Group Cognitive Behavioural Therapy and Group Recreational Activity for Adults with Autism Spectrum Disorders: A Preliminary Randomized Controlled Trial

ERIC Educational Resources Information Center

Hesselmark, Eva; Plenty, Stephanie; Bejerot, Susanne

2014-01-01

Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This "preliminary" randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive…

Optimizing trial design in pharmacogenetics research: comparing a fixed parallel group, group sequential, and adaptive selection design on sample size requirements.

PubMed

Boessen, Ruud; van der Baan, Frederieke; Groenwold, Rolf; Egberts, Antoine; Klungel, Olaf; Grobbee, Diederick; Knol, Mirjam; Roes, Kit

2013-01-01

Two-stage clinical trial designs may be efficient in pharmacogenetics research when there is some but inconclusive evidence of effect modification by a genomic marker. Two-stage designs allow to stop early for efficacy or futility and can offer the additional opportunity to enrich the study population to a specific patient subgroup after an interim analysis. This study compared sample size requirements for fixed parallel group, group sequential, and adaptive selection designs with equal overall power and control of the family-wise type I error rate. The designs were evaluated across scenarios that defined the effect sizes in the marker positive and marker negative subgroups and the prevalence of marker positive patients in the overall study population. Effect sizes were chosen to reflect realistic planning scenarios, where at least some effect is present in the marker negative subgroup. In addition, scenarios were considered in which the assumed 'true' subgroup effects (i.e., the postulated effects) differed from those hypothesized at the planning stage. As expected, both two-stage designs generally required fewer patients than a fixed parallel group design, and the advantage increased as the difference between subgroups increased. The adaptive selection design added little further reduction in sample size, as compared with the group sequential design, when the postulated effect sizes were equal to those hypothesized at the planning stage. However, when the postulated effects deviated strongly in favor of enrichment, the comparative advantage of the adaptive selection design increased, which precisely reflects the adaptive nature of the design. Copyright © 2013 John Wiley & Sons, Ltd.

Sequential parallel comparison design with binary and time-to-event outcomes.

PubMed

Silverman, Rachel Kloss; Ivanova, Anastasia; Fine, Jason

2018-04-30

Sequential parallel comparison design (SPCD) has been proposed to increase the likelihood of success of clinical trials especially trials with possibly high placebo effect. Sequential parallel comparison design is conducted with 2 stages. Participants are randomized between active therapy and placebo in stage 1. Then, stage 1 placebo nonresponders are rerandomized between active therapy and placebo. Data from the 2 stages are pooled to yield a single P value. We consider SPCD with binary and with time-to-event outcomes. For time-to-event outcomes, response is defined as a favorable event prior to the end of follow-up for a given stage of SPCD. We show that for these cases, the usual test statistics from stages 1 and 2 are asymptotically normal and uncorrelated under the null hypothesis, leading to a straightforward combined testing procedure. In addition, we show that the estimators of the treatment effects from the 2 stages are asymptotically normal and uncorrelated under the null and alternative hypothesis, yielding confidence interval procedures with correct coverage. Simulations and real data analysis demonstrate the utility of the binary and time-to-event SPCD. Copyright © 2018 John Wiley & Sons, Ltd.

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.

An analysis of adaptive design variations on the sequential parallel comparison design for clinical trials

PubMed Central

Mi, Michael Y.; Betensky, Rebecca A.

2013-01-01

Background Currently, a growing placebo response rate has been observed in clinical trials for antidepressant drugs, a phenomenon that has made it increasingly difficult to demonstrate efficacy. The sequential parallel comparison design (SPCD) is a clinical trial design that was proposed to address this issue. The SPCD theoretically has the potential to reduce the sample size requirement for a clinical trial and to simultaneously enrich the study population to be less responsive to the placebo. Purpose Because the basic SPCD design already reduces the placebo response by removing placebo responders between the first and second phases of a trial, the purpose of this study was to examine whether we can further improve the efficiency of the basic SPCD and if we can do so when the projected underlying drug and placebo response rates differ considerably from the actual ones. Methods Three adaptive designs that used interim analyses to readjust the length of study duration for individual patients were tested to reduce the sample size requirement or increase the statistical power of the SPCD. Various simulations of clinical trials using the SPCD with interim analyses were conducted to test these designs through calculations of empirical power. Results From the simulations, we found that the adaptive designs can recover unnecessary resources spent in the traditional SPCD trial format with overestimated initial sample sizes and provide moderate gains in power. Under the first design, results showed up to a 25% reduction in person-days, with most power losses below 5%. In the second design, results showed up to a 8% reduction in person-days with negligible loss of power. In the third design using sample size re-estimation, up to 25% power was recovered from underestimated sample size scenarios. Limitations Given the numerous possible test parameters that could have been chosen for the simulations, the study’s results are limited to situations described by the parameters that were used, and may not generalize to all possible scenarios. Furthermore, drop-out of patients is not considered in this study. Conclusions It is possible to make an already complex design such as the SPCD adaptive, and thus more efficient, potentially overcoming the problem of placebo response at lower cost. Ultimately, such a design may expedite the approval of future effective treatments. PMID:23283576

Comparison of intervention effects in split-mouth and parallel-arm randomized controlled trials: a meta-epidemiological study

PubMed Central

2014-01-01

Background Split-mouth randomized controlled trials (RCTs) are popular in oral health research. Meta-analyses frequently include trials of both split-mouth and parallel-arm designs to derive combined intervention effects. However, carry-over effects may induce bias in split- mouth RCTs. We aimed to assess whether intervention effect estimates differ between split- mouth and parallel-arm RCTs investigating the same questions. Methods We performed a meta-epidemiological study. We systematically reviewed meta- analyses including both split-mouth and parallel-arm RCTs with binary or continuous outcomes published up to February 2013. Two independent authors selected studies and extracted data. We used a two-step approach to quantify the differences between split-mouth and parallel-arm RCTs: for each meta-analysis. First, we derived ratios of odds ratios (ROR) for dichotomous data and differences in standardized mean differences (∆SMD) for continuous data; second, we pooled RORs or ∆SMDs across meta-analyses by random-effects meta-analysis models. Results We selected 18 systematic reviews, for 15 meta-analyses with binary outcomes (28 split-mouth and 28 parallel-arm RCTs) and 19 meta-analyses with continuous outcomes (28 split-mouth and 28 parallel-arm RCTs). Effect estimates did not differ between split-mouth and parallel-arm RCTs (mean ROR, 0.96, 95% confidence interval 0.52–1.80; mean ∆SMD, 0.08, -0.14–0.30). Conclusions Our study did not provide sufficient evidence for a difference in intervention effect estimates derived from split-mouth and parallel-arm RCTs. Authors should consider including split-mouth RCTs in their meta-analyses with suitable and appropriate analysis. PMID:24886043

An analysis of adaptive design variations on the sequential parallel comparison design for clinical trials.

PubMed

Mi, Michael Y; Betensky, Rebecca A

2013-04-01

Currently, a growing placebo response rate has been observed in clinical trials for antidepressant drugs, a phenomenon that has made it increasingly difficult to demonstrate efficacy. The sequential parallel comparison design (SPCD) is a clinical trial design that was proposed to address this issue. The SPCD theoretically has the potential to reduce the sample-size requirement for a clinical trial and to simultaneously enrich the study population to be less responsive to the placebo. Because the basic SPCD already reduces the placebo response by removing placebo responders between the first and second phases of a trial, the purpose of this study was to examine whether we can further improve the efficiency of the basic SPCD and whether we can do so when the projected underlying drug and placebo response rates differ considerably from the actual ones. Three adaptive designs that used interim analyses to readjust the length of study duration for individual patients were tested to reduce the sample-size requirement or increase the statistical power of the SPCD. Various simulations of clinical trials using the SPCD with interim analyses were conducted to test these designs through calculations of empirical power. From the simulations, we found that the adaptive designs can recover unnecessary resources spent in the traditional SPCD trial format with overestimated initial sample sizes and provide moderate gains in power. Under the first design, results showed up to a 25% reduction in person-days, with most power losses below 5%. In the second design, results showed up to a 8% reduction in person-days with negligible loss of power. In the third design using sample-size re-estimation, up to 25% power was recovered from underestimated sample-size scenarios. Given the numerous possible test parameters that could have been chosen for the simulations, the study's results are limited to situations described by the parameters that were used and may not generalize to all possible scenarios. Furthermore, dropout of patients is not considered in this study. It is possible to make an already complex design such as the SPCD adaptive, and thus more efficient, potentially overcoming the problem of placebo response at lower cost. Ultimately, such a design may expedite the approval of future effective treatments.

A repeated measures model for analysis of continuous outcomes in sequential parallel comparison design studies.

PubMed

Doros, Gheorghe; Pencina, Michael; Rybin, Denis; Meisner, Allison; Fava, Maurizio

2013-07-20

Previous authors have proposed the sequential parallel comparison design (SPCD) to address the issue of high placebo response rate in clinical trials. The original use of SPCD focused on binary outcomes, but recent use has since been extended to continuous outcomes that arise more naturally in many fields, including psychiatry. Analytic methods proposed to date for analysis of SPCD trial continuous data included methods based on seemingly unrelated regression and ordinary least squares. Here, we propose a repeated measures linear model that uses all outcome data collected in the trial and accounts for data that are missing at random. An appropriate contrast formulated after the model has been fit can be used to test the primary hypothesis of no difference in treatment effects between study arms. Our extensive simulations show that when compared with the other methods, our approach preserves the type I error even for small sample sizes and offers adequate power and the smallest mean squared error under a wide variety of assumptions. We recommend consideration of our approach for analysis of data coming from SPCD trials. Copyright © 2013 John Wiley & Sons, Ltd.

Sample size calculations for the design of cluster randomized trials: A summary of methodology.

PubMed

Gao, Fei; Earnest, Arul; Matchar, David B; Campbell, Michael J; Machin, David

2015-05-01

Cluster randomized trial designs are growing in popularity in, for example, cardiovascular medicine research and other clinical areas and parallel statistical developments concerned with the design and analysis of these trials have been stimulated. Nevertheless, reviews suggest that design issues associated with cluster randomized trials are often poorly appreciated and there remain inadequacies in, for example, describing how the trial size is determined and the associated results are presented. In this paper, our aim is to provide pragmatic guidance for researchers on the methods of calculating sample sizes. We focus attention on designs with the primary purpose of comparing two interventions with respect to continuous, binary, ordered categorical, incidence rate and time-to-event outcome variables. Issues of aggregate and non-aggregate cluster trials, adjustment for variation in cluster size and the effect size are detailed. The problem of establishing the anticipated magnitude of between- and within-cluster variation to enable planning values of the intra-cluster correlation coefficient and the coefficient of variation are also described. Illustrative examples of calculations of trial sizes for each endpoint type are included. Copyright © 2015 Elsevier Inc. All rights reserved.

Stability of tapered and parallel-walled dental implants: A systematic review and meta-analysis.

PubMed

Atieh, Momen A; Alsabeeha, Nabeel; Duncan, Warwick J

2018-05-15

Clinical trials have suggested that dental implants with a tapered configuration have improved stability at placement, allowing immediate placement and/or loading. The aim of this systematic review and meta-analysis was to evaluate the implant stability of tapered dental implants compared to standard parallel-walled dental implants. Applying the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, randomized controlled trials (RCTs) were searched for in electronic databases and complemented by hand searching. The risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool and data were analyzed using statistical software. A total of 1199 studies were identified, of which, five trials were included with 336 dental implants in 303 participants. Overall meta-analysis showed that tapered dental implants had higher implant stability values than parallel-walled dental implants at insertion and 8 weeks but the difference was not statistically significant. Tapered dental implants had significantly less marginal bone loss compared to parallel-walled dental implants. No significant differences in implant failure rate were found between tapered and parallel-walled dental implants. There is limited evidence to demonstrate the effectiveness of tapered dental implants in achieving greater implant stability compared to parallel-walled dental implants. Superior short-term results in maintaining peri-implant marginal bone with tapered dental implants are possible. Further properly designed RCTs are required to endorse the supposed advantages of tapered dental implants in immediate loading protocol and other complex clinical scenarios. © 2018 Wiley Periodicals, Inc.

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.

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.

Beyond the treatment effect: Evaluating the effects of patient preferences in randomised trials.

PubMed

Walter, S D; Turner, R; Macaskill, P; McCaffery, K J; Irwig, L

2017-02-01

The treatments under comparison in a randomised trial should ideally have equal value and acceptability - a position of equipoise - to study participants. However, it is unlikely that true equipoise exists in practice, because at least some participants may have preferences for one treatment or the other, for a variety of reasons. These preferences may be related to study outcomes, and hence affect the estimation of the treatment effect. Furthermore, the effects of preferences can sometimes be substantial, and may even be larger than the direct effect of treatment. Preference effects are of interest in their own right, but they cannot be assessed in the standard parallel group design for a randomised trial. In this paper, we describe a model to represent the impact of preferences on trial outcomes, in addition to the usual treatment effect. In particular, we describe how outcomes might differ between participants who would choose one treatment or the other, if they were free to do so. Additionally, we investigate the difference in outcomes depending on whether or not a participant receives his or her preferred treatment, which we characterise through a so-called preference effect. We then discuss several study designs that have been proposed to measure and exploit data on preferences, and which constitute alternatives to the conventional parallel group design. Based on the model framework, we determine which of the various preference effects can or cannot be estimated with each design. We also illustrate these ideas with some examples of preference designs from the literature.

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

Design, Analysis, and Reporting of Crossover Trials for Inclusion in a Meta-Analysis.

PubMed

Li, Tianjing; Yu, Tsung; Hawkins, Barbara S; Dickersin, Kay

2015-01-01

To evaluate the characteristics of the design, analysis, and reporting of crossover trials for inclusion in a meta-analysis of treatment for primary open-angle glaucoma and to provide empirical evidence to inform the development of tools to assess the validity of the results from crossover trials and reporting guidelines. We searched MEDLINE, EMBASE, and Cochrane's CENTRAL register for randomized crossover trials for a systematic review and network meta-analysis we are conducting. Two individuals independently screened the search results for eligibility and abstracted data from each included report. We identified 83 crossover trials eligible for inclusion. Issues affecting the risk of bias in crossover trials, such as carryover, period effects and missing data, were often ignored. Some trials failed to accommodate the within-individual differences in the analysis. For a large proportion of the trials, the authors tabulated the results as if they arose from a parallel design. Precision estimates properly accounting for the paired nature of the design were often unavailable from the study reports; consequently, to include trial findings in a meta-analysis would require further manipulation and assumptions. The high proportion of poorly reported analyses and results has the potential to affect whether crossover data should or can be included in a meta-analysis. There is pressing need for reporting guidelines for crossover trials.

Evaluation and validation of social and psychological markers in randomised trials of complex interventions in mental health: a methodological research programme.

PubMed

Dunn, Graham; Emsley, Richard; Liu, Hanhua; Landau, Sabine; Green, Jonathan; White, Ian; Pickles, Andrew

2015-11-01

The development of the capability and capacity to evaluate the outcomes of trials of complex interventions is a key priority of the National Institute for Health Research (NIHR) and the Medical Research Council (MRC). The evaluation of complex treatment programmes for mental illness (e.g. cognitive-behavioural therapy for depression or psychosis) not only is a vital component of this research in its own right but also provides a well-established model for the evaluation of complex interventions in other clinical areas. In the context of efficacy and mechanism evaluation (EME) there is a particular need for robust methods for making valid causal inference in explanatory analyses of the mechanisms of treatment-induced change in clinical outcomes in randomised clinical trials. The key objective was to produce statistical methods to enable trial investigators to make valid causal inferences about the mechanisms of treatment-induced change in these clinical outcomes. The primary objective of this report is to disseminate this methodology, aiming specifically at trial practitioners. The three components of the research were (1) the extension of instrumental variable (IV) methods to latent growth curve models and growth mixture models for repeated-measures data; (2) the development of designs and regression methods for parallel trials; and (3) the evaluation of the sensitivity/robustness of findings to the assumptions necessary for model identifiability. We illustrate our methods with applications from psychological and psychosocial intervention trials, keeping the technical details to a minimum, leaving the reporting of the more theoretical and mathematically demanding results for publication in appropriate specialist journals. We show how to estimate treatment effects and introduce methods for EME. We explain the use of IV methods and principal stratification to evaluate the role of putative treatment effect mediators and therapeutic process measures. These results are extended to the analysis of longitudinal data structures. We consider the design of EME trials. We focus on designs to create convincing IVs, bearing in mind assumptions needed to attain model identifiability. A key area of application that has become apparent during this work is the potential role of treatment moderators (predictive markers) in the evaluation of treatment effect mechanisms for personalised therapies (stratified medicine). We consider the role of targeted therapies and multiarm trials and the use of parallel trials to help elucidate the evaluation of mediators working in parallel. In order to demonstrate both efficacy and mechanism, it is necessary to (1) demonstrate a treatment effect on the primary (clinical) outcome, (2) demonstrate a treatment effect on the putative mediator (mechanism) and (3) demonstrate a causal effect from the mediator to the outcome. Appropriate regression models should be applied for (3) or alternative IV procedures, which account for unmeasured confounding, provided that a valid instrument can be identified. Stratified medicine may provide a setting where such instruments can be designed into the trial. This work could be extended by considering improved trial designs, sample size considerations and measurement properties. The project presents independent research funded under the MRC-NIHR Methodology Research Programme (grant reference G0900678).

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.

Randomized, Controlled Trial of CBT Training for PTSD Providers

DTIC Science & Technology

2016-10-29

trial and comparative effectiveness study is to design, implement and evaluate a cost effective, web based self paced training program to provide skills...without web -centered supervision, may provide an effective means to train increasing numbers of mental health providers in relevant, evidence-based...in equal numbers to three parallel intervention condition: a) Web -based training plus web -centered supervision; b) Web - based training alone; and c

An optimal stratified Simon two-stage design.

PubMed

Parashar, Deepak; Bowden, Jack; Starr, Colin; Wernisch, Lorenz; Mander, Adrian

2016-07-01

In Phase II oncology trials, therapies are increasingly being evaluated for their effectiveness in specific populations of interest. Such targeted trials require designs that allow for stratification based on the participants' molecular characterisation. A targeted design proposed by Jones and Holmgren (JH) Jones CL, Holmgren E: 'An adaptive Simon two-stage design for phase 2 studies of targeted therapies', Contemporary Clinical Trials 28 (2007) 654-661.determines whether a drug only has activity in a disease sub-population or in the wider disease population. Their adaptive design uses results from a single interim analysis to decide whether to enrich the study population with a subgroup or not; it is based on two parallel Simon two-stage designs. We study the JH design in detail and extend it by providing a few alternative ways to control the familywise error rate, in the weak sense as well as the strong sense. We also introduce a novel optimal design by minimising the expected sample size. Our extended design contributes to the much needed framework for conducting Phase II trials in stratified medicine. © 2016 The Authors Pharmaceutical Statistics Published by John Wiley & Sons Ltd. © 2016 The Authors Pharmaceutical Statistics Published by John Wiley & Sons Ltd.

Design paper: the DEMO trial: a randomized, parallel-group, observer-blinded clinical trial of aerobic versus non-aerobic versus relaxation training for patients with light to moderate depression.

PubMed

Krogh, Jesper; Petersen, Lone; Timmermann, Michael; Saltin, Bengt; Nordentoft, Merete

2007-01-01

In western countries, the yearly incidence of depression is estimated to be 3-5% and the lifetime prevalence is 17%. In patient populations with chronic diseases the point prevalence may be 20%. Depression is associated with increased risk for various conditions such as osteoporoses, cardiovascular diseases, and dementia. WHO stated in 2000 that depression was the fourth leading cause of disease burden in terms of disability. In 2000 the cost of depression in the US was estimated to 83 billion dollars. A predominance of trials suggests that physical exercise has a positive effect on depressive symptoms. However, a meta-analysis from 2001 stated: "The effectiveness of exercise in reducing symptoms of depression cannot be determined because of a lack of good quality research on clinical populations with adequate follow-up." The major objective for this randomized trial is to compare the effect of non-aerobic, aerobic, and relaxation training on depressive symptoms using the blindly assessed Hamilton depression scale (HAM-D(17)) as primary outcome. The secondary outcome is the effect of the intervention on working status (i.e., lost days from work, employed/unemployed) and the tertiary outcomes consist of biological responses. The trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are recruited through general practitioners and psychiatrist and randomized to three different interventions: 1) non-aerobic, -- progressive resistance training, 2) aerobic training, -- cardio respiratory fitness, and 3) relaxation training with minimal impact on strength or cardio respiratory fitness. Training for all three groups takes place twice a week for 4 months. Evaluation of patients' symptoms takes place four and 12 months after inclusion. The trial is designed to include 45 patients in each group. Statistical analysis will be done as intention to treat (all randomized patients). Results from the DEMO trial will be reported according to the CONSORT guidelines in 2008-2009.

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

Sample size calculations for cluster randomised crossover trials in Australian and New Zealand intensive care research.

PubMed

Arnup, Sarah J; McKenzie, Joanne E; Pilcher, David; Bellomo, Rinaldo; Forbes, Andrew B

2018-06-01

The cluster randomised crossover (CRXO) design provides an opportunity to conduct randomised controlled trials to evaluate low risk interventions in the intensive care setting. Our aim is to provide a tutorial on how to perform a sample size calculation for a CRXO trial, focusing on the meaning of the elements required for the calculations, with application to intensive care trials. We use all-cause in-hospital mortality from the Australian and New Zealand Intensive Care Society Adult Patient Database clinical registry to illustrate the sample size calculations. We show sample size calculations for a two-intervention, two 12-month period, cross-sectional CRXO trial. We provide the formulae, and examples of their use, to determine the number of intensive care units required to detect a risk ratio (RR) with a designated level of power between two interventions for trials in which the elements required for sample size calculations remain constant across all ICUs (unstratified design); and in which there are distinct groups (strata) of ICUs that differ importantly in the elements required for sample size calculations (stratified design). The CRXO design markedly reduces the sample size requirement compared with the parallel-group, cluster randomised design for the example cases. The stratified design further reduces the sample size requirement compared with the unstratified design. The CRXO design enables the evaluation of routinely used interventions that can bring about small, but important, improvements in patient care in the intensive care setting.

A Novel Design of 4-Class BCI Using Two Binary Classifiers and Parallel Mental Tasks

PubMed Central

Geng, Tao; Gan, John Q.; Dyson, Matthew; Tsui, Chun SL; Sepulveda, Francisco

2008-01-01

A novel 4-class single-trial brain computer interface (BCI) based on two (rather than four or more) binary linear discriminant analysis (LDA) classifiers is proposed, which is called a “parallel BCI.” Unlike other BCIs where mental tasks are executed and classified in a serial way one after another, the parallel BCI uses properly designed parallel mental tasks that are executed on both sides of the subject body simultaneously, which is the main novelty of the BCI paradigm used in our experiments. Each of the two binary classifiers only classifies the mental tasks executed on one side of the subject body, and the results of the two binary classifiers are combined to give the result of the 4-class BCI. Data was recorded in experiments with both real movement and motor imagery in 3 able-bodied subjects. Artifacts were not detected or removed. Offline analysis has shown that, in some subjects, the parallel BCI can generate a higher accuracy than a conventional 4-class BCI, although both of them have used the same feature selection and classification algorithms. PMID:18584040

Placebo non-response measure in sequential parallel comparison design studies.

PubMed

Rybin, Denis; Doros, Gheorghe; Pencina, Michael J; Fava, Maurizio

2015-07-10

The Sequential Parallel Comparison Design (SPCD) is one of the novel approaches addressing placebo response. The analysis of SPCD data typically classifies subjects as 'placebo responders' or 'placebo non-responders'. Most current methods employed for analysis of SPCD data utilize only a part of the data collected during the trial. A repeated measures model was proposed for analysis of continuous outcomes that permitted the inclusion of information from all subjects into the treatment effect estimation. We describe here a new approach using a weighted repeated measures model that further improves the utilization of data collected during the trial, allowing the incorporation of information that is relevant to the placebo response, and dealing with the problem of possible misclassification of subjects. Our simulations show that when compared to the unweighted repeated measures model method, our approach performs as well or, under certain conditions, better, in preserving the type I error, achieving adequate power and minimizing the mean squared error. Copyright © 2015 John Wiley & Sons, Ltd.

Methods for Synthesizing Findings on Moderation Effects Across Multiple Randomized Trials

PubMed Central

Brown, C Hendricks; Sloboda, Zili; Faggiano, Fabrizio; Teasdale, Brent; Keller, Ferdinand; Burkhart, Gregor; Vigna-Taglianti, Federica; Howe, George; Masyn, Katherine; Wang, Wei; Muthén, Bengt; Stephens, Peggy; Grey, Scott; Perrino, Tatiana

2011-01-01

This paper presents new methods for synthesizing results from subgroup and moderation analyses across different randomized trials. We demonstrate that such a synthesis generally results in additional power to detect significant moderation findings above what one would find in a single trial. Three general methods for conducting synthesis analyses are discussed, with two methods, integrative data analysis, and parallel analyses, sharing a large advantage over traditional methods available in meta-analysis. We present a broad class of analytic models to examine moderation effects across trials that can be used to assess their overall effect and explain sources of heterogeneity, and present ways to disentangle differences across trials due to individual differences, contextual level differences, intervention, and trial design. PMID:21360061

Methods for synthesizing findings on moderation effects across multiple randomized trials.

PubMed

Brown, C Hendricks; Sloboda, Zili; Faggiano, Fabrizio; Teasdale, Brent; Keller, Ferdinand; Burkhart, Gregor; Vigna-Taglianti, Federica; Howe, George; Masyn, Katherine; Wang, Wei; Muthén, Bengt; Stephens, Peggy; Grey, Scott; Perrino, Tatiana

2013-04-01

This paper presents new methods for synthesizing results from subgroup and moderation analyses across different randomized trials. We demonstrate that such a synthesis generally results in additional power to detect significant moderation findings above what one would find in a single trial. Three general methods for conducting synthesis analyses are discussed, with two methods, integrative data analysis and parallel analyses, sharing a large advantage over traditional methods available in meta-analysis. We present a broad class of analytic models to examine moderation effects across trials that can be used to assess their overall effect and explain sources of heterogeneity, and present ways to disentangle differences across trials due to individual differences, contextual level differences, intervention, and trial design.

Methods for sample size determination in cluster randomized trials

PubMed Central

Rutterford, Clare; Copas, Andrew; Eldridge, Sandra

2015-01-01

Background: The use of cluster randomized trials (CRTs) is increasing, along with the variety in their design and analysis. The simplest approach for their sample size calculation is to calculate the sample size assuming individual randomization and inflate this by a design effect to account for randomization by cluster. The assumptions of a simple design effect may not always be met; alternative or more complicated approaches are required. Methods: We summarise a wide range of sample size methods available for cluster randomized trials. For those familiar with sample size calculations for individually randomized trials but with less experience in the clustered case, this manuscript provides formulae for a wide range of scenarios with associated explanation and recommendations. For those with more experience, comprehensive summaries are provided that allow quick identification of methods for a given design, outcome and analysis method. Results: We present first those methods applicable to the simplest two-arm, parallel group, completely randomized design followed by methods that incorporate deviations from this design such as: variability in cluster sizes; attrition; non-compliance; or the inclusion of baseline covariates or repeated measures. The paper concludes with methods for alternative designs. Conclusions: There is a large amount of methodology available for sample size calculations in CRTs. This paper gives the most comprehensive description of published methodology for sample size calculation and provides an important resource for those designing these trials. PMID:26174515

Obsessive-compulsive tendencies are associated with a focused information processing strategy.

PubMed

Soref, Assaf; Dar, Reuven; Argov, Galit; Meiran, Nachshon

2008-12-01

The study examined the hypothesis that obsessive-compulsive (OC) tendencies are related to a reliance on focused and serial rather than a parallel, speed-oriented information processing style. Ten students with high OC tendencies and 10 students with low OC tendencies performed the flanker task, in which they were required to quickly classify a briefly presented target letter (S or H) that was flanked by compatible (e.g., SSSSS) or incompatible (e.g., HHSHH) noise letters. Participants received 4 blocks of 100 trials each, two with 50% compatible trials and two with 80% compatible trials and were informed of the probability of compatible trials before the beginning of each block. As predicted, high OC participants, as compared to low OC participants, had slower overall reaction time (RT) and lower tendency for parallel processing (defined as incompatible trials RT minus compatible trials RT). Low, more than high OC participants tended to adjust their focused/parallel processing including a shift towards parallel processing in blocks with 80% compatible trials and in trials following compatible trials. Implications of these results to the cognitive theory and therapy of OCD are discussed.

Recommendations for pharmacological clinical trials in children with functional constipation: The Rome foundation pediatric subcommittee on clinical trials.

PubMed

Koppen, I J N; Saps, M; Lavigne, J V; Nurko, S; Taminiau, J A J M; Di Lorenzo, C; Benninga, M A

2018-04-01

Evidence for the efficacy of commonly used drugs in the treatment of childhood functional constipation (FC) is scarce, studies are often of low quality and study designs are heterogeneous. Thus, recommendations for the design of clinical trials in childhood FC are needed. Members of the Rome Foundation and a member of the Pediatric Committee of the European Medicines Agency formed a committee to create recommendations for the design of clinical trials in children with FC. This committee recommends conducting randomized, double-blind, placebo-controlled, parallel-group clinical trials to assess the efficacy of new drugs for the treatment of childhood FC. Pediatric study participants should be included based on fulfilling the Rome IV criteria for FC. A treatment free run-in period for baseline assessment is recommended. The trial duration should be at least 8 weeks. Treatment success is defined as no longer meeting the Rome IV criteria for FC. Stool consistency should be reported based on the Bristol Stool Scale. Endpoints of drug efficacy need to be tailored to the developmental age of the patient population. © 2018 John Wiley & Sons Ltd.

Acute cholecystitis in high risk surgical patients: percutaneous cholecystostomy versus laparoscopic cholecystectomy (CHOCOLATE trial): Study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice. Methods/Design The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs. Discussion The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients. Trial Registration Netherlands Trial Register (NTR): NTR2666 PMID:22236534

Non-image forming effects of illuminance level: Exploring parallel effects on physiological arousal and task performance.

PubMed

Huiberts, Laura M; Smolders, Karin C H J; de Kort, Yvonne A W

2016-10-01

This study investigated diurnal non-image forming (NIF) effects of illuminance level on physiological arousal in parallel to NIF effects on vigilance and working memory performance. We employed a counterbalanced within-subjects design in which thirty-nine participants (mean age=21.2; SD=2.1; 11 male) completed three 90-min sessions (165 vs. 600lx vs. 1700lx at eye level) either in the morning (N=18) or afternoon (N=21). During each session, participants completed four measurement blocks (incl. one baseline block) each consisting of a 10-min Psychomotor Vigilance Task (PVT) and a Backwards Digit-Span Task (BDST) including easy trials (4-6 digits) and difficult trials (7-8 digits). Heart rate (HR), skin conductance level (SCL) and systolic blood pressure (SBP) were measured continuously. The results revealed significant improvements in performance on the BDST difficult trials under 1700lx vs. 165lx (p=0.01), while illuminance level did not affect performance on the PVT and BDST easy trials. Illuminance level impacted HR and SCL, but not SBP. In the afternoon sessions, HR was significantly higher under 1700lx vs. 165lx during PVT performance (p=0.05), while during BDST performance, HR was only slightly higher under 600 vs. 165lx (p=0.06). SCL was significantly higher under 1700lx vs. 165lx during performance on BDST easy trials (p=0.02) and showed similar, but nonsignificant trends during the PVT and BDST difficult trials. Although both physiology and performance were affected by illuminance level, no consistent pattern emerged with respect to parallel changes in physiology and performance. Rather, physiology and performance seemed to be affected independently, via unique pathways. Copyright © 2016. Published by Elsevier Inc.

MODUL-a multicenter randomized clinical trial of biomarker-driven maintenance therapy following first-line standard induction treatment of metastatic colorectal cancer: an adaptable signal-seeking approach.

PubMed

Schmoll, Hans-Joachim; Arnold, Dirk; de Gramont, Aimery; Ducreux, Michel; Grothey, Axel; O'Dwyer, Peter J; Van Cutsem, Eric; Hermann, Frank; Bosanac, Ivan; Bendahmane, Belguendouz; Mancao, Christoph; Tabernero, Josep

2018-06-01

The old approach of one therapeutic for all patients with mCRC is evolving with a need to target specific molecular aberrations or cell-signalling pathways. Molecular screening approaches and new biomarkers are required to fully characterize tumours, identify patients most likely to benefit, and predict treatment response. MODUL is a signal-seeking trial with a design that is highly adaptable, permitting modification of different treatment cohorts and inclusion of further additional cohorts based on novel evidence on new compounds/combinations that emerge during the study. MODUL is ongoing and its adaptable nature permits timely and efficient recruitment of patients into the most appropriate cohort. Recruitment will take place over approximately 5 years in Europe, Asia, Africa, and South America. The design of MODUL with ongoing parallel/sequential treatment cohorts means that the overall size and duration of the trial can be modified/prolonged based on accumulation of new data. The early success of the current trial suggests that the design may provide definitive leads in a patient-friendly and relatively economical trial structure. Along with other biomarker-driven trials that are currently underway, it is hoped that MODUL will contribute to the continuing evolution of clinical trial design and permit a more 'tailored' approach to the treatment of patients with mCRC.

Clamp-Crushing versus stapler hepatectomy for transection of the parenchyma in elective hepatic resection (CRUNSH) - A randomized controlled trial (NCT01049607)

PubMed Central

2011-01-01

Background Hepatic resection is still associated with significant morbidity. Although the period of parenchymal transection presents a crucial step during the operation, uncertainty persists regarding the optimal technique of transection. It was the aim of the present randomized controlled trial to evaluate the efficacy and safety of hepatic resection using the technique of stapler hepatectomy compared to the simple clamp-crushing technique. Methods/Design The CRUNSH Trial is a prospective randomized controlled single-center trial with a two-group parallel design. Patients scheduled for elective hepatic resection without extrahepatic resection at the Department of General-, Visceral- and Transplantation Surgery, University of Heidelberg are enrolled into the trial and randomized intraoperatively to hepatic resection by the clamp-crushing technique and stapler hepatectomy, respectively. The primary endpoint is total intraoperative blood loss. A set of general and surgical variables are documented as secondary endpoints. Patients and outcome-assessors are blinded for the treatment intervention. Discussion The CRUNSH Trial is the first randomized controlled trial to evaluate efficacy and safety of stapler hepatectomy compared to the clamp-crushing technique for parenchymal transection during elective hepatic resection. Trial Registration ClinicalTrials.gov: NCT01049607 PMID:21888669

Biomarker and Clinical Trial Design Support for Disease-Modifying Therapies: Report of a Survey of the EU/US: Alzheimer's Disease Task Force.

PubMed

Cummings, J; Fox, N; Vellas, B; Aisen, P; Shan, G

2018-01-01

Disease-modifying therapies are urgently needed for the treatment of Alzheimer's disease (AD). The European Union/United States (EU/US) Task Force represents a broad range of stakeholders including biopharma industry personnel, academicians, and regulatory authorities. The EU/US Task Force represents a community of knowledgeable individuals who can inform views of evidence supporting disease modification and the development of disease-modifying therapies (DMTs). We queried their attitudes toward clinical trial design and biomarkers in support of DMTs. A survey of members of the EU/US Alzheimer's Disease Task Force was conducted. Ninety-three members (87%) responded. The details were analyzed to understand what clinical trial design and biomarker data support disease modification. Task Force members favored the parallel group design compared to delayed start or staggered withdrawal clinical trial designs to support disease modification. Amyloid biomarkers were regarded as providing mild support for disease modification while tau biomarkers were regarded as providing moderate support. Combinations of biomarkers, particularly combinations of tau and neurodegeneration, were regarded as providing moderate to marked support for disease modification and combinations of all three classes of biomarkers were regarded by a majority as providing marked support for disease modification. Task Force members considered that evidence derived from clinical trials and biomarkers supports clinical meaningfulness of an intervention, and when combined with a single clinical trial outcome, nearly all regarded the clinical trial design or biomarker evidence as supportive of disease modification. A minority considered biomarker evidence by itself as indicative of disease modification in prevention trials. Levels of evidence (A,B,C) were constructed based on these observations. The survey indicates the view of knowledgeable stakeholders regarding evidence derived from clinical trial design and biomarkers in support of disease modification. Results of this survey can assist in designing clinical trials of DMTs.

Study protocol of Prednisone in episodic Cluster Headache (PredCH): a randomized, double-blind, placebo-controlled parallel group trial to evaluate the efficacy and safety of oral prednisone as an add-on therapy in the prophylactic treatment of episodic cluster headache with verapamil

PubMed Central

2013-01-01

Background Episodic cluster headache (ECH) is a primary headache disorder that severely impairs patient’s quality of life. First-line therapy in the initiation of a prophylactic treatment is verapamil. Due to its delayed onset of efficacy and the necessary slow titration of dosage for tolerability reasons prednisone is frequently added by clinicians to the initial prophylactic treatment of a cluster episode. This treatment strategy is thought to effectively reduce the number and intensity of cluster attacks in the beginning of a cluster episode (before verapamil is effective). This study will assess the efficacy and safety of oral prednisone as an add-on therapy to verapamil and compare it to a monotherapy with verapamil in the initial prophylactic treatment of a cluster episode. Methods and design PredCH is a prospective, randomized, double-blind, placebo-controlled trial with parallel study arms. Eligible patients with episodic cluster headache will be randomized to a treatment intervention with prednisone or a placebo arm. The multi-center trial will be conducted in eight German headache clinics that specialize in the treatment of ECH. Discussion PredCH is designed to assess whether oral prednisone added to first-line agent verapamil helps reduce the number and intensity of cluster attacks in the beginning of a cluster episode as compared to monotherapy with verapamil. Trial registration German Clinical Trials Register DRKS00004716 PMID:23889923

The optimal design of stepped wedge trials with equal allocation to sequences and a comparison to other trial designs.

PubMed

Thompson, Jennifer A; Fielding, Katherine; Hargreaves, James; Copas, Andrew

2017-12-01

Background/Aims We sought to optimise the design of stepped wedge trials with an equal allocation of clusters to sequences and explored sample size comparisons with alternative trial designs. Methods We developed a new expression for the design effect for a stepped wedge trial, assuming that observations are equally correlated within clusters and an equal number of observations in each period between sequences switching to the intervention. We minimised the design effect with respect to (1) the fraction of observations before the first and after the final sequence switches (the periods with all clusters in the control or intervention condition, respectively) and (2) the number of sequences. We compared the design effect of this optimised stepped wedge trial to the design effects of a parallel cluster-randomised trial, a cluster-randomised trial with baseline observations, and a hybrid trial design (a mixture of cluster-randomised trial and stepped wedge trial) with the same total cluster size for all designs. Results We found that a stepped wedge trial with an equal allocation to sequences is optimised by obtaining all observations after the first sequence switches and before the final sequence switches to the intervention; this means that the first sequence remains in the control condition and the last sequence remains in the intervention condition for the duration of the trial. With this design, the optimal number of sequences is [Formula: see text], where [Formula: see text] is the cluster-mean correlation, [Formula: see text] is the intracluster correlation coefficient, and m is the total cluster size. The optimal number of sequences is small when the intracluster correlation coefficient and cluster size are small and large when the intracluster correlation coefficient or cluster size is large. A cluster-randomised trial remains more efficient than the optimised stepped wedge trial when the intracluster correlation coefficient or cluster size is small. A cluster-randomised trial with baseline observations always requires a larger sample size than the optimised stepped wedge trial. The hybrid design can always give an equally or more efficient design, but will be at most 5% more efficient. We provide a strategy for selecting a design if the optimal number of sequences is unfeasible. For a non-optimal number of sequences, the sample size may be reduced by allowing a proportion of observations before the first or after the final sequence has switched. Conclusion The standard stepped wedge trial is inefficient. To reduce sample sizes when a hybrid design is unfeasible, stepped wedge trial designs should have no observations before the first sequence switches or after the final sequence switches.

Parallel/Vector Integration Methods for Dynamical Astronomy

NASA Astrophysics Data System (ADS)

Fukushima, Toshio

1999-01-01

This paper reviews three recent works on the numerical methods to integrate ordinary differential equations (ODE), which are specially designed for parallel, vector, and/or multi-processor-unit(PU) computers. The first is the Picard-Chebyshev method (Fukushima, 1997a). It obtains a global solution of ODE in the form of Chebyshev polynomial of large (> 1000) degree by applying the Picard iteration repeatedly. The iteration converges for smooth problems and/or perturbed dynamics. The method runs around 100-1000 times faster in the vector mode than in the scalar mode of a certain computer with vector processors (Fukushima, 1997b). The second is a parallelization of a symplectic integrator (Saha et al., 1997). It regards the implicit midpoint rules covering thousands of timesteps as large-scale nonlinear equations and solves them by the fixed-point iteration. The method is applicable to Hamiltonian systems and is expected to lead an acceleration factor of around 50 in parallel computers with more than 1000 PUs. The last is a parallelization of the extrapolation method (Ito and Fukushima, 1997). It performs trial integrations in parallel. Also the trial integrations are further accelerated by balancing computational load among PUs by the technique of folding. The method is all-purpose and achieves an acceleration factor of around 3.5 by using several PUs. Finally, we give a perspective on the parallelization of some implicit integrators which require multiple corrections in solving implicit formulas like the implicit Hermitian integrators (Makino and Aarseth, 1992), (Hut et al., 1995) or the implicit symmetric multistep methods (Fukushima, 1998), (Fukushima, 1999).

A comparison of two treatments for childhood apraxia of speech: methods and treatment protocol for a parallel group randomised control trial

PubMed Central

2012-01-01

Background Childhood Apraxia of Speech is an impairment of speech motor planning that manifests as difficulty producing the sounds (articulation) and melody (prosody) of speech. These difficulties may persist through life and are detrimental to academic, social, and vocational development. A number of published single subject and case series studies of speech treatments are available. There are currently no randomised control trials or other well designed group trials available to guide clinical practice. Methods/Design A parallel group, fixed size randomised control trial will be conducted in Sydney, Australia to determine the efficacy of two treatments for Childhood Apraxia of Speech: 1) Rapid Syllable Transition Treatment and the 2) Nuffield Dyspraxia Programme – Third edition. Eligible children will be English speaking, aged 4–12 years with a diagnosis of suspected CAS, normal or adjusted hearing and vision, and no comprehension difficulties or other developmental diagnoses. At least 20 children will be randomised to receive one of the two treatments in parallel. Treatments will be delivered by trained and supervised speech pathology clinicians using operationalised manuals. Treatment will be administered in 1-hour sessions, 4 times per week for 3 weeks. The primary outcomes are speech sound and prosodic accuracy on a customised 292 item probe and the Diagnostic Evaluation of Articulation and Phonology inconsistency subtest administered prior to treatment and 1 week, 1 month and 4 months post-treatment. All post assessments will be completed by blinded assessors. Our hypotheses are: 1) treatment effects at 1 week post will be similar for both treatments, 2) maintenance of treatment effects at 1 and 4 months post will be greater for Rapid Syllable Transition Treatment than Nuffield Dyspraxia Programme treatment, and 3) generalisation of treatment effects to untrained related speech behaviours will be greater for Rapid Syllable Transition Treatment than Nuffield Dyspraxia Programme treatment. This protocol was approved by the Human Research Ethics Committee, University of Sydney (#12924). Discussion This will be the first randomised control trial to test treatment for CAS. It will be valuable for clinical decision-making and providing evidence-based services for children with CAS. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12612000744853 PMID:22863021

Pattern Separation and Goal-Directed Behavior in the Aged Canine

ERIC Educational Resources Information Center

Snigdha, Shikha; Yassa, Michael A.; deRivera, Christina; Milgram, Norton W.; Cotman, Carl W.

2017-01-01

The pattern separation task has recently emerged as a behavioral model of hippocampus function and has been used in several pharmaceutical trials. The canine is a useful model to evaluate a multitude of hippocampal-dependent cognitive tasks that parallel those in humans. Thus, this study was designed to evaluate the suitability of pattern…

Pigeons acquire multiple categories in parallel via associative learning: A parallel to human word learning?

PubMed Central

Wasserman, Edward A.; Brooks, Daniel I.; McMurray, Bob

2014-01-01

Might there be parallels between category learning in animals and word learning in children? To examine this possibility, we devised a new associative learning technique for teaching pigeons to sort 128 photographs of objects into 16 human language categories. We found that pigeons learned all 16 categories in parallel, they perceived the perceptual coherence of the different object categories, and they generalized their categorization behavior to novel photographs from the training categories. More detailed analyses of the factors that predict trial-by-trial learning implicated a number of factors that may shape learning. First, we found considerable trial-by-trial dependency of pigeons’ categorization responses, consistent with several recent studies that invoke this dependency to claim that humans acquire words via symbolic or inferential mechanisms; this finding suggests that such dependencies may also arise in associative systems. Second, our trial-by-trial analyses divulged seemingly irrelevant aspects of the categorization task, like the spatial location of the report responses, which influenced learning. Third, those trial-by-trial analyses also supported the possibility that learning may be determined both by strengthening correct stimulus-response associations and by weakening incorrect stimulus-response associations. The parallel between all these findings and important aspects of human word learning suggests that associative learning mechanisms may play a much stronger part in complex human behavior than is commonly believed. PMID:25497520

Cognitive bias modification for social anxiety in adults who stutter: a feasibility study of a randomised controlled trial

PubMed Central

Gascoine, Sally; Carroll, Amy; Humby, Kate; Kingston, Mary; Shepstone, Lee; Risebro, Helen; Mackintosh, Bundy; Thompson, Tammy Davidson; Hodgekins, Jo

2017-01-01

Objective To determine the feasibility and acceptability of a computerised treatment for social anxiety disorder for adults who stutter including identification of recruitment, retention and completion rates, large cost drivers and selection of most appropriate outcome measure(s) to inform the design of a future definitive trial. Design Two-group parallel design (treatment vs placebo), double-blinded feasibility study. Participants: 31 adults who stutter. Intervention Attention training via an online probe detection task in which the stimuli were images of faces displaying neutral and disgusted expressions. Main outcome measures Psychological measures: Structured Clinical Interview Global Assessment of Functioning score; Liebowitz Social Anxiety Scale; Social Phobia and Anxiety Inventory; State-Trait Anxiety Inventory; Unhelpful Thoughts and Beliefs about Stuttering. Speech fluency: percent syllables stuttered. Economic evaluation: resource use questionnaire; EuroQol three-dimension questionnaire. Acceptability: Likert Scale questionnaire of experience of trial, acceptability of the intervention and randomisation procedure. Results Feasibility of recruitment strategy was demonstrated. Participant feedback indicated that the intervention and definitive trial, including randomisation, would be acceptable to adults who stutter. Of the 31 participants who were randomised, 25 provided data at all three data collection points. Conclusions The feasibility study informed components of the intervention. Modifications to the design are needed before a definitive trial can be undertaken. Trial registration number I SRCTN55065978; Post-results. PMID:29061602

A review of evidence of health benefit from artificial neural networks in medical intervention.

PubMed

Lisboa, P J G

2002-01-01

The purpose of this review is to assess the evidence of healthcare benefits involving the application of artificial neural networks to the clinical functions of diagnosis, prognosis and survival analysis, in the medical domains of oncology, critical care and cardiovascular medicine. The primary source of publications is PUBMED listings under Randomised Controlled Trials and Clinical Trials. The rĵle of neural networks is introduced within the context of advances in medical decision support arising from parallel developments in statistics and artificial intelligence. This is followed by a survey of published Randomised Controlled Trials and Clinical Trials, leading to recommendations for good practice in the design and evaluation of neural networks for use in medical intervention.

Placebo Response in Repetitive Transcranial Magnetic Stimulation Trials of Treatment of Auditory Hallucinations in Schizophrenia: A Meta-Analysis

PubMed Central

Dollfus, Sonia; Lecardeur, Laurent; Morello, Rémy; Etard, Olivier

2016-01-01

Several meta-analyses have assessed the response of patients with schizophrenia with auditory verbal hallucinations (AVH) to treatment with repetitive transcranial magnetic stimulation (rTMS); however, the placebo response has never been explored. Typically observed in a therapeutic trial, the placebo effect may have a major influence on the effectiveness of rTMS. The purpose of this meta-analysis is to evaluate the magnitude of the placebo effect observed in controlled studies of rTMS treatment of AVH, and to determine factors that can impact the magnitude of this placebo effect, such as study design considerations and the type of sham used. The study included twenty-one articles concerning 303 patients treated by sham rTMS. A meta-analytic method was applied to obtain a combined, weighted effect size, Hedges’s g. The mean weighted effect size of the placebo effect across these 21 studies was 0.29 (P < .001). Comparison of the parallel and crossover studies revealed distinct results for each study design; placebo has a significant effect size in the 13 parallel studies (g = 0.44, P < 10−4), but not in the 8 crossover studies (g = 0.06, P = .52). In meta-analysis of the 13 parallel studies, the 45° position coil showed the highest effect size. Our results demonstrate that placebo effect should be considered a major source of bias in the assessment of rTMS efficacy. These results fundamentally inform the design of further controlled studies, particularly with respect to studies of rTMS treatment in psychiatry. PMID:26089351

Reference datasets for bioequivalence trials in a two-group parallel design.

PubMed

Fuglsang, Anders; Schütz, Helmut; Labes, Detlew

2015-03-01

In order to help companies qualify and validate the software used to evaluate bioequivalence trials with two parallel treatment groups, this work aims to define datasets with known results. This paper puts a total 11 datasets into the public domain along with proposed consensus obtained via evaluations from six different software packages (R, SAS, WinNonlin, OpenOffice Calc, Kinetica, EquivTest). Insofar as possible, datasets were evaluated with and without the assumption of equal variances for the construction of a 90% confidence interval. Not all software packages provide functionality for the assumption of unequal variances (EquivTest, Kinetica), and not all packages can handle datasets with more than 1000 subjects per group (WinNonlin). Where results could be obtained across all packages, one showed questionable results when datasets contained unequal group sizes (Kinetica). A proposal is made for the results that should be used as validation targets.

UK Dermatology Clinical Trials Network’s STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence. Methods The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis). Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. Trial registration Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14. PMID:22540770

Using re-randomization to increase the recruitment rate in clinical trials - an assessment of three clinical areas.

PubMed

Kahan, Brennan C

2016-12-13

Patient recruitment in clinical trials is often challenging, and as a result, many trials are stopped early due to insufficient recruitment. The re-randomization design allows patients to be re-enrolled and re-randomized for each new treatment episode that they experience. Because it allows multiple enrollments for each patient, this design has been proposed as a way to increase the recruitment rate in clinical trials. However, it is unknown to what extent recruitment could be increased in practice. We modelled the expected recruitment rate for parallel-group and re-randomization trials in different settings based on estimates from real trials and datasets. We considered three clinical areas: in vitro fertilization, severe asthma exacerbations, and acute sickle cell pain crises. We compared the two designs in terms of the expected time to complete recruitment, and the sample size recruited over a fixed recruitment period. Across the different scenarios we considered, we estimated that re-randomization could reduce the expected time to complete recruitment by between 4 and 22 months (relative reductions of 19% and 45%), or increase the sample size recruited over a fixed recruitment period by between 29% and 171%. Re-randomization can increase recruitment most for trials with a short follow-up period, a long trial recruitment duration, and patients with high rates of treatment episodes. Re-randomization has the potential to increase the recruitment rate in certain settings, and could lead to quicker and more efficient trials in these scenarios.

A Randomized Controlled Trial of Trauma-Focused Cognitive Behavioral Therapy for Sexually Exploited, War-Affected Congolese Girls

ERIC Educational Resources Information Center

O'Callaghan, Paul; McMullen, John; Shannon, Ciaran; Rafferty, Harry; Black, Alastair

2013-01-01

Objective: To assess the efficacy of trauma-focused cognitive behavioral therapy (TF-CBT) delivered by nonclinical facilitators in reducing posttraumatic stress, depression, and anxiety and conduct problems and increasing prosocial behavior in a group of war-affected, sexually exploited girls in a single-blind, parallel-design, randomized,…

UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial.

PubMed

Craig, Fiona F; Thomas, Kim S; Mitchell, Eleanor J; Williams, Hywel C; Norrie, John; Mason, James M; Ormerod, Anthony D

2012-04-28

Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis).Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14.

