' g = 0.76 ) and psychological distress on the Kessler-10 ( g = 0.88 ) that were superior to TAU . Only small nonsignificant differences were found for depression outcomes ( g = < 0.35 ) . Participants reported that iCBT was an acceptable treatment for antenatal anxiety and /or depression . LIMITATIONS Lack of an active control condition and long-term postpartum follow-up . CONCLUSIONS This is the first study to evaluate brief unguided iCBT for antenatal anxiety and depression . While our findings are promising , particularly for anxiety reduction , additional RCTs are required to establish treatment efficacy BACKGROUND Bonding is the process of an emotional relationship between mothers and babies . Pregnancy and postpartum periods are most important of developing a mother-child bonding . Here we aim ed to determine the level of mother-baby bonding and identify the influencing factors during pregnancy and the postpartum period and to examine the relationship between bonding level during pregnancy and the postpartum period . SUBJECTS AND METHODS This cross-sectional descriptive study included twelve districts across a range of socioeconomic structures . Every district was selected by a simple r and om sampling method . Data were collected with Prenatal Attachment Inventory , Mother-to-Infant Bonding Scale , Center for Epidemiologic Studies ' Depression Scale and Beck Anxiety Inventory . The study included two home visits . The first visit at gestational age ≥35 weeks and second visit on the seventh or eighth day of the postpartum period . The study was conducted with 227 pregnant women . RESULTS We found that , 50.7 % pregnant women had prenatal depression and 36.6 % pregnant women had postpartum depression . We detected a negative association between depression level during pregnancy and the postpartum period with mother-baby bonding in the postpartum period ( r=0.174 , p=0.009 ; and r=0.221 , p=0.001 , respectively ) . A negative correlation was detected between anxiety level and mother-baby bonding level in the postpartum period ( r=0.151 , p=0.023 ) . It was found that when the prenatal attachment level increases , the level of postpartum bonding is also increases ( r=0.297 , p=0.000 ) . CONCLUSIONS Depression and anxiety levels were higher during pregnancy than the postpartum period . Depression level during pregnancy and postpartum period depression and anxiety level negatively affected mother-baby bonding in the postpartum period . We found that as prenatal attachment level increases , the level of postpartum bonding also increases Importance Depression during pregnancy and the postpartum period is relatively common and can have adverse effects on both mother and child . Objective To systematic ally review benefits and harms of primary care – relevant interventions to prevent perinatal depression , a major or minor depressive episode during pregnancy or up to 1 year after childbirth , to inform the US Preventive Services Task Force . Data Sources MEDLINE , PubMED ( for publisher-supplied records only ) , PsycINFO , and the Cochrane Central Register of Controlled Trials ; surveillance through December 5 , 2018 . Study Selection R and omized clinical trials ( RCTs ) and nonr and omized controlled intervention studies of interventions ( eg , behavior-based , antidepressants , dietary supplements ) to prevent perinatal depression in general population s of pregnant and postpartum individuals or in those at increased risk of perinatal depression . Large cohort studies were considered for harms of antidepressant use only . Data Extraction and Synthesis Two investigators independently review ed abstract s and full-text articles and quality rated included studies . R and om-effects meta- analysis was used to estimate the benefits of the interventions . Main Outcomes and Measures Depression status ; depression symptoms ; maternal , infant , and child health outcomes . Results Fifty studies ( N = 22 385 ) that met inclusion criteria were identified . Counseling interventions were the most widely studied interventions . Compared with controls , counseling interventions were associated with a lower likelihood of onset of perinatal depression ( pooled risk ratio [ RR ] , 0.61 [ 95 % CI , 0.47 - 0.78 ] ; 17 RCTs [ n = 3094 ] ; I2 = 39.0 % ) . The absolute difference in the risk of perinatal depression ranged from 1.3 % greater reduction in the control group to 31.8 % greater reduction in the intervention group . Health system interventions showed a benefit in 3 studies ( n = 5321 ) and had a pooled effect size similar to that of the counseling interventions , but the pooled effect was not statistically significant using a method appropriate for pooling a small number of studies ( restricted maximum likelihood RR , 0.58 [ 95 % CI , 0.22 - 1.53 ] ; n = 4738 ; I2 = 66.3 % ; absolute risk reduction range , −3.1 % to −13.1 % ) . None of the behavior-based interventions reported on harms directly . A smaller percentage of participants prescribed sertraline had a depression recurrence compared with those prescribed placebo ( 7 % vs 50 % , P = .04 ) at 20 weeks postpartum in 1 very small RCT ( n = 22 analyzed ) but with an increased risk of adverse effects to the mother . Conclusions and Relevance Counseling interventions can be effective in preventing perinatal depression , although most evidence was limited to women at increased risk for perinatal depression . A variety of other intervention approaches provided some evidence of effectiveness but lacked a robust evidence base and need further research ABSTRACT Introduction : Since the maternal-fetal attachment level in unplanned pregnancies is weaker than their planned counterparts , this study aim ed to determine the effect of counselling on maternal-fetal attachment in women with unplanned pregnancy . Methods : This was a r and omised controlled clinical trial on pregnant women with unplanned pregnancy and weak-average maternal-fetal attachment scores . Participants were assigned to a control ( n = 40 ) and an intervention ( n = 40 ) group through r and omised blocking . The intervention group attended 1–3 individual and 6 group counselling sessions and the control group received routine care . The participants completed the Maternal-Fetal Attachment Scale before and four weeks after the intervention . Results : The mean ( st and ard deviation ) maternal-fetal attachment score of the intervention group was increased from 73.6 ( 8.9 ) before the intervention to 96.6 ( 9.3 ) after the intervention . However , the mean ( st and ard deviation ) maternal-fetal attachment scores of the control group were 76.0 ( 9.4 ) and 76.5 ( 6.4 ) before and after the intervention , respectively . The mean maternal-fetal attachment score of the counselling group was significantly higher than that of the control group ( adjusted mean difference : 21.7 ; 95 % confidence interval : 18.6 to 24.9 ; P < 0.001 ) . Conclusion : Counseling has a positive contribution to improving maternal-fetal attachment in women with unplanned pregnancies Purpose : The present study aim ed to determine the effect of group counselling on Maternal-Fetal Attachment ( MFA ) in mothers with unwanted pregnancy . Methods : This study was a r and omised clinical trial . The participants were 80 mothers with unwanted pregnancy during 28 - 34 weeks of pregnancy who referred to health centres of Karaj to receive prenatal care in 2018 . The women were r and omly assigned into intervention ( N = 40 ) and control groups ( N = 40 ) . The intervention group received four weekly group counselling sessions to promote MFA and the control group received routine care . Cranley 's Maternal-Fetal Attachment Scale was used to assess the attachment of mother to fetus at baseline and two weeks after counselling . An ANCOVA test was performed to evaluate the effect of intervention and the number of parity . Results : There was no significant difference between the two groups in terms of general health scores and attachment of mother to fetus at baseline , but after the intervention , the mean scores of MFA in the intervention group had a significant difference with the control group ( p < 0.001 ) ; the ANCOVA test indicated that attachment scores were significant in terms of intervention and pregnancy group and attachment scores indicated further increase in the primipara group compared to the multipara group ( p = 0.041 ) . Conclusion : Considering the effectiveness of group counselling in improving MFA in unplanned pregnancy , it can be used in prenatal care Interviews of 120 British adolescents and their parents ( 80 % of a r and om sample of antenatal patients drawn from a representative urban population and followed longitudinally ) revealed that 40 ( 33 % ) had been arrested and /or had a diagnosis of DSM-IV conduct disorder by 16 years of age ; of those , 18 ( 45 % ) had committed violent acts . Depression in pregnancy significantly predicted violence in adolescence , even after controlling for the family environment , the child 's later exposure to maternal depression , the mother 's smoking and drinking during pregnancy , and parents ' antisocial behavior . Mothers with a history of conduct problems were at elevated risk to become depressed in pregnancy , and the offspring of depressed women had a greater chance of becoming violent by age 16 |
1,078 | 29,580,251 | 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 . | Background Proper implementation of evidence -based interventions is necessary for their full impact to be realized .
However , the majority of research to date has overlooked facilitators and barriers existing outside the boundaries of the implementing organization(s ) .
Better underst and ing and measurement of the external implementation context would be particularly beneficial in light of complex health interventions that extend into and interact with the larger environment they are embedded within .
We conducted a integrative systematic literature review to identify external context constructs likely to impact implementation of complex evidence -based interventions . | 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 mental health interventions into early intervention . Offering problemsolving education exp and ed the range of family support options for mothers with depression risk , thereby advancing the goals of the nation ’s program for children from birth to age three who have developmentaldisabilities . Ongoing analysis of clinical trial data will assess the efficacy of problem-solving education to decrease depressive symptoms among mothers of young children with autism . Emily Feinberg , Sc . D. , C.P.N.P. Michael Silverstein , M.D. , M.P.H. Zh and ra Ferreira-Cesar , OBJECTIVES The objective of this study was to improve the immunization rates of primary care practice s using a team approach . METHODS Practice s performed 35 r and om chart abstract ions at 2 time points and completed a survey about immunizations at baseline and 12 months after intervention . Data were collected for the following immunizations : influenza , pneumococcal , tetanus diphtheria (Td)/tetanus diphtheria pertussis ( Tdap ) , hepatitis A , hepatitis B , meningococcal , varicella , herpes zoster , and human papilloma virus . Between baseline and after intervention , practice teams were given feedback reports and access to an online educational tool , and attended quality improvement coaching conference calls . RESULTS Statistically significant improvements were seen for Td/Tdap ( 45.6 % pre-intervention , 55.0 % post-intervention ; P ≤ .01 ) , herpes zoster ( 12.3 % pre-intervention , 19.3 % post-intervention ; P ≤ .01 ) , and pneumococcal ( 52.2 % pre-intervention , 74.5 % post-intervention ; P ≤ .01 ) immunizations . Data also revealed an increase in the number of physicians who discussed herpes zoster and pneumococcal vaccinations with their patients ( 23.2 % pre-intervention , 43.3 % post-intervention ; P ≤ .01 and 19.9 % pre-intervention , 43.0 % post-intervention ; P ≤ .01 , respectively ) as well as an increase in physicians using the Centers for Disease Control and Prevention immunization schedule ( 52.9 % pre-intervention , 88.2 % post-intervention ; P ≤ .02 ) . CONCLUSIONS The immunization rates of the primary care practice s involved in this study improved OBJECTIVE This study evaluated the initial efficacy and feasibility of implementing multifamily group treatment for veterans with traumatic brain injury ( TBI ) . METHODS Veterans at two Veterans Affairs medical centers were prescreened by their providers for participation in an open trial of multifamily group treatment for TBI . Enrollment was limited to consenting veterans with a clinical diagnosis of TBI sustained during the Operation Enduring Freedom-Operation Iraqi Freedom era , a family member or partner consenting to participate , and a score ≥20 on the Mini-Mental State Examination . The nine-month ( April 2010-March 2011 ) trial consisted of individual family sessions , an educational workshop , and bimonthly multifamily problem-solving sessions . Interpersonal functioning and symptomatic distress among veterans and family burden , empowerment , and symptomatic distress among families were assessed before and after treatment . RESULTS Providers referred 34 ( 58 % ) of 59 veterans screened for the study ; of those , 14 ( 41 % ) met criteria and consented to participate , and 11 ( 32 % ) completed the study . Severity of TBI , insufficient knowledge about the benefits of family involvement , and access problems influenced decisions to exclude veterans or refuse to participate . Treatment was associated with decreased veteran anger expression ( p≤.01 ) and increased social support and occupational activity ( p≤.05 ) , with effect sizes ranging from .6 to 1.0 . Caregivers reported decreased burden ( p≤.05 ) and increased empowerment ( p≤.01 ) . CONCLUSIONS The results supported implementation of a r and omized controlled trial , building in education at the provider and family level |
1,079 | 27,338,458 | 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 | The aim of this systematic review and meta- analysis is to summarise the effects of intermittent energy restriction on weight and biological markers in long term intervention studies of > 6 months duration . | 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 , glycaemic control ( HbA1c ) and blood lipids . RESULTS : For all subjects , intensive diet therapy over the 12-week intervention period result ed in a mean reduction in energy intake of 2360±2780 kJ/day ( 564±665 kcal/day ) and significant reductions in weight ( 6.4±4.6 kg ) , waist circumference ( 8.1±4.6 cm ) , percent body fat ( 1.9±1.5 % ) , HbA1c ( 1.0±1.4 % ) and triglyceride levels ( 0.3±0.6 mmol/l ) compared to baseline levels . Intervention group did not affect clinical outcomes , with the exception of percent body fat . A total of 27 ( 52.9 % ) subjects attended the 18-month follow-up visit . At this visit , none of the improvements in clinical parameters was maintained , with all parameters returning to preintervention levels . CONCLUSIONS : A dietary prescription of 6000–7000 kJ/day ( 1400–1700 kcal/day ) was effective in achieving a 6 % weight loss and improving glycaemic control . The method of implementation made no difference to the outcomes between groups at 12 weeks or 18 months . Thus , we propose that it was the intensive weekly contact with a health professional in combination with moderate energy restriction that facilitated the successful short-term results seen OBJECTIVE Research on long-term maintenance of weight loss is hampered by the fact that relapse typically does not occur until after 6 months . We sought to determine whether relapses could be induced earlier by intentionally interrupting the momentum of weight loss during a treatment program and thus provide a model for weight maintenance research . RESEARCH METHODS AND PROCEDURES Subjects ( N = 142 ) were recruited at two centers and r and omly assigned to a control group , a long break group ( LB ) , or a short break group ( SB ) . The control group received a st and ard behavioral weight loss program with 14 weekly sessions ; the LB and SB groups received the same . However , the LB group took a 6-week break after lesson 7 , and the SB group took a 2-week break after lessons 3 , 6 , and 9 . Participants were instructed to stop all weight loss efforts during breaks . RESULTS Participants seemed to take breaks as prescribed , with interruptions in self-monitoring , dietary adherence , and self-weighing ( but not in exercise ) . However , participants quickly resumed these behaviors after the break . Breaks produced a slowing of weight loss or slight regain , but weight losses during the breaks were not significantly different from the control group . Importantly , overall weight losses ( 0 to 5 months or 0 to 11 months ) did not differ between conditions . DISCUSSION This study was not successful in developing a method to experimentally produce weight loss relapses . However , the finding that prescribed breaks do not have adverse effects may have clinical application Effective strategies are needed to help individuals lose weight and maintain weight loss . The primary aim of this study was to investigate the effect of intermittent energy restriction ( IER ) compared to continuous energy restriction ( CER ) on weight loss after 8 weeks and weight loss maintenance after 12 months . Secondary aims were to determine changes in waist and hip measurements and diet quality . In a r and omized parallel study , overweight and obese ( body mass index [ BMI ] ≥ 27 kg m−2 ) women were stratified by age and BMI before r and omization . Participants undertook an 8‐week intensive period with weight , waist and hip circumference measured every 2 weeks , followed by 44 weeks of independent dieting . A food frequency question naire was completed at baseline and 12 months , from which diet quality was determined . Weight loss was not significantly different between the two groups at 8 weeks ( −3.2 ± 2.1 kg CER , n = 20 , −2.0 ± 1.9 kg IER , n = 25 ; P = 0.06 ) or at 12 months ( −4.2 ± 5.6 kg CER , n = 17 −2.1 ± 3.8 kg IER , n = 19 ; P = 0.19 ) . Weight loss between 8 and 52 weeks was –0.7 ± 49 kg CER vs. −1 ± 1.1 kg IER ; P = 0.6 . Waist and hip circumference decreased significantly with time ( P < 0.01 ) , with no difference between groups . There was an increase in the Healthy Eating Index at 12 months in the CER compared with the IER group ( CER 8.4 ± 9.1 vs. IER −0.3 ± 8.4 , P = 0.006 ) . This study indicates that intermittent dieting was as effective as continuous dieting over 8 weeks and for weight loss maintenance at 12 months . This may be useful for individuals who find CER too difficult to maintain |
1,080 | 25,988,763 | 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 | Weight loss from exercise-induced energy deficits is usually less than expected .
The objective of this systematic review was to investigate predictors of energy compensation , which is defined as body energy changes ( fat mass and fat-free mass ) over the total amount of exercise energy expenditure . | 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 program with 3 groups : ( 1 ) high amount/vigorous intensity ( calorically equivalent to approximately 20 miles [ 32.0 km ] of jogging per week at 65%-80 % peak oxygen consumption ) ; ( 2 ) low amount/vigorous intensity ( equivalent to approximately 12 miles [ 19.2 km ] of jogging per week at 65%-80 % ) , and ( 3 ) low amount/moderate intensity ( equivalent to approximately 12 miles [ 19.2 km ] of walking per week at 40%-55 % ) . Subjects were counseled not to change their diet and were encouraged to maintain body weight . MAIN OUTCOME MEASURES Body weight , body composition ( via skinfolds ) , and waist circumference . RESULTS Of 302 subjects screened , 182 met criteria and were r and omized and 120 completed the study . There was a significant ( P<.05 ) dose-response relationship between amount of exercise and amount of weight loss and fat mass loss . The high-amount/vigorous-intensity group lost significantly more body mass ( in mean [ SD ] kilograms ) and fat mass ( in mean [ SD ] kilograms ) ( -2.9 [ 2.8 ] and -4.8 [ 3.0 ] , respectively ) than the low-amount/moderate-intensity group ( -0.9 [ 1.8 ] and -2.0 [ 2.6 ] , respectively ) , the low-amount/vigorous-intensity group ( -0.6 [ 2.0 ] and -2.5 [ 3.4 ] , respectively ) , and the controls ( + 1.0 [ 2.1 ] and + 0.4 [ 3.0 ] , respectively ) . Both low-amount groups had significantly greater improvements than controls but were not different from each other . Compared with controls , all exercise groups significantly decreased abdominal , minimal waist , and hip circumference measurements . There were no significant changes in dietary intake for any group . CONCLUSIONS In nondieting , overweight subjects , the controls gained weight , both low-amount exercise groups lost weight and fat , and the high-amount group lost more of each in a dose-response manner . These findings strongly suggest that , absent changes in diet , a higher amount of activity is necessary for weight maintenance and that the positive caloric imbalance observed in the overweight controls is small and can be reversed by a modest amount of exercise . Most individuals can accomplish this by walking 30 minutes every day CONTEXT A higher duration and intensity of exercise may improve long-term weight loss . OBJECTIVE To compare the effects of different duration s and intensities of exercise on 12-month weight loss and cardiorespiratory fitness . DESIGN , SETTING , AND PARTICIPANTS R and omized trial conducted from January 2000 through December 2001 involving 201 sedentary women ( mean [ SD ] age , 37.0 [ 5.7 ] years ; mean [ SD ] body mass index , 32.6 [ 4.2 ] ) in a university-based weight control program . INTERVENTION Participants were r and omly assigned to 1 of 4 exercise groups ( vigorous intensity/high duration ; moderate intensity/high duration ; moderate intensity/moderate duration ; or vigorous intensity/moderate duration ) based on estimated energy expenditure ( 1000 kcal/wk vs 2000 kcal/wk ) and exercise intensity ( moderate vs vigorous ) . All women were instructed to reduce intake of energy to between 1200 and 1500 kcal/d and dietary fat to between 20 % and 30 % of total energy intake . MAIN OUTCOME MEASURES Body weight , cardiorespiratory fitness , and exercise participation . RESULTS After exclusions , 184 of 196 r and omized participants completed 12 months of treatment ( 94 % ) . In intention-to-treat analysis , mean ( SD ) weight loss following 12 months of treatment was statistically significant ( P < .001 ) in all exercise groups ( vigorous intensity/high duration = 8.9 [ 7.3 ] kg ; moderate intensity/high duration = 8.2 [ 7.6 ] kg ; moderate intensity/moderate duration = 6.3 [ 5.6 ] kg ; vigorous intensity/moderate duration = 7.0 [ 6.4 ] kg ) , with no significant difference between groups . Mean ( SD ) cardiorespiratory fitness levels also increased significantly ( P = .04 ) in all groups ( vigorous intensity/high duration = 22.0 % [ 19.9 % ] ; moderate intensity/high duration = 14.9 % [ 18.6 % ] ; moderate intensity/moderate duration = 13.5 % [ 16.9 % ] ; vigorous intensity/moderate duration = 18.9 % [ 16.9 % ] ) , with no difference between groups . Post hoc analysis revealed that percentage weight loss at 12 months was associated with the level of physical activity performed at 6 and 12 months . Women reporting less than 150 min/wk had a mean ( SD ) weight loss of 4.7 % [ 6.0 % ] ; inconsistent ( other ) pattern of physical activity , 7.0 % [ 6.9 % ] ; 150 min/wk or more , 9.5 % [ 7.9 % ] ; and 200 min/wk or more of exercise , 13.6 % [ 7.8 % ] . CONCLUSIONS Significant weight loss and improved cardiorespiratory fitness were achieved through the combination of exercise and diet during 12 months , although no differences were found based on different exercise duration s and intensities in this group of sedentary , overweight women PURPOSE The purpose of this study was to determine the effectiveness of brief intense interval training as exercise intervention for promoting health and to evaluate potential benefits about common interventions , that is , prolonged exercise and strength training . METHODS Thirty-six untrained men were divided into groups that completed 12 wk of intense interval running ( INT ; total training time 40 min wk(-1 ) ) , prolonged running ( approximately 150 min wk(-1 ) ) , and strength training ( approximately 150 min wk(-1 ) ) or continued their habitual lifestyle without participation in physical training . RESULTS The improvement in cardiorespiratory fitness was superior in the INT ( 14 % + /- 2 % increase in V˙O2max ) compared with the other two exercise interventions ( 7 % + /- 2 % and 3 % + /- 2 % increases ) . The blood glucose concentration 2 h after oral ingestion of 75 g of glucose was lowered to a similar extent after training in the INT ( from 6.1 + /- 0.6 to 5.1 + /- 0.4 mM , P < 0.05 ) and the prolonged running group ( from 5.6 + /- 1.5 to 4.9 + /- 1.1 mM , P < 0.05 ) . In contrast , INT was less efficient than prolonged running for lowering the subjects ' resting HR , fat percentage , and reducing the ratio between total and HDL plasma cholesterol . Furthermore , total bone mass and lean body mass remained unchanged in the INT group , whereas both these parameters were increased by the strength-training intervention . CONCLUSIONS INT for 12 wk is an effective training stimulus for improvement of cardiorespiratory fitness and glucose tolerance , but in relation to the treatment of hyperlipidemia and obesity , it is less effective than prolonged training . Furthermore and in contrast to strength training , 12 wk of INT had no impact on muscle mass or indices of skeletal health Exercise is recommended by public health agencies for weight management ; however , the role of exercise is generally considered secondary to energy restriction . Few studies exist that have verified completion of exercise , measured the energy expenditure of exercise , and prescribed exercise with equivalent energy expenditure across individuals and genders . Objective The objective of this study was to evaluate aerobic exercise , without energy restriction , on weight loss in sedentary overweight and obese men and women . Design and Methods This investigation was a r and omized , controlled , efficacy trial in 141 overweight and obese participants ( body mass index , 31.0 ± 4.6 kg/m2 ; age 22.6 ± 3.9 years ) . Participants were r and omized ( 2:2:1 ratio ) to exercise at either 400 kcal/session or 600 kcal/session or to a non-exercise control . Exercise was supervised , 5 days/week , for 10 months . All participants were instructed to maintain usual ad libitum diets . Due to the efficacy design , completion of ≥ 90 % of exercise sessions was an a priori definition of per protocol , and these participants were included in the analysis . Results Weight loss from baseline to 10 months for the 400 and 600 kcal/session groups was 3.9 ± 4.9 kg ( 4.3 % ) and 5.2 ± 5.6 kg ( 5.7 % ) , respectively compared to weight gain for controls of 0.5 ± 3.5 kg ( 0.5 % ) ( p<0.05 ) . Differences for weight loss from baseline to 10 months between the exercise groups and differences between men and women within groups were not statistically significant . Conclusions Supervised exercise , with equivalent energy expenditure , results in clinical ly significant weight loss with no significant difference between men and women AIM The purpose of this study was intended to evaluate the effects of a high intensity interval training ( HIIT ) program on the body composition , cardiac function and aerobic capacity in overweight young women . METHODS Sixty female university students ( aged 19 - 20 , BMI ≥25kg/m2 and percentage body fat ≥ 30 % ) were chosen and then r and omly assigned to each of the HIIT group , the moderate intensity continuous training ( MICT ) group and the non-training control group . The subjects in both the HIIT and MICT groups underwent exercise training five times per week for 12 weeks . In each of the training sessions , the HIIT group performed interval exercises at the individualized heart rate ( HR ) of 85 % of VO2max and separated by brief periods of low intensity activity ( HR at 50 % of VO2max ) , while the MICT group did continuous walking and /or jogging at the individualized HR of 50 % of VO2max . RESULTS Both of these exercise training programs produced significant improvements in the subjects ' body composition , left ventricular ejection fraction , heart rate at rest , maximal oxygen uptake and ventilatory threshold . However , the HIIT group achieved better results than those in the MICT group , as it was evaluated by the amount of the effect size . The control group did not achieve any change in all of the measured variables . CONCLUSION The tangible results achieved by our relatively large groups of homogeneous subjects have demonstrated that the HIIT program is an effective measure for the treatment of young women who are overweight To examine the effects of regular participation in recreational soccer on health profile , 36 healthy untrained Danish men aged 20–43 years were r and omised into a soccer group ( SO ; n = 13 ) , a running group ( RU ; n = 12 ) and a control group ( CO ; n = 11 ) . Training was performed for 1 h two or three times per week for 12 weeks ; at an average heart rate of 82 % ( SEM 2 % ) and 82 % ( 1 % ) of HRmax for SO and RU , respectively . During the 12 week period , maximal oxygen uptake increased ( p<0.05 ) by 13 % ( 3 % ) and 8 % ( 3 % ) in SO and RU , respectively . In SO , systolic and diastolic blood pressure were reduced ( p<0.05 ) from 130 ( 2 ) to 122 ( 2 ) mm Hg and from 77 ( 2 ) to 72 ( 2 ) mm Hg , respectively , after 12 weeks , with similar decreases observed for RU . After the 12 weeks of training , fat mass was 3.0 % ( 2.7 ( 0.6 ) kg ) and 1.8 % ( 1.8 ( 0.4 ) kg ) lower ( p<0.05 ) for SO and RU , respectively . Only SO had an increase in lean body mass ( 1.7 ( 0.4 ) kg , p<0.05 ) , an increase in lower extremity bone mass ( 41 ( 8) g , p<0.05 ) , a decrease in LDL-cholesterol ( 2.7 ( 0.2 ) to 2.3 ( 0.2 ) mmol/l ; p<0.05 ) and an increase ( p<0.05 ) in fat oxidation during running at 9.5 km/h . The number of capillaries per muscle fibre was 23 % ( 4 % ) and 16 % ( 7 % ) higher ( p<0.05 ) in SO and RU , respectively , after 12 weeks . No changes in any of the measured variables were observed for CO . In conclusion , participation in regular recreational soccer training , organised as small-sided drills , has significant beneficial effects on health profile and physical capacity for untrained men , and in some aspects it is superior to frequent moderate-intensity running This study investigated the efficacy of free-wheel bicycling and tennis as endurance conditioning activities . The subjects were 38 sedentary , middle-aged male volunteers , who were r and omly assigned to one of four groups : bicyling ( N=9 ) ; tennis ( N=10 ) ; jogging ( N=9 ) ; and control ( N=10 ) . Each subject was tested twice at the beginning and once at the conclusion of the 20-week study . Each training group exercised 3 days/week for 30 min/day , following 15 minutes of formal warm-up . The bicycling , tennis and jogging groups had an average attendance of 3.0 , 2.7 , and 2.8 days/week , and maintained theri exercise intensity at 83 , 65 , and 85 % of HR max respectively . Using analysis of covariance , only the bicycle and jogging groups significantly increased treadmill Vo2max ( 14.8 and 13.3 % respectively ) even though there was a 5.7 % improvement for the tennis group . The control group did not change . Vo2max was also assessed on a cycle ergometer for the bicycle and jogging groups , and increased significantly by 17.4 and 14.0 % respectively , thus , specificity of the training response was not identified . VEmax increased significantly in the bicycling and jogging groups , while resting blood pressure did not change for any of the four groups . Relative to body composition , only the bicycle group increased lean body weight . The bicycle and jogging groups had substantial decreases in relative and absolute body fat , but these changes were not statistically significant due to changes in the control group . In conclusion , bicycling and jogging appear to provide comparable physiological benefits . Tennis produced only modest increases in endurance capacity but , since the duration of each training session was only 30 to 50 % of a typical time period for playing tennis , the results of the present study may , in fact , be underestimating changes in Vo2max due to the interaction of intensity and duration in facilitating change Objective : To determine the effects of a 15-week high-intensity intermittent exercise ( HIIE ) program on subcutaneous and trunk fat and insulin resistance of young women . Design and procedures : Subjects were r and omly assigned to one of the three groups : HIIE ( n=15 ) , steady-state exercise ( SSE ; n=15 ) or control ( CONT ; n=15 ) . HIIE and SSE groups underwent a 15-week exercise intervention . Subjects : Forty-five women with a mean BMI of 23.2±2.0 kg m−2 and age of 20.2±2.0 years . Results : Both exercise groups demonstrated a significant improvement ( P<0.05 ) in cardiovascular fitness . However , only the HIIE group had a significant reduction in total body mass ( TBM ) , fat mass ( FM ) , trunk fat and fasting plasma insulin levels . There was significant fat loss ( P<0.05 ) in legs compared to arms in the HIIE group only . Lean compared to overweight women lost less fat after HIIE . Decreases in leptin concentrations were negatively correlated with increases in VO2peak ( r=−0.57 , P<0.05 ) and positively correlated with decreases in TBM ( r=0.47 ; P<0.0001 ) . There was no significant change in adiponectin levels after training . Conclusions : HIIE three times per week for 15 weeks compared to the same frequency of SSE exercise was associated with significant reductions in total body fat , subcutaneous leg and trunk fat , and insulin resistance in young women UNLABELLED The specificity of training principle predicts that combining resistance and endurance training ( concurrent training ) could interfere with the maximum development of strength and endurance capacity that results from either type of training alone . PURPOSE To determine whether endurance and resistance training performed concurrently produces different performance and physiologic responses compared with each type of training alone . METHODS Untrained male volunteers were r and omly assigned to one of three groups : endurance training ( ET , N = 12 ) ; resistance training ( RT , N = 13 ) ; and concurrent training ( CT , N = 16 ) . The following measurements were made on all subjects before and after 12 wk of training : weight , percent body fat , peak oxygen consumption ( VO(2peak ) ) , isokinetic peak torque and average power produced during single-leg flexion and extension at 60 and 180 degrees.s , one-repetition maximum ( 1RM ) leg press , 1RM bench press , vertical jump height , and calculated jump power . RESULTS Weight and lean body mass ( LBM ) increased significantly in the RT and CT groups ( P < 0.05 ) . Percent body fat was significantly decreased in the ET and CT groups . VO(2peak ) was significantly improved only in the ET group . Peak torque during flexion and extension at 180 degrees.s(-1 ) increased in the RT group . Improvements in 1RM leg press and bench press were significant in all groups , but were significantly greater in the RT and CT compared to the ET group . Jump power improved significantly only in the RT group , and no group showed a significant change in vertical jump height . CONCLUSIONS Concurrent training performed by young , healthy men does not interfere with strength development , but may hinder development of maximal aerobic capacity To study the effect of exercise on appetite in men , hunger , thirst , taste perception , energy intake , and macronutrient choice were assessed in relation to exercise and to sauna ; the latter was done to correct for dehydration and rise in body temperature . Since exercise is used to prevent and cure obesity , subjects included obese as well as nonobese men . Thirty subjects ( 25 + /- 7 years , BMI 22.8 + /- 1.6 and 28.5 + /- 1.9 ) were given twice , in r and om order before and after 2 h of cycling at 60 % of Wmax , 2 h of sauna , or 2 h of rest , an ample choice from solid and liquid almost single-macronutrient food items and a taste perception test with solutions of sucrose , citric acid , NaCl , quinine , a mixture of these , and a carbohydrate electrolyte solution . After cycling as well as after sauna , in comparison to after rest , subjects lost 3 + /- 0.5 % of body mass , while thirst , fluid intake , perception of sweet at relatively low concentrations , and percentage of energy coming from carbohydrate increased significantly . Only after cycling compared to after rest did perception of bitterness at a low concentration increase and hunger and energy intake decrease . We conclude that exercise induced a short-term reduction in hunger and energy intake , whereas exercise and sauna induced a short-term increase in taste perception of sweet at the lower concentration , while macronutrient preference of carbohydrate increased The amount of weight loss induced by exercise is often disappointing . A diet-induced negative energy balance triggers compensatory mechanisms , e.g. , lower metabolic rate and increased appetite . However , knowledge about potential compensatory mechanisms triggered by increased aerobic exercise is limited . A r and omized controlled trial was performed in healthy , sedentary , moderately overweight young men to examine the effects of increasing doses of aerobic exercise on body composition , accumulated energy balance , and the degree of compensation . Eighteen participants were r and omized to a continuous sedentary control group , 21 to a moderate-exercise ( MOD ; 300 kcal/day ) , and 22 to a high-exercise ( HIGH ; 600 kcal/day ) group for 13 wk , corresponding to ∼30 and 60 min of daily aerobic exercise , respectively . Body weight ( MOD : -3.6 kg , P < 0.001 ; HIGH : -2.7 kg , P = 0.01 ) and fat mass ( MOD : -4.0 kg , P < 0.001 and HIGH : -3.8 kg , P < 0.001 ) decreased similarly in both exercise groups . Although the exercise-induced energy expenditure in HIGH was twice that of MOD , the result ing accumulated energy balance , calculated from changes in body composition , was not different ( MOD : -39.6 Mcal , HIGH : -34.3 Mcal , not significant ) . Energy balance was 83 % more negative than expected in MOD , while it was 20 % less negative than expected in HIGH . No statistically significant changes were found in energy intake or nonexercise physical activity that could explain the different compensatory responses associated with 30 vs. 60 min of daily aerobic exercise . In conclusion , a similar body fat loss was obtained regardless of exercise dose . A moderate dose of exercise induced a markedly greater than expected negative energy balance , while a higher dose induced a small but quantifiable degree of compensation The relationship between moderate exercise training ( five 45 min sessions/week , brisk walking at 62 beta + /- 2 % VO2max for 15 weeks , psychological well-being and mood state was investigated in a group of 35 sedentary , mildly obese women . A 2 ( exercise ( EX ) ( N = 18 ) , and nonexercise ( NEX ) ( N = 17 ) groups ) x 3 ( baseline , 6-week , 15-week testing sessions ) factorial design was used with data analyzed using repeated measures ANOVA . Four psychological tests were administered : Daily Hassles Scale ( DHS ) , General Well-being Schedule ( GWB ) , Spielberger State Anxiety Inventory ( S-Anxiety ) , and Profile of Mood States ( POMS ) . The EX and NEX groups had significantly different patterns of change over time for GWB total scores [ F(2,66 ) = 5.72 , p = 0.005 ] and the GWB subscales ' energy level ' and ' freedom from health concern or worry ' . Scores for the EX group were elevated at both 6 and 15 weeks . General well-being total scores and subscale ' energy level ' scores were significantly correlated with improvement in submaximal cardiorespiratory fitness ( r = -0.41 , p = 0.014 ; r = -0.40 , p = 0.017 , respectively ) . Exercise training also had a significant effect on frequency but not intensity of DHS scores , and S-Anxiety , with a significant decrease seen in the EX group at 6 weeks but not 15 weeks . Profile of Mood States scores were not significantly related to exercise training . These data support the results of other studies that have reported improvement in general psychological well-being with exercise training OBJECTIVES The effect of national exercise recommendations on adiposity is unknown and may differ by sex . We examined long-term effects of aerobic exercise on adiposity in women and men . RESEARCH METHODS AND PROCEDURES This was a 12-month r and omized , controlled clinical trial testing exercise effect on weight and body composition in men ( N = 102 ) and women ( N = 100 ) . Sedentary/unfit persons , 40 to 75 years old , were recruited through physician practice s and media . The intervention was facility- and home-based moderate-to-vigorous intensity aerobic activity , 60 min/d , 6 days/wk vs. controls ( no intervention ) . RESULTS Exercisers exercised a mean 370 min/wk ( men ) and 295 min/wk ( women ) , and seven dropped the intervention . Exercisers lost weight ( women , -1.4 vs. + 0.7 kg in controls , p = 0.008 ; men , -1.8 vs. -0.1 kg in controls , p = 0.03 ) , BMI ( women , -0.6 vs. + 0.3 kg/m(2 ) in controls , p = 0.006 ; men , -0.5 kg/m(2 ) vs. no change in controls , p = 0.03 ) , waist circumference ( women , -1.4 vs. + 2.2 cm in controls , p < 0.001 ; men , -3.3 vs. -0.4 cm in controls , p = 0.003 ) , and total fat mass ( women , -1.9 vs. + 0.2 kg in controls , p = 0.001 ; men , -3.0 vs. + 0.2 kg in controls , p < 0.001 ) . Exercisers with greater increases in pedometer-measured steps per day had greater decreases in weight , BMI , body fat , and intra-abdominal fat ( all p trend < 0.05 in both men and women ) . Similar trends were observed for increased minutes per day of exercise and for increases in maximal oxygen consumption . DISCUSSION These data support the U.S. Department of Agriculture and Institute of Medicine guidelines of 60 min/d of moderate-to-vigorous physical activity BACKGROUND In light of the current obesity epidemic , treatment models are needed that can prevent weight gain or provide weight loss . We examined the long-term effects of a supervised program of moderate-intensity exercise on body weight and composition in previously sedentary , overweight and moderately obese men and women . We hypothesized that a 16-month program of verified exercise would prevent weight gain or provide weight loss in the exercise group compared with controls . METHODS This was a r and omized controlled efficacy trial . Participants were recruited from 2 midwestern universities and their surrounding communities . One hundred thirty-one participants were r and omized to exercise or control groups , and 74 completed the intervention and all laboratory testing . Exercise was supervised , and the level of energy expenditure of exercise was measured . Controls remained sedentary . All participants maintained ad libitum diets . RESULTS Exercise prevented weight gain in women and produced weight loss in men . Men in the exercise group had significant mean + /- SD decreases in weight ( 5.2 + /- 4.7 kg ) , body mass index ( calculated as weight in kilograms divided by the square of height in meters ) ( 1.6 + /- 1.4 ) , and fat mass ( 4.9 + /- 4.4 kg ) compared with controls . Women in the exercise group maintained baseline weight , body mass index , and fat mass , and controls showed significant mean + /- SD increases in body mass index ( 1.1 + /- 2.0 ) , weight ( 2.9 + /- 5.5 kg ) , and fat mass ( 2.1 + /- 4.8 kg ) at 16 months . No significant changes occurred in fat-free mass in either men or women ; however , both had significantly reduced visceral fat . CONCLUSIONS Moderate-intensity exercise sustained for 16 months is effective for weight management in young adults Sedentary , eumenorrheic women ( N = 27 ) 22 to 40 years of age , with high baseline levels of plasma high-density lipoprotein cholesterol , were r and omly assigned to a walking ( n = 16 ) or a control group ( n = 11 ) . The training program involved treadmill walking 4.8 km ( 3.0 miles ) four times a week for 40 weeks at a mean intensity of 72 % maximal heart rate . Aerobic power ( VO2max ) was improved by 22 % , but no training effect was observed in body composition variables or blood lipid/lipoprotein levels . Despite additional increments in exercise intensity over the final 20 weeks of training , most of the improvement in VO2max was observed over the first 20 weeks of the study . Exercising subjects ' baseline levels of plasma HDL-C were found to be inversely associated with the change ( delta ) scores in the lipoprotein ( r = -0.51 , p < or = .05 ) This study sought to determine whether the ability to improve cardiorespiratory endurance and body composition is affected by the menopausal status of females . Twenty premenopausal females and 18 postmenopausal females , ages 35 - 49 and 47 - 66 yr , respectively , were r and omly assigned to exercise and control groups depending on menopausal status . Both exercise groups ( PRE-EX , N = 16 ; POST-EN , N = 14 ) participated in a progressive walking program ( 4 days/week for 9 weeks ) at an intensity of 80 % the age-adjusted heart rate maximum ( 80 % HRM ) . Following training , both exercise groups significantly improved submaximal exercise capacity ( SEC ) as measured by oxygen consumption ( l/min ; ml/kg . min ) and treadmill walking time at 80 % HRM . The PRE-EX group significantly improved percent body fat and lean body weight , while there was no significant change in total body weight . The POST-EX group significantly improved total body weight and percent body fat with no significant change in lean body weight . Although some of these changes in body composition were statistically significant , overall the alterations were minimal . ANCOVA revealed exercise , not menopause , to be the effective treatment for improving percent body fat and SEC80%HRM . There were no significant differences between the PRE-EX and POST-EX groups in their ability to improve SEC80%HRM or to reduce percent body fat . The POST-EX group had a significantly greater reduction in total body weight , while the PRE-EX group had significantly greater increases in lean body weight . These findings suggest that the ability to favorably alter body composition and cardiorespiratory endurance through the aerobic conditioning of females is independent of menopausal status Few prospect i ve studies have been conducted with women to examine the effects of walking on body composition and serum lipid profiles . Overweight women were r and omly assigned to either an exercise EX ( no. 18 ) or a nonexercise NEX ( no. 18 ) group . The EX group participated in five 45 min sessions/week of brisk walking at 62 + /- 2 % VO2max for 15 weeks . Statistical analysis ( 2 x 3 repeated measures ANOVA ) revealed that the pattern of change in total body weight [ F(2.68 ) = 6.65 , p = 0.002 ] but not body fat percentage , was significantly different between EX and NEX groups ; NEX subjects had a 1.6 + /- 0.5 kg gain in contrast to no change in EX subjects . The pattern of change in serum triglycerides , total cholesterol , and LDL-C was not significantly different between groups . The interaction statistic for HDL-C , however , was significant [ Pillais Trace ( 2.33 ) = 3.73 , p = 0.035 ] with HDL-C tending to rise in the NEX group in contrast to a small decrease in the EX group . Change in kilocalorie intake was positively correlated with change in HDL-C , total cholesterol , and body weight . Change in body weight also correlated positively with change in HDL-C. Our findings suggest that moderate exercise training alone may not be a sufficient stimulus to affect body composition and serum lipid profiles favorably in overweight women Effects of progressive endurance training on energy expenditure ( EE ) were studied in thirteen elderly sedentary subjects ( 62.8 ( SD 2.3 ) years ) after 7 and 14 weeks of training . Daily EE ( DEE ) and energy cost of the various usual activities were measured over 48 h by whole-body indirect calorimetry . Free-living DEE ( DEEFLC ) was calculated from 7 d activity recordings and the energy costs of activities were measured in the calorimeters using the factorial method . DEEFLC did not vary significantly throughout the training period despite the additional energy cost of training sessions ( 0.60 ( SD 0.15 ) MJ/d ) , because energy expended during free-living activities ( EEACT ) decreased by 4.8 ( SD 7.1)% ( P < 0.05 ) and 7.7 ( SD 8.6)% ( P < 0.01 ) after 7 and 14 weeks of training respectively . Measurements in the calorimeters showed that sleeping metabolic rate transiently increased by 4.6 ( SD 3.2)% after 7 weeks of training ( P < 0.001 ) and returned to its initial level after 14 weeks of training . BMR was 7.6 ( SD 7.0)% ( P < 0.01 ) and 4.1 ( SD 6.1)% ( P = NS ) higher after 7 and 14 weeks of training respectively , than before training . Likewise , diet-induced thermogenesis increased from 3.7 ( SD 2.5 ) to 7.2 ( SD 2.8)% energy intake after 7 weeks of training ( P < 0.05 ) , and returned to its initial level after 14 weeks of training ( 4.2 ( SD 2.6)% energy intake ) . Despite these changes , energy expended during activities and the corresponding DEE did not vary throughout the training period . It was concluded that : ( 1 ) DEEFLC remained constant throughout the training period due to a compensatory decrease in free-living EEACT ; ( 2 ) progressive endurance training induced a transient increase in sleeping metabolic rate , BMR and diet-induced thermogenesis after 7 weeks which was not reflected in the energy expended during activities and DEE OBJECTIVE To determine whether exercise intensity effects a change in body composition . DESIGN /SUBJECTS Twelve untrained , moderately overfat , weight-stable women were r and omly assigned to a high-intensity ( 80 % VO2max ) or low-intensity ( 50 % VO2max ) exercise group . Subjects trained four times per week for 12 weeks in monitored sessions , with a duration sufficient to expend 300 kcal . During this time , subjects were instructed to maintain their normal diet and activity patterns . OUTCOME MEASURES Pretesting and posttesting included measurement of height , weight , body fat ( via hydrostatic weighing ) , seven skinfold sites , seven circumference sites , and VO2max . STATISTICAL ANALYSES Results were analyzed using the Student 's t test and paired sample s t test . RESULTS Posttesting revealed no significant between-group differences for change in weight , percent body fat , fat mass , fat-free mass , sum of skinfold measurements , or sum of circumference measurements . Mean weight loss was 0.7 lb for the high-intensity group ( P = .55 ) and 3.3 lb for the low-intensity group ( P = .03 ) . Hydrostatic data revealed that each group lost an identical amount of fat ( 5.0 lb ) , but the high-intensity group gained more than twice as much fat-free mass ( 4.3 vs 1.8 lb ) . The greater increase in fat-free mass by the high-intensity group explains why the low-intensity group had a greater absolute weight loss . APPLICATIONS/ CONCLUSIONS This study suggests that fat loss is a function of energy expended rather than exercise intensity . Therefore , if fat loss is the goal and time is limited , persons should exercise safely at as high an intensity as tolerable to expend as much energy as possible during their allotted time |
1,081 | 27,747,697 | 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 | Dental implant surgery has developed to a widely used procedure for dental rehabilitation and is a secure and predictable procedure .
Local and systemic risk factors can result in higher failure rates .
Diabetes mellitus is a chronic disease that goes in with hyperglycemia and causes multifarious side effects .
Diabetes as a relative contraindication for implant surgery is controversially discussed .
Because the number of patients suffering from diabetes increases , there are more diabetic patients dem and ing implant procedures .
We aim ed to answer the PICO question “ Do diabetic patients with dental implants have a higher complication rate in comparison to healthy controls ? ” | 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 , n = 19 ) , better-controlled T2DM ( BCDM , n = 16 ) , and poorly controlled T2DM ( PCDM , n = 16 ) indicated for implant therapy were recruited . The implant stability quotient ( ISQ ) was determined at implant placement , 3 , 6 , and 12 months . Levels of transforming growth factor- β ( TGF-β ) , fibroblast growth factor ( FGF ) , osteopontin ( OPN ) , osteocalcin ( OC ) , and osteoprotegerin ( OPG ) in the peri-implant fluid were quantified at 15 days , and 3 , 6 , and 12 months , using the Luminex assay . RESULTS OPG and OPN levels were higher in SH at 12 months than at15 days ( p < .05 ) , whereas OC and TGF-β were lower in PCDM at 12 months compared with the 15-day and 3-month follow-ups , respectively ( p < .05 ) . Inter-group analyses showed lower OPN levels in PCDM compared with SH at 12 months ( p < .05 ) . The ISQ was higher at 12 months when compared with baseline and 3 months in SH ( p < .05 ) , whereas no differences were observed during follow-up in diabetics , regardless of glycemic control ( p > .05 ) . No difference in ISQ was observed among groups over time ( p > .05 ) . CONCLUSION Poor glycemic control negatively modulated the bone factors during healing , although T2DM , regardless of glycemic status , had no effect on implant stabilization OBJECTIVES The objective of this prospect i ve , controlled clinical study was to determine the outcomes of dental implant therapy with staged guided bone regeneration procedures in patients with type 2 diabetes . PATIENTS AND METHODS Twenty-four patients were included in the study . Half of the patients were diagnosed with type 2 diabetes mellitus ( group 1 ) while the other half ( group 2 ) of the patients consisted of patients without diabetes . The edentulous maxillary anterior/premolar regions with sufficient vertical height but inadequate horizontal width were treated with staged guided bone regeneration technique and with one or two implant-supported fixed restorations . The patients were followed up at least for 12 months . The parameters that were evaluated were radiographic evaluations on CBCT images and periapical radiographs , histomorphometric analysis , resonance frequency analysis ( RFA ) and wound-healing parameters . The data were analyzed statistically . RESULTS A total of 43 implants were placed in 24 patients ( 22 implants in group 1 and 21 implants in group 2 ) . The survival rates of implants were 100 % for both groups . The success rate of implants was 95 % for group 1 and 100 % for group 2 . None of the parameters including CBCT findings , RFA values , success rates and wound-healing scores showed a significant difference between the two groups . CONCLUSION Staged guided bone regeneration is a feasible augmentation procedure for the treatment of horizontal bone deficiencies of the maxillary anterior/premolar regions in well-controlled type 2 diabetic patients |
1,082 | 27,251,897 | 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 . | Objective To systematic ally review the literature on the clinical outcomes of scapular-focused treatments in participants with subacromial pain syndrome ( SPS ) . | 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 to determine whether scapular dysfunction was predictive of subsequent throwing-related upper extremities sustained . RESULTS There were 12 throwing-related upper extremity injuries sustained in the 246 participants , yielding an injury rate of 1.0 per 1,000 athlete exposures . There were no significant differences in injury rates between the participants with normal scapular function versus subtle scapular dysfunction ( P = .62 ) , normal scapular function versus obvious scapular dysfunction ( P = .26 ) , or subtle versus obvious scapular dysfunction ( P = .45 ) . CONCLUSION This study showed that scapular dysfunction identified during preseason screenings is not associated with subsequent throwing-related upper extremity injury OBJECTIVES The aim of the study was to compare the effects of two different exercise programs on pain , range of motion ( ROM ) , and functional results in frozen shoulder . METHODS Twenty-two female and 7 male patients [ mean age 52.1 years ( range 38 - 65 years ) ] were r and omly allocated into two groups : 14 in the first group and 15 in the second group . The patients were treated for 6 weeks ( 30 sessions ) at hospital under the supervision of physical therapist . Both groups were treated with transcutaneous electrical nerve stimulation , cold pack , and nonsteroidal antiinflammatory drugs ; and were given glenohumeral ROM exercises . The scapulothoracic exercises were performed only by the second group . Functional results were assessed using the modified Constant score , pain was assessed using visual analog scale ( VAS ) , and ROM was measured with a goniometer . Assessment s were performed before treatment and repeated at 6 and 12 weeks of treatment . RESULTS In both groups , the Constant score and ROM were increased , and VAS was decreased at the end of 6 and 12 weeks . The modified Constant score was not significantly different between the groups before and after treatment . VAS score was better in the second group at 6 weeks ( p<0.01 ) . Improvement in ROM was significantly better in the second group at 12 weeks ( p=0.005 ) . CONCLUSION In addition to glenohumeral ROM exercises , scapulothoracic exercises contribute to decreasing pain and increasing ROM in patients with frozen shoulder 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 . OBJECTIVE The aim of this study was to evaluate the initial effects of scapular mobilization ( SM ) on shoulder range of motion ( ROM ) , scapular upward rotation , pain , and function . DESIGN Pretest-posttest for 3 groups ( SM , sham , and control ) . SETTING A double-blinded , r and omized , placebo-controlled trial was conducted to evaluate the initial effect of the SM at a sports physiotherapy clinic . PARTICIPANTS 39 subjects ( 22 women , 17 men ; mean age 54.30 + /- 14.16 y , age range 20 - 77 y ) . INTERVENTIONS A visual analog scale , ROM , scapular upward rotation , and function were assessed before and just after SM . SM ( n = 13 ) consisted of the application of superoinferior gliding , rotations , and distraction to the scapula . The sham ( n = 13 ) condition replicated the treatment condition except for the h and positioning . The control group ( n = 13 ) did not undergo any physiotherapy and rehabilitation program . MAIN OUTCOME MEASURES Pain severity was assessed with a visual analog scale . Scapular upward rotation was measured with a baseline digital inclinometer . Constant Shoulder Score ( CSS ) was used to measure shoulder function . RESULTS After SM , we found significant improvements for shoulder ROM , scapular upward rotation , and CSS between pretreatment and posttreatment compared with the sham and control groups . In the sham group , shoulder-ROM values increased or decreased for the shoulder and scapular upward rotation was not changed . Pain , ROM , and physical function of the shoulder were not significantly different in the sham group than in controls ( P > .05 ) . CONCLUSIONS SM may be a useful manual therapy technique to apply to participants with a painful limitation of the shoulder . SM increases ROM and decreases pain intensity Aim To determine whether rotator cuff strength , glenohumeral joint range of motion and scapular control are associated with shoulder injuries among elite male h and ball players . Methods A total of 206 players in the Norwegian elite h and ball league for men were tested prior to the 2011–2012 season . Measures included : ( 1 ) glenohumeral internal and external rotation range of motion , ( 2 ) isometric internal rotation , external rotation and abduction strength and ( 3 ) assessment of scapular dyskinesis . Players were followed prospect ively for the entire regular season ( 30 weeks ) , with shoulder problems registered bi-weekly using the Oslo Sports Trauma Research Center Overuse Injury Question naire . A cumulative severity score was calculated for each player based on their question naire responses . This was used as the outcome measure in risk factor analyses . Results The average prevalence of shoulder problems throughout the season was 28 % ( 95 % CI 25 % to 31 % ) . The prevalence of substantial shoulder problems , defined as those leading to moderate or severe reductions in h and ball participation or performance , or to time loss , was 12 % ( 95 % CI 11 % to 13 % ) . Significant associations were found between obvious scapular dyskinesis ( OR 8.41 , 95 % CI 1.47 to 48.1 , p<0.05 ) , total rotational motion ( OR 0.77 per 5 ° change , 95 % CI 0.56 to 0.995 , p<0.05 ) and external rotation strength ( OR 0.71 per 10 Nm change , 95 % CI 0.44 to 0.99 , p<0.05 ) and shoulder injury . Conclusions Injury prevention programmes should incorporate interventions aim ed at improving glenohumeral rotational range of motion , external rotation strength and scapular control OBJECTIVE Evidence for effective management of shoulder impingement is limited . The present study aim ed to quantify the clinical , neurophysiological , and biomechanical effects of a scapular motor control retraining for young individuals with shoulder impingement signs . METHOD Sixteen adults with shoulder impingement signs ( mean age 22 ± 1.6 years ) underwent the intervention and 16 healthy participants ( 24.8 ± 3.1years ) provided reference data . Shoulder function and pain were assessed using the Shoulder Pain and Disability Index ( SPADI ) and other question naires . Electromyography ( EMG ) and 3-dimensional motion analysis was used to record muscle activation and kinematic data during arm elevation to 90 ° and lowering in 3 planes . Patients were assessed pre and post a 10-week motor control based intervention , utilizing scapular orientation retraining . RESULTS Pre-intervention , patients reported pain and reduced function compared to the healthy participants ( SPADI in patients 20 ± 9.2 ; healthy 0 ± 0 ) . Post-intervention , the SPADI scores reduced significantly ( P < .001 ) by a mean of 10 points ( ±4 ) . EMG showed delayed onset and early termination of serratus anterior and lower trapezius muscle activity pre-intervention , which improved significantly post-intervention ( P < .05 ) . Pre-intervention , patients exhibited on average 4.6 - 7.4 ° less posterior tilt , which was significantly lower in 2 arm elevation planes ( P < .05 ) than healthy participants . Post-intervention , upward rotation and posterior tilt increased significantly ( P < .05 ) during 2 arm movements , approaching the healthy values . CONCLUSION A 10-week motor control intervention for shoulder impingement increased function and reduced pain . Recovery mechanisms were indicated by changes in muscle recruitment and scapular kinematics . The efficacy of the intervention requires further examined in a r and omized control trial |
1,083 | 23,598,969 | 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 | OBJECTIVE The authors sought to identify factors that moderate outcome in late-life major depression and that identify patients for whom antidepressants have clinical ly meaningful effects . | 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 " real world " setting s. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks . The clinicians were assisted by a clinical research coordinator in the application of measurement-based care , which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures . Remission was defined as an exit score of < or=7 on the 17-item Hamilton Depression Rating Scale ( HAM-D ) ( primary outcome ) or a score of < or=5 on the 16-item Quick Inventory of Depressive Symptomatology , Self-Report ( QIDS-SR ) ( secondary outcome ) . Response was defined as a reduction of > or=50 % in baseline QIDS-SR score . RESULTS Nearly 80 % of the 2,876 out patients in the analyzed sample had chronic or recurrent major depression ; most also had a number of comorbid general medical and psychiatric conditions . The mean exit citalopram dose was 41.8 mg/day . Remission rates were 28 % ( HAM-D ) and 33 % ( QIDS-SR ) . The response rate was 47 % ( QIDS-SR ) . Patients in primary and psychiatric care setting s did not differ in remission or response rates . A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment . Participants who were Caucasian , female , employed , or had higher levels of education or income had higher HAM-D remission rates ; longer index episodes , more concurrent psychiatric disorders ( especially anxiety disorders or drug abuse ) , more general medical disorders , and lower baseline function and quality of life were associated with lower HAM-D remission rates . CONCLUSIONS The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials . The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results BACKGROUND It is well established that subjects participating in controlled clinical trials may not be representative of patients seen in actual practice . Given that efficacy and safety of sertraline have been investigated almost exclusively in controlled clinical trials , the aim of this study was to investigate efficacy , safety , and predictors of treatment response to sertraline in routine clinical practice . METHODS A total of 1878 depressed out patients ( 69.5 % female ; mean age , 50.3 years ) participated in this prospect i ve , open-label , non-interventional , postmarketing surveillance study of sertraline . The primary study outcome was change in depression severity as assessed independently with the Patient Health Question naire ( PHQ-9 ) depression scale and Clinical Global Impression ( CGI ) scales after 12 weeks of treatment . Stepwise logistic regression analyses were used to identify independent predictors of treatment response . RESULTS Using st and ard criteria to define clinical improvement , responder rates were 87.7 % ( PHQ-9 ) and 87.2 % ( CGI ) , respectively . Remission , i.e. a PHQ-9 score of 5 or below , occurred in 56.9 % of patients . Independent baseline predictors of CGI treatment response were : non-chronic course of depression ( OR=2.8 , p < 0.001 ) , non-psychiatric treatment setting ( OR=2.5 , p < 0.001 ) , absence of comorbid physical disease ( OR=1.9 , p < 0.001 ) , depression-related work disability ( OR=1.9 , p < 0.001 ) , and no previous antidepressant medication ( OR=1.5 , p=0.03 ) . Adverse events were reported by 4.8 % of patients . LIMITATIONS Lack of a control group limits the conclusions that can be drawn from this study . CONCLUSIONS For treatment of depressive disorders in routine outpatient setting s , sertraline is safe and efficacious . Patients without prior episodes of depression , without medical comorbidity , and those with higher levels of depression-related functional limitations are most likely to respond to sertraline treatment BACKGROUND Elderly patients with major depression , including those having a first episode , are at high risk for recurrence of depression , disability , and death . METHODS We tested the efficacy of maintenance paroxetine and monthly interpersonal psychotherapy in patients 70 years of age or older who had depression ( 55 percent of whom were having a first episode ) in a 2-by-2 , r and omized , double-blind , placebo-controlled trial . Among patients with a response to treatment with paroxetine and psychotherapy , 116 were r and omly assigned to one of four maintenance-treatment programs ( either paroxetine or placebo combined with either monthly psychotherapy or clinical -management sessions ) for two years or until the recurrence of major depression . Clinical -management sessions , conducted by the same nurses , social workers , and psychologists who provided psychotherapy , involved discussion of symptoms . RESULTS Major depression recurred within two years in 35 percent of the patients receiving paroxetine and psychotherapy , 37 percent of those receiving paroxetine and clinical -management sessions , 68 percent of those receiving placebo and psychotherapy , and 58 percent of those receiving placebo and clinical -management sessions ( P=0.02 ) . After adjustment for the effect of psychotherapy , the relative risk of recurrence among those receiving placebo was 2.4 times ( 95 percent confidence interval , 1.4 to 4.2 ) that among those receiving paroxetine . The number of patients needed to be treated with paroxetine to prevent one recurrence was 4 ( 95 percent confidence interval , 2.3 to 10.9 ) . Patients with fewer and less severe coexisting medical conditions ( such as hypertension or cardiac disease ) received greater benefit from paroxetine ( P=0.03 for the interaction between treatment with paroxetine and baseline severity of medical illness ) . CONCLUSIONS Patients 70 years of age or older with major depression who had a response to initial treatment with paroxetine and psychotherapy were less likely to have recurrent depression if they received two years of maintenance therapy with paroxetine . Monthly maintenance psychotherapy did not prevent recurrent depression . ( Clinical Trials.gov number , NCT00178100 . ) OBJECTIVE This study compared the effects of duloxetine , 60 mg/day , versus placebo on cognition , depression , and pain in elderly patients with recurrent major depressive disorder . METHOD Patients were r and omly assigned ( 2:1 ) to duloxetine , 60 mg/day ( N=207 ) , or placebo ( N=104 ) for 8 weeks in a double-blind study . The primary outcome measure was a prespecified composite cognitive score composed of four individual tests . Secondary measures included the Geriatric Depression Scale , the Hamilton Depression Rating Scale , the Visual Analogue Scale assessing pain , and st and ard safety and tolerability assessment s. RESULTS Patients had a median age of 72 years ( range=65 - 90 ) . Duloxetine demonstrated significantly greater improvement in the composite cognitive score versus placebo ( least-squares mean change from baseline to endpoint : 1.95 versus 0.76 ) , driven by improved verbal learning and memory . Duloxetine treatment showed significantly greater baseline-to-endpoint reductions in both Hamilton depression scale ( -6.49 versus -3.72 ) and Geriatric Depression Scale ( -4.07 versus -1.34 ) total scores compared with placebo . Hamilton depression scale response ( 37.3 % versus 18.6 % ) and remission ( 27.4 % versus 14.7 % ) rates at endpoint were significantly higher for duloxetine than for placebo . Duloxetine significantly improved Visual Analogue Scale scores for back pain and time in pain while awake versus placebo . Significantly fewer patients receiving duloxetine withdrew from the study because of lack of efficacy ( 2.9 % versus 9.6 % ) ; the incidences of discontinuation due to adverse events were similar for duloxetine and placebo ( 9.7 % versus 8.7 % ) . CONCLUSIONS Duloxetine improved cognition , depression , and some pain measures and was safe and well tolerated in elderly patients with recurrent major depressive disorder OBJECTIVE Approximately half of older patients treated for major depressive disorder ( MDD ) do not achieve symptomatic remission and functional recovery with first-line pharmacotherapy . This study aims to characterize sociodemographic , clinical , and neuropsychologic correlates of full , partial , and non-response to escitalopram monotherapy of unipolar MDD in later life . METHODS One hundred and seventy-five patients aged 60 and older were assessed at baseline on demographic variables , depression severity , hopelessness , anxiety , cognitive functioning , co-existing medical illness burden , social support , and quality of life ( disability ) . Subjects received 10 mg/d of open-label escitalopram and were divided into full ( n = 55 ; 31 % ) , partial ( n = 75 ; 42.9 % ) , and non-responder ( n = 45 ; 25.7 % ) groups based on Hamilton depression scores at week 6 . Univariate followed by multivariate analyses tested for differences between the three groups . RESULTS Non-responders to treatment were found to be more severely depressed and anxious at baseline than both full and partial responders , more disabled , and with lower self-esteem than full responders . In general partial responders resembled full responders more than they resembled non-responders . In multivariate models , more severe anxiety symptoms ( both psychological and somatic ) and lower self-esteem predicted worse response status at 6 weeks . CONCLUSION Among treatment-seeking elderly persons with MDD , higher anxiety symptoms and lower self-esteem predict poorer response after six weeks of escitalopram treatment BACKGROUND Despite the high prevalence of depression in elderly patients , few well- design ed , placebo-controlled studies of antidepressants have been conducted in this population . This masked , placebo-controlled trial assessed the efficacy and safety of venlafaxine and fluoxetine in depressed patients older than 65 years . METHOD Three hundred patients were r and omly assigned to treatment with venlafaxine immediate release ( [ IR ] ; N = 104 ) , fluoxetine ( N = 100 ) , or placebo ( N = 96 ) in an eight-week trial . Venlafaxine doses were titrated from 37.5 to 225 mg per day and fluoxetine doses were titrated from 20 to 60 mg per day , as necessary , over 29 days . Efficacy variables included the 21-item Hamilton Depression Rating Scale ( HAM-D21 ) total score , HAM-D21 depressed mood item score , scores on the Montgomery Asberg Depression Rating Scale ( MADRS ) , Clinical Global Impression-Severity of Illness ( CGI-S ) and Improvement ( CGI-I ) scales , and rates of response ( based on change from baseline HAM-D or MADRS score or CGI-I score ) and remission ( HAM-D17 < or = 7 ) . For the purpose s of this report , efficacy analyses are focused on the HAM-D21 total score . Safety assessment s included monitoring of adverse events ( AEs ) , physical examinations , vital signs assessment s , laboratory determinations , and electrocardiograms . RESULTS In all three of the treatment groups , there was a significant reduction at week 8 compared with the baseline HAM-D21 total score . However , there were no significant differences among the three treatment groups on the change in HAM-D21 , MADRS , or CGI scores from baseline to week 8 . There was no statistically significant difference in the proportion of remitters at the last on-therapy visit . The incidence of individual AEs was higher in the venlafaxine group ( 27 % ) compared with patients taking fluoxetine ( 19 % ) or placebo ( 9 % ) . CONCLUSION In this study , there was no significant difference in efficacy among placebo , venlafaxine , and fluoxetine for the treatment of depression BACKGROUND Depression is the second most common neuropsychiatric disorder in older Americans , with significant clinical and public health costs . Despite advances in treatment , late-life depression remains a clinical challenge . Although the selective serotonin reuptake inhibitors ( SSRIs ) are the most common pharmacologic intervention for late-life depression , few placebo-controlled trials have assessed the efficacy of SSRIs for this condition . METHOD In this 12-week , multicenter , placebo-controlled , flexible-dose , double-blind , r and omized trial , 319 elderly patients ( mean age = 70 years ) were treated with controlled-release paroxetine ( paroxetine CR ) up to 50 mg/day ( N = 104 ) , immediate-release paroxetine ( paroxetine IR ) up to 40 mg/day ( N = 106 ) , or placebo ( N = 109 ) . Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) . The primary efficacy measure was change from baseline to endpoint in HAM-D total score . RESULTS The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 ( 95 % confidence interval [ CI ] = -4.47 to -0.73 , p = .007 ) at the week 12 last-observation-carried-forward ( LOCF ) endpoint . The adjusted difference between paroxetine IR and placebo was -2.8 ( 95 % CI = -4.65 to -0.99 , p = .003 ) at week 12 . Paroxetine CR and IR were more effective than placebo , with mean + /- SD endpoint HAM-D total scores of 10.0 + /- 7.41 and 10.0 + /- 7.10 , respectively , for the active treatments compared with 12.6 + /- 7.34 for placebo . Response , defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale , was achieved by 72 % of paroxetine CR patients ( LOCF ; p < .002 vs. placebo ) , 65 % of paroxetine IR patients ( p = .06 vs. placebo ) , and 52 % of placebo patients . Remission , defined as a HAM-D total score < or = 7 , was achieved by 43 % of paroxetine CR patients ( LOCF ; p = .009 vs. placebo ) , 44 % of paroxetine IR patients ( p = .01 vs. placebo ) , and 26 % of placebo patients . In a post hoc analysis , mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients ( duration > 2 years ) and those with short-term ( < or = 2 years ) depression . Dropout rates due to adverse events were 12.5 % for paroxetine CR , 16.0 % for paroxetine IR , and 8.3 % for placebo . CONCLUSION Paroxetine CR and paroxetine IR are effective and well tolerated treatments for major depressive disorder in elderly patients , including those with chronic depression Background / Aims : To evaluate the efficacy and safety of venlafaxine in the treatment of major depression in dementia . Methods : Thirty-one out patients who had dementia and major depression participated in this r and omized , double-blind , placebo-controlled , 6-week , flexible dose clinical trial . The screening measures were Cornell Scale for depression in dementia , DSM-IV for depression and dementia and Mini-Mental State Examination . The outcome measures were response rate , Montgomery-Åsberg Depression Rating scale and Clinical Global Impressions . Results : The percentage of patients defined as Montgomery-Åsberg Depression Rating scale responders was approximately the same in the placebo and in the venlafaxine groups . Clinical Global Impressions showed no significant difference between the groups . The reasons for dropouts show borderline significance between the two groups . There was no statistically significant difference in the incidence of adverse events between the venlafaxine and placebo-treated groups . Conclusions : Our data do not support the hypothesis that venlafaxine improves mood in elderly demented patients OBJECTIVE To evaluate the efficacy and tolerability of low daily doses of controlled-release ( CR ) paroxetine in patients with late-life depression . METHOD This was a 10-week , multicenter , placebo-controlled , double-blind , fixed-dose trial r and omly assigning patients > or= 60 years old to daily doses of paroxetine CR 12.5 mg ( N = 168 ) , paroxetine CR 25 mg ( N = 177 ) , or placebo ( N = 180 ) . Patients had major depressive disorder ( DSM-IV criteria ) and 17-item Hamilton Rating Scale for Depression ( HAM-D ) total scores of > or= 18 . The primary efficacy variable was the change from baseline to study endpoint in total HAM-D scores . The study was conducted from June 2003 to October 2004 . RESULTS The drug/placebo difference in HAM-D change from baseline at study endpoint was -1.8 ( 95 % CI = -3.41 to -0.19 , p = .029 ) for paroxetine CR 12.5 mg , and -3.3 ( 95 % CI = -4.84 to -1.68 , p < .001 ) for paroxetine CR 25 mg . A significantly larger percentage of patients achieved remission ( HAM-D total score < or= 7 at endpoint ) with paroxetine CR 25 mg ( 41 % ) , but not with 12.5 mg ( 31 % ) , as compared with placebo ( 28 % ) ( p = .008 ) . Both doses of paroxetine CR also achieved statistical significance compared to placebo for the Clinical Global Impressions-Severity of Illness scale ( p < .01 ) and the patient-rated measures of depression severity ( p < .05 ) and quality of life ( p < or= .001 ) . Both active treatments were generally well tolerated , with adverse event withdrawal rates of 6 % , 8 % , and 7 % for paroxetine CR 12.5 mg , paroxetine CR 25 mg , and placebo , respectively . CONCLUSION These data demonstrate that paroxetine CR 12.5 mg and 25 mg daily are efficacious and well tolerated in the treatment of major depressive disorder in patients > or= 60 years of age , although effect sizes are relatively smaller with the 12.5 mg/day dose OBJECTIVE This study was design ed to evaluate the comparative efficacy and safety of sertraline and nortriptyline for the treatment of major depressive disorder in older adults . METHOD A double-blind , parallel group design was used to compare 210 out patients , 60 years of age and older , who met DSM-III-R criteria for major depressive episode and had a minimum Hamilton Depression Rating Scale score of 18 . The patients were r and omly assigned to 12 weeks of treatment with either sertraline ( 50 - 150 mg/day ) or nortriptyline ( 25 - 100 mg/day ) . RESULTS The safety profiles of the two treatments were similar except that nortriptyline treatment was associated with a significant increase in pulse rate , whereas sertraline was associated with a nonsignificant decrease . Efficacy of both drugs was similar for both treatments at all time points , with 71.6 % ( N=53 of 74 ) of the sertraline-treated patients and 61.4 % ( N=43 of 70 ) of the nortriptyline-treated patients achieving responder status by week 12 . Time to response was also similar , with more than 75 % of the improvement in scores on the Hamilton depression scale having occurred by week 6 . Secondary efficacy measures ( posttreatment measures of cognitive function , memory , and quality of life ) revealed a significant advantage for sertraline treatment . CONCLUSIONS Primary efficacy measures showed sertraline and nortriptyline to be similarly effective . With secondary outcome measures there was consistent evidence of an advantage for the sertraline-treated group . The clinical impact of these measures on the long-term well-being of elderly depressed patients should be examined in a study of maintenance treatment OBJECTIVE This study determined the efficacy of antidepressant medication for the treatment of depression in the " old-old . " METHOD This r and omized 8-week medication trial compared citalopram , 10 - 40 mg/day , to placebo in the treatment of patients 75 and older with unipolar depression . RESULTS A total of 174 patients who were 58 % women with a mean age of 79.6 years ( SD=4.4 ) and a mean baseline Hamilton Depression Rating Scale score of 24.3 ( SD=4.1 ) were r and omly assigned to treatment at 15 sites . There was a main effect for site but not for treatment condition . The remission rate , defined as a final Hamilton depression scale score < 10 , was 35 % for the citalopram and 33 % for the placebo groups . However , patients with severe depression ( baseline Hamilton depression scale score > 24 ) tended to have a higher remission rate with medication than with placebo ( 35 % versus 19 % ) . CONCLUSIONS In the oldest group of community-dwelling patients to be studied to date , medication was not more effective than placebo for the treatment of depression . However , given the considerable psychosocial support received by all patients , the placebo condition represents more than the ingestion of an inactive pill . Across sites , there was considerable range in response to medication , 18 % to 82 % , and to placebo , 16 % to 80 % OBJECTIVE There have been few placebo-controlled trials of selective serotonin reuptake inhibitors for depressed elderly patients . This placebo-controlled study of sertraline was design ed to confirm the results of non-placebo-controlled trials . METHOD The subjects were out patients age 60 years or older who had a DSM-IV diagnosis of major depressive disorder and a total score on the 17-item Hamilton Depression Rating Scale of 18 or higher . The patients were r and omly assigned to 8 weeks of double-blind treatment with placebo or a flexible daily dose of 50 or 100 mg of sertraline . The primary outcome variables were the Hamilton scale and Clinical Global Impression ( CGI ) scales for severity and improvement . RESULTS A total of 371 patients assigned to sertraline and 376 assigned to placebo took at least one dose . At endpoint , the patients receiving sertraline evidence d significantly greater improvements than those receiving placebo on the Hamilton depression scale and CGI severity and improvement scales . The mean changes from baseline to endpoint in Hamilton score were -7.4 points ( SD=6.3 ) for sertraline and -6.6 points ( SD=6.4 ) for placebo . The rate of CGI-defined response at endpoint was significantly higher for sertraline ( 45 % ) than for placebo ( 35 % ) , and the time to sustained response was significantly shorter for sertraline ( median , 57 versus 61 days ) . There were few discontinuations due to treatment-related adverse events , 8 % for sertraline and 2 % for placebo . CONCLUSIONS Sertraline was effective and well tolerated by older adults with major depression , although the drug-placebo difference was not large in this 8-week trial OBJECTIVE Depression is common in Alzheimer disease ( AD ) , and antidepressants are commonly used for its treatment , however , evidence for antidepressant efficacy in this population is lacking . The authors conducted a multicenter , r and omized , placebo-controlled trial titled " Depression in Alzheimer 's Disease-2 " to assess the efficacy and tolerability of sertraline for depression in AD . METHODS One hundred thirty-one participants from five U.S. medical centers with mild-to-moderate AD ( Mini-Mental State Examination scores 10 - 26 ) and depression of AD were r and omized to double-blinded treatment with sertraline ( N = 67 ) or placebo ( N = 64 ) , with a target dosage of 100 mg daily . Efficacy was assessed using logistic regressions and mixed effects models in an intention-to-treat analysis with imputation of missing data . Principal outcome measures were modified Alzheimer 's Disease Cooperative Study - Clinical Global Impression of Change ( mADCS-CGIC ) , change in Cornell Scale for Depression in Dementia ( CSDD ) scores , and remission defined by both mADCS-CGIC score < or=2 and CSDD score < or=6 . RESULTS mADCS-CGIC ratings ( odd ratio [ OR = 1.01 ] , 95 % confidence interval [ CI ] : 0.52 - 1.97 , p = 0.98 ) , CSDD scores ( median difference at 12 weeks 1.2 , 95 % CI : 1.65 - 4.05 , p = 0.41 ) , and remission at 12 weeks of follow-up ( OR = 2.06 , 95 % CI : 0.84 - 5.04 , p = 0.11 ) did not differ between sertraline ( N = 67 ) and placebo ( N = 64 ) . Sertraline-treated patients experienced more adverse events , most notably gastrointestinal and respiratory , than placebo-treated patients . CONCLUSION Sertraline did not demonstrate efficacy for the treatment depression symptoms in patients with AD . In addition , its use was associated with an increased incidence of adverse events . Thus , selective serotonin reuptake inhibitors may be of limited value for treating depression in patients with AD OBJECTIVES To determine the response to treatment of different subgroups within a sample of physically ill elderly depressed patients . DESIGN Acute geriatric medical in patients with depression , r and omly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine . MAIN OUTCOME MEASURE Response rate as defined by the 17-item Hamilton Depression Rating Scale . RESULTS Data were analysed in subgroups according to diagnosed physical problems and concomitant medication . A logistic regression analysis was performed to identify subgroups valid for separate analysis . Those reaching at least 5 weeks of treatment showed a significant improvement compared with the placebo group if they had serious life-threatening disease , cerebrovascular disease , were not demented , or were either on no analgesics or on analgesics stronger than paracetamol . CONCLUSION While the response to treatment in these subgroups was encouraging , general physicians must not be led to believe that the answer to depression lies only in pharmacological intervention , just as the belief that the risk-benefit ratio of such treatment where indicated is too high must be discouraged CONTEXT Depression observed following acute coronary syndrome ( ACS ) is common and associated with an increased risk of death . The Sertraline Antidepressant Heart Attack Trial ( SADHART ) tested the safety and efficacy of a selective serotonin reuptake inhibitor in this population . No evidence of harm was seen , and sertraline hydrochloride had an overall beneficial effect on mood that occurred primarily in patients with a history of episodes of major depressive disorder ( MDD ) . OBJECTIVES To determine how frequently the MDD began before ACS and whether onset of the current MDD episode before or after the ACS event influenced response to sertraline . DESIGN , SETTING S , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled treatment of 369 patients with ACS and MDD was conducted in 40 outpatient clinics in 10 countries between April 1 , 1997 , and April 30 , 2001 . MAIN OUTCOME MEASURES Diagnosis of MDD , number of previous episodes of depression , and episode onset before or after hospitalization were established using the Diagnostic Interview Schedule . Treatment response was measured with the Clinical Global Impression-Improvement scale . RESULTS Fifty-three percent of MDD episodes began before hospitalization for the index episode of ACS ( for 197 of 369 patients ) , and 94 % of the MDD episodes began more than 30 days before the index ACS episode . Episodes of MDD that began prior to ACS responded more frequently to sertraline than to placebo ( 63 % vs 46 % , respectively ; odds ratio , 2.0 ; 95 % confidence interval , 1.13 - 3.55 ) whereas depression with onset beginning after hospitalization showed a high placebo response rate ( 69 % vs 60 % , respectively ) and low sertraline-placebo response ratio ( 1.15 ) . Multivariate analysis indicated that time of onset of the current episode , history of MDD , and baseline severity independently predicted the sertraline-placebo response ratio . CONCLUSIONS Half of the episodes of major depression associated with ACS began long before ACS and therefore were not caused by ACS . Patients whose current episodes of MDD begin before ACS , those with a history of MDD , and those whose episodes are severe should be treated because they will benefit considerably from sertraline . Since these 3 predictors of sertraline response are independent , having more than 1 of them substantially increases the benefit of sertraline while reducing the chance of spontaneous recovery CONTEXT Major depression affects about 25 % of the patients who have Alzheimer disease and has serious adverse consequences for patients and caregivers . Results of prior antidepressant treatment studies have produced contradictory findings and have not fully assessed the benefits of depression reduction . OBJECTIVES To assess the efficacy and safety of sertraline hydrochloride for the treatment of major depression in Alzheimer disease , and to evaluate the effect of depression reduction on activities of daily living , cognition , and nonmood behavioral disturbance . DESIGN R and omized , placebo-controlled , parallel , 12-week , flexible-dose clinical trial with a 1-week , single-blind placebo phase . The study was conducted between January 1 , 1998 , and July 19 , 2001 . SETTING University outpatient clinic . PARTICIPANTS Forty-four out patients who have probable Alzheimer disease and major depressive episodes . INTERVENTION Sertraline hydrochloride , mean dosage of 95 mg/d , or identical placebo , r and omly assigned . MAIN OUTCOME MEASURES Response rate , Cornell Scale for Depression in Dementia , Hamilton Depression Rating Scale , Mini-Mental State Examination , Psychogeriatric Depression Rating Scale-activities of daily living subscale , and Neuropsychiatric Inventory to quantify patient behavior disturbance and caregiver distress . RESULTS In the sertraline-treated group 9 patients ( 38 % ) were full responders and 11 ( 46 % ) were partial responders compared with 3 ( 20 % ) and 4 ( 15 % ) , respectively , in the placebo-treated group ( P = .007 ) . The sertraline-treated group had greater improvements in the scores for the Cornell Scale for Depression in Dementia ( P = .002 ) and Hamilton Depression Rating Scale ( P = .01 ) , and a statistical trend toward less decline in activities of daily living on the Psychogeriatric Depression Rating Scale-activities of daily living subscale ( P = .07 ) . There was no difference between the treatment groups in Mini-Mental State Examination ( P = .22 ) or Neuropsychiatric Inventory ( P = .32 ) ratings over time . When full responders , partial responders , and nonresponders were compared , full responders only , or full and partial responders had significantly better ratings on activities of daily living ( P = .04 ) , behavioral disturbance ( P = .01 ) , and caregiver distress ( P = .006 ) , but not on the Mini-Mental State Examination ( P = .76 ) . Safety monitoring indicated few differences in adverse effects between the 2 treatment groups . CONCLUSIONS Sertraline is superior to placebo for the treatment of major depression in Alzheimer disease . Depression reduction is accompanied by lessened behavior disturbance and improved activities of daily living , but not improved cognition OBJECTIVE Management of depression in elderly patients presents a significant medical challenge , and there is a need for further clinical trials . The authors examined the efficacy and tolerability of escitalopram and fluoxetine versus placebo in the treatment of elderly patients with major depressive disorder ( MDD ) . METHODS This was an 8-week , r and omized , double-blind comparison of the efficacy and tolerability of escitalopram ( 10 mg/day ) and fluoxetine ( 20 mg/day ) , to placebo in elderly patients with MDD . The prospect ively defined primary efficacy parameter was the change from baseline in mean Montgomery-Asberg Depression Rating Scale ( MADRS ) total score at endpoint , using last observation carried forward . RESULTS The intent-to-treat set comprised 517 patients ; the escitalopram group included 173 patients ; fluoxetine , 164 patients ; and placebo , 180 patients . Mean age was 75 years , with a range of 65 to 93 . Formally , this was a " failed study " ( i.e. , neither active treatment was superior to placebo ) , and the efficacy results should , therefore , be interpreted with caution . On the basis of the primary efficacy parameter , fluoxetine showed significantly lower efficacy than both escitalopram and placebo , which were not significantly different from each other . Rates of withdrawal because of adverse events/lack of efficacy were : placebo ( 2.8%/4.4 % , respectively ) , escitalopram ( 9.8%/1.7 % , respectively ) , and fluoxetine ( 12.2%/1.8 % , respectively ) . No single adverse event occurred at an incidence > or = 10 % in escitalopram-treated patients . CONCLUSIONS Both escitalopram and fluoxetine were well tolerated by elderly patients with MDD . Neither demonstrated superior efficacy on primary endpoint versus placebo BACKGROUND Despite a growing use of selective serotonin reuptake inhibitors in older people , only one trial has examined their prophylactic efficacy in people aged 65 years and over . AIMS To examine the efficacy of sertraline in preventing the recurrence of depression in older people living in the community . METHOD Participants were openly treated with sertraline and then r and omised into a double-blind , placebo-controlled continuation/maintenance study of about 2 years duration . Drug dosage was maintained at levels that achieved remission . RESULTS No significant difference between the sertraline and placebo groups was found in the proportion of recurrences ( -7.9 % ; 95 % CI -28.06 to 12.23 ) . Increased age and minor residual symptoms during the continuation phase were associated with recurrence . CONCLUSIONS Sertraline at therapeutic dosage does not provide significant protection against recurrence Although increased pre-treatment severity of depressive symptoms is thought to suggest better outcome with tricyclic antidepressants , it is unclear if such a pattern exists among those depressed patients treated with newer antidepressants . If such a pattern with newer antidepressants were observed , it would have implication s for the design and conduct of future antidepressant trials . We review ed the data from 329 depressed adult patients that were part of 15 multi-center , r and omized , double blind , placebo-controlled antidepressant clinical trials at our center . Based on patients ' pre-treatment scores on the 17-item Hamilton Depression Rating Scale ( HAM-D ) , patients were sub-grouped to one of four severity of depression groups : low moderate , high moderate , moderately severe , and severe . The effect size was 0.51 in the low moderate group , 0.54 in the high moderate group , 0.77 in the moderately severe group and 1.09 in the severe group . An analysis of variance revealed a statistically significant interaction between treatment and severity of depressive symptoms . A correlational analysis revealed that in the group of depressed patients assigned to antidepressants , higher levels of pre-treatment depressive symptoms were significantly associated with greater changes in response to antidepressant treatment . Although a similar pattern was seen among the depressed patients assigned to placebo , it did not reach statistical significance . The results of this study suggest that antidepressant-placebo differences may be larger among those depressed out patients with higher pre-treatment HAM-D scores compared to those depressed out patients with lower pre-treatment scores . These findings may help in the design of future antidepressant clinical trials BACKGROUND Executive dysfunction is common in geriatric depression and persists after improvement of depressive symptoms . This study examined the relationship of executive impairment to the course of depressive symptoms among elderly patients with major depression . METHODS A total of 112 nondemented elderly patients with major depression participated in an 8-week citalopram trial at a target daily dose of 40 mg . Executive functions were assessed with the initiation/perseveration subscale of the Dementia Rating Scale and the Stroop Color-Word test . Medical burden was rated with the Cumulative Illness Rating Scale . RESULTS Both abnormal initiation/perseveration and abnormal Stroop Color-Word scores were associated with an unfavorable response of geriatric depression to citalopram . In particular , initiation/perseveration scores below the median ( < or = 35 ) and Stroop scores at the lowest quartile ( < or = 22 ) predicted limited change in depressive symptoms . Impairment in other Dementia Rating Scale cognitive domains did not significantly influence the outcome of depression . CONCLUSIONS Executive dysfunction increases the risk for poor response of geriatric depression to citalopram . Because executive functions require frontostriatal-limbic integrity , this observation provides the rationale for investigation of the role of specific frontostriatal-limbic pathways in perpetuating geriatric depression . Depressed elderly patients with executive dysfunction require vigilant clinical attention because they might be at risk to fail treatment with a selective serotonin reuptake inhibiting antidepressant A group of 42 patients , ages 55 and above , suffering from major depression were examined in an attempt to isolate clinical variables that would predict response to antidepressants . These patients were part of a placebo-controlled , double-blind study and were given either nortriptyline or phenelzine for 5 - 7 weeks . There was no significant difference in response rates between patients subclassified as endogenous or nonendogenous by either RDC or Newcastle criteria . No difference in response rates was found between the DSM-III melancholic and nonmelancholic subtypes . Neither drug preferentially treated a subtype . None of the 21 variables representing symptoms , demographic traits , or characteristics of the depressive illness were found to be significant predictors of antidepressant response BACKGROUND We attempted to determine baseline characteristics predicting response in a 6-week , double-blind , geriatric depression trial , which showed a significantly higher remission rate for fluoxetine ( 20 mg daily ) than for placebo ( 31.6 % vs. 18.6 % , p < .001 ) . METHODS Out patients ( N = 671 ) were 60 years or older ( mean + /- SD = 67.7 + /- 5.7 ) , met Diagnostic and Statistical Manual of Mental Disorders ( 3rd ed . , rev . , American Psychiatric Association , 1987 ) criteria for unipolar major depression , had baseline scores on the 17-item Hamilton Depression Rating Scale ( HAMD17 ) of 16 or more , and were r and omized after a 1-week placebo lead-in . Potential baseline predictors of percentage change in last-visit-carried-forward HAMD21 total scores were entered into a stepwise regression model . The sample was r and omly divided into two groups ( development and validation data sets ) so that potential predictors could be confirmed in a second analysis . RESULTS Of the 266 variables considered for their prognostic ability , 13 were found to be significant predictors using the development data set , including ( a ) presence of somatic complaints , absence of agitation , and presence of previous accidental injury for fluoxetine response ; and ( b ) reported feelings of emptiness , absence of somatic complaints , and absence of early insomnia for placebo response . The second analysis using the validation data set failed to confirm statistical significance of predictors identified in the development data set . CONCLUSIONS Although potentially useful baseline characteristics were initially identified as response predictors , conservative statistical methods failed to confirm any significant predictors of differential responses between fluoxetine and placebo in this double-blind , placebo-controlled trial . These results suggest that response predictor analyses require confirmation before conclusions can be generalized |
1,084 | 22,876,153 | 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 . | QUESTIONS What is the optimal strategy for preoperative identification of the adnexal mass suspicious for ovarian cancer ?
