Robust inference for group sequential trials.

PubMed

Ganju, Jitendra; Lin, Yunzhi; Zhou, Kefei

2017-03-01

For ethical reasons, group sequential trials were introduced to allow trials to stop early in the event of extreme results. Endpoints in such trials are usually mortality or irreversible morbidity. For a given endpoint, the norm is to use a single test statistic and to use that same statistic for each analysis. This approach is risky because the test statistic has to be specified before the study is unblinded, and there is loss in power if the assumptions that ensure optimality for each analysis are not met. To minimize the risk of moderate to substantial loss in power due to a suboptimal choice of a statistic, a robust method was developed for nonsequential trials. The concept is analogous to diversification of financial investments to minimize risk. The method is based on combining P values from multiple test statistics for formal inference while controlling the type I error rate at its designated value.This article evaluates the performance of 2 P value combining methods for group sequential trials. The emphasis is on time to event trials although results from less complex trials are also included. The gain or loss in power with the combination method relative to a single statistic is asymmetric in its favor. Depending on the power of each individual test, the combination method can give more power than any single test or give power that is closer to the test with the most power. The versatility of the method is that it can combine P values from different test statistics for analysis at different times. The robustness of results suggests that inference from group sequential trials can be strengthened with the use of combined tests. Copyright © 2017 John Wiley & Sons, Ltd.

Proactive Control: Neural Oscillatory Correlates of Conflict Anticipation and Response Slowing.

PubMed

Chang, Andrew; Ide, Jaime S; Li, Hsin-Hung; Chen, Chien-Chung; Li, Chiang-Shan R

2017-01-01

Proactive control allows us to anticipate environmental changes and adjust behavioral strategy. In the laboratory, investigators have used a number of different behavioral paradigms, including the stop-signal task (SST), to examine the neural processes of proactive control. Previous functional MRI studies of the SST have demonstrated regional responses to conflict anticipation-the likelihood of a stop signal or P(stop) as estimated by a Bayesian model-and reaction time (RT) slowing and how these responses are interrelated. Here, in an electrophysiological study, we investigated the time-frequency domain substrates of proactive control. The results showed that conflict anticipation as indexed by P(stop) was positively correlated with the power in low-theta band (3-5 Hz) in the fixation (trial onset)-locked interval, and go-RT was negatively correlated with the power in delta-theta band (2-8 Hz) in the go-locked interval. Stimulus prediction error was positively correlated with the power in the low-beta band (12-22 Hz) in the stop-locked interval. Further, the power of the P(stop) and go-RT clusters was negatively correlated, providing a mechanism relating conflict anticipation to RT slowing in the SST. Source reconstruction with beamformer localized these time-frequency activities close to brain regions as revealed by functional MRI in earlier work. These are the novel results to show oscillatory electrophysiological substrates in support of trial-by-trial behavioral adjustment for proactive control.

Frontal Theta Reflects Uncertainty and Unexpectedness during Exploration and Exploitation

PubMed Central

Figueroa, Christina M.; Cohen, Michael X; Frank, Michael J.

2012-01-01

In order to understand the exploitation/exploration trade-off in reinforcement learning, previous theoretical and empirical accounts have suggested that increased uncertainty may precede the decision to explore an alternative option. To date, the neural mechanisms that support the strategic application of uncertainty-driven exploration remain underspecified. In this study, electroencephalography (EEG) was used to assess trial-to-trial dynamics relevant to exploration and exploitation. Theta-band activities over middle and lateral frontal areas have previously been implicated in EEG studies of reinforcement learning and strategic control. It was hypothesized that these areas may interact during top-down strategic behavioral control involved in exploratory choices. Here, we used a dynamic reward–learning task and an associated mathematical model that predicted individual response times. This reinforcement-learning model generated value-based prediction errors and trial-by-trial estimates of exploration as a function of uncertainty. Mid-frontal theta power correlated with unsigned prediction error, although negative prediction errors had greater power overall. Trial-to-trial variations in response-locked frontal theta were linearly related to relative uncertainty and were larger in individuals who used uncertainty to guide exploration. This finding suggests that theta-band activities reflect prefrontal-directed strategic control during exploratory choices. PMID:22120491

Design and implementation of a dental caries prevention trial in remote Canadian Aboriginal communities.

PubMed

Harrison, Rosamund; Veronneau, Jacques; Leroux, Brian

2010-05-13

The goal of this cluster randomized trial is to test the effectiveness of a counseling approach, Motivational Interviewing, to control dental caries in young Aboriginal children. Motivational Interviewing, a client-centred, directive counseling style, has not yet been evaluated as an approach for promotion of behaviour change in indigenous communities in remote settings. Aboriginal women were hired from the 9 communities to recruit expectant and new mothers to the trial, administer questionnaires and deliver the counseling to mothers in the test communities. The goal is for mothers to receive the intervention during pregnancy and at their child's immunization visits. Data on children's dental health status and family dental health practices will be collected when children are 30-months of age. The communities were randomly allocated to test or control group by a random "draw" over community radio. Sample size and power were determined based on an anticipated 20% reduction in caries prevalence. Randomization checks were conducted between groups. In the 5 test and 4 control communities, 272 of the original target sample size of 309 mothers have been recruited over a two-and-a-half year period. A power calculation using the actual attained sample size showed power to be 79% to detect a treatment effect. If an attrition fraction of 4% per year is maintained, power will remain at 80%. Power will still be > 90% to detect a 25% reduction in caries prevalence. The distribution of most baseline variables was similar for the two randomized groups of mothers. However, despite the random assignment of communities to treatment conditions, group differences exist for stage of pregnancy and prior tooth extractions in the family. Because of the group imbalances on certain variables, control of baseline variables will be done in the analyses of treatment effects. This paper explains the challenges of conducting randomized trials in remote settings, the importance of thorough community collaboration, and also illustrates the likelihood that some baseline variables that may be clinically important will be unevenly split in group-randomized trials when the number of groups is small. This trial is registered as ISRCTN41467632.

Pre-cue Fronto-Occipital Alpha Phase and Distributed Cortical Oscillations Predict Failures of Cognitive Control

PubMed Central

Hamm, Jordan P.; Dyckman, Kara A.; McDowell, Jennifer E.; Clementz, Brett A.

2012-01-01

Cognitive control is required for correct performance on antisaccade tasks, including the ability to inhibit an externally driven ocular motor repsonse (a saccade to a peripheral stimulus) in favor of an internally driven ocular motor goal (a saccade directed away from a peripheral stimulus). Healthy humans occasionally produce errors during antisaccade tasks, but the mechanisms associated with such failures of cognitive control are uncertain. Most research on cognitive control failures focuses on post-stimulus processing, although a growing body of literature highlights a role of intrinsic brain activity in perceptual and cognitive performance. The current investigation used dense array electroencephalography and distributed source analyses to examine brain oscillations across a wide frequency bandwidth in the period prior to antisaccade cue onset. Results highlight four important aspects of ongoing and preparatory brain activations that differentiate error from correct antisaccade trials: (i) ongoing oscillatory beta (20–30Hz) power in anterior cingulate prior to trial initiation (lower for error trials), (ii) instantaneous phase of ongoing alpha-theta (7Hz) in frontal and occipital cortices immediately before trial initiation (opposite between trial types), (iii) gamma power (35–60Hz) in posterior parietal cortex 100 ms prior to cue onset (greater for error trials), and (iv) phase locking of alpha (5–12Hz) in parietal and occipital cortices immediately prior to cue onset (lower for error trials). These findings extend recently reported effects of pre-trial alpha phase on perception to cognitive control processes, and help identify the cortical generators of such phase effects. PMID:22593071

The contribution of attentional lapses to individual differences in visual working memory capacity.

PubMed

Adam, Kirsten C S; Mance, Irida; Fukuda, Keisuke; Vogel, Edward K

2015-08-01

Attentional control and working memory capacity are important cognitive abilities that substantially vary between individuals. Although much is known about how attentional control and working memory capacity relate to each other and to constructs like fluid intelligence, little is known about how trial-by-trial fluctuations in attentional engagement impact trial-by-trial working memory performance. Here, we employ a novel whole-report memory task that allowed us to distinguish between varying levels of attentional engagement in humans performing a working memory task. By characterizing low-performance trials, we can distinguish between models in which working memory performance failures are caused by either (1) complete lapses of attention or (2) variations in attentional control. We found that performance failures increase with set-size and strongly predict working memory capacity. Performance variability was best modeled by an attentional control model of attention, not a lapse model. We examined neural signatures of performance failures by measuring EEG activity while participants performed the whole-report task. The number of items correctly recalled in the memory task was predicted by frontal theta power, with decreased frontal theta power associated with poor performance on the task. In addition, we found that poor performance was not explained by failures of sensory encoding; the P1/N1 response and ocular artifact rates were equivalent for high- and low-performance trials. In all, we propose that attentional lapses alone cannot explain individual differences in working memory performance. Instead, we find that graded fluctuations in attentional control better explain the trial-by-trial differences in working memory that we observe.

The Contribution of Attentional Lapses to Individual Differences in Visual Working Memory Capacity

PubMed Central

Adam, Kirsten C. S.; Mance, Irida; Fukuda, Keisuke; Vogel, Edward K.

2015-01-01

Attentional control and working memory capacity are important cognitive abilities that substantially vary between individuals. Although much is known about how attentional control and working memory capacity relate to each other and to constructs like fluid intelligence, little is known about how trial-by-trial fluctuations in attentional engagement impact trial-by-trial working memory performance. Here, we employ a novel whole-report memory task that allowed us to distinguish between varying levels of attentional engagement in humans performing a working memory task. By characterizing low-performance trials, we can distinguish between models in which working memory performance failures are caused by either (1) complete lapses of attention or (2) variations in attentional control. We found that performance failures increase with set-size and strongly predict working memory capacity. Performance variability was best modeled by an attentional control model of attention, not a lapse model. We examined neural signatures of performance failures by measuring EEG activity while participants performed the whole-report task. The number of items correctly recalled in the memory task was predicted by frontal theta power, with decreased frontal theta power associated with poor performance on the task. In addition, we found that poor performance was not explained by failures of sensory encoding; the P1/N1 response and ocular artifact rates were equivalent for high- and low-performance trials. In all, we propose that attentional lapses alone cannot explain individual differences in working memory performance. Instead, we find that graded fluctuations in attentional control better explain the trial-by-trial differences in working memory that we observe. PMID:25811710

Incorporation of stochastic engineering models as prior information in Bayesian medical device trials.

PubMed

Haddad, Tarek; Himes, Adam; Thompson, Laura; Irony, Telba; Nair, Rajesh

2017-01-01

Evaluation of medical devices via clinical trial is often a necessary step in the process of bringing a new product to market. In recent years, device manufacturers are increasingly using stochastic engineering models during the product development process. These models have the capability to simulate virtual patient outcomes. This article presents a novel method based on the power prior for augmenting a clinical trial using virtual patient data. To properly inform clinical evaluation, the virtual patient model must simulate the clinical outcome of interest, incorporating patient variability, as well as the uncertainty in the engineering model and in its input parameters. The number of virtual patients is controlled by a discount function which uses the similarity between modeled and observed data. This method is illustrated by a case study of cardiac lead fracture. Different discount functions are used to cover a wide range of scenarios in which the type I error rates and power vary for the same number of enrolled patients. Incorporation of engineering models as prior knowledge in a Bayesian clinical trial design can provide benefits of decreased sample size and trial length while still controlling type I error rate and power.

A brief history of placebos and clinical trials in psychiatry.

PubMed

Shorter, Edward

2011-04-01

The history of placebos in psychiatry can be understood only in the context of randomized controlled trials (RCTs). Placebo treatments are as old as medicine itself, and are particularly effective in dealing with psychosomatic symptoms. In psychiatry, placebos have mainly been featured in clinical drug trials. The earliest controlled trial in psychiatry (not involving drugs) occurred in 1922, followed by the first crossover studies during the 1930s. Meanwhile the concept of randomization was developed during the interwar years by British statistician Ronald A Fisher, and introduced in 3 trials of tuberculosis drugs between 1947 and 1951. These classic studies established the RCT as the gold standard in pharmaceutical trials, and its status was cemented during the mid-1950s. Nevertheless, while the placebo became established as a standard measure of drug action, placebo treatments became stigmatized as unethical. This is unfortunate, as they constitute one of the most powerful therapies in psychiatry. In recent years, moreover, the dogma of the placebo-controlled trial as the only acceptable data for drug licensing is also being increasingly discredited. This backlash has had 2 sources: one is the recognition that the US Food and Drug Administration has been too lax in permitting trials controlled with placebos alone, rather than also using an active agent as a test of comparative efficacy. In addition, there is evidence that in the hands of the pharmaceutical industry, the scientific integrity of RCTs themselves has been degraded into a marketing device. The once-powerful placebo is thus threatened with extinction.

Assessment and Implication of Prognostic Imbalance in Randomized Controlled Trials with a Binary Outcome – A Simulation Study

PubMed Central

Chu, Rong; Walter, Stephen D.; Guyatt, Gordon; Devereaux, P. J.; Walsh, Michael; Thorlund, Kristian; Thabane, Lehana

2012-01-01

Background Chance imbalance in baseline prognosis of a randomized controlled trial can lead to over or underestimation of treatment effects, particularly in trials with small sample sizes. Our study aimed to (1) evaluate the probability of imbalance in a binary prognostic factor (PF) between two treatment arms, (2) investigate the impact of prognostic imbalance on the estimation of a treatment effect, and (3) examine the effect of sample size (n) in relation to the first two objectives. Methods We simulated data from parallel-group trials evaluating a binary outcome by varying the risk of the outcome, effect of the treatment, power and prevalence of the PF, and n. Logistic regression models with and without adjustment for the PF were compared in terms of bias, standard error, coverage of confidence interval and statistical power. Results For a PF with a prevalence of 0.5, the probability of a difference in the frequency of the PF≥5% reaches 0.42 with 125/arm. Ignoring a strong PF (relative risk = 5) leads to underestimating the strength of a moderate treatment effect, and the underestimate is independent of n when n is >50/arm. Adjusting for such PF increases statistical power. If the PF is weak (RR = 2), adjustment makes little difference in statistical inference. Conditional on a 5% imbalance of a powerful PF, adjustment reduces the likelihood of large bias. If an absolute measure of imbalance ≥5% is deemed important, including 1000 patients/arm provides sufficient protection against such an imbalance. Two thousand patients/arm may provide an adequate control against large random deviations in treatment effect estimation in the presence of a powerful PF. Conclusions The probability of prognostic imbalance in small trials can be substantial. Covariate adjustment improves estimation accuracy and statistical power, and hence should be performed when strong PFs are observed. PMID:22629322

Implementing Randomised Control Trials in Open and Distance Learning: A Feasibility Study

ERIC Educational Resources Information Center

Herodotou, Christothea; Heiser, Sarah; Rienties, Bart

2017-01-01

Randomised control trials (RCTs) are an evidence-based research approach which has not yet been adopted and widely used in open and distance education to inform educational policy and practice. Despite the challenges entailed in their application, RCTs hold the power to robustly evaluate the effects of educational interventions in distance…

Estimating statistical power for open-enrollment group treatment trials.

PubMed

Morgan-Lopez, Antonio A; Saavedra, Lissette M; Hien, Denise A; Fals-Stewart, William

2011-01-01

Modeling turnover in group membership has been identified as a key barrier contributing to a disconnect between the manner in which behavioral treatment is conducted (open-enrollment groups) and the designs of substance abuse treatment trials (closed-enrollment groups, individual therapy). Latent class pattern mixture models (LCPMMs) are emerging tools for modeling data from open-enrollment groups with membership turnover in recently proposed treatment trials. The current article illustrates an approach to conducting power analyses for open-enrollment designs based on the Monte Carlo simulation of LCPMM models using parameters derived from published data from a randomized controlled trial comparing Seeking Safety to a Community Care condition for women presenting with comorbid posttraumatic stress disorder and substance use disorders. The example addresses discrepancies between the analysis framework assumed in power analyses of many recently proposed open-enrollment trials and the proposed use of LCPMM for data analysis. Copyright © 2011 Elsevier Inc. All rights reserved.

Leveraging contact network structure in the design of cluster randomized trials.

PubMed

Harling, Guy; Wang, Rui; Onnela, Jukka-Pekka; De Gruttola, Victor

2017-02-01

In settings like the Ebola epidemic, where proof-of-principle trials have provided evidence of efficacy but questions remain about the effectiveness of different possible modes of implementation, it may be useful to conduct trials that not only generate information about intervention effects but also themselves provide public health benefit. Cluster randomized trials are of particular value for infectious disease prevention research by virtue of their ability to capture both direct and indirect effects of intervention, the latter of which depends heavily on the nature of contact networks within and across clusters. By leveraging information about these networks-in particular the degree of connection across randomized units, which can be obtained at study baseline-we propose a novel class of connectivity-informed cluster trial designs that aim both to improve public health impact (speed of epidemic control) and to preserve the ability to detect intervention effects. We several designs for cluster randomized trials with staggered enrollment, in each of which the order of enrollment is based on the total number of ties (contacts) from individuals within a cluster to individuals in other clusters. Our designs can accommodate connectivity based either on the total number of external connections at baseline or on connections only to areas yet to receive the intervention. We further consider a "holdback" version of the designs in which control clusters are held back from re-randomization for some time interval. We investigate the performance of these designs in terms of epidemic control outcomes (time to end of epidemic and cumulative incidence) and power to detect intervention effect, by simulating vaccination trials during an SEIR-type epidemic outbreak using a network-structured agent-based model. We compare results to those of a traditional Stepped Wedge trial. In our simulation studies, connectivity-informed designs lead to a 20% reduction in cumulative incidence compared to comparable traditional study designs, but have little impact on epidemic length. Power to detect intervention effect is reduced in all connectivity-informed designs, but "holdback" versions provide power that is very close to that of a traditional Stepped Wedge approach. Incorporating information about cluster connectivity in the design of cluster randomized trials can increase their public health impact, especially in acute outbreak settings. Using this information helps control outbreaks-by minimizing the number of cross-cluster infections-with very modest cost in terms of power to detect effectiveness.

Powered versus manual toothbrushing for oral health.

PubMed

Yaacob, Munirah; Worthington, Helen V; Deacon, Scott A; Deery, Chris; Walmsley, A Damien; Robinson, Peter G; Glenny, Anne-Marie

2014-06-17

Removing dental plaque may play a key role maintaining oral health. There is conflicting evidence for the relative merits of manual and powered toothbrushing in achieving this. This is an update of a Cochrane review first published in 2003, and previously updated in 2005. To compare manual and powered toothbrushes in everyday use, by people of any age, in relation to the removal of plaque, the health of the gingivae, staining and calculus, dependability, adverse effects and cost. We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 23 January 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE via OVID (1946 to 23 January 2014), EMBASE via OVID (1980 to 23 January 2014) and CINAHL via EBSCO (1980 to 23 January 2014). We searched the US National Institutes of Health Trials Register and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised controlled trials of at least four weeks of unsupervised powered toothbrushing versus manual toothbrushing for oral health in children and adults. We used standard methodological procedures expected by The Cochrane Collaboration. Random-effects models were used provided there were four or more studies included in the meta-analysis, otherwise fixed-effect models were used. Data were classed as short term (one to three months) and long term (greater than three months). Fifty-six trials met the inclusion criteria; 51 trials involving 4624 participants provided data for meta-analysis. Five trials were at low risk of bias, five at high and 46 at unclear risk of bias.There is moderate quality evidence that powered toothbrushes provide a statistically significant benefit compared with manual toothbrushes with regard to the reduction of plaque in both the short term (standardised mean difference (SMD) -0.50 (95% confidence interval (CI) -0.70 to -0.31); 40 trials, n = 2871) and long term (SMD -0.47 (95% CI -0.82 to -0.11; 14 trials, n = 978). These results correspond to an 11% reduction in plaque for the Quigley Hein index (Turesky) in the short term and 21% reduction long term. Both meta-analyses showed high levels of heterogeneity (I(2) = 83% and 86% respectively) that was not explained by the different powered toothbrush type subgroups.With regard to gingivitis, there is moderate quality evidence that powered toothbrushes again provide a statistically significant benefit when compared with manual toothbrushes both in the short term (SMD -0.43 (95% CI -0.60 to -0.25); 44 trials, n = 3345) and long term (SMD -0.21 (95% CI -0.31 to -0.12); 16 trials, n = 1645). This corresponds to a 6% and 11% reduction in gingivitis for the Löe and Silness index respectively. Both meta-analyses showed high levels of heterogeneity (I(2) = 82% and 51% respectively) that was not explained by the different powered toothbrush type subgroups.The number of trials for each type of powered toothbrush varied: side to side (10 trials), counter oscillation (five trials), rotation oscillation (27 trials), circular (two trials), ultrasonic (seven trials), ionic (four trials) and unknown (five trials). The greatest body of evidence was for rotation oscillation brushes which demonstrated a statistically significant reduction in plaque and gingivitis at both time points. Powered toothbrushes reduce plaque and gingivitis more than manual toothbrushing in the short and long term. The clinical importance of these findings remains unclear. Observation of methodological guidelines and greater standardisation of design would benefit both future trials and meta-analyses.Cost, reliability and side effects were inconsistently reported. Any reported side effects were localised and only temporary.

Sample size requirements for separating out the effects of combination treatments: randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis.

PubMed

Wolbers, Marcel; Heemskerk, Dorothee; Chau, Tran Thi Hong; Yen, Nguyen Thi Bich; Caws, Maxine; Farrar, Jeremy; Day, Jeremy

2011-02-02

In certain diseases clinical experts may judge that the intervention with the best prospects is the addition of two treatments to the standard of care. This can either be tested with a simple randomized trial of combination versus standard treatment or with a 2 x 2 factorial design. We compared the two approaches using the design of a new trial in tuberculous meningitis as an example. In that trial the combination of 2 drugs added to standard treatment is assumed to reduce the hazard of death by 30% and the sample size of the combination trial to achieve 80% power is 750 patients. We calculated the power of corresponding factorial designs with one- to sixteen-fold the sample size of the combination trial depending on the contribution of each individual drug to the combination treatment effect and the strength of an interaction between the two. In the absence of an interaction, an eight-fold increase in sample size for the factorial design as compared to the combination trial is required to get 80% power to jointly detect effects of both drugs if the contribution of the less potent treatment to the total effect is at least 35%. An eight-fold sample size increase also provides a power of 76% to detect a qualitative interaction at the one-sided 10% significance level if the individual effects of both drugs are equal. Factorial designs with a lower sample size have a high chance to be underpowered, to show significance of only one drug even if both are equally effective, and to miss important interactions. Pragmatic combination trials of multiple interventions versus standard therapy are valuable in diseases with a limited patient pool if all interventions test the same treatment concept, it is considered likely that either both or none of the individual interventions are effective, and only moderate drug interactions are suspected. An adequately powered 2 x 2 factorial design to detect effects of individual drugs would require at least 8-fold the sample size of the combination trial. Current Controlled Trials ISRCTN61649292.

Design, analysis and presentation of factorial randomised controlled trials

PubMed Central

Montgomery, Alan A; Peters, Tim J; Little, Paul

2003-01-01

Background The evaluation of more than one intervention in the same randomised controlled trial can be achieved using a parallel group design. However this requires increased sample size and can be inefficient, especially if there is also interest in considering combinations of the interventions. An alternative may be a factorial trial, where for two interventions participants are allocated to receive neither intervention, one or the other, or both. Factorial trials require special considerations, however, particularly at the design and analysis stages. Discussion Using a 2 × 2 factorial trial as an example, we present a number of issues that should be considered when planning a factorial trial. The main design issue is that of sample size. Factorial trials are most often powered to detect the main effects of interventions, since adequate power to detect plausible interactions requires greatly increased sample sizes. The main analytical issues relate to the investigation of main effects and the interaction between the interventions in appropriate regression models. Presentation of results should reflect the analytical strategy with an emphasis on the principal research questions. We also give an example of how baseline and follow-up data should be presented. Lastly, we discuss the implications of the design, analytical and presentational issues covered. Summary Difficulties in interpreting the results of factorial trials if an influential interaction is observed is the cost of the potential for efficient, simultaneous consideration of two or more interventions. Factorial trials can in principle be designed to have adequate power to detect realistic interactions, and in any case they are the only design that allows such effects to be investigated. PMID:14633287

Power/Sample Size Calculations for Assessing Correlates of Risk in Clinical Efficacy Trials

PubMed Central

Gilbert, Peter B.; Janes, Holly E.; Huang, Yunda

2016-01-01

In a randomized controlled clinical trial that assesses treatment efficacy, a common objective is to assess the association of a measured biomarker response endpoint with the primary study endpoint in the active treatment group, using a case-cohort, case-control, or two-phase sampling design. Methods for power and sample size calculations for such biomarker association analyses typically do not account for the level of treatment efficacy, precluding interpretation of the biomarker association results in terms of biomarker effect modification of treatment efficacy, with detriment that the power calculations may tacitly and inadvertently assume that the treatment harms some study participants. We develop power and sample size methods accounting for this issue, and the methods also account for inter-individual variability of the biomarker that is not biologically relevant (e.g., due to technical measurement error). We focus on a binary study endpoint and on a biomarker subject to measurement error that is normally distributed or categorical with two or three levels. We illustrate the methods with preventive HIV vaccine efficacy trials, and include an R package implementing the methods. PMID:27037797

Use of historical control data for assessing treatment effects in clinical trials.

PubMed

Viele, Kert; Berry, Scott; Neuenschwander, Beat; Amzal, Billy; Chen, Fang; Enas, Nathan; Hobbs, Brian; Ibrahim, Joseph G; Kinnersley, Nelson; Lindborg, Stacy; Micallef, Sandrine; Roychoudhury, Satrajit; Thompson, Laura

2014-01-01

Clinical trials rarely, if ever, occur in a vacuum. Generally, large amounts of clinical data are available prior to the start of a study, particularly on the current study's control arm. There is obvious appeal in using (i.e., 'borrowing') this information. With historical data providing information on the control arm, more trial resources can be devoted to the novel treatment while retaining accurate estimates of the current control arm parameters. This can result in more accurate point estimates, increased power, and reduced type I error in clinical trials, provided the historical information is sufficiently similar to the current control data. If this assumption of similarity is not satisfied, however, one can acquire increased mean square error of point estimates due to bias and either reduced power or increased type I error depending on the direction of the bias. In this manuscript, we review several methods for historical borrowing, illustrating how key parameters in each method affect borrowing behavior, and then, we compare these methods on the basis of mean square error, power and type I error. We emphasize two main themes. First, we discuss the idea of 'dynamic' (versus 'static') borrowing. Second, we emphasize the decision process involved in determining whether or not to include historical borrowing in terms of the perceived likelihood that the current control arm is sufficiently similar to the historical data. Our goal is to provide a clear review of the key issues involved in historical borrowing and provide a comparison of several methods useful for practitioners. Copyright © 2013 John Wiley & Sons, Ltd.

Use of historical control data for assessing treatment effects in clinical trials

PubMed Central

Viele, Kert; Berry, Scott; Neuenschwander, Beat; Amzal, Billy; Chen, Fang; Enas, Nathan; Hobbs, Brian; Ibrahim, Joseph G.; Kinnersley, Nelson; Lindborg, Stacy; Micallef, Sandrine; Roychoudhury, Satrajit; Thompson, Laura

2014-01-01

Clinical trials rarely, if ever, occur in a vacuum. Generally, large amounts of clinical data are available prior to the start of a study, particularly on the current study’s control arm. There is obvious appeal in using (i.e., ‘borrowing’) this information. With historical data providing information on the control arm, more trial resources can be devoted to the novel treatment while retaining accurate estimates of the current control arm parameters. This can result in more accurate point estimates, increased power, and reduced type I error in clinical trials, provided the historical information is sufficiently similar to the current control data. If this assumption of similarity is not satisfied, however, one can acquire increased mean square error of point estimates due to bias and either reduced power or increased type I error depending on the direction of the bias. In this manuscript, we review several methods for historical borrowing, illustrating how key parameters in each method affect borrowing behavior, and then, we compare these methods on the basis of mean square error, power and type I error. We emphasize two main themes. First, we discuss the idea of ‘dynamic’ (versus ‘static’) borrowing. Second, we emphasize the decision process involved in determining whether or not to include historical borrowing in terms of the perceived likelihood that the current control arm is sufficiently similar to the historical data. Our goal is to provide a clear review of the key issues involved in historical borrowing and provide a comparison of several methods useful for practitioners. PMID:23913901

Design of clinical trials involving multiple hypothesis tests with a common control.

PubMed

Schou, I Manjula; Marschner, Ian C

2017-07-01

Randomized clinical trials comparing several treatments to a common control are often reported in the medical literature. For example, multiple experimental treatments may be compared with placebo, or in combination therapy trials, a combination therapy may be compared with each of its constituent monotherapies. Such trials are typically designed using a balanced approach in which equal numbers of individuals are randomized to each arm, however, this can result in an inefficient use of resources. We provide a unified framework and new theoretical results for optimal design of such single-control multiple-comparator studies. We consider variance optimal designs based on D-, A-, and E-optimality criteria, using a general model that allows for heteroscedasticity and a range of effect measures that include both continuous and binary outcomes. We demonstrate the sensitivity of these designs to the type of optimality criterion by showing that the optimal allocation ratios are systematically ordered according to the optimality criterion. Given this sensitivity to the optimality criterion, we argue that power optimality is a more suitable approach when designing clinical trials where testing is the objective. Weighted variance optimal designs are also discussed, which, like power optimal designs, allow the treatment difference to play a major role in determining allocation ratios. We illustrate our methods using two real clinical trial examples taken from the medical literature. Some recommendations on the use of optimal designs in single-control multiple-comparator trials are also provided. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Control adjustments in speaking: Electrophysiology of the Gratton effect in picture naming.

PubMed

Shitova, Natalia; Roelofs, Ardi; Schriefers, Herbert; Bastiaansen, Marcel; Schoffelen, Jan-Mathijs

2017-07-01

Accumulating evidence suggests that spoken word production requires different amounts of top-down control depending on the prevailing circumstances. For example, during Stroop-like tasks, the interference in response time (RT) is typically larger following congruent trials than following incongruent trials. This effect is called the Gratton effect, and has been taken to reflect top-down control adjustments based on the previous trial type. Such control adjustments have been studied extensively in Stroop and Eriksen flanker tasks (mostly using manual responses), but not in the picture-word interference (PWI) task, which is a workhorse of language production research. In one of the few studies of the Gratton effect in PWI, Van Maanen and Van Rijn (2010) examined the effect in picture naming RTs during dual-task performance. Based on PWI effect differences between dual-task conditions, they argued that the functional locus of the PWI effect differs between post-congruent trials (i.e., locus in perceptual and conceptual encoding) and post-incongruent trials (i.e., locus in word planning). However, the dual-task procedure may have contaminated the results. We therefore performed an electroencephalography (EEG) study on the Gratton effect in a regular PWI task. We observed a PWI effect in the RTs, in the N400 component of the event-related brain potentials, and in the midfrontal theta power, regardless of the previous trial type. Moreover, the RTs, N400, and theta power reflected the Gratton effect. These results provide evidence that the PWI effect arises at the word planning stage following both congruent and incongruent trials, while the amount of top-down control changes depending on the previous trial type. Copyright © 2017 Elsevier Ltd. All rights reserved.

Proactive Control: Neural Oscillatory Correlates of Conflict Anticipation and Response Slowing

PubMed Central

Ide, Jaime S.

2017-01-01

Abstract Proactive control allows us to anticipate environmental changes and adjust behavioral strategy. In the laboratory, investigators have used a number of different behavioral paradigms, including the stop-signal task (SST), to examine the neural processes of proactive control. Previous functional MRI studies of the SST have demonstrated regional responses to conflict anticipation—the likelihood of a stop signal or P(stop) as estimated by a Bayesian model—and reaction time (RT) slowing and how these responses are interrelated. Here, in an electrophysiological study, we investigated the time–frequency domain substrates of proactive control. The results showed that conflict anticipation as indexed by P(stop) was positively correlated with the power in low-theta band (3–5 Hz) in the fixation (trial onset)-locked interval, and go-RT was negatively correlated with the power in delta-theta band (2–8 Hz) in the go-locked interval. Stimulus prediction error was positively correlated with the power in the low-beta band (12–22 Hz) in the stop-locked interval. Further, the power of the P(stop) and go-RT clusters was negatively correlated, providing a mechanism relating conflict anticipation to RT slowing in the SST. Source reconstruction with beamformer localized these time–frequency activities close to brain regions as revealed by functional MRI in earlier work. These are the novel results to show oscillatory electrophysiological substrates in support of trial-by-trial behavioral adjustment for proactive control. PMID:28560315

A Brief History of Placebos and Clinical Trials in Psychiatry

PubMed Central

Shorter, Edward

2013-01-01

The history of placebos in psychiatry can be understood only in the context of randomized controlled trials (RCTs). Placebo treatments are as old as medicine itself, and are particularly effective in dealing with psychosomatic symptoms. In psychiatry, placebos have mainly been featured in clinical drug trials. The earliest controlled trial in psychiatry (not involving drugs) occurred in 1922, followed by the first crossover studies during the 1930s. Meanwhile the concept of randomization was developed during the interwar years by British statistician Ronald A Fisher, and introduced in 3 trials of tuberculosis drugs between 1947 and 1951. These classic studies established the RCT as the gold standard in pharmaceutical trials, and its status was cemented during the mid-1950s. Nevertheless, while the placebo became established as a standard measure of drug action, placebo treatments became stigmatized as unethical. This is unfortunate, as they constitute one of the most powerful therapies in psychiatry. In recent years, moreover, the dogma of the placebo-controlled trial as the only acceptable data for drug licensing is also being increasingly discredited. This backlash has had 2 sources: one is the recognition that the US Food and Drug Administration has been too lax in permitting trials controlled with placebos alone, rather than also using an active agent as a test of comparative efficacy. In addition, there is evidence that in the hands of the pharmaceutical industry, the scientific integrity of RCTs themselves has been degraded into a marketing device. The once-powerful placebo is thus threatened with extinction. PMID:21507275

Design and analysis of three-arm trials with negative binomially distributed endpoints.

PubMed

Mütze, Tobias; Munk, Axel; Friede, Tim

2016-02-20

A three-arm clinical trial design with an experimental treatment, an active control, and a placebo control, commonly referred to as the gold standard design, enables testing of non-inferiority or superiority of the experimental treatment compared with the active control. In this paper, we propose methods for designing and analyzing three-arm trials with negative binomially distributed endpoints. In particular, we develop a Wald-type test with a restricted maximum-likelihood variance estimator for testing non-inferiority or superiority. For this test, sample size and power formulas as well as optimal sample size allocations will be derived. The performance of the proposed test will be assessed in an extensive simulation study with regard to type I error rate, power, sample size, and sample size allocation. For the purpose of comparison, Wald-type statistics with a sample variance estimator and an unrestricted maximum-likelihood estimator are included in the simulation study. We found that the proposed Wald-type test with a restricted variance estimator performed well across the considered scenarios and is therefore recommended for application in clinical trials. The methods proposed are motivated and illustrated by a recent clinical trial in multiple sclerosis. The R package ThreeArmedTrials, which implements the methods discussed in this paper, is available on CRAN. Copyright © 2015 John Wiley & Sons, Ltd.

Sample size requirements for separating out the effects of combination treatments: Randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis

PubMed Central

2011-01-01

Background In certain diseases clinical experts may judge that the intervention with the best prospects is the addition of two treatments to the standard of care. This can either be tested with a simple randomized trial of combination versus standard treatment or with a 2 × 2 factorial design. Methods We compared the two approaches using the design of a new trial in tuberculous meningitis as an example. In that trial the combination of 2 drugs added to standard treatment is assumed to reduce the hazard of death by 30% and the sample size of the combination trial to achieve 80% power is 750 patients. We calculated the power of corresponding factorial designs with one- to sixteen-fold the sample size of the combination trial depending on the contribution of each individual drug to the combination treatment effect and the strength of an interaction between the two. Results In the absence of an interaction, an eight-fold increase in sample size for the factorial design as compared to the combination trial is required to get 80% power to jointly detect effects of both drugs if the contribution of the less potent treatment to the total effect is at least 35%. An eight-fold sample size increase also provides a power of 76% to detect a qualitative interaction at the one-sided 10% significance level if the individual effects of both drugs are equal. Factorial designs with a lower sample size have a high chance to be underpowered, to show significance of only one drug even if both are equally effective, and to miss important interactions. Conclusions Pragmatic combination trials of multiple interventions versus standard therapy are valuable in diseases with a limited patient pool if all interventions test the same treatment concept, it is considered likely that either both or none of the individual interventions are effective, and only moderate drug interactions are suspected. An adequately powered 2 × 2 factorial design to detect effects of individual drugs would require at least 8-fold the sample size of the combination trial. Trial registration Current Controlled Trials ISRCTN61649292 PMID:21288326

Usability research study of a specially engineered sonic powered toothbrush with unique sensing and control technologies.

PubMed

Hunter, Gail; Burns, Laurie; Bone, Brian; Mintel, Thomas; Jimenez, Eduardo

2012-01-01

This paper summarizes the results of a longitudinal usability research study of a specially engineered sonic powered toothbrush with unique sensing and control technologies. The usability test was conducted with fourteen (14) consumers from the St. Louis, MO, USA area who use manual toothbrushes. The study consisted of consumers using the specially engineered sonic powered toothbrush with unique sensing and control technologies for three weeks. During the study, users participated in four toothbrush trials during weekly visits to the research facility. These trials were videotaped and were analyzed regarding brushing time, behavior, and technique. In addition, the users were required to use the toothbrush twice a day for their at-home brushing. The toothbrush had a positive impact on consumers' tooth brushing behavior. Users spent more time brushing their teeth with this toothbrush as compared to their manual toothbrush. In addition, users spent more time keeping the sonic toothbrush in the recommended angle during use. Finally, users perceived their teeth to be cleaner when using the specially engineered sonic powered toothbrush with unique sensing and control technologies. The specially engineered sonic powered toothbrush with unique sensing and control technologies left a positive impression on the users. The users perceived the toothbrush to clean their teeth better than a manual toothbrush.

Powered robotic exoskeletons in post-stroke rehabilitation of gait: a scoping review.

PubMed

Louie, Dennis R; Eng, Janice J

2016-06-08

Powered robotic exoskeletons are a potential intervention for gait rehabilitation in stroke to enable repetitive walking practice to maximize neural recovery. As this is a relatively new technology for stroke, a scoping review can help guide current research and propose recommendations for advancing the research development. The aim of this scoping review was to map the current literature surrounding the use of robotic exoskeletons for gait rehabilitation in adults post-stroke. Five databases (Pubmed, OVID MEDLINE, CINAHL, Embase, Cochrane Central Register of Clinical Trials) were searched for articles from inception to October 2015. Reference lists of included articles were reviewed to identify additional studies. Articles were included if they utilized a robotic exoskeleton as a gait training intervention for adult stroke survivors and reported walking outcome measures. Of 441 records identified, 11 studies, all published within the last five years, involving 216 participants met the inclusion criteria. The study designs ranged from pre-post clinical studies (n = 7) to controlled trials (n = 4); five of the studies utilized a robotic exoskeleton device unilaterally, while six used a bilateral design. Participants ranged from sub-acute (<7 weeks) to chronic (>6 months) stroke. Training periods ranged from single-session to 8-week interventions. Main walking outcome measures were gait speed, Timed Up and Go, 6-min Walk Test, and the Functional Ambulation Category. Meaningful improvement with exoskeleton-based gait training was more apparent in sub-acute stroke compared to chronic stroke. Two of the four controlled trials showed no greater improvement in any walking outcomes compared to a control group in chronic stroke. In conclusion, clinical trials demonstrate that powered robotic exoskeletons can be used safely as a gait training intervention for stroke. Preliminary findings suggest that exoskeletal gait training is equivalent to traditional therapy for chronic stroke patients, while sub-acute patients may experience added benefit from exoskeletal gait training. Efforts should be invested in designing rigorous, appropriately powered controlled trials before powered exoskeletons can be translated into a clinical tool for gait rehabilitation post-stroke.

Telehealth weight management intervention for adults with physical disabilities: a randomized controlled trial.

PubMed

Rimmer, James H; Wang, Edward; Pellegrini, Christine A; Lullo, Carolyn; Gerber, Ben S

2013-12-01

Weight reduction programs are not generally designed or adapted for people with physical disabilities. This study examined the effect of a 9-months remote, telephone-based weight management program for people with physical disabilities using a Web-based system (Personalized Online Weight and Exercise Response System [POWERS]). A total of 102 participants (mean ± SD age, 46.5 ± 12.7 yrs; body mass index, 32.0 ± 5.8 kg/m(2)) with a physical disability (spinal cord injury, multiple sclerosis, spina bifida, cerebral palsy, stroke, or lupus) were randomized to one of three conditions: physical activity only (POWERS), physical activity plus nutrition (POWERS(plus)), and control. The POWERS group received a physical activity tool kit and regular coaching telephone calls. The POWERS(plus) group received an intervention identical to that of the POWERS group plus nutritional information. The control group received the physical activity tool kit and self-guided health promotion resources at the completion of the trial but no coaching. Postintervention differences in body weight were found between the groups. There was a significant group × time interaction (P < 0.01) in postintervention body weight, with both the POWERS and POWERS(plus) groups demonstrating greater reduction in body weight compared with the control group (POWERS: -2.1 ± 5.5 kg, -2.4 ± -5.9%; POWERS(plus): -0.5 ± 5.0 kg, -0.6 ± 4.3%; control: +2.6 ± 5.3 kg, 3.1 ± 7.4%). A low-cost telephone intervention supported with a Web-based remote coaching tool (POWERS) can be an effective strategy for assisting overweight adults with physical disabilities in maintaining or reducing their body weight.

Moderate quality evidence finds statistical benefit in oral health for powered over manual toothbrushes.

PubMed

Niederman, Richard

2014-09-01

The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL, National Institutes of Health Trials Register and the WHO Clinical Trials Registry Platform for ongoing trials. Reference lists of identified articles were also scanned for relevant papers. Identified manufacturers were contacted for additional information. Only randomised controlled trials comparing manual and powered toothbrushes were considered. Crossover trials were eligible for inclusion if the wash-out period length was more than two weeks. Study assessment and data extraction were carried out independently by at least two reviewers. The primary outcome measures were quantified levels of plaque or gingivitis. Risk of bias assessment was undertaken. Standard Cochrane methodological approaches were taken. Random-effects models were used provided there were four or more studies included in the meta-analysis, otherwise fixed-effect models were used. Data were classed as short term (one to three months) and long term (greater than three months). Fifty-six trials were included with 51 (4624 patients) providing data for meta-analysis. The majority (46) were at unclear risk of bias, five at high risk of bias and five at low risk. There was moderate quality evidence that powered toothbrushes provide a statistically significant benefit compared with manual toothbrushes with regard to the reduction of plaque in both the short and long-term. This corresponds to an 11% reduction in plaque for the Quigley Hein index (Turesky) in the short term and a 21% reduction in the long term. There was a high degree of heterogeneity that was not explained by the different powered toothbrush type subgroups.There was also moderate quality evidence that powered toothbrushes again provide a statistically significant reduction in gingivitis when compared with manual toothbrushes both in the short and long term. This corresponds to a 6% and 11% reduction in gingivitis for the Löe and Silness indices respectively. Again there was a high degree of heterogeneity that was not explained by the different powered toothbrush type subgroups. The greatest body of evidence was for rotation oscillation brushes which demonstrated a statistically significant reduction in plaque and gingivitis at both time points. Powered toothbrushes reduce plaque and gingivitis more than manual toothbrushing in the short and long term. The clinical importance of these findings remains unclear. Observation of methodological guidelines and greater standardisation of design would benefit both future trials and meta-analyses. Cost, reliability and side effects were inconsistently reported. Any reported side effects were localised and only temporary.

The Effect of a Microprocessor Prosthetic Foot on Function and Quality of Life in Transtibial Amputees Who Are Limited Community Ambulators

DTIC Science & Technology

2017-09-01

parallel, randomized, controlled clinical trial designed to determine if a microprocessor controlled prosthetic foot (MPF), with greater range of...clinical trial designed to determine if a microprocessor controlled prosthetic foot (MPF), with greater range of motion and active power, will...Department of the Army position, policy or decision unless so designated by other documentation. CONTRACTING ORGANIZATION: University of Tennessee

Changing cluster composition in cluster randomised controlled trials: design and analysis considerations

PubMed Central

2014-01-01

Background There are many methodological challenges in the conduct and analysis of cluster randomised controlled trials, but one that has received little attention is that of post-randomisation changes to cluster composition. To illustrate this, we focus on the issue of cluster merging, considering the impact on the design, analysis and interpretation of trial outcomes. Methods We explored the effects of merging clusters on study power using standard methods of power calculation. We assessed the potential impacts on study findings of both homogeneous cluster merges (involving clusters randomised to the same arm of a trial) and heterogeneous merges (involving clusters randomised to different arms of a trial) by simulation. To determine the impact on bias and precision of treatment effect estimates, we applied standard methods of analysis to different populations under analysis. Results Cluster merging produced a systematic reduction in study power. This effect depended on the number of merges and was most pronounced when variability in cluster size was at its greatest. Simulations demonstrate that the impact on analysis was minimal when cluster merges were homogeneous, with impact on study power being balanced by a change in observed intracluster correlation coefficient (ICC). We found a decrease in study power when cluster merges were heterogeneous, and the estimate of treatment effect was attenuated. Conclusions Examples of cluster merges found in previously published reports of cluster randomised trials were typically homogeneous rather than heterogeneous. Simulations demonstrated that trial findings in such cases would be unbiased. However, simulations also showed that any heterogeneous cluster merges would introduce bias that would be hard to quantify, as well as having negative impacts on the precision of estimates obtained. Further methodological development is warranted to better determine how to analyse such trials appropriately. Interim recommendations include avoidance of cluster merges where possible, discontinuation of clusters following heterogeneous merges, allowance for potential loss of clusters and additional variability in cluster size in the original sample size calculation, and use of appropriate ICC estimates that reflect cluster size. PMID:24884591

REFOCUS Trial: protocol for a cluster randomised controlled trial of a pro-recovery intervention within community based mental health teams

PubMed Central

2011-01-01

Background There is a consensus about the importance of 'recovery' in mental health services, but the evidence base is limited. Methods/Design A two centre, cluster randomised controlled trial. Participants are community-based mental health teams, and service users aged 18-65 years with a primary clinical diagnosis of psychosis. In relation to the REFOCUS Manual researchintorecovery.com/refocus, which describes a 12-month, pro-recovery intervention based on the REFOCUS Model, the objectives are: (1) To establish the effectiveness of the intervention described in the REFOCUS Manual; (2) To validate the REFOCUS Model; (3) To establish and optimise trial parameters for the REFOCUS Manual; and (4) To understand the relationship between clinical outcomes and recovery outcomes. The hypothesis for the main study is that service users in the intervention arm will experience significantly greater increases in measures of personal recovery (as measured by the QPR) compared to service users receiving care from control teams. The hypothesis for the secondary study is that black service users in the intervention arm will experience significantly greater increases in measures of personal recovery (as measured by the QPR) and client satisfaction (as measured by the CSQ) compared to Black service users receiving care from control teams. The intervention comprises treatment as usual plus two components: recovery-promoting relationships and working practices. The control condition is treatment as usual. The primary outcme is the Process of Recovery Questionnaire (QPR). Secondary outcomes are satisfaction, Goal setting - Personal Primary Outcome, hope, well-being, empowerment, and quality of life. Primary outcomes for the secondary study will be QPR and satisfaction. Cost data will be estimated, and clinical outcomes will also be reported (symptomatology, need, social disability, functioning). 29 teams (15 intervention and 14 control) will be randomised. Within each team, 15 services users will be randomly chosen, giving a total sample of 435 service users (225 in intervention and 210 in control). Power for the main study: 336 service users will give power to detect a medium effect size of 0.4 (alpha 0.05, power = 0.8) on both QPR sub-scales. Power for the secondary study: 89 participants will give power to detect an effect size of 0.67 on both QPR sub-scales and on CSQ. A range of approaches are used to minimise bias, although service users and clinicians cannot be blinded. Discussion This cluster-RCT will evaluate a pro-recovery intervention in community mental health teams. Trial registration ISRCTN: ISRCTN02507940 PMID:22112008

Effects of radiant heat exposure on pacing pattern during a 15-km cycling time trial.

PubMed

Levels, Koen; de Koning, Jos; Broekhuijzen, Iris; Zwaan, Tamara; Foster, Carl; Daanen, Hein

2014-01-01

The goal of this study was to investigate the effects of different durations of skin temperature manipulation on pacing patterns and performance during a 15-km cycling time trial. Nineteen well-trained men completed three 15-km cycling time trials in 18 °C and 50% relative humidity with 4.5-km (short-heat), 9.0-km (long-heat) or without (control) radiant heat exposure applied by infrared heaters after 1.5 km in the time trial. During the time trials, power output, mean skin temperature, rectal temperature, heart rate and rating of perceived exertion were assessed. The radiant heat exposure resulted in higher mean skin temperature during the time trial for short-heat (35.0 ± 0.6 °C) and long-heat (35.3 ± 0.5 °C) than for control (32.5 ± 1.0 °C; P < 0.001), whereas rectal temperature was similar (P = 0.55). The mean power output was less for short-heat (273 ± 8 W; P = 0.001) and long-heat (271 ± 9 W; P = 0.02) than for control (287 ± 7 W), but pacing patterns did not differ (P = 0.55). Heart rate was greatest in control (177 ± 9 beats · min(-1); P < 0.001), whereas the rating of perceived exertion remained similar. We concluded that a radiant heat exposure and associated higher skin temperature reduced overall performance, but did not modify pacing pattern during a 15-km cycling time trial, regardless of the duration of the exposure.

A study of sertraline in dialysis (ASSertID): a protocol for a pilot randomised controlled trial of drug treatment for depression in patients undergoing haemodialysis.

PubMed

Friedli, Karin; Almond, Michael; Day, Clara; Chilcot, Joseph; Gane, Maria da Silva; Davenport, Andrew; Guirguis, Ayman; Fineberg, Naomi; Spencer, Benjamin; Wellsted, David; Farrington, Ken

2015-10-26

The prevalence of depression in people receiving haemodialysis is high with estimates varying between 20 and 40 %. There is little research on the effectiveness of antidepressants in dialysis patients with the few clinical trials suffering significant methodological issues. We plan to carry out a study to evaluate the feasibility of conducting a randomised controlled trial in patients on haemodialysis who have diagnosed Major Depressive Disorder. The study has two phases, a screening phase and the randomised controlled trial. Patients will be screened initially with the Beck Depression Inventory to estimate the number of patients who score 16 or above. These patients will be invited to an interview with a psychiatrist who will invite those with a diagnosis of Major Depressive Disorder to take part in the trial. Consenting patients will be randomised to either Sertraline or placebo. Patients will be followed-up for 6 months. Demographic and clinical data will be collected at screening interview, baseline interview and 2 weeks, and every month (up to 6 months) after baseline. The primary outcome is to evaluate the feasibility of conducting a randomised, double blind, placebo pilot trial in haemodialysis patients with depression. Secondary outcomes include estimation of the variability in the outcome measures for the treatment and placebo arms, which will allow for a future adequately powered definitive trial. Analysis will primarily be descriptive, including the number of patients eligible for the trial, drug exposure of Sertraline in haemodialysis patients and the patient experience of participating in this trial. There is an urgent need for this research in the dialysis population because of the dearth of good quality and adequately powered studies. Research with renal patients is particularly difficult as they often have complex medical needs. This research will therefore not only assess the outcome of anti-depressants in haemodialysis patients with depression but also the process of running a randomised controlled trial in this population. Hence, the outputs of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the efficacy of anti-depressants in patient on haemodialysis with depression. ISRCTN registry ISRCTN06146268 and EudraCT reference: 2012-000547-27.

Low power and type II errors in recent ophthalmology research.

PubMed

Khan, Zainab; Milko, Jordan; Iqbal, Munir; Masri, Moness; Almeida, David R P

2016-10-01

To investigate the power of unpaired t tests in prospective, randomized controlled trials when these tests failed to detect a statistically significant difference and to determine the frequency of type II errors. Systematic review and meta-analysis. We examined all prospective, randomized controlled trials published between 2010 and 2012 in 4 major ophthalmology journals (Archives of Ophthalmology, British Journal of Ophthalmology, Ophthalmology, and American Journal of Ophthalmology). Studies that used unpaired t tests were included. Power was calculated using the number of subjects in each group, standard deviations, and α = 0.05. The difference between control and experimental means was set to be (1) 20% and (2) 50% of the absolute value of the control's initial conditions. Power and Precision version 4.0 software was used to carry out calculations. Finally, the proportion of articles with type II errors was calculated. β = 0.3 was set as the largest acceptable value for the probability of type II errors. In total, 280 articles were screened. Final analysis included 50 prospective, randomized controlled trials using unpaired t tests. The median power of tests to detect a 50% difference between means was 0.9 and was the same for all 4 journals regardless of the statistical significance of the test. The median power of tests to detect a 20% difference between means ranged from 0.26 to 0.9 for the 4 journals. The median power of these tests to detect a 50% and 20% difference between means was 0.9 and 0.5 for tests that did not achieve statistical significance. A total of 14% and 57% of articles with negative unpaired t tests contained results with β > 0.3 when power was calculated for differences between means of 50% and 20%, respectively. A large portion of studies demonstrate high probabilities of type II errors when detecting small differences between means. The power to detect small difference between means varies across journals. It is, therefore, worthwhile for authors to mention the minimum clinically important difference for individual studies. Journals can consider publishing statistical guidelines for authors to use. Day-to-day clinical decisions rely heavily on the evidence base formed by the plethora of studies available to clinicians. Prospective, randomized controlled clinical trials are highly regarded as a robust study and are used to make important clinical decisions that directly affect patient care. The quality of study designs and statistical methods in major clinical journals is improving overtime, 1 and researchers and journals are being more attentive to statistical methodologies incorporated by studies. The results of well-designed ophthalmic studies with robust methodologies, therefore, have the ability to modify the ways in which diseases are managed. Copyright © 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Kidney function endpoints in kidney transplant trials: a struggle for power.

PubMed

Ibrahim, A; Garg, A X; Knoll, G A; Akbari, A; White, C A

2013-03-01

Kidney function endpoints are commonly used in randomized controlled trials (RCTs) in kidney transplantation (KTx). We conducted this study to estimate the proportion of ongoing RCTs with kidney function endpoints in KTx where the proposed sample size is large enough to detect meaningful differences in glomerular filtration rate (GFR) with adequate statistical power. RCTs were retrieved using the key word "kidney transplantation" from the National Institute of Health online clinical trial registry. Included trials had at least one measure of kidney function tracked for at least 1 month after transplant. We determined the proportion of two-arm parallel trials that had sufficient sample sizes to detect a minimum 5, 7.5 and 10 mL/min difference in GFR between arms. Fifty RCTs met inclusion criteria. Only 7% of the trials were above a sample size of 562, the number needed to detect a minimum 5 mL/min difference between the groups should one exist (assumptions: α = 0.05; power = 80%, 10% loss to follow-up, common standard deviation of 20 mL/min). The result increased modestly to 36% of trials when a minimum 10 mL/min difference was considered. Only a minority of ongoing trials have adequate statistical power to detect between-group differences in kidney function using conventional sample size estimating parameters. For this reason, some potentially effective interventions which ultimately could benefit patients may be abandoned from future assessment. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Randomized controlled trial of toothbrushing to reduce ventilator-associated pneumonia pathogens and dental plaque in a critical care unit.

PubMed

Needleman, Ian G; Hirsch, Nicholas P; Leemans, Michele; Moles, David R; Wilson, Michael; Ready, Derren R; Ismail, Salim; Ciric, Lena; Shaw, Michael J; Smith, Martin; Garner, Anne; Wilson, Sally

2011-03-01

To investigate the effect of a powered toothbrush on colonization of dental plaque by ventilator-associated pneumonia (VAP)-associated organisms and dental plaque removal. Parallel-arm, single-centre, examiner- and analyst-masked randomized controlled trial. Forty-six adults were recruited within 48 h of admission. Test intervention: powered toothbrush, control intervention: sponge toothette, both used four times per day for 2 min. Groups received 20 ml, 0.2% chlorhexidine mouthwash at each time point. The results showed a low prevalence of respiratory pathogens throughout with no statistically significant differences between groups. A highly statistically significantly greater reduction in dental plaque was produced by the powered toothbrush compared with the control treatment; mean plaque index at day 5, powered toothbrush 0.75 [95% confidence interval (CI) 0.53, 1.00], sponge toothette 1.35 (95% CI 0.95, 1.74), p=0.006. Total bacterial viable count was also highly statistically significantly lower in the test group at day 5; Log(10) mean total bacterial counts: powered toothbrush 5.12 (95% CI 4.60, 5.63), sponge toothette 6.61 (95% CI 5.93, 7.28), p=0.002. Powered toothbrushes are highly effective for plaque removal in intubated patients in a critical unit and should be tested for their potential to reduce VAP incidence and health complications. © 2011 John Wiley & Sons A/S.

Efficacy of an adapted HIV and sexually transmitted infection prevention intervention for incarcerated women: a randomized controlled trial.

PubMed

Fogel, Catherine I; Crandell, Jamie L; Neevel, A M; Parker, Sharon D; Carry, Monique; White, Becky L; Fasula, Amy M; Herbst, Jeffrey H; Gelaude, Deborah J

2015-04-01

We tested the efficacy of an adapted evidence-based HIV-sexually transmitted infection (STI) behavioral intervention (Providing Opportunities for Women's Empowerment, Risk-Reduction, and Relationships, or POWER) among incarcerated women. We conducted a randomized trial with 521 women aged 18 to 60 years in 2 correctional facilities in North Carolina in 2010 and 2011. Intervention participants attended 8 POWER sessions; control participants received a single standard-of-care STI prevention session. We followed up at 3 and 6 months after release. We examined intervention efficacy with mixed-effects models. POWER participants reported fewer male sexual partners than did control participants at 3 months, although this finding did not reach statistical significance; at 6 months they reported significantly less vaginal intercourse without a condom outside of a monogamous relationship and more condom use with a main male partner. POWER participants also reported significantly fewer condom barriers, and greater HIV knowledge, health-protective communication, and tangible social support. The intervention had no significant effects on incident STIs. POWER is a behavioral intervention with potential to reduce risk of acquiring or transmitting HIV and STIs among incarcerated women returning to their communities.

Efficacy of an Adapted HIV and Sexually Transmitted Infection Prevention Intervention for Incarcerated Women: A Randomized Controlled Trial

PubMed Central

Crandell, Jamie L.; Neevel, A. M.; Parker, Sharon D.; Carry, Monique; White, Becky L.; Fasula, Amy M.; Herbst, Jeffrey H.; Gelaude, Deborah J.

2015-01-01

Objectives. We tested the efficacy of an adapted evidence-based HIV–sexually transmitted infection (STI) behavioral intervention (Providing Opportunities for Women’s Empowerment, Risk-Reduction, and Relationships, or POWER) among incarcerated women. Methods. We conducted a randomized trial with 521 women aged 18 to 60 years in 2 correctional facilities in North Carolina in 2010 and 2011. Intervention participants attended 8 POWER sessions; control participants received a single standard-of-care STI prevention session. We followed up at 3 and 6 months after release. We examined intervention efficacy with mixed-effects models. Results. POWER participants reported fewer male sexual partners than did control participants at 3 months, although this finding did not reach statistical significance; at 6 months they reported significantly less vaginal intercourse without a condom outside of a monogamous relationship and more condom use with a main male partner. POWER participants also reported significantly fewer condom barriers, and greater HIV knowledge, health-protective communication, and tangible social support. The intervention had no significant effects on incident STIs. Conclusions. POWER is a behavioral intervention with potential to reduce risk of acquiring or transmitting HIV and STIs among incarcerated women returning to their communities. PMID:25211714

Trial application of reliability technology to emergency diesel generators at the Trojan Nuclear Power Plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, S.M.; Boccio, J.L.; Karimian, S.

1986-01-01

In this paper, a trial application of reliability technology to the emergency diesel generator system at the Trojan Nuclear Power Plant is presented. An approach for formulating a reliability program plan for this system is being developed. The trial application has shown that a reliability program process, using risk- and reliability-based techniques, can be interwoven into current plant operational activities to help in controlling, analyzing, and predicting faults that can challenge safety systems. With the cooperation of the utility, Portland General Electric Co., this reliability program can eventually be implemented at Trojan to track its effectiveness.

Design of a multi-arm randomized clinical trial with no control arm.

PubMed

Magaret, Amalia; Angus, Derek C; Adhikari, Neill K J; Banura, Patrick; Kissoon, Niranjan; Lawler, James V; Jacob, Shevin T

2016-01-01

Clinical trial designs that include multiple treatments are currently limited to those that perform pairwise comparisons of each investigational treatment to a single control. However, there are settings, such as the recent Ebola outbreak, in which no treatment has been demonstrated to be effective; and therefore, no standard of care exists which would serve as an appropriate control. For illustrative purposes, we focused on the care of patients presenting in austere settings with critically ill 'sepsis-like' syndromes. Our approach involves a novel algorithm for comparing mortality among arms without requiring a single fixed control. The algorithm allows poorly-performing arms to be dropped during interim analyses. Consequently, the study may be completed earlier than planned. We used simulation to determine operating characteristics for the trial and to estimate the required sample size. We present a potential study design targeting a minimal effect size of a 23% relative reduction in mortality between any pair of arms. Using estimated power and spurious significance rates from the simulated scenarios, we show that such a trial would require 2550 participants. Over a range of scenarios, our study has 80 to 99% power to select the optimal treatment. Using a fixed control design, if the control arm is least efficacious, 640 subjects would be enrolled into the least efficacious arm, while our algorithm would enroll between 170 and 430. This simulation method can be easily extended to other settings or other binary outcomes. Early dropping of arms is efficient and ethical when conducting clinical trials with multiple arms. Copyright © 2015 Elsevier Inc. All rights reserved.

Treatments for somnambulism in adults: assessing the evidence.

PubMed

Harris, Melanie; Grunstein, Ronald R

2009-08-01

Somnambulism, or sleepwalking, is a parasomnia of non-rapid eye movement (NREM) sleep where movement behaviours usually confined to wakefulness are displayed during sleep. Generally, if sleepwalking is causing distress or danger in spite of safety measures, medical or psychological treatment is indicated. Clinicians will need to assess the evidence for treatment options. MEDLINE, EMBASE, PsycINFO and the Ovid Evidence-Based Medicine Reviews (EBM) multifile databases were searched. No properly powered rigorous controlled trials were found for treatment of sleepwalking in adults. Seven reports described small trials with some kind of control arm, or retrospective case series which included 30 or more patients. With no high quality evidence to underpin recommendations for treatments of somnambulism, full discussion with patients is advised. Adequately powered, well-designed clinical trials are now needed, and multi-centre collaborations may be required to obtain the sample sizes required.

A Bayesian adaptive design for biomarker trials with linked treatments.

PubMed

Wason, James M S; Abraham, Jean E; Baird, Richard D; Gournaris, Ioannis; Vallier, Anne-Laure; Brenton, James D; Earl, Helena M; Mander, Adrian P

2015-09-01

Response to treatments is highly heterogeneous in cancer. Increased availability of biomarkers and targeted treatments has led to the need for trial designs that efficiently test new treatments in biomarker-stratified patient subgroups. We propose a novel Bayesian adaptive randomisation (BAR) design for use in multi-arm phase II trials where biomarkers exist that are potentially predictive of a linked treatment's effect. The design is motivated in part by two phase II trials that are currently in development. The design starts by randomising patients to the control treatment or to experimental treatments that the biomarker profile suggests should be active. At interim analyses, data from treated patients are used to update the allocation probabilities. If the linked treatments are effective, the allocation remains high; if ineffective, the allocation changes over the course of the trial to unlinked treatments that are more effective. Our proposed design has high power to detect treatment effects if the pairings of treatment with biomarker are correct, but also performs well when alternative pairings are true. The design is consistently more powerful than parallel-groups stratified trials. This BAR design is a powerful approach to use when there are pairings of biomarkers with treatments available for testing simultaneously.

Bias, precision and statistical power of analysis of covariance in the analysis of randomized trials with baseline imbalance: a simulation study.

PubMed

Egbewale, Bolaji E; Lewis, Martyn; Sim, Julius

2014-04-09

Analysis of variance (ANOVA), change-score analysis (CSA) and analysis of covariance (ANCOVA) respond differently to baseline imbalance in randomized controlled trials. However, no empirical studies appear to have quantified the differential bias and precision of estimates derived from these methods of analysis, and their relative statistical power, in relation to combinations of levels of key trial characteristics. This simulation study therefore examined the relative bias, precision and statistical power of these three analyses using simulated trial data. 126 hypothetical trial scenarios were evaluated (126,000 datasets), each with continuous data simulated by using a combination of levels of: treatment effect; pretest-posttest correlation; direction and magnitude of baseline imbalance. The bias, precision and power of each method of analysis were calculated for each scenario. Compared to the unbiased estimates produced by ANCOVA, both ANOVA and CSA are subject to bias, in relation to pretest-posttest correlation and the direction of baseline imbalance. Additionally, ANOVA and CSA are less precise than ANCOVA, especially when pretest-posttest correlation ≥ 0.3. When groups are balanced at baseline, ANCOVA is at least as powerful as the other analyses. Apparently greater power of ANOVA and CSA at certain imbalances is achieved in respect of a biased treatment effect. Across a range of correlations between pre- and post-treatment scores and at varying levels and direction of baseline imbalance, ANCOVA remains the optimum statistical method for the analysis of continuous outcomes in RCTs, in terms of bias, precision and statistical power.

Bias, precision and statistical power of analysis of covariance in the analysis of randomized trials with baseline imbalance: a simulation study

PubMed Central

2014-01-01

Background Analysis of variance (ANOVA), change-score analysis (CSA) and analysis of covariance (ANCOVA) respond differently to baseline imbalance in randomized controlled trials. However, no empirical studies appear to have quantified the differential bias and precision of estimates derived from these methods of analysis, and their relative statistical power, in relation to combinations of levels of key trial characteristics. This simulation study therefore examined the relative bias, precision and statistical power of these three analyses using simulated trial data. Methods 126 hypothetical trial scenarios were evaluated (126 000 datasets), each with continuous data simulated by using a combination of levels of: treatment effect; pretest-posttest correlation; direction and magnitude of baseline imbalance. The bias, precision and power of each method of analysis were calculated for each scenario. Results Compared to the unbiased estimates produced by ANCOVA, both ANOVA and CSA are subject to bias, in relation to pretest-posttest correlation and the direction of baseline imbalance. Additionally, ANOVA and CSA are less precise than ANCOVA, especially when pretest-posttest correlation ≥ 0.3. When groups are balanced at baseline, ANCOVA is at least as powerful as the other analyses. Apparently greater power of ANOVA and CSA at certain imbalances is achieved in respect of a biased treatment effect. Conclusions Across a range of correlations between pre- and post-treatment scores and at varying levels and direction of baseline imbalance, ANCOVA remains the optimum statistical method for the analysis of continuous outcomes in RCTs, in terms of bias, precision and statistical power. PMID:24712304

A more powerful test based on ratio distribution for retention noninferiority hypothesis.

PubMed

Deng, Ling; Chen, Gang

2013-03-11

Rothmann et al. ( 2003 ) proposed a method for the statistical inference of fraction retention noninferiority (NI) hypothesis. A fraction retention hypothesis is defined as a ratio of the new treatment effect verse the control effect in the context of a time to event endpoint. One of the major concerns using this method in the design of an NI trial is that with a limited sample size, the power of the study is usually very low. This makes an NI trial not applicable particularly when using time to event endpoint. To improve power, Wang et al. ( 2006 ) proposed a ratio test based on asymptotic normality theory. Under a strong assumption (equal variance of the NI test statistic under null and alternative hypotheses), the sample size using Wang's test was much smaller than that using Rothmann's test. However, in practice, the assumption of equal variance is generally questionable for an NI trial design. This assumption is removed in the ratio test proposed in this article, which is derived directly from a Cauchy-like ratio distribution. In addition, using this method, the fundamental assumption used in Rothmann's test, that the observed control effect is always positive, that is, the observed hazard ratio for placebo over the control is greater than 1, is no longer necessary. Without assuming equal variance under null and alternative hypotheses, the sample size required for an NI trial can be significantly reduced if using the proposed ratio test for a fraction retention NI hypothesis.

Developing stepped care treatment for depression (STEPS): study protocol for a pilot randomised controlled trial.

PubMed

Hill, Jacqueline J; Kuyken, Willem; Richards, David A

2014-11-20

Stepped care is recommended and implemented as a means to organise depression treatment. Compared with alternative systems, it is assumed to achieve equivalent clinical effects and greater efficiency. However, no trials have examined these assumptions. A fully powered trial of stepped care compared with intensive psychological therapy is required but a number of methodological and procedural uncertainties associated with the conduct of a large trial need to be addressed first. STEPS (Developing stepped care treatment for depression) is a mixed methods study to address uncertainties associated with a large-scale evaluation of stepped care compared with high-intensity psychological therapy alone for the treatment of depression. We will conduct a pilot randomised controlled trial with an embedded process study. Quantitative trial data on recruitment, retention and the pathway of patients through treatment will be used to assess feasibility. Outcome data on the effects of stepped care compared with high-intensity therapy alone will inform a sample size calculation for a definitive trial. Qualitative interviews will be undertaken to explore what people think of our trial methods and procedures and the stepped care intervention. A minimum of 60 patients with Major Depressive Disorder will be recruited from an Improving Access to Psychological Therapies service and randomly allocated to receive stepped care or intensive psychological therapy alone. All treatments will be delivered at clinic facilities within the University of Exeter. Quantitative patient-related data on depressive symptoms, worry and anxiety and quality of life will be collected at baseline and 6 months. The pilot trial and interviews will be undertaken concurrently. Quantitative and qualitative data will be analysed separately and then integrated. The outcomes of this study will inform the design of a fully powered randomised controlled trial to evaluate the effectiveness and efficiency of stepped care. Qualitative data on stepped care will be of immediate interest to patients, clinicians, service managers, policy makers and guideline developers. A more informed understanding of the feasibility of a large trial will be obtained than would be possible from a purely quantitative (or qualitative) design. Current Controlled Trials ISRCTN66346646 registered on 2 July 2014.

Improvement of stance control and muscle performance induced by focal muscle vibration in young-elderly women: a randomized controlled trial.

PubMed

Filippi, Guido M; Brunetti, Orazio; Botti, Fabio M; Panichi, Roberto; Roscini, Mauro; Camerota, Filippo; Cesari, Matteo; Pettorossi, Vito E

2009-12-01

Filippi GM, Brunetti O, Botti FM, Panichi R, Roscini M, Camerota F, Cesari M, Pettorossi VE. Improvement of stance control and muscle performance induced by focal muscle vibration in young-elderly women: a randomized controlled trial. To determine the effect of a particular protocol of mechanical vibration, applied focally and repeatedly (repeated muscle vibration [rMV]) on the quadriceps muscles, on stance and lower-extremity muscle power of young-elderly women. Double-blind randomized controlled trial; 3-month follow-up after intervention. Human Physiology Laboratories, University of Perugia, Italy. Sedentary women volunteers (N=60), randomized in 3 groups (mean age +/- SD, 65.3+/-4.2y; range, 60-72). rMV (100Hz, 300-500microm, in three 10-minute sessions a day for 3 consecutive days) was applied to voluntary contracted quadriceps (vibrated and contracted group) and relaxed quadriceps (vibrated and relaxed group). A third group received placebo stimulation (nonvibrated group). Area of sway of the center of pressure, vertical jump height, and leg power. Twenty-four hours after the end of the complete series of applications, the area of sway of the center of pressure decreased significantly by approximately 20%, vertical jump increased by approximately 55%, and leg power increased by approximately 35%. These effects were maintained for at least 90 days after treatment. rMV is a short-lasting and noninvasive protocol that can significantly and persistently improve muscle performance in sedentary young-elderly women.

Validation of the Efficacy of a Solar-Thermal Powered Autoclave System for Off-Grid Medical Instrument Wet Sterilization

PubMed Central

Kaseman, Tremayne; Boubour, Jean; Schuler, Douglas A.

2012-01-01

This work describes the efficacy of a solar-thermal powered autoclave used for the wet sterilization of medical instruments in off-grid settings where electrical power is not readily available. Twenty-seven trials of the solar-thermal powered system were run using an unmodified non-electric autoclave loaded with a simulated bundle of medical instruments and biological test agents. Results showed that in 100% of the trials the autoclave achieved temperatures in excess of 121°C for 30 minutes, indicator tape displayed visible reactions to steam sterilization, and biological tests showed that microbial agents had been eliminated, in compliance with the Centers for Disease Control and Prevention requirements for efficacious wet sterilization. PMID:22848098

Validation of the efficacy of a solar-thermal powered autoclave system for off-grid medical instrument wet sterilization.

PubMed

Kaseman, Tremayne; Boubour, Jean; Schuler, Douglas A

2012-10-01

This work describes the efficacy of a solar-thermal powered autoclave used for the wet sterilization of medical instruments in off-grid settings where electrical power is not readily available. Twenty-seven trials of the solar-thermal powered system were run using an unmodified non-electric autoclave loaded with a simulated bundle of medical instruments and biological test agents. Results showed that in 100% of the trials the autoclave achieved temperatures in excess of 121°C for 30 minutes, indicator tape displayed visible reactions to steam sterilization, and biological tests showed that microbial agents had been eliminated, in compliance with the Centers for Disease Control and Prevention requirements for efficacious wet sterilization.

POWERS forID: Personalized Online Weight and Exercise Response System for Individuals with Intellectual Disability: study protocol for a randomized controlled trial.

PubMed

Neumeier, William H; Guerra, Nichole; Thirumalai, Mohanraj; Geer, Betty; Ervin, David; Rimmer, James H

2017-10-23

Intellectual disability (ID) is characterized by limitations in intellectual functioning and adaptive behavior. Adults with ID exhibit higher rates of obesity and poorer health status compared to the general population. Continuity of care and barriers to health-related activities may contribute to the poorer health status observed in this population. To address this problem, a tailored weight management online health information and communication technology platform, known as POWERS forID , was developed and is being tested to determine if this delivery mechanism can improve weight maintenance/weight loss in adults with ID. Obese adults with mild-to-moderate ID (n = 70) are randomized to the POWERS forID intervention or control group for a 24-week trial. Each group undergoes an assessment that includes body weight, waist circumference, and percent body fat at baseline and at weeks 6, 12, and 24. Physical activity barriers, healthy eating barriers, food frequency, and psychosocial wellbeing are measured at baseline and at weeks 12 and 24. Blood lipids are assessed at baseline and 24 weeks. Participants randomized to POWERS forID receive access to the POWERS forID website and calls from a health coach (weekly during weeks 1-12, biweekly during weeks 13-24). The health coach employs motivational interviewing techniques adapted for individuals with ID to promote behavior change. Participants randomized to the control group receive standard clinical weight-loss care. Differences in weight, waist circumference, blood lipids, percent body fat, and psychosocial self-report will be assessed. Barriers and facilitators of implementation as well as perception of study outcomes will be conducted via qualitative analysis. POWERS forID is a novel information and communication technology platform designed to address health needs for adults with ID. This article describes the development and components of POWERS forID . The overall aim is to assess usability and feasibility of POWERS forID for promoting weight loss for obese adults with ID over the course of a 24-week randomized control trial. Clinicaltrials.gov, NCT03139760 . Registered on XXX.

Influence of environmental temperature on 40 km cycling time-trial performance.

PubMed

Peiffer, Jeremiah J; Abbiss, Chris R

2011-06-01

The purpose of this study was to examine the effect of environmental temperature on variability in power output, self-selected pacing strategies, and performance during a prolonged cycling time trial. Nine trained male cyclists randomly completed four 40 km cycling time trials in an environmental chamber at 17°C, 22°C, 27°C, and 32°C (40% RH). During the time trials, heart rate, core body temperature, and power output were recorded. The variability in power output was assessed with the use of exposure variation analysis. Mean 40 km power output was significantly lower during 32°C (309 ± 35 W) compared with 17°C (329 ± 31 W), 22°C (324 ± 34 W), and 27°C (322 ± 32 W). In addition, greater variability in power production was observed at 32°C compared with 17°C, as evidenced by a lower (P = .03) standard deviation of the exposure variation matrix (2.9 ± 0.5 vs 3.5 ± 0.4 units, respectively). Core temperature was greater (P < .05) at 32°C compared with 17°C and 22°C from 30 to 40 km, and the rate of rise in core temperature throughout the 40 km time trial was greater (P < .05) at 32°C (0.06 ± 0.04°C·km-1) compared with 17°C (0.05 ± 0.05°C·km-1). This study showed that time-trial performance is reduced under hot environmental conditions, and is associated with a shift in the composition of power output. These finding provide insight into the control of pacing strategies during exercise in the heat.

Group-sequential three-arm noninferiority clinical trial designs

PubMed Central

Ochiai, Toshimitsu; Hamasaki, Toshimitsu; Evans, Scott R.; Asakura, Koko; Ohno, Yuko

2016-01-01

We discuss group-sequential three-arm noninferiority clinical trial designs that include active and placebo controls for evaluating both assay sensitivity and noninferiority. We extend two existing approaches, the fixed margin and fraction approaches, into a group-sequential setting with two decision-making frameworks. We investigate the operating characteristics including power, Type I error rate, maximum and expected sample sizes, as design factors vary. In addition, we discuss sample size recalculation and its’ impact on the power and Type I error rate via a simulation study. PMID:26892481

Effects of low-volume high-intensity interval training (HIT) on fitness in adults: a meta-analysis of controlled and non-controlled trials.

PubMed

Weston, Matthew; Taylor, Kathryn L; Batterham, Alan M; Hopkins, Will G

2014-07-01

Low-volume high-intensity interval training (HIT) appears to be an efficient and practical way to develop physical fitness. Our objective was to estimate meta-analysed mean effects of HIT on aerobic power (maximum oxygen consumption [VO(2max)] in an incremental test) and sprint fitness (peak and mean power in a 30-s Wingate test). Five databases (PubMed, MEDLINE, Scopus, BIOSIS and Web of Science) were searched for original research articles published up to January 2014. Search terms included 'high intensity', 'HIT', 'sprint', 'fitness' and 'VO(2max)'. Inclusion criteria were fitness assessed pre- and post-training; training period ≥2 weeks; repetition duration 30-60 s; work/rest ratio <1.0; exercise intensity described as maximal or near maximal; adult subjects aged >18 years. The final data set consisted of 55 estimates from 32 trials for VO(2max), 23 estimates from 16 trials for peak sprint power, and 19 estimates from 12 trials for mean sprint power. Effects on fitness were analysed as percentages via log transformation. Standard errors calculated from exact p values (where reported) or imputed from errors of measurement provided appropriate weightings. Fixed effects in the meta-regression model included type of study (controlled, uncontrolled), subject characteristics (sex, training status, baseline fitness) and training parameters (number of training sessions, repetition duration, work/rest ratio). Probabilistic magnitude-based inferences for meta-analysed effects were based on standardized thresholds for small, moderate and large changes (0.2, 0.6 and 1.2, respectively) derived from between-subject standard deviations (SDs) for baseline fitness. A mean low-volume HIT protocol (13 training sessions, 0.16 work/rest ratio) in a controlled trial produced a likely moderate improvement in the VO(2max) of active non-athletic males (6.2 %; 90 % confidence limits ±3.1 %), when compared with control. There were possibly moderate improvements in the VO(2max) of sedentary males (10.0 %; ±5.1 %) and active non-athletic females (3.6 %; ±4.3 %) and a likely small increase for sedentary females (7.3 %; ±4.8 %). The effect on the VO(2max) of athletic males was unclear (2.7 %; ±4.6 %). A possibly moderate additional increase was likely for subjects with a 10 mL·kg(-1)·min(-1) lower baseline VO(2max) (3.8 %; ±2.5 %), whereas the modifying effects of sex and difference in exercise dose were unclear. The comparison of HIT with traditional endurance training was unclear (-1.6 %; ±4.3 %). Unexplained variation between studies was 2.0 % (SD). Meta-analysed effects of HIT on Wingate peak and mean power were unclear. Low-volume HIT produces moderate improvements in the aerobic power of active non-athletic and sedentary subjects. More studies are needed to resolve the unclear modifying effects of sex and HIT dose on aerobic power and the unclear effects on sprint fitness.

Transabdominal amnioinfusion for preterm premature rupture of membranes: a systematic review and metaanalysis of randomized and observational studies.

PubMed

Porat, Shay; Amsalem, Hagai; Shah, Prakesh S; Murphy, Kellie E

2012-11-01

The purpose of this study was to review systematically the efficacy of transabdominal amnioinfusion (TA) in early preterm premature rupture of membranes (PPROM). We conducted a literature search of EMBASE, MEDLINE, and ClinicalTrials.gov databases and identified studies in which TA was used in cases of proven PPROM and oligohydramnios. Risk of bias was assessed for observational studies and randomized controlled trials. Primary outcomes were latency period and perinatal mortality rates. Four observational studies (n = 147) and 3 randomized controlled trials (n = 165) were eligible. Pooled latency period was 14.4 (range, 8.2-20.6) and 11.41 (range -3.4 to 26.2) days longer in the TA group in the observational and the randomized controlled trials, respectively. Perinatal mortality rates were reduced among the treatment groups in both the observational studies (odds ratio, 0.12; 95% confidence interval, 0.02-0.61) and the randomized controlled trials (odds ratio, 0.33; 95% confidence interval, 0.10-1.12). Serial TA for early PPROM may improve early PPROM-associated morbidity and mortality rates. Additional adequately powered randomized control trials are needed. Copyright © 2012 Mosby, Inc. All rights reserved.

Cortical theta wanes for language.

PubMed

Hermes, Dora; Miller, Kai J; Vansteensel, Mariska J; Edwards, Erik; Ferrier, Cyrille H; Bleichner, Martin G; van Rijen, Peter C; Aarnoutse, Erik J; Ramsey, Nick F

2014-01-15

The role of low frequency oscillations in language areas is not yet understood. Using ECoG in six human subjects, we studied whether different language regions show prominent power changes in a specific rhythm, in similar manner as the alpha rhythm shows the most prominent power changes in visual areas. Broca's area and temporal language areas were localized in individual subjects using fMRI. In these areas, the theta rhythm showed the most pronounced power changes and theta power decreased significantly during verb generation. To better understand the role of this language-related theta decrease, we then studied the interaction between low frequencies and local neuronal activity reflected in high frequencies. Amplitude-amplitude correlations showed that theta power correlated negatively with high frequency activity, specifically across verb generation trials. Phase-amplitude coupling showed that during control trials, high frequency power was coupled to theta phase, but this coupling decreased significantly during verb generation trials. These results suggest a dynamic interaction between the neuronal mechanisms underlying the theta rhythm and local neuronal activity in language areas. As visual areas show a pronounced alpha rhythm that may reflect pulsed inhibition, language regions show a pronounced theta rhythm with highly similar features. © 2013.

Contralateral Delay Activity Tracks Fluctuations in Working Memory Performance.

PubMed

Adam, Kirsten C S; Robison, Matthew K; Vogel, Edward K

2018-01-08

Neural measures of working memory storage, such as the contralateral delay activity (CDA), are powerful tools in working memory research. CDA amplitude is sensitive to working memory load, reaches an asymptote at known behavioral limits, and predicts individual differences in capacity. An open question, however, is whether neural measures of load also track trial-by-trial fluctuations in performance. Here, we used a whole-report working memory task to test the relationship between CDA amplitude and working memory performance. If working memory failures are due to decision-based errors and retrieval failures, CDA amplitude would not differentiate good and poor performance trials when load is held constant. If failures arise during storage, then CDA amplitude should track both working memory load and trial-by-trial performance. As expected, CDA amplitude tracked load (Experiment 1), reaching an asymptote at three items. In Experiment 2, we tracked fluctuations in trial-by-trial performance. CDA amplitude was larger (more negative) for high-performance trials compared with low-performance trials, suggesting that fluctuations in performance were related to the successful storage of items. During working memory failures, participants oriented their attention to the correct side of the screen (lateralized P1) and maintained covert attention to the correct side during the delay period (lateralized alpha power suppression). Despite the preservation of attentional orienting, we found impairments consistent with an executive attention theory of individual differences in working memory capacity; fluctuations in executive control (indexed by pretrial frontal theta power) may be to blame for storage failures.

Frontal Preparatory Neural Oscillations Associated with Cognitive Control: A Developmental Study Comparing Young Adults and Adolescents

PubMed Central

Hwang, Kai; Ghuman, Avniel S.; Manoach, Dara S.; Jones, Stephanie R.; Luna, Beatriz

2016-01-01

Functional magnetic resonance imaging (fMRI) studies suggest that age-related changes in the frontal cortex may underlie developmental improvements in cognitive control. In the present study we used magnetoencephalography (MEG) to identify frontal oscillatory neurodynamics that support age-related improvements in cognitive control during adolescence. We characterized the differences in neural oscillations in adolescents and adults during the preparation to suppress a prepotent saccade (antisaccade trials – AS) compared to preparing to generate a more automatic saccade (prosaccade trials – PS). We found that for adults, AS were associated with increased beta-band (16–38 Hz) power in the dorsal lateral prefrontal cortex (DLPFC), enhanced alpha- to low beta-band (10–18 Hz) power in the frontal eye field (FEF) that predicted performance, and increased cross-frequency alpha-beta (10–26 Hz) amplitude coupling between the DLPFC and the FEF. Developmental comparisons between adults and adolescents revealed similar engagement of DLPFC beta-band power but weaker FEF alpha-band power, and lower cross-frequency coupling between the DLPFC and the FEF in adolescents. These results suggest that lateral prefrontal neural activity associated with cognitive control is adult-like by adolescence; the development of cognitive control from adolescence to adulthood is instead associated with increases in prefrontal connectivity and strengthening of inhibition signaling for suppressing task-incompatible processes. PMID:27173759

REFOCUS Trial: protocol for a cluster randomised controlled trial of a pro-recovery intervention within community based mental health teams.

PubMed

Slade, Mike; Bird, Victoria; Le Boutillier, Clair; Williams, Julie; McCrone, Paul; Leamy, Mary

2011-11-23

There is a consensus about the importance of 'recovery' in mental health services, but the evidence base is limited. A two centre, cluster randomised controlled trial. Participants are community-based mental health teams, and service users aged 18-65 years with a primary clinical diagnosis of psychosis. In relation to the REFOCUS Manual researchintorecovery.com/refocus, which describes a 12-month, pro-recovery intervention based on the REFOCUS Model, the objectives are: (1) To establish the effectiveness of the intervention described in the REFOCUS Manual; (2) To validate the REFOCUS Model; (3) To establish and optimise trial parameters for the REFOCUS Manual; and (4) To understand the relationship between clinical outcomes and recovery outcomes. The hypothesis for the main study is that service users in the intervention arm will experience significantly greater increases in measures of personal recovery (as measured by the QPR) compared to service users receiving care from control teams. The hypothesis for the secondary study is that black service users in the intervention arm will experience significantly greater increases in measures of personal recovery (as measured by the QPR) and client satisfaction (as measured by the CSQ) compared to Black service users receiving care from control teams. The intervention comprises treatment as usual plus two components: recovery-promoting relationships and working practices. The control condition is treatment as usual. The primary outcme is the Process of Recovery Questionnaire (QPR). Secondary outcomes are satisfaction, Goal setting - Personal Primary Outcome, hope, well-being, empowerment, and quality of life. Primary outcomes for the secondary study will be QPR and satisfaction. Cost data will be estimated, and clinical outcomes will also be reported (symptomatology, need, social disability, functioning). 29 teams (15 intervention and 14 control) will be randomised. Within each team, 15 services users will be randomly chosen, giving a total sample of 435 service users (225 in intervention and 210 in control). Power for the main study: 336 service users will give power to detect a medium effect size of 0.4 (alpha 0.05, power = 0.8) on both QPR sub-scales. Power for the secondary study: 89 participants will give power to detect an effect size of 0.67 on both QPR sub-scales and on CSQ. A range of approaches are used to minimise bias, although service users and clinicians cannot be blinded. This cluster-RCT will evaluate a pro-recovery intervention in community mental health teams. ISRCTN: ISRCTN02507940.

A Bayesian adaptive design for biomarker trials with linked treatments

PubMed Central

Wason, James M S; Abraham, Jean E; Baird, Richard D; Gournaris, Ioannis; Vallier, Anne-Laure; Brenton, James D; Earl, Helena M; Mander, Adrian P

2015-01-01

Background: Response to treatments is highly heterogeneous in cancer. Increased availability of biomarkers and targeted treatments has led to the need for trial designs that efficiently test new treatments in biomarker-stratified patient subgroups. Methods: We propose a novel Bayesian adaptive randomisation (BAR) design for use in multi-arm phase II trials where biomarkers exist that are potentially predictive of a linked treatment's effect. The design is motivated in part by two phase II trials that are currently in development. The design starts by randomising patients to the control treatment or to experimental treatments that the biomarker profile suggests should be active. At interim analyses, data from treated patients are used to update the allocation probabilities. If the linked treatments are effective, the allocation remains high; if ineffective, the allocation changes over the course of the trial to unlinked treatments that are more effective. Results: Our proposed design has high power to detect treatment effects if the pairings of treatment with biomarker are correct, but also performs well when alternative pairings are true. The design is consistently more powerful than parallel-groups stratified trials. Conclusions: This BAR design is a powerful approach to use when there are pairings of biomarkers with treatments available for testing simultaneously. PMID:26263479

Use of placebo controls in the evaluation of surgery: systematic review

PubMed Central

Judge, Andrew; Hopewell, Sally; Collins, Gary S; Dean, Benjamin J F; Rombach, Ines; Brindley, David; Savulescu, Julian; Beard, David J; Carr, Andrew J

2014-01-01

Objective To investigate whether placebo controls should be used in the evaluation of surgical interventions. Design Systematic review. Data sources We searched Medline, Embase, and the Cochrane Controlled Trials Register from their inception to November 2013. Study selection Randomised clinical trials comparing any surgical intervention with placebo. Surgery was defined as any procedure that both changes the anatomy and requires a skin incision or use of endoscopic techniques. Data extraction Three reviewers (KW, BJFD, IR) independently identified the relevant trials and extracted data on study details, outcomes, and harms from included studies. Results In 39 out of 53 (74%) trials there was improvement in the placebo arm and in 27 (51%) trials the effect of placebo did not differ from that of surgery. In 26 (49%) trials, surgery was superior to placebo but the magnitude of the effect of the surgical intervention over that of the placebo was generally small. Serious adverse events were reported in the placebo arm in 18 trials (34%) and in the surgical arm in 22 trials (41.5%); in four trials authors did not specify in which arm the events occurred. However, in many studies adverse events were unrelated to the intervention or associated with the severity of the condition. The existing placebo controlled trials investigated only less invasive procedures that did not involve laparotomy, thoracotomy, craniotomy, or extensive tissue dissection. Conclusions Placebo controlled trial is a powerful, feasible way of showing the efficacy of surgical procedures. The risks of adverse effects associated with the placebo are small. In half of the studies, the results provide evidence against continued use of the investigated surgical procedures. Without well designed placebo controlled trials of surgery, ineffective treatment may continue unchallenged. PMID:24850821

Human subthalamic nucleus-medial frontal cortex theta phase coherence is involved in conflict and error related cortical monitoring.

PubMed

Zavala, Baltazar; Tan, Huiling; Ashkan, Keyoumars; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Zaghloul, Kareem; Brown, Peter

2016-08-15

The medial prefrontal cortex (mPFC) is thought to control the shift from automatic to controlled action selection when conflict is present or when mistakes have been recently committed. Growing evidence suggests that this process involves frequency specific communication in the theta (4-8Hz) band between the mPFC and the subthalamic nucleus (STN), which is the main target of deep brain stimulation (DBS) for Parkinson's disease. Key in this hypothesis is the finding that DBS can lead to impulsivity by disrupting the correlation between higher mPFC oscillations and slower reaction times during conflict. In order to test whether theta band coherence between the mPFC and the STN underlies adjustments to conflict and to errors, we simultaneously recorded mPFC and STN electrophysiological activity while DBS patients performed an arrowed flanker task. These recordings revealed higher theta phase coherence between the two sites during the high conflict trials relative to the low conflict trials. These differences were observed soon after conflicting arrows were displayed, but before a response was executed. Furthermore, trials that occurred after an error was committed showed higher phase coherence relative to trials that followed a correct trial, suggesting that mPFC-STN connectivity may also play a role in error related adjustments in behavior. Interestingly, the phase coherence we observed occurred before increases in theta power, implying that the theta phase and power may influence behavior at separate times during cortical monitoring. Finally, we showed that pre-stimulus differences in STN theta power were related to the reaction time on a given trial, which may help adjust behavior based on the probability of observing conflict during a task. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Simulation-based power calculations for planning a two-stage individual participant data meta-analysis.

PubMed

Ensor, Joie; Burke, Danielle L; Snell, Kym I E; Hemming, Karla; Riley, Richard D

2018-05-18

Researchers and funders should consider the statistical power of planned Individual Participant Data (IPD) meta-analysis projects, as they are often time-consuming and costly. We propose simulation-based power calculations utilising a two-stage framework, and illustrate the approach for a planned IPD meta-analysis of randomised trials with continuous outcomes where the aim is to identify treatment-covariate interactions. The simulation approach has four steps: (i) specify an underlying (data generating) statistical model for trials in the IPD meta-analysis; (ii) use readily available information (e.g. from publications) and prior knowledge (e.g. number of studies promising IPD) to specify model parameter values (e.g. control group mean, intervention effect, treatment-covariate interaction); (iii) simulate an IPD meta-analysis dataset of a particular size from the model, and apply a two-stage IPD meta-analysis to obtain the summary estimate of interest (e.g. interaction effect) and its associated p-value; (iv) repeat the previous step (e.g. thousands of times), then estimate the power to detect a genuine effect by the proportion of summary estimates with a significant p-value. In a planned IPD meta-analysis of lifestyle interventions to reduce weight gain in pregnancy, 14 trials (1183 patients) promised their IPD to examine a treatment-BMI interaction (i.e. whether baseline BMI modifies intervention effect on weight gain). Using our simulation-based approach, a two-stage IPD meta-analysis has < 60% power to detect a reduction of 1 kg weight gain for a 10-unit increase in BMI. Additional IPD from ten other published trials (containing 1761 patients) would improve power to over 80%, but only if a fixed-effect meta-analysis was appropriate. Pre-specified adjustment for prognostic factors would increase power further. Incorrect dichotomisation of BMI would reduce power by over 20%, similar to immediately throwing away IPD from ten trials. Simulation-based power calculations could inform the planning and funding of IPD projects, and should be used routinely.

