461 research outputs found
Methodological criteria for the assessment of moderators in systematic reviews of randomised controlled trials : a consensus study
Background: Current methodological guidelines provide advice about the assessment of sub-group analysis within
RCTs, but do not specify explicit criteria for assessment. Our objective was to provide researchers with a set of
criteria that will facilitate the grading of evidence for moderators, in systematic reviews.
Method: We developed a set of criteria from methodological manuscripts (n = 18) using snowballing technique,
and electronic database searches. Criteria were reviewed by an international Delphi panel (n = 21), comprising
authors who have published methodological papers in this area, and researchers who have been active in the
study of sub-group analysis in RCTs. We used the Research ANd Development/University of California Los Angeles
appropriateness method to assess consensus on the quantitative data. Free responses were coded for consensus
and disagreement. In a subsequent round additional criteria were extracted from the Cochrane Reviewers’
Handbook, and the process was repeated.
Results: The recommendations are that meta-analysts report both confirmatory and exploratory findings for subgroups
analysis. Confirmatory findings must only come from studies in which a specific theory/evidence based apriori
statement is made. Exploratory findings may be used to inform future/subsequent trials. However, for
inclusion in the meta-analysis of moderators, the following additional criteria should be applied to each study:
Baseline factors should be measured prior to randomisation, measurement of baseline factors should be of
adequate reliability and validity, and a specific test of the interaction between baseline factors and interventions
must be presented.
Conclusions: There is consensus from a group of 21 international experts that methodological criteria to assess
moderators within systematic reviews of RCTs is both timely and necessary. The consensus from the experts
resulted in five criteria divided into two groups when synthesising evidence: confirmatory findings to support
hypotheses about moderators and exploratory findings to inform future research. These recommendations are
discussed in reference to previous recommendations for evaluating and reporting moderator studies
SmartEx: a case study on user profiling and adaptation in exhibition booths
An investigation into user profiling and adaptation with exhibition booth as a case study is reported. First a review of the field of exhibitions and trade fairs and a summary introduction to adaptation and profiling are given. We then introduce three criteria for the evaluation of exhibition booth: effectiveness, efficiency and affect. Effectiveness is related the amount of information collected, efficiency is a measurement of the time taken to collect the information, and affect is the perception of the experience and the mood booth visitors have during and after their visit. We have selected these criteria to assess adaptive and profiled exhibition booths, we call smart exhibition (SmartEx). The assessment is performed with an experiment with three test conditions (non-profiled/non adaptive, profiled/non-adaptive and profiled adaptive presentations). Results of the experiment are presented along discussion. While there is significant improvements of effectiveness and efficiency between the two-first test conditions, the improvement is not significant for the last test condition, for reasons explained. As for the affect, the results show that it has an under-estimated importance in people minds and that it should be addressed more carefully
Services just for men? Insights from a national study of the well men services pilots.
Men continue to have a lower life expectancy in most countries compared to women. Explanations of this gendered health inequality tend to focus on male risk taking, unhealthy lifestyle choices and resistance to seeking help from health services. In the period 2005-2008 the Scottish Government funded a nationwide community health promotion programme aimed at improving men's health, called Well Men Service Pilots (henceforth WMS)
Centre selection for clinical trials and the generalisability of results: a mixed methods study.
BACKGROUND: The rationale for centre selection in randomised controlled trials (RCTs) is often unclear but may have important implications for the generalisability of trial results. The aims of this study were to evaluate the factors which currently influence centre selection in RCTs and consider how generalisability considerations inform current and optimal practice. METHODS AND FINDINGS: Mixed methods approach consisting of a systematic review and meta-summary of centre selection criteria reported in RCT protocols funded by the UK National Institute of Health Research (NIHR) initiated between January 2005-January 2012; and an online survey on the topic of current and optimal centre selection, distributed to professionals in the 48 UK Clinical Trials Units and 10 NIHR Research Design Services. The survey design was informed by the systematic review and by two focus groups conducted with trialists at the Birmingham Centre for Clinical Trials. 129 trial protocols were included in the systematic review, with a total target sample size in excess of 317,000 participants. The meta-summary identified 53 unique centre selection criteria. 78 protocols (60%) provided at least one criterion for centre selection, but only 31 (24%) protocols explicitly acknowledged generalisability. This is consistent with the survey findings (n = 70), where less than a third of participants reported generalisability as a key driver of centre selection in current practice. This contrasts with trialists' views on optimal practice, where generalisability in terms of clinical practice, population characteristics and economic results were prime considerations for 60% (n = 42), 57% (n = 40) and 46% (n = 32) of respondents, respectively. CONCLUSIONS: Centres are rarely enrolled in RCTs with an explicit view to external validity, although trialists acknowledge that incorporating generalisability in centre selection should ideally be more prominent. There is a need to operationalize 'generalisability' and incorporate it at the design stage of RCTs so that results are readily transferable to 'real world' practice