Systematic review of universal school-based resilience interventions targeting adolescent tobacco, alcohol or illicit drug use: review protocol

PubMed Central

Hodder, Rebecca Kate; Freund, Megan; Wolfenden, Luke; Bowman, Jenny; Gillham, Karen; Dray, Julia; Wiggers, John

2014-01-01

Introduction Tobacco, alcohol and illicit drug use contribute significantly to global rates of morbidity and mortality. Despite evidence suggesting interventions designed to increase adolescent resilience may represent a means of reducing adolescent substance use, and schools providing a key opportunity to implement such interventions, existing systematic reviews assessing the effectiveness of school-based interventions targeting adolescent substance use have not examined this potential. Methods and analysis The aim of the systematic review is to determine whether universal interventions focused on enhancing the resilience of adolescents are effective in reducing adolescent substance use. Eligible studies will: include participants 5–18 years of age; report tobacco use, alcohol consumption or illicit drug use as outcomes; and implement a school-based intervention designed to promote internal (eg, self-esteem) and external (eg, school connectedness) resilience factors. Eligible study designs include randomised controlled trials, cluster randomised controlled trials, staggered enrolment trials, stepped wedged trials, quasi-randomised trials, quasi-experimental trials, time series/interrupted time-series trials, preference trials, regression discontinuity trials and natural experiment studies with a parallel control group. A search strategy including criteria for participants, study design, outcome, setting and intervention will be implemented in various electronic databases and information sources. Two reviewers will independently screen studies to assess eligibility, as well as extract data from, and assess risk of bias of included studies. A third reviewer will resolve any discrepancies. Attempts will be made to quantify trial effects by meta-analysis. Binary outcomes will be pooled and effect size reported using ORs. For continuous data, effect size of trials will be reported using a mean difference where trial outcomes report the same outcome using a consistent measure, or standardised mean difference where trials report a comparable measure. Otherwise, trial outcomes will be described narratively. Dissemination Review findings will be disseminated via peer-reviewed journals and conferences. PMID:24861548

Rationale and design of the SMaRT trial: A randomised, prospective, parallel, non-blinded, one-centre trial to evaluate the use of magnetic resonance imaging in acute setting in patients presenting with suspected scaphoid fracture.

PubMed

Rua, Tiago; Vijayanathan, Sanjay; Parkin, David; Goh, Vicky; McCrone, Paul; Gidwani, Sam

2018-04-01

Background Wrist injury is a common presentation to the Emergency Department in the United Kingdom. Among these injuries, the scaphoid is the most common fractured carpal bone. However, given the limited ability of conventional radiography to accurately diagnose a suspected scaphoid fracture on presentation, its diagnosis and management remain challenging. Despite the vast clinical evidence supporting the superior accuracy of magnetic resonance imaging, there is little to no evidence around the real-world clinical and economic impact of immediate magnetic resonance imaging in the management of suspected scaphoid fractures. Methods Review of design and implementation challenges associated with the identification and subsequent recruitment of eligible patients, implementation of a novel clinical pathway in an acute setting, rationale behind the primary and secondary outcomes selected and measurement of the primary outcome. Results The Scaphoid Magnetic Resonance Imaging in Trauma trial is a single-site prospective, randomised, non-blinded, parallel design trial that aims to evaluate the use of immediate magnetic resonance imaging in the management of patients presenting to the acute setting with suspected scaphoid fractures. The primary outcome is the total 3-month cost per patient associated with the diagnosis and treatment of suspected scaphoid fractures. It is hypothesised that the immediate use of magnetic resonance imaging, a more accurate but expensive imaging modality, in patients with negative findings in the initial four-view radiography, will reduce the overall National Health Service costs by promoting definitive care and avoiding unnecessary diagnostic and treatment procedures. Other rationale design considerations in the recruitment, randomisation, data acquisition and intervention implementation are also discussed. Several of these challenges derive from real-world operational issues associated with the provision of magnetic resonance imaging in an intrinsically complex acute setting. Staff engagement during the trial's planning phase, combined with an extensive training programme rolled out prior to the trial's launch, were essential to raise staff awareness and engagement. Given the acute nature of the clinical condition, the latter was deemed essential as the eligibility assessment, recruitment, randomisation and treatment allocation processes all need to happen in a very tight time frame. Limitations Findings from the Scaphoid Magnetic Resonance Imaging in Trauma trial might not be generalisable to other National Health Service hospitals, foreign healthcare systems nor patient presentations outside normal magnetic resonance imaging working hours. Conclusion The Scaphoid Magnetic Resonance Imaging in Trauma trial was designed to evaluate the costs, patient satisfaction and clinical outcomes around the management of suspected scaphoid fractures and ultimately provide solid evidence on which to base the United Kingdom and international clinical practice. This article discusses the steps considered in the design of this novel trial, with particular emphasis on the issues and lessons learned during the planning and implementation stages.

Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study.

PubMed

Tsutsui, Hiroyuki; Momomura, Shinichi; Saito, Yoshihiko; Ito, Hiroshi; Yamamoto, Kazuhiro; Ohishi, Tomomi; Okino, Naoko; Guo, Weinong

2017-09-01

The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Statistical Approaches to Adjusting Weights for Dependent Arms in Network Meta-analysis.

PubMed

Su, Yu-Xuan; Tu, Yu-Kang

2018-05-22

Network meta-analysis compares multiple treatments in terms of their efficacy and harm by including evidence from randomized controlled trials. Most clinical trials use parallel design, where patients are randomly allocated to different treatments and receive only one treatment. However, some trials use within person designs such as split-body, split-mouth and cross-over designs, where each patient may receive more than one treatment. Data from treatment arms within these trials are no longer independent, so the correlations between dependent arms need to be accounted for within the statistical analyses. Ignoring these correlations may result in incorrect conclusions. The main objective of this study is to develop statistical approaches to adjusting weights for dependent arms within special design trials. In this study, we demonstrate the following three approaches: the data augmentation approach, the adjusting variance approach, and the reducing weight approach. These three methods could be perfectly applied in current statistic tools such as R and STATA. An example of periodontal regeneration was used to demonstrate how these approaches could be undertaken and implemented within statistical software packages, and to compare results from different approaches. The adjusting variance approach can be implemented within the network package in STATA, while reducing weight approach requires computer software programming to set up the within-study variance-covariance matrix. This article is protected by copyright. All rights reserved.

The use of systematic reviews in the planning, design and conduct of randomised trials: a retrospective cohort of NIHR HTA funded trials.

PubMed

Jones, Ashley P; Conroy, Elizabeth; Williamson, Paula R; Clarke, Mike; Gamble, Carrol

2013-03-25

A systematic review, with or without a meta-analysis, should be undertaken to determine if the research question of interest has already been answered before a new trial begins. There has been limited research on how systematic reviews are used within the design of new trials, the aims of this study were to investigate how systematic reviews of earlier trials are used in the planning and design of new randomised trials. Documentation from the application process for all randomised trials funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) between 2006 and 2008 were obtained. This included the: commissioning brief (if appropriate), outline application, minutes of the Board meeting in which the outline application was discussed, full application, detailed project description, referee comments, investigator response to referee comments, Board minutes on the full application and the trial protocol. Data were extracted on references to systematic reviews and how any such reviews had been used in the planning and design of the trial. 50 randomised trials were funded by NIHR HTA during this period and documentation was available for 48 of these. The cohort was predominately individually randomised parallel trials aiming to detect superiority between two treatments for a single primary outcome. 37 trials (77.1%) referenced a systematic review within the application and 20 of these (i.e. 41.7% of the total) used information contained in the systematic review in the design or planning of the new trial. The main areas in which systematic reviews were used were in the selection or definition of an outcome to be measured in the trial (7 of 37, 18.9%), the sample size calculation (7, 18.9%), the duration of follow up (8, 21.6%) and the approach to describing adverse events (9, 24.3%). Boards did not comment on the presence/absence or use of systematic reviews in any application. Systematic reviews were referenced in most funded applications but just over half of these used the review to inform the design. There is an expectation from funders that applicants will use a systematic review to justify the need for a new trial but no expectation regarding further use of a systematic review to aid planning and design of the trial. Guidelines for applicants and funders should be developed to promote the use of systematic reviews in the design and planning of randomised trials, to optimise delivery of new studies informed by the most up-to-date evidence base and to minimise waste in research.

Adaptive graph-based multiple testing procedures

PubMed Central

Klinglmueller, Florian; Posch, Martin; Koenig, Franz

2016-01-01

Multiple testing procedures defined by directed, weighted graphs have recently been proposed as an intuitive visual tool for constructing multiple testing strategies that reflect the often complex contextual relations between hypotheses in clinical trials. Many well-known sequentially rejective tests, such as (parallel) gatekeeping tests or hierarchical testing procedures are special cases of the graph based tests. We generalize these graph-based multiple testing procedures to adaptive trial designs with an interim analysis. These designs permit mid-trial design modifications based on unblinded interim data as well as external information, while providing strong family wise error rate control. To maintain the familywise error rate, it is not required to prespecify the adaption rule in detail. Because the adaptive test does not require knowledge of the multivariate distribution of test statistics, it is applicable in a wide range of scenarios including trials with multiple treatment comparisons, endpoints or subgroups, or combinations thereof. Examples of adaptations are dropping of treatment arms, selection of subpopulations, and sample size reassessment. If, in the interim analysis, it is decided to continue the trial as planned, the adaptive test reduces to the originally planned multiple testing procedure. Only if adaptations are actually implemented, an adjusted test needs to be applied. The procedure is illustrated with a case study and its operating characteristics are investigated by simulations. PMID:25319733

Effects of Study Design and Allocation on participant behaviour--ESDA: study protocol for a randomized controlled trial.

PubMed

Kypri, Kypros; McCambridge, Jim; Wilson, Amanda; Attia, John; Sheeran, Paschal; Bowe, Steve; Vater, Tina

2011-02-14

What study participants think about the nature of a study has been hypothesised to affect subsequent behaviour and to potentially bias study findings. In this trial we examine the impact of awareness of study design and allocation on participant drinking behaviour. A three-arm parallel group randomised controlled trial design will be used. All recruitment, screening, randomisation, and follow-up will be conducted on-line among university students. Participants who indicate a hazardous level of alcohol consumption will be randomly assigned to one of three groups. Group A will be informed their drinking will be assessed at baseline and again in one month (as in a cohort study design). Group B will be told the study is an intervention trial and they are in the control group. Group C will be told the study is an intervention trial and they are in the intervention group. All will receive exactly the same brief educational material to read. After one month, alcohol intake for the past 4 weeks will be assessed. The experimental manipulations address subtle and previously unexplored ways in which participant behaviour may be unwittingly influenced by standard practice in trials. Given the necessity of relying on self-reported outcome, it will not be possible to distinguish true behaviour change from reporting artefact. This does not matter in the present study, as any effects of awareness of study design or allocation involve bias that is not well understood. There has been little research on awareness effects, and our outcomes will provide an indication of the possible value of further studies of this type and inform hypothesis generation. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000846022.

University Students' Attainment and Perceptions of Computer Delivered Assessment; A Comparison between Computer-Based and Traditional Tests in a "High-Stakes" Examination

ERIC Educational Resources Information Center

Escudier, M. P.; Newton, T. J.; Cox, M. J.; Reynolds, P. A.; Odell, E. W.

2011-01-01

This study compared higher education dental undergraduate student performance in online assessments with performance in traditional paper-based tests and investigated students' perceptions of the fairness and acceptability of online tests, and showed performance to be comparable. The project design involved two parallel cross-over trials, one in…

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care

PubMed Central

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-01-01

Objectives To determine the feasibility of a randomised controlled trial of ‘leave on’ emollients for children with eczema. Design Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. Setting General practices in the UK. Participants Children with eczema aged 1 month to <5 years. Outcome measures Primary outcome—proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes—participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Interventions Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. Results 197 children were recruited—107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic (‘app’) form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. Conclusions It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. Trial registration number ISRCTN21828118/EudraCT2013-003001-26. PMID:27852708

Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting

PubMed Central

Wiangkham, Taweewat; Duda, Joan; Haque, M Sayeed; Price, Jonathan; Rushton, Alison

2016-01-01

Introduction Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Methods and analysis Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3–4 physiotherapists) and a focus group (n=6–8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). Ethics and dissemination This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). Trial registration number ISRCTN84528320. PMID:27412105

The next generation of sepsis clinical trial designs: what is next after the demise of recombinant human activated protein C?*.

PubMed

Opal, Steven M; Dellinger, R Phillip; Vincent, Jean-Louis; Masur, Henry; Angus, Derek C

2014-07-01

The developmental pipeline for novel therapeutics to treat sepsis has diminished to a trickle compared to previous years of sepsis research. While enormous strides have been made in understanding the basic molecular mechanisms that underlie the pathophysiology of sepsis, a long list of novel agents have now been tested in clinical trials without a single immunomodulating therapy showing consistent benefit. The only antisepsis agent to successfully complete a phase III clinical trial was human recumbent activated protein C. This drug was taken off the market after a follow-up placebo-controlled trial (human recombinant activated Protein C Worldwide Evaluation of Severe Sepsis and septic Shock [PROWESS SHOCK]) failed to replicate the favorable results of the initial registration trial performed ten years earlier. We must critically reevaluate our basic approach to the preclinical and clinical evaluation of new sepsis therapies. We selected the major clinical studies that investigated interventional trials with novel therapies to treat sepsis over the last 30 years. Phase II and phase III trials investigating new treatments for sepsis and editorials and critiques of these studies. Selected manuscripts and clinical study reports were analyzed from sepsis trials. Specific shortcomings and potential pit falls in preclinical evaluation and clinical study design and analysis were reviewed and synthesized. After review and discussion, a series of 12 recommendations were generated with suggestions to guide future studies with new treatments for sepsis. We need to improve our ability to define appropriate molecular targets for preclinical development and develop better methods to determine the clinical value of novel sepsis agents. Clinical trials must have realistic sample sizes and meaningful endpoints. Biomarker-driven studies should be considered to categorize specific "at risk" populations most likely to benefit from a new treatment. Innovations in clinical trial design such as parallel crossover design, alternative endpoints, or adaptive trials should be pursued to improve the outlook for future interventional trials in sepsis.

Critical appraisal of clinical trials in multiple system atrophy: Toward better quality.

PubMed

Castro Caldas, Ana; Levin, Johannes; Djaldetti, Ruth; Rascol, Olivier; Wenning, Gregor; Ferreira, Joaquim J

2017-10-01

Multiple system atrophy (MSA) is a rare neurodegenerative disease of undetermined cause. Although many clinical trials have been conducted, there is still no treatment that cures the disease or slows its progression. We sought to assess the clinical trials, methodology, and quality of reporting of clinical trails conducted in MSA patients. We conducted a systematic review of all trials with at least 1 MSA patient subject to any pharmacological/nonpharmacological interventions. Two independent reviewers evaluated the methodological characteristics and quality of reporting of trials. A total of 60 clinical trials were identified, including 1375 MSA patients. Of the trials, 51% (n = 31) were single-arm studies. A total of 28% (n = 17) had a parallel design, half of which (n = 13) were placebo controlled. Of the studies, 8 (13.3%) were conducted in a multicenter setting, 3 of which were responsible for 49.3% (n = 678) of the total included MSA patients. The description of primary outcomes was unclear in 60% (n = 40) of trials. Only 10 (16.7%) clinical trials clearly described the randomization process. Blinding of the participants, personnel, and outcome assessments were at high risk of bias in the majority of studies. The number of dropouts/withdrawals was high (n = 326, 23.4% among the included patients). Overall, the design and quality of reporting of the reviewed studies is unsatisfactory. The most frequent clinical trials were small and single centered. Inadequate reporting was related to the information on the randomization process, sequence generation, allocation concealment, blinding of participants, and sample size calculations. Although improved during the recent years, methodological quality and trial design need to be optimized to generate more informative results. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

It’s Only a Little Ice

PubMed Central

2012-01-01

First, parallels are drawn between the conduct of clinical trials and a few events in history that share a management style known as “top-down” management or a hierarchal decision-making process. The author suggests that this process isolates investigative sites from sponsors and contributes to the failure of clinical trials. Trial design, patient recruitment, site selection, the use of electronic data devices, and enrollment timelines are examined in greater detail. Suggestions for a more open or shared process are offered, with the belief that fewer trials might fail and fewer questions might remain in the case of those that do. Next, in the companion commentary, some of the problems arising in drug development and clinical trials are mentioned along with a partial listing of solution providers. An outline of circumstances involved in the decision-making process in drug development are presented along with some factors leading to decreased signal detection. PMID:22468240

Reporting discrepancies between the ClinicalTrials.gov results database and peer-reviewed publications.

PubMed

Hartung, Daniel M; Zarin, Deborah A; Guise, Jeanne-Marie; McDonagh, Marian; Paynter, Robin; Helfand, Mark

2014-04-01

ClinicalTrials.gov requires reporting of result summaries for many drug and device trials. To evaluate the consistency of reporting of trials that are registered in the ClinicalTrials.gov results database and published in the literature. ClinicalTrials.gov results database and matched publications identified through ClinicalTrials.gov and a manual search of 2 electronic databases. 10% random sample of phase 3 or 4 trials with results in the ClinicalTrials.gov results database, completed before 1 January 2009, with 2 or more groups. One reviewer extracted data about trial design and results from the results database and matching publications. A subsample was independently verified. Of 110 trials with results, most were industry-sponsored, parallel-design drug studies. The most common inconsistency was the number of secondary outcome measures reported (80%). Sixteen trials (15%) reported the primary outcome description inconsistently, and 22 (20%) reported the primary outcome value inconsistently. Thirty-eight trials inconsistently reported the number of individuals with a serious adverse event (SAE); of these, 33 (87%) reported more SAEs in ClinicalTrials.gov. Among the 84 trials that reported SAEs in ClinicalTrials.gov, 11 publications did not mention SAEs, 5 reported them as zero or not occurring, and 21 reported a different number of SAEs. Among 29 trials that reported deaths in ClinicalTrials.gov, 28% differed from the matched publication. Small sample that included earliest results posted to the database. Reporting discrepancies between the ClinicalTrials.gov results database and matching publications are common. Which source contains the more accurate account of results is unclear, although ClinicalTrials.gov may provide a more comprehensive description of adverse events than the publication. Agency for Healthcare Research and Quality.

Current globalization of drug interventional clinical trials: characteristics and associated factors, 2011-2013.

PubMed

Jeong, Sohyun; Sohn, Minji; Kim, Jae Hyun; Ko, Minoh; Seo, Hee-Won; Song, Yun-Kyoung; Choi, Boyoon; Han, Nayoung; Na, Han-Sung; Lee, Jong Gu; Kim, In-Wha; Oh, Jung Mi; Lee, Euni

2017-06-21

Clinical trial globalization is a major trend for industry-sponsored clinical trials. There has been a shift in clinical trial sites towards emerging regions of Eastern Europe, Latin America, Asia, the Middle East, and Africa. Our study objectives were to evaluate the current characteristics of clinical trials and to find out the associated multiple factors which could explain clinical trial globalization and its implications for clinical trial globalization in 2011-2013. The data elements of "phase," "recruitment status," "type of sponsor," "age groups," and "design of trial" from 30 countries were extracted from the ClinicalTrials.gov website. Ten continental representative countries including the USA were selected and the design elements were compared to those of the USA. Factors associated with trial site distribution were chosen for a multilinear regression analysis. The USA, Germany, France, Canada, and United Kingdom were the "top five" countries which frequently held clinical trials. The design elements from nine continental representative countries were quite different from those of the USA; phase 1 trials were more prevalent in India (OR 1.517, p < 0.001) while phase 3 trials were much more prevalent in all nine representative countries than in the USA. A larger number of "child" age group trials was performed in Poland (OR 1.852, p < 0.001), Israel (OR 1.546, p = 0.005), and South Africa (OR 1.963, p < 0.001) than in the USA. Multivariate analysis showed that health care expenditure per capita, Economic Freedom Index, Human Capital Index, and Intellectual Property Rights Index could explain the variance of regional distribution of clinical trials by 63.6%. The globalization of clinical trials in the emerging regions of Asia, South Africa, and Eastern Europe developed in parallel with the factors of economic drive, population for recruitment, and regulatory constraints.

The quality of reporting in cluster randomised crossover trials: proposal for reporting items and an assessment of reporting quality.

PubMed

Arnup, Sarah J; Forbes, Andrew B; Kahan, Brennan C; Morgan, Katy E; McKenzie, Joanne E

2016-12-06

The cluster randomised crossover (CRXO) design is gaining popularity in trial settings where individual randomisation or parallel group cluster randomisation is not feasible or practical. Our aim is to stimulate discussion on the content of a reporting guideline for CRXO trials and to assess the reporting quality of published CRXO trials. We undertook a systematic review of CRXO trials. Searches of MEDLINE, EMBASE, and CINAHL Plus as well as citation searches of CRXO methodological articles were conducted to December 2014. Reporting quality was assessed against both modified items from 2010 CONSORT and 2012 cluster trials extension and other proposed quality measures. Of the 3425 records identified through database searching, 83 trials met the inclusion criteria. Trials were infrequently identified as "cluster randomis(z)ed crossover" in title (n = 7, 8%) or abstract (n = 21, 25%), and a rationale for the design was infrequently provided (n = 20, 24%). Design parameters such as the number of clusters and number of periods were well reported. Discussion of carryover took place in only 17 trials (20%). Sample size methods were only reported in 58% (n = 48) of trials. A range of approaches were used to report baseline characteristics. The analysis method was not adequately reported in 23% (n = 19) of trials. The observed within-cluster within-period intracluster correlation and within-cluster between-period intracluster correlation for the primary outcome data were not reported in any trial. The potential for selection, performance, and detection bias could be evaluated in 30%, 81%, and 70% of trials, respectively. There is a clear need to improve the quality of reporting in CRXO trials. Given the unique features of a CRXO trial, it is important to develop a CONSORT extension. Consensus amongst trialists on the content of such a guideline is essential.

The efficacy and safety of Fufangdanshen tablets (Radix Salviae miltiorrhizae formula tablets) for mild to moderate vascular dementia: a study protocol for a randomized controlled trial.

PubMed

Tian, Jinzhou; Shi, Jing; Wei, Mingqing; Qin, Renan; Ni, Jingnian; Zhang, Xuekai; Li, Ting; Wang, Yongyan

2016-06-08

Vascular dementia (VaD) is the second most common subtype of dementia after Alzheimer's disease (AD). Currently, there are no medications approved for treating patients with VaD. Fufangdanshen (FFDS) tablets (Radix Salviae miltiorrhizae formula tablets) are a traditional Chinese medicine that has been reported to improve memory. However, the existing evidence for FFDS tablets in clinical practice derives from methodologically flawed studies. To further investigate the safety, tolerability, and efficacy of FFDS tables in the treatment of mild to moderate VaD, we designed and reported the methodology for a 24-week randomized, double-blind, parallel, multicenter study. This ongoing study is a double-blind, randomized, parallel placebo-controlled trial. A total of 240 patients with mild to moderate VaD will be enrolled. After a 2-week run-in period, the eligible patients will be randomized to receive either three FFDS or placebo tablets three times per day for 24 weeks, with a follow-up 12 weeks after the last treatment. The primary efficacy measurement will be the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Clinician Interview-Based Impression of Change (CIBIC-plus). The secondary efficacy measurements will include the Mini Mental State Examination (MMSE) and activities of daily living (ADL). Adverse events will also be reported. This randomized trial will be the first rigorous study on the efficacy and safety of FFDS tablets for treating cognitive symptoms in patients with VaD using a rational design. ClinicalTrials.gov: NCT01761227 . Registered on 2 January 2013.

Statistical controversies in clinical research: basket trials, umbrella trials, and other master protocols: a review and examples

PubMed Central

Renfro, L. A.; Sargent, D. J.

2017-01-01

Abstract In recent years, cancers once viewed as relatively homogeneous in terms of organ location and treatment strategy are now better understood to be increasingly heterogeneous across biomarker and genetically defined patient subgroups. This has produced a shift toward development of biomarker-targeted agents during a time when funding for cancer research has been limited; as a result, the need for improved operational efficiency in studying many agent-and-target combinations in parallel has emerged. Platform trials, basket trials, and umbrella trials are new approaches to clinical research driven by this need for enhanced efficiency in the modern era of increasingly specific cancer subpopulations and decreased resources to study treatments for individual cancer subtypes in a traditional way. In this review, we provide an overview of these new types of clinical trial designs, including discussions of motivation for their use, recommended terminology, examples, and challenges encountered in their application. PMID:28177494

Screening uptake rates and the clinical and cost effectiveness of screening for gestational diabetes mellitus in primary versus secondary care: study protocol for a randomised controlled trial

PubMed Central

2014-01-01

Background The risks associated with gestational diabetes mellitus (GDM) are well recognized, and there is increasing evidence to support treatment of the condition. However, clear guidance on the ideal approach to screening for GDM is lacking. Professional groups continue to debate whether selective screening (based on risk factors) or universal screening is the most appropriate approach. Additionally, there is ongoing debate about what levels of glucose abnormalities during pregnancy respond best to treatment and which maternal and neonatal outcomes benefit most from treatment. Furthermore, the implications of possible screening options on health care costs are not well established. In response to this uncertainty there have been repeated calls for well-designed, randomised trials to determine the efficacy of screening, diagnosis, and management plans for GDM. We describe a randomised controlled trial to investigate screening uptake rates and the clinical and cost effectiveness of screening in primary versus secondary care settings. Methods/Design This will be an unblinded, two-group, parallel randomised controlled trial (RCT). The target population includes 784 women presenting for their first antenatal visit at 12 to 18 weeks gestation at two hospitals in the west of Ireland: Galway University Hospital and Mayo General Hospital. Participants will be offered universal screening for GDM at 24 to 28 weeks gestation in either primary care (n = 392) or secondary care (n = 392) locations. The primary outcome variable is the uptake rate of screening. Secondary outcomes include indicators of clinical effectiveness of screening at each screening site (primary and secondary) including gestational week at time of screening, time to access antenatal diabetes services for women diagnosed with GDM, and pregnancy and neonatal outcomes for women with GDM. In addition, parallel economic and qualitative evaluations will be conducted. The trial will cover the period from the woman’s first hospital antenatal visit at 12 to 18 weeks gestation, until the completion of the pregnancy. Trial registration Current Controlled Trials: ISRCTN02232125 PMID:24438478

Health benefit for the child and promotion of the common good were the two most important reasons for participation in the FinIP vaccine trial.

PubMed

Nieminen, Heta; Syrjänen, Ritva K; Puumalainen, Taneli; Sirén, Päivi; Palmu, Arto A

2015-07-17

The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was a nationwide cluster-randomised double-blind trial designed to demonstrate the effectiveness of pneumococcal conjugate vaccine in vaccinated children and indirect effects in unvaccinated populations. Together with the parallel carriage/AOM trial, over 47,000 children were enrolled, 52% of the initial target. We conducted a questionnaire study to find out which factors affected parents' decision on their child's study participation. A questionnaire designed to evaluate parents' attitudes to vaccine trial participation in general and the FinIP trial in particular was mailed after the trial enrolment period had ended to parents of randomly selected children: 1484 who participated in the trial and 1485 who did not participate. Altogether 1438 parents (48%) responded to the questionnaire. The response rate was higher among FinIP participants (65%, 965/1484) than among FinIP non-participants (32%, 473/1485). The two most important reasons for giving consent to the FinIP trial were the potential benefit of immunisation against pneumococcal diseases (75% of consenters) and the promotion of the common good and public health (11%). The reasons reported as most important for declining consent were suspicions of vaccine safety (36%) and the double-blind trial design (12%). Up to 65% of the non-consenters declared that drug and vaccine trials should not be conducted in children at all. The expected health benefit for the child was by far the most important reason for consenting to the vaccine trial. Safety concern was the main reason for decline. Importance and necessity of clinical drug and vaccine trials among children and the rationale of the blinded studies should be thoroughly explained to the public. This may increase participation in future vaccine trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

Computer aided design of extrusion forming tools for complex geometry profiles

NASA Astrophysics Data System (ADS)

Goncalves, Nelson Daniel Ferreira

In the profile extrusion, the experience of the die designer is crucial for obtaining good results. In industry, it is quite usual the need of several experimental trials for a specific extrusion die before a balanced flow distribution is obtained. This experimental based trial-and-error procedure is time and money consuming, but, it works, and most of the profile extrusion companies rely on such method. However, the competition is forcing the industry to look for more effective procedures and the design of profile extrusion dies is not an exception. For this purpose, computer aided design seems to be a good route. Nowadays, the available computational rheology numerical codes allow the simulation of complex fluid flows. This permits the die designer to evaluate and to optimize the flow channel, without the need to have a physical die and to perform real extrusion trials. In this work, a finite volume based numerical code was developed, for the simulation of non-Newtonian (inelastic) fluid and non-isothermal flows using unstructured meshes. The developed code is able to model the forming and cooling stages of profile extrusion, and can be used to aid the design of forming tools used in the production of complex profiles. For the code verification three benchmark problems were tested: flow between parallel plates, flow around a cylinder, and the lid driven cavity flow. The code was employed to design two extrusion dies to produce complex cross section profiles: a medical catheter die and a wood plastic composite profile for decking applications. The last was experimentally validated. Simple extrusion dies used to produced L and T shaped profiles were studied in detail, allowing a better understanding of the effect of the main geometry parameters on the flow distribution. To model the cooling stage a new implicit formulation was devised, which allowed the achievement of better convergence rates and thus the reduction of the computation times. Having in mind the solution of large dimension problems, the code was parallelized using graphics processing units (GPUs). Speedups of ten times could be obtained, drastically decreasing the time required to obtain results.

Maternal Opioid Treatment: Human Experimental Research (MOTHER) – Approach, Issues, and Lessons Learned

PubMed Central

Jones, Hendrée E.; Fischer, Gabriele; Heil, Sarah H.; Kaltenbach, Karol; Martin, Peter R.; Coyle, Mara G.; Selby, Peter; Stine, Susan M.; O’Grady, Kevin E.; Arria, Amelia M.

2015-01-01

Aims The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current – and single most comprehensive – research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine. Methods The MOTHER study design is outlined, and its basic features are presented. Conclusions At least seven important lessons have been learned from the MOTHER study: (1) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (2) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment goals, patient populations, and hospital practices that in turn differentially impact recruitment rates, treatment compliance, and attrition; (3) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (4) staff turnover needs to be addressed with a proactive focus on both hiring and training; (5) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (6) timely tracking of data in a multi-site trial is both demanding and unforgiving; and, (7) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results. PMID:23106924

Fast Face-Recognition Optical Parallel Correlator Using High Accuracy Correlation Filter

NASA Astrophysics Data System (ADS)

Watanabe, Eriko; Kodate, Kashiko

2005-11-01

We designed and fabricated a fully automatic fast face recognition optical parallel correlator [E. Watanabe and K. Kodate: Appl. Opt. 44 (2005) 5666] based on the VanderLugt principle. The implementation of an as-yet unattained ultra high-speed system was aided by reconfiguring the system to make it suitable for easier parallel processing, as well as by composing a higher accuracy correlation filter and high-speed ferroelectric liquid crystal-spatial light modulator (FLC-SLM). In running trial experiments using this system (dubbed FARCO), we succeeded in acquiring remarkably low error rates of 1.3% for false match rate (FMR) and 2.6% for false non-match rate (FNMR). Given the results of our experiments, the aim of this paper is to examine methods of designing correlation filters and arranging database image arrays for even faster parallel correlation, underlining the issues of calculation technique, quantization bit rate, pixel size and shift from optical axis. The correlation filter has proved its excellent performance and higher precision than classical correlation and joint transform correlator (JTC). Moreover, arrangement of multi-object reference images leads to 10-channel correlation signals, as sharply marked as those of a single channel. This experiment result demonstrates great potential for achieving the process speed of 10000 face/s.

Pancreatitis, very early compared with normal start of enteral feeding (PYTHON trial): design and rationale of a randomised controlled multicenter trial

PubMed Central

2011-01-01

Background In predicted severe acute pancreatitis, infections have a negative effect on clinical outcome. A start of enteral nutrition (EN) within 24 hours of onset may reduce the number of infections as compared to the current practice of starting an oral diet and EN if necessary at 3-4 days after admission. Methods/Design The PYTHON trial is a randomised controlled, parallel-group, superiority multicenter trial. Patients with predicted severe acute pancreatitis (Imrie-score ≥ 3 or APACHE-II score ≥ 8 or CRP > 150 mg/L) will be randomised to EN within 24 hours or an oral diet and EN if necessary, after 72 hours after hospital admission. During a 3-year period, 208 patients will be enrolled from 20 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of mortality or infections (bacteraemia, infected pancreatic or peripancreatic necrosis, pneumonia) during hospital stay or within 6 months following randomisation. Secondary endpoints include other major morbidity (e.g. new onset organ failure, need for intervention), intolerance of enteral feeding and total costs from a societal perspective. Discussion The PYTHON trial is designed to show that a very early (< 24 h) start of EN reduces the combined endpoint of mortality or infections as compared to the current practice of an oral diet and EN if necessary at around 72 hours after admission for predicted severe acute pancreatitis. Trial Registration ISRCTN: ISRCTN18170985 PMID:21392395

In-Bore Prostate Transperineal Interventions with an MRI-guided Parallel Manipulator: System Development and Preliminary Evaluation

PubMed Central

Eslami, Sohrab; Shang, Weijian; Li, Gang; Patel, Nirav; Fischer, Gregory S.; Tokuda, Junichi; Hata, Nobuhiko; Tempany, Clare M.; Iordachita, Iulian

2015-01-01

Background The robot-assisted minimally-invasive surgery is well recognized as a feasible solution for diagnosis and treatment of the prostate cancer in human. Methods In this paper the kinematics of a parallel 4 Degrees-of-Freedom (DOF) surgical manipulator designed for minimally invasive in-bore prostate percutaneous interventions through the patient's perineum. The proposed manipulator takes advantage of 4 sliders actuated by MRI-compatible piezoelectric motors and incremental rotary encoders. Errors, mostly originating from the design and manufacturing process, need to be identified and reduced before the robot is deployed in the clinical trials. Results The manipulator has undergone several experiments to evaluate the repeatability and accuracy of the needle placement which is an essential concern in percutaneous prostate interventions. Conclusion The acquired results endorse the sustainability, precision (about 1 mm in air (in x or y direction) at the needle's reference point) and reliability of the manipulator. PMID:26111458

Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting.

PubMed

Wiangkham, Taweewat; Duda, Joan; Haque, M Sayeed; Price, Jonathan; Rushton, Alison

2016-07-13

Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3-4 physiotherapists) and a focus group (n=6-8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). ISRCTN84528320. 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/

Do Published Data in Trials Assessing Cancer Drugs Reflect the Real Picture of Efficacy and Safety?

PubMed

Lv, Jia-Wei; Chen, Yu-Pei; Zhou, Guan-Qun; Liu, Xu; Guo, Ying; Mao, Yan-Ping; Ma, Jun; Sun, Ying

2017-11-01

Background: The reporting quality of publications is of vital importance to ensure accurate evidence dissemination. This study aimed to compare the consistency of results reporting between the ClinicalTrials.gov results database and the respective matching publications. Methods: We identified 323 phase III/IV cancer drug trials with a randomized controlled design and searched PubMed for publications in a 50% random sample (n=160). Data were extracted independently from ClinicalTrials.gov and publications. A scoring system was applied to determine characteristics associated with reporting quality. Results: Of 117 reviewed trials with publications, result reporting was significantly more complete in ClinicalTrials.gov for efficacy measurement (92.3% vs 90.6%), serious adverse events (SAEs; 100% vs 43.6%), and other adverse events (OAEs; 100% vs 62.4%). For trials with both posted and published results for design information (n=117), efficacy measurements (n=98), SAEs (n=51), and OAEs (n=73), discrepancies were found in 16 (13.7%), 38 (38.8%), 26 (51.0%), and 54 (74.0%) trials, respectively. Overreporting of treatment effects (7 trials) and alteration of primary end points favoring statistically significant outcomes (11 trials) were the major discrepancies in efficacy reporting; incomplete (66 trials) and underreporting (20 trials) of SAEs were the predominant issues in benefit/risk reporting. Median quality score was 21 (range, 14-28). Trials that had parallel assignment, were phase IV, had primary funding by industry, were completed after 2009, and had earlier results posted possessed better reporting quality. Conclusions: Although most trials showed reasonable completeness and consistency, some discrepancies are prevalent and persistent, jeopardizing evidence-based decision-making. Our findings highlight the need to consult results systematically from both ClinicalTrials.gov and publications. Copyright © 2017 by the National Comprehensive Cancer Network.

The efficacy and safety of Baoji Tablets for treating common cold with summer-heat and dampness syndrome: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Despite the high incidence and the economic impact of the common cold, there are still no effective therapeutic options available. Although traditional Chinese medicine (TCM) is widely used in China to treat the common cold, there is still a lack of high-quality clinical trials. This article sets forth the protocol for a high-quality trial of a new TCM drug, Baoji Tablets, which is designed to treat the common cold with summer-heat and dampness syndrome (CCSDS). The trial is evaluating both the efficacy and safety of Baoji Tablets. Methods/design This study is designed as a multicenter, phase II, parallel-group, double-blind, double-dummy, randomized and placebo-controlled trial. A total of 288 patients will be recruited from four centers. The new tablets group are administered Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. The old pills group are administered dummy Baoji Tablets 0.9 g and Baoji Pills 3.7 g. The placebo control group are administered dummy Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. All drugs are taken three times daily for 3 days. The primary outcome is the duration of all symptoms. Secondary outcomes include the duration of primary and secondary symptoms, changes in primary and secondary symptom scores and cumulative symptom score at day 4, as well as an evaluation of treatment efficacy. Discussion This is the first multicenter, double-blind, double-dummy, randomized and placebo-controlled trial designated to treat CCSDS in an adult population from China. It will establish the basis for a scientific and objective assessment of the efficacy and safety of Baoji Tablets for treating CCSDS, and provide evidence for a phase III clinical trial. Trial registration This study is registered with the Chinese Clinical Trial Registry. The registration number is ChiCTR-TRC-13003197. PMID:24359521

Implementation of a high-speed face recognition system that uses an optical parallel correlator.

PubMed

Watanabe, Eriko; Kodate, Kashiko

2005-02-10

We implement a fully automatic fast face recognition system by using a 1000 frame/s optical parallel correlator designed and assembled by us. The operational speed for the 1:N (i.e., matching one image against N, where N refers to the number of images in the database) identification experiment (4000 face images) amounts to less than 1.5 s, including the preprocessing and postprocessing times. The binary real-only matched filter is devised for the sake of face recognition, and the system is optimized by the false-rejection rate (FRR) and the false-acceptance rate (FAR), according to 300 samples selected by the biometrics guideline. From trial 1:N identification experiments with the optical parallel correlator, we acquired low error rates of 2.6% FRR and 1.3% FAR. Facial images of people wearing thin glasses or heavy makeup that rendered identification difficult were identified with this system.

Accelerating clinical development of HIV vaccine strategies: methodological challenges and considerations in constructing an optimised multi-arm phase I/II trial design.

PubMed

Richert, Laura; Doussau, Adélaïde; Lelièvre, Jean-Daniel; Arnold, Vincent; Rieux, Véronique; Bouakane, Amel; Lévy, Yves; Chêne, Geneviève; Thiébaut, Rodolphe

2014-02-26

Many candidate vaccine strategies against human immunodeficiency virus (HIV) infection are under study, but their clinical development is lengthy and iterative. To accelerate HIV vaccine development optimised trial designs are needed. We propose a randomised multi-arm phase I/II design for early stage development of several vaccine strategies, aiming at rapidly discarding those that are unsafe or non-immunogenic. We explored early stage designs to evaluate both the safety and the immunogenicity of four heterologous prime-boost HIV vaccine strategies in parallel. One of the vaccines used as a prime and boost in the different strategies (vaccine 1) has yet to be tested in humans, thus requiring a phase I safety evaluation. However, its toxicity risk is considered minimal based on data from similar vaccines. We newly adapted a randomised phase II trial by integrating an early safety decision rule, emulating that of a phase I study. We evaluated the operating characteristics of the proposed design in simulation studies with either a fixed-sample frequentist or a continuous Bayesian safety decision rule and projected timelines for the trial. We propose a randomised four-arm phase I/II design with two independent binary endpoints for safety and immunogenicity. Immunogenicity evaluation at trial end is based on a single-stage Fleming design per arm, comparing the observed proportion of responders in an immunogenicity screening assay to an unacceptably low proportion, without direct comparisons between arms. Randomisation limits heterogeneity in volunteer characteristics between arms. To avoid exposure of additional participants to an unsafe vaccine during the vaccine boost phase, an early safety decision rule is imposed on the arm starting with vaccine 1 injections. In simulations of the design with either decision rule, the risks of erroneous conclusions were controlled <15%. Flexibility in trial conduct is greater with the continuous Bayesian rule. A 12-month gain in timelines is expected by this optimised design. Other existing designs such as bivariate or seamless phase I/II designs did not offer a clear-cut alternative. By combining phase I and phase II evaluations in a multi-arm trial, the proposed optimised design allows for accelerating early stage clinical development of HIV vaccine strategies.

Reporting of participant flow diagrams in published reports of randomized trials.

PubMed

Hopewell, Sally; Hirst, Allison; Collins, Gary S; Mallett, Sue; Yu, Ly-Mee; Altman, Douglas G

2011-12-05

Reporting of the flow of participants through each stage of a randomized trial is essential to assess the generalisability and validity of its results. We assessed the type and completeness of information reported in CONSORT (Consolidated Standards of Reporting Trials) flow diagrams published in current reports of randomized trials. A cross sectional review of all primary reports of randomized trials which included a CONSORT flow diagram indexed in PubMed core clinical journals (2009). We assessed the proportion of parallel group trial publications reporting specific items recommended by CONSORT for inclusion in a flow diagram. Of 469 primary reports of randomized trials, 263 (56%) included a CONSORT flow diagram of which 89% (237/263) were published in a CONSORT endorsing journal. Reports published in CONSORT endorsing journals were more likely to include a flow diagram (62%; 237/380 versus 29%; 26/89). Ninety percent (236/263) of reports which included a flow diagram had a parallel group design, of which 49% (116/236) evaluated drug interventions, 58% (137/236) were multicentre, and 79% (187/236) compared two study groups, with a median sample size of 213 participants. Eighty-one percent (191/236) reported the overall number of participants assessed for eligibility, 71% (168/236) the number excluded prior to randomization and 98% (231/236) the overall number randomized. Reasons for exclusion prior to randomization were more poorly reported. Ninety-four percent (223/236) reported the number of participants allocated to each arm of the trial. However, only 40% (95/236) reported the number who actually received the allocated intervention, 67% (158/236) the number lost to follow up in each arm of the trial, 61% (145/236) whether participants discontinued the intervention during the trial and 54% (128/236) the number included in the main analysis. Over half of published reports of randomized trials included a diagram showing the flow of participants through the trial. However, information was often missing from published flow diagrams, even in articles published in CONSORT endorsing journals. If important information is not reported it can be difficult and sometimes impossible to know if the conclusions of that trial are justified by the data presented.

Oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients.

PubMed

Le Cleach, Laurence; Trinquart, Ludovic; Do, Giao; Maruani, Annabel; Lebrun-Vignes, Benedicte; Ravaud, Philippe; Chosidow, Olivier

2014-08-03

Genital herpes is caused by herpes simplex virus 1 (HSV-1) or 2 (HSV-2). Some infected people experience outbreaks of genital herpes, typically, characterized by vesicular and erosive localized painful genital lesions. To compare the effectiveness and safety of three oral antiviral drugs (acyclovir, famciclovir and valacyclovir) prescribed to suppress genital herpes outbreaks in non-pregnant patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the search portal of the World Health Organization International Clinical Trials Registry Platform and pharmaceutical company databases up to February 2014. We also searched US Food and Drug Administration databases and proceedings of seven congresses to a maximum of 10 years. We contacted trial authors and pharmaceutical companies. We selected parallel-group and cross-over randomized controlled trials including patients with recurrent genital herpes caused by HSV, whatever the type (HSV-1, HSV-2, or undetermined), with at least four recurrences per year (trials concerning human immunodeficiency virus (HIV)-positive patients or pregnant women were not eligible) and comparing suppressive oral antiviral treatment with oral acyclovir, famciclovir, and valacyclovir versus placebo or another suppressive oral antiviral treatment. Two review authors independently selected eligible trials and extracted data. The Risk of bias tool was used to assess risk of bias. Treatment effect was measured by the risk ratio (RR) of having at least one genital herpes recurrence. Pooled RRs were derived by conventional pairwise meta-analyses. A network meta-analysis allowed for estimation of all possible two-by-two comparisons between antiviral drugs. A total of 26 trials (among which six had a cross-over design) were included. Among the 6950 randomly assigned participants, 54% (range 0 to 100%) were female, mean age was 35 years (range 26 to 45.1), and the mean number of recurrences per year was 11 (range 6.3 to 17.8). Duration of treatment was two to 12 months. Risk of bias was considered high for half of the studies and unclear for the other half. A total of 14 trials compared acyclovir versus placebo, four trials compared valacyclovir versus placebo and 2 trials compared valacyclovir versus no treatment. Three trials compared famciclovir versus placebo. Two trials compared valacyclovir versus famciclovir and one trial compared acyclovir versus valacyclovir versus placebo.We analyzed data from 22 trials for the outcome: risk of having at least one clinical recurrence. We could not obtain the outcome data for four trials. In placebo-controlled trials, there was a low quality evidence that the risk of having at least one clinical recurrence was reduced with acyclovir (nine parallel-group trials, n = 2049; pooled RR 0.48, 95% confidence interval (CI) 0.39 to 0.58), valacyclovir (four trials, n = 1788; pooled RR 0.41, 95% CI 0.24 to 0.69), or famciclovir (two trials, n = 732; pooled RR 0.57, 95% CI 0.50 to 0.64). The six cross-over trials showed larger treatment effects on average than the parallel-group trials. We found evidence of a small-study effect for acyclovir placebo-controlled trials (adjusted pooled RR 0.61, 95% CI 0.49 to 0.75). In analyzing parallel-group trials by daily dose, no clear evidence was found of a dose-response relationship for any drug. In head-to-head trials, the risk of having at least one recurrence was increased with valacyclovir rather than acyclovir (one trial, n = 1345; RR 1.16, 95% CI 1.01 to 1.34) and was not significantly different from that seen with famciclovir as compared with valacyclovir (one trial, n = 320; RR 1.18, 95% CI 0.86 to 1.63).We included 16 parallel-arm trials in a network meta-analysis and we were unable to determine which of the drugs was most effective in reducing the risk of at least one clinical recurrence (after adjustment for small-study effects, pooled RR 0.83, 95% CI 0.61 to 1.11 for valacyclovir vs acyclovir; pooled RR 1.04, 95% CI, 0.71 to 1.49 for famciclovir vs acyclovir; and pooled RR 1.26, 95% CI 0.89 to 1.75 for famciclovir vs valacyclovir). Safety data were sought but were reported as total numbers of adverse events. Owing to risk of bias and inconsistency, there is low quality evidence that suppressive antiviral therapy with acyclovir, valacyclovir or famciclovir in pacients experiencing at least four recurrences of genital herpes per year decreases the number of pacients with at least one recurrence as compared with placebo. Network meta-analysis of the few direct comparisons and the indirect comparisons did not show superiority of one drug over another.

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

Randomized placebo controlled blinded study to assess valsartan efficacy in preventing left ventricle remodeling in patients with dual chamber pacemaker--Rationale and design of the trial.

PubMed

Tomasik, Andrzej; Jacheć, Wojciech; Wojciechowska, Celina; Kawecki, Damian; Białkowska, Beata; Romuk, Ewa; Gabrysiak, Artur; Birkner, Ewa; Kalarus, Zbigniew; Nowalany-Kozielska, Ewa

2015-05-01

Dual chamber pacing is known to have detrimental effect on cardiac performance and heart failure occurring eventually is associated with increased mortality. Experimental studies of pacing in dogs have shown contractile dyssynchrony leading to diffuse alterations in extracellular matrix. In parallel, studies on experimental ischemia/reperfusion injury have shown efficacy of valsartan to inhibit activity of matrix metalloproteinase-9, to increase the activity of tissue inhibitor of matrix metalloproteinase-3 and preserve global contractility and left ventricle ejection fraction. To present rationale and design of randomized blinded trial aimed to assess whether 12 month long administration of valsartan will prevent left ventricle remodeling in patients with preserved left ventricle ejection fraction (LVEF ≥ 40%) and first implantation of dual chamber pacemaker. A total of 100 eligible patients will be randomized into three parallel arms: placebo, valsartan 80 mg/daily and valsartan 160 mg/daily added to previously used drugs. The primary endpoint will be assessment of valsartan efficacy to prevent left ventricle remodeling during 12 month follow-up. We assess patients' functional capacity, blood plasma activity of matrix metalloproteinases and their tissue inhibitors, NT-proBNP, tumor necrosis factor alpha, and Troponin T. Left ventricle function and remodeling is assessed echocardiographically: M-mode, B-mode, tissue Doppler imaging. If valsartan proves effective, it will be an attractive measure to improve long term prognosis in aging population and increasing number of pacemaker recipients. ClinicalTrials.org (NCT01805804). Copyright © 2015 Elsevier Inc. All rights reserved.

Inefficient conjunction search made efficient by concurrent spoken delivery of target identity.

PubMed

Reali, Florencia; Spivey, Michael J; Tyler, Melinda J; Terranova, Joseph

2006-08-01

Visual search based on a conjunction of two features typically elicits reaction times that increase linearly as a function of the number of distractors, whereas search based on a single feature is essentially unaffected by set size. These and related findings have often been interpreted as evidence of a serial search stage that follows a parallel search stage. However, a wide range of studies has been showing a form of blending of these two processes. For example, when a spoken instruction identifies the conjunction target concurrently with the visual display, the effect of set size is significantly reduced, suggesting that incremental linguistic processing of the first feature adjective and then the second feature adjective may facilitate something approximating a parallel extraction of objects during search for the target. Here, we extend these results to a variety of experimental designs. First, we replicate the result with a mixed-trials design (ruling out potential strategies associated with the blocked design of the original study). Second, in a mixed-trials experiment, the order of adjective types in the spoken query varies randomly across conditions. In a third experiment, we extend the effect to a triple-conjunction search task. A fourth (control) experiment demonstrates that these effects are not due to an efficient odd-one-out search that ignores the linguistic input. This series of experiments, along with attractor-network simulations of the phenomena, provide further evidence toward understanding linguistically mediated influences in real-time visual search processing.

Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial.

PubMed

Zhang, Lina; Zhang, Zhiqin; Chen, Yangmei; Qin, Xinyue; Zhou, Huadong; Zhang, Chaodong; Sun, Hongbin; Tang, Ronghua; Zheng, Jinou; Yi, Lin; Deng, Liying; Li, Jinfang

2013-08-01

Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable--mean adjusted total daily off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

Effects of a Short Course of Eszopiclone on Continuous Positive Airway Pressure Adherence

DTIC Science & Technology

2009-11-17

We collected addi- tional data related to mood and depression, libido and erectile dysfunction , and quality of life that will be in- cluded in...onset of therapy improves long-term CPAP adherence more than placebo in adults with obstructive sleep apnea. Design: Parallel randomized, placebo...collected. (ClinicalTrials.gov registration number: NCT00612157) Setting: Academic sleep disorder center. Patients: 160 adults (mean age, 45.7 years [SD

Response to Placebo in Clinical Epilepsy Trials - Old Ideas and New Insights

PubMed Central

Goldenholz, Daniel M.; Goldenholz, Shira R

2016-01-01

Randomized placebo controlled trials are a mainstay of modern clinical epilepsy research; the success or failure of innovative therapies depends on proving superiority to a placebo. Consequently, understanding what drives response to placebo (including the “placebo effect”) may facilitate evaluation of new therapies. In this review, part one will explore observations about placebos specific to epilepsy, including the relatively higher placebo response in children, apparent increase in placebo response over the past several decades, geographic variation in placebo effect, relationship to baseline epilepsy characteristics, influence of nocebo on clinical trials, the possible increase in (SUDEP) in placebo arms of trials, and patterns that placebo responses appear to follow in individual patients. Part two will discuss the principal causes of placebo responses, including regression to the mean, anticipation, classical conditioning, the Hawthorne effect, expectations from symbols, and the natural history of disease. Included in part two will be a brief overview of recent advances using simulations from large datasets that have afforded new insights into causes of epilepsy related placebo responses. In part three, new developments in study design will be explored, including sequential parallel comparison, two-way enriched design, time to pre-randomization, delayed start, and cohort reduction techniques. PMID:26921852

A noninferiority confirmatory trial of prasugrel versus clopidogrel in Japanese patients with non-cardioembolic stroke: rationale and study design for a randomized controlled trial - PRASTRO-I trial.