What is the most appropriate surgical procedure for a woman who presents with an adnexal mass suspicious for malignancy ?
PERSPECTIVES In Canada in 2010 , 2600 new cases of ovarian cancer were estimated to have been diagnosed , and of those patients , 1750 were estimated to have died , making ovarian cancer the 7th most prevalent form of cancer and the 5th leading cause of cancer death in Canadian women .
Women with ovarian cancer typically have subtle , nonspecific symptoms such as abdominal pain , bloating , changes in bowel frequency , and urinary or pelvic symptoms , making early detection difficult .
Thus , most ovarian cancer cases are diagnosed at an advanced stage , when the cancer has spread outside the pelvis .
Because of late diagnosis , the 5-year relative survival ratio for ovarian cancer in Canada is only 40 % .
Unfortunately , because of the low positive predictive value of potential screening tests ( cancer antigen 125 and ultrasonography ) , there is currently no screening strategy for ovarian cancer .
The purpose of this document is to identify evidence that would inform optimal recommended protocol s for the identification and surgical management of adnexal masses suspicious for malignancy .
IDENTIFICATION OF AN ADNEXAL MASS SUSPICIOUS FOR OVARIAN CANCER : Sonography ( particularly 3-dimensional sonography ) , magnetic resonance imaging ( mri ) , and computed tomography ( ct ) imaging are each recommended for differentiating malignant from benign ovarian masses . | 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 Surgical pathology revealed 123 benign masses and 46 malignant masses . One malignant mass was confirmed by cytologic evaluation of ascitic fluid . On gray-scale analysis , 46 of the 47 malignant masses were classified as suggestive of tumor , and 76 of the 123 benign masses were classified as not suggestive of tumor ( sensitivity , 98 % ; specificity , 62 % ; negative predictive value [ NPV ] , 99 % ; and positive predictive value [ PPV ] , 50 % ) . The use of internal color flow as a predictor of malignant tumor yielded a sensitivity of 77 % , a specificity of 69 % , an NPV of 89 % , and a PPV of 49 % . The PI and RI values were significantly lower ( p < .0001 ) in malignant masses than in benign masses , although the values overlapped considerably . For a PI of less than 1.0 , sensitivity was 67 % , specificity was 66 % , NPV was 83 % , and PPV was 46 % . For an RI of less than 0.4 , sensitivity was 24 % , specificity was 90 % , NPV was 73 % , and PPV was 50 % . CONCLUSION In our series , a gray-scale prediction of benignity was reliable ( NPV = 99 % ) , and a prediction of malignancy was unreliable ( PPV = 50 % ) . Internal color flow was not useful as a predictor of malignancy ( PPV = 49 % ) . Although the absence of internal or peripheral color flow suggested benignity ( NPV = 94 % ) , only 17 ( 16 benign ) of the masses ( about 10 % ) had no flow . Spectral Doppler analysis with RI and PI was not useful , as no reliable discriminatory value with both high sensitivity and high specificity could be found for either parameter because of the overlap in values obtained for benign and malignant masses OBJECTIVE : To estimate whether three-dimensional ultrasonography and three-dimensional power Doppler investigation can contribute to the differentiation between benign and malignant ovarian masses . METHODS : Women scheduled for surgical treatment of an adnexal mass were included in a multicenter prospect i ve study . All women underwent two-dimensional and three-dimensional ultrasonographic examination in the week before surgery . All parameters were compared in women with benign tumors , borderline tumors , and malignant tumors using receiver operating characteristic analysis and likelihood ratios . RESULTS : We included 181 women ; 144 had a benign mass , 26 had a malignancy , and 11 had a borderline tumor . At three-dimensional ultrasonography , the most striking difference was found in the presence of central vessels in an adnexal mass . Central vessels assessed by three-dimensional ultrasonography were present in 15 % ( 21 of 144 ) of the benign masses , 69 % ( 18 of 26 ) of the malignant masses , and 27 % ( 3 of 11 ) of the masses of borderline malignancy . The likelihood ratios for presence of central vessels for a mass being malignant and /or borderline was 4.9 ( 95 % confidence interval 2.1–12 ) . Mean gray index and flow index were also significantly different between the groups , but other features were not . CONCLUSION : The central localization of vessels in an adnexal mass , as observed by three-dimensional ultrasonography , the mean gray index , and the flow index are potentially important parameters for distinguishing benign from malignant adnexal masses . LEVEL OF EVIDENCE : Background Peroperative identification of malignancy is crucial to management planning for ovarian cysts . The aim of this study was to evaluate the performance of laparoscopy in identifying malignant ovarian cysts . Methods Patients undergoing laparoscopy for ovarian cysts from 1998 to 2001 were enrolled prospect ively . Physical findings , Doppler ultrasonography , and serum CA 125 served to compute two risk-of-malignancy indexes ( RMI-1 and RMI-2 ) , and laparoscopy findings served to categorize lesions as benign , possibly malignant , or malignant . Frozen sections were examined as needed . Final histology was the reference . Results Of 313 patients , 294 had benign cysts , six borderline lesions , and 13 malignancies . Sensitivity and specificity were respectively 84 and 93 % for RMI-1 , 92 and 80 % for RMI-2 , 100 and 99 % for laparoscopy , 91 and 100 % for frozen sections , and 100 and 100 % for laparoscopy plus frozen sections , which had 100 % negative predictive value . Six ( 1.8 % ) adverse events occurred . Conclusions Laparoscopy reliably identifies ovarian cancer and borderline disease . Morbidity is low compared to oncologic surgery No r and omised trials have addressed the value of systematic aortic and pelvic lymphadenectomy ( SL ) in ovarian cancer macroscopically confined to the pelvis . This study was conducted to investigate the role of SL compared with lymph nodes sampling ( CONTROL ) in the management of early stage ovarian cancer . A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were r and omised to SL ( N=138 ) or CONTROL ( N=130 ) . The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups . Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm ( 240 vs 150 min , P<0.001 , and 36 vs 22 % , P=0.012 , respectively ) . More patients in the SL group had positive nodes at histologic examination than patients on CONTROL ( 9 vs 22 % , P=0.007 ) . Postoperative chemotherapy was delivered in 66 % and 51 % of patients with negative nodes on CONTROL and SL , respectively ( P=0.03 ) . At a median follow-up of 87.8 months , the adjusted risks for progression ( hazard ratio [HR]=0.72 , 95%CI=0.46–1.21 , P=0.16 ) and death ( HR=0.85 , 95%CI=0.49–1.47 , P=0.56 ) were lower , but not statistically significant , in the SL than the CONTROL arm . Five-year progression-free survival was 71.3 and 78.3 % ( difference=7.0 % , 95 % CI=–3.4–14.3 % ) and 5-year overall survival was 81.3 and 84.2 % ( difference=2.9 % , 95 % CI=−7.0–9.2 % ) respectively for CONTROL and SL . SL detects a higher proportion of patients with metastatic lymph nodes . This trial may have lacked power to exclude clinical ly important effects of SL on progression free and overall survival Background . Previous studies have established that soluble interleukin‐2 receptor alpha ( sIL‐2Rα ) levels are elevated in ascites and sera from individuals with advanced ovarian cancer ( International Federation of Gynecology and Obstetrics [ FIGO ] Stage III/IV ) . This study was undertaken to evaluate sIL‐2Rα levels in individuals with benign ovarian neoplasms and early stage ovarian cancer ( FIGO Stage I/II ) . Comparison with CA 125 levels was performed to assess screening potential OBJECTIVE To determine preoperative method that predicts nature of ovarian tumors . METHODS Fifty patients with complex pelvic masses assessed preoperatively with two-dimensional ultrasound ( 2DUS ) , two-dimensional power Doppler ( 2DPD ) , three-dimensional ultrasound ( 3DUS ) , three-dimensional power Doppler ( 3DPD ) , color Doppler . RESULTS All patients underwent exploration , 19 ( 38 % ) had benign tumors , 31 ( 62 % ) had ovarian cancer . 2DUS identified 29 cases suspicious for malignancy giving sensitivity , specificity , PPV and accuracy of 80 % , 78 % , 86 % , and 80 % . 2DUS with 2DPD identified 28 suspicious cases giving sensitivity , specificity , PPV and accuracy of 80 % , 84 % , 89 % , and 82 % . 3DUS identified 31 suspicious cases including 28 cancers giving sensitivity , specificity , PPV and accuracy of 90 % , 84 % , 90 % , and 88 % . 3DUS with 3DPD , identified 34 suspicious cases including all 31 cancers giving sensitivity , specificity , PPV and accuracy of 100 % , 84 % , 91 % , and 94 % . Color Doppler RI of 0.48 identified 28 cases of 31 cancers giving sensitivity of 90 % . CONCLUSION Evaluation by 3DUS with 3DPD improves diagnostic accuracy of ovarian tumors OBJECTIVE To evaluate the importance of color Doppler combined with conventional sonography in characterizing adnexal masses and to compare the results with those of spectral Doppler analysis alone and conventional sonography alone . MATERIAL S AND METHODS One hundred and fifteen women with 132 adnexal masses ( 98 benign , three borderline , and 31 malignant ) were prospect ively studied with conventional and Doppler sonography ( transabdominal in all patients and transvaginal in 111 ) . Three methods differentiated benign from borderline and malignant masses . In the first , conventional sonography was used . In the second , conventional sonography was combined with color Doppler . In this method , the presence of color flow in an echogenic portion classified as indeterminate or malignant by conventional sonography indicated malignancy ; the absence of color flow in an echogenic portion classified as indeterminant or malignant at conventional sonography indicated benignancy ; the presence or absence of color flow in a regular wall or septum indicated benignancy . The third method used spectral Doppler analysis . Malignancy was indicated by a resistive index ( RI ) less than or equal to 0.4 , a pulsatility index ( PI ) less than or equal to 1 , or a peak systolic velocity ( PSV ) greater than or equal to 15 cm/sec . RESULTS Using conventional sonography alone , accuracy was 83 % , sensitivity was 88 % , and specificity was 82 % . Using conventional sonography and color Doppler , accuracy was 95 % , sensitivity was 88 % , and specificity was 97 % . Using spectral Doppler analysis and an RI less than or equal to 0.4 , accuracy was 77 % , sensitivity was 18 % , and specificity was 98 % . For a PI less than or equal to 1 , accuracy was 68 % , sensitivity was 71 % , and specificity was 67 % . For a PSV greater than or equal to 15 cm/sec , accuracy was 72 % , sensitivity was 47 % , and and specificity was 81 % . CONCLUSION Adding color Doppler to conventional sonography produced a specificity and positive predictive value higher than those of conventional sonography alone . Specificity increased from 82 % to 97 % ( p < .001 ) , and positive predictive value increased from 63 % to 91 % . RI , PI , and PSV were of limited value To determine whether measurement of the levels of multiple tumor markers in the preoperative serum of women presenting with a pelvic mass distinguished benign from malignant disease better than the assay of CA 125 alone , sera from 429 patients , 192 of whom had malignant histology , were assayed for 8 different markers : CA 125 , macrophage colony-stimulating factor , OVX1 , lipid-associated sialic acid ( LASA ) , CA15 - 3 , CA72 - 4 , CA19 - 9 , and CA54/61 . The sensitivity and specificity of CA 125 alone ( > 35 U/ml ) was 78.1 and 76.8 % , respectively . A panel consisting of CA 125 , OVX1 , LASA , CA15 - 3 , and CA72 - 4 had a sensitivity of 83.3 % and specificity of 84.0 % when two or more markers were elevated . Using the concentrations of these five markers , logistic regression analysis had a sensitivity of 85.4 % and a specificity of 83.1 % . Considering the values of markers in different sequences , classification and regression tree analysis substantially improved the sensitivity to 90.6 % and the specificity to 93.2 % . When applied in clinical practice this approach could improve the management of women presenting with a pelvic mass and may also have application in screening for ovarian cancer The goal of this study was to develop a scoring system using combination of Doppler characterization of pelvic/ovarian lesions and serum CA125 level . Our purpose was to maximize the preoperative discrimination between benign and malignant entities . In a prospect i ve study , a total of 101 patients were evaluated preoperatively using a st and ard transvaginal ultrasound and color Doppler imaging with pulse spectral analysis and serum CA125 level within a week prior to surgery . The variables that were analyzed by the multivariate logistic regression method are as follows : tumor structure , ascites , presence of septum , the peak systolic velocity ( PSV ) , the resistance index ( RI ) , and serum CA125 level . Of the 101 patients qualified for the study , 48 patients were diagnosed with benign ( 47.5 % ) and 53 ( 52.5 % ) with malignant tumors . Each criterion used alone provides statistically significant discrimination between benign and malignant tumors . Four criteria could be combined in a malignancy score which is calculated using the product of the serum CA125 level ( 1 if CA125 ≥40 U/mL and 0 if CA125 < 40 U/mL ) , the result of sonography for presence of septum in tumor ( 1 if there was septum ≥3 mm , 0 if there was no septum or <3 mm ) , result of Doppler flow imaging as RI ( 1 if RI ≤0.5 and 0 if RI > 0.5 ) and the PSV ( 1 if PSV ≥40 cm/s and 0 if PSV < 40 cm/s ) . This scoring system devised was statistically more effective discriminator between cancer and benign lesions than formal methods . Using malignancy score cutoff level of two , the sensitivity was 98 % ( CI 88.62–99.9 . ) , the specificity was 85 % ( CI 71.62–93.45 ) , the positive predictive value was 87.5 % , and the negative predictive value was 97.6 % . Area under curve of receiver operative characteristic curves was 0.987 ( CI 0.971–1.004 ) . These values were statistically more significant than those obtained from the independent use of RI , PSV , or serum CA125 level at their optimum decision values ( P < 0.05 ) . There is a need for a prospect i ve evaluation of this score using a larger sample of patients AIMS To evaluate the accuracy of ultrasonography ( US ) and magnetic resonance imaging ( MRI ) in characterizing adnexal masses , and to determine which patients may benefit from MRI . METHODS We prospect ively studied 72 women ( mean age 53 years , range 19 to 86 years ) with clinical ly suspected adnexal masses . A single experienced sonographer performed transabdominal and transvaginal greyscale spectral and colour Doppler examinations . MRI was carried out on a 1.5 T system using T1 , T2 and fat-suppressed T1-weighted sequences before and after intravenous injection of gadolinium . The adnexal masses were categorized as benign or malignant without knowledge of clinical details , according to the imaging features which were compared with the surgical and pathological findings . RESULTS For characterizing lesions as malignant , the sensitivity , specificity and accuracy of MRI were 96.6 % , 83.7 % and 88.9 % , respectively , and of US were 100 % , 39.5 % and 63.9 % , respectively . MRI was more specific ( p<0.05 ) than US . Both MRI and US correctly diagnosed 17 ( 24 % ) cases with benign and 28 ( 39 % ) cases with malignant masses . MRI correctly diagnosed 19 ( 26 % ) cases with benign lesion(s ) , which on US were thought to be malignant . The age , menopausal status and CA-125 levels in these women made benign disease likely , but US features were suggestive of malignancy ( large masses and solid-cystic lesions with nodules ) . CONCLUSION MRI is more specific and accurate than US and Doppler assessment for characterizing adnexal masses . Women who clinical ly have a relatively low risk of malignancy but who have complex sonographic features may benefit from MRI OBJECTIVE To optimize referral to specialized gynaecologists for surgical treatment of ovarian cancer by improving preoperative discrimination between benign and malignant pelvic tumours . STUDY DESIGN In a prospect i ve multicentre study 143 patients with a pelvic mass were included . At several occasions during the diagnostic work-up the gynaecologist estimated the chance of malignancy ( educated guess/expert opinion ) . MRI in the local setting was suggested for uncertain cases . All MRI images were review ed by an expert radiologist . The data sheet design ed for the study further allowed for determining the risk of malignancy index ( RMI ) . RESULTS The diagnostic accuracy of the gynaecologist 's final estimation of the chance of malignancy and the calculated RMI were comparable ( area under the ROC curve of 0.87 and 0.86 ) . MRI did not improve the accuracy of the diagnostic work-up for the study population as a whole . Subgroup analysis did however show improved diagnostic accuracy in cases with an estimated chance of malignancy between 20 and 80 % when the MRI was read by an expert radiologist . CONCLUSION Patient selection for surgery of a pelvic mass should be based on the chance of malignancy as assigned by the referring gynaecologists . In case of uncertainty MRI improves diagnostic accuracy , when judged by an expert The aim of this prospect i ve study was to determine the clinical benefits of introducing peroperative frozen section analysis into the surgical management policy of women referred with an adnexal mass suspicious of ovarian cancer . All women surgically managed at the Northern Gynaecological Oncology Centre , Gateshead , UK , between July 1 , 2002 , and June 30 , 2003 , where frozen section analysis had been utilized were included for analysis . Correlation was determined between cases surgically staged following the frozen section result and the clinical need for staging based on the pathologic diagnosis from the paraffin section . During the 12-month period , 130 women underwent frozen section analysis . Paraffin section diagnoses included 74 benign tumors , 11 borderline tumors , 34 primary epithelial cancers , 5 nonepithelial cancers , and 6 metastatic tumors . All primary epithelial ovarian cancers were correctly identified as requiring a staging procedure based on the frozen section result . Four of seventy-four cases reported as benign on frozen section analysis were underdiagnosed ; two were later diagnosed on paraffin section as borderline tumors and a further two as malignant ( one low- grade adenosarcoma and one primary peritoneal cancer ) . Of the 130 cases , 55 ( 42.3 % ) underwent a staging procedure based on the frozen section result . The value of frozen section analysis in determining the need for the performance of a staging procedure had the following statistical test results : sensitivity = 92 % , specificity = 88 % , positive predictive value = 82 % , and negative predictive value = 95 % . Excluding the borderline tumors , metastatic tumors , and primary peritoneal tumor where staging did not impact subsequent clinical management , the statistical test results for frozen section analysis in determining the need for a staging procedure were sensitivity = 97 % , specificity = 95 % , positive predictive value = 90 % , and negative predictive value = 99 % . The clinical benefits of introducing frozen section analysis in the surgical staging policy of women with an adnexal mass suspicious of ovarian malignancy included avoidance of a surgical staging procedure in 95 % of cases identified on paraffin section analysis to be benign . This benefit was without compromising the avoidance of chemotherapy in true stage I epithelial ovarian cancer cases . Additional benefits included the confirmation of malignancy where extraovarian lesions were suggestive but not indicative of malignant disease , and the intraoperative identification of metastatic disease of nonovarian origin Because of various contradictory reports in the literature and an increasingly urgent need for preoperative evaluation of adnexal masses before laparoscopic surgery , our aim was to disclose if examination by means of color Doppler ultrasound is useful in distinguishing benign from malignant adnexal tumors in our population . Prior to surgery , pulsed color Doppler velocimetry of the adnexal blood supply was performed in a prospect i ve study in 80 patients with benign and 40 with malignant adnexal tumors . Vascularization was equally frequent in both groups of tumors . Blood vessels of benign tumors had a diffuse , intraseptal or intraproliferative location significantly more often and malignant tumor vessels more often exhibited a diffuse , intraseptal or intraproliferative location ( p < 0.01 ) . The mean value of RI+/-SD was 0.56+/-0.14 in benign and 0.33+/-0.13 in malignant tumors . The differences in RI between benign and malignant tumors are statistically significant ( p < 0.01 ) . In detecting malignant adnexal tumors , the sensitivity of RI < or = 0.40 is 82 % , its specificity 97 % , positive predictive value 94 % , negative predictive value 92 % and its accuracy 92 % . The analysis of vascularization presence seems not to have any value in predicting the nature of adnexal tumors , and blood vessels arrangement , as well as measured RI < or = 0.40 , allows us to predict the presence of malignancy with limited reliability The aim of this study was to compare laparoscopic and laparotomic surgical staging in patients with stage I epithelial ovarian cancer in terms of feasibility and safety . A retrospective chart review was undertaken of all patients with apparent stage I epithelial ovarian cancer who underwent laparoscopic ( laparoscopy group ) or laparotomic ( laparotomy group ) surgical staging at the Center for Uterine Cancer , National Cancer Center , Korea , between January 2001 and August 2006 . During the study period , 19 patients underwent laparotomic surgical staging and 17 patients underwent laparoscopic surgical staging . No cases were converted from laparoscopy to laparotomy . The two groups were similar in terms of age , body mass index , procedures performed , number of lymph nodes retrieved , and operating time . The laparoscopy group had less estimated blood loss ( P= 0.001 ) , faster return of bowel movement ( P < 0.001 ) , and a shorter postoperative hospital stay ( P= 0.002 ) compared to the laparotomy group . Transfusions were required only in two laparotomy patients , and postoperative complications occurred only in four laparotomy patients . However , two patients with stage IA grade 1 and 2 disease in laparoscopy group had recurrence with one patient dying of disease . The accuracy and adequacy of laparoscopic surgical staging were comparable to laparotomic approach , and the surgical outcomes were more favorable than laparotomic approach . However , the oncologic safety of laparoscopic staging was not certain . This is the first report on the possible hazards of laparoscopic staging in early-stage ovarian cancer . In the absence of a large prospect i ve trial , this technique should be performed cautiously OBJECTIVE The aim of the study was to evaluate whether the presence of normal ovarian tissue adjacent to an adnexal tumor ( the ' ovarian crescent sign ' ) could assist in the preoperative differential diagnosis of adnexal lesions . METHODS This was a prospect i ve observational study including 100 women with a preoperative diagnosis of an adnexal mass . Demographic and biochemical data were collected and all women underwent a detailed transvaginal ultrasound scan . Tumor volume , morphological characteristics and Doppler features were recorded in each case . In addition , the tissue adjacent to the cyst was systematic ally examined for the presence of normal ovarian tissue . All the findings were compared to the final histological diagnosis . RESULTS Sixty-seven ( 67 % ) of the cysts removed were benign , nine ( 9 % ) were borderline and 24 ( 24 % ) women had invasive malignant lesions . Normal ovarian tissue was seen in 58/76 ( 76 % ) women with non-invasive lesions , and in one woman ( 4 % ) with an invasive malignancy . In the absence of normal ovarian tissue , ovarian cancer was diagnosed with a sensitivity of 96 % and specificity of 76 % . CONCLUSION The presence of normal ovarian tissue adjacent to an ovarian cyst is a useful morphological feature that may be used to help exclude an invasive ovarian malignancy in women with adnexal masses detected on ultrasound scan A prospect i ve study was made of 105 consecutive patients admitted to one department of obstetrics and gynaecology for surgery for adnexal masses . The objective was to investigate if CA 125 level is measurable in the urine or saliva and to correlate these measurements with serum CA 125 level in patients presenting with adnexal masses . The final diagnosis and grouping of patients for analysis were based on histopathological examination of the adnexal masses . Serum , urine and salivary sample s were collected simultaneously from all patients on the morning before surgery . CA 125 levels in each sample were determined in duplicate using Abbott CA 125-E1A monoclonal test kits ( Abbott Laboratories , USA ) . The mean inter-assay variability was 10 % . CA 125 was detectable in the serum , urine and saliva from all the patients and the concentration was highest in the saliva and lowest in urine . There were no discernible differences in the distributions of salivary CA 125 concentrations between patients with ovarian malignancies and those with benign ovarian cysts . In contrast , both serum and urinary CA 125 levels were significantly higher in the ovarian cancer group . There was no correlation in CA 125 concentrations between serum and urine , or between serum and saliva . For detection of ovarian malignancies , the sensitivity , specificity , and positive and negative predictive values for serum CA 125 measurement ( > or = 35 U/mL ) were 88.9 % , 79.2 % , 27.6 % and 98.7 respectively . The corresponding figures for urinary CA 125 measurement ( > or = 10 U/mL ) were 88.9 % , 66.7 % , 19.5 % and 98.4 % respectively . ( ABSTRACT TRUNCATED AT 250 WORDS AIM To determine whether three-dimensional power Doppler can improve the recognition of pelvic tumor morphology and angiogenesis . METHODS Using this technique we analyzed 180 adnexal masses and 110 uterine lesions . Tumor volume , morphology , and vascularity were evaluated in each patient . Irregular and r and omly dispersed vessels with complex branching depicted by comprehensive three dimensional display were suggestive of pelvic malignancy , while linear-like vascular morphology , single vessel arrangement and regular branching were typical for benign structures . RESULTS Addition of qualitative analysis of vascular architecture of adnexal tumor to morphological parameters reached 96.15 % sensitivity and 98.73 % specificity . When endometrial lesions were prospect ively analyzed , sensitivity and specificity were 91.67 % and 98.49 % , respectively . Because the lowest positive predictive value of 16.67 % was obtained for myometrial lesions , this method should not be advised for their eva luation . CONCLUSION Good results achieved by three dimensional ultrasound can be explained by improved recognition of the pelvic lesion anatomy , characterization of the surface features , detection of the tumor infiltration , and precise depiction of the size and volume . Three dimensional power Doppler imaging can detect structural abnormalities of the malignant tumor vessels , such as arteriovenous shunts , microaneurysms , tumoral lakes , disproportional calibration , coiling , and dichotomous branching . Therefore it enhances and facilitates the morphologic and functional evaluation of both benign and malignant pelvic tumors BACKGROUND The stage of ovarian carcinoma at diagnosis directly affects prognosis . Thus , thorough pretreatment evaluation is basic to the successful management of suspected ovarian masses . Among currently available imaging techniques in characterization of suspected ovarian neoplasms , sonography ( US ) is indisputedly the primary imaging approach . When US is inconclusive , magnetic resonance imaging ( MRI ) is generally prefered to computed tomography ( CT ) . MATERIAL S AND METHODS 93 patients , who on the basis of clinical findings were suspected to have ovarian cancer and who were scheduled for subsequent surgical staging underwent preoperative transvaginal and abdominal ultrasound as well as magnetic resonance imaging in a prospect i ve comparative study . US and MR images were evaluated for their information on the characterization and staging of the ovarian masses . RESULTS MRI correctly characterized malignant and benign tumors in 89 % of cases versus 85 % by ultrasound . The site of the primary tumor was correctly diagnosed in 94 % of cases by MRI vs. 90 % by ultrasound . For US , the positive predictive value was 85 % , the negative predictive value 73 % vs. 92 % and 89 % for MRI . In differentiation of nonadvanced disease from advanced malignancy , US showed a false-positive rate of 0.416 and false-negative rate of 0.258 vs. 0.125 and 0.032 respectively , for MRI . CONCLUSION MRI was superior in diagnosis of malignant ovarian masses though US , too , performed well at lesion detection and characterization . With regard to tumor staging MRI is emerging as a problem-solving modality and may allow more appropriate clinical decisions to be made in selected patients with complex adnexal disease OBJECTIVE To analyze the usefulness of transvaginal color Doppler assessment of venous flow in the differential diagnosis of adnexal masses . MATERIAL AND METHODS Ninety-one consecutive patients ( mean age : 46.6 years , range : 16 - 81 years ) diagnosed as having an adnexal mass were evaluated by transvaginal color Doppler sonography prior to surgery . Color Doppler was used to detect and analyze the flow velocity waveform from arterial and venous blood flow within the tumor . For arterial signals the resistance index and peak systolic velocity , and for veins the maximum venous flow velocity , were calculated . Receiver operator characteristic curves were plotted to determine the best venous flow velocity cut-off . According to our previous study using arterial Doppler , a tumor was considered as malignant when flow was detected and the lowest resistance index was < or = 0.45 . Using venous Doppler a mass was considered as malignant when flow was detected and the venous flow velocity was > or = the best cut-off found on the receiver operator characteristic curve . Definitive histopathological diagnosis was obtained in all cases . Sensitivity , specificity , positive predictive value and negative predictive value for B-mode morphology ( evaluation performed according to Sassone 's scoring system ) , arterial Doppler , venous Doppler , and a combination of both arterial and venous Doppler were calculated . RESULTS Twenty-five masses ( 27.5 % ) were malignant and 66 ( 72.5 % ) benign . Arterial and venous flow was found more frequently in malignant than in benign masses ( 92 % vs. 41 % ( P < 0.001 ) and 72 % vs. 21 % ( P < 0.001 ) , respectively ) . The resistance index was significantly lower in malignant tumors ( 0.42 vs. 0.60 , P = 0.0003 ) . No differences were found in peak systolic velocity . Venous flow velocity was significantly higher in malignant masses ( 18.1 cm/s vs. 8.9 cm/s , P = 0.0006 ) . The best cut-off of venous flow velocity was 10 cm/s . Sensitivity , specificity , positive predictive value and negative predictive value for morphology , arterial Doppler , venous Doppler , and the combination of both arterial and venous Doppler were 92 % , 71 % , 45 % , 96 % ; 76 % , 95 % , 87 % , 91 % ; 68 % , 94 % , 81 % , 89 % ; and 88 % , 91 % , 79 % , 95 % , respectively . CONCLUSIONS Our results indicate that preoperative evaluation by venous flow assessment of adnexal masses may be useful to discriminate between malignant and benign tumors OBJECTIVES To evaluate the efficacy of color Doppler ultrasonography as the predictor of malignant ovarian tumors and to compare the results with CA 125 levels and ultrasonographic morphological patterns . METHODS We compared color Doppler ultrasound with sonographic findings and serum CA 125 levels for predicting ovarian malignancy in 16 patients with malignant and 12 patients with benign ovarian tumors . RESULTS There was a significant difference in pulsatility index ( PI ) value of ovarian vessel between benign and malignant tumors ( 2.42 + /- 0.67 for benign and 1.35 + /- 0.78 for malignant , respectively , P < 0.01 ) . The specificity of morphological findings and CA 125 was lower than that of PI measurements , but sensitivity was not different between the three methods . In addition , the combination of color Doppler and CA 125 or morphological assessment s result ed in a sensitivity of 100 % and a negative predictive value of 100 % , respectively . CONCLUSION PI measurements by transvaginal color Doppler ultrasound combined with CA 125 levels or morphological findings could be an accurate and appropriate screening method for ovarian tumors PURPOSE To evaluate the accuracy of magnetic resonance ( MR ) imaging in the detection and characterization of complex adnexal masses , with particular reference to the findings predictive of malignancy , role of gadolinium-enhanced contrast material , and observer variability . MATERIAL S AND METHODS Preoperative MR imaging of the pelvis was performed in 128 consecutive patients with clinical ly or ultrasonographically detected complex adnexal masses . Histopathologic examination demonstrated 187 masses , 96 of which were malignant . MR imaging studies were prospect ively and independently review ed by two radiologists , one of whom reevaluated the studies after a 6-month interval . The predictive value of MR imaging findings was determined with multivariate logistic regression analysis . The value of gadolinium enhancement was assessed by using receiver operating characteristic analysis . Inter- and intraobserver variabilities were assessed by using weighted K statistics . RESULTS Gadolinium-enhanced MR imaging depicted 176 ( 94 % ) of 187 adnexal masses , with an overall accuracy for the diagnosis of malignancy of 93 % . The MR imaging findings that were most predictive of malignancy were necrosis in a solid lesion ( odds ratio , 107 ) and vegetations in a cystic lesion ( odds ratio , 40 ) . Use of gadolinium-based contrast material contributed significantly to lesion characterization . Interobserver ( K , 0.79 - 0.85 ) and intraobserver ( K , 0.84 - 0.86 ) agreement were excellent . CONCLUSION Gadolinium-enhanced MR imaging is highly accurate in the detection and characterization of complex adnexal masses , with excellent inter- and intraobserver agreement OBJECTIVE Our purpose was to evaluate whether intratumoral blood flow velocity measured by transvaginal Doppler ultrasonography would afford better discrimination between benign and malignant adnexal tumors . STUDY DESIGN One hundred two patients with adnexal tumors ( 72 benign , 30 malignant ) were studied with transvaginal B-mode , color , and pulsed Doppler ultrasonography before surgery . RESULTS Sixty-five benign tumors ( 90.3 % ) had abnormal morphologic features suggesting malignancy , and blood flow was detected in 29 ( 40.3 % ) . The peak systolic velocity was 13.1 + /- 9.1 cm/sec and the resistance index was 0.563 + /- 0.177 . All malignant tumors had abnormal morphologic features and blood flow was detectable in all cases . The peak systolic velocity was 23.9 + /- 11.5 cm/sec and the resistance index was 0.488 + /- 0.118 . When 16 cm/sec was considered as the cutoff value of peak systolic velocity , the sensitivity and specificity of peak systolic velocity in detecting malignant adnexal tumors were 83.3 % and 91.6 % , respectively . The sensitivity and specificity of the resistance index ( cutoff value 0.72 ) was 93.3 % and 68.1 % , respectively . There was no significant difference in sensitivity between peak systolic velocity and resistance index . The specificity of the peak systolic velocity was significantly higher than that of the resistance index ( p < 0.05 ) . Moreover , the sensitivity of the peak systolic velocity did not significantly differ from that with transvaginal ultrasonography diagnosis ( 86.7 % ) , and the specificity of the peak systolic velocity was significantly higher than that of transvaginal ultrasonography ( 69.4 % ) . CONCLUSION These results suggest that peak systolic velocity obtained from intratumoral abnormal morphologic features provides a superior means for differentiating malignant from benign adnexal tumors A prospect i ve study was performed in 64 patients suspected of having primary or recurrent ovarian epithelial cancer . Physical examination ( PE ) , ultrasonography ( US ) , computer tomography ( CT ) , and magnetic resonance imaging ( MRI ) were performed and CA 125 serum levels ( CA 125 ) were determined . This evaluation was followed within 3 weeks by laparotomy , which served with the pathology data as the gold st and ard . Both CT and MRI were , independently , evaluated by two experienced radiologists . The accuracy in diagnosing ovarian carcinoma of both CT ( 70 and 91 % ) and MRI ( 64 and 88 % ) in patients suspected of primary and recurrent cancer grouped together differed between the two radiologists , but for each radiologist no difference in overall accuracy between CT and MRI was observed . The accuracy of PE was 64 % , of US , 67 % , and of CA 125 , 72 % . At surgery , 132 separate tumor locations were present . With CT , 41 and 69 % and with MRI , 44 and 56 % of these lesions were recognized by the two radiologists , respectively . This was the case in 27 % with PE and 34 % with US . We conclude that in our setting MRI had no additional value over CT . The interobserver variability was high for both MRI and CT . MRI and CT are both useful diagnostic methods in the diagnosis of ovarian carcinoma Objective Our goal was to determine the sensitivity , specificity , predictive value , and accuracy of pelvic MRI in the prospect i ve evaluation of women with a clinical ly suspected pelvic mass . Material s and Methods One-hundred three patients with clinical ly suspected pelvic masses were prospect ively evaluated by pelvic MRI . Masses were analyzed for size , location , morphological characteristics , and signal behavior . Masses were classified as benign , malignant , or indeterminate and in every case an attempt was made to generate a specific diagnosis according to previously reported characteristic MR appearances . Surgical follow-up was obtained within 3 months of MRI examination for all patients , excepting 11 patients with typically appearing leiomyomas . Results One hundred twenty pelvic masses were confirmed . Magnetic resonance was 100 % sensitive and 99 % specific in prospect ively diagnosing dermoids , 96 % sensitive and 100 % specific in diagnosing subserosal leiomyomas , and 92 % sensitive and 91 % specific in diagnosing endometriomas . Conclusion When physical examination or ultrasound examination is inconclusive , pelvic MRI can aid in the evaluation of women with a suspected pelvic mass . By identifying these common benign gynecologic conditions , unnecessary surgery can be avoided The goal of this prospect i ve study was to develop a new scoring system using transvaginal color and pulsed Doppler characterization of ovarian lesions . Transvaginal color Doppler sonography was performed on 812 women , among whom 174 adnexal masses were found and analyzed . Ovarian lesions were assessed by means of morphological and color Doppler scoring systems . Tumors were characterized ultrasonically as benign or suspected of being malignant . Scoring system results were correlated with histopathological findings . Among our study group , 38 malignant and 136 benign ovarian tumors were found and verified . The color Doppler scoring system was very useful in distinguishing benign from malignant masses , with a sensitivity of 97.3 % and a specificity of 100 % , compared with the morphological scoring system 's sensitivity of 92.1 % and specificity of 94.8 % . We also evaluated a combination of both scoring systems . We believe that new color Doppler scoring system maximizes the ability to discriminate between benign and malignant entities OBJECTIVE To determine the magnetic resonance ( MR ) imaging findings of an ovarian mass which are most predictive of malignancy and assess the value of intravenous gadolinium administration in the characterization of an ovarian mass . METHODS Totally 74 consecutive patients with a clinical ly or sonographically indeterminate adnexal mass underwent MR imaging , of whom 59 had subsequent surgical resection of 70 adnexal masses . These 59 patients formed the study population . MR imaging studies were prospect ively and independently review ed by a senior and a junior radiologist . The senior radiologist also reevaluated the studies in a blind fashion after a minimum 6 months interval . The sensitivity , specificity , positive predictive value , and negative predictive value of contrast-enhanced and unenhanced MR imaging were evaluated . RESULTS The most predictive MR imaging findings for malignancy were presence of vegetations in a cystic lesion and presence of necrosis in a solid lesion . The odds ratio was even higher when the ancillary finding of peritoneal metastasis or ascites was present . Contrast media contributed significantly to lesion characterization . Total 70 ovarian masses were detected by contrast-enhanced MR imaging including 37 malignant ovarian masses and 33 benign ovarian masses with 87 % ( 61/70 ) accuracy , 86 % ( 32/37 ) sensitivity , 88 % ( 29/33 ) specificity , 89 % ( 32/36 ) positive predictive value , and 85 % ( 29/34 ) negative predictive value , whereas 70 ovarian masses were detected by unenhanced MR imaging with 74 % ( 52/70 ) accuracy , 73 % ( 27/37 ) sensitivity , 76 % ( 25/33 ) specificity , 77 % ( 27/35 ) positive predictive value , and 71 % ( 25/35 ) negative predictive value . There were significant differences in accuracy ( P < 0.01 ) , sensitivity ( P < 0.01 ) , specificity ( P < 0.01 ) between contrast-enhanced and unenhanced MR imaging . CONCLUSION Contrast-enhanced MR imaging is highly accurate in detection and characterization of complex adnexal masses PURPOSE To determine the optimal imaging modality for diagnosis and staging of ovarian cancer . MATERIAL S AND METHODS Two hundred eighty women suspected to have ovarian cancer were enrolled in a prospect i ve study before surgery . Doppler ultrasonography ( US ) , computed tomography ( CT ) , and magnetic resonance ( MR ) imaging were used to evaluate the mass ; conventional US , CT , and MR imaging were used to stage spread . RESULTS All three modalities had high accuracy ( 0.91 ) for the overall diagnosis of malignancy . In the ovaries , the accuracy of MR imaging ( 0.91 ) was higher than that of CT and significantly higher than that of Doppler US ( 0.78 ) . In the extraovarian pelvis and in the abdomen , conventional US , CT , and MR imaging had similar accuracies ( 0.87 - 0.95 ) . In differentiation of disease confined to the pelvis from abdominal spread , the specificity of conventional US ( 96 % ) was higher than that of CT and significantly higher than that of MR imaging ( 88 % ) , whereas the sensitivities of MR imaging ( 98 % ) and CT ( 92 % ) were significantly higher than that of conventional US ( 75 % ) . CONCLUSION MR imaging is superior to Doppler US and CT in diagnosis of malignant ovarian masses . There is little variation among conventional US , CT , and MR imaging as regards staging Meticulous pretreatment evaluation is basic to the successful management of suspected ovarian masses . Among currently available imaging techniques , sonography and computerized tomography are the most important diagnostic modalities . The purpose of our study was to determine whether magnetic resonance imaging provided additional information on masses in the true pelvis . 73 patients with masses in the true pelvis underwent preoperative magnetic resonance imaging . MRI was done with a 1.0 T supraconductive magnet ( Magnetom Impact , Siemens ) . The results obtained were compared with sonographic ( transabdominal and transvaginal ) , intraoperative and histopathologic findings . MR images were evaluated for their information on differentiation between benign and malignant neoplasm , tumor staging , lymph node involvement , peritoneal spread , local extension and organ relation . MRI correctly characterized malignant and benign tumors in 97 % of cases versus 81 % on ultrasound . The site of the primary tumor was correctly diagnosed in 94 % of cases on MRI images versus 86 % on ultrasound images . Invasion of adjacent intestinal segments as well as peritoneal carcinomatosis and omental metastases ( metastasis > 1 cm ) were also detected in the majority of cases . Based on our results MRI performs well at lesion detection and characterization in the evaluation of suspected ovarian masses . MRI should be considered in the investigation of patients with complicated findings on ultrasound OBJECTIVE To determine whether the combined use of Lerner 's morphologic score and color Doppler ultrasound examination results in better discrimination of benign and malignant adnexal masses than the use of Lerner 's score alone or Doppler variables alone . DESIGN One hundred and seventy-three consecutive women with a pelvic mass judged clinical ly to be of adnexal origin underwent preoperative ultrasound examination including color and spectral Doppler techniques . One hundred and forty-nine tumors were benign and 24 malignant . The sensitivity and false-positive rate with regard to malignancy were calculated for Lerner 's score , six Doppler variables and combinations of Lerner 's score and Doppler variables . Previously defined gray scale and Doppler criteria of malignancy were used and tested prospect ively . The best method was defined as that detecting most malignancies with the lowest false-positive rate . RESULTS Lerner 's score had a sensitivity of 92 % and a false-positive rate of 36 % . The best Doppler variable -- time-averaged maximum velocity -- had similar diagnostic properties with a sensitivity of 100 % and a false-positive rate of 41 % . Combining Lerner 's score with Doppler measurement of time-averaged maximum velocity -- i.e . requiring both Lerner 's score and time-averaged maximum velocity to indicate malignancy for a malignant diagnosis to be made -- had a sensitivity of 92 % and a false-positive rate of 19 % . CONCLUSIONS The combined use of Lerner 's score and measurement of time-averaged maximum velocity is a better method for discrimination of benign and malignant adnexal masses than the use of Lerner 's score alone or Doppler ultrasound examination alone . The clinical value of the combined method needs to be cross-vali date d prospect ively in a new series of tumors OBJECTIVE The purpose of this study was to determine the diagnostic accuracy of sonography versus magnetic resonance imaging ( MRI ) and positron emission tomography ( PET ) in the characterization of adnexal masses . METHODS One hundred and one patients with asymptomatic adnexal masses , which were scheduled for laparoscopy , underwent preoperative transvaginal ultrasound , MRI , and 2-[(18)F]fluoro-2-deoxy-d-glucose PET . Two different sonomorphological scoring systems were used to distinguish malignant from benign lesions . In addition , transvaginal Doppler flow velocimetry was performed and the resistance index ( RI ) of ovarian blood vessels was calculated . RI values below 0.45 were considered to indicate malignancy . MRI was evaluated on the basis of signal intensity and morphologic features such as wall thickness , septations , fluid or solid components , and vascularity . PET imaging was used to determine 2-[(18)F]fluoro-2-deoxy-D-glucose uptake . Malignancy was suspected if radiotracer uptake equaled or exceeded that of the liver . Based on histologic findings , sensitivity , specificity , positive and negative predictive values , and accuracy were first calculated independently for each imaging technique . Finally , a second session result ed in a consensus diagnosis being made based on the findings of all three modalities . RESULTS Sonographic evaluation of adnexal masses result ed in correct classification of 11 of 12 ovarian malignancies ( sensitivity 92 % ) but with a specificity of only 60 % . With MRI and PET , specificities improved to 84 and 80 % respectively , but sensitivities decreased . When all imaging modalities were combined , sensitivity and specificity were 92 and 85 % , respectively , and accuracy was 86 % . CONCLUSION Combination of ultrasound with MRI and PET may improve accuracy in differentiation of benign from malignant ovarian lesions . However , negative MRI or PET results do not rule out early-stage ovarian cancer or borderline malignancies OBJECTIVE Because external validation of the present models has not been reported , the purpose of the present study was to assess existing diagnostic models that are used to distinguish malignant from benign masses . METHODS We tested the performance of existing models in a prospect ively assembled data set of 170 patients with an adnexal mass . Twenty-one models that have been reported previously were assessed . The models were based on combinations of ultrasound findings , color Doppler tests , CA-125 measurement , age , and /or menopausal status . For each model , we constructed ROC curves and calculated an area under the ROC curve . RESULTS Of the 170 adnexal masses that were operated on , 30 ( 18 % ) were malignant . The area under the ROC curve of 21 models that were externally vali date d varied between 0.69 and 0.90 . We found the performance of the existing models to be inferior to the performance reported in the initial studies . Even models that incorporated multiple diagnostic tools and that were developed using logistic regression models or neural networks had an area under the ROC curve of 0.86 at maximum . In the case where we focused on almost perfect sensitivity , the highest specificities varied between 0.45 and 0.60 . CONCLUSION Although diagnostic models might be of value in the preoperative assessment of the adnexal mass , their diagnostic performance is not as good as that reported in the original publications PURPOSE This study evaluated the feasibility of Tc-99 m MIBI scintigraphy in the differential diagnosis of pelvic masses in female patients before operation . METHODS Seventy-one patients with pelvic masses were studied with planar imaging over the abdomen and pelvis 5 , 15 , 30 , and 60 minutes after injection of 740 MBq ( 20 mCi ) Tc-99 m MIBI . The uptake of the masses was grade d , and other abnormal signs , such as intestinal involvement , lymph node involvement , or peritoneal fluid collection , were also considered in image interpretation . An exploratory laparotomy was performed 3 days to 2 weeks after imaging . The scintigraphic diagnosis was compared with that of computed tomography ( CT ) , CA-125 measurement , and pathologic analysis . RESULTS Forty-one of 46 pelvic masses with no activity were proved benign . Eighteen of 25 with a fixed , focal uptake were malignant . In 19 of 23 masses , intestinal activity noted within 30 minutes was caused by metastases . All three cases with lymph node involvement and six cases with ascites were confirmed malignant . Combining focal uptake with intestinal involvement correctly indicated 22 of 23 malignant conditions before operation , whereas negative scans identified 41 of 48 benign lesions . Four of seven false-positive lesions had a higher cellular component . The diagnostic performance of Tc-99 m MIBI is better than that of CT and CA-125 tests , because CT had eight false-positive and three false-negative results , whereas CA-125 had 12 false-positive and 3 false-negative results , respectively . CONCLUSIONS Tc-99 m MIBI is useful for differentiating benign and malignant pelvic masses in female patients . A fixed focal uptake or intestinal uptake of the radiotracer suggests malignancy , with diagnostic sensitivity , specificity , accuracy , and positive and negative predictive values of 95.6 % , 85.4 % , 88.7 % , 75.9 % , and 97.6 % , respectively , in the current prospect i ve study The purpose of this study was to determine the diagnostic value of CA 125 in comparison with transabdominal ultrasound ( US ) in the evaluation of postmenopausal women with pelvic mass to detect malignant epithelial ovarian tumors . Postmenopausal patients with pelvic mass were studied with gynecologic examination , US and CA 125 determination . Three hundred eighty-eight patients were entered in the study . According to stratification based on US ( probably benign , equivocal , possibly malignant ) and CA 125 ( < 35 U/ml , negative ; between 35 and 65 U/ml , borderline ; > 65 U/ml , positive ) , 290 patients were considered eligible for surgery . Specificity , sensitivity , positive and negative predictive value , and accuracy of US and CA 125 were calculated with respect to histological examination . Out of 290 operated patients , 134 had a benign ovarian pathology , 34 had extraovarian benign pathology , 106 had an ovarian malignancy , and 16 presented with an extraovarian malignant pathology . The results according to ovarian malignant pathology were as follows . CA 125 ( > 65 U/ml ) : Specificity , 92.5 % ; sensitivity , 71.7 % ; accuracy , 83.3 % . CA 125 ( > 35 U/ml ) : Specificity , 82.0 % ; sensitivity , 78.3 % ; accuracy , 80.4 % . US : Specificity , 77.6 % ; sensitivity , 84.9 % ; accuracy , 80.3 % . Combination of US and CA 125 ( > 65 U/ml ) : Specificity , 96.1 % ; sensitivity , 91.7 % ; accuracy , 94.3 % . Determination of CA 125 is a highly specific method in predicting ovarian cancer in postmenopausal women with a pelvic mass . The association with US significantly improves the overall accuracy and may support therapeutical decision making by distinguishing between a significant percentage of women most likely to benefit from prompt intervention and women who may be managed following minor surgical diagnostic approach , such as fine-needle aspiration |
1,085 | 21,678,346 | AUTHORS ' CONCLUSIONS This review found minimal evidence to support the use of antibiotics for bronchiolitis . | BACKGROUND Bronchiolitis is a serious , potentially life-threatening respiratory illness commonly affecting babies .
It is often caused by respiratory syncytial virus ( RSV ) .
Antibiotics are not recommended for bronchiolitis unless there is concern about complications such as secondary bacterial pneumonia or respiratory failure .
Nevertheless , they are used at rates of 34 % to 99 % in uncomplicated cases .
OBJECTIVES To evaluate the effectiveness of antibiotics for bronchiolitis . | 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 bronchiolitis were r and omly assigned to receive 2.5 mg bid of nebulized rhDNase or placebo until discharge . The primary end point was length of hospital stay . Secondary end points were duration of supplemental oxygen , improvement in symptom score , and number of intensive care admissions . RESULTS There were no significant differences between the groups with regard to the length of hospital stay ( p = 0.19 ) or the duration of supplemental oxygen ( p = 0.07 ) . The ratio ( rhDNase/placebo ) of geometric means of length of stay was 1.12 ( 95 % confidence interval , 0.96 to 1.33 ) ; for the duration of supplemental oxygen , the ratio was 1.28 ( 95 % confidence interval , 0.97 to 1.68 ) . There were no significant differences in the rate of improvement of the symptom score or in the number of intensive care admissions . CONCLUSIONS Administration of rhDNase did not reduce the length of hospital stay or the duration of supplemental oxygen in oxygen-dependent infants with RSV bronchiolitis |
1,086 | 20,212,028 | INTERPRETATION Computer reminders produced much smaller improvements than those generally expected from the implementation of computerized order entry and electronic medical record systems . | BACKGROUND The opportunity to improve care using computer reminders is one of the main incentives for implementing sophisticated clinical information systems .