A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients
[[abstract]]Background:Human hepatocellular carcinoma (HCC) cells are largely deficient of argininosuccinate synthetase and thus auxotrophic for arginine. This study aims to investigate the efficacy and pharmacodynamics of pegylated arginine deiminase (ADI-PEG 20), a systemic arginine deprivation agent, in Asian HCC patients. Methods:Patients with advanced HCC who were not candidates for local therapy were eligible and randomly assigned to receive weekly intramuscular injections of ADI-PEG 20 at doses of 160 or 320 IU m-2. The primary end point was disease-control rate (DCR). Results:Of the 71 accruals, 43.6% had failed previous systemic treatment. There were no objective responders. The DCR and the median overall survival (OS) of the intent-to-treat population were 31.0% (95% confidence interval (CI): 20.5-43.1) and 7.3 (95% CI: 4.7-9.9) months respectively. Both efficacy parameters were comparable between the two study arms. The median OS of patients with undetectable circulating arginine for more than or equal to and <4 weeks was 10.0 (95% CI: 2.1-17.9) and 5.8 (95% CI: 1.4-10.1) months respectively (P=0.251, log-rank test). The major treatment-related adverse events were grades 1-2 local and/or allergic reactions. Conclusions:ADI-PEG 20 is safe and efficacious in stabilising the progression of heavily pretreated advanced HCC in an Asian population, and deserves further exploration.British Journal of Cancer advance online publication, 31 August 2010; doi:10.1038/sj.bjc.6605856 www.bjcancer.com
Dealing with heterogeneity of treatment effects: is the literature up to the challenge?
<p>Abstract</p> <p>Background</p> <p>Some patients will experience more or less benefit from treatment than the averages reported from clinical trials; such variation in therapeutic outcome is termed heterogeneity of treatment effects (HTE). Identifying HTE is necessary to individualize treatment. The degree to which heterogeneity is sought and analyzed correctly in the general medical literature is unknown. We undertook this literature sample to track the use of HTE analyses over time, examine the appropriateness of the statistical methods used, and explore the predictors of such analyses.</p> <p>Methods</p> <p>Articles were selected through a probability sample of randomized controlled trials (RCTs) published in <it>Annals of Internal Medicine</it>, <it>BMJ</it>, <it>JAMA</it>, <it>The Lancet</it>, and <it>NEJM </it>during odd numbered months of 1994, 1999, and 2004. RCTs were independently reviewed and coded by two abstractors, with adjudication by a third. Studies were classified as reporting: (1) HTE analysis, utilizing a formal test for heterogeneity or treatment-by-covariate interaction, (2) subgroup analysis only, involving no formal test for heterogeneity or interaction; or (3) neither. Chi-square tests and multiple logistic regression were used to identify variables associated with HTE reporting.</p> <p>Results</p> <p>319 studies were included. Ninety-two (29%) reported HTE analysis; another 88 (28%) reported subgroup analysis only, without examining HTE formally. Major covariates examined included individual risk factors associated with prognosis, responsiveness to treatment, or vulnerability to adverse effects of treatment (56%); gender (30%); age (29%); study site or center (29%); and race/ethnicity (7%). Journal of publication and sample size were significant independent predictors of HTE analysis (p < 0.05 and p < 0.001, respectively).</p> <p>Conclusion</p> <p>HTE is frequently ignored or incorrectly analyzed. An iterative process of exploratory analysis followed by confirmatory HTE analysis will generate the data needed to facilitate an individualized approach to evidence-based medicine.</p
Predictors of Change Following Cognitive-Behavioral Treatment of Children with Anxiety Problems: A Preliminary Investigation on Negative Automatic Thoughts and Anxiety Control
The purpose of the present study was to evaluate negative automatic thoughts and anxiety control as predictors of change produced by cognitive-behavioral treatment of youths with anxiety disorders. Forty-five high-anxious children aged between 9 and 12 years who were selected from the primary school population, received a standardized CBT intervention that was provided in a group format. Before and after the intervention, children completed scales of negative automatic thoughts and perceived control over anxiety-related events as well as a questionnaire for measuring DSM-defined anxiety disorders symptoms, which was the outcome measure. Results indicated that CBT was effective in reducing children’s anxiety symptoms. Most importantly, the reduction of anxiety disorders symptoms was significantly associated with a decrease in negative automatic thoughts and an increase of anxiety control, which provides support for the notion that these variables are candidate mediators of CBT in anxious youths
Branch Mode Selection during Early Lung Development
Many organs of higher organisms, such as the vascular system, lung, kidney,
pancreas, liver and glands, are heavily branched structures. The branching
process during lung development has been studied in great detail and is
remarkably stereotyped. The branched tree is generated by the sequential,
non-random use of three geometrically simple modes of branching (domain
branching, planar and orthogonal bifurcation). While many regulatory components
and local interactions have been defined an integrated understanding of the
regulatory network that controls the branching process is lacking. We have
developed a deterministic, spatio-temporal differential-equation based model of
the core signaling network that governs lung branching morphogenesis. The model
focuses on the two key signaling factors that have been identified in
experiments, fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well
as the SHH receptor patched (Ptc). We show that the reported biochemical
interactions give rise to a Schnakenberg-type Turing patterning mechanisms that
allows us to reproduce experimental observations in wildtype and mutant mice.