PubMed

Nagao, Takehiko; Toyoda, Kazunori; Kitagawa, Kazuo; Kitazono, Takanari; Yamagami, Hiroshi; Uchiyama, Shinichiro; Tanahashi, Norio; Matsumoto, Masayasu; Minematsu, Kazuo; Nagata, Izumi; Nishikawa, Masakatsu; Nanto, Shinsuke; Abe, Kenji; Ikeda, Yasuo; Ogawa, Akira

2018-04-01

This comparison of PRAsugrel and clopidogrel in Japanese patients with ischemic STROke (PRASTRO)-I trial investigates the noninferiority of prasugrel to clopidogrel sulfate in the prevention of recurrence of primary events (ischemic stroke, myocardial infarction, and death from other vascular causes), and the long-term safety of prasugrel in Japanese patients with non-cardioembolic stroke. This was an active-controlled, randomized, double-blind, double-dummy, parallel-group study conducted between July 2011 and March 2016 at multiple centers around Japan. Patients had to meet eligibility criteria before receiving 3.75 mg prasugrel or 75 mg clopidogrel orally once daily for a period of 96-104 weeks. A total of 3747 patients were included in this trial; 1598 in the 3.75 mg prasugrel group and 1551 in the 75 mg clopidogrel group completed the study. During the study period, 287 (15.2%) patients in the prasugrel group and 311 (16.7%) in the clopidogrel group discontinued treatment. Baseline characteristics, safety, and efficacy results are forthcoming and will be published separately. This article presents the study design and rationale for a trial investigating the noninferiority of prasugrel to clopidogrel sulfate with regards to the inhibitory effect on primary events in patients with non-cardioembolic stroke.

The citation of relevant systematic reviews and randomised trials in published reports of trial protocols.

PubMed

Pandis, Nikolaos; Fleming, Padhraig S; Koletsi, Despina; Hopewell, Sally

2016-12-07

It is important that planned randomised trials are justified and placed in the context of the available evidence. The SPIRIT guidelines for reporting clinical trial protocols recommend that a recent and relevant systematic review should be included. The aim of this study was to assess the use of the existing evidence in order to justify trial conduct. Protocols of randomised trials published over a 1-month period (December 2015) indexed in PubMed were obtained. Data on trial characteristics relating to location, design, funding, conflict of interest and type of evidence included for trial justification was extracted in duplicate and independently by two investigators. The frequency of citation of previous research including relevant systematic reviews and randomised trials was assessed. Overall, 101 protocols for RCTs were identified. Most proposed trials were parallel-group (n = 74; 73.3%). Reference to an earlier systematic review with additional randomised trials was found in 9.9% (n = 10) of protocols and without additional trials in 30.7% (n = 31), while reference was made to randomised trials in isolation in 21.8% (n = 22). Explicit justification for the proposed randomised trial on the basis of being the first to address the research question was made in 17.8% (n = 18) of protocols. A randomised controlled trial was not cited in 10.9% (95% CI: 5.6, 18.7) (n = 11), while in 8.9% (95% CI: 4.2, 16.2) (n = 9) of the protocols a systematic review was cited but did not inform trial design. A relatively high percentage of protocols of randomised trials involves prior citation of randomised trials, systematic reviews or both. However, improvements are required to ensure that it is explicit that clinical trials are justified and shaped by contemporary best evidence.

Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials

PubMed Central

Gilbert, Peter B.; Juraska, Michal; deCamp, Allan C.; Karuna, Shelly; Edupuganti, Srilatha; Mgodi, Nyaradzo; Donnell, Deborah J.; Bentley, Carter; Sista, Nirupama; Andrew, Philip; Isaacs, Abby; Huang, Yunda; Zhang, Lily; Capparelli, Edmund; Kochar, Nidhi; Wang, Jing; Eshleman, Susan H.; Mayer, Kenneth H.; Magaret, Craig A.; Hural, John; Kublin, James G.; Gray, Glenda; Montefiori, David C.; Gomez, Margarita M.; Burns, David N.; McElrath, Julie; Ledgerwood, Julie; Graham, Barney S.; Mascola, John R.; Cohen, Myron; Corey, Lawrence

2017-01-01

Background Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. Methods The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Results Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. Conclusions The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark for future vaccine evaluation and constituting a bridge to other bnAb approaches for HIV-1 prevention. PMID:29218117

Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.

PubMed

Gilbert, Peter B; Juraska, Michal; deCamp, Allan C; Karuna, Shelly; Edupuganti, Srilatha; Mgodi, Nyaradzo; Donnell, Deborah J; Bentley, Carter; Sista, Nirupama; Andrew, Philip; Isaacs, Abby; Huang, Yunda; Zhang, Lily; Capparelli, Edmund; Kochar, Nidhi; Wang, Jing; Eshleman, Susan H; Mayer, Kenneth H; Magaret, Craig A; Hural, John; Kublin, James G; Gray, Glenda; Montefiori, David C; Gomez, Margarita M; Burns, David N; McElrath, Julie; Ledgerwood, Julie; Graham, Barney S; Mascola, John R; Cohen, Myron; Corey, Lawrence

2017-01-01

Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark for future vaccine evaluation and constituting a bridge to other bnAb approaches for HIV-1 prevention.

Dual sensory loss: development of a dual sensory loss protocol and design of a randomized controlled trial

PubMed Central

2013-01-01

Background Dual sensory loss (DSL) has a negative impact on health and wellbeing and its prevalence is expected to increase due to demographic aging. However, specialized care or rehabilitation programs for DSL are scarce. Until now, low vision rehabilitation does not sufficiently target concurrent impairments in vision and hearing. This study aims to 1) develop a DSL protocol (for occupational therapists working in low vision rehabilitation) which focuses on optimal use of the senses and teaches DSL patients and their communication partners to use effective communication strategies, and 2) describe the multicenter parallel randomized controlled trial (RCT) designed to test the effectiveness and cost-effectiveness of the DSL protocol. Methods/design To develop a DSL protocol, literature was reviewed and content was discussed with professionals in eye/ear care (interviews/focus groups) and DSL patients (interviews). A pilot study was conducted to test and confirm the DSL protocol. In addition, a two-armed international multi-center RCT will evaluate the effectiveness and cost-effectiveness of the DSL protocol compared to waiting list controls, in 124 patients in low vision rehabilitation centers in the Netherlands and Belgium. Discussion This study provides a treatment protocol for rehabilitation of DSL within low vision rehabilitation, which aims to be a valuable addition to the general low vision rehabilitation care. Trial registration Netherlands Trial Register (NTR) identifier: NTR2843 PMID:23941667

Preference option randomized design (PORD) for comparative effectiveness research: Statistical power for testing comparative effect, preference effect, selection effect, intent-to-treat effect, and overall effect.

PubMed

Heo, Moonseong; Meissner, Paul; Litwin, Alain H; Arnsten, Julia H; McKee, M Diane; Karasz, Alison; McKinley, Paula; Rehm, Colin D; Chambers, Earle C; Yeh, Ming-Chin; Wylie-Rosett, Judith

2017-01-01

Comparative effectiveness research trials in real-world settings may require participants to choose between preferred intervention options. A randomized clinical trial with parallel experimental and control arms is straightforward and regarded as a gold standard design, but by design it forces and anticipates the participants to comply with a randomly assigned intervention regardless of their preference. Therefore, the randomized clinical trial may impose impractical limitations when planning comparative effectiveness research trials. To accommodate participants' preference if they are expressed, and to maintain randomization, we propose an alternative design that allows participants' preference after randomization, which we call a "preference option randomized design (PORD)". In contrast to other preference designs, which ask whether or not participants consent to the assigned intervention after randomization, the crucial feature of preference option randomized design is its unique informed consent process before randomization. Specifically, the preference option randomized design consent process informs participants that they can opt out and switch to the other intervention only if after randomization they actively express the desire to do so. Participants who do not independently express explicit alternate preference or assent to the randomly assigned intervention are considered to not have an alternate preference. In sum, preference option randomized design intends to maximize retention, minimize possibility of forced assignment for any participants, and to maintain randomization by allowing participants with no or equal preference to represent random assignments. This design scheme enables to define five effects that are interconnected with each other through common design parameters-comparative, preference, selection, intent-to-treat, and overall/as-treated-to collectively guide decision making between interventions. Statistical power functions for testing all these effects are derived, and simulations verified the validity of the power functions under normal and binomial distributions.

Investigations of botanicals on food intake, satiety, weight loss, and oxidative stress: a study protocol of a double-blind, placebo-controlled, crossover study

PubMed Central

Anton, Stephen D.; Shuster, Jonathan; Leeuwenburgh, Christiaan

2013-01-01

Background Botanicals represent an important and underexplored source of potential new therapies that may facilitate caloric restriction and thereby produce long-term weight loss. In particular, one promising botanical that may reduce food intake and body weight by affecting neuroendocrine pathways related to satiety is Garcinia cambogia (Garcinia cambogia Desr.)-derived (−)-hydroxycitric acid (HCA). Methods and Design The objective of this article is to describe the protocol of a clinical trial designed to directly test the effect that Garcinia cambogia-derived HCA has on food intake, satiety, weight loss, and oxidative stress levels, and to serve as a model for similar trials. A total of 48 healthy, overweight and obese individuals (body mass index; BMI range = 25.0 – 39.9) between the ages of 50 to 70 will participate in this double-blind, placebo-controlled, crossover study designed to examine the effects of two doses of Garcinia cambogia-derived HCA on food intake, satiety, weight loss, and oxidative stress levels. This trial will take place at the University of Florida (UF)’s Aging and Rehabilitation Research Center (ARRC) and UF Clinical Research Center (CRC). Food intake represents the primary outcome measure and is calculated based on the total calories consumed at breakfast, lunch, and dinner meals during each test meal day at the CRC. This study can be completed with far fewer subjects than a parallel design. Discussion Of the numerous botanical compounds, the compound Garcinia cambogia-derived HCA was selected for testing in the present study because of its potential to safely reduce food intake, body weight, and oxidative stress levels. We will review potential mechanisms of action and safety parameters throughout this clinical trial, which is registered at ClinicalTrials.gov under NCT01238887. Trial registration ClinicalTrials.gov (Identifier: NCT01238887). PMID:22088584

Pre-consultation educational group intervention to improve shared decision-making in postmastectomy breast reconstruction: study protocol for a pilot randomized controlled trial.

PubMed

Platt, Jennica; Baxter, Nancy; Jones, Jennifer; Metcalfe, Kelly; Causarano, Natalie; Hofer, Stefan O P; O'Neill, Anne; Cheng, Terry; Starenkyj, Elizabeth; Zhong, Toni

2013-07-06

The Pre-Consultation Educational Group INTERVENTION pilot study seeks to assess the feasibility and inform the optimal design for a definitive randomized controlled trial that aims to improve the quality of decision-making in postmastectomy breast reconstruction patients. This is a mixed-methods pilot feasibility randomized controlled trial that will follow a single-center, 1:1 allocation, two-arm parallel group superiority design. The University Health Network, a tertiary care cancer center in Toronto, Canada. Adult women referred to one of three plastic and reconstructive surgeons for delayed breast reconstruction or prophylactic mastectomy with immediate breast reconstruction. We designed a multi-disciplinary educational group workshop that incorporates the key components of shared decision-making, decision-support, and psychosocial support for cancer survivors prior to the initial surgical consult. The intervention consists of didactic lectures by a plastic surgeon and nurse specialist on breast reconstruction choices, pre- and postoperative care; a value-clarification exercise led by a social worker; and discussions with a breast reconstruction patient. Usual care includes access to an informational booklet, website, and patient volunteer if desired. Expected pilot outcomes include feasibility, recruitment, and retention targets. Acceptability of intervention and full trial outcomes will be established through qualitative interviews. Trial outcomes will include decision-quality measures, patient-reported outcomes, and service outcomes, and the treatment effect estimate and variability will be used to inform the sample size calculation for a full trial. Our pilot study seeks to identify the (1) feasibility, acceptability, and design of a definitive RCT and (2) the optimal content and delivery of our proposed educational group intervention. Thirty patients have been recruited to date (8 April 2013), of whom 15 have been randomized to one of three decision support workshops. The trial will close as planned in May 2013. NCT01857882.

A parallel randomized trial on the effect of a healthful diet on inflammageing and its consequences in European elderly people: design of the NU-AGE dietary intervention study.

PubMed

Berendsen, Agnes; Santoro, Aurelia; Pini, Elisa; Cevenini, Elisa; Ostan, Rita; Pietruszka, Barbara; Rolf, Katarzyna; Cano, Noël; Caille, Aurélie; Lyon-Belgy, Noëlle; Fairweather-Tait, Susan; Feskens, Edith; Franceschi, Claudio; de Groot, C P G M

2013-01-01

The proportion of European elderly is expected to increase to 30% in 2060. Combining dietary components may modulate many processes involved in ageing. So, it is likely that a healthful diet approach might have greater favourable impact on age-related decline than individual dietary components. This paper describes the design of a healthful diet intervention on inflammageing and its consequences in the elderly. The NU-AGE study is a parallel randomized one-year trial in 1250 apparently healthy, independently living European participants aged 65-80 years. Participants are randomised into either the diet group or control group. Participants in the diet group received dietary advice aimed at meeting the nutritional requirements of the ageing population. Special attention was paid to nutrients that may be inadequate or limiting in diets of elderly, such as vitamin D, vitamin B12, and calcium. C-reactive protein is measured as primary outcome. The NU-AGE study is the first dietary intervention investigating the effect of a healthful diet providing targeted nutritional recommendations for optimal health and quality of life in apparently healthy European elderly. Results of this intervention will provide evidence on the effect of a healthful diet on the prevention of age related decline. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.

PubMed

Karanth, Laxminarayan; Barua, Ankur; Kanagasabai, Sachchithanantham; Nair, Sreekumar

2015-09-09

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated.This is an update of a Cochrane review first published in 2013. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 18 June 2015. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.

PubMed

Karanth, Laxminarayan; Barua, Ankur; Kanagasabai, Sachchithanantham; Nair, N S

2013-04-30

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 28 February 2013. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials.

PubMed

Holmskov, Mathilde; Storebø, Ole Jakob; Moreira-Maia, Carlos R; Ramstad, Erica; Magnusson, Frederik Løgstrup; Krogh, Helle B; Groth, Camilla; Gillies, Donna; Zwi, Morris; Skoog, Maria; Gluud, Christian; Simonsen, Erik

2017-01-01

To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review. We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes. Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found.

UVB phototherapy in an outpatient setting or at home: a pragmatic randomised single-blind trial designed to settle the discussion. The PLUTO study

PubMed Central

Koek, Mayke BG; Buskens, Erik; Steegmans, Paul HA; van Weelden, Huib; Bruijnzeel-Koomen, Carla AFM; Sigurdsson, Vigfús

2006-01-01

Background Home ultraviolet B (UVB) treatment is a much-debated treatment, especially with regard to effectiveness, safety and side effects. However, it is increasingly being prescribed, especially in the Netherlands. Despite ongoing discussions, no randomised research has been performed, and only two studies actually compare two groups of patients. Thus, firm evidence to support or discourage the use of home UVB phototherapy has not yet been obtained. This is the goal of the present study, the PLUTO study (Dutch acronym for "national trial on home UVB phototherapy for psoriasis"). Methods We designed a pragmatic randomised single-blind multi-centre trial. This trial is designed to evaluate the impact of home UVB treatment versus UVB phototherapy in a hospital outpatient clinic as to effectiveness, quality of life and cost-effectiveness. In total 196 patients with psoriasis who were clinically eligible for UVB phototherapy were included. Normally 85% of the patients treated with UVB show a relevant clinical response. With a power of 80% and a 0.05 significance level it will be possible to detect a reduction in effectiveness of 15%. Effectiveness will be determined by calculating differences in the Psoriasis Area and Severity Index (PASI) and the Self Administered PASI (SAPASI) scores. Quality of life is measured using several validated generic questionnaires and a disease-specific questionnaire. Other outcome measures include costs, side effects, dosimetry, concomitant use of medication and patient satisfaction. Patients are followed throughout the therapy and for 12 months thereafter. The study is no longer recruiting patients, and is expected to report in 2006. Discussion In the field of home UVB phototherapy this trial is the first randomised parallel group study. As such, this trial addresses the weaknesses encountered in previous studies. The pragmatic design ensures that the results can be well generalised to the target population. Because, in addition to effectiveness, aspects such as quality of life and cost-effectiveness are also taken into consideration, this study will produce valuable evidence to either support or discourage prescription of home UVB phototherapy. Trial registration Current controlled trials/Nederlands Trial register: ISRCTN83025173. Clinicaltrials.gov: NCT00150930 PMID:16882343

Study design for the "effect of METOprolol in CARDioproteCtioN during an acute myocardial InfarCtion" (METOCARD-CNIC): a randomized, controlled parallel-group, observer-blinded clinical trial of early pre-reperfusion metoprolol administration in ST-segment elevation myocardial infarction.

PubMed

Ibanez, Borja; Fuster, Valentin; Macaya, Carlos; Sánchez-Brunete, Vicente; Pizarro, Gonzalo; López-Romero, Pedro; Mateos, Alonso; Jiménez-Borreguero, Jesús; Fernández-Ortiz, Antonio; Sanz, Ginés; Fernández-Friera, Leticia; Corral, Ervigio; Barreiro, Maria-Victoria; Ruiz-Mateos, Borja; Goicolea, Javier; Hernández-Antolín, Rosana; Acebal, Carlos; García-Rubira, Juan Carlos; Albarrán, Agustín; Zamorano, José Luis; Casado, Isabel; Valenciano, Juan; Fernández-Vázquez, Felipe; de la Torre, José María; Pérez de Prado, Armando; Iglesias-Vázquez, José Antonio; Martínez-Tenorio, Pedro; Iñiguez, Andrés

2012-10-01

Infarct size predicts post-infarction mortality. Oral β-blockade within 24 hours of a ST-segment elevation acute myocardial infarction (STEMI) is a class-IA indication, however early intravenous (IV) β-blockers initiation is not encouraged. In recent magnetic resonance imaging (MRI)-based experimental studies, the β(1)-blocker metoprolol has been shown to reduce infarct size only when administered before coronary reperfusion. To date, there is not a single trial comparing the pre- vs. post-reperfusion β-blocker initiation in STEMI. The METOCARD-CNIC trial is testing whether the early initiation of IV metoprolol before primary percutaneous coronary intervention (pPCI) could reduce infarct size and improve outcomes when compared to oral post-pPCI metoprolol initiation. The METOCARD-CNIC trial is a randomized parallel-group single-blind (to outcome evaluators) clinical effectiveness trial conducted in 5 Counties across Spain that will enroll 220 participants. Eligible are 18- to 80-year-old patients with anterior STEMI revascularized by pPCI ≤6 hours from symptom onset. Exclusion criteria are Killip-class ≥III, atrioventricular block or active treatment with β-blockers/bronchodilators. Primary end point is infarct size evaluated by MRI 5 to 7 days post-STEMI. Prespecified major secondary end points are salvage-index, left ventricular ejection fraction recovery (day 5-7 to 6 months), the composite of (death/malignant ventricular arrhythmias/reinfarction/admission due to heart failure), and myocardial perfusion. The METOCARD-CNIC trial is testing the hypothesis that the early initiation of IV metoprolol pre-reperfusion reduces infarct size in comparison to initiation of oral metoprolol post-reperfusion. Given the implications of infarct size reduction in STEMI, if positive, this trial might evidence that a refined use of an approved inexpensive drug can improve outcomes of patients with STEMI. Copyright © 2012 Mosby, Inc. All rights reserved.

The clinical efficacy of reminiscence therapy in patients with mild-to-moderate Alzheimer disease: Study protocol for a randomized parallel-design controlled trial.

PubMed

Li, Mo; Lyu, Ji-Hui; Zhang, Yi; Gao, Mao-Long; Li, Wen-Jie; Ma, Xin

2017-12-01

Alzheimer disease (AD) is one of the most common diseases among the older adults. Currently, various nonpharmacological interventions are used for the treatment of AD. Such as reminiscence therapy is being widely used in Western countries. However, it is often used as an empirical application in China; the evidence-based efficacy of reminiscence therapy in AD patients remains to be determined. Therefore, the aim of this research is to assess the effectives of reminiscence therapy for Chinese elderly. This is a randomized parallel-design controlled trial. Mild and moderate AD patients who are in the Beijing Geriatric Hospital, China will be randomized into control and intervention groups (n = 45 for each group). For the intervention group, along with conventional drug therapy, participants will be exposed to a reminiscence therapy of 35 to 45 minutes, 2 times/wk for 12 consecutive weeks. Patients in the control group will undergo conventional drug therapy only. The primary outcome measure will be the differences in Alzheimer disease Assessment Scale-Cognitive Section Score. The secondary outcome measures will be the differences in the Cornell scale for depression in dementia, Neuropsychiatric Inventory score, and Barthel Index scores at baseline, at 4 and 12 weeks of treatment, and 12 weeks after treatment. The protocols have been approved by the ethics committee of Beijing Geriatric Hospital of China (approval no. 2015-010). Findings will be disseminated through presentation at scientific conferences and in academic journals. Chinese Clinical Trial Registry identifier ChiCTR-INR-16009505. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Continuous quality improvement interventions to improve long-term outcomes of antiretroviral therapy in women who initiated therapy during pregnancy or breastfeeding in the Democratic Republic of Congo: design of an open-label, parallel, group randomized trial.

PubMed

Yotebieng, Marcel; Behets, Frieda; Kawende, Bienvenu; Ravelomanana, Noro Lantoniaina Rosa; Tabala, Martine; Okitolonda, Emile W

2017-04-26

Despite the rapid adoption of the World Health Organization's 2013 guidelines, children continue to be infected with HIV perinatally because of sub-optimal adherence to the continuum of HIV care in maternal and child health (MCH) clinics. To achieve the UNAIDS goal of eliminating mother-to-child HIV transmission, multiple, adaptive interventions need to be implemented to improve adherence to the HIV continuum. The aim of this open label, parallel, group randomized trial is to evaluate the effectiveness of Continuous Quality Improvement (CQI) interventions implemented at facility and health district levels to improve retention in care and virological suppression through 24 months postpartum among pregnant and breastfeeding women receiving ART in MCH clinics in Kinshasa, Democratic Republic of Congo. Prior to randomization, the current monitoring and evaluation system will be strengthened to enable collection of high quality individual patient-level data necessary for timely indicators production and program outcomes monitoring to inform CQI interventions. Following randomization, in health districts randomized to CQI, quality improvement (QI) teams will be established at the district level and at MCH clinics level. For 18 months, QI teams will be brought together quarterly to identify key bottlenecks in the care delivery system using data from the monitoring system, develop an action plan to address those bottlenecks, and implement the action plan at the level of their district or clinics. If proven to be effective, CQI as designed here, could be scaled up rapidly in resource-scarce settings to accelerate progress towards the goal of an AIDS free generation. The protocol was retrospectively registered on February 7, 2017. ClinicalTrials.gov Identifier: NCT03048669 .

Evaluation of Tai Chi Yunshou exercises on community-based stroke patients with balance dysfunction: a study protocol of a cluster randomized controlled trial.

PubMed

Tao, Jing; Rao, Ting; Lin, Lili; Liu, Wei; Wu, Zhenkai; Zheng, Guohua; Su, Yusheng; Huang, Jia; Lin, Zhengkun; Wu, Jinsong; Fang, Yunhua; Chen, Lidian

2015-02-25

Balance dysfunction after stroke limits patients' general function and participation in daily life. Previous researches have suggested that Tai Chi exercise could offer a positive improvement in older individuals' balance function and reduce the risk of falls. But convincing evidence for the effectiveness of enhancing balance function after stroke with Tai Chi exercise is still inadequate. Considering the difficulties for stroke patients to complete the whole exercise, the current trial evaluates the benefit of Tai Chi Yunshou exercise for patients with balance dysfunction after stroke through a cluster randomization, parallel-controlled design. A single-blind, cluster-randomized, parallel-controlled trial will be conducted. A total of 10 community health centers (5 per arm) will be selected and randomly allocated into Tai Chi Yunshou exercise group or balance rehabilitation training group. Each community health centers will be asked to enroll 25 eligible patients into the trial. 60 minutes per each session, 1 session per day, 5 times per week and the total training round is 12 weeks. Primary and secondary outcomes will be measured at baseline and 4-weeks, 8-weeks, 12-weeks, 6-week follow-up, 12-week follow-up after randomization. Safety and economic evaluation will also be assessed. This protocol aims to evaluate the effectiveness of Tai Chi Yunshou exercise for the balance function of patients after stroke. If the outcome is positive, this project will provide an appropriate and economic balance rehabilitation technology for community-based stroke patients. Chinese Clinical Trial Registry: ChiCTR-TRC-13003641. Registration date: 22 August, 2013 http://www.chictr.org/usercenter/project/listbycreater.aspx .

Reporting of participant flow diagrams in published reports of randomized trials

PubMed Central

2011-01-01

Background Reporting of the flow of participants through each stage of a randomized trial is essential to assess the generalisability and validity of its results. We assessed the type and completeness of information reported in CONSORT (Consolidated Standards of Reporting Trials) flow diagrams published in current reports of randomized trials. Methods A cross sectional review of all primary reports of randomized trials which included a CONSORT flow diagram indexed in PubMed core clinical journals (2009). We assessed the proportion of parallel group trial publications reporting specific items recommended by CONSORT for inclusion in a flow diagram. Results Of 469 primary reports of randomized trials, 263 (56%) included a CONSORT flow diagram of which 89% (237/263) were published in a CONSORT endorsing journal. Reports published in CONSORT endorsing journals were more likely to include a flow diagram (62%; 237/380 versus 29%; 26/89). Ninety percent (236/263) of reports which included a flow diagram had a parallel group design, of which 49% (116/236) evaluated drug interventions, 58% (137/236) were multicentre, and 79% (187/236) compared two study groups, with a median sample size of 213 participants. Eighty-one percent (191/236) reported the overall number of participants assessed for eligibility, 71% (168/236) the number excluded prior to randomization and 98% (231/236) the overall number randomized. Reasons for exclusion prior to randomization were more poorly reported. Ninety-four percent (223/236) reported the number of participants allocated to each arm of the trial. However, only 40% (95/236) reported the number who actually received the allocated intervention, 67% (158/236) the number lost to follow up in each arm of the trial, 61% (145/236) whether participants discontinued the intervention during the trial and 54% (128/236) the number included in the main analysis. Conclusions Over half of published reports of randomized trials included a diagram showing the flow of participants through the trial. However, information was often missing from published flow diagrams, even in articles published in CONSORT endorsing journals. If important information is not reported it can be difficult and sometimes impossible to know if the conclusions of that trial are justified by the data presented. PMID:22141446

Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update.

PubMed

Bautista, Francisco; Fioravantti, Victoria; de Rojas, Teresa; Carceller, Fernando; Madero, Luis; Lassaletta, Alvaro; Moreno, Lucas

2017-11-01

Survival rates for patients with medulloblastoma have improved in the last decades but for those who relapse outcome is dismal and new approaches are needed. Emerging drugs have been tested in the last two decades within the context of phase I/II trials. In parallel, advances in genetic profiling have permitted to identify key molecular alterations for which new strategies are being developed. We performed a systematic review focused on the design and outcome of early-phase trials evaluating new agents in patients with relapsed medulloblastoma. PubMed, clinicaltrials.gov, and references from selected studies were screened to identify phase I/II studies with reported results between 2000 and 2015 including patients with medulloblastoma aged <18 years. A total of 718 studies were reviewed and 78 satisfied eligibility criteria. Of those, 69% were phase I; 31% phase II. Half evaluated conventional chemotherapeutics and 35% targeted agents. Overall, 662 patients with medulloblastoma/primitive neuroectodermal tumors were included. The study designs and the response assessments were heterogeneous, limiting the comparisons among trials and the correct identification of active drugs. Median (range) objective response rate (ORR) for patients with medulloblastoma in phase I/II studies was 0% (0-100) and 6.5% (0-50), respectively. Temozolomide containing regimens had a median ORR of 16.5% (0-100). Smoothened inhibitors trials had a median ORR of 8% (3-8). Novel drugs have shown limited activity against relapsed medulloblastoma. Temozolomide might serve as backbone for new combinations. Novel and more homogenous trial designs might facilitate the development of new drugs. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Impact of non-uniform correlation structure on sample size and power in multiple-period cluster randomised trials.

PubMed

Kasza, J; Hemming, K; Hooper, R; Matthews, Jns; Forbes, A B

2017-01-01

Stepped wedge and cluster randomised crossover trials are examples of cluster randomised designs conducted over multiple time periods that are being used with increasing frequency in health research. Recent systematic reviews of both of these designs indicate that the within-cluster correlation is typically taken account of in the analysis of data using a random intercept mixed model, implying a constant correlation between any two individuals in the same cluster no matter how far apart in time they are measured: within-period and between-period intra-cluster correlations are assumed to be identical. Recently proposed extensions allow the within- and between-period intra-cluster correlations to differ, although these methods require that all between-period intra-cluster correlations are identical, which may not be appropriate in all situations. Motivated by a proposed intensive care cluster randomised trial, we propose an alternative correlation structure for repeated cross-sectional multiple-period cluster randomised trials in which the between-period intra-cluster correlation is allowed to decay depending on the distance between measurements. We present results for the variance of treatment effect estimators for varying amounts of decay, investigating the consequences of the variation in decay on sample size planning for stepped wedge, cluster crossover and multiple-period parallel-arm cluster randomised trials. We also investigate the impact of assuming constant between-period intra-cluster correlations instead of decaying between-period intra-cluster correlations. Our results indicate that in certain design configurations, including the one corresponding to the proposed trial, a correlation decay can have an important impact on variances of treatment effect estimators, and hence on sample size and power. An R Shiny app allows readers to interactively explore the impact of correlation decay.

Study protocol: can a school gardening intervention improve children’s diets?

PubMed Central

2012-01-01

Background The current academic literature suggests there is a potential for using gardening as a tool to improve children’s fruit and vegetable intake. This study is two parallel randomised controlled trials (RCT) devised to evaluate the school gardening programme of the Royal Horticultural Society (RHS) Campaign for School Gardening, to determine if it has an effect on children’s fruit and vegetable intake. Method/Design Trial One will consist of 26 schools; these schools will be randomised into two groups, one to receive the intensive intervention as “Partner Schools” and the other to receive the less intensive intervention as “Associate Schools”. Trial Two will consist of 32 schools; these schools will be randomised into either the less intensive intervention “Associate Schools” or a comparison group with delayed intervention. Baseline data collection will be collected using a 24-hour food diary (CADET) to collect data on dietary intake and a questionnaire exploring children’s knowledge and attitudes towards fruit and vegetables. A process measures questionnaire will be used to assess each school’s gardening activities. Discussion The results from these trials will provide information on the impact of the RHS Campaign for School Gardening on children’s fruit and vegetable intake. The evaluation will provide valuable information for designing future research in primary school children’s diets and school based interventions. Trial registration ISRCTN11396528 PMID:22537179

Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial

PubMed Central

Fernie, Gordon; Currie, James; Perrin, Jennifer S.; Stewart, Caroline A.; Anderson, Virginica; Bennett, Daniel M.; Hay, Steven; Reid, Ian C.

2017-01-01

Background Ketamine has recently become an agent of interest as an acute treatment for severe depression and as the anaesthetic for electroconvulsive therapy (ECT). Subanaesthetic doses result in an acute reduction in depression severity while evidence is equivocal for this antidepressant effect with anaesthetic or adjuvant doses. Recent systematic reviews call for high-quality evidence from further randomised controlled trials (RCTs). Aims To establish if ketamine as the anaesthetic for ECT results in fewer ECT treatments, improvements in depression severity ratings and less memory impairment than the standard anaesthetic. Method Double-blind, parallel-design, RCT of intravenous ketamine (up to 2 mg/kg) with an active comparator, intravenous propofol (up to 2.5 mg/kg), as the anaesthetic for ECT in patients receiving ECT for major depression on an informal basis. (Trial registration: European Clinical Trials Database (EudraCT): 2011-000396-14 and clinicalTrials.gov: NCT01306760.) Results No significant differences were found on any outcome measure during, at the end of or 1 month following the ECT course. Conclusions Ketamine as an anaesthetic does not enhance the efficacy of ECT. PMID:28254962

Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

PubMed

Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

2012-01-01

Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

Pilot Study Assessing the Feasibility of Applying Bilateral Subthalamic Nucleus Deep Brain Stimulation in Very Early Stage Parkinson's Disease: Study design and rationale

PubMed Central

Charles, David; Tolleson, Christopher; Davis, Thomas L.; Gill, Chandler E.; Molinari, Anna L.; Bliton, Mark J.; Tramontana, Michael G.; Salomon, Ronald M.; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T.; Neimat, Joseph S.; Konrad, Peter E.

2014-01-01

Background Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. Objective We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. Methods We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Results Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. Conclusions This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease. PMID:23938229

Cross-sector surveys assessing perceptions of key stakeholders towards barriers, concerns and facilitators to the appropriate use of adaptive designs in confirmatory trials.

PubMed

Dimairo, Munyaradzi; Julious, Steven A; Todd, Susan; Nicholl, Jonathan P; Boote, Jonathan

2015-12-23

Appropriately conducted adaptive designs (ADs) offer many potential advantages over conventional trials. They make better use of accruing data, potentially saving time, trial participants, and limited resources compared to conventional, fixed sample size designs. However, one can argue that ADs are not implemented as often as they should be, particularly in publicly funded confirmatory trials. This study explored barriers, concerns, and potential facilitators to the appropriate use of ADs in confirmatory trials among key stakeholders. We conducted three cross-sectional, online parallel surveys between November 2014 and January 2015. The surveys were based upon findings drawn from in-depth interviews of key research stakeholders, predominantly in the UK, and targeted Clinical Trials Units (CTUs), public funders, and private sector organisations. Response rates were as follows: 30(55 %) UK CTUs, 17(68 %) private sector, and 86(41 %) public funders. A Rating Scale Model was used to rank barriers and concerns in order of perceived importance for prioritisation. Top-ranked barriers included the lack of bridge funding accessible to UK CTUs to support the design of ADs, limited practical implementation knowledge, preference for traditional mainstream designs, difficulties in marketing ADs to key stakeholders, time constraints to support ADs relative to competing priorities, lack of applied training, and insufficient access to case studies of undertaken ADs to facilitate practical learning and successful implementation. Associated practical complexities and inadequate data management infrastructure to support ADs were reported as more pronounced in the private sector. For funders of public research, the inadequate description of the rationale, scope, and decision-making criteria to guide the planned AD in grant proposals by researchers were all viewed as major obstacles. There are still persistent and important perceptions of individual and organisational obstacles hampering the use of ADs in confirmatory trials research. Stakeholder perceptions about barriers are largely consistent across sectors, with a few exceptions that reflect differences in organisations' funding structures, experiences and characterisation of study interventions. Most barriers appear connected to a lack of practical implementation knowledge and applied training, and limited access to case studies to facilitate practical learning.

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

Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials

PubMed Central

Holmskov, Mathilde; Storebø, Ole Jakob; Moreira-Maia, Carlos R.; Ramstad, Erica; Magnusson, Frederik Løgstrup; Krogh, Helle B.; Groth, Camilla; Gillies, Donna; Zwi, Morris; Skoog, Maria; Gluud, Christian; Simonsen, Erik

2017-01-01

Objectives To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review. Methods and findings We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes. Conclusion Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found. PMID:28617801

Vibrating vaginal balls to improve pelvic floor muscle performance in women after childbirth: a protocol for a randomised controlled feasibility trial.

PubMed

Oblasser, Claudia; McCourt, Christine; Hanzal, Engelbert; Christie, Janice

2016-04-01

This paper presents a feasibility trial protocol the purpose of which is to prepare for a future randomised controlled trial to determine the effectiveness of vibrating vaginal pelvic floor training balls for postpartum pelvic floor muscle rehabilitation. Vibrating vaginal pelvic floor training balls are available in Austria to enhance women's pelvic floor muscles and thus prevent or treat urinary incontinence and other pelvic floor problems following childbirth. Nonetheless, there is currently little empirical knowledge to substantiate their use or assess their relative effectiveness in comparison to current standard care, which involves pelvic floor muscle exercises. Single blind, randomised controlled feasibility trial with two parallel groups. It is planned to recruit 56 postpartum women in Vienna, who will be randomised into one of two intervention groups to use either vibrating vaginal balls or a comparator pelvic floor muscle exercises for 12 weeks. As this is a feasibility study, study design features (recruitment, selection, randomisation, intervention concordance, data collection methods and tools) will be assessed and participants' views and experiences will be surveyed. Tested outcome measures, collected before and after the intervention, will be pelvic floor muscle performance as reported by participants and measured by perineometry. Descriptive and inferential statistics and content analysis will serve the preparation of the future trial. The results of this feasibility trial will inform the design and conduct of a full randomised controlled trial and provide insight into the experiences of women regarding the interventions and study participation. © 2015 John Wiley & Sons Ltd.

Designing and conducting a randomized trial for pandemic critical illness: the 2009 H1N1 influenza pandemic.

PubMed

Annane, Djillali; Antona, Marion; Lehmann, Blandine; Kedzia, Cecile; Chevret, Sylvie

2012-01-01

To analyze the hurdles in implementing a randomized trial of corticosteroids for severe 2009 H1N1 influenza infections. This was an investigator-led, multicenter, randomized, placebo-controlled, double-blind trial of corticosteroids in ICU patients with 2009 H1N1 influenza pneumonia requiring mechanical ventilation. The feasibility of and hurdles in designing and initiating a phase III trial in a short-lived pandemic crisis were analyzed. The regulatory agency and ethics committee approved the study's scientific, financial, and ethical aspects within 4 weeks. Hydrocortisone and placebo were prepared centrally and shipped to participating hospitals within 6 weeks. The inclusion period started on November 9, 2009. From August 1, 2009 to March 8, 2010, only 205/224 ICU patients with H1N1 infections required mechanical ventilation. The peak of the wave was missed by 2-3 weeks and only 26 patients were randomized. The two main reasons for non-inclusion were patients' admission before the beginning of the trial and ICU personnel overwhelmed by clinical duties. Parallel rather than sequential regulatory and ethics approval, and preparation and masking of study drugs by local pharmacists would have allowed the study to start 1 month earlier and before the peak of the "flu" wave. A dedicated research team in each participating center would have increased the ratio of screened to randomized patients. This report highlights the main hurdles in implementing a randomized trial for a pandemic critical illness and proposes solutions for future trials.

UVB phototherapy in an outpatient setting or at home: a pragmatic randomised single-blind trial designed to settle the discussion. The PLUTO study.

PubMed

Koek, Mayke B G; Buskens, Erik; Steegmans, Paul H A; van Weelden, Huib; Bruijnzeel-Koomen, Carla A F M; Sigurdsson, Vigfús

2006-08-01

Home ultraviolet B (UVB) treatment is a much-debated treatment, especially with regard to effectiveness, safety and side effects. However, it is increasingly being prescribed, especially in the Netherlands. Despite ongoing discussions, no randomised research has been performed, and only two studies actually compare two groups of patients. Thus, firm evidence to support or discourage the use of home UVB phototherapy has not yet been obtained. This is the goal of the present study, the PLUTO study (Dutch acronym for "national trial on home UVB phototherapy for psoriasis"). We designed a pragmatic randomised single-blind multi-centre trial. This trial is designed to evaluate the impact of home UVB treatment versus UVB phototherapy in a hospital outpatient clinic as to effectiveness, quality of life and cost-effectiveness. In total 196 patients with psoriasis who were clinically eligible for UVB phototherapy were included. Normally 85% of the patients treated with UVB show a relevant clinical response. With a power of 80% and a 0.05 significance level it will be possible to detect a reduction in effectiveness of 15%. Effectiveness will be determined by calculating differences in the Psoriasis Area and Severity Index (PASI) and the Self Administered PASI (SAPASI) scores. Quality of life is measured using several validated generic questionnaires and a disease-specific questionnaire. Other outcome measures include costs, side effects, dosimetry, concomitant use of medication and patient satisfaction. Patients are followed throughout the therapy and for 12 months thereafter. The study is no longer recruiting patients, and is expected to report in 2006. In the field of home UVB phototherapy this trial is the first randomised parallel group study. As such, this trial addresses the weaknesses encountered in previous studies. The pragmatic design ensures that the results can be well generalised to the target population. Because, in addition to effectiveness, aspects such as quality of life and cost-effectiveness are also taken into consideration, this study will produce valuable evidence to either support or discourage prescription of home UVB phototherapy. Current controlled trials/Nederlands Trial register: ISRCTN83025173. Clinicaltrials.gov: NCT00150930.

An approach to combining parallel and cross-over trials with and without run-in periods using individual patient data.

PubMed

Tvete, Ingunn F; Olsen, Inge C; Fagerland, Morten W; Meland, Nils; Aldrin, Magne; Smerud, Knut T; Holden, Lars

2012-04-01

In active run-in trials, where patients may be excluded after a run-in period based on their response to the treatment, it is implicitly assumed that patients have individual treatment effects. If individual patient data are available, active run-in trials can be modelled using patient-specific random effects. With more than one trial on the same medication available, one can obtain a more precise overall treatment effect estimate. We present a model for joint analysis of a two-sequence, four-period cross-over trial (AABB/BBAA) and a three-sequence, two-period active run-in trial (AB/AA/A), where the aim is to investigate the effect of a new treatment for patients with pain due to osteoarthritis. Our approach enables us to separately estimate the direct treatment effect for all patients, for the patients excluded after the active run-in trial prior to randomisation, and for the patients who completed the active run-in trial. A similar model approach can be used to analyse other types of run-in trials, but this depends on the data and type of other trials available. We assume equality of the various carry-over effects over time. The proposed approach is flexible and can be modified to handle other designs. Our results should be encouraging for those responsible for planning cost-efficient clinical development programmes.

Design of the evolution of management strategies of heart failure patients with implantable defibrillators (EVOLVO) study to assess the ability of remote monitoring to treat and triage patients more effectively

PubMed Central

Marzegalli, Maurizio; Landolina, Maurizio; Lunati, Maurizio; Perego, Giovanni B; Pappone, Alessia; Guenzati, Giuseppe; Campana, Carlo; Frigerio, Maria; Parati, Gianfranco; Curnis, Antonio; Colangelo, Irene; Valsecchi, Sergio

2009-01-01

Background Heart failure patients with implantable defibrillators (ICD) frequently visit the clinic for routine device monitoring. Moreover, in the case of clinical events, such as ICD shocks or alert notifications for changes in cardiac status or safety issues, they often visit the emergency department or the clinic for an unscheduled visit. These planned and unplanned visits place a great burden on healthcare providers. Internet-based remote device interrogation systems, which give physicians remote access to patients' data, are being proposed in order to reduce routine and interim visits and to detect and notify alert conditions earlier. Methods The EVOLVO study is a prospective, randomized, parallel, unblinded, multicenter clinical trial designed to compare remote ICD management with the current standard of care, in order to assess its ability to treat and triage patients more effectively. Two-hundred patients implanted with wireless-transmission-enabled ICD will be enrolled and randomized to receive either the Medtronic CareLink® monitor for remote transmission or the conventional method of in-person evaluations. The purpose of this manuscript is to describe the design of the trial. The results, which are to be presented separately, will characterize healthcare utilizations as a result of ICD follow-up by means of remote monitoring instead of conventional in-person evaluations. Trial registration ClinicalTrials.gov: NCT00873899 PMID:19538734

A note on sample size calculation for mean comparisons based on noncentral t-statistics.

PubMed

Chow, Shein-Chung; Shao, Jun; Wang, Hansheng

2002-11-01

One-sample and two-sample t-tests are commonly used in analyzing data from clinical trials in comparing mean responses from two drug products. During the planning stage of a clinical study, a crucial step is the sample size calculation, i.e., the determination of the number of subjects (patients) needed to achieve a desired power (e.g., 80%) for detecting a clinically meaningful difference in the mean drug responses. Based on noncentral t-distributions, we derive some sample size calculation formulas for testing equality, testing therapeutic noninferiority/superiority, and testing therapeutic equivalence, under the popular one-sample design, two-sample parallel design, and two-sample crossover design. Useful tables are constructed and some examples are given for illustration.

Clinical Trials of Potential Cognitive-Enhancing Drugs in Schizophrenia: What Have We Learned So Far?

PubMed Central

Keefe, Richard S. E.; Buchanan, Robert W.; Marder, Stephen R.; Schooler, Nina R.; Dugar, Ashish; Zivkov, Milana; Stewart, Michelle

2013-01-01

In light of the number of studies conducted to examine the treatment of cognitive impairment associated with schizophrenia (CIAS), we critically reviewed recent CIAS trials. Trials were identified through searches of the website “www.clinicaltrials.gov” using the terms “schizophrenia AND cognition,” “schizophrenia AND neurocognition,” “schizophrenia AND neurocognitive tests,” “schizophrenia AND MATRICS,” “schizophrenia AND MCCB,” “schizophrenia AND BACS,” “schizophrenia AND COGSTATE,” and “schizophrenia AND CANTAB” and “first-episode schizophrenia AND cognition.” The cutoff date was 20 April 2011. Included trials were conducted in people with schizophrenia, the effects on cognition were either a primary or secondary outcome, and the effect of a pharmacologically active substance was examined. Drug challenge, pharmacokinetic, pharmacodynamic, or prodrome of psychosis studies were excluded. We identified 118 trials, with 62% using an add-on parallel group design. The large majority of completed trials were underpowered to detect moderate effect sizes, had ≤8 weeks duration, and were performed in samples of participants with chronic stable schizophrenia. The ongoing add-on trials are longer, have larger sample sizes (with a number of them being adequately powered to detect moderate effect sizes), and are more likely to use a widely accepted standardized cognitive battery (eg, the MATRICS Consensus Cognitive Battery) and MATRICS guidelines. Ongoing studies performed in subjects with recent onset schizophrenia may help elucidate which subjects are most likely to show an effect in cognition. New insights into the demands of CIAS trial design and methodology may help increase the probability of identifying treatments with beneficial effect on cognitive impairment in schizophrenia. PMID:22114098

Use of ClinicalTrials.gov to estimate condition-specific nocebo effects and other factors affecting outcomes of analgesic trials.

PubMed

Cepeda, M Soledad; Lobanov, Victor; Berlin, Jesse A

2013-04-01

ClinicalTrials.gov is a registry and results database of federally and privately supported clinical trials conducted worldwide. We sought to answer: what are the characteristics of pain trials; how frequently are these trials stopped and why; what is the magnitude of attrition due to lack of efficacy or adverse events; and whether the withdrawal rates depend on pain syndrome. To facilitate this and subsequent studies, we have developed a system called Sherlock that automatically downloads data from ClinicalTrials.gov into a relational database. We included pain interventional trials. To evaluate attrition, we restricted consideration to prospective randomized, parallel, double-blind, placebo-controlled trials. Of the 82,867 trials, 6% reported results and 5.6% terminated before the planned number of subjects was accrued. Of these early terminations, 38% were due to enrollment difficulties. In the placebo arms, 3.8% of participants withdrew due to lack of efficacy and 4.9% due to adverse events, with proportions differing among pain conditions. Compared with migraine trials, in fibromyalgia trials 5.1% more participants withdrew due to lack of efficacy (95% confidence interval [CI], 2.5-7.8%), and 6.4% more withdrew due to adverse events (95% CI, 4.3-8.6%). Nonsteroidal anti-inflammatory drugs were the treatment class with the lowest adverse events withdrawals. Recruitment challenges account for the largest proportion of noncompleted trials. Attrition rates differ across pain conditions. Migraine studies had the lowest withdrawal rate. Tools like Sherlock facilitate conducting research in the ClinicalTrials.gov registry. ClinicalTrials.gov registry enables researchers to get a snapshot of a specific field and observe changes over time in trial design, including numbers of subjects accrued, and it can inform clinical trial design. We learned that recruitment challenges account for the largest proportion of noncompleted trials, attrition rates differed across pain conditions, and migraine studies had the lowest withdrawal rate. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Review of the influence of pigment dispersion and exfoliation glaucoma diagnosis on intraocular pressure in clinical trials evaluating primary open-angle glaucoma and ocular hypertension.

PubMed

Stewart, William C; DeMill, D L; Wirostko, Barbara M; Nelson, Lindsay A; Stewart, Jeanette A

2013-08-01

To evaluate published, randomized, prospective, parallel clinical trials utilizing currently approved glaucoma medications to determine what influence, if any, pigment dispersion (PD) or exfoliation glaucoma (XFG) patients had on the intraocular pressure. A review of clinical trial articles evaluating currently used topical glaucoma medicines. Articles were published between January 1995 and April 2011. If the articles met the inclusion/exclusion criteria, they were analyzed for PD and XFG. Twenty-four articles were included, containing 49 treatment arms that included PD or XFG patients. The range of PD patients was 0% to 4.5%, with a mean of 1.5±0.9%, and for XFG patients 0% to 6.3%, with a mean of 2.2±2.1%. The treatment arms with PD showed a difference in the intraocular pressures (IOPs), for all studies analyzed together, for the baseline IOPs between clinical trials that did and did not include PD patients (8 AM IOPs: with PD 26.5±0.9 mm Hg and without PD 25.8±1.3 mm Hg, P=0.024; and diurnal curve mean IOPs: with PD 25.3±1.1 mm Hg and without PD 24.5±1.3 mm Hg, P=0.024). The XFG treatment arms showed that there was a difference in the IOPs for all studies analyzed together for diurnal baseline IOPs between clinical trials that did and did not include XFG patients (with XFG 25.2±1.2 mm Hg and without XFG 24.3±1.0 mm Hg, P=0.016). Trial designs for prospective, parallel, glaucoma clinical studies that are performed in the United States generally can include PD and XFG patients with only a small impact on the IOP and a low number of such subjects enrolled.

A single-blinded, randomized, parallel group superiority trial investigating the effects of footwear and custom foot orthoses versus footwear alone in individuals with patellofemoral joint osteoarthritis: a phase II pilot trial protocol.

PubMed

Wyndow, Narelle; Crossley, Kay M; Vicenzino, Bill; Tucker, Kylie; Collins, Natalie J

2017-01-01

Patellofemoral joint osteoarthritis is a common condition, yet information regarding conservative management is lacking. Foot orthoses are an effective intervention for improving pain and function in younger individuals with patellofemoral pain and may be effective in those with patellofemoral osteoarthritis. This pilot study will seek to establish the feasibility of a phase III randomised controlled trial to investigate whether foot orthoses worn in prescribed motion controlled footwear are superior to prescribed motion control footwear alone in the management of patellofemoral osteoarthritis. This phase II pilot clinical trial is designed as a randomized, single-blind, parallel group, two arm, superiority trial. The trial will recruit 44 participants from Queensland and Tasmania, Australia. Volunteers aged 40 years and over must have clinical symptoms and radiographic evidence of patellofemoral osteoarthritis to be eligible for inclusion. Those eligible will be randomized to receive either foot orthoses and prescribed motion control shoes, or prescribed motion control shoes alone, to be worn for a period of 4 months. The feasibility of a phase III clinical trial will be evaluated by assessing factors such as recruitment rate, number of eligible participants, participant compliance with the study protocol, adverse events, and drop-out rate. A secondary aim of the study will be to determine completion rates and calculate effect sizes for patient reported outcome measures such as knee-related symptoms, function, quality of life, kinesiophobia, self-efficacy, general and mental health, and physical activity at 2 and 4 months. Primary outcomes will be reported descriptively while effect sizes and 95% confidence intervals will be calculated for the secondary outcome measures. Data will be analysed using an intention-to-treat principle. The results of this pilot trial will help determine the feasibility of a phase III clinical trial investigating whether foot orthoses plus motion control footwear are superior to motion control footwear alone in individuals with patellofemoral osteoarthritis. A Phase III clinical trial will help guide footwear and foot orthoses recommendations in the clinical management of this disorder. Retrospectively registered with the Australian New Zealand Clinical Trials Registry: ACTRN12615000002583. Date registered: 07/01/15.