We conducted a systematic review to quantify the expected magnitude of improvements in processes of care from computer reminders delivered to clinicians during their routine activities . | 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 ; 27 % ; P < .001 ) , suggesting some spillover effect on the control group . Redosing was formally declined for 19 of the 44 patients in the reminder group without redosing . The rate of surgical-site infection in the reminder group ( 5 of 137 ; 4 % ) was similar to that in the control group ( 8 of 136 ; 6 % ; P = .42 ) , but significantly lower than that in the pre- study period ( 48 of 480 ; 10 % ; P = .02 ) . CONCLUSION The use of an automatic reminder system in the operating room improved compliance with guidelines on perioperative antibiotic prophylaxis OBJECTIVE To evaluate whether an electronic reminder integrated into a routine computer system increases the use of antiplatelet drugs for diabetic patients among Italian general practitioners ( GPs ) . RESEARCH DESIGN AND METHODS A r and omized controlled trial was carried out among 300 GPs and their patients selected from the Health Search Data base . Among these , 150 GPs ( intervention group ) received instructions to activate an electronic reminder plus a letter summarizing the beneficial effects of antiplatelet drugs in diabetic patients with at least one additional cardiovascular risk factor ( " high risk " ) , whereas the other 150 GPs ( control group ) received only the letter . The electronic reminder , integrated into a st and ard software system for the management of the daily clinical practice , was displayed when every participating GP opened the medical record of diabetic patients aged > or = 30 years . Only high-risk diabetic patients were included in the analysis . Patients were considered under antiplatelet treatment if they received two or more prescriptions at baseline and during the follow-up . RESULTS We selected 15,343 high-risk diabetic patients , 7,313 belonging to GPs of the control group and 8,030 belonging to GPs of the intervention group . Overall , 1,672 patients ( 22.9 % ) of the control group and 1,886 ( 23.5 % ) patients of the intervention group received antiplatelet drugs at baseline ( P = N.S. ) . At the end of the follow-up , the number of treated patients was significantly increased in the intervention group ( odds ratio 1.99 , 95 % CI 1.79 - 2.22 ) versus the control group . The effect of the electronic reminder was more relevant among those patients with one or more cardiovascular risk factors but without previous cardiovascular diseases ( CVDs ) , compared with those with CVDs . CONCLUSIONS These findings provide evidence for the effect of an electronic reminder in affecting the prescriptive behavior of GPs BACKGROUND Although they are effective in outpatient setting s , computerized reminders have not been proved to increase preventive care in inpatient setting s. METHODS We conducted a r and omized , controlled trial to determine the effects of computerized reminders on the rates at which four preventive therapies were ordered for in patients . During an 18-month study period , a computerized system processed on-line information for all 6371 patients admitted to a general-medicine service ( for a total of 10,065 hospitalizations ) , generating preventive care reminders as appropriate . Physicians who were in the intervention group viewed these reminders when they were using a computerized order-entry system for in patients . RESULTS The reminder system identified 3416 patients ( 53.6 percent ) as eligible for preventive measures that had not been ordered by the admitting physician . For patients with at least one indication , computerized reminders result ed in higher adjusted ordering rates for pneumococcal vaccination ( 35.8 percent of the patients in the intervention group vs. 0.8 percent of those in the control group , P<0.001 ) , influenza vaccination ( 51.4 percent vs. 1.0 percent , P < 0.001 ) , prophylactic heparin ( 32.2 percent vs. 18.9 percent , P<0.001 ) , and prophylactic aspirin at discharge ( 36.4 percent vs. 27.6 percent , P<0.001 ) . CONCLUSIONS A majority of hospitalized patients in this study were eligible for preventive measures , and computerized reminders significantly increased the rate of delivery of such therapies Systematic review s provide the best evidence on the effectiveness of healthcare interventions including quality improvement strategies . The methods of systematic review of individual patient r and omised trials of healthcare interventions are well developed . We discuss method ological and practice issues that need to be considered when undertaking systematic review s of quality improvement strategies including developing a review protocol , identifying and screening evidence sources , quality assessment and data abstract ion , analytical methods , reporting systematic review s , and appraising systematic review s. This paper builds on our experiences within the Cochrane Effective Practice and Organisation of Care ( EPOC ) review group OBJECTIVE To test effects of a web-based decision support tool , the diabetes Disease Management Application ( DMA ) , developed to improve evidence -based management of type 2 diabetes . RESEARCH DESIGN AND METHODS We conducted a group r and omized controlled trial of 12 intervention and 14 control staff providers and 307 intervention and 291 control patients with type 2 diabetes in a hospital-based internal medicine clinic . Providers were r and omly assigned from May 1998 through April 1999 to have access to the DMA ( intervention ) or not to have access ( control ) . The DMA displays interactive patient-specific clinical data , treatment advice , and links to other web-based care re sources . We compared patients in the intervention and control groups for changes in processes and outcomes of care from the year preceding the study through the year of the study by intention-to-treat analysis . RESULTS The DMA was used for 42 % of scheduled patient visits . The number of HbA(1c ) tests obtained per year increased significantly in the intervention group ( + 0.3 tests/year ) compared with the control group ( -0.04 tests/year , P = 0.008 ) , as did the number of LDL cholesterol tests ( intervention , + 0.2 tests/year ; control , + 0.01 tests/year ; P = 0.02 ) and the proportions of patients undergoing at least one foot examination per year ( intervention , + 9.8 % ; control , -0.7 % ; P = 0.003 ) . Levels of HbA(1c ) decreased by 0.2 in the intervention group and increased by 0.1 in the control group ( P = 0.09 ) ; proportions of patients with LDL cholesterol levels < 130 mg/dl increased by 20.3 % in the intervention group and 10.5 % in the control group ( P = 0.5 ) . CONCLUSIONS Web-based patient-specific decision support has the potential to improve evidence -based parameters of diabetes care OBJECTIVE Errors of omission are a common cause of systems failures . Physicians often fail to order tests or treatments needed to monitor/ameliorate the effects of other tests or treatments . The authors hypothesized that automated , guideline -based reminders to physicians , provided as they wrote orders , could reduce these omissions . DESIGN The study was performed on the inpatient general medicine ward of a public teaching hospital . Faculty and housestaff from the Indiana University School of Medicine , who used computer workstations to write orders , were r and omized to intervention and control groups . As intervention physicians wrote orders for 1 of 87 selected tests or treatments , the computer suggested corollary orders needed to detect or ameliorate adverse reactions to the trigger orders . The physicians could accept or reject these suggestions . RESULTS During the 6-month trial , reminders about corollary orders were presented to 48 intervention physicians and withheld from 41 control physicians . Intervention physicians ordered the suggested corollary orders in 46.3 % of instances when they received a reminder , compared with 21.9 % compliance by control physicians ( p < 0.0001 ) . Physicians discriminated in their acceptance of suggested orders , readily accepting some while rejecting others . There were one third fewer interventions initiated by pharmacists with physicians in the intervention than control groups . CONCLUSION This study demonstrates that physician workstations , linked to a comprehensive electronic medical record , can be an efficient means for decreasing errors of omissions and improving adherence to practice guidelines CONTEXT Prescribing practice s for otitis media are not consistent with current evidence -based recommendations . OBJECTIVE To determine whether point-of-care evidence delivery regarding the use and duration of antibiotics for otitis media decreases the duration of therapy from 10 days and decreases the frequency of prescriptions written . DESIGN R and omized , controlled trial . SETTING Primary care pediatric clinic affiliated with university training program . Intervention . A point-of-care evidence -based message system presenting real time evidence to providers based on their prescribing practice for otitis media . MAIN OUTCOME MEASURES Proportion of prescriptions for otitis media that were for < 10 days and frequency with which antibiotics were prescribed . RESULTS Intervention providers had a 34 % greater reduction in the proportion of time they prescribed antibiotics for < 10 days . Intervention providers were less likely to prescribe antibiotics than were control providers . CONCLUSIONS A point-of-care information system integrated into outpatient pediatric care can significantly influence provider behavior for a common condition Abstract Objective : To assess the effectiveness of tailored interventions to implement guidelines for urinary tract infections in women and sore throat Design : Unblinded , cluster r and omised pretest-post-test trial Setting : 142 general practice s in Norway Participants : 72 practice s received interventions to implement guidelines for urinary tract infection and 70 practice s received interventions to implement guidelines for sore throat , serving as controls for each other . 59 practice s in the urinary tract infection group and 61 practice s in the sore throat group completed the study . Outcomes were measured in 16 939 consultations for sore throat and 9887 consultations for urinary tract infection . Interventions : Interventions were developed to overcome identified barriers to implementing the guidelines . The main components of the tailored interventions were patient educational material , computer based decision support and reminders , an increase in the fee for telephone consultations , and interactive courses for general practitioners and practice assistants Main outcome measures : Changes in rates of use of antibiotics , laboratory tests , and telephone consultations Results : Patients in the sore throat group were 3 % less likely to receive antibiotics after the intervention . Women with symptoms of urinary tract infection in the intervention group were 5.1 % less likely to have a laboratory test ordered . No significant differences were found between the groups for the other outcomes . Large variation was found across the included practice sin the rates of antibiotic prescription , use of laboratory tests and telephone consultations , and in the extent of change for all three outcome measures Conclusions : Passively delivered , complex interventions targeted at identified barriers to change had little effect in changing The statistical methodology of health research experiments published in Lancet , the New Engl and Journal of Medicine , and Medical Care between 1975 and 1980 for the presence or absence of an error of experimental design and analysis was examined . The error is the result of inappropriately using patient-related observations as the unit of analysis to form conclusions about provider behavior or outcomes determined jointly by patients and providers . The error was present in 20 of 28 ( 71 % ) health care experiments addressing an issue of health provider professional performance . Its usual effect is to increase erroneously the power of an experiment to detect differences between experimental and control groups . It is likely that this type of error could be avoided by the explicit and prospect i ve definition of hypotheses and the population s to which they are intended to pertain BACKGROUND Overuse of blood products is common , but prior efforts to improve transfusion decisions have met with limited success . STUDY DESIGN AND METHODS This study examines transfusion practice s before and after a conventional educational intervention followed by a r and omized controlled trial of a decision support ( DS ) intervention with computerized physician order entry ( CPOE ) for red blood cell , platelet , and fresh-frozen plasma orders . The study was conducted in an academic medical center between April 2003 and June 2004 . Orders originating from units not using CPOE with DS ( e.g. , the emergency department ) were excluded . Junior housestaff were r and omly assigned into a control group and an intervention group who received DS for transfusion orders . Transfusion orders were initially classified according to guideline rules as DS-agree or DS-disagree . Chart review s assessed inappropriateness for all DS-disagree orders and a sample of DS-agree orders . The total of inappropriate transfusion orders included chart review confirmed DS-disagree orders and DS-agree orders reclassified as inappropriate . RESULTS The percentages of inappropriate nonemergent transfusion orders during the baseline phase for the entire staff and r and omly assigned junior housestaff were 72.6 percent ( 2154/2967 ) and 71.9 percent ( 1259/1752 ) and improved after conventional education to 63.8 percent ( 1699/2663 ; p < 0.0001 ) and 63.3 percent ( 1263/1996 ; p < 0.0001 ) , respectively . The percentage of inappropriate orders in the DS intervention group continued to improve ( 59.6 % , 804/1350 ; p < 0.0001 ) . Physicians accepted 14 percent ( 133/939 ) of new DS-recommended orders , especially recommendations to increase transfusion doses ( 73 % ) . CONCLUSIONS Education and computerized DS both decreased the percentage of inappropriate transfusions , although the residual amount of inappropriate transfusions remained high Abstract BACKGROUND : In New Zeal and , more than 5 % of people aged 50 years and older have undiagnosed diabetes ; most of them attend family practitioners ( FPs ) at least once a year . OBJECTIVES : To test the effectiveness of patients or computers as reminders to screen for diabetes in patients attending FPs . DESIGN : A r and omized-controlled trial compared screening rates in 4 intervention arms : patient reminders , computer reminders , both reminders , and usual care . The trial lasted 2 months . The patient reminder was a diabetes risk self- assessment sheet filled in by patients and given to the FP during the consultation . The computer reminder was an icon that flashed only for patients considered eligible for screening . PARTICIPANTS : One hundred and seven FPs . MEASUREMENTS : The primary outcome was whether each eligible patient , who attended during the trial , was or was not tested for blood glucose . Analysis was by intention to treat and allowed for clustering by FP . RESULTS : Patient reminders ( odds ratio [ OR ] 1.72 , 95 % confidence interval [ CI ] 1.21 , 2.43 ) , computer reminders ( OR 2.55 , 1.68 , 3.88 ) , and both reminders ( OR 1.69 , 1.11 , 2.59 ) were all effective compared with usual care . Computer reminders were more effective than patient reminders ( OR 1.49 , 1.07 , 2.07 ) . Patients were more likely to be screened if they visited the FP repeatedly , if patients were non-European , if they were “ regular ” patients of the practice , and if their FP had a higher screening rate prior to the study . CONCLUSIONS : Patient and computer reminders were effective methods to increase screening for diabetes . However , the effects were not additive Context Despite evidence showing that even mild elevation of blood pressure above 140/90 mm Hg puts patients at risk for cardiovascular complications , many patients who are treated for hypertension still have high blood pressure . Contribution The authors sought to improve the blood pressure of patients using a health systems approach . They r and omly assigned providers caring for hypertensive patients to receive a Web link to the Seventh Report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ; the Web link and a computer alert notifying them of the patient 's blood pressure ; or the Web link , computer alert , and a letter educating the patient about ways to control his or her blood pressure . Patients of providers r and omly assigned to the third group had greater decreases in blood pressure and were more likely to have a systolic blood pressure less than 140 mm Hg . Caution s The study took place in a Veterans Affairs setting , follow-up blood pressure measures were missing for many patients , and the study was not design ed to detect a mechanism for any observed changes . Implication s A health systems approach that gave providers feedback about their patients ' blood pressure and that gave patients information about ways to control it improved blood pressure control compared with provider education alone . The Editors Currently , more than 50 million persons in the United States have hypertension ( 1 ) . The Seventh Report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC 7 ) promotes blood pressure goals of less than 140/90 mm Hg ( 25 ) . Providers , however , often delay changes in therapy or use higher blood pressure thresholds for the treatment of hypertension ( 2 , 4 , 6 , 7 ) , which leads to a variance in guideline adherence that contributes to a quality gap in care . Despite widespread guideline promotion , 65 % of persons in the United States have poorly controlled hypertension ( 1 , 6 , 8 , 9 ) . Factors contributing to the achievement of hypertension goals include provider decision making and patient adherence to antihypertensive treatment . These factors can be influenced by other factors , such as patient interactions with clinicians , commercial influences , and patient participation in treatment decisions ( 6 , 1017 ) . A review of hypertension goal attainment in primary care ( 18 ) found that interventions with the largest positive change were complex , multifactorial , and involved 4 areas : activities directed at changing clinician behavior , changes to the organization , information enhancement , and educational programs directed at patients . Although these findings suggest opportunities to achieve effective intervention by directing a change at each component ( 2 , 17 , 1923 ) , the impact of each component is less well known . Our aim was 1 ) to improve the quality of care of patients with hypertension at our facility while examining the relative contribution of each aspect of a multifactorial intervention design ed to improve care and 2 ) to show the effects of physician-level clustering on quality assessment . We conducted a cluster r and omized , controlled study to evaluate common components of a multifactorial intervention in veterans with essential hypertension . Methods Study Design and Setting This project was a cluster r and omized , controlled trial design ed to examine the relative contribution of 3 quality improvement interventions of increasing intensity in improving blood pressure control in veterans . This study was the evaluation component of a Veterans Integrated Service Network campaign to improve blood pressure control in patients who are treated in the Tennessee Valley Healthcare System . The health care system comprises 2 teaching hospitals , 2 large community-based outpatient clinics , and 6 small community-based outpatient clinics . There were 523659 outpatient visits made by 69928 veterans during fiscal year 2004 . The institutional review board of V and erbilt University and the VA Tennessee Valley Healthcare System research and development committee for human subjects protection approved this study . Inclusion Criteria We first identified eligible patients and then r and omly assigned providers caring for at least 1 of those patients to receive study interventions . Patients were eligible for inclusion in the study if they were 21 to 90 years of age , filled their medications at Veterans Administration ( VA ) pharmacies , had at least 2 uncontrolled blood pressure measurements in the 6-month baseline period ( systolic blood pressure > 140 mm Hg or diastolic blood pressure 90 mm Hg ) , and were only taking 1 antihypertensive medication . We restricted our study sample to patients with uncontrolled hypertension who were only taking 1 antihypertensive medication because the JNC 7 guidelines propose that most patients with hypertension will require 2 or more medications to achieve their blood pressure goals ( 5 , 12 ) . Therefore , this sample includes patients for whom the quality of hypertension care could be improved . Eligible patients were identified between July and December 2003 by search ing data from the Mid-South Quality Improvement Data warehouse , which are downloaded monthly from Veterans Health Information System and Technology Architecture . The search initially identified 4648 patients with a primary care visit who had a diagnosis of hypertension indicated by International Classification of Diseases , Ninth Revision , Clinical Modification ( ICD-9-CM ) codes 401.1 or 401.9 and who were prescribed only 1 antihypertensive medication ( Figure ) . We excluded 2821 ( 60 % ) patients because they had at least 1 recorded blood pressure reading between July and December 2003 that was at goal ( systolic blood pressure 140 mm Hg and diastolic blood pressure < 90 mm Hg ) . We mailed an assent letter to the remaining 1827 patients in January 2004 asking permission to review their electronic medical record and indicating that their primary provider would potentially receive suggestions to improve their hypertension care . Another 486 patients were excluded after r and omization because they declined chart review ( n= 222 ) or were taking more than 1 antihypertensive medication at the time of chart review ( n= 264 ) . Figure . Study flow diagram . * Excluded providers who cared for patients who declined chart review or those who were taking more than 1 medication at the time of chart review after r and omization . Providers were eligible for r and omization if they provided care for at least 1 patient who fulfilled the eligibility criteria . Providers were classified as attending physicians , resident physicians , or nonphysician clinicians ( nurse practitioner or physician assistant ) and were stratified into providers with at least 30 eligible patients and those with less than 30 eligible patients to help balance the number of patients in each study group . One hundred eighty-two providers were r and omly assigned to study interventions ; after r and omization , 23 providers were additionally excluded because the patients they cared for declined chart review or were taking more than 1 antihypertensive medication at the time of chart review ( Figure ) . Interventions Providers were r and omly assigned to 1 of 3 study groups : provider education only ; provider education and alert ; or provider education , alert , and patient education . All interventions were performed during the week of 14 June through 18 June 2004 , and follow-up continued through 31 December 2004 . Provider Education All providers in the 3 study groups received an e-mail message that explained the planned intervention . Providers who received only the e-mail message were controls for those who received the other 2 more intensive interventions . The e-mail informed providers that they might receive electronic alerts in the computerized patient record requesting reevaluation of a patient 's antihypertensive regimen . It also reported that a letter was being sent to selected patients advocating medication adherence and lifestyle modification to lower blood pressure . The e-mail message included a Web link to the JNC 7 guidelines for the treatment of hypertension ( www.nhlbi.nih.gov/ guidelines /hypertension/jnc7full.pdf ) . The message was sent by the supervisory pharmacist at the VA Tennessee Valley Healthcare System and was signed by the medical director of the network . Provider Education and Alert In the second study group , an alert was added to provider education . The alert was a 1-time patient-specific electronic notification that was sent by the pharmacy to the prescribing provider through each eligible patient 's electronic medical record over a 1-week period in June 2004 . Each time providers signed on to a computer , any medical record that contained an alert was brought to their attention . The alert gave a brief outline of the JNC 7 recommendations ( 5 ) and reminded providers that goal blood pressure should be 140/90 mm Hg or less . It included date s and values of the patient 's last 3 recorded blood pressure measurements and offered the following options : addition of a thiazide or thiazide combination diuretic , addition of another antihypertensive medication , or continuation of current medications and dosages . The alert reminded providers of the available thiazides on the VA formulary and stated that thiazides were contraindicated in patients with renal insufficiency or allergies to sulfa medications . Provider Education , Alert , and Patient Education The third study group combined the provider education and alert described previously with a patient education component . We sent a personalized letter that contained educational information concerning hypertension to each eligible patient in this study group . The letter was labeled Notice : To Veterans with High Blood Pressure and was design ed at an eighth- grade reading level . The letter recommended the use of behavioral strategies , such as medication adherence , low-sodium diet , and exercise , We tested whether off-line data analysis , instead of event monitoring , was a viable method for initiating a clinical quality alert . A cohort of patients eligible for an alert was identified by off-line data analysis and a flag was set in their ambulatory Electronic Medical Records . One hundred clinicians were r and omly assigned either to a control group or to a group that received the alert when viewing the electronic medical record of eligible patients . Primarily due to actions of their clinicians , 315 of the 580 patients ( 54.3 % ) seen by alerted clinicians were no longer eligible for the alert at the end of the one month study , compared to 128 of the 496 patients ( 25.8 % ) seen by control clinicians ( p<.001 ) . When not alerted , Allied Health clinicians were less likely than physicians to prescribe aspirin , but they responded similarly to the alert . There were no differences in response by specialty or gender of the clinician . Off-line data analysis proved to be an effective method of initiating a clinical alert PURPOSE To determine the impact of giving physicians computerized reminders about apparently redundant clinical laboratory tests . SUBJECTS AND METHODS We performed a prospect i ve r and omized controlled trial that included all in patients at a large teaching hospital during a 15-week period . The intervention consisted of computerized reminders at the time a test was ordered that appeared to be redundant . Main outcome measures were the proportions of clinical laboratory orders that were canceled and the proportion of the tests that were actually performed . RESULTS During the study period , there were 939 apparently redundant laboratory tests among the 77,609 study tests that were ordered among the intervention ( n = 5,700 patients ) and control ( n = 5,886 patients ) groups . In the intervention group , 69 % ( 300 of 437 ) of tests were canceled in response to reminders . Of 137 overrides , 41 % appeared to be justified based on chart review . In the control group , 51 % of ordered redundant tests were performed , whereas in the intervention group only 27 % of ordered redundant tests were performed ( P < 0.001 ) . However , the estimated annual savings in laboratory charges was only $ 35,000 . This occurred because only 44 % of redundant tests performed had computer orders , because only half the computer orders were screened for redundancy , and because almost one-third of the reminders were overridden . CONCLUSIONS Reminders about orders for apparently redundant laboratory tests were effective when delivered . However , the overall effect was limited because many tests were performed without corresponding computer orders , and many orders were not screened for redundancy BACKGROUND Prophylaxis against deep-vein thrombosis in hospitalized patients remains underused . We hypothesized that the use of a computer-alert program to encourage prophylaxis might reduce the frequency of deep-vein thrombosis among high-risk hospitalized patients . METHODS We developed a computer program linked to the patient data base to identify consecutive hospitalized patients at risk for deep-vein thrombosis in the absence of prophylaxis . The program used medical-record numbers to r and omly assign 1255 eligible patients to an intervention group , in which the responsible physician was alerted to a patient 's risk of deep-vein thrombosis , and 1251 patients to a control group , in which no alert was issued . The physician was required to acknowledge the alert and could then withhold or order prophylaxis , including graduated compression stockings , pneumatic compression boots , unfractionated heparin , low-molecular-weight heparin , or warfarin . The primary end point was clinical ly diagnosed , objective ly confirmed deep-vein thrombosis or pulmonary embolism at 90 days . RESULTS More patients in the intervention group than in the control group received mechanical prophylaxis ( 10.0 percent vs. 1.5 percent , P<0.001 ) or pharmacologic prophylaxis ( 23.6 percent vs. 13.0 percent , P<0.001 ) . The primary end point occurred in 61 patients ( 4.9 percent ) in the intervention group , as compared with 103 ( 8.2 percent ) in the control group ; the Kaplan-Meier estimates of the likelihood of freedom from deep-vein thrombosis or pulmonary embolism at 90 days were 94.1 percent ( 95 percent confidence interval , 92.5 to 95.4 percent ) and 90.6 percent ( 95 percent confidence interval , 88.7 to 92.2 percent ) , respectively ( P<0.001 ) . The computer alert reduced the risk of deep-vein thrombosis or pulmonary embolism at 90 days by 41 percent ( hazard ratio , 0.59 ; 95 percent confidence interval , 0.43 to 0.81 ; P=0.001 ) . CONCLUSIONS The institution of a computer-alert program increased physicians ' use of prophylaxis and markedly reduced the rates of deep-vein thrombosis and pulmonary embolism among hospitalized patients at risk This paper discusses statistical techniques for the analysis of dichotomous data arising from a design in which the investigator r and omly assigns each of two clusters of possibly varying size to interventions within strata . The problem addressed is that of assessing the statistical significance of the intervention effect over all strata . We propose a weighted paired t-test based on the empirical logistic transform for design s that r and omize large aggregate clusters in each of several strata BACKGROUND : Electronic information systems have been proposed as one means to reduce medical errors of commission ( doing the wrong thing ) and omission ( not providing indicated care ) . OBJECTIVE : To assess the effects of computer-based cardiac care suggestions . DESIGN : A r and omized , controlled trial targeting primary care physicians and pharmacists . SUBJECTS : A total of 706 out patients with heart failure and /or ischemic heart disease . INTERVENTIONS : Evidence -based cardiac care suggestions , approved by a panel of local cardiologists and general internists , were displayed to physicians and pharmacists as they cared for enrolled patients . MEASUREMENTS : Adherence with the care suggestions , generic and condition-specific quality of life , acute exacerbations of their cardiac disease , medication compliance , health care costs , satisfaction with care , and physicians ’ attitudes toward guidelines . RESULTS : Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions . The intervention had no effect on physicians ’ adherence to the care suggestions ( 23 % for intervention patients vs 22 % for controls ) . There were no intervention-control differences in quality of life , medication compliance , health care utilization , costs , or satisfaction with care . Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients . CONCLUSIONS : Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease . Future studies must weigh the benefits and costs of different ( and perhaps more Draconian ) methods of affecting clinician behavior BACKGROUND We conducted a cluster r and omized controlled trial to examine the effectiveness of computerized decision support ( CDS ) design ed to improve hypertension care and outcomes in a racially diverse sample of primary care patients . METHODS We r and omized 2,027 adult patients receiving hypertension care in 14 primary care practice s to either 18 months of their physicians receiving CDS for each hypertensive patient or to usual care without computerized support for the control group . We assessed prescribing of guideline -recommended drug therapy and levels of blood pressure control for patients in each group and examined if the effects of the intervention differed by patients ’ race/ethnicity using interaction terms . MEASUREMENTS AND MAIN RESULTS Rates of blood pressure control were 42 % at baseline and 46 % at the outcome visit with no significant differences between groups . After adjustment for patients ’ demographic and clinical characteristics , number of prior visits , and levels of baseline blood pressure control , there were no differences between intervention groups in the odds of outcome blood pressure control . The use of CDS to providers significantly improved Joint National Committee ( JNC ) guideline adherent medication prescribing compared to usual care ( 7 % versus 5 % , P < 0.001 ) ; the effects of the intervention remained after multivariable adjustment ( odds ratio [ OR ] 1.39 [ CI , 1.13–1.72 ] ) and the effects of the intervention did not differ by patients ’ race and ethnicity . CONCLUSIONS CDS improved appropriate medication prescribing with no improvement in disparities in care and overall blood pressure control . Future work focusing on improvement of these interventions and the study of other practical interventions to reduce disparities in hypertension-related outcomes is needed PRIMARY OBJECTIVE To investigate whether computer decision support software used in the management of patients with asthma improves clinical outcomes . RESEARCH DESIGN R and omized controlled trial with practice s each reporting on 30 patients with asthma over a 6 month period . METHODS AND PROCEDURES 447 patients were r and omly selected from practice asthma registers managed by 17 general practice s from throughout the UK . Intervention practice s used the software during consultations with these patients throughout the study while control practice s did not . MAIN OUTCOMES AND RESULTS Practice consultations , acute exacerbations of asthma , hospital contacts , symptoms on assessment and medication use . A smaller proportion of patients within the intervention group initiated practice consultations for their asthma : 34 ( 22 % ) vs 111 ( 34 % ) , odds ratio ( OR ) = 0.59 , 95 % confidence interval ( CI ) ( 0.37 - 0.95 ) ; and suffered acute asthma exacerbations : 12 ( 8 % ) vs 57 ( 17 % ) , OR = 0.43 , 95 % CI = 0.21 - 0.85 six months after the introduction of the computer decision support software . There were no discernable differences in reported symptoms , maintenance prescribing or use of hospital services between the two groups . CONCLUSION The use of computer decision support software that implements guidelines during patient consultations may improve clinical outcomes for patients with asthma OBJECTIVE Translation of evidence -based guidelines into clinical practice has been inconsistent . We performed a r and omized , controlled trial of guideline -based care suggestions delivered to physicians when writing orders on computer workstations . STUDY SETTING Inner-city academic general internal medicine practice . STUDY DESIGN R and omized , controlled trial of 246 physicians ( 25 percent faculty general internists , 75 percent internal medicine residents ) and 20 outpatient pharmacists . We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease . Care suggestions concerning drugs and monitoring were delivered to a r and om half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations . A 2 x 2 factorial r and omization of practice sessions and pharmacists result ed in four groups of patients : physician intervention , pharmacist intervention , both interventions , and controls . DATA EXTRACTION / COLLECTION METHODS : Adherence to the guidelines and clinical activity was assessed using patients ' electronic medical records . Health-related quality of life , medication adherence , and satisfaction with care were assessed using telephone question naires . PRINCIPAL FINDINGS During their year in the study , patients made an average of five scheduled primary care visits . There were no differences between groups in adherence to the care suggestions , generic or condition-specific quality of life , satisfaction with physicians or pharmacists , medication compliance , emergency department visits , or hospitalizations . Physicians receiving the intervention had significantly higher total health care costs . Physician attitudes toward guidelines were mixed . CONCLUSIONS Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease BACKGROUND Preventive care is an important role for general practitioners , yet opportunities for prevention are often missed . METHOD We provided an automatic electronic record preventive care reminder system for 12 preventive care activities for one 10 doctor practice . All patients who attended were r and omised by the terminal digit of their record number . RESULTS The control uptake of opportunistic prevention was low ; ranging from 1.5 % ( tetanus immunisation ) to 27 % ( influenza immunisation ) . The reminders increased this by significant but small amounts for four out of 12 activities ( immunisation for tetanus and pneumococcus and recording of allergies and weight ) , insignificant increases for four ( mumps , measles and rubella immunisation , recording of smoking , and taking of cervical smears and of blood pressure ) , and insignificantly decreased influenza immunisation , and screening for diabetes and hyperlipidaemia . DISCUSSION Opportunistic electronic reminders have the potential to increase preventive care in general practice To meet the needs of primary care physicians caring for patients with HIV infection , we developed a knowledge-based medical record to allow the on-line patient record to play an active role in the care process . These programs integrate the on-line patient record , rule-based decision support , and full-text information retrieval into a clinical workstation for the practicing clinician . To determine whether use of a knowledge-based medical record was associated with more rapid and complete adherence to practice guidelines and improved quality of care , we performed a controlled clinical trial among physicians and nurse practitioners caring for 349 patients infected with the human immuno-deficiency virus ( HIV ) ; 191 patients were treated by 65 physicians and nurse practitioners assigned to the intervention group , and 158 patients were treated by 61 physicians and nurse practitioners assigned to the control group . During the 18-month study period , the computer generated 303 alerts in the intervention group and 388 in the control group . The median response time of clinicians to these alerts was 11 days in the intervention group and 52 days in the control group ( PJJ0.0001 , log-rank test ) . During the study , the computer generated 432 primary care reminders for the intervention group and 360 reminders for the control group . The median response time of clinicians to these alerts was 114 days in the intervention group and more than 500 days in the control group ( PJJ0.0001 , log-rank test ) . Of the 191 patients in the intervention group , 67 ( 35 % ) had one or more hospitalizations , compared with 70 ( 44 % ) of the 158 patients in the control group ( PJ = J0.04 , Wilcoxon test stratified for initial CD4 count ) . There was no difference in survival between the intervention and control groups ( P = 0.18 , log-rank test ) . We conclude that our clinical workstation significantly changed physicians ' behavior in terms of their response to alerts regarding primary care interventions and that these interventions have led to fewer patients with HIV infection being admitted to the hospital |
1,087 | 28,137,459 | These genes are implicated in hippocampal plasticity and stress reactivity , suggesting that dysregulation of these pathways may contribute to LLD . | ABSTRACT Late‐life depression ( LLD ) is thought to be multifactorial in etiology , including a significant genetic component .
While a number of c and i date gene studies have been carried out , results remain inconclusive . | 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 |
1,088 | 25,946,534 | 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 | null | null |
1,089 | 31,512,111 | 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 . | Over the past few decades , a community-based approach was seen to be the “ gold st and ard ” for health promotion and disease prevention , especially in the field of socially deprived neighborhoods in urban areas .
Up to the beginning of the 2000s , earlier review s provide valuable information on activities in this context .
However , in their conclusions they were limited to North America and Europe .
Therefore , we conducted a systematic literature review on community-based health promotion and prevention programs worldwide . | 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 factor related to participation in neighbourhood development was prior experience of participation , such as attempting to influence city policies by contacting politicians , su bmi tting a citizen proposal , etc . Furthermore , having frequent political discussion s with neighbours was another behavioural factor that was found associated to people 's participation in neighbourhood development . Among socio-demographic factors , only ethnicity was found significant after controlling for other factors ; i.e. people born outside the Nordic countries were less likely to participate Background Cardiovascular disease remains the leading killer of women in most developed areas of the world . Rates of physical inactivity and poor nutrition , which are two of the most important modifiable risk factors for cardiovascular disease in women , are substantial . This study sought to examine the effectiveness of a community-based lifestyle-modification program on increasing women 's physical activity in a r and omized trial guided by community-based participatory research ( CBPR ) methods . Methods A total of 335 healthy , 25–64 years old women who had been selected by a multiple-stage stratified cluster r and om sampling method in Bushehr Port/I.R. Iran , were r and omized into control and intervention groups . The intervention group completed an 8-week lifestyle modification program for increasing their physical activity , based on a revised form of Choose to Move program ; an American Heart Association Physical Activity Program for Women . Audio-taped activity instructions with music and practical usage of the educational package were given to the intervention group in weekly home-visits by 53 volunteers from local non-governmental and community-based organizations . Results Among the participants , the percentage who reported being active ( at lease 30 minutes of moderate intensity physical activity for at least 5 days a week , or at least 20 minutes of vigorous physical activity for at least three days a week ) increased from 3 % and 2.7 % at baseline to 13.4 % and 3 % ( p < 0.0001 ) at the ending of the program in the intervention and control groups , respectively . The participants in the intervention group reported more minutes of physical activity per week ( mean = 139.81 , SE = 23.35 ) than women in the control group ( mean = 40.14 , SE = 12.65 ) at week 8 ( p < 0.0001 ) . The intervention group subjects exhibited a significantly greater decrease in systolic blood pressure ( -10.0 mmHg ) than the control group women ( + 2.0 . mmHg ) . The mean ranks for posttest healthy heart knowledge in the intervention and control groups were 198.91 and 135.77 , respectively ( P < 0.0001 ) . Conclusion An intervention based on CBPR methods can be effective for the short-term adoption of physical activity behavior among women . The development of participatory process to support the adequate delivery of lifestyle-modification programs is feasible and an effective healthcare delivery strategy for cardiovascular community health promotion . Trial Registration BACKGROUND / OBJECTIVES Childhood obesity is a major public health concern but evidence -based approaches to tackle this epidemic sustainably are still lacking . The Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS ( IDEFICS ) study investigated the aetiology of childhood obesity and developed a primary prevention programme . Here , we report on the effects of the IDEFICS intervention on indicators of body fatness . SUBJECTS/ METHODS The intervention modules addressed the community , school and parental level , focusing on diet , physical activity and stress-related lifestyle factors . A cohort of 16,228 children aged 2 - 9.9 years - about 2000 per country - was equally divided over intervention and control regions . ( Participating countries were Sweden , Germany , Estonia , Hungary , Cyprus , Italy , Spain and Belgium . ) We compared the prevalence of overweight/obesity and mean values of body mass index z-score , per cent body fat and waist-to-height ratio over 2 years of follow-up . Mixed models adjusting for age and socioeconomic status of the parents and with an additional r and om effect for country accounted for the clustered study design . RESULTS The prevalence of overweight and obesity increased in both the intervention and control group from 18.0 % at baseline to 22.9 % at follow-up in the control group and from 19.0 % to 23.6 % in the intervention group . The difference in changes between control and intervention was not statistically significant . For the cohort as a whole , the changes in indicators of body fatness did not show any clinical ly relevant differences between the intervention and control groups . Changes in favour of intervention treatment in some indicators were counterbalanced by changes in favour of the control group in some other indicators . CONCLUSIONS Over the 2-year-observation period , the IDEFICS primary prevention programme for childhood obesity has not been successful in reducing the prevalence of overweight and obesity nor in improving indicators of body fatness in the target population as a whole PURPOSE To evaluate the acceptability , feasibility , and effectiveness of a population -based intervention to promote health of youth ( age : 16 - 24 years ) in Goa . METHODS Two pairs of urban and rural communities were selected ; one of each was r and omly assigned to receive a multi-component intervention and the other wait-listed . The intervention comprised educational institution-based peer education and teacher training ( in the urban community ) , community peer education , and health information material s. Effectiveness was assessed through before-after population surveys at baseline and at 18 months . Outcomes were measured using a structured interview schedule with all eligible youth . Logistic regression compared each pair , adjusted for baseline differences , on prevalence of outcomes in the domains of reproductive and sexual health ( RSH ) , violence , mental health , substance use , and help seeking for health concerns . RESULTS In both intervention communities , prevalence of violence perpetrated and probable depression was significantly lower and knowledge and attitudes about RSH significantly higher ( p < .05 ) . The rural sample also reported fewer menstrual complaints and higher levels of help-seeking for RSH complaints by women , and knowledge and attitudes about emotional health and substance use ; and , the urban sample reported significantly lower levels of substance use , suicidal behavior , sexual abuse , and RSH complaints . Although information material s were acceptable and feasible in both communities , community peer education was feasible only in the rural community . The institution-based interventions were generally acceptable and feasible . CONCLUSIONS Multicomponent interventions comprising information material s , educational-institution interventions and , in rural context s , community peer interventions are acceptable and feasible and likely to be effective for youth health promotion Background Early detection and treatment of mental disorders in adolescents and young adults can lead to better health outcomes . Mental health literacy is a key to early recognition and help seeking . Whilst a number of population health initiatives have attempted to improve mental health literacy , none to date have specifically targeted young people nor have they applied the rigorous st and ards of population health models now accepted as best practice in other health areas . This paper describes the outcomes from the application of a health promotion model to the development , implementation and evaluation of a community awareness campaign design ed to improve mental health literacy and early help seeking amongst young people . Method The Compass Strategy was implemented in the western metropolitan Melbourne and Barwon regions of Victoria , Australia . The Precede-Proceed Model guided the population assessment , campaign strategy development and evaluation . The campaign included the use of multimedia , a website , and an information telephone service . Multiple levels of evaluation were conducted . This included a cross-sectional telephone survey of mental health literacy undertaken before and after 14 months of the campaign using a quasi-experimental design . R and omly selected independent sample s of 600 young people aged 12–25 years from the experimental region and another 600 from a comparison region were interviewed at each time point . A series of binary logistic regression analyses were used to measure the association between a range of campaign outcome variables and the predictor variables of region and time . Results The program was judged to have an impact on the following variables , as indicated by significant region-by-time interaction effects ( p < 0.05 ) : awareness of mental health campaigns , self-identified depression , help for depression sought in the previous year , correct estimate of prevalence of mental health problems , increased awareness of suicide risk , and a reduction in perceived barriers to help seeking . These effects may be underestimated because media distribution error result ed in a small amount of print material " leaking " into the comparison region . Conclusion We believe this is the first study to apply the rigorous st and ards of a health promotion model including the use of a control region to a mental health population intervention . The program achieved many of its aims despite the relatively short duration and moderate intensity of the campaign OBJECTIVES To examine the outcomes of the Elderly Persons in the Risk Zone study , which was design ed to evaluate whether it is possible to delay deterioration if a health-promoting intervention is made when an older adult ( ≥80 ) is at risk of becoming frail and whether a multiprofessional group intervention is more effective in delaying deterioration than a single preventive home visit with regard to frailty , self-rated health , and activities of daily living ( ADLs ) at 3-month follow-up . DESIGN R and omized , three-armed , single-blind , controlled trial performed between November 2007 and May 2011 . SETTING Two urban districts of Gothenburg , Sweden . PARTICIPANTS Four hundred fifty-nine community-living adults aged 80 and older not dependent on the municipal home help service . INTERVENTION A preventive home visit or four weekly multiprofessional senior group meetings with one follow-up home visit . MEASUREMENTS Change in frailty , self-rated health , and ADLs between baseline and 3-month follow-up . RESULTS Both interventions delayed deterioration of self-rated health ( odds ratio ( OR ) = 1.99 , 95 % confidence interval ( CI ) = 1.12 - 3.54 ) . Senior meetings were the most beneficial intervention for postponing dependence in ADLs ( OR = 1.95 , 95 % CI = 1.14 - 3.33 ) . No effect on frailty could be demonstrated . CONCLUSION Health-promoting interventions made when older adults are at risk of becoming frail can delay deterioration in self-rated health and ADLs in the short term . A multiprofessional group intervention such as the senior meetings described seems to have a greater effect on delaying deterioration in ADLs than a single preventive home visit . Further research is needed to examine the outcome in the long term and in different context Using a r and omized controlled trial , we tested the efficacy of a fall prevention intervention to reduce falls among adults in a community-based health promotion program . Adults aged 65 and older within two counties were recruited ( control n = 257 ; intervention n = 286 ) . After 12 months , there was a significant decrease in the number of falls in both groups ( odds ratio = 0.45 , p < .04 ) , but the time by group membership interaction was not significant ( χ 2 = 0.15 , p < .69 ) . Multivariate analysis did not find significant differences between the control and intervention groups for physical function as measured by a balance test or a sitting/st and ing test . Further research is needed on effective methods to deliver multifaceted fall interventions to older adults who are already being served by community health promotion programs OBJECTIVE To assess the effectiveness of a brief face-to-face health promotion intervention which included a ' pledge ' using brief negotiation techniques , compared with st and ard advice-giving techniques , delivered in a community setting . DESIGN A parallel group pre-post design using r and omised matched groups . Lifestyle helpers delivered the intervention ( one consultation per participant ) . Diet , physical activity and anthropometric measurements were collected at baseline , 6 months and 12 months . Qualitative data were also collected . SETTING Middlesbrough ( UK ) . SUBJECTS Adults living in low socio-economic areas . RESULTS Recruitment and engagement of lifestyle helpers was difficult , and initial expectations that local health authority staff working in the community and community champions would act as lifestyle helpers were not realised . As a consequence , recruitment of participants was lower than anticipated . One hundred and twenty-eight adults were recruited and the retention rate was 48 % at 12 months . Barriers to participation included poor health and competing commitments . No significant differences in change in diet or physical activity behaviours , or BMI , between the intervention and control groups were observed . The control group had a significantly greater decrease in waist circumference at 12 months compared with the intervention group . CONCLUSIONS This exploratory trial provides important insights in terms of recruiting lifestyle helpers for community-based health promotion interventions , specifically ( i ) the priorities and limitations in terms of time ( regardless of their general enthusiasm ) for staff employed by the local health authority , and ( ii ) the willingness of potential community champions to serve their local community in areas where community identity and ' spirit ' are seen as lacking ' Hartslag Limburg ' ( Dutch for Heartbeat Limburg ) , a regional cardiovascular diseases ( CVD ) prevention program , integrates a community strategy and a high-risk strategy to reduce CVD risk behaviors . The present paper focuses on the effects of the community intervention on fat intake and physical activity . The project was based on community organization principles and health education theories and methods . In order to implement the intervention , nine local Health Committees were set up , each organizing activities that facilitate and encourage people to adopt a healthier lifestyle . A pre-test-post-test control group design with two post-tests was used to evaluate the intervention . At baseline , representative r and om cohort research sample s were selected in the Maastricht region and in a control region . Data on fat intake and physical activity , and on the psychosocial determinants of these behaviors , were gathered by means of mail surveys . The present study indicates that the intervention had a significant effect on fat reduction , especially among respondents aged < or=48 years ( median age ) . Respondents in the Maastricht region were also more realistic about their fat intake at post-test as compared with the control region . Only a limited effect on intentions to increase physical activity was found Objectives . The purpose of this study was to evaluate the effectiveness of the Walk Your Heart to Health ( WYHH ) intervention , one component of the multilevel Community Approaches to Cardiovascular Health : Pathways to Heart Health ( CATCH : PATH ) intervention design ed to promote physical activity and reduce cardiovascular risk among non-Hispanic Black and Hispanic residents of Detroit , Michigan . The study was design ed and implemented using a community-based participatory research approach that actively engaged community residents , health service providers and academic research ers . It was implemented between 2009 and 2012 . Method . WYHH was a 32-week community health promoter – facilitated walking group intervention . Groups met three times per week at community-based or faith-based organizations , and walked for 45 to 90 minutes ( increasing over time ) . The study used a cluster r and omized control design to evaluate effectiveness of WYHH , with participants r and omized into intervention or lagged intervention ( control ) groups . Psychosocial , clinical , and anthropometric data were collected at baseline , 8 , and 32 weeks , and pedometer step data tracked using uploadable peisoelectric pedometers . Results . Participants in the intervention group increased steps significantly more during the initial 8-week intervention period , compared with the control group ( β = 2004.5 , p = .000 ) . Increases in physical activity were associated with reductions in systolic blood pressure , fasting blood glucose , total cholesterol , waist circumference and body mass index at 8 weeks , and maintained at 32 weeks . Conclusion . The WYHH community health promoter – facilitated walking group intervention was associated with significant reductions in multiple indicators of cardiovascular risk among predominantly Hispanic and non-Hispanic Black participants in a low-to-moderate income urban community . Such interventions can contribute to reductions in racial , ethnic , and socioeconomic inequities in cardiovascular mortality PURPOSE To evaluate the impact of a multicomponent health promotion and disease self-management intervention on physical function and health care expenditures among Medicare beneficiaries . To determine if these outcomes vary by urban or rural residence . DESIGN AND METHODS We analyzed data from a 22-month r and omized controlled trial of a health promotion/disease self-management program that included 766 elderly Medicare beneficiaries from western New York , West Virginia , and Ohio . Physical function was measured by changes in self-reported dependencies in activities of daily living over the study period . Total health care expenditures were measured by aggregating expenditures from major sources ( acute , postacute , and long-term care ) . We used ordinary least squares models to examine the effects of the intervention on both physical function and cost outcomes during the 22-month period . RESULTS The results indicated that the intervention reduced physical functional decline by 54 % ( p = .03 ) in the study sample . Stratified analyses showed that the intervention effect was much stronger in the rural sample . Mean total health care expenditures were 11 % ( $ 3,100 , p = .30 ) lower in the intervention group . The effects of the intervention on average health care expenditures were similar among urban and rural participants . IMPLICATION S The intervention offered a promising strategy for reducing decline in physical function and potentially lowering total health care expenditures for high-risk Medicare beneficiaries , especially for those in rural areas . Future studies need to investigate whether the findings can be replicated in other types of rural areas through a refined intervention and better targeting of the study population OBJECTIVE To evaluate the community-based health promotion effect of physical activity . METHODS The residents aged 18 and above from two communities in Gongshu District of Hangzhou City , Zhejiang province , were r and omly selected and recruited for the multi- strategy and comprehensive physical activity intervention . Question naire survey , physical check up and blood biochemistry were conducted . RESULTS After this two-year intervention , the time of the participant spent on weekly physical activity of moderate intensity increased from 464 min to 542 min ( P<0.05 ) , with an average increase of 78 min . Time spent in walking every week increased from 533 min to 678 min ( P<0.05 ) , with an average increase of 145 min . The body weight , waistline , blood pressure and heart rate all reduced significantly ( P<0.05 ) ; the vital capacity increased significantly ( P<0.05 ) ; and the related biochemical indicators were also improved . CONCLUSION Comprehensive and evidence -based physical activity interventions targeting community population can improve the levels of physical activity , related body measurement and biochemical indicators The aim of this study is to assess the reach and effectiveness of an integrated community-based intervention design ed to promote physical activity and healthy eating among older adults in a socioeconomically disadvantaged community in the Netherl and s. The intervention was evaluated with a controlled pre-post quasi-experimental design , with 430 r and omly selected older adults participating in the intervention group and 213 in a control group at baseline . The intervention included a local media campaign and environmental approaches ( e.g. , community involvement ) and was implemented during a 3-month high-intensity period , followed by a 6-month low-intensity one . Levels of physical activity and fruit and vegetable consumption were assessed at baseline and at 3 and 9 months after baseline . At the follow-up measurements , the intervention had reached respectively 68 and 69 % of the participants in the intervention group . No significant differences were found between the intervention group and the control group in changes to any outcome except for transport-related PA at 3 and 9 months follow-up . The systematic ally developed community-based intervention reached a relatively large proportion of the participants , but had only small effects on the levels of physical activity and healthy eating in older adults in the short and medium term |
1,090 | 28,040,335 | 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 . | PURPOSE To compare clinical outcomes of anterior cruciate ligament ( ACL ) reconstruction and investigate whether the clinical results of 4-str and hamstring tendon ( HT ) reconstruction are still inferior to that of the patellar tendon ( PT ) . | 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 ( HS ) and patellar tendon ( PT ) ACL reconstructions over the course of a 2-year follow-up . Patients undergoing primary ACL reconstruction ( n=65 ) were r and omised to receive either a PT or HS autograft . Femoral fixation in both groups was by means of an Endobutton . On the tibial side the PT grafts were fixed using a metallic interference screw , and the HS tendons by sutures tied to a fixation post . The PT grafts were inserted such that the proximal end of the distal bone block was within 10 mm of the tibial articular surface , result ing in a portion of free patellar tendon in the femoral tunnel immediately proximal to the articular surface . Patients were review ed after 4 months and 1 and 2 years . Tunnel enlargement was determined by measuring the widths of the femoral and tibial tunnels with a digital caliper in both lateral and anteroposterior radiographs . Because of the presence of the interference screw and the proximity of the bone block to the tibial articular surface , the tibial tunnel could not be reliably measured in the PT group . Measurements were corrected for magnification , and changes in tunnel width were recorded relative to the diameters drilled at surgery . St and ard clinical measures were also noted . In 32 % of patients in the PT group there was femoral tunnel obliteration from 4 months onwards . For the other patients there was a significantly greater increase in femoral tunnel width in the HS group than in the PT group at each follow-up , but no significant change with time . There was also a marked increase in tibial tunnel width in the HS group at 4 months but not thereafter . There was no relationship between tunnel enlargement and clinical measurements . Although tunnel enlargement is more common and greater with HS grafts , it does not appear to affect the clinical outcome in the first 2 postoperative years . Femoral suspensory fixation does not in itself appear to be the principal cause of femoral tunnel enlargement , at least for PT grafts Background Most of the previous comparative studies between patellar tendon and hamstring tendon anterior cruciate ligament grafts compared grafts of different constructs fixed with different methods . Purpose To compare patellar tendon and hamstring tendon grafts with the same fixation method used to reconstruct the anterior cruciate ligament . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods During the reconstructive procedure , the hamstring tendon graft was prepared as a bone-hamstring-bone graft ; both bone-patellar tendon-bone and bone-hamstring-bone grafts were fixed with interference screws . Eighty consecutive patients who underwent anterior cruciate ligament reconstruction were r and omly assigned to either bone-patellar tendon-bone or bone-hamstring-bone groups . Follow-up examinations were performed for at least 5 years postoperatively . Seventy-two of the 80 patients ( 37 patients in the bone-patellar tendon-bone group and 35 in the bone-hamstring-bone group ) were evaluated , with a mean follow-up period of 87.0 and 80.8 months , respectively . Follow-up examinations were performed using the International Knee Documentation Committee knee ligament st and ard and subjective knee forms . Results The mean KT-1000 arthrometer evaluation results showed no significant difference between the bone-patellar tendon-bone and bone-hamstring-bone groups ( 1.2 ± 2.1 mm and 1.7 ± 1.4 mm , respectively ; P = . 24 ) . However , symptoms related to graft harvest ( anterior kneeling pain ) were more frequently observed in the bone-patellar tendon-bone group , and unsatisfactory results were correlated with severe kneeling pain in 3 patients from this group ( P = . 0056 ) . Significant hamstring muscle weakness without complaint of functional deficit was found in the bone-hamstring-bone group ( P = . 0045 ) . Conclusion Bone-hamstring-bone grafts were shown to reduce the risk of problems at the graft harvest site compared to bone-patellar tendon-bone grafts , with comparable results in the remaining clinical parameters tested The results of intraarticular anterior cruciate ligament reconstruction with either the patellar tendon or the semitendinosus and gracilis tendons ( four str and s ) were prospect ively compared in a consecutive series of 60 patients with chronic injuries . A single surgeon per formed arthroscopically assisted reconstructions in an alternating sequence . Preoperative and operative data revealed no significant differences between the two groups . After 28 months of followup there were no sig nificant differences in the incidence of symptoms , and recurrent giving way was present in only one knee with semitendinosus and gracilis tendon graft . Return to sport participation was more frequent in the patellar ten don group ( 80 % versus 43 % , P < 0.01 ) . A minor ex tension loss ( ≤3 ° ) was more frequent in the patellar tendon group ( 47 % versus 3 % , P < 0.001 ) . Other dif ferences between the two groups were not significant . KT-2000 arthrometer side-to-side difference of anterior displacement > 5 mm at 30 pounds was present in 13 % of the knees with patellar tendon grafts and in 20 % of those with semitendinosus and gracilis ; a patellofemo ral crepitation developed in 17 % and 3 % of the two groups , respectively . Based on these data we routinely use patellar tendon grafts . Semitendinosus and gracilis tendons are preferred in selected cases : older patients , patients with preexisting patellofemoral problems , and those with failed patellar tendon grafts PURPOSE The purpose of this study was to compare intraosseous graft healing between the doubled flexor tendon ( FT ) graft and the bone-patellar tendon-bone ( BPTB ) graft in anterior cruciate ligament ( ACL ) reconstruction . TYPE OF STUDY R and omized trial . METHODS A biomechanical and histologic study was conducted with 24 adult beagle dogs . Bilateral ACL reconstructions were performed in each animal . Autogenous doubled FT and BPTB grafts were used for the left and right knees , respectively . Each end of the 2 grafts was tethered with a polyester suture to a screw post with a washer . The animals were then allowed unrestricted activities in their cages . Eight animals were killed at 3 , 6 , and 12 weeks , respectively . RESULTS Histologically , the FT graft was anchored to the tunnel wall with newly formed collagen fibers resembling Sharpey 's fibers by 12 weeks . These fibers were more abundant in the anterior ( ventral ) gap than in the posterior ( dorsal ) gap . In the BPTB graft , the bone plug was anchored with newly formed bone at 3 weeks , although osteocytes in the plug trabeculae were necrotic for 12 weeks . Degeneration of the tendon-bone junction in the plug progressed at 6 weeks . Tensile testing showed that the weakest site was different not only between the 2 grafts but also between the observation periods . In the FT graft , the weakest site was the graft-wall interface at 3 weeks and the intraosseously grafted tendon at 6 weeks . In the BPTB graft , the weakest site was the graft-wall interface at 3 weeks and the proximal site in the bone plug at 6 weeks . The ultimate failure load of the FT graft was significantly inferior ( 45.8 % ) to that of the BPTB graft at 3 weeks ( P = .021 ) . At 6 weeks , the load of the FT graft was 85 % that of the BPTB graft without a significant difference ( P = .395 ) . CONCLUSIONS As to the clinical relevance , the fixation device chosen for soft-tissue fixation appears to be more important than comparing it to the BPTB graft , although this has yet to be conclusively proven PURPOSE Patellar tendon and hamstrings are both used in anterior cruciate ligament ( ACL ) reconstruction , and comparisons have been reported with different results . The purpose of this clinical study was to compare the results of ACL reconstruction in athletes with 2 different graft types , both using bone-to-bone healing : bone-patellar tendon-bone graft and a quadrupled bone-semitendinosus graft . TYPE OF STUDY Outcomes study . METHODS From 1994 to 1997 , 2 groups of 40 athletes who underwent ACL replacement with patellar tendon and quadrupled bone-semitendinosus grafts were prospect ively evaluated . Preinjury activity level , age , and gender were comparable in both groups . All patients were operated on by the same surgeon within 5 months from injury and underwent group-specific rehabilitation programs . An independent examiner performed the final evaluations at 36 months . Review included clinical examination , radiographs , computed analysis , isokinetic and functional strength tests , and subjective and objective evaluation with st and ard knee scores . Additional procedures were recorded . Statistical analysis was performed with both parametric and nonparametric tests . RESULTS Average surgical time was longer with the semitendinosus graft , and postoperative pain was higher in the patellar tendon group . St and ard knee evaluation scores and subjective assessment revealed no significant differences . Isokinetic testing of flexion-extension and internal-external rotation showed lower quadriceps strength and a mild deficit of external rotation in the patellar tendon group and slightly lower flexor strength in the semitendinosus group at 12 months . Computerized laxity analysis showed no difference between the 2 groups with 90 % of patients having less than 3 mm side-to-side difference , with a gender difference in the semitendinosus group . Kneeling pain was higher in patellar tendon group . CONCLUSIONS The bone-patellar tendon-bone and quadrupled bone-semitendinosus autograft provide excellent grafts for ACL reconstruction . Both techniques are comparable regarding final stability , but in patients with extensor mechanism problems or those who engage in sports with a high incidence of patellar tendonitis , the semitendinosus graft should be considered ACL reconstruction with bone patellar tendon bone ( BPTB ) grafts has been shown to produce dependable results . Recently , reconstructions with double-looped semitendinosus gracilis ( DLSG ) grafts have become common . The prevailing opinion is that ACL reconstruction with patellar tendon graft produces a more stable knee with more anterior knee pain than DLSG grafts , while the functional results and knee scores are similar . The present study evaluates BPTB grafts fixed with metallic interference screws and DLSG grafts fixed with Bone Mulch Screw on the femur and WasherLoc fixation on the tibia . All else being the same , there is no difference in the outcome between the two grafts and fixation methods . This is a prospect i ve r and omized multicenter study . A total of 115 patients with isolated ACL ruptures were r and omized to either reconstruction with BPTB grafts fixed with metal interference screws ( 58 patients ) or DLSG grafts ( 57 patients ) fixed with Bone Mulch Screws and WasherLoc Screws . Follow-up was at one and two years ; the latter by an independent observer . At two years , one ACL revision had been performed in each group . Eight patients in the DLSG group and one in the BPTB group underwent meniscus surgery in the follow-up period ( P = 0.014 ) . Mean Lysholm score at the two year follow-up was 91 ( SD ± 10.3 ) in the DLSG group and also 91 ( SD ± 10.2 ) in the BPTB group . Mean KT-1000 at two years was 1.5 mm in the BPTB group and 1.8 mm in the DLSG group ( n.s . ) . At two years , four patients in the BPTB group and three in the DLSG group had a Lachman test grade 2 or 3 ( n.s . ) . More patients in the BPTB group had pain at the lower pole of the patella ( P = 0.04 ) . Peak flexion torque and total flexion work were lower in the DLSG group at one year ( P = 0.003 and P = 0.000 ) and total flexion work also at two years ( P = 0.05 ) . BPTB ACL reconstruction fixed with interference screws and DLSG fixed with Bone Mulch Screws on the femur and WasherLoc Screws on the tibia produce satisfactory and nearly identical outcomes . Among our patients in the DLSG group , flexion strength was lower , and more patients underwent meniscus surgery in the follow-up period . The BPTB group has more anterior knee pain PURPOSE To evaluate the clinical results of anterior cruciate ligament ( ACL ) reconstruction in patients with ACL-deficient knee in 2 similar groups of patients . TYPE OF STUDY A prospect i ve r and omized comparison of patellar tendon ( PT ) versus semitendinosus and gracilis tendon ( STG ) autografts for ACL reconstruction . METHODS Between 1994 and 1996 , 85 consecutive male patients with chronic ACL-deficient knees underwent arthroscopically assisted reconstruction with either autologous PT or double-loop STG ( 4-str and ) graft . PT grafts were used in patients with even-numbered birth date s and STG grafts for those with odd-numbered birth date s. Preoperatively , no significant differences between the 2 groups were noted with respect to age , level of activity , and degree of laxity ( chi-square analysis ) . A st and ardized rehabilitation program was used for both groups postoperatively that included immediate active extension and early weight bearing and gradual flexion . Return to sports was permitted 8 months postoperatively . Assessment of the patients was carried out using a question naire , clinical assessment , Lysholm knee scores , the International Knee Documentation Committee scale , and radiological examination . RESULTS At a mean follow-up of 81 months , there was no significant difference between the 2 groups with respect to subjective complaints ( recurrent giving way , functional level ) or objective laxity evaluation , including KT-1000 measurement or return to sports . Loss of extension of < or = 5 degrees was greater in the PT group ( 12 patients , 30 % ) than in the STG group ( 8 patients , 17 % ) . There was loss of flexion of < or = 15 degrees in 5 patients ( 12 % ) in the PT group and 1 patient ( 2.2 % ) in the STG group . Anterior knee pain was recorded in 10 patients ( 24 % ) in the PT group and 3 patients ( 5 % ) in the STG group . The Lysholm knee score was 91.6 and 92.7 for the PT and STG groups , respectively , and the Tegner activity score decreased from 8.9 preoperatively for both groups to 7.9 for the PT group and 7.8 for the STG group . CONCLUSION In this study , the 2 groups had comparable results in terms of patient satisfaction , activity level , and knee function . Our study showed that patellofemoral problems and loss of knee motion are more frequent in patients with PT grafts than in those with STG grafts . LEVEL OF EVIDENCE Level I , R and omized Controlled Trial Purpose Several studies compare the short- and long-term results of anterior cruciate ligament ( ACL ) reconstruction using bone-patellar tendon-bone ( BPTB ) graft or double-looped semitendinosus and gracilis ( DLSG ) graft . However , no studies evaluate the long-term results of BPTB grafts fixed with metal interference screws and DLSG grafts fixed with the Bone Mulch Screw and the Washer Loc . This prospect i ve r and omized multicentre study has the null hypothesis that there is no difference in long-term outcome between the two procedures . Methods A total of 114 patients with a symptomatic ACL rupture were r and omized to reconstruction with either a BPTB graft ( N = 58 ) or a DLSG graft ( N = 56 ) . Follow-up was conducted after one , two and seven years . At the seven-year follow-up , 102 of the 114 patients ( 89 % ) were available for evaluation ; however , 16 of these by telephone-interview only . Results Ten patients in the BPTB group and 19 patients in the DLSG group underwent additional knee surgery ( P = 0.048 ) , two and three , respectively , of these were ACL revisions ( n.s . ) . The total flexion work was lower in the DLSG group ( P = 0.001 ) . The mean peak flexion torque and extension work , however , showed no difference between the groups . No significant differences were found between the groups regarding the Tegner activity score , the Lysholm functional score , the Knee injury and osteoarthritis outcome score ( KOOS ) , subjective knee function , anterior knee pain or mobility . There was no significant difference in laxity between the groups on the Lachman test or the KT-1,000 maximum manual force test . Conclusions Both grafts and fixation methods result ed in satisfactory subjective outcome and objective stability . Both these methods can therefore be considered as suitable alternatives for ACL reconstructions . Level of evidence II PURPOSE The aim of this study was to compare the results after arthroscopic anterior cruciate ligament ( ACL ) reconstruction using central -third , bone-patellar tendon-bone ( BPTB group ) , 3-str and semitendinosus ( ST group ) , or 4-str and semitendinosus/gracilis ( ST/G group ) autografts . TYPE OF STUDY Prospect i ve r and omized trial . METHODS A r and omized series of 134 patients , all with unilateral ACL rupture was included in the study . In all 3 groups , interference screw fixation of the graft was used at both ends and 125 of 134 ( 93 % ) of the patients returned for the follow-up examination after 26 months ( range , 20 to 43 months ) . The preoperative assessment s in all 3 groups were similar in terms of gender , Tegner activity level , Lysholm score , KT-1000 measurements , 1-leg hop test , and the knee-walking test . RESULTS At follow-up , the knee-walking test was significantly worse in the BPTB group than in the ST group ( P = .0004 ) and ST/G group ( P < .0001 ) . Furthermore , the knee-walking test was significantly worse at follow-up than preoperatively in the BPTB group ( P < .0001 ) . The corresponding findings were not made in the other 2 groups . A significant reduction in knee laxity and an increase in activity level compared with the preoperative assessment s were found in all 3 groups , without any significant differences between the groups . CONCLUSIONS Two years after ACL reconstruction , the use of ST and ST/G autografts rendered significantly less discomfort during the knee-walking test than the use of BPTB autografts . However , in terms of functional outcome and knee laxity , the groups displayed no significant differences . LEVEL OF EVIDENCE Level Seventy patients with patellar tendon or hamstring tendon autografts for single-incision anterior cruciate ligament reconstruction were evaluated at least 2 years after surgery . All reconstructions were performed by the same surgeon , and metal interference screws were used for fixation of all grafts . No significant differences were noted between groups for Lysholm score , reduction in activity , KT-1000 arthrometer findings , quadriceps muscle size , return to sports , or ability to jump and do hard cuts and pivots . Significantly more patients in the patellar tendon group had patellofemoral pain at 6 months after surgery than did the hamstring tendon patients ( 48 % versus 20 % ) , and at last follow-up the incidence of patellofemoral pain was 42 % and 20 % , respectively . Fourteen patients in the patellar tendon group and seven in the hamstring tendon group had loss of motion ( approximately 5 ° ) . Four patients ( two in each group ) had treatment failures and their results were not included in the clinical examination data . At 2 years ’ follow-up , 97 % of patients with patellar tendon grafts and 100 % of patients with hamstring tendon grafts rated their results as good or excellent . We found that hamstring tendon grafts performed similarly to patellar tendon grafts , although fewer patients in the hamstring tendon group had patellofemoral pain and loss of motion BACKGROUND The choice of graft for anterior cruciate ligament reconstruction is a matter of debate , with patellar and hamstring tendons being the two most popular autologous graft options . The objective of this study was to determine in a prospect i ve , r and omized clinical trial whether two grafts ( bone-patellar tendon-bone or doubled hamstring tendons ) fixed with modern devices affect the two-year minimum clinical and radiographic outcomes of anterior cruciate ligament reconstruction . METHODS One hundred and twenty patients with a chronic unilateral rupture of the anterior cruciate ligament underwent arthroscopically assisted reconstruction with use of either autologous bone-patellar tendon-bone or doubled hamstring tendon grafts , in a strictly alternating manner . Both groups were comparable with regard to demographic data , preoperative activity level , mechanism of injury , interval between the injury and the operation , and the amount of knee laxity present preoperatively . The same well-proven surgical technique and aggressive controlled rehabilitation was used . An independent observer , who was blinded with regard to the involved leg and the type of graft , performed the outcome assessment with use of a visual analog scale , the new International Knee Documentation Committee form , the Knee Injury and Osteoarthritis Outcome Score , the Functional Knee Score for Anterior Knee Pain , and an arthrometric and an isokinetic dynamometric evaluation . Radiographs were also made . RESULTS At the two-year follow-up evaluation , no differences were found in terms of the visual analog score , the Knee Injury and Osteoarthritis Outcome Score , the new International Knee Documentation Committee subjective and objective evaluation scores , the KT-1000 side-to-side laxity measurements , the Functional Knee Score for Anterior Knee Pain , muscle strength recovery , or return to sports activities . In the bone-patellar tendon-bone group , we found a higher prevalence of postoperative kneeling discomfort ( p < 0.01 ) and an increased area of decreased skin sensitivity ( p < 0.001 ) . In the hamstring tendon group , we recorded a higher prevalence of femoral tunnel widening ( p < 0.01 ) . In this group , a correlation was also found between medial meniscectomy and an increased prevalence of pivot-shift glide ( p = 0.035 ) . CONCLUSIONS We believe that , with use of accurate and proven surgical and rehabilitation techniques , both grafts are an equivalent option for anterior cruciate ligament reconstruction Background : There is a lack of prospect i ve studies comparing the long-term outcome of endoscopic anterior cruciate ligament ( ACL ) reconstruction with either a patellar tendon or hamstring tendon autograft . Purpose : This prospect i ve longitudinal study compared the results of isolated endoscopic ACL reconstruction utilizing a 4-str and hamstring tendon ( HT ) or patellar tendon ( PT ) autograft over a 15-year period with respect to reinjury , clinical outcomes , and the development of osteoarthritis . Study Design : Cohort study ; Level of evidence , 2 . Methods : Ninety consecutive patients with isolated ACL rupture were reconstructed with a PT autograft , and 90 patients received an HT autograft , with an identical surgical technique . Patients were assessed at 2 , 5 , 7 , 10 , and 15 years . Assessment included the International Knee Documentation Committee ( IKDC ) knee ligament evaluation including radiographic evaluation , KT-1000 arthrometer testing , and Lysholm knee score . Results : Patients who received the PT graft had significantly worse outcomes compared with those who received the HT graft at 15 years for the variables of radiologically detectable osteoarthritis ( grade A : 46 % in PT and 69 % in HT ; P = .04 ) , motion loss ( extension deficit < 3 ° : 79 % in PT and 94 % in HT ; P = .03 ) , single-legged hop test ( grade A : 65 % in PT and 92 % in HT ; P = .001 ) , participation in strenuous activity ( very strenuous or strenuous : 62 % of PT and 77 % of HT ; P = .04 ) , and kneeling pain ( moderate or greater pain : 42 % of PT and 26 % of HT ; P = .04 ) . There was no significant difference between the HT and PT groups in overall IKDC grade ( grade A : 47 % of PT and 57 % of HT ; P = .35 ) . An ACL graft rupture occurred in 17 % of the HT group and 8 % of the PT group ( P = .07 ) . An ACL graft rupture was associated with nonideal tunnel position ( odds ratio [ OR ] , 5.0 ) and male sex ( OR , 3.2 ) . Contralateral ACL rupture occurred in significantly more PT patients ( 26 % ) than HT patients ( 12 % ) ( P = .02 ) and was associated with age ≤18 years ( OR , 4.1 ) and the PT graft ( OR , 2.6 ) . Conclusion : Anterior cruciate ligament reconstruction using ipsilateral autograft continues to show excellent results in terms of patient satisfaction , symptoms , function , activity level , and stability . The use of HT autograft does , however , show better outcomes than the PT autograft in all of these outcome measures . Additionally , at 15 years , the HT graft – reconstructed ACLs have shown a lower rate of radiological osteoarthritis Purpose The aim of this study was to compare the clinical outcomes of arthroscopic single-bundle anterior cruciate ligament ( ACL ) reconstruction with six-str and hamstring tendon ( HT ) allograft versus bone-patellar tendon-bone ( BPTB ) allograft . Methods The prospect i ve r and omized controlled trial was included 129 patients . Sixty-nine patients received reconstruction with six-str and HT allografts ( HT group ) , whereas 60 patients with BPTB allografts ( BPTB group ) . Outcome assessment included re-rupture findings , International Knee Documentation Committee ( IKDC ) scores , Lysholm scores , KT-1000 arthrometer , Lachman test , pivot-shift test , range of motion ( ROM ) and single-leg hop test . Results At a mean follow-up of 52 months , 113 patients ( HT group , 61 patients ; BPTB group , 52 patients ) completed a minimum 4-year follow-up . Four patients in HT group and six in BPTB group experienced ACL re-rupture ( 6.2 vs. 10.3 % ) and received revision surgery . Significant between-group differences were observed in KT-1000 outcomes and pivot-shift test 1 ( 1.2 ± 1.5 vs. 1.8 ± 1.3 , p = 0.025 ; positive rate 6.5 vs. 18.9 % , p = 0.036 ) , 2 ( 1.1 ± 1.4 vs. 1.6 ± 1.2 , p = 0.044 ; 8.1 vs. 20.7 % , p = 0.039 ) , 4 ( 1.1 ± 1.5 vs. 1.7 ± 1.4 , p = 0.031 ; 9.7 vs. 25 % , p = 0.012 ) years postoperatively . The outcomes between the two groups were comparable in terms of IKDC scores , Lysholm scores , Lachman test , ROM and single-leg hop test . Conclusions Six-str and HT allograft achieved superior anteroposterior and rotational stability after single-bundle ACL reconstruction . It is a reasonable graft substitute for ACL reconstruction . Level of evidence II One hundred and twenty-seven patients who had a rupture of the anterior cruciate ligament agreed to participate in a prospect i ve , r and omized study of three arthroscopically assisted reconstruction techniques . One hundred and twenty-five patients ( 125 reconstructions ) were evaluated after a mean duration of follow-up of forty-two months ( range , two to five years ) . Group I included forty patients who had a two-incision reconstruction with use of an autogenous semitendinosus-gracilis graft , group II consisted of forty patients who had a two-incision reconstruction with use of an autogenous patellar-ligament graft , and group III included forty-five patients who had a single-incision reconstruction ( endoscopic technique ) with use of an autogenous patellar-ligament graft . The male-female ratio , age range , level of athletic activity , interval between the injury and the reconstruction , previous operative procedures , and associated injuries were similar in all three groups . The same postoperative rehabilitation protocol was followed for all patients . Testing with a KT-2000 arthrometer at maximum manual force was done at the follow-up evaluation ; the difference in laxity between the involved knee and the contralateral knee was three millimeters or less in thirty-three patients ( 83 per cent ) in group I , thirty-seven patients ( 93 per cent ) in group II , and thirty-nine patients ( 87 per cent ) in group III . A difference of two millimeters or less was found in thirty patients ( 75 per cent ) in group I , thirty-one patients ( 78 per cent ) in group II , and thirty-five patients ( 78 per cent ) in group III . Thirty-five patients ( 88 per cent ) in group I , thirty-eight patients ( 95 per cent ) in group II , and forty patients ( 89 per cent ) in group III returned to at least the same level of athletic activity . Four grafts ( two in group I and two in group II ) failed as a result of trauma . There was one additional failure in groups I and III , as evidence d by a difference of nine and seven millimeters , respectively , on instrumented testing of laxity . The significant findings were that no knee was rated D according to the system of the International Knee Documentation Committee ( p < 0.002 , 94 per cent confidence level ) and that fewer additional operative procedures were done on patients in group III ( p < 0.08 ) . Also , it was found that the patients in group II returned to a greater level of athletic activity ( p < 0.02 ) and that a higher percentage of the patients in this group had a difference of three millimeters or less on testing with the KT-2000 arthrometer than in the other two groups ( p < 0.08 ) . However , with the numbers available , there were no significant differences in the over-all outcome among the three groups ( p < 0.1 ) . Importantly , the rate of failure was not greater and the outcomes were not less satisfactory for the late reconstructions than they were for the acute reconstructions ( those performed less than three weeks after the injury ) , including those done with an autogenous semitendinosus-gracilis graft in a chronically unstable knee Background Bone-patellar tendon-bone graft has been the most commonly used graft material in anterior cruciate reconstructions , but there has been increasing use of hamstring tendon grafts . However , no existing clinical studies show adequate support for the choice of one graft over the other . Hypothesis Hamstring tendons are equally as good as patellar tendon in anterior cruciate ligament reconstructions . Study Design Prospect i ve r and omized clinical trial . Methods Ninety-nine patients with laxity caused by a torn anterior cruciate ligament underwent arthroscopically assisted reconstruction with graft r and omization according to their birth year . Grafts were either bone-patellar tendon-bone with metal interference screw fixation or double-looped hamstring tendons with metal plate fixation . There were no significant differences between the two groups preoperatively or at operation . St and ard rehabilitation included immediate postoperative mobilization without a knee brace , protected weightbearing for 2 weeks , and return to full activity at 6 to 12 months . Results Forty-three patients in the patellar tendon group and 46 patients in the hamstring tendon group were available for clinical evaluation at a minimum of 21 months after surgery . No statistically significant differences were seen with respect to clinical and instrumented laxity testing , International Knee Documentation Committee Score ratings , isokinetic muscle torque measurements , and Kujala patellofemoral , Lysholm , and Tegner scores . Conclusion Equal results were seen for patellar and hamstring tendon autograft anterior cruciate ligament reconstructions at 2 years after surgery . Both techniques seem to improve patients ' performance Background : Longer-term results of bioabsorbable screws for anterior cruciate ligament reconstruction ( ACLR ) have been reported , but results are specific to the exact screw material and design . Titanium and poly-L-lactic acid with hydroxyapatite ( PLLA-HA ) screw outcomes have been compared only to 2 years . Purpose /Hypothesis : The purpose of this study was to compare the clinical and radiologic outcomes of the PLLA-HA screw versus titanium screw for hamstring tendon ACLR over a 5-year follow-up period . The hypothesis was that there are no differences in clinical scores or tunnel widening between the PLLA-HA and the titanium screws and that the PLLA-HA screw as seen on magnetic resonance imaging ( MRI ) should show high- grade resorption and ossification response over 5 years . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 40 patients undergoing ACLR were r and omized to receive either a PLLA-HA screw ( PLLA-HA group ) or a titanium screw ( titanium group ) for ACL fixation . Blinded evaluation was performed at 2 and 5 years with the International Knee Documentation Committee and Lysholm knee score , KT-1000 arthrometer , single-legged hop test , and MRI to evaluate tunnel and screw volumes , periscrew ossification , graft integration , and cyst formation . Results : There was no difference in any clinical outcome measure at 2- or 5-year follow-up between the 2 groups . At 2 years , the femoral tunnel in the PLLA-HA group was smaller than that in the titanium group ( P = .02 ) ; at 5 years , there was no difference . At 2 years , the femoral PLLA-HA screw was a mean 76 % of its original volume , and by 5 years , it was 36 % . At 2 years , the tibial PLLA-HA screw mean volume was 68 % of its original volume , and by 5 years , it was 46 % . At 5 years in the PLLA-HA group , 88 % of femoral tunnels and 56 % of tibial tunnels demonstrated a significant ossification response . There was no increase in cyst formation in the PLLA-HA group and no screw breakages . Conclusion : There were equivalent clinical results between the PLLA-HA and titanium groups at 2- and 5-year follow-ups . The PLLA-HA screw was not associated with increased tunnel widening or cyst formation when compared with the titanium screw . The PLLA-HA screw demonstrated progressive screw resorption and gradual but incomplete ossification over 5 years Background Debate exists regarding the optimal graft for anterior cruciate ligament reconstruction . Few studies have compared the differences in outcome after reconstruction using similar fixation methods . Hypothesis Similar outcomes will be seen after anterior cruciate ligament reconstruction with bone-patellar tendon-bone or quadruple-str and semitendinosus/gracilis tendons fixed with bioabsorbable interference screws . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Ninety-nine patients were prospect ively r and omized to bone-patellar tendon-bone ( 46 patients ) or quadruple-str and semitendinosus/gracilis ( 53 patients ) reconstruction groups . The bone-patellar tendon-bone group had slightly lower preinjury Tegner scores ( 6.7 vs 7.1 , P = .03 ) ; otherwise , the groups were similar . All surgeries were performed by a single surgeon using an endoscopic technique with bioabsorbable interference screw fixation . Patients were evaluated at 3 , 6 , 12 , and 24 months . Results Forty-six bone-patellar tendon-bone and 50 quadruple-str and semitendinosus/gracilis patients were available at 24 months ( 97 % ) . No differences in International Knee Documentation Committee grade , Lysholm score , Tegner activity level , range of motion , single-legged hop test , KT-1000 arthrometer manual maximum difference , Short Form-36 , or patient knee rating were found . The bone-patellar tendon-bone group had better flexion strength in the operated leg than in the nonoperated leg ( 102 % vs 90 % , P = .0001 ) , fewer patients complaining of difficulty jumping ( 3 % vs 17 % , P = .03 ) , and a greater number of patients returning to preinjury Tegner level ( 51 % vs 26 % , P = .01 ) . The quadruple-str and semitendinosus/gracilis group had better extension strength in the operated leg than in the nonoperated leg ( 92 % vs 85 % , P = .04 ) , fewer patients with sensory deficits ( 14 % vs 83 % , P = .0001 ) , and fewer patients with difficulty kneeling ( 6 % vs 20 % , P = .04 ) . Both groups showed significant improvement in KT-1000 arthrometer manual maximum difference , Lysholm score , Tegner activity level , International Knee Documentation Committee grade , and patient knee rating score . Conclusions Good outcomes were seen in both the bone-patellar tendon-bone and quadruple-str and semitendinosus/gracilis groups . Subtle differences were noted between the groups , which may help guide optimal graft choice PURPOSE The purpose of the study was to quantify the amount of agreement among orthopaedic surgeons regarding the natural history of the anterior cruciate ligament (ACL)-deficient knee , surgery , and rehabilitation , and the treatment of these patients . TYPE OF STUDY Physician mail survey . METHODS Orthopaedic surgeons were r and omly selected from the American Academy of Orthopaedic Surgeons ( AAOS ) directory . Only individuals who treated or referred ACL-insufficient patients for treatment within the past year were asked to complete the 3-page survey . The survey included 25 questions regarding clinical opinion . Clinical agreement was present when 80 % or more of the surgeons agreed on the same response option . RESULTS The total number of surgeons who responded to the survey was 397 ( response rate , 54.8 % ) and the number who had treated or referred ACL-insufficient patients in the past year was 261 . Among surgeons who completed the question naire , the response rates to the individual questions ranged from 92 % to 100 % . The mean response rate for all questions was 97.4 % . The mean age of the surgeons was 48.4 years , and 35.8 % considered their practice to be a subspecialty in sports medicine or knee surgery . For 12 questions ( 48 % ) , there was clinical disagreement among the surgeons . Surgical volume was associated with clinical opinion for 16 of 25 questions ( P < or = .05 ) . CONCLUSIONS Significant variation is seen in clinical opinion and decision-making regarding ACL injuries among members of the AAOS , particularly regarding whether ACL-deficient patients can participate in all recreational sports activities , that ACL reconstruction reduces the rate of arthrosis , and on the use of braces in the postoperative period . Additionally , surgeons disagreed on the effect of 4 patient characteristics ( age over 40 , presence of pain , irreparable meniscal tear , injury involving Workers ' Compensation ) on the decision to perform surgery . Areas of significant clinical uncertainty should be the focus of future research and medical education for orthopaedic surgeons who treat ACL injuries PURPOSE To analyze the long-term evaluation of clinical , functional , and magnetic resonance imaging ( MRI ) results after implant-free press-fit anterior cruciate ligament ( ACL ) reconstruction with bone-patella tendon ( BPT ) versus quadrupled hamstring tendon ( HT ) grafts . METHODS Sixty-two ACL-insufficient patients were included in a prospect i ve , r and omized study ( 31 BPT and 31 HT ) . Both surgical procedures were performed without any implants by a press-fit technique by the senior author . The femoral tunnel was drilled through the anteromedial portal for anatomic placement . At 8.8 years after reconstruction , 53 patients ( 28 BPT and 25 HT ) were examined by different clinical and functional tests . Bilateral MRI scans were performed and interpreted by an independent radiologist . RESULTS On follow-up , the score on the International Knee Documentation Committee evaluation form was significantly better in the HT group . The clinical examination including range of motion , KT-1000 test ( MEDmetric , San Diego , CA ) , and pivot-shift test showed no significant differences . On isokinetic testing , the mean quadriceps strength was close to normal ( 96 % ) in both groups , but the hamstring strength was lower in the HT group ( 100.3%/95.1 % ) . Kneeling ( 1.5/1.1 , P = .002 ) , knee walking ( 1.72/1.14 , P = .002 ) , and single-leg hop test ( 95.8%/99.1 % , P = .057 ) were better in the HT group . The MRI findings about the mean degree of cartilage lesion ( International Cartilage Repair Society protocol ) of the operated ( 2.1/2.1 ) and nonoperated ( 1.4/1.8 ) knee showed no significant differences . No significant difference was found in the grade of medial or lateral meniscal lesion or the number of patients having meniscal lesions when the operated and nonoperated knees were compared . Tunnel measurements , Caton-Deschamps Index , and the sagittal ACL angle were similar . CONCLUSIONS The implant-free press-fit technique for anterior cruciate ligament reconstruction by use of bone-patellar tendon and hamstring grafts with anatomic graft placement is an innovative technique to preserve the cartilage and meniscal status without significant differences between the operated and nonoperated knees in the long term . Significantly less anterior knee pain was noted in the hamstring group , when testing for kneeling and knee walking . LEVEL OF EVIDENCE Level II , prospect i ve comparative study Background Patellar and hamstring tendon autografts are the most frequently used graft types for anterior cruciate ligament reconstruction , but few direct comparisons of outcomes have been published . Hypothesis There is no difference in outcome between the two types of reconstruction . Study Design Prospect i ve r and omized clinical trial . Methods After isolated anterior cruciate ligament rupture , 65 patients were r and omized to receive either a patellar tendon or a four-str and hamstring tendon graft reconstruction , and results were review ed at 4 , 8 , 12 , 24 , and 36 months . Results Pain on kneeling was more common and extension deficits were greater in the patellar tendon group . There were greater quadriceps peak torque deficits in the patellar tendon group at 4 and 8 months but not thereafter . In the hamstring tendon group , active flexion deficits were greater from 8 to 24 months , and KT-1000 arthrometer side-to-side differences in anterior knee laxity at 134 N were greater . Cincinnati knee scores , International Knee Documentation Committee ratings , and rates of return to preinjury activity levels were not significantly different between the two groups . Conclusions Both grafts result ed in satisfactory functional outcomes but with increased morbidity in the patellar tendon group and increased knee laxity and radiographic femoral tunnel widening in the hamstring tendon group Background Controversy remains over the most appropriate graft for anterior cruciate ligament reconstruction . Hypothesis There is no significant difference in outcomes after 4-str and hamstring and patellar tendon autograft anterior cruciate ligament reconstructions using similar fixation techniques . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Between August 2000 and May 2003 , 64 Keller Army Hospital patients with complete anterior cruciate ligament tears were r and omized to hamstring ( n = 32 ) or patellar tendon ( n = 32 ) autograft anterior cruciate ligament reconstruction . Operative graft fixation and rehabilitative techniques were the same for both groups . Follow-up assessment s included the Single Assessment Numeric Evaluation score , Lysholm score , International Knee Documentation Committee score , and Knee Injury and Osteoarthritis Outcome Score . Postoperative radiographs were analyzed for tunnel location and orientation . Results Eleven women and 53 men were r and omized . Eighty-three percent of the patients ( 53 of 64 ) had follow-up of greater than 2 years , or to the point of graft rupture or removal ( average follow-up , 36 months ) . Four hamstring grafts ( 12.5 % ) and three patellar tendon grafts ( 9.4 % ) ( P = .71 ) ruptured . One deep infection in a hamstring graft patient necessitated graft removal . Forty-five of the 56 patients with intact grafts had greater than 2-year follow-up . Patients with patellar tendon grafts had greater Tegner activity scores ( P = .04 ) . Single Assessment Numeric Evaluation scores were 88.5 ( 95 % confidence interval : 83.1 , 93.8 ) and 90.1 ( 95 % confidence interval : 85.2 , 96.1 ) for the hamstring and patellar tendon groups , respectively ( P = .53 ) . Lysholm scores were 90.3 ( 95 % confidence interval : 84.4 , 96.1 ) and 90.4 ( 95 % confidence interval : 84.5 , 96.3 ) for the hamstring and patellar tendon groups , respectively ( P = .97 ) . There were no significant differences in knee laxity , kneeling pain , isokinetic peak torque , International Knee Documentation Committee score , or Knee Injury and Osteoarthritis Outcome Scores . Postoperative graft rupture correlated with more horizontal tibial tunnel orientation . Conclusion Hamstring and patellar tendon autografts provide similar objective , subjective , and functional outcomes when assessed at least 2 years after anterior cruciate ligament reconstruction Background : There are still controversies about graft selection for primary anterior cruciate ligament reconstruction . Prospect i ve , r and omized long-term studies are needed to determine the differences between the graft material s. Hypothesis : Eleven years after anterior cruciate ligament reconstruction there is no difference in functional outcome and quality of life between patients with patellar tendon or hamstring tendon autografts ; however , the patients with patellar tendon autograft would have a higher prevalence of osteoarthritis . Study Design : R and omized controlled trial ; Level of evidence , 2 . Methods : From June 1999 to March 2000 , 64 patients were included in this prospect i ve study . A single surgeon performed primary arthroscopically assisted anterior cruciate ligament reconstruction in an alternating sequence . In 32 patients , anterior cruciate ligament reconstruction was performed with hamstring tendon autograft ( semitendinosus and gracilis [ STG ] group ) while in the other 32 patients the reconstruction was performed with patellar tendon autograft ( PT group ) . Results : At the 11-year follow-up , no statistically significant differences were seen with respect to the Lysholm score and Short Form-36 , KT-1000 arthrometer laxity testing , anterior knee pain , single-legged hop test , or International Knee Documentation Committee ( IKDC ) classification results . Positive pivot-shift test ( 1 + ) was significantly more frequent in the PT group ( P = .036 ) . Twenty-two patients ( 81 % ) in the STG group and 18 patients ( 72 % ) in the PT group were still at their preinjury level of activity . Graft rupture occurred in 2 patients from the STG group ( 6 % ) and in 4 patients from the PT ( 12 % ) . Grade B and C abnormal radiographic findings were seen in 84 % ( 21 of 25 ) of patients in the PT group and in 63 % ( 17 of 27 ) of patients in the STG group ( P = .008 ) . Conclusion : Both hamstring and patellar tendon autografts provided good subjective outcomes and objective stability at 11 years . Positive pivot-shift test ( 1 + ) was significantly more frequent in the PT group . No significant differences in the rate of graft failure were identified . Patients with patellar tendon graft had a greater prevalence of osteoarthritis at 11 years after surgery Background : A number of studies have found comparable results after anterior cruciate ligament ( ACL ) reconstruction with patellar tendon autografts and hamstring autografts ; however , few studies have been large enough to reveal differences in risk of revision with regard to clinical and demographic factors . Purpose : To present the distribution of grafts for ACL reconstruction based on data in the Sc and inavian ACL registries and to compare the risk of revision between patellar tendon autografts and hamstring autografts . Potential associations with other clinical and demographic factors were also explored . Study design : Cohort study ; Level of evidence , 2 . Methods : A total of 45,998 primary ACL reconstructions , including 6736 patellar tendon autografts and 38,666 hamstring autografts , were identified in the Sc and inavian ACL registries . The overall median follow-up time was 3 years ( range , 0 - 8 years ) . To compare the risk of revision between groups of patients , univariate Kaplan-Meier analysis ( with log-rank test ) and the Cox proportional hazard regression model were applied . The hazard rate ratio with 95 % CI was reported as a measure of effect . Results : Patellar tendon and hamstring autografts were used in 14.6 % and 84.1 % of the patients , respectively . The remaining patients received allografts , direct sutures , or other graft types ( 1.3 % ) . The primary ACL injury occurred during soccer , team h and ball , or alpine activities in 67.5 % of the patients in the patellar tendon group and 66.2 % in the hamstring group . A total of 156 patients in the patellar tendon group and 1042 patients in the hamstring group underwent revision . The overall risk of revision was significantly lower in the patellar tendon group versus the hamstring group ( hazard rate ratio = 0.63 ; 95 % CI , 0.53 - 0.74 ) , and it decreased with increasing age at surgery , although not strictly linearly . The lower risk of revision in the patellar tendon group was consistently observed across subgroups of patient sex , age , and concomitant cartilage injury ( P > .05 , test for interaction ) but seemed to be slightly more pronounced for patients injured during certain pivoting activities ( soccer , team h and ball , and alpine activities ) compared with other activities ( hazard rate ratio = 0.57 vs 0.81 ; P = .058 , test for interaction ) . Conclusion : The majority of primary ACL reconstructions in Sc and inavia are performed with hamstring autografts . Results from the present large prospect i ve study show that patients receiving patellar tendon autografts have a statistically significantly lower risk of revision compared with patients receiving hamstring autografts |
1,091 | 21,357,876 | 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 | BACKGROUND Antidepressant drugs are widely used in the treatment of depression in people with chronic physical health problems .