The kinetic parameters as well as the domain shape are based on experimental
data where available. The developed model is robust to small absolute and large
relative changes in the parameter values. At the same time there is a strong
regulatory potential in that the switching between branching modes can be
achieved by targeted changes in the parameter values. We note that the sequence
of different branching events may also be the result of different growth
speeds: fast growth triggers lateral branching while slow growth favours
bifurcations in our model. We conclude that the FGF10-SHH-Ptc1 module is
sufficient to generate pattern that correspond to the observed branching modesComment: Initially published at PLoS Comput Bio
Effect of betaine supplementation on cycling sprint performance
<p>Abstract</p> <p>Purpose</p> <p>To examine the effect of betaine supplementation on cycling sprint performance.</p> <p>Methods</p> <p>Sixteen recreationally active subjects (7 females and 9 males) completed three sprint tests, each consisting of four 12 sec efforts against a resistance equal to 5.5% of body weight; efforts were separated by 2.5 min of cycling at zero resistance. Test one established baseline; test two and three were preceded by seven days of daily consumption of 591 ml of a carbohydrate-electrolyte beverage as a placebo or a carbohydrate-electrolyte beverage containing 0.42% betaine (approximately 2.5 grams of betaine a day); half the beverage was consumed in the morning and the other half in the afternoon. We used a double blind random order cross-over design; there was a 3 wk washout between trials two and three. Average and maximum peak and mean power were analyzed with one-way repeated measures ANOVA and, where indicated, a Student Newman-Keuls.</p> <p>Results</p> <p>Compared to baseline, betaine ingestion increased average peak power (6.4%; p < 0.001), maximum peak power (5.7%; p < 0.001), average mean power (5.4%; p = 0.004), and maximum mean power (4.4%; p = 0.004) for all subjects combined. Compared to placebo, betaine ingestion significantly increased average peak power (3.4%; p = 0.026), maximum peak power max (3.8%; p = 0.007), average mean power (3.3%; p = 0.034), and maximum mean power (3.5%; p = 0.011) for all subjects combined. There were no differences between the placebo and baseline trials.</p> <p>Conclusions</p> <p>One week of betaine ingestion improved cycling sprint power in recreationally active males and females.</p
Efficacy of exposure versus cognitive therapy in anxiety disorders: systematic review and meta-analysis
<p>Abstract</p> <p>Background</p> <p>There is growing evidence of the effectiveness of Cognitive Behavioural Therapy (CBT) for a wide range of psychological disorders. There is a continued controversy about whether challenging maladaptive thoughts rather than use of behavioural interventions alone is associated with the greatest efficacy. However little is known about the relative efficacy of various components of CBT. This review aims to compare the relative efficacy of Cognitive Therapy (CT) versus Exposure (E) for a range of anxiety disorders using the most clinically relevant outcome measures and estimating the summary relative efficacy by combining the studies in a meta-analysis.</p> <p>Methods</p> <p>Psych INFO, MEDLINE and EMBASE were searched from the first available year to May 2010. All randomised controlled studies comparing the efficacy of exposure with cognitive therapy were included. Odds ratios (OR) or standardised means' differences (Hedges' g) for the most clinically relevant primary outcomes were calculated. Outcomes of the studies were grouped according to specific disorders and were combined in meta-analyses exploring short-term and long-term outcomes.</p> <p>Results</p> <p>20 Randomised Controlled Trials with (n = 1,308) directly comparing the efficacy of CT and E in anxiety disorders were included in the meta-analysis. No statistically significant difference in the relative efficacy of CT and E was revealed in Post Traumatic Stress Disorder (PTSD), in Obsessive Compulsive Disorder (OCD) and in Panic Disorder (PD). There was a statistically significant difference favouring CT versus E in Social Phobia both in the short-term (Z = 3.72, p = 0.0002) and the long-term (Z = 3.28, p = 0.001) outcomes.</p> <p>Conclusions</p> <p>On the basis of extant literature, there appears to be no evidence of differential efficacy between cognitive therapy and exposure in PD, PTSD and OCD and strong evidence of superior efficacy of cognitive therapy in social phobia</p
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