The Neural Substrates of Self-Evaluation of Mental Fatigue: A Magnetoencephalography Study

PubMed Central

Ishii, Akira; Tanaka, Masaaki; Watanabe, Yasuyoshi

2014-01-01

There have been several studies of the neural mechanisms underlying sensation of fatigue. However, little is known about the neural mechanisms underlying self-evaluation of the level of fatigue. The aim of this study was to identify the neural substrates involved in self-evaluation of the level of mental fatigue. We used magnetoencephalography (MEG) with high temporal resolution on 14 healthy participants. During MEG recordings, participants were asked to evaluate their level of mental fatigue in time with execution cues (evaluation trials) or to do nothing in time with execution cues (control trials). The MEG data were analyzed with equivalent current dipole (ECD) and spatial filtering methods to localize the neural activity related to the evaluation of mental fatigue. The daily level of fatigue sensation was assessed using the Checklist Individual Strength questionnaire. In evaluation trials, ECDs were observed in the posterior cingulate cortex (PCC) in seven of 14 participants, with a mean latency of 366.0 ms. The proportion of the participants with ECDs in the PCC was higher in evaluation trials than in control trials (P<0.05, McNemar test). The extent of the decreased delta band power in the PCC (Brodmann’s area 31) 600–700 ms after the onset of the execution cue and that in the dorsolateral prefrontal cortex (DLPFC; Brodmann’s area 9) 800–900 ms after the onset of the execution cue were greater in the evaluation trials than in the control trials. The decrease in delta band power in the DLPFC was positively related to that in the PCC and to the daily level of fatigue sensation. These data suggest that the PCC and DLPFC are involved in the self-evaluation of mental fatigue. PMID:24752677

A protocol for a trial of homeopathic treatment for irritable bowel syndrome

PubMed Central

2012-01-01

Background Irritable bowel syndrome is a chronic condition with no known cure. Many sufferers seek complementary and alternative medicine including homeopathic treatment. However there is much controversy as to the effectiveness of homeopathic treatment. This three-armed study seeks to explore the effectiveness of individualised homeopathic treatment plus usual care compared to both an attention control plus usual care and usual care alone, for patients with irritable bowel syndrome. Methods/design This is a three-armed pragmatic randomised controlled trial using the cohort multiple randomised trial methodology. Patients are recruited to an irritable bowel syndrome cohort from primary and secondary care using GP databases and consultants lists respectively. From this cohort patients are randomly selected to be offered, 5 sessions of homeopathic treatment plus usual care, 5 sessions of supportive listening plus usual care or usual care alone. The primary clinical outcome is the Irritable Bowel Syndrome Symptom Severity at 26 weeks. From a power calculation, it is estimated that 33 people will be needed for the homeopathic treatment arm and 132 for the usual care arm, to detect a minimal clinical difference at 80 percent power and 5 percent significance allowing for loss to follow up. An unequal group size has been used for reasons of cost. Analysis will be by intention to treat and will compare homeopathic treatment with usual care at 26 weeks as the primary analysis, and homeopathic treatment with supportive listening as an additional analysis. Discussion This trial has received NHS approval and results are expected in 2013. Trial registration Current Controlled Trials ISRCTN90651143 PMID:23131064

Extent and quality of systematic review evidence related to minimum intervention in dentistry: essential oils, powered toothbrushes, triclosan, xylitol.

PubMed

Mickenautsch, Steffen; Yengopal, Veerasamy

2011-08-01

To investigate extent and quality of current systematic review evidence regarding: powered toothbrushes, triclosan toothpaste, essential oil mouthwashes, xylitol chewing gum. Five databases were searched for systematic reviews until 13 November 2010. relevant to topic, systematic review according to title and/or abstract, published in English. Article exclusion criteria were based on QUOROM recommendations for the reporting of systematic review methods. Systematic review quality was judged using the AMSTAR tool. All trials included by reviews were assessed for selection bias. 119 articles were found, of which 11 systematic reviews were included. Of these, six were excluded and five accepted: one for triclosan toothpaste; one for xylitol chewing gum; two for powered toothbrushes; one for essential oil mouthwashes. AMSTAR scores: triclosan toothpaste 7; powered toothbrushes 9 and 11; xylitol chewing gum 9; essential oil mouthwashes 8. In total, 75 (out of 76) reviewed trials were identified. In-depth assessment showed a high risk of selection bias for all trials. The extent of available systematic review evidence is low. Although the few identified systematic reviews could be rated as of medium and high quality, the validity of their conclusions needs to be treated with caution, owing to high risk of selection bias in the reviewed trials. High quality randomised control trials are needed in order to provide convincing evidence regarding true clinical efficacy. © 2011 FDI World Dental Federation.

'We all want to succeed, but we've also got to be realistic about what is happening': an ethnographic study of relationships in trial oversight and their impact.

PubMed

Daykin, Anne; Selman, Lucy E; Cramer, Helen; McCann, Sharon; Shorter, Gillian W; Sydes, Matthew R; Gamble, Carrol; Macefield, Rhiannon; Lane, J Athene; Shaw, Alison

2017-12-22

The oversight and conduct of a randomised controlled trial involves several stakeholders, including a Trial Steering Committee (TSC), Trial Management Group (TMG), Data Monitoring Committee (DMC), funder and sponsor. We aimed to examine how the relationships between these stakeholders affect the trial oversight process and its rigour, to inform future revision of Good Clinical Practice guidelines. Using an ethnographic study design, we observed the oversight processes of eight trials and conducted semi-structured interviews with members of the trials' TSCs and TMGs, plus other relevant informants, including sponsors and funders of trials. Data were analysed thematically, and findings triangulated and integrated to give a multi-perspective account of current oversight practices in the UK. Eight TSC and six TMG meetings from eight trials were observed and audio-recorded, and 66 semi-structured interviews conducted with 52 purposively sampled key informants. Five themes are presented: (1) Collaboration within the TMG and role of the CTU; (2) Collaboration and conflict between oversight committees; (3) Priorities; (4) Communication between trial oversight groups and (5) Power and accountability. There was evidence of collaborative relationships, based on mutual respect, between CTUs, TMGs and TSCs, but also evidence of conflict. Relationships between trial oversight committees were influenced by stakeholders' priorities, both organisational and individual. Good communication following specific, recognised routes played a central role in ensuring that relationships were productive and trial oversight efficient. Participants described the possession of power over trials as a shifting political landscape, and there was lack of clarity regarding the roles and accountability of each committee, the sponsor and funder. Stakeholders' perceptions of their own power over a trial, and the power of others, influenced relationships between those involved in trial oversight. Recent developments in trial design and conduct have been accompanied by changes in roles and relationships between trial oversight groups. Recognising and respecting the value of differing priorities among those involved in running trials is key to successful relationships between committees, funders and sponsors. Clarity regarding appropriate lines of communication, roles and accountability is needed. We present 10 evidence-based recommendations to inform updates to international trial guidance, particularly the Medical Research Council guidelines.

Clinical trial design for orthodontists.

PubMed

Pandis, Nikolaos; Cobourne, Martyn T

2013-06-01

High-quality research should form the basis of all clinical practice. Randomized controlled trials currently provide the gold standard for investigating the effectiveness of treatment interventions and these are increasingly being used in orthodontics. Here we discuss the reasons why this form of investigation provides the most useful evidence for assessing treatment outcome. The methods available to achieve true randomization, a fundamental component in the design of these trials, are also discussed. In addition, we focus on how to minimize bias in clinical research, not only during the design and management of a trial, but also when disseminating results. We focus on the importance of using control groups correctly and describe methods that are available to adequately power a trial. Finally, we emphasise the importance of accurate and transparent reporting, which facilitates correct communication and assessment of the evidence.

Feasibility of high-intensity interval training and moderate-intensity continuous training in adults with inactive or mildly active Crohn's disease: study protocol for a randomised controlled trial.

PubMed

Tew, Garry A; Carpenter, Roger; Seed, Michael; Anderson, Simon; Langmead, Louise; Fairhurst, Caroline; Bottoms, Lindsay

2017-01-01

Structured exercise training has been proposed as a useful adjunctive therapy for Crohn's disease by improving immune function and psychological health, reducing fatigue and promoting gains in muscle and bone strength. However, the evidence for exercise in Crohn's disease is sparse, with only a handful of small prospective trials [1, 2], with methodological limitations, including the use of non-randomised and non-controlled study designs and small sample sizes. Here, we describe the protocol for a study that aims to assess the feasibility and acceptability of two common types of exercise training-high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)-in adults with inactive or mildly active Crohn's disease (CD). This is a randomised, controlled, assessor-blinded, feasibility trial with three parallel groups. Forty-five adults with inactive or mildly active Crohn's disease will be randomly assigned 1:1:1 to HIIT, MICT or usual care control. Participants in the HIIT and MICT groups will be invited to undertake three sessions of supervised exercise each week for 12 consecutive weeks. HIIT sessions will consist of ten 1-min intervals of cycling exercise at 90% of peak power output separated by 1 min of active recovery. MICT sessions will involve 30 min of continuous cycling at 35% of peak power output. Participants will be assessed before randomisation and 13 and 26 weeks after randomisation. Feasibility outcomes include rates of recruitment, retention and adherence. Interviews with participants will explore the acceptability of the exercise programmes and study procedures. Clinical/health outcomes include cardiorespiratory fitness, body mass index, resting blood pressure, markers of disease activity (faecal calprotectin and Crohn's Disease Activity Index) and activated T cell cytokine profiles. Study questionnaires include the Inflammatory Bowel Disease Quality of Life Questionnaire, EQ-5D-5L, IBD Fatigue Scale, Hospital and Anxiety Depression Scale, and International Physical Activity Questionnaire. This study will provide useful information on the feasibility and acceptability of supervised exercise training in adults with inactive and mildly active Crohn's disease and will inform the design of a subsequent, adequately powered, multi-centre trial. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN13021107). Date registration assigned was 02/12/2015.

Comparison of Time-to-First Event and Recurrent Event Methods in Randomized Clinical Trials.

PubMed

Claggett, Brian; Pocock, Stuart; Wei, L J; Pfeffer, Marc A; McMurray, John J V; Solomon, Scott D

2018-03-27

Background -Most Phase-3 trials feature time-to-first event endpoints for their primary and/or secondary analyses. In chronic diseases where a clinical event can occur more than once, recurrent-event methods have been proposed to more fully capture disease burden and have been assumed to improve statistical precision and power compared to conventional "time-to-first" methods. Methods -To better characterize factors that influence statistical properties of recurrent-events and time-to-first methods in the evaluation of randomized therapy, we repeatedly simulated trials with 1:1 randomization of 4000 patients to active vs control therapy, with true patient-level risk reduction of 20% (i.e. RR=0.80). For patients who discontinued active therapy after a first event, we assumed their risk reverted subsequently to their original placebo-level risk. Through simulation, we varied a) the degree of between-patient heterogeneity of risk and b) the extent of treatment discontinuation. Findings were compared with those from actual randomized clinical trials. Results -As the degree of between-patient heterogeneity of risk was increased, both time-to-first and recurrent-events methods lost statistical power to detect a true risk reduction and confidence intervals widened. The recurrent-events analyses continued to estimate the true RR=0.80 as heterogeneity increased, while the Cox model produced estimates that were attenuated. The power of recurrent-events methods declined as the rate of study drug discontinuation post-event increased. Recurrent-events methods provided greater power than time-to-first methods in scenarios where drug discontinuation was ≤30% following a first event, lesser power with drug discontinuation rates of ≥60%, and comparable power otherwise. We confirmed in several actual trials in chronic heart failure that treatment effect estimates were attenuated when estimated via the Cox model and that increased statistical power from recurrent-events methods was most pronounced in trials with lower treatment discontinuation rates. Conclusions -We find that the statistical power of both recurrent-events and time-to-first methods are reduced by increasing heterogeneity of patient risk, a parameter not included in conventional power and sample size formulas. Data from real clinical trials are consistent with simulation studies, confirming that the greatest statistical gains from use of recurrent-events methods occur in the presence of high patient heterogeneity and low rates of study drug discontinuation.

A Biomechanical Comparison of Proportional Electromyography Control to Biological Torque Control Using a Powered Hip Exoskeleton.

PubMed

Young, Aaron J; Gannon, Hannah; Ferris, Daniel P

2017-01-01

Despite a large increase in robotic exoskeleton research, there are few studies that have examined human performance with different control strategies on the same exoskeleton device. Direct comparison studies are needed to determine how users respond to different types of control. The purpose of this study was to compare user performance using a robotic hip exoskeleton with two different controllers: a controller that targeted a biological hip torque profile and a proportional myoelectric controller. We tested both control approaches on 10 able-bodied subjects using a pneumatically powered hip exoskeleton. The state machine controller targeted a biological hip torque profile. The myoelectric controller used electromyography (EMG) of lower limb muscles to produce a proportional control signal for the hip exoskeleton. Each subject performed two 30-min exoskeleton walking trials (1.0 m/s) using each controller and a 10-min trial with the exoskeleton unpowered. During each trial, we measured subjects' metabolic cost of walking, lower limb EMG profiles, and joint kinematics and kinetics (torques and powers) using a force treadmill and motion capture. Compared to unassisted walking in the exoskeleton, myoelectric control significantly reduced metabolic cost by 13% ( p  = 0.005) and biological hip torque control reduced metabolic cost by 7% ( p  = 0.261). Subjects reduced muscle activity relative to the unpowered condition for a greater number of lower limb muscles using myoelectric control compared to the biological hip torque control. More subjects subjectively preferred the myoelectric controller to the biological hip torque control. Myoelectric control had more advantages (metabolic cost and muscle activity reduction) compared to a controller that targeted a biological torque profile for walking with a robotic hip exoskeleton. However, these results were obtained with a single exoskeleton device with specific control configurations while level walking at a single speed. Further testing on different exoskeleton hardware and with more varied experimental protocols, such as testing over multiple types of terrain, is needed to fully elucidate the potential benefits of myoelectric control for exoskeleton technology.

Power to Detect Intervention Effects on Ensembles of Social Networks

ERIC Educational Resources Information Center

Sweet, Tracy M.; Junker, Brian W.

2016-01-01

The hierarchical network model (HNM) is a framework introduced by Sweet, Thomas, and Junker for modeling interventions and other covariate effects on ensembles of social networks, such as what would be found in randomized controlled trials in education research. In this article, we develop calculations for the power to detect an intervention…

CP function: an alpha spending function based on conditional power.

PubMed

Jiang, Zhiwei; Wang, Ling; Li, Chanjuan; Xia, Jielai; Wang, William

2014-11-20

Alpha spending function and stochastic curtailment are two frequently used methods in group sequential design. In the stochastic curtailment approach, the actual type I error probability cannot be well controlled within the specified significance level. But conditional power (CP) in stochastic curtailment is easier to be accepted and understood by clinicians. In this paper, we develop a spending function based on the concept of conditional power, named CP function, which combines desirable features of alpha spending and stochastic curtailment. Like other two-parameter functions, CP function is flexible to fit the needs of the trial. A simulation study is conducted to explore the choice of CP boundary in CP function that maximizes the trial power. It is equivalent to, even better than, classical Pocock, O'Brien-Fleming, and quadratic spending function as long as a proper ρ0 is given, which is pre-specified CP threshold for efficacy. It also well controls the overall type I error type I error rate and overcomes the disadvantage of stochastic curtailment. Copyright © 2014 John Wiley & Sons, Ltd.

One session of high-intensity interval training (HIIT) every 5 days, improves muscle power but not static balance in lifelong sedentary ageing men: A randomized controlled trial.

PubMed

Sculthorpe, Nicholas F; Herbert, Peter; Grace, Fergal

2017-02-01

Declining muscle power during advancing age predicts falls and loss of independence. High-intensity interval training (HIIT) may improve muscle power, but remains largely unstudied in ageing participants. This randomized controlled trial (RCT) investigated the efficacy of a low-frequency HIIT (LfHIIT) intervention on peak muscle power (peak power output [PPO]), body composition, and balance in lifelong sedentary but otherwise healthy males. Thirty-three lifelong sedentary ageing men were randomly assigned to either intervention (INT; n = 22, age 62.3 ± 4.1 years) or control (n = 11, age 61.6 ± 5.0 years) who were both assessed at 3 distinct measurement points (phase A), after 6 weeks of conditioning exercise (phase B), and after 6 weeks of HIIT once every 5 days in INT (phase C), where control remained inactive throughout the study. Static balance remained unaffected, and both absolute and relative PPO were not different between groups at phases A or B, but increased significantly in INT after LfHIIT (P < 0.01). Lean body mass displayed a significant interaction (P < 0.01) due to an increase in INT between phases B and C (P < 0.05). 6 weeks of LfHIIT exercise feasible and effective method to induce clinically relevant improvements in absolute and relative PPO, but does not improve static balance in sedentary ageing men.

Statistical power in parallel group point exposure studies with time-to-event outcomes: an empirical comparison of the performance of randomized controlled trials and the inverse probability of treatment weighting (IPTW) approach.

PubMed

Austin, Peter C; Schuster, Tibor; Platt, Robert W

2015-10-15

Estimating statistical power is an important component of the design of both randomized controlled trials (RCTs) and observational studies. Methods for estimating statistical power in RCTs have been well described and can be implemented simply. In observational studies, statistical methods must be used to remove the effects of confounding that can occur due to non-random treatment assignment. Inverse probability of treatment weighting (IPTW) using the propensity score is an attractive method for estimating the effects of treatment using observational data. However, sample size and power calculations have not been adequately described for these methods. We used an extensive series of Monte Carlo simulations to compare the statistical power of an IPTW analysis of an observational study with time-to-event outcomes with that of an analysis of a similarly-structured RCT. We examined the impact of four factors on the statistical power function: number of observed events, prevalence of treatment, the marginal hazard ratio, and the strength of the treatment-selection process. We found that, on average, an IPTW analysis had lower statistical power compared to an analysis of a similarly-structured RCT. The difference in statistical power increased as the magnitude of the treatment-selection model increased. The statistical power of an IPTW analysis tended to be lower than the statistical power of a similarly-structured RCT.

A Bayesian sequential design using alpha spending function to control type I error.

PubMed

Zhu, Han; Yu, Qingzhao

2017-10-01

We propose in this article a Bayesian sequential design using alpha spending functions to control the overall type I error in phase III clinical trials. We provide algorithms to calculate critical values, power, and sample sizes for the proposed design. Sensitivity analysis is implemented to check the effects from different prior distributions, and conservative priors are recommended. We compare the power and actual sample sizes of the proposed Bayesian sequential design with different alpha spending functions through simulations. We also compare the power of the proposed method with frequentist sequential design using the same alpha spending function. Simulations show that, at the same sample size, the proposed method provides larger power than the corresponding frequentist sequential design. It also has larger power than traditional Bayesian sequential design which sets equal critical values for all interim analyses. When compared with other alpha spending functions, O'Brien-Fleming alpha spending function has the largest power and is the most conservative in terms that at the same sample size, the null hypothesis is the least likely to be rejected at early stage of clinical trials. And finally, we show that adding a step of stop for futility in the Bayesian sequential design can reduce the overall type I error and reduce the actual sample sizes.

Pharmacological interventions for self-injurious behaviour in adults with intellectual disabilities: Abridged republication of a Cochrane systematic review.

PubMed

Gormez, A; Rana, F; Varghese, S

2014-07-01

We aimed to determine clinical effectiveness of pharmacological interventions for self-injurious behaviour in adults with intellectual disability. We searched the following databases: CENTRAL; MEDLINE; EMBASE; PsycINFO; CINAHL; SCI; SSCI; Conference Proceedings Citation Index - Science; Conference Proceedings Citation Index - Social Science and Humanities; ZETOC; World Cat .We also searched ClinicalTrials.gov,ICTRP and the reference lists of included trials. We included randomised controlled trials that examined drug interventions versus placebo for self-injurious behaviour. We found five double-blind, placebo-controlled trials, which included a total of 50 people. Four trials compared the effects of naltrexone versus placebo and one trial clomipramine versus placebo. We did not identify any relevant placebo-controlled trials for other drugs. We presented a narrative summary, as meta-analysis was not appropriate due to differences in study designs, differences between interventions and heterogeneous outcome measures. There was weak evidence in included trials that any active drug was more effective than placebo for people with intellectual disability demonstrating self-injurious behaviour. Due to sparse data, an absence of power and statistical significance, and high risk of bias for four of the included trials, we are unable to reach any definite conclusions about the relative benefits of naltrexone or clomipramine compared to placebo. © The Author(s) 2014.

Statistical analysis plan for the Pneumatic CompREssion for PreVENting Venous Thromboembolism (PREVENT) trial: a study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen; Al-Hameed, Fahad; Burns, Karen E A; Mehta, Sangeeta; Alsolamy, Sami; Almaani, Mohammed; Mandourah, Yasser; Almekhlafi, Ghaleb A; Al Bshabshe, Ali; Finfer, Simon; Alshahrani, Mohammed; Khalid, Imran; Mehta, Yatin; Gaur, Atul; Hawa, Hassan; Buscher, Hergen; Arshad, Zia; Lababidi, Hani; Al Aithan, Abdulsalam; Jose, Jesna; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Al-Dawood, Abdulaziz

2018-03-15

The Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults. In this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is "incident" proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%. Consistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data. ClinicalTrials.gov , ID: NCT02040103 . Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506 . Registered on 30 October 2013.

(abstract) Experimental Results From Internetworking Data Applications Over Various Wireless Networks Using a Single Flexible Error Control Protocol

NASA Technical Reports Server (NTRS)

Kanai, T.; Kramer, M.; McAuley, A. J.; Nowack, S.; Pinck, D. S.; Ramirez, G.; Stewart, I.; Tohme, H.; Tong, L.

1995-01-01

This paper describes results from several wireless field trials in New Jersey, California, and Colorado, conducted jointly by researchers at Bellcore, JPL, and US West over the course of 1993 and 1994. During these trials, applications communicated over multiple wireless networks including satellite, low power PCS, high power cellular, packet data, and the wireline Public Switched Telecommunications Network (PSTN). Key goals included 1) designing data applications and an API suited to mobile users, 2) investigating internetworking issues, 3) characterizing wireless networks under various field conditions, and 4) comparing the performance of different protocol mechanisms over the diverse networks and applications. We describe experimental results for different protocol mechanisms and parameters, such as acknowledgment schemes and packet sizes. We show the need for powerful error control mechanisms such as selective acknowledgements and combining data from multiple transmissions. We highlight the possibility of a common protocol for all wireless networks, from micro-cellular PCS to satellite networks.

Randomised placebo-controlled trials of surgery: ethical analysis and guidelines.

PubMed

Savulescu, Julian; Wartolowska, Karolina; Carr, Andy

2016-12-01

Use of a placebo control in surgical trials is a divisive issue. We argue that, in principle, placebo controls for surgery are necessary in the same way as for medicine. However, there are important differences between these types of trial, which both increase justification and limit application of surgical studies. We propose that surgical randomised placebo-controlled trials are ethical if certain conditions are fulfilled: (1) the presence of equipoise, defined as a lack of unbiased evidence for efficacy of an intervention; (2) clinically important research question; (3) the risk to patients is minimised and reasonable; (4) there is uncertainty about treatment allocation rather than deception; (5) there is preliminary evidence for efficacy, which justifies a placebo-controlled design; and (6) ideally, the placebo procedure should have some direct benefit to the patient, for example, as a diagnostic tool. Placebo-controlled trials in surgery will most often be justified when surgery is performed to improve function or relieve symptoms and when objective outcomes are not available, while the risk of mortality or significant morbidity is low. In line with medical placebo-controlled trials, the surgical trial (1) should be sufficiently powered and (2) standardised so that its results are valid, (3) consent should be valid, (4) the standard treatment or rescue medication should be provided if possible, and (5) after the trial, the patients should be told which treatment they received and there should be provision for post-trial care if the study may result in long-term negative effects. We comment and contrast our guidelines with those of the American Medical Association. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Pilot and Repeat Trials as Development Tools Associated with Demonstration of Bioequivalence.

PubMed

Fuglsang, Anders

2015-05-01

The purpose of this work is to use simulated trials to study how pilot trials can be implemented in relation to bioequivalence testing, and how the use of the information obtained at the pilot stage can influence the overall chance of showing bioequivalence (power) or the chance of approving a truly bioinequivalent product (type I error). The work also covers the use of repeat pivotal trials since the difference between a pilot trial followed by a pivotal trial and a pivotal trial followed by a repeat trial is mainly a question of whether a conclusion of bioequivalence can be allowed after the first trial. Repeating a pivotal trial after a failed trial involves dual or serial testing of the bioequivalence null hypothesis, and the paper illustrates how this may inflate the type I error up to almost 10%. Hence, it is questioned if such practice is in the interest of patients. Tables for power, type I error, and sample sizes are provided for a total of six different decision trees which allow the developer to use either the observed geometric mean ratio (GMR) from the first or trial or to assume that the GMR is 0.95. In cases when the true GMR can be controlled so as not to deviate more from unity than 0.95, sequential design methods ad modum Potvin may be superior to pilot trials. The tables provide a quantitative basis for choosing between sequential designs and pivotal trials preceded by pilot trials.

Caffeine Ingestion Reverses the Circadian Rhythm Effects on Neuromuscular Performance in Highly Resistance-Trained Men

PubMed Central

Mora-Rodríguez, Ricardo; Pallarés, Jesús García; López-Samanes, Álvaro; Ortega, Juan Fernando; Fernández-Elías, Valentín E.

2012-01-01

Purpose To investigate whether caffeine ingestion counteracts the morning reduction in neuromuscular performance associated with the circadian rhythm pattern. Methods Twelve highly resistance-trained men underwent a battery of neuromuscular tests under three different conditions; i) morning (10:00 a.m.) with caffeine ingestion (i.e., 3 mg kg−1; AMCAFF trial); ii) morning (10:00 a.m.) with placebo ingestion (AMPLAC trial); and iii) afternoon (18:00 p.m.) with placebo ingestion (PMPLAC trial). A randomized, double-blind, crossover, placebo controlled experimental design was used, with all subjects serving as their own controls. The neuromuscular test battery consisted in the measurement of bar displacement velocity during free-weight full-squat (SQ) and bench press (BP) exercises against loads that elicit maximum strength (75% 1RM load) and muscle power adaptations (1 m s−1 load). Isometric maximum voluntary contraction (MVCLEG) and isometric electrically evoked strength of the right knee (EVOKLEG) were measured to identify caffeine's action mechanisms. Steroid hormone levels (serum testosterone, cortisol and growth hormone) were evaluated at the beginning of each trial (PRE). In addition, plasma norepinephrine (NE) and epinephrine were measured PRE and at the end of each trial following a standardized intense (85% 1RM) 6 repetitions bout of SQ (POST). Results In the PMPLAC trial, dynamic muscle strength and power output were significantly enhanced compared with AMPLAC treatment (3.0%–7.5%; p≤0.05). During AMCAFF trial, muscle strength and power output increased above AMPLAC levels (4.6%–5.7%; p≤0.05) except for BP velocity with 1 m s−1 load (p = 0.06). During AMCAFF, EVOKLEG and NE (a surrogate of maximal muscle sympathetic nerve activation) were increased above AMPLAC trial (14.6% and 96.8% respectively; p≤0.05). Conclusions These results indicate that caffeine ingestion reverses the morning neuromuscular declines in highly resistance-trained men, raising performance to the levels of the afternoon trial. Our electrical stimulation data, along with the NE values, suggest that caffeine increases neuromuscular performance having a direct effect in the muscle. PMID:22496767

Accuracy of the Velotron ergometer and SRM power meter.

PubMed

Abbiss, C R; Quod, M J; Levin, G; Martin, D T; Laursen, P B

2009-02-01

The purpose of this study was to determine the accuracy of the Velotron cycle ergometer and the SRM power meter using a dynamic calibration rig over a range of exercise protocols commonly applied in laboratory settings. These trials included two sustained constant power trials (250 W and 414 W), two incremental power trials and three high-intensity interval power trials. To further compare the two systems, 15 subjects performed three dynamic 30 km performance time trials. The Velotron and SRM displayed accurate measurements of power during both constant power trials (<1% error). However, during high-intensity interval trials the Velotron and SRM were found to be less accurate (3.0%, CI=1.6-4.5% and -2.6%, CI=-3.2--2.0% error, respectively). During the dynamic 30 km time trials, power measured by the Velotron was 3.7+/-1.9% (CI=2.9-4.8%) greater than that measured by the SRM. In conclusion, the accuracy of the Velotron cycle ergometer and the SRM power meter appears to be dependent on the type of test being performed. Furthermore, as each power monitoring system measures power at various positions (i.e. bottom bracket vs. rear wheel), caution should be taken when comparing power across the two systems, particularly when power is variable.

A randomized controlled trial on the value of misoprostol for the treatment of retained placenta in a low-resource setting.

PubMed

van Beekhuizen, Heleen J; Tarimo, Vincent; Pembe, Andrea B; Fauteck, Heiner; Lotgering, Fred K

2013-09-01

To evaluate the efficacy and safety of misoprostol among patients with retained placenta in a low-resource setting. A prospective, multicenter, randomized, double-blind, placebo-controlled trial was carried out in Tanzania between April 2008 and November 2011. It included patients who delivered at a gestational age of 28 weeks or more and had blood loss of 750 mL or less at 30 minutes after delivery. Sublingual misoprostol (800 μg) was compared with placebo as the primary treatment. Power analysis showed that 117 patients would be required to observe a reduction of 40% in the incidence of manual removal of the placenta (MRP; P=0.05, 80% power), the primary outcome. The secondary outcomes were blood loss and number of blood transfusions. Interim analysis after recruitment of 95 patients showed that incidence of MRP, total blood loss, and incidence of blood transfusions were similar in the misoprostol (MRP, 40%; blood loss, 803 mL; blood transfusion, 15%) and placebo (MRP, 33%, blood loss 787 mL, blood transfusion, 23%) groups. The trial was stopped because continuation would not alter the interim conclusion that misoprostol was ineffective. Treatment with misoprostol was found to have no clinically significant beneficial effect among women with retained placenta. Current Controlled Trials ISRCTN16104753. Copyright © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Is Neurofeedback an Efficacious Treatment for ADHD? A Randomised Controlled Clinical Trial

ERIC Educational Resources Information Center

Gevensleben, Holger; Holl, Birgit; Albrecht, Bjorn; Vogel, Claudia; Schlamp, Dieter; Kratz, Oliver; Studer, Petra; Rothenberger, Aribert; Moll, Gunther H.; Heinrich, Hartmut

2009-01-01

Background: For children with attention deficit/hyperactivity disorder (ADHD), a reduction of inattention, impulsivity and hyperactivity by neurofeedback (NF) has been reported in several studies. But so far, unspecific training effects have not been adequately controlled for andor studies do not provide sufficient statistical power. To overcome…

Evaluation of Contribution for Voltage Control Ancillary Services Based on Social Surplus

NASA Astrophysics Data System (ADS)

Ueki, Yuji; Hara, Ryoichi; Kita, Hiroyuki; Hasegawa, Jun

Reactive power supply plays an important role in active power supply with adequate system voltages. Various pricing mechanism for reactive power supply have been developed and some of them are adopted in some power systems, however they are in a trial stage. The authors also focus on development of a pricing method for reactive power ancillary services. This problem involves two technical issues: rational estimation of the cost associated with reactive power supply and fair and transparent allocation of the estimated cost among the market participants. This paper proposes methods for evaluating the contribution of generators and demands.

Type-II generalized family-wise error rate formulas with application to sample size determination.

PubMed

Delorme, Phillipe; de Micheaux, Pierre Lafaye; Liquet, Benoit; Riou, Jérémie

2016-07-20

Multiple endpoints are increasingly used in clinical trials. The significance of some of these clinical trials is established if at least r null hypotheses are rejected among m that are simultaneously tested. The usual approach in multiple hypothesis testing is to control the family-wise error rate, which is defined as the probability that at least one type-I error is made. More recently, the q-generalized family-wise error rate has been introduced to control the probability of making at least q false rejections. For procedures controlling this global type-I error rate, we define a type-II r-generalized family-wise error rate, which is directly related to the r-power defined as the probability of rejecting at least r false null hypotheses. We obtain very general power formulas that can be used to compute the sample size for single-step and step-wise procedures. These are implemented in our R package rPowerSampleSize available on the CRAN, making them directly available to end users. Complexities of the formulas are presented to gain insight into computation time issues. Comparison with Monte Carlo strategy is also presented. We compute sample sizes for two clinical trials involving multiple endpoints: one designed to investigate the effectiveness of a drug against acute heart failure and the other for the immunogenicity of a vaccine strategy against pneumococcus. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Low-power polling mode of the next-generation IMES2 implantable wireless EMG sensor.

PubMed

DeMichele, Glenn A; Hu, Zhe; Troyk, Philip R; Chen, Hongnan; Weir, Richard F ff

2014-01-01

The IMES1 Implantable MyoElectric Sensor device is currently in human clinical trials led by the Alfred Mann Foundation. The IMES is implanted in a residual limb and is powered wirelessly using a magnetic field. EMG signals resulting from the amputee's voluntary movement are amplified and transmitted wirelessly by the IMES to an external controller which controls movement of an external motorized prosthesis. Development of the IMES technology is on-going, producing the next-generation IMES2. Among various improvements, a new feature of the IMES2 is a low-power polling mode. In this low-power mode, the IMES2 power consumption can be dramatically reduced when the limb is inactive through the use of a polled sampling. With the onset of EMG activity, the IMES2 system can switch to the normal higher sample rate to allow the acquisition of high-fidelity EMG data for prosthesis control.

Economic evaluation of factorial randomised controlled trials: challenges, methods and recommendations

PubMed Central

Gray, Alastair

2017-01-01

Increasing numbers of economic evaluations are conducted alongside randomised controlled trials. Such studies include factorial trials, which randomise patients to different levels of two or more factors and can therefore evaluate the effect of multiple treatments alone and in combination. Factorial trials can provide increased statistical power or assess interactions between treatments, but raise additional challenges for trial‐based economic evaluations: interactions may occur more commonly for costs and quality‐adjusted life‐years (QALYs) than for clinical endpoints; economic endpoints raise challenges for transformation and regression analysis; and both factors must be considered simultaneously to assess which treatment combination represents best value for money. This article aims to examine issues associated with factorial trials that include assessment of costs and/or cost‐effectiveness, describe the methods that can be used to analyse such studies and make recommendations for health economists, statisticians and trialists. A hypothetical worked example is used to illustrate the challenges and demonstrate ways in which economic evaluations of factorial trials may be conducted, and how these methods affect the results and conclusions. Ignoring interactions introduces bias that could result in adopting a treatment that does not make best use of healthcare resources, while considering all interactions avoids bias but reduces statistical power. We also introduce the concept of the opportunity cost of ignoring interactions as a measure of the bias introduced by not taking account of all interactions. We conclude by offering recommendations for planning, analysing and reporting economic evaluations based on factorial trials, taking increased analysis costs into account. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID:28470760

The Internet and Clinical Trials: Background, Online Resources, Examples and Issues

PubMed Central

Seib, Rachael; Prescott, Todd

2005-01-01

Both the Internet and clinical trials were significant developments in the latter half of the twentieth century: the Internet revolutionized global communications and the randomized controlled trial provided a means to conduct an unbiased comparison of two or more treatments. Large multicenter trials are often burdened with an extensive development time and considerable expense, as well as significant challenges in obtaining, backing up and analyzing large amounts of data. Alongside the increasing complexities of the modern clinical trial has grown the power of the Internet to improve communications, centralize and secure data as well as to distribute information. As more and more clinical trials are required to coordinate multiple trial processes in real time, centers are turning to the Internet for the tools to manage the components of a clinical trial, either in whole or in part, to produce lower costs and faster results. This paper reviews the historical development of the Internet and the randomized controlled trial, describes the Internet resources available that can be used in a clinical trial, reviews some examples of online trials and describes the advantages and disadvantages of using the Internet to conduct a clinical trial. We also extract the characteristics of the 5 largest clinical trials conducted using the Internet to date, which together enrolled over 26000 patients. PMID:15829477

Sample size determination in group-sequential clinical trials with two co-primary endpoints

PubMed Central

Asakura, Koko; Hamasaki, Toshimitsu; Sugimoto, Tomoyuki; Hayashi, Kenichi; Evans, Scott R; Sozu, Takashi

2014-01-01

We discuss sample size determination in group-sequential designs with two endpoints as co-primary. We derive the power and sample size within two decision-making frameworks. One is to claim the test intervention’s benefit relative to control when superiority is achieved for the two endpoints at the same interim timepoint of the trial. The other is when the superiority is achieved for the two endpoints at any interim timepoint, not necessarily simultaneously. We evaluate the behaviors of sample size and power with varying design elements and provide a real example to illustrate the proposed sample size methods. In addition, we discuss sample size recalculation based on observed data and evaluate the impact on the power and Type I error rate. PMID:24676799

Eldecalcitol improves chair-rising time in postmenopausal osteoporotic women treated with bisphosphonates

PubMed Central

Iwamoto, Jun; Sato, Yoshihiro

2014-01-01

An open-label randomized controlled trial was conducted to clarify the effect of eldecalcitol (ED) on body balance and muscle power in postmenopausal osteoporotic women treated with bisphosphonates. A total of 106 postmenopausal women with osteoporosis (mean age 70.8 years) were randomly divided into two groups (n=53 in each group): a bisphosphonate group (control group) and a bisphosphonate plus ED group (ED group). Biochemical markers, unipedal standing time (body balance), and five-repetition chair-rising time (muscle power) were evaluated. The duration of the study was 6 months. Ninety-six women who completed the trial were included in the subsequent analyses. At baseline, the age, body mass index, bone mass indices, bone turnover markers, unipedal standing time, and chair-rising time did not differ significantly between the two groups. During the 6-month treatment period, bone turnover markers decreased significantly from the baseline values similarly in the two groups. Although no significant improvement in the unipedal standing time was seen in the ED group, compared with the control group, the chair-rising time decreased significantly in the ED group compared with the control group. The present study showed that ED improved the chair-rising time in terms of muscle power in postmenopausal osteoporotic women treated with bisphosphonates. PMID:24476669

Hierarchical Commensurate and Power Prior Models for Adaptive Incorporation of Historical Information in Clinical Trials

PubMed Central

Hobbs, Brian P.; Carlin, Bradley P.; Mandrekar, Sumithra J.; Sargent, Daniel J.

2011-01-01

Summary Bayesian clinical trial designs offer the possibility of a substantially reduced sample size, increased statistical power, and reductions in cost and ethical hazard. However when prior and current information conflict, Bayesian methods can lead to higher than expected Type I error, as well as the possibility of a costlier and lengthier trial. This motivates an investigation of the feasibility of hierarchical Bayesian methods for incorporating historical data that are adaptively robust to prior information that reveals itself to be inconsistent with the accumulating experimental data. In this paper, we present several models that allow for the commensurability of the information in the historical and current data to determine how much historical information is used. A primary tool is elaborating the traditional power prior approach based upon a measure of commensurability for Gaussian data. We compare the frequentist performance of several methods using simulations, and close with an example of a colon cancer trial that illustrates a linear models extension of our adaptive borrowing approach. Our proposed methods produce more precise estimates of the model parameters, in particular conferring statistical significance to the observed reduction in tumor size for the experimental regimen as compared to the control regimen. PMID:21361892

Preliminary Effectiveness Study of Coping Power Program for Aggressive Children in Pakistan.

PubMed

Mushtaq, Asia; Lochman, John E; Tariq, Pervaiz N; Sabih, Fazaila

2017-10-01

Aggression is a characteristic feature of many psychiatric disorders. To address the scarceness for evidence-based interventions for behavioral problems in Pakistan, we evaluated the effectiveness of culturally adapted version of Coping Power Program. The purpose of the study was to determine the extent to which Coping Power Program is capable of reducing aggressive behavior and improving competent behavior, when delivered in a different culture, i.e., Pakistan. With randomized control trial (RCT) of pre- and post-testing, 112 fourth grade boys were allocated to Coping Power intervention condition and waitlist control condition. The intervention group showed significant reduction in aggression at post assessment, in comparison to control group. Boys who received Coping Power intervention also showed improvements in behavior, social skills, and social cognitive processes, with better anger control and problem solving strategies, in comparison to the control group. The results of the study provide preliminary evidence, supporting the effectiveness of Coping Power Program for Pakistani children. Despite its limitations, the results of this study are promising and suggest that Coping Power is an effective intervention to reduce behavioral problems and promote healthy and positive behaviors in children, even when implemented in different contexts with greater potential for violence exposure.

Augmenting the logrank test in the design of clinical trials in which non-proportional hazards of the treatment effect may be anticipated.

PubMed

Royston, Patrick; Parmar, Mahesh K B

2016-02-11

Most randomized controlled trials with a time-to-event outcome are designed assuming proportional hazards (PH) of the treatment effect. The sample size calculation is based on a logrank test. However, non-proportional hazards are increasingly common. At analysis, the estimated hazards ratio with a confidence interval is usually presented. The estimate is often obtained from a Cox PH model with treatment as a covariate. If non-proportional hazards are present, the logrank and equivalent Cox tests may lose power. To safeguard power, we previously suggested a 'joint test' combining the Cox test with a test of non-proportional hazards. Unfortunately, a larger sample size is needed to preserve power under PH. Here, we describe a novel test that unites the Cox test with a permutation test based on restricted mean survival time. We propose a combined hypothesis test based on a permutation test of the difference in restricted mean survival time across time. The test involves the minimum of the Cox and permutation test P-values. We approximate its null distribution and correct it for correlation between the two P-values. Using extensive simulations, we assess the type 1 error and power of the combined test under several scenarios and compare with other tests. We investigate powering a trial using the combined test. The type 1 error of the combined test is close to nominal. Power under proportional hazards is slightly lower than for the Cox test. Enhanced power is available when the treatment difference shows an 'early effect', an initial separation of survival curves which diminishes over time. The power is reduced under a 'late effect', when little or no difference in survival curves is seen for an initial period and then a late separation occurs. We propose a method of powering a trial using the combined test. The 'insurance premium' offered by the combined test to safeguard power under non-PH represents about a single-digit percentage increase in sample size. The combined test increases trial power under an early treatment effect and protects power under other scenarios. Use of restricted mean survival time facilitates testing and displaying a generalized treatment effect.

Recombinant activated factor VII for bleeding in patients without inherited bleeding disorders.

PubMed

Selin, S; Tejani, A

2006-03-01

(1) Recombinant activated factor VII (rFVIIa) is licensed in Canada for the prevention and treatment of bleeding in hemophiliacs, but it is increasingly used to control bleeding in non-hemophilic patients during surgery, or during treatment for severe trauma or intracerebral hemorrhage (ICH). (2) In one clinical trial, there was a significant reduction in mortality among patients with ICH treated with rFVIIa. In another trial, administration of rFVIIa significantly reduced the number of trauma patients needing massive blood transfusions although there was no significant difference in mortality. (3) Adequately powered randomized controlled trials are needed to clarify the efficacy and safety of rFVIIa for non-bleeding disorder indications. Phase III trials in ICH and trauma are underway. (4) There is potential for non-hemophilic use, particularly if clinical efficacy and cost effectiveness are established.

Aspirin for in vitro fertilisation.

PubMed

Siristatidis, Charalambos S; Dodd, Susanna R; Drakeley, Andrew J

2011-08-10

Aspirin is used to improve the outcome in women undergoing in vitro fertilisation despite inconsistent evidence of its efficacy. The most appropriate time to commence aspirin therapy and the length of treatment required are also still to be determined. This is an update of the review first published in 2007. To determine the effectiveness and safety of aspirin for improving the outcome of in vitro fertilisation and intracytoplasmic sperm injection treatment cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library January 2011), MEDLINE (1966 to January 2011) and EMBASE (1980 to January 2011) databases. We used the research terms: "(aspirin OR acetylsalicylic acid) AND (in-vitro fertilisation OR intracytoplasmic sperm injection)", combined with the Cochrane Menstrual Disorders and Subfertility Group's search strategy, in order to identify randomised controlled trials on aspirin for women undergoing in vitro fertilisation. Randomised controlled trials. Two authors independently selected studies to include in the review, extracted data and assessed trial quality. The searches identified 13 trials which were eligible for inclusion in the review, including a total of 2653 participants. No significant differences were found between the treatment and control groups for any of the outcomes assessed. No significant differences were found in the meta-analysis of studies investigating the effect of aspirin compared with control on live birth rate (RR 0.91, 95% CI 0.72 to 1.15; three studies and 1053 participants), clinical pregnancy rate (RR 1.03, 95% CI 0.91 to 1.17; 10 studies and 2142 participants), ectopic and miscarriage rates (RR 1.86, 95% CI 0.75 to 4.63; RR 1.10, 95% CI 0.68 to 1.77) respectively (three and five studies involving 1135 and 1497 participants). Use of aspirin for women undergoing in vitro fertilisation cannot be recommended due to lack of evidence from the current trial data. Adequately powered trials are needed. It was proposed in the initial version of this review that a sample size of 350 women in each group would be required in order to demonstrate a 10% improvement from the use of aspirin, with 80% power at the 5% significance level. Until such evidence is available, this treatment can not be recommended.

The "Power Play! Campaign's School Idea & Resource Kits" Improve Determinants of Fruit and Vegetable Intake and Physical Activity among Fourth- and Fifth-Grade Children

ERIC Educational Resources Information Center

Keihner, Angie Jo; Meigs, Reba; Sugerman, Sharon; Backman, Desiree; Garbolino, Tanya; Mitchell, Patrick

2011-01-01

Objective: Examine the effect of the "California Children's Power Play! Campaign's School Idea & Resource Kits" for fourth/fifth grades on the psychosocial determinants of fruit and vegetable (FV) intake and physical activity (PA). Methods: Randomized, controlled trial (n = 31 low-resource public schools; 1,154 children). Ten…

Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions.

PubMed

Coronado-Montoya, Stephanie; Levis, Alexander W; Kwakkenbos, Linda; Steele, Russell J; Turner, Erick H; Thombs, Brett D

2016-01-01

A large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of "positive" results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS databases were searched for randomized controlled trials of mindfulness-based therapy. The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression. Trial registries were searched for mindfulness-based therapy registrations. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS were also searched for mindfulness-based therapy systematic reviews and meta-analyses. 108 (87%) of 124 published trials reported ≥1 positive outcome in the abstract, and 109 (88%) concluded that mindfulness-based therapy was effective, 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 (expected number positive trials = 65.7). Of 21 trial registrations, 13 (62%) remained unpublished 30 months post-trial completion. No trial registrations adequately specified a single primary outcome measure with time of assessment. None of 36 systematic reviews and meta-analyses concluded that effect estimates were overestimated due to reporting biases. The proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice.

Effectiveness and cost-effectiveness of humanistic counselling in schools for young people with emotional distress (ETHOS): study protocol for a randomised controlled trial.

PubMed

Stafford, Megan Rose; Cooper, Mick; Barkham, Michael; Beecham, Jeni; Bower, Peter; Cromarty, Karen; Fugard, Andrew J B; Jackson, Charlie; Pearce, Peter; Ryder, Rebekah; Street, Cathy

2018-03-09

One in ten children in Britain have been identified as experiencing a diagnosable mental health disorder. School-based humanistic counselling (SBHC) may help young people identify, address, and overcome psychological distress. Data from four pilot trials suggest that SBHC may be clinically effective. However, a fully powered randomised controlled trial (RCT) is needed to provide a robust test of its effectiveness, to assess its cost-effectiveness, and to determine the process of change. The Effectiveness and Cost-effectiveness Trial of Humanistic Counselling in Schools (ETHOS) is a two-arm, parallel-group RCT comparing the clinical and cost-effectiveness of SBHC with Pastoral Care as Usual (PCAU) in school settings. Eligibility criteria for young people include being between 13 and 16 years of age and experiencing moderate to severe levels of emotional distress. Participants are randomised to receive either SBHC or PCAU. SBHC is delivered in up to 10 weekly, individual sessions in their school with a qualified, experienced counsellor who has also received training using a clinical practice manual. Adherence to the SBHC model is assessed by a sub-team of auditors and in clinical supervision. PCAU consists of the schools' pre-existing systems for supporting the emotional health and well-being of students. The primary outcomes are psychological distress measured using the Young Person's Clinical Outcomes in Routine Evaluation (YP-CORE) and costs evaluated using the Client Service Receipt Inventory (CSRI). Secondary outcomes include psychological difficulties, levels of depression, anxiety and self-esteem, well-being, school engagement, educational outcomes and achievement of personal goals. Qualitative interviews with participants, parents and school staff will look to identify the mechanisms of change in SBHC. Researchers administering the measures are blind to allocation. The trial requires n = 306 participants (n = 153 in each group), with 90% power to detect a standardised mean difference (SMD) of 0.5. An intention-to-treat analysis will be undertaken. This RCT is powered to detect clinically meaningful differences, and will make a major contribution to the evidence base for mental health provision for adolescents. It will have implications for all stakeholders, including policy-makers, statutory advisory bodies for child welfare, head teachers, children and young people practitioners, child welfare and parenting organisations, and young people. Controlled Trials International Standard Randomised Controlled Trial Number (ISRCTN) Registry, ID: ISRCTN10460622 . Registered on 11 May 2016.

Thromboprophylaxis using combined intermittent pneumatic compression and pharmacologic prophylaxis versus pharmacologic prophylaxis alone in critically ill patients: study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen M; Alsolamy, Sami; Al-Dawood, Abdulaziz; Al-Omari, Awad; Al-Hameed, Fahad; Burns, Karen E A; Almaani, Mohammed; Lababidi, Hani; Al Bshabshe, Ali; Mehta, Sangeeta; Al-Aithan, Abdulsalam M; Mandourah, Yasser; Almekhlafi, Ghaleb; Finfer, Simon; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Sadat, Musharaf

2016-08-03

Venous thromboembolism (VTE) remains a common problem in critically ill patients. Pharmacologic prophylaxis is currently the standard of care based on high-level evidence from randomized controlled trials. However, limited evidence exists regarding the effectiveness of intermittent pneumatic compression (IPC) devices. The Pneumatic compREssion for preventing VENous Thromboembolism (PREVENT trial) aims to determine whether the adjunct use of IPC with pharmacologic prophylaxis compared to pharmacologic prophylaxis alone in critically ill patients reduces the risk of VTE. The PREVENT trial is a multicenter randomized controlled trial, which will recruit 2000 critically ill patients from over 20 hospitals in three countries. The primary outcome is the incidence of proximal lower extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the scans are blinded to intervention allocation, whereas the patients and caregivers are unblinded. The trial has 80 % power to detect a 3 % absolute risk reduction in proximal DVT from 7 to 4 %. The first patient was enrolled in July 2014. As of May 2015, a total of 650 patients have been enrolled from 13 centers in Saudi Arabia, Canada and Australia. The first interim analysis is anticipated in July 2016. We expect to complete recruitment by 2018. Clinicaltrials.gov: NCT02040103 (registered on 3 November 2013). Current controlled trials: ISRCTN44653506 (registered on 30 October 2013).

Interim analyses in 2 x 2 crossover trials.

PubMed

Cook, R J

1995-09-01

A method is presented for performing interim analyses in long term 2 x 2 crossover trials with serial patient entry. The analyses are based on a linear statistic that combines data from individuals observed for one treatment period with data from individuals observed for both periods. The coefficients in this linear combination can be chosen quite arbitrarily, but we focus on variance-based weights to maximize power for tests regarding direct treatment effects. The type I error rate of this procedure is controlled by utilizing the joint distribution of the linear statistics over analysis stages. Methods for performing power and sample size calculations are indicated. A two-stage sequential design involving simultaneous patient entry and a single between-period interim analysis is considered in detail. The power and average number of measurements required for this design are compared to those of the usual crossover trial. The results indicate that, while there is minimal loss in power relative to the usual crossover design in the absence of differential carry-over effects, the proposed design can have substantially greater power when differential carry-over effects are present. The two-stage crossover design can also lead to more economical studies in terms of the expected number of measurements required, due to the potential for early stopping. Attention is directed toward normally distributed responses.

Pacing Strategy in Short Cycling Time Trials.

PubMed

de Jong, Jelle; van der Meijden, Linda; Hamby, Simone; Suckow, Samantha; Dodge, Christopher; de Koning, Jos J; Foster, Carl

2015-11-01

To reach top performance in cycling, optimizing distribution of energy resources is crucial. The purpose of this study was to investigate power output during 250-m, 500-m, and 1000-m cycling time trials and the characteristics of the adopted pacing strategy. Nine trained cyclists completed an incremental test and 3 time trials that they were instructed to finish as quickly as possible. Preceding the trials, peak power during short sprints (PP sprint) and gross efficiency (GE) were measured. During the trials, power output and oxygen consumption were measured to calculate the contribution of the aerobic and anaerobic energy sources. After the trial GE was measured again. Peak power during all trials (PPTT) was lower than PP sprint. In the 250-m trial the PPTT was higher in the 1000-m trial (P = .008). The subjects performed a significantly longer time at high intensity in the 250-m than in the 1000-m (P = .029). GE declined significantly during all trials (P < .01). Total anaerobically attributable work was less in the 250-m than in the 500-m (P = .015) and 1000-m (P < .01) trials. The overall pacing pattern in the 250-m trial appears to follow an all-out strategy, although peak power is still lower than the potential maximal power output. This suggests that a true all-out pattern of power output may not be used in fixed-distance events. The 500-m and 1000-m had a more conservative pacing pattern and anaerobic power output reached a constant magnitude.

The Relieving Effects of BrainPower Advanced, a Dietary Supplement, in Older Adults with Subjective Memory Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Zhu, Jingfen; Shi, Rong; Chen, Su; Dai, Lihua; Shen, Tian; Feng, Yi; Gu, Pingping; Shariff, Mina; Nguyen, Tuong; Ye, Yeats; Rao, Jianyu; Xing, Guoqiang

2016-01-01

Subjective memory complaints (SMCs) are common in older adults that can often predict further cognitive impairment. No proven effective agents are available for SMCs. The effect of BrainPower Advanced, a dietary supplement consisting of herbal extracts, nutrients, and vitamins, was evaluated in 98 volunteers with SMCs, averaging 67 years of age (47-88), in a randomized, double-blind, placebo-controlled trial. Subjective hypomnesis/memory loss (SML) and attention/concentration deficits (SAD) were evaluated before and after 12-week supplementation of BrainPower Advanced capsules (n = 47) or placebo (n = 51), using a 5-point memory questionnaire (1 = no/slight, 5 = severe). Objective memory function was evaluated using 3 subtests of visual/audio memory, abstraction, and memory recall that gave a combined total score. The BrainPower Advanced group had more cases of severe SML (severity ⩾ 3) (44/47) and severe SAD (43/47) than the placebo group (39/51 and 37/51, < 0.05, < 0.05, resp.) before the treatment. BrainPower Advanced intervention, however, improved a greater proportion of the severe SML (29.5%)(13/44) (P < 0.01) and SAD (34.9%)(15/43)(P < 0.01) than placebo (5.1% (2/39) and 13.5% (5/37), resp.). Thus, 3-month BrainPower Advanced supplementation appears to be beneficial to older adults with SMCs.

Multi-arm group sequential designs with a simultaneous stopping rule.

PubMed

Urach, S; Posch, M

2016-12-30

Multi-arm group sequential clinical trials are efficient designs to compare multiple treatments to a control. They allow one to test for treatment effects already in interim analyses and can have a lower average sample number than fixed sample designs. Their operating characteristics depend on the stopping rule: We consider simultaneous stopping, where the whole trial is stopped as soon as for any of the arms the null hypothesis of no treatment effect can be rejected, and separate stopping, where only recruitment to arms for which a significant treatment effect could be demonstrated is stopped, but the other arms are continued. For both stopping rules, the family-wise error rate can be controlled by the closed testing procedure applied to group sequential tests of intersection and elementary hypotheses. The group sequential boundaries for the separate stopping rule also control the family-wise error rate if the simultaneous stopping rule is applied. However, we show that for the simultaneous stopping rule, one can apply improved, less conservative stopping boundaries for local tests of elementary hypotheses. We derive corresponding improved Pocock and O'Brien type boundaries as well as optimized boundaries to maximize the power or average sample number and investigate the operating characteristics and small sample properties of the resulting designs. To control the power to reject at least one null hypothesis, the simultaneous stopping rule requires a lower average sample number than the separate stopping rule. This comes at the cost of a lower power to reject all null hypotheses. Some of this loss in power can be regained by applying the improved stopping boundaries for the simultaneous stopping rule. The procedures are illustrated with clinical trials in systemic sclerosis and narcolepsy. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Effect of voluntary hypocapnic hyperventilation or moderate hypoxia on metabolic and heart rate responses during high-intensity intermittent exercise.

PubMed

Dobashi, Kohei; Fujii, Naoto; Watanabe, Kazuhito; Tsuji, Bun; Sasaki, Yosuke; Fujimoto, Tomomi; Tanigawa, Satoru; Nishiyasu, Takeshi

2017-08-01

To investigate the effect of voluntary hypocapnic hyperventilation or moderate hypoxia on metabolic and heart rate responses during high-intensity intermittent exercise. Ten males performed three 30-s bouts of high-intensity cycling [Ex1 and Ex2: constant-workload at 80% of the power output in the Wingate anaerobic test (WAnT), Ex3: WAnT] interspaced with 4-min recovery periods under normoxic (Control), hypocapnic or hypoxic (2500 m) conditions. Hypocapnia was developed through voluntary hyperventilation for 20 min prior to Ex1 and during each recovery period. End-tidal CO 2 pressure was lower before each exercise in the hypocapnia than control trials. Oxygen uptake ([Formula: see text]) was lower in the hypocapnia than control trials (822 ± 235 vs. 1645 ± 245 mL min -1 ; mean ± SD) during Ex1, but not Ex2 or Ex3, without a between-trial difference in the power output during the exercises. Heart rates (HRs) during Ex1 (127 ± 8 vs. 142 ± 10 beats min -1 ) and subsequent post-exercise recovery periods were lower in the hypocapnia than control trials, without differences during or after Ex2, except at 4 min into the second recovery period. [Formula: see text] did not differ between the control and hypoxia trials throughout. These results suggest that during three 30-s bouts of high-intensity intermittent cycling, (1) hypocapnia reduces the aerobic metabolic rate with a compensatory increase in the anaerobic metabolic rate during the first but not subsequent exercises; (2) HRs during the exercise and post-exercise recovery periods are lowered by hypocapnia, but this effect is diminished with repeated exercise bouts, and (3) moderate hypoxia (2500 m) does not affect the metabolic response during exercise.

A mixture gatekeeping procedure based on the Hommel test for clinical trial applications.

PubMed

Brechenmacher, Thomas; Xu, Jane; Dmitrienko, Alex; Tamhane, Ajit C

2011-07-01

When conducting clinical trials with hierarchically ordered objectives, it is essential to use multiplicity adjustment methods that control the familywise error rate in the strong sense while taking into account the logical relations among the null hypotheses. This paper proposes a gatekeeping procedure based on the Hommel (1988) test, which offers power advantages compared to other p value-based tests proposed in the literature. A general description of the procedure is given and details are presented on how it can be applied to complex clinical trial designs. Two clinical trial examples are given to illustrate the methodology developed in the paper.

The relationship between perceived discomfort of static posture holding and posture holding time.

PubMed

Ogutu, Jack; Park, Woojin

2015-01-01

Few studies have investigated mathematical characteristics of the discomfort-time relationship during prolonged static posture holding (SPH) on an individual basis. Consequently, the discomfort-time relationship is not clearly understood at individual trial level. The objective of this study was to examine discomfort-time sequence data obtained from a large number of maximum-duration SPH trials to understand the perceived discomfort-posture holding time relationship at the individual SPH trial level. Thirty subjects (15 male, 15 female) participated in this study as paid volunteers. The subjects performed maximum-duration SPH trials employing 12 different wholebody static postures. The hand-held load for all the task trials was a ``generic'' box weighing 2 kg. Three mathematical functions, that is, linear, logarithmic and power functions were examined as possible mathematical models for representing individual discomfort-time profiles of SPH trials. Three different time increase patterns (negatively accelerated, linear and positively accelerated) were observed in the discomfort-time sequences data. The power function model with an additive constant term was found to adequately fit most (96.4%) of the observed discomfort-time sequences, and thus, was recommended as a general mathematical representation of the perceived discomfort-posture holding time relationship in SPH. The new knowledge on the nature of the discomfort-time relationship in SPH and the power function representation found in this study will facilitate analyzing discomfort-time data of SPH and developing future posture analysis tools for work-related discomfort control.

Implications of clinical trial design on sample size requirements.

PubMed

Leon, Andrew C

2008-07-01

The primary goal in designing a randomized controlled clinical trial (RCT) is to minimize bias in the estimate of treatment effect. Randomized group assignment, double-blinded assessments, and control or comparison groups reduce the risk of bias. The design must also provide sufficient statistical power to detect a clinically meaningful treatment effect and maintain a nominal level of type I error. An attempt to integrate neurocognitive science into an RCT poses additional challenges. Two particularly relevant aspects of such a design often receive insufficient attention in an RCT. Multiple outcomes inflate type I error, and an unreliable assessment process introduces bias and reduces statistical power. Here we describe how both unreliability and multiple outcomes can increase the study costs and duration and reduce the feasibility of the study. The objective of this article is to consider strategies that overcome the problems of unreliability and multiplicity.

Selection of nontarget arthropod taxa for field research on transgenic insecticidal crops: using empirical data and statistical power.

PubMed

Prasifka, J R; Hellmich, R L; Dively, G P; Higgins, L S; Dixon, P M; Duan, J J

2008-02-01

One of the possible adverse effects of transgenic insecticidal crops is the unintended decline in the abundance of nontarget arthropods. Field trials designed to evaluate potential nontarget effects can be more complex than expected because decisions to conduct field trials and the selection of taxa to include are not always guided by the results of laboratory tests. Also, recent studies emphasize the potential for indirect effects (adverse impacts to nontarget arthropods without feeding directly on plant tissues), which are difficult to predict because of interactions among nontarget arthropods, target pests, and transgenic crops. As a consequence, field studies may attempt to monitor expansive lists of arthropod taxa, making the design of such broad studies more difficult and reducing the likelihood of detecting any negative effects that might be present. To improve the taxonomic focus and statistical rigor of future studies, existing field data and corresponding power analysis may provide useful guidance. Analysis of control data from several nontarget field trials using repeated-measures designs suggests that while detection of small effects may require considerable increases in replication, there are taxa from different ecological roles that are sampled effectively using standard methods. The use of statistical power to guide selection of taxa for nontarget trials reflects scientists' inability to predict the complex interactions among arthropod taxa, particularly when laboratory trials fail to provide guidance on which groups are more likely to be affected. However, scientists still may exercise judgment, including taxa that are not included in or supported by power analyses.

Smart Adaptive Socket to Improve Fit and Relieve Pain in Wounded Warriors

DTIC Science & Technology

2016-10-01

applications were developed for wireless interaction with the socket system firmware. A control algorithm was designed and tested. Clinical trial...interface, Dynamic segmental volume control, Wireless connection, Pressure control system. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...charging jack, and power button are included in the design. A Bluetooth 4 radio is also included to allow for advanced user control via smartphone. The

A best practice fall prevention exercise program to improve balance, strength / power, and psychosocial health in older adults: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background With increasing age neuromuscular deficits (e.g., sarcopenia) may result in impaired physical performance and an increased risk for falls. Prominent intrinsic fall-risk factors are age-related decreases in balance and strength / power performance as well as cognitive decline. Additional studies are needed to develop specifically tailored exercise programs for older adults that can easily be implemented into clinical practice. Thus, the objective of the present trial is to assess the effects of a fall prevention program that was developed by an interdisciplinary expert panel on measures of balance, strength / power, body composition, cognition, psychosocial well-being, and falls self-efficacy in healthy older adults. Additionally, the time-related effects of detraining are tested. Methods/Design Healthy old people (n = 54) between the age of 65 to 80 years will participate in this trial. The testing protocol comprises tests for the assessment of static / dynamic steady-state balance (i.e., Sharpened Romberg Test, instrumented gait analysis), proactive balance (i.e., Functional Reach Test; Timed Up and Go Test), reactive balance (i.e., perturbation test during bipedal stance; Push and Release Test), strength (i.e., hand grip strength test; Chair Stand Test), and power (i.e., Stair Climb Power Test; countermovement jump). Further, body composition will be analysed using a bioelectrical impedance analysis system. In addition, questionnaires for the assessment of psychosocial (i.e., World Health Organisation Quality of Life Assessment-Bref), cognitive (i.e., Mini Mental State Examination), and fall risk determinants (i.e., Fall Efficacy Scale – International) will be included in the study protocol. Participants will be randomized into two intervention groups or the control / waiting group. After baseline measures, participants in the intervention groups will conduct a 12-week balance and strength / power exercise intervention 3 times per week, with each training session lasting 30 min. (actual training time). One intervention group will complete an extensive supervised training program, while the other intervention group will complete a short version ('3 times 3’) that is home-based and controlled by weekly phone calls. Post-tests will be conducted right after the intervention period. Additionally, detraining effects will be measured 12 weeks after program cessation. The control group / waiting group will not participate in any specific intervention during the experimental period, but will receive the extensive supervised program after the experimental period. Discussion It is expected that particularly the supervised combination of balance and strength / power training will improve performance in variables of balance, strength / power, body composition, cognitive function, psychosocial well-being, and falls self-efficacy of older adults. In addition, information regarding fall risk assessment, dose–response-relations, detraining effects, and supervision of training will be provided. Further, training-induced health-relevant changes, such as improved performance in activities of daily living, cognitive function, and quality of life, as well as a reduced risk for falls may help to lower costs in the health care system. Finally, practitioners, therapists, and instructors will be provided with a scientifically evaluated feasible, safe, and easy-to-administer exercise program for fall prevention. Trial registration ClinicalTrials.gov Identifier: NCT01906034 PMID:24106864

Effects of prior warm-up regime on severe-intensity cycling performance.

PubMed

Burnley, Mark; Doust, Jonathan H; Jones, Andrew M

2005-05-01

The purpose of the present study was to determine the effect of three different warm-up regimes on cycling work output during a 7-min performance trial. After habituation to the experimental methods, 12 well-trained cyclists completed a series of 7-min performance trials, involving 2 min of constant-work rate exercise at approximately 90% VO2max and a further 5 min during which subjects attempted to maximize power output. This trial was performed without prior intervention and 10 min after bouts of moderate, heavy, or sprint exercise in a random order. Pulmonary gas exchange was measured breath by breath during all performance trials. At the onset of the performance trial, baseline blood [lactate] was significantly elevated after heavy and sprint but not moderate exercise (mean +/- SD: control, 1.0 +/- 0.3 mM; moderate, 1.0 +/- 0.2 mM; heavy, 3.0 +/- 1.1 mM; sprint, 5.9 +/- 1.5 mM). All three interventions significantly increased the amplitude of the primary VO2 response (control, 2.59 +/- 0.28 L x min(-1); moderate, 2.69 +/- 0.27 L x min(-1); heavy, 2.78 +/- 0.26 L x min(-1); sprint, 2.78 +/- 0.30 L x min(-1)). Mean power output was significantly increased by prior moderate and heavy exercise but not significantly reduced after sprint exercise (control, 330 +/- 42 W; moderate, 338 +/- 39 W; heavy, 339 +/- 42 W; sprint, 324 +/- 45 W). These data indicate that priming exercise performed in the moderate- and heavy-intensity domains can improve severe-intensity cycling performance by ~2-3%, the latter condition doing so despite a mild lactacidosis being present at exercise onset.

The Sentry Autonomous Underwater Vehicle: Field Trial Results and Future Capabilities

NASA Astrophysics Data System (ADS)

Yoerger, D. R.; Bradley, A. M.; Martin, S. C.; Whitcomb, L. L.

2006-12-01

The Sentry autonomous underwater vehicle combines an efficient long range survey capability with the ability to maneuver at low speeds. These attributes will permit Sentry to perform a variety of conventional and unconventional surveys including long range sonar surveys, hydrothermal plume surveys and near-bottom photo surveys. Sentry's streamlined body and fore and aft tilting planes, each possessing an independently controlled thruster, enable efficient operation in both near-bottom and cruising operations. Sentry is capable of being configured in two modes: hover mode, which commands Sentry's control surfaces to be aligned vertically, and forward flight mode, which allows Sentry's control surfaces to actuate between plus or minus 45 degrees. Sentry is equipped for full 6-Degrees of freedom position measurement. Vehicle heading, roll, and pitch are instrumented with a TCM2 PNI heading and attitude sensor. A Systron Donner yaw rate sensor instrumented heading rate. Depth is instrumented by a Paroscientific depth sensor. A 300kHz RD Instruments Doppler Sonar provides altitude and XYZ velocity measurements. In April 2006, we conducted our first deep water field trials of Sentry in Bermuda. These trials enabled us to examine a variety of issues, including the control software, vehicle safety systems, launch and recovery procedures, operation at depth, heading and depth controllers over a range of speeds, and power consumption. Sentry employ's a control system based upon the Jason 2 control system for low-level control, which has proven effective and reliable over several hundred deep-water dives. The Jason 2 control system, developed jointly at Johns Hopkins University and Woods Hole Oceanographic Institution, was augmented to manage Sentry-specific devices (sensors, actuators, and power storage) and to employ a high-level mission controller that supported autonomous mission scripting and error detection and response. This control suite will also support the Nereus Hybrid ROV, also in development at Woods Hole. Both systems performed well during these engineering trials. Sentry's heading and depth controller was tested in a series of trials at different speeds. The heading set point was maintained within approximately ½ degree and appeared to be limited by the precision of the heading sensor. The depth set point, during level flight, was maintained within about 2 centimeters. Based on these tests, we can project Sentry's range as a function of speed. Vehicle speed was measured by a 300 khz bottom-lock Doppler sonar while energy consumption was measured using a coulometer and voltage measurement. The vehicle flew complementary courses at the same levels of forward thrust, which allowed the effects of ambient currents to be eliminated. Assuming a sensor power level consistent with plume survey and bathymetric survey and a 10 kilowatt-hour battery, Sentry will be able to survey 100 km at 2.5 knots and over 150 km at 1.5 knots. Upgrades to Sentry that are presently funded and underway include the addition of an inertial navigation system, improved batteries, a camera system, and a multibeam sonar.

Sample size determination for GEE analyses of stepped wedge cluster randomized trials.

PubMed

Li, Fan; Turner, Elizabeth L; Preisser, John S

2018-06-19

In stepped wedge cluster randomized trials, intact clusters of individuals switch from control to intervention from a randomly assigned period onwards. Such trials are becoming increasingly popular in health services research. When a closed cohort is recruited from each cluster for longitudinal follow-up, proper sample size calculation should account for three distinct types of intraclass correlations: the within-period, the inter-period, and the within-individual correlations. Setting the latter two correlation parameters to be equal accommodates cross-sectional designs. We propose sample size procedures for continuous and binary responses within the framework of generalized estimating equations that employ a block exchangeable within-cluster correlation structure defined from the distinct correlation types. For continuous responses, we show that the intraclass correlations affect power only through two eigenvalues of the correlation matrix. We demonstrate that analytical power agrees well with simulated power for as few as eight clusters, when data are analyzed using bias-corrected estimating equations for the correlation parameters concurrently with a bias-corrected sandwich variance estimator. © 2018, The International Biometric Society.

Does hospital at home for palliative care facilitate death at home? Randomised controlled trial

PubMed Central

Grande, Gunn E; Todd, Chris J; Barclay, Stephen I G; Farquhar, Morag C

1999-01-01

Objective To evaluate the impact on place of death of a hospital at home service for palliative care. Design Pragmatic randomised controlled trial. Setting Former Cambridge health district. Participants 229 patients referred to the hospital at home service; 43 randomised to control group (standard care), 186 randomised to hospital at home. Intervention Hospital at home versus standard care. Main outcome measures Place of death. Results Twenty five (58%) control patients died at home compared with 124 (67%) patients allocated to hospital at home. This difference was not significant; intention to treat analysis did not show that hospital at home increased the number of deaths at home. Seventy three patients randomised to hospital at home were not admitted to the service. Patients admitted to hospital at home were significantly more likely to die at home (88/113; 78%) than control patients. It is not possible to determine whether this was due to hospital at home itself or other characteristics of the patients admitted to the service. The study attained less statistical power than initially planned. Conclusion In a locality with good provision of standard community care we could not show that hospital at home allowed more patients to die at home, although neither does the study refute this. Problems relating to recruitment, attrition, and the vulnerability of the patient group make randomised controlled trials in palliative care difficult. While these difficulties have to be recognised they are not insurmountable with the appropriate resourcing and setting. Key messagesTerminally ill patients allocated to hospital at home were no more likely to die at home than patients receiving standard careAlthough the subsample of patients actually admitted to hospital at home did show a significant increase in likelihood of dying at home, whether this was due to the service itself or the characteristics of patients admitted to hospital at home could not be determinedThe need to balance ideal research design against the realities of evaluation of palliative care had the effect that the trial achieved less statistical power than originally plannedParticular problems were that many patients failed to receive the allocated intervention because of the unpredictable nature of terminal illness, inclusion of other service input alongside hospital at home, and the wide range of standard care availableThe trial illustrated problems associated with randomised controlled trials in palliative care, none of which are insurmountable but which require careful consideration and resourcing before future trials are planned PMID:10582932

Low-Power Polling Mode of the Next-Generation IMES2 Implantable Wireless EMG Sensor

PubMed Central

DeMichele, Glenn A.; Hu, Zhe; Troyk, Philip R.; Chen, Hongnan; Weir, Richard F. ff.

2015-01-01

The IMES1 Implantable MyoElectric Sensor device is currently in human clinical trials led by the Alfred Mann Foundation. The IMES is implanted in a residual limb and is powered wirelessly using a magnetic field. EMG signals resulting from the amputee’s voluntary movement are amplified and transmitted wirelessly by the IMES to an external controller which controls movement of an external motorized prosthesis. Development of the IMES technology is on-going, producing the next-generation IMES2. Among various improvements, a new feature of the IMES2 is a lowpower polling mode. In this low-power mode, the IMES2 power consumption can be dramatically reduced when the limb is inactive through the use of a polled sampling. With the onset of EMG activity, the IMES2 system can switch to the normal higher sample rate to allow the acquisition of high-fidelity EMG data for prosthesis control. PMID:25570642

Comparison of Critical Power and W' Derived From 2 or 3 Maximal Tests.

PubMed

Simpson, Len Parker; Kordi, Mehdi

2017-07-01

Typically, accessing the asymptote (critical power; CP) and curvature constant (W') parameters of the hyperbolic power-duration relationship requires multiple constant-power exhaustive-exercise trials spread over several visits. However, more recently single-visit protocols and personal power meters have been used. This study investigated the practicality of using a 2-trial, single-visit protocol in providing reliable CP and W' estimates. Eight trained cyclists underwent 3- and 12-min maximal-exercise trials in a single session to derive (2-trial) CP and W' estimates. On a separate occasion a 5-min trial was performed, providing a 3rd trial to calculate (3-trial) CP and W'. There were no differences in CP (283 ± 66 vs 282 ± 65 W) or W' (18.72 ± 6.21 vs 18.27 ± 6.29 kJ) obtained from either the 2-trial or 3-trial method, respectively. After 2 familiarization sessions (completing a 3- and a 12-min trial on both occasions), both CP and W' remained reliable over additional separate measurements. The current study demonstrates that after 2 familiarization sessions, reliable CP and W' parameters can be obtained from trained cyclists using only 2 maximal-exercise trials. These results offer practitioners a practical, time-efficient solution for incorporating power-duration testing into applied athlete support.

The Consolidated Standards of Reporting Trials (CONSORT) Statement applied to allergen-specific immunotherapy with inhalant allergens: a Global Allergy and Asthma European Network (GA(2)LEN) article.

PubMed

Bousquet, Philippe J; Calderón, Moisés A; Demoly, Pascal; Larenas, Désirée; Passalacqua, Giovanni; Bachert, Claus; Brozek, Jan; Canonica, G Walter; Casale, Thomas; Fonseca, Joao; Dahl, Ronald; Durham, Stephen R; Merk, Hans; Worm, Margitta; Wahn, Ulrich; Zuberbier, Torsten; Schünemann, Holger J; Bousquet, Jean

2011-01-01

Randomized trials provide evidence to inform treatment decisions. The Consolidated Standards of Reporting Trials (CONSORT) Statement is a set of recommendations for the reporting of trials. We sought to assess the quality of reporting allergen-specific immunotherapy trials according to CONSORT criteria. The reporting of the procedure, randomization, dropouts, strict conduct of intention-to-treat (ITT) analysis, and sample size calculation according to CONSORT were assessed in the 46 subcutaneous and 48 sublingual immunotherapy (SLIT) blind, placebo-controlled randomized trials published between 1996 and 2009 in English. One subcutaneous immunotherapy (2.2%) and 3 SLIT (6.6%) trials met CONSORT Statement criteria. These were used for the registration of sublingual tablets to the European Medicines Agency. In subcutaneous immunotherapy, 16 (35%) studies reported a CONSORT flow chart, and 12 (26%) provided a description of dropouts. Adequate randomization was reported in 9 (35%) studies, and incomplete randomization was reported in 15 (33%). Power analysis was reported in 15 (33%) studies. In SLIT, 20 (42%) studies reported a CONSORT flow chart, and 16 (32%) a description of dropouts. ITT analysis was carried out in 1 (2.2%) SLIT study, and a modified ITT analysis was used in 1 (2.2%) subcutaneous immunotherapy study and 2 (4.4%) SLIT studies. Adequate randomization was reported in 6 (12%) studies, and incomplete randomization was reported in 16 (32%). Power analysis was reported in 15 (27%) studies. As in other areas of medicine, the quality of reporting of most immunotherapy trials is low, and only 4.2% of SLIT randomized controlled trials met all of the criteria of the CONSORT Statement. Use of the CONSORT criteria should be encouraged. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Publication bias was not a good reason to discourage trials with low power.

PubMed

Borm, George F; den Heijer, Martin; Zielhuis, Gerhard A

2009-01-01

The objective was to investigate whether it is justified to discourage trials with less than 80% power. Trials with low power are unlikely to produce conclusive results, but their findings can be used by pooling then in a meta-analysis. However, such an analysis may be biased, because trials with low power are likely to have a nonsignificant result and are less likely to be published than trials with a statistically significant outcome. We simulated several series of studies with varying degrees of publication bias and then calculated the "real" one-sided type I error and the bias of meta-analyses with a "nominal" error rate (significance level) of 2.5%. In single trials, in which heterogeneity was set at zero, low, and high, the error rates were 2.3%, 4.7%, and 16.5%, respectively. In multiple trials with 80%-90% power and a publication rate of 90% when the results were nonsignificant, the error rates could be as high as 5.1%. When the power was 50% and the publication rate of non-significant results was 60%, the error rates did not exceed 5.3%, whereas the bias was at most 15% of the difference used in the power calculation. The impact of publication bias does not warrant the exclusion of trials with 50% power.

Improving Well-being and Health for People with Dementia (WHELD): study protocol for a randomised controlled trial

PubMed Central

2014-01-01

Background People with dementia living in care homes often have complex mental health problems, disabilities and social needs. Providing more comprehensive training for staff working in care home environments is a high national priority. It is important that this training is evidence based and delivers improvement for people with dementia residing in these environments. Well-being and Health for People with Dementia (WHELD) combines the most effective elements of existing approaches to develop a comprehensive but practical staff training intervention. This optimised intervention is based on a factorial study and qualitative evaluation, to combine: training on person-centred care, promoting person-centred activities and interactions, and providing care home staff and general practitioners with updated knowledge regarding the optimal use of psychotropic medications for persons with dementia in care homes. Design The trial will be a randomised controlled two-arm cluster single blind trial that will take place for nine months across 80 care homes in the United Kingdom. Discussion The overarching goal of this trial is to determine whether this optimised WHELD intervention is more effective in improving the quality of life and mental health than the usual care provided to people with dementia living in nursing homes. This study will be the largest and best powered randomised controlled trial (RCT) evaluating the benefits of an augmented person-centred care training intervention in care homes worldwide. Trial registration Current controlled trials ISRCTN62237498 Date registered: 5 September 2013 PMID:25016303

Hydrotherapy improves pain and function in older women with knee osteoarthritis: a randomized controlled trial.

PubMed

Dias, João Marcos; Cisneros, Lígia; Dias, Rosângela; Fritsch, Carolina; Gomes, Wellington; Pereira, Leani; Santos, Mary Luci; Ferreira, Paulo Henrique

Currently, there is poor evidence of the effect of hydrotherapy alone on patients with hip or knee osteoarthritis. The study aimed to assess the impact of hydrotherapy on pain, function, and muscle function in older women with knee osteoarthritis. A randomized controlled trial was conducted to evaluate the efficacy of hydrotherapy in women with knee osteoarthritis. Seventy-three women aged 65 and older were randomized to hydrotherapy (n=36) or a control group (n=37). The hydrotherapy group received the intervention program in a heated pool (twice per week for six weeks) and an educational protocol while the control group received an educational protocol only. Primary outcomes (before and post-treatment) were pain intensity (0-100) and function (0-100), assessed with the WOMAC questionnaire. Secondary outcomes (before and post-treatment) were knee extensor and knee flexor muscle performance (strength, power, and endurance), assessed by an isokinetic dynamometer. The magnitude of change between the groups for the outcomes was calculated using linear regression models adjusted by baseline outcome values. The hydrotherapy group had better outcomes for pain (adjusted mean difference=11 points, 95% CI: 3-18) and function (adjusted mean difference=12 points, 95% CI: 5-18). Patients receiving hydrotherapy had better performance for knee flexor and extensor strength, knee flexor power, and knee extensor endurance. Older women with knee osteoarthritis are likely to have benefits from a course of hydrotherapy exercises. Registry of clinical trials (Trial number RBR-8F57KR) - http://www.ensaiosclinicos.gov.br/rg/RBR-8f57kr/. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Update to a protocol for a feasibility cluster randomised controlled trial of a peer-led school-based intervention to increase the physical activity of adolescent girls (PLAN-A).

PubMed

Sebire, Simon J; Edwards, Mark J; Campbell, Rona; Jago, Russell; Kipping, Ruth; Banfield, Kathryn; Kadir, Bryar; Garfield, Kirsty; Lyons, Ronan A; Blair, Peter S; Hollingworth, William

2016-01-01

Physical activity levels are low amongst adolescent girls, and this population faces specific barriers to being active. Peer influences on health behaviours are important in adolescence, and peer-led interventions might hold promise to change behaviour. This paper describes the protocol for a feasibility cluster randomised controlled trial of Peer-Led physical Activity iNtervention for Adolescent girls (PLAN-A), a peer-led intervention aimed at increasing adolescent girls' physical activity levels. In addition, this paper describes an update that has been made to the protocol for the PLAN-A feasibility cluster randomised controlled trial. A two-arm cluster randomised feasibility trial will be conducted in six secondary schools (intervention n  = 4; control n  = 2) with year 8 (12-13 years old) girls. The intervention will operate at a year group level and consist of year 8 girls nominating influential peers within their year group to become peer supporters. Approximately 15% of the cohort will receive 3 days of training about physical activity and interpersonal communication skills. Peer supporters will then informally diffuse messages about physical activity amongst their friends for 10 weeks. Data will be collected at baseline (time 0 (T0)), immediately after the intervention (time 1 (T1)) and 12 months after baseline measures (time 2 (T2)). In this feasibility trial, the primary interest is in the recruitment of schools and participants (both year 8 girls and peer supporters), delivery and receipt of the intervention, data provision rates and identifying the cost categories for future economic analysis. Physical activity will be assessed using 7-day accelerometry, with the likely primary outcome in a fully powered trial being daily minutes of moderate-to-vigorous physical activity. Participants will also complete psychosocial questionnaires at each time point: assessing motivation, self-esteem and peer physical activity norms. Data analysis will be largely descriptive and focus on recruitment, attendance and data provision rates. The findings will inform the sample size required for a definitive trial. A detailed process evaluation using qualitative and quantitative methods will be conducted with a variety of stakeholders (i.e. pupils, parents, teachers and peer-supporter trainers) to identify areas of success and necessary improvements prior to proceeding to a definitive trial. The study will provide the information necessary to design a fully powered trial should PLAN-A demonstrate evidence of promise. This paper describes an update to the protocol for the PLAN-A feasibility cluster randomised controlled trial related to the data-linkage component. ISRCTN12543546.

Effect of a 5-min cold-water immersion recovery on exercise performance in the heat.

PubMed

Peiffer, J J; Abbiss, C R; Watson, G; Nosaka, K; Laursen, P B

2010-05-01

This study examined the effect of a 5-min cold-water immersion (14 degrees C) recovery intervention on repeated cycling performance in the heat. 10 male cyclists performed two bouts of a 25-min constant-paced (254 (22) W) cycling session followed by a 4-km time trial in hot conditions (35 degrees C, 40% relative humidity). The two bouts were separated by either 15 min of seated recovery in the heat (control) or the same condition with 5-min cold-water immersion (5th-10th minute), using a counterbalanced cross-over design (CP(1)TT(1) --> CWI or CON --> CP(2)TT(2)). Rectal temperature was measured immediately before and after both the constant-paced sessions and 4-km timed trials. Cycling economy and Vo(2) were measured during the constant-paced sessions, and the average power output and completion times were recorded for each time trial. Compared with control, rectal temperature was significantly lower (0.5 (0.4) degrees C) in cold-water immersion before CP(2) until the end of the second 4-km timed trial. However, the increase in rectal temperature (0.5 (0.2) degrees C) during CP(2) was not significantly different between conditions. During the second 4-km timed trial, power output was significantly greater in cold-water immersion (327.9 (55.7) W) compared with control (288.0 (58.8) W), leading to a faster completion time in cold-water immersion (6.1 (0.3) min) compared with control (6.4 (0.5) min). Economy and Vo(2) were not influenced by the cold-water immersion recovery intervention. 5-min cold-water immersion recovery significantly lowered rectal temperature and maintained endurance performance during subsequent high-intensity exercise. These data indicate that repeated exercise performance in heat may be improved when a short period of cold-water immersion is applied during the recovery period.

Immediate chest X-ray for patients at risk of lung cancer presenting in primary care: randomised controlled feasibility trial

PubMed Central

Neal, Richard D; Barham, Allan; Bongard, Emily; Edwards, Rhiannon Tudor; Fitzgibbon, Jim; Griffiths, Gareth; Hamilton, Willie; Hood, Kerenza; Nelson, Annmarie; Parker, David; Porter, Cath; Prout, Hayley; Roberts, Kirsty; Rogers, Trevor; Thomas-Jones, Emma; Tod, Angela; Yeo, Seow Tien; Hurt, Chris N

2017-01-01

Background: Achieving earlier stage diagnosis is one option for improving lung cancer outcomes in the United Kingdom. Patients with lung cancer typically present with symptoms to general practitioners several times before referral or investigation. Methods: We undertook a mixed methods feasibility individually randomised controlled trial (the ELCID trial) to assess the feasibility and inform the design of a definitive, fully powered, UK-wide, Phase III trial of lowering the threshold for urgent investigation of suspected lung cancer. Patients over 60, with a smoking history, presenting with new chest symptoms to primary care, were eligible to be randomised to intervention (urgent chest X-ray) or usual care. Results: The trial design and materials were acceptable to GPs and patients. We randomised 255 patients from 22 practices, although the proportion of eligible patients who participated was lower than expected. Survey responses (89%), and the fidelity of the intervention (82% patients X-rayed within 3 weeks) were good. There was slightly higher anxiety and depression in the control arm in participants aged >75. Three patients (1.2%) were diagnosed with lung cancer. Conclusions: We have demonstrated the feasibility of individually randomising patients at higher risk of lung cancer, to a trial offering urgent investigation or usual care. PMID:28072761

Can wireless text messaging improve adherence to preventive activities? Results of a randomised controlled trial.

PubMed

Cocosila, Mihail; Archer, Norm; Haynes, R Brian; Yuan, Yufei

2009-04-01

To determine the effectiveness of cell phone wireless text messaging for improving adherence to a healthy behaviour. A randomised, unblinded, controlled trial was conducted with 102 subjects, 18 years or older, each having a cell phone and willing to take 1 vitamin C pill per day for 1 month for preventive reasons. Intervention group participants received text messaging reminders and were asked to acknowledge receiving their messages after taking the vitamins, whereas control group subjects had no text messaging activity. Self-reported adherence and the number of participant text messages acknowledging vitamins taken. Both groups reported an increased adherence after the trial: by 246% for the intervention group and by 131% for the control group. There was a non-significant difference between the two groups at endpoint: an average difference of 0.8 between the number of pills missed in the last week of the trial (2.5 out of 7 in the intervention and 3.3 out of 7 in the control group) with a power of 0.54. The study revealed a significant correlation (coefficient=-0.352, sig.=0.01) between the average number of text messaging acknowledgements sent by the intervention group participants and the number of pills they reported missed during the last week of the trial. This was a small randomised controlled trial with inconclusive but encouraging results. It suggests a new approach in addressing insufficient adherence in outpatient conditions and shows that the use of information technology tools for compliance warrants further research.

Blinded sample size re-estimation in three-arm trials with 'gold standard' design.

PubMed

Mütze, Tobias; Friede, Tim

2017-10-15

In this article, we study blinded sample size re-estimation in the 'gold standard' design with internal pilot study for normally distributed outcomes. The 'gold standard' design is a three-arm clinical trial design that includes an active and a placebo control in addition to an experimental treatment. We focus on the absolute margin approach to hypothesis testing in three-arm trials at which the non-inferiority of the experimental treatment and the assay sensitivity are assessed by pairwise comparisons. We compare several blinded sample size re-estimation procedures in a simulation study assessing operating characteristics including power and type I error. We find that sample size re-estimation based on the popular one-sample variance estimator results in overpowered trials. Moreover, sample size re-estimation based on unbiased variance estimators such as the Xing-Ganju variance estimator results in underpowered trials, as it is expected because an overestimation of the variance and thus the sample size is in general required for the re-estimation procedure to eventually meet the target power. To overcome this problem, we propose an inflation factor for the sample size re-estimation with the Xing-Ganju variance estimator and show that this approach results in adequately powered trials. Because of favorable features of the Xing-Ganju variance estimator such as unbiasedness and a distribution independent of the group means, the inflation factor does not depend on the nuisance parameter and, therefore, can be calculated prior to a trial. Moreover, we prove that the sample size re-estimation based on the Xing-Ganju variance estimator does not bias the effect estimate. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Variable Cadence Walking and Ground Adaptive Standing with a Powered Ankle Prosthesis

PubMed Central

Shultz, Amanda H.; Lawson, Brian E.; Goldfarb, Michael

2015-01-01

Abstract This paper describes a control approach that provides walking and standing functionality for a powered ankle prosthesis, and demonstrates the efficacy of the approach in experiments in which a unilateral transtibial amputee subject walks with the prosthesis at variable cadences, and stands on various slopes. Both controllers incorporate a finite-state structure that emulates healthy ankle joint behavior via a series of piecewise passive impedance functions. The walking controller incorporates an algorithm to modify impedance parameters based on estimated cadence, while the standing controller incorporates an algorithm to modulate the ankle equilibrium angle in order to adapt to the ground slope and user posture, and the supervisory controller selects between the walking and standing controllers. The system is shown to reproduce several essential biomechanical features of the healthy joint during walking, particularly relative to a passive prosthesis, and is shown to adapt to variable cadences. The system is also shown to adapt to slopes over a range of ± 15 deg and to provide support to the user in a manner that is biomimetic, as validated by quasi-static stiffness measurements recorded by the prosthesis. Data from standing trials indicate that the user places more weight on the powered prosthesis than on his passive prosthesis when standing on sloped surfaces, particularly at angles of 10 deg or greater. The authors also demonstrated that the prosthesis typically began providing support within 1 s of initial contact with the ground. Further, the supervisory controller was shown to be effective in switching between walking and standing, as well as in determining ground slope just prior to the transition from the standing controller to the walking controller, where the estimated ground slope was within 1.25 deg of the actual ground slope for all trials. PMID:25955789

The impact of blackcurrant juice on attention, mood and brain wave spectral activity in young healthy volunteers.

PubMed

Watson, A W; Okello, E J; Brooker, H J; Lester, S; McDougall, G J; Wesnes, K A

2018-01-17

There is a growing body of evidence from randomized controlled trials which indicates that consumption of berries has a positive effect upon the cognitive function of healthy adults. It has been recommended that studies combining cognitive and physiological measures be undertaken in order to strengthen the evidence base for the putative effects of flavonoid consumption on cognitive outcomes. This pilot study utilized a randomized, double-blind and placebo controlled crossover design to assess the influence of the acute administration of anthocyanin-rich blackcurrant juice, standardized at 500 mg of polyphenols, on mood and attention. Additionally, this trial used electroencephalography (EEG) to assess if any changes in cognitive performance are associated with changes in localized prefrontal cortex neuronal activity in nine healthy young adults. Outcomes from the pilot EEG data highlight an anxiolytic effect of the consumption of a single serve blackcurrant juice, as indexed by a suppression of α spectral power, and an increase in the slow wave δ and θ spectral powers. There was also an indication of greater alertness and lower fatigue, as indexed by an increase in β power and suppression of α spectral power. Outcomes from the CogTrack™ system indicated a small acute increase in reaction times during the digit vigilance task.

Improving data sharing in research with context-free encoded missing data.