AIMS To examine evidence related to efficacy , tolerability and safety of antidepressants for people with depression and with chronic physical health problems . | 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 treatment phase ( mean + /- SD glycosylated hemoglobin level reduction , -0.4 % + /- 1.4 % ; P = .002 ) . Glycosylated hemoglobin levels remained significantly lower than baseline during depression-free maintenance ( P = .002 ) and did not differ between treatment groups ( P = .90 ) . CONCLUSIONS In patients with diabetes , maintenance therapy with sertraline prolongs the depression-free interval following recovery from major depression . Depression recovery with sertraline as well as sustained remission with or without treatment are associated with improvements in glycosylated hemoglobin levels for at least 1 year BACKGROUND AND PURPOSE Patients with poststroke major depression have a greater severity of cognitive impairment than nondepressed patients even when matched for size and location of stroke lesion . Prior treatment studies have consistently failed to show an improvement in cognitive function even when poststroke mood disorders responded to antidepressant therapy . We examined the response of cognitive function to treatment with nortriptyline or placebo in a double-blind trial . METHODS Patients with major ( n=33 ) or minor ( n=14 ) depression participated in a double-blind treatment study with nortriptyline or placebo . They were examined for change in depressive mood , measured by the Hamilton Rating Scale for Depression ( HAM-D ) , and change in cognitive impairment , assessed by the Mini-Mental State Examination ( MMSE ) , after treatment with nortriptyline or placebo . Cognitive treatment response , as measured by the MMSE , was compared between patients whose depression did and did not respond to treatment . RESULTS Patients whose poststroke depression remitted ( predominantly associated with nortriptyline treatment ) had significantly greater recovery in cognitive function over the course of the treatment study than patients whose mood disorder did not remit ( predominantly associated with placebo treatment ) . CONCLUSIONS Our findings support the contention that poststroke major depression leads to a " dementia of depression . " Prior studies failed to show an effect of treatment because the effect size was too small . Successful treatment of depression may constitute one of the major methods of promoting cognitive recovery in victims of stroke Background : The prevalence of major depression ( MD ) in persons with nonpsychiatric medical conditions is an indicator of clinical need in those groups , an indicator of the feasibility of screening and case-finding efforts , and a source of etiologic hypotheses . This analysis explores the prevalence of MD in the general population in relation to various long-term medical conditions . Methods : We used a data set from a large-scale Canadian national health survey , the Canadian Community Health Survey ( CCHS ) . The sample consisted of 115 071 subjects aged 18 years and over , r and omly sample d from the Canadian population . The survey interview recorded self-reported diagnoses of various long-term medical conditions and employed a brief predictive interview for MD , the Composite International Diagnostic Interview Short Form for Major Depression . Logistic regression was used to adjust estimates of association for age and sex . Results : The conditions most strongly associated with MD were chronic fatigue syndrome ( adjusted odds ratio [ AOR ] 7.2 ) and fibromyalgia ( AOR 3.4 ) . The conditions least strongly associated were hypertension ( AOR 1.2 ) , diabetes , heart disease , and thyroid disease ( AOR 1.4 in each case ) . We found associations with various gastrointestinal , neurologic , and respiratory conditions . Conclusions : A diverse set of long-term medical conditions are associated with MD , although previous studies might have lacked power to detect some of these associations . The strength of association in prevalence data , however , varies across specific conditions BACKGROUND AND PURPOSE Early poststroke depression ( PSD ) is a frequent and specific entity that impairs the rehabilitation and functional recovery of hemiplegic patients . This trial was design ed to study the efficacy and tolerance of fluoxetine ( FLX ) in the treatment of early PSD . METHODS This was a multicenter , double-blind , placebo-controlled study . Recent hemiplegic patients ( <3 months ) suffering from major depressive disorder ( determined by International Classification of Diseases , 10th Revision , and Montgomery-Asberg Depression Rating Scale [ MADRS ] > 19 ) were r and omized to receive either 20 mg/d fluoxetine ( FLX ) or placebo for 6 weeks . Patients were evaluated by use of the Motricity Index , Mini-Mental State Examination , Functional Independence Measure , and MADRS . Statistical analysis was performed by using an intent-to-treat approach comparing the 2 groups at day 0 ( baseline ) and days 15 , 30 , and 45 ( end point ) . RESULTS Of 121 patients screened , 31 were included in the study , 16 in the FLX group and 15 in the placebo group . There were no significant differences in baseline characteristics among the 2 groups . The FLX-treated patients compared with placebo-treated patients demonstrated significant improvement in mean MADRS scores at end point ( 11.8+/-6 . 7 [ mean+/-SD ] versus 18.7+/-10.0 , respectively ; P=0.05 ) . FLX-treated patients compared with placebo-treated patients also demonstrated greater response rate ( 62.5 % versus 33.3 % , respectively ) and greater mean decrease of MADRS ( 16.6 versus 8.4 , respectively ; P=0.02 ) . There were no differences in motor , cognitive , or functional improvement and no significant side effects after FLX treatment , except for a patient with a moderate and transient increase of transaminases . CONCLUSIONS FLX is an efficacious and well-tolerated treatment for early PSD . Further research is needed to evaluate the efficacy and safety of long-term treatment in this population OBJECTIVE To compare the efficacy and tolerability of paroxetine ( a selective serotonin reuptake inhibitor ) with that of amitriptyline ( a tricyclic antidepressant ) in the treatment of depression in 191 patients with rheumatoid arthritis ( RA ) . METHODS A r and omized , double blind , double dummy , parallel group study . A placebo washout period of 3 - 7 days was followed by an 8 week active treatment phase during which patients received either paroxetine ( 20 - 40 mg daily ) or amitriptyline ( 75 - 150 mg daily ) . The primary efficacy variable was the change from baseline in Montgomery Asberg Depression Rating Scale score at endpoint . RESULTS Paroxetine was as effective as amitriptyline for the treatment of depression , with similar improvements in RA associated pain and disability also seen in both groups . However , paroxetine was better tolerated than amitriptyline , with an overall frequency of adverse experiences of 56.4 % and 67.7 % in the 2 groups , respectively . The frequency of anticholinergic adverse experiences was much lower in the paroxetine treatment group ( 18.1 % vs 43.8 % taking amitriptyline ) and paroxetine treated patients also experienced fewer severe ( 16.0 % vs 21.9 % ) , serious nonfatal ( 0 % vs 4.2 % ) , and drug related adverse experiences ( 12.8 % vs 29.2 % ) . CONCLUSION Tolerability is an important consideration in this patient population , which is largely composed of elderly patients who are taking additional medications for RA . Paroxetine shows a number of advantages in the management of depression comorbid with RA BACKGROUND This study aims to investigate the efficacy of fluoxetine and paroxetine on the levels of depression-anxiety , quality of life , disability , and metabolic control in type II diabetes mellitus ( DM ) patients . METHODS The patients were first applied the Hospital Anxiety-Depression Scale ( HADS ) . After a psychiatric interview with patients who had scores above the cut-off point , those who were diagnosed as having a major depressive disorder according to DSM-IV criteria were applied the Hamilton Depression Rating Scale ( HDRS ) and the Hamilton Anxiety Rating Scale ( HARS ) . Twenty three patients who scored 16 or above on the HDRS were included in the study and given the Short Form-36 ( SF-36 ) , and the Brief Disability Question naire ( BDQ ) and HbA1c levels were measured . Patients were r and omized on 20 mg/day fluoxetine or 20 mg/day paroxetine treatment . The patients were evaluated with the same scales at the 2(nd ) , 4(th ) , 6(th ) , and the 12(th ) weeks . RESULTS Both groups showed a statistically significant decrease in HDRS , HARS , and BDQ scores with comparison to the index assessment . At the end of treatment , though not statistically significant , a decrease was observed in HbA1c values of the fluoxetine-administered group . CONCLUSIONS Fluoxetine and paroxetine effectively reduce the severity of major depressive disorder in type II DM patients . There is need for further and longer-lasting monitoring studies with more patients in order to determine whether there is any difference in terms of their effects on glycemic control This study investigated the effects of antidepressant treatment on platelet activation in depressed patients with ischemic heart disease ( IHD ) . Plasma levels of platelet alpha-granule release products beta-thromboglobulin ( BTG ) and platelet factor 4 ( PF4 ) were measured in 17 depressed patients with IHD who were treated in a 6-week , double-blind trial with either paroxetine ( 10 patients ) or nortriptyline ( 7 patients ) . Baseline measurements of BTG and PF4 were significantly elevated in both drug treatment groups before the initiation of antidepressant therapy compared with those of healthy control subjects . In the paroxetine group , mean PF4 and BTG levels significantly decreased from these elevated baseline values within 1 week of treatment and remained low at 3- and 6-week measurements . In contrast , the nortriptyline group did not exhibit a significant decrease in PF4 or BTG plasma levels after 1 , 3 , or 6 weeks of treatment . Therefore , platelet activation in depressed patients with IHD seems to be inhibited by the selective serotonin reuptake inhibitor paroxetine . The effect of paroxetine on PF4 and BTG plasma levels suggests that it may reduce platelet aggregation in vivo and may positively impact IHD-related mortality in this population OBJECTIVE This study compared nortriptyline and fluoxetine with placebo in the treatment of depression and in recovery from physical and cognitive impairments after stroke . METHOD A total of 104 patients with acute stroke enrolled between 1991 and 1997 entered a double-blind r and omized study comparing nortriptyline , fluoxetine , and placebo over 12 weeks of treatment . The majority of patients were recruited from a rehabilitation hospital in Des Moines , Iowa , but other enrollment sites were also used . Both depressed and nondepressed patients were enrolled to determine whether improved recovery could be mediated by mechanisms unrelated to depression . Nortriptyline in doses of 25 mg/day gradually increased to 100 mg/day or fluoxetine in doses of 10 mg/day gradually increased to 40 mg/day or identical placebo were given over 12 weeks . Response to treatment of depression for individual patients was defined as a greater-than-50 % reduction in scores on the Hamilton Rating Scale for Depression and no longer fulfilling diagnostic criteria for major or minor depression . Improved recovery for a treatment group was defined as a significantly higher mean score from baseline to end of the treatment trial , compared with patients treated with placebo , on measures of impairment in activities of daily living and levels of cognitive and social functioning . RESULTS Nortriptyline produced a significantly higher response rate than fluoxetine or placebo in treating poststroke depression , in improving anxiety symptoms , and in improving recovery of activities of daily living as measured by the Functional Independence Measure . There was no effect of nortriptyline or fluoxetine on recovery of cognitive or social functioning among depressed or nondepressed patients . Fluoxetine in increasing doses of 10 - 40 mg/day led to an average weight loss of 15 . 1 pounds ( 8 % of initial body weight ) over 12 weeks of treatment that was not seen with nortriptyline or placebo . CONCLUSIONS Given the doses of medication used in this study , nortriptyline was superior to fluoxetine in the treatment of poststroke depression . Demonstrating a benefit of antidepressant treatment in recovery from stroke may require the identification of specific subgroups of patients , alternative measurement scales , or the optimal time of treatment OBJECTIVE Depression is prevalent in patients with diabetes . It is associated with poor glycemic control and is linked to an increased risk for diabetic complications . In this study , we assessed the efficacy of fluoxetine for depression in patients with diabetes . RESEARCH DESIGN AND METHODS Sixty patients with diabetes ( type 1 , n = 26 ; type 2 , n = 34 ) and major depressive disorder entered an 8-week r and omized placebo-controlled double-blind trial . Patients were given daily doses of fluoxetine ( up to 40 mg/day ) . The Beck Depression Inventory ( BDI ) and Hamilton Rating Scale for Depression ( HAMD ) were used to measure the severity of depression and to determine the percentage of patients who achieved substantial improvement or complete remission . GHb levels were obtained to monitor glycemic control . RESULTS Reduction in depression symptoms was significantly greater in patients treated with fluoxetine compared with those receiving placebo ( BDI , -14.0 vs. -8.8 , P = 0.03 ; HAMD , -10.7 vs. -5.2 , P = 0.01 ) . The percentage of patients achieving a significant improvement in depression per the BDI was also higher in the fluoxetine group ( 66.7 vs. 37.0 % , P = 0.03 ) . Additionally , trends toward a greater rate of depression remission ( 48.1 vs. 25.9 % , P = 0.09 per the HAMD ) and greater reduction in GHb ( -0.40 vs. -0.07 % , P = 0.13 ) were observed in the fluoxetine group . CONCLUSIONS Fluoxetine effectively reduces the severity of depression in diabetic patients . Our study demonstrated that after only 8 weeks , this treatment also produced a trend toward better glycemic control Depression is a major complication of cancer . The efficacy and safety of mianserin were evaluated in a r and omized placebo‐controlled trial of 73 depressed women with cancer . According to RDC diagnosis , all patients showed situational major depression . Both groups were well matched for cancer localization , clinical stages , Karnofsky scores , duration of depression , baseline values on the Hamilton Depression Rating Scale ( HDRS ) , Zung Self‐Rating Depression Scale ( ZSRDS ) , and Clinical Global Impression of Illness Severity ( CGI‐S ) , and for type of depression , whether dominantly depressive or depressive‐anxious . Between days 7–21 , there were significantly fewer dropouts with mianserin ( 7 ) than with placebo ( 15 ) . When compared with placebo , there were significant improvements for mianserin for HDRS on days 7 , 21 and 28 , for ZSRDS on days 7 and 28 , and for CGI‐S on days 7 , 14 , 21 and 28 . According to Clinical Global Impression of Illness Improvement ( CGI‐I ) there were significantly more responders with mianserin ( 28 ) than with placebo ( 18 ) . The efficacy index for mianserin was significantly greater than for placebo on days 21 and 28 . At the end of the trial the scores for HDRS sleep disturbance factor and HDRS anxiety‐somatization factor were significantly reduced for mianserin than for placebo . There were no significant differences in side‐effects between treatment groups . It is concluded that mianserin is superior to placebo in reducing the severity and duration of depression which is present especially in patients with advanced cancer . The fact that side‐effects were not a problem with mianserin and that mianserin treatment was safe when used in association with other anticancer drugs suggests that mianserin can be prescribed routinely for alleviating depression in cancer patients The incidence of depression following a hemispheric stroke ranges from 25 to 60 % . The benefit of antidepressant therapy on the outcome of rehabilitation in the subacute post-stroke phase is well known . We studied subjects both with and without evidence of depression , as indicated by any one of three criteria : ( i ) Clinical diagnosis of depression , ( ii ) Abnormal Zung-depression score . ( iii ) Abnormal dexamethasone suppression test ( DST ) . Patients in a stroke rehabilitation program ( 22 ) were r and omized to receive either placebo or 300 mg/day trazodone-HCl , beginning 30 days after the stroke . Patients with either a clinical diagnosis of depression or abnormal Zung depression scores showed a consistent trend towards greater improvement in Barthel activities of daily living ( ADL ) scores , with antidepressant therapy , as compared to patients receiving placebo . An abnormal DST was associated with significant improvement in the ADL scores in subjects receiving trazodone , i.e. , in post-stroke depression such a treatment seems to be beneficial OBJECTIVE The authors ' first objective was to ascertain whether imipramine is superior to placebo in treating axis I depressive disorders in the context of HIV illness . Supplementary questions were whether severity of immunodeficiency is associated with antidepressant response and whether patients with greater immunodeficiency can tolerate st and ard doses of imipramine . Second , the authors sought to determine whether imipramine treatment is associated with changes in immune status . METHOD A double-blind , r and omized placebo-controlled trial of imipramine was conducted in a university-affiliated research outpatient clinic . After 6 weeks of treatment , responders were maintained double-blind for another 6 weeks and nonresponders were removed from the study and treated openly . All patients were offered 26 weeks of treatment . Of the 97 patients who were r and omly assigned to placebo or imipramine , 80 completed the 6-week phase . Main outcome measures included the Clinical Global Impression , the Hamilton Depression Rating Scale , the Brief Symptom Inventory , and CD4 cell count . RESULTS Among study completers , 31 ( 39 % ) had AIDS . The response rate to imipramine was 74 % and the response rate to placebo was 26 % . There was no difference in depression response between patients with more or less severe immunodeficiency , nor was there a difference in medication dose or side effects . Neither type nor duration of treatment influenced CD4 cell count during the course of treatment . CONCLUSIONS Depressed patients with HIV illness respond to imipramine at the same rate as medically healthy depressed patients . Severity of immunosuppression is not associated with imipramine treatment outcome . There is no evidence that imipramine has negative effects on enumerative measures of immune status BACKGROUND Patients with a depressive disorder after myocardial infa rct ion ( MI ) have a significantly increased risk of major cardiac events . The Myocardial INfa rct ion and Depression-Intervention Trial ( MIND-IT ) investigates whether antidepressive treatment can improve the cardiac prognosis for these patients . The rationale and outline of the study are described . METHODS In this multicenter r and omized clinical trial , 2140 patients admitted for MI are screened for depressive symptoms with a question naire 0 , 3 , 6 , 9 , and 12 months after MI . Patients with symptoms undergo a st and ardized psychiatric interview . Those with a post-MI depressive episode are r and omized to intervention ( ie , antidepressive treatment ; n = 190 ) or care-as-usual ( CAU ; n = 130 ) . In the intervention arm , the research diagnosis is to be confirmed by a psychiatrist . First-choice treatment consists of placebo-controlled treatment with mirtazapine . In case of refusal or nonresponse , alternative open treatment with citalopram is offered . In the CAU arm , the patient is not informed about the research diagnosis . Psychiatric treatment outside the study is recorded , but no treatment is offered . Both arms are followed for end points ( cardiac death or hospital admission for MI , unstable angina , heart failure , or ventricular tachyarrhythmia ) during an average period of 27 months . Analysis is on an intention-to-treat basis . CONCLUSION The MIND-IT study will show whether treatment of post-MI depression can improve cardiac prognosis 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 Aim and methods The impact of medical comorbidity on the efficacy and tolerability of duloxetine in elderly patients with major depressive disorder ( MDD ) was investigated in this study . Data were obtained from a multicentre , r and omised , double-blind , placebo-controlled study in 311 patients with MDD aged 65–89 . The primary outcome measure was a prespecified composite cognitive score based on four cognitive tests : ( i ) Verbal Learning and Recall Test ; ( ii ) Symbol Digit Substitution Test ; ( iii ) 2-Digit Cancellation Test and ( iv ) Letter-Number Sequencing Test . Secondary measures included the Geriatric Depression Scale ( GDS ) , 17-Item Hamilton Depression Scale ( HAMD17 ) , Clinical Global Impression-Severity ( CGI-S ) Scale , Visual Analogue Scale ( VAS ) for pain and 36-Item Short Form Health Survey ( SF-36 ) . Tolerability measures included adverse events reported as the reason for discontinuation and treatment-emergent adverse events ( TEAEs ) . The consistency of the effect of duloxetine vs. placebo comparing patients with and without medical comorbidity ( vascular disease , diabetes , arthritis or any of these ) was investigated . Results Overall , duloxetine 60 mg/day demonstrated significantly greater improvement compared with placebo for the composite cognitive score , GDS and HAMD17 total scores , CGI-Severity , HAMD17 response and remission rates , and some of the SF-36 and VAS measures . There were few significant treatment-by-comorbidity subgroup interactions for these efficacy variables , or for adverse events reported as the reason for discontinuation and common TEAEs . Conclusions The present analyses suggested that the efficacy of duloxetine on cognition and depression in elderly patients , and its tolerability , were not largely affected by the comorbidity status . These results further support the use of duloxetine in elderly patients with MDD . Disclosures Dr Wise and Dr Iosifescu have served in consultant/advisory roles for this clinical trial . Dr Iosifescu has received honoraria from Eli Lilly and Company . Neither author has received financial support from Eli Lilly and Company in the form of research funding in the past 2 years . Dr Sheridan has no financial relationship with Eli Lilly and Company . At the time this study was completed , Dr Raskin , Dr Wiltse and Dr Xu were employees of and owned stock in Eli Lilly and Company . What 's known Analyses of primary efficacy data from this elderly study have shown that duloxetine 60 mg/day improved cognitive function . Duloxetine 60 mg/day also produced significant improvements vs. placebo in the Geriatric Depression Scale and HAMD17 total scores , as well as some pain measures . What 's new The present report investigates the impact of medical comorbidity on the efficacy of duloxetine in the treatment of depression , improvement of cognition , as well as quality of life and its tolerability in elderly patients with major depressive disorder Objective Depression and hostility are significant risk factors for mortality and morbidity after myocardial infa rct ion ( MI ) . Much research is still needed to identify effective ways to reduce emotional distress in patients with cardiovascular disease . This double-blind , placebo-controlled study investigated the efficacy and safety of the antidepressant fluoxetine in patients with depression after their first MI . Methods Fifty-four patients with major depression after MI were r and omly assigned to receive a flexible-dose regimen of fluoxetine or placebo for the first 9 weeks of a double-blind , placebo-controlled trial . Patients without serious adverse effects who wished to continue participating in the study were given fluoxetine or placebo for an additional 16 weeks . To evaluate the efficacy of fluoxetine , the 17-item Hamilton Depression Rating Scale ( HAMD-17 ) and the Hostility Scale of the 90-item Symptom Check List ( SCL-90 ) were used as primary measures of outcome . To evaluate the safety of fluoxetine , cardiac function was measured before and after treatment with echocardiography and electrocardiography . Results The a priori difference in antidepressive efficacy ( 4-point difference in HAMD-17 scores between the fluoxetine and placebo groups ) was not met . However , the response rate among patients receiving fluoxetine was significantly greater than that among patients receiving placebo at week 25 ( 48 vs. 26 % , p = .05 ) . Among patients with mild depression ( HAMD-17 score ≤21 ) , HAMD-17 scores were significantly different ( p < .05 ) between the fluoxetine and placebo groups at weeks 9 ( by 5.4 points ) and 25 ( by 5.8 points ) . Also , hostility scores at week 25 were significantly reduced among patients receiving fluoxetine ( p = .02 ) . Analysis of electrocardiographic and echocardiographic parameters revealed no decrease in cardiac function as a result of treatment with fluoxetine . Conclusions : Although the overall difference between the fluoxetine and placebo groups was not significant , there was a trend favoring fluoxetine in this relatively small sample . The response rate in the group receiving fluoxetine was comparable with that observed in other studies of patients with cardiovascular disease . In addition , fluoxetine seemed to be particularly effective in patients with mild depression and was associated with a statistically significant reduction in hostility . The results of this study suggest that fluoxetine can be safely used to treat patients with post-MI depression beginning 3 months after the event OBJECTIVE —The aim was to evaluate over 18 months whether depression was associated with mortality in people with their first foot ulcer . RESEARCH DESIGN AND METHODS —A prospect i ve cohort design was used . Adults with their first diabetic foot ulcer were recruited from foot clinics in southeast London , U.K. At baseline , the Schedules for Clinical Assessment in Neuropsychiatry 2.1 was used to define those who met DSM ( Diagnostic and Statistical Manual of Mental Disorders)-IV criteria for minor and major depressive disorders . Potential covariates were age , sex , marital status , socioeconomic status , smoking , antidepressant use , A1C , macro- and microvascular complications , and University of Texas classification – based severity and size of ulcer . The main outcome was mortality 18 months later , and A1C was the secondary outcome . The proportion who had an amputation , had recurrence , and whose ulcer had healed was recorded . RESULTS —A total of 253 people with their first diabetic foot ulcer were recruited . The prevalence of minor and major depressive disorder was 8.1 % ( n = 21 ) and 24.1 % ( n = 61 ) , respectively . There were 40 ( 15.8 % ) deaths , 36 ( 15.5 % ) amputations , and 99 ( 43.2 % ) recurrences . In the adjusted Cox regression analysis , minor and major depressive disorders were associated with an approximately threefold hazard risk for mortality compared with no depression ( 3.23 [ 95 % CI 1.39–7.51 ] and 2.73 [ 1.38–5.40 ] , respectively ) . There was no association between minor and major depression compared with no depression and A1C ( P = 0.86 and P = 0.43 , respectively ) . CONCLUSIONS —One-third of people with their first diabetic foot ulcer suffer from clinical depression , and this is associated with increased mortality BACKGROUND Depression following myocardial infa rct ion is associated with poor cardiac prognosis . It is unclear whether antidepressant treatment improves long-term depression status and cardiac prognosis . AIMS To evaluate the effects of antidepressant treatment compared with usual care in an effectiveness study . METHOD In a multicentre r and omised controlled trial , 2177 myocardial infa rct ion patients were evaluated for ICD-10 depression and r and omised to intervention ( n=209 ) or care as usual ( n=122 ) . Both arms were evaluated at 18 months post-myocardial infa rct ion for long-term depression status and new cardiac events . RESULTS No differences were observed between intervention and control groups in mean scores on the Beck Depression Inventory ( 11.0 , s.d.=7.5 v.10.2 , s.d.=5.1 , P=0.45 ) or presence of ICD-10 depression ( 30.5 v. 32.1 % , P=0.68 ) . The cardiac event rate was 14 % among the intervention group and 13 % among controls ( OR=1.07 , 95 % CI 0.57 - 2.00 ) . CONCLUSIONS Antidepressant treatment did not alter long-term depression post-myocardial infa rct ion status or improve cardiac prognosis OBJECTIVES To determine the response of physically ill elderly depressed patients to treatment . DESIGN Acute geriatric medical in patients with depression , r and omly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine . MAIN OUTCOME MEASURE Response rate as defined by the 17-item Hamilton Depression Rating Scale . RESULTS Eighty-two patients entered the trial ; 62 patients ( all those who had completed at least 3 weeks of treatment ) were included in the efficacy analysis . Forty-two completed the full 8 weeks ( 21 in each group ) with response rates of 67 % in the fluoxetine group and 38 % in the placebo group . No significant difference was found between the responses of the two groups ( p = 0.12 ) . There was a trend for results in the fluoxetine group to continue to improve with time . On secondary analysis those patients with serious physical illness who completed 5 or more weeks ( N = 37 ) showed a significant improvement in mood if treated with fluoxetine ( p = 0.02 ) . CONCLUSIONS The main benefit of antidepressants is to approximately double the chances of recovery . This trial showed the response rate of the fluoxetine treated group was increased by a factor of 1.8 over the placebo group in an 8-week period . The presence of physical illness , often severe and /or multiple , did not reduce the effectiveness of the medication , which was well tolerated overall . Those with serious physical disease responded significantly better to drug treatment ; this will require further work . Psychological support was also considered to be important OBJECTIVE To determine if the diagnosis of major depression in patients hospitalized following myocardial infa rct ion ( MI ) would have an independent impact on cardiac mortality over the first 6 months after discharge . DESIGN Prospect i ve evaluation of the impact of depression assessed using a modified version of the National Institute of Mental Health Diagnostic Interview Schedule for major depressive episode . Cox proportional hazards regression was used to evaluate the independent impact of depression after control for significant clinical predictors in the data set . SETTING A large , university-affiliated hospital specializing in cardiac care , located in Montreal , Quebec . PATIENTS All consenting patients ( N = 222 ) who met established criteria for MI between August 1991 and July 1992 and who survived to be discharged from the hospital . Patients were interviewed between 5 and 15 days following the MI and were followed up for 6 months . There were no age limits ( range , 24 to 88 years ; mean , 60 years ) . The sample was 78 % male . PRIMARY OUTCOME MEASURE Survival status at 6 months . RESULTS By 6 months , 12 patients had died . All deaths were due to cardiac causes . Depression was a significant predictor of mortality ( hazard ratio , 5.74 ; 95 % confidence interval , 4.61 to 6.87 ; P = .0006 ) . The impact of depression remained after control for left ventricular dysfunction ( Killip class ) and previous MI , the multivariate significant predictors of mortality in the data set ( adjusted hazard ratio , 4.29 ; 95 % confidence interval , 3.14 to 5.44 ; P = .013 ) . CONCLUSION Major depression in patients hospitalized following an MI is an independent risk factor for mortality at 6 months . Its impact is at least equivalent to that of left ventricular dysfunction ( Killip class ) and history of previous MI . Additional study is needed to determine whether treatment of depression can influence post-MI survival and to assess possible underlying mechanisms BACKGROUND Depression after myocardial infa rct ion ( MI ) is associated with higher morbidity and mortality . Although antidepressants are effective in reducing depression , their use in patients with cardiovascular disease remains controversial . OBJECTIVE To undertake a secondary analysis to determine the effects of using antidepressants on morbidity and mortality in post-MI patients who participated in the Enhancing Recovery in Coronary Heart Disease study . DESIGN Observational secondary analysis . SETTING Eight academic sites . PATIENTS The Enhancing Recovery in Coronary Heart Disease clinical trial r and omized 2481 depressed and /or socially isolated patients from October 1 , 1996 , to October 31 , 1999 . Depression was diagnosed using a structured clinical interview . This analysis was conducted on the 1834 patients enrolled with depression ( 849 women and 985 men ) . INTERVENTION Use of antidepressant medication . MAIN OUTCOME MEASURES Event-free survival was defined as the absence of death or recurrent MI . All-cause mortality was also examined . To relate exposure to antidepressants to subsequent morbidity and mortality , the data were analyzed using a time-dependent covariate model . RESULTS During a mean follow-up of 29 months , 457 fatal and nonfatal cardiovascular events occurred . The risk of death or recurrent MI was significantly lower in patients taking selective serotonin reuptake inhibitors ( adjusted hazard ratio [ HR ] , 0.57 ; 95 % confidence interval [ CI ] , 0.38 - 0.84 ) , as were the risk of all-cause mortality ( adjusted HR , 0.59 ; 95 % CI , 0.37 - 0.96 ) and recurrent MI ( adjusted HR , 0.53 ; 95 % CI , 0.32 - 0.90 ) , compared with patients who did not use selective serotonin reuptake inhibitors . For patients taking non-selective serotonin reuptake inhibitor antidepressants , the comparable HRs ( 95 % CIs ) were 0.72 ( 0.44 - 1.18 ) , 0.64 ( 0.34 - 1.22 ) , and 0.73 ( 0.38 - 1.38 ) for risk of death or recurrent MI , all-cause mortality , or recurrent MI , respectively , compared with nonusers . CONCLUSIONS Use of selective serotonin reuptake inhibitors in depressed patients who experience an acute MI might reduce subsequent cardiovascular morbidity and mortality . A controlled trial is needed to examine this important issue Major depression during later life represents a clinical challenge . Conventional antidepressant pharmacotherapy is relatively less well tolerated in geriatric patients compared with younger patients . Despite the striking impairments associated with this disorder , clinical investigations into the relative risk-benefit ratio of various depression treatment strategies have been limited . In this multicentre , placebo-controlled , double-blind trial with fluoxetine , 671 major depressed ( DSM-III-R-compatible ) out patients aged 60 years or older were evaluated . The 21-item Hamilton Depression Rating le ( HAMD21 ) response ( p = 0.014 ) and remission ( p = 0.008 ) criteria favoured fluoxetine over placebo . Analysis of the treatment effect on change in the HAMD21 factors ( anxiety/somatization , cognitive disturbance , psychomotor retardation , and sleep disturbance ) revealed advantages for fluoxetine within the cognitive disturbance and psychomotor retardation factors . Overall , the rate of discontinuation for an adverse event between fluoxetine ( 11.6 % ) and placebo ( 8.6 % ) was not statistically significant . Baseline HAMD21 factor scores were not predictive of adverse events leading to premature treatment discontinuation . Fluoxetine , 20 mg/day , is a well-tolerated and effective treatment option in the management of geriatric major depression BACKGROUND Poststroke depression is a frequent condition and important to treat . The aim of this trial was to study the efficacy and tolerability of sertraline . METHOD In 4 Swedish stroke centers , 123 patients ( aged 70.7 + /- 9.9 years ) were enrolled during the period September 1998 to January 2001 in a r and omized , double-blind , placebo-controlled 26-week trial , at a mean of 128 + /- 97 days ( range , 3 - 375 days ) after stroke , if they fulfilled DSM-IV criteria of major depressive episode ( N = 76 ) or minor depressive disorder ( N = 47 ) . The primary efficacy variable was a change in depression assessed by the Montgomery-Asberg Depression Rating Scale . The Emotional Distress Scale ( EDS ) was administered and the occurrence of emotionalism and quality of life ( QoL ) were assessed , as well as neurologic recovery . Efficacy analyses were intention-to-treat , short-term ( week 6 ) and long-term ( week 26 ) . RESULTS Of the 123 patients , 62 were treated with sertraline ( 50 - 100 mg/day ) and 61 with placebo . Both groups improved substantially , with no differences between the treatments , either for major depressive episode or minor depressive disorder , or for short- or long-term antidepressant effect and neurologic outcome . EDS revealed a better outcome with sertraline at week 6 ( p < .05 ) . At week 26 , the improvement in QoL was better in sertraline patients ( p < .05 ) and there was a trend for emotionalism ( p = .07 ) . No serious side effects were seen . CONCLUSION Poststroke depression as measured by a conventional depression rating scale improved over time irrespective of treatment . Positive effects specific to sertraline were identified in emotional distress , emotionalism , and QoL. The study indicates that poststroke emotional reactions comprise depression and other domains susceptible to pharmacologic therapy Although recent epidemiologic studies have established that patients with chronic medical illness and depressed mood are more disabled than euthymic patients , detailed data on the benefits and risks of antidepressant treatment in medically high-risk patients have been slow to accumulate . The authors have examined multiple outcome indicators in patients with disabling chronic obstructive pulmonary disease and comorbid depression . Thirty patients completed a 12-week , r and omized controlled trial of nortriptyline . Nortriptyline was clearly superior to placebo for treatment of depression . Nortriptyline treatment was accompanied by marked improvements in anxiety , certain respiratory symptoms , overall physical comfort , and day-to-day function ; placebo effects were negligible . Physiological measures reflecting pulmonary insufficiency were generally unaffected by treatment . These data provide impetus for renewed efforts to improve recognition and treatment of mood disorders in even severely disabled medical patients A double-blind r and omised controlled trial of the effect of low dose lofepramine ( 70 mg once daily ) against placebo was carried out on depressed elderly in patients on general medical wards for the elderly , comparing measures of depression and side-effects between the r and omised groups . Patients were identified for the study using the Geriatric Depression Scale ( GDS ) and the Brief Assessment Schedule Depression Cards ( BASDEC ) . Sixty-three subjects were r and omised : 46 patients completed the entire trial of 28 days treatment . BASDEC and GDS were administered on day 8 post-admission , and depressed patients were r and omised double-blind to either low dose lofepramine ( 70 mg daily ) ( n = 23 ) or placebo ( n = 23 ) . Assessment of changes in depressive states were made using the Montgomery Asberg Depression Rating Scale ( MADRS ) on days 8 , 18 and 36 post-admission . Both groups improved by a similar amount during the trial . Lofepramine tended to be more effective than placebo in those patients who were more depressed ( GDS > or = 18 ) . On the other h and , subjects who were less depressed ( i.e. GDS < 18 ) improved more on placebo than lofepramine . Low dose lofepramine may prove useful in moderately or severely depressed patients treated for only 4 weeks . However , low dose lofepramine is not indicated for mild ( GDS 15 - 18 ) depression PURPOSE Fatigue and depression typically occur together in cancer patients , suggesting a common etiology , perhaps based on serotonin . This r and omized clinical trial tested whether paroxetine , a selective serotonin reuptake inhibitor antidepressant known to modulate brain serotonin , would reduce fatigue in cancer patients and whether any reduction was related to depression . PATIENTS AND METHODS Cancer patients undergoing chemotherapy for the first time were assessed for fatigue . Of 704 patients who reported fatigue at their second chemotherapy cycle , 549 patients were r and omly assigned to receive either 20 mg of oral paroxetine hydrochloride daily or placebo for 8 weeks . The assessment s of fatigue and depression were performed at cycles 3 and 4 of chemotherapy . RESULTS A total of 244 patients treated with paroxetine and 235 patients treated with placebo provided assessable data . No difference was detected in fatigue between patient groups . At the end of the study , there was a difference between groups in the mean level of depression ( Center for Epidemiologic Studies Depression scores , 12.0 v 14.8 , respectively ; P < .01 ) . CONCLUSION Paroxetine had no influence on fatigue in patients receiving chemotherapy . A possible explanation is that cancer-related fatigue does not involve a reduction in brain 5-HT levels OBJECTIVE The objective of this study was to evaluate the efficacy of paroxetine in treating major depressive disorder ( MDD ) in persons with multiple sclerosis ( MS ) . METHOD In this double-blind trial , 42 participants with MS and MDD were r and omly assigned to one of two parallel 12-week treatment arms : paroxetine or placebo . The participants started at an initial dose of 10 mg/day paroxetine or placebo , titrated up to 40 mg daily based on symptoms response and side effects . The primary outcome measure was the Hamilton Rating Scale for Depression ( HAM-D ) . Secondary outcomes included fatigue , anxiety and self-reported quality of life . RESULTS Intent-to-treat analyses revealed that both groups improved from pretreatment to posttreatment . Although the treatment group improved more than the control group on most measures , few differences were statistically significant . For the primary outcome , 57.1 % of participants in the treatment arm had at least a 50 % reduction in HAM-D score , compared with 40 % in the control group ( nonsignificant ) . Treatment effects were greater among the participants who completed the study ; 78.6 % of completers had a treatment response compared with 42.1 % of controls ( P=.073 ) . CONCLUSION Although paroxetine may not be efficacious for all persons with MS and MDD , it appears to benefit some individuals Depression is one of the most common psychiatric disturbances in Parkinson 's disease ( PD ) . Recent review s have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD . We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor ( SSRI ) antidepressants differ in their short-term efficacy , because the time to onset of therapeutic benefit remains an important criterion in depression . The short-term efficacy ( after 14 and 30 days ) of two antidepressants ( desipramine , a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram , a SSRI ) was assessed in a double-blind , r and omized , placebo- controlled study of 48 nondemented PD patients suffering from major depression . After 14 days , desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale ( MADRS ) score , compared with citalopram and placebo . Both antidepressants produced significant improvements in the MADRS score after 30 days . Mild adverse events were twice as frequent in the desipramine group as in the other groups . A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI . However , desipramine 's lower tolerability may outweigh its slight short-term clinical advantage PURPOSE Smoking cessation after myocardial infa rct ion reduces cardiovascular mortality , but many smokers can not quit despite state-of-the-art counseling intervention . Bupropion is effective for smoking cessation , but its safety and efficacy in hospitalized smokers with acute cardiovascular disease is unknown . METHODS A five-hospital r and omized double-blind placebo-controlled trial assessed the safety and efficacy of 12 weeks of sustained-release bupropion ( 300 mg ) or placebo in 248 smokers admitted for acute cardiovascular disease , primarily myocardial infa rct ion and unstable angina . All subjects had smoking counseling in the hospital and for 12 weeks after discharge . Cotinine-vali date d 7-day tobacco abstinence , cardiovascular mortality , and new cardiovascular events were assessed at 3 months ( end-of-treatment ) and 1 year . RESULTS Vali date d tobacco abstinence rates in bupropion and placebo groups were 37.1 % vs 26.8 % ( OR 1.61 , 95 % CI , 0.94 - 2.76 ; P=.08 ) at 3 months and 25.0 % vs 21.3 % ( OR , 1.23 , 95 % CI , 0.68 - 2.23 , P=.49 ) at 1 year . The adjusted odds ratio , after controlling for cigarettes per day , depression symptoms , prior bupropion use , hypertension , and length of stay , was 1.91 ( 95 % CI , 1.06 - 3.40 , P=.03 ) at 3 months and 1.51 ( 95 % CI , 0.81 - 2.83 ) at 1 year . Bupropion and placebo groups did not differ in cardiovascular mortality at 1 year ( 0 % vs 2 % ) , in blood pressure at follow-up , or in cardiovascular events at end-of-treatment ( 16 % vs 14 % , incidence rate ratio [IRR]1.22 ( 95 % CI : 0.64 - 2.33 ) or 1 year ( 26 % vs 18 % , IRR 1.56 , 95 % CI 0.91 - 2.69 ) . CONCLUSIONS Bupropion improved short-term but not long-term smoking cessation rates over intensive counseling and appeared to be safe in hospitalized smokers with acute cardiovascular disease OBJECTIVE The purpose of this study was to assess gender differences in the impact of depression on 1-year cardiac mortality in patients hospitalized for an acute myocardial infa rct ion ( MI ) . METHODS Secondary analysis was performed on data from two studies that used the Beck Depression Inventory ( BDI ) to assess depression symptoms during hospitalization : a prospect i ve study of post-MI risk and a r and omized trial of psychosocial intervention ( control group only ) . The sample included 896 patients ( 283 women ) who survived to discharge and received usual posthospital care . Multivariate logistic regression analysis was used to assess the risk of 1-year cardiac mortality associated with baseline BDI scores . RESULTS There were 290 patients ( 133 women ) with BDI scores > or = 10 ( at least mild to moderate symptoms of depression ) ; 8.3 % of the depressed women died of cardiac causes in contrast to 2.7 % of the nondepressed . For depressed men , the rate of cardiac death was 7.0 % in contrast to 2.4 % of the nondepressed . Increased BDI scores were significantly related to cardiac mortality for both genders [ the odds ratio for women was 3.29 ( 95 % confidence interval ( CI ) = 1.02 - 10.59 ) ; for men , the odds ratio was 3.05 ( 95 % CI = 1.29 - 7.17 ) ] . Control for other multivariate predictors of mortality in the data set ( age , Killip class , the interactions of gender by non-Q wave MI , gender by left ventricular ejection fraction , and gender by smoking ) did not change the impact of the BDI for either gender . CONCLUSIONS Depression in hospital after MI is a significant predictor of 1-year cardiac mortality for women as well as for men , and its impact is largely independent of other post-MI risks PURPOSE To determine whether fluoxetine improves overall quality of life ( QOL ) in advanced cancer patients with symptoms of depression revealed by a simple survey . PATIENTS AND METHODS One hundred sixty-three patients with an advanced solid tumor and expected survival between 3 and 24 months were r and omly assigned in a double-blinded fashion to receive either fluoxetine ( 20 mg daily ) or placebo for 12 weeks . Patients were screened for at least minimal depressive symptoms and assessed every 3 to 6 weeks for QOL and depression . Patients with recent exposure to antidepressants were excluded . RESULTS The groups were comparable at baseline in terms of age , sex , disease distribution , performance status , and level of depressive symptoms . One hundred twenty-nine patients ( 79 % ) completed at least one follow-up assessment . Analysis using generalized estimating equation modeling revealed that patients treated with fluoxetine exhibited a significant improvement in QOL as shown by the Functional Assessment of Cancer Therapy-General , compared with patients given placebo ( P = .01 ) . Specifically , the level of depressive symptoms expressed was lower in patients treated with fluoxetine ( P = .0005 ) , and the subgroup of patients showing higher levels of depressive symptoms on the two- question screening survey were the most likely to benefit from treatment . CONCLUSION In this mix of patients with advanced cancer who had symptoms of depression as determined by a two- question bedside survey , use of fluoxetine was well tolerated , overall QOL was improved , and depressive symptoms were reduced We assessed the effect of 3-month treatment of sertraline ( 50 mg ) or low-dose amitriptyline ( 25 mg ) on depression and quality of life in 31 patients with Parkinson 's disease in a prospect i ve single-blind r and omized study . Both drugs significantly reduced the Hamilton Depression Rating Scale ( HDRS-17 ) score . Completion rate was 75 % for sertraline ( 12 of 16 ) and 73 % for amitriptyline ( 11 of 15 ) . Responder rate ( HDRS-17 score reduction > /= 50 % ) was 83.3 % for sertraline and 72.7 % for amitriptyline . Sertraline but not amitriptyline treatment determined a significant benefit on quality of life ( PDQ-39 scale ) . We found no change in Unified Parkinson 's Disease Rating Scale scores . However , the improvement in specific PDQ-39 subscores ( mobility , activities of daily living , and stigma ) suggests that depression affects patient self-perception of motor function and further emphasizes the need for its treatment BACKGROUND Depression is frequently observed in patients with heart failure and is associated with poor quality of life and adverse prognosis . However , the prevalence of depression in heart failure could be overestimated because symptoms of depression overlap with those of heart failure . Similarly , the importance of depression may be overestimated if depression merely reflects worse heart failure . Because the response to depression treatment has not been evaluated in this patient population , we evaluated the efficacy of controlled-release paroxetine ( paroxetine CR ) , a selective serotonin reuptake inhibitor , on depression and quality of life in chronic heart failure . METHODS A double-blind , r and omized , placebo-controlled design was used to evaluate reductions in depression following 12 weeks of treatment with paroxetine CR ( n = 14 , age 62.1 + /- 12.3 years ) or placebo ( n = 14 , age = 61.9 + /- 9.0 years ) . Patients with symptomatic congestive heart failure and a score of at least 10 on the Beck Depression Inventory ( BDI ) were eligible . Beck Depression Inventory was obtained at baseline and 4 , 8 , and 12 weeks of follow-up . Quality of life was assessed using the Medical Outcomes Study Short Form and the Minnesota Living with Heart Failure Question naire . RESULTS Controlled-release paroxetine result ed in significantly more recovery from depression ( BDI < 10 ) than placebo ( 69 % vs 23 % , P = .018 ) and result ed in lower continuous BDI scores throughout the intervention ( P = .024 ) . Controlled-release paroxetine was associated with higher general health levels compared with placebo on the Medical Outcomes Study 36-Item Short Form survey ( 38 + /- 10 vs 30 + /- 6 , P = .016 ) at 12 weeks of follow-up . Reductions in depression were correlated with improvements in psychological aspects of quality of life ( P < .05 ) but not with physical quality of life measures ( P > .10 ) . CONCLUSION Antidepressant therapy with paroxetine CR results in significant reductions in depression among patients with heart failure . The reductions in depression with paroxetine CR are accompanied by improvements in psychological aspects of quality of life . Larger controlled trials are needed to further document the effectiveness of paroxetine CR and other selective serotonin reuptake inhibitors in patients with heart failure and to determine patient subgroups that are most likely to benefit from antidepressive interventions OBJECTIVE Because physical illness may influence quality of life , we assessed its impact on functional status and treatment outcome in older depressed patients who participated in a clinical trial , which showed a significantly higher remission rate for fluoxetine over placebo ( 31.6 % vs 18.6 % , P < .001 ) . DESIGN Six-week , r and omized , double-blind , placebo-controlled trial of fluoxetine , 20 mg daily . SETTING Multiple clinical sites , both university and private . PARTICIPANTS Out patients ( N = 671 ) were > or = 60 years ( mean + /- SD = 67.7 + /- 5.7 ) , met DSM-III-R criteria for unipolar major depression and had baseline scores > or = 16 on the Hamilton Depression Rating Scale . MEASUREMENTS The 36-item short-form health survey ( SF-36 ) was used to measure baseline and posttreatment functional health and well-being . Physical illness was rated by number of current chronic or historical illnesses . Change from baseline to endpoint in the Hamilton Depression Rating Scale total score was used to measure depression outcome . MAIN RESULTS Most patients reported physical illness : 83 % had one or more chronic illness , and 89 % had one or more historical illness . Greater numbers of baseline chronic illness indicated worse physical functioning , general health perceptions , and vitality and greater bodily pain and role limitation from physical problems . Historical physical illness was associated with worse physical functioning , vitality , general health perceptions , social functioning , and mental health . Although the number of chronic illnesses did not influence treatment response , historical physical illness was associated with greater fluoxetine response and lower placebo response . CONCLUSIONS These findings suggest that both current and previous physical illness are associated with lower quality of life in geriatric depression and that depressed older patients with chronic physical illness respond to antidepressants as well as those without such illness . Recovery from previous physical illness should be explored as a potential predictor of antidepressant treatment outcome OBJECTIVE The goals of this study were to determine whether fluoxetine is superior to placebo in treating HIV-seropositive patients with major depression or dysthymia or both , whether severity of immunosuppression is associated with treatment response , and whether fluoxetine treatment is associated with change in immune status as measured by CD4 cell count . METHOD A double-blind , r and omized , placebo-controlled 8-week trial of fluoxetine was conducted in a university-affiliated research outpatient clinic . The fluoxetine-placebo r and omization was 2:1 . All patients were offered 4 months of additional open treatment . Main outcome measures included the Clinical Global Impression , Hamilton Depression Rating Scale , and CD4 cell count . RESULTS Of 120 patients r and omly assigned to fluoxetine or placebo , 87 completed 8 weeks of treatment . In the total group , 51 % had AIDS . All but three were men , 35 % were nonwhite , and 6 % had intravenous drug use as a risk factor . In an intention-to-treat analysis , 57 % of fluoxetine patients and 41 % of placebo patients were responders . Among patients who completed the study , 74 % responded to fluoxetine and 47 % to placebo ; this difference was statistically significant . Severity of immunosuppression was not related to antidepressant response , attrition , or side effects , and fluoxetine treatment was not associated with change in CD4 cell count . CONCLUSIONS Fluoxetine is an effective antidepressant in the context of HIV illness . However , both placebo response and attrition were substantial , suggesting both that nonspecific factors may be more salient and that yet another medication ( i.e. , an antidepressant ) may be less acceptable among patients with serious medical illness already requiring multiple concomitant medications BACKGROUND Brain serotonin is known to possess sympathoinhibitory properties . The aim of this clinical physiologic study was to determine whether sertraline , a selective serotonin reuptake inhibitor , facilitates the rate of recovery of cardiac autonomic function after an acute myocardial infa rct ion ( MI ) in patients with depression . METHODS AND RESULTS Thirty-eight post-MI depressed patients were r and omized to receive either sertraline 50 mg per day or placebo for 6 months . Depression was defined as a score > 15 on the st and ardized Inventory to Diagnose Depression question naire taken at prehospital discharge and again within 2 weeks of the acute infa rct . Eleven stable post-MI nondepressed patients served as a nonr and omized reference group during follow-up . Twenty-seven patients completed the r and omization . All 3 groups were followed up closely in a multidisciplinary post-MI clinic where they underwent serial testing for both time and frequency domain heart rate variability ( HRV ) indices at baseline ( 1 - 2 weeks after MI ) and at 6 , 10 , 14 , 18 , and 22 weeks . The rate of recovery of HRV was determined by use of a growth curve model based on repeated- measures analysis of variance . There was a linear rate of increase in the SD of 24-hour N-N intervals ( SDNN ) in the sertraline-treated group that paralleled that of the nondepressed reference group . This contrasted with a modest but significant decline in SDNN in the placebo group from 2 to 22 weeks ( t = 2.10 , P < .05 ) . However , the short-term power spectral indices , while trending toward a more rapid rate of recovery in the treated group , did not reach statistical significance compared with the placebo group . CONCLUSION In depressed patients who have survived the acute phase of an MI sertraline facilitates the rate of recovery of SDNN , a recognized predictor of clinical outcome The efficacy of low doses ( 10 to 20 mg daily ) of doxepin in the treatment of depressive disorders in elderly in patients was assessed by a double-blind study in 24 patients . The patients were treated for a three-week period to test for an early response . The Hamilton Depression Scale and the Geriatric Depression Scale were used to quantify symptoms of depression . The patients treated with doxepin had a significantly greater reduction in depressive symptoms than did those who received a placebo . No side effects were found and there were no major differences in the degree of physical dependency between the doxepin and placebo groups . A depressive disorder is a common occurrence among elderly in patients and the effectiveness of low dose doxepin therapy without demonstrable side effects argues for the active treatment for this condition BACKGROUND This study was conducted to determine the efficacy and tolerability of fluoxetine and desipramine in treating depressive symptoms in women with cancer . METHOD In this prospect i ve , 6-week , double-blind , placebo-controlled trial , we compared fluoxetine with desipramine in treating depressive symptoms in 40 women diagnosed with cancer . Scales used to measure efficacy and tolerability were the Hamilton Depression Rating Scale ( HAM-D ) , the Hamilton Anxiety Rating Scale ( HAM-A ) , the Clinical and Patient 's Global Impression ( CGI and PGI ) scales , the Functional Living Index for Cancer ( FLIC ) , the Memorial Pain Assessment Card ( MPAC ) , and the SF-36 Health Survey . RESULTS Fluoxetine and desipramine treatments improved depression and anxiety symptoms . There was a trend towards significance in improvement of FLIC scores ( as evidence d by greater numerical improvements with fluoxetine treatment ) . Fluoxetine treatment alone was associated with statistically significant improvements in MPAC Mood scale scores . Both treatments showed statistically significant improvements in the quality of life SF-36 scores in Role Emotional , Social Functioning , Mental Health , and Vitality . CONCLUSIONS Both fluoxetine and desipramine were effective and well-tolerated in improving depressive symptoms and quality of life in women with advanced cancer . Fluoxetine may offer greater benefit to these patients , as evidence d by greater improvements in fluoxetine-treated patients on several quality of life measures . Our results , while meaningful , should be confirmed in a larger patients sample . However , experience from studies of antidepressant use in patients with advanced cancer has shown that intercurrent disease and treatment variables make it difficult to conduct large studies A double‐blind , r and omized 4‐week mianserin vs maprotiline trial was conducted in 48 depressed geriatric medical in patients . The drug dosages were up to 90 mg of mianserin and up to 150 mg of maprotiline per day . Efficacy was measured by the Geriatric Depression Scale , the Hopkins Symptom Check List depression subscale and the Clinical Global Impression Scale . The overall dropout figure was 27 % of the sample . Side effects were relatively similar in the two treatment groups and suggested a safety profile somewhat better than that of the first‐generation antidepressants . Mianserin showed some advantages in efficacy over maprotiline , particularly by the 4th week of the trial , but the overall figures of treatment responders were rather small ( Geriatric Depression Scale : mianserin 48 % , maprotiline 30 % ) . Clinical trials vs placebo are needed to clarify the role of antidepressant pharmacotherapy in depressed geriatric medical in patients OBJECTIVE This study compared the efficacy , tolerability , and safety of paroxetine and nortriptyline in depressed patients with ischemic heart disease . METHOD After a 2-week , single-blind placebo lead-in phase , 81 out patients with DSM-III-R-defined nonpsychotic unipolar major depression and ischemic heart disease were r and omly assigned to double-blind treatment with paroxetine or nortriptyline for 6 weeks . Paroxetine was administered at a fixed-flexible dose of 20 - 30 mg/day . Nortriptyline dose was adjusted with the use of blood-level monitoring to reach a plasma concentration of 50 - 150 ng/ml . RESULTS Twenty-seven of the 41 patients who started treatment with paroxetine and 29 of the 40 patients who started treatment with nortriptyline had an improvement of at least 50 % in their Hamilton Depression Rating Scale scores . Significantly more patients taking nortriptyline discontinued treatment prematurely ( 35 % versus 10 % ) , and more patients taking nortriptyline had adverse events result ing in termination ( 25 % versus 5 % ) . CONCLUSIONS Both treatments were efficacious . Sixty-three percent of all patients improved at least 50 % , and of these , 90 % met the criteria for remission . Paroxetine was better tolerated than nortriptyline and less likely to produce cardiovascular side effects Nineteen patients with L‐DOPA treated parkinsonism involving depressive symptoms , the therapeutic effect of nortriptyline was compared to placebo in a controlled trial . The depressive and neurological symptoms were evaluated by rating scales . Nortriptyline had a clinical significant effect with regard to the depressive symptoms , whereas the neurological parameters were unchanged . The authors suggest the depression in Parkinson 's disease to be of both reactive and endogenous origins The aim of this study was to determine whether treating concomitant depression improves quality of life and exercise tolerance in COPD patients . Out- patients with moderate to severe , stable COPD completed Hospital Anxiety-Depression ( HAD ) and General Health question naires . A psychiatrist interviewed those with high scores . In a r and omised , double-blind fashion , 28 depressed COPD patients took a selective serotonin re-uptake inhibitor , Paroxetine 20 mg daily , or matched placebo for 6 weeks . Subsequently , all patients took un-blinded Paroxetine for 3 months . From these question naires , 35 % of 135 patients had significant depression , but this was confirmed by psychiatric interview in only 21 % . Throughout the study , there were no changes in laboratory lung function nor in home peak flow . Six weeks ' treatment produced no significant differences between placebo and treatment group in either depression , quality of life scores or 6-minute walking distances , although overall improvements in depression , correlated with increases in walking distance . Three months of un-blinded treatment , significantly improved depression scores ( self-complete HAD , Beck 's Depression and psychiatrist-completed Montgomery-Asberg scores ) , walking distances ( 369 to 427 m , p = 0.0003 ) and St. George 's Respiratory Question naire Total Scores ( 65 to 58 , p = 0.033 ) . Although self-complete question naires over-diagnose depression , the condition is nevertheless common in patients with moderately severe COPD . Six weeks of antidepressants is insufficient to improve either depression , quality of life or exercise tolerance . However , our study suggests that a longer course of treatment may be effective and that improvements in depression are associated with improvements in exercise tolerance . A larger , double blind study with a longer treatment period is indicated Objective Depression is a prevalent and chronic condition in diabetes and is associated with poor glucose regulation and poor compliance with diabetes treatment . This investigation evaluated the effects of nortriptyline on depression and glycemic control to see whether depression in diabetes is treatable and whether restoring mental health contributes to improved medical outcome . Method : Sixty-eight diabetic patients with poor glycemic control , 28 of whom had active major depression ( DSM-IIIR ) , completed a r and omized , placebo-controlled , double-blind trial involving 8 weeks of treatment with nortriptyline targeted to therapeutic plasma levels ( 50 - 150 ng/ml ) . Depression improvement was determined with the Beck Depression Inventory ; glucose control was measured by glycated hemoglobin levels . Compliance behavior was assessed using medication dispensing devices and glucometers equipped with electronic memory . Results : The reduction in depression symptoms was significantly greater in depressed patients treated with nortriptyline compared with those receiving placebo ( -10.2 vs -5.8 , p = .03 ) . Nortriptyline was not statistically superior to placebo in reducing glycated hemoglobin of the depressed subjects ( p = .5 ) . However , path analysis indicated that the direct effect of nortriptyline was to worsen glycemic control whereas depression improvement had an independent beneficial effect on glycated hemoglobin . These findings were not explained by the relationships of nortriptyline treatment to weight change ( r = -0.21 , p = .31 ) or depression improvement to compliance with the protocol for self-monitoring of blood glucose ( r = 0.01 , p = .97 ) . Conclusions : Major depression in diabetic patients can be effectively treated with nortriptyline at the expense of a direct hyperglycemic effect . Path analysis demonstrated a treatment-independent effect of depression improvement on glycemic control , suggesting that a more ideal antidepressant agent may both restore mental health and improve medical outcome A double-blind , placebo-controlled study was conducted to assess the relative efficacy and tolerability of fluoxetine and desipramine in depressed , human immunodeficiency virus (HIV)-positive women . Although difficulty in the recruitment and retention of participants led to insufficient power to detect differences between treatment groups , results indicated that participants experienced improvement in their depression . However , for most women , significant depressive symptoms remained after 6 weeks of treatment . In addition , although most participants reported at least one adverse event after treatment began , most of the side effects , regardless of treatment condition , were mild to moderate in severity . Important barriers to study participation and completion are discussed , as well as suggestions for increasing the involvement of depressed , HIV-positive women in future treatment studies BACKGROUND The prevalence of asthma has increased in recent years and depression is common in this population . Minimal data are available on the treatment of depressed asthma patients . METHODS Ninety adults with asthma and current major depressive disorder were r and omized to receive citalopram or placebo for 12 weeks . At each visit , the Hamilton Rating Scale for Depression ( HRSD ) , Inventory of Depressive Symptomatology - Self-Report , Asthma Control Question naire , and Asthma Quality of Life Question naire were administered , and oral corticosteroid use assessed . RESULTS In the evaluable sample ( n = 82 ) , the primary outcome , a r and om regression analysis of HRSD scores , revealed no significant between-group differences . Bonferroni corrected secondary outcomes revealed HRSD scores decreased significantly in both groups with a significantly greater decrease in the citalopram group at week 6 . Changes in asthma symptoms were similar between groups . The groups had similar rates of oral corticosteroid use at baseline , but the citalopram group had less corticosteroid use during the study . Changes in asthma symptom severity correlated with changes in depressive symptom severity . CONCLUSIONS A reduction in depressive symptoms was associated with improvement in asthma . Corticosteroid use , an important measure of severe asthma exacerbations , was lower in the citalopram group . Larger clinical trials in this population are warranted OBJECTIVE This study compared the efficacy and safety of paroxetine and desipramine with those of placebo in the treatment of depressive disorders in adult women with breast cancer , stages I-IV . METHOD In a double-blind , placebo-controlled study , 35 female out patients with breast cancer and DSM-III-R major depression or adjustment disorder with depressed mood were r and omly assigned to treatment with paroxetine ( N=13 ) , desipramine ( N=11 ) , or placebo ( N=11 ) for 6 weeks . Primary efficacy was assessed by change from baseline in score on the 21-item Hamilton Rating Scale for Depression ( HAM-D ) , and the secondary outcome measure was change from baseline in the Clinical Global Impressions-Severity of Illness scale ( CGI-S ) score . RESULTS Mean changes in the total HAM-D and CGI-S scores from baseline to 6-week endpoint for the paroxetine and desipramine groups were not significantly different than those for the placebo-treated group . An unusually high rate of response ( defined as > or=50 % improvement in the HAM-D score ) in the placebo group was observed ( 55 % [ N=6 ] ) ; adverse events precipitated patient discontinuation in the active treatment groups ( 9 % [ N=1 ] for desipramine , 15 % [ N=2 ] for paroxetine ) similar to that in the placebo-treated patients ( 18 % [ N=2 ] ) . Improvement on symptom dimensions within the HAM-D and Hamilton Rating Scale for Anxiety ( depressive , anxiety , cognitive , neurovegetative , or somatic ) was also similar between groups . CONCLUSION The small number of women in this study most likely contributed to the lack of observed differences in efficacy observed during the 6 weeks of treatment . R and omized , placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance Background : While testosterone 's ameliorative effects on depressive disorders and fatigue in HIV-positive patients have been suggested in the literature , no placebo-controlled trial selecting for depressive disorders and including a st and ard antidepressant has been conducted . Accordingly , this double-blind trial was design ed to determine whether testosterone , as well as fluoxetine , is superior to placebo for depression , fatigue , or both . Method : One hundred twenty-three men with HIV/AIDS with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition depressive disorder entered the 8-week trial and were r and omized to testosterone ( up to 400 mg IM testosterone cypionate biweekly ) , fluoxetine ( up to 60 mg/d ) , or double placebo . Outcome variables were the Clinical Global Impressions Scale for mood and for fatigue , the Hamilton Rating Scale for Depression , and the Chalder Fatigue Scale . Results : Ninety men completed the trial . In intention-to-treat analyses , mood response rates were 54 % , 47 % , and 44 % for fluoxetine , testosterone , and placebo , respectively . Among completers , mood response rates were 70 % , 57 % , and 53 % , respectively ; in neither analysis were differences between treatments statistically significant . In contrast , testosterone was superior to fluoxetine and placebo for completers regarding fatigue . In intention-to-treat analysis , response rates were 39 % , 56 % , and 42 % for fluoxetine , testosterone , and placebo , respectively , and for study completers , 41 % , 63 % , and 52 % , respectively , ( P < 0.05 ) , Conclusion : While over 50 % of patients treated with testosterone reported improved mood , this rate was not statistically superior to placebo . Thus , our findings do not support prescription of testosterone as a first-line treatment for depressive disorders in HIV-positive men . However , if vali date d in additional studies , testosterone may be a useful option for medically ill men experiencing significant fatigue as well as depression Objective : To test the safety and efficacy of fluoxetine in patients with renal failure on dialysis . Method : Fourteen patients with major depression and end stage renal disease on hemodialysis were r and omized into two groups for an eight-week study . Subjects as well as investigators were blinded as to which subject received fluoxetine and which placebo . Patients were carefully monitored concerning adverse events , serum fluoxetine and norfluoxetine levels , and psychological measurements of degree of depression . Results : No patients discontinued treatment because of adverse events , all of which were minor . All psychological tests showed improvement in depression at the four-week and eight-weeks point , although statistical significance could only be demonstrated at the fourth week of this study . All patients in the active group had serum plasma concentrations of fluoxetine and norfluoxetine less than 250 ng/ml at eight weeks , similar to levels in patients with normal renal function in a previous open label study . Conclusions : This study confirms the relative safety of fluoxetine in depressed patients in renal failure on hemodialysis . It also suggests that fluoxetine may be efficacious in depressed patients on dialysis BACKGROUND This report documents findings from a small placebo-controlled trial of dextroamphetamine for depression and fatigue in men with the human immunodeficiency virus ( HIV ) . Dextroamphetamine offers the potential for rapid onset of effect and activation properties , both of which are important to persons with medical illness and an uncertain , but limited , life expectancy . METHOD Primary inclusion criteria included the presence of a DSM-IV depressive disorder , debilitating fatigue , and no history of dependence on stimulants . The study consisted of a 2-week r and omized , placebo-controlled trial , with the blind maintained until week 8 for responders , followed by open treatment through the completion of 6 months . RESULTS Of 23 men who entered the study , 22 completed the 2-week trial . Intent-to-treat analysis indicated that 73 % of patients ( 8/11 ) r and omly assigned to dextroamphetamine reported significant improvement in mood and energy , compared with 25 % ( 3/12 ) among placebo patients ( Fisher exact test , p < .05 ) . Both clinician- and self-administered measures indicated significantly improved mood , energy , and quality of life among patients taking dextroamphetamine . There was no evidence of the development of tolerance of , abuse of , or dependence on the medication . CONCLUSION These results suggest that dextroamphetamine is a potentially effective , fast-acting antidepressant treatment for HIV patients with depression and debilitating fatigue |
1,092 | 21,534,932 | Evidence supports that MBSR improves mental health and MBCT prevents depressive relapse . | UNLABELLED Fjorback LO , Arendt M , Ørnbøl E , Fink P , Walach H. Mindfulness-Based Stress Reduction and Mindfulness-Based Cognitive Therapy - a systematic review of r and omized controlled trials .