Robust EM Continual Reassessment Method in Oncology Dose Finding

PubMed Central

Yuan, Ying; Yin, Guosheng

2012-01-01

The continual reassessment method (CRM) is a commonly used dose-finding design for phase I clinical trials. Practical applications of this method have been restricted by two limitations: (1) the requirement that the toxicity outcome needs to be observed shortly after the initiation of the treatment; and (2) the potential sensitivity to the prespecified toxicity probability at each dose. To overcome these limitations, we naturally treat the unobserved toxicity outcomes as missing data, and use the expectation-maximization (EM) algorithm to estimate the dose toxicity probabilities based on the incomplete data to direct dose assignment. To enhance the robustness of the design, we propose prespecifying multiple sets of toxicity probabilities, each set corresponding to an individual CRM model. We carry out these multiple CRMs in parallel, across which model selection and model averaging procedures are used to make more robust inference. We evaluate the operating characteristics of the proposed robust EM-CRM designs through simulation studies and show that the proposed methods satisfactorily resolve both limitations of the CRM. Besides improving the MTD selection percentage, the new designs dramatically shorten the duration of the trial, and are robust to the prespecification of the toxicity probabilities. PMID:22375092

Accelerating Pediatric Cancer Drug Development: Challenges and Opportunities for Pediatric Master Protocols.

PubMed

Khan, Tahira; Stewart, Mark; Blackman, Samuel; Rousseau, Raphaël; Donoghue, Martha; Cohen, Kenneth; Seibel, Nita; Fleury, Mark; Benettaib, Bouchra; Malik, Raleigh; Vassal, Gilles; Reaman, Gregory

2018-01-01

Although outcomes for children with cancer have significantly improved over the past 40 years, there has been little progress in the treatment of some pediatric cancers, particularly when advanced. Additionally, clinical trial options and availability are often insufficient. Improved genomic and immunologic understanding of pediatric cancers, combined with innovative clinical trial designs, may provide an enhanced opportunity to study childhood cancers. Master protocols, which incorporate the use of precision medicine approaches, coupled with the ability to quickly assess the safety and effectiveness of new therapies, have the potential to accelerate early-phase clinical testing of novel therapeutics and which may result in more rapid approval of new drugs for children with cancer. Designing and conducting master protocols for children requires addressing similar principles and requirements as traditional adult oncology trials, but there are also unique considerations for master protocols conducted in children with cancer. The purpose of this paper is to define the key challenges and opportunities associated with this approach in order to ensure that master protocols can be adapted to benefit children and adolescents and ensure that adequate data are captured to advance, in parallel, the clinical development of investigational agents for children with cancer.

NRMC - A GPU code for N-Reverse Monte Carlo modeling of fluids in confined media

NASA Astrophysics Data System (ADS)

Sánchez-Gil, Vicente; Noya, Eva G.; Lomba, Enrique

2017-08-01

NRMC is a parallel code for performing N-Reverse Monte Carlo modeling of fluids in confined media [V. Sánchez-Gil, E.G. Noya, E. Lomba, J. Chem. Phys. 140 (2014) 024504]. This method is an extension of the usual Reverse Monte Carlo method to obtain structural models of confined fluids compatible with experimental diffraction patterns, specifically designed to overcome the problem of slow diffusion that can appear under conditions of tight confinement. Most of the computational time in N-Reverse Monte Carlo modeling is spent in the evaluation of the structure factor for each trial configuration, a calculation that can be easily parallelized. Implementation of the structure factor evaluation in NVIDIA® CUDA so that the code can be run on GPUs leads to a speed up of up to two orders of magnitude.

Effects of clopidogrel, prasugrel and ticagrelor on endothelial function, inflammatory and oxidative stress parameters and platelet function in patients undergoing coronary artery stenting for an acute coronary syndrome. A randomised, prospective, controlled study

PubMed Central

Schnorbus, Boris; Daiber, Andreas; Jurk, Kerstin; Warnke, Silke; König, Jochem; Krahn, Ulrike; Lackner, Karl; Munzel, Thomas; Gori, Tommaso

2014-01-01

Introduction Particularly in the setting of acute coronary syndromes, the interplay between vascular and platelet function has been postulated to have direct clinical implications. The present trial is designed to test the effect of clopidogrel, prasugrel and ticagrelor on multiple parameters of vascular function, platelet aggregation, oxidative and inflammatory stress before and up to 4 weeks after coronary artery stenting. Methods and analysis The study is designed as a three-arm, parallel design, randomised, investigator-blinded study. Patients with unstable angina or non-ST elevation myocardial infarction undergoing coronary intervention with a drug-eluting stent will be randomised to receive 600 mg clopidogrel, 60 mg prasugrel or 180 mg ticagrelor followed by oral therapy with the same drug. The primary endpoint of the trial is the impact of antiplatelet treatments on endothelial function as assessed by flow-mediated dilation at 1 day, 1 week and 1 month in patients who have undergone stenting. Secondary endpoints include the impact of study medications on parameters of macrovascular and microvascular function, platelet reactivity, oxidative and inflammatory stress. The study recruitment is currently ongoing and, after an interim analysis which was performed at 50% of the initially planned population, it is planned to continue until July 2015. Ethics and dissemination The protocol was approved by the local ethics committee. The trial will provide important pathophysiological insight on the relationship between platelet aggregation and endothelial function, two parameters that have been shown to influence patients’ prognosis. Trial registration number ClinicalTrials.gov Identifier: NCT01700322; EudraCT-Nr.: 2011-005305-73. Current V.1.3, from 24 February 2014. PMID:24801283

Randomised social-skills training and parental training plus standard treatment versus standard treatment of children with attention deficit hyperactivity disorder - The SOSTRA trial protocol

PubMed Central

2011-01-01

Background Children with attention deficit hyperactivity disorder (ADHD) are hyperactive and impulsive, cannot maintain attention, and have difficulties with social interactions. Medical treatment may alleviate symptoms of ADHD, but seldom solves difficulties with social interactions. Social-skills training may benefit ADHD children in their social interactions. We want to examine the effects of social-skills training on difficulties related to the children's ADHD symptoms and social interactions. Methods/Design The design is randomised two-armed, parallel group, assessor-blinded trial. Children aged 8-12 years with a diagnosis of ADHD are randomised to social-skills training and parental training plus standard treatment versus standard treatment alone. A sample size calculation estimated that at least 52 children must be included to show a 4-point difference in the primary outcome on the Conners 3rd Edition subscale for 'hyperactivity-impulsivity' between the intervention group and the control group. The outcomes will be assessed 3 and 6 months after randomisation. The primary outcome measure is ADHD symptoms. The secondary outcome is social skills. Tertiary outcomes include the relationship between social skills and symptoms of ADHD, the ability to form attachment, and parents' ADHD symptoms. Discussion We hope that the results from this trial will show that the social-skills training together with medication may have a greater general effect on ADHD symptoms and social and emotional competencies than medication alone. Trial registration ClinicalTrials (NCT): NCT00937469 PMID:21255399

Effectiveness of functional hand splinting and the cognitive orientation to occupational performance (CO-OP) approach in children with cerebral palsy and brain injury: two randomised controlled trial protocols

PubMed Central

2014-01-01

Background Cerebral palsy (CP) and brain injury (BI) are common conditions that have devastating effects on a child’s ability to use their hands. Hand splinting and task-specific training are two interventions that are often used to address deficits in upper limb skills, both in isolation or concurrently. The aim of this paper is to describe the method to be used to conduct two randomised controlled trials (RCT) investigating (a) the immediate effect of functional hand splints, and (b) the effect of functional hand splints used concurrently with task-specific training compared to functional hand splints alone, and to task-specific training alone in children with CP and BI. The Cognitive Orientation to Occupational Performance (CO-OP) approach will be the task-specific training approach used. Methods/Design Two concurrent trials; a two group, parallel design, RCT with a sample size of 30 participants (15 per group); and a three group, parallel design, assessor blinded, RCT with a sample size of 45 participants (15 per group). Inclusion criteria: age 4-15 years; diagnosis of CP or BI; Manual Abilities Classification System (MACS) level I – IV; hand function goals; impaired hand function; the cognitive, language and behavioural ability to participate in CO-OP. Participants will be randomly allocated to one of 3 groups; (1) functional hand splint only (n=15); (2) functional hand splint combined with task-specific training (n=15); (3) task-specific training only (n=15). Allocation concealment will be achieved using sequentially numbered, sealed opaque envelopes opened by an off-site officer after baseline measures. Treatment will be provided for a period of 2 weeks, with outcome measures taken at baseline, 1 hour after randomisation, 2 weeks and 10 weeks. The functional hand splint will be a wrist cock-up splint (+/- thumb support or supination strap). Task-specific training will involve 10 sessions of CO-OP provided in a group of 2-4 children. Primary outcome measures will be the Canadian Occupational Performance Measure (COPM) and the Goal Attainment Scale (GAS). Analysis will be conducted on an intention-to-treat basis. Discussion This paper outlines the protocol for two randomised controlled trials investigating functional hand splints and CO-OP for children with CP and BI. PMID:25023385

Neuroendocrine and Inflammatory Responses to Losartan and Continuous Positive Airway Pressure in Patients with Hypertension and Obstructive Sleep Apnea. A Randomized Controlled Trial.

PubMed

Thunström, Erik; Manhem, Karin; Yucel-Lindberg, Tülay; Rosengren, Annika; Lindberg, Caroline; Peker, Yüksel

2016-11-01

Blood pressure reduction in response to antihypertensive agents is less for patients with obstructive sleep apnea (OSA). Increased sympathetic and inflammatory activity, as well as alterations in the renin-angiotensin-aldosterone system, may play a role in this context. To address the cardiovascular mechanisms involved in response to an angiotensin II receptor antagonist, losartan, and continuous positive airway pressure (CPAP) as add-on treatment for hypertension and OSA. Newly diagnosed hypertensive patients with or without OSA (allocated in a 2:1 ratio for OSA vs. no OSA) were treated with losartan 50 mg daily during a 6-week two-center, open-label, prospective, case-control, parallel-design study. In the second 6-week, sex-stratified, open-label, randomized, parallel-design study, all subjects with OSA continued to receive losartan and were randomly assigned to either CPAP as add-on therapy or to no CPAP (1:1 ratio for CPAP vs. no CPAP). Study subjects without OSA were followed in parallel while they continued to take losartan. Blood samples were collected at baseline, after 6 weeks, and after 12 weeks for analysis of renin, aldosterone, noradrenaline, adrenaline, and inflammatory markers. Fifty-four patients with OSA and 35 without OSA were included in the first 6-week study. Losartan significantly increased renin levels and reduced aldosterone levels in the group without OSA. There was no significant decrease in aldosterone levels among patients with OSA. Add-on CPAP treatment tended to lower aldosterone levels, but reductions were more pronounced in measures of sympathetic activity. No significant changes in inflammatory markers were observed following treatment with losartan and CPAP. Hypertensive patients with OSA responded to losartan treatment with smaller reductions in aldosterone compared with hypertensive patients without OSA. Sympathetic system activity seemed to respond primarily to add-on CPAP treatment in patients with newly discovered hypertension and OSA. Clinical trial registered with www.clinicaltrials.gov (NCT00701428).

ClinicalTrials.gov and Drugs@FDA: A comparison of results reporting for new drug approval trials

PubMed Central

Schwartz, Lisa M.; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A.

2016-01-01

Background Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. Purpose To validate results posted on ClinicalTrials.gov against publicly-available FDA reviews on Drugs@FDA. Data sources ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical/statistical reviews). Study selection 100 parallel-group, randomized trials for new drug approvals (1/2013 – 7/2014) with results posted on ClinicalTrials.gov (3/15/2015). Data extraction Two assessors systematically extracted, and another verified, trial design, primary/secondary outcomes, adverse events, and deaths. Results The 100 trials were mostly phase 3 (90%) double-blind (92%), placebo-controlled (73%), representing 32 drugs from 24 companies. Of 137 primary outcomes from ClinicalTrials.gov, 134 (98%) had corresponding data in Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results; most differences were nominal (i.e. relative difference < 10%). Of 100 trials, primary outcome results in 14 could not be validated . Of 1,927 secondary outcomes from ClinicalTrials.gov, 1,061 (55%) definitions could be validated and 367 (19%) had results. Of 96 trials with ≥ 1 serious adverse event in either source, 14 could be compared and 7 were discordant. Of 62 trials with ≥ 1 death in either source, 25 could be compared and 17 were discordant. Limitations Unknown generalizability to uncontrolled or crossover trial results. Conclusion Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half of secondary outcomes could not be validated because Drugs@FDA only includes “key outcomes” for regulatory decision-making; nor could serious adverse events and deaths because Drugs@FDA frequently only includes results aggregated across multiple trials. PMID:27294570

Electrophysiological evidence for parallel and serial processing during visual search.

PubMed

Luck, S J; Hillyard, S A

1990-12-01

Event-related potentials were recorded from young adults during a visual search task in order to evaluate parallel and serial models of visual processing in the context of Treisman's feature integration theory. Parallel and serial search strategies were produced by the use of feature-present and feature-absent targets, respectively. In the feature-absent condition, the slopes of the functions relating reaction time and latency of the P3 component to set size were essentially identical, indicating that the longer reaction times observed for larger set sizes can be accounted for solely by changes in stimulus identification and classification time, rather than changes in post-perceptual processing stages. In addition, the amplitude of the P3 wave on target-present trials in this condition increased with set size and was greater when the preceding trial contained a target, whereas P3 activity was minimal on target-absent trials. These effects are consistent with the serial self-terminating search model and appear to contradict parallel processing accounts of attention-demanding visual search performance, at least for a subset of search paradigms. Differences in ERP scalp distributions further suggested that different physiological processes are utilized for the detection of feature presence and absence.

The efficacy of traditional acupuncture on patients with chronic neck pain: study protocol of a randomized controlled trial.

PubMed

Yang, Yiling; Yan, Xiaoxia; Deng, Hongmei; Zeng, Dian; Huang, Jianpeng; Fu, Wenbin; Xu, Nenggui; Liu, Jianhua

2017-07-10

A large number of randomized trials on the use of acupuncture to treat chronic pain have been conducted. However, there is considerable controversy regarding the effectiveness of acupuncture. We designed a randomized trial involving patients with chronic neck pain (CNP) to investigate whether acupuncture is more effective than a placebo in treating CNP. A five-arm, parallel, single-blinded, randomized, sham-controlled trial was designed. Patients with CNP of more than 3 months' duration are being recruited from Guangdong Provincial Hospital of Chinese Medicine (China). Following examination, 175 patients will be randomized into one of five groups (35 patients in each group) as follows: a traditional acupuncture group (group A), a shallow-puncture group (group B), a non-acupoint acupuncture group (group C), a non-acupoint shallow-puncture group (group D) and a sham-puncture group (group E). The interventions will last for 20 min and will be carried out twice a week for 5 weeks. The primary outcome will be evaluated by changes in the Northwick Park Neck Pain Questionnaire (NPQ). Secondary outcomes will be measured by the pain threshold, the Short Form McGill Pain Questionnaire-2 (SF-MPQ-2), the 36-Item Short-Form Health Survey (SF-36) and diary entries. Analysis of the data will be performed at baseline, at the end of the intervention and at 3 months' follow-up. The safety of acupuncture will be evaluated at each treatment period. The purpose of this trial is to determine whether traditional acupuncture is more effective for chronic pain relief than sham acupuncture in adults with CNP, and to determine which type of sham acupuncture is the optimal control for clinical trials. Chinese Clinical Trial Registry: ChiCTR-IOR-15006886 . Registered on 2 July 2015.

Clinical trial to assess the effect of physical exercise on endothelial function and insulin resistance in pregnant women

PubMed Central

2009-01-01

Background Preeclampsia (PE) is a common maternal disease that complicates 5 to 10% of pregnancies and remains as the major cause of maternal and neonatal mortality. Cost-effective interventions aimed at preventing the development of preeclampsia are urgently needed. However, the pathogenesis of PE is not well known. Multiple mechanisms such as oxidative stress, endothelial dysfunction and insulin resistance may contribute to its development. Regular aerobic exercise recovers endothelial function; improves insulin resistance and decreases oxidative stress. Therefore the purpose of this clinical trial is to determine the effect of regular aerobic exercise on endothelial function, on insulin resistance and on pregnancy outcome. Methods and design 64 pregnant women will be included in a blind, randomized clinical trial, and parallel assignment. The exercise group will do regular aerobic physical exercise: walking (10 minutes), aerobic exercise (30 minutes), stretching (10 minutes) and relaxation exercise (10 minutes) in three sessions per week. Control group will do the activities of daily living (bathing, dressing, eating, and walking) without counselling from a physical therapist. Trial registration NCT00741312. PMID:19919718

Minimum number of clusters and comparison of analysis methods for cross sectional stepped wedge cluster randomised trials with binary outcomes: A simulation study.

PubMed

Barker, Daniel; D'Este, Catherine; Campbell, Michael J; McElduff, Patrick

2017-03-09

Stepped wedge cluster randomised trials frequently involve a relatively small number of clusters. The most common frameworks used to analyse data from these types of trials are generalised estimating equations and generalised linear mixed models. A topic of much research into these methods has been their application to cluster randomised trial data and, in particular, the number of clusters required to make reasonable inferences about the intervention effect. However, for stepped wedge trials, which have been claimed by many researchers to have a statistical power advantage over the parallel cluster randomised trial, the minimum number of clusters required has not been investigated. We conducted a simulation study where we considered the most commonly used methods suggested in the literature to analyse cross-sectional stepped wedge cluster randomised trial data. We compared the per cent bias, the type I error rate and power of these methods in a stepped wedge trial setting with a binary outcome, where there are few clusters available and when the appropriate adjustment for a time trend is made, which by design may be confounding the intervention effect. We found that the generalised linear mixed modelling approach is the most consistent when few clusters are available. We also found that none of the common analysis methods for stepped wedge trials were both unbiased and maintained a 5% type I error rate when there were only three clusters. Of the commonly used analysis approaches, we recommend the generalised linear mixed model for small stepped wedge trials with binary outcomes. We also suggest that in a stepped wedge design with three steps, at least two clusters be randomised at each step, to ensure that the intervention effect estimator maintains the nominal 5% significance level and is also reasonably unbiased.

The LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre-Operative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial.

PubMed

Boden, Ianthe; Browning, Laura; Skinner, Elizabeth H; Reeve, Julie; El-Ansary, Doa; Robertson, Iain K; Denehy, Linda

2015-12-15

Post-operative pulmonary complications are a significant problem following open upper abdominal surgery. Preliminary evidence suggests that a single pre-operative physiotherapy education and preparatory lung expansion training session alone may prevent respiratory complications more effectively than supervised post-operative breathing and coughing exercises. However, the evidence is inconclusive due to methodological limitations. No well-designed, adequately powered, randomised controlled trial has investigated the effect of pre-operative education and training on post-operative respiratory complications, hospital length of stay, and health-related quality of life following upper abdominal surgery. The Lung Infection Prevention Post Surgery - Major Abdominal- with Pre-Operative Physiotherapy (LIPPSMAck POP) trial is a pragmatic, investigator-initiated, bi-national, multi-centre, patient- and assessor-blinded, parallel group, randomised controlled trial, powered for superiority. Four hundred and forty-one patients scheduled for elective open upper abdominal surgery at two Australian and one New Zealand hospital will be randomised using concealed allocation to receive either i) an information booklet or ii) an information booklet, plus one additional pre-operative physiotherapy education and training session. The primary outcome is respiratory complication incidence using standardised diagnostic criteria. Secondary outcomes include hospital length of stay and costs, pneumonia diagnosis, intensive care unit readmission and length of stay, days/h to mobilise >1 min and >10 min, and, at 6 weeks post-surgery, patient reported complications, health-related quality of life, and physical capacity. The LIPPSMAck POP trial is a multi-centre randomised controlled trial powered and designed to investigate whether a single pre-operative physiotherapy session prevents post-operative respiratory complications. This trial standardises post-operative assisted ambulation and physiotherapy, measures many known confounders, and includes a post-discharge follow-up of complication rates, functional capacity, and health-related quality of life. This trial is currently recruiting. Australian New Zealand Clinical Trials Registry number: ACTRN12613000664741 , 19 June 2013.

Statistical power as a function of Cronbach alpha of instrument questionnaire items.

PubMed

Heo, Moonseong; Kim, Namhee; Faith, Myles S

2015-10-14

In countless number of clinical trials, measurements of outcomes rely on instrument questionnaire items which however often suffer measurement error problems which in turn affect statistical power of study designs. The Cronbach alpha or coefficient alpha, here denoted by C(α), can be used as a measure of internal consistency of parallel instrument items that are developed to measure a target unidimensional outcome construct. Scale score for the target construct is often represented by the sum of the item scores. However, power functions based on C(α) have been lacking for various study designs. We formulate a statistical model for parallel items to derive power functions as a function of C(α) under several study designs. To this end, we assume fixed true score variance assumption as opposed to usual fixed total variance assumption. That assumption is critical and practically relevant to show that smaller measurement errors are inversely associated with higher inter-item correlations, and thus that greater C(α) is associated with greater statistical power. We compare the derived theoretical statistical power with empirical power obtained through Monte Carlo simulations for the following comparisons: one-sample comparison of pre- and post-treatment mean differences, two-sample comparison of pre-post mean differences between groups, and two-sample comparison of mean differences between groups. It is shown that C(α) is the same as a test-retest correlation of the scale scores of parallel items, which enables testing significance of C(α). Closed-form power functions and samples size determination formulas are derived in terms of C(α), for all of the aforementioned comparisons. Power functions are shown to be an increasing function of C(α), regardless of comparison of interest. The derived power functions are well validated by simulation studies that show that the magnitudes of theoretical power are virtually identical to those of the empirical power. Regardless of research designs or settings, in order to increase statistical power, development and use of instruments with greater C(α), or equivalently with greater inter-item correlations, is crucial for trials that intend to use questionnaire items for measuring research outcomes. Further development of the power functions for binary or ordinal item scores and under more general item correlation strutures reflecting more real world situations would be a valuable future study.

A new proposal for randomized start design to investigate disease-modifying therapies for Alzheimer disease.

PubMed

Zhang, Richard Y; Leon, Andrew C; Chuang-Stein, Christy; Romano, Steven J

2011-02-01

The increasing prevalence of Alzheimer disease (AD) and lack of effective agents to attenuate progression have accelerated research and development of disease modifying (DM) therapies. The traditional parallel group design and single time point analysis used in the support of past AD drug approvals address symptomatic benefit over relatively short treatment durations. More recent trials investigating disease modification are by necessity longer in duration and require larger sample sizes. Nevertheless, trial design and analysis remain mostly unchanged and may not be adequate to meet the objective of demonstrating disease modification. Randomized start design (RSD) has been proposed as an option to study DM effects, but its application in AD trials may have been hampered by certain methodological challenges. To address the methodological issues that have impeded more extensive use of RSD in AD trial and to encourage other researchers to develop novel design and analysis methodologies to better ascertain DM effects for the next generation of AD therapies, we propose a stepwise testing procedure to evaluate potential DM effects of novel AD therapies. Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-cog) is used for illustration. We propose to test three hypotheses in a stepwise sequence. The three tests pertain to treatment difference at two separate time points and a difference in the rate of change. Estimation is facilitated by the Mixed-effects Model for Repeated Measures approach. The required sample size is estimated using Monte Carlo simulations and by modeling ADAS-cog data from prior longitudinal AD studies. The greatest advantage of the RSD proposed in this article is its ability to critically address the question on a DM effect. The AD trial using the new approach would be longer (12-month placebo period plus 12-month delay-start period; total 24-month duration) and require more subjects (about 1000 subjects per arm for the non-inferiority margin chosen in the illustration). It would also require additional evaluations to estimate the rate of ADAS-cog change toward the end of the trial. A regulatory claim of disease modification for any compound will likely require additional verification of a drug's effect on a validated biomarker of Alzheimer's pathology. Incorporation of the RSD in AD trials is feasible. With proper trial setup and statistical procedures, this design could support the detection of a disease-modifying effect. In our opinion, a two-phase RSD with a stepwise hypothesis testing procedure could be a reasonable option for future studies.

Beneficial Effects of Pentoxifylline Plus Losartan Dual Therapy in Type 2 Diabetes with Nephropathy.

PubMed

Rabizadeh, Soghra; Dehghani Firouzabadi, Fatemeh; Noshad, Sina; Esteghamati, Sadaf; Afarideh, Mohsen; Ghajar, Alireza; Ganji, Morsaleh; Saadat, Mohammad; Heidari, Behnam; Najafi, Mohammad Taghi; Nakhjavani, Manouchehr; Esteghamati, Alireza

2018-05-01

This study was designed to comparatively assess the effects of add-on pentoxifylline to losartan versus increasing the dose of losartan on serum N-terminal pro-brain natriuretic peptide (NT-proBNP), serum highly sensitive C-reactive protein (hsCRP) and the urinary albumin excretion (UAE) rate in patients with type 2 diabetes and nephropathy. In an open-label, single-center, parallel-group, randomized clinical trial (NCT03006952), 30 patients received b.i.d. dose of pentoxifylline 400mg plus daily dose of losartan 50mg (pentoxifylline arm) and 29 patients received b.i.d. dose of losartan 50mg (losartan arm) during a 12-week follow-up period. Serum NT-proBNP, serum hsCRP and UAE levels all significantly decreased from baseline in both trial arms. The pentoxifylline and losartan trial arms were equally effective in reducing serum NT-proBNP levels during the course of trial (multivariable adjusted model P value = 0.864, effect size = 0.2%). There was a greater decrease in UAE and serum hsCRP levels in the pentoxifylline arm (P = 0.034, effect size = 7.8%; P = 0.009, effect size = 11.7%, respectively). Conversely, patients in the losartan arm achieved better systolic and diastolic blood pressure control (P < 0.001, effect size = 25.4%; P = 0.010, effect size = 11.3%, respectively). Circulating NT-proBNP levels equally and significantly reduced from baseline in the pentoxifylline and losartan treatment arms, in parallel with comparatively superior decreases of UAE and serum hsCRP in the pentoxifylline arm, and larger decreases of systolic and diastolic blood pressures in the losartan arm. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

A randomised controlled trial of clinics in secondary schools for adolescents with asthma.

PubMed Central

Salisbury, Chris; Francis, Caia; Rogers, Chris; Parry, Kate; Thomas, Huw; Chadwick, Stephanie; Turton, Pat

2002-01-01

AIM: To compare a nurse-led clinic in schools versus care in general practice for adolescents with asthma. DESIGN OF STUDY: Randomised controlled trial in four schools; parallel observational study in two schools. SETTING: Six comprehensive schools. METHOD: In the randomised trial, pupils were invited to attend asthma review at a nurse-led clinic either in school, or in general practice. The parallel observational study compared pupils invited to practice care within and outside the randomised trial. Primary outcome measures were attendance for asthma review, symptom control, and quality of life. Secondary outcomes were knowledge, attitudes, inhaler technique, use of steroids, school absence, peak flow rate, preference for future care, health service utilisation, and costs. RESULTS: School clinic pupils were more likely to attend an asthma review than those randomised to practice care (90.8% versus 51.0% overall [P < 0.001, not consistent across schools]). No differences were observed in symptom control (P = 0.42) or quality of life (P = 0.63). Pupils attending school clinics had greater knowledge of asthma (difference = +0.38, 95% CI = 0.19 to 0.56), more positive attitudes (difference = +0.21, 95% CI = 0.05 to 0.36), and better inhaler technique (P < 0.001, not consistent across all schools). No differences were observed in school absence or peak flow rate. A majority (63%) of those who had received care at school preferred this model in future. Median costs of providing care at school and at the practice were 32.10 Pounds and 19.80 Pounds, respectively. No differences were observed between the groups in the observational comparison on any outcome. CONCLUSIONS: The schools asthma clinic increased uptake of asthma reviews. There were improvements in various process measures, but not in clinical outcomes. PMID:12528584

Weight loss intervention for young adults using mobile technology: design and rationale of a randomized controlled trial - Cell Phone Intervention for You (CITY).

PubMed

Batch, Bryan C; Tyson, Crystal; Bagwell, Jacqueline; Corsino, Leonor; Intille, Stephen; Lin, Pao-Hwa; Lazenka, Tony; Bennett, Gary; Bosworth, Hayden B; Voils, Corrine; Grambow, Steven; Sutton, Aziza; Bordogna, Rachel; Pangborn, Matthew; Schwager, Jenifer; Pilewski, Kate; Caccia, Carla; Burroughs, Jasmine; Svetkey, Laura P

2014-03-01

The obesity epidemic has spread to young adults, leading to significant public health implications later in adulthood. Intervention in early adulthood may be an effective public health strategy for reducing the long-term health impact of the epidemic. Few weight loss trials have been conducted in young adults. It is unclear what weight loss strategies are beneficial in this population. To describe the design and rationale of the NHLBI-sponsored Cell Phone Intervention for You (CITY) study, which is a single center, randomized three-arm trial that compares the impact on weight loss of 1) a behavioral intervention that is delivered almost entirely via cell phone technology (Cell Phone group); and 2) a behavioral intervention delivered mainly through monthly personal coaching calls enhanced by self-monitoring via cell phone (Personal Coaching group), each compared to 3) a usual care, advice-only control condition. A total of 365 community-dwelling overweight/obese adults aged 18-35 years were randomized to receive one of these three interventions for 24 months in parallel group design. Study personnel assessing outcomes were blinded to group assignment. The primary outcome is weight change at 24 [corrected] months. We hypothesize that each active intervention will cause more weight loss than the usual care condition. Study completion is anticipated in 2014. If effective, implementation of the CITY interventions could mitigate the alarming rates of obesity in young adults through promotion of weight loss. ClinicalTrial.gov: NCT01092364. Published by Elsevier Inc.

Investigations of botanicals on food intake, satiety, weight loss and oxidative stress: study protocol of a double-blind, placebo-controlled, crossover study.

PubMed

Anton, Stephen D; Shuster, Jonathan; Leeuwenburgh, Christiaan

2011-11-01

Botanicals represent an important and underexplored source of potential new therapies that may facilitate caloric restriction and thereby may produce long-term weight loss. In particular, one promising botanical that may reduce food intake and body weight by affecting neuroendocrine pathways related to satiety is hydroxycitric acid (HCA) derived from Garcinia cambogia Desr. The objective of this article is to describe the protocol of a clinical trial designed to directly test the effects of Garcinia cambogia-derived HCA on food intake, satiety, weight loss and oxidative stress levels, and to serve as a model for similar trials. A total of 48 healthy, overweight or obese individuals (with a body mass index range of 25.0 to 39.9 kg/m(2)) between the ages of 50 to 70 will participate in this double-blind, placebo-controlled, crossover study designed to examine the effects of two doses of Garcinia cambogia-derived HCA on food intake, satiety, weight loss, and oxidative stress levels. Food intake represents the primary outcome measure and is calculated based on the total calories consumed at breakfast, lunch, and dinner meals during each test meal day. This study can be completed with far fewer subjects than a parallel design. Of the numerous botanical compounds, the compound Garcinia cambogia-derived HCA is selected for testing in the present study because of its potential to safely reduce food intake, body weight, and oxidative stress levels. We will review potential mechanisms of action and safety parameters throughout this clinical trial. ClinicalTrials.gov (Identifier: NCT01238887).

Pragmatic clinical trials embedded in healthcare systems: generalizable lessons from the NIH Collaboratory.

PubMed

Weinfurt, Kevin P; Hernandez, Adrian F; Coronado, Gloria D; DeBar, Lynn L; Dember, Laura M; Green, Beverly B; Heagerty, Patrick J; Huang, Susan S; James, Kathryn T; Jarvik, Jeffrey G; Larson, Eric B; Mor, Vincent; Platt, Richard; Rosenthal, Gary E; Septimus, Edward J; Simon, Gregory E; Staman, Karen L; Sugarman, Jeremy; Vazquez, Miguel; Zatzick, Douglas; Curtis, Lesley H

2017-09-18

The clinical research enterprise is not producing the evidence decision makers arguably need in a timely and cost effective manner; research currently involves the use of labor-intensive parallel systems that are separate from clinical care. The emergence of pragmatic clinical trials (PCTs) poses a possible solution: these large-scale trials are embedded within routine clinical care and often involve cluster randomization of hospitals, clinics, primary care providers, etc. Interventions can be implemented by health system personnel through usual communication channels and quality improvement infrastructure, and data collected as part of routine clinical care. However, experience with these trials is nascent and best practices regarding design operational, analytic, and reporting methodologies are undeveloped. To strengthen the national capacity to implement cost-effective, large-scale PCTs, the Common Fund of the National Institutes of Health created the Health Care Systems Research Collaboratory (Collaboratory) to support the design, execution, and dissemination of a series of demonstration projects using a pragmatic research design. In this article, we will describe the Collaboratory, highlight some of the challenges encountered and solutions developed thus far, and discuss remaining barriers and opportunities for large-scale evidence generation using PCTs. A planning phase is critical, and even with careful planning, new challenges arise during execution; comparisons between arms can be complicated by unanticipated changes. Early and ongoing engagement with both health care system leaders and front-line clinicians is critical for success. There is also marked uncertainty when applying existing ethical and regulatory frameworks to PCTS, and using existing electronic health records for data capture adds complexity.

A Parallel Genetic Algorithm for Automated Electronic Circuit Design

NASA Technical Reports Server (NTRS)

Long, Jason D.; Colombano, Silvano P.; Haith, Gary L.; Stassinopoulos, Dimitris

2000-01-01

Parallelized versions of genetic algorithms (GAs) are popular primarily for three reasons: the GA is an inherently parallel algorithm, typical GA applications are very compute intensive, and powerful computing platforms, especially Beowulf-style computing clusters, are becoming more affordable and easier to implement. In addition, the low communication bandwidth required allows the use of inexpensive networking hardware such as standard office ethernet. In this paper we describe a parallel GA and its use in automated high-level circuit design. Genetic algorithms are a type of trial-and-error search technique that are guided by principles of Darwinian evolution. Just as the genetic material of two living organisms can intermix to produce offspring that are better adapted to their environment, GAs expose genetic material, frequently strings of 1s and Os, to the forces of artificial evolution: selection, mutation, recombination, etc. GAs start with a pool of randomly-generated candidate solutions which are then tested and scored with respect to their utility. Solutions are then bred by probabilistically selecting high quality parents and recombining their genetic representations to produce offspring solutions. Offspring are typically subjected to a small amount of random mutation. After a pool of offspring is produced, this process iterates until a satisfactory solution is found or an iteration limit is reached. Genetic algorithms have been applied to a wide variety of problems in many fields, including chemistry, biology, and many engineering disciplines. There are many styles of parallelism used in implementing parallel GAs. One such method is called the master-slave or processor farm approach. In this technique, slave nodes are used solely to compute fitness evaluations (the most time consuming part). The master processor collects fitness scores from the nodes and performs the genetic operators (selection, reproduction, variation, etc.). Because of dependency issues in the GA, it is possible to have idle processors. However, as long as the load at each processing node is similar, the processors are kept busy nearly all of the time. In applying GAs to circuit design, a suitable genetic representation 'is that of a circuit-construction program. We discuss one such circuit-construction programming language and show how evolution can generate useful analog circuit designs. This language has the desirable property that virtually all sets of combinations of primitives result in valid circuit graphs. Our system allows circuit size (number of devices), circuit topology, and device values to be evolved. Using a parallel genetic algorithm and circuit simulation software, we present experimental results as applied to three analog filter and two amplifier design tasks. For example, a figure shows an 85 dB amplifier design evolved by our system, and another figure shows the performance of that circuit (gain and frequency response). In all tasks, our system is able to generate circuits that achieve the target specifications.

What's in a name? The role of graphics, functions, and their interrelationships in icon identification.

PubMed

McDougall, Siné; Isherwood, Sarah

2009-05-01

Communication using icons is now commonplace. It is therefore important to understand the processes involved in icon comprehension and the stimulus cues that individuals utilize to facilitate identification. In this study, we examined predictors of icon identification as participants gained experience with icons over a series of learning trials. A dynamic pattern of findings emerged in which the primary predictors of identification changed as learning progressed. In early learning trials, semantic distance (the closeness of the relationship between icon and function) was the best predictor of performance, accounting for up to 55% of the variance observed, whereas familiarity with the function was more important in later trials. Other stimulus characteristics, such as our familiarity with the graphic in the icon and its concreteness, were also found to be important for icon design. The theoretical implications of these findings are discussed, with particular emphasis on the parallels with picture naming. The icon identification norms from this study may be downloaded from brm.psychonomic-journals.org/content/supplemental.

Pilot parallel randomised controlled trial of protective socks against usual care to reduce skin tears in high risk people: 'STOPCUTS'.

PubMed

Powell, Roy J; Hayward, Christopher J; Snelgrove, Caroline L; Polverino, Kathleen; Park, Linda; Chauhan, Rohan; Evans, Philip H; Byford, Rachel; Charman, Carolyn; Foy, Christopher J W; Pritchard, Colin; Kingsley, Andrew

2017-01-01

Skin tears are common in older adults and those taking steroids and warfarin. They are traumatic, often blunt injuries caused by oblique knocks to the extremities. The epidermis may separate from the dermis or both layers from underlying tissues leaving a skin flap or total loss of tissue, which is painful and prone to infection. 'Dermatuff™' knee-length socks containing Kevlar fibres (used in stab-proof vests and motorcyclists' clothing) aim to prevent skin tears. The acceptability of the socks and the feasibility of a randomised controlled trial (RCT) had not been explored. In this pilot parallel group RCT, 90 people at risk of skin-tear injury from Devon care homes and primary care were randomised to receive the socks or treatment as usual (TAU). The pilot aimed to estimate parameters to inform the design of a substantive trial and record professionals' views and participants' acceptability of the intervention and of study participation. Participants were randomised from July 2013 and followed up until February 2015. Community participants were easier to recruit than care homes residents but were 10 years younger on average and more active. To recruit 90 participants, 395 had to be approached overall as 77% were excluded or declined. Seventy-nine participants (88%) completed the trial and 27/44 (61%) wore the socks for 16 weeks. There were 31 skin tear injuries affecting 18 (20%) of the 90 participants. The TAU group received more injuries, more repeated episodes, and larger tears with greater severity. Common daily diary reasons for not wearing the socks included perceived warmth in hot weather or not being available (holiday, in hospital, bed rest). Resource use data were obtainable and indicated that sock wearing gave a reduction in treatment costs whilst well-completed questionnaires showed improvements in secondary outcomes. This pilot trial has successfully informed the design and conduct of a future definitive cost-effectiveness RCT. It would need to be conducted in primary care with 880 active at-risk, elderly patients (440 per arm). Skin tear incidence and quality of life (from EQ5D5L) over a 4-month period would be the primary and secondary outcomes respectively. ISRCTN, ISRCTN96565376.

Modifying the clinical research infrastructure at a dedicated clinical trials unit: assessment of trial development, activation, and participant accrual

PubMed Central

Tang, Chad; Hess, Kenneth R.; Sanders, Dwana; Davis, Suzanne; Buzdar, Aman; Kurzrock, Razelle; Lee, J. Jack; Meric-Bernstam, Funda; Hong, David

2017-01-01

Purpose Information on processes for trials assessing investigational therapeutics is sparse. We assessed the trial development processes within the Department of Investigational Cancer Therapeutics (ICT) at MD Anderson Cancer Center and analyzed their effects on the trial activation timeline and enrollment. Experimental Design Data were from a prospectively maintained registry that tracks all clinical studies at MD Anderson. From this database we identified 2,261 activated phase I-III trials; 221 were done at the ICT. ICT trials were matched to trials from other MD Anderson departments by phase, sponsorship, and submission year. Trial performance metrics were compared with paired Wilcoxon signed rank tests. Results We identified 3 facets of the ICT research infrastructure: parallel processing of trial approval steps; a physician-led research team; and regular weekly meetings to foster research accountability. Separate analyses were conducted stratified by sponsorship (industry [133 ICT and 133 non-ICT trials] or institutional [68 ICT and 68 non-ICT trials]). ICT trial development was faster from IRB approval to activation (median difference of 1.1 months for industry-sponsored trials vs. 2.3 months for institutional) and from activation to first enrollment (median difference of 0.3 months for industry vs. 1.2 months for institutional) (all matched P<0.05). ICT trials also accrued more patients (median difference of 8 participants for industry vs. 33.5 for institutional) quicker (median difference 4.8 participants/year for industry vs. 11.1 for institutional) (all matched P<0.05). Conclusions Use of a clinical research–focused infrastructure within a large academic cancer center was associated with efficient trial development and participant accrual. PMID:27852698

Modifying the Clinical Research Infrastructure at a Dedicated Clinical Trials Unit: Assessment of Trial Development, Activation, and Participant Accrual.

PubMed

Tang, Chad; Hess, Kenneth R; Sanders, Dwana; Davis, Suzanne E; Buzdar, Aman U; Kurzrock, Razelle; Lee, J Jack; Meric-Bernstam, Funda; Hong, David S

2017-03-15

Purpose: Information on processes for trials assessing investigational therapeutics is sparse. We assessed the trial development processes within the Department of Investigational Cancer Therapeutics (ICT) at MD Anderson Cancer Center (Houston, TX) and analyzed their effects on the trial activation timeline and enrolment. Experimental Design: Data were from a prospectively maintained registry that tracks all clinical studies at MD Anderson. From this database, we identified 2,261 activated phase I-III trials; 221 were done at the ICT. ICT trials were matched to trials from other MD Anderson departments by phase, sponsorship, and submission year. Trial performance metrics were compared with paired Wilcoxon signed rank tests. Results: We identified three facets of the ICT research infrastructure: parallel processing of trial approval steps; a physician-led research team; and regular weekly meetings to foster research accountability. Separate analyses were conducted stratified by sponsorship [industry (133 ICT and 133 non-ICT trials) or institutional (68 ICT and 68 non-ICT trials)]. ICT trial development was faster from IRB approval to activation (median difference of 1.1 months for industry-sponsored trials vs. 2.3 months for institutional) and from activation to first enrolment (median difference of 0.3 months for industry vs. 1.2 months for institutional; all matched P < 0.05). ICT trials also accrued more patients (median difference of 8 participants for industry vs. 33.5 for institutional) quicker (median difference 4.8 participants/year for industry vs. 11.1 for institutional; all matched P < 0.05). Conclusions: Use of a clinical research-focused infrastructure within a large academic cancer center was associated with efficient trial development and participant accrual. Clin Cancer Res; 23(6); 1407-13. ©2016 AACR . ©2016 American Association for Cancer Research.

Performance Evaluation of Parallel Branch and Bound Search with the Intel iPSC (Intel Personal SuperComputer) Hypercube Computer.

DTIC Science & Technology

1986-12-01

17 III. Analysis of Parallel Design ................................................ 18 Parallel Abstract Data ...Types ........................................... 18 Abstract Data Type .................................................. 19 Parallel ADT...22 Data -Structure Design ........................................... 23 Object-Oriented Design

Screen-time Weight-loss Intervention Targeting Children at Home (SWITCH): A randomized controlled trial study protocol

PubMed Central

2011-01-01

Background Approximately one third of New Zealand children and young people are overweight or obese. A similar proportion (33%) do not meet recommendations for physical activity, and 70% do not meet recommendations for screen time. Increased time being sedentary is positively associated with being overweight. There are few family-based interventions aimed at reducing sedentary behavior in children. The aim of this trial is to determine the effects of a 24 week home-based, family oriented intervention to reduce sedentary screen time on children's body composition, sedentary behavior, physical activity, and diet. Methods/Design The study design is a pragmatic two-arm parallel randomized controlled trial. Two hundred and seventy overweight children aged 9-12 years and primary caregivers are being recruited. Participants are randomized to intervention (family-based screen time intervention) or control (no change). At the end of the study, the control group is offered the intervention content. Data collection is undertaken at baseline and 24 weeks. The primary trial outcome is child body mass index (BMI) and standardized body mass index (zBMI). Secondary outcomes are change from baseline to 24 weeks in child percentage body fat; waist circumference; self-reported average daily time spent in physical and sedentary activities; dietary intake; and enjoyment of physical activity and sedentary behavior. Secondary outcomes for the primary caregiver include change in BMI and self-reported physical activity. Discussion This study provides an excellent example of a theory-based, pragmatic, community-based trial targeting sedentary behavior in overweight children. The study has been specifically designed to allow for estimation of the consistency of effects on body composition for Māori (indigenous), Pacific and non-Māori/non-Pacific ethnic groups. If effective, this intervention is imminently scalable and could be integrated within existing weight management programs. Trial Registration ACTRN12611000164998 PMID:21718543

The NEtherlands Cervical Kinematics (NECK) Trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study

PubMed Central

2010-01-01

Background Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Methods/Design Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Discussion Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prothesis is necessary and cost-effective will be determined by this trial. Trial Registration Netherlands Trial Register NTR1289 PMID:20553591

Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study.

PubMed

Balasubramaniam, Gowrie; Parker, Trisha; Turner, David; Parker, Mike; Scales, Jonathan; Harnett, Patrick; Harrison, Michael; Ahmed, Khalid; Bhagat, Sweta; Marianayagam, Thiraupathy; Pitzalis, Costantino; Mallen, Christian; Roddy, Edward; Almond, Mike; Dasgupta, Bhaskar

2017-09-05

Acute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD). ASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies. The London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences. EudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No. NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614-34090. © 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.

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care.

PubMed

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Hollinghurst, Sandra; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-11-16

To determine the feasibility of a randomised controlled trial of 'leave on' emollients for children with eczema. Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. General practices in the UK. Children with eczema aged 1 month to <5 years. Primary outcome-proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes-participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. 197 children were recruited-107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic ('app') form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. ISRCTN21828118/EudraCT2013-003001-26. 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/.

Whole body vibration for older persons: an open randomized, multicentre, parallel, clinical trial

PubMed Central

2011-01-01

Background Institutionalized older persons have a poor functional capacity. Including physical exercise in their routine activities decreases their frailty and improves their quality of life. Whole-body vibration (WBV) training is a type of exercise that seems beneficial in frail older persons to improve their functional mobility, but the evidence is inconclusive. This trial will compare the results of exercise with WBV and exercise without WBV in improving body balance, muscle performance and fall prevention in institutionalized older persons. Methods/Design An open, multicentre and parallel randomized clinical trial with blinded assessment. 160 nursing home residents aged over 65 years and of both sexes will be identified to participate in the study. Participants will be centrally randomised and allocated to interventions (vibration or exercise group) by telephone. The vibration group will perform static/dynamic exercises (balance and resistance training) on a vibratory platform (Frequency: 30-35 Hz; Amplitude: 2-4 mm) over a six-week training period (3 sessions/week). The exercise group will perform the same exercise protocol but without a vibration stimuli platform. The primary outcome measure is the static/dynamic body balance. Secondary outcomes are muscle strength and, number of new falls. Follow-up measurements will be collected at 6 weeks and at 6 months after randomization. Efficacy will be analysed on an intention-to-treat (ITT) basis and 'per protocol'. The effects of the intervention will be evaluated using the "t" test, Mann-Witney test, or Chi-square test, depending on the type of outcome. The final analysis will be performed 6 weeks and 6 months after randomization. Discussion This study will help to clarify whether WBV training improves body balance, gait mobility and muscle strength in frail older persons living in nursing homes. As far as we know, this will be the first study to evaluate the efficacy of WBV for the prevention of falls. Trial Registration ClinicalTrials.gov: NCT01375790 PMID:22192313

Examining longitudinal stimulant use and treatment attendance as parallel outcomes in two contingency management randomized clinical trials

PubMed Central

McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John

2015-01-01

The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one ‘parallel outcomes’ model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β = 0.060, p < 0.05). In the second trial, CM predicted negative urinalysis (−UA) over the 12-week treatment period (β = 0.069, p < 0.05). In both trials, there was a significant, positive relationship between attendance and −UA submission, but in the first trial a −UA at both baseline and over time was related to attendance over time (r = 0.117; r = 0.013, respectively) and in the second trial, a −UA submission at baseline was associated with increased attendance over time (r = 0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This ‘indirect reinforcement’ between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials. PMID:26456717

Examining Longitudinal Stimulant Use and Treatment Attendance as Parallel Outcomes in Two Contingency Management Randomized Clinical Trials.

PubMed

McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John

2016-02-01

The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one 'parallel outcomes' model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β=0.060, p<0.05). In the second trial, CM predicted negative urinalysis ((-)UA) over the 12-week treatment period (β=0.069, p<0.05). In both trials, there was a significant, positive relationship between attendance and (-)UA submission, but in the first trial a (-)UA at both baseline and over time was related to attendance over time (r=0.117; r=0.013, respectively) and in the second trial, a (-)UA submission at baseline was associated with increased attendance over time (r=0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This 'indirect reinforcement' between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials. Copyright © 2015 Elsevier Inc. All rights reserved.

Quantity and source of dietary protein influence metabolite production by gut microbiota and rectal mucosa gene expression: a randomized, parallel, double-blind trial in overweight humans.

PubMed

Beaumont, Martin; Portune, Kevin Joseph; Steuer, Nils; Lan, Annaïg; Cerrudo, Victor; Audebert, Marc; Dumont, Florent; Mancano, Giulia; Khodorova, Nadezda; Andriamihaja, Mireille; Airinei, Gheorghe; Tomé, Daniel; Benamouzig, Robert; Davila, Anne-Marie; Claus, Sandrine Paule; Sanz, Yolanda; Blachier, François

2017-10-01

Background: Although high-protein diets (HPDs) are frequently consumed for body-weight control, little is known about the consequences for gut microbiota composition and metabolic activity and for large intestine mucosal homeostasis. Moreover, the effects of HPDs according to the source of protein need to be considered in this context. Objective: The objective of this study was to evaluate the effects of the quantity and source of dietary protein on microbiota composition, bacterial metabolite production, and consequences for the large intestinal mucosa in humans. Design: A randomized, double-blind, parallel-design trial was conducted in 38 overweight individuals who received a 3-wk isocaloric supplementation with casein, soy protein, or maltodextrin as a control. Fecal and rectal biopsy-associated microbiota composition was analyzed by 16S ribosomal DNA sequencing. Fecal, urinary, and plasma metabolomes were assessed by 1 H-nuclear magnetic resonance. Mucosal transcriptome in rectal biopsies was determined with the use of microarrays. Results: HPDs did not alter the microbiota composition, but induced a shift in bacterial metabolism toward amino acid degradation with different metabolite profiles according to the protein source. Correlation analysis identified new potential bacterial taxa involved in amino acid degradation. Fecal water cytotoxicity was not modified by HPDs, but was associated with a specific microbiota and bacterial metabolite profile. Casein and soy protein HPDs did not induce inflammation, but differentially modified the expression of genes playing key roles in homeostatic processes in rectal mucosa, such as cell cycle or cell death. Conclusions: This human intervention study shows that the quantity and source of dietary proteins act as regulators of gut microbiota metabolite production and host gene expression in the rectal mucosa, raising new questions on the impact of HPDs on the large intestine mucosa homeostasis. This trial was registered at clinicaltrials.gov as NCT02351297. © 2017 American Society for Nutrition.

Understanding the cluster randomised crossover design: a graphical illustraton of the components of variation and a sample size tutorial.