PubMed

Hoevenaar-Blom, Marieke P; Guillemont, Juliette; Ngandu, Tiia; Beishuizen, Cathrien R L; Coley, Nicola; Moll van Charante, Eric P; Andrieu, Sandrine; Kivipelto, Miia; Soininen, Hilkka; Brayne, Carol; Meiller, Yannick; Richard, Edo

2017-01-01

Lack of attention to missing data in research may result in biased results, loss of power and reduced generalizability. Registering reasons for missing values at the time of data collection, or-in the case of sharing existing data-before making data available to other teams, can save time and efforts, improve scientific value and help to prevent erroneous assumptions and biased results. To ensure that encoding of missing data is sufficient to understand the reason why data are missing, it should ideally be context-free. Therefore, 11 context-free codes of missing data were carefully designed based on three completed randomized controlled clinical trials and tested in a new randomized controlled clinical trial by an international team consisting of clinical researchers and epidemiologists with extended experience in designing and conducting trials and an Information System expert. These codes can be divided into missing due to participant and/or participation characteristics (n = 6), missing by design (n = 4), and due to a procedural error (n = 1). Broad implementation of context-free missing data encoding may enhance the possibilities of data sharing and pooling, thus allowing more powerful analyses using existing data.

The role of treatment timing and mode of stimulation in the treatment of primary dysmenorrhea with acupuncture: An exploratory randomised controlled trial.

PubMed

Armour, Mike; Dahlen, Hannah G; Zhu, Xiaoshu; Farquhar, Cindy; Smith, Caroline A

2017-01-01

We examined the effect of changing treatment timing and the use of manual, electro acupuncture on the symptoms of primary dysmenorrhea. A randomised controlled trial was performed with four arms, low frequency manual acupuncture (LF-MA), high frequency manual acupuncture (HF-MA), low frequency electro acupuncture (LF-EA) and high frequency electro acupuncture (HF-EA). A manualised trial protocol was used to allow differentiation and individualized treatment over three months. A total of 74 women were randomly assigned to one of the four groups (LF-MA n = 19, HF-MA n = 18, LF-EA n = 18, HF-EA n = 19). Twelve treatments were performed over three menstrual cycles, either once per week (LF groups) or three times in the week prior to menses (HF groups). All groups received a treatment in the first 48 hours of menses. The primary outcome was the reduction in peak menstrual pain at 12 months from trial entry. During the treatment period and nine month follow-up all groups showed statistically significant (p < .001) reductions in peak and average menstrual pain compared to baseline but there were no differences between groups (p > 0.05). Health related quality of life increased significantly in six domains in groups having high frequency of treatment compared to two domains in low frequency groups. Manual acupuncture groups required less analgesic medication than electro-acupuncture groups (p = 0.02). HF-MA was most effective in reducing secondary menstrual symptoms compared to both-EA groups (p<0.05). Acupuncture treatment reduced menstrual pain intensity and duration after three months of treatment and this was sustained for up to one year after trial entry. The effect of changing mode of stimulation or frequency of treatment on menstrual pain was not significant. This may be due to a lack of power. The role of acupuncture stimulation on menstrual pain needs to be investigated in appropriately powered randomised controlled trials.

The role of treatment timing and mode of stimulation in the treatment of primary dysmenorrhea with acupuncture: An exploratory randomised controlled trial

PubMed Central

Dahlen, Hannah G.; Zhu, Xiaoshu; Farquhar, Cindy; Smith, Caroline A.

2017-01-01

Objectives We examined the effect of changing treatment timing and the use of manual, electro acupuncture on the symptoms of primary dysmenorrhea. Methods A randomised controlled trial was performed with four arms, low frequency manual acupuncture (LF-MA), high frequency manual acupuncture (HF-MA), low frequency electro acupuncture (LF-EA) and high frequency electro acupuncture (HF-EA). A manualised trial protocol was used to allow differentiation and individualized treatment over three months. A total of 74 women were randomly assigned to one of the four groups (LF-MA n = 19, HF-MA n = 18, LF-EA n = 18, HF-EA n = 19). Twelve treatments were performed over three menstrual cycles, either once per week (LF groups) or three times in the week prior to menses (HF groups). All groups received a treatment in the first 48 hours of menses. The primary outcome was the reduction in peak menstrual pain at 12 months from trial entry. Results During the treatment period and nine month follow-up all groups showed statistically significant (p < .001) reductions in peak and average menstrual pain compared to baseline but there were no differences between groups (p > 0.05). Health related quality of life increased significantly in six domains in groups having high frequency of treatment compared to two domains in low frequency groups. Manual acupuncture groups required less analgesic medication than electro-acupuncture groups (p = 0.02). HF-MA was most effective in reducing secondary menstrual symptoms compared to both–EA groups (p<0.05). Conclusion Acupuncture treatment reduced menstrual pain intensity and duration after three months of treatment and this was sustained for up to one year after trial entry. The effect of changing mode of stimulation or frequency of treatment on menstrual pain was not significant. This may be due to a lack of power. The role of acupuncture stimulation on menstrual pain needs to be investigated in appropriately powered randomised controlled trials. PMID:28700680

StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR): study protocol for a randomised controlled clinical trial.

PubMed

Neffendorf, James E; Desai, Riti; Wang, Yanzhong; Kelly, Joanna; Murphy, Caroline; Reeves, Barnaby C; Chakravarthy, Usha; Wordsworth, Sarah; Lewis, Cornelius; Peacock, Janet; Uddin, Shahir; O'Sullivan, Joe M; Jackson, Timothy L

2016-11-24

The standard of care for neovascular age-related macular degeneration (nAMD) involves ongoing intravitreal injections of anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF). The most commonly used anti-VEGF drugs are ranibizumab, bevacizumab and aflibercept. The main objective of the STAR trial is to determine if stereotactic radiotherapy can reduce the number of anti-VEGF injections that patients with nAMD require. STAR is a multicentre, double-masked, randomised, sham-controlled clinical trial. It evaluates a new device (manufactured by Oraya, Newark, CA, USA) designed to deliver stereotactic radiotherapy (SRT) to nAMD lesions. The trial enrols participants with chronic, active nAMD. Participants receive a single SRT treatment (16 Gy or sham) with a concomitant baseline intravitreal injection of 0.5 mg ranibizumab. Thereafter, they attend every month for 24 months, and ranibizumab is administered at the visit if retreatment criteria are met. The primary outcome is the number of pro re nata ranibizumab injections during the first 24 months. Secondary outcomes include visual acuity, lesion morphology, quality of life and safety. Additional visits occur at 36 and 48 months to inspect for radiation retinopathy. The target sample size of 411 participants (randomised 2:1 in favour of radiation) is designed to detect a reduction of 2.5 injections against ranibizumab monotherapy, at 90% power, and a significance level (alpha) of 0.025 (one-sided two-sample t test). This gives 97% power to detect non-inferiority of visual acuity at a five-letter margin. The primary analyses will be by intention to treat. The safety and efficacy outcomes will help determine the role of SRT in the management of chronic, active nAMD. International Standard Randomised Controlled Trial Number: ISRCTN12884465. Registered on 28 November 2014. ClinicalTrials.gov: NCT02243878 . Registered on 17 September 2014.

An exploration of the relationship between placebo and homeopathy and the implications for clinical trial design

PubMed Central

Haresnape, Claire

2013-01-01

Placebo appears to be a real neurobiological phenomenon that has evolved through the selection pressure to be able to heal ourselves. The complex language and social structures of humans means that we can attribute meaning to therapeutic encounters with culturally sanctioned authority figures and we can use our attachment to such figures to generate hope for recovery. Different mechanisms may be involved in the neurobiological aspect of placebo including anxiety, learning, conditioning as well as individual genetic variation. Examination of the published work shows that while some trials do seem to indicate a specific mode of action for homeopathic remedies other trials do not and this is an issue that needs to be addressed at the trial design stage. A clinical trial that includes both a placebo group and a non-participating control arm is the most powerful design for separating the non-specific and polymorphic placebo effect from the specific effects of trial medication. The control variables in a trial of homeopathic medication should also include the process of consultation as this may assume a meaning for the individual that can also be associated with a placebo effect. PMID:24040505

Treatment Trials for Neonatal Seizures: The Effect of Design on Sample Size

PubMed Central

Stevenson, Nathan J.; Boylan, Geraldine B.; Hellström-Westas, Lena; Vanhatalo, Sampsa

2016-01-01

Neonatal seizures are common in the neonatal intensive care unit. Clinicians treat these seizures with several anti-epileptic drugs (AEDs) to reduce seizures in a neonate. Current AEDs exhibit sub-optimal efficacy and several randomized control trials (RCT) of novel AEDs are planned. The aim of this study was to measure the influence of trial design on the required sample size of a RCT. We used seizure time courses from 41 term neonates with hypoxic ischaemic encephalopathy to build seizure treatment trial simulations. We used five outcome measures, three AED protocols, eight treatment delays from seizure onset (Td) and four levels of trial AED efficacy to simulate different RCTs. We performed power calculations for each RCT design and analysed the resultant sample size. We also assessed the rate of false positives, or placebo effect, in typical uncontrolled studies. We found that the false positive rate ranged from 5 to 85% of patients depending on RCT design. For controlled trials, the choice of outcome measure had the largest effect on sample size with median differences of 30.7 fold (IQR: 13.7–40.0) across a range of AED protocols, Td and trial AED efficacy (p<0.001). RCTs that compared the trial AED with positive controls required sample sizes with a median fold increase of 3.2 (IQR: 1.9–11.9; p<0.001). Delays in AED administration from seizure onset also increased the required sample size 2.1 fold (IQR: 1.7–2.9; p<0.001). Subgroup analysis showed that RCTs in neonates treated with hypothermia required a median fold increase in sample size of 2.6 (IQR: 2.4–3.0) compared to trials in normothermic neonates (p<0.001). These results show that RCT design has a profound influence on the required sample size. Trials that use a control group, appropriate outcome measure, and control for differences in Td between groups in analysis will be valid and minimise sample size. PMID:27824913

Improving the power of clinical trials of rheumatoid arthritis by using data on continuous scales when analysing response rates: an application of the augmented binary method

PubMed Central

Jenkins, Martin

2016-01-01

Objective. In clinical trials of RA, it is common to assess effectiveness using end points based upon dichotomized continuous measures of disease activity, which classify patients as responders or non-responders. Although dichotomization generally loses statistical power, there are good clinical reasons to use these end points; for example, to allow for patients receiving rescue therapy to be assigned as non-responders. We adopt a statistical technique called the augmented binary method to make better use of the information provided by these continuous measures and account for how close patients were to being responders. Methods. We adapted the augmented binary method for use in RA clinical trials. We used a previously published randomized controlled trial (Oral SyK Inhibition in Rheumatoid Arthritis-1) to assess its performance in comparison to a standard method treating patients purely as responders or non-responders. The power and error rate were investigated by sampling from this study. Results. The augmented binary method reached similar conclusions to standard analysis methods but was able to estimate the difference in response rates to a higher degree of precision. Results suggested that CI widths for ACR responder end points could be reduced by at least 15%, which could equate to reducing the sample size of a study by 29% to achieve the same statistical power. For other end points, the gain was even higher. Type I error rates were not inflated. Conclusion. The augmented binary method shows considerable promise for RA trials, making more efficient use of patient data whilst still reporting outcomes in terms of recognized response end points. PMID:27338084

Determining the impact of a new physiotherapist-led primary care model for back pain: protocol for a pilot cluster randomized controlled trial.

PubMed

Miller, Jordan; Barber, David; Donnelly, Catherine; French, Simon; Green, Michael; Hill, Jonathan; MacDermid, Joy; Marsh, Jacquelyn; Norman, Kathleen; Richardson, Julie; Taljaard, Monica; Wideman, Timothy; Cooper, Lynn; McPhee, Colleen

2017-11-09

Back pain is a leading contributor to disability, healthcare costs, and lost work. Family physicians are the most common first point of contact in the healthcare system for people with back pain, but physiotherapists (PTs) may be able to support the primary care team through evidence-based primary care. A cluster randomized trial is needed to determine the clinical, health system, and societal impact of a primary care model that integrates physiotherapists at the first visit for people with back pain. Prior to conducting a future fully powered cluster randomized trial, we need to demonstrate feasibility of the methods. Therefore, the purpose of this pilot study will be to: 1) Determine feasibility of patient recruitment, assessment procedures, and retention. 2) Determine the feasibility of training and implementation of a new PT-led primary care model for low back pain (LBP) 3) Explore the perspectives of patients and healthcare providers (HCPs) related to their experiences and attitudes towards the new service delivery model, barriers/facilitators to implementation, perceived satisfaction, perceived value, and impact on clinic processes and patient outcomes. This pilot cluster randomized controlled trial will enroll four sites and randomize them to implement a new PT-led primary care model for back pain or a usual physician-led primary care model. All adults booking a primary care visit for back pain will be invited to participate. Feasibility outcomes will include: recruitment and retention rates, completeness of assessment data, PT training participation and confidence after training, and PT treatment fidelity. Secondary outcomes will include the clinical, health system, cost, and process outcomes planned for the future fully powered cluster trial. Results will be analyzed and reported descriptively and qualitatively. To explore perspectives of both HCPs and patients, we will conduct semi-structured qualitative interviews with patients and focus groups with HCPs from participants in the PT-led primary care sites. If this pilot demonstrates feasibility, a fully powered trial will provide evidence that has the potential to transform primary care for back pain. The full trial will inform future service design, whether these models should be more widely implemented, and training agendas. ClinicalTrials.gov, NCT03320148 . Submitted for registration on 17 September 2017.

Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects.

PubMed

Nugent, Allison C; Ballard, Elizabeth D; Gould, Todd D; Park, Lawrence T; Moaddel, Ruin; Brutsche, Nancy E; Zarate, Carlos A

2018-02-27

Ketamine's mechanism of action was assessed using gamma power from magnetoencephalography (MEG) as a proxy measure for homeostatic balance in 35 unmedicated subjects with major depressive disorder (MDD) and 25 healthy controls enrolled in a double-blind, placebo-controlled, randomized cross-over trial of 0.5 mg/kg ketamine. MDD subjects showed significant improvements in depressive symptoms, and healthy control subjects exhibited modest but significant increases in depressive symptoms for up to 1 day after ketamine administration. Both groups showed increased resting gamma power following ketamine. In MDD subjects, gamma power was not associated with the magnitude of the antidepressant effect. However, baseline gamma power was found to moderate the relationship between post-ketamine gamma power and antidepressant response; specifically, higher post-ketamine gamma power was associated with better response in MDD subjects with lower baseline gamma, with an inverted relationship in MDD subjects with higher baseline gamma. This relationship was observed in multiple regions involved in networks hypothesized to be involved in the pathophysiology of MDD. This finding suggests biological subtypes based on the direction of homeostatic dysregulation and has important implications for inferring ketamine's mechanism of action from studies of healthy controls alone.

Feasibility trial of a scalable psychological intervention for women affected by urban adversity and gender-based violence in Nairobi.

PubMed

Dawson, Katie S; Schafer, Alison; Anjuri, Dorothy; Ndogoni, Lincoln; Musyoki, Caroline; Sijbrandij, Marit; van Ommeren, Mark; Bryant, Richard A

2016-11-18

Living in conditions of chronic adversity renders many women more vulnerable to experiencing gender-based violence (GBV). In addition to GBV's physical and social consequences, the psychological effects can be pervasive. Access to evidence-based psychological interventions that seek to support the mental health of women affected by such adversity is rare in low- and middle-income countries. The current study evaluates a brief evidence-informed psychological intervention developed by the World Health Organization for adults impacted by adversity (Problem Management Plus; PM+). A feasibility randomised control trial (RCT) was conducted to inform a fully powered trial. Community health workers delivered the intervention to 70 women residing in three peri-urban settings in Nairobi, Kenya. Women, among whom 80% were survivors of GBV (N = 56), were randomised to receive five sessions of either PM+ (n = 35) by community health workers or enhanced treatment as usual (ETAU; n = 35). PM+ was not associated with any adverse events. Although the study was not powered to identify effects and accordingly did not identify effects on the primary outcome measure of general psychological distress, women survivors of adversity, including GBV, who received PM+ displayed greater reductions in posttraumatic stress disorder symptoms following treatment than those receiving ETAU. This feasibility study suggests that PM+ delivered by lay health workers is an acceptable and safe intervention to reach women experiencing common mental disorders and be inclusive for those affected by GBV and can be studied in a RCT in this setting. The study sets the stage for a fully powered, definitive controlled trial to assess this potentially effective intervention. ACTRN12614001291673 , 10/12/2014, retrospectively registered during the recruitment phase.

Effects of aquatic resistance training on mobility limitation and lower-limb impairments after knee replacement.

PubMed

Valtonen, Anu; Pöyhönen, Tapani; Sipilä, Sarianna; Heinonen, Ari

2010-06-01

To study the effects of aquatic resistance training on mobility, muscle power, and cross-sectional area. Randomized controlled trial. Research laboratory and hospital rehabilitation pool. Population-based sample (N=50) of eligible women and men 55 to 75 years old 4 to 18 months after unilateral knee replacement with no contraindications who were willing to participate in the trial. Twelve-week progressive aquatic resistance training (n=26) or no intervention (n=24). Mobility limitation assessed by walking speed and stair ascending time, and self-reported physical functional difficulty, pain, and stiffness assessed by Western Ontario and McMaster University Osteoarthritis Index (WOMAC) questionnaire. Knee extensor power and knee flexor power assessed isokinetically, and thigh muscle cross-sectional area (CSA) by computed tomography. Compared with the change in the control group, habitual walking speed increased by 9% (P=.005) and stair ascending time decreased by 15% (P=.006) in the aquatic training group. There was no significant difference between the groups in the WOMAC scores. The training increased knee extensor power by 32% (P<.001) in the operated and 10% (P=.001) in the nonoperated leg, and knee flexor power by 48% (P=.003) in the operated and 8% (P=.002) in the nonoperated leg compared with controls. The mean increase in thigh muscle CSA of the operated leg was 3% (P=.018) and that of the nonoperated leg 2% (P=.019) after training compared with controls. Progressive aquatic resistance training had favorable effects on mobility limitation by increasing walking speed and decreasing stair ascending time. In addition, training increased lower limb muscle power and muscle CSA. Resistance training in water is a feasible mode of rehabilitation that has wide-ranging positive effects on patients after knee replacement surgery. Copyright 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

An approach to trial design and analysis in the era of non-proportional hazards of the treatment effect.

PubMed

Royston, Patrick; Parmar, Mahesh K B

2014-08-07

Most randomized controlled trials with a time-to-event outcome are designed and analysed under the proportional hazards assumption, with a target hazard ratio for the treatment effect in mind. However, the hazards may be non-proportional. We address how to design a trial under such conditions, and how to analyse the results. We propose to extend the usual approach, a logrank test, to also include the Grambsch-Therneau test of proportional hazards. We test the resulting composite null hypothesis using a joint test for the hazard ratio and for time-dependent behaviour of the hazard ratio. We compute the power and sample size for the logrank test under proportional hazards, and from that we compute the power of the joint test. For the estimation of relevant quantities from the trial data, various models could be used; we advocate adopting a pre-specified flexible parametric survival model that supports time-dependent behaviour of the hazard ratio. We present the mathematics for calculating the power and sample size for the joint test. We illustrate the methodology in real data from two randomized trials, one in ovarian cancer and the other in treating cellulitis. We show selected estimates and their uncertainty derived from the advocated flexible parametric model. We demonstrate in a small simulation study that when a treatment effect either increases or decreases over time, the joint test can outperform the logrank test in the presence of both patterns of non-proportional hazards. Those designing and analysing trials in the era of non-proportional hazards need to acknowledge that a more complex type of treatment effect is becoming more common. Our method for the design of the trial retains the tools familiar in the standard methodology based on the logrank test, and extends it to incorporate a joint test of the null hypothesis with power against non-proportional hazards. For the analysis of trial data, we propose the use of a pre-specified flexible parametric model that can represent a time-dependent hazard ratio if one is present.

Incorporating historical information in biosimilar trials: Challenges and a hybrid Bayesian-frequentist approach.

PubMed

Mielke, Johanna; Schmidli, Heinz; Jones, Byron

2018-05-01

For the approval of biosimilars, it is, in most cases, necessary to conduct large Phase III clinical trials in patients to convince the regulatory authorities that the product is comparable in terms of efficacy and safety to the originator product. As the originator product has already been studied in several trials beforehand, it seems natural to include this historical information into the showing of equivalent efficacy. Since all studies for the regulatory approval of biosimilars are confirmatory studies, it is required that the statistical approach has reasonable frequentist properties, most importantly, that the Type I error rate is controlled-at least in all scenarios that are realistic in practice. However, it is well known that the incorporation of historical information can lead to an inflation of the Type I error rate in the case of a conflict between the distribution of the historical data and the distribution of the trial data. We illustrate this issue and confirm, using the Bayesian robustified meta-analytic-predictive (MAP) approach as an example, that simultaneously controlling the Type I error rate over the complete parameter space and gaining power in comparison to a standard frequentist approach that only considers the data in the new study, is not possible. We propose a hybrid Bayesian-frequentist approach for binary endpoints that controls the Type I error rate in the neighborhood of the center of the prior distribution, while improving the power. We study the properties of this approach in an extensive simulation study and provide a real-world example. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neurophysiological study on the effect of various short durations of deep breathing: A randomized controlled trial.

PubMed

Cheng, Kok Suen; Han, Ray P S; Lee, Poh Foong

2018-02-01

The study aims to study the effects of short duration deep breathing on the EEG power with topography based on parallel group randomized controlled trial design which was lacking in prior reports. 50 participants were split into 4 groups: control (CONT), deep breathing (DB) for 5 (DB5), 7 (DB7), and 9 (DB9) minutes. EEG recordings were obtained during baseline, deep breathing session, after deep breathing, and a follow-up session after 7 days of consecutive practice. Frontal theta power of DB5 and DB9 was significantly larger than that of CONT after the deep breathing session (p = 0.027 and p = 0.006, respectively) and the profound finding showed that the theta topography obtained a central-focused distribution for DB7 and DB9. The result obtained was consistent with previous literature, albeit for certain deep breathing durations only, indicating a possible linkage between the deep breathing duration and the neurophysiology of the brain. Copyright © 2017 Elsevier B.V. All rights reserved.

A randomized controlled trial into the effects of neurofeedback, methylphenidate, and physical activity on EEG power spectra in children with ADHD.

PubMed

Janssen, Tieme W P; Bink, Marleen; Geladé, Katleen; van Mourik, Rosa; Maras, Athanasios; Oosterlaan, Jaap

2016-05-01

The clinical and neurophysiological effects of neurofeedback (NF) as treatment for children with ADHD are still unclear. This randomized controlled trial (RCT) examined electroencephalogram (EEG) power spectra before and after NF compared to methylphenidate (MPH) treatment and physical activity (PA) - as semi-active control group - during resting and active (effortful) task conditions to determine whether NF can induce sustained alterations in brain function. Using a multicentre three-way parallel group RCT design, 112 children with a DSM-IV diagnosis of ADHD, aged between 7 and 13 years, were initially included. NF training consisted of 30 sessions of theta/beta training at Cz over a 10-week period. PA training was a semi-active control group, matched in frequency and duration. Methylphenidate was titrated using a double-blind placebo controlled procedure in 6 weeks, followed by a stable dose for 4 weeks. EEG power spectra measures during eyes open (EO), eyes closed (EC) and task (effortful) conditions were available for 81 children at pre- and postintervention (n = 29 NF, n = 25 MPH, n = 27 PA). Train Your Brain? Exercise and Neurofeedback Intervention for ADHD, https://clinicaltrials.gov/show/;NCT01363544, Ref. No. NCT01363544. Both NF and MPH resulted in comparable reductions in theta power from pre- to postintervention during the EO condition compared to PA (ηp (2)  = .08 and .12). For NF, greater reductions in theta were related to greater reductions in ADHD symptoms. During the task condition, only MPH showed reductions in theta and alpha power compared to PA (ηp (2)  = .10 and .12). This study provides evidence for specific neurophysiological effects after theta/beta NF and MPH treatment in children with ADHD. However, for NF these effects did not generalize to an active task condition, potentially explaining reduced behavioural effects of NF in the classroom. © 2016 Association for Child and Adolescent Mental Health.

Cortical thickness as a contributor to abnormal oscillations in schizophrenia?

PubMed

Edgar, J Christopher; Chen, Yu-Han; Lanza, Matthew; Howell, Breannan; Chow, Vivian Y; Heiken, Kory; Liu, Song; Wootton, Cassandra; Hunter, Michael A; Huang, Mingxiong; Miller, Gregory A; Cañive, José M

2014-01-01

Although brain rhythms depend on brain structure (e.g., gray and white matter), to our knowledge associations between brain oscillations and structure have not been investigated in healthy controls (HC) or in individuals with schizophrenia (SZ). Observing function-structure relationships, for example establishing an association between brain oscillations (defined in terms of amplitude or phase) and cortical gray matter, might inform models on the origins of psychosis. Given evidence of functional and structural abnormalities in primary/secondary auditory regions in SZ, the present study examined how superior temporal gyrus (STG) structure relates to auditory STG low-frequency and 40 Hz steady-state activity. Given changes in brain activity as a function of age, age-related associations in STG oscillatory activity were also examined. Thirty-nine individuals with SZ and 29 HC were recruited. 40 Hz amplitude-modulated tones of 1 s duration were presented. MEG and T1-weighted sMRI data were obtained. Using the sources localizing 40 Hz evoked steady-state activity (300 to 950 ms), left and right STG total power and inter-trial coherence were computed. Time-frequency group differences and associations with STG structure and age were also examined. Decreased total power and inter-trial coherence in SZ were observed in the left STG for initial post-stimulus low-frequency activity (~ 50 to 200 ms, ~ 4 to 16 Hz) as well as 40 Hz steady-state activity (~ 400 to 1000 ms). Left STG 40 Hz total power and inter-trial coherence were positively associated with left STG cortical thickness in HC, not in SZ. Left STG post-stimulus low-frequency and 40 Hz total power were positively associated with age, again only in controls. Left STG low-frequency and steady-state gamma abnormalities distinguish SZ and HC. Disease-associated damage to STG gray matter in schizophrenia may disrupt the age-related left STG gamma-band function-structure relationships observed in controls.

Physical activity as intervention for age-related loss of muscle mass and function: protocol for a randomised controlled trial (the LISA study)

PubMed Central

Eriksen, Christian Skou; Garde, Ellen; Reislev, Nina Linde; Wimmelmann, Cathrine Lawaetz; Bieler, Theresa; Ziegler, Andreas Kraag; Gylling, Anne Theil; Dideriksen, Kasper Juel; Siebner, Hartwig Roman; Mortensen, Erik Lykke; Kjaer, Michael

2016-01-01

Introduction Physical and cognitive function decline with age, accelerating during the 6th decade. Loss of muscle power (force×velocity product) is a dominant physical determinant for loss of functional ability, especially if the lower extremities are affected. Muscle strength training is known to maintain or even improve muscle power as well as physical function in older adults, but the optimal type of training for beneficial long-term training effects over several years is unknown. Moreover, the impact of muscle strength training on cognitive function and brain structure remains speculative. The primary aim of this randomised controlled trial is to compare the efficacy of two different 1 year strength training regimens on immediate and long-lasting improvements in muscle power in retirement-age individuals. Secondary aims are to evaluate the effect on muscle strength, muscle mass, physical and cognitive function, mental well-being, health-related quality of life and brain morphology. Methods and analysis The study includes 450 home-dwelling men and women (62–70 years). Participants are randomly allocated to (1) 1 year of supervised, centre-based heavy resistance training, (2) home-based moderate intensity resistance training or (3) habitual physical activity (control). Changes in primary (leg extensor power) and secondary outcomes are analysed according to the intention to treat principle and per protocol at 1, 2, 4, 7 and 10 years. Ethics and dissemination The study is expected to generate new insights into training-induced promotion of functional ability and independency after retirement and will help to formulate national recommendations regarding physical activity schemes for the growing population of older individuals in western societies. Results will be published in scientific peer-reviewed journals, in PhD theses and at public meetings. The study is approved by the Regional Ethical Committee (Capital Region, Copenhagen, Denmark, number H-3-2014-017). Trial registration number NCT02123641. PMID:27913559

Protocol for a feasibility cluster randomised controlled trial of a peer-led school-based intervention to increase the physical activity of adolescent girls (PLAN-A).

PubMed

Sebire, Simon J; Edwards, Mark J; Campbell, Rona; Jago, Russell; Kipping, Ruth; Banfield, Kathryn; Tomkinson, Keeley; Garfield, Kirsty; Lyons, Ronan A; Simon, Joanne; Blair, Peter S; Hollingworth, William

2016-01-01

Physical activity levels are low amongst adolescent girls, and this population faces specific barriers to being active. Peer influences on health behaviours are important in adolescence and peer-led interventions might hold promise to change behaviour. This paper describes the protocol for a feasibility cluster randomised controlled trial of Peer-Led physical Activity iNtervention for Adolescent girls (PLAN-A), a peer-led intervention aimed at increasing adolescent girls' physical activity levels. A two-arm cluster randomised feasibility trial will be conducted in six secondary schools (intervention n  = 4; control n  = 2) with year 8 (12-13 years old) girls. The intervention will operate at a year group level and consist of year 8 girls nominating influential peers within their year group to become peer-supporters. Approximately 15 % of the cohort will receive 3 days of training about physical activity and interpersonal communication skills. Peer-supporters will then informally diffuse messages about physical activity amongst their friends for 10 weeks. Data will be collected at baseline (time 0 (T0)), immediately after the intervention (time 1 (T1)) and 12 months after baseline measures (time 2 (T2)). In this feasibility trial, the primary interest is in the recruitment of schools and participants (both year 8 girls and peer-supporters), delivery and receipt of the intervention, data provision rates and identifying the cost categories for future economic analysis. Physical activity will be assessed using 7-day accelerometry, with the likely primary outcome in a fully-powered trial being daily minutes of moderate-to-vigorous physical activity. Participants will also complete psychosocial questionnaires at each time point: assessing motivation, self-esteem and peer physical activity norms. Data analysis will be largely descriptive and focus on recruitment, attendance and data provision rates. The findings will inform the sample size required for a definitive trial. A detailed process evaluation using qualitative and quantitative methods will be conducted with a variety of stakeholders (i.e. pupils, parents, teachers and peer-supporter trainers) to identify areas of success and necessary improvements prior to proceeding to a definitive trial. This paper describes the protocol for the PLAN-A feasibility cluster randomised controlled trial which will provide the information necessary to design a fully-powered trial should PLAN-A demonstrate evidence of promise. ISRCTN12543546.

A Powered Lower Limb Orthosis for Providing Legged Mobility in Paraplegic Individuals.

PubMed

Quintero, Hugo A; Farris, Ryan J; Hartigan, Clare; Clesson, Ismari; Goldfarb, Michael

2011-01-01

This paper presents preliminary results on the development of a powered lower limb orthosis intended to provide legged mobility (with the use of a stability aid, such as forearm crutches) to paraplegic individuals. The orthosis contains electric motors at both hip and both knee joints, which in conjunction with ankle-foot orthoses, provides appropriate joint kinematics for legged locomotion. The paper describes the orthosis and the nature of the controller that enables the SCI patient to command the device, and presents data from preliminary trials that indicate the efficacy of the orthosis and controller in providing legged mobility.

An exploratory analysis of Go/Nogo event-related potentials in major depression and depression following traumatic brain injury.

PubMed

Bailey, Neil W; Hoy, Kate E; Maller, Jerome J; Segrave, Rebecca A; Thomson, Richard; Williams, Nicholas; Daskalakis, Zafiris J; Fitzgerald, Paul B

2014-12-30

Rates of major depressive disorder (MDD) following traumatic brain injury (TBI) are estimated to be between 20% and 45%, a higher prevalence than that seen in the general population. These increased rates may be due to specific changes in brain function following TBI. Event related potentials (ERPs) are well suited for measuring the electrophysiological differences between groups in areas of cognitive processing impaired in both MDD and TBI, such as response inhibition. The current study presented an emotional Go/Nogo task (with schematic emotional faces as stimuli) to participants with TBI, participants with MDD, and participants with both TBI and MDD (TBI-MDD). Topographical distribution of activity and global field power comparisons were made across stimulus-locked epochs between these groups and healthy controls. The results indicated that ERPs were not altered by TBI alone. Both MDD and TBI-MDD groups showed similar alterations in topographical distribution and global field power in the N2 window, as well as late epoch alterations. The MDD and TBI-MDD groups showed significantly less fronto-central negativity during the N2 window in Nogo trials compared with the control group. The MDD and TBI-MDD groups also showed significantly less global field power in Nogo trials than Go trials during the N2 window while the control group showed the opposite pattern. The MDD and TBI-MDD groups showed no mood-congruent bias in behavioural or ERP measures. The results suggest that TBI-MDD displays similar electrophysiological changes to those found in the MDD group without TBI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR): protocol for a randomised controlled trial.

PubMed

O'Brien, Claire; Bray, Emma P; Bryan, Stirling; Greenfield, Sheila M; Haque, M Sayeed; Hobbs, F D Richard; Jones, Miren I; Jowett, Sue; Kaambwa, Billingsley; Little, Paul; Mant, Jonathan; Penaloza, Cristina; Schwartz, Claire; Shackleford, Helen; Varghese, Jinu; Williams, Bryan; McManus, Richard J

2013-03-23

Self-monitoring of hypertension with self-titration of antihypertensives (self-management) results in lower systolic blood pressure for at least one year. However, few people in high risk groups have been evaluated to date and previous work suggests a smaller effect size in these groups. This trial therefore aims to assess the added value of self-management in high risk groups over and above usual care. The targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR) trial will be a pragmatic primary care based, unblinded, randomised controlled trial of self-management of blood pressure (BP) compared to usual care. Eligible patients will have a history of stroke, coronary heart disease, diabetes or chronic kidney disease and will be recruited from primary care. Participants will be individually randomised to either usual care or self-management. The primary outcome of the trial will be difference in office SBP between intervention and control groups at 12 months adjusted for baseline SBP and covariates. 540 patients will be sufficient to detect a difference in SBP between self-management and usual care of 5 mmHg with 90% power. Secondary outcomes will include self-efficacy, lifestyle behaviours, health-related quality of life and adverse events. An economic analysis will consider both within trial costs and a model extrapolating the results thereafter. A qualitative analysis will gain insights into patients' views, experiences and decision making processes. The results of the trial will be directly applicable to primary care in the UK. If successful, self-management of blood pressure in people with stroke and other high risk conditions would be applicable to many hundreds of thousands of individuals in the UK and beyond. ISRCTN87171227.

Effect of voluntary hypocapnic hyperventilation on the metabolic response during Wingate anaerobic test.

PubMed

Fujii, Naoto; Tsuchiya, Sho-Ichiro; Tsuji, Bun; Watanabe, Kazuhito; Sasaki, Yosuke; Nishiyasu, Takeshi

2015-09-01

We evaluated whether hypocapnia achieved through voluntary hyperventilation diminishes the increases in oxygen uptake elicited by short-term (e.g., ~30 s) all-out exercise without affecting exercise performance. Nine subjects performed 30-s Wingate anaerobic tests (WAnT) in control and hypocapnia trials on separate days in a counterbalanced manner. During the 20-min rest prior to the 30-s WAnT, the subjects in the hypocapnia trial performed voluntary hyperventilation (minute ventilation = 31 L min(-1)), while the subjects in the control trial continued breathing spontaneously (minute ventilation = 14 L min(-1)). The hyperventilation in the hypocapnia trial reduced end-tidal CO2 pressure from 34.8 ± 2.5 mmHg at baseline rest to 19.3 ± 1.0 mmHg immediately before the 30-s WAnT. In the control trial, end-tidal CO2 pressure at baseline rest (35.9 ± 2.5 mmHg) did not differ from that measured immediately before the 30-s WAnT (35.9 ± 3.3 mmHg). Oxygen uptake during the 30-s WAnT was lower in the hypocapnia than the control trial (1.55 ± 0.52 vs. 1.95 ± 0.44 L min(-1)), while the postexercise peak blood lactate concentration was higher in the hypocapnia than control trial (10.4 ± 1.9 vs. 9.6 ± 1.9 mmol L(-1)). In contrast, there was no difference in the 5-s peak (842 ± 111 vs. 850 ± 107 W) or mean (626 ± 74 vs. 639 ± 80 W) power achieved during the 30-s WAnT between the control and hypocapnia trials. These results suggest that during short-period all-out exercise (e.g., 30-s WAnT), hypocapnia induced by voluntary hyperventilation reduces the aerobic metabolic rate without affecting exercise performance. This implies a compensatory elevation in the anaerobic metabolic rate.

The effects of a combined static-dynamic stretching protocol on athletic performance in elite Gaelic footballers: A randomised controlled crossover trial.

PubMed

Loughran, Martin; Glasgow, Philip; Bleakley, Chris; McVeigh, Joseph

2017-05-01

To determine the effect of three different static-dynamic stretching protocols on sprint and jump performance in Gaelic footballers. Double-blind, controlled, crossover trial. Sports Institute research environment. Seventeen male elite level Gaelic footballers, aged 18-30 years, completed three stretching protocols. Athletic performance was measured by countermovement jump height and power, and timed 10 m, 20 m, and 40 m sprints. Static stretching reduced sprint speed by 1.1% over 40 m and 1.0% over 20 m. Static stretching also reduced countermovement jump height by 10.6% and jump power by 6.4%. When static stretching was followed by dynamic stretching, sprint speed improved by 1.0% over 20 m and 0.7% over 40 m (p < 0.05). The static - dynamic stretching protocol also improved countermovement jump height by 8.7% (p < 0.01) and power by 6.7% (p < 0.01). Static stretching reduces sprint speed and jump performance. Static stretching should be followed by dynamic stretching during warm-up to nullify any performance deficits caused by static stretching. Copyright © 2016 Elsevier Ltd. All rights reserved.

Provocative discography screening improves surgical outcome.

PubMed

Margetic, Petra; Pavic, Roman; Stancic, Marin F

2013-10-01

The objective of this study was to compare the surgical outcomes of patients operated on, with or without discography prior to operation. The study was designed as a randomized controlled trial, using power analysis with McNemar's test on two correlated proportions. The study comprised of 310 patients divided into trial (207) and control (103) groups. Inclusion criteria were low back pain resistant to nonsurgical treatment for more than 6 months and conventional radiological findings showing degenerative changes without a clear generator of pain. Exclusion criteria were red flags (tumor, trauma, and infection). After standard radiological diagnostic imaging (X-ray, CT, and MR), patients filled in the Oswestry Disability Index (ODI), SF-36, Zung, and MSP questionnaires. Depending on their radiological findings, patients were included and randomly placed in the trial or control group. At the 1-year follow-up examination, patients filled in the ODI, SF-36, and Likert scale questionnaires. The difference between preoperative and postoperative ODI in the control group degenerative disc disease (DDD) subgroup was 22.07 %. The difference between preoperative and postoperative ODI in the trial group DDD subgroup was 35.04 %. Differences between preoperative and postoperative ODI in the control group other indications subgroup was 26.13 %. Differences between preoperative and postoperative ODI in the trial group other indications subgroup was 28.42 %. DDD treated surgically without discography did not reach the clinically significant improvement of 15 ODI points for the patients treated with fusion. Provocative discography screening with psychological testing in the trial group made improvement following fusion clinically significant.

Social Stories in mainstream schools for children with autism spectrum disorder: a feasibility randomised controlled trial.

PubMed

Marshall, David; Wright, Barry; Allgar, Victoria; Adamson, Joy; Williams, Christine; Ainsworth, Hannah; Cook, Liz; Varley, Danielle; Hackney, Lisa; Dempster, Paul; Ali, Shehzad; Trepel, Dominic; Collingridge Moore, Danielle; Littlewood, Elizabeth; McMillan, Dean

2016-08-11

To assess the feasibility of recruitment, retention, outcome measures and intervention training/delivery among teachers, parents and children. To calculate a sample size estimation for full trial. A single-centre, unblinded, cluster feasibility randomised controlled trial examining Social Stories delivered within a school environment compared with an attentional control. 37 primary schools in York, UK. 50 participants were recruited and a cluster randomisation approach by school was examined. Participants were randomised into the treatment group (n=23) or a waiting list control group (n=27). Acceptability and feasibility of the trial, intervention and of measurements required to assess outcomes in a definitive trial. An assessment of the questionnaire completion rates indicated teachers would be most appropriate to complete the primary outcome measure. 2 outcome measures: the Social Responsiveness Scale (SRS)-2 and a goal-based measure showed both the highest levels of completion rates (above 80%) at the primary follow-up point (6 weeks postintervention) and captured relevant social and behaviour outcomes. Power calculations were based on these 2 outcome measures leading to a total proposed sample size of 180 participant groups. Results suggest that a future trial would be feasible to conduct and could inform the policy and practice of using Social Stories in mainstream schools. ISRCTN96286707; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Effectiveness of a structured education reminiscence-based programme for staff on the quality of life of residents with dementia in long-stay units: a study protocol for a cluster randomised trial.

PubMed

O'Shea, Eamon; Devane, Declan; Murphy, Kathy; Cooney, Adeline; Casey, Dympna; Jordan, Fionnuala; Hunter, Andrew; Murphy, Edel

2011-02-14

Current projections indicate that there will be a significant increase in the number of people with dementia in Ireland, from approximately 40,000 at present to 100,000 by 2036. Psychosocial interventions, such as reminiscence, have the potential to improve the quality of life of people with dementia. However, while reminiscence is used widely in dementia care, its impact on the quality of life of people with dementia remains largely undocumented and there is a need for a robust and fair assessment of its overall effectiveness. The DementiA education programme incorporating REminiscence for Staff study will evaluate the effectiveness of a structured reminiscence-based education programme for care staff on the quality of life of residents with dementia in long-stay units. The study is a two-group, single-blind cluster randomised trial conducted in public and private long-stay residential settings in Ireland. Randomisation to control and intervention is at the level of the long-stay residential unit. Sample size calculations suggest that 18 residential units each containing 17 people with dementia are required for randomisation to control and intervention groups to achieve power of at least 80% with alpha levels of 0.05. Each resident in the intervention group is linked with a nurse and care assistant who have taken the structured reminiscence-based education programme. Participants in the control group will receive usual care. The primary outcome is quality of life of residents as measured by the Quality of Life-AD instrument. Secondary outcomes include agitation, depression and carer burden. Blinded outcome assessment is undertaken at baseline and at 18-22 weeks post-randomisation. Trials on reminiscence-based interventions for people with dementia have been scarce and the quality of the information arising from those that have been done has been undermined by methodological problems, particularly in relation to scale and scope. This trial is powered to deliver more credible and durable results. The trial may also convey process utility to a long-stay system in Ireland that has not been geared for education and training, especially in relation to dementia. The results of this trial are applicable to long-stay residential units in Ireland and internationally. Current Controlled Trials ISRCTN99651465.

Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews.

PubMed

Onasanya, Oluwadamilola; Iyer, Geetha; Lucas, Eleanor; Lin, Dora; Singh, Sonal; Alexander, G Caleb

2016-11-01

Given the conflicting evidence regarding the association between exogenous testosterone and cardiovascular events, we systematically assessed published systematic reviews for evidence of the association between exogenous testosterone and cardiovascular events. We searched PubMed, MEDLINE, Embase, Cochrane Collaboration Clinical Trials, ClinicalTrials.gov, and the US Food and Drug Administration website for systematic reviews of randomised controlled trials published up to July 19, 2016. Two independent reviewers screened 954 full texts from 29 335 abstracts to identify systematic reviews of randomised controlled trials in which the cardiovascular effects of exogenous testosterone on men aged 18 years or older were examined. We extracted data for study characteristics, analytic methods, and key findings, and applied the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist to assess methodological quality of each review. Our primary outcome measure was the direction and magnitude of association between exogenous testosterone and cardiovascular events. We identified seven reviews and meta-analyses, which had substantial clinical heterogeneity, differing statistical methods, and variable methodological quality and quality of data abstraction. AMSTAR scores ranged from 3 to 9 out of 11. Six systematic reviews that each included a meta-analysis showed no significant association between exogenous testosterone and cardiovascular events, with summary estimates ranging from 1·07 to 1·82 and imprecise confidence intervals. Two of these six meta-analyses showed increased risk in subgroup analyses of oral testosterone and men aged 65 years or older during their first treatment year. One meta-analysis showed a significant association between exogenous testosterone and cardiovascular events, in men aged 18 years or older generally, with a summary estimate of 1·54 (95% CI 1·09-2·18). Our optimal information size analysis showed that any randomised controlled trial aiming to detect a true difference in cardiovascular risk between treatment groups receiving exogenous testosterone and their controls (with a two-sided p value of 0·05 and a power of 80%) would require at least 17 664 participants in each trial group. Therefore, given the challenge of adequately powering clinical trials for rare outcomes, rigorous observational studies are needed to clarify the association between testosterone-replacement therapy and major adverse cardiovascular outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antibacterial agents in composite restorations for the prevention of dental caries.

PubMed

Pereira-Cenci, Tatiana; Cenci, Maximiliano S; Fedorowicz, Zbys; Azevedo, Marina

2013-12-17

Dental caries is a multifactorial disease in which the fermentation of food sugars by bacteria from the biofilm (dental plaque) leads to localised demineralisation of tooth surfaces, which may ultimately result in cavity formation. Resin composites are widely used in dentistry to restore teeth. These restorations can fail for a number of reasons, such as secondary caries, and restorative material fracture and other minor reasons. From these, secondary caries, which are caries lesions developed adjacent to restorations, is the main cause for restorations replacement. The presence of antibacterials in both the filling material and the bonding systems would theoretically be able to affect the initiation and progression of caries adjacent to restorations. This is an update of the Cochrane review published in 2009. To assess the effects of antibacterial agents incorporated into composite restorations for the prevention of dental caries. We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 23 July 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 6), MEDLINE via OVID (1946 to 23 July 2013) and EMBASE via OVID (1980 to 23 July 2013). We searched the US National Institutes of Health Trials Register (http://clinicaltrials.gov), the metaRegister of Controlled Trials (www.controlled-trials.com) and the World Health Organization International Clinical Trials Registry platform (www.who.int/trialsearch) for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised controlled trials comparing resin composite restorations containing antibacterial agents with composite restorations not containing antibacterial agents. Two review authors conducted screening of studies in duplicate and independently, and although no eligible trials were identified, the two authors had planned to extract data independently and assess trial quality using standard Cochrane Collaboration methodologies. We retrieved 308 references to studies, none of which matched the inclusion criteria for this review and all of which were excluded. We were unable to identify any randomised controlled trials on the effects of antibacterial agents incorporated into composite restorations for the prevention of dental caries. The absence of high level evidence for the effectiveness of this intervention emphasises the need for well designed, adequately powered, randomised controlled clinical trials. Thus, conclusions remain the same as the previously published review, with no included clinical trials.

Joint probability of statistical success of multiple phase III trials.

PubMed

Zhang, Jianliang; Zhang, Jenny J

2013-01-01

In drug development, after completion of phase II proof-of-concept trials, the sponsor needs to make a go/no-go decision to start expensive phase III trials. The probability of statistical success (PoSS) of the phase III trials based on data from earlier studies is an important factor in that decision-making process. Instead of statistical power, the predictive power of a phase III trial, which takes into account the uncertainty in the estimation of treatment effect from earlier studies, has been proposed to evaluate the PoSS of a single trial. However, regulatory authorities generally require statistical significance in two (or more) trials for marketing licensure. We show that the predictive statistics of two future trials are statistically correlated through use of the common observed data from earlier studies. Thus, the joint predictive power should not be evaluated as a simplistic product of the predictive powers of the individual trials. We develop the relevant formulae for the appropriate evaluation of the joint predictive power and provide numerical examples. Our methodology is further extended to the more complex phase III development scenario comprising more than two (K > 2) trials, that is, the evaluation of the PoSS of at least k₀ (k₀≤ K) trials from a program of K total trials. Copyright © 2013 John Wiley & Sons, Ltd.

Ethical and social dilemmas in community-based controlled trials in situations of poverty: a view from a South African project.

PubMed

Nama, Nosisana; Swartz, Leslie

2002-01-01

All psychological and social research presents ethical dilemmas, many of which centre around the difficulties which flow from the power imbalances between those conducting the research and the research respondents or participants. Issues of power are magnified in research undertaken in contexts of poverty, and there is a burgeoning literature on ethical issues in research in developing countries. In this article, we augment the existing literature by focusing on the experiences of an assessor working in a controlled trial of a mother-infant intervention in a poor South African community. We consider issues of community expectations, the presentation to our project of physical health problems, the issue of HIV/AIDS, cultural beliefs which impact on the research, child protection issues, and the tensions between research assessment and ubuntu--a cultural norm which requires helpful engagement with others. We suggest that our experiences may assist with the development of further research.

Should academic medical centers conduct clinical trials of the efficacy of intercessory prayer?

PubMed

Halperin, E C

2001-08-01

Intercessory prayers for health or healing are requests to an object of worship for the preservation or restoration of health. There has been a recent proliferation of clinical trials that compare the health outcome of a group of prayed-for patients with that of controls, to test the efficacy of intercessory prayer. In this essay, the author defines the concept of intercessory prayer, contrasts it with other forms of prayer, and reviews the literature concerning clinical trials of its efficacy. The arguments put forward in favor of conducting such trials and those against are described and the reader is invited to consider their relative merits. The author concludes by discussing the potential power of faith in healing, reviewing the philosophical basis and pitfalls of clinical trials of intercessory prayer, and urging readers to weigh the arguments for and against such trials in academic medicine.

A matter of timing: harm reduction in learned helplessness.

PubMed

Richter, Sophie Helene; Sartorius, Alexander; Gass, Peter; Vollmayr, Barbara

2014-11-03

Learned helplessness has excellent validity as an animal model for depression, but problems in reproducibility limit its use and the high degree of stress involved in the paradigm raises ethical concerns. We therefore aimed to identify which and how many trials of the learned helplessness paradigm are necessary to distinguish between helpless and non-helpless rats. A trial-by-trial reanalysis of tests from 163 rats with congenital learned helplessness or congenital non-learned helplessness and comparison of 82 rats exposed to inescapable shock with 38 shock-controls revealed that neither the first test trials, when rats showed unspecific hyperlocomotion, nor trials of the last third of the test, when almost all animals responded quickly to the stressor, contributed to sensitivity and specificity of the test. Considering only trials 3-10 improved the classification of helpless and non-helpless rats. The refined analysis allows abbreviation of the test for learned helplessness from 15 trials to 10 trials thereby reducing pain and stress of the experimental animals without losing statistical power.

The Power of Low Back Pain Trials: A Systematic Review of Power, Sample Size, and Reporting of Sample Size Calculations Over Time, in Trials Published Between 1980 and 2012.

PubMed

Froud, Robert; Rajendran, Dévan; Patel, Shilpa; Bright, Philip; Bjørkli, Tom; Eldridge, Sandra; Buchbinder, Rachelle; Underwood, Martin

2017-06-01

A systematic review of nonspecific low back pain trials published between 1980 and 2012. To explore what proportion of trials have been powered to detect different bands of effect size; whether there is evidence that sample size in low back pain trials has been increasing; what proportion of trial reports include a sample size calculation; and whether likelihood of reporting sample size calculations has increased. Clinical trials should have a sample size sufficient to detect a minimally important difference for a given power and type I error rate. An underpowered trial is one within which probability of type II error is too high. Meta-analyses do not mitigate underpowered trials. Reviewers independently abstracted data on sample size at point of analysis, whether a sample size calculation was reported, and year of publication. Descriptive analyses were used to explore ability to detect effect sizes, and regression analyses to explore the relationship between sample size, or reporting sample size calculations, and time. We included 383 trials. One-third were powered to detect a standardized mean difference of less than 0.5, and 5% were powered to detect less than 0.3. The average sample size was 153 people, which increased only slightly (∼4 people/yr) from 1980 to 2000, and declined slightly (∼4.5 people/yr) from 2005 to 2011 (P < 0.00005). Sample size calculations were reported in 41% of trials. The odds of reporting a sample size calculation (compared to not reporting one) increased until 2005 and then declined (Equation is included in full-text article.). Sample sizes in back pain trials and the reporting of sample size calculations may need to be increased. It may be justifiable to power a trial to detect only large effects in the case of novel interventions. 3.

Impact of a Daily SMS Medication Reminder System on Tuberculosis Treatment Outcomes: A Randomized Controlled Trial.

PubMed

Mohammed, Shama; Glennerster, Rachel; Khan, Aamir J

2016-01-01

The rapid uptake of mobile phones in low and middle-income countries over the past decade has provided public health programs unprecedented access to patients. While programs have used text messages to improve medication adherence, there have been no high-powered trials evaluating their impact on tuberculosis treatment outcomes. To measure the impact of Zindagi SMS, a two-way SMS reminder system, on treatment success of people with drug-sensitive tuberculosis. We conducted a two-arm, parallel design, effectiveness randomized controlled trial in Karachi, Pakistan. Individual participants were randomized to either Zindagi SMS or the control group. Zindagi SMS sent daily SMS reminders to participants and asked them to respond through SMS or missed (unbilled) calls after taking their medication. Non-respondents were sent up to three reminders a day. Public and private sector tuberculosis clinics in Karachi, Pakistan. Newly-diagnosed patients with smear or bacteriologically positive pulmonary tuberculosis who were on treatment for less than two weeks; 15 years of age or older; reported having access to a mobile phone; and intended to live in Karachi throughout treatment were eligible to participate. We enrolled 2,207 participants, with 1,110 randomized to Zindagi SMS and 1,097 to the control group. The primary outcome was clinically recorded treatment success based upon intention-to-treat. We found no significant difference between the Zindagi SMS or control groups for treatment success (719 or 83% vs. 903 or 83%, respectively, p = 0·782). There was no significant program effect on self-reported medication adherence reported during unannounced visits during treatment. In this large-scale randomized controlled effectiveness trial of SMS medication reminders for tuberculosis treatment, we found no significant impact. The trial was registered with ClinicalTrials.gov, NCT01690754.

Effectiveness of a Wheelchair Skills Training Program for Powered Wheelchair Users: A Randomized Controlled Trial

PubMed Central

Kirby, R. Lee; Miller, William C.; Routhier, Francois; Demers, Louise; Mihailidis, Alex; Polgar, Jan Miller; Rushton, Paula W.; Titus, Laura; Smith, Cher; McAllister, Mike; Theriault, Chris; Thompson, Kara; Sawatzky, Bonita

2015-01-01

Objectives To test the hypothesis that powered wheelchair users who receive the Wheelchair Skills Training Program (WSTP) improve their wheelchair skills in comparison with a Control group that receives standard care. Our secondary objectives were to assess goal achievement, satisfaction with training, retention, injury rate, confidence with wheelchair use and participation. Design Randomized controlled trial (RCT). Setting Rehabilitation centers and communities. Participants 116 powered wheelchair users. Intervention Five 30-minute WSTP training sessions. Main Outcome Measures Assessments were done at baseline (T1), post-training (T2) and 3 months post-training (T3) using the Wheelchair Skills Test Questionnaire (WST-Q 4.1), Goal Attainment Score (GAS), Satisfaction Questionnaire, Injury Rate, Wheelchair Use Confidence Scale for Power Wheelchair Users (WheelCon) and Life Space Assessment (LSA). Results There was no significant T2-T1 difference between the groups for WST-Q capacity scores (p = 0.600) but the difference for WST-Q performance scores was significant (p = 0.016) with a relative (T2/T1 x 100%) improvement of the median score for the Intervention group of 10.8%. The mean (SD) GAS for the Intervention group after training was 92.8% (11.4) and satisfaction with training was high. The WST-Q gain was not retained at T3. There was no clinically significant difference between the groups in injury rate and no statistically significant differences in WheelCon or LSA scores at T3. Conclusions Powered wheelchair users who receive formal wheelchair skills training demonstrate modest transient post-training improvements in their WST-Q performance scores, they have substantial improvements on individualized goals and they are positive about training. PMID:26232684

Are changes in leg power responsible for clinically meaningful improvements in mobility in older adults?

PubMed

Bean, Jonathan F; Kiely, Dan K; LaRose, Sharon; Goldstein, Richard; Frontera, Walter R; Leveille, Suzanne G

2010-12-01

From among physiological attributes commonly targeted in rehabilitation, to identify those in which changes led to clinically meaningful differences (CMDs) in mobility outcomes. Secondary analysis of data collected for a randomized controlled trial of exercise using binary outcomes defined by recording a large CMD (Short Physical Performance Battery (SPPB)=1 unit; gait speed (GS)=0.1 m/s). Iterative models were performed to evaluate possible confounding between physiological variables and relevant covariates. Outpatient rehabilitation centers. Community-dwelling mobility-limited older adults (n=116) participating in a 16-week randomized controlled trial of two modes of exercise. Physiological measures included leg power, leg strength, balance as measured according to the Performance-Oriented Mobility Assessment (POMA), and rate pressure product at the maximal stage of an exercise tolerance test. Outcomes included GS and SPPB. Leg power and leg strength were measured using computerized pneumatic strength training equipment and recorded in Watts and Newtons, respectively. Participants were 68% female, had a mean age of 75.2, a mean of 5.5 chronic conditions, and a baseline mean SPPB score of 8.7. After controlling for age, site, group assignment, and baseline outcome values, leg power was the only attribute in which changes were significantly associated with a large CMD in SPPB (odds ratio (OR)=1.48, 95% confidence interval (CI)=1.09-2.02) and GS (OR=1.31, 95% CI=1.01-1.70). Improvements in leg power, independent of strength, appear to make an important contribution to clinically meaningful improvements in SPPB and GS. © 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.

Study Design and Rationale for the Phase 3 Clinical Development Program of Enobosarm, a Selective Androgen Receptor Modulator, for the Prevention and Treatment of Muscle Wasting in Cancer Patients (POWER Trials).

PubMed

Crawford, Jeffrey; Prado, Carla M M; Johnston, Mary Ann; Gralla, Richard J; Taylor, Ryan P; Hancock, Michael L; Dalton, James T

2016-06-01

Muscle wasting in cancer is a common and often occult condition that can occur prior to overt signs of weight loss and before a clinical diagnosis of cachexia can be made. Muscle wasting in cancer is an important and independent predictor of progressive functional impairment, decreased quality of life, and increased mortality. Although several therapeutic agents are currently in development for the treatment of muscle wasting or cachexia in cancer, the majority of these agents do not directly inhibit muscle loss. Selective androgen receptor modulators (SARMs) have the potential to increase lean body mass (LBM) and hence muscle mass, without the untoward side effects seen with traditional anabolic agents. Enobosarm, a nonsteroidal SARM, is an agent in clinical development for prevention and treatment of muscle wasting in patients with cancer (POWER 1 and 2 trials). The POWER trials are two identically designed randomized, double-blind, placebo-controlled, multicenter, and multinational phase 3 trials to assess the efficacy of enobosarm for the prevention and treatment of muscle wasting in subjects initiating first-line chemotherapy for non-small-cell lung cancer (NSCLC). To assess enobosarm's effect on both prevention and treatment of muscle wasting, no minimum weight loss is required. These pivotal trials have pioneered the methodological and regulatory fields exploring a therapeutic agent for cancer-associated muscle wasting, a process hereby described. In each POWER trial, subjects will receive placebo (n = 150) or enobosarm 3 mg (n = 150) orally once daily for 147 days. Physical function, assessed as stair climb power (SCP), and LBM, assessed by dual-energy X-ray absorptiometry (DXA), are the co-primary efficacy endpoints in both trials assessed at day 84. Based on extensive feedback from the US Food and Drug Administration (FDA), the co-primary endpoints will be analyzed as a responder analysis. To be considered a physical function responder, a subject must have ≥10 % improvement in physical function compared to baseline. To meet the definition of response on LBM, a subject must have demonstrated no loss of LBM compared with baseline. Secondary endpoints include durability of response assessed at day 147 in those responding at day 84. A combined overall survival analysis for both studies is considered a key secondary safety endpoint. The POWER trials design was established with extensive clinical input and collaboration with regulatory agencies. The efficacy endpoints are a result of this feedback and discussion of the threshold for clinical benefit in patients at risk for muscle wasting. Full results from these studies will soon be published and will further guide the development of future anabolic trials. Clinical Trial ID: NCT01355484. https://clinicaltrials.gov/ct2/show/NCT01355484 , NCT01355497. https://clinicaltrials.gov/ct2/show/NCT01355497?term=g300505&rank=1 .

Measuring neuroplasticity associated with cerebral palsy rehabilitation: An MRI based power analysis.

PubMed

Reid, Lee B; Pagnozzi, Alex M; Fiori, Simona; Boyd, Roslyn N; Dowson, Nicholas; Rose, Stephen E

2017-05-01

Researchers in the field of child neurology are increasingly looking to supplement clinical trials of motor rehabilitation with neuroimaging in order to better understand the relationship between behavioural training, brain changes, and clinical improvements. Randomised controlled trials are typically accompanied by sample size calculations to detect clinical improvements but, despite the large cost of neuroimaging, not equivalent calculations for concurrently acquired imaging neuroimaging measures of changes in response to intervention. To aid in this regard, a power analysis was conducted for two measures of brain changes that may be indexed in a trial of rehabilitative therapy for cerebral palsy: cortical thickness of the impaired primary sensorimotor cortex, and fractional anisotropy of the impaired, delineated corticospinal tract. Power for measuring fractional anisotropy was assessed for both region-of-interest-seeded and fMRI-seeded diffusion tractography. Taking into account practical limitations, as well as data loss due to behavioural and image-processing issues, estimated required participant numbers were 101, 128 and 59 for cortical thickness, region-of-interest-based tractography, and fMRI-seeded tractography, respectively. These numbers are not adjusted for study attrition. Although these participant numbers may be out of reach of many trials, several options are available to improve statistical power, including careful preparation of participants for scanning using mock simulators, careful consideration of image processing options, and enrolment of as homogeneous a cohort as possible. This work suggests that smaller and moderate sized studies give genuine consideration to harmonising scanning protocols between groups to allow the pooling of data. Copyright © 2017 ISDN. All rights reserved.

Development of a Multi-Centre Clinical Trial Data Archiving and Analysis Platform for Functional Imaging

NASA Astrophysics Data System (ADS)

Driscoll, Brandon; Jaffray, David; Coolens, Catherine

2014-03-01

Purpose: To provide clinicians & researchers participating in multi-centre clinical trials with a central repository for large volume dynamic imaging data as well as a set of tools for providing end-to-end testing and image analysis standards of practice. Methods: There are three main pieces to the data archiving and analysis system; the PACS server, the data analysis computer(s) and the high-speed networks that connect them. Each clinical trial is anonymized using a customizable anonymizer and is stored on a PACS only accessible by AE title access control. The remote analysis station consists of a single virtual machine per trial running on a powerful PC supporting multiple simultaneous instances. Imaging data management and analysis is performed within ClearCanvas Workstation® using custom designed plug-ins for kinetic modelling (The DCE-Tool®), quality assurance (The DCE-QA Tool) and RECIST. Results: A framework has been set up currently serving seven clinical trials spanning five hospitals with three more trials to be added over the next six months. After initial rapid image transfer (+ 2 MB/s), all data analysis is done server side making it robust and rapid. This has provided the ability to perform computationally expensive operations such as voxel-wise kinetic modelling on very large data archives (+20 GB/50k images/patient) remotely with minimal end-user hardware. Conclusions: This system is currently in its proof of concept stage but has been used successfully to send and analyze data from remote hospitals. Next steps will involve scaling up the system with a more powerful PACS and multiple high powered analysis machines as well as adding real-time review capabilities.

Control of subterranean termites (Isoptera: Rhinotermitidae) infesting power poles.

PubMed

Horwood, Martin A; Westlake, Terry; Kathuria, Amrit

2010-12-01

A trial was conducted to determine the efficacy of termiticidal dusts (arsenic trioxide, triflumuron, and Metarhizium anisopliae), a timber fumigant (dazomet) and liquid termiticides (bifenthrin, chlorfenapyr, chlorpyrifos, fipronil, and imidacloprid) for controlling subterranean termites (Isoptera: Rhinotermitidae) infesting in-service power poles in New South Wales, Australia. Dusts were applied to parts of the pole where termites were present. Fumigant was inserted into holes drilled into the base of the pole. Liquid termiticides were mixed with soil around the base of the pole and injected into internal voids if present. Poles were inspected for up to 5 yr, and the time taken for reinfestation to occur was recorded. Before the start of the trial, the major Australian pole owners were surveyed to obtain an estimate of the annual national cost of termite infestation to the power supply industry. The annual costs of termite treatment and replacing damaged poles were estimated at AU$2 million and AU$13 million, respectively. Infestation rates were lower for all treatments compared with controls within the first 12 mo of the study. Dazomet, arsenic trioxide, fipronil, and chlorpyrifos were the most efficacious treatments. Efficacy was positively related to the amount of termiticide applied and negatively related to the infestation severity but was unaffected by geographical location. Survival curves were calculated of the time elapsed before the recurrence of termite infestations (survival absence of reinfestation). Survival was highest for poles treated with liquid termiticides.

First Trial of Real-time Poloidal Beta Control in KSTAR

NASA Astrophysics Data System (ADS)

Han, Hyunsun; Hahn, S. H.; Bak, J. G.; Walker, M. L.; Woo, M. H.; Kim, J. S.; Kim, Y. J.; Bae, Y. S.; KSTAR Team

2014-10-01

Sustaining the plasma in a stable and a high performance condition is one of the important control issues for future steady state tokamaks. In the 2014 KSTAR campaign, we have developed a real-time poloidal beta (βp) control technique and carried out preliminary experiments to identify its feasibility. In the control system, the βp is calculated in real time using the measured diamagnetic loop signal (DLM03) with coil pickup corrections, and compared with the target value leading to the change of the neutral beam (NB) heating power using a feedback PID control algorithm. To match the required power of NB which is operated with constant voltage, the duty cycles of the modulation were adjusted as the ratio of the required power to the maximum achievable one. This paper will present the overall procedures of the βp control, the βp estimation process implemented in the plasma control system, and the analysis on the preliminary experimental results. This work is supported by the KSTAR research project funded by the Ministry of Science, ICT & Future Planning of Korea.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

PubMed

Turner, E L; Metcalfe, C; Donovan, J L; Noble, S; Sterne, J A C; Lane, J A; Avery, K N; Down, L; Walsh, E; Davis, M; Ben-Shlomo, Y; Oliver, S E; Evans, S; Brindle, P; Williams, N J; Hughes, L J; Hill, E M; Davies, C; Ng, S Y; Neal, D E; Hamdy, F C; Martin, R M

2014-06-10

Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

A new approach for strawberry disease control

USDA-ARS?s Scientific Manuscript database

Here, we report a new approach demonstrating the killing power of UV-C treatment against fungal pathogens without damaging strawberry plants. UV-C light was followed by a specific dark period. Field trials also included applications of microbial antagonists twice a week. The dark period most like...

The effect of therapeutic horseback riding on balance in community-dwelling older adults: a pilot study.

PubMed

Homnick, Tamara D; Henning, Kim M; Swain, Charlene V; Homnick, Douglas N

2015-02-01

Equine assisted activities (hippotherapy and therapeutic riding) improve balance in patients with disabilities such as cerebral palsy, but have not been systematically studied in older adults, at risk of falls due to balance deficits. We conducted a 10-week, single blind, controlled trial of the effect of a therapeutic horseback riding course on measures of balance in community-dwelling adults 65 years and older. Nine riders and six controls completed the trial. Controls were age matched to riders and all participants were recruited from the local community. Both groups showed improvements in balance during the trial, but did not reach statistical significance. Sample size was small, participants had relatively high initial balance scores, and controls tended to increase their physical activities, likely influencing outcomes. No adverse events occurred and the supervised therapeutic riding program appeared to be a safe and effective form of exercise to improve balance in older adults. A power analysis was performed to estimate numbers of participants needed for a larger study. © The Author(s) 2012.

Novel Control Scheme of Power Assisted Wheelchair for Preventing Overturn (Part I)-Adjustment of Assisted Torque and Performance Evaluation From Field Test-

NASA Astrophysics Data System (ADS)

Seki, Hirokazu; Hata, Naoki; Koyasu, Yuichi; Hori, Yoichi

Aged people and disabled people who have difficulty in walking are increasing. As one of mobility support, significance of power assisted wheelchair which assists driving force using electric motors and spreads their living areas has been enhanced. However, the increased driving force often causes a dangerous overturn of wheelchair. In this paper, control method to prevent power assisted wheelchair from overturning is proposed. It is found the front wheels rising is caused by magnitude and rapid increase of assisted torque. Therefore, feedforward control method to limit the assisted torque by tuning its magnitude or time constant is proposed. In order to emphasize safety and feeling of security, these methods make the front wheels no rise. The effectiveness of the proposed method is verified by the practical experiments and field test based performance evaluation using many trial subjects.

Test-treatment RCTs are susceptible to bias: a review of the methodological quality of randomized trials that evaluate diagnostic tests.

PubMed

Ferrante di Ruffano, Lavinia; Dinnes, Jacqueline; Sitch, Alice J; Hyde, Chris; Deeks, Jonathan J

2017-02-24

There is a growing recognition for the need to expand our evidence base for the clinical effectiveness of diagnostic tests. Many international bodies are calling for diagnostic randomized controlled trials to provide the most rigorous evidence of impact to patient health. Although these so-called test-treatment RCTs are very challenging to undertake due to their methodological complexity, they have not been subjected to a systematic appraisal of their methodological quality. The extent to which these trials may be producing biased results therefore remains unknown. We set out to address this issue by conducting a methodological review of published test-treatment trials to determine how often they implement adequate methods to limit bias and safeguard the validity of results. We ascertained all test-treatment RCTs published 2004-2007, indexed in CENTRAL, including RCTs which randomized patients to diagnostic tests and measured patient outcomes after treatment. Tests used for screening, monitoring or prognosis were excluded. We assessed adequacy of sequence generation, allocation concealment and intention-to-treat, appropriateness of primary analyses, blinding and reporting of power calculations, and extracted study characteristics including the primary outcome. One hundred three trials compared 105 control with 119 experimental interventions, and reported 150 primary outcomes. Randomization and allocation concealment were adequate in 57 and 37% of trials. Blinding was uncommon (patients 5%, clinicians 4%, outcome assessors 21%), as was an adequate intention-to-treat analysis (29%). Overall 101 of 103 trials (98%) were at risk of bias, as judged using standard Cochrane criteria. Test-treatment trials are particularly susceptible to attrition and inadequate primary analyses, lack of blinding and under-powering. These weaknesses pose much greater methodological and practical challenges to conducting reliable RCT evaluations of test-treatment strategies than standard treatment interventions. We suggest a cautious approach that first examines whether a test-treatment intervention can accommodate the methodological safeguards necessary to minimize bias, and highlight that test-treatment RCTs require different methods to ensure reliability than standard treatment trials. Please see the companion paper to this article: http://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-016-0286-0 .

Should high-power posing be integrated in physical therapy?

PubMed

Ge, Weiqing; Bennett, Teale K; Oller, Jeremy C

2017-04-01

[Purpose] Postural assessment and correction is a common approach in patient management to decrease symptoms and improve function for patients. The purpose of this study was to determine the effects of high-power posing on muscle strength and pain threshold. [Subjects and Methods] Thirty-one subjects, 16 females and 15 males, mean age 28.9 (SD 10.8) years old, were recruited through a convenience sampling on the university campus. The research design was a randomized controlled trial. In the experimental group, the subjects were instructed to stand in a high-power posture. In the control group, the subjects were instructed to stand in a low-power posture. Grip strength and pain threshold measurements were conducted before and after the postural intervention. [Results] The grip strength changed by -3.4 (-3.7, 0.3) % and 1.7 (-3.6, 5.3) % for the experimental and control groups, respectively. The pain threshold changed by 0.6 (-9.9, 10.4) % and 15.1 (-9.3, 24.4) % for the experimental and control groups, respectively. However, both changes were not significant as all the 95% CIs included 0. [Conclusions] The data did not show significant benefits of high-power posing in increasing grip strength and pain threshold compared to low-power posing.

Should high-power posing be integrated in physical therapy?

PubMed Central

Ge, Weiqing; Bennett, Teale K.; Oller, Jeremy C.

2017-01-01

[Purpose] Postural assessment and correction is a common approach in patient management to decrease symptoms and improve function for patients. The purpose of this study was to determine the effects of high-power posing on muscle strength and pain threshold. [Subjects and Methods] Thirty-one subjects, 16 females and 15 males, mean age 28.9 (SD 10.8) years old, were recruited through a convenience sampling on the university campus. The research design was a randomized controlled trial. In the experimental group, the subjects were instructed to stand in a high-power posture. In the control group, the subjects were instructed to stand in a low-power posture. Grip strength and pain threshold measurements were conducted before and after the postural intervention. [Results] The grip strength changed by −3.4 (−3.7, 0.3) % and 1.7 (−3.6, 5.3) % for the experimental and control groups, respectively. The pain threshold changed by 0.6 (−9.9, 10.4) % and 15.1 (−9.3, 24.4) % for the experimental and control groups, respectively. However, both changes were not significant as all the 95% CIs included 0. [Conclusions] The data did not show significant benefits of high-power posing in increasing grip strength and pain threshold compared to low-power posing. PMID:28533612

Five-year results of a randomised controlled trial comparing mobile and fixed bearings in total knee replacement.

PubMed

Breeman, S; Campbell, M K; Dakin, H; Fiddian, N; Fitzpatrick, R; Grant, A; Gray, A; Johnston, L; MacLennan, G S; Morris, R W; Murray, D W

2013-04-01

There is conflicting evidence about the merits of mobile bearings in total knee replacement, partly because most randomised controlled trials (RCTs) have not been adequately powered. We report the results of a multicentre RCT of mobile versus fixed bearings. This was part of the knee arthroplasty trial (KAT), where 539 patients were randomly allocated to mobile or fixed bearings and analysed on an intention-to-treat basis. The primary outcome measure was the Oxford Knee Score (OKS) plus secondary measures including Short Form-12, EuroQol EQ-5D, costs, cost-effectiveness and need for further surgery. There was no significant difference between the groups pre-operatively: mean OKS was 17.18 (sd 7.60) in the mobile-bearing group and 16.49 (sd 7.40) in the fixed-bearing group. At five years mean OKS was 33.19 (sd 16.68) and 33.65 (sd 9.68), respectively. There was no significant difference between trial groups in OKS at five years (-1.12 (95% confidence interval -2.77 to 0.52) or any of the other outcome measures. Furthermore, there was no significant difference in the proportion of patients with knee-related re-operations or in total costs. In this appropriately powered RCT, over the first five years after total knee replacement functional outcomes, re-operation rates and healthcare costs appear to be the same irrespective of whether a mobile or fixed bearing is used.

A Mobile Phone App to Support Young People in Making Shared Decisions in Therapy (Power Up): Study Protocol

PubMed Central

Martin, Kate; Webber, Helen; Craven, Michael P; Hollis, Chris; Deighton, Jessica; Law, Roslyn; Fonagy, Peter; Wolpert, Miranda

2017-01-01

Background Evidence suggests that young people want to be active participants in their care and involved in decisions about their treatment. However, there is a lack of digital shared decision-making tools available to support young people in child and adolescent mental health services (CAMHS). Objective The primary aim of this paper is to present the protocol of a feasibility trial for Power Up, a mobile phone app to empower young people in CAMHS to make their voices heard and participate in decisions around their care. Methods In the development phase, 30 young people, parents, and clinicians will take part in interviews and focus groups to elicit opinions on an early version of the app. In the feasibility testing phase, 60 young people from across 7 to 10 London CAMHS sites will take part in a trial looking at the feasibility and acceptability of measuring the impact of Power Up on shared decision making. Results Data collection for the development phase ended in December 2016. Data collection for the feasibility testing phase will end in December 2017. Conclusions Findings will inform the planning of a cluster controlled trial and contribute to the development and implementation of a shared decision-making app to be integrated into CAMHS. Trial Registration ISRCTN77194423; http://www.isrctn.com/ISRCTN77194423 (Archived by WebCite at http://www.webcitation.org/6td6MINP0). ClinicalTrials.gov NCT02987608; https://clinicaltrials.gov/ct2/show/NCT02987608 (Archived by WebCite at http://www.webcitation.org/6td6PNBZM) PMID:29084708

Robust inference from multiple test statistics via permutations: a better alternative to the single test statistic approach for randomized trials.

PubMed

Ganju, Jitendra; Yu, Xinxin; Ma, Guoguang Julie

2013-01-01

Formal inference in randomized clinical trials is based on controlling the type I error rate associated with a single pre-specified statistic. The deficiency of using just one method of analysis is that it depends on assumptions that may not be met. For robust inference, we propose pre-specifying multiple test statistics and relying on the minimum p-value for testing the null hypothesis of no treatment effect. The null hypothesis associated with the various test statistics is that the treatment groups are indistinguishable. The critical value for hypothesis testing comes from permutation distributions. Rejection of the null hypothesis when the smallest p-value is less than the critical value controls the type I error rate at its designated value. Even if one of the candidate test statistics has low power, the adverse effect on the power of the minimum p-value statistic is not much. Its use is illustrated with examples. We conclude that it is better to rely on the minimum p-value rather than a single statistic particularly when that single statistic is the logrank test, because of the cost and complexity of many survival trials. Copyright © 2013 John Wiley & Sons, Ltd.

A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial

PubMed Central

Deeks, Jonathan J; Griffith, Michael; Lip, Gregory YH; Mehta, Samir; Slinn, Gemma; Stanbury, Mary; Steeds, Richard P; Townend, Jonathan N

2017-01-01

Background and objective Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article, we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being. Design and intervention The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF. Participants Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice. Outcome measures The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF. Ethics and dissemination East Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications. Trial registration Clinicaltrials.gov: NCT02391337; ISRCTN: 95259705. Pre-results. PMID:28729311

Addition of transcranial direct current stimulation to quadriceps strengthening exercise in knee osteoarthritis: A pilot randomised controlled trial

PubMed Central

Chang, Wei-Ju; Bennell, Kim L.; Hodges, Paul W.; Hinman, Rana S.; Young, Carolyn L.; Buscemi, Valentina; Liston, Matthew B.

2017-01-01

A randomised, assessor- and participant-blind, sham-controlled trial was conducted to assess the safety and feasibility of adding transcranial direct current stimulation (tDCS) to quadriceps strengthening exercise in knee osteoarthritis (OA), and provide data to inform a fully powered trial. Participants were randomised to receive active tDCS+exercise (AT+EX) or sham tDCS+exercise (ST+EX) twice weekly for 8 weeks whilst completing home exercises twice per week. Feasibility, safety, patient-perceived response, pain, function, pressure pain thresholds (PPTs) and conditioned pain modulation (CPM) were assessed before and after treatment. Fifty-seven people were screened for eligibility. Thirty (52%) entered randomisation and 25 (84%) completed the trial. One episode of headache in the AT+EX group was reported. Pain reduced in both groups following treatment (AT+EX: p<0.001, partial η2 = 0.55; ST+EX: p = 0.026, partial η2 = 0.18) but no between-group differences were observed (p = 0.18, partial η2 = 0.08). Function improved in the AT+EX (p = 0.01, partial η2 = 0.22), but not the ST+EX (p = 0.16, partial η2 = 0.08) group, between-group differences did not reach significance (p = 0.28, partial η2 = 0.052). AT+EX produced greater improvements in PPTs than ST+EX (p<0.05) (superolateral knee: partial η2 = 0.17; superior knee: partial η2 = 0.3; superomedial knee: partial η2 = 0.26). CPM only improved in the AT+EX group but no between-group difference was observed (p = 0.054, partial η2 = 0.158). This study provides the first feasibility and safety data for the addition of tDCS to quadriceps strengthening exercise in knee OA. Our data suggest AT+EX may improve pain, function and pain mechanisms beyond that of ST+EX, and provides support for progression to a fully powered randomised controlled trial. PMID:28665989

Linear Combinations of Multiple Outcome Measures to Improve the Power of Efficacy Analysis ---Application to Clinical Trials on Early Stage Alzheimer Disease

PubMed Central

Xiong, Chengjie; Luo, Jingqin; Morris, John C; Bateman, Randall

2018-01-01

Modern clinical trials on Alzheimer disease (AD) focus on the early symptomatic stage or even the preclinical stage. Subtle disease progression at the early stages, however, poses a major challenge in designing such clinical trials. We propose a multivariate mixed model on repeated measures to model the disease progression over time on multiple efficacy outcomes, and derive the optimum weights to combine multiple outcome measures by minimizing the sample sizes to adequately power the clinical trials. A cross-validation simulation study is conducted to assess the accuracy for the estimated weights as well as the improvement in reducing the sample sizes for such trials. The proposed methodology is applied to the multiple cognitive tests from the ongoing observational study of the Dominantly Inherited Alzheimer Network (DIAN) to power future clinical trials in the DIAN with a cognitive endpoint. Our results show that the optimum weights to combine multiple outcome measures can be accurately estimated, and that compared to the individual outcomes, the combined efficacy outcome with these weights significantly reduces the sample size required to adequately power clinical trials. When applied to the clinical trial in the DIAN, the estimated linear combination of six cognitive tests can adequately power the clinical trial. PMID:29546251

A Powered Lower Limb Orthosis for Providing Legged Mobility in Paraplegic Individuals

PubMed Central

Quintero, Hugo A.; Farris, Ryan J.; Hartigan, Clare; Clesson, Ismari; Goldfarb, Michael

2012-01-01

This paper presents preliminary results on the development of a powered lower limb orthosis intended to provide legged mobility (with the use of a stability aid, such as forearm crutches) to paraplegic individuals. The orthosis contains electric motors at both hip and both knee joints, which in conjunction with ankle-foot orthoses, provides appropriate joint kinematics for legged locomotion. The paper describes the orthosis and the nature of the controller that enables the SCI patient to command the device, and presents data from preliminary trials that indicate the efficacy of the orthosis and controller in providing legged mobility. PMID:22707874

Manual-guided psychosocial treatment. A new virtual requirement for pharmacotherapy trials?

PubMed

Carroll, K M

1997-10-01

The conduct of randomized clinical trials to evaluate the efficacy of pharmacotherapies for mental disorders is guided by research standards (at a high level of rigor) that govern most design elements, including randomization of subjects, use of placebo controls, formulation and dosage of the therapeutic agent, and monitoring of serum levels. In contrast, no such widely accepted guidelines are recognized for standardization of an essential, if unacknowledged, element of all such studies: the concomitant provision of at least a minimal form of psychosocial treatment. Standardized provision of psychosocial treatments in pharmacotherapy trials will foster replicability of findings and address several common problems (e.g., attrition, medication noncompliance, reduction of error variance, and ethical issues associated with placebo controls). Careful selection and standardization of the psychosocial context in which medications are delivered will improve the validity, precision, and power of pharmacotherapy efficacy research, and should be considered a virtual requirement in research design.

A new topology of fuel cell hybrid power source for efficient operation and high reliability

NASA Astrophysics Data System (ADS)

Bizon, Nicu

2011-03-01

This paper analyzes a new fuel cell Hybrid Power Source (HPS) topology having the feature to mitigate the current ripple of the fuel cell inverter system. In the operation of the inverter system that is grid connected or supplies AC motors in vehicle application, the current ripple normally appears at the DC port of the fuel cell HPS. Consequently, if mitigation measures are not applied, this ripple is back propagated to the fuel cell stack. Other features of the proposed fuel cell HPS are the Maximum Power Point (MPP) tracking, high reliability in operation under sharp power pulses and improved energy efficiency in high power applications. This topology uses an inverter system directly powered from the appropriate fuel cell stack and a controlled buck current source as low power source used for ripple mitigation. The low frequency ripple mitigation is based on active control. The anti-ripple current is injected in HPS output node and this has the LF power spectrum almost the same with the inverter ripple. Consequently, the fuel cell current ripple is mitigated by the designed active control. The ripple mitigation performances are evaluated by indicators that are defined to measure the mitigation ratio of the low frequency harmonics. In this paper it is shown that good performances are obtained by using the hysteretic current control, but better if a dedicated nonlinear controller is used. Two ways to design the nonlinear control law are proposed. First is based on simulation trials that help to draw the characteristic of ripple mitigation ratio vs. fuel cell current ripple. The second is based on Fuzzy Logic Controller (FLC). The ripple factor is up to 1% in both cases.

Ethnography, fidelity, and the evidence that anthropology adds: supplementing the fidelity process in a clinical trial of supported employment.

PubMed

Smith-Morris, Carolyn; Lopez, Gilberto; Ottomanelli, Lisa; Goetz, Lance; Dixon-Lawson, Kimberly

2014-06-01

This discussion considers the role and findings of ethnographic research within a clinical trial of supported employment for veterans with spinal cord injury. Contributing to qualitative evaluation research and to debates over anthropological evidence vis-à-vis clinical trials, we demonstrate how enactors of a randomized controlled trial can simultaneously attend to both the trial's evidentiary and procedural requirements and to the lived experiences and needs of patients and clinicians. Three major findings are described: (1) contextual information essential to fidelity efforts within the trial; (2) the role of human interrelationships and idiosyncratic networks in the trial's success; and (3) a mapping of the power and authority structures relevant to the staff's ability to perform the protocol. We emphasize strengths of anthropological ethnography in clinical trials that include the provision of complementary, qualitative data, the capture of otherwise unmeasured parts of the trial, and the realization of important information for the translation of the clinical findings into new settings. © 2014 by the American Anthropological Association.

An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

PubMed Central

2012-01-01

Background To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation. Methods An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews. Results The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises. Conclusions It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability. Trial registration UKCRN 7090; ISRCTN: 80875696 PMID:22676069

Testosterone facilitates the sense of agency.

PubMed

van der Westhuizen, Donné; Moore, James; Solms, Mark; van Honk, Jack

2017-11-01

Sense of agency (SoA) refers to feelings of being in control of one's actions. Evidence suggests that SoA might contribute towards higher-order feelings of personal control - a key attribute of powerful individuals. Whether testosterone, a steroid hormone linked to power in dominance hierarchies, also influences the SoA is not yet established. In a repeated-measures design, 26 females participated in a double-blind, placebo-controlled trial to test the effects of 0.5 mg testosterone on SoA, using an implicit measure based upon perceived shifts in time between a voluntary action and its outcome. Illusions of control, as operationalized by optimism in affective forecasting, were also assessed. Testosterone increased action binding but there was no significant effect on tone binding. Affective forecasting was found to be significantly more positive on testosterone. SoA and optimistic expectations are basic manifestations of power which may contribute to feelings of infallibility often associated with dominance and testosterone. Copyright © 2017 Elsevier Inc. All rights reserved.

Design and Methodology of the Trial to Assess Chelation Therapy (TACT)

PubMed Central

Lamas, Gervasio A.; Goertz, Christine; Boineau, Robin; Mark, Daniel B.; Rozema, Theodore; Nahin, Richard L.; Drisko, Jeanne A.; Lee, Kerry L.

2011-01-01

The Trial to Assess Chelation Therapy (TACT) is an NIH-sponsored, randomized, double blind, placebo-controlled, 2×2 factorial clinical trial testing the benefits and risks of 40 infusions of a multi-component Na2EDTA-chelation solution compared with placebo, and of an oral, high-dose multivitamin and mineral supplement. TACT has randomized and will follow 1708 patients for an average of approximately 4 years. The primary endpoint is a composite of all cause mortality, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. A 900 patient substudy will examine quality of life outcomes. The trial is designed to have >85% power to detect a 25% relative reduction in the primary endpoint for each treatment factor. Enrollment began in September 2003 and completed in October 2010. PMID:22172430

The effect of extrinsic motivation on cycle time trial performance.

PubMed

Hulleman, Michiel; De Koning, Jos J; Hettinga, Florentina J; Foster, Carl

2007-04-01

Athletes occasionally follow pacing patterns that seem unreasonably aggressive compared with those of prerace performances, potentially because of the motivation provided by competition. This study evaluated the effect of extrinsic motivation on cyclists' time trial performance. Well-trained recreational cyclists (N=7) completed four 1500-m laboratory time trials including a practice trial, two self-paced trials, and a trial where a monetary reward was offered. Time, total power output, power output attributable to aerobic and anaerobic metabolic sources, VO2, and HR were measured. The time required for the second, third, and last (extrinsically motivated) time trials was 133.1 +/- 2.1, 134.1 +/- 3.4, and 133.6 +/- 3.0 s, respectively, and was not different (P>0.05). There were no differences for total (396 +/- 19, 397 +/- 23, and 401 +/- 17 W), aerobic (253 +/- 12, 254 +/- 10, and 246 +/- 13 W), and anaerobic (143 +/- 14, 143 +/- 21, and 155 +/- 11 W) power output. The highest VO2 was not different over consecutive time trials (3.76 +/- 0.19, 3.73 +/- 0.16, and 3.71 +/- 0.22 L x min(-1)). When ranked by performance, without reference to the extrinsic motivation (131.9 +/- 2.4, 133.4 +/- 2.4, and 135.4 +/- 2.5 s), there was a significant difference for the first 100 m and from 100 to 300 m in power output, with a larger total power (560 +/- 102, 491 +/- 82, and 493 +/- 93; and 571 +/- 94, 513 +/- 41, and 484 +/- 88 W) and power attributable to anaerobic sources (446 +/- 100, 384 +/- 80, and 324 +/- 43; and 381 +/- 87, 383 +/- 90, and 289 +/- 91 W) for the fastest trial. Extrinsic motivation did not change the time trial performance, suggesting that 1500-m performance is extremely stable and not readily changeable with simple external motivation. The results suggest that spontaneous improvement in performance for time trials of this duration is attributable to greater early power output, which is primarily attributable to anaerobic metabolic sources.

Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials.

PubMed

Lebwohl, Mark G; Papp, Kim A; Marangell, Lauren B; Koo, John; Blauvelt, Andrew; Gooderham, Melinda; Wu, Jashin J; Rastogi, Shipra; Harris, Susan; Pillai, Radhakrishnan; Israel, Robert J

2018-01-01

Individuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB). To distinguish between the underlying risk and potential for treatment-induced psychiatric adverse events in patients with psoriasis being treated with brodalumab, a fully human anti-interleukin 17 receptor A monoclonal antibody. Data were evaluated from a placebo-controlled, phase 2 clinical trial; the open-label, long-term extension of the phase 2 clinical trial; and three phase 3, randomized, double-blind, controlled clinical trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis. The analysis included 4464 patients with 9161.8 patient-years of brodalumab exposure. The follow-up time-adjusted incidence rates of SIB events were comparable between the brodalumab and ustekinumab groups throughout the 52-week controlled phases (0.20 vs 0.60 per 100 patient-years). In the brodalumab group, 4 completed suicides were reported, 1 of which was later adjudicated as indeterminate; all patients had underlying psychiatric disorders or stressors. There was no comparator arm past week 52. Controlled study periods were not powered to detect differences in rare events such as suicide. Comparison with controls and the timing of events do not indicate a causal relationship between SIB and brodalumab treatment. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A generalized concept of power helped to choose optimal endpoints in clinical trials.

PubMed

Borm, George F; van der Wilt, Gert J; Kremer, Jan A M; Zielhuis, Gerhard A

2007-04-01

A clinical trial may have multiple objectives. Sometimes the results for several parameters may need to be significant or meet certain other criteria. In such cases, it is important to evaluate the probability that all these objectives will be met, rather than the probability that each will be met. The purpose of this article is to introduce a definition of power that is tailored to handle this situation and that is helpful for the design of such trials. We introduce a generalized concept of power. It can handle complex situations, for example, in which there is a logical combination of partial objectives. These may be formulated not only in terms of statistical tests and of confidence intervals, but also in nonstatistical terms, such as "selecting the optimal by dose." The power of a trial was calculated for various objectives and combinations of objectives. The generalized concept of power may lead to power calculations that closely match the objectives of the trial and contribute to choosing more efficient endpoints and designs.

Personalized Medicine Enrichment Design for DHA Supplementation Clinical Trial.

PubMed

Lei, Yang; Mayo, Matthew S; Carlson, Susan E; Gajewski, Byron J

2017-03-01

Personalized medicine aims to match patient subpopulation to the most beneficial treatment. The purpose of this study is to design a prospective clinical trial in which we hope to achieve the highest level of confirmation in identifying and making treatment recommendations for subgroups, when the risk levels in the control arm can be ordered. This study was motivated by our goal to identify subgroups in a DHA (docosahexaenoic acid) supplementation trial to reduce preterm birth (gestational age<37 weeks) rate. We performed a meta-analysis to obtain informative prior distributions and simulated operating characteristics to ensure that overall Type I error rate was close to 0.05 in designs with three different models: independent, hierarchical, and dynamic linear models. We performed simulations and sensitivity analysis to examine the subgroup power of models and compared results to a chi-square test. We performed simulations under two hypotheses: a large overall treatment effect and a small overall treatment effect. Within each hypothesis, we designed three different subgroup effects scenarios where resulting subgroup rates are linear, flat, or nonlinear. When the resulting subgroup rates are linear or flat, dynamic linear model appeared to be the most powerful method to identify the subgroups with a treatment effect. It also outperformed other methods when resulting subgroup rates are nonlinear and the overall treatment effect is big. When the resulting subgroup rates are nonlinear and the overall treatment effect is small, hierarchical model and chi-square test did better. Compared to independent and hierarchical models, dynamic linear model tends to be relatively robust and powerful when the control arm has ordinal risk subgroups.