OBJECTIVE To systematic ally review the evidence for MBSR and MBCT . | 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 unchanged from baseline to post-intervention ( time x treatment condition interaction , p=.02 ) . This effect was independent of antiretroviral ( ARV ) medication use . Additional analyses indicated that treatment adherence to the mindfulness meditation program , as measured by class attendance , mediated the effects of mindfulness meditation training on buffering CD4 + T lymphocyte declines . These findings provide an initial indication that mindfulness meditation training can buffer CD4 + T lymphocyte declines in HIV-1 infected adults . CLINICAL TRIALS REGISTRATION clinical trials.gov , Identifier : NCT00600561 The purpose of this study was to gather data on the efficacy of a newly developed psychosocial group intervention for cancer patients , called mindfulness-based art therapy ( MBAT ) . One hundred and eleven women with a variety of cancer diagnoses were paired by age and r and omized to either an eight-week MBAT intervention group or a wait-list control group . Ninety-three participants ( 84 % ) completed both the pre- and post- study measurements . As compared to the control group , the MBAT group demonstrated a significant decrease in symptoms of distress ( as measured by the Symptoms Checklist-90-Revised ) and significant improvements in key aspects of health-related quality of life ( as measured by the Medical Outcomes Study Short-Form Health Survey ) . This investigation of MBAT provides initial encouraging data that support a possible future role for the intervention as a psychosocial treatment option for cancer patients Recovered recurrently depressed patients were r and omized to treatment as usual ( TAU ) or TAU plus mindfulness-based cognitive therapy ( MBCT ) . Replicating previous findings , MBCT reduced relapse from 78 % to 36 % in 55 patients with 3 or more previous episodes ; but in 18 patients with only 2 ( recent ) episodes corresponding figures were 20 % and 50 % . MBCT was most effective in preventing relapses not preceded by life events . Relapses were more often associated with significant life events in the 2-episode group . This group also reported less childhood adversity and later first depression onset than the 3-or-more-episode group , suggesting that these groups represented distinct population s. MBCT is an effective and efficient way to prevent relapse/recurrence in recovered depressed patients with 3 or more previous episodes Principal applicant and corresponding author : Prof Samuel Yeung-shan Wong 4/F , Department of Community and Family Medicine , The Chinese University of Hong Kong , School of Public Health , Prince of Wales Hospital , Shatin , NT , Hong Kong SAR , China Tel : ( 852 ) 2252 8774 Fax : ( 852 ) 2606 3500 E-mail : [email protected] SYS Wong 黃仰山 Effect of mindfulness-based stress reduction programme on pain and quality of life in chronic pain patients : a r and omised controlled clinical This study evaluated mindfulness-based cognitive therapy ( MBCT ) , a group intervention design ed to train recovered recurrently depressed patients to disengage from dysphoria-activated depressogenic thinking that may mediate relapse/recurrence . Recovered recurrently depressed patients ( n = 145 ) were r and omized to continue with treatment as usual or , in addition , to receive MBCT . Relapse/recurrence to major depression was assessed over a 60-week study period . For patients with 3 or more previous episodes of depression ( 77 % of the sample ) , MBCT significantly reduced risk of relapse/recurrence . For patients with only 2 previous episodes , MBCT did not reduce relapse/recurrence . MBCT offers a promising cost-efficient psychological approach to preventing relapse/recurrence in recovered recurrently depressed patients OBJECTIVE To assess the effect of a meditation training program , Mindfulness-Based Stress Reduction ( MBSR ) , on depressive symptoms , psychological status , and disease activity in patients with rheumatoid arthritis ( RA ) through a r and omized , waitlist-controlled pilot study . METHODS Participants were r and omized to either an MBSR group , where they attended an 8-week course and 4-month maintenance program , or to a waitlist control group , where they attended all assessment visits and received MBSR free of charge after study end . Participants received usual care from their rheumatologists throughout the trial . Self-report question naires were used to evaluate depressive symptoms , psychological distress , well-being , and mindfulness . Evaluation of RA disease activity ( by Disease Activity Score in 28 joints ) included examination by a physician masked to treatment status . Adjusted means and mean changes in outcomes were estimated in mixed model repeated measures analyses . RESULTS Sixty-three participants were r and omized : 31 to MBSR and 32 to control . At 2 months , there were no statistically significant differences between groups in any outcomes . At 6 months , there was significant improvement in psychological distress and well-being ( P = 0.04 and P = 0.03 , respectively ) , and marginally significant improvement in depressive symptoms and mindfulness ( P = 0.08 and P = 0.09 , respectively ) . There was a 35 % reduction in psychological distress among those treated . The intervention had no impact on RA disease activity . CONCLUSION An 8-week MBSR class was not associated with change in depressive symptoms or other outcomes at 2-month followup . Significant improvements in psychological distress and well-being were observed following MBSR plus a 4-month program of continued reinforcement . Mindfulness meditation may complement medical disease management by improving psychological distress and strengthening well-being in patients with RA OBJECTIVE This study evaluated the effectiveness of mindfulness-based cognitive therapy ( MBCT ) for individuals with a diagnosis of cancer . METHOD Participants ( N = 115 ) diagnosed with cancer , across site and stage , were r and omly allocated to either the treatment or the wait-list condition . Treatment was conducted at 1 site , by a single therapist , and involved participation in 8 weekly 2-hr sessions that focused on mindfulness . Participants meditated for up to 1 hr daily and attended an additional full-day session during the course . Participants were assessed before treatment and 10 weeks later ; this second assessment occurred immediately after completion of the program for the treatment condition . The treatment condition was also assessed at 3 months postintervention . All postinitial assessment s were completed by assessors who were blind to treatment allocation . RESULTS There were large and significant improvements in mindfulness ( effect size [ ES ] = 0.55 ) , depression ( ES = 0.83 ) , anxiety ( ES = 0.59 ) , and distress ( ES = 0.53 ) as well as a trend for quality of life ( ES = 0.30 ) for MBCT participants compared to those who had not received the training . The wait-list group was assessed before and after receiving the intervention and demonstrated similar change . CONCLUSIONS These improvements represent clinical ly meaningful change and provide evidence for the provision of MBCT within oncology setting OBJECTIVE To determine the effectiveness of an intensive dietary intervention on diet and body mass in women with breast cancer . DESIGN R and omized clinical trial . SUBJECTS 172 women aged 20 to 65 years with stage I or II breast cancer . INTERVENTION A 15-session , mainly group-based and dietitian-led nutrition education program ( NEP ) was compared to a mindfulness-based stress reduction clinic program ( SRC ) ; or usual supportive care ( UC ) . MAIN OUTCOME MEASURES Dietary fat , complex carbohydrates , fiber , and body mass were measured . STATISTICAL ANALYSIS In addition to descriptive statistics , analysis of variance was conducted to test for differences according to intervention group . RESULTS Of the 157 women with complete dietary data at baseline , 149 had complete data immediately postintervention ( at 4 months ) and 146 had complete data at 1 year . Women r and omized to NEP ( n = 50 ) experienced a large reduction in fat consumption ( 5.8 % of energy as fat ) at 4 months and much of this reduction was preserved at 1 year ( 4.1 % of energy ) ( both P < .0002 ) vs no change in either SRC ( n = 51 ) or UC ( n = 56 ) . A 1.3-kg reduction in body mass was evident at 4 months in the NEP group ( P = .003 ) vs no change in the SRC and UC groups . Women who had higher-than-average expectations of a beneficial effect of the intervention experienced larger changes . APPLICATIONS Dietitians ' use of group nutrition interventions appear to be warranted . Increasing their effectiveness and maintaining high levels of adherence may require additional support , including the involvement of significant others , periodic individual meetings , or group booster sessions Mindfulness-based stress reduction ( MBSR ) has been reported to reduce anxiety in a broad range of clinical population s. However , its efficacy in alleviating core symptoms of specific anxiety disorders is not well established . We conducted a r and omized trial to evaluate how well MBSR compared to a first-line psychological intervention for social anxiety disorder ( SAD ) . Fifty-three patients with DSM-IV generalized SAD were r and omized to an 8-week course of MBSR or 12 weekly sessions of cognitive-behavioral group therapy ( CBGT ) . Although patients in both treatment groups improved , patients receiving CBGT had significantly lower scores on clinician- and patient-rated measures of social anxiety . Response and remission rates were also significantly greater with CBGT . Both interventions were comparable in improving mood , functionality and quality of life . The results confirm that CBGT is the treatment of choice of generalized SAD and suggest that MBSR may have some benefit in the treatment of generalized SAD To comprehend the result of a r and omized controlled trial ( RCT ) , readers must underst and its design , conduct , analysis and interpretation . That goal can be achieved only through complete transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by using a checklist and flow diagram . The revised CONSORT statement presented in this article incorporates new evidence and addresses some criticism of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Comment . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage or participants through an RCT . The revised flow diagram depicts information from 4 stages of a trial ( enrollment , intervention allocation , follow-up and analysis ) . The diagram explicitly includes the number of participants , according to each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting or an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results & NA ; The objectives of this pilot study were to assess the feasibility of recruitment and adherence to an eight‐session mindfulness meditation program for community‐dwelling older adults with chronic low back pain ( CLBP ) and to develop initial estimates of treatment effects . It was design ed as a r and omized , controlled clinical trial . Participants were 37 community‐dwelling older adults aged 65 years and older with CLBP of moderate intensity occurring daily or almost every day . Participants were r and omized to an 8‐week mindfulness‐based meditation program or to a wait‐list control group . Baseline , 8‐week and 3‐month follow‐up measures of pain , physical function , and quality of life were assessed . Eighty‐nine older adults were screened and 37 found to be eligible and r and omized within a 6‐month period . The mean age of the sample was 74.9 years , 21/37 ( 57 % ) of participants were female and 33/37 ( 89 % ) were white . At the end of the intervention 30/37 ( 81 % ) participants completed 8‐week assessment s. Average class attendance of the intervention arm was 6.7 out of 8 . They meditated an average of 4.3 days a week and the average minutes per day was 31.6 . Compared to the control group , the intervention group displayed significant improvement in the Chronic Pain Acceptance Question naire Total Score and Activities Engagement subscale ( P = .008 , P = .004 ) and SF‐36 Physical Function ( P = .03 ) . An 8‐week mindfulness‐based meditation program is feasible for older adults with CLBP . The program may lead to improvement in pain acceptance and physical function Objective The objective of this study was to assess the effects of participation in a mindfulness meditation – based stress reduction program on mood disturbance and symptoms of stress in cancer out patients . Methods A r and omized , wait-list controlled design was used . A convenience sample of eligible cancer patients enrolled after giving informed consent and were r and omly assigned to either an immediate treatment condition or a wait-list control condition . Patients completed the Profile of Mood States and the Symptoms of Stress Inventory both before and after the intervention . The intervention consisted of a weekly meditation group lasting 1.5 hours for 7 weeks plus home meditation practice . Results Ninety patients ( mean age , 51 years ) completed the study . The group was heterogeneous in type and stage of cancer . Patients ’ mean preintervention scores on dependent measures were equivalent between groups . After the intervention , patients in the treatment group had significantly lower scores on Total Mood Disturbance and subscales of Depression , Anxiety , Anger , and Confusion and more Vigor than control subjects . The treatment group also had fewer overall Symptoms of Stress ; fewer Cardiopulmonary and Gastrointestinal symptoms ; less Emotional Irritability , Depression , and Cognitive Disorganization ; and fewer Habitual Patterns of stress . Overall reduction in Total Mood Disturbance was 65 % , with a 31 % reduction in Symptoms of Stress . Conclusions This program was effective in decreasing mood disturbance and stress symptoms in both male and female patients with a wide variety of cancer diagnoses , stages of illness , and ages OBJECTIVE Depressive symptoms are common among patients with fibromyalgia , and behavioral intervention has been recommended as a major treatment component for this illness . The objective of this study was to test the effects of the Mindfulness-Based Stress Reduction ( MBSR ) intervention on depressive symptoms in patients with fibromyalgia . METHODS This r and omized controlled trial examined effects of the 8-week MBSR intervention on depressive symptoms in 91 women with fibromyalgia who were r and omly assigned to treatment ( n = 51 ) or a waiting-list control group ( n = 40 ) . Eligible patients were at least 18 years old , willing to participate in a weekly group , and able to provide physician verification of a fibromyalgia diagnosis . Of 166 eligible participants who responded to local television news publicizing , 49 did not appear for a scheduled intake , 24 enrolled but did not provide baseline data , and 2 were excluded due to severe mental illness , leaving 91 participants . The sample averaged 48 years of age and had 14.7 years of education . The typical participant was white , married , and employed . Patients r and omly assigned to treatment received MBSR . Eight weekly 2.5-hour sessions were led by a licensed clinical psychologist with mindfulness training . Somatic and cognitive symptoms of depression were assessed using the Beck Depression Inventory administered at baseline , immediately postprogram , and at followup 2 months after the conclusion of the intervention . RESULTS Change in depressive symptoms was assessed using slopes analyses of intervention effects over time . Depressive symptoms improved significantly in treatment versus control participants over the 3 assessment s. CONCLUSION This meditation-based intervention alleviated depressive symptoms among patients with fibromyalgia This research examined whether cognitive behavioral therapy and mindfulness interventions that target responses to chronic stress , pain , and depression reduce pain and improve the quality of everyday life for adults with rheumatoid arthritis ( RA ) . The 144 RA participants were clustered into groups of 6 - 10 participants and r and omly assigned to 1 of 3 treatments : cognitive behavioral therapy for pain ( P ) ; mindfulness meditation and emotion regulation therapy ( M ) ; or education-only group ( E ) , which served as an attention placebo control . The authors took a multi method approach , employing daily diaries and laboratory assessment of pain and mitogen-stimulated levels of interleukin-6 ( IL-6 ) , a proinflammatory cytokine . Participants receiving P showed the greatest Pre to Post improvement in self-reported pain control and reductions in the IL-6 ; both P and M groups showed more improvement in coping efficacy than did the E group . The relative value of the treatments varied as a function of depression history . RA patients with recurrent depression benefited most from M across several measures , including negative and positive affect and physicians ' ratings of joint tenderness , indicating that the emotion regulation aspects of that treatment were most beneficial to those with chronic depressive features Abstract The goals of this work were to assess the effects of participation in a mindfulness meditation-based stress reduction program on mood disturbance and symptoms of stress in cancer out patients immediately after and 6 months after program completion . A convenience sample of eligible cancer patients were enrolled after they had given informed consent . All patients completed the Profile of Mood States ( POMS ) and Symptoms of Stress Inventory ( SOSI ) both before and after the intervention and 6 months later . The intervention consisted of a mindfulness meditation group lasting 1.5 h each week for 7 weeks , plus daily home meditation practice . A total of 89 patients , average age 51 , provided pre-intervention data . Eighty patients provided post-intervention data , and 54 completed the 6-month follow-up The participants were heterogeneous with respect to type and stage of cancer . Patients ' scores decreased significantly from before to after the intervention on the POMS and SOSI total scores and most subscales , indicating less mood disturbance and fewer symptoms of stress , and these improvements were maintained at the 6-month follow-up . More advanced stages of cancer were associated with less initial mood disturbance , while more home practice and higher initial POMS scores predicted improvements on the POMS between the pre- and post-intervention scores . Female gender and more education were associated with higher initial SOSI scores , and improvements on the SOSI were predicted by more education and greater initial mood disturbance . This program was effective in decreasing mood disturbance and stress symptoms for up to 6 months in both male and female patients with a wide variety of cancer diagnoses , stages of illness , and educational background , and with disparate ages |
1,093 | 29,104,864 | CT is still the st and ard method for the evaluation of therapy response despite its several limitations . | Purpose Improvement of the therapeutic approaches in gastrointestinal stromal tumors ( GIST ) by the introduction of targeted therapies requires appropriate diagnostic tools , which allow sufficient assessment of therapeutic response , including differentiation of true progression from pseudoprogression due to myxoid degeneration or intratumoral hemorrhage .
In this literature review the impact and limitations of different imaging modalities used in GIST therapy monitoring are discussed .
Results Morphological imaging modalities like computed tomography ( CT ) are primarily used for both diagnosis and therapy monitoring .
However , therapy with tyrosine kinase inhibitors and other targeted therapies in GIST may lead only to a minor tumor volume reduction even in cases of response .
Therefore , the use of Response Evaluation Criteria in Solid Tumors ( RECIST ) has limitations .
To overcome those limitations , modified response criteria have been introduced for the CT-based therapy assessment , like the Choi criteria as well as criteria based on dual energy CT studies .
Functional imaging techniques , mostly based on FDG PET-CT are in use , in particular for the assessment of early treatment response . | 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 of vascularised areas of GIST manifestations Purpose : To evaluate sunitinib activity and potential cellular and molecular correlates in gastrointestinal stromal tumor ( GIST ) patients after imatinib failure , in addition to assessing the safety and pharmacokinetics ( PK ) of different dose schedules . Experimental Design : In this open-label , dose-ranging , phase I/II study , 97 patients with metastatic imatinib-resistant/intolerant GIST received sunitinib at doses of 25 , 50 , or 75 mg/d on one of three schedules . Serial tumor imaging was done using computed tomography and [18F]fluoro-2-deoxy-d-glucose positron emission tomography scanning . PK and cell proliferation and KIT phosphorylation status in tumor biopsies were also analyzed . Results : Clinical benefit was observed in 52 patients ( 54 % : 7 objective partial responses , 45 stable disease ≥6 months ) . Decreased tumor glycolytic activity was shown in most patients within 7 days of starting sunitinib using [18F]fluoro-2-deoxy-d-glucose positron emission tomography . Sunitinib treatment was associated with reduced tumor cell proliferation by > 25 % in 52 % of cases analyzed and reduced levels of phospho-KIT in tumor biopsies ( indicating target modulation ) . The recommended dose schedule was 50 mg/d for 4 weeks followed by 2 weeks off treatment . On the 50-mg dose across all schedules , 79 % of PK-evaluable patients achieved total drug trough concentrations above the target concentration ( 50 ng/mL ) within 14 days of dosing . In addition , adverse events were generally mild to moderate in severity . Conclusion : Cellular and molecular analyses showed that sunitinib clinical activity is associated with inhibition of KIT in GIST following imatinib failure , illustrating the rational approach used to develop a therapy aim ed at the underlying oncogenic signaling pathway aberrancy . ( Clin Cancer Res 2009;15(18):5902–9 Purpose Gastrointestinal stromal tumours ( GIST ) are mesenchymal neoplasms of the gastrointestinal tract that are unresponsive to st and ard sarcoma chemotherapy . Imaging of GIST patients is done with structural and functional methods such as contrast-enhanced helical computed tomography ( ceCT ) and positron emission tomography ( PET ) with 18F-fluorodeoxyglucose ( FDG ) . The aim of this study was to compare the prognostic power of PET and ceCT and to evaluate the clinical role of PET/CT imaging . Methods All patients with GIST undergoing PET or PET/CT examinations were prospect ively included in this study , and the median overall survival , time to progression and treatment duration were documented . The prognostic significance of PET and ceCT criteria of treatment response was assessed and PET/CT was compared with PET and ceCT imaging . Data for 34 patients ( 19 male , 15 female , 21–76 years ) undergoing PET or PET/CT for staging or restaging were analysed . Results In 28 patients , PET/CT and ceCT were available after introduction of treatment with the tyrosine kinase inhibitor imatinib mesylate ( Gleevec ; Novartis , Basel , Switzerl and ) . Patients without FDG uptake after the start of treatment had a better prognosis than patients with residual activity . In contrast , ceCT criteria provided insufficient prognostic power . However , more lesions were found on ceCT images than on PET images , and FDG uptake was sometimes very variable . PET/CT delineated active lesions better than did the combination of PET and ceCT imaging . Conclusion Both PET and PET/CT provide important prognostic information and have an impact on clinical decision-making in GIST patients . PET/CT precisely delineates lesions and thus allows for the correct planning of surgical interventions BACKGROUND Gastrointestinal stromal tumors ( GISTs ) and desmoid tumors ( DTs ) are two rare mesenchymal tumor . Anecdotal reports of individuals with both diseases led us to make the hypothesis that the association is a nonr and om event as the probability would be extremely low to observe such cases if they were independent events . PATIENTS AND METHODS We evaluated the existence of patients with GIST and DT in a large multicenter cohort at 10 institutions in the United States , Australia and Europe . Data on gender , age at diagnosis , KIT , PDGFRA , CTNNB1 mutation status and follow-up time after diagnosis were collected . RESULTS We identified 28 patients diagnosed with both tumors . DT was diagnosed after GIST in 75 % of patients and concomitantly in 21 % . In only one case ( 4 % ) , GIST was diagnosed after DT . KIT or PDGFRA mutations were detected in 12 of 14 GIST , 9 in KIT exon 11 , 2 in KIT exon 9 and 1 in PDGFRA . CONCLUSION A statistical analysis of these 28 cases suggests a nonr and om association between GIST and DT . Further studies may be able to eluci date the underlying biology responsible for this association PURPOSE To prospect ively investigate the use of the apparent diffusion coefficient ( ADC ) as an early response indicator in patients with gastrointestinal stromal tumors ( GISTs ) treated with imatinib mesylate . MATERIAL S AND METHODS This study was approved by the institutional review board and written informed consent was obtained from all patients . Diffusion-weighted magnetic resonance ( MR ) imaging was performed in 32 patients with GISTs before and 1 , 4 , and 12 weeks after treatment with a tyrosine kinase inhibitor , imatinib mesylate . The measurable lesions were classified as having responded well or poorly according to size alterations at clinical evaluation following the first round of treatment ( 3 months ) . A linear mixed-effects model was applied to analyze changes in the ADCs of tumors during treatment and to compare the variation and slopes of the time-dependent ADC curves between the good- and poor-response groups . RESULTS There were 56 lesions in the good-response group and 35 in the poor-response group . An early ( 1 week after therapy ) noticeable and statistically significant ( P < .001 ) increase in the ADC was observed in the good-response group ( median ADC increase , 44.8 % ) but not in the poor-response group ( median ADC increase , 1.5 % ) . The time-dependent ADC variation was significantly different between the good- and poor-response groups , with a sharper median ADC increase displayed in the former ( week 1 : 44.8 % vs 1.5 % ; week 4 : 80.4 % vs 7.8 % ; week 12 : 89.6 % vs 16.7 % ; F = 25.78 , P < .001 ) . The largest difference in the weekly percentage increase in ADC between the good- and poor-response groups was observed at 1 week after therapy ( week 0 - 1 : 44.8 % vs 1.5 % ; week 1 - 4 : 7.0 % vs 2.8 % ; week 4 - 12 : 1.6 % vs 0.7 % ) . The pretherapy mean ADC ( ± st and ard deviation ) of lesions in the good-response group ( 1.06 [ ×10(-3 ) mm(2)/sec ] ± 0.27 ) was significantly lower than that in the poor-response group ( 1.24 [ ×10(-3 ) mm(2)/sec ] ± 0.32 ) ( F = 8.34 , P = .005 ) . CONCLUSION Comparatively low pretherapy ADC and marked ADC increase at 1 week after therapy is associated with good response to imatinib mesylate in patients with GISTs Purpose : Cediranib is a potent VEGF signaling inhibitor with activity against all three VEGF receptors and KIT . This phase II study evaluated the antitumor activity of cediranib in patients with metastatic gastrointestinal stromal tumor ( GIST ) resistant/intolerant to imatinib , or metastatic soft-tissue sarcomas ( STS ; Clinical Trials.gov , NCT00385203 ) . Experimental Design : Patients received cediranib 45 mg/day . Primary objective was to determine the antitumor activity of cediranib according to changes in 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography ( 18FDG-PET ) tumor uptake in patients with GIST using maximum st and ardized uptake values ( SUVmax ) . Secondary objectives included objective tumor response and tolerability in patients with GIST/STS . Results : Thirty-four of 36 enrolled patients were treated ( GIST n = 24 ; STS n = 10 ) . At day 29 , five patients had confirmed decreases in SUVmax ( ≥10 % from day 8) and two had confirmed partial metabolic responses ( ≥25 % decrease ) , but arithmetic mean percentage changes in SUVmax , averaged across the cohort , were not significant at day 8 [ 6.8 % ; 95 % confidence interval ( CI ) , 19.95–33.54 ) or day 29 ( 4.6 % ; 95 % CI , 8.05–17.34 ) . Eleven patients with GIST achieved a best objective tumor response of stable disease ; eight achieved stable disease ≥16 weeks . In patients with STS , four of six with alveolar soft-part sarcoma ( ASPS ) achieved confirmed and durable partial responses . The commonest adverse events were diarrhea ( 85 % ) , fatigue ( 74 % ) , and hypertension ( 68 % ) . Conclusions : In patients progressing on imatinib/sunitinib , cediranib 45 mg/day demonstrated evidence of activity by 18FDG-PET , but did not reduce average SUVmax . Evidence of antitumor activity was seen in ASPS . Clin Cancer Res ; 20(13 ) ; 3603–12 . © 2014 AACR PURPOSE To compare performance of various tumour response criteria ( TRCs ) in assessment of regorafenib activity in patients with advanced gastrointestinal stromal tumour ( GIST ) with prior failure of imatinib and sunitinib . METHODS Twenty participants in a phase II trial received oral regorafenib ( median duration 47 weeks ; interquartile range ( IQR ) 24 - 88 ) with computed tomography ( CT ) imaging at baseline and every two months thereafter . Tumour response was prospect ively determined on using Response Evaluation Criteria in Solid Tumours ( RECIST ) 1.1 , and retrospectively reassessed for comparison per RECIST 1.0 , World Health Organization ( WHO ) and Choi criteria , using the same target lesions . Clinical benefit rate [ CBR ; complete or partial response ( CR or PR ) or stable disease (SD)≥16 weeks ] and progression-free survival ( PFS ) were compared between various TRCs using kappa statistics . Performance of TRCs in predicting overall survival ( OS ) was compared by comparing OS in groups with progression-free intervals less than or greater than 20 weeks by each TRC using c-statistics . RESULTS PR was more frequent by Choi ( 90 % ) than RECIST 1.1 , RECIST 1.0 and WHO ( 20 % each ) , however , CBR was similar between various TRCs ( overall CBR 85 - 90 % , 95 - 100 % agreement between all TRC pairs ) . PFS per RECIST 1.0 was similar to RECIST 1.1 ( median 44 weeks versus 58 weeks ) , and shorter for WHO ( median 34 weeks ) and Choi ( median 24 weeks ) . With RECIST 1.1 , RECIST 1.0 and WHO , there was moderate concordance between PFS and OS ( c-statistics 0.596 - 0.679 ) . Choi criteria had less favourable concordance ( c-statistic 0.506 ) . CONCLUSIONS RECIST 1.1 and WHO performed somewhat better than Choi criteria as TRC for response evaluation in patients with advanced GIST after prior failure on imatinib and sunitinib PURPOSE From February 2001 to February 2002 , 946 patients with advanced GI stromal tumors ( GISTs ) treated with imatinib were included in a controlled EORTC/ISG/AGITG ( European Organisation for Research and Treatment of Cancer/Italian Sarcoma Group/Australasian Gastro-Intestinal Trials Group ) trial . This analysis investigates whether the response classification assessed by RECIST ( Response Evaluation Criteria in Solid Tumors ) , predicts for time to progression ( TTP ) and overall survival ( OS ) . PATIENTS AND METHODS Per protocol , the first three disease assessment s were done at 2 , 4 , and 6 months . For the purpose of the analysis ( l and mark method ) , disease response was subclassified in six categories : partial response ( PR ; > 30 % size reduction ) , minor response ( MR ; 10 % to 30 % reduction ) , no change ( NC ) as either NC- ( 0 % to 10 % reduction ) or NC+ ( 0 % to 20 % size increase ) , progressive disease ( PD ; > 20 % increase/new lesions ) , and subjective PD ( clinical progression ) . RESULTS A total of 906 patients had measurable disease at entry . At all measurement time points , complete response ( CR ) , PR , and MR result ed in similar TTP and OS ; this was also true for NC- and NC+ , and for PD and subjective PD . Patients were subsequently classified as responders ( CR/PR/MR ) , NC ( NC+/NC- ) , or PD . This three-class response categorization was found to be highly predictive of further progression or survival for the first two measurement points . After 6 months of imatinib , responders ( CR/PR/MR ) had the same survival prognosis as patients classified as NC . CONCLUSION RECIST perfectly enables early discrimination between patients who benefited long term from imatinib and those who did not . After 6 months of imatinib , if the patient is not experiencing PD , the pattern of radiologic response by tumor size criteria has no prognostic value for further outcome . Imatinib needs to be continued as long as there is no progression according to RECIST Gastrointestinal stromal tumor ( GIST ) is the most common sarcoma arising in the gastrointestinal ( GI ) tract . Imatinib mesylate ( imatinib ) is efficacious in treating advanced and metastatic GIST . Patients undergoing resection of GIST realize a highly variable median disease-free survival ( DFS ) . In the absence of prospect i ve data , we conducted a r and omized , phase II study to assess the safety and efficacy of preoperative and postoperative imatinib for the treatment of GIST . Nineteen GIST patients undergoing surgical resection were r and omized to receive 3 , 5 , or 7 days of preoperative imatinib ( 600 mg daily ) . Patients received postoperative imatinib for 2 years . Perioperative adverse events were compared with those in an imatinib-naïve historical control . The efficacy of imatinib was assessed by 18fluorodeoxyglucose positron emission tomography ( 18FDG-PET ) , dynamic computed tomography ( dCT ) , terminal deoxynucleotidyl transferase dUTP nick end labeling ( TUNEL ) assay , and DFS . Imatinib did not affect surgical morbidity as compared with an imatinib-naïve cohort ( p ≥ 0.1 ) . Most patients responded to preoperative imatinib by 18FDG-PET and dCT ( 69 % and 71 % , respectively ) . Tumor cell apoptosis increased by an average of 12 % ( range 0–33 % ) and correlated with the duration of preoperative imatinib ( p = 0.04 ) . Median DFS of patients treated with surgery and imatinib was 46 months ( range 10–46 months ) . Tumor size was a predictor of recurrence after postoperative imatinib ( p = 0.02 ) . Imatinib appears to be safe and may be considered for patients undergoing surgical resection of their GIST . Radiographic response and tumor cell apoptosis occur within the first week of imatinib therapy OBJECTIVE We correlated changes in tumor density on CT with changes in glucose metabolism , or the maximum st and ardized uptake value ( SUV(max ) ) , on FDG PET and sought to develop CT imaging criteria that can be used to objective ly evaluate tumor response in patients with metastatic gastrointestinal stromal tumors ( GISTs ) who undergo treatment with imatinib mesylate . MATERIAL S AND METHODS Using the criteria established by the Response Evaluation Criteria in Solid Tumors ( RECIST ) group , we selected 173 tumors ( in 36 patients ) for study . Tumor size and density were determined objective ly , and overall tumor response ( OTR ) was evaluated subjectively on CT images . The changes in these parameters before and after treatment were correlated with changes in SUV(max ) . RESULTS Significant decreases were seen in both tumor density ( mean , 12.3 H [ 16.5 % ] ; p < 0.0001 ) and SUV(max ) ( mean , 3.43 [ 64.9 % ] ; p < 0.0001 ) . OTR evaluated subjectively , correlated well with changes in SUV(max ) ( p < 0.0001 ) . No statistically significant association was found between changes in tumor density and changes in SUV(max ) ( p = 0.3088 ) , but 70 % ( 14/20 ) of the patients with tumors that showed response on FDG PET exhibited at least a partial response by a change in tumor density . Tumor size was found to have decreased significantly 2 months after treatment ( p = 0.0070 ) . However , in 75 % of the patients , the disease was stable according to the traditional tumor response criteria of RECIST . CONCLUSION FDG PET is sensitive and specific for evaluating tumor response but can not be used in patients whose baseline FDG PET results are negative for tumors . Although subjective evaluation was a better indicator of treatment response than was tumor density alone , the tumor density measurement is a good indicator and provides a reliable quantitative means of monitoring the tumor . RECIST , using only tumor size , was unreliable for monitoring GISTs during the early stage of imatinib mesylate treatment Purpose : Heat shock protein 90 ( HSP90 ) is required for the proper folding , function , and stability of various client proteins , two of which ( KIT and PDGFRα ) are critical in the pathogenesis and progression of gastrointestinal stromal tumors ( GIST ) . This phase I study investigated the safety and maximum tolerated dose ( MTD ) of retaspimycin hydrochloride ( IPI-504 ) , a novel potent and selective HSP90 inhibitor , in patients with metastatic and /or unresectable GIST or other soft-tissue sarcomas ( STS ) . Experimental Design : IPI-504 was administered intravenously at doses ranging from 90 to 500 mg/m2 twice weekly for 2 weeks on/1 week off . Safety , pharmacokinetic , and pharmacodynamic profiles were determined . Response was assessed by Response Evaluation Criteria for Solid Tumors ( RECIST ) 1.0 and optionally via 18-fluorodeoxyglucose positron emission tomography ( 18-FDG-PET ) imaging . Results : Fifty-four patients received IPI-504 ; 37 with GIST and 17 with other STS . The MTD was 400 mg/m2 twice weekly for 2 weeks on/1 week off . Common related adverse events were fatigue ( 59 % ) , headache ( 44 % ) , and nausea ( 43 % ) . Exposure to IPI-504 , 17-AAG , and 17-AG increased with IPI-504 dose . Stable disease ( SD ) was observed in 70 % ( 26 of 37 ) of patients with GIST and 59 % ( 10 of 17 ) of patients with STS . There was one confirmed partial response ( PR ) in a patient with GIST and one PR in a patient with liposarcoma . Metabolic partial responses occurred in 11 of 29 ( 38 % ) patients with GIST . Conclusions : In this study of advanced GIST or other STS , IPI-504 was generally well-tolerated with some evidence of antitumor activity , serving as a clinical proof-of-concept that HSP90 inhibition remains a promising strategy . Clin Cancer Res ; 19(21 ) ; 6020–9 . © 2013 AACR UNLABELLED This study was implemented to compare the value of PET , CT , and dual-modality PET/CT imaging for assessing gastrointestinal stromal tumor ( GIST ) response to imatinib therapy . METHODS Twenty patients with histologically proven GIST underwent (18)F-FDG PET/CT imaging before and 1 , 3 , and 6 mo after the start of imatinib therapy . Separate PET and CT data sets , side-by-side PET and CT data sets , and fused PET/CT images were evaluated according to World Health Organization , Response Evaluation Criteria in Solid Tumors , and European Organisation for Research and Treatment of Cancer criteria for therapy response . Hounsfield units ( HU ) were assessed on CT images . A mean follow-up period of 381 + /- 134 d served as the st and ard of reference . RESULTS The numbers of lesions detected in all patients were 135 with PET , 249 with CT , 279 on side-by-side evaluation , and 282 on fused PET/CT images . Tumor response was correctly characterized in 95 % of patients after 1 mo and 100 % after 3 and 6 mo with PET/CT . PET and CT images viewed side by side were correct in 90 % of patients at 1 mo and 100 % at 3 and 6 mo . PET accurately diagnosed tumor response in 85 % of patients at 1 mo and 100 % at 3 and 6 mo . CT was found to be accurate in 44 % of patients at 1 mo , 60 % at 3 mo , and 57 % at 6 mo . HU were found to decrease by at least 25 % in 12 of 14 responders after 1 mo . CONCLUSION Tumor response to imatinib should be assessed with a combination of morphologic and functional imaging . Image fusion with combined PET/CT can provide additional information in individual cases when compared with side-by-side PET and CT Background The new anti-cancer drug imatinib mesylate inhibits the tyrosine kinase growth factor receptor , c-KIT , and has shown spectacular activity in patients with gastrointestinal stromal tumours ( GISTs ) . Objective To assess whether fluorodeoxyglucose positron emission tomography ( FDG PET ) is suitable for response evaluation of this new type of tumour treatment . Methods Sixteen consecutive patients with irresectable or metastasized GIST or another c-KIT ( CD117 ) positive mesenchymal tumour underwent FDG PET before and 1 week after the start of treatment with imatinib mesylate ( Glivec ® ) . Visual findings and st and ard uptake values ( SUVs ) were compared with the overall response to treatment , based on clinical and radiological response . Results PET visualized all known and some unknown tumour locations . The separation by PET after 1 week of treatment in ‘ PET responders ’ ( 11/16 patients , mean SUV reduction 65 % ) versus ‘ PET non-responders ’ ( 5/16 patients , mean SUV increase 16 % ) appeared to match almost perfectly with overall treatment response and proved correct in 14/15 patients ( prediction sensitivity 93 % ) . FDG uptake changes after 1 week of treatment were of greater magnitude than tumour volume changes on computed tomography at 8 weeks . Progression-free survival was significantly better in patients with a PET response ( P=0.002 ) . PET response predicted treatment outcome better than the radiological response . Finally , PET was helpful during follow-up , in discriminating side effects from tumour progression . Conclusion FDG PET is a valuable tool in patients with gastrointestinal stromal tumours treated with imatinib mesylate . It improves staging , accurately separates responders from non-responders in an early phase , and is helpful during follow-up Imatinib mesylate ( Glivec , formerly STI571 ) is the first effective systemic treatment for gastrointestinal stromal tumours ( GISTs ) . Major changes in tumour volume , however , tend to occur late after the start of treatment . The aim of this study was to evaluate if [18F]-fluorodeoxyglucose-positron emission tomography ( FDG-PET ) can be used for the early evaluation of response to imatinib mesylate treatment in soft-tissue sarcomas ( STS ) . 21 patients ( 17 GIST , 4 other STS ) underwent FDG-PET imaging prior to and 8 days after the start of treatment . PET response ( European Organization for Research and Treatment ( EORTC ) guidelines ) was observed in 13 GISTs ( 11 Complete Responders , 2 partial responders . Subsequent computerised tomography ( CT ) response Response Evaluation Criteria in Solid Tumours ( RECIST ) was observed in 10 of these patients after a median follow up of 8 weeks . Stable or progressive disease was observed on PET in 8 patients and none of them achieved a response on CT . PET response was also associated with a longer progression-free survival ( PFS ) ( 92 % versus 12 % at 1 year , P=0.00107 ) . We conclude that FDG-PET is an early and sensitive method to evaluate an early response to imatinib treatment PURPOSE Positron emission tomography with (18)F-fluorodeoxyglucose ( FDG-PET ) was used to evaluate treatment response in patients with gastrointestinal stromal tumors ( GIST ) after administration of sunitinib , a multitargeted tyrosine kinase inhibitor , after imatinib failure . PATIENTS AND METHODS Tumor metabolism was assessed with FDG-PET before and after the first 4 weeks of sunitinib therapy in 23 patients who received one to 12 cycles of sunitinib therapy ( 4 weeks of 50 mg/d , 2 weeks off ) . Treatment response was expressed as the percent change in maximal st and ardized uptake values ( SUV ) . The primary end point of time to tumor progression was compared with early PET results on the basis of traditional Response Evaluation Criteria in Solid Tumors ( RECIST ) criteria . RESULTS Progression-free survival ( PFS ) was correlated with early FDG-PET metabolic response ( P < .0001 ) . Using -25 % and + 25 % thresholds for SUV variations from baseline , early FDG-PET response was stratified in metabolic partial response , metabolically stable disease , or metabolically progressive disease ; median PFS rates were 29 , 16 , and 4 weeks , respectively . Similarly , when a single FDG-PET positive/negative was considered after 4 weeks of sunitinib , the median PFS was 29 weeks for SUVs less than 8 g/mL versus 4 weeks for SUVs of 8 g/mL or greater ( P < .0001 ) . None of the patients with metabolically progressive disease subsequently responded according to RECIST criteria . Multivariate analysis showed shorter PFS in patients who had higher residual SUVs ( P < .0001 ) , primary resistance to imatinib ( P = .024 ) , or nongastric GIST ( P = .002 ) , regardless of the mutational status of the KIT and PDGFRA genes . CONCLUSION Week 4 FDG-PET is useful for early assessment of treatment response and for the prediction of clinical outcome . Thus , it offers opportunities to individualize and optimize patient therapy |
1,094 | 26,384,035 | 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 . | BACKGROUND Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis ( RRMS ) , including immunomodulators , immunosuppressants and biologics .
Although there is consensus that these therapies reduce the frequency of relapses , their relative benefit in delaying new relapses or disability worsening remains unclear due to the limited number of direct comparison trials .
OBJECTIVES To compare the benefit and acceptability of interferon beta-1b , interferon beta-1a ( Avonex , Rebif ) , glatiramer acetate , natalizumab , mitoxantrone , fingolimod , teriflunomide , dimethyl fumarate , alemtuzumab , pegylated interferon beta-1a , daclizumab , laquinimod , azathioprine and immunoglobulins for the treatment of people with RRMS and to provide a ranking of these treatments according to their benefit and acceptability , defined as the proportion of participants who withdrew due to any adverse event .
First , the benefit of all of these treatments beyond two years is uncertain and this is a relevant issue for a disease with a duration of 30 to 40 years . | 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 % ) of 231 patients r and omly allocated interferon beta 1a and 426 ( 98 % ) of 436 patients r and omly allocated alemtuzumab 12 mg were included in the primary analyses . 104 ( 51 % ) patients in the interferon beta 1a group relapsed ( 201 events ) compared with 147 ( 35 % ) patients in the alemtuzumab group ( 236 events ; rate ratio 0·51 [ 95 % CI 0·39 - 0·65 ] ; p<0·0001 ) , corresponding to a 49·4 % improvement with alemtuzumab . 94 ( 47 % ) patients in the interferon beta 1a group were relapse-free at 2 years compared with 278 ( 65 % ) patients in the alemtuzumab group ( p<0·0001 ) . 40 ( 20 % ) patients in the interferon beta 1a group had sustained accumulation of disability compared with 54 ( 13 % ) in the alemtuzumab group ( hazard ratio 0·58 [ 95 % CI 0·38 - 0·87 ] ; p=0·008 ) , corresponding to a 42 % improvement in the alemtuzumab group . For 435 patients allocated alemtuzumab 12 mg , 393 ( 90 % ) had infusion-associated reactions , 334 ( 77 % ) had infections ( compared with 134 [ 66 % ] of 202 patients in the interferon beta 1a group ) that were mostly mild-moderate with none fatal , 69 ( 16 % ) had thyroid disorders , and three ( 1 % ) had immune thrombocytopenia . INTERPRETATION For patients with first-line treatment-refractory relapsing-remitting multiple sclerosis , alemtuzumab could be used to reduce relapse rates and sustained accumulation of disability . Suitable risk management strategies allow for early identification of alemtuzumab 's main adverse effect of secondary autoimmunity . FUNDING Genzyme ( Sanofi ) and Bayer Schering Pharma BACKGROUND BG-12 ( dimethyl fumarate ) was shown to have antiinflammatory and cytoprotective properties in pre clinical experiments and to result in significant reductions in disease activity on magnetic resonance imaging ( MRI ) in a phase 2 , placebo-controlled study involving patients with relapsing-remitting multiple sclerosis . METHODS We conducted a r and omized , double-blind , placebo-controlled phase 3 study involving patients with relapsing-remitting multiple sclerosis . Patients were r and omly assigned to receive oral BG-12 at a dose of 240 mg twice daily , BG-12 at a dose of 240 mg three times daily , or placebo . The primary end point was the proportion of patients who had a relapse by 2 years . Other end points included the annualized relapse rate , the time to confirmed progression of disability , and findings on MRI . RESULTS The estimated proportion of patients who had a relapse was significantly lower in the two BG-12 groups than in the placebo group ( 27 % with BG-12 twice daily and 26 % with BG-12 thrice daily vs. 46 % with placebo , P<0.001 for both comparisons ) . The annualized relapse rate at 2 years was 0.17 in the twice-daily BG-12 group and 0.19 in the thrice-daily BG-12 group , as compared with 0.36 in the placebo group , representing relative reductions of 53 % and 48 % with the two BG-12 regimens , respectively ( P<0.001 for the comparison of each BG-12 regimen with placebo ) . The estimated proportion of patients with confirmed progression of disability was 16 % in the twice-daily BG-12 group , 18 % in the thrice-daily BG-12 group , and 27 % in the placebo group , with significant relative risk reductions of 38 % with BG-12 twice daily ( P=0.005 ) and 34 % with BG-12 thrice daily ( P=0.01 ) . BG-12 also significantly reduced the number of gadolinium-enhancing lesions and of new or enlarging T(2)-weighted hyperintense lesions ( P<0.001 for the comparison of each BG-12 regimen with placebo ) . Adverse events associated with BG-12 included flushing and gastrointestinal events , such as diarrhea , nausea , and upper abdominal pain , as well as decreased lymphocyte counts and elevated liver aminotransferase levels . CONCLUSIONS In patients with relapsing-remitting multiple sclerosis , both BG-12 regimens , as compared with placebo , significantly reduced the proportion of patients who had a relapse , the annualized relapse rate , the rate of disability progression , and the number of lesions on MRI . ( Funded by Biogen Idec ; DEFINE Clinical Trials.gov number , NCT00420212 . ) 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 Objective : To measure the effects of disease-modifying drugs ( DMDs ) on the development of cortical lesions ( CL ) and cortical atrophy in patients with relapsing – remitting multiple sclerosis ( RRMS ) . Methods : RRMS patients ( n = 165 ) were r and omized to subcutaneous ( sc ) interferon ( IFN ) beta-1a ( 44 mcg three times weekly ) , intramuscular ( i m ) IFN beta-1a ( 30 mcg weekly ) or glatiramer acetate ( GA ; 20 mg daily ) . The reference population comprised 50 untreated patients . Clinical and MRI examinations were performed at baseline , 12 months and 24 months . Results : One hundred and forty-one treated patients completed the study . After 12 months , 37/50 ( 74 % ) of untreated patients developed ≥1 new CL ( mean 1.6 ) , compared with 30/47 ( 64 % ) of i m IFN beta-1a-treated patients ( mean 1.2 , p = 0.021 ) , 24/48 ( 50 % ) of GA-treated patients ( mean 0.8 , p = 0.001 ) and 12/46 ( 26 % ) of sc IFN beta-1a-treated patients ( mean 0.4 , p < 0.001 ) . After 24 months , ≥1 new CL was observed in 41/50 ( 82 % ) of untreated ( mean 3.0 ) , 34/47 ( 72 % ) of i m IFN beta-1a-treated ( mean 1.6 , p < 0.001 ) , 30/48 ( 62 % ) of GA-treated ( mean 1.3 , p < 0.001 ) and 24/46 ( 52 % ) of sc IFN beta-1a-treated patients ( mean 0.8 , p < 0.001 ) . Mean grey matter fraction decrease in DMD-treated patients at 24 months ranged from 0.7 to 0.8 versus 1.0 in untreated patients ( p = 0.023 ) . Conclusions : Disease-modifying drugs significantly decreased new CL development and cortical atrophy progression compared with untreated patients , with faster and more pronounced effects seen with sc IFN beta-1a than with i m IFN beta-1a or GA BACKGROUND Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis , but the drug can induce neutralising antibodies against itself , which might reduce effectiveness . We aim ed to assess the clinical effect of neutralising antibodies . METHODS We measured neutralising antibodies every 12 months for up to 60 months in 541 patients with multiple sclerosis , r and omly selected from all patients who started treatment with interferon beta between 1996 and 1999 . Patients left the study if they changed or discontinued therapy . Antibodies were measured blindly , using antiviral neutralisation bioassays with high , medium , and low sensitivity , and with different neutralising capacities as cutoff value for definition of a neutralising-antibody-positive result . FINDINGS Patients developed neutralising antibodies independent of age , sex , disease duration , and progression index at start of treatment . Relapse rates were significantly higher during antibody-positive periods ( 0.64 - 0.70 ) than they were during antibody-negative periods ( 0.43 - 0.46 ; p<0.03 ) . When comparing the number of relapses in the neutralising-antibody-positive and neutralising-antibody-negative periods we found odds ratios in the range 1.51 to 1.58 ( p<0.03 ) . Time to first relapse was significantly increased by 244 days in patients who were antibody-negative at 12 months ( log rank test 6.83 , p=0.009 ) . During this short-term study , presence of neutralising antibodies did not affect disease progression measured with the exp and ed disability status scale . INTERPRETATION Our findings suggest that the presence of neutralising antibodies against interferon beta reduces the clinical effect of the drug . In patients who are not doing well on interferon beta , the presence of such antibodies should prompt consideration about change of treatment BACKGROUND Daclizumab , a humanised monoclonal antibody , modulates interleukin-2 signalling by blocking the α subunit ( CD25 ) of the interleukin-2 receptor . We assessed whether daclizumab high-yield process ( HYP ) would be effective when given as monotherapy for a 1 year treatment period in patients with relapsing-remitting multiple sclerosis . METHODS We did a r and omised , double-blind , placebo-controlled trial at 76 centres in the Czech Republic , Germany , Hungary , India , Pol and , Russia , Ukraine , Turkey , and the UK between Feb 15 , 2008 , and May 14 , 2010 . Patients aged 18 - 55 years with relapsing-remitting multiple sclerosis were r and omly assigned ( 1:1:1 ) , via a central interactive voice response system , to subcutaneous injections of daclizumab HYP 150 mg or 300 mg , or placebo , every 4 weeks for 52 weeks . Patients and study personnel were masked to treatment assignment , except for the site pharmacist who prepared the study drug for injection , but had no interaction with the patient . The primary endpoint was annualised relapse rate . Analysis was by intention to treat . The trial is registered with Clinical Trials.gov , number NCT00390221 . FINDINGS 204 patients were assigned to receive placebo , 208 to daclizumab HYP 150 mg , and 209 to daclizumab HYP 300 mg , of whom 188 ( 92 % ) , 192 ( 92 % ) , and 197 ( 94 % ) , respectively , completed follow-up to week 52 . The annualised relapse rate was lower for patients given daclizumab HYP 150 mg ( 0·21 , 95 % CI 0·16 - 0·29 ; 54 % reduction , 95 % CI 33 - 68 % ; p<0·0001 ) or 300 mg ( 0·23 , 0·17 - 0·31 , 50 % reduction , 28 - 65 % ; p=0·00015 ) than for those given placebo ( 0·46 , 0·37 - 0·57 ) . More patients were relapse free in the daclizumab HYP 150 mg ( 81 % ) and 300 mg ( 80 % ) groups than in the placebo group ( 64 % ; p<0·0001 in the 150 mg group and p=0·0003 in the 300 mg group ) . 12 ( 6 % ) patients in the placebo group , 15 ( 7 % ) of those in the daclizumab 150 mg group , and 19 ( 9 % ) in the 300 mg group had serious adverse events excluding multiple sclerosis relapse . One patient given daclizumab HYP 150 mg who was recovering from a serious rash died because of local complication of a psoas abscess . INTERPRETATION Subcutaneous daclizumab HYP administered every 4 weeks led to clinical ly important effects on multiple sclerosis disease activity during 1 year of treatment . Our findings support the potential for daclizumab HYP to offer an additional treatment option for relapsing-remitting disease . FUNDING Biogen Idec and AbbVie Biotherapeutics 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 . ) To evaluate the safety , tolerability , and efficacy of glatiramer acetate ( GA ) 40 mg compared to a 20 mg dose A pilot study was undertaken to test the safety and establish the side effect profile of recombinant human interferon-beta 1b ( Betaseron , Berlex Laboratories , Richmond , CA ) , in patients with relapsing-remitting multiple sclerosis ( RRMS ) . During the initial dose finding period ( 24 weeks ) , five groups of 6 patients each were treated by subcutaneous injection three times each week with either 0.8 , 4 , 8 , or 16 million units ( mU ) of Betaseron or placebo ( WHO St and ard ) . Although some side effects were noted in all groups , a dose-related trend in reduction of exacerbation frequency and side-effect profile was noted . Patients given 16 mU had no exacerbations during the initial dosing period , but associated side effects led to dose reduction or dropout . An 8 mU dose was selected for further study after 24 weeks , and continuous dosing at 8 mU in 15 patients has now exceeded 6 years . Side effects abated over time . Neutralizing antibody developed in most patients , but titers were variable , fluctuated independently of clinical course , and tended to fall with prolonged treatment . A dose-dependent rise in neopterin levels was observed during the initial dosing period . This pilot study has demonstrated responsiveness to Betaseron , shown a stable safety profile over time , and established guidelines for a dosing regimen to evaluate and optimize further the efficacy of Betaseron in RRMS The phase III placebo-controlled BRAVO study assessed laquinimod effects in patients with relapsing-remitting MS ( RRMS ) , and descriptively compared laquinimod with interferon beta (IFNβ)-1a ( Avonex ® reference arm ) . RRMS patients age 18–55 years with Exp and ed Disability Status Scale ( EDSS ) scores of 0–5.5 and documented pre- study relapse ( ≥ 1 in previous year , 2 in previous 2 years , or 1 in previous 1–2 years and ≥ 1 GdE lesion in the previous year ) were r and omized ( 1:1:1 ) to laquinimod 0.6 mg once-daily , matching oral placebo , or IFNβ-1a IM 30 μg once-weekly ( rater-blinded design ) , for 24 months . The primary endpoint was annualized relapse rate ( ARR ) ; secondary endpoints included percent brain volume change ( PBVC ) and 3-month confirmed disability worsening . In all , 1,331 patients were r and omized : laquinimod ( n = 434 ) , placebo ( n = 450 ) , and IFNβ-1a ( n = 447 ) . ARR was not significantly reduced with laquinimod [ −18 % , risk ratio ( RR ) = 0.82 , 95 % CI 0.66–1.02 ; p = 0.075 ] vs. placebo . Laquinimod significantly reduced PBVC ( 28 % , p < 0.001 ) . Confirmed disability worsening was infrequent ( 10 % laquinimod , 13 % placebo ) . The change in confirmed disability worsening with laquinimod measured using EDSS was −31 % [ hazard ratio ( HR ) 0.69 , p = 0.063 ] , and using Multiple Sclerosis Functional Composite ( MSFC ) z-score was −77 % ( p = 0.150 ) , vs. placebo . IFNβ-1a reduced ARR 26 % ( RR = 0.74 , 95 % CI 0.60–0.92 , p = 0.007 ) , showed no effect on PBVC loss ( + 11 % , p = 0.14 ) , and changes in disability worsening were −26 and −66 % as measured using the EDSS ( HR 0.742 , p = 0.13 ) and MSFC ( p = 0.208 ) , respectively . Adverse events occurred in 75 , 82 , and 70 % of laquinimod , IFNβ-1a , and placebo patients , respectively . Once-daily oral laquinimod 0.6 mg result ed in statistically nonsignificant reductions in ARR and disability progression , but significant reductions in brain atrophy vs. placebo . Laquinimod was well-tolerated For almost three decades in many countries azathioprine has been used to treat relapsing-remitting multiple sclerosis . However its efficacy was usually considered marginal and following approval of β interferons for this indication it was no longer recommended as first line treatment , even if presently no conclusive direct β interferon-azathioprine comparison exists . To compare azathioprine efficacy versus the currently available β interferons in relapsing-remitting multiple sclerosis , a multicenter , r and omized , controlled , single-blinded , non-inferiority trial was conducted in 30 Italian multiple sclerosis centers . Eligible patients ( relapsing-remitting course ; ≥2 relapses in the last 2 years ) were r and omly assigned to azathioprine or β interferons . The primary outcome was annualized relapse rate ratio ( RR ) over 2 years . Key secondary outcome was number of new brain MRI lesions . Patients ( n = 150 ) were r and omized in 2 groups ( 77 azathioprine , 73 β interferons ) . At 2 years , clinical evaluation was completed in 127 patients ( 62 azathioprine , 65 β interferons ) . Annualized relapse rate was 0.26 ( 95 % Confidence Interval , CI , 0.19–0.37 ) in the azathioprine and 0.39 ( 95 % CI 0.30–0.51 ) in the interferon group . Non-inferiority analysis showed that azathioprine was at least as effective as β interferons ( relapse RRAZA/IFN 0.67 , one-sided 95 % CI 0.96 ; p<0.01 ) . MRI outcomes were analyzed in 97 patients ( 50 azathioprine and 47 β interferons ) . Annualized new T2 lesion rate was 0.76 ( 95 % CI 0.61–0.95 ) in the azathioprine and 0.69 ( 95 % CI 0.54–0.88 ) in the interferon group . Treatment discontinuations due to adverse events were higher ( 20.3 % vs. 7.8 % , p = 0.03 ) in the azathioprine than in the interferon group , and concentrated within the first months of treatment , whereas in the interferon group discontinuations occurred mainly during the second year . The results of this study indicate that efficacy of azathioprine is not inferior to that of β interferons for patients with relapsing-remitting multiple sclerosis . Considering also the convenience of the oral administration , and the low cost for health service providers , azathioprine may represent an alternative to interferon treatment , while the different side effect profiles of both medications have to be taken into account . Trial Registration EudraCT 2006 - 004937 - BACKGROUND The anti-CD52 monoclonal antibody alemtuzumab reduced disease activity in a phase 2 trial of previously untreated patients with relapsing-remitting multiple sclerosis . We aim ed to assess efficacy and safety of first-line alemtuzumab compared with interferon beta 1a in a phase 3 trial . METHODS In our 2 year , rater-masked , r and omised controlled phase 3 trial , we enrolled adults aged 18 - 50 years with previously untreated relapsing-remitting multiple sclerosis . Eligible participants were r and omly allocated in a 2:1 ratio by an interactive voice response system , stratified by site , to receive intravenous alemtuzumab 12 mg per day or subcutaneous interferon beta 1a 44 μg . Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and once per day for 3 days at 12 months . Co primary endpoints were relapse rate and time to 6 month sustained accumulation of disability in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT00530348 . FINDINGS 187 ( 96 % ) of 195 patients r and omly allocated interferon beta 1a and 376 ( 97 % ) of 386 patients r and omly allocated alemtuzumab were included in the primary analyses . 75 ( 40 % ) patients in the interferon beta 1a group relapsed ( 122 events ) compared with 82 ( 22 % ) patients in the alemtuzumab group ( 119 events ; rate ratio 0·45 [ 95 % CI 0·32 - 0·63 ] ; p<0.0001 ) , corresponding to a 54·9 % improvement with alemtuzumab . Based on Kaplan-Meier estimates , 59 % of patients in the interferon beta 1a group were relapse-free at 2 years compared with 78 % of patients in the alemtuzumab group ( p<0·0001 ) . 20 ( 11 % ) of patients in the interferon beta 1a group had sustained accumulation of disability compared with 30 ( 8 % ) in the alemtuzumab group ( hazard ratio 0·70 [ 95 % CI 0·40 - 1·23 ] ; p=0·22 ) . 338 ( 90 % ) of patients in the alemtuzumab group had infusion-associated reactions ; 12 ( 3 % ) of which were regarded as serious . Infections , predominantly of mild or moderate severity , occurred in 253 ( 67 % ) patients treated with alemtuzumab versus 85 ( 45 % ) patients treated with interferon beta 1a . 62 ( 16 % ) patients treated with alemtuzumab had herpes infections ( predominantly cutaneous ) compared with three ( 2 % ) patients treated with interferon beta 1a . By 24 months , 68 ( 18 % ) patients in the alemtuzumab group had thyroid-associated adverse events compared with 12 ( 6 % ) in the interferon beta 1a group , and three ( 1 % ) had immune thrombocytopenia compared with none in the interferon beta 1a group . Two patients in the alemtuzumab group developed thyroid papillary carcinoma . INTERPRETATION Alemtuzumab 's consistent safety profile and benefit in terms of reductions of relapse support its use for patients with previously untreated relapsing-remitting multiple sclerosis ; however , benefit in terms of disability endpoints noted in previous trials was not observed here . FUNDING Genzyme ( Sanofi ) and Bayer Schering Pharma BACKGROUND Daclizumab , a humanised monoclonal antibody , reduced multiple sclerosis disease activity in previous non-r and omised studies . We aim ed to assess whether daclizumab reduces disease activity in patients with active relapsing multiple sclerosis who are receiving interferon beta treatment . METHODS We did a phase 2 , r and omised , double-blind , placebo-controlled study at 51 centres in the USA , Canada , Germany , Italy , and Spain . Patients with active relapsing multiple sclerosis who were taking interferon beta were r and omly assigned to receive add-on subcutaneous daclizumab 2 mg/kg every 2 weeks ( interferon beta and high-dose daclizumab group ) , daclizumab 1 mg/kg every 4 weeks ( interferon beta and low-dose daclizumab group ) , or interferon beta and placebo for 24 weeks . The r and omisation scheme was generated by Facet Biotech . All patients and assessors were masked to treatment with the exception of Facet Biotech bioanalysts who prepared data for the data safety monitoring board or generated pharmacokinetic or pharmacodynamic data , a drug accountability auditor , and the site pharmacist . The primary endpoint was total number of new or enlarged gadolinium contrast-enhancing lesions measured on brain MRI scans every 4 weeks between weeks 8 and 24 . Effects of daclizumab on prespecified subsets of lymphocytes and quantitative T-cell proliferative response were assessed in an exploratory pharmacodynamic sub study . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00109161 . FINDINGS From May , 2005 , to March , 2006 , 288 patients were assessed for eligibility , and 230 were r and omly assigned to receive interferon beta and high-dose daclizumab ( n=75 ) , interferon beta and low-dose daclizumab ( n=78 ) , or interferon beta and placebo ( n=77 ) . The adjusted mean number of new or enlarged gadolinium contrast-enhancing lesions was 4.75 in the interferon beta and placebo group compared with 1.32 in the interferon beta and high-dose daclizumab group ( difference 72 % , 95 % CI 34 % to 88 % ; p=0.004 ) and 3.58 in the interferon beta and low-dose daclizumab group ( 25 % , -76 % to 68 % ; p=0.51 ) . In the pharmacodynamic sub study , daclizumab was not associated with significant changes in absolute numbers of T cells , B cells , or natural killer cells , or T-cell proliferative response compared with interferon beta alone . The number of CD56(bright ) natural killer cells was seven to eight times higher in both daclizumab groups than in the interferon beta and placebo group ( interferon beta and low-dose daclizumab group p=0.002 ; interferon beta and high-dose daclizumab group p<0.0001 ) . Common adverse events were equally distributed across groups . INTERPRETATION Add-on daclizumab treatment reduced the number of new or enlarged gadolinium contrast-enhancing lesions compared with interferon beta alone and might reduce multiple sclerosis disease activity to a greater extent than interferon beta alone . FUNDING Facet Biotech and Biogen Idec BACKGROUND Oral fingolimod , a sphingosine-1-phosphate-receptor modulator that prevents the egress of lymphocytes from lymph nodes , significantly improved relapse rates and end points measured on magnetic resonance imaging ( MRI ) , as compared with either placebo or intramuscular interferon beta-1a , in phase 2 and 3 studies of multiple sclerosis . METHODS In our 24-month , double-blind , r and omized study , we enrolled patients who had relapsing-remitting multiple sclerosis , were 18 to 55 years of age , had a score of 0 to 5.5 on the Exp and ed Disability Status Scale ( which ranges from 0 to 10 , with higher scores indicating greater disability ) , and had had one or more relapses in the previous year or two or more in the previous 2 years . Patients received oral fingolimod at a dose of 0.5 mg or 1.25 mg daily or placebo . End points included the annualized relapse rate ( the primary end point ) and the time to disability progression ( a secondary end point ) . RESULTS A total of 1033 of the 1272 patients ( 81.2 % ) completed the study . The annualized relapse rate was 0.18 with 0.5 mg of fingolimod , 0.16 with 1.25 mg of fingolimod , and 0.40 with placebo ( P<0.001 for either dose vs. placebo ) . Fingolimod at doses of 0.5 mg and 1.25 mg significantly reduced the risk of disability progression over the 24-month period ( hazard ratio , 0.70 and 0.68 , respectively ; P=0.02 vs. placebo , for both comparisons ) . The cumulative probability of disability progression ( confirmed after 3 months ) was 17.7 % with 0.5 mg of fingolimod , 16.6 % with 1.25 mg of fingolimod , and 24.1 % with placebo . Both fingolimod doses were superior to placebo with regard to MRI-related measures ( number of new or enlarged lesions on T(2)-weighted images , gadolinium-enhancing lesions , and brain-volume loss ; P<0.001 for all comparisons at 24 months ) . Causes of study discontinuation and adverse events related to fingolimod included bradycardia and atrioventricular conduction block at the time of fingolimod initiation , macular edema , elevated liver-enzyme levels , and mild hypertension . CONCLUSIONS As compared with placebo , both doses of oral fingolimod improved the relapse rate , the risk of disability progression , and end points on MRI . These benefits will need to be weighed against possible long-term risks . ( Clinical Trials.gov number , NCT00289978 . Background : Inferences about long-term effects of therapies in multiple sclerosis ( MS ) have been based on surrogate markers studied in short-term trials . Preventing progressive disability is the key therapeutic goal but there remains no vali date d definition for its measurement in a trial context . Meanwhile , MS trials continue to shorten and to depend on unvali date d surrogates . Since there have been no treatment cl aims for improving unremitting disability , worsening of disability in the placebo/control arm must occur for effectiveness on this outcome to be shown . Methods : We examined widely-used clinical surrogates of long-term disability progression in individual patients with MS within a unique data base from the placebo arms of 31 r and omized clinical trials . Results : Detection of treatment effects in secondary progressive MS trials is undermined by noise in disability measurement . Whereas existing measures can be partially vali date d in secondary progressive MS , this is not the case in relapsing-remitting MS . Here , examination of widely used definitions of treatment failure demonstrated that disability progression was no more likely than similarly defined improvement . Existing definitions of disease progression in short-term intervention trials in relapsing-remitting patients reflect r and om variation , measurement error , and remitting relapses . Conclusion : Clinical surrogates of unremitting disability used in trials of relapsing-remitting multiple sclerosis can not be vali date d. Trials have been too short or degrees of disability change too small to measure the key outcomes . These analyses highlight the difficulty in determining effectiveness of therapy in chronic diseases Objective : To assess the safety , tolerability , and efficacy of interferon beta-1a ( IFNβ-1a ) combined with methotrexate ( MTX ) , IV methylprednisolone ( IVMP ) , or both in patients with relapsing-remitting multiple sclerosis ( RRMS ) with continued disease activity on IFNβ-1a monotherapy . Methods : Eligibility criteria included RRMS , Exp and ed Disability Status Scale score 0–5.5 , and ≥1 relapse or gadolinium-enhancing MRI lesion in the prior year on IFNβ-1a monotherapy . Participants continued weekly IFNβ-1a 30 μg IM and were r and omized in a 2 × 2 factorial design to adjunctive weekly placebo or MTX 20 mg PO , with or without bimonthly IVMP 1,000 mg/day for 3 days . The primary endpoint was new or enlarged T2 lesion number at month 12 vs baseline . The study was industry-supported , collaboratively design ed , and governed by an investigator Steering Committee with independent Advisory and Data Safety Monitoring committees . Study operations , MRI analyses , and aggregated data were managed by an academic coordinating center . Results : The 313 participants had clinical and MRI characteristics typical of RRMS . Combinations of IFNβ-1a with MTX or IVMP were generally safe and well tolerated . Although trends suggesting modest benefit were seen for some outcomes for IVMP , the results did not demonstrate significant benefit for either adjunctive therapy . The data suggested IVMP reduced anti-IFNβ neutralizing antibody titers . Conclusions : This trial did not demonstrate benefit of adding low-dose oral methotrexate or every other month IV methylprednisolone to interferon beta-1a in relapsing-remitting multiple sclerosis . ACT = Avonex Combination Trial ; BPF = brain parenchymal fraction ; DEXA= dual energy X-ray absorptiometry ; EDSS = Exp and ed Disability Status Scale ; GdE = gadolinium-enhancing ; IFNβ-1a = interferon beta-1a ; IVMP = IV methylprednisolone ; MSFC = MS Functional Composite ; MTX = methotrexate ; N/E = new or enlarged ; NAb = neutralizing antibody ; OR = odds ratio ; RRMS = relapsing-remitting multiple sclerosis ; SENTINEL = Safety and Efficacy of Natalizumab in Combination with Interferon β-1a in Patients with Relapsing-Remitting MS Abstract We design ed a r and omized , placebo-controlled , multicentre trial involving 51 relapsing-remitting multiple sclerosis patients to determine the clinical efficacy of mitoxantrone treatment over 2 years . Patients were allocated either to the mitoxantrone group ( 27 patients receiving IV infusion of mitoxantrone every month for 1 year at the dosage of 8 mg/m2 ) or to the placebo group ( 24 patients , receiving IV infusion of saline every month for 1 year ) using a central ized r and omization system . Disability at entry and at 12–24 months was evaluated by four blinded neurologists trained in the application of the Kurtzke Exp and ed Disability Scale ( EDSS ) . In addition , the number and clinical characteristics of the exacerbations over the 24 months were recorded by the local investigators . MRI , at 0,12 and 24 months , was performed with a 0.2 T permanent unit . MRI data were analysed by two blinded neuroradiologists . All patients underwent a clinical evaluation . A statistically significant difference in the mean number of exacerbations was observed between the mitoxantrone group and placebo group both during the 1st and the 2nd year . Although there was no statistically significant benefit in terms of mean EDSS progression over 2 years , the proportion of patients with confirmed progression of the disease , as measured by a one point increase on the EDSS scale , was significantly reduced at the 2nd year evaluation in the mitoxantrone group . Forty-two ( 23 mitoxantrone , 19 placebo ) patients underwent all MRI examinations during the 24-month period . We observed a trend towards a reduction in the number of new lesions on T2-weighted images in the mitoxantrone group . Our study suggests that mitoxantrone might be effective in reducing disease activity , both by decreasing the mean number of exacerbations and by slowing the clinical progression sustained by most patients after 1 year from the end of treatment BACKGROUND B lymphocytes are implicated in the pathogenesis of multiple sclerosis . We aim ed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis . METHODS We did a multicentre , r and omised , parallel , double-blind , placebo-controlled study involving 79 centres in 20 countries . Patients aged 18 - 55 years with relapsing-remitting multiple sclerosis were r and omly assigned ( 1:1:1:1 ) via an interactive voice response system to receive either placebo , low-dose ( 600 mg ) or high-dose ( 2000 mg ) ocrelizumab in two doses on days 1 and 15 , or intramuscular interferon beta-1a ( 30 μg ) once a week . The r and omisation list was not disclosed to the study centres , monitors , project statisticians or to the project team at Roche . All groups were double blinded to group assignment , except the interferon beta-1a group who were rater masked . At week 24 , patients in the initial placebo , 600 mg ocrelizumab , and interferon beta-1a groups received ocrelizumab 600 mg ; the 2000 mg group received 1000 mg . Our primary endpoint was the total number of gadolinium-enhancing lesions ( GEL ) and T1-weighted MRI at weeks 12 , 16 , 20 , and 24 . Analyses were done on an intention-to-treat basis . This trial is registered with Clinical Trials.gov , number NCT00676715 . FINDINGS 218 ( 99 % ) of the 220 r and omised patients received at least one dose of ocrelizumab , 204 ( 93 % ) completed 24 weeks of the study and 196 ( 89 % ) completed 48 weeks . In the intention-to-treat population of 218 patients , at week 24 , the number of gadolinium-enhancing lesions was 89 % ( 95 % CI 68 - 97 ; p<0·0001 ) lower in the 600 mg ocrelizumab group than in the placebo group , and 96 % ( 89 - 99 ; p<0·0001 ) lower in the 2000 mg group . In exploratory analyses , both 600 mg and 2000 mg ocrelizumab groups were better than interferon beta-1a for GEL reduction . We noted serious adverse events in two of 54 ( 4 % ; 95 % CI 3·0 - 4·4 ) patients in the placebo group , one of 55 ( 2 % ; 1·3 - 2·3 ) in the 600 mg ocrelizumab group , three of 55 ( 5 % ; 4·6 - 6·3 ) in the 2000 mg group , and two of 54 ( 4 % ; 3·0 - 4·4 ) in the interferon beta-1a group . INTERPRETATION The similarly pronounced effects of B-cell depletion with both ocrelizumab doses on MRI and relapse-related outcomes support a role for B-cells in disease pathogenesis and warrant further assessment in large , long-term trials . FUNDING F Hoffmann-La Roche Ltd , Biogen Idec Background : Fingolimod ( FTY720 ) has previously shown clinical efficacy in phase II/III studies of predominantly Caucasian population s with multiple sclerosis ( MS ) . Objectives : To report six-month efficacy and safety outcomes in Japanese patients with relapsing MS treated with fingolimod . Methods : In this double-blind , parallel-group , phase II study , 171 Japanese patients with relapsing MS were r and omized to receive once-daily fingolimod 0.5 mg or 1.25 mg , or matching placebo for six months . The primary and secondary endpoints were the percentages of patients free from gadolinium (Gd)-enhanced lesions at months 3 and 6 , and relapses over six months , respectively ; safety outcomes were also assessed . Results : 147 patients completed the study . Higher proportions of patients were free from Gd-enhanced lesions at months 3 and 6 with fingolimod ( 0.5 mg : 70 % , p = 0.004 ; 1.25 mg : 86 % , p < 0.001 ) than with placebo ( 40 % ) . Odds ratios for the proportions of relapse-free patients over six months favoured fingolimod versus placebo but were not significant . Adverse events related to fingolimod included transient bradycardia and atrioventricular block at treatment initiation , and elevated liver enzyme levels . Conclusions : This study demonstrated the clinical efficacy of fingolimod for the first time in Japanese patients with MS , consistent with the established effects of fingolimod in Caucasian patients BACKGROUND Interferon beta-1a and glatiramer acetate are commonly prescribed for relapsing-remitting multiple sclerosis ( RRMS ) , but no published r and omised trials have directly compared these two drugs . Our aim in the REGARD ( REbif vs Glatiramer Acetate in Relapsing MS Disease ) study was to compare interferon beta-1a with glatiramer acetate in patients with RRMS . METHODS In this multicentre , r and omised , comparative , parallel-group , open-label study , patients with RRMS diagnosed with the McDonald criteria who had had at least one relapse within the previous 12 months were r and omised to receive 44 mug subcutaneous interferon beta-1a three times per week or 20 mg subcutaneous glatiramer acetate once per day for 96 weeks to assess the time to first relapse . A sub population of 460 patients ( 230 from each group ) also had serial MRI scans to assess T2-weighted and gadolinium-enhancing lesion number and volume . Treatments were assigned by a computer-generated r and omisation list that was stratified by centre . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00078338 . FINDINGS Between February and December , 2004 , 764 patients were r and omly assigned : 386 to interferon beta-1a and 378 to glatiramer acetate . After 96 weeks , there was no significant difference between groups in time to first relapse ( hazard ratio 0.94 , 95 % CI 0.74 to 1.21 ; p=0.64 ) . Relapse rates were lower than expected : 258 patients ( 126 in the interferon beta-1a group and 132 in the glatiramer acetate group ) had one or more relapses ( the expected number was 460 ) . For secondary outcomes , there were no significant differences for the number and change in volume of T2 active lesions or for the change in the volume of gadolinium-enhancing lesions , although patients treated with interferon beta-1a had significantly fewer gadolinium-enhancing lesions ( 0.24 vs 0.41 lesions per patient per scan , 95 % CI -0.4 to 0.1 ; p=0.0002 ) . Safety and tolerability profiles were consistent with the known profiles for both compounds . The overall number and severity of adverse events were similar between the treatments and were not an important cause for discontinuation of the trial during the 96 weeks . INTERPRETATION There was no significant difference between interferon beta-1a and glatiramer acetate in the primary outcome . The ability to predict clinical superiority on the basis of results from previous studies might be limited by a trial population with low disease activity , which is an important consideration for ongoing and future trials in patients with RRMS We conducted a double-blind , placebo-controlled study of 40 patients ( aged 19 to 60 years ) with clinical definite relapsing remitting ( RR ) MS and brain MRI confirmed . Patients were r and omly assigned to receive a loading dose of immunoglobulin IgG ( 0.4 g/kg/body weight per day for 5 consecutive days ) , followed by single booster doses ( 0.4 g/kg/body weight ) or placebo once every 2 months for 2 years . The primary outcome measures were change in the yearly exacerbation rate ( YER ) , proportion of exacerbation-free patients , and time until first exacerbation . Neurologic disability , exacerbation severity , and changes in brain MRI lesion score were the secondary outcome measures , all determined at baseline , 1 year , and on completion . Treated patients showed a reduction in YER from 1.85 to 0.75 after 1 year and 0.42 after 2 years versus 1.55 to 1.8 after 1 year and to 1.4 after 2 years in the placebo group ( p = 0.0006 , overall ) , reflecting a 38.6 % reduction in relapse rate . Six patients in the IVIg group were exacerbation free throughout the 2—year period of the study , whereas none were exacerbation free in the placebo group . The median time to first exacerbation was 233 days in the IVIg group versus 82 days in the placebo group ( p = 0.003 ) . Neurologic disability as measured by the Exp and ed Disability Status Scale ( EDSS score ) decreased by 0.3 in the IVIg group and increased by 0.15 in the placebo group . Total lesion score evaluated by brain MRI did not show a significant difference between groups . Side effects were minor and occurred in only 19 of 630 ( 3.0 % ) infusions administered in both groups . Our results suggest that IVIg may be safe and effective in reducing the frequency of exacerbations in RR-MS BACKGROUND Interferon beta is commonly used to treat patients with relapsing-remitting multiple sclerosis ; however , the treatment is only partially effective in reducing relapses and progression of disability . Corticosteroids are used to treat relapses in patients with multiple sclerosis . We therefore aim ed to investigate the combination of cyclic methylprednisolone and interferon beta for the treatment of relapsing-remitting multiple sclerosis . METHODS In 2001 , we design ed a multicentre , double-blind , r and omised , parallel-group trial , termed the methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis ( MECOMBIN ) study . Patients were recruited between October , 2002 , and March , 2005 from 50 neurology departments in eight countries . We included treatment-naive patients with relapsing-remitting multiple sclerosis who had an exp and ed disability status scale ( EDSS ) score of 4 or less . Patients all started to receive interferon beta-1a and after 3 months were r and omly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3 - 4 years . Placebo tablets were identical to methylprednisolone tablets . Treating physicians , examining physicians , and patients were masked to treatment allocation . Patients were clinical ly assessed every 3 months and had brain MRI at baseline and 3 years later . The primary outcome was time to onset of disability progression , according to an increase in EDSS score sustained over 6 months . All patients who received at least one dose of study drug were included in all planned analyses . This trial is registered with Clinical Trials.gov , NCT00168766 . FINDINGS 341 patients were r and omly assigned to methylprednisolone ( n=172 ) or placebo ( n=169 ) ; 171 patients in the methylprednisolone group and 167 in the placebo group received at least one dose of study drug . 90 patients had sustained disability progression : 44 of 167 in the methylprednisolone group and 46 of 171 in the placebo group . The time to sustained progression did not differ between groups ( hazard ratio 0.879 , 95 % CI 0.566 - 1.365 ; p=0.57 ) . There were 1436 adverse events , 24 of which were serious , in the methylprednisolone group and 1070 events , 35 of which were serious , in the placebo group . INTERPRETATION Monthly pulses of methylprednisolone in combination with interferon beta-1a do not seem to affect disability progression any more than interferon beta-1a treatment alone . More research is required to assess whether this treatment regimen might benefit particular subsets of patients . FUNDING Biogen Idec Background : In previous studies , teriflunomide significantly reduced the annualised relapse rate ( ARR ) and disability progression . Objective : This phase 3 , rater-blinded study ( NCT00883337 ) compared teriflunomide with interferon-beta-1a ( IFNβ-1a ) . Methods : Patients with relapsing multiple sclerosis were r and omised ( 1:1:1 ) to oral teriflunomide 7-or 14 mg , or subcutaneous IFNβ-1a 44 µg . The primary composite endpoint was time to failure , defined as first occurrence of confirmed relapse or permanent treatment discontinuation for any cause . Secondary endpoints included ARR , Fatigue Impact Scale ( FIS ) and Treatment Satisfaction Question naire for Medication ( TSQM ) . The study was completed 48 weeks after the last patient was r and omised . Results : Some 324 patients were r and omised ( IFNβ-1a : 104 ; teriflunomide 7 mg : 109 ; teriflunomide 14 mg : 111 ) . No difference in time to failure was observed . There was no difference in ARR between teriflunomide 14 mg and IFNβ-1a , but ARR was significantly higher with teriflunomide 7 mg . FIS scores indicated more frequent fatigue with IFNβ-1a , though differences were only significant with teriflunomide 7 mg . TSQM scores were significantly higher with teriflunomide . There were no unexpected safety findings . Conclusion : Effects on time to failure were comparable between teriflunomide and IFNβ-1a . There was no difference between teriflunomide 14 mg and IFNβ-1a on ARR , though ARR was higher with teriflunomide 7 mg . The teriflunomide safety profile was consistent with previous studies The accepted st and ard treatment of relapsing multiple sclerosis consists of medications for disease symptoms , including treatment for acute exacerbations . However , currently there is no therapy that alters the progression of physical disability associated with this disease . The purpose of this study was to determine whether interferon beta‐1a could slow the progressive , irreversible , neurological disability of relapsing multiple sclerosis . Three hundred one patients with relapsing multiple sclerosis were r and omized into a double‐blinded , placebo‐controlled , multicenter phase I11 trial of interferon beta‐la . Interferon beta‐la , 6.0 million units ( 30 μg ) , was administered by intramuscular injection weekly . The primary outcome variable was time to sustained disability progression of at least 1.0 point on the Kurtzke Exp and ed Disability Status Scale ( EDSS ) . Interferon beta‐la treatment produced a significant delay in time to sustained EDSS progression ( p equals ; 0.02 ) . The Kaplan‐Meier estimate of the proportion of patients progressing by the end of 104 weeks was 34.9 % in the placebo group and 21.9 % in the interferon beta‐la‐treated group . Patients treated with interferon beta‐la also had significantly fewer exacerbations ( p = 0.03 ) and a significantly lower number and volume of gadolinium‐enhanced brain lesions on magnetic resonance images ( pvalues ranging between 0.02 and 0.05 ) . Over 2 years , the annual exacerbation rate was 0.90 in placebo‐treated patients versus 0.61 in interferon beta‐la‐treated patients . There were no major adverse events related to treatment . Interferon beta‐ la had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability , exacerbation frequency , and disease activity measured by gadolinium‐enhanced lesions on brain magnetic resonance images . This treatment may alter the hndamen‐ tal course of relapsing multiple sclerosis BACKGROUND Oral fumarate ( BG00012 ) might have dual anti-inflammatory and neuroprotective effects . Our aim was to assess the efficacy and safety of BG00012 in patients with relapsing-remitting multiple sclerosis . METHODS 257 patients , aged 18 - 55 years , with relapsing-remitting multiple sclerosis were r and omly assigned to receive 120 mg once daily ( n=64 ) , 120 mg three times daily ( n=64 ) , or 240 mg three times daily ( n=64 ) BG00012 , or placebo ( n=65 ) for 24 weeks . During an extension period of 24 weeks for safety assessment , patients treated with placebo received BG00012 240 mg three times daily . The primary endpoint was total number of new gadolinium enhancing ( GdE ) lesions on brain MRI scans at weeks 12 , 16 , 20 , and 24 . Additional endpoints included cumulative number of new GdE lesions ( weeks 4 - 24 ) , new or enlarging T2-hyperintense lesions , new T1-hypointense lesions at week 24 , and annualised relapse rate . Analysis was done on the efficacy-evaluable population . Safety and tolerability were also assessed . This study is registered with Clinical Trials.gov , number NCT00168701 . FINDINGS Treatment with BG00012 240 mg three times daily reduced by 69 % the mean total number of new GdE lesions from week 12 to 24 compared with placebo ( 1.4 vs 4.5 , p<0.0001 ) . It also reduced number of new or enlarging T2-hyperintense ( p=0.0006 ) and new T1-hypointense ( p=0.014 ) lesions compared with placebo . BG00012 reduced annualised relapse rate by 32 % ( 0.44 vs 0.65 for placebo ; p=0.272 ) . Adverse events more common in patients given BG00012 than in those given placebo included abdominal pain , flushing , and hot flush . Dose-related adverse events in patients on BG00012 were headache , fatigue , and feeling hot . INTERPRETATION The anti-inflammatory effects and favourable safety profile of BG00012 warrant further long-term phase III studies in large patient groups Glatiramer acetate ( GA ; Copaxone ) is a r and om sequence polypeptide used in the treatment of relapsing remitting multiple sclerosis ( RR MS ) . We have recently demonstrated that prior to treatment , GA induces proliferation of resting T cells and is not cross-reactive with myelin antigens . Daily GA injections induce a significant loss of this GA responsiveness , which is associated with the induction of highly cross-reactive Th2-type T cells potentially capable of suppressing inflammatory responses . The mechanism of action by which GA induces T cell nonresponsiveness leading to T cell receptor degeneracy in patients with RR MS is unknown . Here , we examined the effects of daily GA administration on the induction of T cell hyporesponsiveness . The frequency of GA-reactive T cells in peripheral blood of seven patients with RR MS was measured by limiting dilution analysis prior to and during 6 months of treatment . In addition , a model in which GA-reactive T cells were stimulated in vitro was developed to better characterize the selection of T cell population s over time . In vivo treatment with GA induced a decrease in GA-reactive T cell frequencies and hyporesponsiveness of CD4(+ ) T cell reactivity to GA in vitro that was only partially reversed by the addition of IL-2 . These data suggest that T cell peripheral tolerance to GA was achieved in vivo during treatment . Thus , our in vitro data suggest that the underlying changes in GA-reactive CD4(+ ) T cell reactivity could be explained by the induction of T cell anergy and clonal elimination Objectives : We present the first study to explore safety and efficacy of the human CD20 monoclonal antibody ofatumumab in relapsing-remitting multiple sclerosis ( RRMS ) . Methods : In this r and omized , double-blind , placebo-controlled study , patients received 2 ofatumumab infusions ( 100 mg , 300 mg , or 700 mg ) or placebo 2 weeks apart . At week 24 , patients received alternate treatment . Safety and efficacy were assessed . Results : Thirty-eight patients were r and omized ( ofatumumab/placebo , n = 26 ; placebo/ofatumumab , n = 12 ) and analyzed ; 36 completed the study . Two patients in the 300-mg group withdrew from the study because of adverse events . No unexpected safety signals emerged . Infusion-related reactions were common on the first infusion day but not observed on the second infusion day . None of the patients developed human anti-human antibodies . Ofatumumab was associated with profound selective reduction of B cells as measured by CD19 + expression . New brain MRI lesion activity was suppressed ( > 99 % ) in the first 24 weeks after ofatumumab administration ( all doses ) , with statistically significant reductions ( p < 0.001 ) favoring ofatumumab found in new T1 gadolinium-enhancing lesions , total enhancing T1 lesions , and new and /or enlarging T2 lesions . Conclusions : Ofatumumab ( up to 700 mg ) given 2 weeks apart was not associated with any unexpected safety concerns and was well tolerated in patients with RRMS . MRI data suggest a clinical ly meaningful effect of ofatumumab for all doses studied . Results warrant further exploration of ofatumumab in RRMS . Classification of evidence : This study provides Class II evidence that in patients with RRMS , ofatumumab compared with placebo does not increase the number of serious adverse events and decreases the number of new MRI lesions BACKGROUND Interferon (IFN)-beta therapy represents an important advance in the management of relapsing multiple sclerosis ( MS ) , but information about the relative benefits and risks of available preparations is limited . OBJECTIVE This report describes the full results of the Evidence of Interferon Dose-response-European North American Comparative Efficacy ( EVIDENCE ) study , combining analyses that were previously reported in separate publications for different phases of the study . METHODS The EVIDENCE study was a multicenter , r and omized , assessor-blinded comparison of 2 IFN-beta dosing regimens . In the study , patients with relapsing MS were r and omly assigned to SC IFN-beta1a 44 lag TIW ( Rebif , Serono Inc. , Geneva , Switzerl and ) or IM IFN-betala 30 mug QW ( Avonex , Biogen Idec , Cambridge , Massachusetts ) for 1 to 2 years . The primary clinical end point during the comparative phase was the proportion of patients who remained free from relapses ; secondary and tertiary clinical end points included the annualized relapse rate and time to first relapse , re- spectively . All clinical and magnetic resonance imaging ( MRI ) evaluations were performed by blinded assessors . In the crossover phase of the study , patients who were originally r and omized to low-dose QW treatment switched to the high-dose TIW treatment for an additional 8 months . Adverse events were determined by spontaneous reporting and monthly laboratory testing during the comparative phase . RESULTS A total of 677 patients were enrolled in the study and evenly r and omized to treatment ; 605 patients completed the comparative phase and 439 completed the crossover phase . During the comparative phase , a significantly higher proportion of patients in the high-dose TIW treatment group remained free from relapses when compared with patients in the low-dose QW treatment group ( adjusted odds ratio , 1.5 ; 95 % CI , 1.1 - 2.0 ; P = 0.023 ) . The high-dose TIW regimen was also associated with a significant reduction in the annualized relapse rate ( -17 % ; P = 0.033 ) and a prolonged time to first relapse ( hazard ratio , 0.70 ; P = 0.002 ) . MRI measures of disease activity were significantly reduced in the high-dose TIW group compared with the low-dose QW treatment . During the crossover phase , a 50 % reduction in mean relapse rates was observed in patients who converted from low-dose QW treatment to high-dose TIW treatment ( P < 0.001 ) , with significant concomitant reductions in MRI activity . Injection-site reactions were significantly more common with high-dose TIW treatment than with low-dose QW treatment ( 85 % vs 33 % ; P < 0.001 ) . Neutralizing antibody formation was more common with high-dose TIW treatment than with low-dose QW treatment ( 26 % vs 3 % ; P < 0.001 ) . CONCLUSIONS The comparative phase of the EVIDENCE study found that treatment of MS with SC IFN-beta1a 44 microg TIW was associated with a significant reduction in clinical and imaging measures of disease activity over 1 to 2 years , when compared with IM IFN-betala 30 microg QW treatment . The crossover phase found that patients who changed from low-dose QW treatment to high-dose TIW treatment experienced enhanced benefits of treatment without a substantial increase in adverse events BACKGROUND The three interferon beta preparations approved for treatment of relapsing-remitting multiple sclerosis ( MS ) differ in dose and frequency of administration . Interferon beta-1a 30 microg is administered once a week , interferon beta-1a 22 microg or 44 microg is given three times a week , and interferon beta-1b 250 microg is administered on alternate days . No clinical study directly comparing the different regimens has been published . The INCOMIN study was design ed to compare the clinical and magnetic resonance imaging ( MRI ) benefits of on-alternate-day interferon beta-1b 250 microg with once-weekly interferon beta-1a 30 microg . METHODS INCOMIN was a 2-year , prospect i ve , r and omised , multicentre study . 188 patients with relapsing-remitting MS were assigned to interferon beta-1b ( n=96 ) or interferon beta-1a ( n=92 ) . Primary outcome measures were the proportion of patients free from relapses and that of patients free from new proton density/T2 lesions at MRI assessment . Several secondary outcome measures were also assessed . Analysis was by intention to treat . FINDINGS Over 2 years , 49 ( 51 % ) individuals administered interferon beta-1b remained relapse-free compared with 33 ( 36 % ) given interferon beta-1a relative risk of relapse 0.76 ; 95 % CI 0.59 - 0.9 ; p=0.03 ) ; and 42 ( 55 % ) compared with 19 ( 26 % ) , respectively , remained free from new T2 lesions at MRI ( relative risk of new T2 lesion 0.6 ; 0.45 - 0.8 ; p<0.0003 ) . In both groups , the differences between the two treatments increased during the second year . There were also significant differences in favour of interferon beta-1b in most of the secondary outcome measures , including delay of confirmed disease progression . INTERPRETATION High-dose interferon beta-1b administered every other day is more effective than interferon beta-1a given once a week BACKGROUND : Methotrexate , a toxic antimetabolite that limits cellular reproduction by acting as an antagonist to folic acid , has been used to control autoimmune disease with different results . The aim of this study was to evaluate the effectiveness of low dose Methotrexate in the relapsing-remitting multiple sclerosis ( RRMS ) . METHODS : Eighty patients with definite RRMS aged 15 to 55 years were r and omly allocated to receive a 12-month treatment course of either oral Methotrexate ( 7.5 mg/week ) or intramuscular Interferon β-1α ( 30 μg/week ) . Response to treatment was assessed at 12 months after start of therapy . RESULTS : The results of the study demonstrated significant reduction in relapse rate in both groups ( p < 0.01 ) . In 40 patients treated by Methotrexate , the mean value ( SD ) of relapse rate decreased from 1.75 ( 0.74 ) to 0.97 ( 0.83 ) ( p < 0.01 ) . Correspondingly , the mean value ( SD ) of relapse rate in patients treated by Interferon β-1α decreased from 1.52 ( 0.59 ) to 0.57 ( 0.78 ) ( p < 0.01 ) . Decrease of relapse rate in Interferon β-1α group was more than that in the other group ( p = 0.06 ) . CONCLUSIONS : This study suggests that although treatment with Methotrexate may significantly reduce relapse rate and slow progression of disease in patients with RRMS , its efficacy is less than Interferon β-1α and it may be better used as add-on therapy This study clinical ly evaluated a novel PEGylated form of interferon beta-1a ( PEG-IFN beta-1a ) , a potential first-line treatment for relapsing multiple sclerosis , in healthy volunteers . Two r and omized , blinded phase I studies were conducted : a single-dose study ( n = 60 ) comparing subcutaneous or intramuscular PEG-IFN beta-1a ( 63 , 125 , or 188 µg ) with intramuscular unmodified IFN beta-1a 30 µg and a multiple-dose study ( n = 69 ) comparing subcutaneous PEG-IFN beta-1a dosed once every 2 or 4 weeks with placebo . Assessment s included pharmacokinetic and pharmacodynamic ( serum neopterin and 2',5'-OAS ) measures , exploratory immune assessment s , safety , and tolerability . A dose-proportional increase in PEG-IFN beta-1a exposure was observed , with a 4-fold greater exposure at 63 µg ( 6 million international units [ MIU ] ) of PEG-IFN beta-1a than with 30 µg ( 6 MIU ) intramuscular unmodified IFN beta-1a . Increases in neopterin and 2',5'-OAS levels and changes in T helper cell pathway gene expression and lymphocyte subsets were greater and more sustained with PEG-IFN beta-1a than with unmodified IFN beta-1a . PEG-IFN beta-1a was well tolerated , with only transient reductions in absolute neutrophils and some lymphocytes . Flu-like symptoms were a commonly reported adverse event . These data support the continued clinical development of PEG-IFN beta-1a as a potentially effective treatment for patients with relapsing multiple sclerosis we studied copolymer 1 ( Copaxone ) in a multicenter ( 11-university ) phase III trial of patients with relapsing-remitting multiple sclerosis ( MS ) . Two hundred fifty-one patients were r and omized to receive copolymer 1 ( n = 125 ) or placebo ( n = 126 ) at a dosage of 20 mg by daily subcutaneous injection for 2 years . The primary end point was a difference in the MS relapse rate . The final 2-year relapse rate was 1.19 ± 0.13 for patients receiving copolymer 1 and 1.68 ± 0.13 for those receiving placebo , a 29 % reduction in favor of copolymer 1 ( p = 0.007 ) ( annualized rates = 0.59 for copolymer 1 and 0.84 for placebo ) . Trends in the proportion of relapse-free patients and median time to first relapse favored copolymer 1 . Disability was measured by the Exp and ed Disability Status Scale ( EDSS ) , using a two-neurologist ( examining and treating ) protocol . When the proportion of patients who improved , were unchanged , or worsened by ≥1 EDSS step from baseline to conclusion ( 2 years ) was evaluated , significantly more patients receiving copolymer 1 were found to have improved and more receiving placebo worsened ( p = 0.037 ) . Patient withdrawals were 19 ( 15.2 % ) from the copolymer 1 group and 17 ( 13.5 % ) from the placebo group at approximately the same intervals . The treatment was well tolerated . The most common adverse experience was an injection-site reaction . Rarely , a transient self-limited systemic reaction followed the injection in 15.2 % of those receiving copolymer 1 and 3.2 % of those receiving placebo . This reaction was characterized by flushing or chest tightness with palpitations , anxiety , or dyspnea and commonly lasted for 30 seconds to 30 minutes . This rigorous study confirmed the findings of a previous pilot trial and demonstrated that copolymer 1 treatment can significantly and beneficially alter the course of relapsing-remitting MS in a well-tolerated fashion BACKGROUND Fingolimod ( FTY720 ) is a new oral immunomodulating agent under evaluation for the treatment of relapsing multiple sclerosis . METHODS We r and omly assigned 281 patients to receive oral fingolimod , at a dose of 1.25 mg or 5.0 mg , or a placebo once daily , and we followed these patients for 6 months with magnetic resonance imaging ( MRI ) and clinical evaluations ( core study , months 0 to 6 ) . The primary end point was the total number of gadolinium-enhanced lesions recorded on T(1)-weighted MRI at monthly intervals for 6 months . In an extension study in which the investigators and patients remained unaware of the dose assignments ( months 7 to 12 ) , patients who received placebo underwent r and omization again to one of the fingolimod doses . RESULTS A total of 255 patients completed the core study . The median total number of gadolinium-enhanced lesions on MRI was lower with 1.25 mg of fingolimod ( 1 lesion , P<0.001 ) and 5.0 mg of fingolimod ( 3 lesions , P=0.006 ) than with placebo ( 5 lesions ) . The annualized relapse rate was 0.77 in the placebo group , as compared with 0.35 in the group given 1.25 mg of fingolimod ( P=0.009 ) and 0.36 in the group given 5.0 mg of fingolimod ( P=0.01 ) . For the 227 patients who completed the extension study , the number of gadolinium-enhanced lesions and relapse rates remained low in the groups that received continuous fingolimod , and both measures decreased in patients who switched from placebo to fingolimod . Adverse events included nasopharyngitis , dyspnea , headache , diarrhea , and nausea . Clinical ly asymptomatic elevations of alanine aminotransferase levels were more frequent with fingolimod ( 10 to 12 % , vs. 1 % in the placebo group ) . One case of the posterior reversible encephalopathy syndrome occurred in the 5.0-mg group . Fingolimod was also associated with an initial reduction in the heart rate and a modest decrease in the forced expiratory volume in 1 second . CONCLUSIONS In this proof-of-concept study , fingolimod reduced the number of lesions detected on MRI and clinical disease activity in patients with multiple sclerosis . Evaluation in larger , longer-term studies is warranted . ( Clinical trials.gov numbers , NCT00333138 [ core study ] and NCT00235430 [ Clinical Trials.gov ] [ extension ] . ) BACKGROUND The aim of the Betaferon Efficacy Yielding Outcomes of a New Dose ( BEYOND ) trial was to compare the efficacy , safety , and tolerability of 250 microg or 500 microg interferon beta-1b with glatiramer acetate for treating relapsing-remitting multiple sclerosis . METHODS Between November , 2003 , and June , 2005 , 2447 patients with relapsing-remitting multiple sclerosis were screened and 2244 patients were enrolled in this prospect i ve , multicentre , r and omised trial . Patients were r and omly assigned 2:2:1 by block r and omisation with regional stratification to receive one of two doses of interferon beta-1b ( 250 microg or 500 microg ) subcutaneously every other day or 20 mg glatiramer acetate subcutaneously every day . The primary outcome was relapse risk , defined as new or recurrent neurological symptoms separated by at least 30 days from the preceding event and that lasted at least 24 h. Secondary outcomes were progression on the exp and ed disability status scale ( EDSS ) and change in T1-hypointense lesion volume . Clinical outcomes were assessed quarterly for 2.0 - 3.5 years ; MRI was done at screening and annually thereafter . Analysis was by per protocol . This study is registered , number NCT00099502 . FINDINGS We found no differences in relapse risk , EDSS progression , T1-hypointense lesion volume , or normalised brain volume among treatment groups . Flu-like symptoms were more common in patients treated with interferon beta-1b ( p<0.0001 ) , whereas injection-site reactions were more common in patients treated with glatiramer acetate ( p=0.0005 ) . Patient attrition rates were 17 % ( 153 of 888 ) on 250 microg interferon beta-1b , 26 % ( 227 of 887 ) on 500 microg interferon beta-1b , and 21 % ( 93 of 445 ) for glatiramer acetate . INTERPRETATION 500 microg interferon beta-1b was not more effective than the st and ard 250 microg dose , and both doses had similar clinical effects to glatiramer acetate . Although interferon beta-1b and glatiramer acetate had different adverse event profiles , the overall tolerability to both drugs was similar . FUNDING Bayer HealthCare Pharmaceuticals BACKGROUND Teriflunomide is an oral disease-modifying therapy approved for treatment of relapsing or relapsing-remitting multiple sclerosis . We aim ed to provide further evidence for the safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis . METHODS This international , r and omised , double-blind , placebo-controlled , phase 3 study enrolled adults aged 18 - 55 years with relapsing multiple sclerosis , one or more relapse in the previous 12 months or two or more in the previous 24 months but no relapse in the previous 30 days , and an Exp and ed Disability Status Scale ( EDSS ) score of 5.5 points or less . Patients were recruited from 189 sites in 26 countries and r and omly assigned ( 1:1:1 ) to once-daily placebo , teriflunomide 7 mg , or teriflunomide 14 mg via an interactive voice recognition system . Treatment duration was variable , ending 48 weeks after the last patient was included . The primary endpoint was annualised relapse rate ( number of relapses per patient-year ) and the key secondary endpoint was time to sustained accumulation of disability ( an EDSS score increase of at least 1 EDSS point sustained for a minimum of 12 weeks ) , both analysed in the modified intention-to-treat population ( all patients who received at least one dose of assigned study medication ) . This study is registered with Clinical Trials.gov , number NCT00751881 . FINDINGS Between Sept 17 , 2008 , and Feb 17 , 2011 , 1169 patients were r and omly assigned to a treatment group , of whom 388 , 407 , and 370 patients received at least one dose of placebo , teriflunomide 7 mg , or teriflunomide 14 mg , respectively . By the end of the study , the annualised relapse rate was higher in patients assigned to placebo ( 0.50 [ 95 % CI 0.43 - 0.58 ] ) than in those assigned to teriflunomide 14 mg ( 0.32 [ 0.27 - 0.38 ] ; p=0.0001 ) or teriflunomide 7 mg ( 0.39 [ 0.33 - 0.46 ] ; p=0.0183 ) . Compared with placebo , teriflunomide 14 mg reduced the risk of sustained accumulation of disability ( hazard ratio [ HR ] 0.68 [ 95 % CI 0.47 - 1.00 ] ; log-rank p=0.0442 ) ; however , teriflunomide 7 mg had no effect on sustained accumulation of disability ( HR 0.95 [ 0.68 - 1.35 ] ; log-rank p=0.7620 ) . The most common adverse events were alanine aminotransferase increases ( 32 [ 8 % ] of 385 patients in the placebo group vs 46 [ 11 % ] of 409 patients in the teriflunomide 7 mg group vs 52 [ 14 % ] of 371 patients in the teriflunomide 14 mg group ) , hair thinning ( 17 [ 4 % ] vs 42 [ 10 % ] vs 50 [ 13 % ] ) , and headache ( 42 [ 11 % ] vs 60 [ 15 % ] vs 46 [ 12 % ] ) . Incidence of serious adverse events was similar in all treatment groups ( 47 [ 12 % ] vs 52 [ 13 % ] vs 44 [ 12 % ] ) . Four deaths occurred , none of which was considered to be related to study drug ( respiratory infection in the placebo group , traffic accident in the teriflunomide 7 mg group , and suicide and septicaemia due to Gram-negative infection complicated by disseminated intravascular coagulopathy in the teriflunomide 14 mg group ) . INTERPRETATION Teriflunomide 14 mg was associated with a lower relapse rate and less disability accumulation compared with placebo , with a similar safety and tolerability profile to that reported in previous studies . These results confirm the dose effect reported in previous trials and support the use of teriflunomide 14 mg in patients with relapsing multiple sclerosis . FUNDING Genzyme , a Sanofi company Cop 1 is a r and om polymer ( molecular weight , 14,000 to 23,000 ) simulating myelin basic protein . It is synthesized by polymerizing L-alanine , L-glutamic acid , L-lysine , and L-tyrosine . It suppresses but does not induce experimental allergic encephalomyelitis , an animal model of multiple sclerosis . It is not toxic in animals . In a double-blind , r and omized , placebo-controlled pilot trial , we studied 50 patients with the exacerbating-remitting form of multiple sclerosis , who self-injected either 20 mg of Cop 1 dissolved in 1 ml of saline or saline alone daily for two years . Six of 23 patients in the placebo group ( 26 percent ) and 14 of 25 patients in the Cop 1 group ( 56 percent ) had no exacerbations ( P = 0.045 ) . There were 62 exacerbations in the placebo group and 16 in the Cop 1 group , yielding two-year averages of 2.7 and 0.6 per patient , respectively . Among patients who were less disabled on entry ( Kurtzke disability score , 0 to 2 ) , there were 2.7 exacerbations in the placebo group and 0.3 in the Cop 1 group over two years . Among patients who were more affected ( Kurtzke disability score , 3 to 6 ) , there was an average of 2.7 exacerbations in the placebo group and 1.0 in the Cop 1 group . Over two years , less disabled patients taking Cop 1 improved an average of 0.5 Kurtzke units ; those taking placebo worsened an average of 1.2 Kurtzke units . More disabled patients worsened by 0.3 ( Cop 1 group ) and 0.4 ( placebo group ) unit . Irritation at injection sites and rare , transient vasomotor responses were observed as side effects . These results suggest that Cop 1 may be beneficial in patients with the exacerbating-remitting form of multiple sclerosis , but we emphasize that the study is a preliminary one and our data require confirmation by a more extensive clinical trial We r and omized 59 patients with relapsing-remitting multiple sclerosis to receive azathioprine ( AZA ) 3.0 mg/kg daily or placebo in a double-masked therapeutic trial . Analysis of data for predetermined primary outcome measures demonstrated a significant difference favoring AZA for observed mean exacerbation rate after 2 years of therapy and time to deterioration in both Ambulation Index and Kurtzke Exp and ed Disability Status Scale score . This study confirms a modest therapeutic benefit for azathioprine previously reported by other investigators Two prior double‐blind , placebo‐controlled , r and omized trials demonstrated that glatiramer acetate ( GA ) reduces relapse rates in patients with relapsing remitting multiple sclerosis ( RRMS ) . This study was design ed to determine the effect , onset , and durability of any effect of GA on disease activity monitored with magnetic resonance imaging ( MRI ) in patients with RRMS . Two hundred thirty‐nine eligible patients were r and omized to receive either 20 mg GA ( n = 119 ) or placebo ( n = 120 ) by daily subcutaneous injection . Eligibility required one or more relapses in the 2 years before entry and at least one enhancing lesion on a screening MRI . The study was a r and omized , double‐blind , placebo‐controlled phase during which all patients studied underwent monthly MRI scans and clinical assessment s over 9 months . The primary outcome measure was the total number of enhancing lesions on T1‐weighted images . Secondary outcome measures included the proportion of patients with enhancing lesions , the number of new enhancing lesions and change in their volume ; the number of new lesions detected on T2‐weighted images and change in their volume , and the change in volume of hypointense lesions seen on unenhanced T1‐weighted images . Clinical measures of disease activity were also evaluated . The active treatment and placebo groups were comparable at entry for all demographic , clinical , and MRI variables . Treatment with GA showed a significant reduction in the total number of enhancing lesions compared with placebo ( −10.8 , 95 % confidence interval −18.0 to −3.7 ; p = 0.003 ) . Consistent differences favoring treatment with GA were seen for almost all secondary end points examined : number of new enhancing lesions ( p < 0.003 ) , monthly change in the volume of enhancing lesions ( p = 0.01 ) , and change in volume ( p = 0.006 ) and number of new lesions seen on T2‐weighted images ( p < 0.003 ) . The relapse rate was also significantly reduced by 33 % for GA‐treated patients ( p = 0.012 ) . All effects increased over time . Glatiramer acetate significantly reduced MRI‐measured disease activity and burden . Ann Neurol BACKGROUND Alemtuzumab , a humanized monoclonal antibody that targets CD52 on lymphocytes and monocytes , may be an effective treatment for early multiple sclerosis . METHODS In this phase 2 , r and omized , blinded trial involving previously untreated , early , relapsing-remitting multiple sclerosis , we assigned 334 patients with scores of 3.0 or less on the Exp and ed Disability Status Scale and a disease duration of 3 years or less to receive either subcutaneous interferon beta-1a ( at a dose of 44 microg ) three times per week or annual intravenous cycles of alemtuzumab ( at a dose of either 12 mg or 24 mg per day ) for 36 months . In September 2005 , alemtuzumab therapy was suspended after immune thrombocytopenic purpura developed in three patients , one of whom died . Treatment with interferon beta-1a continued throughout the study . RESULTS Alemtuzumab significantly reduced the rate of sustained accumulation of disability , as compared with interferon beta-1a ( 9.0 % vs. 26.2 % ; hazard ratio , 0.29 ; 95 % confidence interval [ CI ] , 0.16 to 0.54 ; P<0.001 ) and the annualized rate of relapse ( 0.10 vs. 0.36 ; hazard ratio , 0.26 ; 95 % CI , 0.16 to 0.41 ; P<0.001 ) . The mean disability score on a 10-point scale improved by 0.39 point in the alemtuzumab group and worsened by 0.38 point in the interferon beta-1a group ( P<0.001 ) . In the alemtuzumab group , the lesion burden ( as seen on T(2)-weighted magnetic resonance imaging ) was reduced , as compared with that in the interferon beta-1a group ( P=0.005 ) . From month 12 to month 36 , brain volume ( as seen on T(1)-weighted magnetic resonance imaging ) increased in the alemtuzumab group but decreased in the interferon beta-1a group ( P=0.02 ) . Adverse events in the alemtuzumab group , as compared with the interferon beta-1a group , included autoimmunity ( thyroid disorders [ 23 % vs. 3 % ] and immune thrombocytopenic purpura [ 3 % vs. 1 % ] ) and infections ( 66 % vs. 47 % ) . There were no significant differences in outcomes between the 12-mg dose and the 24-mg dose of alemtuzumab . CONCLUSIONS In patients with early , relapsing-remitting multiple sclerosis , alemtuzumab was more effective than interferon beta-1a but was associated with autoimmunity , most seriously manifesting as immune thrombocytopenic purpura . The study was not powered to identify uncommon adverse events . ( Clinical Trials.gov number , NCT00050778 . OBJECTIVES To survey the frequency of use of indirect comparisons in systematic review s and evaluate the methods used in their analysis and interpretation . Also to identify alternative statistical approaches for the analysis of indirect comparisons , to assess the properties of different statistical methods used for performing indirect comparisons and to compare direct and indirect estimates of the same effects within review s. DATA SOURCES Electronic data bases . REVIEW METHODS The Data base of Abstract s of Review s of Effects ( DARE ) was search ed for systematic review s involving meta- analysis of r and omised controlled trials ( RCTs ) that reported both direct and indirect comparisons , or indirect comparisons alone . A systematic review of MEDLINE and other data bases was carried out to identify published methods for analysing indirect comparisons . Study design s were created using data from the International Stroke Trial . R and om sample s of patients receiving aspirin , heparin or placebo in 16 centres were used to create meta-analyses , with half of the trials comparing aspirin and placebo and half heparin and placebo . Methods for indirect comparisons were used to estimate the contrast between aspirin and heparin . The whole process was repeated 1000 times and the results were compared with direct comparisons and also theoretical results . Further detailed case studies comparing the results from both direct and indirect comparisons of the same effects were undertaken . RESULTS Of the review s identified through DARE , 31/327 ( 9.5 % ) included indirect comparisons . A further five review s including indirect comparisons were identified through electronic search ing . Few review s carried out a formal analysis and some based analysis on the naive addition of data from the treatment arms of interest . Few method ological papers were identified . Some valid approaches for aggregate data that could be applied using st and ard software were found : the adjusted indirect comparison , meta-regression and , for binary data only , multiple logistic regression ( fixed effect models only ) . Simulation studies showed that the naive method is liable to bias and also produces over-precise answers . Several methods provide correct answers if strong but unverifiable assumptions are fulfilled . Four times as many similarly sized trials are needed for the indirect approach to have the same power as directly r and omised comparisons . Detailed case studies comparing direct and indirect comparisons of the same effect show considerable statistical discrepancies , but the direction of such discrepancy is unpredictable . CONCLUSIONS Direct evidence from good- quality RCTs should be used wherever possible . Without this evidence , it may be necessary to look for indirect comparisons from RCTs . However , the results may be susceptible to bias . When making indirect comparisons within a systematic review , an adjusted indirect comparison method should ideally be used employing the r and om effects model . If both direct and indirect comparisons are possible within a review , it is recommended that these be done separately before considering whether to pool data . There is a need to evaluate methods for the analysis of indirect comparisons for continuous data and for empirical research into how different methods of indirect comparison perform in cases where there is a large treatment effect . Further study is needed into when it is appropriate to look at indirect comparisons and when to combine both direct and indirect comparisons . Research into how evidence from indirect comparisons compares to that from non-r and omised studies may also be warranted . Investigations using individual patient data from a meta- analysis of several RCTs using different protocol s and an evaluation of the impact of choosing different binary effect measures for the inverse variance method would also be useful We performed a double-blind , placebo-controlled study to evaluate the efficacy of low and high dose of intravenous immunoglobulins ( IVIG ) in relapsing/remitting ( RR ) multiple sclerosis ( MS ) . Patients ( n = 49 ) with clinical definite RR MS were r and omly allocated to three groups and treated with 0.2 g/kg ( n = 17 ) or 0.4 g/kg ( n = 15 ) once a month of IVIG and placebo ( n = 17 ) for 12 months . Clinical data were assessed monthly and magnetic resonance imaging ( MRI ) was performed every 3 months during the study period . Annual relapse rate ( ARR ) and change of the mean Exp and ed Disability Status Scale ( EDSS ) and Neurological Rating Scale Score ( NRSS ) from baseline to study conclusion were used as the clinical end-points . For MRI activity total lesion volume on T2-weighted image ( T2WI ) , new lesions and gadolinium (Gd)-enhanced lesions on T1WI were analysed . ARR in both IVIG groups ( 0.88 for 0.2 g/kg and 0.86 for 0.4 g/kg ) was reduced compared with placebo ( 1.24 ) during treatment period . Neurological disability measured with EDSS decreased slightly in both the IVIG groups ( 0.029 and 0.066 , respectively ) and increased by 0.29 in placebo ( P = 0.0117 ) . The neurologic impairment measured by NRSS showed similar trend . The total lesion volume on T2WI increased by 13.56 % in placebo whereas in the 0.4 g/kg IVIG group decreased by -3.95 % and in the 0.2 g/kg IVIG group increased by 3.6 % . The cumulative numbers of Gd-enhancing lesions and new T2WI lesions in the IVIG groups were reduced in comparison with the placebo group . Our findings suggest that the dose 0.2 g/kg of IVIG is equally effective as 0.4 g/kg in reducing MS activity BACKGROUND Natalizumab is the first alpha4 integrin antagonist in a new class of selective adhesion-molecule inhibitors . We report the results of a two-year phase 3 trial of natalizumab in patients with relapsing multiple sclerosis . METHODS Of a total of 942 patients , 627 were r and omly assigned to receive natalizumab ( at a dose of 300 mg ) and 315 to receive placebo by intravenous infusion every four weeks for more than two years . The primary end points were the rate of clinical relapse at one year and the rate of sustained progression of disability , as measured by the Exp and ed Disability Status Scale , at two years . RESULTS Natalizumab reduced the risk of sustained progression of disability by 42 percent over two years ( hazard ratio , 0.58 ; 95 percent confidence interval , 0.43 to 0.77 ; P<0.001 ) . The cumulative probability of progression ( on the basis of Kaplan-Meier analysis ) was 17 percent in the natalizumab group and 29 percent in the placebo group . Natalizumab reduced the rate of clinical relapse at one year by 68 percent ( P<0.001 ) and led to an 83 percent reduction in the accumulation of new or enlarging hyperintense lesions , as detected by T2-weighted magnetic resonance imaging ( MRI ) , over two years ( mean numbers of lesions , 1.9 with natalizumab and 11.0 with placebo ; P<0.001 ) . There were 92 percent fewer lesions ( as detected by gadolinium-enhanced MRI ) in the natalizumab group than in the placebo group at both one and two years ( P<0.001 ) . The adverse events that were significantly more frequent in the natalizumab group than in the placebo group were fatigue ( 27 percent vs. 21 percent , P=0.048 ) and allergic reaction ( 9 percent vs. 4 percent , P=0.012 ) . Hypersensitivity reactions of any kind occurred in 25 patients receiving natalizumab ( 4 percent ) , and serious hypersensitivity reactions occurred in 8 patients ( 1 percent ) . CONCLUSIONS Natalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in patients with relapsing multiple sclerosis . Adhesion-molecule inhibitors hold promise as an effective treatment for relapsing multiple sclerosis . ( Clinical Trials.gov number , NCT00027300 . ) Multiple sclerosis ( MS ) is thought to be an autoimmune disease mediated by T lymphocytes that recognize myelin components of the central nervous system . In a 1-year double-blind study , 30 individuals with relapsing-remitting MS received daily capsules of bovine myelin or a control protein to determine the effect of oral tolerization to myelin antigens on the disease . Six of 15 individuals in the myelin-treated group had at least one major exacerbation ; 12 or 15 had an attack in the control group . T cells reactive with myelin basic protein were reduced in the myelin-treated group . No toxicity or side effects were noted . Although conclusions about efficacy can not be drawn from these data , they open an area of investigation for MS and other autoimmune diseases BACKGROUND Depletion of B lymphocytes is associated with suppression of inflammatory activity in multiple sclerosis . We aim ed to assess the safety and efficacy of atacicept , a recombinant fusion protein that suppresses B-cell function and antibody production . METHODS In this placebo-controlled , double-blind , 36-week , phase 2 trial ( ATAMS ) in Australia , Canada , Europe , and the USA , patients aged 18 - 60 years with relapsing multiple sclerosis were r and omly assigned via an interactive voice response system in a 1:1:1:1 ratio , stratified by geographical region , to receive weekly subcutaneous injections with atacicept ( 25 , 75 , or 150 mg ) or placebo . Both patients and study personnel were masked to treatment assignment . The primary endpoint was the change in mean number of gadolinium-enhancing lesions on T1-weighted MRI per patient per scan between weeks 12 and 36 . Efficacy endpoints were analysed in the intention-to-treat population . Patients who completed week 36 were eligible to participate in a long-term extension study ( ATAMS EXT ) , consisting of a double-blind phase followed by an open-label phase , for a total study time of up to 5 years . The study was terminated early after the independent data and safety monitoring board noted an increased annualised relapse rate with atacicept . The protocol was subsequently amended to include a 60-week safety follow-up , to allow treatment with approved multiple sclerosis drugs , and to change the primary endpoint to gadolinium-enhancing T1 lesions per scan during the entire double-blind period of ATAMS . Both the trial and the extension are registered with Clinical Trials.gov , numbers NCT00642902 ( ATAMS ) and NCT00853762 ( ATAMS EXT ) . FINDINGS Between April 23 , 2008 , and early study termination on Sept 11 , 2009 , 255 patients were r and omly assigned : 63 to placebo , 63 to atacicept 25 mg , 64 to 75 mg , and 65 to 150 mg . 90 ( 35 % ) patients completed the week 36 treatment visit , 26 ( 10 % ) discontinued before study termination ( including one who dropped out before receiving study treatment ) , and 139 ( 55 % ) discontinued because of study termination . During the double-blind period of ATAMS , annualised relapse rates were higher in the atacicept groups than in the placebo group ( atacicept 25 mg , 0·86 , 95 % CI 0·43 - 1·74 ; 75 mg , 0·79 , 0·40 - 1·58 ; 150 mg , 0·98 , 0·52 - 1·81 ; placebo , 0·38 , 0·17 - 0·87 ) . Mean numbers of gadolinium-enhancing T1 lesions per scan were similar in all groups ( 25 mg , 2·26 , 0·97 - 5·27 ; 75 mg , 2·30 , 1·08 - 4·92 ; 150 mg , 2·49 , 1·18 - 5·27 ; placebo , 3·07 , 1·40 - 6·77 ) . Seven patients ( one taking placebo and six atacicept ) discontinued treatment because of adverse events . One death occurred in the placebo group . During the safety follow-up , immunoglobulin concentrations and B-cell counts returned towards predose values and annualised relapse rates in the atacicept groups decreased until they were similar to that of the placebo group INTERPRETATION Increased clinical disease activity associated with atacicept suggests that the role of B cells and humoral immunity in multiple sclerosis is complex . For studies that explore therapeutic immunomodulation in multiple sclerosis , rigorous monitoring for negative effects on clinical and MRI outcomes is warranted . FUNDING Merck Serono ( Merck KGaA ) and EMD Serono ( Merck KGaA ) BACKGROUND Interferon beta is used to modify the course of relapsing multiple sclerosis . Despite interferon beta therapy , many patients have relapses . Natalizumab , an alpha4 integrin antagonist , appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies . METHODS We r and omly assigned 1171 patients who , despite interferon beta-1a therapy , had had at least one relapse during the 12-month period before r and omization to receive continued interferon beta-1a in combination with 300 mg of natalizumab ( 589 patients ) or placebo ( 582 patients ) intravenously every 4 weeks for up to 116 weeks . The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks , as measured by the Exp and ed Disability Status Scale , at 2 years . RESULTS Combination therapy result ed in a 24 percent reduction in the relative risk of sustained disability progression ( hazard ratio , 0.76 ; 95 percent confidence interval , 0.61 to 0.96 ; P=0.02 ) . Kaplan-Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone . Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone ( 0.34 vs. 0.75 , P<0.001 ) and with fewer new or enlarging lesions on T(2)-weighted magnetic resonance imaging ( 0.9 vs. 5.4 , P<0.001 ) . Adverse events associated with combination therapy were anxiety , pharyngitis , sinus congestion , and peripheral edema . Two cases of progressive multifocal leukoencephalopathy , one of which was fatal , were diagnosed in natalizumab-treated patients . CONCLUSIONS Natalizumab added to interferon beta-1a was significantly more effective than interferon beta-1a alone in patients with relapsing multiple sclerosis . Additional research is needed to eluci date the benefits and risks of this combination treatment . ( Clinical Trials.gov number , NCT00030966 . ) To assess the efficacy and safety of glatiramer acetate ( GA ) 40 mg administered 3 × weekly ( tiw ) compared with placebo in patients with relapsing – remitting multiple sclerosis ( RRMS ) BACKGROUND Subcutaneous pegylated interferon ( peginterferon ) beta-1a is being developed for treatment of relapsing multiple sclerosis , with less frequent dosing than currently available first-line injectable treatments . We assessed the safety and efficacy of peginterferon beta-1a after 48 weeks of treatment in the placebo-controlled phase of the ADVANCE trial , a study of patients with relapsing-remitting multiple sclerosis . METHODS We did this 2-year , double-blind , parallel group , phase 3 study , with a placebo-controlled design for the first 48 weeks , at 183 sites in 26 countries . Patients with relapsing-remitting multiple sclerosis ( age 18 - 65 years , with Exp and ed Disability Status Scale score ≤5 ) were r and omly assigned ( 1:1:1 ) via an interactive voice response or web system , and stratified by site , to placebo or subcutaneous peginterferon beta-1a 125 μg once every 2 weeks or every 4 weeks . The primary endpoint was annualised relapse rate at 48 weeks . This trial is registered with Clinical Trials.gov , number NCT00906399 . FINDINGS We screened 1936 patients and enrolled 1516 , of whom 1512 were r and omly assigned ( 500 to placebo , 512 to peginterferon every 2 weeks , 500 to peginterferon every 4 weeks ) ; 1332 ( 88 % ) patients completed 48 weeks of treatment . Adjusted annualised relapse rates were 0·397 ( 95 % CI 0·328 - 0·481 ) in the placebo group versus 0·256 ( 0·206 - 0·318 ) in the every 2 weeks group and 0·288 ( 0·234 - 0·355 ) in the every 4 weeks group ( rate ratio for every 2 weeks group 0·644 , 95 % CI 0·500 - 0·831 , p=0·0007 ; rate ratio for the every 4 weeks group 0·725 , 95 % CI 0·565 - 0·930 , p=0·0114 ) . 417 ( 83 % ) patients taking placebo , 481 ( 94 % ) patients taking peginterferon every 2 weeks , and 472 ( 94 % ) patients taking peginterferon every 4 weeks reported adverse events including relapses . The most common adverse events associated with peginterferon beta-1a were injection site reactions , influenza-like symptoms , pyrexia , and headache . 76 ( 15 % ) patients taking placebo , 55 ( 11 % ) patients taking study drug every 2 weeks , and 71 ( 14 % ) patients taking study drug every 4 weeks reported serious adverse events ; relapse , pneumonia , and urinary tract infection were the most common . INTERPRETATION After 48 weeks , peginterferon beta-1a significantly reduced relapse rate compared with placebo . The drug might be an effective treatment for relapsing-remitting multiple sclerosis with less frequent administration than available treatments . FUNDING Biogen Idec BACKGROUND Two proof-of-concept clinical trials have provided evidence that laquinimod reduces disease activity in patients with relapsing-remitting multiple sclerosis . METHODS We conducted a r and omized , double-blind , phase 3 study at 139 sites in 24 countries . A total of 1106 patients with relapsing-remitting multiple sclerosis were r and omly assigned in a 1:1 ratio to receive oral laquinimod at a dose of 0.6 mg once daily or placebo for 24 months . The primary end point was the annualized relapse rate during the 24-month period . Secondary end points included confirmed disability progression ( defined as an increase in the score on the Exp and ed Disability Status Scale that was sustained for at least 3 months ) and the cumulative number of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted magnetic resonance imaging . RESULTS Treatment with laquinimod as compared with placebo was associated with a modest reduction in the mean ( ±SE ) annualized relapse rate ( 0.30±0.02 vs. 0.39±0.03 , P=0.002 ) and with a reduction in the risk of confirmed disability progression ( 11.1 % vs. 15.7 % ; hazard ratio , 0.64 ; 95 % confidence interval , 0.45 to 0.91 ; P=0.01 ) . The mean cumulative numbers of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted images were lower for patients receiving laquinimod than for those receiving placebo ( 1.33±0.14 vs. 2.12±0.22 and 5.03±0.08 vs. 7.14±0.07 , respectively ; P<0.001 for both comparisons ) . Transient elevations in alanine aminotransferase levels to greater than three times the upper limit of the normal range were observed in 24 patients receiving laquinimod ( 5 % ) and 8 receiving placebo ( 2 % ) . CONCLUSIONS In this phase 3 study , oral laquinimod administered once daily slowed the progression of disability and reduced the rate of relapse in patients with relapsing-remitting multiple sclerosis . ( Funded by Teva Pharmaceutical Industries ; Clinical Trials.gov number , NCT00509145 . ) BACKGROUND Fingolimod ( FTY720 ) , a sphingosine-1-phosphate-receptor modulator that prevents lymphocyte egress from lymph nodes , showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis . METHODS In this 12-month , double-blind , double-dummy study , we r and omly assigned 1292 patients with relapsing-remitting multiple sclerosis who had a recent history of at least one relapse to receive either oral fingolimod at a daily dose of either 1.25 or 0.5 mg or intramuscular interferon beta-1a ( an established therapy for multiple sclerosis ) at a weekly dose of 30 microg . The primary end point was the annualized relapse rate . Key secondary end points were the number of new or enlarged lesions on T(2)-weighted magnetic resonance imaging ( MRI ) scans at 12 months and progression of disability that was sustained for at least 3 months . RESULTS A total of 1153 patients ( 89 % ) completed the study . The annualized relapse rate was significantly lower in both groups receiving fingolimod--0.20 ( 95 % confidence interval [ CI ] , 0.16 to 0.26 ) in the 1.25-mg group and 0.16 ( 95 % CI , 0.12 to 0.21 ) in the 0.5-mg group -- than in the interferon group ( 0.33 ; 95 % CI , 0.26 to 0.42 ; P<0.001 for both comparisons ) . MRI findings supported the primary results . No significant differences were seen among the study groups with respect to progression of disability . Two fatal infections occurred in the group that received the 1.25-mg dose of fingolimod : disseminated primary varicella zoster and herpes simplex encephalitis . Other adverse events among patients receiving fingolimod were nonfatal herpesvirus infections , bradycardia and atrioventricular block , hypertension , macular edema , skin cancer , and elevated liver-enzyme levels . CONCLUSIONS This trial showed the superior efficacy of oral fingolimod with respect to relapse rates and MRI outcomes in patients with multiple sclerosis , as compared with intramuscular interferon beta-1a . Longer studies are needed to assess the safety and efficacy of treatment beyond 1 year . ( Clinical Trials.gov number , NCT00340834 . Background Studies evaluating interferon beta ( IFNβ ) for multiple sclerosis ( MS ) showed only partial efficacy . In many patients , IFNβ does not halt relapses or disability progression . One strategy to potentially enhance efficacy is to combine IFNβ with classical immunosuppressive agents , such as azathioprine ( AZA ) or corticosteroids , commonly used for other autoimmune disorders . Objective The Avonex – Steroids – Azathioprine study was placebo-controlled trial and evaluated efficacy of IFNβ-1a alone and combined with low-dose AZA alone or low-dose AZA and low-dose corticosteroids as initial therapy . Methods A total of 181 patients with relapsing – remitting MS ( RRMS ) were r and omized to receive IFNβ-1a 30 μg intramuscularly ( IM ) once weekly , IFNβ-1a 30 μg IM once weekly plus AZA 50 mg orally once daily , or IFNβ-1a 30 μg IM once weekly plus AZA 50 mg orally once daily plus prednisone 10 mg orally every other day . The primary end point was annualized relapse rate ( ARR ) at 2 years . Patients were eligible for enrollment in a 3-year extension . Results At 2 years , adjusted ARR was 1.05 for IFNβ-1a , 0.91 for IFNβ-1a plus AZA , and 0.73 for combination . The cumulative probability of sustained disability progression was 16.8 % for IFNβ-1a , 20.7 % for IFNβ-1a plus AZA , and 17.5 % for combination . There were no statistically significant differences among groups for either measure at 2 and 5 years . Percent T2 lesion volume change at 2 years was significantly lower for combination ( + 14.5 % ) versus IFNβ-1a alone ( + 30.3 % , P < 0.05 ) . Groups had similar safety profiles . Conclusion In IFNβ-naïve patients with early active RRMS , combination treatment did not show superiority over IFNβ-1a monotherapy Objective : To evaluate the safety and tolerability of natalizumab when added to glatiramer acetate ( GA ) in patients with relapsing multiple sclerosis . The primary outcome assessed whether this combination would increase the rate of development of new active lesions on cranial MRI scans vs GA alone . Methods : This phase 2 , r and omized , double-blind , placebo-controlled study included patients aged 19 to 55 years who were treated with GA for at least 1 year before r and omization and experienced at least one relapse during the previous year . Patients received IV natalizumab 300 mg ( n = 55 ) or placebo ( n = 55 ) once every 4 weeks plus GA 20 mg subcutaneously once daily for ≤20 weeks . Results : The mean rate of development of new active lesions was 0.03 with combination therapy vs 0.11 with GA alone ( p = 0.031 ) . Combination therapy result ed in lower mean numbers of new gadolinium-enhancing lesions ( 0.6 vs 2.3 for GA alone , p = 0.020 ) and new/newly enlarging T2-hyperintense lesions ( 0.5 vs 1.3 , p = 0.029 ) . The incidence of infection and infusion reactions was similar in both groups ; no hypersensitivity reactions were observed . One serious adverse event occurred with combination therapy ( elective hip surgery ) . With the exception of an increase in anti-natalizumab antibodies with combination therapy , laboratory data were consistent with previous clinical studies of natalizumab alone . Conclusion : The combination of natalizumab and glatiramer acetate seemed safe and well tolerated during 6 months of therapy . GLOSSARYAE = adverse event ; CONSORT = Consoli date d St and ards of Reporting Trials ; EDSS = Exp and ed Disability Status Scale ; GA = glatiramer acetate ; Gd+ = gadolinium-enhancing ; GLANCE = Glatiramer Acetate and Natalizumab Combination Evaluation ; IFN&bgr ; = interferon & bgr ; ; MS = multiple sclerosis ; PML = progressive multifocal leukoencephalopathy Background : There are no published MRI studies comparing interferon beta 1b ( IFNβ-1b ) and glatiramer acetate ( GA ) for treatment of relapsing multiple sclerosis ( MS ) . Objective : To compare the efficacy of IFNβ-1b and GA for suppression of MS disease activity as evidence d on frequent brain MRI . Methods : A total of 75 patients with relapsing-remitting MS or clinical ly isolated syndromes were r and omized to st and ard doses of IFNβ-1b or GA and followed by monthly brain MRI for up to 2 years with a protocol optimized to detect enhancement . The primary outcome was the number of combined active lesions ( CAL ) per patient per scan during the first year , which included all enhancing lesions and nonenhancing new T2/fluid-attenuated inversion recovery ( FLAIR ) lesions . Secondary outcomes were the number of new lesions and clinical exacerbations over 2 years . Results : Baseline characteristics were similar between the groups . The primary outcome showed similar median ( 75th percentile ) CAL per patient per scan for months 1–12 , 0.63 ( 2.76 ) for IFNβ-1b , and 0.58 ( 2.45 ) for GA ( p = 0.58 ) . There were no differences in new lesion or clinical relapses for 2 years . Only 4.4 % of CAL on monthly MRI scans were nonenhancing new T2/FLAIR lesions . Conclusion : Patients with relapsing multiple sclerosis r and omized to interferon beta 1b or glatiramer acetate showed similar MRI and clinical activity |
1,095 | 20,439,566 | 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 . | BACKGROUND Previous meta-analyses suggest that treatment with erythropoiesis-stimulating agents ( ESAs ) in chronic kidney disease ( CKD ) increases the risk for death .
Additional r and omized trials have been recently completed .