PubMed

Arnup, Sarah J; McKenzie, Joanne E; Hemming, Karla; Pilcher, David; Forbes, Andrew B

2017-08-15

In a cluster randomised crossover (CRXO) design, a sequence of interventions is assigned to a group, or 'cluster' of individuals. Each cluster receives each intervention in a separate period of time, forming 'cluster-periods'. Sample size calculations for CRXO trials need to account for both the cluster randomisation and crossover aspects of the design. Formulae are available for the two-period, two-intervention, cross-sectional CRXO design, however implementation of these formulae is known to be suboptimal. The aims of this tutorial are to illustrate the intuition behind the design; and provide guidance on performing sample size calculations. Graphical illustrations are used to describe the effect of the cluster randomisation and crossover aspects of the design on the correlation between individual responses in a CRXO trial. Sample size calculations for binary and continuous outcomes are illustrated using parameters estimated from the Australia and New Zealand Intensive Care Society - Adult Patient Database (ANZICS-APD) for patient mortality and length(s) of stay (LOS). The similarity between individual responses in a CRXO trial can be understood in terms of three components of variation: variation in cluster mean response; variation in the cluster-period mean response; and variation between individual responses within a cluster-period; or equivalently in terms of the correlation between individual responses in the same cluster-period (within-cluster within-period correlation, WPC), and between individual responses in the same cluster, but in different periods (within-cluster between-period correlation, BPC). The BPC lies between zero and the WPC. When the WPC and BPC are equal the precision gained by crossover aspect of the CRXO design equals the precision lost by cluster randomisation. When the BPC is zero there is no advantage in a CRXO over a parallel-group cluster randomised trial. Sample size calculations illustrate that small changes in the specification of the WPC or BPC can increase the required number of clusters. By illustrating how the parameters required for sample size calculations arise from the CRXO design and by providing guidance on both how to choose values for the parameters and perform the sample size calculations, the implementation of the sample size formulae for CRXO trials may improve.

Pre-operative use of dexamethasone does not reduce incidence or intensity of bleaching-induced tooth sensitivity. A triple-blind, parallel-design, randomized clinical trial.

PubMed

da Costa Poubel, Luiz Augusto; de Gouvea, Cresus Vinicius Deppes; Calazans, Fernanda Signorelli; Dip, Etyene Castro; Alves, Wesley Veltri; Marins, Stella Soares; Barcelos, Roberta; Barceleiro, Marcos Oliveira

2018-04-25

This study evaluated the effect of the administration of pre-operative dexamethasone on tooth sensitivity stemming from in-office bleaching. A triple-blind, parallel-design, randomized clinical trial was conducted on 70 volunteers who received dexamethasone or placebo capsules. The drugs were administered in a protocol of three daily 8-mg doses of the drug, starting 48 h before the in-office bleaching treatment. Two bleaching sessions with 37.5% hydrogen peroxide gel were performed with a 1-week interval. Tooth sensitivity (TS) was recorded on visual analog scales (VAS) and numeric rating scales (NRS) in different periods up to 48 h after bleaching. The color evaluations were also performed. The absolute risk of TS and its intensity were evaluated by using Fisher's exact test. Comparisons of the TS intensity (NRS and VAS data) were performed by using the Mann-Whitney U test and a two-way repeated measures ANOVA and Tukey's test, respectively. In both groups, a high risk of TS (Dexa 80% x Placebo 94%) was detected. No significant difference was observed in terms of TS intensity. A whitening of approximately 3 shade guide units of the VITA Classical was detected in both groups, which were statistically similar. It was concluded that the administration pre-operatively of dexamethasone, in the proposed protocol, does not reduce the incidence or intensity of bleaching-induced tooth sensitivity. The use of dexamethasone drug before in-office bleaching treatment does not reduce incidence or intensity of tooth sensitivity. NCT02956070.

A novel dynamic exercise initiative for older people to improve health and well-being: study protocol for a randomised controlled trial.

PubMed

Sales, Myrla Patricia Reis; Polman, Remco; Hill, Keith D; Karaharju-Huisman, Tuire; Levinger, Pazit

2015-06-24

Exercise is an important and effective approach to preventing falls in older people, but adherence to exercise participation remains a persistent problem. A unique purpose-built exercise park was designed to provide a fun but physically challenging environment to support exercise in a community setting. This project is a randomised controlled trial designed to evaluate the effectiveness of an exercise intervention using an exercise park specifically designed for older people in reducing the risk of falls. This study will be a parallel randomised control trial with pre and post intervention design. One hundred and twenty people aged between 60 and 90 years old will be recruited from Melbourne suburbs and will be randomly allocated to either an exercise park intervention group (EPIG) or a control group (CG). The CG will receive social activities and an educational booklet on falls prevention. The BOOMER balance test will be used as the primary outcome measure. Secondary outcome measures will include hand grip strength, two minute walk test, lower limb strength test, spatio-temporal walking parameters, health related quality of life, feasibility, adherence, safety, and a number of other psychosocial measures. Outcome assessment will be conducted at baseline and at 18 and 26 weeks after intervention commencement. Participants will inform their falls and physical activity history for a 12-month period via monthly calendars. Mixed linear modelling incorporating intervention and control groups at the baseline and two follow up time points (18 weeks and 26 weeks after intervention commencement) will be used to assess outcomes. This planned trial will be the first to provide evidence if the exercise park can improve functional and physiological health, psychological and well-being. In addition, this study will provide empirical evidence for effectiveness and explore the barriers to participation and the acceptability of the senior exercise park in the Australian older community. This trial is registered with the Australian New Zealand Clinical Trials Registry-Registry No. ACTRN12614000700639 registered on Jul 3rd 2014.

The potential for improvement of outcomes by personalized insulin treatment of type 1 diabetes as assessed by analysis of single-patient data from a randomized controlled cross-over insulin trial.

PubMed

Pedersen-Bjergaard, Ulrik; Kristensen, Peter L; Beck-Nielsen, Henning; Nørgaard, Kirsten; Perrild, Hans; Christiansen, Jens S; Jensen, Tonny; Parving, Hans-Henrik; Thorsteinsson, Birger; Tarnow, Lise

2017-01-01

The evidence for optimal insulin treatment in type 1 diabetes is mainly based on randomised controlled trials applying a parallel-group design. Such trials yield robust general results but crucial individual treatment effects cannot be extracted. We aimed to assess the potential for further improvement of outcomes by personalized insulin therapy by analyzing data from a cross-over trial at individual level. Post hoc analysis of data from a two-year multicentre, prospective, randomised, open, blinded endpoint (PROBE) trial (the HypoAna trial). In a cross-over design 114 patients with type 1 diabetes and recurrent severe hypoglycemia were treated with basal-bolus therapy based on analog (detemir/aspart) or human (NPH/regular) insulin aiming at maintenance of baseline HbA1c levels. For each patient a superior outcome was defined as fewer events of severe hypoglycemia defined by need for third party treatment assistance or a more than 0.4% (4.4mmol/mol) lower HbA1c. Only one quarter had comparable outcome of the two treatments in terms of rate of severe hypoglycemia or HbA1c. Twice as many patients had superior outcome of analog-based as compared to human insulin-based insulin treatment. The rate of severe hypoglycemia with the superior treatment was lower compared to the rates obtained with analog insulin and with human insulin (0.67, 1.09, and 1.57 episode per patient-year, respectively (p<0.0001)). Personalized insulin treatment of type 1 diabetes based on single-patient evidence may improve outcomes significantly compared to a general treatment approach. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Design innovations and baseline findings in a long-term Parkinson's trial: the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease Long-Term Study-1.

PubMed

Elm, Jordan J

2012-10-01

Based on the preclinical data and the results of a phase II futility study, creatine was selected for an efficacy trial in Parkinson's disease (PD). We present the design rationale and a description of the study cohort at baseline. A randomized, multicenter, double-blind, parallel-group, placebo-controlled phase III study of creatine (10 g daily) in participants with early, treated PD, the Long-term Study-1 (LS-1), is being conducted by the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease network. The study utilizes a global statistical test (GST) encompassing five clinical rating scales to provide a multidimensional assessment of disease progression. A total of 1,741 PD participants from 45 sites in the United States and Canada were randomized 1:1 to either 10 g of creatine/day or matching placebo. Participants are being evaluated for a minimum of 5 years. The LS-1 baseline cohort includes participants treated with dopaminergic therapy and generally mild PD. LS-1 represents the largest cohort of patients with early treated PD ever enrolled in a clinical trial. The GST approach should provide high power to test the hypothesis that daily administration of creatine (10 g/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5-year follow-up visit against the background of dopaminergic therapy and best PD care. Copyright © 2012 Movement Disorder Society.

A mixed method pilot study: the researchers' experiences.

PubMed

Secomb, Jacinta M; Smith, Colleen

2011-08-01

This paper reports on the outcomes of a small well designed pilot study. Pilot studies often disseminate limited or statistically meaningless results without adding to the body knowledge on the comparative research benefits. The design a pre-test post-test group parallel randomised control trial and inductive content analysis of focus group transcripts was tested specifically to increase outcomes in a proposed larger study. Strategies are now in place to overcome operational barriers and recruitment difficulties. Links between the qualitative and quantitative arms of the proposed larger study have been made; it is anticipated that this will add depth to the final report. More extensive reporting on the outcomes of pilot studies would assist researchers and increase the body of knowledge in this area.

Definition, reporting, and interpretation of composite outcomes in clinical trials: systematic review

PubMed Central

Cordoba, Gloria; Schwartz, Lisa; Woloshin, Steven; Bae, Harold

2010-01-01

Objective To study how composite outcomes, which have combined several components into a single measure, are defined, reported, and interpreted. Design Systematic review of parallel group randomised clinical trials published in 2008 reporting a binary composite outcome. Two independent observers extracted the data using a standardised data sheet, and two other observers, blinded to the results, selected the most important component. Results Of 40 included trials, 29 (73%) were about cardiovascular topics and 24 (60%) were entirely or partly industry funded. Composite outcomes had a median of three components (range 2–9). Death or cardiovascular death was the most important component in 33 trials (83%). Only one trial provided a good rationale for the choice of components. We judged that the components were not of similar importance in 28 trials (70%); in 20 of these, death was combined with hospital admission. Other major problems were change in the definition of the composite outcome between the abstract, methods, and results sections (13 trials); missing, ambiguous, or uninterpretable data (9 trials); and post hoc construction of composite outcomes (4 trials). Only 24 trials (60%) provided reliable estimates for both the composite and its components, and only six trials (15%) had components of similar, or possibly similar, clinical importance and provided reliable estimates. In 11 of 16 trials with a statistically significant composite, the abstract conclusion falsely implied that the effect applied also to the most important component. Conclusions The use of composite outcomes in trials is problematic. Components are often unreasonably combined, inconsistently defined, and inadequately reported. These problems will leave many readers confused, often with an exaggerated perception of how well interventions work. PMID:20719825

An analysis of registered clinical trials in otolaryngology from 2007 to 2010: ClinicalTrials.gov.

PubMed

Witsell, David L; Schulz, Kristine A; Lee, Walter T; Chiswell, Karen

2013-11-01

To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Database analysis. Trial registration data downloaded from ClinicalTrials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field.

Split-mouth and parallel-arm trials to compare pain with intraosseous anaesthesia delivered by the computerised Quicksleeper system and conventional infiltration anaesthesia in paediatric oral healthcare: protocol for a randomised controlled trial

PubMed Central

Smaïl-Faugeron, Violaine; Muller-Bolla, Michèle; Sixou, Jean-Louis; Courson, Frédéric

2015-01-01

Introduction Local anaesthesia is commonly used in paediatric oral healthcare. Infiltration anaesthesia is the most frequently used, but recent developments in anaesthesia techniques have introduced an alternative: intraosseous anaesthesia. We propose to perform a split-mouth and parallel-arm multicentre randomised controlled trial (RCT) comparing the pain caused by the insertion of the needle for the injection of conventional infiltration anaesthesia, and intraosseous anaesthesia by the computerised QuickSleeper system, in children and adolescents. Methods and analysis Inclusion criteria are patients 7–15 years old with at least 2 first permanent molars belonging to the same dental arch (for the split-mouth RCT) or with a first permanent molar (for the parallel-arm RCT) requiring conservative or endodontic treatment limited to pulpotomy. The setting of this study is the Department of Paediatric Dentistry at 3 University dental hospitals in France. The primary outcome measure will be pain reported by the patient on a visual analogue scale concerning the insertion of the needle and the injection/infiltration. Secondary outcomes are latency, need for additional anaesthesia during the treatment and pain felt during the treatment. We will use a computer-generated permuted-block randomisation sequence for allocation to anaesthesia groups. The random sequences will be stratified by centre (and by dental arch for the parallel-arm RCT). Only participants will be blinded to group assignment. Data will be analysed by the intent-to-treat principle. In all, 160 patients will be included (30 in the split-mouth RCT, 130 in the parallel-arm RCT). Ethics and dissemination This protocol has been approved by the French ethics committee for the protection of people (Comité de Protection des Personnes, Ile de France I) and will be conducted in full accordance with accepted ethical principles. Findings will be reported in scientific publications and at research conferences, and in project summary papers for participants. Trial registration number ClinicalTrials.gov NCT02084433. PMID:26163031

Recruitment, adherence, and retention of endometrial cancer survivors in a behavioural lifestyle programme: the Diet and Exercise in Uterine Cancer Survivors (DEUS) parallel randomised pilot trial.

PubMed

Koutoukidis, Dimitrios A; Beeken, Rebecca J; Manchanda, Ranjit; Michalopoulou, Moscho; Burnell, Matthew; Knobf, M Tish; Lanceley, Anne

2017-10-08

Healthy eating and physical activity may help endometrial cancer survivors (ECS) improve their quality of life. However, most ECS do not meet the relevant guidelines. This pilot trial aimed to test the study feasibility procedures for a definitive trial of a behavioural lifestyle programme. This 24-week parallel two-arm randomised pilot trial took place in two hospitals in London, UK (April 2015-June 2016). Sixty disease-free ECS within 3 years of diagnosis. Participants were randomised using minimisation to receive the intervention or care as usual. The 'Shape-Up following cancer treatment' programme used self-monitoring, goal-setting, self-incentives, problem-solving and group social support for 12 hours over 8 weeks to help survivors improve their eating and physical activity. The main outcome measures were recruitment, adherence, and retention rates. Further outcomes included barriers to participation and feedback on programme satisfaction. Of the 296 potentially eligible ECS, 20% (n=60) were randomly allocated to the active intervention (n=29) or control group (n=31). Three participants in each arm were deemed ineligible after randomisation and excluded from analysis. Twenty participants (77%; 95% CI 61% to 93%) adhered to the intervention and provided generally favourable feedback. At 24 weeks, 25/26 (96%; 95% CI 89% to 100%) intervention and 24/28 (86%; 95% CI 73% to 99%) control participants completed their assessment. No intervention-related adverse events were reported. Among eligible survivors who declined study participation (n=83), inconvenience (78%; 95% CI 69% to 87%) was the most common barrier. The trial was feasible to deliver based on the a priori feasibility criteria. Enhancing recruitment and adherence in a definitive trial will require designs that promote convenience and consider ECS-reported barriers. NCT02433080; Pre-results. University College London, St. Bartholomew's Hospital Nurses League, and NIHR University College London Hospitals Biomedical Research Centre. © 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.

Why caution is recommended with post-hoc individual patient matching for estimation of treatment effect in parallel-group randomized controlled trials: the case of acute stroke trials.

PubMed

Jafari, Nahid; Hearne, John; Churilov, Leonid

2013-11-10

A post-hoc individual patient matching procedure was recently proposed within the context of parallel group randomized clinical trials (RCTs) as a method for estimating treatment effect. In this paper, we consider a post-hoc individual patient matching problem within a parallel group RCT as a multi-objective decision-making problem focussing on the trade-off between the quality of individual matches and the overall percentage of matching. Using acute stroke trials as a context, we utilize exact optimization and simulation techniques to investigate a complex relationship between the overall percentage of individual post-hoc matching, the size of the respective RCT, and the quality of matching on variables highly prognostic for a good functional outcome after stroke, as well as the dispersion in these variables. It is empirically confirmed that a high percentage of individual post-hoc matching can only be achieved when the differences in prognostic baseline variables between individually matched subjects within the same pair are sufficiently large and that the unmatched subjects are qualitatively different to the matched ones. It is concluded that the post-hoc individual matching as a technique for treatment effect estimation in parallel-group RCTs should be exercised with caution because of its propensity to introduce significant bias and reduce validity. If used with appropriate caution and thorough evaluation, this approach can complement other viable alternative approaches for estimating the treatment effect. Copyright © 2013 John Wiley & Sons, Ltd.

HPCC Methodologies for Structural Design and Analysis on Parallel and Distributed Computing Platforms

NASA Technical Reports Server (NTRS)

Farhat, Charbel

1998-01-01

In this grant, we have proposed a three-year research effort focused on developing High Performance Computation and Communication (HPCC) methodologies for structural analysis on parallel processors and clusters of workstations, with emphasis on reducing the structural design cycle time. Besides consolidating and further improving the FETI solver technology to address plate and shell structures, we have proposed to tackle the following design related issues: (a) parallel coupling and assembly of independently designed and analyzed three-dimensional substructures with non-matching interfaces, (b) fast and smart parallel re-analysis of a given structure after it has undergone design modifications, (c) parallel evaluation of sensitivity operators (derivatives) for design optimization, and (d) fast parallel analysis of mildly nonlinear structures. While our proposal was accepted, support was provided only for one year.

Design innovations and baseline findings in a long-term Parkinson’s trial: NET-PD LS-1

PubMed Central

2012-01-01

Background Based on the pre-clinical and the results of a phase 2 futility study, creatine was selected for an efficacy trial in Parkinson’s disease (PD). We present the design rationale and a description of the study cohort at baseline. Methods A randomized, multicenter, double-blind, parallel group, placebo controlled Phase 3 study of creatine (10 gm daily) in participants with early, treated PD, the Long-term Study – 1 (LS-1) is being conducted by the NINDS Exploratory Trials in Parkinson’s Disease (NET-PD) network. The study utilizes a global statistical test (GST) encompassing multiple clinical rating scales to provide a multidimensional assessment of disease progression. Results A total of 1,741 PD participants from 45 sites in the U.S. and Canada were randomized 1:1 to either 10-gm creatine/day or matching placebo. Participants are being evaluated for a minimum of 5 years. The LS-1 baseline cohort includes participants treated with dopaminergic therapy and generally mild PD. Conclusions LS-1 represents the largest cohort of patients with early treated PD ever enrolled in a clinical trial. The GST approach should provide high power to test the hypothesis that daily administration of creatine (10gm/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5 year follow-up visit against the background of dopaminergic therapy and best PD care. PMID:23079770

Protection of xenon against postoperative oxygen impairment in adults undergoing Stanford Type-A acute aortic dissection surgery

PubMed Central

Jin, Mu; Cheng, Yi; Yang, Yanwei; Pan, Xudong; Lu, Jiakai; Cheng, Weiping

2017-01-01

Abstract Objectives: The available evidence shows that hypoxemia after Stanford Type-A acute aortic dissection (AAD) surgery is a frequent cause of several adverse consequences. The pathogenesis of postoperative hypoxemia after AAD surgery is complex, and ischemia/reperfusion and inflammation are likely to be underlying risk factors. Xenon, recognized as an ideal anesthetic and anti-inflammatory treatment, might be a possible treatment for these adverse effects. Methods/Design: The trial is a prospective, double-blind, 4-group, parallel, randomized controlled, a signal-center clinical trial. We will recruit 160 adult patients undergoing Stanford type-A AAD surgery. Patients will be allocated a study number and will be randomized on a 1:1:1:1 basis to receive 1 of the 3 treatment options (pulmonary inflated with 50% xenon, 75% xenon, or 100% xenon) or no treatment (control group, pulmonary inflated with 50% nitrogen). The aims of this study are to clarify the lung protection capability of xenon and its possible mechanisms in patients undergoing the Stanford type-A AAD surgery. Discussion: This trial uses an innovative design to account for the xenon effects of postoperative oxygen impairment, and it also delineates the mechanism for any benefit from xenon. The investigational xenon group is considered a treatment intervention, as it includes 3 groups of pulmonary static inflation with 50%, 75%, and 100% xenon. It is suggested that future trials might define an appropriate concentration of xenon for the best practice intervention. PMID:28834897

British government, industry agree to fund Hotel launcher studies

NASA Astrophysics Data System (ADS)

Brown, D. A.

1986-02-01

A program status assessment is presented for the horizontal takeoff and landing 'Hotol' single-stage-to-orbit space launcher, for which parallel, two-year airframe and propulsion system proof-of-concept studies have been approved. A two-year initial development program for the airframe would be followed by a four-year development and manufacturing phase that would begin upon the propulsion system concept's successful demonstration. Flight trials could begin in 1996. A number of significant modifications have already been made to the initial design concept, such as to the foreplanes, afterbody, engine intake, and orbital control system.

Development of a Novel Six-Month Nutrition Intervention for a Randomized Trial in Older Men with Mobility Limitations.

PubMed

Apovian, C M; Singer, M R; Campbell, W W; Bhasin, S; McCarthy, A C; Shah, M; Basaria, S; Moore, L L

2017-01-01

Nutrition impacts the development of sarcopenia and protein intake is an important modulator of skeletal muscle mass loss in older people. The Optimizing Protein Intake in Older Men with Mobility Limitation (OPTIMEN) Trial was designed to assess the independent and combined effects of higher protein intake and a promyogenic agent, testosterone, on lean body mass, muscle strength and physical function in older men with mobility disability. The purpose of this paper is to describe the experimental design and nutrition intervention, including techniques used by research dietitians to develop and deliver energy and protein-specific meals to the homes of community-dwelling participants. Strategies to enhance long-term dietary compliance are detailed. Randomized, double-blind, placebo-controlled six-month intervention trial. Participants were recruited from Boston MA USA and surrounding communities. Older men who were mobility-limited (Short Physical Performance Battery (SPPB) 3-10) and consuming less protein (<0.83 g/kg/day) were recruited for this study. Here we report the successful implementation of a double-blind, placebo-controlled, parallel group, randomized controlled trial with a 6-month intervention period among community-living men, age 65 years and older with a mobility limitation. A controlled feeding plan was used to deliver required energy intakes and prescribed protein quantities of 0.8 or 1.3 grams/kilogram/day (g/kg/d) in three meals plus snacks and supplements. A 2x2 factorial design was used to assess the effects of protein level alone and in combination with testosterone (vs. placebo) on changes in lean body mass (primary outcome), muscle strength, and physical function. A total of 154 men met the eligibility criteria; 112 completed a 2-week run-in period designed to evaluate compliance with the nutrition intervention. Of these, 92 subjects met compliance eligibility criteria and agreed to be randomized; 85% completed the full trial. The study successfully delivered three meals per day to subjects, with a high degree of compliance and subject satisfaction. Overall self-reported compliance rates were 80% and 93% for the meals and supplements, respectively. Details of compliance strategies are discussed. This community-based study design may serve as a model for longer-term nutritional interventions requiring monitoring of dietary compliance in a home-based feeding and supplementation trial.

The effectiveness and cost-effectiveness of a mindfulness training programme in schools compared with normal school provision (MYRIAD): study protocol for a randomised controlled trial.

PubMed

Kuyken, Willem; Nuthall, Elizabeth; Byford, Sarah; Crane, Catherine; Dalgleish, Tim; Ford, Tamsin; Greenberg, Mark T; Ukoumunne, Obioha C; Viner, Russell M; Williams, J Mark G

2017-04-26

Mindfulness-based approaches for adults are effective at enhancing mental health, but few controlled trials have evaluated their effectiveness or cost-effectiveness for young people. The primary aim of this trial is to evaluate the effectiveness and cost-effectiveness of a mindfulness training (MT) programme to enhance mental health, wellbeing and social-emotional behavioural functioning in adolescence. To address this aim, the design will be a superiority, cluster randomised controlled, parallel-group trial in which schools offering social and emotional provision in line with good practice (Formby et al., Personal, Social, Health and Economic (PSHE) Education: A mapping study of the prevalent models of delivery and their effectiveness, 2010; OFSTED, Not Yet Good Enough: Personal, Social, Health and Economic Education in schools, 2013) will be randomised to either continue this provision (control) or include MT in this provision (intervention). The study will recruit and randomise 76 schools (clusters) and 5700 school students aged 12 to 14 years, followed up for 2 years. The study will contribute to establishing if MT is an effective and cost-effective approach to promoting mental health in adolescence. International Standard Randomised Controlled Trials, identifier: ISRCTN86619085 . Registered on 3 June 2016.

Effect of Cosmos caudatus (Ulam raja) supplementation in patients with type 2 diabetes: Study protocol for a randomized controlled trial.

PubMed

Cheng, Shi-Hui; Ismail, Amin; Anthony, Joseph; Ng, Ooi Chuan; Hamid, Azizah Abdul; Yusof, Barakatun-Nisak Mohd

2016-02-27

Type 2 diabetes mellitus is a major health threat worldwide. Cosmos caudatus is one of the medicinal plants used to treat type 2 diabetes. Therefore, this study aims to determine the effectiveness and safety of C. caudatus in patients with type 2 diabetes. Metabolomic approach will be carried out to compare the metabolite profiles between C. Caudatus treated diabetic patients and diabetic controls. This is a single-center, randomized, controlled, two-arm parallel design clinical trial that will be carried out in a tertiary hospital in Malaysia. In this study, 100 patients diagnosed with type 2 diabetes will be enrolled. Diabetic patients who meet the eligibility criteria will be randomly allocated to two groups, which are diabetic C. caudatus treated(U) group and diabetic control (C) group. Primary and secondary outcomes will be measured at baseline, 4, 8, and 12 weeks. The serum and urine metabolome of both groups will be examined using proton NMR spectroscopy. The study will be the first randomized controlled trial to assess whether C. caudatus can confer beneficial effect in patients with type 2 diabetes. The results of this trial will provide clinical evidence on the effectiveness and safety of C. caudatus in patients with type 2 diabetes. ClinicalTrials.gov identifier: NCT02322268.

Design and rationale for the Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease (EUCLID) trial.

PubMed

Berger, Jeffrey S; Katona, Brian G; Jones, W Schuyler; Patel, Manesh R; Norgren, Lars; Baumgartner, Iris; Blomster, Juuso; Mahaffey, Kenneth W; Held, Peter; Millegård, Marcus; Heizer, Gretchen; Reist, Craig; Fowkes, F Gerry; Hiatt, William R

2016-05-01

Despite overwhelming data demonstrating the efficacy of antiplatelet therapy in heart disease and stroke, data in peripheral artery disease (PAD) are less compelling. Aspirin has modest evidence supporting a reduction in cardiovascular events in patients with PAD, whereas clopidogrel monotherapy may be more effective in PAD. Ticagrelor, a potent, reversibly binding P2Y12 receptor antagonist, is beneficial in patients with acute coronary syndrome and prior myocardial infarction. The EUCLID trial is designed to address the need for effective antiplatelet therapy in PAD to decrease the risk of cardiovascular events. EUCLID is a randomized, double-blind, parallel-group, multinational clinical trial designed to evaluate the efficacy and safety of ticagrelor compared with clopidogrel for the prevention of major adverse cardiovascular events in subjects with symptomatic PAD. Subjects with established PAD will be randomized in a 1:1 fashion to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. The primary end point is a composite of cardiovascular death, myocardial infarction, or ischemic stroke. Other end points address limb events including acute leg ischemia, need for revascularization, disease progression by ankle-brachial index, and quality of life. The primary safety objective is Thrombolysis in Myocardial Infarction-defined major bleeding. Recruitment began in December 2012 and was completed in March 2014; 13,887 patients were randomized. The trial will continue until at least 1,364 adjudicated primary end points occur. The EUCLID study is investigating whether treatment with ticagrelor versus clopidogrel, given as antiplatelet monotherapy, will reduce the incidence of cardiovascular and limb-specific events in patients with symptomatic PAD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The feasibility of a pragmatic randomised controlled trial to compare usual care with usual care plus individualised homeopathy, in children requiring secondary care for asthma.

PubMed

Thompson, E A; Shaw, A; Nichol, J; Hollinghurst, S; Henderson, A J; Thompson, T; Sharp, D

2011-07-01

To test the feasibility of a pragmatic trial design with economic evaluation and nested qualitative study, comparing usual care (UC) with UC plus individualised homeopathy, in children requiring secondary care for asthma. This included recruitment and retention, acceptability of outcome measures patients' and health professionals' views and experiences and a power calculation for a definitive trial. In a pragmatic parallel group randomised controlled trial (RCT) design, children on step 2 or above of the British Thoracic Society Asthma Guidelines (BTG) were randomly allocated to UC or UC plus a five visit package of homeopathic care (HC). Outcome measures included the Juniper Asthma Control Questionnaire, Quality of Life Questionnaire and a resource use questionnaire. Qualitative interviews were used to gain families' and health professionals' views and experiences. 226 children were identified from hospital clinics and related patient databases. 67 showed an interest in participating, 39 children were randomised, 18 to HC and 21 to UC. Evidence in favour of adjunctive homeopathic treatment was lacking. Economic evaluation suggests that the cost of additional consultations was not offset by the reduced cost of homeopathic remedies and the lower use of primary care by children in the homeopathic group. Qualitative data gave insights into the differing perspectives of families and health care professionals within the research process. A future study using this design is not feasible, further investigation of a potential role for homeopathy in asthma management might be better conducted in primary care with children with less severe asthma. Copyright © 2011 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Feasibility and Efficacy of an mHealth Game for Managing Anxiety: "Flowy" Randomized Controlled Pilot Trial and Design Evaluation.

PubMed

Pham, Quynh; Khatib, Yasmin; Stansfeld, Stephen; Fox, Simon; Green, Tobias

2016-02-01

Meeting the complex needs of patients with chronic common mental health disorders (CMHDs) may be the greatest challenge facing organized medical practice. On the basis of a well-established and proven theoretical foundation for controlled respiration as a behavioral intervention for CMHDs, as well as preliminary evidence that gamification can improve health outcomes through increasing patient engagement, this randomized controlled pilot study evaluated the feasibility and clinical efficacy of a mobile health game called "Flowy" ( www.flowygame.com ) that digitally delivered breathing retraining exercises for anxiety, panic, and hyperventilation symptom management. We designed an unblinded, Web-based, parallel-group randomized controlled trial focusing on feasibility, clinical efficacy, and design proof of concept. In the intervention condition (n = 31), participants received free access to "Flowy" for 4 weeks. In the control condition (n = 32), participants were placed on a waitlist for 4 weeks before being offered free access to "Flowy." Online measurements using psychological self-report questionnaires were made at 2 and 4 weeks post-baseline. At trial conclusion, participants found "Flowy" acceptable as an anxiety management intervention. "Flowy" engaged participants sufficiently to endorse proactive gameplay. Intent-to-treat analysis revealed a reduction in anxiety, panic, and self-report hyperventilation scores in both trial arms, with the intervention arm experiencing greater quality of life. Participants perceived "Flowy" as a fun and useful intervention, proactively used "Flowy" as part of their care, and would recommend "Flowy" to family and friends. Our results suggest that a digital delivery of breathing retraining exercises through a mobile health game can manage anxiety, panic, and hyperventilation symptoms associated with CMHDs.

Minimum envelope roughness pulse design for reduced amplifier distortion in parallel excitation.

PubMed

Grissom, William A; Kerr, Adam B; Stang, Pascal; Scott, Greig C; Pauly, John M

2010-11-01

Parallel excitation uses multiple transmit channels and coils, each driven by independent waveforms, to afford the pulse designer an additional spatial encoding mechanism that complements gradient encoding. In contrast to parallel reception, parallel excitation requires individual power amplifiers for each transmit channel, which can be cost prohibitive. Several groups have explored the use of low-cost power amplifiers for parallel excitation; however, such amplifiers commonly exhibit nonlinear memory effects that distort radio frequency pulses. This is especially true for pulses with rapidly varying envelopes, which are common in parallel excitation. To overcome this problem, we introduce a technique for parallel excitation pulse design that yields pulses with smoother envelopes. We demonstrate experimentally that pulses designed with the new technique suffer less amplifier distortion than unregularized pulses and pulses designed with conventional regularization.

Lidcombe Program Webcam Treatment for Early Stuttering: A Randomized Controlled Trial.

PubMed

Bridgman, Kate; Onslow, Mark; O'Brian, Susan; Jones, Mark; Block, Susan

2016-10-01

Webcam treatment is potentially useful for health care in cases of early stuttering in which clients are isolated from specialized treatment services for geographic and other reasons. The purpose of the present trial was to compare outcomes of clinic and webcam deliveries of the Lidcombe Program treatment (Packman et al., 2015) for early stuttering. The design was a parallel, open plan, noninferiority randomized controlled trial of the standard Lidcombe Program treatment and the experimental webcam Lidcombe Program treatment. Participants were 49 children aged 3 years 0 months to 5 years 11 months at the start of treatment. Primary outcomes were the percentage of syllables stuttered at 9 months postrandomization and the number of consultations to complete Stage 1 of the Lidcombe Program. There was insufficient evidence of a posttreatment difference of the percentage of syllables stuttered between the standard and webcam Lidcombe Program treatments. There was insufficient evidence of a difference between the groups for typical stuttering severity measured by parents or the reported clinical relationship with the treating speech-language pathologist. This trial confirmed the viability of the webcam Lidcombe Program intervention. It appears to be as efficacious and economically viable as the standard, clinic Lidcombe Program treatment.

Rationale and design of the Sodium Lowering In Dialysate (SoLID) trial: a randomised controlled trial of low versus standard dialysate sodium concentration during hemodialysis for regression of left ventricular mass

PubMed Central

2013-01-01

Background The current literature recognises that left ventricular hypertrophy makes a key contribution to the high rate of premature cardiovascular mortality in dialysis patients. Determining how we might intervene to ameliorate left ventricular hypertrophy in dialysis populations has become a research priority. Reducing sodium exposure through lower dialysate sodium may be a promising intervention in this regard. However there is clinical equipoise around this intervention because the benefit has not yet been demonstrated in a robust prospective clinical trial, and several observational studies have suggested sodium lowering interventions may be deleterious in some dialysis patients. Methods/design The Sodium Lowering in Dialysate (SoLID) study is funded by the Health Research Council of New Zealand. It is a multi-centre, prospective, randomised, single-blind (outcomes assessor), controlled parallel assignment 3-year clinical trial. The SoLID study is designed to study what impact low dialysate sodium has upon cardiovascular risk in dialysis patients. The study intends to enrol 118 home hemodialysis patients from 6 sites in New Zealand over 24 months and follow up each participant over 12 months. Key exclusion criteria are: patients who dialyse more frequently than 3.5 times per week, pre-dialysis serum sodium of <135 mM, and maintenance hemodiafiltration. In addition, some medical conditions, treatments or participation in other dialysis trials, which contraindicate the SoLID study intervention or confound its effects, will be exclusion criteria. The intervention and control groups will be dialysed using dialysate sodium 135 mM and 140 mM respectively, for 12 months. The primary outcome measure is left ventricular mass index, as measured by cardiac magnetic resonance imaging, after 12 months of intervention. Eleven or more secondary outcomes will be studied in an attempt to better understand the physiologic and clinical mechanisms by which lower dialysate sodium alters the primary end point. Discussion The SoLID study is designed to clarify the effect of low dialysate sodium upon the cardiovascular outcomes of dialysis patients. The study results will provide much needed information about the efficacy of a cost effective, economically sustainable solution to a condition which is curtailing the lives of so many dialysis patients. Trial registration Australian and New Zealand Clinical Trials Registry number: ACTRN12611000975998 PMID:23855560

Mixed-Meal Tolerance Test Versus Glucagon Stimulation Test for the Assessment of β-Cell Function in Therapeutic Trials in Type 1 Diabetes

PubMed Central

Greenbaum, Carla J.; Mandrup-Poulsen, Thomas; McGee, Paula Friedenberg; Battelino, Tadej; Haastert, Burkhard; Ludvigsson, Johnny; Pozzilli, Paolo; Lachin, John M.; Kolb, Hubert

2008-01-01

OBJECTIVE—β-Cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. RESEARCH DESIGN AND METHODS—In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. RESULTS—Among individuals with up to 4 years’ duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R2 = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group. CONCLUSIONS—The MMTT is preferred for the assessment of β-cell function in therapeutic trials in type 1 diabetes. PMID:18628574

ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials.

PubMed

Schwartz, Lisa M; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A

2016-09-20

Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA. ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews). 100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015). 2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths. Most trials were phase 3 (90%), double-blind (92%), and placebo-controlled (73%) and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 (98%) had corresponding data at Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results. Most differences were nominal (that is, relative difference <10%). Primary outcome results in 14 trials could not be validated. Of 1927 secondary outcomes from ClinicalTrials.gov, Drugs@FDA mentioned 1061 (55%) and included results data for 367 (19%). Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant. Unknown generalizability to uncontrolled or crossover trial results. Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only "key outcomes" for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials. National Library of Medicine.

A critical appraisal of the reporting quality of published randomized controlled trials in the fall injuries.

PubMed

Asghari Jafarabadi, Mohammad; Sadeghi-Bazrgani, Homayoun; Dianat, Iman

2018-06-01

To evaluate the quality of reporting in published randomized controlled trials (RTCs) in the field of fall injuries. The 188 RTCs published between 2001 and 2011, indexed in EMBASE and Medline databases were extracted through searching by appropriate keywords and EMTree classification terms. The evaluation trustworthiness was assured through parallel evaluations of two experts in epidemiology and biostatistics. About 40%-75% of papers had problems in reporting random allocation method, allocation concealment, random allocation implementation, blinding and similarity among groups, intention to treat and balancing benefits and harms. Moreover, at least 10% of papers inappropriately/not reported the design, protocol violations, sample size justification, subgroup/adjusted analyses, presenting flow diagram, drop outs, recruitment time, baseline data, suitable effect size on outcome, ancillary analyses, limitations and generalizability. Considering the shortcomings found and due to the importance of the RCTs for fall injury prevention programmes, their reporting quality should be improved.

An international randomized study of a home-based self-management program for severe COPD: the COMET.

PubMed

Bourbeau, Jean; Casan, Pere; Tognella, Silvia; Haidl, Peter; Texereau, Joëlle B; Kessler, Romain

2016-01-01

Most hospitalizations and costs related to COPD are due to exacerbations and insufficient disease management. The COPD patient Management European Trial (COMET) is investigating a home-based multicomponent COPD self-management program designed to reduce exacerbations and hospital admissions. Multicenter parallel randomized controlled, open-label superiority trial. Thirty-three hospitals in four European countries. A total of 345 patients with Global initiative for chronic Obstructive Lung Disease III/IV COPD. The program includes extensive patient coaching by health care professionals to improve self-management (eg, develop skills to better manage their disease), an e-health platform for reporting frequent health status updates, rapid intervention when necessary, and oxygen therapy monitoring. Comparator is the usual management as per the center's routine practice. Yearly number of hospital days for acute care, exacerbation number, quality of life, deaths, and costs.

COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): statistical and economic analysis plan for a randomised controlled trial.

PubMed

Robinson, Emily J; Goldstein, Laura H; McCrone, Paul; Perdue, Iain; Chalder, Trudie; Mellers, John D C; Richardson, Mark P; Murray, Joanna; Reuber, Markus; Medford, Nick; Stone, Jon; Carson, Alan; Landau, Sabine

2017-06-06

Dissociative seizures (DSs), also called psychogenic non-epileptic seizures, are a distressing and disabling problem for many patients in neurological settings with high and often unnecessary economic costs. The COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES) trial is an evaluation of a specifically tailored psychological intervention with the aims of reducing seizure frequency and severity and improving psychological well-being in adults with DS. The aim of this paper is to report in detail the quantitative and economic analysis plan for the CODES trial, as agreed by the trial steering committee. The CODES trial is a multicentre, pragmatic, parallel group, randomised controlled trial performed to evaluate the clinical effectiveness and cost-effectiveness of 13 sessions of cognitive behavioural therapy (CBT) plus standardised medical care (SMC) compared with SMC alone for adult outpatients with DS. The objectives and design of the trial are summarised, and the aims and procedures of the planned analyses are illustrated. The proposed analysis plan addresses statistical considerations such as maintaining blinding, monitoring adherence with the protocol, describing aspects of treatment and dealing with missing data. The formal analysis approach for the primary and secondary outcomes is described, as are the descriptive statistics that will be reported. This paper provides transparency to the planned inferential analyses for the CODES trial prior to the extraction of outcome data. It also provides an update to the previously published trial protocol and guidance to those conducting similar trials. ISRCTN registry ISRCTN05681227 (registered on 5 March 2014); ClinicalTrials.gov NCT02325544 (registered on 15 December 2014).

Comparative efficacy of the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy for early onset chronic depression: design and rationale of a multisite randomized controlled trial

PubMed Central

2011-01-01

Background Effective treatment strategies for chronic depression are urgently needed since it is not only a common and particularly disabling disorder, but is also considered treatment resistant by most clinicians. There are only a few studies on chronic depression indicating that traditional psycho- and pharmacological interventions are not as effective as in acute, episodic depression. Current medications are no more effective than those introduced 50 years ago whereas the only psychotherapy developed specifically for the subgroup of chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), faired well in one large trial. However, CBASP has never been directly compared to a non-specific control treatment. Methods/Design The present article describes the study protocol of a multisite parallel-group randomized controlled trial in Germany. The purpose of the study is to estimate the efficacy of CBASP compared to supportive psychotherapy in 268 non-medicated early-onset chronically depressed outpatients. The intervention includes 20 weeks of acute treatment with 24 individual sessions followed by 28 weeks of continuation treatment with another 8 sessions. Depressive symptoms are evaluated 20 weeks after randomisation by means of the 24-item Hamilton Rating Scale of Depression (HRSD). Secondary endpoints are depressive symptoms after 12 and 48 weeks, and remission after 12, 20, and 48 weeks. Primary outcome will be analysed using analysis of covariance (ANCOVA) controlled for pre-treatment scores and site. Analyses of continuous secondary variables will be performed using linear mixed models. For remission rates, chi-squared tests and logistic regression will be applied. Discussion The study evaluates the comparative effects of a disorder-specific psychotherapy and a well designed non-specific psychological approach in the acute and continuation treatment phase in a large sample of early-onset chronically depressed patients. Trial registration ClinicalTrials.gov (NCT00970437). PMID:21849054

Effectiveness of a smartphone application for improving healthy lifestyles, a randomized clinical trial (EVIDENT II): study protocol

PubMed Central

2014-01-01

Background New technologies could facilitate changes in lifestyle and improve public health. However, no large randomized, controlled studies providing scientific evidence of the benefits of their use have been made. The aims of this study are to develop and validate a smartphone application, and to evaluate the effect of adding this tool to a standardized intervention designed to improve adherence to the Mediterranean diet and to physical activity. An evaluation is also made of the effect of modifying habits upon vascular structure and function, and therefore on arterial aging. Methods/Design A randomized, double-blind, multicenter, parallel group clinical trial will be carried out. A total of 1215 subjects under 70 years of age from the EVIDENT trial will be included. Counseling common to both groups (control and intervention) will be provided on adaptation to the Mediterranean diet and on physical activity. The intervention group moreover will receive training on the use of a smartphone application designed to promote a healthy diet and increased physical activity, and will use the application for three months. The main study endpoints will be the changes in physical activity, assessed by accelerometer and the 7-day Physical Activity Recall (PAR) interview, and adaptation to the Mediterranean diet, as evaluated by an adherence questionnaire and a food frequency questionnaire (FFQ). Evaluation also will be made of vascular structure and function based on central arterial pressure, the radial augmentation index, pulse velocity, the cardio-ankle vascular index, and carotid intima-media thickness. Discussion Confirmation that the new technologies are useful for promoting healthier lifestyles and that their effects are beneficial in terms of arterial aging will have important clinical implications, and may contribute to generalize their application in favor of improved population health. Trial registration Clinical Trials.gov Identifier: NCT02016014 PMID:24628961

The language parallel Pascal and other aspects of the massively parallel processor

NASA Technical Reports Server (NTRS)

Reeves, A. P.; Bruner, J. D.

1982-01-01

A high level language for the Massively Parallel Processor (MPP) was designed. This language, called Parallel Pascal, is described in detail. A description of the language design, a description of the intermediate language, Parallel P-Code, and details for the MPP implementation are included. Formal descriptions of Parallel Pascal and Parallel P-Code are given. A compiler was developed which converts programs in Parallel Pascal into the intermediate Parallel P-Code language. The code generator to complete the compiler for the MPP is being developed independently. A Parallel Pascal to Pascal translator was also developed. The architecture design for a VLSI version of the MPP was completed with a description of fault tolerant interconnection networks. The memory arrangement aspects of the MPP are discussed and a survey of other high level languages is given.

Rationale, design and organization of the delayed antibiotic prescription (DAP) trial: a randomized controlled trial of the efficacy and safety of delayed antibiotic prescribing strategies in the non-complicated acute respiratory tract infections in general practice

PubMed Central

2013-01-01

Background Respiratory tract infections are an important burden in primary care and it’s known that they are usually self-limited and that antibiotics only alter its course slightly. This together with the alarming increase of bacterial resistance due to increased use of antimicrobials calls for a need to consider strategies to reduce their use. One of these strategies is the delayed prescription of antibiotics. Methods Multicentric, parallel, randomised controlled trial comparing four antibiotic prescribing strategies in acute non-complicated respiratory tract infections. We will include acute pharyngitis, rhinosinusitis, acute bronchitis and acute exacerbation of chronic bronchitis or chronic obstructive pulmonary disease (mild to moderate). The therapeutic strategies compared are: immediate antibiotic treatment, no antibiotic treatment, and two delayed antibiotic prescribing (DAP) strategies with structured advice to use a course of antibiotics in case of worsening of symptoms or not improving (prescription given to patient or prescription left at the reception of the primary care centre 3 days after the first medical visit). Discussion Delayed antibiotic prescription has been widely used in Anglo-Saxon countries, however, in Southern Europe there has been little research about this topic. The DAP trial wil evaluate two different delayed strategies in Spain for the main respiratory infections in primary care. Trial registration This trial is registered with ClinicalTrials.gov, number http://NCT01363531. PMID:23682979

A feasibility study investigating the acceptability and design of a multicentre randomised controlled trial of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contractures of the fingers (HAND-1): study protocol for a randomised controlled trial.

PubMed

Harrison, Eleanor; Tan, Wei; Mills, Nicola; Karantana, Alexia; Sprange, Kirsty; Duley, Lelia; Elliott, Daisy; Blazeby, Jane; Hollingworth, William; Montgomery, Alan A; Davis, Tim

2017-08-25

Dupuytren's contractures are fibrous cords under the skin of the palm of the hand. The contractures are painless but cause one or more fingers to curl into the palm, resulting in loss of function. Standard treatment within the NHS is surgery to remove (fasciectomy) or divide (fasciotomy) the contractures, and the treatment offered is frequently determined by surgeon preference. This study aims to determine the feasibility of conducting a large, multicentre randomised controlled trial to assess the clinical and cost-effectiveness of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contracture. HAND-1 is a parallel, two-arm, multicentre, randomised feasibility trial. Eligible patients aged 18 years or over who have one or more fingers with a Dupuytren's contracture of more than 30° in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints, well-defined cord(s) causing contracture, and have not undergone previous surgery for Dupuytren's on the same hand will be randomised (1:1) to treatment with either needle fasciotomy or limited fasciectomy. Participants will be followed-up for up to 6 months post surgery. Feasibility outcomes include number of patients screened, consented and randomised, adherence with treatment, completion of follow-up and identification of an appropriate patient-reported outcome measure (PROM) to use as primary outcome for a main trial. Embedded qualitative research, incorporating a QuinteT Recruitment Intervention, will focus on understanding and optimising the recruitment process, and exploring patients' experiences of trial participation and the interventions. This study will assess whether a large multicentre trial comparing the clinical and cost-effectiveness of needle fasciotomy and limited fasciectomy for the treatment of Dupuytren's contractures is feasible, and if so will provide data to inform its design and successful conduct. International Standard Registered Clinical/soCial sTudy Number: ISRCTN11164292 . Registered on 28 August 2015.

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 randomised clinical trial of comprehensive cardiac rehabilitation versus usual care for patients treated for infective endocarditis—the CopenHeartIE trial protocol

PubMed Central

Rasmussen, Trine Bernholdt; Zwisler, Ann-Dorthe; Sibilitz, Kirstine Lærum; Risom, Signe Stelling; Bundgaard, Henning; Gluud, Christian; Moons, Philip; Winkel, Per; Thygesen, Lau Caspar; Hansen, Jane Lindschou; Norekvål, Tone Merete; Berg, Selina Kikkenborg

2012-01-01

Introduction Infective endocarditis (IE) is among the most serious infectious diseases in the western world. Treatment requires lengthy hospitalisation, high-dosage antibiotic therapy and possible valve replacement surgery. Despite advances in treatment, the 1-year mortality remains at 20–40%. Studies indicate that patients experience persisting physical symptoms, diminished quality of life and difficulties returning to work up to a year postdischarge. No studies investigating the effects of rehabilitation have been published. We present the rationale and design of the CopenHeartIE trial, which investigates the effect of comprehensive cardiac rehabilitation versus usual care for patients treated for IE. Methods and analysis We will conduct a randomised clinical trial to investigate the effects of comprehensive cardiac rehabilitation versus usual care on the physical and psychosocial functioning of patients treated for IE. The trial is a multicentre, parallel design trial with 1 : 1 individual randomisation to either the intervention or control group. The intervention consists of five psychoeducational consultations provided by specialised nurses and a 12-week exercise training programme. The primary outcome is mental health (MH) measured by the standardised Short Form 36 (SF-36). The secondary outcome is peak oxygen uptake measured by the bicycle ergospirometry test. Furthermore, a number of exploratory analyses will be performed. Based on sample size calculation, 150 patients treated for left-sided (native or prosthetic valve) or cardiac device endocarditis will be included in the trial. A qualitative and a survey-based complementary study will be undertaken, to investigate postdischarge experiences of the patients. A qualitative postintervention study will explore rehabilitation participation experiences. Ethics and dissemination The study complies with the Declaration of Helsinki and was approved by the regional research ethics committee (no H-1-2011-129) and the Danish Data Protection Agency (no 2007-58-0015). Study findings will be disseminated widely through peer-reviewed publications and conference presentations. Registration Clinicaltrials.gov identifier: NCT01512615. PMID:23175738

A randomised clinical trial of comprehensive cardiac rehabilitation versus usual care for patients treated for infective endocarditis--the CopenHeartIE trial protocol.

PubMed

Rasmussen, Trine Bernholdt; Zwisler, Ann-Dorthe; Sibilitz, Kirstine Lærum; Risom, Signe Stelling; Bundgaard, Henning; Gluud, Christian; Moons, Philip; Winkel, Per; Thygesen, Lau Caspar; Hansen, Jane Lindschou; Norekvål, Tone Merete; Berg, Selina Kikkenborg

2012-01-01

Infective endocarditis (IE) is among the most serious infectious diseases in the western world. Treatment requires lengthy hospitalisation, high-dosage antibiotic therapy and possible valve replacement surgery. Despite advances in treatment, the 1-year mortality remains at 20-40%. Studies indicate that patients experience persisting physical symptoms, diminished quality of life and difficulties returning to work up to a year postdischarge. No studies investigating the effects of rehabilitation have been published. We present the rationale and design of the CopenHeart(IE) trial, which investigates the effect of comprehensive cardiac rehabilitation versus usual care for patients treated for IE. We will conduct a randomised clinical trial to investigate the effects of comprehensive cardiac rehabilitation versus usual care on the physical and psychosocial functioning of patients treated for IE. The trial is a multicentre, parallel design trial with 1 : 1 individual randomisation to either the intervention or control group. The intervention consists of five psychoeducational consultations provided by specialised nurses and a 12-week exercise training programme. The primary outcome is mental health (MH) measured by the standardised Short Form 36 (SF-36). The secondary outcome is peak oxygen uptake measured by the bicycle ergospirometry test. Furthermore, a number of exploratory analyses will be performed. Based on sample size calculation, 150 patients treated for left-sided (native or prosthetic valve) or cardiac device endocarditis will be included in the trial. A qualitative and a survey-based complementary study will be undertaken, to investigate postdischarge experiences of the patients. A qualitative postintervention study will explore rehabilitation participation experiences. The study complies with the Declaration of Helsinki and was approved by the regional research ethics committee (no H-1-2011-129) and the Danish Data Protection Agency (no 2007-58-0015). Study findings will be disseminated widely through peer-reviewed publications and conference presentations. Clinicaltrials.gov identifier: NCT01512615.

Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials.