Rationale and design of the Investigator-Steered Project on intravascular Renal Denervation for Management of Drug-Resistant Hypertension (INSPiRED) trial

PubMed Central

Jin, Yu; Jacobs, Lotte; Baelen, Marie; Thijs, Lutgarde; Renkin, Jean; Hammer, Frank; Kefer, Joelle; Petit, Thibault; Verhamme, Peter; Janssens, Stefan; Sinnaeve, Peter; Lengelé, Jean-Philippe; Persu, Alexandre

2014-01-01

The SYMPLICITY studies showed that renal denervation (RDN) is feasible as novel treatment for resistant hypertension. However, RDN is a costly and invasive procedure, the long-term efficacy and safety of which has not yet been proven. Therefore, we designed the INSPiRED trial to compare the blood pressure lowering efficacy and safety of RDN vs usual medical therapy. INSPiRED is a randomized controlled trial enrolling 240 treatment-resistant hypertensive patients at 16 expert hypertension centres in Belgium. Eligible patients, aged 20–69 years old, have a 24-h ambulatory blood pressure of 130 mmHg systolic or 80 mmHg diastolic or more, while taking at least three antihypertensive drugs. They are randomized to RDN (EnligHTNTM, SJM system) plus usual care (intervention group) or usual care alone (control group) in a ratio of 1:1. The primary endpoints for efficacy and safety, measured after 6 months, are the baseline-adjusted between-group differences in 24h systolic blood pressure and in glomerular filtration rate as estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. Follow-up will continue up to 36 months after randomization. INSPiRED is powered to demonstrate a 10-mmHg difference in systolic blood pressure between randomized groups with a two-sided p-value of 0.01 and 90% power. It will generate long-term efficacy and safety data, identify the subset of treatment-resistant hypertensive patients responsive to RDN, provide information on cost-effectiveness, and by doing so INSPiRED will inform guideline committees and health policy makers. Trial registration: ClinicalTrials.gov Identifier: NCT 01505010. PMID:24742341

Ethical implications of excessive cluster sizes in cluster randomised trials.

PubMed

Hemming, Karla; Taljaard, Monica; Forbes, Gordon; Eldridge, Sandra M; Weijer, Charles

2018-02-20

The cluster randomised trial (CRT) is commonly used in healthcare research. It is the gold-standard study design for evaluating healthcare policy interventions. A key characteristic of this design is that as more participants are included, in a fixed number of clusters, the increase in achievable power will level off. CRTs with cluster sizes that exceed the point of levelling-off will have excessive numbers of participants, even if they do not achieve nominal levels of power. Excessively large cluster sizes may have ethical implications due to exposing trial participants unnecessarily to the burdens of both participating in the trial and the potential risks of harm associated with the intervention. We explore these issues through the use of two case studies. Where data are routinely collected, available at minimum cost and the intervention poses low risk, the ethical implications of excessively large cluster sizes are likely to be low (case study 1). However, to maximise the social benefit of the study, identification of excessive cluster sizes can allow for prespecified and fully powered secondary analyses. In the second case study, while there is no burden through trial participation (because the outcome data are routinely collected and non-identifiable), the intervention might be considered to pose some indirect risk to patients and risks to the healthcare workers. In this case study it is therefore important that the inclusion of excessively large cluster sizes is justifiable on other grounds (perhaps to show sustainability). In any randomised controlled trial, including evaluations of health policy interventions, it is important to minimise the burdens and risks to participants. Funders, researchers and research ethics committees should be aware of the ethical issues of excessively large cluster sizes in cluster trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The effect of changing movement and posture using motion-sensor biofeedback, versus guidelines-based care, on the clinical outcomes of people with sub-acute or chronic low back pain-a multicentre, cluster-randomised, placebo-controlled, pilot trial.

PubMed

Kent, Peter; Laird, Robert; Haines, Terry

2015-05-29

The aims of this pilot trial were to (i) test the hypothesis that modifying patterns of painful lumbo-pelvic movement using motion-sensor biofeedback in people with low back pain would lead to reduced pain and activity limitation compared with guidelines-based care, and (ii) facilitate sample size calculations for a fully powered trial. A multicentre (8 clinics), cluster-randomised, placebo-controlled pilot trial compared two groups of patients seeking medical or physiotherapy primary care for sub-acute and chronic back pain. It was powered for longitudinal analysis, but not for adjusted single-time point comparisons. The intervention group (n = 58) received modification of movement patterns augmented by motion-sensor movement biofeedback (ViMove, dorsaVi.com) plus guidelines-based medical or physiotherapy care. The control group (n = 54) received a placebo (wearing the motion-sensors without biofeedback) plus guidelines-based medical or physiotherapy care. Primary outcomes were self-reported pain intensity (VAS) and activity limitation (Roland Morris Disability Questionnaire (RMDQ), Patient Specific Functional Scale (PSFS)), all on 0-100 scales. Both groups received 6-8 treatment sessions. Outcomes were measured seven times during 10-weeks of treatment and at 12, 26 and 52 week follow-up, with 17.0 % dropout. Patients were not informed of group allocation or the study hypothesis. Across one-year, there were significant between-group differences favouring the intervention group [generalized linear model coefficient (95 % CI): group effect RMDQ -7.1 (95 % CI-12.6;-1.6), PSFS -10.3 (-16.6; -3.9), QVAS -7.7 (-13.0; -2.4); and group by time effect differences (per 100 days) RMDQ -3.5 (-5.2; -2.2), PSFS -4.7 (-7.0; -2.5), QVAS -4.8 (-6.1; -3.5)], all p < 0.001. Risk ratios between groups of probability of improving by >30 % at 12-months = RMDQ 2.4 (95 % CI 1.5; 4.1), PSFS 2.5 (1.5; 4.0), QVAS 3.3 (1.8; 5.9). The only device-related side-effects involved transient skin irritation from tape used to mount motion sensors. Individualised movement retraining using motion-sensor biofeedback resulted in significant and sustained improvements in pain and activity limitation that persisted after treatment finished. This pilot trial also refined the procedures and sample size requirements for a fully powered RCT. This trial (Australian New Zealand Clinical Trials Registry NCT01572779) was equally funded by dorsaVi P/L and the Victorian State Government.

Morita therapy for depression and anxiety (Morita Trial): study protocol for a pilot randomised controlled trial.

PubMed

Sugg, Holly Victoria Rose; Richards, David A; Frost, Julia

2016-03-24

Morita Therapy, a psychological therapy for common mental health problems, is in sharp contrast to established western psychotherapeutic approaches in teaching that undesired symptoms are natural features of human emotion rather than something to control or eliminate. The approach is widely practiced in Japan, but untested and little known in the UK. A clinical trial of Morita Therapy is required to establish the effectiveness of Morita Therapy for a UK population. However, a number of methodological, procedural and clinical uncertainties associated with such a trial first require addressing. The Morita Trial is a mixed methods study addressing the uncertainties associated with an evaluation of Morita Therapy compared with treatment as usual for depression and anxiety. We will undertake a pilot randomised controlled trial with embedded qualitative study. Sixty participants with major depressive disorder, with or without anxiety disorders, will be recruited predominantly from General Practice record searches and randomised to receive Morita Therapy plus treatment as usual or treatment as usual alone. Morita Therapy will be delivered by accredited psychological therapists. We will collect quantitative data on depressive symptoms, general anxiety, attitudes and quality of life at baseline and four month follow-up to inform future sample size calculations; and rates of recruitment, retention and treatment adherence to assess feasibility. We will undertake qualitative interviews in parallel with the trial, to explore people's views of Morita Therapy. We will conduct separate and integrated analyses on the quantitative and qualitative data. The outcomes of this study will prepare the ground for the design and conduct of a fully-powered evaluation of Morita Therapy plus treatment as usual versus treatment as usual alone, or inform a conclusion that such a trial is not feasible and/or appropriate. We will obtain a more comprehensive understanding of these issues than would be possible from either a quantitative or qualitative approach alone. Current Controlled Trials ISRCTN17544090 registered on 23 July 2015.

Protocol for a randomised controlled trial of fetal scalp blood lactate measurement to reduce caesarean sections during labour: the Flamingo trial [ACTRN12611000172909].

PubMed

East, Christine E; Kane, Stefan C; Davey, Mary-Ann; Kamlin, C Omar; Brennecke, Shaun P

2015-11-03

The rate of caesarean sections around the world is rising each year, reaching epidemic proportions. Although many caesarean sections are performed for concerns about fetal welfare on the basis of abnormal cardiotocography, the majority of babies are shown to be well at birth, meaning that the operation, with its inherent short and long term risks, could have been avoided without compromising the baby's health. Previously, fetal scalp blood sampling for pH estimation was performed in the context of an abnormal cardiotocograph, to improve the identification of babies in need of expedited delivery. This test has largely been replaced by lactate measurement, although its validity is yet to be established through a randomised controlled trial. This study aims to test the hypothesis that the performance of fetal scalp blood lactate measurement for women in labour with an abnormal cardiotocograph will reduce the rate of birth by caesarean section from 38 % to 25 % (a 35 % relative reduction). Prospective unblinded randomised controlled trial conducted at a single tertiary perinatal centre. Women labouring with a singleton fetus in cephalic presentation at 37 or more weeks' gestation with ruptured membranes and with an abnormal cardiotocograph will be eligible. Participants will be randomised to one of two groups: fetal monitoring by cardiotocography alone, or cardiotocography augmented by fetal scalp blood lactate analysis. Decisions regarding the timing and mode of delivery will be made by the treating team, in accordance with hospital protocols. The primary study endpoint is caesarean section with secondary outcomes collected from maternal, fetal and neonatal clinical course and morbidities. A cost effectiveness analysis will also be performed. A sample size of 600 will provide 90 % power to detect the hypothesised difference in the proportion of women who give birth by caesarean section. This world-first trial is adequately powered to determine the impact of fetal scalp blood lactate measurement on rates of caesarean section. Preventing unnecessary caesarean sections will reduce the health and financial burdens associated with this operation, both in the index and any future pregnancies. Australian New Zealand Clinical Trials Registry ACTRN12611000172909.

Reporting of sample size calculations in analgesic clinical trials: ACTTION systematic review.

PubMed

McKeown, Andrew; Gewandter, Jennifer S; McDermott, Michael P; Pawlowski, Joseph R; Poli, Joseph J; Rothstein, Daniel; Farrar, John T; Gilron, Ian; Katz, Nathaniel P; Lin, Allison H; Rappaport, Bob A; Rowbotham, Michael C; Turk, Dennis C; Dworkin, Robert H; Smith, Shannon M

2015-03-01

Sample size calculations determine the number of participants required to have sufficiently high power to detect a given treatment effect. In this review, we examined the reporting quality of sample size calculations in 172 publications of double-blind randomized controlled trials of noninvasive pharmacologic or interventional (ie, invasive) pain treatments published in European Journal of Pain, Journal of Pain, and Pain from January 2006 through June 2013. Sixty-five percent of publications reported a sample size calculation but only 38% provided all elements required to replicate the calculated sample size. In publications reporting at least 1 element, 54% provided a justification for the treatment effect used to calculate sample size, and 24% of studies with continuous outcome variables justified the variability estimate. Publications of clinical pain condition trials reported a sample size calculation more frequently than experimental pain model trials (77% vs 33%, P < .001) but did not differ in the frequency of reporting all required elements. No significant differences in reporting of any or all elements were detected between publications of trials with industry and nonindustry sponsorship. Twenty-eight percent included a discrepancy between the reported number of planned and randomized participants. This study suggests that sample size calculation reporting in analgesic trial publications is usually incomplete. Investigators should provide detailed accounts of sample size calculations in publications of clinical trials of pain treatments, which is necessary for reporting transparency and communication of pre-trial design decisions. In this systematic review of analgesic clinical trials, sample size calculations and the required elements (eg, treatment effect to be detected; power level) were incompletely reported. A lack of transparency regarding sample size calculations may raise questions about the appropriateness of the calculated sample size. Copyright © 2015 American Pain Society. All rights reserved.

Lee Silverman Voice Treatment versus standard speech and language therapy versus control in Parkinson's disease: a pilot randomised controlled trial (PD COMM pilot).

PubMed

Sackley, Catherine M; Smith, Christina H; Rick, Caroline E; Brady, Marian C; Ives, Natalie; Patel, Smitaa; Woolley, Rebecca; Dowling, Francis; Patel, Ramilla; Roberts, Helen; Jowett, Sue; Wheatley, Keith; Kelly, Debbie; Sands, Gina; Clarke, Carl E

2018-01-01

Speech-related problems are common in Parkinson's disease (PD), but there is little evidence for the effectiveness of standard speech and language therapy (SLT) or Lee Silverman Voice Treatment (LSVT LOUD®). The PD COMM pilot was a three-arm, assessor-blinded, randomised controlled trial (RCT) of LSVT LOUD®, SLT and no intervention (1:1:1 ratio) to assess the feasibility and to inform the design of a full-scale RCT. Non-demented patients with idiopathic PD and speech problems and no SLT for speech problems in the past 2 years were eligible. LSVT LOUD® is a standardised regime (16 sessions over 4 weeks). SLT comprised individualised content per local practice (typically weekly sessions for 6-8 weeks). Outcomes included recruitment and retention, treatment adherence, and data completeness. Outcome data collected at baseline, 3, 6, and 12 months included patient-reported voice and quality of life measures, resource use, and assessor-rated speech recordings. Eighty-nine patients were randomised with 90% in the therapy groups and 100% in the control group completing the trial. The response rate for Voice Handicap Index (VHI) in each arm was ≥ 90% at all time-points. VHI was highly correlated with the other speech-related outcome measures. There was a trend to improvement in VHI with LSVT LOUD® (difference at 3 months compared with control: - 12.5 points; 95% CI - 26.2, 1.2) and SLT (difference at 3 months compared with control: - 9.8 points; 95% CI - 23.2, 3.7) which needs to be confirmed in an adequately powered trial. Randomisation to a three-arm trial of speech therapy including a no intervention control is feasible and acceptable. Compliance with both interventions was good. VHI and other patient-reported outcomes were relevant measures and provided data to inform the sample size for a substantive trial. International Standard Randomised Controlled Trial Number Register: ISRCTN75223808. registered 22 March 2012.

A Monte Carlo analysis of breast screening randomized trials.

PubMed

Zamora, Luis I; Forastero, Cristina; Guirado, Damián; Lallena, Antonio M

2016-12-01

To analyze breast screening randomized trials with a Monte Carlo simulation tool. A simulation tool previously developed to simulate breast screening programmes was adapted for that purpose. The history of women participating in the trials was simulated, including a model for survival after local treatment of invasive cancers. Distributions of time gained due to screening detection against symptomatic detection and the overall screening sensitivity were used as inputs. Several randomized controlled trials were simulated. Except for the age range of women involved, all simulations used the same population characteristics and this permitted to analyze their external validity. The relative risks obtained were compared to those quoted for the trials, whose internal validity was addressed by further investigating the reasons of the disagreements observed. The Monte Carlo simulations produce results that are in good agreement with most of the randomized trials analyzed, thus indicating their methodological quality and external validity. A reduction of the breast cancer mortality around 20% appears to be a reasonable value according to the results of the trials that are methodologically correct. Discrepancies observed with Canada I and II trials may be attributed to a low mammography quality and some methodological problems. Kopparberg trial appears to show a low methodological quality. Monte Carlo simulations are a powerful tool to investigate breast screening controlled randomized trials, helping to establish those whose results are reliable enough to be extrapolated to other populations and to design the trial strategies and, eventually, adapting them during their development. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Effect of volatile compounds on excimer laser power delivery.

PubMed

Van Horn, Stewart D; Hovanesian, John A; Maloney, Robert K

2002-01-01

To determine whether vapors from perfume, hairspray, oil-based paint, or water-based paint affect excimer laser beam power delivery at the corneal surface. We measured the power delivery of an Apex Plus laser before, during, and after exposure to vapors from the following volatile compounds: three types of perfume, hair spray, an oil-based paint, and a water-based paint. A digital calorimeter was used to measure the steady-state beam power of the laser during laser discharge at the corneal plane. Multiple trials were run with each compound, and the change in laser energy over time was examined to determine if any of the compounds caused degradation of the laser optics. The presence of a volatile compound in the room caused no change in mean laser energy in comparison to before and after the compound was present. However, perfumes caused a progressive decline in laser beam power throughout the trials. Controlling for this progressive decline, there was no significant difference from perfume to perfume. None of the compounds tested caused a decline in laser beam power while present in the room. However, the presence of any perfume caused a deterioration in beam power over time, suggesting a degradation of the laser optics for all perfumes. Laser centers should consider advising their patients and staff to not wear perfumes in the laser suite.

Effects of shoe cleat position on physiology and performance of competitive cyclists.

PubMed

Paton, Carl D

2009-12-01

Aerobic economy is an important factor that affects the performance of competitive cyclists. It has been suggested that placing the foot more anteriorly on the bicycle pedals may improve economy over the traditional foot position by improving pedaling efficiency. The current study examines the effects of changing the anterior-posterior pedal foot position on the physiology and performance of well-trained cyclists. In a crossover study, 10 competitive cyclists completed two maximal incremental and two submaximal tests in either their preferred (control) or a forward (arch) foot position. Maximum oxygen consumption and peak power output were determined from the incremental tests for both foot positions. On two further occasions, cyclists also completed a two-part 60-min submaximal test that required them to maintain a constant power output (equivalent to 60% of their incremental peak power) for 30 min, during which respiratory and blood lactate samples were taken at predetermined intervals. Thereafter, subjects completed a 30-min self-paced maximal effort time trial. Relative to the control, the mean changes (+/-90% confidence limits) in the arch condition were as follows: maximum oxygen consumption, -0.5% (+/-2.0%); incremental peak power output, -0.8% (+/-1.3%); steady-state oxygen consumption at 60%, -2.4% (+/-1.1%); steady-state heart rate 60%, 0.4% (+/-1.7%); lactate concentration 60%, 8.7% (+/-14.4%); and mean time trial power, -1.5% (+/-2.9%). We conclude that there was no substantial physiological or performance advantage in this group using an arch-cleat shoe position in comparison with a cyclist's normal preferred condition.

A Systematic Review of the Effectiveness of Medical Cannabis for Psychiatric, Movement and Neurodegenerative Disorders.

PubMed

Lim, Keane; See, Yuen Mei; Lee, Jimmy

2017-11-30

The discovery of endocannabinoid's role within the central nervous system and its potential therapeutic benefits have brought forth rising interest in the use of cannabis for medical purposes. The present review aimed to synthesize and evaluate the available evidences on the efficacy of cannabis and its derivatives for psychiatric, neurodegenerative and movement disorders. A systematic search of randomized controlled trials of cannabis and its derivatives were conducted via databases (PubMed, Embase and the Cochrane Central Register of Controlled Trials). A total of 24 reports that evaluated the use of medical cannabis for Alzheimer's disease, anorexia nervosa, anxiety, dementia, dystonia, Huntington's disease, Parkinson's disease, post-traumatic stress disorder (PTSD), psychosis and Tourette syndrome were included in this review. Trial quality was assessed with the Cochrane risk of bias tool. There is a lack of evidence on the therapeutic effects of cannabinoids for amyotrophic lateral sclerosis and dystonia. Although trials with positive findings were identified for anorexia nervosa, anxiety, PTSD, psychotic symptoms, agitation in Alzheimer's disease and dementia, Huntington's disease, and Tourette syndrome, and dyskinesia in Parkinson's disease, definitive conclusion on its efficacy could not be drawn. Evaluation of these low-quality trials, as rated on the Cochrane risk of bias tools, was challenged by methodological issues such as inadequate description of allocation concealment, blinding and underpowered sample size. More adequately powered controlled trials that examine the long and short term efficacy, safety and tolerability of cannabis for medical use, and the mechanisms underpinning the therapeutic potential are warranted.

Cognitive behaviour therapy to prevent harmful compliance with command hallucinations (COMMAND): a randomised controlled trial.

PubMed

Birchwood, Max; Michail, Maria; Meaden, Alan; Tarrier, Nicholas; Lewis, Shon; Wykes, Til; Davies, Linda; Dunn, Graham; Peters, Emmanuelle

2014-06-01

Acting on command hallucinations in psychosis can have serious consequences for the individual and for other people and is a major cause of clinical and public concern. No evidence-based treatments are available to reduce this risk behaviour. We therefore tested our new cognitive therapy to challenge the perceived power of voices to inflict harm on the voice hearer if commands are not followed, thereby reducing the hearer's motivation to comply. In COMMAND, a single-blind, randomised controlled trial, eligible participants from three centres in the UK who had command hallucinations for at least 6 months leading to major episodes of harm to themselves or other people were assigned in a 1: 1 ratio to cognitive therapy for command hallucinations + treatment as usual versus just treatment as usual for 9 months. Only the raters were masked to treatment assignment. The primary outcome was harmful compliance. Analysis was by intention to treat. The trial is registered, number ISRCTN62304114. 98 (50%) of 197 participants were assigned to cognitive therapy for command hallucinations + treatment as usual and 99 (50%) to treatment as usual. At 18 months, 39 (46%) of 85 participants in the treatment as usual group fully complied with the voices compared with 22 (28%) of 79 in the cognitive therapy for command hallucinations + treatment as usual group (odds ratio 0·45, 95% CI 0·23-0·88, p=0·021). At 9 months the treatment effect was not significant (0·74, 0·40-1·39, p=0·353). However, the treatment by follow-up interaction was not significant and the treatment effect common to both follow-up points was 0·57 (0·33-0·98, p=0·042). This is the first trial to show a clinically meaningful reduction in risk behaviour associated with commanding voices. We will next determine if change in power was the mediator of change. Further more complex trials are needed to identify the most influential components of the treatment in reducing power and compliance. UK Medical Research Council and the National Institute for Health Research. Copyright © 2014 Elsevier Ltd. All rights reserved.

Culturally adaptive storytelling method to improve hypertension control in Vietnam - "We talk about our hypertension": study protocol for a feasibility cluster-randomized controlled trial.

PubMed

Allison, Jeroan J; Nguyen, Hoa L; Ha, Duc A; Chiriboga, Germán; Ly, Ha N; Tran, Hanh T; Phan, Ngoc T; Vu, Nguyen C; Kim, Minjin; Goldberg, Robert J

2016-01-14

Vietnam is experiencing an epidemiologic transition with an increased prevalence of non-communicable diseases. At present, the major risk factors for cardiovascular disease (CVD) are either on the rise or at alarming levels in Vietnam; inasmuch, the burden of CVD will continue to increase in this country unless effective prevention and control measures are put in place. A national survey in 2008 found that the prevalence of hypertension (HTN) was approximately 25 % among Vietnamese adults and it increased with advancing age. Therefore, novel, large-scale, and sustainable interventions for public health education to promote engagement in the process of detecting and treating HTN in Vietnam are urgently needed. A feasibility randomized trial will be conducted in Hung Yen province, Vietnam to evaluate the feasibility and acceptability of a novel community-based intervention using the "storytelling" method to enhance the control of HTN in adults residing in four rural communities. The intervention will center on stories about living with HTN, with patients speaking in their own words. The stories will be obtained from particularly eloquent patients, or "video stars," identified during Story Development Groups. The study will involve two phases: (i) developing a HTN intervention using the storytelling method, which is designed to empower patients to facilitate changes in their lifestyle practices, and (ii) conducting a feasibility cluster-randomized trial to investigate the feasibility, acceptability, and potential efficacy of the intervention compared with usual care in HTN control among rural residents. The trial will be conducted at four communes, and within each commune, 25 individuals 50 years or older with HTN will be enrolled in the trial resulting in a total sample size of 100 patients. This feasibility trial will provide the necessary groundwork for a subsequent large-scale, fully powered, cluster-randomized controlled trial to test the efficacy of our novel community-based intervention. Results from the full-scale trial will provide health policy makers with practical evidence on how to combat a key risk factor for CVD using a feasible, sustainable, and cost-effective intervention that could be used as a national program for controlling HTN in Vietnam and other developing countries. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02483780 (registration date June 22, 2015).

Podiatry intervention versus usual care to prevent falls in care homes: pilot randomised controlled trial (the PIRFECT study).

PubMed

Wylie, Gavin; Menz, Hylton B; McFarlane, Sarah; Ogston, Simon; Sullivan, Frank; Williams, Brian; Young, Zoe; Morris, Jacqui

2017-07-12

Common foot problems are independent risk factors for falls in older people. There is evidence that podiatry can prevent falls in community-dwelling populations. The feasibility of implementing a podiatry intervention and trial in the care home population is unknown. To inform a potential future definitive trial, we performed a pilot randomised controlled trial to assess: (i) the feasibility of a trial of a podiatry intervention to reduce care home falls, and (ii) the potential direction and magnitude of the effect of the intervention in terms of number of falls in care home residents. Informed by Medical Research Council guidance on developing and evaluating complex interventions, we conducted a single blind, pilot randomised controlled trial in six care homes in the East of Scotland. Participants were randomised to either: (i) a three month podiatry intervention comprising core podiatry care, foot and ankle exercises, orthoses and footwear provision or (ii) usual care. Falls-related outcomes (number of falls, time to first fall) and feasibility-related outcomes (recruitment, retention, adherence, data collection rates) were collected. Secondary outcomes included: generic health status, balance, mobility, falls efficacy, and ankle joint strength. 474 care home residents were screened. 43 (9.1%) participants were recruited: 23 to the intervention, 20 to control. Nine (21%) participants were lost to follow-up due to declining health or death. It was feasible to deliver the trial elements in the care home setting. 35% of participants completed the exercise programme. 48% reported using the orthoses 'all or most of the time'. Completion rates of the outcome measures were between 93% and 100%. No adverse events were reported. At the nine month follow-up period, the intervention group per-person fall rate was 0.77 falls vs. 0.83 falls in the control group. A podiatry intervention to reduce falls can be delivered to care home residents within a pilot randomised controlled trial of the intervention. Although not powered to determine effectiveness, these preliminary data provide justification for a larger trial, incorporating a full process evaluation, to determine whether this intervention can significantly reduce falls in this high-risk population. ClinicalTrials.gov identifier: NCT02178527 ; Date of registration: 17 June 2014.

A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial.

PubMed

Kotecha, Dipak; Calvert, Melanie; Deeks, Jonathan J; Griffith, Michael; Kirchhof, Paulus; Lip, Gregory Yh; Mehta, Samir; Slinn, Gemma; Stanbury, Mary; Steeds, Richard P; Townend, Jonathan N

2017-07-20

Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article , we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being. The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF. Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice. The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF. East Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications. Clinicaltrials.gov: NCT02391337; ISRCTN: 95259705. Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Predicting High-Power Performance in Professional Cyclists.

PubMed

Sanders, Dajo; Heijboer, Mathieu; Akubat, Ibrahim; Meijer, Kenneth; Hesselink, Matthijs K

2017-03-01

To assess if short-duration (5 to ~300 s) high-power performance can accurately be predicted using the anaerobic power reserve (APR) model in professional cyclists. Data from 4 professional cyclists from a World Tour cycling team were used. Using the maximal aerobic power, sprint peak power output, and an exponential constant describing the decrement in power over time, a power-duration relationship was established for each participant. To test the predictive accuracy of the model, several all-out field trials of different durations were performed by each cyclist. The power output achieved during the all-out trials was compared with the predicted power output by the APR model. The power output predicted by the model showed very large to nearly perfect correlations to the actual power output obtained during the all-out trials for each cyclist (r = .88 ± .21, .92 ± .17, .95 ± .13, and .97 ± .09). Power output during the all-out trials remained within an average of 6.6% (53 W) of the predicted power output by the model. This preliminary pilot study presents 4 case studies on the applicability of the APR model in professional cyclists using a field-based approach. The decrement in all-out performance during high-intensity exercise seems to conform to a general relationship with a single exponential-decay model describing the decrement in power vs increasing duration. These results are in line with previous studies using the APR model to predict performance during brief all-out trials. Future research should evaluate the APR model with a larger sample size of elite cyclists.

Comparison of rheumatoid arthritis clinical trial outcome measures: a simulation study.

PubMed

Anderson, Jennifer J; Bolognese, James A; Felson, David T

2003-11-01

Isolated studies have suggested that continuous measures of response may be better than predefined, dichotomous definitions (e.g., the American College of Rheumatology 20% improvement criteria [ACR20]) for discriminating between rheumatoid arthritis (RA) treatments. Our goal was to determine the statistical power of predefined dichotomous outcome measures (termed "a priori"), compared with that of continuous measures derived from trial data in which there was no predefined response threshold (termed "data driven"), and to evaluate the sensitivity to change of these measures in the context of different treatments and early versus later-stage disease. In order to generalize beyond results from a single trial, we performed simulation studies. We obtained summary data from trials comparing disease-modifying antirheumatic drugs (DMARDs) and from comparative coxib-placebo trials to test the power of 2 a priori outcomes, the ACR20 and improvement of the Disease Activity Score (DDAS), as well as 2 data-driven outcomes. We studied patients with early RA and those with later-stage RA (duration of <4 years and 4-9 years, respectively). We performed simulation studies, using the interrelationship of ACR core set measures in the trials to generate multiple trial data sets consistent with the original data. The data-driven outcomes had greater power than did the a priori measures. The DMARD comparison was more powerful in early disease than in later-stage disease (the sample sizes needed to achieve 80% power for the most powerful test were 64 for early disease versus 100 for later disease), but the coxib-versus-placebo comparison was less powerful in early disease than in later disease (the sample sizes needed to achieve 80% power were 200 and 100, respectively). When the effects of treatment on core set items were small and/or inconsistent, power was reduced, particularly for a less broadly based outcome (e.g., DDAS) compared with the ACR20. The simulation studies demonstrate that data-driven outcome definitions can provide better sensitivity to change than does the ACR20 or DDAS. Using such methods would improve power, but at the expense of trial standardization. The studies also show how patient population and treatment characteristics affect the power of specific outcome measures in RA clinical trials, and provide quantification of those effects.

Cortical thickness as a contributor to abnormal oscillations in schizophrenia?☆

PubMed Central

Edgar, J. Christopher; Chen, Yu-Han; Lanza, Matthew; Howell, Breannan; Chow, Vivian Y.; Heiken, Kory; Liu, Song; Wootton, Cassandra; Hunter, Michael A.; Huang, Mingxiong; Miller, Gregory A.; Cañive, José M.

2013-01-01

Introduction Although brain rhythms depend on brain structure (e.g., gray and white matter), to our knowledge associations between brain oscillations and structure have not been investigated in healthy controls (HC) or in individuals with schizophrenia (SZ). Observing function–structure relationships, for example establishing an association between brain oscillations (defined in terms of amplitude or phase) and cortical gray matter, might inform models on the origins of psychosis. Given evidence of functional and structural abnormalities in primary/secondary auditory regions in SZ, the present study examined how superior temporal gyrus (STG) structure relates to auditory STG low-frequency and 40 Hz steady-state activity. Given changes in brain activity as a function of age, age-related associations in STG oscillatory activity were also examined. Methods Thirty-nine individuals with SZ and 29 HC were recruited. 40 Hz amplitude-modulated tones of 1 s duration were presented. MEG and T1-weighted sMRI data were obtained. Using the sources localizing 40 Hz evoked steady-state activity (300 to 950 ms), left and right STG total power and inter-trial coherence were computed. Time–frequency group differences and associations with STG structure and age were also examined. Results Decreased total power and inter-trial coherence in SZ were observed in the left STG for initial post-stimulus low-frequency activity (~ 50 to 200 ms, ~ 4 to 16 Hz) as well as 40 Hz steady-state activity (~ 400 to 1000 ms). Left STG 40 Hz total power and inter-trial coherence were positively associated with left STG cortical thickness in HC, not in SZ. Left STG post-stimulus low-frequency and 40 Hz total power were positively associated with age, again only in controls. Discussion Left STG low-frequency and steady-state gamma abnormalities distinguish SZ and HC. Disease-associated damage to STG gray matter in schizophrenia may disrupt the age-related left STG gamma-band function–structure relationships observed in controls. PMID:24371794

Detecting and accounting for violations of the constancy assumption in non-inferiority clinical trials.

PubMed

Koopmeiners, Joseph S; Hobbs, Brian P

2018-05-01

Randomized, placebo-controlled clinical trials are the gold standard for evaluating a novel therapeutic agent. In some instances, it may not be considered ethical or desirable to complete a placebo-controlled clinical trial and, instead, the placebo is replaced by an active comparator with the objective of showing either superiority or non-inferiority to the active comparator. In a non-inferiority trial, the experimental treatment is considered non-inferior if it retains a pre-specified proportion of the effect of the active comparator as represented by the non-inferiority margin. A key assumption required for valid inference in the non-inferiority setting is the constancy assumption, which requires that the effect of the active comparator in the non-inferiority trial is consistent with the effect that was observed in previous trials. It has been shown that violations of the constancy assumption can result in a dramatic increase in the rate of incorrectly concluding non-inferiority in the presence of ineffective or even harmful treatment. In this paper, we illustrate how Bayesian hierarchical modeling can be used to facilitate multi-source smoothing of the data from the current trial with the data from historical studies, enabling direct probabilistic evaluation of the constancy assumption. We then show how this result can be used to adapt the non-inferiority margin when the constancy assumption is violated and present simulation results illustrating that our method controls the type-I error rate when the constancy assumption is violated, while retaining the power of the standard approach when the constancy assumption holds. We illustrate our adaptive procedure using a non-inferiority trial of raltegravir, an antiretroviral drug for the treatment of HIV.

Detecting and Accounting for Violations of the Constancy Assumption in Non-Inferiority Clinical Trials

PubMed Central

Koopmeiners, Joseph S.; Hobbs, Brian P.

2016-01-01

Randomized, placebo-controlled clinical trials are the gold standard for evaluating a novel therapeutic agent. In some instances, it may not be considered ethical or desirable to complete a placebo-controlled clinical trial and, instead, the placebo is replaced by an active comparator (AC) with the objective of showing either superiority or non-inferiority to the AC. In a non-inferiority trial, the experimental treatment is considered non-inferior if it retains a pre-specified proportion of the effect of the AC as represented by the non-inferiority margin. A key assumption required for valid inference in the non-inferiority setting is the constancy assumption, which requires that the effect of the AC in the non-inferiority trial is consistent with the effect that was observed in previous trials. It has been shown that violations of the constancy assumption can result in a dramatic increase in the rate of incorrectly concluding non-inferiority in the presence of ineffective or even harmful treatment. In this paper, we illustrate how Bayesian hierarchical modeling can be used to facilitate multi-source smoothing of the data from the current trial with the data from historical studies, enabling direct probabilistic evaluation of the constancy assumption. We then show how this result can be used to adapt the non-inferiority margin when the constancy assumption is violated and present simulation results illustrating that our method controls the type-I error rate when the constancy assumption is violated, while retaining the power of the standard approach when the constancy assumption holds. We illustrate our adaptive procedure using a non-inferiority trial of raltegravir, an antiretroviral drug for the treatment of HIV. PMID:27587591

Randomized Controlled Trials in Music Therapy: Guidelines for Design and Implementation.

PubMed

Bradt, Joke

2012-01-01

Evidence from randomized controlled trials (RCTs) plays a powerful role in today's healthcare industry. At the same time, it is important that multiple types of evidence contribute to music therapy's knowledge base and that the dialogue of clinical effectiveness in music therapy is not dominated by the biomedical hierarchical model of evidence-based practice. Whether or not one agrees with the hierarchical model of evidence in the current healthcare climate, RCTs can contribute important knowledge to our field. Therefore, it is important that music therapists are prepared to design trials that meet current methodological standards and, equally important, are able to respond appropriately to those design aspects that may not be feasible in music therapy research. To provide practical guidelines to music therapy researchers for the design and implementation of RCTs as well as to enable music therapists to be well-informed consumers of RCT evidence. This article reviews key design aspects of RCTs and discusses how to best implement these standards in music therapy trials. A systematic presentation of basic randomization methods, allocation concealment strategies, issues related to blinding in music therapy trials and strategies for implementation, the use of treatment manuals, types of control groups, outcome selection, and sample size computation is provided. Despite the challenges of meeting all key design demands typical of an RCT, it is possible to design rigorous music therapy RCTs that accurately estimate music therapy treatment benefits.

[Evaluation of the efficacy of powered and manual toothbrushes in preventing oral diseases (Systematic review with meta-analysis)].

PubMed

Nagy, Pál; Kövér, Krisztián; Gera, István; Horváth, Attila

2016-03-01

The removal of dental plaque plays an essential role in the maintenance of oral health. Numerous powered and manual toothbrushes were manufactured to achieve this goal, but even up to this day different opinions and research results have been revealed to assess the priority of the mentioned devices. Comparison of powered and manual toothbrushes on the basis of periodontal parameters and safety. Electronic search of the databases of MEDLINE and EMBASE (until May 2014) was carried out with the help of keywords in order to find relevant trials. The inclusion criteria were as follows: randomised controlled clinical trials, adult population, the presence of at least 15 permanent teeth. Split-mouth trials and interventions carried out by dental professionals, were excluded. Primary outcomes were the changes of plaque and gingival indices, while secondary outcomes were probing pocket depth (PPD), safety and quality assessment. The effect-size of the interventions was expressed by the standardised mean difference (SMD) with 95% confidence interval (CI). Random-effects models were performed. Electronic search resulted in 173 hits. 21 trials with the total number of 1500 subjects were then eligible for the meta-analysis. Both toothbrushes were safe, without considerable side effects on soft or hard tissues. Powered toothbrushes seemed to be generally more effective in removing plaque (-9%), reducing gingivitis (-6%) and preventing calculus formation. The SMDs for plaque and gingival indices were -0,40 (95% Cl: -0,95 to -0,16) and -0,29 (95% Cl: -0,56 to -0,03) respectively, in favour of the powered devices. There was no significant difference in changes of PPD. By further dividing the powered toothbrushes according to their mode of action, the plaque removal effect of the rotation oscillation (plus three dimensional), side to side sonic and ultrasonic toothbrushes seemed to be significantly better, than their manual ones, while the counter oscillation and the ionic toothbrushes did not perform better. Quality assessment and sensitivity analysis revealed various types of bias up to a certain extent. Consequently, no trial was found to be eligible for the highest quality criteria. The investigated rotation oscillation and vibrating toothbrushes appeared to be statistically more effective than their manual counterparts, although there is little known about its clinical relevance. The advantage of the electric toothbrushes disappears in case of adequately instructed and motivated patients that highlights the importance of individualised oral hygiene education. The design of the trials shows high heterogeneity, therefore their clinical implications should be handled carefully.

The group-based social skills training SOSTA-FRA in children and adolescents with high functioning autism spectrum disorder - study protocol of the randomised, multi-centre controlled SOSTA - net trial

PubMed Central

2013-01-01

Background Group-based social skills training (SST) has repeatedly been recommended as treatment of choice in high-functioning autism spectrum disorder (HFASD). To date, no sufficiently powered randomised controlled trial has been performed to establish efficacy and safety of SST in children and adolescents with HFASD. In this randomised, multi-centre, controlled trial with 220 children and adolescents with HFASD it is hypothesized, that add-on group-based SST using the 12 weeks manualised SOSTA–FRA program will result in improved social responsiveness (measured by the parent rated social responsiveness scale, SRS) compared to treatment as usual (TAU). It is further expected, that parent and self reported anxiety and depressive symptoms will decline and pro-social behaviour will increase in the treatment group. A neurophysiological study in the Frankfurt HFASD subgroup will be performed pre- and post treatment to assess changes in neural function induced by SST versus TAU. Methods/design The SOSTA – net trial is designed as a prospective, randomised, multi-centre, controlled trial with two parallel groups. The primary outcome is change in SRS score directly after the intervention and at 3 months follow-up. Several secondary outcome measures are also obtained. The target sample consists of 220 individuals with ASD, included at the six study centres. Discussion This study is currently one of the largest trials on SST in children and adolescents with HFASD worldwide. Compared to recent randomised controlled studies, our study shows several advantages with regard to in- and exclusion criteria, study methods, and the therapeutic approach chosen, which can be easily implemented in non-university-based clinical settings. Trial registration ISRCTN94863788 – SOSTA – net: Group-based social skills training in children and adolescents with high functioning autism spectrum disorder. PMID:23289935

A Mixed-Methods, Randomized, Controlled Feasibility Trial to Inform the Design of a Phase III Trial to Test the Effect of the Handheld Fan on Physical Activity and Carer Anxiety in Patients With Refractory Breathlessness.

PubMed

Johnson, Miriam J; Booth, Sara; Currow, David C; Lam, Lawrence T; Phillips, Jane L

2016-05-01

The handheld fan is an inexpensive and safe way to provide facial airflow, which may reduce the sensation of chronic refractory breathlessness, a frequently encountered symptom. To test the feasibility of developing an adequately powered, multicenter, multinational randomized controlled trial comparing the efficacy of a handheld fan and exercise advice with advice alone in increasing activity in people with chronic refractory breathlessness from a variety of medical conditions, measuring recruitment rates; data quality; and potential primary outcome measures. This was a Phase II, multisite, international, parallel, nonblinded, mixed-methods randomized controlled trial. Participants were centrally randomized to fan or control. All received breathlessness self-management/exercise advice and were followed up weekly for four weeks. Participants/carers were invited to participate in a semistructured interview at the study's conclusion. Ninety-seven people were screened, 49 randomized (mean age 68 years; 49% men), and 43 completed the study. Site recruitment varied from 0.25 to 3.3/month and screening:randomization from 1.1:1 to 8.5:1. There were few missing data except for the Chronic Obstructive Pulmonary Disease Self-Efficacy Scale (two-thirds of data missing). No harms were observed. Three interview themes included 1) a fan is a helpful self-management strategy, 2) a fan aids recovery, and 3) a symptom control trial was welcome. A definitive, multisite trial to study the use of the handheld fan as part of self-management of chronic refractory breathlessness is feasible. Participants found the fan useful. However, the value of information for changing practice or policy is unlikely to justify the expense of such a trial, given perceived benefits, the minimal costs, and an absence of harms demonstrated in this study. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Evaluating efficacy and feasibility of transcutaneous electrical nerve stimulation for postoperative pain after video-assisted thoracoscopic surgery: A randomized pilot trial.

PubMed

Engen, Deborah J; Carns, Paul E; Allen, Mark S; Bauer, Brent A; Loehrer, Laura L; Cha, Stephen S; Chartrand, Christine M; Eggler, Eric J; Cutshall, Susanne M; Wahner-Roedler, Dietlind L

2016-05-01

Transcutaneous electrical nerve stimulation (TENS) has been applied for pain relief after surgical procedures. This study evaluated whether TENS after video-assisted thoracoscopic surgery (VATS), in addition to opioid administration, decreased postoperative pain and pain medication use. In a controlled trial, 56 patients scheduled to undergo VATS were randomly assigned to TENS plus opioids (Group 1) or opioids alone (Group 2) for 48 h. Forty patients completed the study. Pain scores and use of oral morphine equivalents (OMEs) were not significantly different between the groups during the first and second 24 h. A decreased use of OMEs between the first and second 24 h was significant for Group 1 (P = .005) but not for Group 2 (P = .11); a decreased use of OMEs between groups was not significant (P = .35). A larger, well-powered clinical trial is indicated to evaluate the effects of TENS for pain control after a VATS procedure. Clinical Trial No.: NCT01046695. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

RNAi therapeutics and applications of microRNAs in cancer treatment.

PubMed

Uchino, Keita; Ochiya, Takahiro; Takeshita, Fumitaka

2013-06-01

RNA interference-based therapies are proving to be powerful tools for combating various diseases, including cancer. Scientists are researching the development of safe and efficient systems for the delivery of small RNA molecules, which are extremely fragile in serum, to target organs and cells in the human body. A dozen pre-clinical and clinical trials have been under way over the past few years involving biodegradable nanoparticles, lipids, chemical modification and conjugation. On the other hand, microRNAs, which control the balance of cellular biological processes, have been studied as attractive therapeutic targets in cancer treatment. In this review, we provide an overview of RNA interference-based therapeutics in clinical trials and discuss the latest technology for the systemic delivery of nucleic acid drugs. Furthermore, we focus on dysregulated microRNAs in human cancer, which have progressed in pre-clinical trials as therapeutic targets, and describe a wide range of strategies to control the expression levels of endogenous microRNAs. Further development of RNA interference technologies and progression of clinical trials will contribute to the achievement of practical applications of nucleic acid drugs.

The Power of 'Evidence': Reliable Science or a Set of Blunt Tools?

ERIC Educational Resources Information Center

Wrigley, Terry

2018-01-01

In response to the increasing emphasis on 'evidence-based teaching', this article examines the privileging of randomised controlled trials and their statistical synthesis (meta-analysis). It also pays particular attention to two third-level statistical syntheses: John Hattie's "Visible learning" project and the EEF's "Teaching and…

Mouth Rinsing with Maltodextrin Solutions Fails to Improve Time Trial Endurance Cycling Performance in Recreational Athletes.

PubMed

Kulaksız, Tuğba Nilay; Koşar, Şükran Nazan; Bulut, Suleyman; Güzel, Yasemin; Willems, Marcus Elisabeth Theodorus; Hazir, Tahir; Turnagöl, Hüseyin Hüsrev

2016-05-09

The carbohydrate (CHO) concentration of a mouth rinsing solution might influence the CHO sensing receptors in the mouth, with consequent activation of brain regions involved in reward, motivation and regulation of motor activity. The purpose of the present study was to examine the effects of maltodextrin mouth rinsing with different concentrations (3%, 6% and 12%) after an overnight fast on a 20 km cycling time trial performance. Nine recreationally active, healthy males (age: 24 ± 2 years; V ˙ O 2 m a x : 47 ± 5 mL·kg(-1)·min(-1)) participated in this study. A double-blind, placebo-controlled randomized study was conducted. Participants mouth-rinsed every 2.5 km for 5 s. Maltodextrin mouth rinse with concentrations of 3%, 6% or 12% did not change time to complete the time trial and power output compared to placebo (p > 0.05). Time trial completion times were 40.2 ± 4.0, 40.1 ± 3.9, 40.1 ± 4.4, and 39.3 ± 4.2 min and power output 205 ± 22, 206 ± 25, 210 ± 24, and 205 ± 23 W for placebo, 3%, 6%, and 12% maltodextrin conditions, respectively. Heart rate, lactate, glucose, and rating of perceived exertion did not differ between trials (p > 0.05). In conclusion, mouth rinsing with different maltodextrin concentrations after an overnight fast did not affect the physiological responses and performance during a 20 km cycling time trial in recreationally active males.

Short-term effects of goal-setting focusing on the life goal concept on subjective well-being and treatment engagement in subacute inpatients: a quasi-randomized controlled trial

PubMed Central

Ogawa, Tatsuya; Omon, Kyohei; Yuda, Tomohisa; Ishigaki, Tomoya; Imai, Ryota; Ohmatsu, Satoko; Morioka, Shu

2016-01-01

Objective: To investigate the short-term effects of the life goal concept on subjective well-being and treatment engagement, and to determine the sample size required for a larger trial. Design: A quasi-randomized controlled trial that was not blinded. Setting: A subacute rehabilitation ward. Subjects: A total of 66 patients were randomized to a goal-setting intervention group with the life goal concept (Life Goal), a standard rehabilitation group with no goal-setting intervention (Control 1), or a goal-setting intervention group without the life goal concept (Control 2). Interventions: The goal-setting intervention in the Life Goal and Control 2 was Goal Attainment Scaling. The Life Goal patients were assessed in terms of their life goals, and the hierarchy of goals was explained. The intervention duration was four weeks. Main measures: Patients were assessed pre- and post-intervention. The outcome measures were the Hospital Anxiety and Depression Scale, 12-item General Health Questionnaire, Pittsburgh Rehabilitation Participation Scale, and Functional Independence Measure. Results: Of the 296 potential participants, 66 were enrolled; Life Goal (n = 22), Control 1 (n = 22) and Control 2 (n = 22). Anxiety was significantly lower in the Life Goal (4.1 ±3.0) than in Control 1 (6.7 ±3.4), but treatment engagement was significantly higher in the Life Goal (5.3 ±0.4) compared with both the Control 1 (4.8 ±0.6) and Control 2 (4.9 ±0.5). Conclusions: The life goal concept had a short-term effect on treatment engagement. A sample of 31 patients per group would be required for a fully powered clinical trial. PMID:27496700

Design of a cluster-randomized minority recruitment trial: RECRUIT.

PubMed

Tilley, Barbara C; Mainous, Arch G; Smith, Daniel W; McKee, M Diane; Amorrortu, Rossybelle P; Alvidrez, Jennifer; Diaz, Vanessa; Ford, Marvella E; Fernandez, Maria E; Hauser, Robert A; Singer, Carlos; Landa, Veronica; Trevino, Aron; DeSantis, Stacia M; Zhang, Yefei; Daniels, Elvan; Tabor, Derrick; Vernon, Sally W

2017-06-01

Racial/ethnic minority groups remain underrepresented in clinical trials. Many strategies to increase minority recruitment focus on minority communities and emphasize common diseases such as hypertension. Scant literature focuses on minority recruitment to trials of less common conditions, often conducted in specialty clinics and dependent on physician referrals. We identified trust/mistrust of specialist physician investigators and institutions conducting medical research and consequent participant reluctance to participate in clinical trials as key-shared barriers across racial/ethnic groups. We developed a trust-based continuous quality improvement intervention to build trust between specialist physician investigators and community minority-serving physicians and ultimately potential trial participants. To avoid the inherent biases of non-randomized studies, we evaluated the intervention in the national Randomized Recruitment Intervention Trial (RECRUIT). This report presents the design of RECRUIT. Specialty clinic follow-up continues through April 2017. We hypothesized that specialist physician investigators and coordinators trained in the trust-based continuous quality improvement intervention would enroll a greater proportion of minority participants in their specialty clinics than specialist physician investigators in control specialty clinics. Specialty clinic was the unit of randomization. Using continuous quality improvement, the specialist physician investigators and coordinators tailored recruitment approaches to their specialty clinic characteristics and populations. Primary analyses were adjusted for clustering by specialty clinic within parent trial and matching covariates. RECRUIT was implemented in four multi-site clinical trials (parent trials) supported by three National Institutes of Health institutes and included 50 associated specialty clinics from these parent trials. Using current data, we have 88% power or greater to detect a 0.15 or greater difference from the currently observed control proportion adjusting for clustering. We detected no differences in baseline matching criteria between intervention and control specialty clinics (all p values > 0.17). RECRUIT was the first multi-site randomized control trial to examine the effectiveness of a trust-based continuous quality improvement intervention to increase minority recruitment into clinical trials. RECRUIT's innovations included its focus on building trust between specialist investigators and minority-serving physicians, the use of continuous quality improvement to tailor the intervention to each specialty clinic's specific racial/ethnic populations and barriers to minority recruitment, and the use of specialty clinics from more than one parent multi-site trial to increase generalizability. The effectiveness of the RECRUIT intervention will be determined after the completion of trial data collection and planned analyses.

Testing moderation in network meta-analysis with individual participant data

PubMed Central

Dagne, Getachew A.; Brown, C. Hendricks; Howe, George; Kellam, Sheppard G.; Liu, Lei

2016-01-01

Summary Meta-analytic methods for combining data from multiple intervention trials are commonly used to estimate the effectiveness of an intervention. They can also be extended to study comparative effectiveness, testing which of several alternative interventions is expected to have the strongest effect. This often requires network meta-analysis (NMA), which combines trials involving direct comparison of two interventions within the same trial and indirect comparisons across trials. In this paper, we extend existing network methods for main effects to examining moderator effects, allowing for tests of whether intervention effects vary for different populations or when employed in different contexts. In addition, we study how the use of individual participant data (IPD) may increase the sensitivity of NMA for detecting moderator effects, as compared to aggregate data NMA that employs study-level effect sizes in a meta-regression framework. A new network meta-analysis diagram is proposed. We also develop a generalized multilevel model for NMA that takes into account within- and between-trial heterogeneity, and can include participant-level covariates. Within this framework we present definitions of homogeneity and consistency across trials. A simulation study based on this model is used to assess effects on power to detect both main and moderator effects. Results show that power to detect moderation is substantially greater when applied to IPD as compared to study-level effects. We illustrate the use of this method by applying it to data from a classroom-based randomized study that involved two sub-trials, each comparing interventions that were contrasted with separate control groups. PMID:26841367

Corticosteroids for the common cold.

PubMed

Hayward, Gail; Thompson, Matthew J; Perera, Rafael; Del Mar, Chris B; Glasziou, Paul P; Heneghan, Carl J

2015-10-13

The common cold is a frequent illness, which, although benign and self limiting, results in many consultations to primary care and considerable loss of school or work days. Current symptomatic treatments have limited benefit. Corticosteroids are an effective treatment in other upper respiratory tract infections and their anti-inflammatory effects may also be beneficial in the common cold. This updated review has included one additional study. To compare corticosteroids versus usual care for the common cold on measures of symptom resolution and improvement in children and adults. We searched Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 4), which includes the Acute Respiratory Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects (DARE) (2015, Issue 2), NHS Health Economics Database (2015, Issue 2), MEDLINE (1948 to May week 3, 2015) and EMBASE (January 2010 to May 2015). Randomised, double-blind, controlled trials comparing corticosteroids to placebo or to standard clinical management. Two review authors independently extracted data and assessed trial quality. We were unable to perform meta-analysis and instead present a narrative description of the available evidence. We included three trials (353 participants). Two trials compared intranasal corticosteroids to placebo and one trial compared intranasal corticosteroids to usual care; no trials studied oral corticosteroids. In the two placebo-controlled trials, no benefit of intranasal corticosteroids was demonstrated for duration or severity of symptoms. The risk of bias overall was low or unclear in these two trials. In a trial of 54 participants, the mean number of symptomatic days was 10.3 in the placebo group, compared to 10.7 in those using intranasal corticosteroids (P value = 0.72). A second trial of 199 participants reported no significant differences in the duration of symptoms. The single-blind trial in children aged two to 14 years, who were also receiving oral antibiotics, had inadequate reporting of outcome measures regarding symptom resolution. The overall risk of bias was high for this trial. Mean symptom severity scores were significantly lower in the group receiving intranasal steroids in addition to oral amoxicillin. One placebo-controlled trial reported the presence of rhinovirus in nasal aspirates and found no differences. Only one of the three trials reported on adverse events; no differences were found. Two trials reported secondary bacterial infections (one case of sinusitis, one case of acute otitis media; both in the corticosteroid groups). A lack of comparable outcome measures meant that we were unable to combine the data. Current evidence does not support the use of intranasal corticosteroids for symptomatic relief from the common cold. However, there were only three trials, one of which was very poor quality, and there was limited statistical power overall. Further large, randomised, double-blind, placebo-controlled trials in adults and children are required to answer this question.

A novel intranasal breath-powered delivery system for sumatriptan: a review of technology and clinical application of the investigational product AVP-825 in the treatment of migraine.

PubMed

Cady, Roger

2015-01-01

AVP-825, formerly 'OptiNose Sumatriptan,' is an investigational Breath-Powered(TM) Bi-Directional(TM) intranasal delivery system containing low-dose sumatriptan (22 mg intranasal powder) that avoids limitations of other types of intranasal administration by taking advantage of unique features of nasal anatomy and physiology. This review summarizes intranasal drug delivery for migraine, how the breath-powered technology works, and AVP-825 pharmacokinetic, efficacy and safety/tolerability findings. To identify AVP-825 clinical studies, a PubMed/MEDLINE database search was conducted with the terms AVP-825, OptiNose, OptiNose Sumatriptan, Breath-Powered Nasal Delivery or sumatriptan powder. Of 20 articles, 5 clinical studies were identified, including the head-to-head comparative COMPASS trial (AVP-825 vs oral sumatriptan) and two placebo-controlled studies. AVP-825 has faster sumatriptan absorption versus oral tablets or traditional liquid nasal spray. In Phase II/III randomized, double-blind, placebo-controlled trials, AVP-825 produced early and sustained efficacy with minimal triptan-related adverse effects. In COMPASS, AVP-825 produced earlier reduction of migraine pain intensity and migraine-associated symptoms than 100 mg oral sumatriptan, and higher early rates of pain relief and pain freedom, similar sustained efficacy, and fewer atypical sensations. AVP-825 has the potential to provide migraine patients with improved intranasal administration of sumatriptan that may enhance efficacy and tolerability.

Physiotherapy for sleep disturbance in chronic low back pain: a feasibility randomised controlled trial

PubMed Central

2010-01-01

Background Sleep disturbance is becoming increasingly recognised as a clinically important symptom in people with chronic low back pain (CLBP, low back pain >12 weeks), associated with physical inactivity and depression. Current research and international clinical guidelines recommend people with CLBP assume a physically active role in their recovery to prevent chronicity, but the high prevalence of sleep disturbance in this population may be unknowingly limiting their ability to participate in exercise-based rehabilitation programmes and contributing to poor outcomes. There is currently no knowledge concerning the effectiveness of physiotherapy on sleep disturbance in people with chronic low back pain and no evidence of the feasibility of conducting randomized controlled trials that comprehensively evaluate sleep as an outcome measure in this population. Methods/Design This study will evaluate the feasibility of a randomised controlled trial (RCT), exploring the effects of three forms of physiotherapy (supervised general exercise programme, individualized walking programme and usual physiotherapy, which will serve as the control group) on sleep quality in people with chronic low back pain. A presenting sample of 60 consenting patients will be recruited in the physiotherapy department of Beaumont Hospital, Dublin, Ireland, and randomly allocated to one of the three groups in a concealed manner. The main outcomes will be sleep quality (self-report and objective measurement), and self-reported functional disability, pain, quality of life, fear avoidance, anxiety and depression, physical activity, and patient satisfaction. Outcome will be evaluated at baseline, 3 months and 6 months. Qualitative telephone interviews will be embedded in the research design to obtain feedback from a sample of participants' about their experiences of sleep monitoring, trial participation and interventions, and to inform the design of a fully powered future RCT. Planned analysis will explore trends in the data, effect sizes and clinically important effects (quantitative data), and thematic analysis (qualitative data). Discussion This study will evaluate the feasibility of a randomised controlled trial exploring the effects of three forms of physiotherapy (supervised general exercise programme, individualized walking programme and usual physiotherapy, which will serve as the control group) on sleep quality in people with chronic low back pain. Trial Registration Current controlled trial ISRCTN54009836 PMID:20398349

Pain Ratings, Psychological Functioning and Quantitative EEG in a Controlled Study of Chronic Back Pain Patients

PubMed Central

Schmidt, Stefan; Naranjo, José Raúl; Brenneisen, Christina; Gundlach, Julian; Schultz, Claudia; Kaube, Holger; Hinterberger, Thilo; Jeanmonod, Daniel

2012-01-01

Objectives Several recent studies report the presence of a specific EEG pattern named Thalamocortical Dysrhythmia (TCD) in patients with severe chronic neurogenic pain. This is of major interest since so far no neuroscientific indicator of chronic pain could be identified. We investigated whether a TCD-like pattern could be found in patients with moderate chronic back pain, and we compared patients with neuropathic and non-neuropathic pain components. We furthermore assessed the presence of psychopathology and the degree of psychological functioning and examined whether the strength of the TCD-related EEG markers is correlated with psychological symptoms and pain ratings. Design Controlled clinical trial with age and sex matched healthy controls. Methods Spontaneous EEG was recorded in 37 back pain patients and 37 healthy controls. Results We were not able to observe a statistically significant TCD effect in the EEG data of the whole patient group, but a subsample of patients with evidence for root damage showed a trend in this direction. Pain patients showed markedly increased psychopathology. In addition, patients' ratings of pain intensity within the last 1 to 12 months showed strong correlations with EEG power, while psychopathology was correlated to the peak frequency. Conclusion Out of several possible interpretations the most likely conclusion is that only patients with severe pain as well as root lesions with consecutive thalamic deafferentation develop the typical TCD pattern. Our primary method of defining ‘neuropathic pain’ could not reliably determine if such a deafferentation was present. Nevertheless the analysis of a specific subsample as well as correlations between pain ratings, psychopathology and EEG power and peak frequency give some support to the TCD concept. Trial Registration ClinicalTrials.gov NCT00744575 PMID:22431961

Catheter ablation in patients with persistent atrial fibrillation

PubMed Central

Kirchhof, Paulus; Calkins, Hugh

2017-01-01

Catheter ablation is increasingly offered to patients who suffer from symptoms due to atrial fibrillation (AF), based on a growing body of evidence illustrating its efficacy compared with antiarrhythmic drug therapy. Approximately one-third of AF ablation procedures are currently performed in patients with persistent or long-standing persistent AF. Here, we review the available information to guide catheter ablation in these more chronic forms of AF. We identify the following principles: Our clinical ability to discriminate paroxysmal and persistent AF is limited. Pulmonary vein isolation is a reasonable and effective first approach for catheter ablation of persistent AF. Other ablation strategies are being developed and need to be properly evaluated in controlled, multicentre trials. Treatment of concomitant conditions promoting recurrent AF by life style interventions and medical therapy should be a routine adjunct to catheter ablation of persistent AF. Early rhythm control therapy has a biological rationale and trials evaluating its value are underway. There is a clear need to generate more evidence for the best approach to ablation of persistent AF beyond pulmonary vein isolation in the form of adequately powered controlled multi-centre trials. PMID:27389907

Testing moderation in network meta-analysis with individual participant data.

PubMed

Dagne, Getachew A; Brown, C Hendricks; Howe, George; Kellam, Sheppard G; Liu, Lei

2016-07-10

Meta-analytic methods for combining data from multiple intervention trials are commonly used to estimate the effectiveness of an intervention. They can also be extended to study comparative effectiveness, testing which of several alternative interventions is expected to have the strongest effect. This often requires network meta-analysis (NMA), which combines trials involving direct comparison of two interventions within the same trial and indirect comparisons across trials. In this paper, we extend existing network methods for main effects to examining moderator effects, allowing for tests of whether intervention effects vary for different populations or when employed in different contexts. In addition, we study how the use of individual participant data may increase the sensitivity of NMA for detecting moderator effects, as compared with aggregate data NMA that employs study-level effect sizes in a meta-regression framework. A new NMA diagram is proposed. We also develop a generalized multilevel model for NMA that takes into account within-trial and between-trial heterogeneity and can include participant-level covariates. Within this framework, we present definitions of homogeneity and consistency across trials. A simulation study based on this model is used to assess effects on power to detect both main and moderator effects. Results show that power to detect moderation is substantially greater when applied to individual participant data as compared with study-level effects. We illustrate the use of this method by applying it to data from a classroom-based randomized study that involved two sub-trials, each comparing interventions that were contrasted with separate control groups. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Using simulation to aid trial design: Ring-vaccination trials.

PubMed

Hitchings, Matt David Thomas; Grais, Rebecca Freeman; Lipsitch, Marc

2017-03-01

The 2014-6 West African Ebola epidemic highlights the need for rigorous, rapid clinical trial methods for vaccines. A challenge for trial design is making sample size calculations based on incidence within the trial, total vaccine effect, and intracluster correlation, when these parameters are uncertain in the presence of indirect effects of vaccination. We present a stochastic, compartmental model for a ring vaccination trial. After identification of an index case, a ring of contacts is recruited and either vaccinated immediately or after 21 days. The primary outcome of the trial is total vaccine effect, counting cases only from a pre-specified window in which the immediate arm is assumed to be fully protected and the delayed arm is not protected. Simulation results are used to calculate necessary sample size and estimated vaccine effect. Under baseline assumptions about vaccine properties, monthly incidence in unvaccinated rings and trial design, a standard sample-size calculation neglecting dynamic effects estimated that 7,100 participants would be needed to achieve 80% power to detect a difference in attack rate between arms, while incorporating dynamic considerations in the model increased the estimate to 8,900. This approach replaces assumptions about parameters at the ring level with assumptions about disease dynamics and vaccine characteristics at the individual level, so within this framework we were able to describe the sensitivity of the trial power and estimated effect to various parameters. We found that both of these quantities are sensitive to properties of the vaccine, to setting-specific parameters over which investigators have little control, and to parameters that are determined by the study design. Incorporating simulation into the trial design process can improve robustness of sample size calculations. For this specific trial design, vaccine effectiveness depends on properties of the ring vaccination design and on the measurement window, as well as the epidemiologic setting.

EEG source reconstruction reveals frontal-parietal dynamics of spatial conflict processing.

PubMed

Cohen, Michael X; Ridderinkhof, K Richard

2013-01-01

Cognitive control requires the suppression of distracting information in order to focus on task-relevant information. We applied EEG source reconstruction via time-frequency linear constrained minimum variance beamforming to help elucidate the neural mechanisms involved in spatial conflict processing. Human subjects performed a Simon task, in which conflict was induced by incongruence between spatial location and response hand. We found an early (∼200 ms post-stimulus) conflict modulation in stimulus-contralateral parietal gamma (30-50 Hz), followed by a later alpha-band (8-12 Hz) conflict modulation, suggesting an early detection of spatial conflict and inhibition of spatial location processing. Inter-regional connectivity analyses assessed via cross-frequency coupling of theta (4-8 Hz), alpha, and gamma power revealed conflict-induced shifts in cortical network interactions: Congruent trials (relative to incongruent trials) had stronger coupling between frontal theta and stimulus-contrahemifield parietal alpha/gamma power, whereas incongruent trials had increased theta coupling between medial frontal and lateral frontal regions. These findings shed new light into the large-scale network dynamics of spatial conflict processing, and how those networks are shaped by oscillatory interactions.

Design of the value of imaging in enhancing the wellness of your heart (VIEW) trial and the impact of uncertainty on power.

PubMed

Ambrosius, Walter T; Polonsky, Tamar S; Greenland, Philip; Goff, David C; Perdue, Letitia H; Fortmann, Stephen P; Margolis, Karen L; Pajewski, Nicholas M

2012-04-01

Although observational evidence has suggested that the measurement of coronary artery calcium (CAC) may improve risk stratification for cardiovascular events and thus help guide the use of lipid-lowering therapy, this contention has not been evaluated within the context of a randomized trial. The Value of Imaging in Enhancing the Wellness of Your Heart (VIEW) trial is proposed as a randomized study in participants at low intermediate risk of future coronary heart disease (CHD) events to evaluate whether CAC testing leads to improved patient outcomes. To describe the challenges encountered in designing a prototypical screening trial and to examine the impact of uncertainty on power. The VIEW trial was designed as an effectiveness clinical trial to examine the benefit of CAC testing to guide therapy on a primary outcome consisting of a composite of nonfatal myocardial infarction, probable or definite angina with revascularization, resuscitated cardiac arrest, nonfatal stroke (not transient ischemic attack (TIA)), CHD death, stroke death, other atherosclerotic death, or other cardiovascular disease (CVD) death. Many critical choices were faced in designing the trial, including (1) the choice of primary outcome, (2) the choice of therapy, (3) the target population with corresponding ethical issues, (4) specifications of assumptions for sample size calculations, and (5) impact of uncertainty in these assumptions on power/sample size determination. We have proposed a sample size of 30,000 (800 events), which provides 92.7% power. Alternatively, sample sizes of 20,228 (539 events), 23,138 (617 events), and 27,078 (722 events) provide 80%, 85%, and 90% power. We have also allowed for uncertainty in our assumptions by computing average power integrated over specified prior distributions. This relaxation of specificity indicates a reduction in power, dropping to 89.9% (95% confidence interval (CI): 89.8-89.9) for a sample size of 30,000. Samples sizes of 20,228, 23,138, and 27,078 provide power of 78.0% (77.9-78.0), 82.5% (82.5-82.6), and 87.2% (87.2-87.3), respectively. These power estimates are dependent on form and parameters of the prior distributions. Despite the pressing need for a randomized trial to evaluate the utility of CAC testing, conduct of such a trial requires recruiting a large patient population, making efficiency of critical importance. The large sample size is primarily due to targeting a study population at relatively low risk of a CVD event. Our calculations also illustrate the importance of formally considering uncertainty in power calculations of large trials as standard power calculations may tend to overestimate power.

Design of the Value of Imaging in Enhancing the Wellness of Your Heart (VIEW) Trial and the Impact of Uncertainty on Power

PubMed Central

Ambrosius, Walter T.; Polonsky, Tamar S.; Greenland, Philip; Goff, David C.; Perdue, Letitia H.; Fortmann, Stephen P.; Margolis, Karen L.; Pajewski, Nicholas M.

2014-01-01

Background Although observational evidence has suggested that the measurement of CAC may improve risk stratification for cardiovascular events and thus help guide the use of lipid-lowering therapy, this contention has not been evaluated within the context of a randomized trial. The Value of Imaging in Enhancing the Wellness of Your Heart (VIEW) trial is proposed as a randomized study in participants at low intermediate risk of future coronary heart disease (CHD) events to evaluate whether coronary artery calcium (CAC) testing leads to improved patient outcomes. Purpose To describe the challenges encountered in designing a prototypical screening trial and to examine the impact of uncertainty on power. Methods The VIEW trial was designed as an effectiveness clinical trial to examine the benefit of CAC testing to guide therapy on a primary outcome consisting of a composite of non-fatal myocardial infarction, probable or definite angina with revascularization, resuscitated cardiac arrest, non-fatal stroke (not transient ischemic attack (TIA)), CHD death, stroke death, other atherosclerotic death, or other cardiovascular disease (CVD) death. Many critical choices were faced in designing the trial, including: (1) the choice of primary outcome, (2) the choice of therapy, (3) the target population with corresponding ethical issues, (4) specifications of assumptions for sample size calculations, and (5) impact of uncertainty in these assumptions on power/sample size determination. Results We have proposed a sample size of 30,000 (800 events) which provides 92.7% power. Alternatively, sample sizes of 20,228 (539 events), 23,138 (617 events) and 27,078 (722 events) provide 80, 85, and 90% power. We have also allowed for uncertainty in our assumptions by computing average power integrated over specified prior distributions. This relaxation of specificity indicates a reduction in power, dropping to 89.9% (95% confidence interval (CI): 89.8 to 89.9) for a sample size of 30,000. Samples sizes of 20,228, 23,138, and 27,078 provide power of 78.0% (77.9 to 78.0), 82.5% (82.5 to 82.6), and 87.2% (87.2 to 87.3), respectively. Limitations These power estimates are dependent on form and parameters of the prior distributions. Conclusions Despite the pressing need for a randomized trial to evaluate the utility of CAC testing, conduct of such a trial requires recruiting a large patient population, making efficiency of critical importance. The large sample size is primarily due to targeting a study population at relatively low risk of a CVD event. Our calculations also illustrate the importance of formally considering uncertainty in power calculations of large trials as standard power calculations may tend to overestimate power. PMID:22333998

Aggregated data from two double-blind base station provocation studies comparing individuals with idiopathic environmental intolerance with attribution to electromagnetic fields and controls.

PubMed

Eltiti, Stacy; Wallace, Denise; Russo, Riccardo; Fox, Elaine

2015-02-01

Data from two previous studies were aggregated to provide a statistically powerful test of whether exposure to electromagnetic fields (EMFs) produced by telecommunication base stations negatively affects well-being in individuals who report idiopathic environmental illness with attribution to electromagnetic fields (IEI-EMF) and control participants. A total of 102 IEI-EMF and 237 controls participated in open provocation trials and 88 IEI-EMF and 231 controls went on to complete double-blind trials in which they were exposed to EMFs from a base station emitting either a Global System for Mobile Communication and Universal Mobile Telecommunications System or a Terrestrial Trunked Radio Telecommunications System signal. Both experiments included a comparison sham condition. Visual analog and symptom scales measured subjective well-being. Results showed that IEI-EMF participants reported lower levels of well-being during real compared to sham exposure during open provocation, but not during double-blind trials. Additionally, participants reported lower levels of well-being during high compared to low load trials and this did not interact with radiofrequency-EMF exposure. These findings are consistent with a growing body of literature indicating there is no causal relationship between short-term exposure to EMFs and subjective well-being in members of the public whether or not they report perceived sensitivity to EMFs. © 2015 Wiley Periodicals, Inc.

Interventions for dysarthria due to stroke and other adult-acquired, non-progressive brain injury.

PubMed

Mitchell, Claire; Bowen, Audrey; Tyson, Sarah; Butterfint, Zoe; Conroy, Paul

2017-01-25

Dysarthria is an acquired speech disorder following neurological injury that reduces intelligibility of speech due to weak, imprecise, slow and/or unco-ordinated muscle control. The impact of dysarthria goes beyond communication and affects psychosocial functioning. This is an update of a review previously published in 2005. The scope has been broadened to include additional interventions, and the title amended accordingly. To assess the effects of interventions to improve dysarthric speech following stroke and other non-progressive adult-acquired brain injury such as trauma, infection, tumour and surgery. We searched the Cochrane Stroke Group Trials Register (May 2016), CENTRAL (Cochrane Library 2016, Issue 4), MEDLINE, Embase, and CINAHL on 6 May 2016. We also searched Linguistics and Language Behavioral Abstracts (LLBA) (1976 to November 2016) and PsycINFO (1800 to September 2016). To identify further published, unpublished and ongoing trials, we searched major trials registers: WHO ICTRP, the ISRCTN registry, and ClinicalTrials.gov. We also handsearched the reference lists of relevant articles and contacted academic institutions and other researchers regarding other published, unpublished or ongoing trials. We did not impose any language restrictions. We selected randomised controlled trials (RCTs) comparing dysarthria interventions with 1) no intervention, 2) another intervention for dysarthria (this intervention may differ in methodology, timing of delivery, duration, frequency or theory), or 3) an attention control. Three review authors selected trials for inclusion, extracted data, and assessed risk of bias. We attempted to contact study authors for clarification and missing data as required. We calculated standardised mean difference (SMD) and 95% confidence interval (CI), using a random-effects model, and performed sensitivity analyses to assess the influence of methodological quality. We planned to conduct subgroup analyses for underlying clinical conditions. We included five small trials that randomised a total of 234 participants. Two studies were assessed as low risk of bias; none of the included studies were adequately powered. Two studies used an attention control and three studies compared to an alternative intervention, which in all cases was one intervention versus usual care intervention. The searches we carried out did not find any trials comparing an intervention with no intervention. The searches did not find any trials of an intervention that compared variations in timing, dose, or intensity of treatment using the same intervention. Four studies included only people with stroke; one included mostly people with stroke, but also those with brain injury. Three studies delivered interventions in the first few months after stroke; two recruited people with chronic dysarthria. Three studies evaluated behavioural interventions, one investigated acupuncture and another transcranial magnetic stimulation. One study included people with dysarthria within a broader trial of people with impaired communication.Our primary analysis of a persisting (three to nine months post-intervention) effect at the activity level of measurement found no evidence in favour of dysarthria intervention compared with any control (SMD 0.18, 95% CI -0.18 to 0.55; 3 trials, 116 participants, GRADE: low quality, I² = 0%). Findings from sensitivity analysis of studies at low risk of bias were similar, with a slightly wider confidence interval and low heterogeneity (SMD 0.21, 95% CI -0.30 to 0.73, I² = 32%; 2 trials, 92 participants, GRADE: low quality). Subgroup analysis results for stroke were similar to the primary analysis because few non-stroke participants had been recruited to trials (SMD 0.16, 95% CI -0.23 to 0.54, I² = 0%; 3 trials, 106 participants, GRADE: low quality).Similar results emerged from most of the secondary analyses. There was no evidence of a persisting effect at the impairment (SMD 0.07, 95% CI -0.91 to 1.06, I² = 70%; 2 trials, 56 participants, GRADE: very low quality) or participation level (SMD -0.11, 95% CI -0.56 to 0.33, I² = 0%; 2 trials, 79 participants, GRADE: low quality) but substantial heterogeneity on the former. Analyses of immediate post-intervention outcomes provided no evidence of any short-term benefit on activity (SMD 0.29, 95% CI -0.07 to 0.66, I² = 0%; 3 trials, 117 participants, GRADE: very low quality); or participation (SMD -0.24, 95% CI -0.94 to 0.45; 1 study, 32 participants) levels of measurement.There was a statistically significant effect favouring intervention at the immediate, impairment level of measurement (SMD 0.47, 95% CI 0.02 to 0.92, P = 0.04, I² = 0%; 4 trials, 99 participants, GRADE: very low quality) but only one of these four trials had a low risk of bias. We found no definitive, adequately powered RCTs of interventions for people with dysarthria. We found limited evidence to suggest there may be an immediate beneficial effect on impairment level measures; more, higher quality research is needed to confirm this finding.Although we evaluated five studies, the benefits and risks of interventions remain unknown and the emerging evidence justifies the need for adequately powered clinical trials into this condition.People with dysarthria after stroke or brain injury should continue to receive rehabilitation according to clinical guidelines.

A systematic review of randomised controlled trials in rheumatoid arthritis: the reporting and handling of missing data in composite outcomes.

PubMed

Ibrahim, Fowzia; Tom, Brian D M; Scott, David L; Prevost, Andrew Toby

2016-06-02

Most reported outcome measures in rheumatoid arthritis (RA) trials are composite, whose components comprise single measures that are combined into one outcome. The aims of this review were to assess the range of missing data rates in primary composite outcomes and to document the current practice for handling and reporting missing data in published RA trials compared to the Consolidated Standards of Reporting Trials (CONSORT) recommendations. A systematic search for randomised controlled trials was conducted for RA trials published between 2008 and 2013 in four rheumatology and four high impact general medical journals. A total of 51 trials with a composite primary outcome were identified, of which 38 (75 %) used the binary American College of Rheumatology responder index and 13 (25 %) used the Disease Activity Score for 28 joints (DAS28). Forty-four trials (86 %) reported on an intention-to-treat analysis population, while 7 trials (14 %) analysed according to a modified intention-to-treat population. Missing data rates for the primary composite outcome ranged from 2-53 % and were above 30 % in 9 trials, 20-30 % in 11 trials, 10-20 % in 18 trials and below 10 % in 13 trials. Thirty-eight trials (75 %) used non-responder imputation and 10 (20 %) used last observation carried forward to impute missing composite outcome data at the primary time point. The rate of dropout was on average 61 % times higher in the placebo group compared to the treatment group in the 34 placebo controlled trials (relative rate 1.61, 95 % CI: 1.29, 2.02). Thirty-seven trials (73 %) did not report the use of sensitivity analyses to assess the handling of missing data in the primary analysis as recommended by CONSORT guidelines. This review highlights an improvement in rheumatology trial practice since the revision of CONSORT guidelines, in terms of power calculation and participant's flow diagram. However, there is a need to improve the handling and reporting of missing composite outcome data and their components in RA trials. In particular, sensitivity analyses need to be more widely used in RA trials because imputation is widespread and generally uses single imputation methods, and in this area the missing data rates are commonly differentially higher in the placebo group.

Protocol design and current status of CLIVIT: a randomized controlled multicenter relevance trial comparing clips versus ligatures in thyroid surgery

PubMed Central

Seiler, CM; Fröhlich, BE; Veit, JA; Gazyakan, E; Wente, MN; Wollermann, C; Deckert, A; Witte, S; Victor, N; Buchler, MW; Knaebel, HP

2006-01-01

Background Annually, more than 90000 surgical procedures of the thyroid gland are performed in Germany. Strategies aimed at reducing the duration of the surgical procedure are relevant to patients and the health care system especially in the context of reducing costs. However, new techniques for quick and safe hemostasis have to be tested in clinically relevance randomized controlled trials before a general recommendation can be given. The current standard for occlusion of blood vessels in thyroid surgery is ligatures. Vascular clips may be a safe alternative but have not been investigated in a large RCT. Methods/design CLIVIT (Clips versus Ligatures in Thyroid Surgery) is an investigator initiated, multicenter, patient-blinded, two-group parallel relevance randomized controlled trial designed by the Study Center of the German Surgical Society. Patients scheduled for elective resection of at least two third of the gland for benign thyroid disease are eligible for participation. After surgical exploration patients are randomized intraoperatively into either the conventional ligature group, or into the clip group. The primary objective is to test for a relevant reduction in operating time (at least 15 min) when using the clip technique. Since April 2004, 121 of the totally required 420 patients were randomized in five centers. Discussion As in all trials the different forms of bias have to be considered, and as in this case, a surgical trial, the role of surgical expertise plays a key role, and will be documented and analyzed separately. This is the first randomized controlled multicenter relevance trial to compare different vessel occlusion techniques in thyroid surgery with adequate power and other detailed information about the design as well as framework. If significant, the results might be generalized and may change the current surgical practice. PMID:16948853

Central nervous system antiretroviral efficacy in HIV infection: a qualitative and quantitative review and implications for future research.

PubMed

Cysique, Lucette A; Waters, Edward K; Brew, Bruce J

2011-11-22

There is conflicting information as to whether antiretroviral drugs with better central nervous system (CNS) penetration (neuroHAART) assist in improving neurocognitive function and suppressing cerebrospinal fluid (CSF) HIV RNA. The current review aims to better synthesise existing literature by using an innovative two-phase review approach (qualitative and quantitative) to overcome methodological differences between studies. Sixteen studies, all observational, were identified using a standard citation search. They fulfilled the following inclusion criteria: conducted in the HAART era; sample size > 10; treatment effect involved more than one antiretroviral and none had a retrospective design. The qualitative phase of review of these studies consisted of (i) a blind assessment rating studies on features such as sample size, statistical methods and definitions of neuroHAART, and (ii) a non-blind assessment of the sensitivity of the neuropsychological methods to HIV-associated neurocognitive disorder (HAND). During quantitative evaluation we assessed the statistical power of studies, which achieved a high rating in the qualitative analysis. The objective of the power analysis was to determine the studies ability to assess their proposed research aims. After studies with at least three limitations were excluded in the qualitative phase, six studies remained. All six found a positive effect of neuroHAART on neurocognitive function or CSF HIV suppression. Of these six studies, only two had statistical power of at least 80%. Studies assessed as using more rigorous methods found that neuroHAART was effective in improving neurocognitive function and decreasing CSF viral load, but only two of those studies were adequately statistically powered. Because all of these studies were observational, they represent a less compelling evidence base than randomised control trials for assessing treatment effect. Therefore, large randomised trials are needed to determine the robustness of any neuroHAART effect. However, such trials must be longitudinal, include the full spectrum of HAND, ideally carefully control for co-morbidities, and be based on optimal neuropsychology methods.

Cortical Oscillatory Mechanisms Supporting the Control of Human Social-Emotional Actions.

PubMed

Bramson, Bob; Jensen, Ole; Toni, Ivan; Roelofs, Karin

2018-06-20

The human anterior prefrontal cortex (aPFC) is involved in regulating social-emotional behavior, presumably by modulating effective connectivity with downstream parietal, limbic, and motor cortices. Regulating that connectivity might rely on theta-band oscillations (4-8 Hz), a brain rhythm known to create overlapping periods of excitability between distant regions by temporally releasing neurons from inhibition. Here, we used MEG to understand how aPFC theta-band oscillations implement control over prepotent social-emotional behaviors; that is, the control over automatically elicited approach and avoidance actions. Forty human male participants performed a social approach-avoidance task in which they approached or avoided visually displayed emotional faces (happy or angry) by pulling or pushing a joystick. Approaching angry and avoiding happy faces (incongruent condition) requires rapid application of cognitive control to override prepotent habitual action tendencies to approach appetitive and to avoid aversive situations. In the time window before response delivery, trial-by-trial variations in aPFC theta-band power (6 Hz) predicted reaction time increases during emotional control and were inversely related to beta-band power (14-22 Hz) over parietofrontal cortex. In sensorimotor areas contralateral to the moving hand, premovement gamma-band rhythms (60-90 Hz) were stronger during incongruent than congruent trials, with power increases phase locked to peaks of the aPFC theta-band oscillations. These findings define a mechanistic relation between cortical areas involved in implementing rapid control over human social-emotional behavior. The aPFC may bias neural processing toward rule-driven actions and away from automatic emotional tendencies by coordinating tonic disinhibition and phasic enhancement of parietofrontal circuits involved in action selection. SIGNIFICANCE STATEMENT Being able to control social-emotional behavior is crucial for successful participation in society, as is illustrated by the severe social and occupational difficulties experienced by people suffering from social motivational disorders such as social anxiety. In this study, we show that theta-band oscillations in the anterior prefrontal cortex (aPFC), which are thought to provide temporal organization for neural firing during communication between distant brain areas, facilitate this control by linking aPFC to parietofrontal beta-band and sensorimotor gamma-band oscillations involved in action selection. These results contribute to a mechanistic understanding of cognitive control over automatic social-emotional action and point to frontal theta-band oscillations as a possible target of rhythmic neurostimulation techniques during treatment for social anxiety. Copyright © 2018 the authors 0270-6474/18/385739-11$15.00/0.

Rationale and study design of PROVHILO - a worldwide multicenter randomized controlled trial on protective ventilation during general anesthesia for open abdominal surgery.

PubMed

Hemmes, Sabrine N T; Severgnini, Paolo; Jaber, Samir; Canet, Jaume; Wrigge, Hermann; Hiesmayr, Michael; Tschernko, Edda M; Hollmann, Markus W; Binnekade, Jan M; Hedenstierna, Göran; Putensen, Christian; de Abreu, Marcelo Gama; Pelosi, Paolo; Schultz, Marcus J

2011-05-06

Post-operative pulmonary complications add to the morbidity and mortality of surgical patients, in particular after general anesthesia >2 hours for abdominal surgery. Whether a protective mechanical ventilation strategy with higher levels of positive end-expiratory pressure (PEEP) and repeated recruitment maneuvers; the "open lung strategy", protects against post-operative pulmonary complications is uncertain. The present study aims at comparing a protective mechanical ventilation strategy with a conventional mechanical ventilation strategy during general anesthesia for abdominal non-laparoscopic surgery. The PROtective Ventilation using HIgh versus LOw positive end-expiratory pressure ("PROVHILO") trial is a worldwide investigator-initiated multicenter randomized controlled two-arm study. Nine hundred patients scheduled for non-laparoscopic abdominal surgery at high or intermediate risk for post-operative pulmonary complications are randomized to mechanical ventilation with the level of PEEP at 12 cmH(2)O with recruitment maneuvers (the lung-protective strategy) or mechanical ventilation with the level of PEEP at maximum 2 cmH(2)O without recruitment maneuvers (the conventional strategy). The primary endpoint is any post-operative pulmonary complication. The PROVHILO trial is the first randomized controlled trial powered to investigate whether an open lung mechanical ventilation strategy in short-term mechanical ventilation prevents against postoperative pulmonary complications. ISRCTN: ISRCTN70332574.

A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder.

PubMed

Amsterdam, Jay D; Li, Yimei; Soeller, Irene; Rockwell, Kenneth; Mao, Jun James; Shults, Justine

2009-08-01

We conducted a randomized, double-blind, placebo-controlled efficacy and tolerability trial of Matricaria recutita (chamomile) extract therapy in patients with mild to moderate generalized anxiety disorder (GAD). We hypothesized that chamomile would be superior to placebo in reducing GAD symptoms with a comparable tolerability profile. Sixty-one outpatients with mild to moderate GAD were enrolled, and 57 were randomized to either double-blind chamomile extract (n = 28) or placebo therapy (n = 29) for 8 weeks. The study was powered to detect a statistically significant and clinically meaningful group difference in change over time in total Hamilton Anxiety Rating (HAM-A) scores. Secondary outcomes included change in the Beck Anxiety Inventory, Psychological Well Being, and Clinical Global Impression Severity scores and the proportion of patients with 50% reduction or more in baseline HAM-A score. We observed a significantly greater reduction in mean total HAM-A score during chamomile versus placebo therapy (P = 0.047). Although the study was not powered to identify small to moderate differences in secondary outcomes, we observed a positive change in all secondary outcomes in the same direction as the primary outcome measure. One patient in each treatment group discontinued therapy for adverse events. The proportion of patients experiencing 0, 1, 2, or 3 adverse events or more was not significantly different between groups (P = 0.417). This is the first controlled clinical trial of chamomile extract for GAD. The results suggest that chamomile may have modest anxiolytic activity in patients with mild to moderate GAD. Future studies are needed to replicate these observations.

Impaired Midline Theta Power and Connectivity During Proactive Cognitive Control in Schizophrenia.

PubMed

Ryman, Sephira G; Cavanagh, James F; Wertz, Christopher J; Shaff, Nicholas A; Dodd, Andrew B; Stevens, Brigitte; Ling, Josef; Yeo, Ronald A; Hanlon, Faith M; Bustillo, Juan; Stromberg, Shannon F; Lin, Denise S; Abrams, Swala; Mayer, Andrew R

2018-05-25

Disrupted proactive cognitive control, a form of early selection and active goal maintenance, is hypothesized to underlie the broad cognitive deficits observed in patients with schizophrenia (SPs). Current research suggests that the disrupted activation within and connectivity between regions of the cognitive control network contribute to disrupted proactive cognitive control; however, no study has examined these mechanisms using an AX Continuous Performance Test task in schizophrenia. Twenty-six SPs (17 male subjects; mean age 34.46 ± 8.77 years) and 28 healthy control participants (HCs; 16 male subjects; mean age 31.43 ± 7.23 years) underwent an electroencephalogram while performing the AX Continuous Performance Test. To examine the extent of activation and level of connectivity within the cognitive control network, power, intertrial phase clustering, and intersite phase clustering metrics were calculated and analyzed. SPs exhibited expected general decrements in behavioral performance relative to HCs and a more selective deficit in conditions requiring proactive cognitive control. Additionally, SPs exhibited deficits in midline theta power and connectivity during proactive cognitive control trials. Specifically, HCs exhibited significantly greater theta power for B cues relative to A cues, whereas SPs exhibited no significant differences between A- and B-cue theta power. Additionally, differential theta connectivity patterns were observed in SPs and HCs. Behavioral measures of proactive cognitive control predicted functional outcomes in SPs. This study suggests that low-frequency midline theta activity is selectively disrupted during proactive cognitive control in SPs. The disrupted midline theta activity may reflect a failure of SPs to proactively recruit cognitive control processes. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Promoting smoking cessation in Pakistani and Bangladeshi men in the UK: pilot cluster randomised controlled trial of trained community outreach workers

PubMed Central

2011-01-01

Background Smoking prevalence is high among Pakistani and Bangladeshi men in the UK, but there are few tailored smoking cessation programmes for Pakistani and Bangladeshi communities. The aim of this study was to pilot a cluster randomised controlled trial comparing the effectiveness of Pakistani and Bangladeshi smoking cessation outreach workers with standard care to improve access to and the success of English smoking cessation services. Methods A pilot cluster randomised controlled trial was conducted in Birmingham, UK. Geographical lower layer super output areas were used to identify natural communities where more than 10% of the population were of Pakistani and Bangladeshi origin. 16 agglomerations of super output areas were randomised to normal care controls vs. outreach intervention. The number of people setting quit dates using NHS services, validated abstinence from smoking at four weeks, and stated abstinence at three and six months were assessed. The impact of the intervention on choice and adherence to treatments, attendance at clinic appointments and patient satisfaction were also assessed. Results We were able to randomise geographical areas and deliver the outreach worker-based services. More Pakistani and Bangladeshi men made quit attempts with NHS services in intervention areas compared with control areas, rate ratio (RR) 1.32 (95%CI: 1.03-1.69). There was a small increase in the number of 4-week abstinent smokers in intervention areas (RR 1.30, 95%CI: 0.82-2.06). The proportion of service users attending weekly appointments was lower in intervention areas than control areas. No difference was found between intervention and control areas in choice and adherence to treatments or patient satisfaction with the service. The total cost of the intervention was £124,000; an estimated cost per quality-adjusted life year (QALY) gained of £8,500. Conclusions The intervention proved feasible and acceptable. Outreach workers expanded reach of smoking cessation services in diverse locations of relevance to Pakistani and Bangladeshi communities. The outreach worker model has the potential to increase community cessation rates and could prove cost-effective, but needs evaluating definitively in a larger, appropriately powered, randomised controlled trial. These future trials of outreach interventions need to be of sufficient duration to allow embedding of new models of service delivery. Trial registration Current Controlled Trials ISRCTN82127540 PMID:21854596

A study protocol of a randomised controlled trial incorporating a health economic analysis to investigate if additional allied health services for rehabilitation reduce length of stay without compromising patient outcomes

PubMed Central

2010-01-01

Background Reducing patient length of stay is a high priority for health service providers. Preliminary information suggests additional Saturday rehabilitation services could reduce the time a patient stays in hospital by three days. This large trial will examine if providing additional physiotherapy and occupational therapy services on a Saturday reduces health care costs, and improves the health of hospital inpatients receiving rehabilitation compared to the usual Monday to Friday service. We will also investigate the cost effectiveness and patient outcomes of such a service. Methods/Design A randomised controlled trial will evaluate the effect of providing additional physiotherapy and occupational therapy for rehabilitation. Seven hundred and twelve patients receiving inpatient rehabilitation at two metropolitan sites will be randomly allocated to the intervention group or control group. The control group will receive usual care physiotherapy and occupational therapy from Monday to Friday while the intervention group will receive the same amount of rehabilitation as the control group Monday to Friday plus a full physiotherapy and occupational therapy service on Saturday. The primary outcomes will be patient length of stay, quality of life (EuroQol questionnaire), the Functional Independence Measure (FIM), and health utilization and cost data. Secondary outcomes will assess clinical outcomes relevant to the goals of therapy: the 10 metre walk test, the timed up and go test, the Personal Care Participation Assessment and Resource Tool (PC PART), and the modified motor assessment scale. Blinded assessors will assess outcomes at admission and discharge, and follow up data on quality of life, function and health care costs will be collected at 6 and 12 months after discharge. Between group differences will be analysed with analysis of covariance using baseline measures as the covariate. A health economic analysis will be carried out alongside the randomised controlled trial. Discussion This paper outlines the study protocol for the first fully powered randomised controlled trial incorporating a health economic analysis to establish if additional Saturday allied health services for rehabilitation inpatients reduces length of stay without compromising discharge outcomes. If successful, this trial will have substantial health benefits for the patients and for organizations delivering rehabilitation services. Clinical trial registration number Australian and New Zealand Clinical Trials Registry ACTRN12609000973213 PMID:21073703

Formulation and experimental evaluation of closed-form control laws for the rapid maneuvering of reactor neutronic power

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernard, J.A.

1989-09-01

This report describes both the theoretical development and the experimental evaluation of a novel, robust methodology for the time-optimal adjustment of a reactor's neutronic power under conditions of closed-loop digital control. Central to the approach are the MIT-SNL Period-Generated Minimum Time Control Laws' which determine the rate at which reactivity should be changed in order to cause a reactor's neutronic power to conform to a specified trajectory. Using these laws, reactor power can be safely raised by five to seven orders of magnitude in a few seconds. The MIT-SNL laws were developed to facilitate rapid increases of neutronic power onmore » spacecraft reactors operating in an SDI environment. However, these laws are generic and have other applications including the rapid recovery of research and test reactors subsequent to an unanticipated shutdown, power increases following the achievement of criticality on commercial reactors, power adjustments on commercial reactors so as to minimize thermal stress, and automated startups. The work reported here was performed by the Massachusetts Institute of Technology under contract to the Sandia National Laboratories. Support was also provided by the US Department of Energy's Division of University and Industry Programs. The work described in this report is significant in that a novel solution to the problem of time-optimal control of neutronic power was identified, in that a rigorous description of a reactor's dynamics was derived in that the rate of change of reactivity was recognized as the proper control signal, and in that extensive experimental trials were conducted of these newly developed concepts on actual nuclear reactors. 43 refs., 118 figs., 11 tabs.« less

Event-rate and delta inflation when evaluating mortality as a primary outcome from randomized controlled trials of nutritional interventions during critical illness: a systematic review.