PURPOSE To summarize the effects of ESA treatment on clinical outcomes in patients with anemia and CKD . | 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-dialysis , haemodialysis ( HD ) and peritoneal dialysis patients ] were r and omized to reach a normal haemoglobin of 135 - 160 g/l ( n=216 ) or a subnormal haemoglobin of 90 - 120 g/l ( n=200 ) with or without epoetin alfa . Study duration was 48 - 76 weeks . QoL was measured using Kidney Disease Question naires in 253 Swedish dialysis patients . Safety was examined in all patients . RESULTS QoL improved , measured as a decrease in physical symptoms ( P=0.02 ) , fatigue ( P=0.05 ) , depression ( P=0.01 ) and frustration ( P=0.05 ) in the Swedish dialysis patients when haemoglobin was normalized . In pre-dialysis patients , diastolic blood pressure was higher in the normal compared with the subnormal haemoglobin group after 48 weeks . However , the progression rate of chronic renal failure was comparable . In the normal haemoglobin group ( N-Hb ) , 51 % had at least one serious adverse event compared with 49 % in the subnormal haemoglobin group ( S-Hb ) ( P=0.32 ) . The incidence of thrombovascular events and vascular access thrombosis in HD patients did not differ . The mortality rate was 13.4 % in the N-Hb group and 13.5 % in the S-Hb group ( P=0.98 ) . Mortality decreased with increasing mean haemoglobin in both groups . CONCLUSIONS Normalization of haemoglobin improved QoL in the subgroup of dialysis patients , appears to be safe and can be considered in many patients with end-stage renal disease BACKGROUND In patients with end-stage renal disease , anemia develops as a result of erythropoietin deficiency , and recombinant human erythropoietin ( epoetin ) is prescribed to correct the anemia partially . We examined the risks and benefits of normalizing the hematocrit in patients with cardiac disease who were undergoing hemodialysis . METHODS We studied 1233 patients with clinical evidence of congestive heart failure or ischemic heart disease who were undergoing hemodialysis : 618 patients were assigned to receive increasing doses of epoetin to achieve and maintain a hematocrit of 42 percent , and 615 were assigned to receive doses of epoetin sufficient to maintain a hematocrit of 30 percent throughout the study . The median duration of treatment was 14 months . The primary end point was the length of time to death or a first nonfatal myocardial infa rct ion . RESULTS After 29 months , there were 183 deaths and 19 first nonfatal myocardial infa rct ions among the patients in the normal-hematocrit group and 150 deaths and 14 nonfatal myocardial infa rct ions among those in the low-hematocrit group ( risk ratio for the normal-hematocrit group as compared with the low-hematocrit group , 1.3 ; 95 percent confidence interval , 0.9 to 1.9 ) . Although the difference in event-free survival between the two groups did not reach the prespecified statistical stopping boundary , the study was halted . The causes of death in the two groups were similar . The mortality rates decreased with increasing hematocrit values in both groups . The patients in the normal-hematocrit group had a decline in the adequacy of dialysis and received intravenous iron dextran more often than those in the low-hematocrit group . CONCLUSIONS In patients with clinical ly evident congestive heart failure or ischemic heart disease who are receiving hemodialysis , administration of epoetin to raise their hematocrit to 42 percent is not recommended We administered recombinant human erythropoietin to 25 anemic patients with end-stage renal disease who were undergoing hemodialysis . The recombinant human erythropoietin was given intravenously three times weekly after dialysis , and transfusion requirements , hematocrit , ferrokinetics , and reticulocyte responses were monitored . Over a range of doses between 15 and 500 units per kilogram of body weight , dose-dependent increases in effective erythropoiesis were noted . At 500 units per kilogram , changes in the hematocrit of as much as 10 percentage points were seen within three weeks , and increases in ferrokinetics of three to four times basal values , as measured by erythron transferrin uptake , were observed . Of 18 patients receiving effective doses of recombinant human erythropoietin , 12 who had required transfusions no longer needed them , and in 11 the hematocrit increased to 35 percent or more . Along with the rise in hematocrit , four patients had an increase in blood pressure , and a majority had increases in serum creatinine and potassium levels . No organ dysfunction or other toxic effects were observed , and no antibodies to the recombinant hormone were formed . These results demonstrate that recombinant human erythropoietin is effective , can eliminate the need for transfusions with their risks of immunologic sensitization , infection , and iron overload , and can restore the hematocrit to normal in many patients with the anemia of end-stage renal disease BACKGROUND Erythropoietin is known to improve outcomes in patients with anemia from chronic renal disease . However , there is uncertainty about the optimal timing of initiation of erythropoietin treatment in predialysis patients with non-severe anemia . METHODS We conducted a r and omized controlled trial of early versus deferred initiation of erythropoietin in nondiabetic predialysis patients with serum creatinine 2 to 6 mg/dL and hemoglobin 9 to 11.6 g/dL. The early treatment arm was immediately started on 50 U/kg/wk of erythropoietin alpha with appropriate titration aim ing for hemoglobin of > or = 13 g/dL. The deferred treatment arm would start erythropoietin only when hemoglobin decreased to < 9 g/dL. The primary end point was a composite of doubling of creatinine , renal replacement , or death . RESULTS Eighty-eight patients were r and omized ( early treatment N= 45 , deferred treatment N= 43 ) and followed for a median of 22.5 months . During follow-up , 13 versus 23 patients reached the primary end point in the two arms , respectively ( log-rank P= 0.0078 ) . The relative hazard for reaching an end point was 0.42 ( P= 0.012 ) . Adjusting for baseline serum creatinine , the adjusted relative hazard was 0.37 ( P= 0.004 ) , while the risk increased 2.23-fold ( P < 0.001 ) per 1 mg/dL higher creatinine at baseline . The benefit was similar regardless of the baseline hemoglobin and proteinuria . No patients had any severe adverse events . CONCLUSION Early initiation of erythropoietin in predialysis patients with non-severe anemia significantly slows the progression of renal disease and delays the initiation of renal replacement therapy PURPOSE The purpose of this study was to determine the efficacy of recombinant human erythropoietin ( rHuEPO ) given subcutaneously three times/week in patients with chronic renal failure and anemia ( predialysis ) . PATIENTS AND METHODS Eleven patients with predialysis chronic renal failure participated in a double-blind , placebo-controlled study of subcutaneously administered erythropoietin . For 12 weeks , patients received either rHuEPO 100 mu/kg body weight three times/week subcutananeously or a placebo . After 12 weeks of placebo , patients now also received rHuEPO in a dose up to 150 mu/kg three times/week until target hematocrit was achieved . Throughout the study , blood pressure was monitored closely and blood work was obtained regularly for hemoglobin , hematocrit , reticulocyte count , and iron profile determinations . RESULTS At 12 weeks , the hematocrit of the treated group had risen from 29 % + /- 2 % to 35 % + /- 2 % ( p less than 0.001 ) . The placebo group baseline hematocrit was 28 % + /- 2 % and at 12 weeks 26 % + /- 2 % After 12 weeks of rHuEPO therapy , the hematocrit of the prior placebo group was 32 % + /- 2 % ( p less than 0.001 versus baseline ) . No significant change in biochemical parameters was noted . Mean blood pressure values were comparable before and after treatment . All protein ultimately required iron supplementation . In two patients , the rate of progression of renal failure appeared to increase as their hematocrit rose and rHuEPO was discontinued . CONCLUSIONS It is concluded that rHuEPO given subcutaneously is an effective and safe therapy for patients with chronic renal failure who are anemic and who are not receiving dialysis It is not known whether prevention of anemia among patients with chronic kidney disease would affect the development or progression of left ventricular ( LV ) hypertrophy . A r and omized controlled trial was performed with 155 patients with chronic kidney disease ( creatinine clearance , 15 to 50 ml/min ) , with entry hemoglobin concentrations ( [ Hb ] ) of 110 to 120 g/L ( female patients ) or 110 to 130 g/L ( male patients ) . Patients were monitored for 2 yr or until they required dialysis ; the patients were r and omized to receive epoetin alpha as necessary to maintain [ Hb ] between 120 and 130 g/L ( group A ) or between 90 and 100 g/L ( group B ) . [ Hb ] increased for group A ( from 112 + /- 9 to 121 + /- 14 g/L , mean + /- SD ) and decreased for group B ( from 112 + /- 8 to 108 + /- 13 g/L ) ( P < 0.001 , group A versus group B ) . On an intent-to-treat analysis , the changes in LV mass index for the groups during the 2-yr period were not significantly different ( 2.5 + /- 20 g/m(2 ) for group A versus 4.5 + /- 20 g/m(2 ) for group B , P = NS ) . There was no significant difference between the groups in 2-yr mean unadjusted systolic BP ( 141 + /- 14 versus 138 + /- 13 mmHg ) or diastolic BP ( 80 + /- 6 versus 79 + /- 7 mmHg ) . The decline in renal function in 2 yr , as assessed with nuclear estimations of GFR , also did not differ significantly between the groups ( 8 + /- 9 versus 6 + /- 8 ml/min per 1.73 m(2 ) ) . In conclusion , maintenance of [ Hb ] above 120 g/L , compared with 90 to 100 g/L , had similar effects on the LV mass index and did not clearly affect the development or progression of LV hypertrophy . The maintenance of [ Hb ] above 100 g/L for many patients in group B might have been attributable to the relative preservation of renal function In a two-way study , we treated renal anemia in chronic hemodialysis patients with recombinant human erythropoietin ( rh-EPO ) and followed heart morphology and function dynamics by echocardiography . Thirty-eight patients were r and omly divided in two equal groups : the therapy group , treated with rh-EPO for 24 months , and the control group , not treated during the first 12 months and treated with rh-EPO during the second 12 months . Anemia was corrected , and hematocrit was maintained between 30 and 35 vol% by subcutaneous rh-EPO administration . Echocardiographic assessment was performed at the end of the untreated control phase and was repeated after 12 months of rh-EPO treatment in the control group and after 12 and 24 months of treatment in the therapy group . The results revealed significant morphologic , hemodynamic , and eventually functional changes . After 12 months of rh-EPO treatment , the end-diastolic volume ( EDV ) decreased from 135.8 + /- 23.7 to 109.8 + /- 25.3 ml , p < 0.001 ; stroke volume ( SV ) from 91.9 + /- 17.6 to 71.3 + /- 12.4 ml , p < 0.001 ; left ventricular mass-Devereux ( LVMD ) from 297.2 + /- 57.8 to 218.0 + /- 50.4 g , p < 0.01 ; cardiac output ( CO ) from 7,279 + /- 1,932 to 5,711 + /- 1,276 ml/min , p < 0.002 ; total peripheral resistance ( TPR ) rose from 1,330 + /- 390 to 1,707 + /- 373 dynes x s/cm5 , p < 0.007 . After 24 months , LVMD decreased further from 224.6 + /- 43.1 to 195.7 + /- 46.3 g , p < 0.004 . The relaxation time index ( RTI ) decreased from 64.7 + /- 20.4 to 52.4 + /- 18.0 ms , p < 0.045 , suggesting improved diastolic function . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND This study is part of a 3-country study testing whether normal levels of hemoglobin ( Hgb ) delay the progression of left ventricular ( LV ) growth in chronic kidney disease ( CKD ) patients not on dialysis . METHODS This was an open-label , r and omized , multicenter , controlled trial conducted in 27 tertiary-care hospitals in Italy . Treated subjects ( n=46 ) received epoetin-alpha ( EPO-alpha ) to maintain Hgb levels in the range 12 - 14 g/dL. Control subjects ( n=49 ) were not treated unless their Hgb decreased to 9.0 g/dL. Primary outcome was LV mass index ( MI ) change after 24 months . Subcutaneous EPO-alpha was withdrawn in Europe and the study prematurely terminated ; therefore , a 12-month analysis was carried out . RESULTS Mean age was 57 years ( 38 % were women , 18 % with diabetes , 76 % taking ACEI or ARB and 22 % statins ) . EPO-alpha median final dose was 2,000 IU/week . Hgb significantly increased ( 12.4 -/+ 1.1 g/L ) for the treatment group and decreased for controls ( 11.3 -/+ 1.3 g/L ; p<0.001 ) . The intention-to-treat analysis was conducted in 78 patients . Mean baseline LVMI for treated patients and controls was 109.5 -/+ 23 g/m2 and 108.7 -/+ 29 g/m2 , respectively . LVMI did not change among controls , whereas it decreased slightly , though not significantly , among treated patients . CONCLUSIONS The current Italian trial was negative , maybe due to its limitations : lack of power , 1-year follow-up and normal LVMI in some patients at start ; however , it was consistent with other published studies . Thus , it is unlikely that targeting hemoglobin in the normal range for CKD patients is of benefit OBJECTIVE To evaluate the use of hematocrit as a surrogate end point for survival among end-stage renal disease ( ESRD ) patients treated with epoetin . STUDY DESIGN AND SETTING Using United States Renal Data System ( USRDS ) data , we conducted an observational prospect i ve study to analyze the relationships among epoetin dose , hematocrit , and survival for 31,301 facility-based hemodialysis patients incident to ESRD therapy in 1998 . To address our objective , we used criteria developed by Prentice based on results from a Cox regression model . RESULTS Results indicate that hematocrit is inversely associated with epoetin dose . For the same epoetin treatment-related achieved hematocrit levels , there were widely varying treatment-related survival outcomes , thereby challenging a central criterion required to empirically vali date a surrogate end point . CONCLUSION Our results support earlier clinical trial and epidemiological data suggesting that hematocrit may not be a valid surrogate for survival among the epoetin-treated renal failure population . We hypothesize that hematocrit may not be in the causal pathway or that epoetin may have important mechanisms of action apart from increasing hematocrit . Effective treatment for anemia may therefore not be simply a matter of increasing hematocrit . This study has potential implication s for revising the existing treatment guidelines for anemia management and selecting an appropriate treatment regimen BACKGROUND This multicentre , open-label prospect i ve , r and omized , comparative-group study evaluated the effects of maintaining haemoglobin ( Hb ) in pre-dialysis chronic kidney disease ( CKD ) patients . METHODS A total of 197 patients were r and omized to start subcutaneous epoetin-alpha ( SC-EPO ; EPREX ; 1000 U twice weekly ) at an early stage of anaemia to maintain Hb at 11.0 + /- 1.0 g/dl ( group A , n = 65 ) , or to allow Hb to fall to < or = 9.0 g/dl before starting SC-EPO ( group B , n = 132 ) ( 2000 U three times weekly ) ; and subsequently maintaining Hb at 11.0 + /- 1.0 g/dl . RESULTS Of 132 patients r and omized to group B , 55 progressed to treatment ( -trigger ) . The study was prematurely terminated due to contraindication of the subcutaneous administration route . Mean weekly EPO doses at 1 year were 1471 U for group A ; 820 U for group B ; final doses were 2281 U for group A ; 2099 U for group B. There was no significant difference between groups A and B with regard to left ventricular mass ( -12.5 vs -9.7 % ; P = 0.82 ) . In groups A and B , 48 % and 52 % , respectively , terminated the study because of dialysis/death , after a median of 36.3 and 27.3 months , respectively . CONCLUSION Early intervention to correct anaemia in CKD patients did not have a significant impact on LVM , the primary efficacy variable . Time to dialysis/death was not significantly different between groups A and BACKGROUND Hemoglobin levels below 10 g/dL lead to left ventricular ( LV ) hypertrophy , LV dilation , a lower quality of life , higher cardiac morbidity , and a higher mortality rate in end-stage renal disease . The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown . METHODS One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were r and omly assigned to receive doses of epoetin alpha design ed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks . The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation . RESULTS In patients with concentric LV hypertrophy , the changes in LV mass index were similar in the normal and low target hemoglobin groups . The changes in cavity volume index were similar in both targets in the LV dilation group . Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved ( 8 mL/m2 per 1 g/dL hemoglobin decrement , P = 0.009 ) . Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation . Normalization of hemoglobin led to improvements in fatigue ( P = 0.009 ) , depression ( P = 0.02 ) , and relationships ( P = 0.004 ) . CONCLUSIONS Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation . It may , however , prevent the development of LV dilation , and it leads to improved quality of life A r and omized , double-blind , placebo-controlled , multicenter trial was performed to assess the safety and efficacy of subcutaneous recombinant erythropoietin ( EPO ) in peritoneal dialysis patients . Seventy-eight patients were r and omized to receive EPO and 74 received placebo during the first 12 wk . After this , placebo patients with hematocrit less than 32 % entered the EPO maintenance phase along with the initial EPO patients . Hematocrit rose significantly in the EPO group from 23.8 to 32 % after 6 wk , and this was sustained at 33.7 % at 12 wk . In the placebo group , the pre study hematocrit was 23.8 % as well , and no significant change in hematocrit occurred over 12 wk . Concomitant with the rise in hematocrit , transfusion requirements fell only in the EPO group . Eighty-eight percent of patients receiving EPO had their anemia ameliorated by Week 12 of the study . There was a wide range of dosage requirements during the maintenance phase , ranging from 8,000 U thrice weekly to 4,000 U every other week . Adverse events after EPO were similar to those seen in hemodialysis patients given this agent , with hypertension developing or worsening in 55 % of EPO patients during the initial 12 wk of therapy . Blood pressure was more likely to rise in patients with hypertension before receiving EPO . EPO is safe and effective in peritoneal dialysis patients , as it is in hemodialysis patients . Other than a rise in blood pressure , which is manageable with antihypertensives and ultrafiltration with dialysis , no serious side effects are seen . The optimal target hematocrit , effects of anemia improvement on quality of life , and end-organ ( heart , brain ) effects of anemia improvement in this patient population require further study It is unclear whether physiologic hemoglobin targets lead to cardiac benefit in incident hemodialysis patients without symptomatic heart disease and left ventricular dilation . In this r and omized , double-blind study , lower ( 9.5 to 11.5 g/dl ) and higher ( 13.5 to 14.5 g/dl ) hemoglobin targets were generated with epoetin alpha over 24 wk and maintained for an additional 72 wk . Major eligibility criteria included recent hemodialysis initiation and absence of symptomatic cardiac disease and left ventricular dilation . The primary outcome measure was left ventricular volume index ( LVVI ) . The study enrolled 596 patients . Mean age , duration of dialysis therapy , baseline predialysis hemoglobin , and LVVI were 50.8 yr , 0.8 yr , 11.0 g/dl , and 69 ml/m2 , respectively ; 18 % had diabetic nephropathy . Mean hemoglobin levels in the higher and lower target groups were 13.3 and 10.9 g/dl , respectively , at 24 wk . Percentage changes in LVVI between baseline and last value were similar ( 7.6 % in the higher and 8.3 % in the lower target group ) as were the changes in left ventricular mass index ( 16.8 versus 14.2 % ) . For the secondary outcomes , the only between-group difference was an improved SF-36 Vitality score in the higher versus the lower target group ( 1.21 versus -2.31 ; P = 0.036 ) . Overall adverse event rates were similar in both target groups ; higher ( P < 0.05 ) rates of skeletal pain , surgery , and dizziness were seen in the lower target group , and headache and cerebrovascular events were seen in the higher target group . Normalization of hemoglobin in incident hemodialysis patients does not have a beneficial effect on cardiac structure , compared with partial correction Since the earliest reports of the use of Epoetin alfa in hemodialysis patients , it has been described that Epoetin alfa may exacerbate preexisting hypertension or induce hypertension in End Stage Renal Disease ( ESRD ) patients not previously hypertensive . We undertook this study to determine if the correction of anemia in ESRD patients with cardiac disease from a hematocrit of 30 ± 3 % to 42 ± 3 % with the use of Epoetin alfa would result in increased blood pressure . This study was a sub study of the “ Normal hematocrit Study ” . Methods Thirty-one patients were r and omized into one of two arms . Patients in Group A had their hematocrit increased with the use of slowly escalating doses of Epoetin alfa to 42 ± 3 % and patients in Group B were maintained with a hematocrit of 30 ± 3 % throughout the course of the study . All patients had their blood pressure recorded with a 24 hour ambulatory BP device at study entry and at 28 weeks following r and omization when they had achieved their target hematocrit . Pre-dialysis systolic and diastolic BP was also recorded . Results The mean hematocrit increased in Group A from 29.1 ± 2.4 % to 40.8 ± 5.2 % after 30 weeks . The hematocrit in Group B remained stable at 30 ± 3 % throughout the course of the study . There was no difference in mean daytime , mean nighttime or 24 hour systolic or diastolic blood pressure between Groups A and B at either baseline or follow-up . Neither was there a difference in mean pre-dialysis systolic or diastolic BP between Groups A or B at baseline or Follow-up . Four patients in Group A and 4 patients in Group B required an increase in their antihypertensive medication during the course of the study . Conclusion It is possible to increase hematocrit to normal levels in hemodialysis with the administration of Epoetin alfa . The increase in hematocrit from 30 ± 3 % to 42 ± 3 % is not associated with increased blood pressure Fourteen nondialyzed patients with chronic renal insufficiency ( serum creatinine 265 to 972 mumol/L [ 3.0 to 11.0 mg/dL ] ) and severe anemia ( hematocrit less than 30 % ) were r and omized to receive either recombinant human erythropoietin ( r-HuEPO ) or a placebo subcutaneously thrice weekly for 12 weeks or until reaching a hematocrit of 38 % to 40 % . Anemia was significantly ameliorated in the treated patients . No acceleration in the progression of renal failure ( 1/serum creatinine v time ) or change in serum potassium was noted for either the placebo or treated group over the 12-week period . Six of seven treated patients had a significant decrease in serum ferritin and percent transferrin saturation ( plasma iron/total iron-binding capacity ) . This result ed in functional iron deficiency and the requirement for iron supplementation . The average systolic and diastolic blood pressure did not differ significantly between the two groups of patients during the study . Quality of life was improved in all r-HuEPO-treated patients but not in those in the placebo group . This study demonstrates the safety and efficacy of r-HuEPO in the correction of anemia in predialysis patients without adverse effects on renal function over a 12-week period . Improved patient well-being as a result of the correction of anemia result ed in one patient refusing appropriate initiation of dialysis therapy BACKGROUND Hypertension is a recognized complication of partial correction of anemia with recombinant human erythropoietin ( epoetin ) in hemodialysis patients . We used interdialytic ambulatory blood pressure ( ABP ) monitoring to study the effects of partially corrected anemia versus normal hematocrit ( hct ) on BP in hemodialysis patients . METHODS Repeated interdialytic ABP monitoring was performed for up to one year in 28 chronic hemodialysis patients with cardiac disease who were r and omized to achieve and maintain normal hct levels ( 42 + /- 3 % , group A ) or anemic hct levels ( 30 + /- 3 % , group B ) with epoetin . Routine BP measurements obtained at dialysis treatments were also evaluated . RESULTS Mean hct levels were 30.7 + /- 0.7 % in group A and 30.6 + /- 0.7 % in group B at baseline , then 39.3 + /- 1.2 % ( group A ) and 33.5 + /- 0.6 % ( group B ) at four months , and 42.0 + /- 1.1 % ( group A ) and 30.4 + /- 1.0 % ( group B ) at 12 months . Baseline ABP and routine dialysis unit BP levels were not different between the groups . At 2 , 4 , 8 , and 12 months of follow-up , there were no statistically significant differences in any BP parameters between groups or increases in any BP parameters in either group A or group B patients compared with baseline . At 12 months , the mean nighttime diastolic BP ( DBP ) in group A patients was slightly but significantly lower than the mean daytime DBP ( daytime DBP 76.6 + /- 1.9 mm Hg vs. nighttime DBP 72.9 + /- 2.1 mm Hg , P < 0.05 ) . The mean daytime and nighttime BPs were not different from each other at two , four , and eight months in group A or at any time in group B , and in both groups , most patients had little diurnal change in BP . CONCLUSION Correction of hct to normal with epoetin in chronic hemodialysis patients with cardiac disease did not cause increased BP as assessed by interdialytic ABP monitoring or by the measurement of routine predialysis and postdialysis BP . There was little diurnal change in systolic or diastolic BP at baseline or after correction of anemia to normal levels , and although mean nighttime DBP was lower than mean daytime DBP at 12 months in group A , the maintenance of normal hct levels did not affect the abnormal diurnal BP pattern seen at moderately anemic hct levels in most patients Therapy with human recombinant erythropoietin ( EPO ) has been accepted as effective for renal anemia in dialysis patients . However , studies in rats have shown that correcting anemia with EPO may affect the progression of renal dysfunction . In humans , however , the effect of EPO on residual renal function is a matter of controversy . We , therefore , investigated whether the long-term administration of EPO to predialysis patients influences residual renal function . Anemic patients at the predialysis stage with a serum creatinine ( Cr ) concentration ranging from 2 to 4 ( average 2.9 ) mg/dl and a hematocrit ( Ht ) of less than 30 % were r and omly assigned to two groups which consisted of anemic patients not treated with EPO ( group I , untreated anemic controls , n = 31 ) and anemic patients treated with EPO ( group II , treated anemics , n = 42 ) . Patients with nonsevere or moderate anemia ( Ht > 30 % ) with a Cr ranging from 2 to 4 ( average 2.6 ) mg/dl were also recruited as nonanemic controls ( group III , untreated nonanemic controls , n = 35 ) . Blood pressure was controlled to the same degree among the three groups by combined treatment with calcium antagonists and angiotensin-converting enzyme inhibitors . All patients were kept strictly on a low-protein ( 0.6 g/kg/day ) and a low-salt ( 7 g/day ) diet . The degree of control of dietary protein and blood pressure and the frequency of angiotensin-converting enzyme inhibitor administration were comparable among the three groups . The primary end point for each patient was a doubling of the baseline Cr which yielded cumulative renal survival rates which were plotted against time . Ht rose significantly from 27.0+/-2.3 to 32.1+/-3.2 % in group II ( n = 42 , p < 0.001 ) with a rate of increase of 0.4+/-0.06%/week . However , it declined from 27.9+/-1.8 to 25.3+/-1.9 % in group I ( n = 31 , p < 0.001 ) and from 35.9+/-3.5 to 32.2+/-3.9 % in group III ( n = 35 , p < 0.001 ) . Cr doubled in 26 patients ( 84 % ) in group I as compared with 22 ( 52 % ) in group II and 21 ( 60 % ) in group III . The cumulative renal survival rates in groups II and III were significantly better than that in group I : p = 0.0003 ( group I vs. group II ) and p = 0.0024 ( group I vs. group III ) . However , there was no difference in the renal survival rate between groups II and III ( p = 0.3111 ) . The better survival rate obtained in group II was attributable to the better survival rate for the nondiabetic patients in this group . The present study suggests that anemia , per se , is a factor in the progression of end-stage renal failure and that reversal of anemia by EPO can retard the progression of renal failure , especially in nondiabetic patients , provided that blood pressure control , rate of increase in Ht , and dietary protein restriction are appropriate Anemia is already present in patients with moderate renal failure and is a major cause of the decline in exercise capacity seen in these patients . We examined the effects of erythropoietin ( EPO ) treatment in 12 predialytic uremic patients ( EPO group : mean age 46 + /- 12 years ; 6 men , 6 women ) with a mean glomerular filtration rate ( GFR ) of 10 + /- 4 ml/min x 1.73 m2 . These patients were compared to a control group of 8 patients ( 5 men , 3 women ) . The observation period was 3 months . The EPO group received 300 U/kg body weight i.v . once a week . The EPO group increased their total hemoglobin ( THb ) from 323 + /- 89 to 466 + /- 128 g ( p less than 0.001 ) and their hemoglobin concentration from 86 + /- 8 to 117 + /- 11 milligrams ( p less than 0.001 ) . Their exercise capacity , measured by a st and ardized exercise test on a bicycle ergometer , increased from 128 + /- 45 to 147 + /- 57 W ( p less than 0.01 ) . The control group did not change their THb ( 349 + /- 124 and 357 + /- 131 g ) , hemoglobin ( 93 + /- 8 and 94 + /- 10 milligrams ) or exercise capacity ( 98 + /- 49 and 101 + /- 50 W ) during the observation period . There was a significant correlation between the increase in THb and the increase in exercise capacity in the EPO group ( r = 0.81 , p less than 0.005 ) . The GFR was unchanged in both groups ( EPO group : 10 + /- 4 and 10 + /- 6 ml/min x 1.73 m2 ; control group : 8 + /- 3 and 8 + /- 3 ml/min x 1.73 m2 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Patients with heart failure ( HF ) and anaemia have greater functional impairment , worse symptoms , increased rates of hospital admission , and a higher risk of death , compared with non-anaemic HF patients . Whether correcting anaemia can improve outcomes is unknown . OBJECTIVE The Reduction of Events with Darbepoetin alfa in Heart Failure trial ( RED-HF ; Clinical Trials.gov NCT 003 58215 ) was design ed to evaluate the effect of the long-acting erythropoietin-stimulating agent darbepoetin alfa on mortality and morbidity ( and quality of life ) in patients with HF and anaemia . METHODS Approximately 2600 patients with New York Heart Association class II-IV , an ejection fraction < or = 40 % , and a haemoglobin ( Hb ) consistently < or = 12.0 g/dL but > or = 9.0 g/dL will be enrolled . Patients are r and omized 1:1 to double-blind subcutaneous administration of darbepoetin alfa or placebo . Investigators are also blinded to Hb measurements and darbepoetin alfa is dosed to achieve an Hb concentration of 13.0 g/dL ( but not exceeding 14.5 g/dL ) with sham adjustments of the dose of placebo . The primary endpoint is the time to death from any cause or first hospital admission for worsening HF , whichever occurs first . The study will complete when approximately 1150 subjects experience a primary endpoint BACKGROUND Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established . METHODS We r and omly assigned 603 patients with an estimated glomerular filtration rate ( GFR ) of 15.0 to 35.0 ml per minute per 1.73 m2 of body-surface area and mild-to-moderate anemia ( hemoglobin level , 11.0 to 12.5 g per deciliter ) to a target hemoglobin value in the normal range ( 13.0 to 15.0 g per deciliter , group 1 ) or the subnormal range ( 10.5 to 11.5 g per deciliter , group 2 ) . Subcutaneous erythropoietin ( epoetin beta ) was initiated at r and omization ( group 1 ) or only after the hemoglobin level fell below 10.5 g per deciliter ( group 2 ) . The primary end point was a composite of eight cardiovascular events ; secondary end points included left ventricular mass index , quality -of-life scores , and the progression of chronic kidney disease . RESULTS During the 3-year study , complete correction of anemia did not affect the likelihood of a first cardiovascular event ( 58 events in group 1 vs. 47 events in group 2 ; hazard ratio , 0.78 ; 95 % confidence interval , 0.53 to 1.14 ; P=0.20 ) . Left ventricular mass index remained stable in both groups . The mean estimated GFR was 24.9 ml per minute in group 1 and 24.2 ml per minute in group 2 at baseline and decreased by 3.6 and 3.1 ml per minute per year , respectively ( P=0.40 ) . Dialysis was required in more patients in group 1 than in group 2 ( 127 vs. 111 , P=0.03 ) . General health and physical function improved significantly ( P=0.003 and P<0.001 , respectively , in group 1 , as compared with group 2 ) . There was no significant difference in the combined incidence of adverse events between the two groups , but hypertensive episodes and headaches were more prevalent in group 1 . CONCLUSIONS In patients with chronic kidney disease , early complete correction of anemia does not reduce the risk of cardiovascular events . ( Clinical Trials.gov number , NCT00321919 [ Clinical Trials.gov ] . ) BACKGROUND Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease . Although darbepoetin alfa can effectively increase hemoglobin levels , its effect on clinical outcomes in these patients has not been adequately tested . METHODS In this study involving 4038 patients with diabetes , chronic kidney disease , and anemia , we r and omly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo , with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter . The primary end points were the composite outcomes of death or a cardiovascular event ( nonfatal myocardial infa rct ion , congestive heart failure , stroke , or hospitalization for myocardial ischemia ) and of death or end-stage renal disease . RESULTS Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo ( hazard ratio for darbepoetin alfa vs. placebo , 1.05 ; 95 % confidence interval [ CI ] , 0.94 to 1.17 ; P=0.41 ) . Death or end-stage renal disease occurred in 652 patients assigned to darbepoetin alfa and 618 patients assigned to placebo ( hazard ratio , 1.06 ; 95 % CI , 0.95 to 1.19 ; P=0.29 ) . Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo ( hazard ratio , 1.92 ; 95 % CI , 1.38 to 2.68 ; P<0.001 ) . Red-cell transfusions were administered to 297 patients assigned to darbepoetin alfa and 496 patients assigned to placebo ( P<0.001 ) . There was only a modest improvement in patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group . CONCLUSIONS The use of darbepoetin alfa in patients with diabetes , chronic kidney disease , and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes ( either death or a cardiovascular event or death or a renal event ) and was associated with an increased risk of stroke . For many persons involved in clinical decision making , this risk will outweigh the potential benefits . ( Clinical Trials.gov number , NCT00093015 . |
1,096 | 27,245,061 | 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 . | Background Previous review s have shown balance in older adults to be improved with exercise .
However , it is currently unclear whether postural control , indicated by centre of pressure ( COP ) measurement , can be improved in older adults and thus whether postural control could be a mechanism to improve balance .
Objectives The purpose of this systematic review was to assess the effectiveness of force platform COP variables to identify changes in postural control following exercise interventions in older adults .
In addition , a secondary purpose was to determine whether the exercise types ( balance , resistance or multi-component exercise interventions ) are equally effective to improve postural control . | 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 of exercise training . RESULTS Double-stance measurements were unchanged after training . The mean displacement of the center of pressure in single stance improved 17 % in the combined training group and did not change in the flexibility training group . A repeated- measures analysis of variance revealed that the difference in improvement between the combined training and flexibility training groups was not significant . DISCUSSION AND CONCLUSION This is the first intervention trial to demonstrate improvements in single-stance postural sway in older women with exercise training . Additional studies with more subjects will be needed to determine whether a combined training program of resistance training , walking , and postural exercises can improve balance more than a program of postural control exercises alone Elderly patients with diabetes and peripheral neuropathy are more likely to experience falls . However , the information available on how such falls can be prevented is scarce . We investigated the effects of whole-body vibration ( WBV ) combined with a balance exercise program on balance , muscle strength , and glycosylated hemoglobin ( HbA1c ) in elderly patients with diabetic peripheral neuropathy . Fifty-five elderly patients with diabetic neuropathy were r and omly assigned to WBV with balance exercise group , balance exercise ( BE ) group , and control group . The WBV and BE groups performed the balance exercise program for 60 min per day , 2 times per week , for 6 weeks . Further , the WBV group performed WBV training ( up to 3 × 3 min , 3 times per week , for 6 weeks ) . The control group did not participate in any training . The main outcome measures were assessed at baseline and after 6 weeks of training ; namely , we assessed the postural sway and one leg stance ( OLS ) for static balance ; Berg balance scale ( BBS ) , timed up- and -go ( TUG ) test , and functional reach test ( FRT ) for dynamic balance ; five-times-sit-to-st and ( FTSTS ) test for muscle strength ; and HbA1c for predicting the progression of diabetes . Significant improvements were noted in the static balance , dynamic balance , muscle strength , and HbA1c in the WBV group , compared to the BE and control groups ( P < 0.05 ) . Thus , in combination with the balance exercise program , the short-term WBV therapy is beneficial in improving balance , muscle strength and HbA1c , in elderly patients with diabetic neuropathy who are at high risk for suffering falls UNLABELLED Lelard T , Doutrellot P-L , David P , Ahmaidi S. Effects of a 12-week Tai Chi Chuan program versus a balance training program on postural control and walking ability in older people . OBJECTIVE To compare the respective effects of 2 balance training programs : a Tai Chi ( TC ) program and a balance training program on static postural control and walking ability . DESIGN R and omized controlled trial . SETTING General community . PARTICIPANTS Older subjects ( N=28 ) participated in the study . INTERVENTIONS The TC group ( n=14 ; mean age + /- SD , 76.8+/-5.1y ) and the balance training group ( n=14 ; 77.0+/-4.5y ) were both trained for 12 weeks . MAIN OUTCOME MEASURES Static postural control was assessed via measurement of center of pressure sway under eyes open ( EO ) and eyes closed ( EC ) conditions . Walking speed over a 10-meter course was also assessed . RESULTS After the 12-week training period , there were no significant differences in walking speed or postural parameters in either the EO or EC conditions for the TC and balance training groups . Performance in the EC condition was lower than in the EO condition in pretest and posttest for the balance training and TC groups . The Romberg quotient ( EO/EC ratio ) was significantly higher after the balance training program than the TC program ( P<.05 ) . CONCLUSIONS We can not conclude that the balance training program has better effects than the TC program on postural control or walking ability . None of the outcome measures showed significant change posttraining in either the TC or the balance training groups . However , the differences described in the Romberg quotient after the training period between the TC and the balance training groups suggest that TC should be helpful to limit the deleterious effects of eye closure on postural balance OBJECTIVE To test the feasibility and effectiveness of whole-body vibration ( WBV ) therapy on fall risk , functional dependence and health-related quality of life in nursing home residents aged 80 + years . DESIGN Twenty-nine 80 - 95 years old volunteers , nursing home residents were r and omized to an eight-week WBV intervention group ) ( n=15 ) or control group ( n=14 ) . Functional mobility was assessed using the timed up and go ( TUG ) test . Lower limb performance was evaluated using the 30-s Chair Sit to St and ( 30-s CSTS ) test . Postural stability was measured using a force platform . The Barthel Index was used to assess functional dependence and the EuroQol ( EQ-5D ) was used to evaluate Health-Related Quality of Life . All outcome measures were assessed at baseline and at a follow-up after 8 weeks . RESULTS At the 8-week follow up , TUG test ( p<0.001 ) , 30-s CSTS number of times ( p=0.006 ) , EQ-5Dmobility ( p<0.001 ) , EQ-5DVAS ( p<0.014 ) , EQ-5Dutility ( p<0.001 ) and Barthel index ( p=0.003 ) improved in the WBV intervention group when compared to the control group . CONCLUSIONS An 8-week WBV-based intervention in a nursing home setting is effective in reducing fall risk factors and quality of life in nursing home residents aged 80 + Fifty female subjects , aged 72 - 92 ( mean 82 ) years , were enrolled in a 12-week ( 36 classes ) exercise program aim ed at increasing postural stability . Subjects were residents of sheltered apartments , rest homes or nursing homes , well enough and mobile enough to participate in the classes . The subjects were r and omized into an exercise or a control group . Their postural sway , st and ing at rest on a force platform , was measured with eyes open and eyes closed . The groups were well matched in all respects . The results showed no improvement in the postural sway as a result of the exercise program . We hypothesize that increasing postural sway in the elderly represents a deterioration in , for the most part , the nervous system and may at this extreme of life indicate an irreversible loss of function . For this reason no improvement in postural sway may be possible Different types of exercise are indicated for the elderly to prevent functional capacity limitations due to aging and reduce the risk of falls . This study aim ed to evaluate the effect of three different exercises ( mini-trampoline , MT ; aquatic gymnastics , AG and general floor gymnastics , GG ) on postural balance in elderly women . Seventy-four physically independent elderly women , mean age 69±4 years , were r and omly assigned to three intervention groups : ( 1 ) MT ( n=23 ) , ( 2 ) AG ( n=28 ) , and ( 3 ) GG ( n=23 ) . Each group performed physical training , including cardiorespiratory , muscular strength and endurance , flexibility and sensory-motor exercises for 12 weeks . To determine the effects on each intervention group , five postural balance tasks were performed on a force platform ( BIOMEC 400 ) : the two-legged st and with eyes open ( TLEO ) and two-legged st and with eyes closed ( TLEC ) ; the semi-t and em st and with eyes open ( STEO ) and semi-t and em st and with eyes closed ( STEC ) and the one-legged st and . Three trials were performed for each task ( with 30s of rest between them ) and the mean was used to compute balance parameters such as center of pressure ( COP ) sway movements . All modalities investigated such as the MT , AG and GG were significantly ( P<0.05 ) efficient in improving the postural balance of elderly women after 12 weeks of training . These results provide further evidence concerning exercise and balance for promoting health in elderly women Objective : To investigate the effects of dual task balance training in the elderly on st and ing postural control while performing a cognitive task . Design : A r and omized two-group parallel controlled trial . Participants : Forty-three subjects ( all > 65 years old ) were enrolled in the study and were assigned r and omly to either an experimental group ( n = 21 ) or a control group ( n = 22 ) . Interventions : Subjects in the experimental group were given strength and balance training while performing cognitive tasks simultaneously . Subjects in the control group were given strength and balance training only . The training was administered twice a week for three months . Measurements : The Chair St and Test , Functional Reach Test , Timed Up and Go Test and Trail Making Test were measured . The sway length of the centre of gravity was measured during st and ing while performing the Stroop task . The rate of Stroop task was also measured . All measurements were collected at baseline and after the training period . Results : There were no significant differences in Functional Reach Test , Timed Up and Go Test and sway length at baseline and after training between the two groups . However , the rate of Stroop task ( P < 0.05 ) was significantly higher after training in the experimental group than in the control group . Conclusions : These results suggest that dual task balance training in elderly people improves their dual task performance during st and ing postural control |
1,097 | 21,491,398 | 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 . | BACKGROUND Mild cognitive impairment ( MCI ) is an intermediate state between normal cognition and dementia in which daily function is largely intact .
This condition may present an opportunity for research into the prevention of dementia .
Carbohydrate is an essential and easily accessible macronutrient which influences cognitive performance .
A better underst and ing of carbohydrate-driven cognitive changes in normal cognition and mild cognitive impairment may suggest ways to prevent or reduce cognitive decline .
OBJECTIVES To assess the effectiveness of carbohydrates in improving cognitive function in older adults . | 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 . 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 CONTEXT Higher adherence to a Mediterranean-type diet is linked to lower risk for mortality and chronic diseases , but its association with cognitive decline is unclear . OBJECTIVE To investigate the association of a Mediterranean diet with change in cognitive performance and risk for dementia in elderly French persons . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 1410 adults ( > or = 65 years ) from Bordeaux , France , included in the Three-City cohort in 2001 - 2002 and reexamined at least once over 5 years . Adherence to a Mediterranean diet ( scored as 0 to 9 ) was computed from a food frequency question naire and 24-hour recall . MAIN OUTCOME MEASURES Cognitive performance was assessed on 4 neuropsychological tests : the Mini-Mental State Examination ( MMSE ) , Isaacs Set Test ( IST ) , Benton Visual Retention Test ( BVRT ) , and Free and Cued Selective Reminding Test ( FCSRT ) . Incident cases of dementia ( n = 99 ) were vali date d by an independent expert committee of neurologists . RESULTS Adjusting for age , sex , education , marital status , energy intake , physical activity , depressive symptomatology , taking 5 medications/d or more , apolipoprotein E genotype , cardiovascular risk factors , and stroke , higher Mediterranean diet score was associated with fewer MMSE errors ( beta = -0.006 ; 95 % confidence interval [ CI ] , -0.01 to -0.0003 ; P = .04 for 1 point of the Mediterranean diet score ) . Performance on the IST , BVRT , or FCSRT over time was not significantly associated with Mediterranean diet adherence . Greater adherence as a categorical variable ( score 6 - 9 ) was not significantly associated with fewer MMSE errors and better FCSRT scores in the entire cohort , but among individuals who remained free from dementia over 5 years , the association for the highest compared with the lowest group was significant ( adjusted for all factors , for MMSE : beta = -0.03 ; 95 % CI , -0.05 to -0.001 ; P = .04 ; for FCSRT : beta = 0.21 ; 95 % CI , 0.008 to 0.41 ; P = .04 ) . Mediterranean diet adherence was not associated with the risk for incident dementia ( fully adjusted model : hazard ratio , 1.12 ; 95 % CI , 0.60 to 2.10 ; P = .72 ) , although power to detect a difference was limited . CONCLUSIONS Higher adherence to a Mediterranean diet was associated with slower MMSE cognitive decline but not consistently with other cognitive tests . Higher adherence was not associated with risk for incident dementia OBJECTIVE The study aim ed to assess the clinical utility of the Informant Question naire on Cognitive Decline in the Elderly ( IQCODE ) in patients referred to memory clinics , alone and in combination with the Addenbrooke 's Cognitive Examination-Revised ( ACE-R ) and the Mini-mental State Examination ( MMSE ) . METHODS This pragmatic prospect i ve study was based on consecutive referrals attending with an informant ( n = 144 ) to two memory clinics over a 12-month period . Patients were diagnosed using st and ard clinical diagnostic criteria for dementia ( DSM-IV ) as gold st and ard ( dementia prevalence = 59 % ) . The IQCODE was administered to informants , and the ACE-R and /or MMSE to most patients . RESULTS The IQCODE proved acceptable to informants , and was quick and easy to use . Using traditional parameters of diagnostic utility ( sensitivity , specificity , positive predictive value , likelihood ratios ) , the performance of the IQCODE at optimal test accuracy was highly sensitive ( 0.86 ) for the diagnosis of dementia but specificity was poor ( 0.39 ) with suboptimal positive predictive value ( 0.67 ) and small or unimportant likelihood ratios . Overall diagnostic accuracy based on area under the receiver operating characteristic ( ROC ) curve was 0.71 . Combining the IQCODE with either ACE-R or MMSE greatly improved accuracy , specificity and positive predictive value when the tests were used in series , but not when used in parallel . CONCLUSION In a memory clinic based population , the IQCODE proved sensitive for the diagnosis of dementia but overall diagnostic accuracy was suboptimal . Combining the IQCODE in series with the ACE-R or MMSE greatly improved diagnostic utility Background Cost-effective interventions to improve diet and physical activity are a public health priority . Alive ! is an email-based intervention to increase physical activity , reduce saturated and trans fats and added sugars , and increase fruit and vegetable consumption . It was shown to improve these behaviors in a large r and omized controlled trial . Objective ( 1 ) To describe the components and behavioral principles underlying Alive ! , and ( 2 ) to report effects of the intervention on the secondary outcomes : health-related quality of life , presenteeism , self-efficacy , and stage of change . Methods The Alive ! behavior change model is design ed to elicit healthy behaviors and promote their maintenance . Behavioral strategies include assessment s followed by individualized feedback , weekly goal - setting , individually tailored goals and tips , reminders , and promotion of social support . Alive ! was tested among non-medical employees of Kaiser Permanente of Northern California , who were r and omized to either the intervention group or the wait-list control group . After r and omization , intervention group participants chose one topic to undertake for the intervention period : increasing physical activity , increasing fruits and vegetables , or decreasing saturated and trans fats and added sugars . Pre-post question naires assessed changes in SF-8 health-related quality of life , presenteeism , self-efficacy , and stage of change . Mixed effects multiple linear regression and ordinal logistic regression models were used , with department as a r and om effect factor . Analyses were by intention to treat : the 30 % ( 238/787 ) who did not respond to the follow-up question naires were assigned change scores of zero . Results Participants were 19 to 65 years ( mean 44.0 + /- 10.6 ) , and 74.3 % ( 585/787 ) were female . Mean SF-8 Physical quality of life score increased significantly more in the intervention group than in the control group , 1.84 ( 95 % CI 0.96 - 2.72 ) vs 0.72 ( 95 % CI -0.15 - 1.58 ) respectively , P = .02 . SF8 Mental score also improved significantly more in the intervention group than in the control group ( P = .02 ) . The odds ratio for improvement in self-assessed health status was 1.57 ( 95 % CI 1.21 - 2.04 , P < .001 ) for the intervention group compared to the control group . The odds ratio for having a reduction in difficulty accomplishing work tasks because of physical or emotional problems , a measure of presenteeism , was 1.47 ( 95 % CI 1.05 - 2.05 , P = .02 ) for the intervention group compared to the control group . The odds of having an improvement in self-efficacy for changing diet was 2.05 ( 95 % CI 1.44 - 2.93 ) for the intervention vs the control group ( P < .001 ) . Greater improvement in stage of change for physical activity ( P = .05 ) , fats ( P = .06 ) , and fruits/vegetables ( P = .006 ) was seen in the intervention group compared to the control group . Significant effects on diet and physical activity behavior change are reported elsewhere . Conclusions Cost-effective methods that can reach large population s with science-based interventions are urgently needed . Alive ! is a fully automated low-cost intervention shown to effect significant improvements in important health parameters . Trial Registration Clinical trials.gov NCT00607009 ; http:// clinical trials.gov/ct2/show/NCT00607009 ( Archived by WebCite at http://www.webcitation.org/5cLpCWcT6 Cortisol responses to stress have important physiological effects on several target tissues throughout the body , including the central nervous system and the immune system . The ability of target tissues to receive cortisol signals has been shown to vary between individuals and over time . Conflicting data exist on whether different target tissues ' glucocorticoid ( GC ) sensitivity is related . In a double-blind , placebo-controlled design , n=19 participants ( n=15 men , n=4 women ) received an oral dose of 30 mg of cortisol and placebo in r and omized order . Memory retrieval of previously learned neutral and emotional words was tested after cortisol or placebo application . Peripheral GC sensitivity was tested by measuring in-vitro stimulated production of interleukin-6 ( IL-6 ) in whole blood before and after cortisol vs. placebo application . Cortisol treatment reduced retrieval of neutral and emotional words ( marginally significant at p=0.07 ) , and significantly reduced stimulated IL-6 production ( p<0.001 ) . Relative suppression of IL-6 production was associated with impairment of memory retrieval of emotional ( r=0.48 ; p=0.039 ) , but not neutral words ( r=-0.17 ; p=0.48 ) . In summary , results show an association of peripheral glucocorticoid sensitivity with emotional , but not neutral , memory retrieval . Given that these findings can be extended to clinical population s , the association of peripheral glucocorticoid sensitivity with emotional memory retrieval might have important implication s for underst and ing and treatment of stress-related disorders We investigated a carbohydrate‐rich nutrient‐drink mix for treatment of seasonal affective disorder ( SAD ) . This mixture may contribute to brain serotonin synthesis , potentially exerting an antidepressant effect and controlling carbohydrate cravings . Two successive double‐blind placebo‐controlled studies were performed . In Study 1 , 18 subjects ( 50 % women ; mean age 43 ± 15 years ) with SCID‐diagnosed SAD were r and omized to 12 days of twice daily carbohydrate beverage ( CHO ) containing mixed starches , or a placebo beverage ( PRO ) containing the CHO mix plus casein protein to dampen serotonin synthesis . Following a 2‐day washout , subjects were crossed over to the other treatment for 12 days . In Study 2 , 32 subjects ( 63 % women ; mean age 46 ± 14 years ) with SCID‐diagnosed SAD were r and omized to 21 days of CHO or PRO . Efficacy in both studies was determined by the first 17 items of the Hamilton Depression Rating Scale ( HAM‐D‐28 ) , an appetite question naire , and regular weighing . In Study 1 , response rates were 50 % for both groups . Remission rates favored CHO ( 50 % vs. 38 % ) , as did the decrease in the HAM‐D‐17 score , but differences were nonsignificant . In Study 2 , response rates were 71 % for CHO and 76 % for PRO , and remission rates were 71 % for each group . Both treatment groups experienced significant improvement in HAM‐D‐17 scores within 1 week of treatment , which continued through the entire study period . Weight change did not differ significantly between treatment groups in either study . The drink mix was well tolerated and treatment adherence was high . Both the active and placebo intervention were effective in alleviating symptoms of SAD . Replication studies in larger sample s appear warranted CONTEXT Both higher adherence to a Mediterranean-type diet and more physical activity have been independently associated with lower Alzheimer disease ( AD ) risk but their combined association has not been investigated . OBJECTIVE To investigate the combined association of diet and physical activity with AD risk . DESIGN , SETTING , AND PATIENTS Prospect i ve cohort study of 2 cohorts comprising 1880 community-dwelling elders without dementia living in New York , New York , with both diet and physical activity information available . St and ardized neurological and neuropsychological measures were administered approximately every 1.5 years from 1992 through 2006 . Adherence to a Mediterranean-type diet ( scale of 0 - 9 ; trichotomized into low , middle , or high ; and dichotomized into low or high ) and physical activity ( sum of weekly participation in various physical activities , weighted by the type of physical activity [ light , moderate , vigorous ] ; trichotomized into no physical activity , some , or much ; and dichotomized into low or high ) , separately and combined , were the main predictors in Cox models . Models were adjusted for cohort , age , sex , ethnicity , education , apolipoprotein E genotype , caloric intake , body mass index , smoking status , depression , leisure activities , a comorbidity index , and baseline Clinical Dementia Rating score . MAIN OUTCOME MEASURE Time to incident AD . RESULTS A total of 282 incident AD cases occurred during a mean ( SD ) of 5.4 ( 3.3 ) years of follow-up . When considered simultaneously , both Mediterranean-type diet adherence ( compared with low diet score , hazard ratio [ HR ] for middle diet score was 0.98 [ 95 % confidence interval { CI } , 0.72 - 1.33 ] ; the HR for high diet score was 0.60 [ 95 % CI , 0.42 - 0.87 ] ; P = .008 for trend ) and physical activity ( compared with no physical activity , the HR for some physical activity was 0.75 [ 95 % CI , 0.54 - 1.04 ] ; the HR for much physical activity was 0.67 [ 95 % CI , 0.47 - 0.95 ] ; P = .03 for trend ) were associated with lower AD risk . Compared with individuals neither adhering to the diet nor participating in physical activity ( low diet score and no physical activity ; absolute AD risk of 19 % ) , those both adhering to the diet and participating in physical activity ( high diet score and high physical activity ) had a lower risk of AD ( absolute risk , 12 % ; HR , 0.65 [ 95 % CI , 0.44 - 0.96 ] ; P = .03 for trend ) . CONCLUSION In this study , both higher Mediterranean-type diet adherence and higher physical activity were independently associated with reduced risk for AD gal-1 ( galectin-1 ) mediates cell – cell and cell – extracellular matrix adhesion , essentially by interacting with β-galactoside-containing glycans of cell-surface glycoconjugates . Although most structural studies with gal-1 have investigated its binding to simple carbohydrates , in particular lactose and N-acetyl-lactosamine , this view is limited , because gal-1 functions at the cell surface by interacting with more complex glycans that are heterogeneous in size and composition . In the present study we used NMR spectroscopy to investigate the interaction of human gal-1 with a large ( 120 kDa ) complex glycan , GRG ( galactorhamnogalacturonate glycan ) , that contains non-r and omly distributed mostly terminal β(1→4)-linked galactose side chains . We used 15N–1H-HSQC ( heteronuclear single quantum coherence ) NMR experiments with 15N-enriched gal-1 to identify the GRG-binding region on gal-1 and found that this region covers a large surface area on gal-1 that includes the quintessential lactose-binding site and runs from that site through a broad valley or cleft towards the dimer interface . HSQC and pulsed-field-gradient NMR diffusion experiments also show that gal-1 binds GRG with a gal-1:GRG stoichiometry of about 5:1 ( or 6:1 ) and with average macroscopic and microscopic equilibrium dissociation constants ( Kd ) of 8 × 10−6 M and 40 × 10−6 M ( or 48 × 10−6 M ) respectively , indicating stronger binding than to lactose ( Kd=520 × 10−6 M ) . Although gal-1 may bind GRG in various ways , the glycan can be competed for by lactose , suggesting that there is one major mode of interaction . Furthermore , even though terminal motifs on GRG are Gal-β(1→4)-Gal rather than the traditional Gal-β(1→4)-Glc/GlcNAc ( where GlcNAc is N-acetylglucosamine ) , we show that the disaccharide Gal-β(1→4)-Gal can bind gal-1 at the lactose-binding domain . In addition , gal-1 binding to GRG disrupts inter-glycan interactions and decreases glycan-mediated solution viscosity , a glycan decongestion effect that may help explain why gal-1 promotes membrane fluidity and lateral diffusion of glycoconjugates within cell membranes . Overall , our results provide an insight into the function of galectin in situ and have potential significant biological consequences OBJECTIVE The goal of this project was to evaluate the effects of energy supplementation , as liquid carbohydrate ( CHO ) , on facilitating recovery of cognitive function in soldiers who have been exposed to sustained psychological and physical stress during Survival School Training . PROJECT DESIGN : A double-blind , placebo-controlled design was used . Healthy , male volunteers attending survival training were recruited for participation in the study . At the conclusion of the mock captivity phase of survival training and before a recovery night of sleep , subjects participated in cognitive testing . After this , subjects were r and omly assigned to one of three treatment groups . Subjects received either a 6 % CHO ( 35.1 kJ/kg ) , 12 % CHO ( 70.2 kJ/kg ) , or placebo beverage in four isovolemic doses . In the morning of the following day , all subjects participated in a second assessment of cognitive functioning . RESULTS Compared to subjects who received placebo , those who received supplemental CHO beverages exhibited significantly improved performance on a complex cognitive task ( i.e. , Stroop Test ) involving concentration effectiveness associated with selective attention and response inhibition . No differences were observed on a variety of cognitive tasks of lesser complexity . DISCUSSION These data suggest nutritional interventions enhance the rapid recovery of complex cognitive functions impaired by exposure to significant or sustained stressful conditions . In addition to enhancing speed of recovery of function between operational intervals , the current data suggest that dietary supplement strategies may hold promise for enhancing field performance and a capacity to assist in sustaining operations by military personnel over time BACKGROUND Previous research has been inconclusive regarding the impact of glucose ingestion and gluco-regulatory control on cognitive performance in healthy older adults . The aim of this research was to determine whether glucose specifically enhanced episodic memory in an older population . In addition , the link between individual differences in glucose regulation and the magnitude of the enhancement effect was examined . DESIGN AND SUBJECTS A within subjects , counterbalanced , crossover design was used with 20 participants ( 60 - 80 year olds ) , each serving as his/her control . METHODS Episodic memory was tested by presenting unrelated paired associates followed by immediate and delayed cued recall , and delayed recognition , under single and dual task conditions . In addition , a battery of cognitive tests was administered , including tests of semantic memory , working memory and speed of processing . RESULTS Glucose ingestion was found to largely facilitate performance of episodic memory . Furthermore , subsidiary analyses found that gluco-regulatory efficiency predicted episodic memory performance in both control and glucose conditions . CONCLUSIONS A boost in performance after glucose ingestion was particularly seen in the episodic memory domain . Notably , strong evidence was provided for the utility of gluco-regulatory control measures as indicators of cognitive decline in the elderly We r and omly assigned 23 older adults with mild cognitive impairment to either a high carbohydrate or very low carbohydrate diet . Following the 6-week intervention period , we observed improved verbal memory performance for the low carbohydrate subjects ( p = 0.01 ) as well as reductions in weight ( p < 0.0001 ) , waist circumference ( p < 0.0001 ) , fasting glucose ( p = 0.009 ) , and fasting insulin ( p = 0.005 ) . Level of depressive symptoms was not affected . Change in calorie intake , insulin level , and weight were not correlated with memory performance for the entire sample , although a trend toward a moderate relationship between insulin and memory was observed within the low carbohydrate group . Ketone levels were positively correlated with memory performance ( p = 0.04 ) . These findings indicate that very low carbohydrate consumption , even in the short term , can improve memory function in older adults with increased risk for Alzheimer 's disease . While this effect may be attributable in part to correction of hyperinsulinemia , other mechanisms associated with ketosis such as reduced inflammation and enhanced energy metabolism also may have contributed to improved neurocognitive function . Further investigation of this intervention is warranted to evaluate its preventive potential and mechanisms of action in the context of early neurodegeneration BACKGROUND The course of weight loss associated with dementia is unclear , particularly prior to and around the onset of the clinical syndrome . OBJECTIVE To compare the natural history of weight change from mid to late life in men with and without dementia in late life . DESIGN AND SETTING The Honolulu-Asia Aging Study , a 32-year , prospect i ve , population -based study of Japanese American men who had been weighed on 6 occasions between 1965 and 1999 and who had been screened for dementia 3 times between 1991 and 1999 . PARTICIPANTS Of 1890 men ( aged 77 - 98 years ) , 112 with incident dementia were compared with 1778 without dementia at the sixth examination ( 1997 - 1999 ) . MAIN OUTCOME MEASURE Weight change up to and including the sixth examination was treated as the dependent variable and estimated using a repeated measures analysis . RESULTS Groups with and without dementia did not differ with respect to baseline weight or change in weight from mid to late life ( first 26 years ' follow-up ) . In the late-life examinations ( final 6 years ) , mean age- and education-adjusted weight loss was -0.22 kg/y ( 95 % confidence intervals , -0.26 to -0.18 ) in participants without dementia . Men with incident dementia at the same examination had an additional yearly weight loss of -0.36 kg ( 95 % confidence interval , -0.53 to -0.19 ) . This was not changed substantially with adjustment for risk factors for vascular disease or functional impairment and was significant for both Alzheimer disease and vascular dementia subtypes . CONCLUSIONS Dementia-associated weight loss begins before the onset of the clinical syndrome and accelerates by the time of diagnosis . The potential impact on prognosis should be considered in the case of elderly persons at risk for dementia Rationale Glucose enhancing effects have been observed in older adults mainly for episodic memory , but have been under-investigated for attentional functions , which are very sensitive to aging . Objective The present study examined the acute effects of glucose ingestion on different attentional tasks in fasting healthy older adults . Methods In a between-subjects design , 44 participants ( 60 years and older ) were r and omly assigned to a glucose ( 50 g ) or saccharin ( placebo ) condition after 12 h of fasting . Participants were tested on neuropsychological tests of attention ( trail A and B , modified Stroop ) and on a computerized dual-task . Results Participants in the glucose group were faster than the placebo group to complete the switching condition of the modified Stroop test ( p < 0.01 ) and showed a smaller dual-task cost in the divided attention task ( p < 0.05 ) . Conclusions Glucose ingestion appears to momentarily enhance attentional performances in seniors who have fasted for 12 h in tasks requiring switching and dividing attention It is still unknown what if any relationships exist between intake of macronutrients by the elderly , and their functional or cognitive h and icaps , particularly for free living elderly people . We investigated 226 men and 215 women , aged 65 or more , free living and in good health . They were r and omly selected in the département of Bas-Rhin , after stratification for age , sex and residence ( rural or urban ) . H and icaps and cognitive functions of each subject were assessed with the Géronte scale and the Mini- Mental State Examination ( MMSE ) , respectively . Food intake was measured by a three-day record . A multiple correspondence analysis concluded that functional parameters and macronutrient intakes were rather independent . The relationships found were detailed by a backward stepwise logistic regression . In men , alcohol intake was associated with an improvement in functional and cognitive parameters , and polyunsaturated fatty acids with the capacity to move outside the home . In women , lipid intake increased the MMSE score . Overweight in women was linked with better functional and cognitive performances , and in men with the capacity to move outside the home . In both sexes , age worsened the score of functional and cognitive parameters . In conclusion , macronutrient intakes and functional or cognitive parameters were found to be mutually independent ; this suggests that macronutrient deficiencies are of little importance in the worsening functional or mental autonomy of the elderly . The relationships found between functional variables and alcohol or polyunsaturated fatty acid intakes in men , and lipid intakes in women , and overweight in both sexes might evidence a better state of health . ( Aging Clin . Exp . Res . 7 : 67–74 , 1995 Abstract Recent studies indicate that some aspects of memory can be enhanced by the administration of oxygen or glucose . Considering the dependency of glucose metabolism upon oxygen supply , the present study predicted that administering a combination of 100 % oxygen with glucose would have greater memory-enhancing effects than when either substance was administered alone . In a placebo-controlled study , 104 healthy adults were given a glucose or placebo drink , and inhaled 100 % oxygen or air for 1 min , before carrying out a number of everyday memory tasks design ed to measure short-term and long-term memory . Results showed support for the enhancing effects of oxygen ( but not for glucose ) on delayed recall . These findings are discussed in relation to the possible cholinergic properties of oxygen and glucose and the implication s for their clinical use The aim of the present study was to examine the effects of consuming cereal bars , given either for breakfast or a mid-morning snack , on mood and memory . Thirty-two volunteers ( 16 males , 16 females ; mean age , 20 years 9 months ) were r and omly assigned to one of four groups formed by combining breakfast ( cereal bar versus no breakfast ) and snack ( cereal bar versus no snack ) conditions . A baseline session was completed at 08:30 h followed by breakfast at 9:00 h , another test at 10:00 h , followed by a mid-morning snack and then a final test at 12:00 h. In each session , volunteers rated their mood and carried out four memory tasks : free recall ; recognition memory ; a verbal reasoning task ; and a semantic processing task . The results showed that volunteers who consumed a cereal bar for breakfast felt more alert , happy and sociable and less anxious . In addition , they also recalled more words in a free recall task . When the cereal bar was consumed as a mid-morning snack , alertness and hedonic tone increased , especially in the group who received no breakfast . The group who had no breakfast reported reduced anxiety after consumption of the snack . Recall was also improved after the snack . These findings show that consuming cereal bars in the early and mid-morning leads to beneficial behavioural effects . The results confirm earlier research on effects of breakfast and extend our knowledge of effects of snacks . Consumption of cereal bars may have important practical applications especially in situations where preparation of breakfast is difficult Interventions aim ed at improving glucose regulatory mechanisms have been suggested as a possible source of cognitive enhancement in the elderly . In particular , previous research has identified episodic memory as a target for facilitation after either moderate increases in glycaemia ( after a glucose drink ) or after improvements in glucose regulation . The present study aim ed to extend this research by examining the joint effects of glucose ingestion and glucose regulation on cognition . In addition , risk factors associated with the development of poor glucose regulation in middle-aged adults were considered . In a repeated measures design , thirty-three middle-aged adults ( aged 35 - 55 years ) performed a battery of memory and non-memory tasks after either 25 g or 50 g glucose or a sweetness matched placebo drink . To assess the impact of individual differences in glucose regulation , blood glucose measurements were taken on four occasions during testing . A lifestyle and diet question naire was also administered . Consistent with previous research , episodic memory ability benefited from glucose ingestion when task dem and s were high . Blood glucose concentration was also found to predict performance across a number of cognitive domains . Interestingly , the risk factors associated with poor glucose regulation were linked to dietary impacts traditionally associated with poor health , e.g. the consumption of high-sugar sweets and drinks . The research replicates earlier work suggesting that task dem and s are critical to the glucose facilitation effect . Importantly , the data demonstrate clear associations between elevated glycaemia and relatively poor cognitive performance , which may be partly due to the effect of dietary and lifestyle factors Glucocorticoids ( GCs ) have a variety of effects on the brain including site-preferential , inhibitory effects on hippocampal neurons . In the case of dexamethasone ( DEX ) , extended rather than single-dose treatment in vivo may be required for binding to brain rather than peripheral ( e.g. , pituitary ) GC receptors and for maximizing other biologic effects in hippocampus ( e.g. , GC receptor downregulation , inhibition of glucose transport ) . Based on the contributory role of hippocampal neurons in declarative memory performance , we investigated the cognitive consequences of DEX treatment in normal adult human subjects , hypothesizing a decrease in declarative memory performance after extended but not overnight treatment . Double-blind , placebo-controlled treatment with DEX was given at 2300 hr for four consecutive days ( 0.5 , 1 , 1 , 1 mg , respectively ) . Plasma sampling ( 0800 and 1600 hr ) and cognitive testing ( 1600 hr ) were performed on study days 0 ( baseline ) , 1 , and 4 , and 7 d posttreatment . Repeated- measures ANOVA found a significant interaction between study day and treatment condition for correct recall during a paragraph recall task [ F(3,51 ) = 3.52 , p = 0.02 ] . DEX ( n = 10 ) in comparison to placebo ( n = 9 ) treatment decreased correct paragraph recall on study day 4 [ F(1,17 ) = 5.01 , p = 0.04 ] and study day 11 [ F(1,17 ) = 5.82 , p = 0.03 ] , with the lowest level of performance occurring on day 4 followed by a return toward baseline performance level by day 11 . In the placebo-treated subjects , correct paragraph recall improved over the course of treatment , consistent with practice . ( ABSTRACT TRUNCATED AT 250 WORDS We previously reported that glucose intake amplifies cortisol response to psychosocial stress and smoking in healthy young men , while low blood glucose levels prevented the stress-induced activation of the hypothalamus pituitary adrenal ( HPA ) axis . However , it remains unknown whether this modulation is specific for glucose load or a more common effect of energy availability . To eluci date this question , 37 healthy men , who fasted for at least 8 h before the experiment , were r and omly assigned to four experimental groups , who received glucose ( n = 8) , protein ( n = 10 ) , fat ( n = 10 ) , and water ( n = 9 ) , one h before their exposure to the Trier Social Stress Test ( TSST ) . Blood glucose levels were measured at baseline and following stress , while salivary cortisol was assessed repeatedly measured before after the TSST . The results show that both absolute cortisol levels and net cortisol increase were greater in the glucose group in comparison to the other groups ( F(3,33 ) = 3.00 , P < 0.05 and F(3,33 ) = 3.08 , P < 0.05 , respectively . No group differences were observed with respect to perceived stress and mood . Furthermore , the cortisol response was positively correlated with blood glucose changes ( r = 0.49 , P < 0.002 ) . In conclusion , the results suggest a central mechanism responsible for regulation of energy balance and HPA axis activation , rather than peripheral mechanisms . We thus recommend controlling for blood glucose levels when study ing HPA axis responsiveness OBJECTIVE —Carbohydrate counting is an effective approach to mealtime insulin adjustment in type 1 diabetes but has not been rigorously assessed in type 2 diabetes . We sought to compare an insulin-to-carbohydrate ratio with a simple algorithm for adjusting the dose of pr and ial insulin glusiline . RESEARCH AND DESIGN METHODS —This 24-week , multicenter , r and omized , controlled study compared two algorithms for adjusting mealtime ( glulisine ) insulin along with a st and ard algorithm for adjusting background ( glargine ) insulin in 273 intent-to-treat patients with type 2 diabetes . Glulisine and glargine were adjusted weekly in both groups based on self-monitored blood glucose ( SMBG ) results from the previous week . The simple algorithm group was provided set doses of glulisine to take before each meal . The carbohydrate counting ( carb count ) group was provided an insulin-to-carbohydrate ratio to use for each meal and adjusted their glulisine dose based on the amount of carbohydrate consumed . RESULTS —A1C levels at week 24 were 6.70 % ( simple algorithm ) and 6.54 % ( carb count ) . The respective mean A1C changes from baseline to 24 weeks were −1.46 and −1.59 % ( P = 0.24 ) . A1C < 7.0 % was achieved by 73.2 % ( simple algorithm ) and 69.2 % ( carb count ) ( P = 0.70 ) of subjects ; respective values for A1C < 6.5 % were 44.3 and 49.5 % ( P = 0.28 ) . The total daily dose of insulin was lower , and there was a trend toward less weight gain in carb count group patients . Severe hypoglycemia rates were low and equal in the two groups . CONCLUSIONS —Weekly basal-bolus insulin adjustments based on premeal and bedtime glucose patterns result ed in significant reductions in A1C . Having two effective approaches to delivering and adjusting rapid-acting mealtime insulin may increase physicians ' and patients ' willingness to advance therapy to a basal-bolus insulin regimen In previous studies , adults with Alzheimer 's disease ( AD ) showed memory enhancement when plasma insulin levels were raised to 85 microU/ml , whereas normal adults ' memory was unchanged . Degree of memory enhancement was also related to apolipoprotein E ( apoE ) genotype status for AD patients . Response differences between normal and AD groups could reflect dose-response differences for insulin . To examine this question , 22 adults with AD and 15 normal adults received five doses of insulin on separate days in counterbalanced order , result ing in five plasma insulin levels ( 10 , 25 , 35 , 85 and 135 microU/ml ) , while plasma glucose levels of ~100 mg/dl were maintained . Cognitive performance and plasma APP levels were measured after 120 min of infusion . Relative to baseline , AD patients who were not apoE- epsilon 4 homozygotes had improved memory at higher insulin levels of 35 and 85 microuU/ml , whereas normal adults and AD patients who were epsilon 4 homozygotes showed improved memory at insulin levels of 25 microU/ml . Normal adults ' memory was also improved at insulin levels of 85 microU/ml . Plasma APP was lowered for adults with AD without the epsilon 4 allele at higher levels ( 85 microU/ml ) than for normal adults and epsilon 4 homozygotes , who showed decreased APP at the 35 microU/ml level . AD patients with a single epsilon 4 allele showed a different pattern of insulin effects on APP than did other subjects . In general , few effects of insulin were seen at the highest dose for any subject group . These results support a role for insulin in normal memory and APP modulation that follows a curvilinear response pattern , and suggest that AD patients who are not epsilon 4 homozygotes have reduced sensitivity to insulin that may interfere with such modulation Animal studies suggest that diets low in calories and rich in unsaturated fatty acids ( UFA ) are beneficial for cognitive function in age . Here , we tested in a prospect i ve interventional design whether the same effects can be induced in humans . Fifty healthy , normal- to overweight elderly subjects ( 29 females , mean age 60.5 years , mean body mass index 28 kg/m2 ) were stratified into 3 groups : ( i ) caloric restriction ( 30 % reduction ) , ( ii ) relative increased intake of UFAs ( 20 % increase , unchanged total fat ) , and ( iii ) control . Before and after 3 months of intervention , memory performance was assessed under st and ardized conditions . We found a significant increase in verbal memory scores after caloric restriction ( mean increase 20 % ; P < 0.001 ) , which was correlated with decreases in fasting plasma levels of insulin and high sensitive C-reactive protein , most pronounced in subjects with best adherence to the diet ( all r values < −0.8 ; all P values < 0.05 ) . Levels of brain-derived neurotrophic factor remained unchanged . No significant memory changes were observed in the other 2 groups . This interventional trial demonstrates beneficial effects of caloric restriction on memory performance in healthy elderly subjects . Mechanisms underlying this improvement might include higher synaptic plasticity and stimulation of neurofacilitatory pathways in the brain because of improved insulin sensitivity and reduced inflammatory activity . Our study may help to generate novel prevention strategies to maintain cognitive functions into old age Background / Objectives : Previous research investigating the impact of glucose ingestion and /or improvements in glucose regulation has found selective cognitive facilitation on episodic memory tasks in successful ageing and dementia . The present study aim ed to extend this research to mild cognitive impairment (MCI).Subjects/ Methods : In a repeated- measures design , 24 older adults with and 24 older adults without MCI performed a battery of memory and attention tasks after 25 g of glucose or a sweetness matched placebo . In addition , to assess the impact of individual differences in glucose regulation , blood glucose measurements were taken throughout the testing session . Results : Consistent with previous research , cognitive facilitation was observed for episodic memory tasks only in both successful ageing and MCI . Older adults with MCI had a similar glucose regulatory response as controls but their fasting levels were elevated . Notably , higher levels of blood glucose were associated with impaired memory performance in both the glucose and placebo conditions . Importantly , both blood glucose and memory performance indices were significant predictors of MCI status . Conclusions : The utility of glucose supplementation and the use of glucose regulation as a biological marker are discussed in relation to these data Abstract Recent research findings indicate that glucose administration enhances some aspects of cognitive functioning . To date , those studies which have investigated the effects of glucose on memory in human participants have concentrated on its apparent ability to attenuate memory impairment . Relatively little research has been done in humans investigating the effects of glucose on memory performance in young healthy participants in whom no memory deficits exist . Moreover , the work which has been conducted in this population has produced somewhat equivocal findings . In this study , after overnight fasting the influence of a 25 g oral dosage of glucose on a range of measures of memory performance was investigated in healthy young female participants . Two control treatments ( saccharin and water ) were also administered . There was a significant glucose facilitation effect upon performance of long-term verbal free and cued recall tasks which did not vary with test delay . Performance on these free and cued verbal recall measures correlated significantly with blood glucose levels across all participants . No glucose-related facilitation was observed on either a test of short-term verbal memory ( forwards/backwards digit recall ) or a test of long-term non-verbal memory ( complex figure reproduction ) . However , the significant glucose-related effects observed with long-term free and cued recall remained after controlling for participants ’ differential baseline blood glucose levels and individual levels of immediate memory performance . Therefore , memory improvement after glucose ingestion was not merely a consequence of lower baseline blood glucose or lower immediate memory performance in the glucose treatment group . These findings indicate that there may be some fractionation in the memory facilitation effects of glucose : the memory enhancing effect of glucose administration in healthy young adults may be greatest on tests of long-term verbal recall . The results suggest that glucose may enhance retention in and /or retrieval from long-term verbal memory Raising insulin acutely in the periphery and in brain improves verbal memory . Intranasal insulin administration , which raises insulin acutely in the CNS without raising plasma insulin levels , provides an opportunity to determine whether these effects are mediated by central insulin or peripheral processes . Based on prior research with intravenous insulin , we predicted that the treatment response would differ between subjects with ( epsilon4 + ) and without ( epsilon4- ) the APOE-epsilon4 allele . On separate mornings , 26 memory-impaired subjects ( 13 with early Alzheimer 's disease and 13 with amnestic mild cognitive impairment ) and 35 normal controls each underwent three intranasal treatment conditions consisting of saline ( placebo ) or insulin ( 20 or 40 IU ) . Cognition was tested 15 min post-treatment , and blood was acquired at baseline and 45 min after treatment . Intranasal insulin treatment did not change plasma insulin or glucose levels . Insulin treatment facilitated recall on two measures of verbal memory in memory-impaired epsilon4- adults . These effects were stronger for memory-impaired epsilon4- subjects than for memory-impaired epsilon4 + subjects and normal adults . Unexpectedly , memory-impaired epsilon4 + subjects showed poorer recall following insulin administration on one test of memory . These findings suggest that intranasal insulin administration may have therapeutic benefit without the risk of peripheral hypoglycemia and provide further evidence for apolipoprotein E ( APOE ) related differences in insulin metabolism Rationale The cognition-enhancing effects of glucose administration to humans have been well-documented ; however , it remains unclear whether this effect preferentially targets episodic memory or other cognitive domains . Objectives The effect of glucose on the allocation of attentional re sources during memory encoding was assessed using a sensitive dual-attention paradigm . Material s and methods One hundred and twenty volunteers ( mean age 21.60 , SD 4.89 , 77 females ) took part in this r and omised , double-blind , placebo-controlled , parallel groups study where each consumed a 25-g glucose drink or a placebo . Half of the participants in each drink condition attempted to track a moving on-screen target during auditory word presentation . The distance between the cursor and the tracking target was used as an index of attentional cost during encoding . Effects of drink and tracking on recognition memory and drink on tracking performance were assessed . Self-rated appetite and mood were co-monitored . Results Co-performing the tracking task significantly impaired memory performance irrespective of drink condition . In the placebo – tracking condition , there was a cost to tracking manifest as greater deviation from target during and immediately following word presentation . Compared with placebo , the glucose drink significantly improved tracking performance during encoding . There were significant time-related changes in thirst and alertness ratings but these were not differentially affected by drink or tracking conditions . Conclusion Tracking but not memory was enhanced by glucose . This finding suggests that , under certain task conditions , glucose administrations does not preferentially enhance memory performance . One mechanism through which glucose acts as a cognition enhancer is through allowing greater allocation of attentional re sources Rationale Reduced brain serotonin function is acknowledged as a vulnerability factor for affective disturbances . Since the production of serotonin is limited by the availability of its plasma dietary amino acid precursor tryptophan ( TRP ) , the beneficial effects of tryptophan-rich alpha-lactalbumin whey protein ( ALAC ) have recently been studied . The effects of ALAC remain rather modest , and alternative protein sources of tryptophan may be more effective . Objectives We tested whether hydrolyzed protein ( HPROT ) has greater effects on the plasma TRP/large neutral amino acids ( LNAA ) ratio and mood than intact ALAC protein in healthy volunteers . Material s and methods In a double-blind , r and omized cross-over study , plasma amino acids and mood were repeatedly measured in 18 healthy subjects before and after intake of ALAC and HPROT as well as after placebo protein , pure tryptophan , and a tryptophan-containing synthetic peptide . Except for the placebo protein , all interventions contained 0.8 g TRP . Results Significantly faster and greater increases in plasma TRP/LNAA were found after HPROT than after ALAC . In addition , the effects of HPROT on plasma TRP/LNAA were comparable with the effects of the tryptophan-containing synthetic peptide and even exceeded the effect of pure tryptophan . Sixty minutes after intake , mood was improved only following intake of HPROT and pure tryptophan , whereas longer-lasting mood effects were only found after intake of HPROT . Conclusions The use of a tryptophan-rich hydrolyzed protein source may be more adequate to increase brain tryptophan and 5-HT function compared with intact alpha-lactalbumin protein or pure tryptophan 1 . In a multicenter , placebo-controlled , double-blind clinical trial in 155 elderly patients with cognitive decline , glycosaminoglycan polysulfate was found to be a therapeutically effective agent in the treatment of old age dementias . 2 . Treatment with glycosaminoglycan polysulfate in the daily dosage of 600 LRU , administered on the basis of a divided dosage schedule for 12 weeks , was significantly superior to an inactive placebo on several outcome measures including the Wechsler Memory Scale-Russell Revision ( Easy Paired Associates Learning and Immediate Visual Reproduction ) , Mini Mental State Examination , the S and oz Clinical Assessment Geriatric ( Cognitive Dysfunction and Depression ) , Hachinski Dementia Scale , Brief Psychiatric Rating Scale ( Confusion and Depressive Withdrawal ) and Global Improvement Scale of the Clinical Global Impression . 