PubMed

Teo, Koon; Yusuf, Salim; Sleight, Peter; Anderson, Craig; Mookadam, Farouk; Ramos, Barbara; Hilbrich, Lutz; Pogue, Janice; Schumacher, Helmut

2004-07-01

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, myocardial infarction, stroke, heart failure, need for revascularization, nephropathy, and diabetes and its complications. Although angiotensin-II receptor blockers (ARBs) have been less extensively evaluated, theoretically they may have "protective" effects similar to those of ACE inhibitors, but with better tolerability. Currently, there is uncertainty about the role of ARBs when used alone or in combination with an ACE inhibitor in high-risk populations with controlled hypertension. Primary objectives of the ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) are to determine if the combination of the ARB telmisartan and the ACE inhibitor ramipril is more effective than ramipril alone, and if telmisartan is at least as effective as ramipril. The Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease (TRANSCEND) will determine if telmisartan is superior to placebo in patients who are intolerant of ACE inhibitors. The primary outcome for both trials is the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. High-risk patients with coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage are being recruited and followed for 3.5 to 5.5 years in 2 parallel, randomized, double-blind clinical trials. Recruitment from 730 centers in 40 countries for ONTARGET (n = 25,620) was completed in July 2003. For TRANSCEND, 5776 patients (out of a projected total of 6000) have been recruited (by May 10, 2004). Baseline patient characteristics are comparable to the Heart Outcomes Prevention Evaluation (HOPE) trial, the basis of the design of the current study, confirming that patients are at high-risk.

Effects of Pre-Trial Response Requirements on Self-Control Choices by Rats and Pigeons

ERIC Educational Resources Information Center

Mazur, James E.

2012-01-01

Parallel experiments with rats and pigeons examined whether the size of a pre-trial ratio requirement would affect choices in a self-control situation. In different conditions, either 1 response or 40 responses were required before each trial. In the first half of each experiment, an adjusting-ratio schedule was used, in which subjects could…

A multicentre, pragmatic, parallel group, randomised controlled trial to compare the clinical and cost-effectiveness of three physiotherapy-led exercise interventions for knee osteoarthritis in older adults: the BEEP trial protocol (ISRCTN: 93634563)

PubMed Central

2014-01-01

Background Exercise is consistently recommended for older adults with knee pain related to osteoarthritis. However, the effects from exercise are typically small and short-term, likely linked to insufficient individualisation of the exercise programme and limited attention to supporting exercise adherence over time. The BEEP randomised trial aims to improve patients’ short and long-term outcomes from exercise. It will test the overall effectiveness and cost-effectiveness of two physiotherapy-led exercise interventions (Individually Tailored Exercise and Targeted Exercise Adherence) to improve the individual tailoring of, and adherence to exercise, compared with usual physiotherapy care. Methods/design Based on the learning from a pilot study (ISRCTN 23294263), the BEEP trial is a multi-centre, pragmatic, parallel group, individually randomised controlled trial, with embedded longitudinal qualitative interviews. 500 adults in primary care, aged 45 years and over with knee pain will be randomised to 1 of 3 treatment groups delivered by fully trained physiotherapists in up to 6 NHS services. These are: Usual Physiotherapy Care (control group consisting of up to 4 treatment sessions of advice and exercise), Individually Tailored Exercise (an individualised, supervised and progressed lower-limb exercise programme) or Targeted Exercise Adherence (supporting patients to adhere to exercise and to engage in general physical activity over the longer-term). The primary outcomes are pain and function as measured by the Western Ontario and McMaster Osteoarthritis index. A comprehensive range of secondary outcomes are also included. Outcomes are measured at 3, 6 (primary outcome time-point), 9, 18 and 36 months. Data on adverse events will also be collected. Semi-structured, qualitative interviews with a subsample of 30 participants (10 from each treatment group) will be undertaken at two time-points (end of treatment and 12 to 18 months later) and analysed thematically. Discussion This trial will contribute to the evidence base for management of older adults with knee pain attributable to osteoarthritis in primary care. The findings will have important implications for healthcare commissioners, general practitioners and physiotherapy service providers and it will inform future education of healthcare practitioners. It may also serve to delay or prevent some individuals from becoming surgical candidates. Trial registration ISRCTN: ISRCTN93634563. PMID:25064573

Randomized controlled trial of video self-modeling following speech restructuring treatment for stuttering.

PubMed

Cream, Angela; O'Brian, Sue; Jones, Mark; Block, Susan; Harrison, Elisabeth; Lincoln, Michelle; Hewat, Sally; Packman, Ann; Menzies, Ross; Onslow, Mark

2010-08-01

In this study, the authors investigated the efficacy of video self-modeling (VSM) following speech restructuring treatment to improve the maintenance of treatment effects. The design was an open-plan, parallel-group, randomized controlled trial. Participants were 89 adults and adolescents who undertook intensive speech restructuring treatment. Post treatment, participants were randomly assigned to 2 trial arms: standard maintenance and standard maintenance plus VSM. Participants in the latter arm viewed stutter-free videos of themselves each day for 1 month. The addition of VSM did not improve speech outcomes, as measured by percent syllables stuttered, at either 1 or 6 months postrandomization. However, at the latter assessment, self-rating of worst stuttering severity by the VSM group was 10% better than that of the control group, and satisfaction with speech fluency was 20% better. Quality of life was also better for the VSM group, which was mildly to moderately impaired compared with moderate impairment in the control group. VSM intervention after treatment was associated with improvements in self-reported outcomes. The clinical implications of this finding are discussed.

Study protocol: a randomized controlled trial investigating the effects of a psychosexual training program for adolescents with autism spectrum disorder.

PubMed

Visser, Kirsten; Greaves-Lord, Kirstin; Tick, Nouchka T; Verhulst, Frank C; Maras, Athanasios; van der Vegt, Esther J M

2015-08-28

Previous research shows that adolescents with autism spectrum disorder (ASD) run several risks in their psychosexual development and that these adolescents can have limited access to reliable information on puberty and sexuality, emphasizing the need for specific guidance of adolescents with ASD in their psychosexual development. Few studies have investigated the effects of psychosexual training programs for adolescents with ASD and to date no randomized controlled trials are available to study the effects of psychosexual interventions for this target group. The randomized controlled trial (RCT) described in this study protocol aims to investigate the effects of the Tackling Teenage Training (TTT) program on the psychosexual development of adolescents with ASD. This parallel clinical trial, conducted in the South-West of the Netherlands, has a simple equal randomization design with an intervention and a waiting-list control condition. Two hundred adolescents and their parents participate in this study. We assess the participants in both conditions using self-report as well as parent-report questionnaires at three time points during 1 year: at baseline (T1), post-treatment (T2), and for follow-up (T3). To our knowledge, the current study is the first that uses a randomized controlled design to study the effects of a psychosexual training program for adolescents with ASD. It has a number of methodological strengths, namely a large sample size, a wide range of functionally relevant outcome measures, the use of multiple informants, and a standardized research and intervention protocol. Also some limitations of the described study are identified, for instance not making a comparison between two treatment conditions, and no use of blinded observational measures to investigate the ecological validity of the research results. Dutch Trial Register NTR2860. Registered on 20 April 2011.

Underestimation of the efficacy, effectiveness, tolerability, and safety of weekly low-dose methotrexate in information presented to physicians and patients.

PubMed

Pincus, T; Furer, V; Sokka, T

2010-01-01

Ten specific examples of the underestimation of the efficacy, effectiveness and tolerability, and overestimation of adverse events of weekly, low-dose methotrexate, administered with folic acid, in treatment of rheumatic diseases are summarised. These examples include: 1) meta-analyses of clinical trials suggest that methotrexate has an efficacy similar to other disease-modifying anti-rheumatic drugs (DMARDs); 2) information in textbooks and websites may overstate adverse events and drug interactions associated with weekly low-dose methotrexate; 3) information presented to patients when filling a prescription for methotrexate understates 'side effects' of RA and overstates those of methotrexate; 4) an admonition to patients to refrain entirely from consumption of alcohol while taking methotrexate may be unnecessary; 5) frequent blood testing in patients who take methotrexate may be overused; 6) eligibility of only a small minority of patients for clinical trials to compare biologic agents and methotrexate; 7) Step-up design in most comparisons of biologic agents with methotrexate includes only patients who had experienced an incomplete response to methotrexate; 8) in parallel design trials, the efficacy of biologic agents is not substantially greater than that of methotrexate; 9) low, inflexible dosage schedules of methotrexate and requirement for withdrawal with minimal liver function abnormalities in many clinical trials may underestimate efficacy, effectiveness, tolerability and safety; 10) interpretation of clinical trial results may overstate the clinical significance of lower radiographic progression in patients treated with biologic agents versus patients treated with methotrexate. More accurate interpretation of information for physicians and other health professionals, as well as patients, concerning use of weekly low-dose methotrexate in contemporary care could improve care and outcomes for patients with RA and other rheumatic diseases.

Quality of reporting randomized controlled trials (RCTs) in diabetes in Iran; a systematic review.

PubMed

Gohari, Faeze; Baradaran, Hamid Reza; Tabatabaee, Morteza; Anijidani, Shabnam; Mohammadpour Touserkani, Fatemeh; Atlasi, Rasha; Razmgir, Maryam

2015-01-01

To determine the quality of randomized controlled clinical trial (RCT) reports in diabetes research in Iran. Systematized review. We included RCTs conducted on diabetes mellitus in Iran. Animal studies, educational interventions, and non-randomized trials were excluded. We excluded duplicated publications reporting the same groups of participants and intervention. Two independent reviewers identify all eligible articles specifically designed data extraction form. We searched through international databases; Scopus, ProQuest, EBSCO, Science Direct, Web of Science, Cochrane Library, PubMed; and national databases (In Persian language) such as Magiran, Scientific Information Database (SID) and IranMedex from January 1995 to January of 2013 Two investigators assessed the quality of reporting by CONSORT 2010 (Consolidated Standards of Reporting Trials) checklist statemen.t,. Discrepancies were resolved by third reviewer consulting. One hundred and eight five (185) studies were included and appraised. Half of them (55.7 %) were published in Iranian journals. Most (89.7 %) were parallel RCTs, and being performed on type2 diabetic patients (77.8 %). Less than half of the CONSORT items (43.2 %) were reported in studies, totally. The reporting of randomization and blinding were poor. A few studies 15.1 % mentioned the method of random sequence generation and strategy of allocation concealment. And only 34.8 % of trials report how blinding was applied. The findings of this study show that the quality of RCTs conducted in Iran in diabetes research seems suboptimal and the reporting is also incomplete however an increasing trend of improvement can be seen over time. Therefore, it is suggested Iranian researchers pay much more attention to design and methodological quality in conducting and reporting of diabetes RCTs.

The long-term effect of minimalist shoes on running performance and injury: design of a randomised controlled trial

PubMed Central

Fuller, Joel T; Thewlis, Dominic; Tsiros, Margarita D; Brown, Nicholas A T; Buckley, Jonathan D

2015-01-01

Introduction The outcome of the effects of transitioning to minimalist running shoes is a topic of interest for runners and scientists. However, few studies have investigated the longer term effects of running in minimalist shoes. The purpose of this randomised controlled trial (RCT) is to investigate the effects of a 26 week transition to minimalist shoes on running performance and injury risk in trained runners unaccustomed to minimalist footwear. Methods and analysis A randomised parallel intervention design will be used. Seventy-six trained male runners will be recruited. To be eligible, runners must be aged 18–40 years, run with a habitual rearfoot footfall pattern, train with conventional shoes and have no prior experience with minimalist shoes. Runners will complete a standardised transition to either minimalist or control shoes and undergo assessments at baseline, 6 and 26 weeks. 5 km time-trial performance (5TT), running economy, running biomechanics, triceps surae muscle strength and lower limb bone mineral density will be assessed at each time point. Pain and injury will be recorded weekly. Training will be standardised during the first 6 weeks. Primary statistical analysis will compare 5TT between shoe groups at the 6-week time point and injury incidence across the entire 26-week study period. Ethics and dissemination This RCT has been approved by the Human Research Ethics Committee of the University of South Australia. Participants will be required to provide their written informed consent prior to participation in the study. Study findings will be disseminated in the form of journal publications and conference presentations after completion of planned data analysis. Trial registration number This RCT has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000642785). PMID:26297368

Impact of a Brief Group Intervention to Enhance Parenting and the Home Learning Environment for Children Aged 6-36 Months: a Cluster Randomised Controlled Trial.

PubMed

Hackworth, N J; Berthelsen, D; Matthews, J; Westrupp, E M; Cann, W; Ukoumunne, O C; Bennetts, S K; Phan, T; Scicluna, A; Trajanovska, M; Yu, M; Nicholson, J M

2017-04-01

This study evaluated the effectiveness of a group parenting intervention designed to strengthen the home learning environment of children from disadvantaged families. Two cluster randomised controlled superiority trials were conducted in parallel and delivered within existing services: a 6-week parenting group (51 locations randomised; 986 parents) for parents of infants (aged 6-12 months), and a 10-week facilitated playgroup (58 locations randomised; 1200 parents) for parents of toddlers (aged 12-36 months). Each trial had three conditions: intervention (smalltalk group-only); enhanced intervention with home coaching (smalltalk plus); and 'standard'/usual practice controls. Parent-report and observational measures were collected at baseline, 12 and 32 weeks follow-up. Primary outcomes were parent verbal responsivity and home learning activities at 32 weeks. In the infant trial, there were no differences by trial arm for the primary outcomes at 32 weeks. In the toddler trial at 32-weeks, participants in the smalltalk group-only trial showed improvement compared to the standard program for parent verbal responsivity (effect size (ES) = 0.16; 95% CI 0.01, 0.36) and home learning activities (ES = 0.17; 95% CI 0.01, 0.38) but smalltalk plus did not. For the secondary outcomes in the infant trial, several initial differences favouring smalltalk plus were evident at 12 weeks, but not maintained to 32 weeks. For the toddler trial, differences in secondary outcomes favouring smalltalk plus were evident at 12 weeks and maintained to 32 weeks. These trials provide some evidence of the benefits of a parenting intervention focused on the home learning environment for parents of toddlers but not infants. 8 September 2011; ACTRN12611000965909 .

Exploring threats to generalisability in a large international rehabilitation trial (AVERT)

PubMed Central

Bernhardt, Julie; Raffelt, Audrey; Churilov, Leonid; Lindley, Richard I; Speare, Sally; Ancliffe, Jacqueline; Katijjahbe, Md Ali; Hameed, Shahul; Lennon, Sheila; McRae, Anna; Tan, Dawn; Quiney, Jan; Williamson, Hannah C; Collier, Janice; Dewey, Helen M; Donnan, Geoffrey A; Langhorne, Peter; Thrift, Amanda G

2015-01-01

Objective The purpose of this paper is to examine potential threats to generalisability of the results of a multicentre randomised controlled trial using data from A Very Early Rehabilitation Trial (AVERT). Design AVERT is a prospective, parallel group, assessor-blinded randomised clinical trial. This paper presents data assessing the generalisability of AVERT. Setting Acute stroke units at 44 hospitals in 8 countries. Participants The first 20 000 patients screened for AVERT, of whom 1158 were recruited and randomised. Model We use the Proximal Similarity Model, which considers the person, place, and setting and practice, as a framework for considering generalisability. As well as comparing the recruited patients with the target population, we also performed an exploratory analysis of the demographic, clinical, site and process factors associated with recruitment. Results The demographics and stroke characteristics of the included patients in the trial were broadly similar to population-based norms, with the exception that AVERT had a greater proportion of men. The most common reason for non-recruitment was late arrival to hospital (ie, >24 h). Overall, being older and female reduced the odds of recruitment to the trial. More women than men were excluded for most of the reasons, including refusal. The odds of exclusion due to early deterioration were particularly high for those with severe stroke (OR=10.4, p<0.001, 95% CI 9.27 to 11.65). Conclusions A model which explores person, place, and setting and practice factors can provide important information about the external validity of a trial, and could be applied to other clinical trials. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12606000185561) and Clinicaltrials.gov (NCT01846247). PMID:26283667

Parallelizing serial code for a distributed processing environment with an application to high frequency electromagnetic scattering

NASA Astrophysics Data System (ADS)

Work, Paul R.

1991-12-01

This thesis investigates the parallelization of existing serial programs in computational electromagnetics for use in a parallel environment. Existing algorithms for calculating the radar cross section of an object are covered, and a ray-tracing code is chosen for implementation on a parallel machine. Current parallel architectures are introduced and a suitable parallel machine is selected for the implementation of the chosen ray-tracing algorithm. The standard techniques for the parallelization of serial codes are discussed, including load balancing and decomposition considerations, and appropriate methods for the parallelization effort are selected. A load balancing algorithm is modified to increase the efficiency of the application, and a high level design of the structure of the serial program is presented. A detailed design of the modifications for the parallel implementation is also included, with both the high level and the detailed design specified in a high level design language called UNITY. The correctness of the design is proven using UNITY and standard logic operations. The theoretical and empirical results show that it is possible to achieve an efficient parallel application for a serial computational electromagnetic program where the characteristics of the algorithm and the target architecture critically influence the development of such an implementation.

Predictors of short- and long-term adherence with a Mediterranean-type diet intervention: the PREDIMED randomized trial.

PubMed

Downer, Mary Kathryn; Gea, Alfredo; Stampfer, Meir; Sánchez-Tainta, Ana; Corella, Dolores; Salas-Salvadó, Jordi; Ros, Emilio; Estruch, Ramón; Fitó, Montserrat; Gómez-Gracia, Enrique; Arós, Fernando; Fiol, Miquel; De-la-Corte, Francisco Jose Garcia; Serra-Majem, Lluís; Pinto, Xavier; Basora, Josep; Sorlí, José V; Vinyoles, Ernest; Zazpe, Itziar; Martínez-González, Miguel-Ángel

2016-06-14

Dietary intervention success requires strong participant adherence, but very few studies have examined factors related to both short-term and long-term adherence. A better understanding of predictors of adherence is necessary to improve the design and execution of dietary intervention trials. This study was designed to identify participant characteristics at baseline and study features that predict short-term and long-term adherence with interventions promoting the Mediterranean-type diet (MedDiet) in the PREvención con DIeta MEDiterránea (PREDIMED) randomized trial. Analyses included men and women living in Spain aged 55-80 at high risk for cardiovascular disease. Participants were randomized to the MedDiet supplemented with either complementary extra-virgin olive oil (EVOO) or tree nuts. The control group and participants with insufficient information on adherence were excluded. PREDIMED began in 2003 and ended in 2010. Investigators assessed covariates at baseline and dietary information was updated yearly throughout follow-up. Adherence was measured with a validated 14-point Mediterranean-type diet adherence score. Logistic regression was used to examine associations between baseline characteristics and adherence at one and four years of follow-up. Participants were randomized to the MedDiet supplemented with EVOO (n = 2,543; 1,962 after exclusions) or tree nuts (n = 2,454; 2,236 after exclusions). A higher number of cardiovascular risk factors, larger waist circumference, lower physical activity levels, lower total energy intake, poorer baseline adherence to the 14-point adherence score, and allocation to MedDiet + EVOO each independently predicted poorer adherence. Participants from PREDIMED recruiting centers with a higher total workload (measured as total number of persons-years of follow-up) achieved better adherence. No adverse events or side effects were reported. To maximize dietary adherence in dietary interventions, additional efforts to promote adherence should be used for participants with lower baseline adherence to the intended diet and poorer health status. The design of multicenter nutrition trials should prioritize few large centers with more participants in each, rather than many small centers. This study was registered at controlled-trials.com (http://www.controlled-trials. com/ISRCTN35739639). International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005. parallel randomized trial.

Pressure RElieving Support SUrfaces: a Randomised Evaluation 2 (PRESSURE 2): study protocol for a randomised controlled trial.

PubMed

Brown, Sarah; Smith, Isabelle L; Brown, Julia M; Hulme, Claire; McGinnis, Elizabeth; Stubbs, Nikki; Nelson, E Andrea; Muir, Delia; Rutherford, Claudia; Walker, Kay; Henderson, Valerie; Wilson, Lyn; Gilberts, Rachael; Collier, Howard; Fernandez, Catherine; Hartley, Suzanne; Bhogal, Moninder; Coleman, Susanne; Nixon, Jane E

2016-12-20

Pressure ulcers represent a major burden to patients, carers and the healthcare system, affecting approximately 1 in 17 hospital and 1 in 20 community patients. They impact greatly on an individual's functional status and health-related quality of life. The mainstay of pressure ulcer prevention practice is the provision of pressure redistribution support surfaces and patient repositioning. The aim of the PRESSURE 2 study is to compare the two main mattress types utilised within the NHS: high-specification foam and alternating pressure mattresses, in the prevention of pressure ulcers. PRESSURE 2 is a multicentre, open-label, randomised, double triangular, group sequential, parallel group trial. A maximum of 2954 'high-risk' patients with evidence of acute illness will be randomised on a 1:1 basis to receive either a high-specification foam mattress or alternating-pressure mattress in conjunction with an electric profiling bed frame. The primary objective of the trial is to compare mattresses in terms of the time to developing a new Category 2 or above pressure ulcer by 30 days post end of treatment phase. Secondary endpoints include time to developing new Category 1 and 3 or above pressure ulcers, time to healing of pre-existing Category 2 pressure ulcers, health-related quality of life, cost-effectiveness, incidence of mattress change and safety. Validation objectives are to determine the responsiveness of the Pressure Ulcer Quality of Life-Prevention instrument and the feasibility of having a blinded endpoint assessment using photography. The trial will have a maximum of three planned analyses with unequally spaced reviews at event-driven coherent cut-points. The futility boundaries are constructed as non-binding to allow a decision for stopping early to be overruled by the Data Monitoring and Ethics Committee. The double triangular, group sequential design of the PRESSURE 2 trial will provide an efficient design through the possibility of early stopping for demonstrating either superiority, inferiority of mattresses or futility of the trial. The trial optimises the potential for producing robust clinical evidence on the effectiveness of two commonly used mattresses in clinical practice earlier than in a conventional design. ISRCTN01151335 . Registered on 14 May 2013. Protocol version: 5.0, dated 25 September 2015 Trial sponsor: Clare Skinner, Faculty Head of Research Support, University of Leeds, Leeds, LS2 9JT; 0113 343 4897; C.E.Skinner@leeds.ac.uk.

A Parallel Particle Swarm Optimization Algorithm Accelerated by Asynchronous Evaluations

NASA Technical Reports Server (NTRS)

Venter, Gerhard; Sobieszczanski-Sobieski, Jaroslaw

2005-01-01

A parallel Particle Swarm Optimization (PSO) algorithm is presented. Particle swarm optimization is a fairly recent addition to the family of non-gradient based, probabilistic search algorithms that is based on a simplified social model and is closely tied to swarming theory. Although PSO algorithms present several attractive properties to the designer, they are plagued by high computational cost as measured by elapsed time. One approach to reduce the elapsed time is to make use of coarse-grained parallelization to evaluate the design points. Previous parallel PSO algorithms were mostly implemented in a synchronous manner, where all design points within a design iteration are evaluated before the next iteration is started. This approach leads to poor parallel speedup in cases where a heterogeneous parallel environment is used and/or where the analysis time depends on the design point being analyzed. This paper introduces an asynchronous parallel PSO algorithm that greatly improves the parallel e ciency. The asynchronous algorithm is benchmarked on a cluster assembled of Apple Macintosh G5 desktop computers, using the multi-disciplinary optimization of a typical transport aircraft wing as an example.

Rationale and design of the HepZero study: a prospective, multicenter, international, open, randomized, controlled clinical study with parallel groups comparing heparin-free dialysis with heparin-coated dialysis membrane (Evodial) versus standard care: study protocol for a randomized controlled trial.

PubMed

Rossignol, Patrick; Dorval, Marc; Fay, Renaud; Ros, Joan Fort; Loughraieb, Nathalie; Moureau, Frédérique; Laville, Maurice

2013-06-01

Anticoagulation for chronic dialysis patients with contraindications to heparin administration is challenging. Current guidelines state that in patients with increased bleeding risks, strategies that can induce systemic anticoagulation should be avoided. Heparin-free dialysis using intermittent saline flushes is widely adopted as the method of choice for patients at risk of bleeding, although on-line blood predilution may also be used. A new dialyzer, Evodial (Gambro, Lund, Sweden), is grafted with unfractionated heparin during the manufacturing process and may allow safe and efficient heparin-free hemodialysis sessions. In the present trial, Evodial was compared to standard care with either saline flushes or blood predilution. The HepZero study is the first international (seven countries), multicenter (10 centers), randomized, controlled, open-label, non-inferiority (and if applicable subsequently, superiority) trial with two parallel groups, comprising 252 end-stage renal disease patients treated by maintenance hemodialysis for at least 3 months and requiring heparin-free dialysis treatments. Patients will be treated during a maximum of three heparin-free dialysis treatments with either saline flushes or blood predilution (control group), or Evodial. The first heparin-free dialysis treatment will be considered successful when there is: no complete occlusion of air traps or dialyzer rendering dialysis impossible; no additional saline flushes to prevent clotting; no change of dialyzer or blood lines because of clotting; and no premature termination (early rinse-back) because of clotting.The primary objectives of the study are to determine the effectiveness of the Evodial dialyzer, compared with standard care in terms of successful treatments during the first heparin-free dialysis. If the non-inferiority of Evodial is demonstrated then the superiority of Evodial over standard care will be tested. The HepZero study results may have major clinical implications for patient care. ClinicalTrials.gov NCT01318486.

The effectiveness of a web-based brief alcohol intervention in reducing heavy drinking among adolescents aged 15 to 20 years with a low educational background: study protocol for a randomized controlled trial.

PubMed

Voogt, Carmen V; Poelen, Evelien A P; Lemmers, Lex A C J; Engels, Rutger C M E

2012-06-15

The serious negative health consequences of heavy drinking among adolescents is cause for concern, especially among adolescents aged 15 to 20 years with a low educational background. In the Netherlands, there is a lack of alcohol prevention programs directed to the drinking patterns of this specific target group. The study described in this protocol will test the effectiveness of a web-based brief alcohol intervention that aims to reduce alcohol use among heavy drinking adolescents aged 15 to 20 years with a low educational background. The effectiveness of the What Do You Drink (WDYD) web-based brief alcohol intervention will be tested among 750 low-educated, heavy drinking adolescents. It will use a two-arm parallel group cluster randomized controlled trial. Classes of adolescents from educational institutions will be randomly assigned to either the experimental (n = 375: web-based brief alcohol intervention) or control condition (n = 375: no intervention). Primary outcomes measures will be: 1) the percentage of participants who drink within the normative limits of the Dutch National Health Council for low-risk drinking, 2) reductions in mean weekly alcohol consumption, and 3) frequency of binge drinking. The secondary outcome measures include the alcohol-related cognitions, attitudes, self-efficacy, and subjective norms, which will be measured at baseline and at one and six months after the intervention. This study protocol presents the study design of a two-arm parallel-group randomized controlled trial to evaluate the effectiveness of the WDYD web-based brief alcohol intervention. We hypothesized a reduction in mean weekly alcohol consumption and in the frequency of binge drinking in the experimental condition, resulting from the web-based brief alcohol intervention, compared to the control condition. Netherlands Trial Register NTR2971.

‘Alzheimer’s Progression Score’: Development of a Biomarker Summary Outcome for AD Prevention Trials

PubMed Central

Leoutsakos, J.-M.; Gross, A.L.; Jones, R.N.; Albert, M.S.; Breitner, J.C.S.

2017-01-01

BACKGROUND Alzheimer’s disease (AD) prevention research requires methods for measurement of disease progression not yet revealed by symptoms. Preferably, such measurement should encompass multiple disease markers. OBJECTIVES Evaluate an item response theory (IRT) model-based latent variable Alzheimer Progression Score (APS) that uses multi-modal disease markers to estimate pre-clinical disease progression. DESIGN Estimate APS scores in the BIOCARD observational study, and in the parallel PREVENT-AD Cohort and its sister INTREPAD placebo-controlled prevention trial. Use BIOCARD data to evaluate whether baseline and early APS trajectory predict later progression to MCI/dementia. Similarly, use longitudinal PREVENT-AD data to assess test measurement invariance over time. Further, assess portability of the PREVENT-AD IRT model to baseline INTREPAD data, and explore model changes when CSF markers are added or withdrawn. SETTING BIOCARD was established in 1995 and participants were followed up to 20 years in Baltimore, USA. The PREVENT-AD and INTREPAD trial cohorts were established between 2011–2015 in Montreal, Canada, using nearly identical entry criteria to enroll high-risk cognitively normal persons aged 60+ then followed for several years. PARTICIPANTS 349 cognitively normal, primarily middle-aged participants in BIOCARD, 125 high-risk participants aged 60+ in PREVENT-AD, and 217 similar subjects in INTREPAD. 106 INTREPAD participants donated up to four serial CSF samples. MEASUREMENTS Global cognitive assessment and multiple structural, functional, and diffusion MRI metrics, sensori-neural tests, and CSF concentrations of tau, Aβ42 and their ratio. RESULTS Both baseline values and early slope of APS scores in BIOCARD predicted later progression to MCI or AD. Presence of CSF variables strongly improved such prediction. A similarly derived APS in PREVENT-AD showed measurement invariance over time and portability to the parallel INTREPAD sample. CONCLUSIONS An IRT-based APS can summarize multimodal information to provide a longitudinal measure of pre-clinical AD progression, and holds promise as an outcome for AD prevention trials. PMID:29034223

Methylphenidate for attention deficit hyperactivity disorder and drug relapse in criminal offenders with substance dependence: a 24-week randomized placebo-controlled trial

PubMed Central

Konstenius, Maija; Jayaram-Lindström, Nitya; Guterstam, Joar; Beck, Olof; Philips, Björn; Franck, Johan

2014-01-01

Aim To test the efficacy and safety of osmotic release oral system (OROS) methylphenidate (MPH) in doses up to 180 mg/day to treat attention deficit hyperactivity disorder (ADHD) and prevent any drug relapse in individuals with a co-diagnosis of ADHD and amphetamine dependence. Design Randomized placebo-controlled 24-week double-blind trial with parallel groups design. Setting Participants were recruited from medium security prisons in Sweden. The medication started within 2 weeks before release from prison and continued in out-patient care with twice-weekly visits, including once-weekly cognitive behavioural therapy. Participants Fifty-four men with a mean age of 42 years, currently incarcerated, meeting DSM-IV criteria for ADHD and amphetamine dependence. Measurements Change in self-reported ADHD symptoms, relapse to any drug use (amphetamine and other drugs) measured by urine toxicology, retention to treatment, craving and time to relapse. Findings The MPH-treated group reduced their ADHD symptoms during the trial (P = 0.011) and had a significantly higher proportion of drug-negative urines compared with the placebo group (P = 0.047), including more amphetamine-negative urines (P = 0.019) and better retention to treatment (P = 0.032). Conclusions Methylphenidate treatment reduces attention deficit hyperactivity disorder symptoms and the risk for relapse to substance use in criminal offenders with attention deficit hyperactivity disorder and substance dependence. PMID:24118269

Clinical Evaluation of Effects of Chronic Resveratrol Supplementation on Cerebrovascular Function, Cognition, Mood, Physical Function and General Well-Being in Postmenopausal Women-Rationale and Study Design.

PubMed

Evans, Hamish Michael; Howe, Peter Ranald Charles; Wong, Rachel Heloise Xiwen

2016-03-09

This methodological paper presents both a scientific rationale and a methodological approach for investigating the effects of resveratrol supplementation on mood and cognitive performance in postmenopausal women. Postmenopausal women have an increased risk of cognitive decline and dementia, which may be at least partly due to loss of beneficial effects of estrogen on the cerebrovasculature. We hypothesise that resveratrol, a phytoestrogen, may counteract this risk by enhancing cerebrovascular function and improving regional blood flow in response to cognitive demands. A clinical trial was designed to test this hypothesis. Healthy postmenopausal women were recruited to participate in a randomised, double-blind, placebo-controlled (parallel comparison) dietary intervention trial to evaluate the effects of resveratrol supplementation (75 mg twice daily) on cognition, cerebrovascular responsiveness to cognitive tasks and overall well-being. They performed the following tests at baseline and after 14 weeks of supplementation: Rey Auditory Verbal Learning Test, Cambridge Semantic Memory Battery, the Double Span and the Trail Making Task. Cerebrovascular function was assessed simultaneously by monitoring blood flow velocity in the middle cerebral arteries using transcranial Doppler ultrasound. This trial provides a model approach to demonstrate that, by optimising circulatory function in the brain, resveratrol and other vasoactive nutrients may enhance mood and cognition and ameliorate the risk of developing dementia in postmenopausal women and other at-risk populations.

Effectiveness of a standardised exercise programme for recurrent neck and low back pain: a multicentre, randomised, two-arm, parallel group trial across 34 fitness clubs in Finland.

PubMed

Suni, Jaana H; Rinne, Marjo; Tokola, Kari; Mänttäri, Ari; Vasankari, Tommi

2017-01-01

Neck and low back pain (LBP) are common in office workers. Exercise trials to reduce neck and LBP conducted in sport sector are lacking. We investigated the effectiveness of the standardised Fustra20Neck&Back exercise program for reducing pain and increasing fitness in office workers with recurrent non-specific neck and/or LBP. Volunteers were recruited through newspaper and Facebook. The design is a multi-centre randomised, two-arm, parallel group trial across 34 fitness clubs in Finland. Eligibility was determined by structured telephone interview. Instructors were specially educated professionals. Neuromuscular exercise was individually guided twice weekly for 10 weeks. Webropol survey, and objective measurements of fitness, physical activity, and sedentary behavior were conducted at baseline, and at 3 and 12 months. Mean differences between study groups (Exercise vs Control) were analysed using a general linear mixed model according to the intention-to-treat principle. At least moderate intensity pain (≥40 mm) in both the neck and back was detected in 44% of participants at baseline. Exercise compliance was excellent: 92% participated 15-20 times out of 20 possible. Intensity and frequency of neck pain, and strain in neck/shoulders decreased significantly in the Exercise group compared with the Control group. No differences in LBP and strain were detected. Neck/shoulder and trunk flexibility improved, as did quality of life in terms of pain and physical functioning. The Fustra20Neck&Back exercise program was effective for reducing neck/shoulder pain and strain, but not LBP. Evidence-based exercise programs of sports clubs have potential to prevent persistent, disabling musculoskeletal problems.

Weight loss intervention for young adults using mobile technology: design and rationale of a randomized controlled trial – Cell phone Intervention for You (CITY)

PubMed Central

Batch, Bryan C.; Tyson, Crystal; Bagwell, Jacqueline; Corsino, Leonor; Intille, Stephen; Lin, Pao-Hwa; Lazenka, Tony; Bennett, Gary; Bosworth, Hayden B.; Voils, Corrine; Grambow, Steven; Sutton, Aziza; Bordogna, Rachel; Pangborn, Matthew; Schwager, Jenifer; Pilewski, Kate; Caccia, Carla; Burroughs, Jasmine; Svetkey, Laura P.

2014-01-01

Background The obesity epidemic has spread to young adults, leading to significant public health implications later in adulthood. Intervention in early adulthood may be an effective public health strategy for reducing the long-term health impact of the epidemic. Few weight loss trials have been conducted in young adults. It is unclear what weight loss strategies are beneficial in this population. Purpose To describe the design and rationale of the NHLBI-sponsored Cell Phone Intervention for You (CITY) study, which is a single center, randomized three-arm trial that compares the impact on weight loss of 1) a behavioral intervention that is delivered almost entirely via cell phone technology (Cell Phone group); and 2) a behavioral intervention delivered mainly through monthly personal coaching calls enhanced by self-monitoring via cell phone (Personal Coaching group), each compared to; 3) a usual care, advice-only control condition. Methods A total of 365 community-dwelling overweight/obese adults aged 18–35 years were randomized to receive one of these three interventions for 24 months in parallel group design. Study personnel assessing outcomes were blinded to group assignment. The primary outcome is weight change at 12 months. We hypothesize that each active intervention will cause more weight loss than the usual care condition. Study completion is anticipated in 2014. Conclusions If effective, implementation of the CITY interventions could mitigate the alarming rates of obesity in young adults through promotion of weight loss. PMID:24462568

Self-Administered Computer Therapy for Apraxia of Speech: Two-Period Randomized Control Trial With Crossover.

PubMed

Varley, Rosemary; Cowell, Patricia E; Dyson, Lucy; Inglis, Lesley; Roper, Abigail; Whiteside, Sandra P

2016-03-01

There is currently little evidence on effective interventions for poststroke apraxia of speech. We report outcomes of a trial of self-administered computer therapy for apraxia of speech. Effects of speech intervention on naming and repetition of treated and untreated words were compared with those of a visuospatial sham program. The study used a parallel-group, 2-period, crossover design, with participants receiving 2 interventions. Fifty participants with chronic and stable apraxia of speech were randomly allocated to 1 of 2 order conditions: speech-first condition versus sham-first condition. Period 1 design was equivalent to a randomized controlled trial. We report results for this period and profile the effect of the period 2 crossover. Period 1 results revealed significant improvement in naming and repetition only in the speech-first group. The sham-first group displayed improvement in speech production after speech intervention in period 2. Significant improvement of treated words was found in both naming and repetition, with little generalization to structurally similar and dissimilar untreated words. Speech gains were largely maintained after withdrawal of intervention. There was a significant relationship between treatment dose and response. However, average self-administered dose was modest for both groups. Future software design would benefit from incorporation of social and gaming components to boost motivation. Single-word production can be improved in chronic apraxia of speech with behavioral intervention. Self-administered computerized therapy is a promising method for delivering high-intensity speech/language rehabilitation. URL: http://orcid.org/0000-0002-1278-0601. Unique identifier: ISRCTN88245643. © 2016 American Heart Association, Inc.

Implementing Single Source: The STARBRITE Proof-of-Concept Study

PubMed Central

Kush, Rebecca; Alschuler, Liora; Ruggeri, Roberto; Cassells, Sally; Gupta, Nitin; Bain, Landen; Claise, Karen; Shah, Monica; Nahm, Meredith

2007-01-01

Objective Inefficiencies in clinical trial data collection cause delays, increase costs, and may reduce clinician participation in medical research. In this proof-of-concept study, we examine the feasibility of using point-of-care data capture for both the medical record and clinical research in the setting of a working clinical trial. We hypothesized that by doing so, we could increase reuse of patient data, eliminate redundant data entry, and minimize disruption to clinic workflow. Design We developed and used a point-of-care electronic data capture system to record data during patient visits. The standards-based system was used for clinical research and to generate the clinic note for the medical record. The system worked in parallel with data collection procedures already in place for an ongoing multicenter clinical trial. Our system was iteratively designed after analyzing case report forms and clinic notes, and observing clinic workflow patterns and business procedures. Existing data standards from CDISC and HL7 were used for database insertion and clinical document exchange. Results Our system was successfully integrated into the clinic environment and used in two live test cases without disrupting existing workflow. Analyses performed during system design yielded detailed information on practical issues affecting implementation of systems that automatically extract, store, and reuse healthcare data. Conclusion Although subject to the limitations of a small feasibility study, our study demonstrates that electronic patient data can be reused for prospective multicenter clinical research and patient care, and demonstrates a need for further development of therapeutic area standards that can facilitate researcher use of healthcare data. PMID:17600107

Parallel optimization algorithms and their implementation in VLSI design

NASA Technical Reports Server (NTRS)

Lee, G.; Feeley, J. J.

1991-01-01

Two new parallel optimization algorithms based on the simplex method are described. They may be executed by a SIMD parallel processor architecture and be implemented in VLSI design. Several VLSI design implementations are introduced. An application example is reported to demonstrate that the algorithms are effective.

Separating the Laparoscopic Camera Cord From the Monopolar "Bovie" Cord Reduces Unintended Thermal Injury From Antenna Coupling: A Randomized Controlled Trial.

PubMed

Robinson, Thomas N; Jones, Edward L; Dunn, Christina L; Dunne, Bruce; Johnson, Elizabeth; Townsend, Nicole T; Paniccia, Alessandro; Stiegmann, Greg V

2015-06-01

The monopolar "Bovie" is used in virtually every laparoscopic operation. The active electrode and its cord emit radiofrequency energy that couples (or transfers) to nearby conductive material without direct contact. This phenomenon is increased when the active electrode cord is oriented parallel to another wire/cord. The parallel orientation of the "Bovie" and laparoscopic camera cords cause transfer of energy to the camera cord resulting in cutaneous burns at the camera trocar incision. We hypothesized that separating the active electrode/camera cords would reduce thermal injury occurring at the camera trocar incision in comparison to parallel oriented active electrode/camera cords. In this prospective, blinded, randomized controlled trial, patients undergoing standardized laparoscopic cholecystectomy were randomized to separated active electrode/camera cords or parallel oriented active electrode/camera cords. The primary outcome variable was thermal injury determined by histology from skin biopsied at the camera trocar incision. Eighty-four patients participated. Baseline demographics were similar in the groups for age, sex, preoperative diagnosis, operative time, and blood loss. Thermal injury at the camera trocar incision was lower in the separated versus parallel group (31% vs 57%; P = 0.027). Separation of the laparoscopic camera cord from the active electrode cord decreases thermal injury from antenna coupling at the camera trocar incision in comparison to the parallel orientation of these cords. Therefore, parallel orientation of these cords (an arrangement promoted by integrated operating rooms) should be abandoned. The findings of this study should influence the operating room setup for all laparoscopic cases.

RAPP, a systematic e-assessment of postoperative recovery in patients undergoing day surgery: study protocol for a mixed-methods study design including a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies

PubMed Central

Dahlberg, K; Odencrants, S; Hagberg, L

2016-01-01

Introduction Day surgery is a well-established practice in many European countries, but only limited information is available regarding postoperative recovery at home though there is a current lack of a standard procedure regarding postoperative follow-up. Furthermore, there is also a need for improvement of modern technology in assessing patient-related outcomes such as mobile applications. This article describes the Recovery Assessment by Phone Points (RAPP) study protocol, a mixed-methods study to evaluate if a systematic e-assessment follow-up in patients undergoing day surgery is cost-effective and improves postoperative recovery, health and quality of life. Methods and analysis This study has a mixed-methods study design that includes a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies. 1000 patients >17 years of age who are undergoing day surgery will be randomly assigned to either e-assessed postoperative recovery follow-up daily in 14 days measured via smartphone app including the Swedish web-version of Quality of Recovery (SwQoR) or to standard care (ie, no follow-up). The primary aim is cost-effectiveness. Secondary aims are (A) to explore whether a systematic e-assessment follow-up after day surgery has a positive effect on postoperative recovery, health-related quality of life (QoL) and overall health; (B) to determine whether differences in postoperative recovery have an association with patient characteristic, type of surgery and anaesthesia; (C) to determine whether differences in health literacy have a substantial and distinct effect on postoperative recovery, health and QoL; and (D) to describe day surgery patient and staff experiences with a systematic e-assessment follow-up after day surgery. The primary aim will be measured at 2 weeks postoperatively and secondary outcomes (A–C) at 1 and 2 weeks and (D) at 1 and 4 months. Trial registration number NCT02492191; Pre-results. PMID:26769788

Beyond silence: protocol for a randomized parallel-group trial comparing two approaches to workplace mental health education for healthcare employees.

PubMed

Moll, Sandra; Patten, Scott Burton; Stuart, Heather; Kirsh, Bonnie; MacDermid, Joy Christine

2015-04-16

Mental illness is a significant and growing problem in Canadian healthcare organizations, leading to tremendous personal, social and financial costs for individuals, their colleagues, their employers and their patients. Early and appropriate intervention is needed, but unfortunately, few workers get the help that they need in a timely way due to barriers related to poor mental health literacy, stigma, and inadequate access to mental health services. Workplace education and training is one promising approach to early identification and support for workers who are struggling. Little is known, however, about what approach is most effective, particularly in the context of healthcare work. The purpose of this study is to compare the impact of a customized, contact-based education approach with standard mental health literacy training on the mental health knowledge, stigmatized beliefs and help-seeking/help-outreach behaviors of healthcare employees. A multi-centre, randomized, two-group parallel group trial design will be adopted. Two hundred healthcare employees will be randomly assigned to one of two educational interventions: Beyond Silence, a peer-led program customized to the healthcare workplace, and Mental Health First Aid, a standardized literacy based training program. Pre, post and 3-month follow-up surveys will track changes in knowledge (mental health literacy), attitudes towards mental illness, and help-seeking/help-outreach behavior. An intent-to-treat, repeated measures analysis will be conducted to compare changes in the two groups over time in terms of the primary outcome of behavior change. Linear regression modeling will be used to explore the extent to which knowledge, and attitudes predict behavior change. Qualitative interviews with participants and leaders will also be conducted to examine process and implementation of the programs. This is one of the first experimental studies to compare outcomes of standard mental health literacy training to an intervention with an added anti-stigma component (using best-practices of contact-based education). Study findings will inform recommendations for designing workplace mental health education to promote early intervention for employees with mental health issues in the context of healthcare work. May 2014 - ClinicalTrials.gov: NCT02158871.

Evaluation of piezocision and laser-assisted flapless corticotomy in the acceleration of canine retraction: a randomized controlled trial.

PubMed

Alfawal, Alaa M H; Hajeer, Mohammad Y; Ajaj, Mowaffak A; Hamadah, Omar; Brad, Bassel

2018-02-17

To evaluate the effectiveness of two minimally invasive surgical procedures in the acceleration of canine retraction: piezocision and laser-assisted flapless corticotomy (LAFC). Trial design: A single-centre randomized controlled trial with a compound design (two-arm parallel-group design and a split-mouth design for each arm). 36 Class II division I patients (12 males, 24 females; age range: 15 to 27 years) requiring first upper premolars extraction followed by canine retraction. piezocision group (PG; n = 18) and laser-assisted flapless corticotomy group (LG; n = 18). A split-mouth design was applied for each group where the flapless surgical intervention was randomly allocated to one side and the other side served as a control side. the rate of canine retraction (primary outcome), anchorage loss and canine rotation, which were assessed at 1, 2, 3 and 4 months following the onset of canine retraction. Also the duration of canine retraction was recorded. Random sequence: Computer-generated random numbers. Allocation concealment: sequentially numbered, opaque, sealed envelopes. Blinding: Single blinded (outcomes' assessor). Seventeen patients in each group were enrolled in the statistical analysis. The rate of canine retraction was significantly greater in the experimental side than in the control side in both groups by two-fold in the first month and 1.5-fold in the second month (p < 0.001). Also the overall canine retraction duration was significantly reduced in the experimental side as compared with control side in both groups about 25% (p ≤ 0.001). There were no significant differences between the experimental and the control sides regarding loss of anchorage and upper canine rotation in both groups (p > 0.05). There were no significant differences between the two flapless techniques regarding the studied variables during all evaluation times (p > 0.05). Piezocision and laser-assisted flapless corticotomy appeared to be effective treatment methods for accelerating canine retraction without any significant untoward effect on anchorage or canine rotation during rapid retraction. ClinicalTrials.gov (Identifier: NCT02606331 ).

A randomized study comparing outcomes of stapled and hand-sutured anastomoses in patients undergoing open gastrointestinal surgery.

PubMed

Chandramohan, S M; Gajbhiye, Raj Narenda; Agwarwal, Anil; Creedon, Erin; Schwiers, Michael L; Waggoner, Jason R; Tatla, Daljit

2013-08-01

Although stapling is an alternative to hand-suturing in gastrointestinal surgery, recent trials specifically designed to evaluate differences between the two in surgery time, anastomosis time, and return to bowel activity are lacking. This trial compared the outcomes of the two in subjects undergoing open gastrointestinal surgery. Adult subjects undergoing emergency or elective surgery requiring a single gastric, small, or large bowel anastomosis were enrolled into this open-label, prospective, randomized, interventional, parallel, multicenter, controlled trial. Randomization was assigned in a 1:1 ratio between the hand-sutured group (n = 138) and the stapled group (n = 142). Anastomosis time, surgery time, and time to bowel activity were collected and compared as primary endpoints. A total of 280 subjects were enrolled from April 2009 to September 2010. Only the time of anastomosis was significantly different between the two arms: 17.6 ± 1.90 min (stapled) and 20.6 ± 1.90 min (hand-sutured). This difference was deemed not clinically or economically meaningful. Safety outcomes and other secondary endpoints were similar between the two arms. Mechanical stapling is faster than hand-suturing for the construction of gastrointestinal anastomoses. Apart from this, stapling and hand-suturing are similar with respect to the outcomes measured in this trial.

Efficacy trial of Camouflage Syringe to reduce dental fear and anxiety.

PubMed

Ujaoney, S; Mamtani, M; Thakre, T; Tote, J; Hazarey, V; Hazarey, P; Kulkarni, H

2013-12-01

Dental fear and anxiety in early childhood are widely prevalent and contribute to dental problems and behaviour in adulthood. Novel ways to reduce dental fear and anxiety in children are needed. Our aim was to conduct an efficacy trial of a novel Camouflage Syringe to reduce dental fear and anxiety in children. randomised controlled trial of efficacy of the Camouflage Syringe. We designed a Camouflage Syringe with a toy-like appearance that veils the conventional syringe to permit topical application and injection of local anaesthesia and ensure more involvement of the patient in the treatment process. We conducted a concurrent parallel, randomised controlled trial (NCT01398007) on the efficacy of this Camouflage Syringe to reduce the dental fear and anxiety in children seeking dental treatment who required the use of local anaesthesia. Using Venham's clinical rating scale, Venham's picture test, parental stress questionnaire and recall questionnaire, the efficacy of the Camouflage Syringe to reduce dental fear and anxiety ranged from 82% to 97% for various outcomes and from 60% to 100% for prevention of related adverse outcomes. For all outcomes, the number needed to treat was close to unity. Our results strongly favour the use of Camouflage Syringe to reduce dental fear and anxiety in children.

Study protocol: can a school gardening intervention improve children's diets?

PubMed

Christian, Meaghan S; El Evans, Charlotte; Conner, Mark; Ransley, Joan K; Cade, Janet E

2012-04-26

The current academic literature suggests there is a potential for using gardening as a tool to improve children's fruit and vegetable intake. This study is two parallel randomised controlled trials (RCT) devised to evaluate the school gardening programme of the Royal Horticultural Society (RHS) Campaign for School Gardening, to determine if it has an effect on children's fruit and vegetable intake. Trial One will consist of 26 schools; these schools will be randomised into two groups, one to receive the intensive intervention as "Partner Schools" and the other to receive the less intensive intervention as "Associate Schools". Trial Two will consist of 32 schools; these schools will be randomised into either the less intensive intervention "Associate Schools" or a comparison group with delayed intervention. Baseline data collection will be collected using a 24-hour food diary (CADET) to collect data on dietary intake and a questionnaire exploring children's knowledge and attitudes towards fruit and vegetables. A process measures questionnaire will be used to assess each school's gardening activities. The results from these trials will provide information on the impact of the RHS Campaign for School Gardening on children's fruit and vegetable intake. The evaluation will provide valuable information for designing future research in primary school children's diets and school based interventions. ISRCTN11396528.

From Surveillance to Intervention: Overview and Baseline Findings for the Active City of Liverpool Active Schools and SportsLinx (A-CLASS) Project

PubMed Central

McWhannell, Nicola; Henaghan, Jayne L.

2018-01-01

This paper outlines the implementation of a programme of work that started with the development of a population-level children’s health, fitness and lifestyle study in 1996 (SportsLinx) leading to selected interventions one of which is described in detail: the Active City of Liverpool, Active Schools and SportsLinx (A-CLASS) Project. The A-CLASS Project aimed to quantify the effectiveness of structured and unstructured physical activity (PA) programmes on children’s PA, fitness, body composition, bone health, cardiac and vascular structures, fundamental movement skills, physical self-perception and self-esteem. The study was a four-arm parallel-group school-based cluster randomised controlled trial (clinical trials no. NCT02963805), and compared different exposure groups: a high intensity PA (HIPA) group, a fundamental movement skill (FMS) group, a PA signposting (PASS) group and a control group, in a two-schools-per-condition design. Baseline findings indicate that children’s fundamental movement skill competence levels are low-to-moderate, yet these skills are inversely associated with percentage body fat. Outcomes of this project will make an important contribution to the design and implementation of children’s PA promotion initiatives.

Evidence regarding lingual fixed orthodontic appliances' therapeutic and adverse effects is insufficient.

