A pragmatic randomised trial of stretching before and after physical activity to prevent injury and soreness

OBJECTIVE: To determine the effects of stretching before and after physical activity on risks of injury and soreness in a community population. DESIGN: Internet-based pragmatic randomised trial conducted between January 2008 and January 2009. SETTING: International. PARTICIPANTS: A total of 2377 adults who regularly participated in physical activity. INTERVENTIONS: Participants in the stretch group were asked to perform 30 s static stretches of seven lower limb and trunk muscle groups before and after physical activity for 12 weeks. Participants in the control group were asked not to stretch. MAIN OUTCOME MEASUREMENTS: Participants provided weekly on-line reports of outcomes over 12 weeks. Primary outcomes were any injury to the lower limb or back, and bothersome soreness of the legs, buttocks or back. Injury to muscles, ligaments and tendons was a secondary outcome. RESULTS: Stretching did not produce clinically important or statistically significant reductions in all-injury risk (HR=0.97, 95% CI 0.84 to 1.13), but did reduce the risk of experiencing bothersome soreness (mean risk of bothersome soreness in a week was 24.6% in the stretch group and 32.3% in the control group; OR=0.69, 95% CI 0.59 to 0.82). Stretching reduced the risk of injuries to muscles, ligaments and tendons (incidence rate of 0.66 injuries per person-year in the stretch group and 0.88 injuries per person-year in the control group; HR=0.75, 95% CI 0.59 to 0.96). CONCLUSION: Stretching before and after physical activity does not appreciably reduce all-injury risk but probably reduces the risk of some injuries, and does reduce the risk of bothersome soreness. TRIAL REGISTRATION: anzctr.org.au 12608000044325

Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression

Background: Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection. Discussion: To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population. Summary: We propose a list of measures to be taken to improve the external validity of double-blind, placebocontrolled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself

Risk of selection bias in randomised trials

Background: Selection bias occurs when recruiters selectively enrol patients into the trial based on what the next treatment allocation is likely to be. This can occur even if appropriate allocation concealment is used if recruiters can guess the next treatment assignment with some degree of accuracy. This typically occurs in unblinded trials when restricted randomisation is implemented to force the number of patients in each arm or within each centre to be the same. Several methods to reduce the risk of selection bias have been suggested; however, it is unclear how often these techniques are used in practice. Methods: We performed a review of published trials which were not blinded to assess whether they utilised methods for reducing the risk of selection bias. We assessed the following techniques: (a) blinding of recruiters; (b) use of simple randomisation; (c) avoidance of stratification by site when restricted randomisation is used; (d) avoidance of permuted blocks if stratification by site is used; and (e) incorporation of prognostic covariates into the randomisation procedure when restricted randomisation is used. We included parallel group, individually randomised phase III trials published in four general medical journals (BMJ, Journal of the American Medical Association, The Lancet, and New England Journal of Medicine) in 2010. Results: We identified 152 eligible trials. Most trials (98%) provided no information on whether recruiters were blind to previous treatment allocations. Only 3% of trials used simple randomisation; 63% used some form of restricted randomisation, and 35% did not state the method of randomisation. Overall, 44% of trials were stratified by site of recruitment; 27% were not, and 29% did not report this information. Most trials that did stratify by site of recruitment used permuted blocks (58%), and only 15% reported using random block sizes. Many trials that used restricted randomisation also included prognostic covariates in the randomisation procedure (56%). Conclusions: The risk of selection bias could not be ascertained for most trials due to poor reporting. Many trials which did provide details on the randomisation procedure were at risk of selection bias due to a poorly chosen randomisation methods. Techniques to reduce the risk of selection bias should be more widely implemented

Design Characteristics Influence Performance of Clinical Prediction Rules in Validation: A Meta-Epidemiological Study