PubMed

Summers, Matthew J; Chapple, Lee-anne S; McClave, Stephen A; Deane, Adam M

2016-04-01

There is a lack of high-quality evidence that proves that nutritional interventions during critical illness reduce mortality. We evaluated whether power calculations for randomized controlled trials (RCTs) of nutritional interventions that used mortality as the primary outcome were realistic, and whether overestimation was systematic in the studies identified to determine whether this was due to overestimates of event rate or delta. A systematic review of the literature between 2005 and 2015 was performed to identify RCTs of nutritional interventions administered to critically ill adults that had mortality as the primary outcome. Predicted event rate (predicted mortality during the control), predicted mortality during intervention, predicted delta (predicted difference between mortality during the control and intervention), actual event rate (observed mortality during control), observed mortality during intervention, and actual delta (difference between observed mortality during the control and intervention) were recorded. The event-rate gap (predicted event rate minus observed event rate), the delta gap (predicted delta minus observed delta), and the predicted number needed to treat were calculated. Data are shown as median (range). Fourteen articles were extracted, with power calculations provided for 10 studies. The predicted event rate was 29.9% (20.0–52.4%), and the predicted delta was 7.9% (3.0–20.0%). If the study hypothesis was proven correct then, on the basis of the power calculations, the number needed to treat would have been 12.7 (5.0–33.3) patients. The actual event rate was 25.3% (6.1–50.0%), the observed mortality during the intervention was 24.4% (6.3–39.7%), and the actual delta was 0.5% (−10.2–10.3%), such that the event-rate gap was 2.6% (−3.9–23.7%) and delta gap was 7.5% (3.2–25.2%). Overestimates of delta occur frequently in RCTs of nutritional interventions in the critically ill that are powered to determine a mortality benefit. Delta inflation may explain the number of "negative" studies in this field of research.

A Multi-state Model for Designing Clinical Trials for Testing Overall Survival Allowing for Crossover after Progression

PubMed Central

Xia, Fang; George, Stephen L.; Wang, Xiaofei

2015-01-01

In designing a clinical trial for comparing two or more treatments with respect to overall survival (OS), a proportional hazards assumption is commonly made. However, in many cancer clinical trials, patients pass through various disease states prior to death and because of this may receive treatments other than originally assigned. For example, patients may crossover from the control treatment to the experimental treatment at progression. Even without crossover, the survival pattern after progression may be very different than the pattern prior to progression. The proportional hazards assumption will not hold in these situations and the design power calculated on this assumption will not be correct. In this paper we describe a simple and intuitive multi-state model allowing for progression, death before progression, post-progression survival and crossover after progression and apply this model to the design of clinical trials for comparing the OS of two treatments. For given values of the parameters of the multi-state model, we simulate the required number of deaths to achieve a specified power and the distribution of time required to achieve the requisite number of deaths. The results may be quite different from those derived using the usual PH assumption. PMID:27239255

Methods to Prove 20+ Year Life of CPV Products (in less than 20 Years)

NASA Astrophysics Data System (ADS)

Bowman, John; Spencer, Mark

2011-12-01

Due to the long term life expectations of photovoltaic products and the short duration of most introduced CPV technologies, it is critical for CPV companies to carefully construct field trials to prove product life. Because of the complicated geometric, thermal, and spectral characteristics of CPV systems, conducting very precise power output measurements reproducibly over many months is very difficult. Robust normalization methods specific to the exact optical system and PV cell type must be developed. Once the performance over a specific duration, e.g. one year, is established, then some justification is required to extrapolate to future performance. Comparisons to accelerated test results provide this justification. SolFocus has been conducting field trials of the SF-1100S CPV system for over two years. These field trials consist of controlled populations of SF-1100P modules, operating in grid-tied systems, which have been repeatedly measured at the individual module level over the duration of the trials. In this paper, field data will be presented along with normalization methodology and statistical methods for determining power degradation slope distributions for populations of individual modules. These results will be correlated with accelerated field tests which have been ongoing for 1.5 years and are estimated to be equivalent to 10 to 15 years of non-accelerated operation.

A randomised controlled trial of caseload midwifery care: M@NGO (Midwives @ New Group practice Options).

PubMed

Tracy, Sally K; Hartz, Donna; Hall, Bev; Allen, Jyai; Forti, Amanda; Lainchbury, Anne; White, Jan; Welsh, Alec; Tracy, Mark; Kildea, Sue

2011-10-26

Australia has an enviable record of safety for women in childbirth. There is nevertheless growing concern at the increasing level of intervention and consequent morbidity amongst childbearing women. Not only do interventions impact on the cost of services, they carry with them the potential for serious morbidities for mother and infant.Models of midwifery have proliferated in an attempt to offer women less fragmented hospital care. One of these models that is gaining widespread consumer, disciplinary and political support is caseload midwifery care. Caseload midwives manage the care of approximately 35-40 a year within a small Midwifery Group Practice (usually 4-6 midwives who plan their on call and leave within the Group Practice.) We propose to compare the outcomes and costs of caseload midwifery care compared to standard or routine hospital care through a randomised controlled trial. A two-arm RCT design will be used. Women will be recruited from tertiary women's hospitals in Sydney and Brisbane, Australia. Women allocated to the caseload intervention will receive care from a named caseload midwife within a Midwifery Group Practice. Control women will be allocated to standard or routine hospital care. Women allocated to standard care will receive their care from hospital rostered midwives, public hospital obstetric care and community based general medical practitioner care. All midwives will collaborate with obstetricians and other health professionals as necessary according to the woman's needs. Data will be collected at recruitment, 36 weeks antenatally, six weeks and six months postpartum by web based or postal survey. With 750 women or more in each of the intervention and control arms the study is powered (based on 80% power; alpha 0.05) to detect a difference in caesarean section rates of 29.4 to 22.9%; instrumental birth rates from 11.0% to 6.8%; and rates of admission to neonatal intensive care of all neonates from 9.9% to 5.8% (requires 721 in each arm). The study is not powered to detect infant or maternal mortality, however all deaths will be reported. Other significant findings will be reported, including a comprehensive process and economic evaluation. Australian New Zealand Clinical Trials Registry ACTRN12609000349246.

1 MeV, 10 kW DC electron accelerator for industrial applications

NASA Astrophysics Data System (ADS)

Nayak, B.; Acharya, S.; Bhattacharjee, D.; Bakhtsingh, R. I.; Rajan, R.; Sharma, D. K.; Dewangan, S.; Sharma, V.; Patel, R.; Tiwari, R.; Benarjee, S.; Srivastava, S. K.

2016-03-01

Several modern applications of radiation processing like medical sterilization, rubber vulcanization, polymerization, cross-linking and pollution control from thermal power stations etc. require D.C. electron accelerators of energy ranging from a few hundred keVs to few MeVs and power from a few kilowatts to hundreds of kilowatts. To match these requirements, a 3 MeV, 30 kW DC electron linac has been developed at BARC, Mumbai and current operational experience of 1 MeV, 10 kW beam power will be described in this paper. The LINAC composed mainly of Electron Gun, Accelerating Tubes, Magnets, High Voltage source and provides 10 kW beam power at the Ti beam window stably after the scanning section. The control of the LINAC is fully automated. Here Beam Optics study is carried out to reach the preferential parameters of Accelerating as well as optical elements. Beam trials have been conducted to find out the suitable operation parameters of the system.

VARIABLE SELECTION FOR QUALITATIVE INTERACTIONS IN PERSONALIZED MEDICINE WHILE CONTROLLING THE FAMILY-WISE ERROR RATE

PubMed Central

Gunter, Lacey; Zhu, Ji; Murphy, Susan

2012-01-01

For many years, subset analysis has been a popular topic for the biostatistics and clinical trials literature. In more recent years, the discussion has focused on finding subsets of genomes which play a role in the effect of treatment, often referred to as stratified or personalized medicine. Though highly sought after, methods for detecting subsets with altering treatment effects are limited and lacking in power. In this article we discuss variable selection for qualitative interactions with the aim to discover these critical patient subsets. We propose a new technique designed specifically to find these interaction variables among a large set of variables while still controlling for the number of false discoveries. We compare this new method against standard qualitative interaction tests using simulations and give an example of its use on data from a randomized controlled trial for the treatment of depression. PMID:22023676

Video noise reduction

NASA Astrophysics Data System (ADS)

Drewery, J. O.; Storey, R.; Tanton, N. E.

1984-07-01

A video noise and film grain reducer is described which is based on a first-order recursive temporal filter. Filtering of moving detail is avoided by inhibiting recursion in response to the amount of motion in a picture. Motion detection is based on the point-by-point power of the picture difference signal coupled with a knowledge of the noise statistics. A control system measures the noise power and adjusts the working point of the motion detector accordingly. A field trial of a manual version of the equipment at Television Center indicated that a worthwhile improvement in the quality of noisy or grainy pictures received by the viewer could be obtained. Subsequent trials of the automated version confirmed that the improvement could be maintained. Commercial equipment based on the design is being manufactured and marketed by Pye T.V.T. under license. It is in regular use on both the BBC1 and BBC2 networks.

Subthreshold muscle twitches dissociate oscillatory neural signatures of conflicts from errors.

PubMed

Cohen, Michael X; van Gaal, Simon

2014-02-01

We investigated the neural systems underlying conflict detection and error monitoring during rapid online error correction/monitoring mechanisms. We combined data from four separate cognitive tasks and 64 subjects in which EEG and EMG (muscle activity from the thumb used to respond) were recorded. In typical neuroscience experiments, behavioral responses are classified as "error" or "correct"; however, closer inspection of our data revealed that correct responses were often accompanied by "partial errors" - a muscle twitch of the incorrect hand ("mixed correct trials," ~13% of the trials). We found that these muscle twitches dissociated conflicts from errors in time-frequency domain analyses of EEG data. In particular, both mixed-correct trials and full error trials were associated with enhanced theta-band power (4-9Hz) compared to correct trials. However, full errors were additionally associated with power and frontal-parietal synchrony in the delta band. Single-trial robust multiple regression analyses revealed a significant modulation of theta power as a function of partial error correction time, thus linking trial-to-trial fluctuations in power to conflict. Furthermore, single-trial correlation analyses revealed a qualitative dissociation between conflict and error processing, such that mixed correct trials were associated with positive theta-RT correlations whereas full error trials were associated with negative delta-RT correlations. These findings shed new light on the local and global network mechanisms of conflict monitoring and error detection, and their relationship to online action adjustment. © 2013.

Efficacy and side-effect profiles of lactulose, docusate sodium, and sennosides compared to PEG in opioid-induced constipation: a systematic review.

PubMed

Ruston, Teresa; Hunter, Kathleen; Cummings, Greta; Lazarescu, Adriana

2013-01-01

Opioid-induced constipation (OIC) is a side effect of opioid therapy that can affect quality of life, adherence to treatment, and morbidity and possibly mortality. To investigate whether docusate sodium, sennosides, and lactulose have equal efficacy and side effect profiles compared to PEG in the management of OIC in adults. A systematic review was undertaken. Randomized controlled trials of adults taking opioids for cancer or non-cancer pain were considered if they met inclusion criteria. Statistical pooling was not possible as no studies met inclusion criteria. Large, well-powered, randomized controlled trials are feasible. Standard definitions of OIC would assist with the execution of these studies and contribute to their internal and external validity. Further research is strongly encouraged.

Independent but Coordinated Trials: Insights from the Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group

PubMed Central

Yeh, Hsin-Chieh; Clark, Jeanne M.; Emmons, Karen M.; Moore, Renee H.; Bennett, Gary G; Warner, Erica T.; Sarwer, Davis B.; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A.; Wells, Barbara; Wadden, Thomas A.; Colditz, Graham A.; Appel, Lawrence J.

2011-01-01

Background The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the “Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.” Purpose We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. Methods The Collaborative Research Group consists of three individual studies: “Be Fit, Be Well“(Washington University in St. Louis/Harvard University), “POWER Hopkins” (Johns Hopkins), and “POWER-UP” (University of Pennsylvania). There are a total of 15 participating clinics with ~1,100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. Results The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. Limitations The challenges of the organizational design include the complex decision making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols. Conclusions The POWER Trials Collaborative Research Group is a case study of an alternative organizational model to conduct independent, yet coordinated trials. Such a model is increasingly being used in NHLBI supported trials , especially given the interest in comparative effectiveness research. Nevertheless, the ultimate utility of this model will not be fully understood until the trials are completed. PMID:20573639

Beta/Gamma Oscillations and Event-Related Potentials Indicate Aberrant Multisensory Processing in Schizophrenia

PubMed Central

Balz, Johanna; Roa Romero, Yadira; Keil, Julian; Krebber, Martin; Niedeggen, Michael; Gallinat, Jürgen; Senkowski, Daniel

2016-01-01

Recent behavioral and neuroimaging studies have suggested multisensory processing deficits in patients with schizophrenia (SCZ). Thus far, the neural mechanisms underlying these deficits are not well understood. Previous studies with unisensory stimulation have shown altered neural oscillations in SCZ. As such, altered oscillations could contribute to aberrant multisensory processing in this patient group. To test this assumption, we conducted an electroencephalography (EEG) study in 15 SCZ and 15 control participants in whom we examined neural oscillations and event-related potentials (ERPs) in the sound-induced flash illusion (SIFI). In the SIFI multiple auditory stimuli that are presented alongside a single visual stimulus can induce the illusory percept of multiple visual stimuli. In SCZ and control participants we compared ERPs and neural oscillations between trials that induced an illusion and trials that did not induce an illusion. On the behavioral level, SCZ (55.7%) and control participants (55.4%) did not significantly differ in illusion rates. The analysis of ERPs revealed diminished amplitudes and altered multisensory processing in SCZ compared to controls around 135 ms after stimulus onset. Moreover, the analysis of neural oscillations revealed altered 25–35 Hz power after 100 to 150 ms over occipital scalp for SCZ compared to controls. Our findings extend previous observations of aberrant neural oscillations in unisensory perception paradigms. They suggest that altered ERPs and altered occipital beta/gamma band power reflect aberrant multisensory processing in SCZ. PMID:27999553

A best practice fall prevention exercise program to improve balance, strength / power, and psychosocial health in older adults: study protocol for a randomized controlled trial.

PubMed

Gschwind, Yves J; Kressig, Reto W; Lacroix, Andre; Muehlbauer, Thomas; Pfenninger, Barbara; Granacher, Urs

2013-10-09

With increasing age neuromuscular deficits (e.g., sarcopenia) may result in impaired physical performance and an increased risk for falls. Prominent intrinsic fall-risk factors are age-related decreases in balance and strength / power performance as well as cognitive decline. Additional studies are needed to develop specifically tailored exercise programs for older adults that can easily be implemented into clinical practice. Thus, the objective of the present trial is to assess the effects of a fall prevention program that was developed by an interdisciplinary expert panel on measures of balance, strength / power, body composition, cognition, psychosocial well-being, and falls self-efficacy in healthy older adults. Additionally, the time-related effects of detraining are tested. Healthy old people (n = 54) between the age of 65 to 80 years will participate in this trial. The testing protocol comprises tests for the assessment of static / dynamic steady-state balance (i.e., Sharpened Romberg Test, instrumented gait analysis), proactive balance (i.e., Functional Reach Test; Timed Up and Go Test), reactive balance (i.e., perturbation test during bipedal stance; Push and Release Test), strength (i.e., hand grip strength test; Chair Stand Test), and power (i.e., Stair Climb Power Test; countermovement jump). Further, body composition will be analysed using a bioelectrical impedance analysis system. In addition, questionnaires for the assessment of psychosocial (i.e., World Health Organisation Quality of Life Assessment-Bref), cognitive (i.e., Mini Mental State Examination), and fall risk determinants (i.e., Fall Efficacy Scale - International) will be included in the study protocol. Participants will be randomized into two intervention groups or the control / waiting group. After baseline measures, participants in the intervention groups will conduct a 12-week balance and strength / power exercise intervention 3 times per week, with each training session lasting 30 min. (actual training time). One intervention group will complete an extensive supervised training program, while the other intervention group will complete a short version ('3 times 3') that is home-based and controlled by weekly phone calls. Post-tests will be conducted right after the intervention period. Additionally, detraining effects will be measured 12 weeks after program cessation. The control group / waiting group will not participate in any specific intervention during the experimental period, but will receive the extensive supervised program after the experimental period. It is expected that particularly the supervised combination of balance and strength / power training will improve performance in variables of balance, strength / power, body composition, cognitive function, psychosocial well-being, and falls self-efficacy of older adults. In addition, information regarding fall risk assessment, dose-response-relations, detraining effects, and supervision of training will be provided. Further, training-induced health-relevant changes, such as improved performance in activities of daily living, cognitive function, and quality of life, as well as a reduced risk for falls may help to lower costs in the health care system. Finally, practitioners, therapists, and instructors will be provided with a scientifically evaluated feasible, safe, and easy-to-administer exercise program for fall prevention.

The Suppression of Beta Oscillations in the Primate Supplementary Motor Complex Reflects a Volatile State During the Updating of Action Sequences.

PubMed

Hosaka, Ryosuke; Nakajima, Toshi; Aihara, Kazuyuki; Yamaguchi, Yoko; Mushiake, Hajime

2016-08-01

The medial motor areas play crucial but flexible roles in the temporal organizations of multiple movements. The beta oscillation of local field potentials is the predominant oscillatory activity in the motor areas, but the manner in which increases and decreases in beta power contribute to updating of multiple action plans is not yet fully understood. In the present study, beta and high-gamma activities in the supplementary motor area (SMA) and pre-SMA of monkeys were analyzed during performance of a bimanual motor sequence task that required updating and maintenance of the memory of action sequences. Beta power was attenuated during early delay periods of updating trials but was increased during maintenance trials, while there was a reciprocal increase in high-gamma power during updating trials. Moreover, transient attenuation of beta power during maintenance trials resulted in the erroneous selection of an action sequence. Therefore, it was concluded that the suppression of beta power during the early delay period reflects volatility of neural representation of the action sequence. This neural representation would be properly updated to the appropriate instructed action sequence via increases in high-gamma power in updating trials whereas it would be erroneously updated without the appropriate updating signal in maintenance trials. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effective Recruitment of Schools for Randomized Clinical Trials: Role of School Nurses.

PubMed

Petosa, R L; Smith, L

2017-01-01

In school settings, nurses lead efforts to improve the student health and well-being to support academic success. Nurses are guided by evidenced-based practice and data to inform care decisions. The randomized controlled trial (RCT) is considered the gold standard of scientific rigor for clinical trials. RCTs are critical to the development of evidence-based health promotion programs in schools. The purpose of this article is to present practical solutions to implementing principles of randomization to RCT trials conducted in school settings. Randomization is a powerful sampling method used to build internal and external validity. The school's daily organization and educational mission provide several barriers to randomization. Based on the authors' experience in conducting school-based RCTs, they offer a host of practical solutions to working with schools to successfully implement randomization procedures. Nurses play a critical role in implementing RCTs in schools to promote rigorous science in support of evidence-based practice.

CORE-Hom: a powerful and exhaustive database of clinical trials in homeopathy.

PubMed

Clausen, Jürgen; Moss, Sian; Tournier, Alexander; Lüdtke, Rainer; Albrecht, Henning

2014-10-01

The CORE-Hom database was created to answer the need for a reliable and publicly available source of information in the field of clinical research in homeopathy. As of May 2014 it held 1048 entries of clinical trials, observational studies and surveys in the field of homeopathy, including second publications and re-analyses. 352 of the trials referenced in the database were published in peer reviewed journals, 198 of which were randomised controlled trials. The most often used remedies were Arnica montana (n = 103) and Traumeel(®) (n = 40). The most studied medical conditions were respiratory tract infections (n = 126) and traumatic injuries (n = 110). The aim of this article is to introduce the database to the public, describing and explaining the interface, features and content of the CORE-Hom database. Copyright © 2014 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Modafinil for Clozapine-Treated Schizophrenia Patients: A Double-Blind, Placebo-Controlled Pilot Trial

PubMed Central

Freudenreich, Oliver; Henderson, David C.; Macklin, Eric A.; Evins, A. Eden; Fan, Xiaoduo; Cather, Cori; Walsh, Jared P.; Goff, Donald C.

2016-01-01

Background Patients with schizophrenia often suffer from cognitive deficits and negative symptoms that are poorly responsive to antipsychotics including clozapine. Clozapine-induced sedation can worsen cognition and impair social and occupational functioning. Objectives To evaluate the efficacy, tolerability, and safety of modafinil for negative symptoms, cognition, and wakefulness/fatigue in DSM-IV–diagnosed schizophrenia patients treated with clozapine. Method A double-blind, placebo-controlled, flexible-dosed 8-week pilot trial was conducted between September 2003 and September 2007, adding modafinil up to 300 mg/d to stabilized schizophrenia outpatients receiving clozapine. Psychopathology, cognition, and wakefulness/fatigue were assessed with standard rating scales. Results Thirty-five patients were randomly assigned to treatment with study drug and included in the analysis. Modafinil did not reduce negative symptoms or wakefulness/fatigue or improve cognition compared to placebo. Modafinil was well tolerated and did not worsen psychosis. Conclusions Results of this pilot trial do not support routine use of modafinil to treat negative symptoms, cognitive deficits, or wakefulness/fatigue in patients on clozapine. However, given our limited power to detect a treatment effect and the clear possibility of a type II error, larger trials are needed to resolve or refute a potential therapeutic effect of uncertain magnitude. Trial Registration clinicaltrials.gov Identifier: NCT00573417 PMID:19689921

Virtual colonoscopy, optical colonoscopy, or fecal occult blood testing for colorectal cancer screening: results of a pilot randomized controlled trial.

PubMed

You, John J; Liu, Yudong; Kirby, John; Vora, Parag; Moayyedi, Paul

2015-07-09

No head-to-head randomized controlled trials have demonstrated the superiority of one colorectal screening modality over another in reducing colorectal cancer mortality. We conducted a pilot randomized controlled trial of fecal occult blood testing (FOBT), optical colonoscopy (OC), and virtual colonoscopy (VC), to inform the planning of a larger evaluative trial. Eligible patients (aged 50 to 70) were recruited from five primary care practices in Hamilton, ON, Canada, between March 23, 2010 and August 11, 2010, and randomized 1:1:1 in a parallel design using an automated, centralized telephone service to either FOBT, OC, or VC. To reflect conventional practice, patients received no additional reminders to complete their allocated screening test beyond those received in usual practice. The primary outcome was completion of the assigned screening procedure. Results of the index test and any follow-up investigations were ascertained at 6 months. Participants, caregivers, and outcome assessors were not blinded to group assignment. The trial was stopped early due to lack of ongoing funding. A total of 198 participants were enrolled, of whom 67 were allocated to FOBT, 66 to OC, and 65 to VC. The allocated screening procedure was completed by 43 (64%) subjects allocated to FOBT (95% confidence interval [CI], 52-75%), 53 (80%) subjects allocated to OC (95% CI, 69-88%), and 50 (77%) subjects allocated to VC (95% CI, 65-85%); because the trial stopped early, we had insufficient statistical power to detect clinically relevant differences in completion rates. During 6 months follow-up, colorectal adenomas were detected in 0 (0%) subjects allocated to FOBT, 12 (18%) subjects allocated to OC, and 2 (3%) subjects allocated to VC. One subject in the OC arm had histological evidence of high-grade dysplasia. No subjects were diagnosed with colorectal cancer. In this pilot randomized controlled trial of colorectal cancer screening in a primary care setting, 64-80% of subjects completed their allocated screening test. These findings may be of value to investigators planning clinical trials to evaluate the effectiveness of colorectal cancer screening. ClinicalTrials.gov NCT00865527. https://clinicaltrials.gov/ct2/show/NCT00865527.

Noninvasive Ventilatory Correction in Patients With Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

PubMed

Tsivgoulis, Georgios; Alexandrov, Andrei V; Katsanos, Aristeidis H; Barlinn, Kristian; Mikulik, Robert; Lambadiari, Vaia; Bonakis, Anastasios; Alexandrov, Anne W

2017-08-01

Even though current guidelines suggest that noninvasive ventilatory correction (NIVC) could be considered for acute ischemic stroke patients with obstructive sleep apnea, available evidence is conflicting, with no adequately powered randomized clinical trial being available to date. We conducted a systematic review and meta-analysis of all available literature data evaluating the effect of NIVC on neurological improvement (based on decrease in National Institutes of Health Stroke Scale score), vascular events (recurrent stroke, transient ischemic attack, myocardial infarction and unstable angina), and mortality during the follow-up period. We identified 4 randomized clinical trials and 1 prospectively matched observational cohort, comprising a total of 389 patients (59.8% males, mean age: 64.4 years). The risk of both performance and detection bias was considered high in most of the included randomized clinical trials because of the lack of blinding in participants, personnel and/or outcome assessors. The mean decrease in National Institutes of Health Stroke Scale scores during the first (≤30) days of acute ischemic stroke was found to be greater in NIVC-treated patients in comparison to controls (standardized mean difference, 0.38; 95% confidence interval, 0.11-0.66; P =0.007). However, no significant differences were detected between NIVC-treated acute ischemic stroke patients and controls on both the risk of vascular events (risk ratio, 0.53; 95% confidence interval, 0.25-1.14; P =0.11) and mortality (risk ratio, 0.71; 95% confidence interval, 0.37-1.36; P =0.30). No evidence of heterogeneity ( I 2 =0%; P for Cochran Q>0.50) or publication bias were detected in all analyses. NIVC seems to be associated with greater short-term neurological improvement in acute ischemic stroke patients with obstructive sleep apnea. This finding deserves further investigation within the settings of an adequately powered, sham-control, randomized clinical trial. © 2017 American Heart Association, Inc.

Power Calculations and Placebo Effect for Future Clinical Trials in Progressive Supranuclear Palsy

PubMed Central

Stamelou, Maria; Schöpe, Jakob; Wagenpfeil, Stefan; Ser, Teodoro Del; Bang, Jee; Lobach, Iryna Y.; Luong, Phi; Respondek, Gesine; Oertel, Wolfgang H.; Boxer, Adam L.; Höglinger, Günter U.

2016-01-01

Background Two recent randomized, placebo-controlled trials of putative disease-modifying agents (davunetide, tideglusib) in progressive supranuclear palsy (PSP) failed to show efficacy, but generated data relevant for future trials. Methods We provide sample size calculations based on data collected in 187 PSP patients assigned to placebo in these trials. A placebo effect was calculated. Results The total PSP-Rating Scale required the least number of patients per group (N = 51) to detect a 50% change in the 1-year progression and 39 when including patients with ≤ 5 years disease duration. The Schwab and England Activities of Daily Living required 70 patients per group and was highly correlated with the PSP-Rating Scale. A placebo effect was not detected in these scales. Conclusions We propose the 1-year PSP-Rating Scale score change as the single primary readout in clinical neuroprotective or disease-modifying trials. The Schwab and England Activities of Daily Living could be used as a secondary outcome. PMID:26948290

Toxoplasma gondii and schizophrenia: a review of published RCTs.

PubMed

Chorlton, Sam D

2017-07-01

Over the last 60 years, accumulating evidence has suggested that acute, chronic, and maternal Toxoplasma gondii infections predispose to schizophrenia. More recent evidence suggests that chronically infected patients with schizophrenia present with more severe disease. After acute infection, parasites form walled cysts in the brain, leading to lifelong chronic infection and drug resistance to commonly used antiparasitics. Chronic infection is the most studied and closely linked with development and severity of schizophrenia. There are currently four published randomized controlled trials evaluating antiparasitic drugs, specifically azithromycin, trimethoprim, artemisinin, and artemether, in patients with schizophrenia. No trials have demonstrated a change in psychopathology with adjunctive treatment. Published trials have either selected drugs without evidence against chronic infection or used them at doses too low to reduce brain cyst burden. Furthermore, trials have failed to achieve sufficient power or account for confounders such as previous antipsychotic treatment, sex, age, or rhesus status on antiparasitic effect. There are currently no ongoing trials of anti-Toxoplasma therapy in schizophrenia despite ample evidence to justify further testing.

Selenium and glutamine supplements: where are we heading? A critical care perspective.

PubMed

Andrews, Peter J D

2010-03-01

There is considerable interest in glutamine and selenium in critical care as both offer the potential to enhance host defences, through different but complimentary mechanisms and may reduce subsequent infections and mortality. The SIGNET trial (randomized controlled factorial trial) is the largest, critical care study of both supplements. The data have been presented publicly, but the data are not published or available for review and will therefore not be discussed fully in this update. In the present review I will explore the recently available (past 1-2 years) published literature. The current literature demonstrates that there are currently insufficient data to enable confident recommendations on the optimal route, timing, duration and dosage of each of these nutritional supplements. The pending results of SIGNET, the largest critical care trial of parenteral nutrition supplemented by glutamine and or selenium promises to clarify some of the current ambiguities and inform future practice. To be able to confidently establish or refute the hypothesis that either glutamine or selenium alone or in combination improves outcome in critical care requires a well designed prospective randomized controlled trial. To design such a trial we require the optimal dose and duration of the nutritional supplement (balancing efficacy and toxicity, ease of administration and cost) and then conduct an adequately powered trial. Such a trial is still lacking for these two agents. There are some supportive data for selenium but the case is less strong for parenteral glutamine and weakest for enteral glutamine.

Bayesian methods for the design and interpretation of clinical trials in very rare diseases

PubMed Central

Hampson, Lisa V; Whitehead, John; Eleftheriou, Despina; Brogan, Paul

2014-01-01

This paper considers the design and interpretation of clinical trials comparing treatments for conditions so rare that worldwide recruitment efforts are likely to yield total sample sizes of 50 or fewer, even when patients are recruited over several years. For such studies, the sample size needed to meet a conventional frequentist power requirement is clearly infeasible. Rather, the expectation of any such trial has to be limited to the generation of an improved understanding of treatment options. We propose a Bayesian approach for the conduct of rare-disease trials comparing an experimental treatment with a control where patient responses are classified as a success or failure. A systematic elicitation from clinicians of their beliefs concerning treatment efficacy is used to establish Bayesian priors for unknown model parameters. The process of determining the prior is described, including the possibility of formally considering results from related trials. As sample sizes are small, it is possible to compute all possible posterior distributions of the two success rates. A number of allocation ratios between the two treatment groups can be considered with a view to maximising the prior probability that the trial concludes recommending the new treatment when in fact it is non-inferior to control. Consideration of the extent to which opinion can be changed, even by data from the best feasible design, can help to determine whether such a trial is worthwhile. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd. PMID:24957522

Study protocol for a controlled trial of Strengths Model Case Management in mental health services in Hong Kong.

PubMed

Tsoi, Wing-See Emily; Tse, Samson; Fukui, Sadaaki; Jones, Steven

2015-10-06

Although strengths-based models are popular within recovery-oriented approaches, there is still a lack of conclusive research to guide how they should be implemented. A recent meta-analysis confirmed the lack of clarity in how this perspective is operationalised and that fidelity monitoring during the implementation process is lacking. Hence, there is a clear need to evaluate the feasibility of delivering and evaluating a clearly operationalised strengths-based intervention that incorporates fidelity checks to inform more definitive research. This protocol therefore describes a controlled trial of Strengths Model Case Management (SMCM), a complex intervention, for people with severe mental illnesses in Hong Kong. This trial follows the guidelines of the Medical Research Council as a phase 2 trial. Hence, it is a pilot study that tests the feasibility and effectiveness of the model. This is a 9-month controlled trial that uses the Kansas Model. Participants and a matched control group are recruited on a voluntary basis, after screening for eligibility. Effectiveness of the SMCM will be measured through outcome measures taken at baseline, the mid-point and at the end of the trial. Outcomes for service users include personal recovery, hope, subjective well-being, psychiatric symptoms, perceived level of recovery features within the organisation, therapeutic alliance and achievement of recovery goals. Outcomes for care workers will include job burnout, organisational features of recovery and perceived supervisory support. With a 2×3 analysis of variance design and a moderate intervention effect (Cohen's d=0.50), a total of 86 participants will be needed for a statistical power of 0.80. Ethical approval has been obtained from the Human Research Ethics Committee for Non-Clinical Faculties at The University of Hong Kong (HRECNCF: EA140913). Australian New Zealand Clinical Trial Registry (ACTRN)12613001120763. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cycling performance is superior for time-to-exhaustion versus time-trial in endurance laboratory tests.

PubMed

Coakley, Sarah L; Passfield, Louis

2018-06-01

Time-to-exhaustion (TTE) trials are used in a laboratory setting to measure endurance performance. However, there is some concern with their ecological validity compared with time-trials (TT). Consequently, we aimed to compare cycling performance in TTE and TT where the duration of the trials was matched. Seventeen trained male cyclists completed three TTE trials at 80, 100 and 105% of maximal aerobic power (MAP). On a subsequent visit they performed three TT over the same duration as the TTE. Participants were blinded to elapsed time, power output, cadence and heart rate (HR). Average TTE was 865 ± 345 s, 165 ± 98 s and 117 ± 45 s for the 80, 100 and 105% trials respectively. Average power output was higher for TTE (294 ± 44 W) compared to TT (282 ± 43 W) at 80% MAP (P < 0.01), but not at 100 and 105% MAP (P > 0.05). There was no difference in cadence, HR, or RPE for any trial (P > 0.05). Critical power (CP) was also higher when derived from TTE compared to TT (P < 0.01). It is concluded that TTE results in a higher average power output compared to TT at 80% MAP. When determining CP, TTE rather than TT protocols appear superior.

Effect of a combination of whole body vibration exercise and squat training on body balance, muscle power, and walking ability in the elderly.

PubMed

Osugi, Tomohiro; Iwamoto, Jun; Yamazaki, Michio; Takakuwa, Masayuki

2014-01-01

A randomized controlled trial was conducted to clarify the beneficial effect of whole body vibration (WBV) exercise plus squat training on body balance, muscle power, and walking ability in the elderly with knee osteoarthritis and/or spondylosis. Of 35 ambulatory patients (14 men and 21 women) who were recruited at our outpatient clinic, 28 (80.0%, 12 men and 16 women) participated in the trial. The subjects (mean age 72.4 years) were randomly divided into two groups (n=14 in each group), ie, a WBV exercise alone group and a WBV exercise plus squat training group. A 4-minute WBV exercise (frequency 20 Hz) was performed 2 days per week in both groups; squat training (20 times per minute) was added during the 4-minute WBV training session in the WBV exercise plus squat training group. The duration of the trial was 6 months. The exercise and training program was safe and well tolerated. WBV exercise alone improved indices of body balance and walking velocity from baseline values. However, WBV exercise plus squat training was more effective for improving tandem gait step number and chair-rising time compared with WBV exercise alone. These results suggest the benefit and safety of WBV exercise plus squat training for improving physical function in terms of body balance and muscle power in the elderly.

Feasibility study and pilot cluster-randomised controlled trial of the GoActive intervention aiming to promote physical activity among adolescents: outcomes and lessons learnt

PubMed Central

Corder, Kirsten; Brown, Helen E; Schiff, Annie; van Sluijs, Esther M F

2016-01-01

Objectives Assess the feasibility of implementing the GoActive intervention in secondary schools, to identify improvements, test study procedures, determine preliminary effectiveness to increase moderate-to-vigorous physical activity (MVPA), and inform power calculations to establish programme effectiveness. Setting Feasibility study (1 school) and pilot cluster-randomised controlled trial (CRCT; 2 intervention; 1 control school(s)). Participants 460 participants (46.6% female; 13.2 (0.4) years old). Interventions 8-week intervention (2013) involved: classes choosing weekly activities encouraged by mentors (older adolescents) and in-class peer leaders. Students gain points for trying activities which are entered into an intramural competition. Primary and secondary outcome measures Planned quantitative (questionnaire) and qualitative (focus groups) process evaluation addressed enjoyment, confidence, participation, suggested improvements. Outcomes were assessed at baseline and follow-up (week 8) in pilot CRCT and included accelerometer-assessed MVPA; adolescent-reported activity type, well-being, peer support, shyness, sociability. Analysis of covariance was used to assess preliminary effectiveness as change in MVPA adjusted for baseline. Results All year 9 students in intervention schools were exposed to the intervention; over all schools 77% of eligible students were measured. 71% boys and 74% girls found GoActive ‘fun’; 38% boys and 32% girls said it increased confidence, and 64% boys and 59% girls said they would continue with a GoActive activity. Suggested improvements included more mentorship; improved training; streamlined points recording. Pilot results indicated potential effectiveness ((adjusted mean difference (95% CI) p value; MVPA mins; 5.1 (1.1 to 9.2) p=0.014)) and suggest recruitment of 16 schools (2400 adolescents) for a full trial. Compared with control, intervention students reported greater peer support 0.5 (0.1 to 0.9) p=0.03, well-being 1.8 (0.1 to 3.4) p=0.04 but no difference in shyness/sociability. Participation in activity types approached significance (intervention group 2.3 (−0.2 to 4.7) p=0.07 more activity types). Conclusions Results suggest feasibility and indicate potential effectiveness of GoActive to increase MVPA and support a fully powered evaluation of effectiveness and cost-effectiveness. Process evaluation data were used to refine GoActive prior to a full trial. Trial registration number ISRCTN31583496; pre-results. PMID:27836873

TCSC based filtering and improvement of power quality

NASA Astrophysics Data System (ADS)

Arulvendhan, K.; Dilli srinivasan, J.; Vinil, M.

2018-04-01

Thyristor Controlled Series Capacitor (TCSC) as a dynamic system, also its competence in growing power allocation in transmission lines, can be used to improve different power system problems. TCSC’s dissimilar advantages can be categorised as steady-state and transient ones. During a fault, TCSC can increase power quality by reducing the current and benefit to keep the voltage as high as conceivable. In this paper, the application of TCSC to enrich one of the vital power quality issues, i.e., voltage sag is investigated. Different operating modes of TCSC have dissimilar influences on the voltage of the bus that the line armed with TCSC is connected to. Relocating to bypass mode upon manifestation of a fault is a significant feature of TCSC to advance voltage sag. The simulations on a trial network disclose these facts.

Nocturnal temperature controlled laminar airflow for treating atopic asthma: a randomised controlled trial

PubMed Central

Boyle, Robert J; Pedroletti, Christophe; Wickman, Magnus; Bjermer, Leif; Valovirta, Erkka; Dahl, Ronald; Von Berg, Andrea; Zetterström, Olof

2011-01-01

Objective To determine whether environmental control using nocturnal temperature controlled laminar airflow (TLA) treatment could improve the quality of life of patients with persistent atopic asthma. Design Randomised, double-blind, placebo-controlled, parallel-group trial. Setting Nineteen European asthma clinics. Participants 312 patients aged 7–70 with inadequately controlled persistent atopic asthma. Main outcome measure Proportion of patients with an increase of ≥0.5 points in asthma quality of life score after 1 year of treatment. Results TLA devices were successfully installed in the bedrooms of 282 (90%) patients included in the primary efficacy analysis. There was a difference in treatment response rate between active (143 of 189, 76%) and placebo (56 of 92, 61%) groups, difference 14.8% (95% CI 3.1 to 26.5, p=0.02).3 In patients aged ≥12, on whom the study was powered, the difference in response rate was similar-active 106 of 143 (74%), placebo 42 of 70 (60%), difference 14.1% (0.6 to 27.7, p=0.059). There was a difference between groups in fractional exhaled nitric oxide change of −7.1 ppb (−13.6 to −0.7, p=0.03). Active treatment was associated with less increase in cat-specific IgE than placebo. There was no difference in adverse event rates between treatment groups. Conclusion Inhalant exposure reduction with TLA improves quality of life, airway inflammation and systemic allergy in patients with persistent atopic asthma. TLA may be a treatment option for patients with inadequately controlled persistent atopic asthma. Trial registration number Clinical Trials NCT00986323. PMID:22131290

The efficacy of early initiated, supervised, progressive resistance training compared to unsupervised, home-based exercise after unicompartmental knee arthroplasty: a single-blinded randomized controlled trial.

PubMed

Jørgensen, Peter B; Bogh, Søren B; Kierkegaard, Signe; Sørensen, Henrik; Odgaard, Anders; Søballe, Kjeld; Mechlenburg, Inger

2017-01-01

To examine if supervised progressive resistance training was superior to home-based exercise in rehabilitation after unicompartmental knee arthroplasty. Single blinded, randomized clinical trial. Surgery, progressive resistance training and testing was carried out at Aarhus University Hospital and home-based exercise was carried out in the home of the patient. Fifty five patients were randomized to either progressive resistance training or home-based exercise. Patients were randomized to either progressive resistance training (home based exercise five days/week and progressive resistance training two days/week) or control group (home based exercise seven days/week). Preoperative assessment, 10-week (primary endpoint) and one-year follow-up were performed for leg extension power, spatiotemporal gait parameters and knee injury and osteoarthritis outcome score (KOOS). Forty patients (73%) completed 1-year follow-up. Patients in the progressive resistance training group participated in average 11 of 16 training sessions. Leg extension power increased from baseline to 10-week follow-up in progressive resistance training group (progressive resistance training: 0.28 W/kg, P= 0.01, control group: 0.01 W/kg, P=0.93) with no between-group difference. Walking speed and KOOS scores increased from baseline to 10-week follow-up in both groups with no between-group difference (six minutes walk test P=0.63, KOOS P>0.29). Progressive resistance training two days/week combined with home based exercise five days/week was not superior to home based exercise seven days/week in improving leg extension power of the operated leg.

Assessment of power output in jump tests for applicants to a sports sciences degree.

PubMed

Lara, A J; Abián, J; Alegre, L M; Jiménez, L; Aguado, X

2006-09-01

Our study aimed: 1) to describe the jump performance in a population of male applicants to a Faculty of Sports Sciences, 2) to apply different power equations from the literature to assess their accuracy, and 3) to develop a new regression equation from this population. The push off phases of the counter-movement jumps (CMJ) on a force platform of 161 applicants (age: 19+/-2.9 years; weight: 70.4+/-8.3 kg) to a Spanish Faculty of Sports Sciences were recorded and subsequently analyzed. Their hands had to be placed on the hips and the knee angle during the counter movement was not controlled. Each subject had 2 trials to reach a minimum of 29 cm of jump height, and when 2 jumps were performed the best trial was analyzed. Multiple regression analysis was performed to develop a new regression equation. Mean jump height was 34.6+/-4.3 cm, peak vertical force 1 663.9+/-291.1 N and peak power 3524.4+/-562 W. All the equations underestimated power, from 74% (Lewis) to 8% (Sayers). However, there were high and significant correlations between peak power measured on the force platform, and those assessed by the equations. The results of the present study support the development of power equations for specific populations, to achieve more accurate assessments. The power equation from this study [Power = (62.5 x jump height (cm)) + (50.3 x body mass (kg)) 2184.7] can be used accurately in populations of male physical education students.

Gaining power and precision by using model-based weights in the analysis of late stage cancer trials with substantial treatment switching.

PubMed

Bowden, Jack; Seaman, Shaun; Huang, Xin; White, Ian R

2016-04-30

In randomised controlled trials of treatments for late-stage cancer, it is common for control arm patients to receive the experimental treatment around the point of disease progression. This treatment switching can dilute the estimated treatment effect on overall survival and impact the assessment of a treatment's benefit on health economic evaluations. The rank-preserving structural failure time model of Robins and Tsiatis (Comm. Stat., 20:2609-2631) offers a potential solution to this problem and is typically implemented using the logrank test. However, in the presence of substantial switching, this test can have low power because the hazard ratio is not constant over time. Schoenfeld (Biometrika, 68:316-319) showed that when the hazard ratio is not constant, weighted versions of the logrank test become optimal. We present a weighted logrank test statistic for the late stage cancer trial context given the treatment switching pattern and working assumptions about the underlying hazard function in the population. Simulations suggest that the weighted approach can lead to large efficiency gains in either an intention-to-treat or a causal rank-preserving structural failure time model analysis compared with the unweighted approach. Furthermore, violation of the working assumptions used in the derivation of the weights only affects the efficiency of the estimates and does not induce bias or inflate the type I error rate. The weighted logrank test statistic should therefore be considered for use as part of a careful secondary, exploratory analysis of trial data affected by substantial treatment switching. ©2015 The Authors. Statistics inMedicine Published by John Wiley & Sons Ltd.

Rationale and design of the Investigator-Steered Project on Intravascular Renal Denervation for Management of Drug-Resistant Hypertension (INSPiRED) trial.

PubMed

Jin, Yu; Jacobs, Lotte; Baelen, Marie; Thijs, Lutgarde; Renkin, Jean; Hammer, Frank; Kefer, Joelle; Petit, Thibault; Verhamme, Peter; Janssens, Stefan; Sinnaeve, Peter; Lengelé, Jean-Philippe; Persu, Alexandre; Staessen, Jan A

2014-06-01

The SYMPLICITY studies showed that renal denervation (RDN) is feasible as novel treatment for resistant hypertension. However, RDN is a costly and invasive procedure, the long-term efficacy and safety of which has not yet been proven. Therefore, we designed the INSPiRED trial to compare the blood pressure lowering efficacy and safety of RDN vs usual medical therapy. INSPiRED is a randomized controlled trial enrolling 240 treatment-resistant hypertensive patients at 16 expert hypertension centres in Belgium. Eligible patients, aged 20-69 years old, have a 24-h ambulatory blood pressure of 130 mmHg systolic or 80 mmHg diastolic or more, while taking at least three antihypertensive drugs. They are randomized to RDN (EnligHTN(TM), SJM system) plus usual care (intervention group) or usual care alone (control group) in a ratio of 1:1. The primary endpoints for efficacy and safety, measured after 6 months, are the baseline-adjusted between-group differences in 24h systolic blood pressure and in glomerular filtration rate as estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. Follow-up will continue up to 36 months after randomization. INSPiRED is powered to demonstrate a 10-mmHg difference in systolic blood pressure between randomized groups with a two-sided p-value of 0.01 and 90% power. It will generate long-term efficacy and safety data, identify the subset of treatment-resistant hypertensive patients responsive to RDN, provide information on cost-effectiveness, and by doing so INSPiRED will inform guideline committees and health policy makers. ClinicalTrials.gov Identifier: NCT 01505010.

Effect of the combination of ginseng, oriental bezoar and glycyrrhiza on autonomic nervous activity and immune system under mental arithmetic stress.

PubMed

Zheng, Aisong; Moritani, Toshio

2008-06-01

Stress reduces physical and mental tolerances (immune potential) of humans and it induces progression of existing illness or causes latent disorders to become active. Thus, the control and suppression of stress plays an important role in the improvement of quality of life and prevention of diseases. Ginseng, oriental bezoar and glycyrrhiza have been used for Kampo (herbal treatment) for thousand years and a number of pharmacological and clinical studies have reported their effects. However, it has not been previously described how the combination of these most commonly used herbs affect mental stress. This is a randomized, double-blind, placebo-controlled experiment to examine the effectiveness of reducing stress response by taking Kampo. Ten healthy males (mean age 27+/-1) participated in the study. The effectiveness of stress reduction was assessed by measuring ECG, salivary chromogranin A (CgA), blood glucose, WBC, granulocytes, lymphocytes, NK cell activity, etc. Salivary and blood measurement values of pre- and post-mental arithmetic stress were compared. In addition, ECG measurement values of pre- and mid-mental arithmetic stress were compared. we observed a higher HF power and a lower SNS index, HR, CgA, WBC and granulocytes in the Kampo trial than those in the placebo trial. The HR, HF power and SNS index were changed significantly (p<0.05) and CgA, WBC and granulocytes tended to show some differences between the two trials (p<0.1). However, blood glucose, lymphocytes, and NK cell activity showed no significant differences between the Kampo and placebo trials. The result suggests that the Kampo should be useful in reducing mental stress.

Participant recruitment into a randomised controlled trial of exercise therapy for people with multiple sclerosis.

PubMed

Carter, Anouska; Humphreys, Liam; Snowdon, Nicky; Sharrack, Basil; Daley, Amanda; Petty, Jane; Woodroofe, Nicola; Saxton, John

2015-10-15

The success of a clinical trial is often dependant on whether recruitment targets can be met in the required time frame. Despite an increase in research into the benefits of exercise in people with multiple sclerosis (PwMS), no trial has reported detailed data on effective recruitment strategies for large-scale randomised controlled trials. The main purpose of this report is to provide a detailed outline of recruitment strategies, rates and estimated costs in the Exercise Intervention for Multiple Sclerosis (ExIMS) trial to identify best practices for future trials involving multiple sclerosis (MS) patient recruitment. The ExIMS researchers recruited 120 PwMS to participate in a 12-week exercise intervention. Participants were randomly allocated to either exercise or usual-care control groups. Participants were sedentary, aged 18-65 years and had Expanded Disability Status Scale scores of 1.0-6.5. Recruitment strategies included attendance at MS outpatient clinics, consultant mail-out and trial awareness-raising activities. A total of 120 participants were recruited over the course of 34 months. To achieve this target, 369 potentially eligible and interested participants were identified. A total of 60 % of participants were recruited via MS clinics, 29.2 % from consultant mail-outs and 10.8 % through trial awareness. The randomisation yields were 33.2 %, 31.0 % and 68.4 % for MS clinic, consultant mail-outs and trial awareness strategies, respectively. The main reason for ineligibility was being too active (69.2 %), whilst for eligible participants the most common reason for non-participation was the need to travel to the study site (15.8 %). Recruitment via consultant mail-out was the most cost-effective strategy, with MS clinics being the most time-consuming and most costly. To reach recruitment targets in a timely fashion, a variety of methods were employed. Although consultant mail-outs were the most cost-effective recruitment strategy, use of this method alone would not have allowed us to obtain the predetermined number of participants in the required time period, thus leading to costly extensions of the project or failure to reach the number of participants required for sufficient statistical power. Thus, a multifaceted approach to recruitment is recommended for future trials. International Standard Randomised Controlled Trial Registry number: ISRCTN41541516 ; date registered: 5 February 2009.

Selective outcome reporting and sponsorship in randomized controlled trials in IVF and ICSI.

PubMed

Braakhekke, M; Scholten, I; Mol, F; Limpens, J; Mol, B W; van der Veen, F

2017-10-01

Are randomized controlled trials (RCTs) on IVF and ICSI subject to selective outcome reporting and is this related to sponsorship? There are inconsistencies, independent from sponsorship, in the reporting of primary outcome measures in the majority of IVF and ICSI trials, indicating selective outcome reporting. RCTs are subject to bias at various levels. Of these biases, selective outcome reporting is particularly relevant to IVF and ICSI trials since there is a wide variety of outcome measures to choose from. An established cause of reporting bias is sponsorship. It is, at present, unknown whether RCTs in IVF/ICSI are subject to selective outcome reporting and whether this is related with sponsorship. We systematically searched RCTs on IVF and ICSI published between January 2009 and March 2016 in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the publisher subset of PubMed. We analysed 415 RCTs. Per included RCT, we extracted data on impact factor of the journal, sample size, power calculation, and trial registry and thereafter data on primary outcome measure, the direction of trial results and sponsorship. Of the 415 identified RCTs, 235 were excluded for our primary analysis, because the sponsorship was not reported. Of the 180 RCTs included in our analysis, 7 trials did not report on any primary outcome measure and 107 of the remaining 173 trials (62%) reported on surrogate primary outcome measures. Of the 114 registered trials, 21 trials (18%) provided primary outcomes in their manuscript that were different from those in the trial registry. This indicates selective outcome reporting. We found no association between selective outcome reporting and sponsorship. We ran additional analyses to include the trials that had not reported sponsorship and found no outcomes that differed from our primary analysis. Since the majority of the trials did not report on sponsorship, there is a risk on sampling bias. IVF and ICSI trials are subject, to a large extent, to selective outcome reporting. Readers should be aware of this to avoid implementation of false or misleading results in clinical practice. No funding received and there are no conflicts of interest. N/A. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

P-value interpretation and alpha allocation in clinical trials.

PubMed

Moyé, L A

1998-08-01

Although much value has been placed on type I error event probabilities in clinical trials, interpretive difficulties often arise that are directly related to clinical trial complexity. Deviations of the trial execution from its protocol, the presence of multiple treatment arms, and the inclusion of multiple end points complicate the interpretation of an experiment's reported alpha level. The purpose of this manuscript is to formulate the discussion of P values (and power for studies showing no significant differences) on the basis of the event whose relative frequency they represent. Experimental discordance (discrepancies between the protocol's directives and the experiment's execution) is linked to difficulty in alpha and beta interpretation. Mild experimental discordance leads to an acceptable adjustment for alpha or beta, while severe discordance results in their corruption. Finally, guidelines are provided for allocating type I error among a collection of end points in a prospectively designed, randomized controlled clinical trial. When considering secondary end point inclusion in clinical trials, investigators should increase the sample size to preserve the type I error rates at acceptable levels.

Acceptance and Commitment Therapy for Inpatients with Psychosis (the REACH Study): Protocol for Treatment Development and Pilot Testing

PubMed Central

Gaudiano, Brandon A.; Davis, Carter H.; Epstein-Lubow, Gary; Johnson, Jennifer E.; Mueser, Kim T.; Miller, Ivan W.

2017-01-01

Patients with schizophrenia-spectrum disorders frequently require treatment at inpatient hospitals during periods of acute illness for crisis management and stabilization. Acceptance and Commitment Therapy (ACT), a “third wave” cognitive-behavioral intervention that employs innovative mindfulness-based strategies, has shown initial efficacy in randomized controlled trials for improving acute and post-discharge outcomes in patients with psychosis when studied in acute-care psychiatric hospitals in the U.S. However, the intervention has not been widely adopted in its current form because of its use of an individual-only format and delivery by doctoral-level research therapists with extensive prior experience using ACT. The aim of the Researching the Effectiveness of Acceptance-based Coping during Hospitalization (REACH) Study is to adapt a promising acute-care psychosocial treatment for inpatients with psychosis, and to pilot test its effectiveness in a routine inpatient setting. More specifically, we describe our plans to: (a) further develop and refine the treatment and training protocols, (b) conduct an open trial and make further modifications based on the experience gained, and (c) conduct a pilot randomized controlled trial in preparation for a future fully-powered clinical trial testing the effectiveness of ACT. PMID:28475123

Power output measurement during treadmill cycling.

PubMed

Coleman, D A; Wiles, J D; Davison, R C R; Smith, M F; Swaine, I L

2007-06-01

The study aim was to consider the use of a motorised treadmill as a cycling ergometry system by assessing predicted and recorded power output values during treadmill cycling. Fourteen male cyclists completed repeated cycling trials on a motorised treadmill whilst riding their own bicycle fitted with a mobile ergometer. The speed, gradient and loading via an external pulley system were recorded during 20-s constant speed trials and used to estimate power output with an assumption about the contribution of rolling resistance. These values were then compared with mobile ergometer measurements. To assess the reliability of measured power output values, four repeated trials were conducted on each cyclist. During level cycling, the recorded power output was 257.2 +/- 99.3 W compared to the predicted power output of 258.2 +/- 99.9 W (p > 0.05). For graded cycling, there was no significant difference between measured and predicted power output, 268.8 +/- 109.8 W vs. 270.1 +/- 111.7 W, p > 0.05, SEE 1.2 %. The coefficient of variation for mobile ergometer power output measurements during repeated trials ranged from 1.5 % (95 % CI 1.2 - 2.0 %) to 1.8 % (95 % CI 1.5 - 2.4 %). These results indicate that treadmill cycling can be used as an ergometry system to assess power output in cyclists with acceptable accuracy.

Towards the application of one-dimensional sonomyography for powered upper-limb prosthetic control using machine learning models.

PubMed

Guo, Jing-Yi; Zheng, Yong-Ping; Xie, Hong-Bo; Koo, Terry K

2013-02-01

The inherent properties of surface electromyography limit its potential for multi-degrees of freedom control. Our previous studies demonstrated that wrist angle could be predicted by muscle thickness measured from B-mode ultrasound, and hence, it could be an alternative signal for prosthetic control. However, an ultrasound imaging machine is too bulky and expensive. We aim to utilize a portable A-mode ultrasound system to examine the feasibility of using one-dimensional sonomyography (i.e. muscle thickness signals detected by A-mode ultrasound) to predict wrist angle with three different machine learning models - (1) support vector machine (SVM), (2) radial basis function artificial neural network (RBF ANN), and (3) back-propagation artificial neural network (BP ANN). Feasibility study using nine healthy subjects. Each subject performed wrist extension guided at 15, 22.5, and 30 cycles/minute, respectively. Data obtained from 22.5 cycles/minute trials was used to train the models and the remaining trials were used for cross-validation. Prediction accuracy was quantified by relative root mean square error (RMSE) and correlation coefficients (CC). Excellent prediction was noted using SVM (RMSE = 13%, CC = 0.975), which outperformed the other methods. It appears that one-dimensional sonomyography could be an alternative signal for prosthetic control. Clinical relevance Surface electromyography has inherent limitations that prohibit its full functional use for prosthetic control. Research that explores alternative signals to improve prosthetic control (such as the one-dimensional sonomyography signals evaluated in this study) may revolutionize powered prosthesis design and ultimately benefit amputee patients.

Variation in neurophysiological function and evidence of quantitative electroencephalogram discordance: predicting cocaine-dependent treatment attrition.

PubMed

Venneman, Sandy; Leuchter, Andrew; Bartzokis, George; Beckson, Mace; Simon, Sara L; Schaefer, Melodie; Rawson, Richard; Newton, Tom; Cook, Ian A; Uijtdehaage, Sebastian; Ling, Walter

2006-01-01

Cocaine treatment trials suffer from a high rate of attrition. We examined pretreatment neurophysiological factors to identify participants at greatest risk. Twenty-five participants were divided into concordant and discordant groups following electroencephalogram (EEG) measures recorded prior to a double-blind, placebo-controlled treatment trial. Three possible outcomes were examined: successful completion, dropout, and removal. Concordant (high perfusion correlate) participants had an 85% rate of successful completion, while discordant participants had a 15% rate of successful completion. Twenty-five percent of dropouts and 50% of participants removed were discordant (low perfusion correlate), while only 25% of those who completed were discordant. Failure to complete the trial was not explained by depression, craving, benzoylecgonine levels or quantitative electroencephalogram (QEEG) power; thus cordance may help identify attrition risk.

Short-term creatine supplementation has no impact on upper-body anaerobic power in trained wrestlers.

PubMed

Aedma, Martin; Timpmann, Saima; Lätt, Evelin; Ööpik, Vahur

2015-01-01

Creatine (CR) is considered an effective nutritional supplement having ergogenic effects, which appears more pronounced in upper-body compared to lower-body exercise. Nevertheless, results regarding the impact of CR loading on repeated high-intensity arm-cranking exercise are scarce and in some cases conflicting. Interestingly, few of the conducted studies have structured their research designs to mimic real world sporting events. Therefore, our purpose was to address the hypothesis that CR ingestion would increase anaerobic power output in consecutive upper-body intermittent sprint performance (UBISP) tests designed to simulate wrestling matches on a competition-day. In a double-blind, placebo-controlled, parallel-group study, 20 trained wrestlers were assigned to either placebo or CR supplemented group (0.3 g ∙ kg(-1) of body mass per day). Four 6-min UBISP tests interspersed with 30-min recovery periods were performed before (trial 1) and after 5 days (trial 2) of supplementation. Each test consisted of six 15-s periods of arm-cranking at maximal executable cadence against resistance of 0.04 kg ∙ kg(-1) body mass interspersed with 40-s unloaded easy cranking periods and 5-s acceleration intervals (T1-T4). Mean power (MP), peak power (PP), fatigue index and heart rate parameters were measured during UBISP tests. Also, body weight and hydration status were assessed. Principle measures were statistical analysed with mixed-model ANOVAs. Mean individual CR consumption in the CR group was 24.8 ± 2.5 g ∙ d(-1). No significant (P > 0.05) differences occurred in body mass or hydration status indices between the groups or across trials. MP, PP and fatigue index responses were unaffected by supplementation; although, a significant reduction in MP and PP did occurred from T1 to T4 in both trial 1 and 2 (P < 0.001). Overall heart rate responses in the tests tended to be higher in the CR than PLC group (P < 0.05); but, trends in responses in trials and tests were comparable (P > 0.05). These results suggest that 5-day CR supplementation has no impact on upper-body muscle anaerobic power output in consecutive UBISP anaerobic tests mimicking wrestling matches on a competition day.

Automatic Setting Procedure for Exoskeleton-Assisted Overground Gait: Proof of Concept on Stroke Population

PubMed Central

Gandolla, Marta; Guanziroli, Eleonora; D'Angelo, Andrea; Cannaviello, Giovanni; Molteni, Franco; Pedrocchi, Alessandra

2018-01-01

Stroke-related locomotor impairments are often associated with abnormal timing and intensity of recruitment of the affected and non-affected lower limb muscles. Restoring the proper lower limbs muscles activation is a key factor to facilitate recovery of gait capacity and performance, and to reduce maladaptive plasticity. Ekso is a wearable powered exoskeleton robot able to support over-ground gait training. The user controls the exoskeleton by triggering each single step during the gait cycle. The fine-tuning of the exoskeleton control system is crucial—it is set according to the residual functional abilities of the patient, and it needs to ensure lower limbs powered gait to be the most physiological as possible. This work focuses on the definition of an automatic calibration procedure able to detect the best Ekso setting for each patient. EMG activity has been recorded from Tibialis Anterior, Soleus, Rectus Femoris, and Semitendinosus muscles in a group of 7 healthy controls and 13 neurological patients. EMG signals have been processed so to obtain muscles activation patterns. The mean muscular activation pattern derived from the controls cohort has been set as reference. The developed automatic calibration procedure requires the patient to perform overground walking trials supported by the exoskeleton while changing parameters setting. The Gait Metric index is calculated for each trial, where the closer the performance is to the normative muscular activation pattern, in terms of both relative amplitude and timing, the higher the Gait Metric index is. The trial with the best Gait Metric index corresponds to the best parameters set. It has to be noted that the automatic computational calibration procedure is based on the same number of overground walking trials, and the same experimental set-up as in the current manual calibration procedure. The proposed approach allows supporting the rehabilitation team in the setting procedure. It has been demonstrated to be robust, and to be in agreement with the current gold standard (i.e., manual calibration performed by an expert engineer). The use of a graphical user interface is a promising tool for the effective use of an automatic procedure in a clinical context. PMID:29615890

Gender-transformative Bandebereho couples’ intervention to promote male engagement in reproductive and maternal health and violence prevention in Rwanda: Findings from a randomized controlled trial

PubMed Central

Barker, Gary; Bastian, Gautam G.; Bingenheimer, Jeffrey B.; Kazimbaya, Shamsi; Nzabonimpa, Anicet; Pulerwitz, Julie; Sayinzoga, Felix; Sharma, Vandana; Shattuck, Dominick

2018-01-01

Background Rigorous evidence of the effectiveness of male engagement interventions, particularly on how these interventions impact relationship power dynamics and women’s decision-making, remains limited. This study assessed the impact of the Bandebereho gender-transformative couples’ intervention on impact on multiple behavioral and health-related outcomes influenced by gender norms and power relations. Methods We conducted a multi-site randomised controlled trial in four Rwandan districts with expectant/current fathers and their partners, who were randomised to the intervention (n = 575 couples) or control group (n = 624 couples). Primary outcomes include women’s experience of physical and sexual IPV, women’s attendance and men’s accompaniment at ANC, modern contraceptive use, and partner support during pregnancy. At 21-months post-baseline, 1123 men and 1162 partners were included in intention to treat analysis. Generalized estimating equations with robust standard errors were used to fit the models. Findings The Bandebereho intervention led to substantial improvements in multiple reported outcomes. Compared to the control group, women in the intervention group reported: less past-year physical (OR 0.37, p<0.001) and sexual IPV (OR 0.34, p<0.001); and greater attendance (IRR 1.09, p<0.001) and male accompaniment at antenatal care (IRR 1.50, p<0.001); and women and men in the intervention group reported: less child physical punishment (women: OR 0.56, p = 0.001; men: OR 0.66, p = 0.005); greater modern contraceptive use (women: OR 1.53, p = 0.004; men: OR 1.65, p = 0.001); higher levels of men’s participation in childcare and household tasks (women: beta 0.39, p<0.001; men: beta 0.33, p<0.001); and less dominance of men in decision-making. Conclusions Our study strengthens the existing evidence on male engagement approaches; together with earlier studies our findings suggest that culturally adapted gender-transformative interventions with men and couples can be effective at changing deeply entrenched gender inequalities and a range of health-related behavioral outcomes. Trial registration ClinicalTrials.gov NCT02694627 PMID:29617375

Automatic Setting Procedure for Exoskeleton-Assisted Overground Gait: Proof of Concept on Stroke Population.

PubMed

Gandolla, Marta; Guanziroli, Eleonora; D'Angelo, Andrea; Cannaviello, Giovanni; Molteni, Franco; Pedrocchi, Alessandra

2018-01-01

Stroke-related locomotor impairments are often associated with abnormal timing and intensity of recruitment of the affected and non-affected lower limb muscles. Restoring the proper lower limbs muscles activation is a key factor to facilitate recovery of gait capacity and performance, and to reduce maladaptive plasticity. Ekso is a wearable powered exoskeleton robot able to support over-ground gait training. The user controls the exoskeleton by triggering each single step during the gait cycle. The fine-tuning of the exoskeleton control system is crucial-it is set according to the residual functional abilities of the patient, and it needs to ensure lower limbs powered gait to be the most physiological as possible. This work focuses on the definition of an automatic calibration procedure able to detect the best Ekso setting for each patient. EMG activity has been recorded from Tibialis Anterior, Soleus, Rectus Femoris, and Semitendinosus muscles in a group of 7 healthy controls and 13 neurological patients. EMG signals have been processed so to obtain muscles activation patterns. The mean muscular activation pattern derived from the controls cohort has been set as reference. The developed automatic calibration procedure requires the patient to perform overground walking trials supported by the exoskeleton while changing parameters setting. The Gait Metric index is calculated for each trial, where the closer the performance is to the normative muscular activation pattern, in terms of both relative amplitude and timing, the higher the Gait Metric index is. The trial with the best Gait Metric index corresponds to the best parameters set. It has to be noted that the automatic computational calibration procedure is based on the same number of overground walking trials, and the same experimental set-up as in the current manual calibration procedure. The proposed approach allows supporting the rehabilitation team in the setting procedure. It has been demonstrated to be robust, and to be in agreement with the current gold standard (i.e., manual calibration performed by an expert engineer). The use of a graphical user interface is a promising tool for the effective use of an automatic procedure in a clinical context.

Impact of rapid antigen detection testing on antibiotic prescription in acute pharyngitis in adults. FARINGOCAT STUDY: a multicentric randomized controlled trial

PubMed Central

2010-01-01

Background Acute pharyngitis is one of the most frequent consultations to the general practitioner and in most of the cases an antibiotic is prescribed in primary care in Spain. Bacterial etiology, mainly by group A beta-hemolytic streptococcus (GABHS), accounts for 10-20% of all these infections in adults. The purpose of this study is to assess the impact of rapid antigen detection testing (RADT) to identify GABHS in acute pharyngitis on the utilization of antibiotics in primary care. Methods/design Multicentric randomized controlled trial in which antibiotic prescription between two groups of patients with acute pharyngitis will be compared. The trial will include two arms, a control and an intervention group in which RADT will be performed. The primary outcome measure will be the proportion of inappropriate antibiotic prescription in each group. Two hundred seventy-six patients are required to detect a reduction in antibiotic prescription from 85% in the control group to 75% in the intervention group with a power of 90% and a level of significance of 5%. Secondary outcome measures will be specific antibiotic treatment, antibiotic resistance rates, secondary effects, days without working, medical visits during the first month and patient satisfaction. Discussion The implementation of RADT would allow a more rational use of antibiotics and would prevent adverse effects of antibiotics, emergence of antibiotic resistance and the growth of inefficient health expenses. Trial registration ISRCTN23587778 PMID:20331895

Performance Evaluation of a Lower Limb Exoskeleton for Stair Ascent and Descent with Paraplegia*

PubMed Central

Farris, Ryan J.; Quintero, Hugo A.; Goldfarb, Michael

2013-01-01

This paper describes the application of a powered lower limb exoskeleton to aid paraplegic individuals in stair ascent and descent. A brief description of the exoskeleton hardware is provided along with an explanation of the control methodology implemented to allow stair ascent and descent. Tests were performed with a paraplegic individual (T10 complete injury level) and data is presented from multiple trials, including the hip and knee joint torque and power required to perform this functionality. Joint torque and power requirements are summarized, including peak hip and knee joint torque requirements of 0.75 Nm/kg and 0.87 Nm/kg, respectively, and peak hip and knee joint power requirements of approximately 0.65 W/kg and 0.85 W/kg, respectively. PMID:23366287

A cluster randomised feasibility trial evaluating six-month nutritional interventions in the treatment of malnutrition in care home-dwelling adults: recruitment, data collection and protocol.

PubMed

Stow, Ruth; Rushton, Alison; Ives, Natalie; Smith, Christina; Rick, Caroline

2015-01-01

Protein energy malnutrition predisposes individuals to disease, delays recovery from illness and reduces quality of life. Care home residents are especially vulnerable, with an estimated 30%-42% at risk. There is no internationally agreed protocol for the nutritional treatment of malnutrition in the care home setting. Widely used techniques include food-based intervention and/or the use of prescribed oral nutritional supplements, but a trial comparing the efficacy of interventions is necessary. In order to define outcomes and optimise the design for an adequately powered, low risk of bias cluster randomised controlled trial, a feasibility trial with 6-month intervention is being run, to assess protocol procedures, recruitment and retention rates, consent processes and resident and staff acceptability. Trial recruitment began in September 2013 and concluded in December 2013. Six privately run care homes in Solihull, England, were selected to establish feasibility within different care home types. Residents with or at risk of malnutrition with no existing dietetic intervention in place were considered for receipt of the allocated intervention. Randomisation took place at the care home level, using a computer-generated random number list to allocate each home to either a dietetic intervention arm (food-based or prescribed supplements) or the standard care arm, continued for 6 months. Dietetic intervention aimed to increase daily calorie intake by 600 kcal and protein by 20-25 g. The primary outcomes will be trial feasibility and acceptability of trial design and allocated interventions. A range of outcome assessments and data collection tools will be evaluated for feasibility, including change in nutrient intake, anthropometric parameters and patient-centric measures, such as quality of life and self-perceived appetite. The complexities inherent in care home research has resulted in the under representation of this population in research trials. The results of this feasibility trial will be used to inform the development and design of a future cluster randomised controlled trial to compare food-based intervention with prescribed oral nutritional supplements (ONS) in the treatment of malnutrition within the care home population. Current Controlled Trials ISRCTN38047922.

MEDUCATE trial: effectiveness of an intensive EDUCATional intervention for IT-mediated MEDication management in the outpatient clinic - study protocol for a cluster randomized controlled trial.

PubMed

van Stiphout, F; Zwart-van Rijkom, J E F; Aarts, J E C M; Koffijberg, H; Klarenbeek-deJonge, E; Krulder, M; Roes, K C B; Egberts, A C G; ter Braak, E W M T

2015-05-22

Using information technology for medication management is an opportunity to help physicians to improve the quality of their documentation and communication and ultimately to improve patient care and patient safety. Physician education is necessary to take full advantage of information technology systems. In this trial, we seek to determine the effectiveness of an intensive educational intervention compared with the standard approach in improving information technology-mediated medication management and in reducing potential adverse drug events in the outpatient clinic. We are conducting a multicenter, cluster randomized controlled trial. The participants are specialists and residents working in the outpatient clinic of internal medicine, cardiology, pulmonology, geriatrics, gastroenterology and rheumatology. The intensive educational intervention is composed of a small-group session and e-learning. The primary outcome is discrepancies between registered medication (by physicians) and actually used medication (by patients). The key secondary outcomes are potential adverse events caused by missed drug-drug interactions. The primary and key secondary endpoints are being assessed shortly after the educational intervention is completed. Sample size will be calculated to ensure sufficient power. A sample size of 40 physicians per group and 20 patients per physician will ensure a power of >90 %, which means we will need a total of 80 physicians and 1,600 patients. We performed an exploratory trial wherein we tested the recruitment process, e-learning, time schedule, and methods for data collection, data management and data analysis. Accordingly, we refined the processes and content: the recruitment strategy was intensified, extra measures were taken to facilitate smooth conductance of the e-learning and parts were made optional. First versions of the procedures for data collection were determined. Data entry and analysis was further standardized by using the G-standard database in the telephone questionnaire. ISRCTN registry: ISRCTN50890124 . Registered 10 June 2013.

The Diabetes Manual trial protocol – a cluster randomized controlled trial of a self-management intervention for type 2 diabetes [ISRCTN06315411

PubMed Central

Sturt, Jackie; Hearnshaw, Hilary; Farmer, Andrew; Dale, Jeremy; Eldridge, Sandra

2006-01-01

Background The Diabetes Manual is a type 2 diabetes self-management programme based upon the clinically effective 'Heart Manual'. The 12 week programme is a complex intervention theoretically underpinned by self-efficacy theory. It is a one to one intervention meeting United Kingdom requirements for structured diabetes-education and is delivered within routine primary care. Methods/design In a two-group cluster randomized controlled trial, GP practices are allocated by computer minimisation to an intervention group or a six-month deferred intervention group. We aim to recruit 250 participants from 50 practices across central England. Eligibility criteria are adults able to undertake the programme with type 2 diabetes, not taking insulin, with HbA1c over 8% (first 12 months) and following an agreed protocol change over 7% (months 13 to 18). Following randomisation, intervention nurses receive two-day training and delivered the Diabetes Manual programme to participants. Deferred intervention nurses receive the training following six-month follow-up. Primary outcome is HbA1c with total and HDL cholesterol; blood pressure, body mass index; self-efficacy and quality of life as additional outcomes. Primary analysis is between-group HbA1c differences at 6 months powered to give 80% power to detect a difference in HbA1c of 0.6%. A 12 month cohort analysis will assess maintenance of effect and assess relationship between self-efficacy and outcomes, and a qualitative study is running alongside. Discussion This trial incorporates educational and psychological diabetes interventions into a single programme and assesses both clinical and psychosocial outcomes. The trial will increase our understanding of intervention transferability between conditions, those diabetes related health behaviours that are more or less susceptible to change through efficacy enhancing mechanisms and how this impacts on clinical outcomes. PMID:16846517

The Diabetes Manual trial protocol - a cluster randomized controlled trial of a self-management intervention for type 2 diabetes [ISRCTN06315411].

PubMed

Sturt, Jackie; Hearnshaw, Hilary; Farmer, Andrew; Dale, Jeremy; Eldridge, Sandra

2006-07-17

The Diabetes Manual is a type 2 diabetes self-management programme based upon the clinically effective 'Heart Manual'. The 12 week programme is a complex intervention theoretically underpinned by self-efficacy theory. It is a one to one intervention meeting United Kingdom requirements for structured diabetes-education and is delivered within routine primary care. In a two-group cluster randomized controlled trial, GP practices are allocated by computer minimisation to an intervention group or a six-month deferred intervention group. We aim to recruit 250 participants from 50 practices across central England. Eligibility criteria are adults able to undertake the programme with type 2 diabetes, not taking insulin, with HbA1c over 8% (first 12 months) and following an agreed protocol change over 7% (months 13 to 18). Following randomisation, intervention nurses receive two-day training and delivered the Diabetes Manual programme to participants. Deferred intervention nurses receive the training following six-month follow-up. Primary outcome is HbA1c with total and HDL cholesterol; blood pressure, body mass index; self-efficacy and quality of life as additional outcomes. Primary analysis is between-group HbA1c differences at 6 months powered to give 80% power to detect a difference in HbA1c of 0.6%. A 12 month cohort analysis will assess maintenance of effect and assess relationship between self-efficacy and outcomes, and a qualitative study is running alongside. This trial incorporates educational and psychological diabetes interventions into a single programme and assesses both clinical and psychosocial outcomes. The trial will increase our understanding of intervention transferability between conditions, those diabetes related health behaviours that are more or less susceptible to change through efficacy enhancing mechanisms and how this impacts on clinical outcomes.

Selection and quantification of infection endpoints for trials of vaccines against intestinal helminths

PubMed Central

Alexander, Neal; Cundill, Bonnie; Sabatelli, Lorenzo; Bethony, Jeffrey M.; Diemert, David; Hotez, Peter; Smith, Peter G.; Rodrigues, Laura C.; Brooker, Simon

2011-01-01

Vaccines against human helminths are being developed but the choice of optimal parasitological endpoints and effect measures to assess their efficacy has received little attention. Assuming negative binomial distributions for the parasite counts, we rank the statistical power of three measures of efficacy: ratio of mean parasite intensity at the end of the trial, the odds ratio of infection at the end of the trial, and the rate ratio of incidence of infection during the trial. We also use a modelling approach to estimate the likely impact of trial interventions on the force of infection, and hence statistical power. We conclude that (1) final mean parasite intensity is a suitable endpoint for later phase vaccine trials, and (2) mass effects of trial interventions are unlikely to appreciably reduce the force of infection in the community – and hence statistical power – unless there is a combination of high vaccine efficacy and a large proportion of the population enrolled. PMID:21435404

Study design and rationale of the 'Balloon-Expandable Cobalt Chromium SCUBA Stent versus Self-Expandable COMPLETE-SE Nitinol Stent for the Atherosclerotic ILIAC Arterial Disease (SENS-ILIAC Trial) Trial': study protocol for a randomized controlled trial.

PubMed

Choi, Woong Gil; Rha, Seung Woon; Choi, Cheol Ung; Kim, Eung Ju; Oh, Dong Joo; Cho, Yoon Hyung; Park, Sang Ho; Lee, Seung Jin; Hur, Ae Yong; Ko, Young Guk; Park, Sang Min; Kim, Ki Chang; Kim, Joo Han; Kim, Min Woong; Kim, Sang Min; Bae, Jang Ho; Bong, Jung Min; Kang, Won Yu; Seo, Jae Bin; Jung, Woo Yong; Cho, Jang Hyun; Kim, Do Hoi; Ahn, Ji Hoon; Kim, Soo Hyun; Jang, Ji Yong

2016-06-25

The self-expandable COMPLETE™ stent (Medtronic) has greater elasticity, allowing it to regain its shape after the compression force reduces, and has higher trackability, thus is easier to maneuver through tortuous vessels, whereas the balloon-expandable SCUBA™ stent (Medtronic) has higher radial stiffness and can afford more accurate placement without geographic miss, which is important in aortoiliac bifurcation lesions. To date, there have been no randomized control trials comparing efficacy and safety between the self-expanding stent and balloon-expandable stent in advanced atherosclerotic iliac artery disease. The purpose of our study is to examine primary patency (efficacy) and incidence of stent fracture and geographic miss (safety) between two different major representative stents, the self-expanding nitinol stent (COMPLETE-SE™) and the balloon-expanding cobalt-chromium stent (SCUBA™), in stenotic or occlusive iliac arterial lesions. This trial is designed as a prospective, randomized, multicenter trial to demonstrate a noninferiority of SCUBA™ stent to COMPLETE-SE™ stent following balloon angioplasty in iliac arterial lesions, and a total of 280 patients will be enrolled. The primary end point of this study is the rate of primary patency in the treated segment at 12 months after intervention as determined by catheter angiography, computed tomography angiography, or duplex ultrasound. The SENS-ILIAC trial will give powerful insight into whether the stent choice according to deployment mechanics would impact stent patency, geographic miss, or stent fracture in patients undergoing stent implantation in iliac artery lesions. National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT01834495 ), registration date: May 8, 2012.

Rationale for the Assessment of Metoprolol in the Prevention of Vasovagal Syncope in Aging Subjects Trial (POST5).

PubMed

Raj, Satish R; Faris, Peter D; Semeniuk, Lisa; Manns, Braden; Krahn, Andrew D; Morillo, Carlos A; Benditt, David G; Sheldon, Robert S

2016-04-01

Vasovagal syncope (VVS) is a common problem associated with a poor quality of life, which improves when syncope frequency is reduced. Effective pharmacological therapies for VVS are lacking. Metoprolol is a β-adrenergic receptor antagonist that is ineffective in younger patients, but may benefit older (≥40 years) VVS patients. Given the limited therapeutic options, a placebo-controlled clinical trial of metoprolol for the prevention of VVS in older patients is needed. The POST5 is a multicenter, international, randomized, placebo-controlled study of metoprolol in the prevention of VVS in patients ≥40 years old. The primary endpoint is the time to first recurrence of syncope. Patients will be randomized 1:1 to receive metoprolol 25 to 100 mg BID or matching placebo, and followed up for 1 year. Secondary end points include syncope frequency, presyncope, quality of life, and cost analysis. Primary analysis will be intention to treat, with a secondary on-treatment analysis. A sample size of 222, split equally between the groups achieves 85% power to detect a hazard rate of 0.3561 when the event rates are 50% and 30% in the placebo and metoprolol arms. Allowing for 10% dropout, we propose to enroll 248 patients. This study will be the first adequately powered trial to determine whether metoprolol is effective in preventing VVS in patients ≥40 years. If effective, metoprolol may become the first line pharmacological therapy for these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

A study protocol of a randomised controlled trial incorporating a health economic analysis to investigate if additional allied health services for rehabilitation reduce length of stay without compromising patient outcomes.

PubMed

Taylor, Nicholas F; Brusco, Natasha K; Watts, Jennifer J; Shields, Nora; Peiris, Casey; Sullivan, Natalie; Kennedy, Genevieve; Teo, Cheng Kwong; Farley, Allison; Lockwood, Kylee; Radia-George, Camilla

2010-11-12

Reducing patient length of stay is a high priority for health service providers. Preliminary information suggests additional Saturday rehabilitation services could reduce the time a patient stays in hospital by three days. This large trial will examine if providing additional physiotherapy and occupational therapy services on a Saturday reduces health care costs, and improves the health of hospital inpatients receiving rehabilitation compared to the usual Monday to Friday service. We will also investigate the cost effectiveness and patient outcomes of such a service. A randomised controlled trial will evaluate the effect of providing additional physiotherapy and occupational therapy for rehabilitation. Seven hundred and twelve patients receiving inpatient rehabilitation at two metropolitan sites will be randomly allocated to the intervention group or control group. The control group will receive usual care physiotherapy and occupational therapy from Monday to Friday while the intervention group will receive the same amount of rehabilitation as the control group Monday to Friday plus a full physiotherapy and occupational therapy service on Saturday. The primary outcomes will be patient length of stay, quality of life (EuroQol questionnaire), the Functional Independence Measure (FIM), and health utilization and cost data. Secondary outcomes will assess clinical outcomes relevant to the goals of therapy: the 10 metre walk test, the timed up and go test, the Personal Care Participation Assessment and Resource Tool (PC PART), and the modified motor assessment scale. Blinded assessors will assess outcomes at admission and discharge, and follow up data on quality of life, function and health care costs will be collected at 6 and 12 months after discharge. Between group differences will be analysed with analysis of covariance using baseline measures as the covariate. A health economic analysis will be carried out alongside the randomised controlled trial. This paper outlines the study protocol for the first fully powered randomised controlled trial incorporating a health economic analysis to establish if additional Saturday allied health services for rehabilitation inpatients reduces length of stay without compromising discharge outcomes. If successful, this trial will have substantial health benefits for the patients and for organizations delivering rehabilitation services. Australian and New Zealand Clinical Trials Registry ACTRN12609000973213.

DHA-rich Fish Oil Increases the Omega-3 Index and Lowers the Oxygen Cost of Physiologically Stressful Cycling in Trained Individuals.

PubMed

Hingley, Lachlan; Macartney, Michael J; Brown, Marc A; McLennan, Peter L; Peoples, Gregory E

2017-08-01

Dietary fish oil, providing docosahexaenoic acid (DHA) modulates oxygen consumption and fatigue in animal models. However, in humans predominately supplemented with high eicosapentaenoic acid (EPA), there is no evidence of endurance performance enhancement. Therefore, this study examined if DHA-rich fish oil could improve repeated bouts of physiologically stressful cycling and a subsequent time trial in a state of fatigue. Twenty-six trained males took part in a double-blind study and were supplemented with either 2 × 1g/day soy oil, Control) or DHA-rich tuna fish oil (Nu-Mega) (FO) (560mg DHA / 140mg eicosapentaenoic acid (EPA), for 8 weeks. Maximal cycling power (3 × 6s), isometric quadriceps strength (MVC), Wingate cycling protocol (6 × 30s) and a 5min cycling time-trial were assessed at baseline and eight weeks. The Omega-3 Index was not different at baseline (Control: 4.2 ± 0.2; FO: 4.7 ± 0.2%) and increased in the FO group after eight weeks (Control: 3.9 ± 0.2; FO: 6.3 ± 0.3%, p < .01). There was no effect of DHA-rich fish oil on power output of maximal 6s cycle sprinting (Control: Pre 1100 ± 49 Post 1067 ± 51; FO: Pre 1070 ± 46 Post 1042 ± 46W), during 5min time trail (Control: Pre 267 ± 19 Post 278 ± 20; FO: Pre 253 ± 16 Post 265 ± 16 W) or maximal voluntary contraction force (Control: Pre 273 ± 19 Post 251 ± 19; FO: Pre 287 ± 17 Post 283 ± 16 Nm). Nevertheless, relative oxygen consumption was reduced the FO group during the cycling time trial (Control: -23 ± 26; FO: -154 ± 59ml O2/min/100W p < .05) suggesting improved economy of cycling. We conclude that DHA-rich fish oil, successful at elevating the Omega-3 Index, and reflective of skeletal muscle membrane incorporation, can modulate oxygen consumption during intense exercise.

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF ORAL MATRICARIA RECUTITA (CHAMOMILE) EXTRACT THERAPY OF GENERALIZED ANXIETY DISORDER

PubMed Central

Amsterdam, Jay D.; Li, Yimei; Soeller, Irene; Rockwell, Kenneth; Mao, Jun James; Shults, Justine

2013-01-01

Objective We conducted a randomized, double-blind, placebo-controlled efficacy and tolerability trial of Matricaria recutita (chamomile) extract therapy in patients with mild to moderate Generalized Anxiety Disorder (GAD). We hypothesized that chamomile would be superior to placebo in reducing GAD symptoms with a comparable tolerability profile. Materials & Methods 61 outpatients with mild to moderate GAD were enrolled and 57 were randomized to either double blind chamomile extract (n=28) or placebo (n=29) therapy for 8 weeks. The study was powered to detect a statistically significant and clinically meaningful group difference in change over time in total Hamilton Anxiety Rating (HAM-A) scores. Secondary outcomes included change in the Beck Anxiety Inventory score, Psychological Well Being score, Clinical Global Impression Severity score, and the proportion of patients with ≥50% reduction in baseline HAM-A score. Results We observed a significantly greater reduction in mean total HAM-A score during chamomile versus placebo therapy (p=0.047). Although the study was not powered to identify small to moderate differences in secondary outcomes, we observed a positive change in all secondary outcomes in the same direction as the primary outcome measure. One patient in each treatment group discontinued therapy for adverse events. The proportion of patients experiencing 0, 1, 2, or ≥3 adverse events was not significantly different between groups (p=0.417). Conclusion This is the first, controlled clinical trial of chamomile extract for GAD. The results suggest that chamomile may have modest anxiolytic activity in patients with mild to moderate GAD. Future studies are needed to replicate these observations. PMID:19593179

An Evaluation of Oral Midazolam for Anxiety and Pain in First-Trimester Surgical Abortion: A Randomized Controlled Trial.

PubMed

Bayer, Lisa L; Edelman, Alison B; Fu, Rongwei; Lambert, William E; Nichols, Mark D; Bednarek, Paula H; Miller, Kelsey; Jensen, Jeffrey T

2015-07-01

To estimate the effect of oral midazolam on patient pain and anxiety perception during first-trimester surgical abortion. Between May and December 2013, we conducted a randomized, double-blind, placebo-controlled trial. Patients between 6 0/7 and 10 6/7 weeks of gestation received 10 mg oral midazolam or placebo 30-60 minutes before surgical abortion. All patients received ibuprofen and a paracervical block. We powered the study (power=80%; significance level=.025) to detect a 15-mm difference in our two a priori primary outcomes of pain and anxiety with uterine aspiration on a 100-mm visual analog scale. Secondary outcomes were pain and anxiety at additional time points, memory, satisfaction, side effects, and adverse events. Demographics were similar between groups (placebo=62, midazolam=62). Compared with those randomized to placebo, patients who received midazolam had significantly less anxiety preoperatively (room entry: 51.4 mm compared with 34.5 mm, P<.001; positioning: 56.6 mm compared with 45.4 mm, P=.02). There was no difference in pain (P=.28) or anxiety (P=.14) during uterine aspiration or at other procedural time points. A significantly greater number of patients in the midazolam group reported partial amnesia (31/61 compared with 16/61, P=.005) and dizziness (30/61 compared with 18/61, P=.03). Controlling for baseline differences, patients who received midazolam reported more postoperative sleepiness (P<.001) and less postoperative nausea (P=.004). There was no difference in overall satisfaction (P=.88). Although oral midazolam reduces preprocedural anxiety, it does not reduce pain or anxiety with uterine aspiration during first-trimester surgical abortions. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01830881. I.

Dynamic Changes in Phase-Amplitude Coupling Facilitate Spatial Attention Control in Fronto-Parietal Cortex

PubMed Central

Szczepanski, Sara M.; Crone, Nathan E.; Kuperman, Rachel A.; Auguste, Kurtis I.; Parvizi, Josef; Knight, Robert T.

2014-01-01

Attention is a core cognitive mechanism that allows the brain to allocate limited resources depending on current task demands. A number of frontal and posterior parietal cortical areas, referred to collectively as the fronto-parietal attentional control network, are engaged during attentional allocation in both humans and non-human primates. Numerous studies have examined this network in the human brain using various neuroimaging and scalp electrophysiological techniques. However, little is known about how these frontal and parietal areas interact dynamically to produce behavior on a fine temporal (sub-second) and spatial (sub-centimeter) scale. We addressed how human fronto-parietal regions control visuospatial attention on a fine spatiotemporal scale by recording electrocorticography (ECoG) signals measured directly from subdural electrode arrays that were implanted in patients undergoing intracranial monitoring for localization of epileptic foci. Subjects (n = 8) performed a spatial-cuing task, in which they allocated visuospatial attention to either the right or left visual field and detected the appearance of a target. We found increases in high gamma (HG) power (70–250 Hz) time-locked to trial onset that remained elevated throughout the attentional allocation period over frontal, parietal, and visual areas. These HG power increases were modulated by the phase of the ongoing delta/theta (2–5 Hz) oscillation during attentional allocation. Critically, we found that the strength of this delta/theta phase-HG amplitude coupling predicted reaction times to detected targets on a trial-by-trial basis. These results highlight the role of delta/theta phase-HG amplitude coupling as a mechanism for sub-second facilitation and coordination within human fronto-parietal cortex that is guided by momentary attentional demands. PMID:25157678

Bayesian adaptive trials offer advantages in comparative effectiveness trials: an example in status epilepticus.

PubMed

Connor, Jason T; Elm, Jordan J; Broglio, Kristine R

2013-08-01

We present a novel Bayesian adaptive comparative effectiveness trial comparing three treatments for status epilepticus that uses adaptive randomization with potential early stopping. The trial will enroll 720 unique patients in emergency departments and uses a Bayesian adaptive design. The trial design is compared to a trial without adaptive randomization and produces an efficient trial in which a higher proportion of patients are likely to be randomized to the most effective treatment arm while generally using fewer total patients and offers higher power than an analogous trial with fixed randomization when identifying a superior treatment. When one treatment is superior to the other two, the trial design provides better patient care, higher power, and a lower expected sample size. Copyright © 2013 Elsevier Inc. All rights reserved.

Muscle Power Is an Independent Determinant of Pain and Quality of Life in Knee Osteoarthritis.

PubMed

Reid, Kieran F; Price, Lori Lyn; Harvey, William F; Driban, Jeffrey B; Hau, Cynthia; Fielding, Roger A; Wang, Chenchen

2015-12-01

This study examined the relationships between leg muscle strength, power, and perceived disease severity in subjects with knee osteoarthritis (OA) in order to determine whether dynamic leg extensor muscle power would be associated with pain and quality of life in knee OA. Baseline data on 190 subjects with knee OA (mean ± SD age 60.2 ± 10.4 years, body mass index 32.7 ± 7.2 kg/m(2) ) were obtained from a randomized controlled trial. Knee pain was measured using the Western Ontario and McMaster Universities Osteoarthritis Index, and health-related quality of life was assessed using the Short Form 36 (SF-36). One-repetition maximum (1RM) strength was assessed using the bilateral leg press, and peak muscle power was measured during 5 maximum voluntary velocity repetitions at 40% and 70% of 1RM. In univariate analysis, greater muscle power was significantly associated with pain (r = -0.17, P < 0.02) and also significantly and positively associated with SF-36 physical component summary (PCS) scores (r = 0.16, P < 0.05). After adjustment for multiple covariates, muscle power was a significant independent predictor of pain (P ≤ 0.05) and PCS scores (P ≤ 0.04). However, muscle strength was not an independent determinant of pain or quality of life (P ≥ 0.06). Muscle power is an independent determinant of pain and quality of life in knee OA. Compared to strength, muscle power may be a more clinically important measure of muscle function within this population. New trials to systematically examine the impact of muscle power training interventions on disease severity in knee OA are particularly warranted. © 2015, American College of Rheumatology.

Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

PubMed

Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

2015-08-12

Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 25 June 2015.Date of latest search of all other sources: 10 December 2014. Any randomised or quasi-randomised control trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care. We identified 19 papers, describing 13 unique trials which were potentially eligible for inclusion in the review. However, after assessment, no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found. No randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found. As no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease were found for inclusion in this review, the research evidence for current policy recommendations is limited to non-randomised studies.Information from well-designed, adequately powered, randomised trials is desirable in order to make more robust recommendations for practice. However, such trials must also consider the legal, ethical, and cultural barriers to implementation of preconception genetic risk assessment.