PubMed

Afrashtehfar, Kelvin I

2016-06-01

Data sourcesMedline, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Virtual Health Library and Web of Science were systematically searched up to July 2015 without limitations. Scopus, Google Scholar, ClinicalTrials.gov, the ISRCTN registry as well as reference lists of the trials included and relevant reviews were manually searched.Study selectionRandomised (RCTs) and prospective non-randomised clinical trials (non-RCTs) on human patients that compared therapeutic and adverse effects of lingual and labial appliances were considered. One reviewer initially screened titles and subsequently two reviewers independently screened the selected abstracts and full texts.Data extraction and synthesisThe data were extracted independently by the reviewers. Missing or unclear information, ongoing trials and raw data from split-mouth trials were requested from the authors of the trials. The quality of the included trials and potential bias across studies were assessed using Cochrane's risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. For parallel trials, mean difference (MD) and the relative risk (RR) were used for continuous (objective speech performance, subjective speech performance, intercanine width, intermolar width and sagittal anchorage loss) and binary outcomes (eating difficulty), respectively. The standardised mean difference (SMD) was chosen to pool, after conversion, the outcome (oral discomfort) that assessed both binary and continuous. Random-effects meta-analyses were conducted, followed by subgroup and sensitivity analyses.ResultsThirteen papers pertaining to 11 clinical trials (three parallel RCTs, one split-mouth RCT and seven parallel prospective non-RCTs) were included with a total of 407 (34% male/66% female) patients. All trials had at least one bias domain at high risk of bias. Compared with labial appliances, lingual appliances were associated with increased overall oral discomfort, increased speech impediment (measured using auditory analysis), worse speech performance assessed by laypersons, increased eating difficulty and decreased intermolar width. On the other hand, lingual appliances were associated with increased intercanine width and significantly decreased anchorage loss of the maxillary first molar during space closure. However, the quality of all analyses included was judged as very low because of the high risk of bias of the included trials, inconsistency and imprecision.ConclusionsBased on existing trials there is insufficient evidence to make robust recommendations for lingual fixed orthodontic appliances regarding their therapeutic or adverse effects, as the quality of evidence was low.

PANSAID-PAracetamol and NSAID in combination: detailed statistical analysis plan for a randomised, blinded, parallel, four-group multicentre clinical trial.

PubMed

Thybo, Kasper Højgaard; Jakobsen, Janus Christian; Hägi-Pedersen, Daniel; Pedersen, Niels Anker; Dahl, Jørgen Berg; Schrøder, Henrik Morville; Bülow, Hans Henrik; Bjørck, Jan Gottfrid; Overgaard, Søren; Mathiesen, Ole; Wetterslev, Jørn

2017-10-10

Effective postoperative pain management is essential for the rehabilitation of the surgical patient. The PANSAID trial evaluates the analgesic effects and safety of the combination of paracetamol and ibuprofen. This paper describes in detail the statistical analysis plan for the primary publication to prevent outcome reporting bias and data-driven analysis results. The PANSAID trial is a multicentre, randomised, controlled, parallel, four-group clinical trial comparing the beneficial and harmful effects of different doses and combinations of paracetamol and ibuprofen in patients having total hip arthroplastic surgery. Patients, caregivers, physicians, investigators, and statisticians are blinded to the intervention. The two co-primary outcomes are 24-h consumption of morphine and proportion of patients with one or more serious adverse events within 90 days after surgery. Secondary outcomes are pain scores during mobilisation and at rest at 6 and 24 h postoperatively, and the proportion of patients with one or more adverse events within 24 h postoperatively. PANSAID will provide a large trial with low risk of bias regarding benefits and harms of the combination of paracetamol and ibuprofen used in a perioperative setting. ClinicalTrials.org identifier: NCT02571361 . Registered on 7 October 2015.

Rationale and design of the Clinical Evaluation of Magnetic Resonance Imaging in Coronary heart disease 2 trial (CE-MARC 2): A prospective, multicenter, randomized trial of diagnostic strategies in suspected coronary heart disease

PubMed Central

Ripley, David P.; Brown, Julia M.; Everett, Colin C.; Bijsterveld, Petra; Walker, Simon; Sculpher, Mark; McCann, Gerry P.; Berry, Colin; Plein, Sven; Greenwood, John P.

2015-01-01

Background A number of investigative strategies exist for the diagnosis of coronary heart disease (CHD). Despite the widespread availability of noninvasive imaging, invasive angiography is commonly used early in the diagnostic pathway. Consequently, approximately 60% of angiograms reveal no evidence of obstructive coronary disease. Reducing unnecessary angiography has potential financial savings and avoids exposing the patient to unnecessary risk. There are no large-scale comparative effectiveness trials of the different diagnostic strategies recommended in international guidelines and none that have evaluated the safety and efficacy of cardiovascular magnetic resonance. Trial Design CE-MARC 2 is a prospective, multicenter, 3-arm parallel group, randomized controlled trial of patients with suspected CHD (pretest likelihood 10%-90%) requiring further investigation. A total of 1,200 patients will be randomized on a 2:2:1 basis to receive 3.0-T cardiovascular magnetic resonance–guided care, single-photon emission computed tomography–guided care (according to American College of Cardiology/American Heart Association appropriate-use criteria), or National Institute for Health and Care Excellence guidelines–based management. The primary (efficacy) end point is the occurrence of unnecessary angiography as defined by a normal (>0.8) invasive fractional flow reserve. Safety of each strategy will be assessed by 3-year major adverse cardiovascular event rates. Cost-effectiveness and health-related quality-of-life measures will be performed. Conclusions The CE-MARC 2 trial will provide comparative efficacy and safety evidence for 3 different strategies of investigating patients with suspected CHD, with the intension of reducing unnecessary invasive angiography rates. Evaluation of these management strategies has the potential to improve patient care, health-related quality of life, and the cost-effectiveness of CHD investigation. PMID:25497243

Split-mouth and parallel-arm trials to compare pain with intraosseous anaesthesia delivered by the computerised Quicksleeper system and conventional infiltration anaesthesia in paediatric oral healthcare: protocol for a randomised controlled trial.

PubMed

Smaïl-Faugeron, Violaine; Muller-Bolla, Michèle; Sixou, Jean-Louis; Courson, Frédéric

2015-07-10

Local anaesthesia is commonly used in paediatric oral healthcare. Infiltration anaesthesia is the most frequently used, but recent developments in anaesthesia techniques have introduced an alternative: intraosseous anaesthesia. We propose to perform a split-mouth and parallel-arm multicentre randomised controlled trial (RCT) comparing the pain caused by the insertion of the needle for the injection of conventional infiltration anaesthesia, and intraosseous anaesthesia by the computerised QuickSleeper system, in children and adolescents. Inclusion criteria are patients 7-15 years old with at least 2 first permanent molars belonging to the same dental arch (for the split-mouth RCT) or with a first permanent molar (for the parallel-arm RCT) requiring conservative or endodontic treatment limited to pulpotomy. The setting of this study is the Department of Paediatric Dentistry at 3 University dental hospitals in France. The primary outcome measure will be pain reported by the patient on a visual analogue scale concerning the insertion of the needle and the injection/infiltration. Secondary outcomes are latency, need for additional anaesthesia during the treatment and pain felt during the treatment. We will use a computer-generated permuted-block randomisation sequence for allocation to anaesthesia groups. The random sequences will be stratified by centre (and by dental arch for the parallel-arm RCT). Only participants will be blinded to group assignment. Data will be analysed by the intent-to-treat principle. In all, 160 patients will be included (30 in the split-mouth RCT, 130 in the parallel-arm RCT). This protocol has been approved by the French ethics committee for the protection of people (Comité de Protection des Personnes, Ile de France I) and will be conducted in full accordance with accepted ethical principles. Findings will be reported in scientific publications and at research conferences, and in project summary papers for participants. ClinicalTrials.gov NCT02084433. 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.

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol

PubMed Central

2012-01-01

Background Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. Methods/Design We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Discussion Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Trial registration Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18. PMID:22305183

Hand-suture versus stapling for closure of loop ileostomy: HASTA-Trial: a study rationale and design for a randomized controlled trial

PubMed Central

2011-01-01

Background Colorectal cancer is the second most common tumor in developed countries, with a lifetime prevalence of 5%. About one third of these tumors are located in the rectum. Surgery in terms of low anterior resection with mesorectal excision is the central element in the treatment of rectal cancer being the only option for definite cure. Creating a protective diverting stoma prevents complications like anastomotic failure and meanwhile is the standard procedure. Bowel obstruction is one of the main and the clinically and economically most relevant complication following closure of loop ileostomy. The best surgical technique for closure of loop ileostomy has not been defined yet. Methods/Design A study protocol was developed on the basis of the only randomized controlled mono-center trial to solve clinical equipoise concerning the optimal surgical technique for closure of loop ileostomy after low anterior resection due to rectal cancer. The HASTA trial is a multi-center pragmatic randomized controlled surgical trial with two parallel groups to compare hand-suture versus stapling for closure of loop ileostomy. It will include 334 randomized patients undergoing closure of loop ileostomy after low anterior resection with protective ileostomy due to rectal cancer in approximately 20 centers consisting of German hospitals of all level of health care. The primary endpoint is the rate of bowel obstruction within 30 days after ileostomy closure. In addition, a set of surgical and general variables including quality of life will be analyzed with a follow-up of 12 months. An investigators meeting with a practical session will help to minimize performance bias and enforce protocol adherence. Centers are monitored centrally as well as on-site before and during recruitment phase to assure inclusion, treatment and follow up according to the protocol. Discussion Aim of the HASTA trial is to evaluate the efficacy of hand-suture versus stapling for closure of loop ileostomy in patients with rectal cancer. Trial registration German Clinical Trial Register Number: DRKS00000040 PMID:21303515

Effectiveness and micro-costing of the KiVa school-based bullying prevention programme in Wales: study protocol for a pragmatic definitive parallel group cluster randomised controlled trial.

PubMed

Clarkson, Suzy; Axford, Nick; Berry, Vashti; Edwards, Rhiannon Tudor; Bjornstad, Gretchen; Wrigley, Zoe; Charles, Joanna; Hoare, Zoe; Ukoumunne, Obioha C; Matthews, Justin; Hutchings, Judy

2016-02-01

Bullying refers to verbal, physical or psychological aggression repeated over time that is intended to cause harm or distress to the victims who are unable to defend themselves. It is a key public health priority owing to its widespread prevalence in schools and harmful short- and long-term effects on victims' well-being. There is a need to strengthen the evidence base by testing innovative approaches to preventing bullying. KiVa is a school-based bullying prevention programme with universal and indicated elements and an emphasis on changing bystander behaviour. It achieved promising results in a large trial in Finland, and now requires testing in other countries. This paper describes the protocol for a cluster randomised controlled trial (RCT) of KiVa in Wales. The study uses a two-arm waitlist control pragmatic definitive parallel group cluster RCT design with an embedded process evaluation and calculation of unit cost. Participating schools will be randomised a using a 1:1 ratio to KiVa plus usual provision (intervention group) or usual provision only (control group). The trial has one primary outcome, child self-reported victimisation from bullying, dichotomised as 'victimised' (bullied at least twice a month in the last couple of months) versus 'not victimised'. Secondary outcomes are: bullying perpetration; aspects of child social and emotional well-being (including emotional problems, conduct, peer relations, prosocial behaviour); and school attendance. Follow-up is at 12 months post-baseline. Implementation fidelity is measured through teacher-completed lesson records and independent school-wide observation. A micro-costing analysis will determine the costs of implementing KiVa, including recurrent and non-recurrent unit costs. Factors related to the scalability of the programme will be examined in interviews with head teachers and focus groups with key stakeholders in the implementation of school-based bullying interventions. The results from this trial will provide evidence on whether the KiVa programme is transportable from Finland to Wales in terms of effectiveness and implementation. It will provide information about the costs of delivery and generate insights into factors related to the scalability of the programme. Current Controlled Trials ISRCTN23999021 Date 10-6-13.

“Everybody Brush!”: Protocol for a Parallel-Group Randomized Controlled Trial of a Family-Focused Primary Prevention Program With Distribution of Oral Hygiene Products and Education to Increase Frequency of Toothbrushing

PubMed Central

2015-01-01

Background Twice daily toothbrushing with fluoridated toothpaste is the most widely advocated preventive strategy for dental caries (tooth decay) and is recommended by professional dental associations. Not all parents, children, or adolescents follow this recommendation. This protocol describes the methods for the implementation and evaluation of a quality improvement health promotion program. Objective The objective of the study is to show a theory-informed, evidence-based program to improve twice daily toothbrushing and oral health-related quality of life that may reduce dental caries, dental treatment need, and costs. Methods The design is a parallel-group, pragmatic randomized controlled trial. Families of Medicaid-insured children and adolescents within a large dental care organization in central Oregon will participate in the trial (n=21,743). Families will be assigned to one of three groups: a test intervention, an active control, or a passive control condition. The intervention aims to address barriers and support for twice-daily toothbrushing. Families in the test condition will receive toothpaste and toothbrushes by mail for all family members every three months. In addition, they will receive education and social support to encourage toothbrushing via postcards, recorded telephone messages, and an optional participant-initiated telephone helpline. Families in the active control condition will receive the kit of supplies by mail, but no additional instructional information or telephone support. Families assigned to the passive control will be on a waiting list. The primary outcomes are restorative dental care received and, only for children younger than 36 months old at baseline, the frequency of twice-daily toothbrushing. Data will be collected through dental claims records and, for children younger than 36 months old at baseline, parent interviews and clinical exams. Results Enrollment of participants and baseline interviews have been completed. Final results are expected in early summer, 2017. Conclusions If proven effective, this simple intervention can be sustained by the dental care organization and replicated by other organizations and government. Trial Registration Trial Registration: ClinicalTrials.gov NCT02327507; http://clinicaltrials.gov/ct2/show/NCT02327507 (Archived by WebCite at http://www.webcitation.org/6YCIxJSor). PMID:26002091

Successful applications of computer aided drug discovery: moving drugs from concept to the clinic.

PubMed

Talele, Tanaji T; Khedkar, Santosh A; Rigby, Alan C

2010-01-01

Drug discovery and development is an interdisciplinary, expensive and time-consuming process. Scientific advancements during the past two decades have changed the way pharmaceutical research generate novel bioactive molecules. Advances in computational techniques and in parallel hardware support have enabled in silico methods, and in particular structure-based drug design method, to speed up new target selection through the identification of hits to the optimization of lead compounds in the drug discovery process. This review is focused on the clinical status of experimental drugs that were discovered and/or optimized using computer-aided drug design. We have provided a historical account detailing the development of 12 small molecules (Captopril, Dorzolamide, Saquinavir, Zanamivir, Oseltamivir, Aliskiren, Boceprevir, Nolatrexed, TMI-005, LY-517717, Rupintrivir and NVP-AUY922) that are in clinical trial or have become approved for therapeutic use.

Efficacy of maropitant for preventing vomiting associated with motion sickness in dogs.

PubMed

Benchaoui, H A; Siedek, E M; De La Puente-Redondo, V A; Tilt, N; Rowan, T G; Clemence, R G

2007-09-29

Maropitant is a neurokinin-1 inhibitor that acts to prevent and treat vomiting by blocking stimuli to the final common pathway in the emetic centre of the brain. The field efficacy and safety of a single oral dose of maropitant were investigated for the prevention of vomiting in dogs with a history of motion sickness resulting from transportation by car in two blinded, placebo-controlled studies. In an exploratory study designed as a two-way crossover trial with 17 dogs, 10 of the dogs given the placebo vomited during a car journey but only three of the dogs vomited under maropitant treatment. In a larger multicentred parallel design study, 69 of 105 dogs treated with the placebo vomited during the journey compared with 15 of 106 dogs treated with maropitant (P < 0.0001).

Second International Workshop on Software Engineering and Code Design in Parallel Meteorological and Oceanographic Applications

NASA Technical Reports Server (NTRS)

OKeefe, Matthew (Editor); Kerr, Christopher L. (Editor)

1998-01-01

This report contains the abstracts and technical papers from the Second International Workshop on Software Engineering and Code Design in Parallel Meteorological and Oceanographic Applications, held June 15-18, 1998, in Scottsdale, Arizona. The purpose of the workshop is to bring together software developers in meteorology and oceanography to discuss software engineering and code design issues for parallel architectures, including Massively Parallel Processors (MPP's), Parallel Vector Processors (PVP's), Symmetric Multi-Processors (SMP's), Distributed Shared Memory (DSM) multi-processors, and clusters. Issues to be discussed include: (1) code architectures for current parallel models, including basic data structures, storage allocation, variable naming conventions, coding rules and styles, i/o and pre/post-processing of data; (2) designing modular code; (3) load balancing and domain decomposition; (4) techniques that exploit parallelism efficiently yet hide the machine-related details from the programmer; (5) tools for making the programmer more productive; and (6) the proliferation of programming models (F--, OpenMP, MPI, and HPF).

A Parallel Trade Study Architecture for Design Optimization of Complex Systems

NASA Technical Reports Server (NTRS)

Kim, Hongman; Mullins, James; Ragon, Scott; Soremekun, Grant; Sobieszczanski-Sobieski, Jaroslaw

2005-01-01

Design of a successful product requires evaluating many design alternatives in a limited design cycle time. This can be achieved through leveraging design space exploration tools and available computing resources on the network. This paper presents a parallel trade study architecture to integrate trade study clients and computing resources on a network using Web services. The parallel trade study solution is demonstrated to accelerate design of experiments, genetic algorithm optimization, and a cost as an independent variable (CAIV) study for a space system application.

Conceptual design of a hybrid parallel mechanism for mask exchanging of TMT

NASA Astrophysics Data System (ADS)

Wang, Jianping; Zhou, Hongfei; Li, Kexuan; Zhou, Zengxiang; Zhai, Chao

2015-10-01

Mask exchange system is an important part of the Multi-Object Broadband Imaging Echellette (MOBIE) on the Thirty Meter Telescope (TMT). To solve the problem of stiffness changing with the gravity vector of the mask exchange system in the MOBIE, the hybrid parallel mechanism design method was introduced into the whole research. By using the characteristics of high stiffness and precision of parallel structure, combined with large moving range of serial structure, a conceptual design of a hybrid parallel mask exchange system based on 3-RPS parallel mechanism was presented. According to the position requirements of the MOBIE, the SolidWorks structure model of the hybrid parallel mask exchange robot was established and the appropriate installation position without interfering with the related components and light path in the MOBIE of TMT was analyzed. Simulation results in SolidWorks suggested that 3-RPS parallel platform had good stiffness property in different gravity vector directions. Furthermore, through the research of the mechanism theory, the inverse kinematics solution of the 3-RPS parallel platform was calculated and the mathematical relationship between the attitude angle of moving platform and the angle of ball-hinges on the moving platform was established, in order to analyze the attitude adjustment ability of the hybrid parallel mask exchange robot. The proposed conceptual design has some guiding significance for the design of mask exchange system of the MOBIE on TMT.

Recommendations for pharmacological clinical trials in children with irritable bowel syndrome: the Rome foundation pediatric subcommittee on clinical trials.

PubMed

Saps, M; van Tilburg, M A L; Lavigne, J V; Miranda, A; Benninga, M A; Taminiau, J A; Di Lorenzo, C

2016-11-01

There is little published evidence of efficacy for the most commonly used treatments. Thus, there is an urgent need to conduct clinical trials on existing and novel therapies. In order to address these issues the Rome Foundation and members of the Pediatric Committee of the European Medicines Agency formed a subcommittee on clinical trials to develop guidelines for the design of clinical trials in children with irritable bowel syndrome (IBS). The following recommendations are based on evidence from published data when available and expert opinion. The subcommittee recommends randomized, double-blind, placebo-controlled, parallel-group, clinical trials to assess the efficacy of new drugs. The combined endpoints for abdominal pain are a decrease in intensity of at least 30% compared with baseline and to meet or exceed the Reliable Change Index (RCI) for the sample. Stool consistency is measured with the Bristol Stool Scale Form (BSFS). The subcommittee recommends as entry criteria for abdominal pain a weekly average of worst abdominal pain in past 24 h of at least 3.0 on a 0-10 point scale or at least 30 mm in 100 mm Visual Analog Scale. For stool endpoints the committee recommends an average stool consistency lower than 3 in the BSFS during the run-in period for clinical trials on IBS-C and an average stool consistency greater than 5 in the BSFS during the run-in period for clinical trials on IBS-D. Changes in stool consistency are the primary endpoints for both IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C). © 2016 John Wiley & Sons Ltd.

Design and realization of photoelectric instrument binocular optical axis parallelism calibration system

NASA Astrophysics Data System (ADS)

Ying, Jia-ju; Chen, Yu-dan; Liu, Jie; Wu, Dong-sheng; Lu, Jun

2016-10-01

The maladjustment of photoelectric instrument binocular optical axis parallelism will affect the observe effect directly. A binocular optical axis parallelism digital calibration system is designed. On the basis of the principle of optical axis binocular photoelectric instrument calibration, the scheme of system is designed, and the binocular optical axis parallelism digital calibration system is realized, which include four modules: multiband parallel light tube, optical axis translation, image acquisition system and software system. According to the different characteristics of thermal infrared imager and low-light-level night viewer, different algorithms is used to localize the center of the cross reticle. And the binocular optical axis parallelism calibration is realized for calibrating low-light-level night viewer and thermal infrared imager.

Parallel Ray Tracing Using the Message Passing Interface

DTIC Science & Technology

2007-09-01

software is available for lens design and for general optical systems modeling. It tends to be designed to run on a single processor and can be very...Cameron, Senior Member, IEEE Abstract—Ray-tracing software is available for lens design and for general optical systems modeling. It tends to be designed to...National Aeronautics and Space Administration (NASA), optical ray tracing, parallel computing, parallel pro- cessing, prime numbers, ray tracing

A Comparison of Parallelism in Interface Designs for Computer-Based Learning Environments

ERIC Educational Resources Information Center

Min, Rik; Yu, Tao; Spenkelink, Gerd; Vos, Hans

2004-01-01

In this paper we discuss an experiment that was carried out with a prototype, designed in conformity with the concept of parallelism and the Parallel Instruction theory (the PI theory). We designed this prototype with five different interfaces, and ran an empirical study in which 18 participants completed an abstract task. The five basic designs…

Health trainer-led motivational intervention plus usual care for people under community supervision compared with usual care alone: a study protocol for a parallel-group pilot randomised controlled trial (STRENGTHEN)

PubMed Central

Thompson, Tom P; Callaghan, Lynne; Hazeldine, Emma; Quinn, Cath; Walker, Samantha; Byng, Richard; Wallace, Gary; Creanor, Siobhan; Green, Colin; Hawton, Annie; Annison, Jill; Sinclair, Julia; Senior, Jane; Taylor, Adrian H

2018-01-01

Introduction People with experience of the criminal justice system typically have worse physical and mental health, lower levels of mental well-being and have less healthy lifestyles than the general population. Health trainers have worked with offenders in the community to provide support for lifestyle change, enhance mental well-being and signpost to appropriate services. There has been no rigorous evaluation of the effectiveness and cost-effectiveness of providing such community support. This study aims to determine the feasibility and acceptability of conducting a randomised trial and delivering a health trainer intervention to people receiving community supervision in the UK. Methods and analysis A multicentre, parallel, two-group randomised controlled trial recruiting 120 participants with 1:1 individual allocation to receive support from a health trainer and usual care or usual care alone, with mixed methods process evaluation. Participants receive community supervision from an offender manager in either a Community Rehabilitation Company or the National Probation Service. If they have served a custodial sentence, then they have to have been released for at least 2 months. The supervision period must have at least 7 months left at recruitment. Participants are interested in receiving support to change diet, physical activity, alcohol use and smoking and/or improve mental well-being. The primary outcome is mental well-being with secondary outcomes related to smoking, physical activity, alcohol consumption and diet. The primary outcome will inform sample size calculations for a definitive trial. Ethics and dissemination The study has been approved by the Health and Care Research Wales Ethics Committee (REC reference 16/WA/0171). Dissemination will include publication of the intervention development process and findings for the stated outcomes, parallel process evaluation and economic evaluation in peer-reviewed journals. Results will also be disseminated to stakeholders and trial participants. Trial registration numbers ISRCTN80475744; Pre-results. PMID:29866736

Knee Joint Kinetics in Relation to Commonly Prescribed Squat Loads and Depths

PubMed Central

Cotter, Joshua A.; Chaudhari, Ait M.; Jamison, Steve T.; Devor, Steven T.

2014-01-01

Controversy exists regarding the safety and performance benefits of performing the squat exercise to depths beyond 90° of knee flexion. Our aim was to compare the net peak external knee flexion moments (pEKFM) experienced over typical ranges of squat loads and depths. Sixteen recreationally trained males (n = 16; 22.7 ± 1.1 yrs; 85.4 ± 2.1 kg; 177.6 ± 0.96 cm; mean ± SEM) with no previous lower limb surgeries or other orthopedic issues and at least one year of consistent resistance training experience while utilizing the squat exercise performed single repetition squat trials in a random order at squat depths of above parallel, parallel, and below parallel. Less than one week before testing, one repetition maximum (1RM) values were found for each squat depth. Subsequent testing required subjects to perform squats at the three depths with three different loads: unloaded, 50% 1RM, and 85% 1RM (nine total trials). Force platform and kinematic data were collected to calculate pEKFM. To assess differences among loads and depths, a two-factor (load and depth) repeated-measures ANOVA with significance set at the P < 0.05 level was used. Squat 1RM significantly decreased 13.6% from the above parallel to parallel squat and another 3.6% from the parallel to the below parallel squat (P < 0.05). Net peak external knee flexion moments significantly increased as both squat depth and load were increased (P ≤ 0.02). Slopes of pEKFM were greater from unloaded to 50% 1RM than when progressing from 50% to 85% 1RM (P < 0.001). The results suggest that that typical decreases in squat loads used with increasing depths are not enough to offset increases in pEKFM. PMID:23085977

Electroacupuncture for chemotherapy-induced peripheral neuropathy: study protocol for a pilot multicentre randomized, patient-assessor-blinded, controlled trial

PubMed Central

2013-01-01

Background Chemotherapy-induced peripheral neuropathy (CIPN) is the main dose-limiting side effect of neurotoxic chemotherapeutic agents. CIPN can lead not only to loss of physical function, difficulties in activities of daily living (ADLs), and decreased quality of life, but also to dose reduction, delay or even cessation of treatment. Currently, there are few proven effective treatments for CIPN. This randomized controlled clinical trial is designed to evaluate the effects and safety of electroacupuncture (EA) for patients with CIPN. Methods/design This is a multicenter, two-armed, parallel-design, patient-assessor-blinded, randomized, sham-controlled clinical trial. Forty eligible patients with CIPN will be randomized in a ratio of 1:1 to the EA or sham EA arms. During the treatment phase, patients will undergo eight sessions of verum EA or sham EA twice weekly for four weeks, and then will be followed-up for eight weeks. Electrical stimulation in the EA group will consist of a mixed frequency of 2/120 Hz and 80% of bearable intensity. Sham EA will be applied to non-acupoints, with shallow needle insertion and no current. All outcomes and analyses of results will be assessed by researchers blinded to treatment allocation. The effects of EA on CIPN will be evaluated according to both subjective and objective outcome measures. The primary outcome measure will be the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire to assess CIPN (QLQ-CIPN20). The secondary outcome measures will be the results on the numerical rating scale, the Semmes-Weinstein monofilament test, the nerve conduction study, and the EORTC QLQ-C30, as well as the patient’s global impression of change and adverse events. Safety will be assessed at each visit. Discussion The results of this on-going study will provide clinical evidence for the effects and safety of EA for CIPN compared with sham EA. Trial registration Clinical Research Information Service: KCT0000506 PMID:23945074

Effectiveness of a Proactive Mail-Based Alcohol Internet Intervention for University Students: Dismantling the Assessment and Feedback Components in a Randomized Controlled Trial

PubMed Central

McCambridge, Jim; Bendtsen, Marcus; Karlsson, Nadine; Nilsen, Per

2012-01-01

Background University students in Sweden routinely receive proactive mail-based alcohol Internet interventions sent from student health services. This intervention provides personalized normative feedback on alcohol consumption with suggestions on how to decrease drinking. Earlier feasibility trials by our group and others have examined effectiveness in simple parallel-groups designs. Objective To evaluate the effectiveness of electronic screening and brief intervention, using a randomized controlled trial design that takes account of baseline assessment reactivity (and other possible effects of the research process) due to the similarity between the intervention and assessment content. The design of the study allowed for exploration of the magnitude of the assessment effects per se. Methods This trial used a dismantling design and randomly assigned 5227 students to 3 groups: (1) routine practice assessment and feedback, (2) assessment-only without feedback, and (3) neither assessment nor feedback. At baseline all participants were blinded to study participation, with no contact being made with group 3. We approached students 2 months later to participate in a cross-sectional alcohol survey. All interventions were fully automated and did not have any human involvement. All data used in the analysis were based on self-assessment using questionnaires. The participants were unaware that they were participating in a trial and thus were also blinded to which group they were randomly assigned. Results Overall, 44.69% (n = 2336) of those targeted for study completed follow-up. Attrition was similar in groups 1 (697/1742, 40.01%) and 2 (737/1742, 42.31% retained) and lower in group 3 (902/1743, 51.75% retained). Intention-to-treat analyses among all participants regardless of their baseline drinking status revealed no differences between groups in all alcohol parameters at the 2-month follow-up. Per-protocol analyses of groups 1 and 2 among those who accepted the email intervention (36.2% of the students who were offered the intervention in group 1 and 37.3% of the students in group2 ) and who were risky drinkers at baseline (60.7% follow-up rate in group 1 and 63.5% in group 2) suggested possible small beneficial effects on weekly consumption attributable to feedback. Conclusions This approach to outcome evaluation is highly conservative, and small benefits may follow the actual uptake of feedback intervention in students who are risky drinkers, the precise target group. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 24735383; http://www.controlled-trials.com/ISRCTN24735383 (Archived by WebCite at http://www.webcitation.org/6Awq7gjXG) PMID:23113955

Quantitative Relationship Between AUEC of Absolute Neutrophil Count and Duration of Severe Neutropenia for G-CSF in Breast Cancer Patients.

PubMed

Li, Liang; Ma, Lian; Schrieber, Sarah J; Rahman, Nam Atiqur; Deisseroth, Albert; Farrell, Ann T; Wang, Yaning; Sinha, Vikram; Marathe, Anshu

2018-02-02

The aim of the study was to evaluate the quantitative relationship between duration of severe neutropenia (DSN, the efficacy endpoint) and area under effect curve of absolute neutrophil counts (ANC-AUEC, the pharmacodynamic endpoint), based on data from filgrastim products, a human granulocyte colony-stimulating factor (G-CSF). Clinical data from filgrastim product comparator and test arms of two randomized, parallel-group, phase III studies in breast cancer patients treated with myelosuppressive chemotherapy were utilized. A zero-inflated Poisson regression model best described the negative correlation between DSN and ANC-AUEC. The models predicted that with 10 × 10 9 day/L of increase in ANC-AUEC, the mean DSN would decrease from 1.1 days to 0.93 day in Trial 1 and from 1.2 days to 1.0 day in Trial 2. The findings of the analysis provide useful information regarding the relationship between ANC and DSN that can be used for dose selection and optimization of clinical trial design for G-CSF. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Cocoa polyphenols enhance positive mood states but not cognitive performance: a randomized, placebo-controlled trial.

PubMed

Pase, Matthew P; Scholey, Andrew B; Pipingas, Andrew; Kras, Marni; Nolidin, Karen; Gibbs, Amy; Wesnes, Keith; Stough, Con

2013-05-01

This study aimed to examine the acute and sub-chronic effects of cocoa polyphenols on cognition and mood. In a randomized, double-blind study, healthy middle-aged participants received a dark chocolate drink mix standardized to contain 500 mg, 250 mg or 0 mg of polyphenols (placebo) in a parallel-groups design. Participants consumed their assigned treatment once daily for 30 days. Cognition was measured with the Cognitive Drug Research system and self-rated mood with the Bond-Lader Visual Analogue Scale. Participants were tested at baseline, at 1, 2.5 and 4 h after a single acute dose and again after receiving 30 days of treatment. In total, 72 participants completed the trial. After 30 days, the high dose of treatment significantly increased self-rated calmness and contentedness relative to placebo. Mood was unchanged by treatment acutely while cognition was unaffected by treatment at all time points. This randomized controlled trial is perhaps the first to demonstrate the positive effects of cocoa polyphenols on mood in healthy participants. This provides a rationale for exploring whether cocoa polyphenols can ameliorate the symptoms associated with clinical anxiety or depression.

Investigation of pajama properties on skin under mild cold conditions: the interaction between skin and clothing.

PubMed

Yao, Lei; Gohel, Mayur D I; Li, Yi; Chung, Waiyee J

2011-07-01

Clothing is considered the second skin of the human body. The aim of this study was to determine clothing-wearer interaction on skin physiology under mild cold conditions. Skin physiological parameters, subjective sensory response, stress level, and physical properties of clothing fabric from two longitude parallel-designed wear trials were studied. The wear trials involved four kinds of pajamas made from cotton or polyester material that had hydrophilic or hydrophobic treatment, conducted for three weeks under mild cold conditions. Statistical tools, factor analysis, hierarchical linear regression, and logistic regression were applied to analyze the strong predictors of skin physiological parameters, stress level, and sensory response. A framework was established to illustrate clothing-wearer interactions with clothing fabric properties, skin physiology, stress level, and sensory response under mild cold conditions. Fabric has various effects on the human body under mild cold conditions. A fabric's properties influence skin physiology, sensation, and psychological response. © 2011 The International Society of Dermatology.

Effects of a probiotic intervention in acute canine gastroenteritis--a controlled clinical trial.

PubMed

Herstad, H K; Nesheim, B B; L'Abée-Lund, T; Larsen, S; Skancke, E

2010-01-01

To evaluate the effect of a probiotic product in acute self-limiting gastroenteritis in dogs. Thirty-six dogs suffering from acute diarrhoea or acute diarrhoea and vomiting were included in the study. The trial was performed as a randomised, double blind and single centre study with stratified parallel group design. The animals were allocated to equal looking probiotic or placebo treatment by block randomisation with a fixed block size of six. The probiotic cocktail consisted of thermo-stabilised Lactobacillus acidophilus and live strains of Pediococcus acidilactici, Bacillus subtilis, Bacillus licheniformis and Lactobacillus farciminis. The time from initiation of treatment to the last abnormal stools was found to be significantly shorter (P = 0.04) in the probiotic group compared to placebo group, the mean time was 1.3 days and 2.2 days, respectively. The two groups were found nearly equal with regard to time from start of treatment to the last vomiting episode. The probiotic tested may reduce the convalescence time in acute self-limiting diarrhoea in dogs.

A double-blind randomized placebo-controlled feasibility study evaluating individualized homeopathy in managing pain of knee osteoarthritis.

PubMed

Koley, Munmun; Saha, Subhranil; Ghosh, Shubhamoy

2015-07-01

Few homeopathic complexes seemed to produce significant effects in osteoarthritis; still, individualized homeopathy remained untested. We evaluated the feasibility of conducting an efficacy trial of individualized homeopathy in osteoarthritis. A prospective, parallel-arm, double-blind, randomized, placebo-controlled pilot study was conducted from January to October 2014 involving 60 patients (homeopathy, n = 30; placebo, n = 30) who were suffering from acute painful episodes of knee osteoarthritis and visiting the outpatient clinic of Mahesh Bhattacharyya Homeopathic Medical College and Hospital, West Bengal, India. Statistically significant reduction was achieved in 3 visual analog scales (measuring pain, stiffness, and loss of function) and Osteoarthritis Research Society International scores in both groups over 2 weeks (P < .05); however, group differences were not significant (P > .05). Overall, homeopathy did not appear to be superior to placebo; still, further rigorous evaluation in this design involving a larger sample size seems feasible in future. Clinical Trials Registry, India (CTRI/2014/05/004589). © The Author(s) 2015.

Does Oral Implant Design Affect Marginal Bone Loss? Results of a Parallel-Group Randomized Controlled Equivalence Trial

PubMed Central

Bateli, Maria; Ben Rahal, Ghada; Christmann, Marin; Vach, Kirstin; Kohal, Ralf-Joachim

2018-01-01

Objective To test whether or not the modified design of the test implant (intended to increase primary stability) has an equivalent effect on MBL compared to the control. Methods Forty patients were randomly assigned to receive test or control implants to be installed in identically dimensioned bony beds. Implants were radiographically monitored at installation, at prosthetic delivery, and after one year. Treatments were considered equivalent if the 90% confidence interval (CI) for the mean difference (MD) in MBL was in between −0.25 and 0.25 mm. Additionally, several soft tissue parameters and patient-reported outcome measures (PROMs) were evaluated. Linear mixed models were fitted for each patient to assess time effects on response variables. Results Thirty-three patients (21 males, 12 females; 58.2 ± 15.2 years old) with 81 implants (47 test, 34 control) were available for analysis after a mean observation period of 13.9 ± 4.5 months (3 dropouts, 3 missed appointments, and 1 missing file). The adjusted MD in MBL after one year was −0.13 mm (90% CI: −0.46–0.19; test group: −0.49; control group: −0.36; p = 0.507). Conclusion Both implant systems can be considered successful after one year of observation. Concerning MBL in the presented setup, equivalence of the treatments cannot be concluded. Registration This trial is registered with the German Clinical Trials Register (ID: DRKS00007877). PMID:29610765

Transcranial direct current stimulation for depression in Alzheimer's disease: study protocol for a randomized controlled trial.

PubMed

Narita, Zui; Yokoi, Yuma

2017-06-19

Patients with Alzheimer's disease frequently elicit neuropsychiatric symptoms as well as cognitive deficits. Above all, depression is one of the most common neuropsychiatric symptoms in Alzheimer's disease but antidepressant drugs have not shown significant beneficial effects on it. Moreover, electroconvulsive therapy has not ensured its safety for potential severe adverse events although it does show beneficial clinical effect. Transcranial direct current stimulation can be the safe alternative of neuromodulation, which applies weak direct electrical current to the brain. Although transcranial direct current stimulation has plausible evidence for its effect on depression in young adult patients, no study has explored it in older subjects with depression in Alzheimer's disease. Therefore, we present a study protocol designed to evaluate the safety and clinical effect of transcranial direct current stimulation on depression in Alzheimer's disease in subjects aged over 65 years. This is a two-arm, parallel-design, randomized controlled trial, in which patients and assessors will be blinded. Subjects will be randomized to either an active or a sham transcranial direct current stimulation group. Participants in both groups will be evaluated at baseline, immediately, and 2 weeks after the intervention. This study investigates the safety and effect of transcranial direct current stimulation that may bring a significant impact on both depression and cognition in patients with Alzheimer's disease, and may be useful to enhance their quality of life. ClinicalTrials.gov, NCT02351388 . Registered on 27 January 2015. Last updated on 30 May 2016.

Parallel algorithms for placement and routing in VLSI design. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Brouwer, Randall Jay

1991-01-01

The computational requirements for high quality synthesis, analysis, and verification of very large scale integration (VLSI) designs have rapidly increased with the fast growing complexity of these designs. Research in the past has focused on the development of heuristic algorithms, special purpose hardware accelerators, or parallel algorithms for the numerous design tasks to decrease the time required for solution. Two new parallel algorithms are proposed for two VLSI synthesis tasks, standard cell placement and global routing. The first algorithm, a parallel algorithm for global routing, uses hierarchical techniques to decompose the routing problem into independent routing subproblems that are solved in parallel. Results are then presented which compare the routing quality to the results of other published global routers and which evaluate the speedups attained. The second algorithm, a parallel algorithm for cell placement and global routing, hierarchically integrates a quadrisection placement algorithm, a bisection placement algorithm, and the previous global routing algorithm. Unique partitioning techniques are used to decompose the various stages of the algorithm into independent tasks which can be evaluated in parallel. Finally, results are presented which evaluate the various algorithm alternatives and compare the algorithm performance to other placement programs. Measurements are presented on the parallel speedups available.

Reading aids for adults with low vision

PubMed Central

Virgili, Gianni; Acosta, Ruthy; Grover, Lori L; Bentley, Sharon A; Giacomelli, Giovanni

2014-01-01

Background The purpose of low-vision rehabilitation is to allow people to resume or to continue to perform daily living tasks, with reading being one of the most important. This is achieved by providing appropriate optical devices and special training in the use of residual-vision and low-vision aids, which range from simple optical magnifiers to high-magnification video magnifiers. Objectives To assess the effects of reading aids for adults with low vision. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to January 2013), EMBASE (January 1980 to January 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2013), 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/) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 31 January 2013. We searched the reference lists of relevant articles and used the Science Citation Index to find articles that cited the included studies and contacted investigators and manufacturers of low-vision aids. We handsearched the British Journal of Visual Impairment from 1983 to 1999 and the Journal of Visual Impairment and Blindness from 1976 to 1991. Selection criteria This review includes randomised and quasi-randomised trials in which any device or aid used for reading had been compared to another device or aid in people aged 16 or over with low vision as defined by the study investigators. Data collection and analysis At least two authors independently assessed trial quality and extracted data. Main results We included nine small studies with a cross-over-like design (181 people overall) and one study with three parallel arms (243 participants) in the review. All studies reported the primary outcome, results for reading speed. Two studies including 92 participants found moderate- or low-quality evidence suggesting that reading speed is higher with stand-mounted electronic devices or electronic devices with the camera mounted in a ‘mouse’ than with optical magnifiers, which in these trials were generally stand-mounted or, less frequently, hand-held magnifiers or microscopic lenses. In another study of 20 participants there was moderate-quality evidence that optical devices are better than head-mounted electronic devices (four types). There was low-quality evidence from three studies (93 participants) that reading using head-mounted electronic devices is slower than with stand-based electronic devices. The technology of electronic devices may have changed and improved since these studies were conducted. One study suggested no difference between a diffractive spectacle-mounted magnifier and either refractive (15 participants) or aplanatic (15 participants) magnifiers. One study of 10 people suggested that several overlay coloured filters were no better and possibly worse than a clear filter. A parallel-arm study including 243 participants with age-related macular degeneration found that custom or standard prism spectacles were no different from conventional reading spectacles, although the data did not allow precise estimates of performance to be made. Authors' conclusions There is insufficient evidence on the effect of different types of low-vision aids on reading performance. It would be necessary to investigate which patient characteristics predict performance with different devices, including costly electronic devices. Better-quality research should also focus on assessing sustained long-term use of each device. Authors of studies testing several devices on the same person should consider design and reporting issues related to their sequential presentation and to the cross-over-like study design. PMID:24154864

Healing of Postextraction Sockets Preserved With Autologous Platelet Concentrates. A Systematic Review and Meta-Analysis.

PubMed

Del Fabbro, Massimo; Bucchi, Cristina; Lolato, Alessandra; Corbella, Stefano; Testori, Tiziano; Taschieri, Silvio

2017-08-01

The true benefit of autologous platelet concentrates (APCs) for enhancing the healing of postextraction sites is still a matter of debate, and in recent years several clinical trials have addressed this issue. The purpose of this study was to determine the effectiveness of an APC adjunct in the preservation of fresh extraction sockets. An electronic search was performed on Medline, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Only controlled clinical trials or randomized clinical trials were included. Selected articles underwent risk-of-bias assessment. The outcomes were complications and adverse events, discomfort and quality of life, bone healing and remodeling assessed by histologic and radiographic techniques, and soft tissue healing. Thirty-three comparative studies were included. Nine articles had a parallel design and 24 had a split-mouth design. Twenty studies were considered to have a low risk of bias and 13 were considered to have a high risk. Overall, 1,193 teeth were extracted from 911 patients. Meta-analysis showed that soft tissue healing, probing depth at 3 months, and bone density at 1, 3, and 6 months were statistically better for the APC group. Qualitative analysis suggested that APCs might be associated with a decrease in swelling and trismus. However, no relevant difference among groups was found for probing depth at 1 month, incidence of alveolar osteitis, acute inflammation or infection, percentage of new bone, and indirect measurement of bone metabolism. APCs should be used in postextraction sites to improve clinical and radiographic outcomes such as bone density and soft tissue healing and postoperative symptoms. The actual benefit of APCs on decreasing pain in extraction sockets is still not quantifiable. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Effectiveness of a smartphone application for improving healthy lifestyles, a randomized clinical trial (EVIDENT II): study protocol.

PubMed

Recio-Rodríguez, José I; Martín-Cantera, Carlos; González-Viejo, Natividad; Gómez-Arranz, Amparo; Arietaleanizbeascoa, Maria S; Schmolling-Guinovart, Yolanda; Maderuelo-Fernandez, Jose A; Pérez-Arechaederra, Diana; Rodriguez-Sanchez, Emiliano; Gómez-Marcos, Manuel A; García-Ortiz, Luis

2014-03-15

New technologies could facilitate changes in lifestyle and improve public health. However, no large randomized, controlled studies providing scientific evidence of the benefits of their use have been made. The aims of this study are to develop and validate a smartphone application, and to evaluate the effect of adding this tool to a standardized intervention designed to improve adherence to the Mediterranean diet and to physical activity. An evaluation is also made of the effect of modifying habits upon vascular structure and function, and therefore on arterial aging. A randomized, double-blind, multicenter, parallel group clinical trial will be carried out. A total of 1215 subjects under 70 years of age from the EVIDENT trial will be included. Counseling common to both groups (control and intervention) will be provided on adaptation to the Mediterranean diet and on physical activity. The intervention group moreover will receive training on the use of a smartphone application designed to promote a healthy diet and increased physical activity, and will use the application for three months. The main study endpoints will be the changes in physical activity, assessed by accelerometer and the 7-day Physical Activity Recall (PAR) interview, and adaptation to the Mediterranean diet, as evaluated by an adherence questionnaire and a food frequency questionnaire (FFQ). Evaluation also will be made of vascular structure and function based on central arterial pressure, the radial augmentation index, pulse velocity, the cardio-ankle vascular index, and carotid intima-media thickness. Confirmation that the new technologies are useful for promoting healthier lifestyles and that their effects are beneficial in terms of arterial aging will have important clinical implications, and may contribute to generalize their application in favor of improved population health. Clinical Trials.gov Identifier: NCT02016014.

Treatment outcomes in palliative care: the TOPCare study. A mixed methods phase III randomised controlled trial to assess the effectiveness of a nurse-led palliative care intervention for HIV positive patients on antiretroviral therapy

PubMed Central

2012-01-01

Background Patients with HIV/AIDS on Antiretroviral Therapy (ART) suffer from physical, psychological and spiritual problems. Despite international policy explicitly stating that a multidimensional approach such as palliative care should be delivered throughout the disease trajectory and alongside treatment, the effectiveness of this approach has not been tested in ART-experienced populations. Methods/design This mixed methods study uses a Randomised Controlled Trial (RCT) to test the null hypothesis that receipt of palliative care in addition to standard HIV care does not affect pain compared to standard care alone. An additional qualitative component will explore the mechanism of action and participant experience. The sample size is designed to detect a statistically significant decrease in reported pain, determined by a two tailed test and a p value of ≤0.05. Recruited patients will be adults on ART for more than one month, who report significant pain or symptoms which have lasted for more than two weeks (as measured by the African Palliative Care Association (APCA) African Palliative Outcome Scale (POS)). The intervention under trial is palliative care delivered by an existing HIV facility nurse trained to a set standard. Following an initial pilot the study will be delivered in two African countries, using two parallel independent Phase III clinical RCTs. Qualitative data will be collected from semi structured interviews and documentation from clinical encounters, to explore the experience of receiving palliative care in this context. Discussion The data provided by this study will provide evidence to inform the improvement of outcomes for people living with HIV and on ART in Africa. ClinicalTrials.gov Identifier: NCT01608802 PMID:23130740

Effectiveness of Virtual Reality Exercises in STroke Rehabilitation (EVREST): rationale, design, and protocol of a pilot randomized clinical trial assessing the Wii gaming system.

PubMed

Saposnik, G; Mamdani, M; Bayley, M; Thorpe, K E; Hall, J; Cohen, L G; Teasell, R

2010-02-01

Evidence suggests that increasing intensity of rehabilitation results in better motor recovery. Limited evidence is available on the effectiveness of an interactive virtual reality gaming system for stroke rehabilitation. EVREST was designed to evaluate feasibility, safety and efficacy of using the Nintendo Wii gaming virtual reality (VRWii) technology to improve arm recovery in stroke patients. Pilot randomized study comparing, VRWii versus recreational therapy (RT) in patients receiving standard rehabilitation within six months of stroke with a motor deficit of > or =3 on the Chedoke-McMaster Scale (arm). In this study we expect to randomize 20 patients. All participants (age 18-85) will receive customary rehabilitative treatment consistent of a standardized protocol (eight sessions, 60 min each, over a two-week period). The primary feasibility outcome is the total time receiving the intervention. The primary safety outcome is the proportion of patients experiencing intervention-related adverse events during the study period. Efficacy, a secondary outcome measure, will be measured by the Wolf Motor Function Test, Box and Block Test, and Stroke Impact Scale at the four-week follow-up visit. From November, 2008 to September, 2009 21 patients were randomized to VRWii or RT. Mean age, 61 (range 41-83) years. Mean time from stroke onset 25 (range 10-56) days. EVREST is the first randomized parallel controlled trial assessing the feasibility, safety, and efficacy of virtual reality using Wii gaming technology in stroke rehabilitation. The results of this study will serve as the basis for a larger multicentre trial. ClinicalTrials.gov registration# NTC692523.

Study protocol for a randomised pragmatic trial comparing the clinical and cost effectiveness of lithium and quetiapine augmentation in treatment resistant depression (the LQD study).

PubMed

Marwood, L; Taylor, R; Goldsmith, K; Romeo, R; Holland, R; Pickles, A; Hutchinson, J; Dietch, D; Cipriani, A; Nair, R; Attenburrow, M-J; Young, A H; Geddes, J; McAllister-Williams, R H; Cleare, A J

2017-06-26

Approximately 30-50% of patients with major depressive disorder can be classed as treatment resistant, widely defined as a failure to respond to two or more adequate trials of antidepressants in the current episode. Treatment resistant depression is associated with a poorer prognosis and higher mortality rates. One treatment option is to augment an existing antidepressant with a second agent. Lithium and the atypical antipsychotic quetiapine are two such add-on therapies and are currently recommended as first line options for treatment resistant depression. However, whilst neither treatment has been established as superior to the other in short-term studies, they have yet to be compared head-to-head in longer term studies, or with a superiority design in this patient group. The Lithium versus Quetiapine in Depression (LQD) study is a parallel group, multi-centre, pragmatic, open-label, patient randomised clinical trial designed to address this gap in knowledge. The study will compare the clinical and cost effectiveness of the decision to prescribe lithium or quetiapine add-on therapy to antidepressant medication for patients with treatment resistant depression. Patients will be randomised 1:1 and followed up over 12 months, with the hypothesis being that quetiapine will be superior to lithium. The primary outcomes will be: (1) time to all-cause treatment discontinuation over one year, and (2) self-rated depression symptoms rated weekly for one year via the Quick Inventory of Depressive Symptomatology. Other outcomes will include between group differences in response and remission rates, quality of life, social functioning, cost-effectiveness and the frequency of serious adverse events and side effects. The trial aims to help shape the treatment pathway for patients with treatment resistant depression, by determining whether the decision to prescribe quetiapine is superior to lithium. Strengths of the study include its pragmatic superiority design, broad inclusion criteria (external validity) and longer follow up than previous studies. ISRCTN registry: ISRCTN16387615 , registered 28 February 2016. ClinicalTrials.gov: NCT03004521 , registered 17 November 2016.