BACKGROUND: Many new clinical prediction rules are derived and validated. But the design and reporting quality of clinical prediction research has been less than optimal. We aimed to assess whether design characteristics of validation studies were associated with the overestimation of clinical prediction rules' performance. We also aimed to evaluate whether validation studies clearly reported important methodological characteristics. METHODS: Electronic databases were searched for systematic reviews of clinical prediction rule studies published between 2006 and 2010. Data were extracted from the eligible validation studies included in the systematic reviews. A meta-analytic meta-epidemiological approach was used to assess the influence of design characteristics on predictive performance. From each validation study, it was assessed whether 7 design and 7 reporting characteristics were properly described. RESULTS: A total of 287 validation studies of clinical prediction rule were collected from 15 systematic reviews (31 meta-analyses). Validation studies using case-control design produced a summary diagnostic odds ratio (DOR) 2.2 times (95% CI: 1.2-4.3) larger than validation studies using cohort design and unclear design. When differential verification was used, the summary DOR was overestimated by twofold (95% CI: 1.2 -3.1) compared to complete, partial and unclear verification. The summary RDOR of validation studies with inadequate sample size was 1.9 (95% CI: 1.2 -3.1) compared to studies with adequate sample size. Study site, reliability, and clinical prediction rule was adequately described in 10.1%, 9.4%, and 7.0% of validation studies respectively. CONCLUSION: Validation studies with design shortcomings may overestimate the performance of clinical prediction rules. The quality of reporting among studies validating clinical prediction rules needs to be improved

Comparative effectiveness of antihypertensive medication for primary prevention of cardiovascular disease: systematic review and multiple treatments meta-analysis

Background: We conducted a systematic review of evidence from randomized controlled trials to answer the following research question: What are the relative effects of different classes of antihypertensive drugs in reducing the incidence of cardiovascular disease outcomes for healthy people at risk of cardiovascular disease? Methods: We searched MEDLINE, EMBASE, AMED (up to February 2011) and CENTRAL (up to May 2009), and reference lists in recent systematic reviews. Titles and abstracts were assessed for relevance and those potentially fulfilling our inclusion criteria were then assessed in full text. Two reviewers made independent assessments at each step. We selected the following main outcomes: total mortality, myocardial infarction and stroke. We also report on angina, heart failure and incidence of diabetes. We conducted a multiple treatments meta-analysis using random-effects models. We assessed the quality of the evidence using the GRADE-instrument. Results: We included 25 trials. Overall, the results were mixed, with few significant dif-ferences, and with no drugclass standing out as superior across multiple outcomes. The only significant finding for total mortality based on moderate to high quality evidence was that beta-blockers (atenolol) were inferior to angiotensin receptor blockers (ARB) (relative risk (RR) 1.14; 95% credibility interval (CrI) 1.02 to 1.28). Angiotensin converting enzyme (ACE)- inhibitors came out inferior to calcium-channel blockers (CCB) regarding stroke-risk (RR 1.19; 1.03 to 1.38), but superior regarding risk of heart failure (RR 0.82; 0.69 to 0.94), both based on moderate quality evidence. Diuretics reduced the risk of myocardial infarction compared to beta-blockers (RR 0.82; 0.68 to 0.98), and lowered the risk of heart failure compared to CCB (RR 0.73; 0.62 to 0.84), beta-blockers (RR 0.73; 0.54 to 0.96), and alpha-blockers (RR 0.51; 0.40 to 0.64). The risk of diabetes increased with diuretics compared to ACE-inhibitors (RR 1.43; 1.12 to 1.83) and CCB (RR 1.27; 1.05 to 1.57). Conclusion: Based on the available evidence, there seems to be little or no difference between commonly used blood pressure lowering medications for primary prevention of cardiovascular disease. Beta-blockers (atenolol) and alpha-blockers may not be first-choice drugs as they were the only drug-classes that were not significantly superior to any other, for any outcomes

Evaluation of a Web Portal for Improving Public Access to Evidence-Based Health Information and Health Literacy Skills: A Pragmatic Trial

Background: Using the conceptual framework of shared decision-making and evidence-based practice, a web portal was developed to serve as a generic (non disease-specific) tailored intervention to improve the lay public’s health literacy skills. Objective: To evaluate the effects of the web portal compared to no intervention in a real-life setting. Methods: A pragmatic randomised controlled parallel trial using simple randomisation of 96 parents who had children aged ,4 years. Parents were allocated to receive either access to the portal or no intervention, and assigned three tasks to perform over a three-week period. These included a searching task, a critical appraisal task, and reporting on perceptions about participation. Data were collected from March through June 2011. Results: Use of the web portal was found to improve attitudes towards searching for health information. This variable was identified as the most important predictor of intention to search in both samples. Participants considered the web portal to have good usability, usefulness, and credibility. The intervention group showed slight increases in the use of evidencebased information, critical appraisal skills, and participation compared to the group receiving no intervention, but these differences were not statistically significant. Conclusion: Despite the fact that the study was underpowered, we found that the web portal may have a positive effect on attitudes towards searching for health information. Furthermore, participants considered the web portal to be a relevant tool. It is important to continue experimenting with web-based resources in order to increase user participation in health care decision-making. Trial Registration: ClinicalTrials.gov NCT0126679