Electroacupuncture for postoperative pain and gastrointestinal motility after laparoscopic appendectomy (AcuLap): study protocol for a randomized controlled trial.

PubMed

Kim, Gangmi

2015-10-14

Acupuncture is a widely serviced complementary medicine. Although acupuncture is suggested for managing postoperative ileus and pain, supporting evidence is weak. The AcuLap trial is designed to provide high-level evidence regarding whether or not electroacupuncture is effective in promoting gastrointestinal motility and controlling pain after laparoscopic surgery. This study is a prospective randomized controlled trial with a three-arm, parallel-group structure evaluating the efficacy of electroacupuncture for gastrointestinal motility and postoperative pain after laparoscopic appendectomy. Patients with appendicitis undergoing laparoscopic surgery are included and randomized into three groups: 1) electroacupuncture group, 2) sham acupuncture group, and 3) control group. Patients receive 1) acupuncture with electrostimulation or 2) fake electroacupuncture with sham device twice a day or 3) no acupuncture after laparoscopic appendectomy. The primary outcome is time to first passing flatus after operation. Secondary outcomes include postoperative pain, analgesics, nausea/vomiting, bowel motility, time to tolerable diet, complications, hospital stay, readmission rates, time to recovery, quality of life, medical costs, and protocol failure rate. Patients and hospital staff (physicians and nurses) are blinded to which group the patient is assigned, electroacupuncture or sham acupuncture. Data analysis personnel are blinded to group assignment among all three groups. Estimated sample size to detect a minimum difference of time to first flatus with 80 % power, 5 % significance, and 10 % drop rate is 29 × 3 groups = 87 patients. Analysis will be performed according to the intention-to-treat principle. The AcuLap trial will provide evidence on the merits and/or demerits of electroacupuncture for bowel motility recovery and pain relief after laparoscopic appendectomy. The trial was registered in Clinical Research Information Service (CRiS), Republic of Korea ( KCT0001486 ) on 14 May 2015.

Slow-release L-Cysteine (Acetium®) Lozenge Is an Effective New Method in Smoking Cessation. A Randomized, Double-blind, Placebo-controlled Intervention.

PubMed

Syrjänen, Kari; Eronen, Katja; Hendolin, Panu; Paloheimo, Lea; Eklund, Carita; Bäckström, Anna; Suovaniemi, Osmo

2017-07-01

Because of the major health problems and annual economic burden caused by cigarette smoking, effective new tools for smoking intervention are urgently needed. Our previous randomized controlled trial (RCT) provided promising results on the efficacy of slow-release L-cysteine lozenge in smoking intervention, but the study was not adequately powered. To confirm in an adequately-powered study the results of the previous RCT implicating that effective elimination of acetaldehyde in saliva by slow-release L-cysteine (Acetium® lozenge, Biohit Oyj, Helsinki), would assist in smoking cessation by reducing acetaldehyde-enhanced nicotine addiction. On this matter, we undertook a double-blind, randomized, placebo-controlled trial comparing Acetium® lozenge and placebo in smoking intervention. A cohort of 1,998 cigarette smokers were randomly allocated to intervention (n=996) and placebo arms (n=1,002). At baseline, smoking history was recorded by a questionnaire, with nicotine dependence testing according to the Fagerström scale (FTND). The subjects used smoking diary recording the daily numbers of cigarettes, lozenges and subjective sensations of smoking. The data were analysed separately for point prevalence of abstinence (PPA) and prolonged abstinence (PA) endpoints. Altogether, 753 study subjects completed the trial per protocol (PP), 944 with violations (mITT), and the rest (n=301) were lost to follow-up (LTF). During the 6-month intervention, 331 subjects stopped smoking; 181 (18.2%) in the intervention arm and 150 (15.0%) in the placebo arm (OR=1.43; 95%CI=1.09-1.88); p=0.010). In the PP group, 170 (45.3%) quitted smoking in the intervention arm compared to 134 (35.4%) in the placebo arm (OR=1.51, 95%CI=1.12-2.02; p=0.006). In multivariate (Poisson regression) model, decreased level of smoking pleasure (p=0.010) and "smoking sensations changed" were powerful independent predictors of quit events (IRR=12.01; 95%CI=1.5-95.6). Acetium® lozenge, herein confirmed in an adequately powered study to be an effective means to aid smoking quit, represents a major breakthrough in the development of smoking intervention methods, because slow-release L-cysteine is non-toxic, with no side-effects or limitations of use. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The effect of funding sources on donepezil randomised controlled trial outcome: a meta-analysis.

PubMed

Killin, Lewis O J; Russ, Tom C; Starr, John M; Abrahams, Sharon; Della Sala, Sergio

2014-04-07

To investigate whether there is a difference in the treatment effect of donepezil on cognition in Alzheimer disease between industry-funded and independent randomised controlled trials. Fixed effects meta-analysis of standardised effects of donepezil on cognition as measured by the Mini Mental State Examination and the Alzheimer's Disease Assessment Scale-cognitive subscale. Studies included in the meta-analyses reported in the National Institute for Health and Care Excellence (NICE) technical appraisal 217 updated with new studies through a PubMed search. Inclusion criteria were double-blind, placebo-controlled trials of any length comparing patients diagnosed with probable Alzheimer disease (according to the NINCDS-ADRDA/DSM-III/IV criteria) taking any dosage of donepezil. Studies of combination therapies (eg, donepezil and memantine) were excluded, as were studies that enrolled patients with a diagnosis of Alzheimer disease associated with other disorders (eg, Parkinson's disease and Down's syndrome). Our search strategy identified 14 relevant trials (4 independent) with suitable data. Trials sponsored by pharmaceutical companies reported a larger effect of donepezil on standardised cognitive tests than trials published by independent research groups (standardised mean difference (SMD)=0.46, 95% CI 0.37 to 0.55 vs SMD=0.33, 95% CI 0.18 to 0.48, respectively). This difference remained when only data representing change up to 12 weeks from baseline were analysed (industry SMD=0.44, 95% CI 0.34 to 0.53 vs independent SMD=0.35, 95% CI 0.18 to 0.52). Analysis revealed that the effect of funding as a moderator variable of study heterogeneity was not statistically significant at either time point. The effect size of donepezil on cognition is larger in industry-funded than independent trials and this is not explained by the longer duration of industry-funded trials. The lack of a statistically significant moderator effect may indicate that the differences are due to chance, but may also result from lack of power.

Children’s Oxygen Administration Strategies Trial (COAST):  A randomised controlled trial of high flow versus oxygen versus control in African children with severe pneumonia

PubMed Central

Maitland, Kathryn; Kiguli, Sarah; Opoka, Robert O.; Olupot-Olupot, Peter; Engoru, Charles; Njuguna, Patricia; Bandika, Victor; Mpoya, Ayub; Bush, Andrew; Williams, Thomas N.; Grieve, Richard; Sadique, Zia; Fraser, John; Harrison, David; Rowan, Kathy

2018-01-01

Background: In Africa, the clinical syndrome of pneumonia remains the leading cause of morbidity and mortality in children in the post-neonatal period. This represents a significant burden on in-patient services. The targeted use of oxygen and simple, non-invasive methods of respiratory support may be a highly cost-effective means of improving outcome, but the optimal oxygen saturation threshold that results in benefit and the best strategy for delivery are yet to be tested in adequately powered randomised controlled trials. There is, however, an accumulating literature about the harms of oxygen therapy across a range of acute and emergency situations that have stimulated a number of trials investigating permissive hypoxia. Methods: In 4200 African children, aged 2 months to 12 years, presenting to 5 hospitals in East Africa with respiratory distress and hypoxia (oxygen saturation < 92%), the COAST trial will simultaneously evaluate two related interventions (targeted use of oxygen with respect to the optimal oxygen saturation threshold for treatment and mode of delivery) to reduce shorter-term mortality at 48-hours (primary endpoint), and longer-term morbidity and mortality to 28 days in a fractional factorial design, that compares: Liberal oxygenation (recommended care) compared with a strategy that permits hypoxia to SpO 2 > or = 80% (permissive hypoxia); andHigh flow using AIrVO 2 TM compared with low flow delivery (routine care). Discussion: The overarching objective is to address the key research gaps in the therapeutic use of oxygen in resource-limited setting in order to provide a better evidence base for future management guidelines. The trial has been designed to address the poor outcomes of children in sub-Saharan Africa, which are associated with high rates of in-hospital mortality, 9-10% (for those with oxygen saturations of 80-92%) and 26-30% case fatality for those with oxygen saturations <80%. Clinical trial registration: ISRCTN15622505 Trial status: Recruiting PMID:29383331

Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid (TPOP): study protocol for a randomized controlled trial.

PubMed

Matsuoka, Yutaka; Nishi, Daisuke; Yonemoto, Naohiro; Hamazaki, Kei; Matsumura, Kenta; Noguchi, Hiroko; Hashimoto, Kenji; Hamazaki, Tomohito

2013-01-05

Preclinical and clinical studies suggest that supplementation with omega-3 fatty acids after trauma might reduce subsequent posttraumatic stress disorder (PTSD). To date, we have shown in an open trial that PTSD symptoms in critically injured patients can be reduced by taking omega-3 fatty acids, hypothesized to stimulate hippocampal neurogenesis. The primary aim of the present randomized controlled trial is to examine the efficacy of omega-3 fatty acid supplementation in the secondary prevention of PTSD following accidental injury, as compared with placebo. This paper describes the rationale and protocol of this trial. The Tachikawa Project for Prevention of Posttraumatic Stress Disorder with Polyunsaturated Fatty Acid (TPOP) is a double-blinded, parallel group, randomized controlled trial to assess whether omega-3 fatty acid supplementation can prevent PTSD symptoms among accident-injured patients consecutively admitted to an intensive care unit. We plan to recruit accident-injured patients and follow them prospectively for 12 weeks. Enrolled patients will be randomized to either the omega-3 fatty acid supplement group (1,470 mg docosahexaenoic acid and 147 mg eicosapentaenoic acid daily) or placebo group. Primary outcome is score on the Clinician-Administered PTSD Scale (CAPS). We will need to randomize 140 injured patients to have 90% power to detect a 10-point difference in mean CAPS scores with omega-3 fatty acid supplementation compared with placebo. Secondary measures are diagnosis of PTSD and major depressive disorder, depressive symptoms, physiologic response in the experiment using script-driven imagery and acoustic stimulation, serum brain-derived neurotrophic factor, health-related quality of life, resilience, and aggression. Analyses will be by intent to treat. The trial was initiated on December 13 2008, with 104 subjects randomized by November 30 2012. This study promises to be the first trial to provide a novel prevention strategy for PTSD among traumatized people. ClinicalTrials.gov Identifier NCT00671099.

The size of a pilot study for a clinical trial should be calculated in relation to considerations of precision and efficiency.

PubMed

Sim, Julius; Lewis, Martyn

2012-03-01

To investigate methods to determine the size of a pilot study to inform a power calculation for a randomized controlled trial (RCT) using an interval/ratio outcome measure. Calculations based on confidence intervals (CIs) for the sample standard deviation (SD). Based on CIs for the sample SD, methods are demonstrated whereby (1) the observed SD can be adjusted to secure the desired level of statistical power in the main study with a specified level of confidence; (2) the sample for the main study, if calculated using the observed SD, can be adjusted, again to obtain the desired level of statistical power in the main study; (3) the power of the main study can be calculated for the situation in which the SD in the pilot study proves to be an underestimate of the true SD; and (4) an "efficient" pilot size can be determined to minimize the combined size of the pilot and main RCT. Trialists should calculate the appropriate size of a pilot study, just as they should the size of the main RCT, taking into account the twin needs to demonstrate efficiency in terms of recruitment and to produce precise estimates of treatment effect. Copyright © 2012 Elsevier Inc. All rights reserved.

Caution regarding the choice of standard deviations to guide sample size calculations in clinical trials.

PubMed

Chen, Henian; Zhang, Nanhua; Lu, Xiaosun; Chen, Sophie

2013-08-01

The method used to determine choice of standard deviation (SD) is inadequately reported in clinical trials. Underestimations of the population SD may result in underpowered clinical trials. This study demonstrates how using the wrong method to determine population SD can lead to inaccurate sample sizes and underpowered studies, and offers recommendations to maximize the likelihood of achieving adequate statistical power. We review the practice of reporting sample size and its effect on the power of trials published in major journals. Simulated clinical trials were used to compare the effects of different methods of determining SD on power and sample size calculations. Prior to 1996, sample size calculations were reported in just 1%-42% of clinical trials. This proportion increased from 38% to 54% after the initial Consolidated Standards of Reporting Trials (CONSORT) was published in 1996, and from 64% to 95% after the revised CONSORT was published in 2001. Nevertheless, underpowered clinical trials are still common. Our simulated data showed that all minimal and 25th-percentile SDs fell below 44 (the population SD), regardless of sample size (from 5 to 50). For sample sizes 5 and 50, the minimum sample SDs underestimated the population SD by 90.7% and 29.3%, respectively. If only one sample was available, there was less than 50% chance that the actual power equaled or exceeded the planned power of 80% for detecting a median effect size (Cohen's d = 0.5) when using the sample SD to calculate the sample size. The proportions of studies with actual power of at least 80% were about 95%, 90%, 85%, and 80% when we used the larger SD, 80% upper confidence limit (UCL) of SD, 70% UCL of SD, and 60% UCL of SD to calculate the sample size, respectively. When more than one sample was available, the weighted average SD resulted in about 50% of trials being underpowered; the proportion of trials with power of 80% increased from 90% to 100% when the 75th percentile and the maximum SD from 10 samples were used. Greater sample size is needed to achieve a higher proportion of studies having actual power of 80%. This study only addressed sample size calculation for continuous outcome variables. We recommend using the 60% UCL of SD, maximum SD, 80th-percentile SD, and 75th-percentile SD to calculate sample size when 1 or 2 samples, 3 samples, 4-5 samples, and more than 5 samples of data are available, respectively. Using the sample SD or average SD to calculate sample size should be avoided.

Utility-based designs for randomized comparative trials with categorical outcomes

PubMed Central

Murray, Thomas A.; Thall, Peter F.; Yuan, Ying

2016-01-01

A general utility-based testing methodology for design and conduct of randomized comparative clinical trials with categorical outcomes is presented. Numerical utilities of all elementary events are elicited to quantify their desirabilities. These numerical values are used to map the categorical outcome probability vector of each treatment to a mean utility, which is used as a one-dimensional criterion for constructing comparative tests. Bayesian tests are presented, including fixed sample and group sequential procedures, assuming Dirichlet-multinomial models for the priors and likelihoods. Guidelines are provided for establishing priors, eliciting utilities, and specifying hypotheses. Efficient posterior computation is discussed, and algorithms are provided for jointly calibrating test cutoffs and sample size to control overall type I error and achieve specified power. Asymptotic approximations for the power curve are used to initialize the algorithms. The methodology is applied to re-design a completed trial that compared two chemotherapy regimens for chronic lymphocytic leukemia, in which an ordinal efficacy outcome was dichotomized and toxicity was ignored to construct the trial’s design. The Bayesian tests also are illustrated by several types of categorical outcomes arising in common clinical settings. Freely available computer software for implementation is provided. PMID:27189672

EEG Source Reconstruction Reveals Frontal-Parietal Dynamics of Spatial Conflict Processing

PubMed Central

Cohen, Michael X; Ridderinkhof, K. Richard

2013-01-01

Cognitive control requires the suppression of distracting information in order to focus on task-relevant information. We applied EEG source reconstruction via time-frequency linear constrained minimum variance beamforming to help elucidate the neural mechanisms involved in spatial conflict processing. Human subjects performed a Simon task, in which conflict was induced by incongruence between spatial location and response hand. We found an early (∼200 ms post-stimulus) conflict modulation in stimulus-contralateral parietal gamma (30–50 Hz), followed by a later alpha-band (8–12 Hz) conflict modulation, suggesting an early detection of spatial conflict and inhibition of spatial location processing. Inter-regional connectivity analyses assessed via cross-frequency coupling of theta (4–8 Hz), alpha, and gamma power revealed conflict-induced shifts in cortical network interactions: Congruent trials (relative to incongruent trials) had stronger coupling between frontal theta and stimulus-contrahemifield parietal alpha/gamma power, whereas incongruent trials had increased theta coupling between medial frontal and lateral frontal regions. These findings shed new light into the large-scale network dynamics of spatial conflict processing, and how those networks are shaped by oscillatory interactions. PMID:23451201

Pharmacological interventions for acute pancreatitis.

PubMed

Moggia, Elisabetta; Koti, Rahul; Belgaumkar, Ajay P; Fazio, Federico; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-21

In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure. To assess the effects of different pharmacological interventions in people with acute pancreatitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials. We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review. Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model. We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this condition. Most trials included either only participants with severe acute pancreatitis or included a mixture of participants with mild acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk of bias in trials was unclear or high for all but one of the trials. seven trials were not funded or funded by agencies without vested interest in results. Pharmaceutical companies partially or fully funded 21 trials. The source of funding was not available from the remaining trials.Since we considered short-term mortality as the most important outcome, we presented only these results in detail in the abstract. Sixty-seven studies including 6638 participants reported short-term mortality. There was no evidence of any differences in short-term mortality in any of the comparisons (very low-quality evidence). With regards to other primary outcomes, serious adverse events (number) were lower than control in participants taking lexipafant (rate ratio 0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence), octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low-quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to 0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence). The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence). The proportion of people with sepsis was lower in lexipafant than control (OR 0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There was no evidence of differences in any of the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life. Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).

Enhancing the parent-child relationship: a Hong Kong community-based randomized controlled trial.

PubMed

Fabrizio, Cecilia S; Stewart, Sunita M; Ip, Alison K Y; Lam, Tai Hing

2014-02-01

Adolescence is a critical risk period for negative academic and behavioral outcomes, but a strong parent-child relationship can be a powerful protective factor. Our previous pilot of an academic-community agency collaborative randomized controlled trial (RCT) demonstrated initial evidence of benefit for a parenting intervention with preadolescents in Hong Kong. The present RCT assessed the effect of brief training in positive discipline parenting skills on parental satisfaction with the parent-child relationship. A community sample of 461 Hong Kong Chinese parents of children aged 10-13 years were randomized to (a) the Harmony@Home intervention, (b) an attention control, or (c) a third active intervention that shared the control group. Participants were followed for 12 months and multiple methods of assessment were used. Compared with the control group, the Harmony@Home group reported an increase in the primary outcome of satisfaction with the parent-child relationship at 3 months' postintervention. Although results are mixed, this study demonstrates how a culturally adaptive community intervention can improve the parental behaviors that serve as protective factors against negative academic and behavioral outcomes for Chinese adolescents.

Comparison Groups in Yoga Research: A Systematic Review and Critical Evaluation of the Literature

PubMed Central

Groessl, Erik; Maiya, Meghan; Sarkin, Andrew; Eisen, Susan V.; Riley, Kristen; Elwy, A. Rani

2014-01-01

Objectives Comparison groups are essential for accurate testing and interpretation of yoga intervention trials. However, selecting proper comparison groups is difficult because yoga comprises a very heterogeneous set of practices and its mechanisms of effect have not been conclusively established. Methods We conducted a systematic review of the control and comparison groups used in published randomized controlled trials (RCTs) of yoga. Results We located 128 RCTs that met our inclusion criteria; of these, 65 included only a passive control and 63 included at least one active comparison group. Primary comparison groups were physical exercise (43%), relaxation/meditation (20%), and education (16%). Studies rarely provided a strong rationale for choice of comparison. Considering year of publication, the use of active controls in yoga research appears to be slowly increasing over time. Conclusions Given that yoga has been established as a potentially powerful intervention, future research should use active control groups. Further, care is needed to select comparison conditions that help to isolate the specific mechanisms of yoga’s effects. PMID:25440384

Predictive factors for the placebo effect in clinical trials for dry eye: a pooled analysis of three clinical trials.

PubMed

Imanaka, Takahiro; Sato, Izumi; Tanaka, Shiro; Kawakami, Koji

2017-11-01

Placebo effect is one of the methodological difficulties in dry eye clinical trials. If we could elucidate the tendencies of the placebo response and find predictors, we could reduce the placebo response in clinical trials for dry eye. In this study, we investigated the predictive factors for the placebo effect in dry eye clinical trials. A total of 205 patients with dry eye assigned to the placebo arms of three placebo-controlled randomised clinical trials were analysed by simple and multivariable regression analysis. The corneal fluorescein (FL) staining score and dry eye symptoms were studied at week 4. The variables of interest included gender, age, complications of Sjögren's syndrome, Schirmer's test I value, tear break-up time and conjunctival hyperaemia score. We also conducted a stratified analysis according to the patients' age. Among all the studied endpoints, the baseline scores were significantly related to the corresponding placebo response. In addition, for the FL score and the dryness score, age was a significant predictor of the placebo response (p=0.04 and p<0.0001, respectively). Stratified analysis by age showed that patients more than 40 years of age are more likely to have a stronger placebo response in the FL and dryness scores. The baseline scores and age were predictive factors of the placebo response in frequently used endpoints, such as FL score or dryness symptoms. These patient characteristics can be controlled by study design, and our findings enable the design of more efficient placebo-controlled studies with good statistical power. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Intention to treat (ITT) analysis as reported in orthodontic randomized controlled trials-evaluations of methodology and recommendations for the accurate use of ITT analysis and handling dropouts.

PubMed

Bondemark, Lars; Abdulraheem, Salem

2017-10-21

To systematically evaluate in five orthodontic journals how many randomized controlled trials (RCTs) use intention to treat (ITT) analysis and to assess the methodological quality of the ITT analysis, and finally, to demonstrate in an academic way how outcomes can be affected when not implementing the ITT analysis. A search of the database, Medline, was performed via PubMed for publication type 'randomized controlled trial' published for each journal between 1 January 2013 and 30 April 2017. The five orthodontic journals assessed were the American Journal of Orthodontics and Dentofacial Orthopedics, Angle Orthodontics, European Journal of Orthodontics, Journal of Orthodontics, and Orthodontics and Craniofacial Research. Two independent reviewers assessed each RCT to determine whether the trial reported an ITT or not or if a per-protocol analysis was accomplished. The initial search generated 137 possible trials. After applying the inclusion and exclusion criteria, 90 RCTs were included and assessed. Seventeen out of 90 RCTs (18.9%) either reported an ITT analysis in the text and/or supported the ITT by flow diagrams or tables. However, six RCTs applied and reported the ITT analysis correctly, while the majority performed a per-protocol analysis instead. Nearly all the trials that applied the ITT analysis incorrectly analysed the results using a per-protocol analysis, and thus, overestimating the results and/or having a reduced sample size which then could produce a diminished statistical power. © The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

Canadian Phase III Randomized Trial of Stereotactic Body Radiotherapy Versus Conventionally Hypofractionated Radiotherapy for Stage I, Medically Inoperable Non-Small-Cell Lung Cancer - Rationale and Protocol Design for the Ontario Clinical Oncology Group (OCOG)-LUSTRE Trial.

PubMed

Swaminath, Anand; Wierzbicki, Marcin; Parpia, Sameer; Wright, James R; Tsakiridis, Theodoros K; Okawara, Gordon S; Kundapur, Vijayananda; Bujold, Alexis; Ahmed, Naseer; Hirmiz, Khalid; Kurien, Elizabeth; Filion, Edith; Gabos, Zsolt; Faria, Sergio; Louie, Alexander V; Owen, Timothy; Wai, Elaine; Ramchandar, Kevin; Chan, Elisa K; Julian, Jim; Cline, Kathryn; Whelan, Timothy J

2017-03-01

We describe a Canadian phase III randomized controlled trial of stereotactic body radiotherapy (SBRT) versus conventionally hypofractionated radiotherapy (CRT) for the treatment of stage I medically inoperable non-small-cell lung cancer (OCOG-LUSTRE Trial). Eligible patients are randomized in a 2:1 fashion to either SBRT (48 Gy in 4 fractions for peripherally located lesions; 60 Gy in 8 fractions for centrally located lesions) or CRT (60 Gy in 15 fractions). The primary outcome of the study is 3-year local control, which we hypothesize will improve from 75% with CRT to 87.5% with SBRT. With 85% power to detect a difference of this magnitude (hazard ratio = 0.46), a 2-sided α = 0.05 and a 2:1 randomization, we require a sample size of 324 patients (216 SBRT, 108 CRT). Important secondary outcomes include overall survival, disease-free survival, toxicity, radiation-related treatment death, quality of life, and cost-effectiveness. A robust radiation therapy quality assurance program has been established to assure consistent and high quality SBRT and CRT delivery. Despite widespread interest and adoption of SBRT, there still remains a concern regarding long-term control and risks of toxicity (particularly in patients with centrally located lesions). The OCOG-LUSTRE study is the only randomized phase III trial testing SBRT in a medically inoperable population, and the results of this trial will attempt to prove that the benefits of SBRT outweigh the potential risks. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevention of Chronic Kidney Disease and Subsequent Effect on Mortality: A Systematic Review and Meta-Analysis

PubMed Central

Khan, Usman A.; Garg, Amit X.; Parikh, Chirag R.; Coca, Steven G.

2013-01-01

Objectives To perform a systematic review of randomized controlled trials to determine whether prevention or slowing of progression of chronic kidney disease would translate into improved mortality, and if so, the attributable risk due to CKD itself on mortality. Background CKD is associated with increased mortality. This association is largely based on evidence from the observational studies and evidence from randomized controlled trials is lacking. Methods We searched Ovid, Medline and Embase for RCTs in which an intervention was given to prevent or slow the progression of CKD and mortality was reported as primary, secondary or adverse outcomes were eligible and selected. For the first phase, pooled relative risks for renal endpoints were assessed. For the second phase, we assessed the effect on mortality in trials of interventions that definitively reduced CKD endpoints. Results Among 52 studies selected in first phase, only renin-angiotensin-aldosterone-system blockade vs. placebo (n = 18 trials, 32,557 participants) met the efficacy criteria for further analysis in the second phase by reducing renal endpoints 15 to 27% compared to placebo. There was no difference in all-cause mortality (RR 0.99, 95% CI 0.92 to 1.08) or CV death (RR 0.97, 95% CI 0.78 to 1.21) between the treatment and control groups in these trials. There was sufficient statistical power to detect a 9% relative risk reduction in all-cause mortality and a 14% relative risk reduction in cardiovascular mortality. Conclusions Firm evidence is lacking that prevention of CKD translates into reductions in mortality. Larger trials with longer follow-up time are needed to determine the benefit of CKD prevention on survival. PMID:24009665

Effect of music on power, pain, depression and disability.

PubMed

Siedliecki, Sandra L; Good, Marion

2006-06-01

This paper reports a study testing the effect of music on power, pain, depression and disability, and comparing the effects of researcher-provided music (standard music) with subject-preferred music (patterning music). Chronic non-malignant pain is characterized by pain that persists in spite of traditional interventions. Previous studies have found music to be effective in decreasing pain and anxiety related to postoperative, procedural and cancer pain. However, the effect of music on power, pain, depression, and disability in working age adults with chronic non-malignant pain has not been investigated. A randomized controlled clinical trial was carried out with a convenience sample of 60 African American and Caucasian people aged 21-65 years with chronic non-malignant pain. They were randomly assigned to a standard music group (n = 22), patterning music group (n = 18) or control group (n = 20). Pain was measured with the McGill Pain Questionnaire short form; depression was measured with the Center for Epidemiology Studies Depression scale; disability was measured with the Pain Disability Index; and power was measured with the Power as Knowing Participation in Change Tool (version II). The music groups had more power and less pain, depression and disability than the control group, but there were no statistically significant differences between the two music interventions. The model predicting both a direct and indirect effect for music was supported. Nurses can teach patients how to use music to enhance the effects of analgesics, decrease pain, depression and disability, and promote feelings of power.

A Randomized Trial of Soft Multifocal Contact Lenses for Myopia Control: Baseline Data and Methods.

PubMed

Walline, Jeffrey J; Gaume Giannoni, Amber; Sinnott, Loraine T; Chandler, Moriah A; Huang, Juan; Mutti, Donald O; Jones-Jordan, Lisa A; Berntsen, David A

2017-09-01

The Bifocal Lenses In Nearsighted Kids (BLINK) study is the first soft multifocal contact lens myopia control study to compare add powers and measure peripheral refractive error in the vertical meridian, so it will provide important information about the potential mechanism of myopia control. The BLINK study is a National Eye Institute-sponsored, double-masked, randomized clinical trial to investigate the effects of soft multifocal contact lenses on myopia progression. This article describes the subjects' baseline characteristics and study methods. Subjects were 7 to 11 years old, had -0.75 to -5.00 spherical component and less than 1.00 diopter (D) astigmatism, and had 20/25 or better logMAR distance visual acuity with manifest refraction in each eye and with +2.50-D add soft bifocal contact lenses on both eyes. Children were randomly assigned to wear Biofinity single-vision, Biofinity Multifocal "D" with a +1.50-D add power, or Biofinity Multifocal "D" with a +2.50-D add power contact lenses. We examined 443 subjects at the baseline visits, and 294 (66.4%) subjects were enrolled. Of the enrolled subjects, 177 (60.2%) were female, and 200 (68%) were white. The mean (± SD) age was 10.3 ± 1.2 years, and 117 (39.8%) of the eligible subjects were younger than 10 years. The mean spherical equivalent refractive error, measured by cycloplegic autorefraction was -2.39 ± 1.00 D. The best-corrected binocular logMAR visual acuity with glasses was +0.01 ± 0.06 (20/21) at distance and -0.03 ± 0.08 (20/18) at near. The BLINK study subjects are similar to patients who would routinely be eligible for myopia control in practice, so the results will provide clinical information about soft bifocal contact lens myopia control as well as information about the mechanism of the treatment effect, if one occurs.

A Mobile Phone App to Support Young People in Making Shared Decisions in Therapy (Power Up): Study Protocol.

PubMed

Chapman, Louise; Edbrooke-Childs, Julian; Martin, Kate; Webber, Helen; Craven, Michael P; Hollis, Chris; Deighton, Jessica; Law, Roslyn; Fonagy, Peter; Wolpert, Miranda

2017-10-30

Evidence suggests that young people want to be active participants in their care and involved in decisions about their treatment. However, there is a lack of digital shared decision-making tools available to support young people in child and adolescent mental health services (CAMHS). The primary aim of this paper is to present the protocol of a feasibility trial for Power Up, a mobile phone app to empower young people in CAMHS to make their voices heard and participate in decisions around their care. In the development phase, 30 young people, parents, and clinicians will take part in interviews and focus groups to elicit opinions on an early version of the app. In the feasibility testing phase, 60 young people from across 7 to 10 London CAMHS sites will take part in a trial looking at the feasibility and acceptability of measuring the impact of Power Up on shared decision making. Data collection for the development phase ended in December 2016. Data collection for the feasibility testing phase will end in December 2017. Findings will inform the planning of a cluster controlled trial and contribute to the development and implementation of a shared decision-making app to be integrated into CAMHS. ISRCTN77194423; http://www.isrctn.com/ISRCTN77194423 (Archived by WebCite at http://www.webcitation.org/6td6MINP0). ClinicalTrials.gov NCT02987608; https://clinicaltrials.gov/ct2/show/NCT02987608 (Archived by WebCite at http://www.webcitation.org/6td6PNBZM). ©Louise Chapman, Julian Edbrooke-Childs, Kate Martin, Helen Webber, Michael P Craven, Chris Hollis, Jessica Deighton, Roslyn Law, Peter Fonagy, Miranda Wolpert. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 30.10.2017.

Power corrupts co-operation: cognitive and motivational effects in a double EEG paradigm.

PubMed

Kanso, Riam; Hewstone, Miles; Hawkins, Erin; Waszczuk, Monika; Nobre, Anna Christina

2014-02-01

This study investigated the effect of interpersonal power on co-operative performance. We used a paired electro-encephalogram paradigm: pairs of participants performed an attention task, followed by feedback indicating monetary loss or gain on every trial. Participants were randomly allocated to the power-holder, subordinate or neutral group by creating different levels of control over how a joint monetary reward would be allocated. We found that power was associated with reduced behavioural accuracy. Event-related potential analysis showed that power-holders devoted less motivational resources to their targets than did subordinates or neutrals, but did not differ at the level of early conflict detection. Their feedback potential results showed a greater expectation of rewards but reduced subjective magnitude attributed to losses. Subordinates, on the other hand, were asymmetrically sensitive to power-holders' targets. They expected fewer rewards, but attributed greater significance to losses. Our study shows that power corrupts balanced co-operation with subordinates.

Power corrupts co-operation: cognitive and motivational effects in a double EEG paradigm

PubMed Central

Kanso, Riam; Hewstone, Miles; Hawkins, Erin; Waszczuk, Monika; Nobre, Anna Christina

2014-01-01

This study investigated the effect of interpersonal power on co-operative performance. We used a paired electro-encephalogram paradigm: pairs of participants performed an attention task, followed by feedback indicating monetary loss or gain on every trial. Participants were randomly allocated to the power-holder, subordinate or neutral group by creating different levels of control over how a joint monetary reward would be allocated. We found that power was associated with reduced behavioural accuracy. Event-related potential analysis showed that power-holders devoted less motivational resources to their targets than did subordinates or neutrals, but did not differ at the level of early conflict detection. Their feedback potential results showed a greater expectation of rewards but reduced subjective magnitude attributed to losses. Subordinates, on the other hand, were asymmetrically sensitive to power-holders’ targets. They expected fewer rewards, but attributed greater significance to losses. Our study shows that power corrupts balanced co-operation with subordinates. PMID:23160813

Fibrin Sealants in Dura Sealing: A Systematic Literature Review

PubMed Central

2016-01-01

Background Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. Methods A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. Results A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. Conclusions A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety. PMID:27119993

Fibrin Sealants in Dura Sealing: A Systematic Literature Review.

PubMed

Esposito, Felice; Angileri, Filippo Flavio; Kruse, Peter; Cavallo, Luigi Maria; Solari, Domenico; Esposito, Vincenzo; Tomasello, Francesco; Cappabianca, Paolo

2016-01-01

Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety.

Polysaccharide vaccines for preventing serogroup A meningococcal meningitis.

PubMed

Patel, M; Lee, C K

2001-01-01

Controlled trials over two decades ago showed that the polysaccharide vaccine prevented serogroup A meningococcal meningitis. Subsequent non-experimental studies suggested age-specific variations in the duration of protection among young children. To determine the effect of polysaccharide serogroup A vaccine for preventing serogroup A meningococcal meningitis. MEDLINE and the Cochrane Controlled Trials Register. The first stage of the review included prospective controlled trials. The second stage included non-experimental studies that addressed questions unanswered by the trials, i.e. the duration of protection and the effect of a booster dose in children under 2 years of age. One reviewer assessed the methodological quality of the trials, and two reviewers independently identified and assessed the non-experimental studies. Data from the trials were pooled using the Exact method to assess vaccine efficacy at 1, 2 and 3 years post- vaccination. The protective effect within the first year was consistent across all 8 trials, vaccine efficacy was 95% (Exact 95% CI 87%, 99%). Protection extended into the second and third year after vaccination, but the results did not attain statistical significance. The only trial that assessed the effect of a booster dose in children less than 18 months old, lacked adequate statistical power. In the three other trials that included children less than 6 years old (one in Sudan and two in Nigeria), none of the vaccinated children developed meningitis, but the results did not attain statistical significance. Data from the two non-experimental studies included in this review were not pooled with the trial data because of methodological limitations. For the first year after vaccination, the vaccine was strongly protective in participants over 5 years of age. It was also protective beyond the first year after vaccination, but the level of vaccine efficacy could not be determined with precision. Children aged 1 to 5 years in developing countries were protected, but the level of efficacy among the youngest children could not be determined. While the vaccine was strongly protective among children aged 3 months and over in developed countries, the number of participants aged under 2 years was too small to draw firm conclusions on the protective effect of, or need for, a booster dose of vaccine.

Evidence of emotion-antecedent appraisal checks in electroencephalography and facial electromyography.

PubMed

Coutinho, Eduardo; Gentsch, Kornelia; van Peer, Jacobien; Scherer, Klaus R; Schuller, Björn W

2018-01-01

In the present study, we applied Machine Learning (ML) methods to identify psychobiological markers of cognitive processes involved in the process of emotion elicitation as postulated by the Component Process Model (CPM). In particular, we focused on the automatic detection of five appraisal checks-novelty, intrinsic pleasantness, goal conduciveness, control, and power-in electroencephalography (EEG) and facial electromyography (EMG) signals. We also evaluated the effects on classification accuracy of averaging the raw physiological signals over different numbers of trials, and whether the use of minimal sets of EEG channels localized over specific scalp regions of interest are sufficient to discriminate between appraisal checks. We demonstrated the effectiveness of our approach on two data sets obtained from previous studies. Our results show that novelty and power appraisal checks can be consistently detected in EEG signals above chance level (binary tasks). For novelty, the best classification performance in terms of accuracy was achieved using features extracted from the whole scalp, and by averaging across 20 individual trials in the same experimental condition (UAR = 83.5 ± 4.2; N = 25). For power, the best performance was obtained by using the signals from four pre-selected EEG channels averaged across all trials available for each participant (UAR = 70.6 ± 5.3; N = 24). Together, our results indicate that accurate classification can be achieved with a relatively small number of trials and channels, but that averaging across a larger number of individual trials is beneficial for the classification for both appraisal checks. We were not able to detect any evidence of the appraisal checks under study in the EMG data. The proposed methodology is a promising tool for the study of the psychophysiological mechanisms underlying emotional episodes, and their application to the development of computerized tools (e.g., Brain-Computer Interface) for the study of cognitive processes involved in emotions.

A pragmatic randomised controlled trial assessing the non-inferiority of counselling for depression versus cognitive-behaviour therapy for patients in primary care meeting a diagnosis of moderate or severe depression (PRaCTICED): Study protocol for a randomised controlled trial.

PubMed

Saxon, David; Ashley, Kate; Bishop-Edwards, Lindsey; Connell, Janice; Harrison, Phillippa; Ohlsen, Sally; Hardy, Gillian E; Kellett, Stephen; Mukuria, Clara; Mank, Toni; Bower, Peter; Bradburn, Mike; Brazier, John; Elliott, Robert; Gabriel, Lynne; King, Michael; Pilling, Stephen; Shaw, Sue; Waller, Glenn; Barkham, Michael

2017-03-01

NICE guidelines state cognitive behavioural therapy (CBT) is a front-line psychological treatment for people presenting with depression in primary care. Counselling for Depression (CfD), a form of Person-Centred Experiential therapy, is also offered within Improving Access to Psychological Therapies (IAPT) services for moderate depression but its effectiveness for severe depression has not been investigated. A full-scale randomised controlled trial to determine the efficacy and cost-effectiveness of CfD is required. PRaCTICED is a two-arm, parallel group, non-inferiority randomised controlled trial comparing CfD against CBT. It is embedded within the local IAPT service using a stepped care service delivery model where CBT and CfD are routinely offered at step 3. Trial inclusion criteria comprise patients aged 18 years or over, wishing to work on their depression, judged to require a step 3 intervention, and meeting an ICD-10 diagnosis of moderate or severe depression. Patients are randomised using a centralised, web-based system to CfD or CBT with each treatment being delivered up to a maximum 20 sessions. Both interventions are manualised with treatment fidelity tested via supervision and random sampling of sessions using adherence/competency scales. The primary outcome measure is the Patient Health Questionnaire-9 collected at baseline, 6 and 12 months. Secondary outcome measures tap depression, generic psychological distress, anxiety, functioning and quality of life. Cost-effectiveness is determined by a patient service receipt questionnaire. Exit interviews are conducted with patients by research assessors blind to treatment allocation. The trial requires 500 patients (250 per arm) to test the non-inferiority hypothesis of -2 PHQ-9 points at the one-sided, 2.5% significance level with 90% power, assuming no underlying difference and a standard deviation of 6.9. The primary analysis will be undertaken on all patients randomised (intent to treat) alongside per-protocol and complier-average causal effect analyses as recommended by the extension to the CONSORT statement for non-inferiority trials. This large-scale trial utilises routinely collected outcome data as well as specific trial data to provide evidence of the comparative efficacy and cost-effectiveness of Counselling for Depression compared with Cognitive Behaviour Therapy as delivered within the UK government's Improving Access to Psychological Therapies initiative. Controlled Trials ISRCTN Registry, ISRCTN06461651 . Registered on 14 September 2014.

Can exergaming contribute to improving physical activity levels and health outcomes in children?

PubMed

Daley, Amanda J

2009-08-01

Physical inactivity among children is a serious public health problem. It has been suggested that high levels of screen time are contributory factors that encourage sedentary lifestyles in young people. As physical inactivity and obesity levels continue to rise in young people, it has been proposed that new-generation active computer- and video-console games (otherwise known as "exergaming") may offer the opportunity to contribute to young people's energy expenditure during their free time. Although studies have produced some encouraging results regarding the energy costs involved in playing active video-console games, the energy costs of playing the authentic versions of activity-based video games are substantially larger, highlighting that active gaming is no substitute for real sports and activities. A small number of exergaming activities engage children in moderate-intensity activity, but most do not. Only 3 very small trials have considered the effects of exergaming on physical activity levels and/or other health outcomes in children. Evidence from these trials has been mixed; positive trends for improvements in some health outcomes in the intervention groups were noted in 2 trials. No adequately powered randomized, controlled trial has been published to date, and no trial has assessed the long-term impact of exergaming on children's health. We now need high-quality randomized, controlled trials to evaluate the effectiveness and sustainability of exergaming, as well as its clinical relevance; until such studies take place, we should remain cautious about its ability to positively affect children's health.

Intravenous tranexamic acid for hyperacute primary intracerebral hemorrhage: Protocol for a randomized, placebo-controlled trial.

PubMed

Sprigg, Nikola; Robson, Katie; Bath, Philip; Dineen, Robert; Roberts, Ian; Robinson, Tom; Roffe, Christine; Werring, David; Al-Shahi Salman, Rustam; Pocock, Stuart; Duley, Lelia; England, Tim; Whynes, David; Ciccone, Alfonso; Laska, Ann Charlotte; Christensen, Hanne; Ozturk, Serefnur; Collins, Ronan; Bereczki, Daniel; Egea-Guerrero, Juan Jose; Law, Zhe Kang; Czlonkowska, Anna; Seiffge, David; Beredzie, Maia

2016-08-01

Outcome after intracerebral hemorrhage remains poor. Tranexamic acid is easy to administer, readily available, inexpensive, and effective in other hemorrhagic conditions. This randomized trial aims to test the hypothesis that intravenous tranexamic acid given within 8 h of spontaneous intracerebral hemorrhage reduces death or dependency. Phase III prospective double-blind randomized placebo-controlled trial. Participants within 8 h of spontaneous intracerebral hemorrhage are randomized to receive either intravenous tranexamic acid 1 g 10 min bolus followed by 1 g 8 h infusion, or placebo. A trial of 2000 participants (300 from start-up phase and 1700 from main phase) will have 90% power to detect an ordinal shift of the modified Rankin Scale with odds ratio 0.79. The primary outcome is death or dependency measured by ordinal shift analysis of the 7 level mRS at day 90. Secondary outcomes are neurological impairment at day 7 and disability, quality of life, cognition, and mood at day 90. Safety outcomes are death, serious adverse events, thromboembolic events, and seizures. Cost outcomes are length of stay in hospital, readmission, and institutionalization. This pragmatic trial is assessing efficacy of tranexamic acid after spontaneous intracerebral hemorrhage. Recruitment started in 2013; as of 15th January 2016 1355 participants have been enrolled, from 95 centers in seven countries. Recruitment is due to end in 2017. TICH-2 Trial is registered as ISRCTN93732214. © 2016 World Stroke Organization.

The NordICC Study: Rationale and design of a randomized trial on colonoscopy screening for colorectal cancer

PubMed Central

F.Kaminski, Michal; Bretthauer, Michael; Zauber, Ann G.; Kuipers, Ernst J.; Adami, Hans-Olov; van Ballegooijen, Marjolein; Regula, Jaroslaw; van Leerdam, Monique; Stefansson, Tryggvi; Påhlman, Lars; Dekker, Evelien; Hernán, Miguel A.; Garborg, Kjetil; Hoff, Geir

2017-01-01

Background While colonoscopy screening is widely used in several European countries and the United States, no randomised trials exist to quantify its benefits. The Nordic-European Initiative on Colorectal Cancer (NordICC) is a multinational, randomized controlled trial aiming at investigating the effect of colonoscopy screening on CRC incidence and mortality. This paper describes the rationale and design of the NordICC trial. Material and methods Men and women age 55 to 64 years are drawn from the population registries in the participating countries and randomly assigned to either once-only colonoscopy screening with removal of all detected lesions, or no screening (standard of care in the trial regions). All individuals are followed for 15 years after inclusion using dedicated national registries. Results The primary endpoints of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow up. We hypothesize a 50% CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50% compliance, yielding a 25% mortality reduction among those invited to screening. For 90% power and a two-sided alpha level of 0.05, using a 2:1 randomisation, 45,600 individuals will be randomised to control, and 22,800 individuals to the colonoscopy group. Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10 years follow-up. Conclusions The aim of the NordICC trial is to quantify the effectiveness of population-based colonoscopy screening. This will allow development of evidence-based guidelines for CRC screening in the general population. PMID:22723185

Effect of Korean red ginseng on cold hypersensitivity in the hands and feet: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Cold hypersensitivity in the hands and feet (CHHF) is one of the most common complaints among Asians, especially in women. Korean red ginseng (KRG), which is a steamed form of Panax ginseng, has vasodilating action in the peripheral vessels and increases blood flow under cold stress. However, few studies have evaluated the effect of KRG on cold hypersensitivity. Methods/Design This trial is a randomized, double-blind, placebo-controlled trial in 80 CHHF patients. The trial will be implemented at Kyung Hee University Hospital at Gangdong in Seoul, Korea. The participants will take KRG or a placebo for eight weeks, after which they will be followed-up for four weeks. During the administration period, six capsules of 500 mg KRG or placebo will be provided twice a day. The primary outcome is change of skin temperature in the hands between baseline and after treatment. The secondary outcomes include the visual analogue scale scores of cold hypersensitivity in the hands, change of skin temperature and the VAS scores of cold hypersensitivity in the feet, the recovery rate of the skin temperature by the cold stress test of the hands, the distal-dorsal difference of the hands, power variables of heart rate variability, and the 36-item short form health survey. Discussion This study is the first trial to evaluate the efficacy of KRG on CHHF by using infrared thermography. Our study will provide basic evidence regarding CHHF. Trial registration CliniacalTrials.gov NCT01664156 PMID:24354675

Vaccine approaches to malaria control and elimination: Insights from mathematical models.

PubMed

White, Michael T; Verity, Robert; Churcher, Thomas S; Ghani, Azra C

2015-12-22

A licensed malaria vaccine would provide a valuable new tool for malaria control and elimination efforts. Several candidate vaccines targeting different stages of the malaria parasite's lifecycle are currently under development, with one candidate, RTS,S/AS01 for the prevention of Plasmodium falciparum infection, having recently completed Phase III trials. Predicting the public health impact of a candidate malaria vaccine requires using clinical trial data to estimate the vaccine's efficacy profile--the initial efficacy following vaccination and the pattern of waning of efficacy over time. With an estimated vaccine efficacy profile, the effects of vaccination on malaria transmission can be simulated with the aid of mathematical models. Here, we provide an overview of methods for estimating the vaccine efficacy profiles of pre-erythrocytic vaccines and transmission-blocking vaccines from clinical trial data. In the case of RTS,S/AS01, model estimates from Phase II clinical trial data indicate a bi-phasic exponential profile of efficacy against infection, with efficacy waning rapidly in the first 6 months after vaccination followed by a slower rate of waning over the next 4 years. Transmission-blocking vaccines have yet to be tested in large-scale Phase II or Phase III clinical trials so we review ongoing work investigating how a clinical trial might be designed to ensure that vaccine efficacy can be estimated with sufficient statistical power. Finally, we demonstrate how parameters estimated from clinical trials can be used to predict the impact of vaccination campaigns on malaria using a mathematical model of malaria transmission. Copyright © 2015 Elsevier Ltd. All rights reserved.

A multicenter, randomized controlled trial comparing the identification rate of stigmata of recent hemorrhage and rebleeding rate between early and elective colonoscopy in outpatient-onset acute lower gastrointestinal bleeding: study protocol for a randomized controlled trial.

PubMed

Niikura, Ryota; Nagata, Naoyoshi; Yamada, Atsuo; Doyama, Hisashi; Shiratori, Yasutoshi; Nishida, Tsutomu; Kiyotoki, Shu; Yada, Tomoyuki; Fujita, Tomoki; Sumiyoshi, Tetsuya; Hasatani, Kenkei; Mikami, Tatsuya; Honda, Tetsuro; Mabe, Katsuhiro; Hara, Kazuo; Yamamoto, Katsumi; Takeda, Mariko; Takata, Munenori; Tanaka, Mototsugu; Shinozaki, Tomohiro; Fujishiro, Mitsuhiro; Koike, Kazuhiko

2018-04-03

The clinical benefit of early colonoscopy within 24 h of arrival in patients with severe acute lower gastrointestinal bleeding (ALGIB) remains controversial. This trial will compare early colonoscopy (performed within 24 h) versus elective colonoscopy (performed between 24 and 96 h) to examine the identification rate of stigmata of recent hemorrhage (SRH) in ALGIB patients. We hypothesize that, compared with elective colonoscopy, early colonoscopy increases the identification of SRH and subsequently improves clinical outcomes. This trial is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial examining the superiority of early colonoscopy over elective colonoscopy (standard therapy) in ALGIB patients. The primary outcome measure is the identification of SRH. Secondary outcomes include 30-day rebleeding, success of endoscopic treatment, need for additional endoscopic examination, need for interventional radiology, need for surgery, need for transfusion during hospitalization, length of stay, 30-day thrombotic events, 30-day mortality, preparation-related adverse events, and colonoscopy-related adverse events. The sample size will enable detection of a 9% SRH rate in elective colonoscopy patients and a SRH rate of ≥ 26% in early colonoscopy patients with a risk of type I error of 5% and a power of 80%. This trial will provide high-quality data on the benefits and risks of early colonoscopy in ALGIB patients. UMIN-CTR Identifier, UMIN000021129 . Registered on 21 February 2016; ClinicalTrials.gov Identifier, NCT03098173 . Registered on 24 March 2017.

Behavioral neurocardiac training in hypertension: a randomized, controlled trial.

PubMed

Nolan, Robert P; Floras, John S; Harvey, Paula J; Kamath, Markad V; Picton, Peter E; Chessex, Caroline; Hiscock, Natalie; Powell, Jonathan; Catt, Michael; Hendrickx, Hilde; Talbot, Duncan; Chen, Maggie H

2010-04-01

It is not established whether behavioral interventions add benefit to pharmacological therapy for hypertension. We hypothesized that behavioral neurocardiac training (BNT) with heart rate variability biofeedback would reduce blood pressure further by modifying vagal heart rate modulation during reactivity and recovery from standardized cognitive tasks ("mental stress"). This randomized, controlled trial enrolled 65 patients with uncomplicated hypertension to BNT or active control (autogenic relaxation), with six 1-hour sessions over 2 months with home practice. Outcomes were analyzed with linear mixed models that adjusted for antihypertensive drugs. BNT reduced daytime and 24-hour systolic blood pressures (-2.4+/-0.9 mm Hg, P=0.009, and -2.1+/-0.9 mm Hg, P=0.03, respectively) and pulse pressures (-1.7+/-0.6 mm Hg, P=0.004, and -1.4+/-0.6 mm Hg, P=0.02, respectively). No effect was observed for controls (P>0.10 for all indices). BNT also increased RR-high-frequency power (0.15 to 0.40 Hz; P=0.01) and RR interval (P<0.001) during cognitive tasks. Among controls, high-frequency power was unchanged (P=0.29), and RR interval decreased (P=0.03). Neither intervention altered spontaneous baroreflex sensitivity (P>0.10). In contrast to relaxation therapy, BNT with heart rate variability biofeedback modestly lowers ambulatory blood pressure during wakefulness, and it augments tonic vagal heart rate modulation. It is unknown whether efficacy of this treatment can be improved with biofeedback of baroreflex gain. BNT, alone or as an adjunct to drug therapy, may represent a promising new intervention for hypertension.

Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials.

PubMed

Roth, Daniel E; Leung, Michael; Mesfin, Elnathan; Qamar, Huma; Watterworth, Jessica; Papp, Eszter

2017-11-29

Objectives  To estimate the effects of vitamin D supplementation during pregnancy on 11 maternal and 27 neonatal/infant outcomes; to determine frequencies at which trial outcome data were missing, unreported, or inconsistently reported; and to project the potential contributions of registered ongoing or planned trials. Design  Systematic review and meta-analysis of randomised controlled trials; systematic review of registered but unpublished trials. Data sources  Medline, Embase, PubMed, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to September 2017; manual searches of reference lists of systematic reviews identified in the electronic search; and online trial registries for unpublished, ongoing, or planned trials. Eligibility criteria for study selection  Trials of prenatal vitamin D supplementation with randomised allocation and control groups administered placebo, no vitamin D, or vitamin D ≤600 IU/day (or its equivalent), and published in a peer reviewed journal. Results  43 trials (8406 participants) were eligible for meta-analyses. Median sample size was 133 participants. Vitamin D increased maternal/cord serum concentration of 25-hydroxyvitamin D, but the dose-response effect was weak. Maternal clinical outcomes were rarely ascertained or reported, but available data did not provide evidence of benefits. Overall, vitamin D increased mean birth weight of 58.33 g (95% confidence interval 18.88 g to 97.78 g; 37 comparisons) and reduced the risk of small for gestational age births (risk ratio 0.60, 95% confidence interval 0.40 to 0.90; seven comparisons), but findings were not robust in sensitivity and subgroup analyses. There was no effect on preterm birth (1.0, 0.77 to 1.30; 15 comparisons). There was strong evidence that prenatal vitamin D reduced the risk of offspring wheeze by age 3 years (0.81, 0.67 to 0.98; two comparisons). For most outcomes, meta-analyses included data from a minority of trials. Only eight of 43 trials (19%) had an overall low risk of bias. Thirty five planned/ongoing randomised controlled trials could contribute 12 530 additional participants to future reviews. Conclusions  Most trials on prenatal vitamin D published by September 2017 were small and of low quality. The evidence to date seems insufficient to guide clinical or policy recommendations. Future trials should be designed and powered to examine clinical endpoints, including maternal conditions related to pregnancy (such as pre-eclampsia), infant growth, and respiratory outcomes. Systematic review registration  PROSPERO CRD42016051292. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Superior Inhibitory Control and Resistance to Mental Fatigue in Professional Road Cyclists.

PubMed

Martin, Kristy; Staiano, Walter; Menaspà, Paolo; Hennessey, Tom; Marcora, Samuele; Keegan, Richard; Thompson, Kevin G; Martin, David; Halson, Shona; Rattray, Ben

2016-01-01

Given the important role of the brain in regulating endurance performance, this comparative study sought to determine whether professional road cyclists have superior inhibitory control and resistance to mental fatigue compared to recreational road cyclists. After preliminary testing and familiarization, eleven professional and nine recreational road cyclists visited the lab on two occasions to complete a modified incongruent colour-word Stroop task (a cognitive task requiring inhibitory control) for 30 min (mental exertion condition), or an easy cognitive task for 10 min (control condition) in a randomized, counterbalanced cross-over order. After each cognitive task, participants completed a 20-min time trial on a cycle ergometer. During the time trial, heart rate, blood lactate concentration, and rating of perceived exertion (RPE) were recorded. The professional cyclists completed more correct responses during the Stroop task than the recreational cyclists (705±68 vs 576±74, p = 0.001). During the time trial, the recreational cyclists produced a lower mean power output in the mental exertion condition compared to the control condition (216±33 vs 226±25 W, p = 0.014). There was no difference between conditions for the professional cyclists (323±42 vs 326±35 W, p = 0.502). Heart rate, blood lactate concentration, and RPE were not significantly different between the mental exertion and control conditions in both groups. The professional cyclists exhibited superior performance during the Stroop task which is indicative of stronger inhibitory control than the recreational cyclists. The professional cyclists also displayed a greater resistance to the negative effects of mental fatigue as demonstrated by no significant differences in perception of effort and time trial performance between the mental exertion and control conditions. These findings suggest that inhibitory control and resistance to mental fatigue may contribute to successful road cycling performance. These psychobiological characteristics may be either genetic and/or developed through the training and lifestyle of professional road cyclists.

Implementing practice change in chronic cancer pain management: clinician response to a phase III study of ketamine.

PubMed

Hardy, J R; Spruyt, O; Quinn, S J; Devilee, L R; Currow, D C

2014-06-01

An adequately powered, double-blind, multisite, randomised controlled trial has shown no net clinical benefit for subcutaneous ketamine over placebo in the management of cancer pain refractory to combination opioid and co-analgesic therapy. The results of the trial were disseminated widely both nationally and internationally. To determine whether the trial had impacted on clinical practice in Australasia. Members of the Australia and New Zealand Society of Palliative Medicine were sent an online ketamine utilisation survey. A total of 123/392 clinicians responded (31% response rate). The majority of respondents had practised for more than 10 years in a metropolitan hospital setting. Ketamine had been prescribed by 91% of respondents, and 92% were aware of the trial. As a result, 65% of respondents had changed practice (17% no longer prescribed ketamine, 46% used less and 2% more). Thirty-five per cent had not changed practice. Reasons for change included belief in the results of the study, concerns over the toxicity reported or because there were alternatives for pain control. Of those who prescribed less, over 80% were more selective and would now only use the drug in certain clinical situations or pain types, or when all other medications had failed. Although two-thirds of respondents reported practice change as a result of the randomised controlled trial, a minority remained convinced of the benefit of the drug from their own observations and would require additional evidence. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Low-level laser therapy for the treatment of androgenic alopecia: a review.

PubMed

Darwin, Evan; Heyes, Alexandra; Hirt, Penelope A; Wikramanayake, Tongyu Cao; Jimenez, Joaquin J

2018-02-01

There are many new low-level laser technologies that have been released commercially that claim to support hair regrowth. In this paper, we will examine the clinical trials to determine whether the body of evidence supports the use of low-level laser therapy (LLLT) to treat androgenic alopecia (AGA). A literature search was conducted through Pubmed, Embase, and Clinicaltrials.gov for clinical trials using LLLT to treat AGA. Thirteen clinical trials were assessed. Review articles were not included. Ten of 11 trials demonstrated significant improvement of androgenic alopecia in comparison to baseline or controls when treated with LLLT. In the remaining study, improvement in hair counts and hair diameter was recorded, but did not reach statistical significance. Two trials did not include statistical analysis, but showed marked improvement by hair count or by photographic evidence. Two trials showed efficacy for LLLT in combination with topical minoxidil. One trial showed efficacy when accompanying finasteride treatment. LLLT appears to be a safe, alternative treatment for patients with androgenic alopecia. Clinical trials have indicated efficacy for androgenic alopecia in both men and women. It may be used independently or as an adjuvant of minoxidil or finasteride. More research needs to be undertaken to determine the optimal power and wavelength to use in LLLT as well as LLLT's mechanism of action.

Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration

PubMed Central

Pitcher, Alex; Emberson, Jonathan; Lacro, Ronald V.; Sleeper, Lynn A.; Stylianou, Mario; Mahony, Lynn; Pearson, Gail D.; Groenink, Maarten; Mulder, Barbara J.; Zwinderman, Aeilko H.; De Backer, Julie; De Paepe, Anne M.; Arbustini, Eloisa; Erdem, Guliz; Jin, Xu Yu; Flather, Marcus D.; Mullen, Michael J.; Child, Anne H.; Forteza, Alberto; Evangelista, Arturo; Chiu, Hsin-Hui; Wu, Mei-Hwan; Sandor, George; Bhatt, Ami B.; Creager, Mark A.; Devereux, Richard B.; Loeys, Bart; Forfar, J. Colin; Neubauer, Stefan; Watkins, Hugh; Boileau, Catherine; Jondeau, Guillaume; Dietz, Harry C.; Baigent, Colin

2015-01-01

Rationale A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial. Design A prospective, collaborative meta-analysis based on individual patient data from all randomized trials in Marfan syndrome of (i) ARBs versus placebo (or open-label control) and (ii) ARBs versus β-blockers will be performed. A prospective study design, in which the principal hypotheses, trial eligibility criteria, analyses, and methods are specified in advance of the unblinding of the component trials, will help to limit bias owing to data-dependent emphasis on the results of particular trials. The use of individual patient data will allow for analysis of the effects of ARBs in particular patient subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis protocol summarized in this report was written on behalf of the Marfan Treatment Trialists' Collaboration and finalized in late 2012, without foreknowledge of the results of any component trial, and will be made available online (http://www.ctsu.ox.ac.uk/research/meta-trials). PMID:25965707

Measuring Behavioral Outcomes Associated with Comprehensive Character Education Programs: A Practical Approach to Using Fewer Schools in School-Randomized Controlled Trials While Maintaining Adequate Statistical Power

ERIC Educational Resources Information Center

Holtzapple, Carol K.

2011-01-01

Character education programs support the development of positive character traits in children and adults. Effective violence prevention programs improve pro-social competencies and reduce negative behaviors in students by enhancing protective factors (strong bonds with teachers; clear rules of conduct that are consistently enforced) and targeting…

Wright Brothers National Memorial: Site of the First Controlled Powered Flight. Teaching with Historic Places.

ERIC Educational Resources Information Center

Olio, Brenda K.

Wilbur and Orville Wright undertook the first test airplane flight on December 17, 1903, at the Outer Banks of North Carolina. Their success represented the culmination of four years of painstaking research and trials in which they designed and improved their flying machines at home in Dayton, Ohio, and tested them each year near Kitty Hawk, North…

Clinical trials bureaucracy: unintended consequences of well-intentioned policy.

PubMed

Califf, Robert M

2006-01-01

As randomized controlled trials have become the 'gold standard' for medical research, a complex regulatory structure for the conduct of clinical trials has emerged. However, this structure has not been adequately assessed to ensure that regulations governing human subjects research actually produce the desired effects. Our purpose is to identify some of the major shortcomings in the current regulatory system of human clinical trials oversight, and to propose some potential solutions to these problems. We discuss the evolution of the current US regulatory environment and its application in the context of several widely-used drug therapies. Despite numerous randomized controlled trials, performed within a structure of extensive documentation and data collection, serious shortcomings in a number of pharmaceutical therapies were not detected until after the drugs were approved and widely adopted by clinicians. The current system of regulatory bureaucracy in clinical trials has led to an extremely expensive research paradigm that, in spite of complex systems of oversight and exhaustive data collection, cannot be shown to adequately ensure the integrity of the research process and the protection of human research subjects. Some parts of the system, including Research Ethics Review Boards, may not be well-suited to carrying out their core mission of overseeing research conduct, and other aspects of clinical trials regulatory structure, such as monitoring/auditing review and adverse event reporting, may constitute a waste of money and resources. Misdirected data collection and adverse events reporting divert valuable resources and hamper development of large, simple clinical trials powered to definitively answer important research questions. Careful scrutiny of the utility of current or proposed regulatory schemes is required to ensure the integrity of human subjects research and to enhance the effectiveness of research dollars.

The effect of a behavioral activation program on improving mental and physical health complaints associated with radiation stress among mothers in Fukushima: a randomized controlled trial.

PubMed

Imamura, Kotaro; Sekiya, Yuki; Asai, Yumi; Umeda, Maki; Horikoshi, Naoko; Yasumura, Seiji; Yabe, Hirooki; Akiyama, Tsuyoshi; Kawakami, Norito

2016-11-08

Mothers living with small children in Fukushima prefecture may experience radiation anxiety and related symptoms after the Fukushima Dai'ich Nuclear Power Plant Accident. A behavioral activation (BA) program was developed to improve their psychosomatic symptoms. The purpose of this randomized controlled trial was to examine the effectiveness of a BA program for improving psychological distress and physical symptoms among mothers with preschool children in Fukushima-prefecture 3 years after the Fukushima Daiichi Nuclear Power Plant accident. Participants were recruited from mothers living with a preschool child(ren) in Fukushima city and surrounding areas though a newspaper advertisement, posters, and flyers. Participants allocated to the intervention group received a newly developed group-based BA program, which consisted of two 90- min lessons with a 1-week interval. Psychological distress and physical symptoms as a primary outcome, and radiation anxiety and positive well-being (liveliness and life satisfaction) as a secondary outcome, were measured at baseline, 1- and 3-month follow-ups. Participants were randomly allocated to either an intervention or a control group (18 and 19, respectively). The BA program showed a marginally significant intervention effect on psychological distress (p = 0.051) and physical symptoms (p = 0.07) at 1-month follow-up, while the effect became smaller at 3-month follow-up. The effect sizes at 1-month were medium to large (-0.72 and -0.56, respectively). There was a significant intervention effect on increasing liveliness at 3-month follow-up (p = 0.02); and there were marginally significant effects on life satisfaction at 1- and 3-month follow-ups (both p = 0.09). This BA program may be effective for improving psychological distress, physical symptoms, and well-being, at least for a short duration, among mothers with preschool children after the nuclear power plant accident in Fukushima, while a further large-scale study is needed. The UMIN Clinical Trials Registry (UMIN-CTR; ID =  UMIN000014081 ). Registered 27 May 2014.

Comparative study of outcome measures and analysis methods for traumatic brain injury trials.

PubMed

Alali, Aziz S; Vavrek, Darcy; Barber, Jason; Dikmen, Sureyya; Nathens, Avery B; Temkin, Nancy R

2015-04-15

Batteries of functional and cognitive measures have been proposed as alternatives to the Extended Glasgow Outcome Scale (GOSE) as the primary outcome for traumatic brain injury (TBI) trials. We evaluated several approaches to analyzing GOSE and a battery of four functional and cognitive measures. Using data from a randomized trial, we created a "super" dataset of 16,550 subjects from patients with complete data (n=331) and then simulated multiple treatment effects across multiple outcome measures. Patients were sampled with replacement (bootstrapping) to generate 10,000 samples for each treatment effect (n=400 patients/group). The percentage of samples where the null hypothesis was rejected estimates the power. All analytic techniques had appropriate rates of type I error (≤5%). Accounting for baseline prognosis either by using sliding dichotomy for GOSE or using regression-based methods substantially increased the power over the corresponding analysis without accounting for prognosis. Analyzing GOSE using multivariate proportional odds regression or analyzing the four-outcome battery with regression-based adjustments had the highest power, assuming equal treatment effect across all components. Analyzing GOSE using a fixed dichotomy provided the lowest power for both unadjusted and regression-adjusted analyses. We assumed an equal treatment effect for all measures. This may not be true in an actual clinical trial. Accounting for baseline prognosis is critical to attaining high power in Phase III TBI trials. The choice of primary outcome for future trials should be guided by power, the domain of brain function that an intervention is likely to impact, and the feasibility of collecting outcome data.

Comparative Study of Outcome Measures and Analysis Methods for Traumatic Brain Injury Trials

PubMed Central

Alali, Aziz S.; Vavrek, Darcy; Barber, Jason; Dikmen, Sureyya; Nathens, Avery B.

2015-01-01

Abstract Batteries of functional and cognitive measures have been proposed as alternatives to the Extended Glasgow Outcome Scale (GOSE) as the primary outcome for traumatic brain injury (TBI) trials. We evaluated several approaches to analyzing GOSE and a battery of four functional and cognitive measures. Using data from a randomized trial, we created a “super” dataset of 16,550 subjects from patients with complete data (n=331) and then simulated multiple treatment effects across multiple outcome measures. Patients were sampled with replacement (bootstrapping) to generate 10,000 samples for each treatment effect (n=400 patients/group). The percentage of samples where the null hypothesis was rejected estimates the power. All analytic techniques had appropriate rates of type I error (≤5%). Accounting for baseline prognosis either by using sliding dichotomy for GOSE or using regression-based methods substantially increased the power over the corresponding analysis without accounting for prognosis. Analyzing GOSE using multivariate proportional odds regression or analyzing the four-outcome battery with regression-based adjustments had the highest power, assuming equal treatment effect across all components. Analyzing GOSE using a fixed dichotomy provided the lowest power for both unadjusted and regression-adjusted analyses. We assumed an equal treatment effect for all measures. This may not be true in an actual clinical trial. Accounting for baseline prognosis is critical to attaining high power in Phase III TBI trials. The choice of primary outcome for future trials should be guided by power, the domain of brain function that an intervention is likely to impact, and the feasibility of collecting outcome data. PMID:25317951

Efficacy of treadmill exercises on arterial blood oxygenation, oxygen consumption and walking distance in healthy elderly people: a controlled trial.

PubMed

Bichay, Ashraf Adel Fahmy; Ramírez, Juan M; Núñez, Víctor M; Lancho, Carolina; Poblador, María S; Lancho, José L

2016-05-25

Regular physical exercise and healthy lifestyle can improve aerobic power of the elderly, although lung capacity gradually deteriorates with age. The aims of the study are: a) to evaluate the therapeutic effect of a treadmill exercise program on arterial blood oxygenation (SaO2), maximum oxygen consumption (VO2max) and maximum walking distance (MWD) in healthy elderly people; b) to examine the outcome of the program at a supervised short-term and at an unsupervised long-term. A prospective, not-randomized controlled intervention trial (NRCT) was conducted. Eighty participants were allocated into two homogeneous groups (training group, TG, n = 40; control group, CG, n = 40). Each group consisted of 20 men and 20 women. Pre-intervention measures of SaO2, VO2max and MWD were taken of each participant 1-week before the training program to establish the baseline. Also, during the training program, the participants were followed up at the 12, 30 and 48th week. The exercise program consisted of walking on a treadmill with fixed 0 % grade of inclination 3 times weekly for 48 weeks; the first 12 weeks were supervised and the remaining 36 weeks of the program were unsupervised. Participants in the control group were encouraged to walk twice a week during 45 min, and received standard recommendations for proper health. Related to the baseline, the SaO2, VO2max, and MWD is greater in the intervention group at the 12(th) (p <.001), 30(th) (p <.001) and 48(th) week (p <.001). Compared with the control group, there was also a significant improvement of SaO2, VO2max, and MWD valuesin the intervention group (p <.001) at the 12(th) (p <.001), 30(th) (p <.001) and 48(th) week (p <.001). Supervised intervention shows greater improvement of SaO2, VO2max, and MWD values than in the unsupervised one. These results show that performing moderate exercise, specifically walking 3 days a week, is highly recommended for healthy older people, improving aerobic power. Current Controlled Trials ISRCTN12621097 .

What is the ideal dose and power output of low-level laser therapy (810 nm) on muscle performance and post-exercise recovery? Study protocol for a double-blind, randomized, placebo-controlled trial.

PubMed

de Oliveira, Adriano Rodrigues; Vanin, Adriane Aver; De Marchi, Thiago; Antonialli, Fernanda Colella; Grandinetti, Vanessa dos Santos; de Paiva, Paulo Roberto Vicente; Albuquerque Pontes, Gianna Móes; Santos, Larissa Aline; Aleixo Junior, Ivo de Oliveira; de Carvalho, Paulo de Tarso Camillo; Bjordal, Jan Magnus; Leal-Junior, Ernesto Cesar Pinto

2014-02-27

Recent studies involving phototherapy applied prior to exercise have demonstrated positive results regarding the attenuation of muscle fatigue and the expression of biochemical markers associated with recovery. However, a number of factors remain unknown, such as the ideal dose and application parameters, mechanisms of action and long-term effects on muscle recovery. The aims of the proposed project are to evaluate the long-term effects of low-level laser therapy on post-exercise musculoskeletal recovery and identify the best dose andapplication power/irradiation time. A double-blind, randomized, placebo-controlled clinical trial with be conducted. After fulfilling the eligibility criteria, 28 high-performance athletes will be allocated to four groups of seven volunteers each. In phase 1, the laser power will be 200 mW and different doses will be tested: Group A (2 J), Group B (6 J), Group C (10 J) and Group D (0 J). In phase 2, the best dose obtained in phase 1 will be used with the same distribution of the volunteers, but with different powers: Group A (100 mW), Group B (200 mW), Group C (400 mW) and Group D (0 mW). The isokinetic test will be performed based on maximum voluntary contraction prior to the application of the laser and after the eccentric contraction protocol, which will also be performed using the isokinetic dynamometer. The following variables related to physical performance will be analyzed: peak torque/maximum voluntary contraction, delayed onset muscle soreness (algometer), biochemical markers of muscle damage, inflammation and oxidative stress. Our intention, is to determine optimal laser therapy application parameters capable of slowing down the physiological muscle fatigue process, reducing injuries or micro-injuries in skeletal muscle stemming from physical exertion and accelerating post-exercise muscle recovery. We believe that, unlike drug therapy, LLLT has a biphasic dose-response pattern. The protocol for this study is registered with the Protocol Registry System, ClinicalTrials.gov identifier NCT01844271.

Diabetes and chocolate: friend or foe?

PubMed

Mellor, Duane D; Sathyapalan, Thozhukat; Kilpatrick, Eric S; Atkin, Stephen L

2015-11-18

Polyphenols and other compounds found in cocoa and chocolate have therapeutic potential in the management of diabetes in humans. Polyphenol benefits have been proposed supported by in vitro studies, animal work, and clinical trials, which have been conducted mostly in healthy volunteers. The energy-dense formulations of many cocoa and chocolate products, which can be up to 50% sugar by weight, have given the perception that chocolate may be harmful through its contribution to obesity. A review of both clinical trial databases and published literature yielded 15 registered trials and 7 published studies. The published data interventions reported are diverse and vary widely in quality, including poor selection of control products or inadequate blinding procedures. There are also inconsistencies in reporting of data with limited information on the effect of cocoa and chocolate supplementation on weight and glycemic control despite the potential benefits reported with respect to the cardiovascular risk factors of endothelial function and lipids. More studies are required powered for primary clinical outcomes together with the development of standardized product formulations that optimize the dose of polyphenols within a palatable and energy-restricted product.

Olive Oil, Sunflower Oil or no Oil for Baby Dry Skin or Massage: A Pilot, Assessor-blinded, Randomized Controlled Trial (the Oil in Baby SkincaRE [OBSeRvE] Study).

PubMed

Cooke, Alison; Cork, Michael J; Victor, Suresh; Campbell, Malcolm; Danby, Simon; Chittock, John; Lavender, Tina

2016-03-01

Topical oils on baby skin may contribute to development of childhood atopic eczema. A pilot, assessor-blinded, randomized controlled trial assessed feasibility of a definitive trial investigating their impact in neonates. One-hundred and fifteen healthy, full-term neonates were randomly assigned to olive oil, sunflower oil or no oil, twice daily for 4 weeks, stratified by family history of atopic eczema. We measured spectral profile of lipid lamellae, trans-epidermal water loss (TEWL), stratum corneum hydration and pH and recorded clinical observations, at baseline, and 4 weeks post-birth. Recruitment was challenging (recruitment 11.1%; retention 80%), protocol adherence reasonable (79-100%). Both oil groups had significantly improved hydration but significantly less improvement in lipid lamellae structure compared to the no oil group. There were no significant differences in TEWL, pH or erythema/skin scores. The study was not powered for clinical significance, but until further research is conducted, caution should be exercised when recommending oils for neonatal skin.

Brain-machine interfaces for controlling lower-limb powered robotic systems.

PubMed

He, Yongtian; Eguren, David; Azorín, José M; Grossman, Robert G; Luu, Trieu Phat; Contreras-Vidal, Jose L

2018-04-01

Lower-limb, powered robotics systems such as exoskeletons and orthoses have emerged as novel robotic interventions to assist or rehabilitate people with walking disabilities. These devices are generally controlled by certain physical maneuvers, for example pressing buttons or shifting body weight. Although effective, these control schemes are not what humans naturally use. The usability and clinical relevance of these robotics systems could be further enhanced by brain-machine interfaces (BMIs). A number of preliminary studies have been published on this topic, but a systematic understanding of the experimental design, tasks, and performance of BMI-exoskeleton systems for restoration of gait is lacking. To address this gap, we applied standard systematic review methodology for a literature search in PubMed and EMBASE databases and identified 11 studies involving BMI-robotics systems. The devices, user population, input and output of the BMIs and robot systems respectively, neural features, decoders, denoising techniques, and system performance were reviewed and compared. Results showed BMIs classifying walk versus stand tasks are the most common. The results also indicate that electroencephalography (EEG) is the only recording method for humans. Performance was not clearly presented in most of the studies. Several challenges were summarized, including EEG denoising, safety, responsiveness and others. We conclude that lower-body powered exoskeletons with automated gait intention detection based on BMIs open new possibilities in the assistance and rehabilitation fields, although the current performance, clinical benefits and several key challenging issues indicate that additional research and development is required to deploy these systems in the clinic and at home. Moreover, rigorous EEG denoising techniques, suitable performance metrics, consistent trial reporting, and more clinical trials are needed to advance the field.

Brain-machine interfaces for controlling lower-limb powered robotic systems

NASA Astrophysics Data System (ADS)

He, Yongtian; Eguren, David; Azorín, José M.; Grossman, Robert G.; Phat Luu, Trieu; Contreras-Vidal, Jose L.

2018-04-01

Objective. Lower-limb, powered robotics systems such as exoskeletons and orthoses have emerged as novel robotic interventions to assist or rehabilitate people with walking disabilities. These devices are generally controlled by certain physical maneuvers, for example pressing buttons or shifting body weight. Although effective, these control schemes are not what humans naturally use. The usability and clinical relevance of these robotics systems could be further enhanced by brain-machine interfaces (BMIs). A number of preliminary studies have been published on this topic, but a systematic understanding of the experimental design, tasks, and performance of BMI-exoskeleton systems for restoration of gait is lacking. Approach. To address this gap, we applied standard systematic review methodology for a literature search in PubMed and EMBASE databases and identified 11 studies involving BMI-robotics systems. The devices, user population, input and output of the BMIs and robot systems respectively, neural features, decoders, denoising techniques, and system performance were reviewed and compared. Main results. Results showed BMIs classifying walk versus stand tasks are the most common. The results also indicate that electroencephalography (EEG) is the only recording method for humans. Performance was not clearly presented in most of the studies. Several challenges were summarized, including EEG denoising, safety, responsiveness and others. Significance. We conclude that lower-body powered exoskeletons with automated gait intention detection based on BMIs open new possibilities in the assistance and rehabilitation fields, although the current performance, clinical benefits and several key challenging issues indicate that additional research and development is required to deploy these systems in the clinic and at home. Moreover, rigorous EEG denoising techniques, suitable performance metrics, consistent trial reporting, and more clinical trials are needed to advance the field.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hagen Schempf; Daphne D'Zurko

Under funding from the Department of Energy (DOE) and the Northeast Gas Association (NGA), Carnegie Mellon University (CMU) developed an untethered, wireless remote controlled inspection robot dubbed Explorer. The project entailed the design and prototyping of a wireless self-powered video-inspection robot capable of accessing live 6- and 8-inch diameter cast-iron and steel mains, while traversing turns and Ts and elbows under real-time control with live video feedback to an operator. The design is that of a segmented actively articulated and wheel-leg powered robot design, with fisheye imaging capability and self-powered battery storage and wireless real-time communication link. The prototype wasmore » functionally tested in an above ground pipe-network, in order to debug all mechanical, electrical and software subsystems, and develop the necessary deployment and retrieval, as well as obstacle-handling scripts. A pressurized natural gas test-section was used to certify it for operation in natural gas at up to 60 psig. Two subsequent live-main field-trials in both cast-iron and steel pipe, demonstrated its ability to be safely launched, operated and retrieved under real-world conditions. The system's ability to safely and repeatably exidrecover from angled and vertical launchers, traverse multi-thousand foot long pipe-sections, make T and varied-angle elbow-turns while wirelessly sending live video and handling command and control messages, was clearly demonstrated. Video-inspection was clearly shown to be a viable tool to understand the state of this critical buried infrastructure, irrespective of low- (cast-iron) or high-pressure (steel) conditions. This report covers the different aspects of specifications, requirements, design, prototyping, integration and testing and field-trialing of the Explorer platform.« less

Power of an Adaptive Trial Design for Endovascular Stroke Studies: Simulations Using IMS (Interventional Management of Stroke) III Data.

PubMed

Lansberg, Maarten G; Bhat, Ninad S; Yeatts, Sharon D; Palesch, Yuko Y; Broderick, Joseph P; Albers, Gregory W; Lai, Tze L; Lavori, Philip W

2016-12-01

Adaptive trial designs that allow enrichment of the study population through subgroup selection can increase the chance of a positive trial when there is a differential treatment effect among patient subgroups. The goal of this study is to illustrate the potential benefit of adaptive subgroup selection in endovascular stroke studies. We simulated the performance of a trial design with adaptive subgroup selection and compared it with that of a traditional design. Outcome data were based on 90-day modified Rankin Scale scores, observed in IMS III (Interventional Management of Stroke III), among patients with a vessel occlusion on baseline computed tomographic angiography (n=382). Patients were categorized based on 2 methods: (1) according to location of the arterial occlusive lesion and onset-to-randomization time and (2) according to onset-to-randomization time alone. The power to demonstrate a treatment benefit was based on 10 000 trial simulations for each design. The treatment effect was relatively homogeneous across categories when patients were categorized based on arterial occlusive lesion and time. Consequently, the adaptive design had similar power (47%) compared with the fixed trial design (45%). There was a differential treatment effect when patients were categorized based on time alone, resulting in greater power with the adaptive design (82%) than with the fixed design (57%). These simulations, based on real-world patient data, indicate that adaptive subgroup selection has merit in endovascular stroke trials as it substantially increases power when the treatment effect differs among subgroups in a predicted pattern. © 2016 American Heart Association, Inc.

Surgical interventions for high grade vulval intraepithelial neoplasia

PubMed Central

Kaushik, Sonali; Pepas, Litha; Nordin, Andy; Bryant, Andrew; Dickinson, Heather O

2014-01-01

Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin. This uncommon chronic skin condition of the vulva is associated with a high risk of recurrence and the potential to progress to vulval cancer. The condition is complicated by its’ multicentric and multifocal nature. The incidence of this condition appears to be rising particularly in the younger age group. There is a lack of consensus on the optimal surgical treatment method. However, the rationale for surgical treatment of VIN has been to treat symptoms and exclude underlying malignancy with the continued aim of preservation of vulval anatomy and function. Repeated treatments affect local cosmesis and cause psychosexual morbidity thus impacting on the patients’ quality of life. Objectives To evaluate the effectiveness and safety of surgical interventions for high grade VIN. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 3, 2010, Cochrane Gynaecological Cancer Group Trials Register, MEDLINE and EMBASE up to September 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that compared surgical interventions, in adult women diagnosed with high grade vulval intraepithelial neoplasia. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We found only one RCT which included 30 women that met our inclusion criteria and this trial reported data on carbon dioxide laser (CO2 laser) versus ultrasonic surgical aspiration (USA). There was no statistically significant difference in the risk of disease recurrence after one year follow-up, pain, presence of scarring, dysuria or burning, adhesions, infection, abnormal discharge and eschar between women who received CO2 laser and those who received USA. The trial lacked statistical power due to the small number of women in each group and the low number of observed events, but was at low risk of bias. Authors’ conclusions The included trial lacked statistical power due to the small number of women in each group and the low number of observed events. Therefore in the absence of reliable evidence regarding the effectiveness and safety of the two surgical techniques for the management of vulval intraepithelial neoplasia precludes any definitive guidance or recommendations for clinical practice. PMID:21249698

Born to Yawn? Understanding Yawning as a Warning of the Rise in Cortisol Levels: Randomized Trial

PubMed Central

Bishop, Phil

2012-01-01

Background Yawning consistently poses a conundrum to the medical profession and neuroscientists. Despite neurological evidence such as parakinesia brachialis oscitans in stroke patients and thermo-irregulation in multiple sclerosis patients, there is considerable debate over the reasons for yawning with the mechanisms and hormonal pathways still not fully understood. Cortisol is implicated during yawning and may link many neurological disorders. Evidence was found in support of the Thompson cortisol hypothesis that proposes cortisol levels are elevated during yawning just as they tend to rise during stress and fatigue. Objectives To investigate whether saliva cortisol levels rise during yawning and, therefore, support the Thompson cortisol hypothesis. Methods We exposed 20 male and female volunteers aged between 18 and 53 years to conditions that provoked a yawning response in a randomized controlled trial. Saliva samples were collected at the start and again after the yawning response, or at the end of the stimuli presentations if the participant did not yawn. In addition, we collected electromyographic data of the jaw muscles to determine rest and yawning phases of neural activity. Yawning susceptibility scale, Hospital Anxiety and Depression Scale, General Health Questionnaire, and demographic and health details were also collected from each participant. A comprehensive data set allowed comparison between yawners and nonyawners, as well as between rest and yawning phases. Collecting electromyographic data from the yawning phase is novel, and we hope this will provide new information about neuromuscular activity related to cortisol levels. Exclusion criteria included chronic fatigue, diabetes, fibromyalgia, heart conditions, high blood pressure, hormone replacement therapy, multiple sclerosis, and stroke. We compared data between and within participants. Results In the yawning group, there was a significant difference between saliva cortisol samples (t 10 = –3.071, P = .01). Power and effect size were computed based on repeated-measures t tests for both the yawning and nonyawning groups. There was a medium effect size for the nonyawners group (r = .467) but low power (36%). Results were similar for the yawners group: medium effect size (r = .440) and low power (33%). Conclusions There was significant evidence in support of the Thompson cortisol hypothesis that suggests cortisol levels are elevated during yawning. A further longitudinal study is planned to test neurological patients. We intend to devise a diagnostic tool based on changes in cortisol levels that may assist in the early diagnosis of neurological disorders based on the data collected. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 61942768; http://www.controlled-trials.com/ISRCTN61942768/61942768 (Archived by WebCite at http://www.webcitation.org/6A75ZNYvr) PMID:23611879

Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

PubMed

Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

2018-03-14

Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. This is an update of a previously published review. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 20 June 2017.Date of latest search of all other sources: 16 November 2017. Any randomised or quasi-randomised controlled trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care. We identified 25 papers, describing 16 unique trials which were potentially eligible for inclusion in the review. However, after assessment, no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found. No randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were included. One ongoing trial has been identified which may potentially eligible for inclusion once completed. As no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease were found for inclusion in this review, the research evidence for current policy recommendations is limited to non-randomised studies.Information from well-designed, adequately powered, randomised trials is desirable in order to make more robust recommendations for practice. However, such trials must also consider the legal, ethical, and cultural barriers to implementation of preconception genetic risk assessment.

Trial Sequential Analysis in systematic reviews with meta-analysis.

PubMed

Wetterslev, Jørn; Jakobsen, Janus Christian; Gluud, Christian

2017-03-06

Most meta-analyses in systematic reviews, including Cochrane ones, do not have sufficient statistical power to detect or refute even large intervention effects. This is why a meta-analysis ought to be regarded as an interim analysis on its way towards a required information size. The results of the meta-analyses should relate the total number of randomised participants to the estimated required meta-analytic information size accounting for statistical diversity. When the number of participants and the corresponding number of trials in a meta-analysis are insufficient, the use of the traditional 95% confidence interval or the 5% statistical significance threshold will lead to too many false positive conclusions (type I errors) and too many false negative conclusions (type II errors). We developed a methodology for interpreting meta-analysis results, using generally accepted, valid evidence on how to adjust thresholds for significance in randomised clinical trials when the required sample size has not been reached. The Lan-DeMets trial sequential monitoring boundaries in Trial Sequential Analysis offer adjusted confidence intervals and restricted thresholds for statistical significance when the diversity-adjusted required information size and the corresponding number of required trials for the meta-analysis have not been reached. Trial Sequential Analysis provides a frequentistic approach to control both type I and type II errors. We define the required information size and the corresponding number of required trials in a meta-analysis and the diversity (D 2 ) measure of heterogeneity. We explain the reasons for using Trial Sequential Analysis of meta-analysis when the actual information size fails to reach the required information size. We present examples drawn from traditional meta-analyses using unadjusted naïve 95% confidence intervals and 5% thresholds for statistical significance. Spurious conclusions in systematic reviews with traditional meta-analyses can be reduced using Trial Sequential Analysis. Several empirical studies have demonstrated that the Trial Sequential Analysis provides better control of type I errors and of type II errors than the traditional naïve meta-analysis. Trial Sequential Analysis represents analysis of meta-analytic data, with transparent assumptions, and better control of type I and type II errors than the traditional meta-analysis using naïve unadjusted confidence intervals.

Investigating the Effects of Typical Rowing Strength Training Practices on Strength and Power Development and 2,000 m Rowing Performance

PubMed Central

Caplan, Nicholas; Christian Gibbon, Karl; Howatson, Glyn; Grant Thompson, Kevin

2016-01-01

Abstract This study aimed to determine the effects of a short-term, strength training intervention, typically undertaken by club-standard rowers, on 2,000 m rowing performance and strength and power development. Twenty-eight male rowers were randomly assigned to intervention or control groups. All participants performed baseline testing involving assessments of muscle soreness, creatine kinase activity (CK), maximal voluntary contraction (leg-extensors) (MVC), static-squat jumps (SSJ), counter-movement jumps (CMJ), maximal rowing power strokes (PS) and a 2,000 m rowing ergometer time-trial (2,000 m) with accompanying respiratory-exchange and electromyography (EMG) analysis. Intervention group participants subsequently performed three identical strength training (ST) sessions, in the space of five days, repeating all assessments 24 h following the final ST. The control group completed the same testing procedure but with no ST. Following ST, the intervention group experienced significant elevations in soreness and CK activity, and decrements in MVC, SSJ, CMJ and PS (p < 0.01). However, 2,000 m rowing performance, pacing strategy and gas exchange were unchanged across trials in either condition. Following ST, significant increases occurred for EMG (p < 0.05), and there were non-significant trends for decreased blood lactate and anaerobic energy liberation (p = 0.063 – 0.086). In summary, club-standard rowers, following an intensive period of strength training, maintained their 2,000 m rowing performance despite suffering symptoms of muscle damage and disruption to muscle function. This disruption likely reflected the presence of acute residual fatigue, potentially in type II muscle fibres as strength and power development were affected. PMID:28149354

Electroencephalographic identifiers of motor adaptation learning

NASA Astrophysics Data System (ADS)

Özdenizci, Ozan; Yalçın, Mustafa; Erdoğan, Ahmetcan; Patoğlu, Volkan; Grosse-Wentrup, Moritz; Çetin, Müjdat

2017-08-01

Objective. Recent brain-computer interface (BCI) assisted stroke rehabilitation protocols tend to focus on sensorimotor activity of the brain. Relying on evidence claiming that a variety of brain rhythms beyond sensorimotor areas are related to the extent of motor deficits, we propose to identify neural correlates of motor learning beyond sensorimotor areas spatially and spectrally for further use in novel BCI-assisted neurorehabilitation settings. Approach. Electroencephalographic (EEG) data were recorded from healthy subjects participating in a physical force-field adaptation task involving reaching movements through a robotic handle. EEG activity recorded during rest prior to the experiment and during pre-trial movement preparation was used as features to predict motor adaptation learning performance across subjects. Main results. Subjects learned to perform straight movements under the force-field at different adaptation rates. Both resting-state and pre-trial EEG features were predictive of individual adaptation rates with relevance of a broad network of beta activity. Beyond sensorimotor regions, a parieto-occipital cortical component observed across subjects was involved strongly in predictions and a fronto-parietal cortical component showed significant decrease in pre-trial beta-powers for users with higher adaptation rates and increase in pre-trial beta-powers for users with lower adaptation rates. Significance. Including sensorimotor areas, a large-scale network of beta activity is presented as predictive of motor learning. Strength of resting-state parieto-occipital beta activity or pre-trial fronto-parietal beta activity can be considered in BCI-assisted stroke rehabilitation protocols with neurofeedback training or volitional control of neural activity for brain-robot interfaces to induce plasticity.

Understanding Statistical Power in Cluster Randomized Trials: Challenges Posed by Differences in Notation and Terminology

ERIC Educational Resources Information Center

Spybrook, Jessaca; Hedges, Larry; Borenstein, Michael

2014-01-01

Research designs in which clusters are the unit of randomization are quite common in the social sciences. Given the multilevel nature of these studies, the power analyses for these studies are more complex than in a simple individually randomized trial. Tools are now available to help researchers conduct power analyses for cluster randomized…

A General Framework for Power Analysis to Detect the Moderator Effects in Two- and Three-Level Cluster Randomized Trials

ERIC Educational Resources Information Center

Dong, Nianbo; Spybrook, Jessaca; Kelcey, Ben

2016-01-01

The purpose of this study is to propose a general framework for power analyses to detect the moderator effects in two- and three-level cluster randomized trials (CRTs). The study specifically aims to: (1) develop the statistical formulations for calculating statistical power, minimum detectable effect size (MDES) and its confidence interval to…

Bayesian adaptive bandit-based designs using the Gittins index for multi-armed trials with normally distributed endpoints.

PubMed

Smith, Adam L; Villar, Sofía S

2018-01-01

Adaptive designs for multi-armed clinical trials have become increasingly popular recently because of their potential to shorten development times and to increase patient response. However, developing response-adaptive designs that offer patient-benefit while ensuring the resulting trial provides a statistically rigorous and unbiased comparison of the different treatments included is highly challenging. In this paper, the theory of Multi-Armed Bandit Problems is used to define near optimal adaptive designs in the context of a clinical trial with a normally distributed endpoint with known variance. We report the operating characteristics (type I error, power, bias) and patient-benefit of these approaches and alternative designs using simulation studies based on an ongoing trial. These results are then compared to those recently published in the context of Bernoulli endpoints. Many limitations and advantages are similar in both cases but there are also important differences, specially with respect to type I error control. This paper proposes a simulation-based testing procedure to correct for the observed type I error inflation that bandit-based and adaptive rules can induce.

Estrogen, aging and the cardiovascular system

PubMed Central

Stice, James P.; Lee, Jennifer S.; Pechenino, Angela S.; Knowlton, Anne A.