3 . Adverse effects with glycosaminoglycan polysulfate were few and mild . The drug was equally well tolerated and equally effective in the two major dementias of old age , i.e. , primary degenerative and multi-infa rct . The number of abnormal laboratory test readings remained essentially unchanged from pre-treatment to post-treatment Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration Energy-restricted low glycemic load diets are being used increasingly for weight loss . However , the long-term effects of such regimens on mood and cognitive performance are not known . We assessed the effects of low glycemic load ( LG ) and high glycemic load ( HG ) energy-restricted diets on mood and cognitive performance during 6 months of a r and omized controlled trial when all food was provided . Subjects were 42 healthy overweight adults ( age 35+/-5 years ; BMI 27.8+/-1.6 kg/m(2 ) ) with a mean weight loss of 8.7+/-5.0 % that did not differ significantly by diet r and omization . Mood was assessed by using the Profile of Mood States ( POMS ) question naire . Cognitive performance was assessed by using computerized tests of simple reaction time , vigilance , learning , short-term memory and attention , and language -based logical reasoning . Worsening mood outcome over time was observed in the HG diet group compared to the LG for the depression subscale of POMS ( p=0.009 after including hunger as a covariate ) . There was no significant change over time in any cognitive performance values . These findings suggest a negative effect of an HG weight loss diet on sub- clinical depression but , in contrast to a previous suggestion , provide no support for differential effects of LG versus HD diets on cognitive performance A high intake of saturated fat and cholesterol and a low intake of polyunsaturated fatty acids have been related to an increased risk of cardiovascular disease . Cardiovascular disease has been associated with dementia . We investigated the association between fat intake and incident dementia among participants , age 55 years or older , from the population ‐based prospect i ve Rotterdam Study . Food intake of 5,386 nondemented participants was assessed at baseline with a semiquantitative food‐frequency question naire . At baseline and after an average of 2.1 years of follow‐up , we screened for dementia with a three‐step protocol that included a clinical examination . The risk of dementia at follow‐up ( RR [ 95 % CI ] ) was assessed with logistic regression . After adjustment for age , sex , education , and energy intake , high intakes of the following nutrients were associated with an increased risk of dementia : total fat ( RR = 2.4 [ 1.1–5.2 ] ) , saturated fat ( RR = 1.9 [ 0.9–4.0 ] ) , and cholesterol ( RR = 1.7 [ 0.9–3.2 ] ) . Dementia with a vascular component was most strongly related to total fat and saturated fat . Fish consumption , an important source of n‐3 polyunsaturated fatty acids , was inversely related to incident dementia ( RR = 0.4 [ 0.2–0.9 ] ) , and in particular to Alzheimer 's disease ( RR = 0.3 [ 0.1–0.9 ] ) . This study suggests that a high saturated fat and cholesterol intake increases the risk of dementia , whereas fish consumption may decrease this risk The effect of different carbohydrate to protein ratios in food on cognitive functions and the relation between postpr and ial metabolic and cognitive changes were studied in 15 healthy male students . Subjects were tested in three sessions , separated by 1 week , for short-term changes in mood states , objective cognitive functions , blood parameters , and indirect calorimetry using a repeated- measures , counterbalanced cross-over design . Measurements were made after an overnight fast before and hourly during 3.5 h after test meal ingestion . The isoenergetic ( 1670 kJ ) test meals consisted of three carbohydrate to protein ratios , i.e. a carbohydrate-rich ( CHO[4:1 ] ) , balanced ( BAL[1:1 ] ) , and protein-rich ( PRO[1:4 ] ) meal , respectively . Overall accuracy in short-term memory was best after the PRO[1:4 ] meal concomitant to the least variation in glucose metabolism and glucagon to insulin ratio ( GIR ) . Related to changes in glucose metabolism and /or in the ratios of large neutral amino acids ( LNAA ) , respectively , attention and decision times were transiently improved within the first hour after the CHO[4:1 ] meal , whereas after the first hour the BAL[1:1 ] and PRO[1:4 ] meal result ed in improved performance . Overall reaction times of a central task were fastest after the BAL[1:1 ] meal concomitant to the highest overall tyrosine ( Tyr ) to LNAA ratio . Our findings suggest that the carbohydrate to protein ratio in food specifically influences higher cognitive functions in the morning . Except for a transient positive effect of rising blood glucose after a carbohydrate-rich meal , a protein-rich or balanced meal seems to result in better overall cognitive performance presumably because of less variation in glucose metabolism and /or higher modulation in LNAA ratios indicated by the overall GIR Background : Postpr and ial plasma glucose ( PPG ) excursion is a significant determinant of overall metabolic control as well as an increased risk for diabetic complications . Older persons with type 2 diabetes mellitus ( DM2 ) are more likely to have moderate cognitive deficits and neurophysiologic and structural changes in brain tissue . Considering that poor metabolic control is considered a deranging factor for tissue/organ damage in diabetics , the authors hypothesized that PPG excursion is associated with a decline in cognitive functioning and that a tighter control of PPG may prevent cognitive decline . Methods : Two groups of aged diabetic patients were r and omly selected to be treated with repaglinide ( n = 77 ) or glibenclamide ( n = 79 ) . Results : Coefficient of variation of PPG ( CV-PPG ) was associated with Mini-Mental State Examination ( MMSE ) scores ( r = –0.3410 ; p < 0.001 ) and a composite score of executive and attention functioning ( r = –0.3744 ; p < 0.001 ) after adjusting for multiple confounders . Both groups showed a significant decline in hemoglobin A1c ( HbA1c ) and fasting plasma glucose ( FPG ) , but only the repaglinide group demonstrated a significant decline of CV-PPG over time . In models investigating the change in cognitive functioning over time , adjusted for HbA1c and CV-FPG , a decline in cognitive functioning was observed only in the glibenclamide group ( p < 0.001 ) . After adjusting for CV-PPG , the authors no longer found a decline in executive and attention functioning composite score ( p = 0.085 ) or the MMSE ( p = 0.080 ) with glibenclamide . Conclusions : Exaggerated postpr and ial glucose ( PPG ) excursions are associated with a derangement of both global , executive , and attention functioning . A tighter control of PPG may prevent cognitive decline in older diabetic individuals Cognitive performance has been found to decline after exposure to stress , particularly in stress-prone subjects . The present study investigated whether a carbohydrate-rich , protein-poor ( CR/PP ) diet , which may enhance cerebral serotonin function in stress-prone subjects due to increases in the available tryptophan , improves the performance of stress-prone subjects after exposure to acute laboratory stress . Twenty-two high-stress-prone ( HS ) subjects and twenty-one low-stress-prone ( LS ) subjects aged between 19 and 26 years performed a memory scanning task after controllable and uncontrollable stress , following either a CR/PP diet or a protein-rich , carbohydrate-poor ( PR/CP ) isoenergetic diet . Uncontrollable stress reduced feelings of control ( F(1,38 ) 9.30 ; P = 0.004 ) , whereas pulse rate and skin conductance increased after both stress tasks ( F(1,38 ) 78.34 ; P = 0.0005 and F(1,37 ) 83.16 ; P = 0.0004 ) . Diet , stress-proneness and stress-controllability interacted ( F(1,36 ) 9.46 ; P = 0.004 ) in such a way that performance in HS subjects was better with the CR/PP diet than with the PR/CP diet , but only after controllable stress . As the CR/PP diet has been found to increase the plasma tryptophan : large neutral amino acids ratio , indicating an increased availability of cerebral tryptophan and , thus , higher serotonin levels , it appears that there may be an increased availability of brain serotonin in HS subjects after controllable laboratory stress The effects of gastric infusions of fat and carbohydrate on physiological and psychological measures were compared using a within subject design in 9 healthy subjects ( 6 males ) . Each subject received isovolaemic rapid gastric infusions of sucrose solution ( 100 % energy carbohydrate ) , lipid emulsion ( 100 % energy fat , 20 % Intralipid ) , and a non-nutrient control ( 0.9 % saline ) in a r and omised order . Nutrient infusions were isoenergetic , containing one-third of an individual subject 's estimated daily energy requirements ( mean , 3227 kJ ; range , 2479 - 3971 kJ ) . Measures of heart rate ( HR ) , energy expenditure ( EE ) , mood , and sleepiness were collected before the infusions and every 0.5 h for 3.5 h. Mean postingestive HR , EE , and satiation were significantly greater after the nutrient infusions than after the control . Sucrose induced a rapid increase in HR and EE , whereas lipid had a lesser and more delayed effect . Thirty minutes after the gastric infusions , HR and EE were significantly higher after the sucrose than after the lipid and saline . Hedonic tone was greater and tension lower after the saline and sucrose infusions than after the lipid infusion . From 3 to 3.5 h after ingestion , subjects felt significantly more sleepy after the lipid infusion than they did at these times after the saline infusion , and significantly more dreamy after the lipid infusion than they did after the sucrose infusion . In conclusion , the presence of lipid and sucrose in the intestine induces significant and differing physiological and psychological effects , which are independent of cognitive and orosensory influences Although Lycium barbarum ( goji ) and active compounds , Lycium barbarum polysaccharides ( LBP ) , have a high in vitro antioxidant score as determined by simple chemical reaction methods , their in vivo antioxidant effects in humans have not been extensively examined . After our earlier report that an LBP-st and ardized Lycium barbarum preparation ( GoChi ) helps prevent oxidant stress-related conditions in humans , our present study examined the hypothesis that the antioxidant effects of GoChi result from its ability to enhance endogenous antioxidant factors . We investigated the effects of GoChi in a 30-day r and omized , double-blind , placebo-controlled clinical study . The study population included 50 Chinese healthy adults aged 55 to 72 years . In vivo antioxidant markers , consisting of serum levels of superoxide dismutase ( SOD ) , glutathione peroxidase ( GSH-Px ) , and lipid peroxidation ( indicated by decreased levels of malondialdehyde , MDA ) were examined preintervention and postintervention with GoChi or placebo ( 120 mL/d ) . In the GoChi group , antioxidant markers significantly increased by 8.4 % for SOD and 9.9 % for GSH-Px between the preintervention and postintervention measurements , whereas MDA were significantly decreased by 8.7 % . In addition , the SOD , GSH-Px , and MDA levels in the GoChi group were significantly different from those in the placebo group at the postintervention time point , with increases of 8.1 % and 9.0 % and a decrease of 6.0 % , respectively . No significant differences were detected between the preintervention and postintervention time points in the placebo group . These results indicate that GoChi increased antioxidant efficacies in humans by stimulating endogenous factors and suggest that continued use beyond 30 days might help prevent or reduce free radical-related conditions OBJECTIVES To examine whether providing a midmorning nutrition supplement increases habitual energy intake in seniors with probable Alzheimer 's disease ( AD ) and to investigate the effects of body weight status and cognitive and behavioral function on the response to the intervention . DESIGN R and omized , crossover , nonblinded clinical trial . SETTING A fully accredited geriatric teaching facility affiliated with the University of Toronto 's Medical School with a home for the aged . PARTICIPANTS Thirty-four institutionalized seniors with probable AD who ate independently . INTERVENTION Nutrition supplements were provided between breakfast and lunch for 21 consecutive days and compared with 21 consecutive days of habitual intake . MEASUREMENTS Investigator-weighed food intake , body weight , cognitive function ( Severe Impairment Battery and Global Deterioration Scale ) , behavioral disturbances ( Neuropsychiatric Inventory-Nursing Home Version ) , and behavioral function ( London Psychogeriatric Rating Scale ) . RESULTS Relative to habitual intake , group mean analyses showed increased 24-hour energy , protein , and carbohydrate intake during the supplement phase , but five of 31 subjects who finished all study phases completely compensated for the energy provided by the supplement by reducing lunch intake , and 24-hour energy intake was enhanced in only 21 of 31 subjects . Compensation at lunch was more likely in subjects with lower body mass indices , increased aberrant motor behavior , poorer attention , and increased mental disorganization/confusion . CONCLUSION Nutrition supplements were least likely to enhance habitual energy intake in subjects who would normally be targeted for nutrition intervention-those with low body weight status . Those likely to benefit include those with higher body mass indices , less aberrant motor problems , less mental disorganization , and increased attention Background : Lifestyle and vascular factors have been linked to dementia and Alzheimer ’s disease ( AD ) , but the role of dietary fats in the development of dementia is less clear . Methods : Participants were derived from r and om , population -based sample s initially studied in midlife ( 1972 , 1977 , 1982 , or 1987 ) . Fat intake from spreads and milk products was assessed using a structured question naire and an interview . After an average follow-up of 21 years , a total of 1,449 ( 73 % ) individuals aged 65–80 years participated in the re-examination in 1998 . Altogether 117 persons had dementia . Results : Moderate intake of polyunsaturated fats at midlife decreased the risk of dementia even after adjustment for demographic variables , other subtypes of fats , vascular risk factors and disorders , and apolipoprotein E ( ApoE ) genotype ( OR 0.40 , CI 0.17–0.94 for the 2nd quartile vs. 1st quartile ) , whereas saturated fat intake was associated with an increased risk ( OR 2.45 , CI 1.10–5.47 for the 2nd quartile ) . The associations were seen only among the ApoE Ε4 carriers . Conclusions : Moderate intake of unsaturated fats at midlife is protective , whereas a moderate intake of saturated fats may increase the risk of dementia and AD , especially among ApoE Ε4 carriers . Thus , dietary interventions may potentially modify the risk of dementia , particularly among genetically susceptible individuals OBJECTIVE To assess the association between food combination and Alzheimer disease ( AD ) risk . Because foods are not consumed in isolation , dietary pattern ( DP ) analysis of food combination , taking into account the interactions among food components , may offer method ological advantages . DESIGN Prospect i ve cohort study . SETTING Northern Manhattan , New York , New York . PATIENTS OR OTHER PARTICIPANTS Two thous and one hundred forty-eight community-based elderly subjects ( aged > or = 65 years ) without dementia in New York provided dietary information and were prospect ively evaluated with the same st and ardized neurological and neuropsychological measures approximately every 1.5 years . Using reduced rank regression , we calculated DPs based on their ability to explain variation in 7 potentially AD-related nutrients : saturated fatty acids , monounsaturated fatty acids , omega-3 polyunsaturated fatty acids , omega-6 polyunsaturated fatty acids , vitamin E , vitamin B(12 ) , and folate . The associations of reduced rank regression-derived DPs with AD risk were then examined using a Cox proportional hazards model . Main Outcome Measure Incident AD risk . RESULTS Two hundred fifty-three subjects developed AD during a follow-up of 3.9 years . We identified a DP strongly associated with lower AD risk : compared with subjects in the lowest tertile of adherence to this pattern , the AD hazard ratio ( 95 % confidence interval ) for subjects in the highest DP tertile was 0.62 ( 0.43 - 0.89 ) after multivariable adjustment ( P for trend = .01 ) . This DP was characterized by higher intakes of salad dressing , nuts , fish , tomatoes , poultry , cruciferous vegetables , fruits , and dark and green leafy vegetables and a lower intake of high-fat dairy products , red meat , organ meat , and butter . CONCLUSION Simultaneous consideration of previous knowledge regarding potentially AD-related nutrients and multiple food groups can aid in identifying food combinations that are associated with AD risk Purpose : This research sought to answer the following question : To what extent is the functional status of elderly people explained by gender , age , geographical residence , level of cognitive function , and depression ? Method : Two hundred r and omly selected community‐dwelling elderly people aged 65 to 80 years old completed the Mini‐Mental State Examination ( MMSE ) , Geriatric Depression Scale ( GDS ) , and Physical Performance Test ( PPT ) . Results : Correlation analysis and simple linear regression models showed that age , MMSE , GDS , and geographical residence were significantly associated with the functional level , whereas gender was not . In the multiple regression model , MMSE and geographical residence together explained 40 % of the variance in functional status ; age and GDS did not add to the explanation . Conclusion : Since cognitive function had the strongest association with functional performance to an extent greater than the other variables , adding a treatment regimen that stimulates cognitive function might further enhance functional level or prevent decline of functional status compared with an exercise intervention alone Rationale . Glucose is the main metabolic fuel of the brain . The rate of glucose delivery from food to the bloodstream depends on the nature of carbohydrates in the diet , which can be summarized as the glycaemic index ( GI ) . Objectives . To assess the benefit of a low versus high GI breakfast on cognitive performances within the following 4 h. Methods . The influence of the GI of the breakfast on verbal memory of young adults was measured throughout the morning in parallel to the assessment of blood glucose levels . The learning abilities of rats performing an operant-conditioning test 3 h after a breakfast-like meal of various GI was also examined . Results . A low GI rather than high GI diet improved memory in humans , especially in the late morning ( 150 and 210 min after breakfast ) . Similarly , rats displayed better learning performance 180 min after they were fed with a low rather than high GI diet . Conclusion . Although performances appeared to be only remotely related to blood glucose , our data provide evidence that a low GI breakfast allows better cognitive performances later in the morning A great deal of research has been devoted to the issue of whether the ingestion of a glucose containing drink facilitates cognitive performance . However , it remains unclear exactly how age and individual differences in gluco-regulatory control mediate a boost in cognitive functioning . The present study investigates these issues further . A repeated measures ( 25 g vs 50 g glucose vs placebo ) counterbalanced , double-blind design was used with 25 younger and middle-aged adults . A battery of memory and non-memory tasks was administered ; including tests of episodic and semantic memory , attention and visuospatial functioning . Glucose ingestion largely facilitated performance on tasks with a memory component . Notably , task dem and s and age ( young vs middle-aged ) contributed to the magnitude of memory enhancement . This finding suggests an age- and load-specific benefit of glucose intake . In addition , evidence suggests greater facilitation in individuals with good glucose regulation . These data are discussed in relation to the idea that glucose specifically affects neural mechanisms supporting memory functioning ( i.e. the hippocampus ) , which are known to decline in ageing . Importantly , the present investigation adds to the growing body of literature showing the utility of glucose supplementation as memory enhancers Objective To test the efficacy of a specially-formulated , carbohydrate-rich beverage ( one known to increase the serum ratio of tryptophan to other large neutral amino acids ) on the mood , cognitive , and appetitive disturbances of premenstrual syndrome ( PMS ) . Methods Twenty-four women with confirmed PMS were enrolled in a double-blind , crossover study to test the efficacy of the specially-formulated beverage compared with two other isocaloric products on PMS symptoms . The study was conducted over three menstrual cycles preceded by a 1-month placebo run-in . Patients were tested at home or work using an interactive computer-telephone system . St and ardized measurements of mood , cognitive performance , and food cravings were made before and 30 , 90 , and 180 minutes after consumption of active and placebo beverages during the late luteal phase of the menstrual cycle . Results The experimental carbohydrate intervention significantly decreased self-reported depression , anger , confusion , and carbohydrate craving 90–180 minutes after intake . Memory word recognition was also improved significantly compared with scores obtained during the placebo run-in month ( P < .05 ) . The isocaloric placebo interventions had no significant effect on any of these measures . Conclusion The results suggest that the psychological and appetitive symptoms of PMS can be relieved after consuming a specially-formulated , carbohydrate-rich beverage known to increase serum tryptophan levels It is accepted that acetylcholine-mediated neurones modulate memory . As lecithin , carnitine and glucose all influence acetylcholine metabolism , the possibility of synergistic interactions was considered . Four hundred young adult females r and omly , and under a double-blind procedure , received capsules for 3 days that contained a placebo , lecithin ( 1.6 g/day ) , carnitine ( 500 mg/day ) or carnitine plus lecithin . A battery of cognitive tests was administered prior to taking the capsules , after 3 days of taking the supplements , and for a third time after consuming either a glucose drink or a placebo . Reaction times were more rapid when carnitine and a glucose drink were taken together . Memory was enhanced in those taking a glucose rather than placebo drink . Neither mood nor the ability to sustain attention were influenced by these procedures . The hypothesis that memory would be facilitated by offering supplements of lecithin , carnitine and glucose was not supported The metabolic and behavioral effects of nutrients after exercise on vigilance level , performance , and mood have been minimally studied and have given contradictory results . In order to increase the underst and ing of the relationships between nutrition , exercise and performance , this experiment compared the effects on mood and performance of a protein- rich meal and a protein- poor meal , eaten just after an acute session of exercise . Vigilance and mood were evaluated by visual analog scales , and memory was measured by memory search task from the AGARD STRES battery , based on the Sternberg paradigm . Forty-two subjects were involved in this experiment . All subjects participated in the study of the effect of exercise after two kinds of meals ( protein and nonprotein ) . Two groups of fourteen subjects we used to evaluate the effect of the exercise and the effect of the delay of meal intake after exercise in the two kinds of diet . The results show no difference in memory performance between exercise and rest conditions , nor between " protein " and " no protein " meal groups . They do show , however , that subjects feel happier after a meal with protein than after a meal without protein . The effects of the " no protein " meal on drowsiness differ with the glucide content of the meal . Subjects are less drowsy when they eat between 125 and 150 g of glucide than when they eat more than 150 g. The rousing effect induced by physical exercise is counterbalanced when subjects eat more than 150 g of carbohydrate . The anxiolytic effect of glucide is re-established BACKGROUND Very low-carbohydrate ( LC ) diets are often used to promote weight loss , but the long-term effects on psychological function remain unknown . METHODS A total of 106 overweight and obese participants ( mean [ SE ] age , 50.0 [ 0.8 ] years ; mean [ SE ] body mass index [ calculated as weight in kilograms divided by height in meters squared ] , 33.7 [ 0.4 ] ) were r and omly assigned either to an energy-restricted ( approximately 1433 - 1672 kcal [ to convert to kilojoules , multiply by 4.186 ] ) , planned isocaloric , very low-carbohydrate , high-fat ( LC ) diet or to a high-carbohydrate , low-fat ( LF ) diet for 1 year . Changes in body weight , psychological mood and well-being ( Profile of Mood States , Beck Depression Inventory , and Spielberger State Anxiety Inventory scores ) , and cognitive functioning ( working memory and speed of processing ) were assessed . RESULTS By 1 year , the overall mean ( SE ) weight loss was 13.7 ( 1.8 ) kg , with no significant difference between groups ( P = .26 ) . Over the course of the study , there were significant time x diet interactions for Spielberger State Anxiety Inventory , Beck Depression Inventory , and Profile of Mood States scores for total mood disturbance , anger-hostility , confusion-bewilderment , and depression-dejection ( P < .05 ) as a result of greater improvements in these psychological mood states for the LF diet compared with the LC diet . Working memory improved by 1 year ( P < .001 for time ) , but speed of processing remained largely unchanged , with no effect of diet composition on either cognitive domain . CONCLUSIONS Over 1 year , there was a favorable effect of an energy-restricted LF diet compared with an isocaloric LC diet on mood state and affect in overweight and obese individuals . Both diets had similar effects on working memory and speed of processing . Trial Registration anzctr.org.au Identifier : 12606000203550 We prospect ively examined fruit and vegetable intake in relation to cognitive function and decline among aging women . Participants were followed from in 1976 with biennial question naires , and food frequency question naires were administered in 1984 , 1986 , and every 4 years thereafter . From 1995 to 2001 , we administered , by telephone , six cognitive tests measuring general cognition , verbal memory , category fluency , and working memory . We repeated assessment s two years later for 13,388 women ( > 90 % follow‐up ) . We averaged dietary intakes from 1984 through the first cognitive assessment , and used linear regression to obtain multivariable‐adjusted mean differences in performance and decline in performance across intake levels . Fruits were not associated with cognition or cognitive decline . However , total vegetable intake was significantly associated with less decline . Specifically , on a global score combining all tests , women in the highest quintile of cruciferous vegetables declined slower ( by 0.04 unit ; 95 % confidence interval , 0.003 , 0.07 ; p trend = 0.1 ) compared with the lowest quintile . Women consuming the most green leafy vegetables also experienced slower decline than women consuming the least amount ( by 0.05 unit ; 95 % confidence interval , 0.02 , 0.09 ; p trend < 0.001 ) . These mean differences were equivalent to those observed for women about 1 to 2 years apart in age . Ann Neurol Objective : To examine the association between rates of cognitive change and dietary consumption of fruits and vegetables among older persons . Methods : The authors conducted a prospect i ve cohort study of 3,718 participants , aged 65 years and older of the Chicago Health and Aging Project . Participants completed a food frequency question naire and were administered at least two of three cognitive assessment s at baseline , 3-year , and 6-year follow-ups . Cognitive function was measured using the average z-score of four tests : the East Boston Tests of immediate memory and delayed recall , the Mini-Mental State Examination , and the Symbol Digit Modalities Test . Results : The mean cognitive score at baseline for the analyzed cohort was 0.18 ( range : –3.5 to 1.6 ) , and the overall mean change in score per year was a decline of 0.04 st and ardized units . In mixed effects models adjusted for age , sex , race , and education , compared with the rate of cognitive decline among persons in the lowest quintile of vegetable intake ( median of 0.9 servings/day ) , the rate for persons in the fourth quintile ( median , 2.8 servings/day ) was slower by 0.019 st and ardized units per year ( p = 0.01 ) , a 40 % decrease , and by 0.018 st and ardized units per year ( p = 0.02 ) for the fifth quintile ( median , 4.1 servings/day ) , or a 38 % decrease in rates . The association remained significant ( p for linear trend = 0.02 ) with further control of cardiovascular-related conditions and risk factors . Fruit consumption was not associated with cognitive change . Conclusion : High vegetable but not fruit consumption may be associated with slower rate of cognitive decline with older age OBJECTIVES To test the effect of nutritional support on older patient 's quality of life . DESIGN Double-blind , r and omized , placebo-controlled trial conducted from March 2001 to January 2004 . SETTING United Kingdom . PARTICIPANTS Two hundred twenty-five hospitalized acutely ill older patients . INTERVENTION Normal hospital diet plus 400-mL oral nutritional supplements daily for 6 weeks . The composition of the supplement was such as to provide 995 kcal for energy and 100 % of the Reference Nutrient Intakes for a healthy older person for vitamins and minerals . MEASUREMENTS Baseline , 6-week , and 6-month nutritional status and quality of life . RESULTS R and omization to the supplement group led to significantly better quality -of-life scores than in the placebo group at 6 months but not at 6 weeks , after adjustment for baseline quality of life , age , and sex . The effect of supplementation was seen in higher physical function , role physical , and social function scores . Corresponding treatment effects were 7.0 ( 95 % confidence interval (CI)=0.5 - 13.6 , P=.04 ) , 10.2 ( 95 % CI=0.1 - 20.2 , P=.047 ) , and 7.8 ( 95 % CI=0.0 - 15.5 , P=.05 ) , respectively . There was no evidence of difference in Barthel scores at 6 months . CONCLUSION Oral nutritional supplementation of acutely ill hospitalized older patients led to a statistically significant benefit in quality of life The availability of energy appears to exert important regulatory functions in pituitary-adrenal stress responses . In two studies , the effects of short-term fasting and subsequent glucose administration on the free cortisol response to psychological stress and nicotine consumption were investigated . Study 1 : After fasting for 8 - 11 h , healthy young men ingested either 100 g glucose ( n = 13 ) or water ( n = 12 ) . One hour later they were exposed to a psychosocial stress task ( Trier Social Stress Test ) . A third group also ingested 100 g glucose , but they were not exposed to any additional treatment ( n = 10 ) . Capillary blood glucose levels were in the lower euglycemic range before and significantly elevated after the glucose load ( 64.9 + /- 9.8 vs. 162.5 + /- 43.5 mg/dL ; F = 149.04 , P < 0.001 ) . Although glucose load per se did not affect free cortisol levels , psychosocial stress induced a large cortisol response in glucose-treated subjects . In contrast , fasted subjects who received tap water did not respond to the Trier Social Stress Test with significant changes in cortisol levels ( F = 6.27 , P < 0.001 ) . Both groups responded with a similar increase in heart rates ( F = 33.53 , P < 0.001 ) with no statistically significant difference between glucose and water-treated subjects . Study 2 : Twelve habitual smokers received 100 g glucose or tap water after fasting for at least 8 h on two separate sessions ( cross-over , r and om sequence ) . Forty-five min after glucose/water ingestion , they smoked two cigarettes with a nicotine content of 1.0 mg/cigarette . Subjects were euglycemic before smoking , with a significant rise of glucose levels after consumption of 100 g glucose ( 64.4 + /- 8.3 vs. 143.5 + /- 40.0 mg/dL ; F = 40.25 , P < 0.001 ) . As in Exp 1 , subjects showed a substantially larger free cortisol response to nicotine under glucose load compared with water load ( F = 4.91 , P < 0.001 ) . From these data we conclude that the free cortisol response to stimulation is under significant control of center responsible for monitoring energy availability . Low glucose levels appear to inhibit adrenocortical responsiveness in healthy subjects . In agreement with results from animal studies , the present results suggest that ready access to energy is a prerequisite for hypothalamus-pituitary-adrenal stress responses PURPOSE The study tested whether nutritional support of older patients during acute illness leads to a clinical benefit . METHODS In this r and omized , double-blind , placebo-controlled study , we r and omly assigned 445 hospitalized patients aged 65 to 92 years to receive either a normal hospital diet plus 400 mL oral nutritional supplements ( 223 subjects ) or a normal hospital diet plus a placebo ( 222 subjects ) daily for 6 weeks . The composition of the supplement was such as to provide 995 kcal of energy and 100 % of the Reference Nutrient Intakes for vitamins and minerals for a healthy older person . Patients had three assessment s : at baseline , at 6 weeks , and at 6 months post-r and omization . Outcome measures were 6 months of disability , non-elective readmission and length of hospital stay , discharge destination , morbidity , and mortality . RESULTS R and omization to the supplement group led to a significant improvement in nutritional status . Over 6 months , 65 patients ( 29 % ) in the supplements group were readmitted to the hospital compared with 89 patients ( 40 % ) in the placebo group ( adjusted hazard ratio 0.68 [ 95 % confidence interval 0.49 - 0.94 ] ) . The mean length of hospital stay was 9.4 days in the supplements group compared with 10.1 days in the placebo group . Thirty-two people ( 14 % ) died in the supplement group compared with 19 people ( 9 % ) in the placebo group at 6 months ( adjusted hazard ratio 1.65 [ 95 % confidence interval , 0.93 - 2.92 ] ) . CONCLUSION Oral nutritional supplementation of acutely ill patients improved nutritional status and led to a statistically significant reduction in the number of non-elective readmissions Glucose is a major energy source for the brain , and along with several monosaccharide derivatives as components of brain gangliosides , they play important roles in neurologic function . However , there is little information available on the role of glucose and other monosaccharides on resting brain activity . This study was design ed to evaluate the effects of a single dose of a carbohydrate supplement containing glucose and several of its derivatives on resting brain activity in 20 healthy male college students . The supplement provided an insignificant amount of carbohydrate ( 3.9 g ) , protein ( 0.28 g ) , fat ( 0 g ) , and calories ( 14 kcal ) . The amount of glucose in the supplement was 0.5 g ( 1 % the amount of glucose used in adult studies of cognitive functioning and memory ) . We hypothesized that the glyconutrient supplement would enhance brain activity associated with alertness and attention . The study design was double blind , with subjects r and omly assigned to one of two orders , either carbohydrate supplement week one followed by placebo a week later , or the opposite . Electrical brain activity was monitored by 15 electrodes positioned at nine st and ard international 10–20 system locations , including three bilateral pairs at frontal , parietal , and occipital sites . Thirty minutes following ingestion of a placebo or carbohydrate supplement drink , EEG activity was recorded for 10-mins while subjects focused on a stationary visual target . Spectral power of resting brain activity was computed and analyzed contrasting the placebo and supplement groups . Relative to placebo , the carbohydrate supplement significantly enhanced power in three brain wave frequencies ( theta , alpha , and beta ) that are known to be associated with attention and arousal . Since changes were observed in the supplement but not placebo group , our study suggests that additional sugars in the glyconutritional supplement facilitate enhancement of brain electrical activity . Whether the apparent enhancement of arousal in baseline recordings is associated with improved task performance remains to be determined We examined the relationship between dietary intake and cognitive performance in Korean elderly people . Data for dietary intake , anthropometric measurements and cognitive function tests were collected and the relationships of the variables were analyzed . A r and om sample of 210 men and 239 women in Korea , aged 60 and over , was selected . Subjects were free-living elderly people who had not experienced major cognitive function impairment . Main outcome measures , 24 h dietary recall method , food behaviour variables , anthropometrics indices , health variables , and Kwon 's Mini-Mental State Examination for Koreans ( MMSE-K ) for cognitive function test . The prevalence rate of poor cognitive function ( MMSE-K score < or = 19 ) of Korean elderly was 22.3 % : women with poor cognitive function had a higher rate ( 31.0 % ) than that in men ( 12.3 % ) . Cognitive ability was related negatively with age and positively with school education level . Female subjects of poor cognitive function had significantly lower intakes of total amount of foods , cereals , vegetables , fruits , milk , spices , and also , energy , protein , fat , carbohydrate , Ca , P , Fe , vitamin A , thiamin , riboflavin , and niacin than those of the normal cognitive score ( > or = 24 ) group ( P < 0.05 ) . Male subjects of poor cognitive function had significantly lower intakes of fruits , fiber , and vitamin C than the normal subjects ( P < 0.05 ) . The MMSE-K score of female subjects showed a significant positive correlation with total amount of foods , cereals , beans , fruits , milk , oil , spices , and energy , protein , fat , carbohydrate , Ca , Fe , P , riboflavin and niacin intakes . The consumption of adequate nutrients , by taking sufficient amounts and variety of foods , may be important in maintaining adequate cognitive function in elderly Koreans The possible impact of diet , particularly the intake of fatty acids , on cognitive decline and dementia was addressed recently by several studies . We investigated the role of dietary fatty acids on the rate of mild cognitive impairment ( MCI ) in a population -based , prospect i ve study carried out on 278 and 186 nondemented elderly subjects ( 65 - 84 years ) at the 1st ( 1992 - 1993 ) and 2nd ( 1995 - 1996 ) survey from the cohort of Casamassima , Bari , Italy ( n=704 ) , one of the eight centers of the Italian Longitudinal Study on Aging . During the median follow-up of 2.6 years , 18 new events of MCI were diagnosed , and high polyunsaturated fatty acids ( PUFA ) intake appeared to be a protective factor against the development of MCI [ hazard ratio ( HR ) : 0.65 , 95 % confidence interval ( CI ) : 0.43 - 0.98 , trend-test , df=1 , p<0.04 ] . However , when we controlled for the possible confounders ( age , sex , education , Charlson comorbidity index , and total energy intake ) , the HR slightly changed , and the highly skewed 95 % CI , while not statistically significant , may be important ( HR : 0.62 , 95 % CI : 0.34 - 1.13 , p=0.12 ) . In our population , dietary fatty acids intakes were not associated with incident MCI in older age , only high PUFA intake evidence d a borderline nonsignificant trend for a protective effect against the development of MCI Theeffects of glucose administration and emotionality of target material on heart rate and memorywere examined in a double-blind , placebo-controlled , balanced crossover study . Memory for neutral and emotional words was tested in 20 young adults following a glucose drink and a placebo . Heart rate and blood glucose were also measured . Emotional words were recalled and recognized better than neutral words in both drink conditions but there was no direct effect of drink type on memory . During the neutral word memory tasks , similar heart rate deceleration was observed in both drink conditions . However , during the processing of emotional material , heart rates were lowered in the placebo condition and relatively increased in the glucose condition . These results further differentiate the physiological responses involved during memory for affective and neutral material BACKGROUND Growing evidence suggests that oxidative damage caused by the beta-amyloid peptide in the pathogenesis of Alzheimer 's disease may be hydrogen peroxide mediated . Many polyphenols , the most abundant dietary antioxidants , possess stronger neuroprotection against hydrogen peroxide than antioxidant vitamins . METHODS We tested whether consumption of fruit and vegetable juices , containing a high concentration of polyphenols , decreases the risk of incident probable Alzheimer 's disease in the Kame Project cohort , a population -based prospect i ve study of 1836 Japanese Americans in King County , Washington , who were dementia-free at baseline ( 1992 - 1994 ) and were followed through 2001 . RESULTS After adjustment for potential confounders , the hazard ratio for probable Alzheimer 's disease was 0.24 ( 95 % confidence interval [ CI ] , 0.09 - 0.61 ) comparing subjects who drank juices at least 3 times per week with those who drank less often than once per week with a hazard ratio of 0.84 ( 95 % CI , 0.31 - 2.29 ) for those drinking juices 1 to 2 times per week ( P for trend < .01 ) . This inverse association tended to be more pronounced among those with an apolipoprotein Eepsilon-4 allele and those who were not physically active . Conversely , no association was observed for dietary intake of vitamins E , C , or beta-carotene or tea consumption . CONCLUSIONS Fruit and vegetable juices may play an important role in delaying the onset of Alzheimer 's disease , particularly among those who are at high risk for the disease . These results may lead to a new avenue of inquiry in the prevention of Alzheimer 's disease Effects of a combination of caffeine and glucose were assessed in two double-blind , placebo-controlled , cross-over studies during extended performance of cognitively dem and ing tasks . In the first study , 30 participants received two drinks containing carbohydrate and caffeine ( 68 g/38 mg ; 68 g/46 mg , respectively ) and a placebo drink , in counter-balanced order , on separate days . In the second study 26 participants received a drink containing 60 g of carbohydrate and 33 mg of caffeine and a placebo drink . In both studies , participants completed a 10-min battery of tasks comprising 2-min versions of Serial 3s and Serial 7s subtraction tasks and a 5-min version of the Rapid Visual Information Processing task ( RVIP ) , plus a rating of ' mental fatigue ' , once before the drink and six times in succession commencing 10 min after its consumption . In comparison to placebo , all three active drinks improved the accuracy of RVIP performance and both the drink with the higher level of caffeine in first study and the active drink in the second study result ed in lower ratings of mental fatigue . These results indicate that a combination of caffeine and glucose can ameliorate deficits in cognitive performance and subjective fatigue during extended periods of cognitive dem and Objective : To evaluate the cognitive effects of topiramate ( TPM ) and gabapentin ( GBP ) . Methods : Forty healthy volunteers were r and omized to a 12-week course of TPM , GBP , or placebo . Doses were gradually escalated over 10 weeks to a maximum of 400 mg/day of TPM or 3,600 mg/day of GBP or to the highest tolerated dose . Subjects were interviewed and examined biweekly . Cognitive testing was performed prior to initiating the drug and again 12 weeks later , at least 2 weeks after achieving plateau dosing . For each subject and cognitive measure , test – retest Z scores were calculated based on regression equations derived from 73 healthy volunteers . Group comparisons utilized the Wilcoxon test . Results : There were significant TPM vs GBP and TPM vs placebo differences in test – retest Z scores for four of six target cognitive measures ( Digit Symbol , Story Recall , Selective Reminding , Controlled Oral Word Association ) , always indicating worse retest performance for subjects receiving TPM . Overall , 12 of 24 cognitive measures were similarly affected . TPM effects were large , and several target measures averaged > 2 SD of negative change . One measure was significantly affected by GBP . Conclusions : Topiramate ( TPM ) impaired cognitive test performance , whereas gabapentin had minimal effects . The effects of TPM were of sufficient magnitude potentially to affect daily and occupational function BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline . Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias Eighteen subjects consumed low-fat/high-carbohydrate ( LFHC ) ( 29 % fat , 54 % carbohydrate , 15 % protein ) , medium-fat/medium-carbohydrate ( MFMC ) ( 45 % fat , 42 % carbohydrate , 12 % protein ) , and high-fat/low-carbohydrate ( HFLC ) ( 62 % fat , 24 % carbohydrate , 13 % protein ) isocaloric lunches in r and om order on 3 separate days . The MFMC lunch was similar in energy and macronutrient composition to the habitual lunchtime intake of the subjects . A battery of cognitive performance tasks together with mood and appetite ratings were carried out before and during the 3 h after lunch . Results showed longer reaction times following the LFHC and HFLC lunches compared to the MFMC lunch , which produced an improvement in performance on this task . In addition , subjects rated themselves as more drowsy , uncertain and muddled , and less cheerful after the LFHC and HFLC lunches compared to the MFMC lunch , and as less tense after the LFHC meal . These findings indicate that the macronutrient content of lunch can have significant acute effects on subsequent mood and performance . In particular , higher than usual proportions of fat or carbohydrate produced a relative impairment of cognitive efficiency 1 . Glycosaminoglycan polysulfate is a mixture of sulfo-muco-polysaccharides with hypolipidemic activity . A number of clinical studies have indicated that it is effective in improving psychopathology in patients with cardiac and /or cerebral disease associated with arteriosclerosis . 2 . A multicenter clinical trial was performed to compare the effects of two different dosages of glycosaminoglycan polysulfate upon depressive symptomatology in patients with multi-infa rct dementia and primary degenerative dementia . 3 . A total of 39 patients were treated in an 18-week clinical trial which followed a single-blind parallel design . 4 . Results indicated that patients with both diagnoses improved significantly in depressive symptomatology over the course of treatment , with particular improvement noted in cognitive disturbance . Drug dosage was not a significant determinant of treatment response for either diagnostic group OBJECTIVE To evaluate associations of cognitive impairment and disease burden with disability in an elderly population . METHODS The Mini-Cog was used as a cognitive screen in a population -based survey of health and functional status of 2,192 r and omly selected older adults ( age 65 + years ) in 11 regions of Italy . Associations of cognitive and disease measures with functional outcomes were calculated using hierarchical logistic regressions including age , Mini-Cog score , disease burden , age , education , and geographic region . Statistical significance was assigned at p < 0.01 . RESULTS Mini-Cog scores were related to all functional indicators ( activities of daily living [ ADLs ] , social activities , exercise , telephone and face-to-face conversation , urinary control , and ability to read the newspaper ) as well as stroke , falls , and dementia diagnoses . In univariate analyses , low education was associated with Mini-Cog scores , disease burden , and disability . However , in logistic regressions , Mini-Cog score and disease burden , but not education , remained significant predictors of all basic ADLs and most higher-order functions . Functional disability was best predicted by a Mini-Cog cutoff score of 1 out of 5 . Overall , although both are significant , the impact of cognitive impairment on basic ADL impairment was over four times greater than that of disease burden ( accounting for 14 % versus 3 % of variance ) . CONCLUSION Cognitive impairment assessed by the Mini-Cog is a more powerful predictor of impaired ADLs than disease burden in older adults . The association of education with Mini-Cog score did not bias its ability to predict functional status . Results suggest that the Mini-Cog could be useful in assessing older population assistance needs OBJECTIVE To investigate the association of midlife dietary fat intake to cognitive performance , and to the occurrence of clinical mild cognitive impairment ( MCI ) later in life in a non-demented population . DESIGN A longitudinal population -based study . SETTING Population s of Kuopio and Joensuu , Eastern Finl and . PARTICIPANTS AND METHODS Participants of the CAIDE study were derived from r and om , population -based sample s studied at midlife ( 1972 , 1977 , 1982 or 1987 ) . After an average follow-up of 21 years , a total of 1449 ( 72 % ) individuals aged 65 - 80 years participated in the re-examination in 1998 . Altogether 82 ( 5.7 % ) people were diagnosed as having MCI . Dietary information was collected with a structured question naire and an interview at midlife . MAIN OUTCOME MEASURES MCI , global cognitive and executive functions , episodic , semantic and prospect i ve memory and psychomotor speed . RESULTS Abundant saturated fat ( SFA ) intake from milk products and spreads at midlife was associated with poorer global cognitive function and prospect i ve memory and with an increased risk of MCI ( OR 2.36 , 95 % CI 1.17 - 4.74 ) after adjusting for demographic and vascular factors , other fats and ApoE. On the contrary , high intake of polyunsaturated fatty acids ( PUFA ) was associated with better semantic memory . Also frequent fish consumption was associated with better global cognitive function and semantic memory . Further , higher PUFA-SFA ratio was associated with better psychomotor speed and executive function . CONCLUSIONS Our data suggests that dietary fat intake at midlife affects cognitive performance and occurrence of MCI later in life . The impact of dietary interventions needs to be tested in clinical trials |
1,098 | 21,343,903 | 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 . | Objective : Obesity is related to increased risk of several health complications , including depression .
Many studies have reported improvements in mood with weight loss , but results have been equivocal .
The present meta- analysis examined changes in symptoms of depression that were reported in trials of weight loss interventions .
Between-groups comparisons of different weight loss methods ( for example , lifestyle modification , diet-alone and pharmacotherapy ) were examined , as were within-group changes for each treatment type . | 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 of the psychological responses of diabetic subjects to these diets . Research Design and Methods This study examined changes in hunger , depression , and anxiety in 33 obese type II diabetic subjects who were r and omly assigned to behavior modification programs that used either a balanced diet of 4185–6277 J∕day ( 1000–1500 cal∕day ) throughout or included an 8-wk period of a very-low-calorie diet ( 1674 J∕day or 400 cal∕day of lean meat , fish , or fowl ) . Subjects completed the Beck Depression Inventory , the Spielberger State Anxiety Question naire , and self-report measures of hunger frequently throughout the 20-wk program . Results Both groups experienced significant improvements in depressive symptomatology , anxiety , and lessening of hunger during the course of the program , with no significant differences observed between the balanced diet and the very-low-calorie diet groups . Conclusions Very-low-calorie diets , used in the context of a behavioral weight-control program , result in reductions in hunger and improvements in mood state comparable to those observed on more moderate weight-loss regimens OBJECTIVE : To evaluate a modified cognitive – behavioural treatment ( M-CBT ) for weight management which addresses both the psychosocial costs and the physiological health risks of obesity , without a focus on weight loss . DESIGN : R and omized controlled trial comparing M-CBT with st and ard cognitive – behavioural therapy (S-CBT).SUBJECTS : Sixty-three overweight women with body mass index ( BMI ) ≥28 kg/m2 , mean age=47.5 and mean BMI = 35.4 . MEASURES : Weight , waist and hip circumference , blood lipids , blood glucose , blood pressure , psychological well-being , depression , self esteem , stress , binge eating , eating style , body image , nutrient intake , aerobic fitness , activity levels , patient satisfaction with treatment . RESULTS : Both M-CBT and S-CBT achieved improvements in a broad range of physical , psychological and behavioural variables . Weight loss in the S-CBT group was greater than in the M-CBT group immediately after treatment , but both groups lost weight . Participants in the M-CBT group continued to lose weight up to the 1 y follow-up . M-CBT was evaluated positively by participants . CONCLUSIONS : Both M-CBT and S-CBT programmes were successful at inducing modest weight loss , as well as improving emotional well-being , reducing distress , increasing activity and fitness , improving dietary quality and reducing cardio-vascular disease risk factors . The improvements were maintained or continued at 1 y follow-up . These results suggest that treatment based on the new weight-control paradigm which emphasizes sustained lifestyle change without emphasis on dieting , can produce modest benefits to health and well-being OBJECTIVE This study tested a secondary hypothesis of the CALERIE trial ( Heilbronn et al. , 2006 ) that a 12-month period of intentional dietary restriction would be associated with an increase in eating disorder symptoms . DESIGN To test this hypothesis , 48 overweight adults were r and omly assigned to four treatment arms in a 12-month study : ( 1 ) 25 % calorie restriction , ( 2 ) 12.5 % calorie restriction and 12.5 % increased energy expenditure by structured exercise , ( 3 ) low-calorie diet , and ( 4 ) healthy diet ( no-calorie restriction ) . MAIN OUTCOME MEASURES Primary outcome measures for the study were changes in : eating disorder symptoms , mood , dietary restraint , body weight , and energy balance . RESULTS All three dietary restriction arms were associated with increased dietary restraint and negative energy balance , but not with increased ED symptoms or other harmful psychological effects . Participants in the three calorie restriction arms lost significant amounts of body weight . The psychological and behavioral effects were maintained during a 6-month follow-up period . CONCLUSION These results did not support the hypothesis that caloric restriction causes increased eating disorder symptoms in overweight adults . In general , caloric restriction had either benign or beneficial psychological and behavioral effects Phone and Internet-based interventions can improve the management of depression in primary care , and interventions using these communication channels are increasingly used to improve behaviors such as diet and physical activity . Increased physical activity has been shown to improve depressive symptoms , but to date there are no reports of the effects of a phone and Internet diet and exercise intervention on symptoms of depression in patients seen in primary care . This study assessed depressive symptoms in 401 participants in a r and omized control trial of a 12-month primary care , phone and Internet-based behavioral intervention for overweight women . A one-way analysis of variance examining the mean change in Center for Epidemiological Studies Depression ( CESD ) score from baseline to 12 months , controlling for age , education , marital status , and employment showed that those receiving the intervention significantly decreased their CESD scores ( P=.03 ) more than those receiving st and ard care . Although the intervention did not target depressed individuals or present material relating to mood management , those with probable depression ( 27 % of the whole sample ) showed clinical ly important improvements-a mean five-point change on the CESD short form . Participants who engaged more readily with the intervention were more likely to reduce their depression scores . A 1-year primary care based phone and Internet diet and exercise intervention can improve depressive symptoms in overweight women . Given the promise of phone and Internet-based interventions to improve both depression and lifestyle-related behaviors , and given that such interventions could extend the reach of primary care to many individuals at relatively low cost , these results suggest the need for further research , including the effects of additional mood management components OBJECTIVE —The effectiveness of intentional weight loss in reducing cardiovascular disease ( CVD ) events in type 2 diabetes is unknown . This report describes 1-year changes in CVD risk factors in a trial design ed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events . RESEARCH DESIGN AND METHODS —This study consisted of a multicentered , r and omized , controlled trial of 5,145 individuals with type 2 diabetes , aged 45–74 years , with BMI > 25 kg/m2 ( > 27 kg/m2 if taking insulin ) . An intensive lifestyle intervention ( ILI ) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education ( DSE ) condition . RESULTS — Participants assigned to ILI lost an average 8.6 % of their initial weight vs. 0.7 % in DSE group ( P < 0.001 ) . Mean fitness increased in ILI by 20.9 vs. 5.8 % in DSE ( P < 0.001 ) . A greater proportion of ILI participants had reductions in diabetes , hypertension , and lipid-lowering medicines . Mean A1C dropped from 7.3 to 6.6 % in ILI ( P < 0.001 ) vs. from 7.3 to 7.2 % in DSE . Systolic and diastolic pressure , triglycerides , HDL cholesterol , and urine albumin-to-creatinine ratio improved significantly more in ILI than DSE participants ( all P < 0.01 ) . CONCLUSIONS —At 1 year , ILI result ed in clinical ly significant weight loss in people with type 2 diabetes . This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE . Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk Background The literature on changes in health-related quality of life ( HRQOL ) in weight loss studies is inconsistent , and few studies use more than one type of measure . The purpose of the current study was to compare one-year changes in HRQOL as a function of weight change using three different measures : a weight-related measure ( Impact of Weight on Quality of Life-Lite [ IWQOL-Lite ) ] ) and two generic measures ( SF-36 ; EQ-5D ) . Methods Data were obtained from 926 participants ( mean Body Mass Index ( BMI ) ( kg/m2 ) = 35.4 ; 84 % female ; mean age = 49.5 years ) in a placebo-controlled r and omized trial for weight loss . At baseline and one-year , participants completed all three HRQOL measures . HRQOL was compared across weight change categories ( ≥ 5 % and 0–4.9 % gain , 0–4.9 % , 5.0–9.9 % and ≥ 10 % loss ) , using effect sizes . Results The weight-related measure of HRQOL exhibited greater improvements with one-year weight loss than either of the generic instruments , with effect sizes ranging from 0.24 to 0.62 for 5–9.9 % weight reductions and 0.44 to 0.95 for ≥ 10 % reductions . IWQOL-Lite Self-Esteem also showed a small improvement with weight gain . Changes in the two generic measures of HRQOL were inconsistent with each other , and in the case of the SF-36 , variable across domains . For participants gaining ≥ 5 % of weight , the greatest reductions in HRQOL occurred with respect to SF-36 Mental Health , MCS , and Vitality , with effect sizes of -0.82 , -0.70 , and -0.63 respectively . Conclusion This study found differences between weight-related and generic measures of health-related quality of life in a one-year weight loss trial , reflecting the potential value of using more than one measure in a trial . Although weight loss was generally associated with improved IWQOL-Lite , physical SF-36 subscale and EQ-5D scores , a small amount of weight gain was associated with a slight improvement on weight-specific HRQOL and almost no change on the EQ-5D , suggesting the need for further research to more fully study these relationships . We believe our findings have relevance for weight loss patients and obesity clinicians/ research ers in informing them of likely HRQOL outcomes associated with varying amounts of weight loss or gain PURPOSE Epidemiological studies have suggested that cholesterol lowering could affect psychological functioning . This study was design ed to test whether cholesterol-lowering diets adversely affect mood and cognitive function.5.2 mM [ 198 mg/dL ] ) to either a low-fat diet , a Mediterranean diet , or a waiting-list control . Cholesterol levels , psychological well-being ( depression , anxiety , hostility ) , and cognitive function were assessed at baseline , 6 weeks , and 12 weeks . RESULTS Total serum cholesterol levels fell significantly more in the intervention groups ( 8.2 % reduction ) than in the control group ( P < 0.001 ) . All three groups showed a modest improvement in psychological well-being during the 12-week treatment period , but there were no differences among the groups . There were no between-group differences on three measures of cognitive function , but for a fourth measure , which involved the task with the greatest processing load , the two intervention groups did significantly worse ( P < 0.001 ) than the control group . The change in performance was correlated with the change in total serum cholesterol level ( r = 0 . 21 , P = 0.01 ) . CONCLUSIONS Two dietary interventions that successfully lowered serum cholesterol levels had no adverse effect on mood . There was some evidence for a relative impairment in cognitive function in the treated groups in one of four cognitive tests , but additional studies will be required to determine the relevance of this finding Because little is known about risk factors for obesity , the authors tested whether certain psychological and behavioral variables predicted future onset of obesity . The authors used data from a prospect i ve study of 496 adolescent girls who completed a baseline assessment at age 11 - 15 years and 4 annual follow-ups . Self-reported dietary restraint , radical weight-control behaviors , depressive symptoms , and perceived parental obesity -- but not high-fat food consumption , binge eating , or exercise frequency-predicted obesity onset . Results provide support for certain etiologic theories of obesity , including the affect regulation model . The fact that self-reported , weight-control behaviors identified girls at risk for obesity implies that high-risk youths are not engaging in effective weight-control methods and suggests the need to promote more effective strategies OBJECTIVE To study the impact of a weight-loss program on sex hormones and sexual function among 38 middle-aged obese men ( BMI > or=35 kg/m(2 ) ) . RESEARCH METHODS AND PROCEDURES A r and omized controlled clinical trial was conducted . The treatment group ( n = 19 ) participated in a 4-month weight-loss program including 10 weeks on a very-low-energy diet ( VLED ) and 17 behavior modification visits . There was no intervention in the control group ( n = 19 ) . Both groups were followed for 8 months , i.e. , 22 weeks after the active weight loss in the treatment group . The outcome measures ( weight , sex hormones , sexual function , leptin , and metabolic variables ) were obtained at baseline and at three time-points during follow-up . RESULTS The mean weight loss in the treatment group was 21 kg at the end of the 10-week VLED . At the end of follow-up , the maintained weight loss was 17 kg of baseline weight . The control group was weight stable throughout the study . In the treatment group , increases in sex hormone-binding globulin , testosterone , and high-density lipoprotein-cholesterol , as well as decreases in insulin and leptin , were maintained until the end of follow-up , although with VLED , the level of several hormones and metabolic variables improved transiently during the rapid weight loss . There were no significant changes in the question naire scores on sexual function in either group . DISCUSSION We conclude that obese men lose weight and increase their serum testosterone level on a weight-loss program with VLED and behavior modification . However , they do not change their sexual function scores OBJECTIVE The specific aim was to determine whether a multifaceted approach to weight loss and physical readiness could be implemented onboard a deployed combatant ship of the U.S. Navy . RESEARCH METHODS AND PROCEDURES Thirty-nine men ( 31+/-6 years old , mean+/-st and ard deviation ) assigned to the USS ENTERPRISE ( CVN 65 ) during a 6-month Mediterranean deployment who had failed their previous Physical Readiness Test due to excessive body weight ( 108+/-11 kg overweight ) were r and omly assigned to nutrition , cognitive-behavioral obesity treatment plus exercise or to the Navy 's usual treatment ( control ) , which is exercise alone . RESULTS Outcomes for the treatment group were significantly better than the controls , with 8.6+/-5.0 vs. 5.0+/-4.1 kg weight loss , 8 % vs. 5 % reduction in original body weight , and body fat loss of 7 % vs. 5 % . Triglycerides declined significantly greater in the treatment group than the controls ( 145 mg/dL to 109 mg/dL vs. 146 mg/dL to 145 mg/dL , p<0.05 ) , whereas depression and eating behaviors significantly improved among treated men . Problematic environmental factors were the limited variety of heart healthy foods in the galley , short meal breaks , and long mess hall lines that led to eating snacks from vending machines and frequent port calls . DISCUSSION Although greater weight loss than would be expected of a Navy usual care group diluted the treatment effect , the treated men still fared significantly better . The physical readiness implication of this research has the potential to impact Navy health promotion programs and policy , the health and well-being of its personnel , and the Navy 's ability to meet mission requirements OBJECTIVE This study examined the psychological consequences of a modest weight loss in a sample of healthy women aged 44 to 50 . METHOD Five hundred and thirty-five women , with body mass indices ( BMI s ) ranging from 20 to 34 , were r and omly assigned either to an intensive behavioral lifestyle intervention or to a no-treatment control group . Women in the lifestyle intervention received weight loss goals of 5 to 15 lb , depending on baseline BMI , and attended 20 weekly group meetings during which they received information on lowering dietary fat intake and increasing physical activity levels . Psychological measures administered at baseline and at a 6-month examination assessed perceived stress , mood , dietary restraint , and binge eating behaviors . RESULTS Intervention subjects showed significant decreases in depressive symptoms over time , relative to control subjects , and this effect was observed for normal-weight , as well as heavier , subjects . Binge eating scores for all subjects declined significantly over time , with heavier subjects in the intervention showing the greatest decrease in scores . DISCUSSION The current study found no evidence of negative psychological sequelae of participation in a behavioral lifestyle change program , regardless of weight status . Results further suggest that participation in these types of programs may exert a positive influence on the psychological status of both normal-weight and heavier women Twenty-four obese women were r and omly assigned to 1 of 2 group treatments : behavioral choice treatment ( BCT ) or traditional behavioral treatment ( TBT ) . BCT uses decision theory to promote moderate behavior change that can be comfortably , and therefore permanently , maintained . Groups completed a moderate-intensity walking program and obtained feedback from computerized eating dairies . The TBT group evidence d greater weight loss at posttreatment . However , the TBT group also evidence d a trend to regain weight , whereas the BCT group continued a slow weight loss during follow-up . Exercise followed a similar pattern . Both groups decreased in restraint and increased in self-esteem Exercise is an important behavior for long-term weight control in overweight and obese patients . However , little evidence exists confirming such findings in patients with advanced heart failure ( HF ) . Using a prospect i ve , experimental design , the effects of 24 weeks of a low-level , home-based walking program on weight loss were studied in overweight and obese ( body mass index > or = 27 kg/m(2 ) ) patients with advanced HF who were r and omized to exercise ( n = 48 ) and control ( n = 51 ) groups . Weight changes between the 2 groups at baseline and 6 months were compared using repeated- measures analysis of variance . Patients were on average aged 53.3 + /- 10.1 years and predominantly male ( 75 % ) , Caucasian ( 57 % ) , and married ( 55 % ) . Most patients were in New York Heart Association class III or IV ( 67 % ) , with a mean ejection fraction of 25 % . Patients in the exercise group showed significant weight reduction from baseline to 6 months compared with those in the control group ( -6.37 + /- 11.7 vs -0.33 + /- 9.3 kg , p = 0.002 ) . No significant differences were noted between the 2 groups in 6-minute walk distance or depression , although the changes were in the anticipated direction . Modest weight losses of > 5 % were associated with cardiopulmonary exercise test-documented workload levels at 6 months ( r = 0.331 , p = 0.006 ) , as well as decreased depression ( r = -0.315 , p = 0.01 ) and hostility ( r = -0.355 , p = 0.005 ) . The number of hospital admissions was significantly smaller for patients in the exercise group compared with those in the control group ( 0.63 + /- 0.94 vs 1.07 + /- 0.95 , p < 0.05 ) . In conclusion , the findings demonstrate the beneficial effects of a low-level , home-based walking program on weight loss in overweight and obese patients with advanced HF BACKGROUND Adolescent obesity is a strong predictor of adult obesity , and adult obesity has been associated with depression , especially in women . Studies have also suggested an association between depression in adolescence and higher body mass index ( BMI ) in adulthood . Whether depression leads to obesity or obesity causes depression is unclear . OBJECTIVE To determine in longitudinal analyses whether depressed mood predicts the development and persistence of obesity in adolescents . METHODS A prospect i ve cohort study of 9374 adolescents in grade s 7 through 12 who completed in-home interviews for the National Longitudinal Study of Adolescent Health . Assessment s were made at baseline ( 1995 ) and at follow-up 1 year later . Depressed mood was assessed with the Center for Epidemiologic Studies Depression Scale . BMI ( kg/m2 ) was calculated from self-reported height and weight . BMI percentiles and z scores were computed using the 2000 Centers for Disease Control and Prevention growth charts . Obesity was defined as BMI > or = 95th percentile , overweight as BMI > or = 85th percentile and < 95th percentile , and normal weight as BMI < 85th percentile . A parental respondent gave information on household income , parental education , and parental obesity . RESULTS At baseline , 12.9 % were overweight , 9.7 % were obese , and 8.8 % had depressed mood . Baseline depression was not significantly correlated with baseline obesity . Among the 9.7 % who were obese at follow-up , 79.6 % were obese at baseline , 18.6 % were overweight at baseline , and 1.8 % were normal weight at baseline . Having depressed mood at baseline independently predicted obesity at follow-up ( odds ratio : 2.05 ; 95 % confidence interval : 1.18 , 3.56 ) after controlling for BMI z score at baseline , age , race , gender , parental obesity , number of parents in the home , and family socioeconomic status . This finding persisted after controlling further for the adolescents ' report of smoking , self-esteem , delinquent behavior ( conduct disorder ) , and physical activity . After controlling for all these same factors , depressed mood at baseline also predicted obesity at follow-up among those not obese at baseline ( odds ratio : 2.05 ; 95 % confidence interval : 1.04 , 4.06 ) and follow-up BMI z score among those obese at baseline ( beta = 0.11 ; st and ard error beta = 0.05 ) . In contrast , baseline obesity did not predict follow-up depression . CONCLUSIONS Depressed adolescents are at increased risk for the development and persistence of obesity during adolescence . Underst and ing the shared biological and social determinants linking depressed mood and obesity may inform the prevention and treatment of both disorders Recent studies of rimonabant have re-awakened interest in the possible adverse psychiatric effects of weight loss , as well as of weight loss medications . This study examined changes in symptoms of depression in 194 obese participants ( age = 43.7 + /- 10.2 years ; BMI = 37.6 + /- 4.1 kg/m(2 ) ) in a 1-year r and omized trial of lifestyle modification and medication . Participants were assigned to ( i ) sibutramine alone ; ( ii ) lifestyle modification alone ; ( iii ) sibutramine plus lifestyle modification ( i.e. , combined therapy ) ; or ( iv ) sibutramine plus brief therapy . Participants completed the Beck Depression Inventory-II ( BDI-II ) at baseline and weeks 6 , 10 , 18 , 26 , 40 , and 52 . At 1 year , participants in combined therapy lost the most weight and those in sibutramine alone the least ( 12.1 + /- 8.8 % vs. 5.5 + /- 6.5 % ; P < 0.01 ) . Mean BDI-II scores across all participants declined from 8.1 + /- 6.9 to 6.2 + /- 7.7 at 1 year ( P < 0.001 ) , with no significant differences among groups . Despite this favorable change , 13.9 % of participants ( across the four groups ) reported potentially discernible increases ( > or= 5 points on the BDI-II ) in symptoms of depression at week 52 . They lost significantly less weight than participants in the rest of the sample ( 5.4 + /- 7.8 % vs. 9.0 + /- 7.8 % , respectively ; P < 0.03 ) . The baseline prevalence of suicidal ideation was 3.6 % . Seven new cases of suicidal ideation were observed during the year , with three in lifestyle modification alone . Further research is needed to identify characteristics of obese patients at risk of negative mood changes ( and suicidal ideation ) in response to behavioral and pharmacologic therapies Acupuncture has been anecdotally reported to induce weight loss in obese patients . This pilot study examines its efficacy in a r and omised , placebo-controlled clinical trial . Forty ( 33 F , 7 M ) obese ( BMI > 30 kg/m2 ) out patients were r and omised to either placebo or acupuncture ( 12 weekly sessions of minimal acupuncture and somatic moxibustion-acupuncture associated with auriculopuncture respectively ) . BMI , eating attitudes ( BES ) , anxiety ( STAI ) , depression ( BDI ) , and obesity-related quality of life ( ORWELL 97 ) were measured at the beginning and end of the treatment . Six ( 30 % ) patients in the treatment group and 12 ( 60 % ) in the placebo group dropped out . Intention-to-treat analysis did not show any significant effect of acupuncture on BMI and obesity-related quality of life ; eating attitudes improved in both groups , possibly because of the placebo effect . A significant improvement in anxiety and depression was only observed in the acupuncture group . In conclusion , acupuncture does not promote weight loss and is not recommendable in the treatment of obesity . It may , however , improve the psychological status of obese patients BACKGROUND Rimonabant , a selective cannabinoid type 1 receptor blocker , reduces bodyweight and improves cardiovascular and metabolic risk factors in non-diabetic overweight or obese patients . The aim of the RIO-Diabetes trial was to assess the efficacy and safety of rimonabant in overweight or obese patients with type 2 diabetes that was inadequately controlled by metformin or sulphonylureas . METHODS 1047 overweight or obese type 2 diabetes patients ( body-mass index 27 - 40 kg/m2 ) with a haemoglobin A1c ( HbA1c ) concentration of 6.5 - 10.0 % ( mean 7.3 % [ SD 0.9 ] at baseline ) already on metformin or sulphonylurea monotherapy were given a mild hypocaloric diet and advice for increased physical activity , and r and omly assigned placebo ( n=348 ) , 5 mg/day rimonabant ( 360 ) or 20 mg/day rimonabant ( 339 ) for 1 year . Two individuals in the 5 mg/day group did not receive double-blind treatment and were thus not included in the final analysis . The primary endpoint was weight change from baseline after 1 year of treatment . Analyses were done on an intention-to-treat basis . This trial is registered at Clinical Trials.gov , number NCT00029848 . FINDINGS 692 patients completed the 1 year follow-up ; numbers in each group after 1 year were much the same . Weight loss was significantly greater after 1 year in both rimonabant groups than in the placebo group ( placebo : -1.4 kg [ SD 3.6 ] ; 5 mg/day : -2.3 kg [ 4.2 ] , p=0.01 vs placebo ; 20 mg/day : -5.3 kg [ 5.2 ] , p<0.0001 vs placebo ) . Rimonabant was generally well tolerated . The incidence of adverse events that led to discontinuation was slightly greater in the 20 mg/day rimonabant group , mainly due to depressed mood disorders , nausea , and dizziness . INTERPRETATION These data indicate that 20 mg/day rimonabant , in combination with diet and exercise , can produce a clinical ly meaningful reduction in bodyweight and improve HbA1c and a number of cardiovascular and metabolic risk factors in overweight or obese patients with type 2 diabetes inadequately controlled by metformin or sulphonylureas BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin OBJECTIVE We compared health outcomes in obese adults who underwent 12 wk of exercise counseling with or without dietary counseling , followed by 12 wk of observational monitoring . METHODS Ninety adults ( 77 women and 13 men ; 42.6 + /- 6.0 y ; body mass index , 31.5 + /- 2.8 kg/m(2 ) ) were r and omly assigned to exercise-only ( EX ) or diet-plus-exercise ( DEX ) groups and counseled weekly by exercise physiologists on a 12-wk walking program . DEX subjects were also counseled by dietitians on a hypocaloric diet ( -500 kcal/d ) . From weeks 12 to 24 , subjects were monitored but not counseled . At weeks 0 , 12 , and 24 , data collection included body composition ( air displacement plethysmography ) , fitness ( maximum oxygen consumption , 3-min step-test , and timed mile ) , plasma lipids , weight loss efficacy ( Weight Efficacy Life-Style Question naire ) , quality of life ( Medical Outcomes Study Health Survey-Short Form 36 ) , and mood ( Profile of Mood States ) . RESULTS At 12 and 24 wk , weight and body mass index decreased in DEX subjects ( both P < 0.05 ) but not in EX subjects . However , lean body mass increased significantly in EX ( 24 wk , P < 0.05 ) but not in DEX subjects . In both groups , fat mass decreased ( P < 0.05 for EX subjects at 24 wk ; P < 0.05 for DEX subjects at 12 and 24 wk ) and waist circumference decreased ( P < 0.05 for EX subjects at 12 and 24 wk ; P < 0.05 for DEX subjects at 12 and 24 wk ) . At 12 and 24 wk , DEX subjects showed decreased levels of total plasma cholesterol and triacylglycerols ( both P < 0.05 ) and improvements with regard to the Weight Efficacy Life-Style Question naire ( P < 0.05 ) , three domains of the Medical Outcomes Study Health Survey-Short Form 36 ( all P < 0.05 ) , and three domains of the Profile of Mood States ( all P < 0.05 ) that were not seen in EX subjects . CONCLUSIONS Exercise counseling for 12 wk in obese adults improves some body composition indices that can be sustained over 12 wk of monitoring . The addition of dietary counseling increases improvements in body composition , lipid profiles , and several psychological parameters Changes in weight , thyroid hormones and mood were examined in 15 obese ( 113 kg ) women over an 18-week period . After 4 weeks of a 1200 kcal/day diet , patients were r and omly assigned to one of two dietary conditions : very low calorie diet ( VLCD ) ( n = 8) or balanced deficit diet ( BDD ) ( n = 7 ) . VLCD patients consumed 400 kcal/day for 8 weeks and then gradually returned to a 1200 kcal/day diet . BDD patients consumed 1200 kcal/day for the entire 18 weeks . Differences in weight losses between the conditions were statistically significant only during the consumption of the VLCD . Serum T3 decreased by as much as 66 percent in VLCD patients during consumption of the 400 kcal/day diet , whereas rT3 increased by as much as 27 percent . T3 increased when patients were realimented with a 1000 kcal/day balanced diet but remained a significant 22 percent below baseline at the end of the study . BDD patients also showed marked reductions in T3 , as great as 40 percent , so that the differences between the two conditions were not statistically significant . Multiple regression analyses , collapsing across conditions ( n = 15 ) , indicated that weight loss at week 12 and baseline T3 accounted for 63 percent of the variance in the change in T3 at week 12 . Patients in both conditions showed improvements in mood . Changes in depression were not associated with changes in serum T3 OBJECTIVE The effect of 12 weeks of exercise training ( five 45-minute walking sessions/week at 60 % to 75 % maximum heart rate ) and /or moderate energy restriction ( 4.19 to 5.44 MJ or 1200 to 1300 kcal/day ) on psychological general well-being ( GWB ) and profile of mood states ( POMS ) was studied in obese women ( n = 91 , age 45.6 + /- 1.1 years , body mass index 33.1 + /- 0.6 kg/m2 ) . METHODS Subjects were r and omized to one of four groups : control ( C ) ; exercise ( E ) ; diet ( D ) ; and exercise and diet ( ED ) . Psychological variables were measured in all subjects at three timepoints -- pre study , 3 weeks , and post study -- and analyzed using a 4 x 3 repeated measures design . RESULTS GWB but not POMS was improved in ED ( but not E or D ) relative to C post study , especially in four of six subscales : freedom from health concern or worry , life satisfaction ; cheerful versus depressed mood ; and relaxed versus tense feelings . CONCLUSION These data demonstrate that the combination of moderate energy restriction and exercise training during a 12-week period improves psychological general well-being scores but not mood states in obese subjects Objective To test the effectiveness of three commercially available partial meal replacement products on weight-loss outcomes . Methods In a r and omized controlled clinical trial , 164 eligible overweight and obese adults ( ages 18–65 years ; body mass index ≥25 kg/m2 ) were r and omly assigned to a Control group ( CN ) or to one of three intervention groups , including ‘ Cereal Substitution plus Nutrient Bar ’ ( CB ) , ‘ Cereal and Waffle Substitution plus Nutrient Bar ’ ( CWB ) , and ‘ Cereal Substitution , no Nutrient Bar ’ ( CR ) . Results Compared with the CN group , the CB , CWB , and CR groups evidence d significantly greater reductions in weight , body mass index , waist , hip , and thigh measurements , and the CB and CR groups evidence d significantly greater reductions in percentage body fat . Despite strong adherence ( 88 % ) and retention ( 80 % ) , the groups did not differ in cardiovascular risk profile , mood , or satiety . Conclusions A variety of ready-to-eat cereal products may be safely and effectively used as meal replacements in weight-loss programs CONTEXT Physical inactivity contributes to weight gain , but only 22 % of Americans are regularly active . OBJECTIVE To examine short- and long-term changes in weight , body composition , and cardiovascular risk profiles produced by diet combined with either structured aerobic exercise or moderate-intensity lifestyle activity . DESIGN Sixteen-week r and omized controlled trial with 1-year follow-up , conducted from August 1995 to December 1996 . PARTICIPANTS AND SETTING Forty obese women ( mean body mass index [ weight in kilograms divided by the square of height in meters ] , 32.9 kg/m2 ; mean weight , 89.2 kg ) with a mean age of 42.9 years ( range , 21 - 60 years ) seen in a university-based weight management program . INTERVENTIONS Structured aerobic exercise or moderate lifestyle activity ; low-fat diet of about 1200 kcal/d . MAIN OUTCOME MEASURES Changes in body weight , body composition , cardiovascular risk profiles , and physical fitness at 16 weeks and at 1 year . RESULTS Mean ( SD ) weight losses during the 16-week treatment program were 8.3 ( 3.8 ) kg for the aerobic group and 7.9 ( 4.2 ) kg for the lifestyle group ( within groups , P<.001 ; between groups , P = .08 ) . The aerobic group lost significantly less fat-free mass ( 0.5 [ 1.3 ] kg ) than the lifestyle group ( 1.4 [ 1.3 ] kg ; P = .03 ) . During the 1-year follow-up , the aerobic group regained 1.6 [ 5.5 ] kg , while the lifestyle group regained 0.08 ( 4.6 ) kg . At week 16 , serum triglyceride levels and total cholesterol levels were reduced significantly ( P<.001 ) from baseline ( 16.3 % and 10.1 % reductions , respectively ) but did not differ significantly between groups and were not different from baseline or between groups at week 68 . CONCLUSIONS A program of diet plus lifestyle activity may offer similar health benefits and be a suitable alternative to diet plus structured aerobic activity for obese women This study examined the effects of matching participants to treatments on the basis of their preferences for either individual or group therapy for obesity . Seventy-five obese adults who expressed a clear preference for either individual or group therapy were r and omly assigned to either their preferred or their nonpreferred treatment modality within a 2 ( individual vs. group therapy ) x 2 ( preferred vs. nonpreferred modality ) factorial design . At posttreatment , group therapy produced significantly greater reductions in weight and body mass than individual therapy , and no significant effects were observed for treatment preference or the interaction for treatment preference by type of therapy . All treatment conditions showed equivalent improvements in psychological functioning . These findings suggest that group therapy produces greater weight loss than individual therapy , even among those clients who express a preference for individual treatment The aim was to study the effect of placebo EA , electroacupuncture ( EA ) , and diet on obesity and accompanying psychological symptoms . One hundred and sixty-five volunteer women participated in the study . There were three groups : ( i ) Placebo EA , ( ii ) EA , and ( iii ) diet restriction group . EA was performed by using three ear and six body points . There was a 4.8 % reduction in weight of patients with EA application , whereas patients with a diet restriction and placebo EA had a 2.5 % and 2.7 % weight reduction , respectively . There were significant decreases in phobia , anger , anxiety , obsession , paranoid symptoms , and depression in the EA groups compared to those of the placebo EA and diet groups . It was suggested that electroacupuncture may be an effective therapy for obesity including the psychological signs and symptoms in women OBJECTIVE Adding exercise to a comprehensive weight-loss program might not only attenuate any psychological distress associated with weight-loss attempts but also may provide psychological benefits . This study examined whether a diet-plus-exercise weight-loss program improved psychological outcomes more than a diet-only weight-loss program or an assessment -only control group . RESEARCH METHODS AND PROCEDURES This study was part of a larger 1-year r and omized weight-loss trial examining the effects of diet and exercise on cardiovascular disease risk factors in 264 overweight adults . Psychological measures specific to weight control ( e.g. , cognitive restraint , disinhibition , hunger , and body dissatisfaction ) as well as traditional measures of psychological distress ( e.g. , symptoms of depression , anxiety , and stress ) were obtained at baseline and 1 year . RESULTS Men and women in either weight-loss program reported greater restraint , less disinhibition , and less hunger at 1 year than those in no program . Men in the diet-plus-exercise program experienced additional increases in restraint and decreases in hunger than did men in the diet-only program . Women in the diet-plus-exercise program did not experience additional psychological benefits specific to weight control than those in the diet-only program , despite increases in aerobic capacity . DISCUSSION The pattern seen for overweight men in the diet-plus-exercise program at 1 year-greater restraint , less disinhibition , and less hunger-is similar to the pattern seen in successful weight maintainers . These results underscore the need for innovative strategies that will enhance and sustain the pattern of psychological benefits specific to weight control associated with successful weight loss , especially for overweight women This study compared the psychological effects of a low-protein high-carbohydrate ( LPHC ) diet and a high-protein low-carbohydrate ( HPLC ) diet in women with polycystic ovary syndrome ( PCOS ) . Twenty-five overweight women with PCOS were matched for age , weight , and whether they were trying to conceive . They were r and omly allocated to the LPHC or HPLC diet for 16 weeks . All participants attended a weekly exercise , group support and educational program . The Hospital Anxiety and Depression Scale and the Rosenberg Self Esteem Scale were administered at the beginning and end of the study . The HPLC diet was associated with significant reduction in depression and improvement in self-esteem . There was no change in any psychological measures for the LPHC group . There was no difference in weight loss between the groups . Due to enhanced feelings of well-being , it is possible that HPLC diets may be associated with better compliance and hence be more successful in the long term treatment of obesity OBJECTIVE Morbidly obese individuals are unlikely to reach and maintain normative weights . Thus , interventions aim ed at alleviating corollary problems , independent of attempts at weight loss , are appropriate . A cognitive group treatment program ( CT ) was developed which incorporated a nondieting approach , regular exercise , and use of alternative coping skills . Weight loss per se was not a focus of the intervention . The purpose of the current work was to evaluate this program in a controlled , comparative treatment outcome study . METHOD Sixty-two obese women with a history of treatment failures were r and omly assigned to the CT program , a behavior therapy weight loss program ( BT ) , or a wait-list control group . RESULTS For CT participants , depression , anxiety , and eating-related psychopathology decreased significantly over the course of treatment while perceptions of self-control increased ; BT and control subjects showed no significant changes in these variables . Women in both active treatment groups lost significant amounts of weight , while members of the control group showed a nonsignificant increase in weight . At 6-month follow-up , treatment benefits were maintained . DISCUSSION Findings suggest that interventions not directly aim ed at weight loss can enhance psychological well-being and thus may be appropriate for some obese women |
1,099 | 25,154,506 | 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 . | Background Citalopram and escitalopram , selective serotonin reuptake inhibitors , are primarily metabolized by cytochrome P450 ( CYP ) 2C19 , which is a highly polymorphic enzyme known to cause inter-individual differences in pharmacokinetics .
However , the impact of CYP2C19 polymorphisms on citalopram or escitalopram exposure has yet to be fully clarified , especially with regard to the quantitative impact of the CYP2C19 * 17 allele .
Objective The objective of this study was to quantify the effect of functional CYP2C19 allele variants on citalopram/escitalopram exposure . | 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 sequence*sex*CYP2C19*CYP2D6 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 that the influence of CYP2D6 is more probable in volunteers with at least one defective allele of CYP2C19 |
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