2014-01-01

Estrogen is a powerful hormone with pleiotropic effects. Estrogens have potent antioxidant effects and are able to reduce inflammation, induce vasorelaxation and alter gene expression in both the vasculature and the heart. Estrogen treatment of cultured cardiac myocytes and endothelial cells rapidly activates NFκB, induces heat-shock protein (HSP)-72, a potent intracellular protective protein, and protects cells from simulated ischemia. In in vivo models, estrogens protect against ischemia and trauma/hemorrhage. Estrogens may decrease the expression of soluble epoxide hydrolase, which has deleterious effects on the cardiovascular system through metabolism of epoxyeicosatrienoic acids. Natural (endogenous) estrogens in premenopausal women appear to protect against cardiovascular disease and yet controlled clinical trials have not indicated a benefit from estrogen replacement postmenopause. Much remains to be understood in regards to the many properties of this powerful hormone and how changes in this hormone interact with aging-associated changes. The unexpected negative results of trials of estrogen replacement postmenopause probably arise from our lack of understanding of the many effects of this hormone. PMID:19371207

Willingness to pay for small solar powered bed net fans: results of a Becker-DeGroot-Marschak auction in Ghana.

PubMed

Yukich, Joshua O; Briët, Olivier J T; Ahorlu, Collins K; Nardini, Peter; Keating, Joseph

2017-08-07

Long-lasting insecticidal nets (LLINs) are one of the main interventions recommended by the World Health Organization for malaria vector control. LLINs are ineffective if they are not being used. Subsequent to the completion of a cluster randomized cross over trial conducted in rural Greater Accra where participants were provided with the 'Bɔkɔɔ System'-a set of solar powered net fan and light consoles with a solar panel and battery-or alternative household water filters, all trial participants were invited to participate in a Becker-DeGroot-Marschak auction to determine the mean willingness to pay (WTP) for the fan and light consoles and to estimate the demand curve for the units. Results demonstraed a mean WTP of approximately 55 Cedis (~13 USD). Demand results suggested that at a price which would support full manufacturing cost recovery, a majority of households in the area would be willing to purchase at least one such unit.

Brief intervention to reduce risky drinking in pregnancy: study protocol for a randomized controlled trial.

PubMed

Wilson, Graeme B; McGovern, Ruth; Antony, Grace; Cassidy, Paul; Deverill, Mark; Graybill, Erin; Gilvarry, Eilish; Hodgson, Moira; Kaner, Eileen F S; Laing, Kirsty; McColl, Elaine; Newbury-Birch, Dorothy; Rankin, Judith

2012-09-24

Risky drinking in pregnancy by UK women is likely to result in many alcohol-exposed pregnancies. Studies from the USA suggest that brief intervention has promise for alcohol risk reduction in antenatal care. However, further research is needed to establish whether this evidence from the USA is applicable to the UK. This pilot study aims to investigate whether pregnant women can be recruited and retained in a randomized controlled trial of brief intervention aimed at reducing risky drinking in women receiving antenatal care. The trial will rehearse the parallel-group, non-blinded design and procedures of a subsequent definitive trial. Over 8 months, women aged 18 years and over (target number 2,742) attending their booking appointment with a community midwife (n = 31) in north-east England will be screened for alcohol consumption using the consumption questions of the Alcohol Use Disorders Identification Test (AUDIT-C). Those screening positive, without a history of substance use or alcohol dependence, with no pregnancy complication, and able to give informed consent, will be invited to participate in the trial (target number 120). Midwives will be randomized in a 1:1 ratio to deliver either treatment as usual (control) or structured brief advice and referral for a 20-minute motivational interviewing session with an alcohol health worker (intervention). As well as demographic and health information, baseline measures will include two 7-day time line follow-back questionnaires and the EuroQoL EQ-5D-3 L questionnaire. Measures will be repeated in telephone follow-ups in the third trimester and at 6 months post-partum, when a questionnaire on use of National Health Service and social care resources will also be completed. Information on pregnancy outcomes and stillbirths will be accessed from central health service records before the follow-ups. Primary outcomes will be rates of eligibility, recruitment, intervention delivery, and retention in the study population, to inform power calculations for a definitive trial. The health-economics component will establish how cost-effectiveness will be assessed, and examine which data on health service resource use should be collected in a main trial. Participants' views on instruments and procedures will be sought to confirm their acceptability. The study will produce a full trial protocol with robust sample-size calculations to extend evidence on effectiveness of screening and brief intervention. Current Controlled Trials ISRCTN43218782.

The STRIDE (Strategies to Increase confidence, InDependence and Energy) study: cognitive behavioural therapy-based intervention to reduce fear of falling in older fallers living in the community - study protocol for a randomised controlled trial.

PubMed

Parry, Steve W; Deary, Vincent; Finch, Tracy; Bamford, Claire; Sabin, Neil; McMeekin, Peter; O'Brien, John; Caldwell, Alma; Steen, Nick; Whitney, Susan L; Macdonald, Claire; McColl, Elaine

2014-06-06

Around 30% to 62% of older individuals fall each year, with adverse consequences of falls being by no means limited to physical injury and escalating levels of dependence. Many older individuals suffer from a variety of adverse psychosocial difficulties related to falling including fear, anxiety, loss of confidence and subsequent increasing activity avoidance, social isolation and frailty. Such 'fear of falling' is common and disabling, but definitive studies examining the effective management of the syndrome are lacking. Cognitive behavioural therapy has been trialed with some success in a group setting, but there is no adequately powered randomised controlled study of an individually based cognitive behavioural therapy intervention, and none using non-mental health professionals to deliver the intervention. We are conducting a two-phase study examining the role of individual cognitive behavioural therapy delivered by healthcare assistants in improving fear of falling in older adults. In Phase I, the intervention was developed and taught to healthcare assistants, while Phase II is the pragmatic randomised controlled study examining the efficacy of the intervention in improving fear of falling in community-dwelling elders attending falls services. A qualitative process evaluation study informed by Normalization Process Theory is being conducted throughout to examine the potential promoters and inhibitors of introducing such an intervention into routine clinical practice, while a health economic sub-study running alongside the trial is examining the costs and benefits of such an approach to the wider health economy. Current Controlled Trials ISRCTN78396615.

Examination of Cognitive Function During Six Months of Calorie Restriction: Results of a Randomized Controlled Trial

PubMed Central

Martin, Corby K.; Anton, Stephen D.; Han, Hongmei; York-Crowe, Emily; Redman, Leanne M.; Ravussin, Eric; Williamson, Donald A.

2009-01-01

Background Calorie restriction increases longevity in many organisms, and calorie restriction or its mimetic might increase longevity in humans. It is unclear if calorie restriction/dieting contributes to cognitive impairment. During this randomized controlled trial, the effect of 6 months of calorie restriction on cognitive functioning was tested. Methods Participants (n = 48) were randomized to one of four groups: (1) control (weight maintenance), (2) calorie restriction (CR; 25% restriction), (3) CR plus structured exercise (CR + EX, 12.5% restriction plus 12.5% increased energy expenditure via exercise), or (4) low-calorie diet (LCD; 890 kcal/d diet until 15% weight loss, followed by weight maintenance). Cognitive tests (verbal memory, visual memory, attention/concentration) were conducted at baseline and months 3 and 6. Mixed linear models tested if cognitive function changed significantly from baseline to months 3 and 6, and if this change differed by group. Correlation analysis was used to determine if average daily energy deficit (quantified from change in body energy stores) was associated with change in cognitive test performance for the three dieting groups combined. Results No consistent pattern of verbal memory, visual retention/memory, or attention/concentration deficits emerged during the trial. Daily energy deficit was not significantly associated with change in cognitive test performance. Conclusions This randomized controlled trial suggests that calorie restriction/dieting was not associated with a consistent pattern of cognitive impairment. These conclusions must be interpreted in the context of study limitations, namely small sample size and limited statistical power. Previous reports of cognitive impairment might reflect sampling biases or information processing biases. PMID:17518698

Effect of low-level laser therapy (LLLT) and light-emitting diodes (LEDT) applied during combined training on performance and post-exercise recovery: protocol for a randomized placebo-controlled trial.

PubMed

Machado, Aryane Flauzino; Micheletti, Jéssica Kirsch; Vanderlei, Franciele Marques; Nakamura, Fabio Yuzo; Leal-Junior, Ernesto Cesar Pinto; Netto Junior, Jayme; Pastre, Carlos Marcelo

Previous studies have shown positive results of phototherapy for improving performance and accelerating recovery; however, the effects of phototherapy during training and after a primary adaptation remain unclear. The aim of this randomized controlled trial is to analyze the effects of phototherapy and combined training on clinical, functional, and psychological outcomes and on vascular endothelial growth factor. This randomized placebo-controlled trial by stratified sample will involve 45 healthy male participants. In phase 1, the participants will undergo six weeks of combined training (sprints and squats). In phase 2, participants will be allocated through stratified randomization (based on adaptation capacity) into three groups: active phototherapy group (AG), placebo group (PG), and non-treatment control group (CG). A new six-week training program will then start and the participants will receive the recovery strategy between sprints and squats. The primary outcome will be maximal isometric contraction. The secondary outcomes include strength and power testing, maximal incremental test, squat jump, sprint test, muscle soreness, pain threshold, perceptions of exertion and recovery, psychological questionnaire, and vascular endothelial growth factor. This will be the first trial to include phototherapy during training. We believe that this strategy will combine the ergogenic and prophylactic effects in the same session. Furthermore, an application protocol performed after primary adaptation may reflect the real effect of the technique. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Internet-delivered cognitive behaviour therapy for depression in people with diabetes: study protocol for a randomised controlled trial

PubMed Central

Robins, Lisa; Newby, Jill; Wilhelm, Kay; Smith, Jessica; Fletcher, Therese; Ma, Trevor; Finch, Adam; Campbell, Lesley; Andrews, Gavin

2015-01-01

Introduction Depression substantially contributes to the personal burden and healthcare costs of living with diabetes mellitus (DM). Comorbid depression and DM are associated with poorer quality of life, poorer self-management and glycemic control, increased risk for DM complications and higher mortality rates, and higher health service utilization. Depression remains under-recognized and undertreated in people with DM, which may, in part, result from barriers associated with accessing face-to-face treatment. This study will examine the efficacy of an internet-based cognitive behaviour therapy programme for major depressive disorder (iCBT-MDD) in people with DM. Methods and analysis A CONSORT 2010 compliant, registered randomised controlled trial of the intervention (iCBT-MDD) versus a treatment as usual control group will be conducted. The study will include 100 adults aged 18 years and over with a diagnosis of type 1 or type 2 DM and self-reported symptoms that satisfy MDD which will enable us to detect a statistically significant difference with a group effect size of 0.6 at a power of 80% and significance level of p=0.05. Participants will be randomised to receive the iCBT-MDD programme immediately, or to wait 10 weeks before accessing the programme. Primary outcomes will be self-reported depression severity, DM-related distress, and glycemic control (glycosylated hemoglobin). Secondary outcomes will be general distress and disability, generalized anxiety, lifestyle behaviours, somatization, eating habits, alcohol use, and acceptability of the iCBT programme to participants, and practicality for clinicians. Data will be analyzed with linear mixed models for each outcome measure. Ethics and dissemination The Human Research Ethics Committee of St Vincent's Hospital Australia have given ethics approval (HREC/13/SVH/291). Results will be disseminated via peer-reviewed publication and social media channels of Australian Diabetes Consumer Representative Bodies. Trial registration number The trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12613001198718). PMID:26688735

A Pilot Randomized Controlled Trial of a Guided Self-Help Intervention to Manage Chronic Orofacial Pain.

PubMed

Goldthorpe, Joanna; Lovell, Karina; Peters, Sarah; McGowan, Linda; Nemeth, Imola; Roberts, Christopher; Aggarwal, Vishal R

2017-01-01

To conduct a pilot trial to test the feasibility of a guided self-help intervention for chronic orofacial pain. A pilot randomized controlled trial was conducted to compare the intervention with usual treatment. A total of 37 patients with chronic orofacial pain were randomized into either the intervention group (n = 19) or the usual treatment (control) group (n = 18). Validated outcome measures were used to measure the potential effectiveness of the intervention over a number of domains: physical and mental functioning (Short Form 36 [SF-36]); anxiety and depression (Hospital Anxiety and Depression Scale [HADS]); pain intensity and interference with life (Brief Pain Inventory [BPI]); disability (Manchester Orofacial Pain Disability Scale [MOPDS]); and illness behavior (Revised Illness Perceptions Questionnaire [IPQr]). Bootstrap confidence intervals were computed for the treatment effect (ES) posttreatment and at 3 months follow-up and adjusted for baseline values of the outcome measure by using analysis of covariance. At posttreatment and the 3-month follow-up, 11 participants in the intervention group and 7 in the control group failed to complete outcome measures. The intervention was acceptable and could be feasibly delivered face to face or over the telephone. Although the pilot trial was not powered to draw conclusions about the effectiveness, it showed significant (P < .05) effects of the intervention on physical and mental functioning and treatment control. The self-help intervention was acceptable to patients and allowed them to better understand and self-manage chronic orofacial pain. It showed potential effectiveness on outcome domains related to functioning and illness perception. Further research is needed to understand the cost effectiveness of the intervention for chronic orofacial pain.

Prestimulus Alpha Power Influences Tactile Temporal Perceptual Discrimination and Confidence in Decisions.

PubMed

Baumgarten, Thomas J; Schnitzler, Alfons; Lange, Joachim

2016-03-01

Recent studies have demonstrated that prestimulus alpha-band activity substantially influences perception of near-threshold stimuli. Here, we studied the influence of prestimulus alpha power fluctuations on temporal perceptual discrimination of suprathreshold tactile stimuli and subjects' confidence regarding their perceptual decisions. We investigated how prestimulus alpha-band power influences poststimulus decision-making variables. We presented electrical stimuli with different stimulus onset asynchronies (SOAs) to human subjects, and determined the SOA for which temporal perceptual discrimination varied on a trial-by-trial basis between perceiving 1 or 2 stimuli, prior to recording brain activity with magnetoencephalography. We found that low prestimulus alpha power in contralateral somatosensory and occipital areas predicts the veridical temporal perceptual discrimination of 2 stimuli. Additionally, prestimulus alpha power was negatively correlated with confidence ratings in correctly perceived trials, but positively correlated for incorrectly perceived trials. Finally, poststimulus event-related fields (ERFs) were modulated by prestimulus alpha power and reflect the result of a decisional process rather than physical stimulus parameters around ∼150 ms. These findings provide new insights into the link between spontaneous prestimulus alpha power fluctuations, temporal perceptual discrimination, decision making, and decisional confidence. The results suggest that prestimulus alpha power modulates perception and decisions on a continuous scale, as reflected in confidence ratings. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

An overview of 37 randomised trials of blood pressure lowering agents among 270,000 individuals. World Health Organization-International Society of Hypertension Blood Pressure Lowering Treatment Trialists' Collaboration.

PubMed

Neal, B; MacMahon, S

1999-01-01

Overviews (meta-analyses) of the major ongoing randomized trials of blood pressure lowering drugs will be conducted to determine the effects of: first, newer versus older classes of blood pressure lowering drugs in patients with hypertension; and second, blood pressure lowering treatments versus untreated or less treated control conditions in patient groups at high risk of cardiovascular events. The principal study outcomes are stroke, coronary heart disease, total cardiovascular events and total cardiovascular deaths. The overviews have been prospectively designed and will be conducted on individual patient data. The analyses will be conducted as a collaboration between the principal investigators of participating trials involving about 270,000 patients. Full data should be available in 2003, with the first round of analyses performed in 1999-2000. The combination of trial results should provide good statistical power to detect even modest differences between the effects on the main study outcomes.

Use of nonintrusive sensor-based information and communication technology for real-world evidence for clinical trials in dementia.

PubMed

Teipel, Stefan; König, Alexandra; Hoey, Jesse; Kaye, Jeff; Krüger, Frank; Robillard, Julie M; Kirste, Thomas; Babiloni, Claudio

2018-06-21

Cognitive function is an important end point of treatments in dementia clinical trials. Measuring cognitive function by standardized tests, however, is biased toward highly constrained environments (such as hospitals) in selected samples. Patient-powered real-world evidence using information and communication technology devices, including environmental and wearable sensors, may help to overcome these limitations. This position paper describes current and novel information and communication technology devices and algorithms to monitor behavior and function in people with prodromal and manifest stages of dementia continuously, and discusses clinical, technological, ethical, regulatory, and user-centered requirements for collecting real-world evidence in future randomized controlled trials. Challenges of data safety, quality, and privacy and regulatory requirements need to be addressed by future smart sensor technologies. When these requirements are satisfied, these technologies will provide access to truly user relevant outcomes and broader cohorts of participants than currently sampled in clinical trials. Copyright © 2018. Published by Elsevier Inc.

The REFORM study protocol: a cohort randomised controlled trial of a multifaceted podiatry intervention for the prevention of falls in older people

PubMed Central

Cockayne, Sarah; Adamson, Joy; Corbacho Martin, Belen; Fairhurst, Caroline; Hewitt, Catherine; Hicks, Kate; Hull, Robin; Keenan, Anne Maree; Lamb, Sarah E; Loughrey, Lorraine; McIntosh, Caroline; Menz, Hylton B; Redmond, Anthony C; Rodgers, Sara; Vernon, Wesley; Watson, Judith; Torgerson, David

2014-01-01

Introduction Falls and fall-related injuries are a serious cause of morbidity and cost to society. Foot problems and inappropriate footwear may increase the risk of falls; therefore podiatric interventions may play a role in reducing falls. Two Cochrane systematic reviews identified only one study of a podiatry intervention aimed to reduce falls, which was undertaken in Australia. The REFORM trial aims to evaluate the clinical and cost-effectiveness of a multifaceted podiatry intervention in reducing falls in people aged 65 years and over in a UK and Irish setting. Methods and analysis This multicentre, cohort randomised controlled trial will recruit 2600 participants from routine podiatry clinics in the UK and Ireland to the REFORM cohort. In order to detect a 10% point reduction in falls from 50% to 40%, with 80% power 890 participants will be randomised to receive routine podiatry care and a falls prevention leaflet or routine podiatry care, a falls prevention leaflet and a multifaceted podiatry intervention. The primary outcome is rate of falls (falls/person/time) over 12 months assessed by patient self-report falls diary. Secondary self-report outcome measures include: the proportion of single and multiple fallers and time to first fall over a 12-month period; Short Falls Efficacy Scale—International; fear of falling in the past 4 weeks; Frenchay Activities Index; fracture rate; Geriatric Depression Scale; EuroQoL-five dimensional scale 3-L; health service utilisation at 6 and 12 months. A qualitative study will examine the acceptability of the package of care to participants and podiatrists. Ethics and dissemination The trial has received a favourable opinion from the East of England—Cambridge East Research Ethics Committee and Galway Research Ethics Committee. The trial results will be published in peer-reviewed journals and at conference presentations. Trial registration number Current Controlled Trials ISRCTN68240461assigned 01/07/2011. PMID:25518875

Appendectomy versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

PubMed Central

Eaton, Simon; Abbo, Olivier; Arnaud, Alexis P; Beaudin, Marianne; Brindle, Mary; Bütter, Andreana; Davies, Dafydd; Jancelewicz, Tim; Johnson, Kathy; Keijzer, Richard; Lapidus-Krol, Eveline; Offringa, Martin; Piché, Nelson; Rintala, Risto; Skarsgard, Erik; Svensson, Jan F; Ungar, Wendy J; Wester, Tomas; Willan, Andrew R; Zani, Augusto; St Peter, Shawn D; Pierro, Agostino

2017-01-01

Background Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of non-operative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed. Methods Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5–16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis will be randomised (1:1 ratio) to receive either laparoscopic appendectomy or treatment with intravenous (minimum 12 hours) followed by oral antibiotics (total course 10 days). Allocation to groups will be stratified by gender, duration of symptoms (> or <48 hours) and centre. Children in both treatment groups will follow a standardised treatment pathway. Primary outcome is treatment failure defined as additional intervention related to appendicitis requiring general anaesthesia within 1 year of randomisation (including recurrent appendicitis) or negative appendectomy. Important secondary outcomes will be reported and a cost-effectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin. Planned sample size is 978 children. Discussion The APPY trial will be the first multicentre randomised trial comparing non-operative treatment with appendectomy for acute uncomplicated appendicitis in children. The results of this trial have the potential to revolutionise the treatment of this common gastrointestinal emergency. The randomised design will limit the effect of bias on outcomes seen in other studies. Trial registration number clinicaltrials.gov: NCT02687464. Registered on Jan 13th 2016. PMID:29637088

Slimming World in Stop Smoking Services (SWISSS): study protocol for a randomized controlled trial.

PubMed

Lycett, Deborah; Aveyard, Paul; Farmer, Andrew; Lewis, Amanda; Munafò, Marcus

2013-06-19

Quitting smokers gain weight. This deters some from trying to stop smoking and may explain the increased incidence of type 2 diabetes after cessation. Dieting when stopping smoking may be counterproductive. Hunger increases cravings for smoking and tackling two behaviours together may undermine quitting success. A meta-analysis of randomized controlled trials (RCTs) showed individualized dietary support may prevent weight gain, although there is insufficient evidence whether it undermines smoking cessation. Commercial weight management providers (CWMPs), such as Slimming World, provide individualized dietary support for National Health Service (NHS) patients; however, there is no evidence that they can prevent cessation-related weight gain.Our objective is to determine whether attending Slimming World from quit date, through referral from NHS Stop Smoking Services, is more effective than usual care at preventing cessation-related weight gain. This RCT will examine the effectiveness of usual cessation support plus referral to Slimming World compared to usual cessation support alone. Healthy weight, overweight and obese adult smokers attending Stop Smoking Services will be included. The primary outcome is weight change in quitters 12 weeks post-randomization. Multivariable linear regression analysis will compare weight change between trial arms and adjust for known predictors of cessation-related weight gain.We will recruit 320 participants, with 160 participants in each arm. An alpha error rate of 5% and 90% power will detect a 2 kg (SD = 2.5) difference in weight gain at 12 weeks, assuming 20% remain abstinent by then. This trial will establish whether referral to the 12-week Slimming World programme plus usual care is an effective intervention to prevent cessation-related weight gain. If so, we will seek to establish whether weight control comes at the expense of a successful quit attempt in a further non-inferiority trial.Positive results from both these trials would provide a potential solution to cessation-related weight gain, which could be rolled out across England within Stop Smoking Services to better meet the needs of 0.75 million smokers stopping with NHS support every year. Current Controlled Trials ISRCTN65705512.

Spinal cord stimulation for chronic pain.

PubMed

Mailis-Gagnon, A; Furlan, A D; Sandoval, J A; Taylor, R

2004-01-01

Spinal cord stimulation (SCS) is a form of therapy used to treat certain types of chronic pain. It involves an electrical generator that delivers pulses to a targeted spinal cord area. The leads can be implanted by laminectomy or percutaneously and the source of power is supplied by an implanted battery or by an external radio-frequency transmitter. The exact mechanism of action of SCS is poorly understood. To assess the efficacy and effectiveness of spinal cord stimulation in relieving certain kinds of pain, as well as the complications and adverse effects of this procedure. We searched MEDLINE and EMBASE to September 2003; the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2003); textbooks and reference lists in retrieved articles. We also contacted experts in the field of pain and the main manufacturer of the stimulators. We included trials with a control group, either randomized controlled trials (RCTs) or non-randomized controlled clinical trials (CCTs), that assessed spinal cord stimulation for chronic pain. Two independent reviewers selected the studies, assessed study quality and extracted the data. One of the assessors of methodological quality was blinded to authors, dates and journals. The data were analysed using qualitative methods (best evidence synthesis). Two RCTs (81 patients in total) met our inclusion criteria. One was judged as being of high quality (score of 3 on Jadad scale) and the other of low quality (score of 1 on Jadad scale). One trial included patients with Complex Regional Pain Syndrome Type I (reflex sympathetic dystrophy) and the other patients with Failed Back Surgery Syndrome. The follow-up periods varied from 6 to 12 months. Both studies reported that SCS was effective, however, meta-analysis was not undertaken because of the small number of patients and the heterogeneity of the study population. Although there is limited evidence in favour of SCS for Failed Back Surgery Syndrome and Complex Regional Pain Syndrome Type I, more trials are needed to confirm whether SCS is an effective treatment for certain types of chronic pain. In addition, there needs to be a debate about trial designs that will provide the best evidence for assessing this type of intervention.

Finnish Degenerative Meniscal Lesion Study (FIDELITY): a protocol for a randomised, placebo surgery controlled trial on the efficacy of arthroscopic partial meniscectomy for patients with degenerative meniscus injury with a novel ‘RCT within-a-cohort’ study design

PubMed Central

Sihvonen, Raine; Paavola, Mika; Malmivaara, Antti; Järvinen, Teppo L N

2013-01-01

Introduction Arthroscopic partial meniscectomy (APM) to treat degenerative meniscus injury is the most common orthopaedic procedure. However, valid evidence of the efficacy of APM is lacking. Controlling for the placebo effect of any medical intervention is important, but seems particularly pertinent for the assessment of APM, as the symptoms commonly attributed to a degenerative meniscal injury (medial joint line symptoms and perceived disability) are subjective and display considerable fluctuation, and accordingly difficult to gauge objectively. Methods and analysis A multicentre, parallel randomised, placebo surgery controlled trial is being carried out to assess the efficacy of APM for patients from 35 to 65 years of age with a degenerative meniscus injury. Patients with degenerative medial meniscus tear and medial joint line symptoms, without clinical or radiographic osteoarthritis of the index knee, were enrolled and then randomly assigned (1 : 1) to either APM or diagnostic arthroscopy (placebo surgery). Patients are followed up for 12 months. According to the prior power calculation, 140 patients were randomised. The two randomised patient groups will be compared at 12 months with intention-to-treat analysis. To safeguard against bias, patients, healthcare providers, data collectors, data analysts, outcome adjudicators and the researchers interpreting the findings will be blind to the patients’ interventions (APM/placebo). Primary outcomes are Lysholm knee score (a generic knee instrument), knee pain (using a numerical rating scale), and WOMET score (a disease-specific, health-related quality of life index). The secondary outcome is 15D (a generic quality of life instrument). Further, in one of the five centres recruiting patients for the randomised controlled trial (RCT), all patients scheduled for knee arthroscopy due to a degenerative meniscus injury are prospectively followed up using the same protocol as in the RCT to provide an external validation cohort. In this article, we present and discuss our study design, focusing particularly on the internal and external validity of our trial and the ethics of carrying out a placebo surgery controlled trial. Ethics and dissemination The protocol has been approved by the institutional review board of the Pirkanmaa Hospital District and the trial has been duly registered at ClinicalTrials.gov. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations. Trial registration ClinicalTrials.gov, number NCT00549172. PMID:23474796

Engagement and Retention of Suicide Attempters in Clinical Research

PubMed Central

Gibbons, Carly J.; Stirman, Shannon Wiltsey; Brown, Gregory K.; Beck, Aaron T.

2010-01-01

Background High attrition rates in longitudinal research can limit study generalizability, threaten internal validity, and decrease statistical power. Research has demonstrated that there can be significant differences between participants who complete a research study and those who drop out prematurely, and that treatment outcomes may be dependent on retention in a treatment protocol. Aims The current paper describes the challenges encountered when implementing a randomized controlled trial of cognitive therapy for the prevention of suicide attempts and the solutions developed to overcome these problems. Methods Problems unique to suicide attempters are discussed, and strategies successfully implemented to boost retention rates are provided. Results The methods implemented appeared to increase retention rates in the randomized controlled trial. Conclusions Many steps can be taken to work with this difficult population, and researchers are encouraged to be as involved and flexible with participants as possible. PMID:20418211

HeartMate II left ventricular assist system: from concept to first clinical use.

PubMed

Griffith, B P; Kormos, R L; Borovetz, H S; Litwak, K; Antaki, J F; Poirier, V L; Butler, K C

2001-03-01

The HeartMate II left ventricular assist device (LVAD) (ThermoCardiosystems, Inc, Woburn, MA) has evolved from 1991 when a partnership was struck between the McGowan Center of the University of Pittsburgh and Nimbus Company. Early iterations were conceptually based on axial-flow mini-pumps (Hemopump) and began with purge bearings. As the project developed, so did the understanding of new bearings, computational fluid design and flow visualization, and speed control algorithms. The acquisition of Nimbus by ThermoCardiosystems, Inc (TCI) sped developments of cannulas, controller, and power/monitor units. The system has been successfully tested in more than 40 calves since 1997 and the first human implant occurred in July 2000. Multicenter safety and feasibility trials are planned for Europe and soon thereafter a trial will be started in the United States to test 6-month survival in end-stage heart failure.

Do personalised e-mail invitations increase the response rates of breast cancer survivors invited to participate in a web-based behaviour change intervention? A quasi-randomised 2-arm controlled trial.

PubMed

Short, Camille E; Rebar, Amanda L; Vandelanotte, Corneel

2015-08-19

Previous research has shown that the personalisation of study invitations improves response rates in survey-based research. To examine if this finding extends to experimental studies, we examined the impact of personalised study invitation e-mails on the response rates of potentially eligible breast cancer survivors for participation in a 6 month randomised controlled trial testing the efficacy of a physical activity intervention. Potential participants (n = 344) were sent either a personalised email or a generic email. Those sent the personalised email were 1.5 times (95 % CI = 1.18-1.93) more likely to respond than those sent the generic email. These findings suggest that personalisation may be a useful and potentially powerful tool that can be utilised when recruiting participants into experimental studies in order to boost response rates.

Hematopoietic stem cell transplantation for people with ß-thalassaemia major.

PubMed

Jagannath, Vanitha A; Fedorowicz, Zbys; Al Hajeri, Amani; Sharma, Akshay

2016-11-30

Thalassemia is an inherited autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions. This results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In ß-thalassaemia major there is an underproduction of ß-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their destruction (haemolysis) and ineffective erythropoiesis. The conventional approach to treatment is based on the correction of haemoglobin status through regular blood transfusions and iron chelation therapy for iron overload. Although conventional treatment has the capacity to improve the quality of life of people with ß-thalassaemia major, allogeneic hematopoietic stem cell transplantation is the only currently available procedure which has the curative potential. This is an update of a previously published Cochrane Review. To evaluate the effectiveness and safety of different types of allogeneic hematopoietic stem cell transplantation, in people with severe transfusion-dependant ß-thalassaemia major, ß-thalassaemia intermedia or ß0/+- thalassaemia variants requiring chronic blood transfusion. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 18 August 2016. Randomised controlled trials and quasi-randomised controlled trials comparing allogeneic hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen). Two review authors independently screened studies and had planned to extract data and assess risk of bias using standard Cochrane methodologies but no studies were identified for inclusion. No relevant studies were retrieved after a comprehensive search of the literature. We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of allogeneic stem cell transplantation in people with severe transfusion-dependant ß-thalassaemia major or ß0/+- thalassaemia variants requiring chronic blood transfusion. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.

Hematopoietic stem cell transplantation for people with ß-thalassaemia major.

PubMed

Jagannath, Vanitha A; Fedorowicz, Zbys; Al Hajeri, Amani; Sharma, Akshay

2014-10-15

Thalassemia is an inherited blood disorder, caused by mutations in regulatory genes and transmitted as an autosomal recessive disorder, which results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In ß-thalassaemia major there is an underproduction of ß-globin chains combined with excess of free α-globin chains. The excess free α-globin chains damage the red blood cell membranes, leading to their destruction and a phenomenon termed ineffective erythropoiesis. The conventional approach to treatment is based on the correction of haemoglobin status through regular blood transfusions and iron chelation therapy for iron overload. Although conventional treatment has the capacity to improve the quality of life of people with ß-thalassaemia major, allogeneic hematopoietic stem cell transplantation is the only currently available procedure which has the potential to definitively cure the disease. To evaluate the effectiveness and safety of different types of allogeneic hematopoietic stem cell transplantation, in people with severe transfusion-dependant ß-thalassaemia major, ß-thalassaemia intermedia or ß0/+- thalassaemia variants requiring chronic blood transfusion. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 11 November 2013. Randomised controlled trials and quasi-randomised controlled trials comparing allogeneic hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen). Two review authors independently screened studies and had planned to extract data and assess risk of bias using standard Cochrane Collaboration methodologies but no studies were identified for inclusion. No relevant studies were retrieved after a comprehensive search of the literature. We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of allogeneic stem cell transplantation in people with severe transfusion-dependant ß-thalassaemia major or ß0/+- thalassaemia variants requiring chronic blood transfusion. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial

PubMed Central

Quintana, D S; Westlye, L T; Hope, S; Nærland, T; Elvsåshagen, T; Dørum, E; Rustan, Ø; Valstad, M; Rezvaya, L; Lishaugen, H; Stensønes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G; Andreassen, O A

2017-01-01

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin’s dose–response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η2=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure. PMID:28534875

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.

PubMed

Quintana, D S; Westlye, L T; Hope, S; Nærland, T; Elvsåshagen, T; Dørum, E; Rustan, Ø; Valstad, M; Rezvaya, L; Lishaugen, H; Stensønes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G; Andreassen, O A

2017-05-23

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η 2 =0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

Factorial versus multi-arm multi-stage designs for clinical trials with multiple treatments.

PubMed

Jaki, Thomas; Vasileiou, Despina

2017-02-20

When several treatments are available for evaluation in a clinical trial, different design options are available. We compare multi-arm multi-stage with factorial designs, and in particular, we will consider a 2 × 2 factorial design, where groups of patients will either take treatments A, B, both or neither. We investigate the performance and characteristics of both types of designs under different scenarios and compare them using both theory and simulations. For the factorial designs, we construct appropriate test statistics to test the hypothesis of no treatment effect against the control group with overall control of the type I error. We study the effect of the choice of the allocation ratios on the critical value and sample size requirements for a target power. We also study how the possibility of an interaction between the two treatments A and B affects type I and type II errors when testing for significance of each of the treatment effects. We present both simulation results and a case study on an osteoarthritis clinical trial. We discover that in an optimal factorial design in terms of minimising the associated critical value, the corresponding allocation ratios differ substantially to those of a balanced design. We also find evidence of potentially big losses in power in factorial designs for moderate deviations from the study design assumptions and little gain compared with multi-arm multi-stage designs when the assumptions hold. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Effect of a web-based chronic disease management system on asthma control and health-related quality of life: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Asthma is a prevalent and costly disease resulting in reduced quality of life for a large proportion of individuals. Effective patient self-management is critical for improving health outcomes. However, key aspects of self-management such as self-monitoring of behaviours and symptoms, coupled with regular feedback from the health care team, are rarely addressed or integrated into ongoing care. Health information technology (HIT) provides unique opportunities to facilitate this by providing a means for two way communication and exchange of information between the patient and care team, and access to their health information, presented in personalized ways that can alert them when there is a need for action. The objective of this study is to evaluate the acceptability and efficacy of using a web-based self-management system, My Asthma Portal (MAP), linked to a case-management system on asthma control, and asthma health-related quality of life. Methods The trial is a parallel multi-centered 2-arm pilot randomized controlled trial. Participants are randomly assigned to one of two conditions: a) MAP and usual care; or b) usual care alone. Individuals will be included if they are between 18 and 70, have a confirmed asthma diagnosis, and their asthma is classified as not well controlled by their physician. Asthma control will be evaluated by calculating the amount of fast acting beta agonists recorded as dispensed in the provincial drug database, and asthma quality of life using the Mini Asthma Related Quality of Life Questionnaire. Power calculations indicated a needed total sample size of 80 subjects. Data are collected at baseline, 3, 6, and 9 months post randomization. Recruitment started in March 2010 and the inclusion of patients in the trial in June 2010. Discussion Self-management support from the care team is critical for improving chronic disease outcomes. Given the high volume of patients and time constraints during clinical visits, primary care physicians have limited time to teach and reinforce use of proven self-management strategies. HIT has the potential to provide clinicians and a large number of patients with tools to support health behaviour change. Trial Registration Current Controlled Trials ISRCTN34326236. PMID:22168530

Nifedipine as a uterine relaxant for external cephalic version: a randomized controlled trial.

PubMed

Kok, Marjolein; Bais, Joke M; van Lith, Jan M; Papatsonis, Dimitri M; Kleiverda, Gunilla; Hanny, Dahrs; Doornbos, Johannes P; Mol, Ben W; van der Post, Joris A

2008-08-01

To estimate the effectiveness of nifedipine as a uterine relaxant during external cephalic version to correct breech presentation. In this randomized, double-blind, placebo-controlled trial, women with a singleton fetus in breech presentation and a gestational age of 36 weeks or more were eligible for enrollment. Participating women received two doses of either nifedipine 10 mg or placebo, 30 and 15 minutes before the external cephalic version attempt. The primary outcome was a cephalic-presenting fetus immediately after the procedure. Secondary outcome measures were cephalic presentation at delivery, mode of delivery, and adverse events. A sample size of 292 was calculated to provide 80% power to detect a 17% improvement of the external cephalic version success rate, assuming a placebo group rate of 40% and alpha of .05. Outcome data for 310 of 320 randomly assigned participants revealed no significant difference in external cephalic version success rates between treatment (42%) and control group (37%) (relative risk 1.1, 95%; 95% confidence interval 0.85-1.5). The cesarean delivery rate was 51% in the treatment group and 46% in the control group (relative risk 1.1, 95% confidence interval 0.88-1.4). Nifedipine did not significantly improve the success of external cephalic version. Future use of nifedipine to improve the outcome of external cephalic version should be limited to large clinical trials.

Biomedical research and corporate interests: a question of academic freedom.

PubMed

McHenry, Leemon

2008-01-01

The current situation in medicine has been described as a crisis of credibility, as the profit motive of industry has taken control of clinical trials and the dissemination of data. Pharmaceutical companies maintain a stranglehold over the content of medical journals in three ways: (1) by ghostwriting articles that bias the results of clinical trials, (2) by the sheer economic power they exert on journals due to the purchase of drug advertisements and journal reprints, and (3) by the threat of legal action against those researchers who seek to correct the misrepresentation of study results. This paper argues that Karl Popper's critical rationalism provides a corrective to the failure of academic freedom in biomedical research.

Biomedical Research and Corporate Interests: A Question of Academic Freedom

PubMed Central

McHenry, Leemon

2008-01-01

The current situation in medicine has been described as a crisis of credibility, as the profit motive of industry has taken control of clinical trials and the dissemination of data. Pharmaceutical companies maintain a stranglehold over the content of medical journals in three ways: (1) by ghostwriting articles that bias the results of clinical trials, (2) by the sheer economic power they exert on journals due to the purchase of drug advertisements and journal reprints, and (3) by the threat of legal action against those researchers who seek to correct the misrepresentation of study results. This paper argues that Karl Popper's critical rationalism provides a corrective to the failure of academic freedom in biomedical research. PMID:22013356

Low-power laser therapy for carpal tunnel syndrome: effective optical power

PubMed Central

Chen, Yan; Zhao, Cheng-qiang; Ye, Gang; Liu, Can-dong; Xu, Wen-dong

2016-01-01

Low-power laser therapy has been used for the non-surgical treatment of mild to moderate carpal tunnel syndrome, although its efficacy has been a long-standing controversy. The laser parameters in low-power laser therapy are closely related to the laser effect on human tissue. To evaluate the efficacy of low-power laser therapy, laser parameters should be accurately measured and controlled, which has been ignored in previous clinical trials. Here, we report the measurement of the effective optical power of low-power laser therapy for carpal tunnel syndrome. By monitoring the backside reflection and scattering laser power from human skin at the wrist, the effective laser power can be inferred. Using clinical measurements from 30 cases, we found that the effective laser power differed significantly among cases, with the measured laser reflection coefficient ranging from 1.8% to 54%. The reflection coefficient for 36.7% of these 30 cases was in the range of 10–20%, but for 16.7% of cases, it was higher than 40%. Consequently, monitoring the effective optical power during laser irradiation is necessary for the laser therapy of carpal tunnel syndrome. PMID:27630706

Pin site care for preventing infections associated with external bone fixators and pins.

PubMed

Lethaby, Anne; Temple, Jenny; Santy-Tomlinson, Julie

2013-12-03

Metal pins are used to apply skeletal traction or external fixation devices in the management of orthopaedic fractures. These percutaneous pins protrude through the skin, and the way in which they are treated after insertion may affect the incidence of pin site infection. This review set out to summarise the evidence of pin site care on infection rates. To assess the effect on infection rates of different methods of cleansing and dressing orthopaedic percutaneous pin sites. In September 2013, for this third update, we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We evaluated all randomised controlled trials (RCTs) that compared the effect on infection and other complication rates of different methods of cleansing or dressing orthopaedic percutaneous pin sites. Two review authors independently assessed the citations retrieved by the search strategies for reports of relevant RCTs, then independently selected trials that satisfied the inclusion criteria, extracted data and undertook quality assessment. A total of eleven trials (572 participants) were eligible for inclusion in the review but not all participants contributed data to each comparison. Three trials compared a cleansing regimen (saline, alcohol, hydrogen peroxide or antibacterial soap) with no cleansing (application of a dry dressing), three trials compared alternative sterile cleansing solutions (saline, alcohol, peroxide, povidone iodine), three trials compared methods of cleansing (one trial compared identical pin site care performed daily or weekly and the two others compared sterile with non sterile techniques), one trial compared daily pin site care with no care and six trials compared different dressings (using different solutions/ointments and dry and impregnated gauze or sponges). One small blinded study of 38 patients found that the risk of pin site infection was significantly reduced with polyhexamethylene biguanide (PHMB) gauze when compared to plain gauze (RR 0.23, 95% CI 0.12 to 0.44) (infection rate of 1% in the PHMB group and 4.5% in the control group) but this study was at high risk of bias as the unit of analysis was observations rather than patients. There were no other statistically significant differences between groups in any of the other trials. The available trial evidence was not extensive, was very heterogeneous and generally of poor quality, so there was insufficient evidence to be able to identify a strategy of pin site care that minimises infection rates. Adequately-powered randomised trials are required to examine the effects of different pin care regimens, and co-interventions - such as antibiotic use - and other extraneous factors must be controlled in the study designs.

Rhodiola rosea therapy for major depressive disorder: a study protocol for a randomized, double-blind, placebo- controlled trial

PubMed Central

Mao, Jun J; Li, Qing S.; Soeller, Irene; Xie, Sharon X; Amsterdam, Jay D.

2014-01-01

Background Rhodiola rosea (R. rosea), a botanical of both western and traditional Chinese medicine, has been used as a folk remedy for improving stamina and reducing stress. However, few controlled clinical trials have examined the safety and efficacy of R. rosea for the treatment of major depressive disorder (MDD). This study seeks to evaluate the safety and efficacy of R. rosea in a 12-week, randomized, double-blind, placebo-controlled, parallel group study design. Methods / Design Subjects with MDD not receiving antidepressant therapy will be randomized to either R. rosea extract 340–1,360 mg daily; sertraline 50–200 mg daily, or placebo for 12 weeks. The primary outcome measure will be change over time in the mean 17-item Hamilton Depression Rating score. Secondary outcome measures will include safety and quality of life ratings. Statistical procedures will include mixed-effects models to assess efficacy for primary and secondary outcomes. Discussion This study will provide valuable preliminary information on the safety and efficacy data of R. rosea versus conventional antidepressant therapy of MDD. It will also inform additional hypotheses and study design of future, fully powered, phase III clinical trials with R. rosea to determine its safety and efficacy in MDD. PMID:25610752

Systematic review and meta-analyses of randomized controlled trials examining tinnitus management

PubMed Central

Hoare, Derek J; Kowalkowski, Victoria L; Kang, Sujin; Hall, Deborah A

2011-01-01

Objectives/Hypothesis To evaluate the existing level of evidence for tinnitus management strategies identified in the UK Department of Health's Good Practice Guideline. Study Design Systematic review of peer-reviewed literature and meta-analyses. Methods Searches were conducted in PubMed, Cambridge Scientific Abstracts, Web of Science, and EMBASE (earliest to August 2010), supplemented by hand searches in October 2010. Only randomized controlled trials that used validated questionnaire measures of symptoms (i.e., measures of tinnitus distress, anxiety, depression) were included. Results Twenty-eight randomized controlled trials met our inclusion criteria, most of which provide moderate levels of evidence for the effects they reported. Levels of evidence were generally limited by the lack of blinding, lack of power calculations, and incomplete data reporting in these studies. Only studies examining cognitive behavioral therapy were numerous and similar enough to perform meta-analysis, from which the efficacy of cognitive behavioral therapy (moderate effect size) appears to be reasonably established. Antidepressants were the only drug class to show any evidence of potential benefit. Conclusions The efficacy of most interventions for tinnitus benefit remains to be demonstrated conclusively. In particular, high-level assessment of the benefit derived from those interventions most commonly used in practice, namely hearing aids, maskers, and tinnitus retraining therapy needs to be performed. PMID:21671234

Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients with Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial

PubMed Central

Coggan, Andrew R.; Leibowitz, Joshua L.; Spearie, Catherine Anderson; Kadkhodayan, Ana; Thomas, Deepak P.; Ramamurthy, Sujata; Mahmood, Kiran; Park, Soo; Waller, Suzanne; Farmer, Marsha; Peterson, Linda R.

2015-01-01

Background Skeletal muscle strength, velocity, and power are markedly reduced in heart failure (HF) patients, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially due to decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3−) would increase NO production and improve muscle function in patients with HF due to systolic dysfunction. Methods and Results Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3− in nine HF patients. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol NO3−. Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3− increased (P<0.05–0.001) breath NO by 35–50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the two highest movement velocities tested (i.e., 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (i.e., 4.74±0.41 vs. 4.20±0.33 W/kg; P<0.05) after dietary NO3− intake. Calculated maximal velocity of knee extension was also higher following NO3− ingestion (i.e., 12.48±0.95 vs. 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred. Conclusions In this pilot study, acute dietary NO3− intake was well-tolerated and enhanced NO bioavailability and muscle power in patients with systolic HF. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356. PMID:26179185

L-alanyl-L-glutamine ingestion maintains performance during a competitive basketball game.

PubMed

Hoffman, Jay R; Williams, David R; Emerson, Nadia S; Hoffman, Mattan W; Wells, Adam J; McVeigh, Daniele M; McCormack, William P; Mangine, Gerald T; Gonzalez, Adam M; Fragala, Maren S

2012-03-07

The purpose of this study was to examine the efficacy of L-alanyl-L-glutamine (AG) ingestion on basketball performance, including jump power, reaction time, shooting accuracy and fatigue. Ten women (21.2 ± 1.6 years; height: 177.8 ± 8.7 cm; body mass: 73.5 ± 8.0 kg), all scholarship NCAA Division I basketball players, volunteered for this study. Subjects participated in four trials, each consisting of a 40-min basketball game with controlled time-outs for rehydration. During the first trial (DHY) subjects were not allowed to rehydrate, and the total weight lost during the contest was used to determine fluid replenishment during the subsequent three trials. During one trial subjects consumed only water (W), while during the other two trials subjects consumed the AG supplement mixed in water using either a low dose (1 g per 500 ml) (AG1) or high dose (2 g per 500 ml) (AG2) concentration. All data assessed prior to and following each game were converted into a Δ score (Post results - Pre results). All performance data were then analyzed using a one-way repeated measures analysis of variance. During DHY subjects lost 1.72 ± 0.42 kg (2.3%) of their body mass. No differences in fluid intake (1.55 ± 0.43 L) were seen between rehydration trials. A 12.5% (p = 0.016) difference in basketball shooting performance was noted between DHY and AG1 and an 11.1% (p = 0.029) difference was seen between AG1 and W. Visual reaction time was significantly greater following AG1 (p = 0.014) compared to DHY. Differences (p = 0.045) in fatigue, as determined by player loads, were seen only between AG2 and DHY. No differences were seen in peak or mean vertical jump power during any trial. Rehydration with AG appears to maintain basketball skill performance and visual reaction time to a greater extent than water only.

Effects of caffeine on prolonged intermittent-sprint ability in team-sport athletes.

PubMed

Schneiker, Knut Thomas; Bishop, David; Dawson, Brian; Hackett, Laurence Peter

2006-03-01

Caffeine can be a powerful ergogenic aid for the performance of prolonged, submaximal exercise. Little evidence, however, supports an ergogenic effect of caffeine on intermittent-sprint performance. Hence, this study was conducted to examine the effects of acute caffeine ingestion on prolonged intermittent-sprint performance. Using a double-blind, placebo-controlled design, 10 male team-sport athletes (amateur level, VO2peak 56.5 +/- 8.0 mL x kg(-1) x min(-1)) completed two exercise trials, separated by 7 d, 60 min after ingestion of either 6 mg x kg(-1) caffeine or placebo. The exercise trial was performed on a front-access cycle ergometer and consisted of 2 x 36-min halves, each composed of 18 x 4-s sprints with 2-min active recovery at 35% VO2peak between each sprint. Urinary caffeine levels were measured after exercise. The total amount of sprint work performed during the caffeine trial was 8.5% greater than that performed during the placebo trial in the first half (75,165.4 +/- 3,902.9 vs 69,265.6 +/- 3,719.7 J, P < 0.05), and was 7.6% greater in the second half (73,978.7 +/- 4,092.6 vs 68,783.2 +/- 3,574.4 J, P < 0.05). Similarly, the mean peak power score achieved during sprints in the caffeine trial was 7.0% greater than that achieved during the placebo trial in the first half (1330.9 +/- 68.2 vs 1244.2 +/- 60.7 W, P < 0.05), and was 6.6% greater in the second half (1314.5 +/- 68.4 vs 1233.2 +/- 59.9 W, P < 0.05). Urinary caffeine levels following the caffeine trial ranged from 3.5 to 9.1 microg x mL(-1) (6.9 +/- 0.6 microg x mL(-1)). This study revealed that acute caffeine ingestion can significantly enhance performance of prolonged, intermittent-sprint ability in competitive, male, team-sport athletes.

For whom does interpersonal psychotherapy work? A systematic review.

PubMed

Bernecker, Samantha L; Coyne, Alice E; Constantino, Michael J; Ravitz, Paula

2017-08-01

The efficacy of interpersonal psychotherapy (IPT) to treat depression and other disorders is well established, yet it remains unknown which patients will benefit more from IPT than another treatment. This review summarizes 46years of clinical trial research on patient characteristics that moderate the relative efficacy of IPT vs. different treatments. Across 57 studies from 33 trials comparing IPT to pharmacotherapy, another psychotherapy, or control, there were few consistent indicators of when IPT would be more or less effective than another treatment. However, IPT may be superior to school counseling for adolescents with elevated interpersonal conflict, and to minimal controls for patients with severe depression. Cognitive-behavioral therapy may outpace IPT for patients with avoidant personality disorder symptoms. There was some preliminary evidence that IPT is more beneficial than alternatives for patients in some age groups, African-American patients, and patients in an index episode of depression. The included studies suffered from several limitations and high risk of Type I and II error. Obstacles that may explain the difficulty in identifying consistent moderators, including low statistical power and heterogeneity in samples and treatments, are discussed. Possible remedies include within-subjects designs, manipulation of single treatment ingredients, and strategies for increasing power such as improving measurement. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of weighted composite compared to traditional composite endpoints for the design of randomized controlled trials.

PubMed

Bakal, Jeffrey A; Westerhout, Cynthia M; Armstrong, Paul W

2015-12-01

Composite endpoints are commonly used in cardiovascular clinical trials. When using a composite endpoint a subject is considered to have an event when the first component endpoint has occurred. The use of composite endpoints offers the ability to incorporate several clinically important endpoint events thereby augmenting the event rate and increasing statistical power for a given sample size. One assumption of the composite is that all component events are of equal clinical importance. This assumption is rarely achieved given the diversity of component endpoints included. One means of adjusting for this diversity is to adjust the outcomes using severity weights determined a priori. The use of a weighted endpoint also allows for the incorporation of multiple endpoints per patient. Although weighting the outcomes lowers the effective number of events, it offers additional information that reduces the variance of the estimate. We created a series of simulation studies to examine the effect on power as the individual components of a typical composite were changed. In one study, we noted that the weighted composite was able to offer discriminative power when the component outcomes were altered, while the traditional method was not. In the other study, we noted that the weighted composite offered a similar level of power to the traditional composite when the change was driven by the more severe endpoints. © The Author(s) 2011.

The effectiveness of mobile-health technology-based health behaviour change or disease management interventions for health care consumers: a systematic review.

PubMed

Free, Caroline; Phillips, Gemma; Galli, Leandro; Watson, Louise; Felix, Lambert; Edwards, Phil; Patel, Vikram; Haines, Andy

2013-01-01

Mobile technologies could be a powerful media for providing individual level support to health care consumers. We conducted a systematic review to assess the effectiveness of mobile technology interventions delivered to health care consumers. We searched for all controlled trials of mobile technology-based health interventions delivered to health care consumers using MEDLINE, EMBASE, PsycINFO, Global Health, Web of Science, Cochrane Library, UK NHS HTA (Jan 1990-Sept 2010). Two authors extracted data on allocation concealment, allocation sequence, blinding, completeness of follow-up, and measures of effect. We calculated effect estimates and used random effects meta-analysis. We identified 75 trials. Fifty-nine trials investigated the use of mobile technologies to improve disease management and 26 trials investigated their use to change health behaviours. Nearly all trials were conducted in high-income countries. Four trials had a low risk of bias. Two trials of disease management had low risk of bias; in one, antiretroviral (ART) adherence, use of text messages reduced high viral load (>400 copies), with a relative risk (RR) of 0.85 (95% CI 0.72-0.99), but no statistically significant benefit on mortality (RR 0.79 [95% CI 0.47-1.32]). In a second, a PDA based intervention increased scores for perceived self care agency in lung transplant patients. Two trials of health behaviour management had low risk of bias. The pooled effect of text messaging smoking cessation support on biochemically verified smoking cessation was (RR 2.16 [95% CI 1.77-2.62]). Interventions for other conditions showed suggestive benefits in some cases, but the results were not consistent. No evidence of publication bias was demonstrated on visual or statistical examination of the funnel plots for either disease management or health behaviours. To address the limitation of the older search, we also reviewed more recent literature. Text messaging interventions increased adherence to ART and smoking cessation and should be considered for inclusion in services. Although there is suggestive evidence of benefit in some other areas, high quality adequately powered trials of optimised interventions are required to evaluate effects on objective outcomes.

A randomized controlled trial of a money management-based substance use intervention.

PubMed

Rosen, Marc I; Carroll, Kathleen M; Stefanovics, Elina; Rosenheck, Robert A

2009-04-01

Money management has been implemented, often in bundled interventions, as a strategy to counteract spending of public support checks and other funds on drugs and alcohol. The authors conducted a randomized controlled trial of a voluntary money management program as an adjunctive treatment for patients in treatment for mental illness, substance use disorders, or both. In the advisor-teller money manager (ATM) intervention, a money manager stores patients' checkbooks and automated bank cards, trains patients to manage their own funds, and links spending to activities related to their treatment goals. Eighty-five veterans with recent use of alcohol or cocaine were randomly assigned to 36 weeks of the ATM intervention or a control intervention (completion of a simple financial workbook). With ATM, 75% of veterans gave their checkbook to their money manager to hold, and participants attended significantly more therapy sessions than those assigned to the control therapy (mean of 20.6 versus 8.1 sessions). Although participants assigned to ATM did not show significantly greater improvement over time on the primary outcomes (self-reported abstinence from alcohol and cocaine and negative urine tests for cocaine metabolite), they reduced their Addiction Severity Index drug and alcohol use composite scale scores more rapidly than the control group. High rates of abstinence in both groups created a ceiling effect, limiting the power to detect improved abstinence rates. In this relatively small trial, ATM, a money management intervention, showed promise in engaging patients, improving their money management, and improving some substance abuse outcomes.

Sickle cell disease and venous thromboembolism in pregnancy and the puerperium.

PubMed

Noubouossie, Denis; Key, Nigel S

2015-02-01

Recent data strongly suggest an increased risk of venous thromboembolism in subjects with sickle cell disease and to a lesser extent, sickle cell trait. However, most studies have been retrospective, case-control or cross-sectional based on data obtained from administrative databases. More data from adequately powered prospective studies that include matched controls are needed to definitely establish the link between venous thromboembolism during pregnancy and sickle hemoglobin disorders. Similarly, there remains a need for properly designed randomized control trials to establish the safety of various hormonal contraceptive methods in women with sickle cell disorders. © 2015 Elsevier Ltd. All rights reserved.

A group sequential adaptive treatment assignment design for proof of concept and dose selection in headache trials.

PubMed

Hall, David B; Meier, Ulrich; Diener, Hans-Cristoph

2005-06-01

The trial objective was to test whether a new mechanism of action would effectively treat migraine headaches and to select a dose range for further investigation. The motivation for a group sequential, adaptive, placebo-controlled trial design was (1) limited information about where across the range of seven doses to focus attention, (2) a need to limit sample size for a complicated inpatient treatment and (3) a desire to reduce exposure of patients to ineffective treatment. A design based on group sequential and up and down designs was developed and operational characteristics were explored by trial simulation. The primary outcome was headache response at 2 h after treatment. Groups of four treated and two placebo patients were assigned to one dose. Adaptive dose selection was based on response rates of 60% seen with other migraine treatments. If more than 60% of treated patients responded, then the next dose was the next lower dose; otherwise, the dose was increased. A stopping rule of at least five groups at the target dose and at least four groups at that dose with more than 60% response was developed to ensure that a selected dose would be statistically significantly (p=0.05) superior to placebo. Simulations indicated good characteristics in terms of control of type 1 error, sufficient power, modest expected sample size and modest bias in estimation. The trial design is attractive for phase 2 clinical trials when response is acute and simple, ideally binary, placebo comparator is required, and patient accrual is relatively slow allowing for the collection and processing of results as a basis for the adaptive assignment of patients to dose groups. The acute migraine trial based on this design was successful in both proof of concept and dose range selection.

Empirical likelihood inference in randomized clinical trials.

PubMed

Zhang, Biao

2017-01-01

In individually randomized controlled trials, in addition to the primary outcome, information is often available on a number of covariates prior to randomization. This information is frequently utilized to undertake adjustment for baseline characteristics in order to increase precision of the estimation of average treatment effects; such adjustment is usually performed via covariate adjustment in outcome regression models. Although the use of covariate adjustment is widely seen as desirable for making treatment effect estimates more precise and the corresponding hypothesis tests more powerful, there are considerable concerns that objective inference in randomized clinical trials can potentially be compromised. In this paper, we study an empirical likelihood approach to covariate adjustment and propose two unbiased estimating functions that automatically decouple evaluation of average treatment effects from regression modeling of covariate-outcome relationships. The resulting empirical likelihood estimator of the average treatment effect is as efficient as the existing efficient adjusted estimators 1 when separate treatment-specific working regression models are correctly specified, yet are at least as efficient as the existing efficient adjusted estimators 1 for any given treatment-specific working regression models whether or not they coincide with the true treatment-specific covariate-outcome relationships. We present a simulation study to compare the finite sample performance of various methods along with some results on analysis of a data set from an HIV clinical trial. The simulation results indicate that the proposed empirical likelihood approach is more efficient and powerful than its competitors when the working covariate-outcome relationships by treatment status are misspecified.

BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints.

PubMed

Zhou, Heng; Lee, J Jack; Yuan, Ying

2017-09-20

We propose a flexible Bayesian optimal phase II (BOP2) design that is capable of handling simple (e.g., binary) and complicated (e.g., ordinal, nested, and co-primary) endpoints under a unified framework. We use a Dirichlet-multinomial model to accommodate different types of endpoints. At each interim, the go/no-go decision is made by evaluating a set of posterior probabilities of the events of interest, which is optimized to maximize power or minimize the number of patients under the null hypothesis. Unlike other existing Bayesian designs, the BOP2 design explicitly controls the type I error rate, thereby bridging the gap between Bayesian designs and frequentist designs. In addition, the stopping boundary of the BOP2 design can be enumerated prior to the onset of the trial. These features make the BOP2 design accessible to a wide range of users and regulatory agencies and particularly easy to implement in practice. Simulation studies show that the BOP2 design has favorable operating characteristics with higher power and lower risk of incorrectly terminating the trial than some existing Bayesian phase II designs. The software to implement the BOP2 design is freely available at www.trialdesign.org. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Pelvic floor muscle training versus watchful waiting or pessary treatment for pelvic organ prolapse (POPPS): design and participant baseline characteristics of two parallel pragmatic randomized controlled trials in primary care.

PubMed

Wiegersma, Marian; Panman, Chantal M C R; Kollen, Boudewijn J; Vermeulen, Karin M; Schram, Aaltje J; Messelink, Embert J; Berger, Marjolein Y; Lisman-Van Leeuwen, Yvonne; Dekker, Janny H

2014-02-01

Pelvic floor muscle training (PFMT) and pessaries are commonly used in the conservative treatment of pelvic organ prolapse (POP). Because there is a lack of evidence regarding the optimal choice between these two interventions, we designed the "Pelvic Organ prolapse in primary care: effects of Pelvic floor muscle training and Pessary treatment Study" (POPPS). POPPS consists of two parallel open label randomized controlled trials performed in primary care, in women aged ≥55 years, recruited through a postal questionnaire. In POPPS trial 1, women with mild POP receive either PFMT or watchful waiting. In POPPS trial 2, women with advanced POP receive either PFMT or pessary treatment. Patient recruitment started in 2009 and was finished in December 2012. Primary outcome of both POPPS trials is improvement in POP-related symptoms. Secondary outcomes are quality of life, sexual function, POP-Q stage, pelvic floor muscle function, post-void residual volume, patients' perception of improvement, and costs. All outcomes are measured 3, 12, and 24 months after the start of treatment. Cost-effectiveness will be calculated based on societal costs, using the PFDI-20 and the EQ-5D as outcomes. In this paper the POPPS design, the encountered challenges and our solutions, and participant baseline characteristics are presented. For both trials the target numbers of patients in each treatment group are achieved, giving this study sufficient power to lead to promising results. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Effect of supersaturated oxygen delivery on infarct size after percutaneous coronary intervention in acute myocardial infarction.

PubMed

Stone, Gregg W; Martin, Jack L; de Boer, Menko-Jan; Margheri, Massimo; Bramucci, Ezio; Blankenship, James C; Metzger, D Christopher; Gibbons, Raymond J; Lindsay, Barbara S; Weiner, Bonnie H; Lansky, Alexandra J; Krucoff, Mitchell W; Fahy, Martin; Boscardin, W John

2009-10-01

Myocardial salvage is often suboptimal after percutaneous coronary intervention in ST-segment elevation myocardial infarction. Posthoc subgroup analysis from a previous trial (AMIHOT I) suggested that intracoronary delivery of supersaturated oxygen (SSO(2)) may reduce infarct size in patients with large ST-segment elevation myocardial infarction treated early. A prospective, multicenter trial was performed in which 301 patients with anterior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention within 6 hours of symptom onset were randomized to a 90-minute intracoronary SSO(2) infusion in the left anterior descending artery infarct territory (n=222) or control (n=79). The primary efficacy measure was infarct size in the intention-to-treat population (powered for superiority), and the primary safety measure was composite major adverse cardiovascular events at 30 days in the intention-to-treat and per-protocol populations (powered for noninferiority), with Bayesian hierarchical modeling used to allow partial pooling of evidence from AMIHOT I. Among 281 randomized patients with tc-99m-sestamibi single-photon emission computed tomography data in AMIHOT II, median (interquartile range) infarct size was 26.5% (8.5%, 44%) with control compared with 20% (6%, 37%) after SSO(2). The pooled adjusted infarct size was 25% (7%, 42%) with control compared with 18.5% (3.5%, 34.5%) after SSO(2) (P(Wilcoxon)=0.02; Bayesian posterior probability of superiority, 96.9%). The Bayesian pooled 30-day mean (+/-SE) rates of major adverse cardiovascular events were 5.0+/-1.4% for control and 5.9+/-1.4% for SSO(2) by intention-to-treat, and 5.1+/-1.5% for control and 4.7+/-1.5% for SSO(2) by per-protocol analysis (posterior probability of noninferiority, 99.5% and 99.9%, respectively). Among patients with anterior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention within 6 hours of symptom onset, infusion of SSO(2) into the left anterior descending artery infarct territory results in a significant reduction in infarct size with noninferior rates of major adverse cardiovascular events at 30 days. Clinical Trial Registration- clinicaltrials.gov Identifier: NCT00175058.

Guided, internet-based, rumination-focused cognitive behavioural therapy (i-RFCBT) versus a no-intervention control to prevent depression in high-ruminating young adults, along with an adjunct assessment of the feasibility of unguided i-RFCBT, in the REducing Stress and Preventing Depression trial (RESPOND): study protocol for a phase III randomised controlled trial.

PubMed

Cook, Lorna; Watkins, Edward

2016-01-04

Depression is a global health challenge. Prevention is highlighted as a priority to reduce its prevalence. Although effective preventive interventions exist, the efficacy and coverage can be improved. One proposed means to increase efficacy is by using interventions to target specific risk factors, such as rumination. Rumination-focused CBT (RFCBT) was developed to specifically target depressive rumination and reduces acute depressive symptoms and relapse for patients with residual depression in a randomised controlled trial. Preliminary findings from a Dutch randomised prevention trial in 251 high-risk 15- to 22-year-old subjects selected with elevated worry and rumination found that both supported internet-RFBCT and group-delivered RFCBT equally reduced depressive symptoms and the onset of depressive cases over a period of 1 year, relative to the no-intervention control. A phase III randomised controlled trial following the Medical Research Council (MRC) Complex Interventions Framework will extend a Dutch trial to the United Kingdom, with the addition of diagnostic interviews, primarily to test whether guided internet-RFCBT reduces the onset of depression relative to a no-intervention control. High-risk young adults (aged 18 to 24 years), selected with elevated worry/rumination and recruited through university and internet advertisement, will be randomised to receive either guided internet-RFCBT, supported by clinical psychologists or mental health paraprofessionals, or a no-intervention control. As an adjunct arm, participants are also randomised to unguided internet-RFCBT self-help to provide an initial test of the feasibility and effect size of this intervention. While participants are also randomised to unguided internet-RFCBT, the trial was designed and powered as a phase III trial comparing guided internet-RFCBT versus a no-intervention control. In the comparison between these two arms, the primary outcomes are as follows: a) onset of major depressive episode over a 12-month period, assessed with a Structured Clinical Interview for Diagnosis at 3 months (post-intervention), 6 months and 15 months after randomisation. The following secondary outcomes will be recorded: the incidence of generalized anxiety disorder, symptoms of depression and anxiety, and levels of worry and rumination, measured at baseline and at the same follow-up intervals. In relation to the pilot investigation of unguided internet-RFCBT (the adjunct intervention arm), we will assess the feasibility and acceptability of the data-collection procedures, levels of attrition, effect size and acceptability of the unguided internet-RFCBT intervention. Widespread implementation is necessary for effective prevention, suggesting that the internet may be a valuable mode of delivery. Previous research suggests that guided internet-RFCBT reduces incidence rates relative to controls. We are also interested in developing and evaluating an unguided version to potentially increase the availability and reduce the costs. Current Controlled Trials ISRCTN12683436 . Date of registration: 27 October 2014.

Optimizing Social Network Support to Families Living With Parental Cancer: Research Protocol for the Cancer-PEPSONE Study

PubMed Central

2015-01-01

Background Parental cancer can have a significant impact on a family's psychosocial functioning and quality of life, whereby the children’s situation is strongly related to parental coping and capacity. Such parents ask for more help in order to increase their care capacity, while the network is often insecure about how to help and thereby withdraw. They ask for guidance and training to be able to support cancer families. Based on this, the Cancer- Psycho-Educational Program for the SOcial NEtwork (PEPSONE) study was developed. Objective To optimize social network support through a psycho-educational program for families living with parental cancer and their network members in order to increase parental capacity and thereby secure the children’s safety and quality of life. Methods A randomized controlled trial (RCT) in which families (N=60) living with parental cancer will be randomized to either an intervention group or a control group. The intervention will last for 3 hours and includes (1) introduction, (2) psycho-education (living with cancer in the family and the importance of social network support), and (3) discussion (this family’s need for social support). Primary outcomes are social support, mental health, and quality of life, and secondary outcomes are resilience and parental capacity. Data will be collected by a set of questionnaires distributed to healthy parents (N=60) living with a partner with cancer, one child in the family between 8-18 years of age (N=60), and network members (N=210) of the intervention families at inclusion, and after 3 and 6 months. Comparing differences between the intervention group (n=30) and the control group (n=30), the power analysis shows that P<.05 and a statistical power = .80 would detect effect sizes of clinical interest. Results This paper presents the Cancer-PEPSON study’s protocol to provide a broader understanding of the background and content of the program. The study is ongoing until August 2016 and the first results are anticipated to be finished by November 2015. Conclusions To our knowledge, this will be the first RCT study to optimize social network support through a psycho-educational program for families living with parental cancer and their network members, as well as provide an evidence basis for social network support. The results may provide important knowledge that is useful for clinical practice and further research. The trial is reported according to the CONSORT checklist. ClinicalTrial International Standard Randomized Controlled Trial Number (ISRCTN): 15982171; http://www.controlled-trials.com/ISRCTN15982171/15982171 (Archived by WebCite at http://www.webcitation.org/6cg9zunS0) PMID:26733339

Epilepsy and Neuromodulation—Randomized Controlled Trials

PubMed Central

Kwon, Churl-Su; Ripa, Valeria; Al-Awar, Omar; Panov, Fedor; Ghatan, Saadi; Jetté, Nathalie

2018-01-01

Neuromodulation is a treatment strategy that is increasingly being utilized in those suffering from drug-resistant epilepsy who are not appropriate for resective surgery. The number of double-blinded RCTs demonstrating the efficacy of neurostimulation in persons with epilepsy is increasing. Although reductions in seizure frequency is common in these trials, obtaining seizure freedom is rare. Invasive neuromodulation procedures (DBS, VNS, and RNS) have been approved as therapeutic measures. However, further investigations are necessary to delineate effective targeting, minimize side effects that are related to chronic implantation and to improve the cost effectiveness of these devices. The RCTs of non-invasive modes of neuromodulation whilst showing much promise (tDCS, eTNS, rTMS), require larger powered studies as well as studies that focus at better targeting techniques. We provide a review of double-blinded randomized clinical trials that have been conducted for neuromodulation in epilepsy. PMID:29670050

Design of the Intravenous Magnesium Efficacy in Acute Stroke (IMAGES) trial.

PubMed

Bradford, Andrew; Lees, Kennedy

2000-01-01

The Intravenous Magnesium Efficacy in Acute Stroke (IMAGES) trial is a multicentre,randomised, placebo-controlled trial of magnesium sulphate (MgSO4) funded by the UK Medical Research Council. When complete, it will be the largest single neuroprotective study undertaken to date. Conscious patients presenting within 12 h of acute stroke with limb weakness are eligible. The primary outcome measure is combined death and disability as measured using the Barthel Index at 90-day follow up. By randomizing 2700 patients, the study will have 84% power to detect a 5.5% absolute reduction in the primary end-point. By April 2000, 86 centres were participating, with representation in Canada, USA, Europe, South America, Singapore and Australia. So far, 1206 patients have been randomised, of whom 37% were treated within 6 h. Overall 3-month mortality was 20% and the primary outcome event rate was 43%. The study is ongoing and centres worldwide are encouraged to participate.

The preparation effect in task switching: carryover of SOA.

PubMed

Altmann, Erik M

2004-01-01

A common finding in task-switching studies is switch preparation (commonly known as the preparation effect), in which a longer interval between task cue and trial stimulus (i.e., a longer stimulus onset asynchrony, or SOA) reduces the cost of switching to a different task. Three experiments link switch preparation to within-subjects manipulations of SOA. In Experiment 1, SOA was randomized within subjects, producing switch preparation that was more pronounced when the SOA switched from the previous trial than when the SOA repeated. In Experiment 2, SOA was blocked within subjects, producing switch preparation but not on the first block of trials. In Experiment 3, SOA was manipulated between subjects with sufficient statistical power to detect switch preparation, but the effect was absent. The results favor an encoding view of cognitive control, but show that any putative switching mechanism reacts lazily when exposed to only one SOA.

T55 power turbine rotor multiplane-multispeed balancing study

NASA Technical Reports Server (NTRS)

Martin, M. R.

1982-01-01

A rotordynamic analysis of the T55-L-11C engine was used to evaluate the balancing needs of the power turbine and to optimize the balancing procedure. As a result, recommendations were made for implementation of a multiplane-multispeed balancing plan. Precision collars for the attachment of trial weights to a slender rotor were designed enabling demonstration balancing on production hardware. The quality of the balance was then evaluated by installing a high speed balanced power turbine in an engine and running in a test cell at the Corpus Christi Army depot. The engine used had been tested prior to the turbine changeout and showed acceptable overall vibration levels for the engine were significantly reduced, demonstrating the ability of multiplane-multispeed balancing to control engine vibration.

A Cluster-Randomized Controlled Trial of a Simplified Multifaceted Management Program for Individuals at High Cardiovascular Risk (SimCard Trial) in Rural Tibet, China and Haryana, India

PubMed Central

Tian, Maoyi; Ajay, Vamadevan S.; Dunzhu, Danzeng; Hameed, Safraj S.; Li, Xian; Liu, Zhong; Li, Cong; Chen, Hao; Cho, KaWing; Li, Ruilai; Zhao, Xingshan; Jindal, Devraj; Rawal, Ishita; Ali, Mohammed K.; Peterson, Eric D.; Ji, Jiachao; Amarchand, Ritvik; Krishnan, Anand; Tandon, Nikhil; Xu, Li-Qun; Wu, Yangfeng; Prabhakaran, Dorairaj; Yan, Lijing L.

2015-01-01

Background In rural areas in China and India, cardiovascular disease burden is high but economic and healthcare resources are limited. This study aims to develop and evaluate a simplified cardiovascular management program (SimCard) delivered by community health workers (CHWs) with the aid of a smartphone-based electronic decision support system. Methods and Results The SimCard study was a yearlong cluster-randomized controlled trial conducted in 47 villages (27 in China and 20 in India). 2,086 ‘high cardiovascular risk’ individuals (aged 40 years or older with self-reported history of coronary heart disease, stroke, diabetes, and/or measured systolic blood pressure ≥160 mmHg) were recruited. Participants in the intervention villages were managed by CHWs through an Android-powered “app” on a monthly basis focusing on two medication use and two lifestyle modifications. Compared with the control group, the intervention group had a 25.5% (P<0.001) higher net increase in the primary outcome of the proportion of patient-reported anti-hypertensive medication use pre-and-post intervention. There were also significant differences in certain secondary outcomes: aspirin use (net difference 17.1%, P<0.001) and systolic blood pressure (−2.7 mmHg, P=0.04). However, no significant changes were observed in the lifestyle factors. The intervention was culturally tailored and country-specific results revealed important differences between the regions. Conclusions The results indicate that the simplified cardiovascular management program improved quality of primary care and clinical outcomes in resource-poor settings in China and India. Larger trials in more places are needed to ascertain potential impacts on mortality and morbidity outcomes. Clinical Trial Registration Information clinicaltrials.gov. Identifier: NCT01503814. PMID:26187183

Treatment of retained placenta with misoprostol: a randomised controlled trial in a low-resource setting (Tanzania).

PubMed

van Beekhuizen, Heleen J; Pembe, Andrea B; Fauteck, Heiner; Lotgering, Fred K

2009-10-23

Retained placenta is one of the common causes of maternal mortality in developing countries where access to appropriate obstetrical care is limited. Current treatment of retained placenta is manual removal of the placenta under anaesthesia, which can only take place in larger health care facilities. Medical treatment of retained placenta with prostaglandins E1 (misoprostol) could be cost-effective and easy-to-use and could be a life-saving option in many low-resource settings. The aim of this study is to assess the efficacy and safety of sublingually administered misoprostol in women with retained placenta in a low resource setting. Multicentered randomised, double-blind, placebo-controlled trial, to be conducted in 5 hospitals in Tanzania, Africa. Women with retained placenta, at a gestational age of 28 weeks or more and blood loss less than 750 ml, 30 minutes after delivery of the newborn despite active management of third stage of labour. Trial Entry & Randomisation & Study Medication: After obtaining informed consent, eligible women will be allocated randomly to the treatment groups using numbered envelopes that will be randomized in variable blocks containing identical capsules with either 800 microgram of misoprostol or placebo. The drugs will be given sublingually. The women, maternal care providers and researchers will be blinded to treatment allocation. 117 women, to show a 40% reduction in manual removals of the placenta (p = 0.05, 80% power). The randomization will be misoprostol: placebo = 2:1. PRIMARY STUDY OUTCOME: Expulsion of the placenta without manual removal. Secondary outcome is the number of blood transfusions. This is a protocol for a randomized trial in a low resource setting to assess if medical treatment of women with retained placenta with misoprostol reduces the incidence of manual removal of the placenta. Current Controlled Trials ISRCTN16104753.

Massage therapy for children with autism spectrum disorders: a systematic review.

PubMed

Lee, Myeong Soo; Kim, Jong-In; Ernst, Edzard

2011-03-01

We aimed to assess the effectiveness of massage as a treatment option for autism. We searched the following electronic databases using the time of their inception through March 2010: MEDLINE, AMED, CINAHL, EMBASE, PsycINFO, Health Technology Assessment, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Psychology and Behavioral Sciences Collection, 6 Korean medical databases (KSI, DBpia, KISTEP, RISS, KoreaMed, and National Digital Library), China Academic Journal (through China National Knowledge Infrastructure), and 3 Japanese medical databases (Journal@rchive, Science Links Japan, and Japan Science & Technology link). The search phrase used was "(massage OR touch OR acupressure) AND (autistic OR autism OR Asperger's syndrome OR pervasive developmental disorder)." The references in all located articles were also searched. No language restrictions were imposed. Prospective controlled clinical studies of any type of massage therapy for autistic patients were included. Trials in which massage was part of a complex intervention were also included. Case studies, case series, qualitative studies, uncontrolled trials, studies that failed to provide detailed results, and trials that compared one type of massage with another were excluded. All articles were read by 2 independent reviewers (M.S.L. and J-I.K.), who extracted data from the articles according to predefined criteria. Risk of bias was assessed using the Cochrane classification. Of 132 articles, only 6 studies met our inclusion criteria. One randomized clinical trial found that massage plus conventional language therapy was superior to conventional language therapy alone for symptom severity (P < .05) and communication attitude (P < .01). Two randomized clinical trials reported a significant benefit of massage for sensory profile (P < .01), adaptive behavior (P < .05), and language and social abilities (P < .01) as compared with a special education program. The fourth randomized clinical trial showed beneficial effects of massage for social communication (P < .05). Two nonrandomized controlled clinical trials suggested that massage therapy is effective. However, all of the included trials have high risk of bias. The main limitations of the included studies were small sample sizes, predefined primary outcome measures, inadequate control for nonspecific effects, and a lack of power calculations or adequate follow-up. Limited evidence exists for the effectiveness of massage as a symptomatic treatment of autism. Because the risk of bias was high, firm conclusions cannot be drawn. Future, more rigorous randomized clinical trials seem to be warranted. © Copyright 2011 Physicians Postgraduate Press, Inc.

"In God we trust" and other factors influencing trial of labor versus Repeat cesarean section.

PubMed

Pomeranz, Meir; Arbib, Nissim; Haddif, Limor; Reissner, Hana; Romem, Yitzhak; Biron, Tal

2018-07-01

To investigate factors influencing women's decisions to undergo trial of labor after cesarean (TOLAC) or elective repeat cesarean delivery (ERCD) based on the Multidimensional Health Locus of Control (MHLC), religious observance and family planning. Cross-sectional study of candidates for TOLAC or ERCD at two hospitals in Israel. Eligible women completed a demographic questionnaire and Form C of the MHLC scale. The study included 197 women. Those who chose TOLAC (N = 101) were more religiously observant, wanted more children and had higher Internal and Chance health locus of control. Women who chose ERCD (N = 96) were more likely to be secular and had a higher health locus of control influenced by Powerful Others, notably physicians. Women not influenced by others were more likely to choose TOLAC. A woman's choice of TOLAC or ERCD is influenced by her sense of control over her health, degree of religious observance and number of children desired. Healthcare providers can use this information to better understand, counsel and educate women regarding appropriate delivery decisions. Women who feel in control of their health, educated about delivery options and are less influenced by provider preference, might choose TOLAC; thus, reducing the rate of unnecessary ERCD.

Role of 3D animation in periodontal patient education: a randomized controlled trial.

PubMed

Cleeren, Gertjan; Quirynen, Marc; Ozcelik, Onur; Teughels, Wim

2014-01-01

This randomized controlled parallel trial investigates the effect of 3D animation on the increase and recall of knowledge on periodontitis by patients with periodontitis. The effects of a 3D animation (3D animation group) were compared with narration and drawing (control group) for periodontal patient education. A total of 68 periodontitis patients were stratified according to educational level and then randomly allocated to control or 3D animation groups. All patients received: (1) a pre-test (baseline knowledge), (2) a patient education video (3D animation or control video), (3) a post-test (knowledge immediately after looking at the video), and (4) a follow-up test (knowledge recall after 2 weeks). Each test contained 10 multiple-choice questions. There was no significant difference in baseline knowledge. Patients receiving the 3D animations had significantly higher scores for both the post-test and the follow-up test, when compared with patients receiving sketch animations. 3D animations are more effective than real-time drawings for periodontal patient education in terms of knowledge recall. 3D animations may be a powerful tool for assisting in the information process. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prestimulus alpha power predicts fidelity of sensory encoding in perceptual decision making.

PubMed

Lou, Bin; Li, Yun; Philiastides, Marios G; Sajda, Paul

2014-02-15

Pre-stimulus α power has been shown to correlate with the behavioral accuracy of perceptual decisions. In most cases, these correlations have been observed by comparing α power for different behavioral outcomes (e.g. correct vs incorrect trials). In this paper we investigate such covariation within the context of behaviorally-latent fluctuations in task-relevant post-stimulus neural activity. Specially we consider variations of pre-stimulus α power with post-stimulus EEG components in a two alternative forced choice visual discrimination task. EEG components, discriminative of stimulus class, are identified using a linear multivariate classifier and only the variability of the components for correct trials (regardless of stimulus class, and for nominally identical stimuli) are correlated with the corresponding pre-stimulus α power. We find a significant relationship between the mean and variance of the pre-stimulus α power and the variation of the trial-to-trial magnitude of an early post-stimulus EEG component. This relationship is not seen for a later EEG component that is also discriminative of stimulus class and which has been previously linked to the quality of evidence driving the decision process. Our results suggest that early perceptual representations, rather than temporally later neural correlates of the perceptual decision, are modulated by pre-stimulus state. © 2013 Elsevier Inc. All rights reserved.

Prestimulus alpha power predicts fidelity of sensory encoding in perceptual decision making

PubMed Central

Lou, Bin; Li, Yun; Philiastides, Marios G.; Sajda, Paul

2013-01-01

Pre-stimulus α power has been shown to correlate with the behavioral accuracy of perceptual decisions. In most cases, these correlations have been observed by comparing α power for different behavioral outcomes (e.g. correct vs incorrect trials). In this paper we investigate such covariation within the context of behaviorally-latent fluctuations in task-relevant post-stimulus neural activity. Specially we consider variations of pre-stimulus α power with post-stimulus EEG components in a two alternative forced choice visual discrimination task. EEG components, discriminative of stimulus class, are identified using a linear multivariate classifier and only the variability of the components for correct trials (regardless of stimulus class, and for nominally identical stimuli) are correlated with the corresponding pre-stimulus α power. We find a significant relationship between the mean and variance of the pre-stimulus α power and the variation of the trial-to-trial magnitude of an early post-stimulus EEG component. This relationship is not seen for a later EEG component that is also discriminative of stimulus class and which has been previously linked to the quality of evidence driving the decision process. Our results suggest that early perceptual representations, rather than temporally later neural correlates of the perceptual decision, are modulated by pre-stimulus state. PMID:24185020

Lifestyle Advice Combined with Personalized Estimates of Genetic or Phenotypic Risk of Type 2 Diabetes, and Objectively Measured Physical Activity: A Randomized Controlled Trial

PubMed Central

van Sluijs, Esther M. F.; Marteau, Theresa M.; Sutton, Stephen

2016-01-01

Background Information about genetic and phenotypic risk of type 2 diabetes is now widely available and is being incorporated into disease prevention programs. Whether such information motivates behavior change or has adverse effects is uncertain. We examined the effect of communicating an estimate of genetic or phenotypic risk of type 2 diabetes in a parallel group, open, randomized controlled trial. Methods and Findings We recruited 569 healthy middle-aged adults from the Fenland Study, an ongoing population-based, observational study in the east of England (Cambridgeshire, UK). We used a computer-generated random list to assign participants in blocks of six to receive either standard lifestyle advice alone (control group, n = 190) or in combination with a genetic (n = 189) or a phenotypic (n = 190) risk estimate for type 2 diabetes (intervention groups). After 8 wk, we measured the primary outcome, objectively measured physical activity (kJ/kg/day), and also measured several secondary outcomes (including self-reported diet, self-reported weight, worry, anxiety, and perceived risk). The study was powered to detect a between-group difference of 4.1 kJ/kg/d at follow-up. 557 (98%) participants completed the trial. There were no significant intervention effects on physical activity (difference in adjusted mean change from baseline: genetic risk group versus control group 0.85 kJ/kg/d (95% CI −2.07 to 3.77, p = 0.57); phenotypic risk group versus control group 1.32 (95% CI −1.61 to 4.25, p = 0.38); and genetic risk group versus phenotypic risk group −0.47 (95% CI −3.40 to 2.46, p = 0.75). No significant differences in self-reported diet, self-reported weight, worry, and anxiety were observed between trial groups. Estimates of perceived risk were significantly more accurate among those who received risk information than among those who did not. Key limitations include the recruitment of a sample that may not be representative of the UK population, use of self-reported secondary outcome measures, and a short follow-up period. Conclusions In this study, we did not observe short-term changes in behavior associated with the communication of an estimate of genetic or phenotypic risk of type 2 diabetes. We also did not observe changes in worry or anxiety in the study population. Additional research is needed to investigate the conditions under which risk information might enhance preventive strategies. (Current Controlled Trials ISRCTN09650496; Date applied: April 4, 2011; Date assigned: June 10, 2011). Trial Registration The trial is registered with Current Controlled Trials, ISRCTN09650496. PMID:27898672

Physiotherapy Post Lumbar Discectomy: Prospective Feasibility and Pilot Randomised Controlled Trial

PubMed Central

Rushton, Alison; Goodwin, Peter C.

2015-01-01

Objectives To evaluate: acceptability and feasibility of trial procedures; distribution of scores on the Roland Morris Disability Questionnaire (RMDQ, planned primary outcome); and efficient working of trial components. Design and Setting A feasibility and external pilot randomised controlled trial (ISRCTN33808269, assigned 10/12/2012) was conducted across 2 UK secondary care outpatient physiotherapy departments associated with regional spinal surgery centres. Participants Consecutive consenting patients aged >18 years; post primary, single level, lumbar discectomy. Interventions Participants were randomised to either 1:1 physiotherapy outpatient management including patient leaflet, or patient leaflet alone. Main Outcome Measures Blinded assessments were made at 4 weeks post surgery (baseline) and 12 weeks post baseline (proposed primary end point). Secondary outcomes included: Global Perceived Effect, back/leg pain, straight leg raise, return to work/function, quality of life, fear avoidance, range of movement, medication, re-operation. Results At discharge, 110 (44%) eligible patients gave consent to be contacted. 59 (54%) patients were recruited. Loss to follow up was 39% at 12 weeks, with one site contributing 83% losses. Mean (SD) RMDQ was 10.07 (5.58) leaflet and 10.52 (5.94) physiotherapy/leaflet at baseline; and 5.37 (4.91) leaflet and 5.53 (4.49) physiotherapy/leaflet at 12 weeks. 5.1% zero scores at 12 weeks illustrated no floor effect. Sensitivity to change was assessed at 12 weeks with mean (SD) change -4.53 (6.41), 95%CI -7.61 to -1.44 for leaflet; and -6.18 (5.59), 95%CI -9.01 to -3.30 for physiotherapy/leaflet. RMDQ mean difference (95%CI) between change from baseline to twelve weeks was 1.65(-2.46 to 5.75). Mean difference (95%CI) between groups at 12 weeks was -0.16 (-3.36 to 3.04). Participant adherence with treatment was good. No adverse events were reported. Conclusions Both interventions were acceptable, and it is promising that they both demonstrated a trend in reducing disability in this population. A randomised controlled trial, using a different trial design, is needed to ascertain the effectiveness of combining the interventions into a stepped care intervention and comparing to a no intervention arm. Findings will guide design changes for an adequately powered randomised controlled trial, using RMDQ as the primary outcome. Trial Registration ISRCTN registry 33808269 PMID:26562660

Electronically delivered, multicomponent intervention to reduce unnecessary antibiotic prescribing for respiratory infections in primary care: a cluster randomised trial using electronic health records—REDUCE Trial study original protocol

PubMed Central

Juszczyk, Dorota; Charlton, Judith; McDermott, Lisa; Soames, Jamie; Sultana, Kirin; Ashworth, Mark; Fox, Robin; Hay, Alastair D; Little, Paul; Moore, Michael V; Yardley, Lucy; Prevost, A Toby; Gulliford, Martin C

2016-01-01

Introduction Respiratory tract infections (RTIs) account for about 60% of antibiotics prescribed in primary care. This study aims to test the effectiveness, in a cluster randomised controlled trial, of electronically delivered, multicomponent interventions to reduce unnecessary antibiotic prescribing when patients consult for RTIs in primary care. The research will specifically evaluate the effectiveness of feeding back electronic health records (EHRs) data to general practices. Methods and analysis 2-arm cluster randomised trial using the EHRs of the Clinical Practice Research Datalink (CPRD). General practices in England, Scotland, Wales and Northern Ireland are being recruited and the general population of all ages represents the target population. Control trial arm practices will continue with usual care. Practices in the intervention arm will receive complex multicomponent interventions, delivered remotely to information systems, including (1) feedback of each practice's antibiotic prescribing through monthly antibiotic prescribing reports estimated from CPRD data; (2) delivery of educational and decision support tools; (3) a webinar to explain and promote effective usage of the intervention. The intervention will continue for 12 months. Outcomes will be evaluated from CPRD EHRs. The primary outcome will be the number of antibiotic prescriptions for RTIs per 1000 patient years. Secondary outcomes will be: the RTI consultation rate; the proportion of consultations for RTI with an antibiotic prescribed; subgroups of age; different categories of RTI and quartiles of intervention usage. There will be more than 80% power to detect an absolute reduction in antibiotic prescription for RTI of 12 per 1000 registered patient years. Total healthcare usage will be estimated from CPRD data and compared between trial arms. Ethics and dissemination Trial protocol was approved by the National Research Ethics Service Committee (14/LO/1730). The pragmatic design of the trial will enable subsequent translation of effective interventions at scale in order to achieve population impact. Trial registration number ISRCTN95232781; Pre-results. PMID:27491663

Cost-effectiveness of blended vs. face-to-face cognitive behavioural therapy for severe anxiety disorders: study protocol of a randomized controlled trial.

PubMed

Romijn, Geke; Riper, Heleen; Kok, Robin; Donker, Tara; Goorden, Maartje; van Roijen, Leona Hakkaart; Kooistra, Lisa; van Balkom, Anton; Koning, Jeroen

2015-12-12

Anxiety disorders are among the most prevalent psychiatric conditions, and are associated with poor quality of life and substantial economic burden. Cognitive behavioural therapy is an effective treatment to reduce anxiety symptoms, but is also costly and labour intensive. Cost-effectiveness could possibly be improved by delivering cognitive behavioural therapy in a blended format, where face-to-face sessions are partially replaced by online sessions. The aim of this trial is to determine the cost-effectiveness of blended cognitive behavioural therapy for adults with anxiety disorders, i.e. panic disorder, social phobia or generalized anxiety disorder, in specialized mental health care settings compared to face-to-face cognitive behavioural therapy. In this paper, we present the study protocol. It is hypothesized that blended cognitive behavioural therapy for anxiety disorders is clinically as effective as face-to-face cognitive behavioural therapy, but that intervention costs may be reduced. We thus hypothesize that blended cognitive behavioural therapy is more cost-effective than face-to-face cognitive behavioural therapy. In a randomised controlled equivalence trial 156 patients will be included (n = 78 in blended cognitive behavioural therapy, n = 78 in face-to-face cognitive behavioural therapy) based on a power of 0.80, calculated by using a formula to estimate the power of a cost-effectiveness analysis: [Formula: see text]. Measurements will take place at baseline, midway treatment (7 weeks), immediately after treatment (15 weeks) and 12-month follow-up. At baseline a diagnostic interview will be administered. Primary clinical outcomes are changes in anxiety symptom severity as measured with the Beck Anxiety Inventory. An incremental cost-effectiveness ratio will be calculated to obtain the costs per quality-adjusted life years (QALYs) measured by the EQ-5D (5-level version). Health-economic outcomes will be explored from a societal and health care perspective. This trial will be one of the first to provide information on the cost-effectiveness of blended cognitive behavioural therapy for anxiety disorders in routine specialized mental health care settings, both from a societal and a health care perspective. Netherlands Trial Register NTR4912. Registered 13 November 2014.

Propranolol and Oxandrolone Therapy Accelerated Muscle Recovery in Burned Children.

PubMed

Chao, Tony; Porter, Craig; Herndon, David N; Siopi, Aikaterina; Ideker, Henry; Mlcak, Ronald P; Sidossis, Labros S; Suman, Oscar E

2018-03-01

Severe burns result in prolonged hypermetabolism and skeletal muscle catabolism. Rehabilitative exercise training (RET) programs improved muscle mass and strength in severely burned children. The combination of RET with β-blockade or testosterone analogs showed improved exercise-induced benefits on body composition and muscle function. However, the effect of RET combined with multiple drug therapy on muscle mass, strength, cardiorespiratory fitness, and protein turnover are unknown. In this placebo-controlled randomized trial, we hypothesize that RET combined with oxandrolone and propranolol (Oxprop) will improve muscle mass and function and protein turnover in severely burned children compared with burned children undergoing the same RET with a placebo. We studied 42 severely burned children (7-17 yr) with severe burns over 30% of the total body surface area. Patients were randomized to placebo (22 control) or to Oxprop (20) and began drug administration within 96 h of admission. All patients began RET at hospital discharge as part of their standardized care. Muscle strength (N·m), power (W), V˙O2peak, body composition, and protein fractional synthetic rate and fractional breakdown rate were measured pre-RET (PRE) and post-RET (POST). Muscle strength and power, lean body mass, and V˙O2peak increased with RET in both groups (P < 0.01). The increase in strength and power was significantly greater in Oxprop versus control (P < 0.01), and strength and power was greater in Oxprop over control POST (P < 0.05). Fractional synthetic rate was significantly higher in Oxprop than control POST (P < 0.01), resulting in improved protein net balance POST (P < 0.05). Rehabilitative exercise training improves body composition, muscle function, and cardiorespiratory fitness in children recovering from severe burns. Oxprop therapy augments RET-mediated improvements in muscle strength, power, and protein turnover.

Deliberate self harm: systematic review of efficacy of psychosocial and pharmacological treatments in preventing repetition

PubMed Central

Hawton, Keith; Arensman, Ella; Townsend, Ellen; Bremner, Sandy; Feldman, Eleanor; Goldney, Robert; Gunnell, David; Hazell, Philip; van Heeringen, Kees; House, Allan; Owens, David; Sakinofsky, Isaac; Träskman-Bendz, Lil

1998-01-01

Objective: To identify and synthesise the findings from all randomised controlled trials that have examined the effectiveness of treatments of patients who have deliberately harmed themselves. Design: Systematic review of randomised controlled trials of psychosocial and physical treatments. Studies categorised according to type of treatment. When there was more than one investigation in a particular category a summary odds ratio was estimated with the Mantel-Haenszel method. Setting: Randomised trials available in electronic databases in 1996, in the Cochrane Controlled Trials Register in 1997, and from hand searching of journals to 1997. Subjects: Patients who had deliberately harmed themselves shortly before entry into the trials with information on repetition of behaviour. The included trials comprised 2452 randomised participants with outcome data. Main outcome measure: Repetition of self harm. Results: 20 trials reported repetition of self harm as an outcome variable, classified into 10 categories. Summary odds ratio (all for comparison with standard aftercare) indicated reduced repetition for problem solving therapy (0.73; 95% confidence interval 0.45 to 1.18) and for provision of an emergency contact card in addition to standard care (0.45; 0.19 to 1.07). The summary odds ratios were 0.83 (0.61 to 1.14) for trials of intensive aftercare plus outreach and 1.19 (0.53 to 2.67) for antidepressant treatment compared with placebo. Significantly reduced rates of further self harm were observed for depot flupenthixol versus placebo in multiple repeaters (0.09; 0.02 to 0.50) and for dialectical behaviour therapy versus standard aftercare (0.24; 0.06 to 0.93). Conclusion: There remains considerable uncertainty about which forms of psychosocial and physical treatments of patients who harm themselves are most effective. Further larger trials of treatments are needed. Key messages A systematic review of the effectiveness of psychosocial and drug treatments of patients who deliberately harm themselves identified 20 randomised controlled trials in which repetition of self harm was reported as an outcome Promising results were found for problem solving therapy, provision of a card to allow patients to make emergency contact with services, depot flupenthixol for recurrent self harm, and long term psychological therapy for female patients with borderline personality disorder and recurrent self harm Assertive outreach can help to keep patients in treatment Nearly all the trials included too few patients to detect clinically significant differences in repetition of self harm, and even synthesis of results by meta-analysis did not have the power to detect such differences There is an urgent need for large trials of promising therapies for this substantial clinical population PMID:9703526

Topical cyclosporine for atopic keratoconjunctivitis.

PubMed

González-López, Julio J; López-Alcalde, Jesús; Morcillo Laiz, Rafael; Fernández Buenaga, Roberto; Rebolleda Fernández, Gema

2012-09-12

Atopic keratoconjunctivitis (AKC) is a chronic ocular surface non-infectious inflammatory condition that atopic dermatitis patients may suffer at any time point in the course of their dermatologic disease and is independent of its degree of severity. AKC is usually not self resolving and it poses a higher risk of corneal injuries and severe sequelae. Management of AKC should prevent or treat corneal damage. Although topical corticosteroids remain the standard treatment for patients with AKC, prolonged use may lead to complications. Topical cyclosporine A (CsA) may improve AKC signs and symptoms, and be used as a corticosteroid sparing agent. To determine the efficacy and gather evidence on safety from randomised controlled trials (RCTs) of topical CsA in patients with AKC. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to July 2012), EMBASE (January 1980 to July 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2012), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to July 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en), the IFPMA Clinical Trials Portal (http://clinicaltrials.ifpma.org/no_cache/en/myportal/index.htm) and Web of Science Conference Proceedings Citation Index- Science (CPCI-S). We did not use any date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 9 July 2012. We also handsearched the following conference proceedings: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, International Council of Opthalmology and Societas Ophthalmologica Europaea from 2005 to July 2011. We included randomised controlled trials only. Two review authors independently extracted data. Due to the small number of studies and the diversity of outcome measures, interventions and participants, we presented results narratively. We found three RCTs with a total of 58 participants that were eligible for inclusion. There was significant variability between the trials in interventions, methodology and outcome measures and therefore we did not perform meta-analysis.One study reported on the use of 2% CsA in maize oil and two on the use of a commercial emulsion of 0.05% CsA. Of these three studies, one showed a beneficial effect of topical CsA in controlling signs and symptoms of AKC, one in controlling signs of AKC and one did not show evidence of an improvement. Only two studies analysed the effect of topical CsA in reducing topical steroid use; one showed a significant reduction in topical steroid use with CsA, but the other did not show evidence of this improvement. No serious adverse events were reported in the trials. This systematic review highlights the relative scarcity of controlled clinical trials assessing the efficacy of topical CsA therapy in AKC and suggests that evidence on the efficacy and safety of topical CsA treatment in patients with CsA remains limited. However, the data suggest that topical CsA may provide clinical and symptomatic relief in AKC and may help to reduce topical steroid use in patients with steroid-dependent or steroid-resistant AKC. No serious adverse events were reported. Reported adverse events in patients treated with topical CsA include intense stinging and eyelid skin maceration. One patient in the placebo group developed a severe allergic response to maize antigens. However, the total number of patients in the trials was too small to assess the safety of this treatment.Additional well-designed and powered RCTs of topical CsA in AKC are needed. Ideal study designs should include adequate randomisation and concealment of allocation; masking of participants, personnel and outcome assessors; adequate follow-up periods and minimisation of attrition bias; and comparison groups with similar clinical and epidemiologic characteristics. Samples should be large enough to provide sufficient statistical power to assess the safety of CsA and to detect clinically relevant treatment effect sizes of the primary outcomes. Analyses should be appropriate to the study's design and outcome measures. Moreover, standardisation of outcome measures and follow-up periods across studies would be beneficial to maximise study comparability.

Dissonance-based eating disorder program reduces cardiac risk: A preliminary trial.

PubMed

Green, Melinda A; Willis, Mary; Fernandez-Kong, Kristen; Reyes, Shuhan; Linkhart, Ruby; Johnson, Molly; Thorne, Tyler; Kroska, Emily; Woodward, Halley; Lindberg, Jessica

2017-04-01

We conducted a randomized, controlled preliminary trial to examine the effect of a dissonance-based eating disorder program on eating disorder symptoms and cardiac risk indices in a community sample of women with subclinical and clinical symptoms (N = 47), examining the efficacy of the program in both the indicated prevention and treatment realms. Eating disorder symptoms, body mass index, and biomarkers of cardiac risk were examined in dissonance and assessment-only control conditions at baseline, postintervention, and 2-month follow-up. Specifically, we assessed mean R wave amplitude, QT interval length, vagal tone (high frequency spectral power of heart rate variability), and sympathetic tone (low/high frequency spectral power ratio) via electocardiography (ECG) at each assessment period. We predicted a statistically significant 2 (condition: control, dissonance) × 3 (time: baseline, postintervention, 2-month follow-up) interaction in the mixed factorial MANOVA results. Results confirmed this hypothesis. Eating disorder symptoms and cardiac risk indices decreased significantly among participants in the dissonance condition at postintervention and 2-month follow-up compared with baseline. Results provide support for the efficacy of a dissonance-based program in the reduction of eating disorder symptoms and cardiac risk indices among women with subclinical and clinical eating disorder symptoms. Findings establish the efficaciousness of this dissonance-based approach in the indicated prevention and treatment realms and establish its efficacy in reducing cardiac risk indicators. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Effect of Simulation on the Confidence of University Nursing Students in Applying Cardiopulmonary Assessment Skills: A Randomized Controlled Trial.

PubMed

Tawalbeh, Loai I

2017-08-01

Simulation is an effective teaching strategy. However, no study in Jordan has examined the effect of simulation on the confidence of university nursing students in applying heart and lung physical examination skills. The current study aimed to test the effect of simulation on the confidence of university nursing students in applying heart and lung physical examination skills. A randomized controlled trial design was applied. The researcher introduced the simulation scenario regarding cardiopulmonary examination skills. This scenario included a 1-hour PowerPoint presentation and video for the experimental group (n= 35) and a PowerPoint presentation and a video showing a traditional demonstration in the laboratory for the control group (n = 34). Confidence in applying cardiopulmonary physical examination skills was measured for both groups at baseline and at 1 day and 3 months posttest. A paired t test showed that confidence was significantly higher in the posttest than in the pretest for both groups. An independent t test showed a statistically significant difference (t(67) = -42.95, p < .001) between the two groups in terms of the difference between the first posttest and second posttest scores (t(67) = -43.36, p < .001) for confidence in applying physical examination skills. Both simulation and traditional training in the laboratory significantly improved the confidence of participants in applying cardiopulmonary assessment skills. However, the simulation training had a more significant effect than usual training in enhancing the confidence of nursing students in applying physical examination skills.

Interventions for managing asthma in pregnancy.

PubMed

Bain, Emily; Pierides, Kristen L; Clifton, Vicki L; Hodyl, Nicolette A; Stark, Michael J; Crowther, Caroline A; Middleton, Philippa

2014-10-21

Asthma is the most common respiratory disorder complicating pregnancy, and is associated with a range of adverse maternal and perinatal outcomes. There is strong evidence however, that the adequate control of asthma can improve health outcomes for mothers and their babies. Despite known risks of poorly controlled asthma during pregnancy, a large proportion of women have sub-optimal asthma control, due to concerns surrounding risks of pharmacological agents, and uncertainties regarding the effectiveness and safety of different management strategies. To assess the effects of interventions (pharmacologic and non-pharmacologic) for managing women's asthma in pregnancy on maternal and fetal/infant outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 June 2014) and the Cochrane Airways Group's Trials Register (4 June 2014). Randomised and quasi-randomised controlled trials comparing any intervention used to manage asthma in pregnancy, with placebo, no intervention, or an alternative intervention. We included pharmacological and non-pharmacological interventions (including combined interventions). Cluster-randomised trials were eligible for inclusion (but none were identified). Cross-over trials were not eligible for inclusion.We included multi-armed trials along with two-armed trials. We also included studies published as abstracts only. At least two review authors independently assessed trial eligibility and quality and extracted data. Data were checked for accuracy. We included eight trials in this review, involving 1181 women and their babies. Overall we judged two trials to be at low risk of bias, two to be of unclear risk of bias, and four to be at moderate risk of bias.Five trials assessed pharmacological agents, including inhaled corticosteroids (beclomethasone or budesonide), inhaled magnesium sulphate, intravenous theophylline, and inhaled beclomethasone verus oral theophylline. Three trials assessed non-pharmacological interventions, including a fractional exhaled nitric oxide (FENO)-based algorithm versus a clinical guideline-based algorithm to adjust inhaled corticosteroid therapy, a pharmacist-led multi-disciplinary approach to management versus standard care, and progressive muscle relaxation (PMR) versus sham training.The eight included trials were assessed under seven separate comparisons. Pharmacological interventionsPrimary outcomes: one trial suggested that inhaled magnesium sulphate in addition to usual treatment could reduce exacerbation frequency in acute asthma (mean difference (MD) -2.80; 95% confidence interval (CI) -3.21 to -2.39; 60 women). One trial assessing the addition of intravenous theophylline to standard care in acute asthma did not report on exacerbations (65 women). No clear difference was shown in the risk of exacerbations with the use of inhaled beclomethasone in addition to usual treatment for maintenance therapy in one trial (risk ratio (RR) 0.36; 95% CI 0.13 to 1.05; 60 women); a second trial also showed no difference, however data were not clearly reported to allow inclusion in a meta-analysis. No difference was shown when inhaled beclomethasone was compared with oral theophylline for maintenance therapy (RR 0.88; 95% CI 0.59 to 1.33; one trial, 385 women). None of these trials reported on neonatal intensive care admissions. inhaled magnesium sulphate in acute asthma was shown to improve lung function measures (one trial, 60 women); intravenous theophylline in acute asthma was not associated with benefits (one trial, 65 women). No clear differences were seen with the addition of inhaled corticosteroids to routine treatment in three trials (374 women). While inhaled beclomethasone, compared with oral theophylline, significantly reduced treatment discontinuation due to adverse effects in one trial (384 women), no other differences were observed, except for higher treatment adherence with theophylline. Four of the five trials did not report on adverse effects. Non-pharmacological interventionsPrimary outcomes: in one trial, the use of a FENO-based algorithm was shown to significantly reduce asthma exacerbations (RR 0.61; 95% CI 0.41 to 0.90; 220 women); and a trend towards fewer neonatal hospitalisations was observed (RR 0.46; 95% CI 0.21 to 1.02; 214 infants). No exacerbations occurred in one trial assessing pharmacist-led management; this approach did not reduce neonatal intensive care admissions (RR 1.50; 95% CI 0.27 to 8.32; 58 infants). One trial (64 women) assessing PMR did not report on exacerbations or neonatal intensive care admissions. the use of a FENO-based algorithm to adjust therapy led to some improvements in quality of life scores, as well as more frequent use of inhaled corticosteroids and long-acting β-agonists, and less frequent use of short-acting β-agonists (one trial, 220 women). The FENO-based algorithm was associated with fewer infants with recurrent episodes of bronchiolitis in their first year of life, and a trend towards fewer episodes of croup for infants. Pharmacist-led management improved asthma control scores at six months (one trial, 60 women); PMR improved lung function and quality of life measures (one trial, 64 women). No other differences between comparisons were observed. Based on eight included trials, of moderate quality overall, no firm conclusions about optimal interventions for managing asthma in pregnancy can be made. Five trials assessing pharmacological interventions did not provide clear evidence of benefits or harms to support or refute current practice. While inhaled magnesium sulphate for acute asthma was shown to reduce exacerbations, this was in one small trial of unclear quality, and thus this finding should be interpreted with caution. Three trials assessing non-pharmacological interventions provided some support for the use of such strategies, however were not powered to detect differences in important maternal and infant outcomes. While a FENO-based algorithm reduced exacerbations, the effects on perinatal outcomes were less certain, and thus widespread implementation is not yet appropriate. Similarly, though positive effects on asthma control were shown with PMR and pharmacist-led management, the evidence to date is insufficient to draw definitive conclusions.In view of the limited evidence base, further randomised trials are required to determine the most effective and safe interventions for asthma in pregnancy. Future trials must be sufficiently powered, and well-designed, to allow differences in important outcomes for mothers and babies to be detected. The impact on health services requires evaluation. Any further trials assessing pharmacological interventions should assess novel agents or those used in current practice. Encouragingly, at least five trials have been identified as planned or underway.

Beneficial effects of Lactobacillus casei strain Shirota on academic stress-induced sleep disturbance in healthy adults: a double-blind, randomised, placebo-controlled trial.

PubMed

Takada, M; Nishida, K; Gondo, Y; Kikuchi-Hayakawa, H; Ishikawa, H; Suda, K; Kawai, M; Hoshi, R; Kuwano, Y; Miyazaki, K; Rokutan, K

2017-04-26

The present study examined whether Lactobacillus casei strain Shirota (LcS) improves sleep quality under psychological stress. A double-blind, placebo-controlled trial was conducted in healthy 4 th year medical students exposed to academic examination stress. The trial was repeated over two consecutive years in different groups of students, and the data were pooled. For 8 weeks prior to and 3 weeks after a national standardised examination, a total of 48 and 46 subjects received a daily dose of 100 ml of LcS-fermented milk or non-fermented placebo milk, respectively. Study measures included subjective anxiety, overnight single-channel electroencephalography (EEG) recordings, and the Oguri-Shirakawa-Azumi (OSA) sleep inventory scores of subjective sleep quality. Total OSA scores were significantly lower than baseline on the day before the exam and recovered after the exam, indicating a stress-induced decline in sleep quality. There was a significant positive effect of LcS treatment on OSA factors for sleepiness on rising and sleep length. Sleep latency measured by EEG lengthened as the exam approached in the placebo group but was significantly suppressed in the LcS group. The percentage of stage 3 non-REM (N3) sleep decreased in the placebo group as the exam approached, whereas it was maintained in the LcS group throughout the trial. Delta power during the first sleep cycle, measured as an index of sleep intensity, increased as the exam approached in the LcS group and was significantly higher than in the placebo group. These findings suggest that daily consumption of LcS may help to maintain sleep quality during a period of increasing stress. The observed retention of N3 sleep and increased delta power in the LcS group may have contributed to higher perceived sleep satisfaction.

Design of a randomized trial to determine the optimum protein intake to preserve lean body mass and to optimize response to a promyogenic anabolic agent in older men with physical functional limitation.

PubMed

Bhasin, Shalender; Apovian, Caroline M; Travison, Thomas G; Pencina, Karol; Huang, Grace; Moore, Lynn L; Campbell, Wayne W; Howland, Andrew; Chen, Ruo; Singer, Martha R; Shah, Mitali; Eder, Richard; Schram, Haley; Bearup, Richelle; Beleva, Yusnie M; McCarthy, Ashley C; Li, Zhouying; Woodbury, Erin; McKinnon, Jennifer; Storer, Thomas W; Basaria, Shehzad

2017-07-01

The dietary protein allowance for older men to maintain lean body mass and muscle strength and to accrue optimal anabolic responses to promyogenic stimuli is poorly characterized. The OPTIMEN trial was designed to assess in older men with moderate physical dysfunction and insufficient habitual protein intake (

Effect of a mass radio campaign on family behaviours and child survival in Burkina Faso: a repeated cross-sectional, cluster-randomised trial.

PubMed

Sarrassat, Sophie; Meda, Nicolas; Badolo, Hermann; Ouedraogo, Moctar; Some, Henri; Bambara, Robert; Murray, Joanna; Remes, Pieter; Lavoie, Matthiew; Cousens, Simon; Head, Roy

2018-03-01

Media campaigns can potentially reach a large audience at relatively low cost but, to our knowledge, no randomised controlled trials have assessed their effect on a health outcome in a low-income country. We aimed to assess the effect of a radio campaign addressing family behaviours on all-cause post-neonatal under-5 child mortality in rural Burkina Faso. In this repeated cross-sectional, cluster randomised trial, clusters (distinct geographical areas in rural Burkina Faso with at least 40 000 inhabitants) were selected by Development Media International based on their high radio listenership (>60% of women listening to the radio in the past week) and minimum distances between radio stations to exclude population-level contamination. Clusters were randomly allocated to receive the intervention (a comprehensive radio campaign) or control group (no radio media campaign). Household surveys were performed at baseline (from December, 2011, to February, 2012), midline (in November, 2013, and after 20 months of campaigning), and endline (from November, 2014, to March, 2015, after 32 months of campaigning). Primary analyses were done on an intention-to-treat basis, based on cluster-level summaries and adjusted for imbalances between groups at baseline. The primary outcome was all-cause post-neonatal under-5 child mortality. The trial was designed to detect a 20% reduction in the primary outcome with a power of 80%. Routine data from health facilities were also analysed for evidence of changes in use and these data had high statistical power. The indicators measured were new antenatal care attendances, facility deliveries, and under-5 consultations. This trial is registered with ClinicalTrial.gov, number NCT01517230. The intervention ran from March, 2012, to January, 2015. 14 clusters were selected and randomly assigned to the intervention group (n=7) or the control group (n=7). The average number of villages included per cluster was 34 in the control group and 29 in the intervention group. 2269 (82%) of 2784 women in the intervention group reported recognising the campaign's radio spots at endline. Post-neonatal under-5 child mortality decreased from 93·3 to 58·5 per 1000 livebirths in the control group and from 125·1 to 85·1 per 1000 livebirths in the intervention group. There was no evidence of an intervention effect (risk ratio 1·00, 95% CI 0·82-1·22; p>0·999). In the first year of the intervention, under-5 consultations increased from 68 681 to 83 022 in the control group and from 79 852 to 111 758 in the intervention group. The intervention effect using interrupted time-series analysis was 35% (95% CI 20-51; p<0·0001). New antenatal care attendances decreased from 13 129 to 12 997 in the control group and increased from 19 658 to 20 202 in the intervention group in the first year (intervention effect 6%, 95% CI 2-10; p=0·004). Deliveries in health facilities decreased from 10 598 to 10 533 in the control group and increased from 12 155 to 12 902 in the intervention group in the first year (intervention effect 7%, 95% CI 2-11; p=0·004). A comprehensive radio campaign had no detectable effect on child mortality. Substantial decreases in child mortality were observed in both groups over the intervention period, reducing our ability to detect an effect. This, nevertheless, represents the first randomised controlled trial to show that mass media alone can change health-seeking behaviours. Wellcome Trust and Planet Wheeler Foundation. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

A pragmatic randomised controlled trial of the effectiveness and cost-effectiveness of screening older women for the prevention of fractures: rationale, design and methods for the SCOOP study.

PubMed

Shepstone, L; Fordham, R; Lenaghan, E; Harvey, I; Cooper, C; Gittoes, N; Heawood, A; Peters, T J; O'Neill, T; Torgerson, D; Holland, R; Howe, A; Marshall, T; Kanis, J A; McCloskey, E

2012-10-01

SCOOP is a UK seven-centre, pragmatic, randomised controlled trial with 5-year follow-up, including 11,580 women aged 70 to 85 years, to assess the effectiveness and cost-effectiveness of a community-based screening programme to reduce fractures. It utilises the FRAX algorithm and DXA to assess the 10-year probability of fracture. Introduction Osteoporotic, or low-trauma, fractures present a considerable burden to the National Health Service and have major adverse effects on quality of life, disability and mortality for the individual. Methods Given the availability of efficacious treatments and a risk assessment tool based upon clinical risk factors and bone mineral density, a case exists to undertake a community-based controlled evaluation of screening for subjects at high risk of fracture, under the hypothesis that such a screening programme would reduce fractures in this population. Results This study is a UK seven-centre, unblinded, pragmatic, randomised controlled trial with a 5-year follow-up period. A total of 11,580 women, aged 70 to 85 years and not on prescribed bone protective therapy will be consented to the trial by post via primary care providing 90% power to detect an 18% decrease in fractures. Conclusions Participants will be randomised to either a screening arm or control. Those undergoing screening will have a 10-year fracture probability computed from baseline risk factors together with bone mineral density measured by DXA in selected subjects. Individuals above an age-dependent threshold of fracture probability will be recommended for treatment for the duration of the trial. Subjects in the control arm will receive 'usual care'. Participants will be followed up 6 months after randomisation and annually by postal questionnaires with independent checking of hospital and primary care records. The primary outcome will be the proportion of individuals sustaining fractures in each group. An economic analysis will be carried out to assess cost-effectiveness of screening. A qualitative evaluation will be conducted to examine the acceptability of the process to participants.

The effect of low glucose degradation product, neutral pH versus standard peritoneal dialysis solutions on peritoneal membrane function: the balANZ trial

PubMed Central

Johnson, David W.; Brown, Fiona G.; Clarke, Margaret; Boudville, Neil; Elias, Tony J.; Foo, Marjorie W.Y.; Jones, Bernard; Kulkarni, Hemant; Langham, Robyn; Ranganathan, Dwarakanathan; Schollum, John; Suranyi, Michael G.; Tan, Seng H.; Voss, David

2012-01-01

Background The balANZ trial recently reported that neutral pH, low glucose degradation product (biocompatible) peritoneal dialysis (PD) solutions significantly delayed anuria and reduced peritonitis rates compared with conventional solutions. This article reports a secondary outcome analysis of the balANZ trial with respect to peritoneal membrane function. Methods Adult, incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. Peritoneal equilibration tests were performed at 1, 6, 12, 18 and 24 months. Peritoneal small solute clearances and ultra-filtration (UF) were measured at 3, 6, 9, 12, 18 and 24 months. Results Of the 185 patients recruited into the trial, 85 patients in the Balance group and 82 patients in the control group had peritoneal membrane function evaluated. Mean 4-h dialysate:plasma creatinine ratios (D:P Cr 4h) at 1 month were significantly higher in the Balance group compared with controls (0.67 ± 0.10 versus 0.62 ± 0.10, P = 0.002). Over the 2-year study period, mean D:P Cr 4 h measurements remained stable in the Balance group but increased significantly in controls [difference −0.004 per month, 95% confidence interval (95% CI) −0.005 to −0.002, P < 0.001]. Similar results were obtained for dialysate glucose ratios (D/D0 glucose). Peritoneal UF was significantly lower in the Balance group than in controls at 3 and 6 months. Over the 2-year study period, peritoneal UF increased significantly in the Balance group but remained stable in controls (difference 24 mL/day/month, 95% CI 9–39, P = 0.002). No differences in peritoneal small solute clearances, prescribed dialysate fill volumes or peritoneal glucose exposure were observed between the two groups. Conclusions Biocompatible and conventional PD solutions exert differential effects on peritoneal small solute transport rate and UF over time. Adequately powered trials assessing the impact of these differential membrane effects on PD technique and patient survival rates are warranted. PMID:22859794

Testing for qualitative heterogeneity: An application to composite endpoints in survival analysis.

PubMed

Oulhaj, Abderrahim; El Ghouch, Anouar; Holman, Rury R

2017-01-01

Composite endpoints are frequently used in clinical outcome trials to provide more endpoints, thereby increasing statistical power. A key requirement for a composite endpoint to be meaningful is the absence of the so-called qualitative heterogeneity to ensure a valid overall interpretation of any treatment effect identified. Qualitative heterogeneity occurs when individual components of a composite endpoint exhibit differences in the direction of a treatment effect. In this paper, we develop a general statistical method to test for qualitative heterogeneity, that is to test whether a given set of parameters share the same sign. This method is based on the intersection-union principle and, provided that the sample size is large, is valid whatever the model used for parameters estimation. We propose two versions of our testing procedure, one based on a random sampling from a Gaussian distribution and another version based on bootstrapping. Our work covers both the case of completely observed data and the case where some observations are censored which is an important issue in many clinical trials. We evaluated the size and power of our proposed tests by carrying out some extensive Monte Carlo simulations in the case of multivariate time to event data. The simulations were designed under a variety of conditions on dimensionality, censoring rate, sample size and correlation structure. Our testing procedure showed very good performances in terms of statistical power and type I error. The proposed test was applied to a data set from a single-center, randomized, double-blind controlled trial in the area of Alzheimer's disease.

Enhanced oscillatory activity in the hippocampal-prefrontal network is related to short-term memory function after early-life seizures

PubMed Central

Kleen, Jonathan K.; Wu, Edie X.; Holmes, Gregory L.; Scott, Rod C.; Lenck-Santini, Pierre-Pascal

2011-01-01

Neurological insults during development are associated with later impairments in learning and memory. Although remedial training can help restore cognitive function, the neural mechanisms of this recovery in memory systems are largely unknown. To examine this issue we measured electrophysiological oscillatory activity in the hippocampus (both CA3 and CA1) and prefrontal cortex of adult rats that had experienced repeated seizures in the first weeks of life, while they were remedially trained on a delayed-nonmatch-to-sample memory task. Seizure-exposed rats showed initial difficulties learning the task but performed similar to control rats after extra training. Whole-session analyses illustrated enhanced theta power in all three structures while seizure rats learned response tasks prior to the memory task. Whilst performing the memory task, dynamic oscillation patterns revealed that prefrontal cortex theta power was increased among seizure-exposed rats. This enhancement appeared after the first memory training steps using short delays and plateaued at the most difficult steps which included both short and long delays. Further, seizure rats showed enhanced CA1-prefrontal theta coherence in correct trials compared to incorrect trials when long delays were imposed, suggesting increased hippocampal-prefrontal synchrony for the task in this group when memory demand was high. Seizure-exposed rats also showed heightened gamma power and coherence among all three structures during the trials. Our results demonstrate the first evidence of hippocampal-prefrontal enhancements following seizures in early development. Dynamic compensatory changes in this network and interconnected circuits may underpin cognitive rehabilitation following other neurological insults to higher cognitive systems. PMID:22031886

RELIABILITY OF THE ONE REPETITION-MAXIMUM POWER CLEAN TEST IN ADOLESCENT ATHLETES

PubMed Central

Faigenbaum, Avery D.; McFarland, James E.; Herman, Robert; Naclerio, Fernando; Ratamess, Nicholas A.; Kang, Jie; Myer, Gregory D.

2013-01-01

Although the power clean test is routinely used to assess strength and power performance in adult athletes, the reliability of this measure in younger populations has not been examined. Therefore, the purpose of this study was to determine the reliability of the one repetition maximum (1 RM) power clean in adolescent athletes. Thirty-six male athletes (age 15.9 ± 1.1 yrs, body mass 79.1 ± 20.3 kg, height 175.1 ±7.4 cm) who had more than 1 year of training experience with weightlifting exercises performed a 1 RM power clean on two nonconsecutive days in the afternoon following standardized procedures. All test procedures were supervised by a senior level weightlifting coach and consisted of a systematic progression in test load until the maximum resistance that could be lifted for one repetition using proper exercise technique was determined. Data were analyzed using an intraclass correlation coefficient (ICC [2,k]), Pearson correlation coefficient (r), repeated measures ANOVA, Bland-Altman plot, and typical error analyses. Analysis of the data revealed that the test measures were highly reliable demonstrating a test-retest ICC of 0.98 (95% CI = 0.96–0.99). Testing also demonstrated a strong relationship between 1 RM measures on trial 1 and trial 2 (r=0.98, p<0.0001) with no significant difference in power clean performance between trials (70.6 ± 19.8 vs. 69.8 ± 19.8 kg). Bland Altman plots confirmed no systematic shift in 1 RM between trial 1 and trial 2. The typical error to be expected between 1 RM power clean trials is 2.9 kg and a change of at least 8.0 kg is indicated to determine a real change in lifting performance between tests in young lifters. No injuries occurred during the study period and the testing protocol was well-tolerated by all subjects. These findings indicate that 1 RM power clean testing has a high degree of reproducibility in trained male adolescent athletes when standardized testing procedures are followed and qualified instruction is present. PMID:22233786

Rational and design of a stepped-wedge cluster randomized trial evaluating quality improvement initiative for reducing cardiovascular events among patients with acute coronary syndromes in resource-constrained hospitals in China.

PubMed

Li, Shenshen; Wu, Yangfeng; Du, Xin; Li, Xian; Patel, Anushka; Peterson, Eric D; Turnbull, Fiona; Lo, Serigne; Billot, Laurent; Laba, Tracey; Gao, Runlin

2015-03-01

Acute coronary syndromes (ACSs) are a major cause of morbidity and mortality, yet effective ACS treatments are frequently underused in clinical practice. Randomized trials including the CPACS-2 study suggest that quality improvement initiatives can increase the use of effective treatments, but whether such programs can impact hard clinical outcomes has never been demonstrated in a well-powered randomized controlled trial. The CPACS-3 study is a stepped-wedge cluster-randomized trial conducted in 104 remote level 2 hospitals without PCI facilities in China. All hospitalized ACS patients will be recruited consecutively over a 30-month period to an anticipated total study population of more than 25,000 patients. After a 6-month baseline period, hospitals will be randomized to 1 of 4 groups, and a 6-component quality improvement intervention will be implemented sequentially in each group every 6months. These components include the following: establishment of a quality improvement team, implementation of a clinical pathway, training of physicians and nurses, hospital performance audit and feedback, online technical support, and patient education. All patients will be followed up for 6months postdischarge. The primary outcome will be the incidence of in-hospital major adverse cardiovascular events comprising all-cause mortality, myocardial infarction or reinfarction, and nonfatal stroke. The CPACS-3 study will be the first large randomized trial with sufficient power to assess the effects of a multifaceted quality of care improvement initiative on hard clinical outcomes, in patients with ACS. Copyright © 2014 Elsevier Inc. All rights reserved.

Smoking Cessation Intervention for severe Mental Ill Health Trial (SCIMITAR): a pilot randomised control trial of the clinical effectiveness and cost-effectiveness of a bespoke smoking cessation service.

PubMed

Peckham, Emily; Man, Mei-See; Mitchell, Natasha; Li, Jinshuo; Becque, Taeko; Knowles, Sarah; Bradshaw, Tim; Planner, Claire; Parrott, Steve; Michie, Susan; Shepherd, Charles; Gilbody, Simon

2015-03-01

There is a high prevalence of smoking among people who experience severe mental ill health (SMI). Helping people with disorders such as bipolar illness and schizophrenia to quit smoking would help improve their health, increase longevity and also reduce health inequalities. Around half of people with SMI who smoke express an interest in cutting down or quitting smoking. There is limited evidence that smoking cessation can be achieved for people with SMI. Those with SMI rarely access routine NHS smoking cessation services. This suggests the need to develop and evaluate a behavioural support and medication package tailored to the needs of people with SMI. The objective in this project was to conduct a pilot trial to establish acceptability of the intervention and to ensure the feasibility of recruitment, randomisation and follow-up. We also sought preliminary estimates of effect size in order to design a fully powered trial of clinical effectiveness and cost-effectiveness. The pilot should inform a fully powered trial to compare the clinical effectiveness and cost-effectiveness of a bespoke smoking cessation (BSC) intervention with usual general practitioner (GP) care for people with SMI. A pilot pragmatic two-arm individually randomised controlled trial (RCT). Simple randomisation was used following a computer-generated random number sequence. Participants and practitioners were not blinded to allocation. Primary care and secondary care mental health services in England. Smokers aged > 18 years with a severe mental illness who would like to cut down or quit smoking. A BSC intervention delivered by mental health specialists trained to deliver evidence-supported smoking cessation interventions compared with usual GP care. The primary outcome was carbon monoxide-verified smoking cessation at 12 months. Smoking-related secondary outcomes were reduction of number of cigarettes smoked, Fagerstrom test of nicotine dependence and motivation to quit (MTQ). Other secondary outcomes were Patient Health Questionnaire-9 items and Short Form Questionnaire-12 items to assess whether there were improvements or deterioration in mental health and quality of life. We also measured body mass index to assess whether or not smoking cessation was associated with weight gain. These were measured at 1, 6 and 12 months post randomisation. The trial recruited 97 people aged 19-73 years who smoked between 5 and 60 cigarettes per day (mean 25 cigarettes). Participants were recruited from four mental health trusts and 45 GP surgeries. Forty-six people were randomised to the BSC intervention and 51 people were randomised to usual GP care. The odds of quitting at 12 months was higher in the BSC intervention (36% vs. 23%) but did not reach statistical significance (odds ratio 2.9; 95% confidence interval 0.8% to 10.5%). At 3 and 6 months there was no evidence of difference in self-reported smoking cessation. There was a non-significant reduction in the number of cigarettes smoked and nicotine dependence. MTQ and number of quit attempts all increased in the BSC group compared with usual care. There was no difference in terms of quality of life at any time point, but there was evidence of an increase in depression scores at 12 months for the BSC group. There were no serious adverse events thought likely to be related to the trial interventions. The pilot economic analysis demonstrated that it was feasible to carry out a full economic analysis. It was possible to recruit people with SMI from primary and secondary care to a trial of a smoking cessation intervention based around behavioural support and medication. The overall direction of effect was a positive trend in relation to biochemically verified smoking cessation and it was feasible to obtain follow-up in a substantial proportion of participants. A definitive trial of a bespoke cessation intervention has been prioritised by the National Institute for Health Research (NIHR) and the SCIMITAR pilot trial forms a template for a fully powered RCT to examine clinical effectiveness and cost-effectiveness. Current Controlled Trials ISRCTN79497236. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment, Vol. 19, No. 25. See the NIHR Journals Library website for further project information.

Cognitive Behaviour therapy for Older Adults with Insomnia and Depression: A Randomized Controlled Trial in Community Mental Health Services.

PubMed

Sadler, Paul; McLaren, Suzanne; Klein, Britt; Harvey, Jack; Jenkins, Megan

2018-05-24

To investigate whether cognitive behaviour therapy was effective for older adults with comorbid insomnia and depression in a community mental health setting, and explore whether an advanced form of cognitive behaviour therapy for insomnia produced better outcomes compared to a standard form of cognitive behaviour therapy for insomnia. An 8 week randomized controlled clinical trial was conducted within community mental health services, Victoria, Australia. Seventy-two older adults (56% female, M age 75 years ± 7) with diagnosed comorbid insomnia and depression participated. Three conditions were tested using a group therapy format: cognitive behaviour therapy for insomnia (CBT-I, standard), cognitive behaviour therapy for insomnia plus positive mood strategies (CBT-I+, advanced), psychoeducation control group (PCG, control). The primary outcomes were insomnia severity (Insomnia Severity Index) and depression severity (Geriatric Depression Scale). Primary and secondary measures were collected at pre (week 0), post (week 8), and follow-up (week 20). CBT-I and CBT-I+ both generated significantly greater reductions in insomnia and depression severity compared to PCG from pre to post (p < .001), which were maintained at follow-up. Although the differences between outcomes of the two treatment conditions were not statistically significant, the study was not sufficiently powered to detect either superiority of one treatment or equivalence of the two treatment conditions. CBT-I and CBT-I+ were both effective at reducing insomnia and depression severity for older adults. Mental health services that deliver treatment for comorbid insomnia with cognitive behaviour therapy may improve recovery outcomes for older adults with depression. Australian and New Zealand Clinical Trials Registry (ANZCTR) URL: https://www.anzctr.org.au Trial ID: ACTRN12615000067572 Date Registered: 12th December 2014.

Rehab-let: touchscreen tablet for self-training impaired dexterity post stroke: study protocol for a pilot randomized controlled trial.

PubMed

Rand, Debbie; Zeilig, Gabi; Kizony, Rachel

2015-06-18

Impaired dexterity of the weaker upper extremity is common post stroke and it is recommended that these individuals practice many repetitions of movement to regain function. However, stroke rehabilitation methods do not achieve the required intensity to be effective. Touchscreen tablet technology may be used as a motivating tool for self-training impaired dexterity of the weaker upper extremity post stroke. Rehab-let is a self-training protocol utilizing game apps on a touchscreen for practicing movement of the weaker upper extremity. We will conduct a pilot randomized controlled trial to assess Rehab-let compared to traditional self-training to improve dexterity of the weaker hand, and to increase self-training time and satisfaction in individuals with subacute stroke. Forty individuals with stroke undergoing subacute rehabilitation will be randomly allocated to Rehab-let or a traditional self-training program using therapeutic aids such as balls, blocks and pegs. All participants will be requested to perform self-training for 60 minutes a day, 5 times a week for 4 weeks. Dexterity assessed by The Nine Hole Peg Test is the main outcome measure. Assessments will be administered pre and post the self-training intervention by assessors blind to the group allocation. The outcomes of this study will inform the design of a fully powered randomized controlled trial to evaluate the effectiveness of Rehab-let. If found to be effective, Rehab-let can be used during subacute rehabilitation to increase treatment intensity and improve dexterity. Potentially, Rehab-let can also be used after discharge and might be ideal for individuals with mild stroke who are often not referred to formal rehabilitation. Current Controlled Trials NCT02136433 registered on 17 September 2014.

Design and methods for a pilot randomized clinical trial involving exercise and behavioral activation to treat comorbid type 2 diabetes and major depressive disorder

PubMed Central

Schneider, Kristin L.; Pagoto, Sherry L.; Handschin, Barbara; Panza, Emily; Bakke, Susan; Liu, Qin; Blendea, Mihaela; Ockene, Ira S.; Ma, Yunsheng

2011-01-01

Background The comorbidity of type 2 diabetes mellitus (T2DM) and depression is associated with poor glycemic control. Exercise has been shown to improve mood and glycemic control, but individuals with comorbid T2DM and depression are disproportionately sedentary compared to the general population and report more difficulty with exercise. Behavioral activation, an evidence-based depression psychotherapy, was designed to help people with depression make gradual behavior changes, and may be helpful to build exercise adherence in sedentary populations. This pilot randomized clinical trial will test the feasibility of a group exercise program enhanced with behavioral activation strategies among women with comorbid T2DM and depression. Methods/Design Sedentary women with inadequately controlled T2DM and depression (N=60) will be randomly assigned to one of two conditions: exercise or usual care. Participants randomized to the exercise condition will attend 38 behavioral activation-enhanced group exercise classes over 24 weeks in addition to usual care. Participants randomized to the usual care condition will receive depression treatment referrals and print information on diabetes management via diet and physical activity. Assessments will occur at baseline and 3-, 6-, and 9-months following randomization. The goals of this pilot study are to demonstrate feasibility and intervention acceptability, estimate the resources and costs required to deliver the intervention and to estimate the standard deviation of continuous outcomes (e.g., depressive symptoms and glycosylated hemoglobin) in preparation for a fully-powered randomized clinical trial. Discussion A novel intervention that combines exercise and behavioral activation strategies could potentially improve glycemic control and mood in women with comorbid type 2 diabetes and depression. Trial registration NCT01024790 PMID:21765864

A novel early intervention for preschool depression: findings from a pilot randomized controlled trial.

PubMed

Luby, Joan; Lenze, Shannon; Tillman, Rebecca

2012-03-01

Validation for depression in preschool children has been established; however, to date no empirical investigations of interventions for the early onset disorder have been conducted. Based on this and the modest efficacy of available treatments for childhood depression, the need for novel early interventions has been emphasized. Large effect sizes (ES) for preschool psychotherapies for several Axis I disorders suggest that earlier intervention in depression may also be promising. Therefore, a novel form of treatment for preschool depression, Parent-Child Interaction Therapy Emotion Development (PCIT-ED) was developed and tested. A preliminary randomized controlled trial (RCT) was conducted comparing PCIT-ED to psycho-education in depressed 3- to 7-year-olds and their caregivers. A total of 54 patients met symptom criteria for DSM-IV major depressive disorder and were randomized, 19 patients completed the active treatment (n = 8 dropouts) and 10 completed psycho-education (n = 17 dropouts). Both groups showed significant improvement in several domains, with PCIT-ED showing significance in a greater number of domains. An intent-to-treat analysis suggested that PCIT-ED was significantly more effective than psycho-education on executive functioning (p = .011, ES = 0.12) and emotion recognition skills (p = .002, ES = 0.83). The RCT proved feasible and suggests an individual control condition should be used in future trials to minimize differential dropout. These pilot data, although limited by power, suggest that PCIT-ED may be a promising early intervention for depression. Larger scale randomized controlled trials of PCIT-ED for depressed preschoolers are now warranted. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.

A video-based transdiagnostic REBT universal prevention program for internalizing problems in adolescents: study protocol of a cluster randomized controlled trial.

PubMed

Păsărelu, Costina Ruxandra; Dobrean, Anca

2018-04-13

Internalizing problems are the most prevalent mental health problems in adolescents. Transdiagnostic programs are promising manners to treat multiple problems within the same protocol, however, there is limited research regarding the efficacy of such programs delivered as universal prevention programs in school settings. Therefore, the present study aims to investigate the efficacy of a video-based transdiagnostic rational emotive behavioral therapy (REBT) universal prevention program, for internalizing problems. The second objective of the present paper will be to investigate the subsequent mechanisms of change, namely maladaptive cognitions. A two-arm parallel randomized controlled trial will be conducted, with two groups: a video-based transdiagnostic REBT universal prevention program and a wait list control. Power analysis indicated that the study will involve 338 participants. Adolescents with ages between 12 and 17 years old, from several middle schools and high schools, will be invited to participate. Assessments will be conducted at four time points: baseline (T 1 ), post-intervention (T 2 ), 3 months follow-up (T 3 ) and 12 months follow-up (T 4 ). Intent-to-treat analysis will be used in order to investigate significant differences between the two groups in both primary and secondary outcomes. This is the first randomized controlled trial that aims to investigate the efficacy and mechanisms of change of a video-based transdiagnostic REBT universal prevention program, delivered in a school context. The present study has important implications for developing efficient prevention programs, interactive, that will aim to target within the same protocol both anxiety and depressive symptoms. ClinicalTrials.gov: NCT02756507 . Registered on 25 April 2016.

Effects of endovascular cooling on infarct size in ST-segment elevation myocardial infarction: A patient-level pooled analysis from randomized trials.

PubMed

Dae, Michael; O'Neill, William; Grines, Cindy; Dixon, Simon; Erlinge, David; Noc, Marko; Holzer, Michael; Dee, Anne

2018-06-01

This study sought to examine the relationship between temperature at reperfusion and infarct size. Hypothermia consistently reduces infarct size when administered prior to reperfusion in animal studies, however, clinical results have been inconsistent. We performed a patient-level pooled analysis from six randomized control trials of endovascular cooling during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) in 629 patients in which infarct size was assessed within 1 month after randomization by either single-photon emission computed tomography (SPECT) or cardiac magnetic resonance imaging (cMR). In anterior infarct patients, after controlling for variability between studies, mean infarct size in controls was 21.3 (95%CI 17.4-25.3) and in patients with hypothermia <35°C it was 14.8 (95%CI 10.1-19.6), which was a statistically significant absolute reduction of 6.5%, or a 30% relative reduction in infarct size (P = 0.03). There was no significant difference in infarct size in anterior ≥35°C, or inferior infarct patients. There was no difference in the incidence of death, ventricular arrhythmias, or re-infarction due to stent thrombosis between hypothermia and control patients. The present study, drawn from a patient-level pooled analysis of six randomized trials of endovascular cooling during primary PCI in STEMI, showed a significant reduction in infarct size in patients with anterior STEMI who were cooled to <35°C at the time of reperfusion. The results support the need for trials in patients with anterior STEMI using more powerful cooling devices to optimize the delivery of hypothermia prior to reperfusion. © 2017 The Authors. Journal of Interventional Cardiology Published by Wiley Periodicals, Inc.

Effect of contrast water therapy duration on recovery of cycling performance: a dose-response study.

PubMed

Versey, Nathan; Halson, Shona; Dawson, Brian

2011-01-01

This study investigated whether contrast water therapy (CWT) has a dose-response effect on recovery from high-intensity cycling. Eleven trained male cyclists completed four trials, each commencing with a 75-min cycling protocol containing six sets of five 15-s sprints and three 5-min time-trials in thermoneutral conditions. Ten minutes post-exercise, participants performed one of four recovery protocols: CWT for 6 min (CWT6), 12 min (CWT12), or 18 min (CWT18) duration, or a seated rest control trial. The CWT commenced in hot water (38.4 ± 0.6°C) and alternated between hot and cold water (14.6 ± 0.3°C) every minute with a 5-s changeover. The cycling protocol was repeated 2 h after completion of exercise bout one. Prior to exercise bout two, core temperature was lower in CWT12 (-0.19 ± 0.14°C, mean ± 90% CL) and CWT18 (-0.21 ± 0.10°C) than control. Compared with control, CWT6 substantially improved time-trial (1.5 ± 2.1%) and sprint performance (3.0 ± 3.1%), and CWT12 substantially improved sprint total work (4.3 ± 3.4%) and peak power (2.7 ± 3.8%) in exercise bout two. All CWT conditions generally improved thermal sensation, whole body fatigue and muscle soreness compared with control, but no differences existed between conditions in heart rate or rating of perceived exertion. In conclusion, CWT duration did not have a dose-response effect on recovery from high-intensity cycling; however, CWT for up to 12 min assisted recovery of cycling performance.

Independent but coordinated trials: insights from the practice-based Opportunities for Weight Reduction Trials Collaborative Research Group.

PubMed

Yeh, Hsin-Chieh; Clark, Jeanne M; Emmons, Karen E; Moore, Reneé H; Bennett, Gary G; Warner, Erica T; Sarwer, David B; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A; Wells, Barbara; Wadden, Thomas A; Colditz, Graham A; Appel, Lawrence J

2010-08-01

The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the 'Practice-based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.' We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. The Collaborative Research Group consists of three individual studies: 'Be Fit, Be Well' (Washington University in St. Louis/Harvard University), 'POWER Hopkins' (Johns Hopkins), and 'POWER-UP' (University of Pennsylvania). There are a total of 15 participating clinics with ~1100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. The challenges of the organizational design include the complex decision-making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols.

Efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II trial): study protocol for a randomized controlled trial.

PubMed

Tamura, Tomoyoshi; Hayashida, Kei; Sano, Motoaki; Onuki, Shuko; Suzuki, Masaru

2017-10-23

Hydrogen gas inhalation (HI) improved survival and neurological outcomes in an animal model of post-cardiac arrest syndrome (PCAS). The feasibility and safety of HI for patients with PCAS was confirmed in a pilot study. The objective of this study is to evaluate the efficacy of HI for patients with PCAS. The efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II) trial is an investigator-initiated, randomized, double-blind, placebo-controlled trial designed to enroll 360 adult comatose (Glasgow Coma Scale score < 8) patients who will be resuscitated following an out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized (1:1) to either the HI or control group. Patients in the HI group will inhale 2% hydrogen with 24% to 50% oxygen, and those in the control group will inhale 24% to 50% oxygen for 18 h after admission via mechanical ventilation. Multidisciplinary post-arrest care, including targeted temperature management (TTM) between 33 °C and 36 °C, will be provided in accordance with the latest guidelines. The primary outcome of interest is the 90-day neurological outcome, as evaluated using the Cerebral Performance Categories scale (CPC). The secondary outcomes of interest are the 90-day survival rate and other neurological outcomes. This study will provide 80% power to detect a 15% change in the proportion of patients with good neurological outcomes (CPCs of 1 and 2), from 50% to 65%, with an overall significance level of 0.05. The first multicenter randomized trial is underway to confirm the efficacy of HI on neurological outcomes in comatose out-of-hospital cardiac arrest survivors. Our study has the potential to address HI as an appealing and innovative therapeutic strategy for PCAS in combination with TTM. University Hospital Medical Information Network (UMIN), 000019820 . Registered on 17 November 2015.

The mPED randomized controlled clinical trial: applying mobile persuasive technologies to increase physical activity in sedentary women protocol

PubMed Central

2011-01-01

Background Despite the significant health benefits of regular physical activity, approximately half of American adults, particularly women and minorities, do not meet the current physical activity recommendations. Mobile phone technologies are readily available, easily accessible and may provide a potentially powerful tool for delivering physical activity interventions. However, we need to understand how to effectively apply these mobile technologies to increase and maintain physical activity in physically inactive women. The purpose of this paper is to describe the study design and protocol of the mPED (mobile phone based physical activity education) randomized controlled clinical trial that examines the efficacy of a 3-month mobile phone and pedometer based physical activity intervention and compares two different 6-month maintenance interventions. Methods A randomized controlled trial (RCT) with three arms; 1) PLUS (3-month mobile phone and pedometer based physical activity intervention and 6-month mobile phone diary maintenance intervention), 2) REGULAR (3-month mobile phone and pedometer based physical activity intervention and 6-month pedometer maintenance intervention), and 3) CONTROL (pedometer only, but no intervention will be conducted). A total of 192 physically inactive women who meet all inclusion criteria and successfully complete a 3-week run-in will be randomized into one of the three groups. The mobile phone serves as a means of delivering the physical activity intervention, setting individualized weekly physical activity goals, and providing self-monitoring (activity diary), immediate feedback and social support. The mobile phone also functions as a tool for communication and real-time data capture. The primary outcome is objectively measured physical activity. Discussion If efficacy of the intervention with a mobile phone is demonstrated, the results of this RCT will be able to provide new insights for current behavioral sciences and mHealth. Trial Registration ClinicalTrials.gov#:NCTO1280812 PMID:22168267

Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials.

PubMed

Atri, Alireza; O'Brien, Jacqueline L; Sreenivasan, Aishwarya; Rastegar, Sarah; Salisbury, Sibyl; DeLuca, Amy N; O'Keefe, Kelly M; LaViolette, Peter S; Rentz, Dorene M; Locascio, Joseph J; Sperling, Reisa A

2011-05-01

To examine the feasibility and test-retest reliability of encoding-task functional magnetic resonance imaging (fMRI) in mild Alzheimer disease (AD). Randomized, double-blind, placebo-controlled study. Memory clinical trials unit. We studied 12 patients with mild AD (mean [SEM] Mini-Mental State Examination score, 24.0 [0.7]; mean Clinical Dementia Rating score, 1.0) who had been taking donepezil hydrochloride for more than 6 months from the placebo arm of a larger 24-week study (n = 24, 4 scans on weeks 0, 6, 12, and 24, respectively). Placebo and 3 face-name, paired-associate encoding, block-design blood oxygenation level-dependent fMRI scans in 12 weeks. We performed whole-brain t maps (P < .001, 5 contiguous voxels) and hippocampal regions-of-interest analyses of extent (percentage of active voxels) and magnitude (percentage of signal change) for novel-greater-than-repeated face-name contrasts. We also calculated intraclass correlation coefficients and power estimates for hippocampal regions of interest. Task tolerability and data yield were high (95 of 96 scans yielded favorable-quality data). Whole-brain maps were stable. Right and left hippocampal regions-of-interest intraclass correlation coefficients were 0.59 to 0.87 and 0.67 to 0.74, respectively. To detect 25.0% to 50.0% changes in week-0 to week-12 hippocampal activity using left-right extent or right magnitude with 80.0% power (2-sided α = .05) requires 14 to 51 patients. Using left magnitude requires 125 patients because of relatively small signal to variance ratios. Encoding-task fMRI was successfully implemented in a single-site, 24-week, AD randomized controlled trial. Week 0 to 12 whole-brain t maps were stable, and test-retest reliability of hippocampal fMRI measures ranged from moderate to substantial. Right hippocampal magnitude may be the most promising of these candidate measures in a leveraged context. These initial estimates of test-retest reliability and power justify evaluation of encoding-task fMRI as a potential biomarker for signal of effect in exploratory and proof-of-concept trials in mild AD. Validation of these results with larger sample sizes and assessment in multisite studies is warranted.

Randomised controlled trial and economic analysis of an internet-based weight management programme: POWeR+ (Positive Online Weight Reduction).

PubMed Central

Little, Paul; Stuart, Beth; Hobbs, Fd Richard; Kelly, Jo; Smith, Emily R; Bradbury, Katherine J; Hughes, Stephanie; Smith, Peter Wf; Moore, Michael V; Lean, Mike Ej; Margetts, Barrie M; Byrne, Christopher D; Griffin, Simon; Davoudianfar, Mina; Hooper, Julie; Yao, Guiqing; Zhu, Shihua; Raftery, James; Yardley, Lucy

2017-01-01

BACKGROUND Behavioural counselling with intensive follow-up for obesity is effective, but in resource-constrained primary care settings briefer approaches are needed. OBJECTIVES To estimate the clinical effectiveness and cost-effectiveness of an internet-based behavioural intervention with regular face-to-face or remote support in primary care, compared with brief advice. DESIGN Individually randomised three-arm parallel trial with health economic evaluation and nested qualitative interviews. SETTING Primary care general practices in the UK. PARTICIPANTS Patients with a body mass index of ≥ 30 kg/m(2) (or ≥ 28 kg/m(2) with risk factors) identified from general practice records, recruited by postal invitation. INTERVENTIONS Positive Online Weight Reduction (POWeR+) is a 24-session, web-based weight management intervention completed over 6 months. Following online registration, the website randomly allocated participants using computer-generated random numbers to (1) the control intervention (n = 279), which had previously been demonstrated to be clinically effective (brief web-based information that minimised pressure to cut down foods, instead encouraging swaps to healthier choices and increasing fruit and vegetables, plus 6-monthly nurse weighing); (2) POWeR+F (n = 269), POWeR+ supplemented by face-to-face nurse support (up to seven contacts); or (3) POWeR+R (n = 270), POWeR+ supplemented by remote nurse support (up to five e-mails or brief telephone calls). MAIN OUTCOME MEASURES The primary outcome was a modelled estimate of average weight reduction over 12 months, assessed blind to group where possible, using multiple imputation for missing data. The secondary outcome was the number of participants maintaining a 5% weight reduction at 12 months. RESULTS A total of 818 eligible individuals were randomised using computer-generated random numbers. Weight change, averaged over 12 months, was documented in 666 out of 818 participants (81%; control, n = 227; POWeR+F, n = 221; POWeR+R, n = 218). The control group maintained nearly 3 kg of weight loss per person (mean weight per person: baseline, 104.4 kg; 6 months, 101.9 kg; 12 months, 101.7 kg). Compared with the control group, the estimated additional weight reduction with POWeR+F was 1.5 kg [95% confidence interval (CI) 0.6 to 2.4 kg; p = 0.001] and with POWeR+R was 1.3 kg (95% CI 0.34 to 2.2 kg; p = 0.007). By 12 months the mean weight loss was not statistically significantly different between groups, but 20.8% of control participants, 29.2% of POWeR+F participants (risk ratio 1.56, 95% CI 0.96 to 2.51; p = 0.070) and 32.4% of POWeR+R participants (risk ratio 1.82, 95% CI 1.31 to 2.74; p = 0.004) maintained a clinically significant 5% weight reduction. The POWeR+R group had fewer individuals who reported doing another activity to help lose weight [control, 47.1% (64/136); POWeR+F, 37.2% (51/137); POWeR+R, 26.7% (40/150)]. The incremental cost to the health service per kilogram weight lost, compared with the control group, was £18 (95% CI -£129 to £195) for POWeR+F and -£25 (95% CI -£268 to £157) for POWeR+R. The probability of being cost-effective at a threshold of £100 per kilogram was 88% and 98% for POWeR+F and POWeR+R, respectively. POWeR+R was dominant compared with the control group. No harms were reported and participants using POWeR+ felt more enabled in managing their weight. The qualitative studies documented that POWeR+ was viewed positively by patients and that health-care professionals generally enjoyed supporting patients using POWeR+. STUDY LIMITATIONS Maintenance of weight loss after 1 year is unknown. FUTURE WORK Identifying strategies for longer-term engagement, impact in community settings and increasing physical activity. CONCLUSION Clinically valuable weight loss (> 5%) is maintained in 20% of individuals using novel written materials with brief follow-up. A web-based behavioural programme and brief support results in greater mean weight loss and 10% more participants maintain valuable weight loss; it achieves greater enablement and fewer participants undertaking other weight-loss activities; and it is likely to be cost-effective. TRIAL REGISTRATION Current Controlled Trials ISRCTN21244703. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 4. See the NIHR Journals Library website for further project information. PMID:28122658

Effects of a guided web-based smoking cessation program with telephone counseling: a cluster randomized controlled trial.

PubMed

Mehring, Michael; Haag, Max; Linde, Klaus; Wagenpfeil, Stefan; Schneider, Antonius

2014-09-24

Preliminary findings suggest that Web-based interventions may be effective in achieving significant smoking cessation. To date, very few findings are available for primary care patients, and especially for the involvement of general practitioners. Our goal was to examine the short-term effectiveness of a fully automated Web-based coaching program in combination with accompanied telephone counseling in smoking cessation in a primary care setting. The study was an unblinded cluster-randomized trial with an observation period of 12 weeks. Individuals recruited by general practitioners randomized to the intervention group participated in a Web-based coaching program based on education, motivation, exercise guidance, daily short message service (SMS) reminding, weekly feedback through Internet, and active monitoring by general practitioners. All components of the program are fully automated. Participants in the control group received usual care and advice from their practitioner without the Web-based coaching program. The main outcome was the biochemically confirmed smoking status after 12 weeks. We recruited 168 participants (86 intervention group, 82 control group) into the study. For 51 participants from the intervention group and 70 participants from the control group, follow-up data were available both at baseline and 12 weeks. Very few patients (9.8%, 5/51) from the intervention group and from the control group (8.6%, 6/70) successfully managed smoking cessation (OR 0.86, 95% CI 0.25-3.0; P=.816). Similar results were found within the intent-to-treat analysis: 5.8% (5/86) of the intervention group and 7.3% (6/82) of the control group (OR 1.28, 95% CI 0.38-4.36; P=.694). The number of smoked cigarettes per day decreased on average by 9.3 in the intervention group and by 6.6 in the control group (2.7 mean difference; 95% CI -5.33 to -0.58; P=.045). After adjustment for the baseline value, age, gender, and height, this significance decreases (mean difference 2.2; 95% CI -4.7 to 0.3; P=.080). This trial did not show that the tested Web-based intervention was effective for achieving smoking cessation compared to usual care. The limited statistical power and the high drop-out rate may have reduced the study's ability to detect significant differences between the groups. Further randomized controlled trials are needed in larger populations and to investigate the long-term outcome. German Register for Clinical Trials, registration number DRKS00003067; http://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ ID=DRKS00003067 (Archived by WebCite at http://www.webcitation.org/6Sff1YZpx).

The Basilar Artery International Cooperation Study (BASICS): study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Despite recent advances in acute stroke treatment, basilar artery occlusion (BAO) is associated with a death or disability rate of close to 70%. Randomised trials have shown the safety and efficacy of intravenous thrombolysis (IVT) given within 4.5 h and have shown promising results of intra-arterial thrombolysis given within 6 h of symptom onset of acute ischaemic stroke, but these results do not directly apply to patients with an acute BAO because only few, if any, of these patients were included in randomised acute stroke trials. Recently the results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry of patients with acute symptomatic BAO challenged the often-held assumption that intra-arterial treatment (IAT) is superior to IVT. Our observations in the BASICS registry underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely. Design BASICS is a randomised controlled, multicentre, open label, phase III intervention trial with blinded outcome assessment, investigating the efficacy and safety of additional IAT after IVT in patients with BAO. The trial targets to include 750 patients, aged 18 to 85 years, with CT angiography or MR angiography confirmed BAO treated with IVT. Patients will be randomised between additional IAT followed by optimal medical care versus optimal medical care alone. IVT has to be initiated within 4.5 h from estimated time of BAO and IAT within 6 h. The primary outcome parameter will be favourable outcome at day 90 defined as a modified Rankin Scale score of 0–3. Discussion The BASICS registry was observational and has all the limitations of a non-randomised study. As the IAT approach becomes increasingly available and frequently utilised an adequately powered randomised controlled phase III trial investigating the added value of this therapy in patients with an acute symptomatic BAO is needed (clinicaltrials.gov: NCT01717755). PMID:23835026

Psycho-educational interventions for children and young people with Type 1 Diabetes in the UK: How effective are they? A systematic review and meta-analysis

PubMed Central

Hesketh, Kathryn R.; Amin, Rakesh; Paes, Veena Mazarello; Viner, Russell M.; Stephenson, Terence

2017-01-01

Aims To synthesise evidence from UK-based randomised trials of psycho-educational interventions in children and young people (CYP) with Type 1 Diabetes (T1D) to inform the evidence-base for adoption of such interventions into the NHS. Methods We searched Medline, Embase, Cochrane, PsycINFO, CINAHL, and Web of Science up to March 2016. Two reviewers independently selected UK-based randomised trials comparing psycho-educational interventions for improving management of T1D for CYP with a control group of usual care or attention control. The main outcome was glycaemic control measured by percentage of glycated haemoglobin (HbA1c); secondary outcomes included psychosocial functioning, diabetes knowledge, adverse and other clinical outcomes. A narrative synthesis and meta-analysis were conducted. Pooled effect sizes of standardised mean difference (SMD) were calculated. Results Ten eligible trials of three educational and seven psycho-educational interventions were identified. Most interventions were delivered by non-psychologists and targeted adolescents with more than one year duration of diabetes. Meta-analysis of nine of these trials (N = 1,838 participants) showed a non-significant reduction in HbA1c attributable to the intervention (pooled SMD = -0.06, 95% CI: -0.21 to 0.09). Psycho-educational interventions aiming to increase children’s self-efficacy had a moderate, beneficial effect (SMD = 0.50, 95% CI: 0.13 to 0.87). No benefits on diabetes knowledge and other indicators of psychosocial functioning were identified. Conclusions There is insufficient evidence to recommend the use of particular psycho-educational programme for CYP with T1D in the UK. Further trials with sufficient power and reporting standards are needed. Future trials could consider active involvement of psychological specialists in the delivery of psychologically informed interventions and implementation of psycho-educational interventions earlier in the course of the disease. Systematic review registration PROSPERO CRD42015010701 PMID:28665946

Photorefractive keratectomy (PRK) versus laser-assisted in-situ keratomileusis (LASIK) for myopia.

PubMed

Shortt, A J; Allan, B D S

2006-04-19

Myopia (also known as short-sightedness or near-sightedness) is an ocular condition in which the refractive power of the eye is greater than is required, resulting in light from distant objects being focused in front of the retina instead of directly on it. The two most commonly used surgical techniques to permanently correct myopia are photorefractive keratectomy (PRK) and laser-assisted in-situ keratomileusis (LASIK). The aim of this review was to compare the effectiveness and safety of PRK and LASIK for correction of myopia. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2005, Issue 3), MEDLINE (1966 to September 2005), EMBASE (1980 to September 2005) and LILACs (1982 to 3 November 2005). We also searched the reference lists of the studies and the Science Citation Index. We included randomised controlled trials comparing PRK and LASIK for correction of any degree of myopia. We also included data on adverse events from prospective multicentre consecutive case series in the Food and Drugs Administration (FDA) trials database (http//www.fda.gov/cdrh/LASIK/lasers.htm). Two authors independently assessed trial quality and extracted data. Data were summarised using odds ratio and mean difference. Odds ratios were combined using a random-effects model after testing for heterogeneity. This review included six randomised controlled trials involving a total of 417 eyes, of which 201 were treated with PRK and 216 with LASIK. We found that although LASIK gives a faster visual recovery than PRK, the effectiveness of these two procedures is comparable. We found some evidence that LASIK may be less likely than PRK to result in loss of best spectacle-corrected visual acuity. LASIK gives a faster visual recovery than PRK but the effectiveness of these two procedures is comparable. Further trials using contemporary techniques are required to determine whether LASIK and PRK are equally safe.

Optimizing Social Network Support to Families Living With Parental Cancer: Research Protocol for the Cancer-PEPSONE Study.

PubMed

Hauken, May Aasebø; Senneseth, Mette; Dyregrov, Atle; Dyregrov, Kari

2015-12-30

Parental cancer can have a significant impact on a family's psychosocial functioning and quality of life, whereby the children's situation is strongly related to parental coping and capacity. Such parents ask for more help in order to increase their care capacity, while the network is often insecure about how to help and thereby withdraw. They ask for guidance and training to be able to support cancer families. Based on this, the Cancer- Psycho-Educational Program for the SOcial NEtwork (PEPSONE) study was developed. To optimize social network support through a psycho-educational program for families living with parental cancer and their network members in order to increase parental capacity and thereby secure the children's safety and quality of life. A randomized controlled trial (RCT) in which families (N=60) living with parental cancer will be randomized to either an intervention group or a control group. The intervention will last for 3 hours and includes (1) introduction, (2) psycho-education (living with cancer in the family and the importance of social network support), and (3) discussion (this family's need for social support). Primary outcomes are social support, mental health, and quality of life, and secondary outcomes are resilience and parental capacity. Data will be collected by a set of questionnaires distributed to healthy parents (N=60) living with a partner with cancer, one child in the family between 8-18 years of age (N=60), and network members (N=210) of the intervention families at inclusion, and after 3 and 6 months. Comparing differences between the intervention group (n=30) and the control group (n=30), the power analysis shows that P<.05 and a statistical power = .80 would detect effect sizes of clinical interest. This paper presents the Cancer-PEPSON study's protocol to provide a broader understanding of the background and content of the program. The study is ongoing until August 2016 and the first results are anticipated to be finished by November 2015. To our knowledge, this will be the first RCT study to optimize social network support through a psycho-educational program for families living with parental cancer and their network members, as well as provide an evidence basis for social network support. The results may provide important knowledge that is useful for clinical practice and further research. The trial is reported according to the CONSORT checklist. International Standard Randomized Controlled Trial Number (ISRCTN): 15982171; http://www.controlled-trials.com/ISRCTN15982171/15982171 (Archived by WebCite at http://www.webcitation.org/6cg9zunS0).

One session of high-intensity interval training (HIIT) every 5 days, improves muscle power but not static balance in lifelong sedentary ageing men

PubMed Central

Sculthorpe, Nicholas F.; Herbert, Peter; Grace, Fergal

2017-01-01

Abstract Background: Declining muscle power during advancing age predicts falls and loss of independence. High-intensity interval training (HIIT) may improve muscle power, but remains largely unstudied in ageing participants. Methods: This randomized controlled trial (RCT) investigated the efficacy of a low-frequency HIIT (LfHIIT) intervention on peak muscle power (peak power output [PPO]), body composition, and balance in lifelong sedentary but otherwise healthy males. Methods: Thirty-three lifelong sedentary ageing men were randomly assigned to either intervention (INT; n = 22, age 62.3 ± 4.1 years) or control (n = 11, age 61.6 ± 5.0 years) who were both assessed at 3 distinct measurement points (phase A), after 6 weeks of conditioning exercise (phase B), and after 6 weeks of HIIT once every 5 days in INT (phase C), where control remained inactive throughout the study. Results: Static balance remained unaffected, and both absolute and relative PPO were not different between groups at phases A or B, but increased significantly in INT after LfHIIT (P < 0.01). Lean body mass displayed a significant interaction (P < 0.01) due to an increase in INT between phases B and C (P < 0.05). Conclusions: 6 weeks of LfHIIT exercise feasible and effective method to induce clinically relevant improvements in absolute and relative PPO, but does not improve static balance in sedentary ageing men. PMID:28178145

Creatine for women in pregnancy for neuroprotection of the fetus.

PubMed

Dickinson, Hayley; Bain, Emily; Wilkinson, Dominic; Middleton, Philippa; Crowther, Caroline A; Walker, David W

2014-12-19

Creatine is an amino acid derivative and, when phosphorylated (phosphocreatine), is involved in replenishing adenosine triphosphate (ATP) via the creatine kinase reaction. Cells obtain creatine from a diet rich in fish, meat, or dairy and by endogenous synthesis from the amino acids arginine, glycine, and methionine in an approximate 50:50 ratio. Animal studies have shown that creatine may provide fetal neuroprotection when given to the mother through her diet in pregnancy. It is important to assess whether maternally administered creatine in human pregnancy (at times of known, suspected, or potential fetal compromise) may offer neuroprotection to the fetus and may accordingly reduce the risk of adverse neurodevelopmental outcomes, such as cerebral palsy and associated impairments and disabilities arising from fetal brain injury. To assess the effects of creatine when used for neuroprotection of the fetus. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2014). We planned to include all published, unpublished, and ongoing randomised trials and quasi-randomised trials. We planned to include studies reported as abstracts only as well as full-text manuscripts. Trials using a cross-over or cluster-randomised design were not eligible for inclusion.We planned to include trials comparing creatine given to women in pregnancy for fetal neuroprotection (regardless of the route, timing, dose, or duration of administration) with placebo, no treatment, or with an alternative agent aimed at providing fetal neuroprotection. We also planned to include comparisons of different regimens for administration of creatine. We identified no completed or ongoing randomised controlled trials. We found no randomised controlled trials for inclusion in this review. As we did not identify any randomised controlled trials for inclusion in this review, we are unable to comment on implications for practice. Although evidence from animal studies has supported a fetal neuroprotective role for creatine when administered to the mother during pregnancy, no trials assessing creatine in pregnant women for fetal neuroprotection have been published to date. If creatine is established as safe for the mother and her fetus, research efforts should first be directed towards randomised trials comparing creatine with either no intervention (ideally using a placebo), or with alternative agents aimed at providing fetal neuroprotection (including magnesium sulphate for the very preterm infant). If appropriate, these trials should then be followed by studies comparing different creatine regimens (dosage and duration of exposure). Such trials should be high quality and adequately powered to evaluate maternal and infant short and longer-term outcomes (including neurodevelopmental disabilities such as cerebral palsy), and should consider utilisation/costs of health care.

Mindfulness-based resilience training to reduce health risk, stress reactivity, and aggression among law enforcement officers: A feasibility and preliminary efficacy trial.

PubMed

Christopher, Michael S; Hunsinger, Matthew; Goerling, Lt Richard J; Bowen, Sarah; Rogers, Brant S; Gross, Cynthia R; Dapolonia, Eli; Pruessner, Jens C

2018-06-01

The primary objective of this study was to assess feasibility and gather preliminary outcome data on Mindfulness-Based Resilience Training (MBRT) for law enforcement officers. Participants (n = 61) were randomized to either an 8-week MBRT course or a no intervention control group. Self-report and physiological data were collected at baseline, post-training, and three months following intervention completion. Attendance, adherence, post-training participant feedback, and interventionist fidelity to protocol all demonstrated feasibility of MBRT for law enforcement officers. Compared to no intervention controls, MBRT participants experienced greater reductions in salivary cortisol, self-reported aggression, organizational stress, burnout, sleep disturbance, and reported increases in psychological flexibility and non-reactivity at post-training; however, group differences were not maintained at three-month follow-up. This initial randomized trial suggests MBRT is a feasible intervention. Outcome data suggest MBRT targets key physiological, psychological, and health risk factors in law enforcement officers, consistent with the potential to improve officer health and public safety. However, follow-up training or "booster" sessions may be needed to maintain training gains. A fully powered longitudinal randomized trial is warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

Adjusted regression trend test for a multicenter clinical trial.

PubMed

Quan, H; Capizzi, T

1999-06-01

Studies using a series of increasing doses of a compound, including a zero dose control, are often conducted to study the effect of the compound on the response of interest. For a one-way design, Tukey et al. (1985, Biometrics 41, 295-301) suggested assessing trend by examining the slopes of regression lines under arithmetic, ordinal, and arithmetic-logarithmic dose scalings. They reported the smallest p-value for the three significance tests on the three slopes for safety assessments. Capizzi et al. (1992, Biometrical Journal 34, 275-289) suggested an adjusted trend test, which adjusts the p-value using a trivariate t-distribution, the joint distribution of the three slope estimators. In this paper, we propose an adjusted regression trend test suitable for two-way designs, particularly for multicenter clinical trials. In a step-down fashion, the proposed trend test can be applied to a multicenter clinical trial to compare each dose with the control. This sequential procedure is a closed testing procedure for a trend alternative. Therefore, it adjusts p-values and maintains experimentwise error rate. Simulation results show that the step-down trend test is overall more powerful than a step-down least significant difference test.

The power of instructions: Proactive configuration of stimulus-response translation.

PubMed

Meiran, Nachshon; Pereg, Maayan; Kessler, Yoav; Cole, Michael W; Braver, Todd S

2015-05-01

Humans are characterized by an especially highly developed ability to use instructions to prepare toward upcoming events; yet, it is unclear just how powerful instructions can be. Although prior work provides evidence that instructions can be sufficiently powerful to proactively program working memory to execute stimulus-response (S-R) translations, in a reflexlike fashion (intention-based reflexivity [IBR]), the results to date have been equivocal. To overcome this shortcoming, we developed, and tested in 4 studies, a novel paradigm (the NEXT paradigm) that isolates IBR effects even prior to first task execution. In each miniblock, participants received S-R mapping instructions for a new task. Prior to implementing this mapping, responses were required to advance through screens during a preparatory (NEXT) phase. When the NEXT response was incompatible with the instructed S-R mapping, interference (IBR effect) was observed. This NEXT compatibility effect and performance in the implementation (GO) trials barely changed when prior practice of a few trials was provided. Finally, a manipulation that encouraged preparation resulted in relatively durable NEXT compatibility effects (indicating durable preparatory efforts) coupled with improved GO performance (indicating the success of these efforts). Together, these findings establish IBR as a marker of instructed proactive control. (c) 2015 APA, all rights reserved).

Oxytocin reduces amygdala activity, increases social interactions and reduces anxiety-like behavior irrespective of NMDAR antagonism

PubMed Central

Sobota, Rosanna; Mihara, Takuma; Forrest, Alexandra; Featherstone, Robert E.; Siegel, Steven J.

2015-01-01

Standard dopamine therapies for schizophrenia are not efficacious for negative symptoms of the disease, including asociality. This reduced social behavior may be due to glutamatergic dysfunction within the amygdala leading to increased fear and social anxiety. Several studies have demonstrated the pro-social effects of oxytocin in schizophrenia patients. Therefore, this study evaluates the effect of sub-chronic oxytocin on electroencephalographic (EEG) activity in amygdala of mice during performance of the three chamber social choice and open field tests following acute ketamine as a model of glutamatergic dysfunction. Oxytocin did not restore social deficits introduced by ketamine, but did significantly increase sociality in comparison to the control group. Ketamine had no effect on time spent in the center during the open field trials, while oxytocin increased overall center time across all groups, suggesting a reduction in anxiety. Amygdala activity was consistent across all drug groups during social and nonsocial behavioral trials. However, oxytocin reduced overall amygdala EEG power during the two behavioral tasks. Alternatively, ketamine did not significantly affect EEG power throughout the tasks. Decreased EEG power in the amygdala, as caused by oxytocin, may be related to both reduced anxiety and increased social behaviors. Data suggest that separate pro-social and social anxiety pathways may mediate social preference. PMID:26214213

A two-way enriched clinical trial design: combining advantages of placebo lead-in and randomized withdrawal.

PubMed

Ivanova, Anastasia; Tamura, Roy N

2015-12-01

A new clinical trial design, designated the two-way enriched design (TED), is introduced, which augments the standard randomized placebo-controlled trial with second-stage enrichment designs in placebo non-responders and drug responders. The trial is run in two stages. In the first stage, patients are randomized between drug and placebo. In the second stage, placebo non-responders are re-randomized between drug and placebo and drug responders are re-randomized between drug and placebo. All first-stage data, and second-stage data from first-stage placebo non-responders and first-stage drug responders, are utilized in the efficacy analysis. The authors developed one, two and three degrees of freedom score tests for treatment effect in the TED and give formulae for asymptotic power and for sample size computations. The authors compute the optimal allocation ratio between drug and placebo in the first stage for the TED and compare the operating characteristics of the design to the standard parallel clinical trial, placebo lead-in and randomized withdrawal designs. Two motivating examples from different disease areas are presented to illustrate the possible design considerations. © The Author(s) 2011.

Cerebral near-infrared spectroscopy monitoring for prevention of brain injury in very preterm infants.

PubMed

Hyttel-Sorensen, Simon; Greisen, Gorm; Als-Nielsen, Bodil; Gluud, Christian

2017-09-04

Cerebral injury and long-term neurodevelopmental impairment is common in extremely preterm infants. Cerebral near-infrared spectroscopy (NIRS) enables continuous estimation of cerebral oxygenation. This diagnostic method coupled with appropriate interventions if NIRS is out of normal range (that is cerebral oxygenation within the 55% to 85% range) may offer benefits without causing more harms. Therefore, NIRS coupled with appropriate responses to abnormal findings on NIRS needs assessment in a systematic review of randomised clinical trials and quasi-randomised studies. To evaluate the benefits and harms of interventions that attempt to alter cerebral oxygenation guided by cerebral NIRS monitoring in order to prevent cerebral injury, improve neurological outcome, and increase survival in preterm infants born more than 8 weeks preterm. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 8), MEDLINE via PubMed (1966 to 10 September 2016), Embase (1980 to 10 September 2016), and CINAHL (1982 to 10 September 2016). We also searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised clinical trials and quasi-randomised studies. Randomised clinical trials and quasi-randomised clinical studies comparing continuous cerebral NIRS monitoring for at least 24 hours versus blinded NIRS or versus no NIRS monitoring. Two review authors independently selected, assessed the quality of, and extracted data from the included trials and studies. If necessary, we contacted authors for further information. We conducted assessments of risks of bias; risks of design errors; and controlled the risks of random errors with Trial Sequential Analysis. We assessed the quality of the evidence with GRADE. One randomised clinical trial met inclusion criteria, including infants born more than 12 weeks preterm. The trial employed adequate methodologies and was assessed at low risk of bias. One hundred and sixty-six infants were randomised to start continuous cerebral NIRS monitoring less than 3 hours after birth until 72 hours after birth plus appropriate interventions if NIRS was out of normal range according to a guideline versus conventional monitoring with blinded NIRS. There was no effect of NIRS plus guideline of mortality until term-equivalent age (RR 0.50, 95% CI 0.29 to 1.00; one trial; 166 participants). There were no effects of NIRS plus guideline on intraventricular haemorrhages: all grades (RR 0.93, 95% CI 0.65 to 1.34; one trial; 166 participants); grade III/IV (RR 0.57, 95% CI 0.25 to 1.31; one trial; 166 participants); and cystic periventricular leukomalacia (which did not occur in either group). Likewise, there was no effect of NIRS plus guideline on the occurrence of a patent ductus arteriosus (RR 1.96, 95% CI 0.94 to 4.08; one trial; 166 participants); chronic lung disease (RR 1.27, 95% CI 0.94 to 1.50; one trial; 166 participants); necrotising enterocolitis (RR 0.83, 95% CI 0.33 to 1.94; one trial; 166 participants); and retinopathy of prematurity (RR 1.64, 95% CI 0.75 to 3.00; one trial; 166 participants). There were no serious adverse events in any of the intervention groups. NIRS plus guideline caused more skin marks from the NIRS sensor in the control group than in the experimental group (unadjusted RR 0.31, 95% CI 0.10 to 0.92; one trial; 166 participants). There are no data regarding neurodevelopmental outcome, renal impairment or air leaks.The quality of evidence for all comparisons discussed above was assessed as very low apart from all-cause mortality and adverse events: these were assessed as low and moderate, respectively. The validity of all comparisons is hampered by a small sample of randomised infants, risk of bias due to lack of blinding, and indirectness of outcomes. The only eligible randomised clinical trial did not demonstrate any consistent effects of NIRS plus a guideline on the assessed clinical outcomes. The trial was, however, only powered to detect difference in cerebral oxygenation, not morbidities or mortality. Our systematic review did not reach sufficient power to prove or disprove effects on clinical outcomes. Further randomised clinical trials with low risks of bias and low risks of random errors are needed.

An imbalance in cluster sizes does not lead to notable loss of power in cross-sectional, stepped-wedge cluster randomised trials with a continuous outcome.

PubMed

Kristunas, Caroline A; Smith, Karen L; Gray, Laura J

2017-03-07

The current methodology for sample size calculations for stepped-wedge cluster randomised trials (SW-CRTs) is based on the assumption of equal cluster sizes. However, as is often the case in cluster randomised trials (CRTs), the clusters in SW-CRTs are likely to vary in size, which in other designs of CRT leads to a reduction in power. The effect of an imbalance in cluster size on the power of SW-CRTs has not previously been reported, nor what an appropriate adjustment to the sample size calculation should be to allow for any imbalance. We aimed to assess the impact of an imbalance in cluster size on the power of a cross-sectional SW-CRT and recommend a method for calculating the sample size of a SW-CRT when there is an imbalance in cluster size. The effect of varying degrees of imbalance in cluster size on the power of SW-CRTs was investigated using simulations. The sample size was calculated using both the standard method and two proposed adjusted design effects (DEs), based on those suggested for CRTs with unequal cluster sizes. The data were analysed using generalised estimating equations with an exchangeable correlation matrix and robust standard errors. An imbalance in cluster size was not found to have a notable effect on the power of SW-CRTs. The two proposed adjusted DEs resulted in trials that were generally considerably over-powered. We recommend that the standard method of sample size calculation for SW-CRTs be used, provided that the assumptions of the method hold. However, it would be beneficial to investigate, through simulation, what effect the maximum likely amount of inequality in cluster sizes would be on the power of the trial and whether any inflation of the sample size would be required.

The EMPOWER study: randomized, prospective, double-blind, multicenter trial of vagal blockade to induce weight loss in morbid obesity.

PubMed

Sarr, Michael G; Billington, Charles J; Brancatisano, Roy; Brancatisano, Anthony; Toouli, James; Kow, Lilian; Nguyen, Ninh T; Blackstone, Robin; Maher, James W; Shikora, Scott; Reeds, Dominic N; Eagon, J Christopher; Wolfe, Bruce M; O'Rourke, Robert W; Fujioka, Ken; Takata, Mark; Swain, James M; Morton, John M; Ikramuddin, Sayeed; Schweitzer, Michael; Chand, Bipan; Rosenthal, Raul

2012-11-01

Intermittent, reversible intraabdominal vagal blockade (VBLOC® Therapy) demonstrated clinically important weight loss in feasibility trials. EMPOWER, a randomized, double-blind, prospective, controlled trial was conducted in USA and Australia. Five hundred three subjects were enrolled at 15 centers. After informed consent, 294 subjects were implanted with the vagal blocking system and randomized to the treated (n = 192) or control (n = 102) group. Main outcome measures were percent excess weight loss (percent EWL) at 12 months and serious adverse events. Subjects controlled duration of therapy using an external power source; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission. Devices in both groups performed regular, low-energy safety checks. Data are mean ± SEM. Study subjects consisted of 90 % females, body mass index of 41 ± 1 kg/m(2), and age of 46 ± 1 years. Device-related complications occurred in 3 % of subjects. There was no mortality. 12-month percent EWL was 17 ± 2 % for the treated and 16 ± 2 % for the control group. Weight loss was related linearly to hours of device use; treated and controls with ≥ 12 h/day use achieved 30 ± 4 and 22 ± 8 % EWL, respectively. VBLOC® therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of device use. Post-study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group.

Shamba Maisha: Randomized controlled trial of an agricultural and finance intervention to improve HIV health outcomes in Kenya

PubMed Central

WEISER, Sheri D.; BUKUSI, Elizabeth A.; STEINFELD, Rachel L.; FRONGILLO, Edward A.; WEKE, Elly; DWORKIN, Shari L.; PUSATERI, Kyle; SHIBOSKI, Stephen; SCOW, Kate; BUTLER, Lisa M.; COHEN, Craig R.

2015-01-01

Objectives Food insecurity and HIV/AIDS outcomes are inextricably linked in sub-Saharan Africa. We report on health and nutritional outcomes of a multisectoral agricultural intervention trial among HIV-infected adults in rural Kenya. Design Pilot cluster randomized controlled trial Methods The intervention included a human-powered water pump, a microfinance loan to purchase farm commodities, and education in sustainable farming practices and financial management. Two health facilities in Nyanza Region, Kenya were randomly assigned as intervention or control. HIV-infected adults 18 to 49 years old who were on antiretroviral therapy and had access to surface water and land were enrolled beginning in April 2012 and followed quarterly for one year. Data were collected on nutritional parameters, CD4 T lymphocyte counts, and HIV RNA. Difference in difference fixed-effects regression models were used to test whether patterns in health outcomes differed over time from baseline between the intervention and control arms. Results We enrolled 72 and 68 participants in the intervention and control groups, respectively. At 12 months follow-up, we found a statistically significant increase in CD4 cell counts (165 cells/mm3, p<0.001) and proportion virologically suppressed in the intervention arm compared to the control arm (comparative improvement in proportion of 0.33 suppressed, OR 7.6, 95% CI: 2.2–26.8). Intervention participants experienced significant improvements in food security (3.6 scale points higher, p<0.001) and frequency of food consumption (9.4 times per week greater frequency, p=0.013) compared to controls. Conclusion Livelihood interventions may be a promising approach to tackle the intersecting problems of food insecurity, poverty and HIV/AIDS morbidity. PMID:26214684

Shamba Maisha: randomized controlled trial of an agricultural and finance intervention to improve HIV health outcomes.

PubMed

Weiser, Sheri D; Bukusi, Elizabeth A; Steinfeld, Rachel L; Frongillo, Edward A; Weke, Elly; Dworkin, Shari L; Pusateri, Kyle; Shiboski, Stephen; Scow, Kate; Butler, Lisa M; Cohen, Craig R

2015-09-10

Food insecurity and HIV/AIDS outcomes are inextricably linked in sub-Saharan Africa. We report on health and nutritional outcomes of a multisectoral agricultural intervention trial among HIV-infected adults in rural Kenya. This is a pilot cluster randomized controlled trial. The intervention included a human-powered water pump, a microfinance loan to purchase farm commodities, and education in sustainable farming practices and financial management. Two health facilities in Nyanza Region, Kenya were randomly assigned as intervention or control. HIV-infected adults 18 to 49 years' old who were on antiretroviral therapy and had access to surface water and land were enrolled beginning in April 2012 and followed quarterly for 1 year. Data were collected on nutritional parameters, CD4 T-lymphocyte counts, and HIV RNA. Differences in fixed-effects regression models were used to test whether patterns in health outcomes differed over time from baseline between the intervention and control arms. We enrolled 72 and 68 participants in the intervention and control groups, respectively. At 12 months follow-up, we found a statistically significant increase in CD4 cell counts (165 cells/μl, P < 0.001) and proportion virologically suppressed in the intervention arm compared with the control arm (comparative improvement in proportion of 0.33 suppressed, odds ratio 7.6, 95% confidence interval: 2.2-26.8). Intervention participants experienced significant improvements in food security (3.6 scale points higher, P < 0.001) and frequency of food consumption (9.4 times per week greater frequency, P = 0.013) compared to controls. Livelihood interventions may be a promising approach to tackle the intersecting problems of food insecurity, poverty and HIV/AIDS morbidity.

Comparison of design strategies for a three-arm clinical trial with time-to-event endpoint: Power, time-to-analysis, and operational aspects.

PubMed

Asikanius, Elina; Rufibach, Kaspar; Bahlo, Jasmin; Bieska, Gabriele; Burger, Hans Ulrich

2016-11-01

To optimize resources, randomized clinical trials with multiple arms can be an attractive option to simultaneously test various treatment regimens in pharmaceutical drug development. The motivation for this work was the successful conduct and positive final outcome of a three-arm randomized clinical trial primarily assessing whether obinutuzumab plus chlorambucil in patients with chronic lympocytic lymphoma and coexisting conditions is superior to chlorambucil alone based on a time-to-event endpoint. The inference strategy of this trial was based on a closed testing procedure. We compare this strategy to three potential alternatives to run a three-arm clinical trial with a time-to-event endpoint. The primary goal is to quantify the differences between these strategies in terms of the time it takes until the first analysis and thus potential approval of a new drug, number of required events, and power. Operational aspects of implementing the various strategies are discussed. In conclusion, using a closed testing procedure results in the shortest time to the first analysis with a minimal loss in power. Therefore, closed testing procedures should be part of the statistician's standard clinical trials toolbox when planning multiarm clinical trials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Calibrated Power Prior Approach to Borrow Information from Historical Data with Application to Biosimilar Clinical Trials.

PubMed

Pan, Haitao; Yuan, Ying; Xia, Jielai

2017-11-01

A biosimilar refers to a follow-on biologic intended to be approved for marketing based on biosimilarity to an existing patented biological product (i.e., the reference product). To develop a biosimilar product, it is essential to demonstrate biosimilarity between the follow-on biologic and the reference product, typically through two-arm randomization trials. We propose a Bayesian adaptive design for trials to evaluate biosimilar products. To take advantage of the abundant historical data on the efficacy of the reference product that is typically available at the time a biosimilar product is developed, we propose the calibrated power prior, which allows our design to adaptively borrow information from the historical data according to the congruence between the historical data and the new data collected from the current trial. We propose a new measure, the Bayesian biosimilarity index, to measure the similarity between the biosimilar and the reference product. During the trial, we evaluate the Bayesian biosimilarity index in a group sequential fashion based on the accumulating interim data, and stop the trial early once there is enough information to conclude or reject the similarity. Extensive simulation studies show that the proposed design has higher power than traditional designs. We applied the proposed design to a biosimilar trial for treating rheumatoid arthritis.

Simultaneous sequential monitoring of efficacy and safety led to masking of effects.

PubMed

van Eekelen, Rik; de Hoop, Esther; van der Tweel, Ingeborg

2016-08-01

Usually, sequential designs for clinical trials are applied on the primary (=efficacy) outcome. In practice, other outcomes (e.g., safety) will also be monitored and influence the decision whether to stop a trial early. Implications of simultaneous monitoring on trial decision making are yet unclear. This study examines what happens to the type I error, power, and required sample sizes when one efficacy outcome and one correlated safety outcome are monitored simultaneously using sequential designs. We conducted a simulation study in the framework of a two-arm parallel clinical trial. Interim analyses on two outcomes were performed independently and simultaneously on the same data sets using four sequential monitoring designs, including O'Brien-Fleming and Triangular Test boundaries. Simulations differed in values for correlations and true effect sizes. When an effect was present in both outcomes, competition was introduced, which decreased power (e.g., from 80% to 60%). Futility boundaries for the efficacy outcome reduced overall type I errors as well as power for the safety outcome. Monitoring two correlated outcomes, given that both are essential for early trial termination, leads to masking of true effects. Careful consideration of scenarios must be taken into account when designing sequential trials. Simulation results can help guide trial design. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of recovery interventions on cycling performance and pacing strategy in the heat.

PubMed

De Pauw, Kevin; Roelands, Bart; Vanparijs, Jef; Meeusen, Romain

2014-03-01

To determine the effect of active recovery (AR), passive rest (PR), and cold-water immersion (CWI) after 90 min of intensive cycling on a subsequent 12-min time trial (TT2) and the applied pacing strategy in TT2. After a maximal test and familiarization trial, 9 trained male subjects (age 22 ± 3 y, VO2max 62.1 ± 5.3 mL · min-1 · kg-1) performed 3 experimental trials in the heat (30°C). Each trial consisted of 2 exercise tasks separated by 1 h. The first was a 60-min constant-load trial at 55% of the maximal power output followed by a 30-min time trial (TT1). The second comprised a 12-min simulated time trial (TT2). After TT1, AR, PR, or CWI was applied for 15 min. No significant TT2 performance differences were observed, but a 1-sample t test (within each condition) revealed different pacing strategies during TT2. CWI resulted in an even pacing strategy, while AR and PR resulted in a gradual decline of power output after the onset of TT2 (P ≤ .046). During recovery, AR and CWI showed a trend toward faster blood lactate ([BLa]) removal, but during TT2 significantly higher [BLa] was only observed after CWI compared with PR (P = .011). The pacing strategy during subsequent cycling performance in the heat is influenced by the application of different postexercise recovery interventions. Although power was not significantly altered between groups, CWI enabled a differently shaped power profile, likely due to decreased thermal strain.