The By-Band study: gastric bypass or adjustable gastric band surgery to treat morbid obesity: study protocol for a multi-centre randomised controlled trial with an internal pilot phase

PubMed Central

2014-01-01

Background The prevalence of severe and complex obesity is increasing worldwide and surgery may offer an effective and lasting treatment. Laparoscopic adjustable gastric band and Roux-en-Y gastric bypass surgery are the two main surgical procedures performed. Design This open parallel-group randomised controlled trial will compare the effectiveness, cost-effectiveness and acceptability of gastric band (Band) versus gastric bypass (Bypass) in adults with severe and complex obesity. It has an internal pilot phase (in two centres) with integrated qualitative research to establish effective and optimal methods for recruitment. Adults with a body mass index (BMI) of 40 kg/m2 or more, or a BMI of 35 kg/m2 or more and other co-morbidities will be recruited. At the end of the internal pilot the study will expand into more centres if the pre-set progression criteria of numbers and rates of eligible patients screened and randomised are met and if the expected rates of retention and adherence to treatment allocation are achieved. The trial will test the joint hypotheses that Bypass is non-inferior to Band with respect to more than 50% excess weight loss and that Bypass is superior to Band with respect to health related quality of life (HRQOL, EQ-5D) at three years. Secondary outcomes include other weight loss measures, waist circumference and remission/resolution of co-morbidities; generic and symptom-specific HRQOL; nutritional blood test results; resource use; eating behaviours and adverse events. A core outcome set for reporting the results of obesity surgery will be developed and a systematic review of the evidence for sleeve gastrectomy undertaken to inform the main study design. Discussion By-Band is the first pragmatic study to compare the two most commonly performed bariatric surgical procedures for severe and complex obesity. The design will enable and empower surgeons to learn to recruit and participate in a randomised study. Early evidence shows that timely recruitment is possible. Trial registration Current Controlled Trials ISRCTN00786323. PMID:24517309

Stainless steel versus titanium volar multi-axial locking plates for fixation of distal radius fractures: a randomised clinical trial

PubMed Central

2014-01-01

Background Distal radius fractures are among the most common fractures seen in the hospital emergency department. Of these, over 40% are considered unstable and require some form of fixation. In recent years with the advent of low profile plating, open reduction and internal fixation (ORIF) using volar plates has become the surgical treatment of choice in many hospitals. However, it is currently unknown which plating system has the lowest complication rate and/or superior clinical and radiological outcomes following surgery. Few studies have compared different types of plates, which may have various features, different plate and screw designs or may be manufactured from different materials (for example, stainless steel or titanium). This study will specifically investigate and compare the clinical and radiological outcomes and complication rates of two commonly used volar plating systems for fixation of distal radius fractures: one made from stainless steel (Trimed™ Volar Plate, Trimed™, California, USA) and the other made from titanium (Medartis® Aptus Volar Plate, Medartis®, Basel, Switzerland). The primary aim of this study is to determine if there is a difference on the Patient Reported Wrist Evaluation six months following ORIF using a volar plate for adult patients with a distal radius fracture. Methods/Design This study will implement a randomized prospective clinical trial study design evaluating the outcomes of two different types of volar plates: one plate manufactured from stainless steel (Trimed™ Volar Plate) and one plate manufactured from titanium (Medartis® Aptus Volar Plate). The surgery will be performed at a major trauma hospital in Brisbane, Australia. Outcome measures including function, adverse events, range of movement, strength, disability, radiological findings and health-related quality of life will be collected at 6 weeks, 3, 6, 12 and 24 months following surgery. A parallel economic analysis will also be performed. This randomized clinical trial is due to deliver results in December 2016. Discussion Results from this trial will contribute to the evidence on operative management of distal radius fractures and plate material type. Trial registration ACTRN12612000969864 PMID:24612524

Parallel digital forensics infrastructure.

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

Liebrock, Lorie M.; Duggan, David Patrick

2009-10-01

This report documents the architecture and implementation of a Parallel Digital Forensics infrastructure. This infrastructure is necessary for supporting the design, implementation, and testing of new classes of parallel digital forensics tools. Digital Forensics has become extremely difficult with data sets of one terabyte and larger. The only way to overcome the processing time of these large sets is to identify and develop new parallel algorithms for performing the analysis. To support algorithm research, a flexible base infrastructure is required. A candidate architecture for this base infrastructure was designed, instantiated, and tested by this project, in collaboration with New Mexicomore » Tech. Previous infrastructures were not designed and built specifically for the development and testing of parallel algorithms. With the size of forensics data sets only expected to increase significantly, this type of infrastructure support is necessary for continued research in parallel digital forensics. This report documents the implementation of the parallel digital forensics (PDF) infrastructure architecture and implementation.« less

Quality of reporting of randomized clinical trials in implant dentistry. A systematic review on critical aspects in design, outcome assessment and clinical relevance.

PubMed

Cairo, Francesco; Sanz, Ignacio; Matesanz, Paula; Nieri, Michele; Pagliaro, Umberto

2012-02-01

The aim of this systematic review (SR) was to assess the quality of reporting randomized clinical trials (RCTs) in the field of implant dentistry, its evolution over time and the possible relations between quality items and reported outcomes. RCTs in implant dentistry were retrieved through electronic and hand searches. Risk of bias in individual studies was assessed focusing on study design, outcome assessment and clinical relevance. Associations between quality items and year of publication of RCTs or reporting of statistically significant outcomes were tested. Among the 495 originally screened manuscripts published from 1989 to April 2011, 276 RCTs were assessed in this SR; 59% of them were published between 2006 and 2011. RCTs were mainly parallel (65%), with a single centre (83%) and a superiority design (88%). Trials in implant dentistry showed several methodological flaws: only 37% showed a random sequence generation at low risk of bias, 75% did not provide information on allocation concealment, only 12% performed a correct sample size calculation, the examiner was blind solely in 42% of studies where blinding was feasible. In addition, only 21% of RCTs declared operator experience and 31% reported patient-related outcomes. Many quality items improved over time. Allocation concealment at high risk of bias (p = 0.0125), no information on drop-out (p = 0.0318) and lack of CONSORT adherence (p = 0.0333) were associated with statistically significant reported outcomes. The overall quality of reporting of RCTs in implant dentistry is poor and only partially improved in the last years. Caution is suggested when interpreting these RCTs since risk of bias was associated with higher chance of reporting of statistically significant results. © 2012 John Wiley & Sons A/S.

Rationale and design of the SERVE-HF study: treatment of sleep-disordered breathing with predominant central sleep apnoea with adaptive servo-ventilation in patients with chronic heart failure.

PubMed

Cowie, Martin R; Woehrle, Holger; Wegscheider, Karl; Angermann, Christiane; d'Ortho, Marie-Pia; Erdmann, Erland; Levy, Patrick; Simonds, Anita; Somers, Virend K; Zannad, Faiez; Teschler, Helmut

2013-08-01

Central sleep apnoea/Cheyne-Stokes respiration (CSA/CSR) is a risk factor for increased mortality and morbidity in heart failure (HF). Adaptive servo-ventilation (ASV) is a non-invasive ventilation modality for the treatment of CSA/CSR in patients with HF. SERVE-HF is a multinational, multicentre, randomized, parallel trial designed to assess the effects of addition of ASV (PaceWave, AutoSet CS; ResMed) to optimal medical management compared with medical management alone (control group) in patients with symptomatic chronic HF, LVEF ≤45%, and predominant CSA. The trial is based on an event-driven group sequential design, and the final analysis will be performed when 651 events have been observed or the study is terminated at one of the two interim analyses. The aim is to randomize ∼1200 patients to be followed for a minimum of 2 years. Patients are to stay in the trial up to study termination. The first patient was randomized in February 2008 and the study is expected to end mid 2015. The primary combined endpoint is the time to first event of all-cause death, unplanned hospitalization (or unplanned prolongation of a planned hospitalization) for worsening (chronic) HF, cardiac transplantation, resuscitation of sudden cardiac arrest, or appropriate life-saving shock for ventricular fibrillation or fast ventricular tachycardia in implantable cardioverter defibrillator patients. The SERVE-HF study is a randomized study that will provide important data on the effect of treatment with ASV on morbidity and mortality, as well as the cost-effectiveness of this therapy, in patients with chronic HF and predominantly CSA/CSR. ISRCTN19572887.

The DiaS trial: dialectical behavior therapy versus collaborative assessment and management of suicidality on self-harm in patients with a recent suicide attempt and borderline personality disorder traits - study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background In Denmark 8,000 to 10,000 people will attempt suicide each year. The Centre of Excellence in Suicide Prevention in the Capital Region of Denmark is treating patients with suicidal behavior, and a recent survey has shown that 30% of the patients are suffering from borderline personality disorder. The majority of patients (70% to 75%) with borderline personality disorder have a history of deliberate self-harm and 10% have a lifetime risk to die by suicide. The DiaS trial is comparing dialectical behavior therapy with collaborative assessment and management of suicidality-informed supportive psychotherapy, for the risk of repetition of deliberate self-harm in patients with a recent suicide attempt and personality traits within the spectrum of borderline personality disorder. Both treatments have previously shown effects in this group of patients on suicide ideation and self-harm compared with treatment as usual. Methods/Design The trial is designed as a single-center, two-armed, parallel-group observer-blinded randomized clinical superiority trial. We will recruit 160 participants with a recent suicide attempt and at least two traits of the borderline personality disorder from the Centre of Excellence in Suicide Prevention, Capital Region of Denmark. Randomization will be performed though a centralized and computer-generated approach that conceals the randomization sequence. The interventions that are offered are a modified version of a dialectical behavior therapy program lasting 16 weeks versus collaborative assessment and management of suicidality-informed supportive psychotherapy, where the duration treatment will vary in accordance with established methods up to 16 weeks. The primary outcome measure is the ratio of deliberate self-harming acts including suicide attempts measured at week 28. Other exploratory outcomes are included such as severity of symptoms, suicide intention and ideation, depression, hopelessness, self-esteem, impulsivity, anger, and duration of respective treatments. Trial registration Clinical Trial.gov: NCT01512602. PMID:24885904

The evaluation of enhanced feedback interventions to reduce unnecessary blood transfusions (AFFINITIE): protocol for two linked cluster randomised factorial controlled trials.

PubMed

Hartley, Suzanne; Foy, Robbie; Walwyn, Rebecca E A; Cicero, Robert; Farrin, Amanda J; Francis, Jill J; Lorencatto, Fabiana; Gould, Natalie J; Grant-Casey, John; Grimshaw, Jeremy M; Glidewell, Liz; Michie, Susan; Morris, Stephen; Stanworth, Simon J

2017-07-03

Blood for transfusion is a frequently used clinical intervention, and is also a costly and limited resource with risks. Many transfusions are given to stable and non-bleeding patients despite no clear evidence of benefit from clinical studies. Audit and feedback (A&F) is widely used to improve the quality of healthcare, including appropriate use of blood. However, its effects are often inconsistent, indicating the need for coordinated research including more head-to-head trials comparing different ways of delivering feedback. A programmatic series of research projects, termed the 'Audit and Feedback INterventions to Increase evidence-based Transfusion practIcE' (AFFINITIE) programme, aims to test different ways of developing and delivering feedback within an existing national audit structure. The evaluation will comprise two linked 2×2 factorial, cross-sectional cluster-randomised controlled trials. Each trial will estimate the effects of two feedback interventions, 'enhanced content' and 'enhanced follow-on support', designed in earlier stages of the AFFINITIE programme, compared to current practice. The interventions will be embedded within two rounds of the UK National Comparative Audit of Blood Transfusion (NCABT) focusing on patient blood management in surgery and use of blood transfusions in patients with haematological malignancies. The unit of randomisation will be National Health Service (NHS) trust or health board. Clusters providing care relevant to the audit topics will be randomised following each baseline audit (separately for each trial), with stratification for size (volume of blood transfusions) and region (Regional Transfusion Committee). The primary outcome for each topic will be the proportion of patients receiving a transfusion coded as unnecessary. For each audit topic a linked, mixed-method fidelity assessment and cost-effectiveness analysis will be conducted in parallel to the trial. AFFINITIE involves a series of studies to explore how A&F may be refined to change practice including two cluster randomised trials linked to national audits of transfusion practice. The methodology represents a step-wise increment in study design to more fully evaluate the effects of two enhanced feedback interventions on patient- and trust-level clinical, cost, safety and process outcomes. http://www.isrctn.com/ISRCTN15490813.

A pilot randomised double blind controlled trial of the efficacy of purified fatty acids for the treatment of women with endometriosis-associated pain (PurFECT): study protocol.

PubMed

Abokhrais, Ibtisam M; Saunders, Philippa T K; Denison, Fiona C; Doust, Ann; Williams, Linda; Horne, Andrew W

2018-01-01

Endometriosis affects 6-10% of women and is associated with debilitating pelvic pain. It costs the UK > £2.8 billion per year in loss of productivity. Endometriosis can be managed by surgical excision or medically by ovarian suppression. However, ~ 75% symptoms recur after surgery and available medical treatments have undesirable side effects and are contraceptive. Omega-3 purified fatty acids (PUFA) have been shown in animal models to reduce factors that are thought to lead to endometriosis-associated pain, have minimal side effects, and no effects on fertility. This paper presents a protocol for a two-arm, pilot parallel randomised controlled trial (RCT) which aims to inform the planning of a future multicentre trial to evaluate the efficacy of Omega-3 PUFA in the management of endometriosis-associated pain in women. The study will recruit women with endometriosis over a 12-month period in the National Health Service (NHS) Lothian, UK, and randomise them to 8 weeks of treatment with Omega-3 PUFA or comparator (olive oil). The primary objective is to assess recruitment and retention rates. The secondary objectives are to determine the effectiveness/acceptability to participants of the proposed methods of recruitment/randomisation/treatments/questionnaires, to inform the sample size calculation and to refine the research methodology for a future large randomised controlled trial. Response to treatment will be monitored by pain scores and questionnaires assessing physical and emotional function compared at baseline and 8 weeks. We recognise that there may be potential difficulties in mounting a large randomised controlled trial for endometriosis to assess Omega-3 PUFA because they are a dietary supplement readily available over the counter and already used by women with endometriosis. We have therefore designed this pilot study to assess practical feasibility and following the 'Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials' recommendations for the design of chronic pain trials. ISRCTN44202346.

Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101--Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI.

PubMed

Pituskin, Edith; Haykowsky, Mark; Mackey, John R; Thompson, Richard B; Ezekowitz, Justin; Koshman, Sheri; Oudit, Gavin; Chow, Kelvin; Pagano, Joseph J; Paterson, Ian

2011-07-27

MANTICORE 101 - Breast (Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research) is a randomized trial to determine if conventional heart failure pharmacotherapy (angiotensin converting enzyme inhibitor or beta-blocker) can prevent trastuzumab-mediated left ventricular remodeling, measured with cardiac MRI, among patients with HER2+ early breast cancer. One hundred and fifty-nine patients with histologically confirmed HER2+ breast cancer will be enrolled in a parallel 3-arm, randomized, placebo controlled, double-blind design. After baseline assessments, participants will be randomized in a 1:1:1 ratio to an angiotensin-converting enzyme inhibitor (perindopril), beta-blocker (bisoprolol), or placebo. Participants will receive drug or placebo for 1 year beginning 7 days before trastuzumab therapy. Dosages for all groups will be systematically up-titrated, as tolerated, at 1 week intervals for a total of 3 weeks. The primary objective of this randomized clinical trial is to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer, as measured by 12 month change in left ventricular end-diastolic volume using cardiac MRI. Secondary objectives include 1) determine the evolution of left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer, 2) understand the mechanism of trastuzumab mediated cardiac toxicity by assessing for the presence of myocardial injury and apoptosis on serum biomarkers and cardiac MRI, and 3) correlate cardiac biomarkers of myocyte injury and extra-cellular matrix remodeling with left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer. Cardiac toxicity as a result of cancer therapies is now recognized as a significant health problem of increasing prevalence. To our knowledge, MANTICORE will be the first randomized trial testing proven heart failure pharmacotherapy in the prevention of trastuzumab-mediated cardiotoxicity. We expect the findings of this trial to provide important evidence in the development of guidelines for preventive therapy. ClinicalTrials.gov: NCT01016886.

A Randomized, Rater-Blinded, Parallel Trial of Intensive Speech Therapy in Sub-Acute Post-Stroke Aphasia: The SP-I-R-IT Study

ERIC Educational Resources Information Center

Martins, Isabel Pavao; Leal, Gabriela; Fonseca, Isabel; Farrajota, Luisa; Aguiar, Marta; Fonseca, Jose; Lauterbach, Martin; Goncalves, Luis; Cary, M. Carmo; Ferreira, Joaquim J.; Ferro, Jose M.

2013-01-01

Background: There is conflicting evidence regarding the benefits of intensive speech and language therapy (SLT), particularly because intensity is often confounded with total SLT provided. Aims: A two-centre, randomized, rater-blinded, parallel study was conducted to compare the efficacy of 100 h of SLT in a regular (RT) versus intensive (IT)…

Integrated Task And Data Parallel Programming: Language Design

NASA Technical Reports Server (NTRS)

Grimshaw, Andrew S.; West, Emily A.

1998-01-01

his research investigates the combination of task and data parallel language constructs within a single programming language. There are an number of applications that exhibit properties which would be well served by such an integrated language. Examples include global climate models, aircraft design problems, and multidisciplinary design optimization problems. Our approach incorporates data parallel language constructs into an existing, object oriented, task parallel language. The language will support creation and manipulation of parallel classes and objects of both types (task parallel and data parallel). Ultimately, the language will allow data parallel and task parallel classes to be used either as building blocks or managers of parallel objects of either type, thus allowing the development of single and multi-paradigm parallel applications. 1995 Research Accomplishments In February I presented a paper at Frontiers '95 describing the design of the data parallel language subset. During the spring I wrote and defended my dissertation proposal. Since that time I have developed a runtime model for the language subset. I have begun implementing the model and hand-coding simple examples which demonstrate the language subset. I have identified an astrophysical fluid flow application which will validate the data parallel language subset. 1996 Research Agenda Milestones for the coming year include implementing a significant portion of the data parallel language subset over the Legion system. Using simple hand-coded methods, I plan to demonstrate (1) concurrent task and data parallel objects and (2) task parallel objects managing both task and data parallel objects. My next steps will focus on constructing a compiler and implementing the fluid flow application with the language. Concurrently, I will conduct a search for a real-world application exhibiting both task and data parallelism within the same program m. Additional 1995 Activities During the fall I collaborated with Andrew Grimshaw and Adam Ferrari to write a book chapter which will be included in Parallel Processing in C++ edited by Gregory Wilson. I also finished two courses, Compilers and Advanced Compilers, in 1995. These courses complete my class requirements at the University of Virginia. I have only my dissertation research and defense to complete.

Effects of Time between Trials on Rats' and Pigeons' Choices with Probabilistic Delayed Reinforcers

ERIC Educational Resources Information Center

Mazur, James E.; Biondi, Dawn R.

2011-01-01

Parallel experiments with rats and pigeons examined reasons for previous findings that in choices with probabilistic delayed reinforcers, rats' choices were affected by the time between trials whereas pigeons' choices were not. In both experiments, the animals chose between a standard alternative and an adjusting alternative. A choice of the…

Effectiveness of a Web-Based Intervention to Reduce Alcohol Consumption among French Hazardous Drinkers: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Guillemont, Juliette; Cogordan, Chloé; Nalpas, Bertrand; Nguyen-Thanh, Vi?t; Richard, Jean-Baptiste; Arwidson, Pierre

2017-01-01

This study aims to evaluate the effectiveness of a web-based intervention to reduce alcohol consumption among hazardous drinkers. A two-group parallel randomized controlled trial was conducted among adults identified as hazardous drinkers according to the Alcohol Use Disorders Identification Test. The intervention delivers personalized normative…

Cumulative proportion of responders analysis (CPRA) as a tool to assess treatment outcome in alcohol clinical trials.

PubMed

Falk, Daniel E; Litten, Raye Z; Anton, Raymond F; Kranzler, Henry R; Johnson, Bankole A

2014-03-01

Several definitions of treatment response have been proposed for alcohol clinical trials (e.g., abstinence and no heavy drinking). However, each of these outcomes allows only one definition of successful response. In contrast, the cumulative proportion of responders analysis (CPRA) includes all of the possible drinking response cutoff points, providing a more complete picture of the therapeutic effects of a treatment. CPRA has been used to examine the efficacy of analgesics but not alcohol pharmacotherapy. To demonstrate its potential utility, we conducted CPRA in two large alcohol treatment trials: the COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) trial (naltrexone) and a multisite topiramate trial. CPRA was used to demonstrate the efficacy of naltrexone and topiramate on continuous measures of in-treatment drinking-heavy drinking days and drinks per day-and their reductions from pretreatment. All possible cutoff points were portrayed for each measure. We provide graphs to illustrate the effects of the active medications compared with placebo and examined them statistically over a number of salient drinking outcomes to evaluate their efficacy. Treatment group responder curves were not parallel across the entire range of cutoff points; rather, they separated only at lower levels of drinking. In general, effect sizes increased by 0.10-0.15 when going from the lowest drinking level cutoff (i.e., abstinence and no heavy drinking) to the cutoff associated with the maximal treatment effect. CPRA may be useful in designing subsequent trials and helping to illustrate for treatment providers the likelihood of treatment success given various definitions of a positive response.

Isoperistaltic versus antiperistaltic side-to-side anastomosis after right laparoscopic hemicolectomy for cancer (ISOVANTI) trial: study protocol for a randomised clinical trial.

PubMed

Ibañez, N; Abrisqueta, J; Luján, J; Hernández, Q; Parrilla, P

2017-09-01

It is believed that loosing ileocecal valve is well tolerated in patients who do not have short bowel syndrome or Crohn disease. From the hypothesis of colonic peristalsis and transit is regulated by that ileocecal valvular mechanism, we try to find out if the creation of a new pseudo-valvular mechanism as antiperistaltic anastomosis could be considered after right hemicolectomy can cause any short- or long-term changes in gastrointestinal habits. The purpose of the study at primary endpoint is to compare early (occurring within 30 days of surgery) and late (occurring during the follow-up) postoperative complications between both groups The purpose of the study at secondary endpoint is to compare intraoperative and postoperative events between experimental and control groups in terms of operating time, first oral tolerance day, first flatus and faeces, length of hospital stay and orocecal transit; comparing rates of gastrointestinal life quality and comparing mortality rates between both groups. The ISOVANTI trial is a randomized controlled single-centre trial comparing isoperistaltic versus antiperistaltic side-to-side anastomosis after right laparoscopic hemicolectomy. It is designed as a parallel group superiority trial. It is unknown if a pseudo-valvular mechanism as antiperistaltic anastomosis can be considered has short- or long-term consequences in gastrointestinal habit. Considering the impact that ileocolic anastomosis configuration could have on the restitution of bowel transit after right hemicolectomy, we think it is indicated and necessary a randomized trial comparing iso- and antiperistaltic modalities. NCT02309931.

Lifestyle intervention using Internet of Things (IoT) for the elderly: A study protocol for a randomized control trial (the BEST-LIFE study).

PubMed

Kato, Sawako; Ando, Masahiko; Kondo, Takaaki; Yoshida, Yasuko; Honda, Hiroyuki; Maruyama, Shoichi

2018-05-01

Modification of lifestyle habits, including diet and physical activity, is essential for the prevention and control of type 2 diabetes mellitus (T2DM) in elderly patients. However, individualized treatment is more critical for the elderly than for general patients. This study aimed to determine lifestyle interventions that resulted in lowering hemoglobin A 1c (HbA 1c ) in Japanese pre- and early diabetic elderly subjects. The BEST-LIFE trial is an ongoing, open-label, 6-month, randomized (1:1) parallel group trial. Subjects with HbA 1c of ≥5.6%-randomly assigned to the intervention or control group -use wearable monitoring devices loaded with Internet of things (IoT) systems that aids them with self-management and obtaining monthly remote health guidance from a public health nurse. The primary outcome is changes in HbA 1c after a 6-month intervention relative to the baseline values. The secondary outcome is the change of behavior modification stages. The background, rationale, and study design of this trial are also presented. One hundred forty-five subjects have already been enrolled in this lifestyle intervention program, which will end in 2019. The BEST-LIFE trial will provide new evidence regarding the effectiveness and safety of our program on lowering HbA 1c in elderly subjects with T2DM. It will also investigate whether information communication technology tools and monitoring devices loaded with IoT can support health care in elderly subjects. The trial registration number is UMIN-CTR: UMIN 000023356.

Protection of xenon against postoperative oxygen impairment in adults undergoing Stanford Type-A acute aortic dissection surgery: Study protocol for a prospective, randomized controlled clinical trial.

PubMed

Jin, Mu; Cheng, Yi; Yang, Yanwei; Pan, Xudong; Lu, Jiakai; Cheng, Weiping

2017-08-01

The available evidence shows that hypoxemia after Stanford Type-A acute aortic dissection (AAD) surgery is a frequent cause of several adverse consequences. The pathogenesis of postoperative hypoxemia after AAD surgery is complex, and ischemia/reperfusion and inflammation are likely to be underlying risk factors. Xenon, recognized as an ideal anesthetic and anti-inflammatory treatment, might be a possible treatment for these adverse effects. The trial is a prospective, double-blind, 4-group, parallel, randomized controlled, a signal-center clinical trial. We will recruit 160 adult patients undergoing Stanford type-A AAD surgery. Patients will be allocated a study number and will be randomized on a 1:1:1:1 basis to receive 1 of the 3 treatment options (pulmonary inflated with 50% xenon, 75% xenon, or 100% xenon) or no treatment (control group, pulmonary inflated with 50% nitrogen). The aims of this study are to clarify the lung protection capability of xenon and its possible mechanisms in patients undergoing the Stanford type-A AAD surgery. This trial uses an innovative design to account for the xenon effects of postoperative oxygen impairment, and it also delineates the mechanism for any benefit from xenon. The investigational xenon group is considered a treatment intervention, as it includes 3 groups of pulmonary static inflation with 50%, 75%, and 100% xenon. It is suggested that future trials might define an appropriate concentration of xenon for the best practice intervention.

Parallel machine architecture and compiler design facilities

NASA Technical Reports Server (NTRS)

Kuck, David J.; Yew, Pen-Chung; Padua, David; Sameh, Ahmed; Veidenbaum, Alex

1990-01-01

The objective is to provide an integrated simulation environment for studying and evaluating various issues in designing parallel systems, including machine architectures, parallelizing compiler techniques, and parallel algorithms. The status of Delta project (which objective is to provide a facility to allow rapid prototyping of parallelized compilers that can target toward different machine architectures) is summarized. Included are the surveys of the program manipulation tools developed, the environmental software supporting Delta, and the compiler research projects in which Delta has played a role.

Parallel Treatments Design: A Nested Single Subject Design for Comparing Instructional Procedures.

ERIC Educational Resources Information Center

Gast, David L.; Wolery, Mark

1988-01-01

This paper describes the parallel treatments design, a nested single subject experimental design that combines two concurrently implemented multiple probe designs, allows control for effects of extraneous variables through counterbalancing, and replicates its effects across behaviors. Procedural guidelines for the design's use and issues related…

Software Design for Real-Time Systems on Parallel Computers: Formal Specifications.

DTIC Science & Technology

1996-04-01

This research investigated the important issues related to the analysis and design of real - time systems targeted to parallel architectures. In...particular, the software specification models for real - time systems on parallel architectures were evaluated. A survey of current formal methods for...uniprocessor real - time systems specifications was conducted to determine their extensibility in specifying real - time systems on parallel architectures. In

Gender and body size affect the response of erythrocyte folate to folic acid treatment.

PubMed

Winkels, Renate M; Brouwer, Ingeborg A; Verhoef, Petra; van Oort, Floor V A; Durga, Jane; Katan, Martijn B

2008-08-01

The recommended dietary allowance (RDA) differs between men and women for some vitamins, but not for folate. The RDA for folate is derived mainly from metabolic studies in women. We assessed if men differ from women in their response of erythrocyte folate to folic acid supplementation. We used data from 2 randomized placebo-controlled trials with folic acid: a 3-y trial in which subjects ingested 800 mug/d of folic acid (294 men and 112 women) and a 12-wk trial in which 187 men and 129 women ingested 0, 50, 100, 200, 400, 600, or 800 microg/d of folic acid in a parallel design (n = 38-42 per treatment group). In the 3-y trial, the erythrocyte folate concentration increased 10% (143 nmol/L, [95%CI 46, 241]) less in men than in women. In the 12-wk trial, regression analysis showed that the response of erythrocyte folate upon folic acid intake for men was 47 nmol/L lower than for women (P for beta(gender) = 0.022); for an intake of 800 microg/d folic acid, this resulted in a 5% lower response in men than in women. Differences in lean body size explained 56% of the difference in response of erythrocyte folate between men and women in the 3-y trial and 70% in the 12-wk trial. Men need more folic acid than women to achieve the same erythrocyte folate concentration, mainly because men have a larger lean body mass. This could be an indication that the RDA for folate should be higher for men than for women, or that the RDA should be expressed per kilogram of lean body mass.

Multifamily psychoeducation for improvement of mental health among relatives of patients with major depressive disorder lasting more than one year: study protocol for a randomized controlled trial.

PubMed

Katsuki, Fujika; Takeuchi, Hiroshi; Watanabe, Norio; Shiraishi, Nao; Maeda, Tohru; Kubota, Yosuke; Suzuki, Masako; Yamada, Atsurou; Akechi, Tatsuo

2014-08-12

Major depressive disorder (MDD) is a long-lasting disorder with frequent relapses that have significant effects on the patient's family. Family psychoeducation is recognized as part of the optimal treatment for patients with psychotic disorder. A previous randomized controlled trial has found that family psychoeducation is effective in enhancing the treatment of MDD. Although MDD can easily become a chronic illness, there has been no intervention study on the families of patients with chronic depression. In the present study, we design a randomized controlled trial to examine the effectiveness of family psychoeducation in improving the mental health of relatives of patients with MDD lasting more than one year. Participants are patients with MDD lasting more than one year and their relatives. Individually randomized, parallel-group trial design will be employed. Participants will be allocated to one of two treatment conditions: relatives will receive (a) family psychoeducation (four, two-hour biweekly multifamily psychoeducation sessions) plus treatment-as-usual for the patient (consultation by physicians), or (b) counseling for the family (one counseling session from a nurse) plus treatment-as-usual for the patient. The primary outcome measure will be relatives' mental health as measured by K6 that was developed to screen for DSM-IV depressive and anxiety disorder. Additionally, the severity of depressive symptoms in patients measured by the Beck Depression Inventory-II (BDI-II) scale will be assessed. Data from the intention-to-treat sample will be analyzed 16 weeks after randomization. This is the first study to evaluate the effectiveness of family psychoeducation for relatives of patients with MDD lasting more than one year. If this type of intervention is effective, it could be a new method of rehabilitation for patients with MDD lasting more than one year. Clinical Trials.gov NCT01734291 (registration date: 18 October 2012).

The NEtherlands Cervical Kinematics (NECK) trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study.

PubMed

Arts, Mark P; Brand, Ronald; van den Akker, Elske; Koes, Bart W; Peul, Wilco C

2010-06-16

Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prosthesis is necessary and cost-effective will be determined by this trial. Netherlands Trial Register NTR1289.

A controlled time-series trial of clinical reminders: using computerized firm systems to make quality improvement research a routine part of mainstream practice.

PubMed Central

Goldberg, H. I.; Neighbor, W. E.; Cheadle, A. D.; Ramsey, S. D.; Diehr, P.; Gore, E.

2000-01-01

OBJECTIVE: To explore the feasibility of conducting unobtrusive interventional research in community practice settings by integrating firm-system techniques with time-series analysis of relational-repository data. STUDY SETTING: A satellite teaching clinic divided into two similar, but geographically separated, primary care group practices called firms. One firm was selected by chance to receive the study intervention. Forty-two providers and 2,655 patients participated. STUDY DESIGN: A nonrandomized controlled trial of computer-generated preventive reminders. Net effects were determined by quantitatively combining population-level data from parallel experimental and control interrupted time series extending over two-month baseline and intervention periods. DATA COLLECTION: Mean rates at which mammography, colorectal cancer screening, and cholesterol testing were performed on patients due to receive each maneuver at clinic visits were the trial's outcome measures. PRINCIPAL FINDINGS: Mammography performance increased on the experimental firm by 154 percent (0.24 versus 0.61, p = .03). No effect on fecal occult blood testing was observed. Cholesterol ordering decreased on both the experimental (0.18 versus 0.1 1, p = .02) and control firms (0.13 versus 0.07, p = .03) coincident with national guidelines retreating from recommending screening for young adults. A traditional uncontrolled interrupted time-series design would have incorrectly attributed the experimental-firm decrease to the introduction of reminders. The combined analysis properly indicated that no net prompting effect had occurred, as the difference between firms in cholesterol testing remained stochastically stable over time (0.05 versus 0.04, p = .75). A logistic-regression analysis applied to individual-level data produced equivalent findings. The trial incurred no supplementary data collection costs. CONCLUSIONS: The apparent validity and practicability of our reminder implementation study should encourage others to develop computerized firm systems capable of conducting controlled time-series trials. Images Fig. 1 PMID:10737451

Group-based antenatal birth and parent preparation for improving birth outcomes and parenting resources: study protocol for a randomised trial.

PubMed

Koushede, Vibeke; Brixval, Carina Sjöberg; Axelsen, Solveig Forberg; Lindschou, Jane; Winkel, Per; Maimburg, Rikke Damkjær; Due, Pernille

2013-10-01

To examine the efficacy and cost-effectiveness of group based antenatal education for improving childbirth and parenting resources compared to auditorium based education. 2350 Danish pregnant women and their partners ≥18 years old, recruited before 20+0 gestational weeks. Population-based individually randomised superiority trial with two parallel arms: Four sessions of birth and parent preparation in small groups (experimental group); two lectures in an auditorium (control group). Data is collected by (1) questionnaires at baseline (≈18 weeks of gestation), 37 weeks of gestation, 9 weeks-, 6 months-, and 1 year post-partum, (2) the hospital obstetric database, (3) national registers. use of epidural analgesia. stress, parenting alliance; explorative outcomes: depressive symptoms, use of health care services, self-efficacy, well-being, family break-ups. Analyses will be intention-to-treat as well as per protocol. Process evaluation will be conducted using questionnaires and qualitative interviews. The incremental societal cost of the intervention will be computed and compared to the measured outcomes in a cost-effectiveness analysis. To the best of our knowledge this is the largest well-designed randomised trial of its kind to date. The trial will bring much-needed evidence for decision makers of the content and form of antenatal education. Copyright © 2013 Elsevier B.V. All rights reserved.

"GET-UP" study rationale and protocol: a cluster randomised controlled trial to evaluate the effects of reduced sitting on toddlers' cognitive development.

PubMed

Santos, Rute; Cliff, Dylan P; Howard, Steven J; Veldman, Sanne L; Wright, Ian M; Sousa-Sá, Eduarda; Pereira, João R; Okely, Anthony D

2016-11-09

The educational and cognitive differences associated with low socioeconomic status begin early in life and tend to persist throughout life. Coupled with the finding that levels of sedentary time are negatively associated with cognitive development, and time spent active tends to be lower in disadvantaged circumstances, this highlights the need for interventions that reduce the amount of time children spend sitting and sedentary during childcare. The proposed study aims to assess the effects of reducing sitting time during Early Childhood Education and Care (ECEC) services on cognitive development in toddlers from low socio-economic families. We will implement a 12-months 2-arm parallel group cluster randomised controlled trial (RCT) with Australian toddlers, aged 12 to 26 months at baseline. Educators from the ECEC services allocated to the intervention group will receive professional development on how to reduce sitting time while children attend ECEC. Participants' cognitive development will be assessed as a primary outcome, at baseline and post-intervention, using the cognitive sub-test from the Bayley Scales of Infant and Toddler Development. This trial has the potential to inform programs and policies designed to optimize developmental and health outcomes in toddlers, specifically in those from disadvantaged backgrounds. Australian New Zealand Clinical Trials Registry: ACTRN12616000471482 , 11/04/2016, retrospectively registered.

The TRACTISS Protocol: a randomised double blind placebo controlled clinical TRial of Anti-B-Cell Therapy In patients with primary Sjögren’s Syndrome

PubMed Central

2014-01-01

Background Primary Sjögren’s Syndrome (PSS) mainly affects women (9:1 female:male ratio) and is one of the commonest autoimmune diseases with a prevalence of 0.1 – 0.6% of adult women. For patients with PSS there is currently no effective therapy that can alter the progression of the disease. The aim of the TRACTISS study is to establish whether in patients with PSS, treatment with rituximab improves clinical outcomes. Methods/design TRACTISS is a UK multi-centre, double-blind, randomised, controlled, parallel group trial of 110 patients with PSS. Patients will be randomised on a 1:1 basis to receive two courses of either rituximab or placebo infusion in addition to standard therapy, and will be followed up for up to 48 weeks. The primary objective is to assess the extent to which rituximab improves symptoms of fatigue and oral dryness. Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow, patient quality of life, measures of disease damage and disease activity, serological and peripheral blood biomarkers, and glandular histology and composition. Discussion The TRACTISS trial will provide direct evidence as to whether rituximab in patients with PSS leads to an improvement in patient symptoms and a reduction in disease damage and activity. Trial registration UKCRN Portfolio ID: 9809 ISRCTN65360827. PMID:24438039

[Clinical research. XIII. Research design contribution in the structured revision of an article].

PubMed

Talavera, Juan O; Rivas-Ruiz, Rodolfo

2013-01-01

The quality of information obtained in accordance to research design is integrated to the revision structured in relation to the causality model, used in the article "Reduction in the Incidence of Nosocomial Pneumonia Poststroke by Using the 'Turn-mob' Program", which corresponds to a clinical trial design. Points to identify and analyze are ethical issues in order to safeguard the security and respect for patients, randomization that seek to create basal homogeneous groups, subjects with the same probability of receiving any of the maneuvers in comparison, with the same pre maneuver probability of adherence, and which facilitate the blinding of outcome measurement and the distribution between groups of subjects with the same probability of leaving the study for reasons beyond the maneuvers. Other aspects are the relativity of comparison, the blinding of the maneuver, the parallel application of comparative maneuver, early stopping, and analysis according to the degree of adherence. The analysis in accordance with the design is complementary, since it is done based on the architectural model of causality, and the statistical and clinical relevance consideration.

A randomized evaluation of a computer-based physician's workstation: design considerations and baseline results.

PubMed Central

Rotman, B. L.; Sullivan, A. N.; McDonald, T.; DeSmedt, P.; Goodnature, D.; Higgins, M.; Suermondt, H. J.; Young, C. Y.; Owens, D. K.

1995-01-01

We are performing a randomized, controlled trial of a Physician's Workstation (PWS), an ambulatory care information system, developed for use in the General Medical Clinic (GMC) of the Palo Alto VA. Goals for the project include selecting appropriate outcome variables and developing a statistically powerful experimental design with a limited number of subjects. As PWS provides real-time drug-ordering advice, we retrospectively examined drug costs and drug-drug interactions in order to select outcome variables sensitive to our short-term intervention as well as to estimate the statistical efficiency of alternative design possibilities. Drug cost data revealed the mean daily cost per physician per patient was 99.3 cents +/- 13.4 cents, with a range from 0.77 cent to 1.37 cents. The rate of major interactions per prescription for each physician was 2.9% +/- 1%, with a range from 1.5% to 4.8%. Based on these baseline analyses, we selected a two-period parallel design for the evaluation, which maximized statistical power while minimizing sources of bias. PMID:8563376

Testing equality and interval estimation of the generalized odds ratio in ordinal data under a three-period crossover design.

PubMed

Lui, Kung-Jong; Chang, Kuang-Chao; Lin, Chii-Dean

2017-06-01

The crossover design can be of use to save the number of patients or improve power of a parallel groups design in studying treatments to noncurable chronic diseases. We propose using the generalized odds ratio for paired sample data to measure the relative effects in ordinal data between treatments and between periods. We show that one can apply the commonly used asymptotic and exact test procedures for stratified analysis in epidemiology to test non-equality of treatments in ordinal data, as well as obtain asymptotic and exact interval estimators for the generalized odds ratio under a three-period crossover design. We further show that one can apply procedures for testing the homogeneity of the odds ratio under stratified sampling to examine whether there are treatment-by-period interactions. We use the data taken from a three-period crossover trial studying the effects of low and high doses of an analgesic versus a placebo for the relief of pain in primary dysmenorrhea to illustrate the use of these test procedures and estimators proposed here.

A parallel-group, randomised controlled trial of a multimedia, self-directed, coping skills training intervention for patients with cancer and their partners: design and rationale

PubMed Central

Lambert, Sylvie D; Girgis, Afaf; McElduff, Patrick; Turner, Jane; Levesque, Janelle V; Kayser, Karen; Mihalopoulos, Cathrine; Shih, Sophy T F; Barker, Daniel

2013-01-01

Introduction Coping skills training interventions have been found to be efficacious in helping both patients and their partners manage the physical and emotional challenges they face following a cancer diagnosis. However, many of these interventions are costly and not sustainable. To overcome these issues, a self-directed format is increasingly used. The efficacy of self-directed interventions for patients has been supported; however, no study has reported on the outcomes for their partners. This study will test the efficacy of Coping-Together—a multimedia, self-directed, coping skills training intervention for patients with cancer and their partners. Methods and analysis The proposed three-group, parallel, randomised controlled trial will recruit patients diagnosed in the past 4 months with breast, prostate, colorectal cancer or melanoma through their treating clinician. Patients and their partners will be randomised to (1) a minimal ethical care (MEC) condition—selected Cancer Council New South Wales booklets and a brochure for the Cancer Council Helpline, (2) Coping-Together generic—MEC materials, the six Coping-Together booklets and DVD, the Cancer Council Queensland relaxation audio CD and login to the Coping-Together website or (3) Coping-Together tailored—MEC materials, the Coping-Together DVD, the login to the website and only those Coping-Together booklet sections that pertain to their direct concerns. Anxiety (primary outcome), distress, depression, dyadic adjustment, quality of life, illness or caregiving appraisal, self-efficacy and dyadic and individual coping will be assessed before receiving the study material (ie, baseline) and again at 3, 6 and 12 months postbaseline. Intention-to-treat and per protocol analysis will be conducted. Ethics and dissemination This study has been approved by the relevant local area health and University ethics committees. Study findings will be disseminated not only through peer-reviewed publications and conference presentations but also through educational outreach visits, publication of lay research summaries in consumer newsletters and publications targeting clinicians. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613000491763 (03/05/2013) PMID:23883890

"Everybody brush!": protocol for a parallel-group randomized controlled trial of a family-focused primary prevention program with distribution of oral hygiene products and education to increase frequency of toothbrushing.

PubMed

Cunha-Cruz, Joana; Milgrom, Peter; Shirtcliff, R Michael; Huebner, Colleen E; Ludwig, Sharity; Allen, Gary; Scott, JoAnna

2015-05-22

Twice daily toothbrushing with fluoridated toothpaste is the most widely advocated preventive strategy for dental caries (tooth decay) and is recommended by professional dental associations. Not all parents, children, or adolescents follow this recommendation. This protocol describes the methods for the implementation and evaluation of a quality improvement health promotion program. The objective of the study is to show a theory-informed, evidence-based program to improve twice daily toothbrushing and oral health-related quality of life that may reduce dental caries, dental treatment need, and costs. The design is a parallel-group, pragmatic randomized controlled trial. Families of Medicaid-insured children and adolescents within a large dental care organization in central Oregon will participate in the trial (n=21,743). Families will be assigned to one of three groups: a test intervention, an active control, or a passive control condition. The intervention aims to address barriers and support for twice-daily toothbrushing. Families in the test condition will receive toothpaste and toothbrushes by mail for all family members every three months. In addition, they will receive education and social support to encourage toothbrushing via postcards, recorded telephone messages, and an optional participant-initiated telephone helpline. Families in the active control condition will receive the kit of supplies by mail, but no additional instructional information or telephone support. Families assigned to the passive control will be on a waiting list. The primary outcomes are restorative dental care received and, only for children younger than 36 months old at baseline, the frequency of twice-daily toothbrushing. Data will be collected through dental claims records and, for children younger than 36 months old at baseline, parent interviews and clinical exams. Enrollment of participants and baseline interviews have been completed. Final results are expected in early summer, 2017. If proven effective, this simple intervention can be sustained by the dental care organization and replicated by other organizations and government. ClinicalTrials.gov NCT02327507; http://clinicaltrials.gov/ct2/show/NCT02327507 (Archived by WebCite at http://www.webcitation.org/6YCIxJSor).

Cerebral mechanism of puncturing at He-Mu point combination for functional dyspepsia: study protocol for a randomized controlled parallel trial.

PubMed

Yin, Shuai; Chen, Yuan; Lei, Du; Sun, Rui-Rui; Ma, Ting-Ting; Feng, Pei-Min; He, Zhao-Xuan; Suo, Xue-Ling; Ma, Pei-Hong; Qu, Yu-Zhu; Qiu, Ke; Jing, Miao-Miao; Gong, Qi-Yong; Liang, Fan-Rong; Chen, Jiao; Zeng, Fang

2017-05-01

Acupuncture is widely used to treat functional dyspepsia with satisfactory outcomes. Combination of the He and Mu acupoints is commonly used and has a synergistic effect on functional dyspepsia; however, its underlying mechanisms remain unclear. Therefore, a randomized controlled parallel clinical trial is currently underway at Chengdu University of Traditional Chinese Medicine, China. This trial is designed to explore the efficacy of and central responses to the He-Mu point combination in patients with functional dyspepsia using functional magnetic resonance imaging. A total of 105 patients with functional dyspepsia will be allocated into 3 groups: the low-He point group (puncturing at Zusanli (ST36)), Mu point group (puncturing at Zhongwan (CV12)), and He-Mu point combination group (puncturing at ST36 and CV12). Every participant will receive 20 sessions of manual acupuncture for 4 weeks. The needles will be inserted perpendicularly to a depth of 1 to 2 cun. The angle of rotation and twisting will range from 90 to 180 degrees, while lifting and thrusting will range from 0.3 to 0.5 cm. The various manipulations will be performed 60 to 90 times per minute. The needles will remain in place for 30 minutes, during which manipulation will be applied every 10 minutes. Magnetic resonance imaging will be performed before and after 20 sessions of acupuncture. The primary outcome is symptom improvement according to the Chinese version of the Nepean Dyspepsia Index. Secondary outcomes include the Leeds dyspepsia questionnaire, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Beck Anxiety Inventory, Beck Depression Inventory, and visual analogue scale scores before and after 10 and 20 sessions of acupuncture. Needle sensation and adverse events will be used to assess the therapeutic effects. This study will promote more widespread awareness of the benefits of acupoint combination in the clinical setting and provide a further explanation of the neuromechanism by which acupuncture at the He-Mu point combination for functional dyspepsia. Registration: Chinese Clinical Trial Registry, ChiCTR-IOR-15006402.

Effectiveness of adjuvant radiotherapy in patients with oropharyngeal and floor of mouth squamous cell carcinoma and concomitant histological verification of singular ipsilateral cervical lymph node metastasis (pN1-state) - A prospective multicenter randomized controlled clinical trial using a comprehensive cohort design

PubMed Central

2009-01-01

Background Modern radiotherapy plays an important role in therapy of advanced head and neck carcinomas. However, no clinical studies have been published addressing the effectiveness of postoperative radiotherapy in patients with small tumor (pT1, pT2) and concomitant ipsilateral metastasis of a single lymph node (pN1), which would provide a basis for a general treatment recommendation. Methods/Design The present study is a non-blinded, prospective, multi-center randomized controlled trial (RCT). As the primary clinical endpoint, overall-survival in patients receiving postoperative radiation therapy vs. patients without adjuvant therapy following curative intended surgery is compared. The aim of the study is to enroll 560 adult males and females for 1:1 randomization to one of the two treatment arms (irradiation/no irradiation). Since patients with small tumor (T1/T2) but singular lymph node metastasis are rare and the amount of patients consenting to randomization is not predictable in advance, all patients rejecting randomization will be treated as preferred and enrolled in a prospective observational study (comprehensive cohort design) after giving informed consent. This observational part of the trial will be performed with maximum consistency to the treatment and observation protocol of the RCT. Because the impact of patient preference for a certain treatment option is not calculable, parallel design of RCT and observational study may provide a maximum of evidence and efficacy for evaluation of treatment outcome. Secondary clinical endpoints are as follows: incidence and time to tumor relapse (locoregional relapse, lymph node involvement and distant metastatic spread), Quality of life as reported by EORTC (QLQ-C30 with H&N 35 module), and time from operation to orofacial rehabilitation. All tumors represent a homogeneous clinical state and therefore additional investigation of protein expression levels within resection specimen may serve for establishment of surrogate parameters of patient outcome. Conclusion The inherent challenges of a rare clinical condition (pN1) and two substantially different therapy arms would limit the practicality of a classical randomized study. The concept of a Comprehensive Cohort Design combines the preference of a randomized study, with the option of careful data interpretation within an observational study. Trial registration ClinicalTrials.gov: NCT00964977 PMID:20028566

The influence of multiple trials and computer-mediated communication on collaborative and individual semantic recall.

PubMed

Hinds, Joanne M; Payne, Stephen J

2018-04-01

Collaborative inhibition is a phenomenon where collaborating groups experience a decrement in recall when interacting with others. Despite this, collaboration has been found to improve subsequent individual recall. We explore these effects in semantic recall, which is seldom studied in collaborative retrieval. We also examine "parallel CMC", a synchronous form of computer-mediated communication that has previously been found to improve collaborative recall [Hinds, J. M., & Payne, S. J. (2016). Collaborative inhibition and semantic recall: Improving collaboration through computer-mediated communication. Applied Cognitive Psychology, 30(4), 554-565]. Sixty three triads completed a semantic recall task, which involved generating words beginning with "PO" or "HE" across three recall trials, in one of three retrieval conditions: Individual-Individual-Individual (III), Face-to-face-Face-to-Face-Individual (FFI) and Parallel-Parallel-Individual (PPI). Collaborative inhibition was present across both collaborative conditions. Individual recall in Recall 3 was higher when participants had previously collaborated in comparison to recalling three times individually. There was no difference between face-to-face and parallel CMC recall, however subsidiary analyses of instance repetitions and subjective organisation highlighted differences in group members' approaches to recall in terms of organisation and attention to others' contributions. We discuss the implications of these findings in relation to retrieval strategy disruption.

Design of the NL-ENIGMA study: Exploring the effect of Souvenaid on cerebral glucose metabolism in early Alzheimer's disease.

PubMed

Scheltens, Nienke M E; Kuyper, Ingrid S; Boellaard, Ronald; Barkhof, Frederik; Teunissen, Charlotte E; Broersen, Laus M; Lansbergen, Marieke M; van der Flier, Wiesje M; van Berckel, Bart N M; Scheltens, Philip

2016-11-01

Alzheimer's disease is associated with early synaptic loss. Specific nutrients are known to be rate limiting for synapse formation. Studies have shown that administering specific nutrients may improve memory function, possibly by increasing synapse formation. This Dutch study explores the Effect of a specific Nutritional Intervention on cerebral Glucose Metabolism in early Alzheimer's disease (NL-ENIGMA, Dutch Trial Register NTR4718, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4718). The NL-ENIGMA study is designed to test whether the specific multinutrient combination Fortasyn Connect present in the medical food Souvenaid influences cerebral glucose metabolism as a marker for improved synapse function. This study is a double-blind, randomized controlled parallel-group single-center trial. Forty drug-naive patients with mild cognitive impairment or mild dementia with evidence of amyloid deposition are 1:1 randomized to receive either the multinutrient combination or placebo once daily. Main exploratory outcome parameters include absolute quantitative positron emission tomography with 18 F-fluorodeoxyglucose (including arterial sampling) and standard uptake value ratios normalized for the cerebellum or pons after 24 weeks. We expect the NL-ENIGMA study to provide further insight in the potential of this multinutrient combination to improve synapse function.

A prospective 2-site parallel intervention trial of a research-based film to increase exercise amongst older hemodialysis patients.

PubMed

Kontos, Pia; Alibhai, Shabbir M H; Miller, Karen-Lee; Brooks, Dina; Colobong, Romeo; Parsons, Trisha; Jassal, Sarbjit Vanita; Thomas, Alison; Binns, Malcolm; Naglie, Gary

2017-01-26

Evidence suggests that exercise training for hemodialysis patients positively improves morbidity and mortality outcomes, yet exercise programs remain rare and are not systematically incorporated into care. We developed a research-based film, Fit for Dialysis, designed to introduce, motivate, and sustain exercise for wellness amongst older hemodialysis patients, and exercise counseling and support by nephrologists, nurses, and family caregivers. The objective of this clinical trial is to determine whether and in what ways Fit for Dialysis improves outcomes and influences knowledge/attitudes regarding the importance of exercise for wellness in the context of end-stage renal disease. This 2-site parallel intervention trial will recruit 60 older hemodialysis patients from two urban hospitals. The trial will compare the film + a 16-week exercise program in one hospital, with a 16-week exercise-only program in another hospital. Physical fitness and activity measures will be performed at baseline, 8 and 16 weeks, and 12 weeks after the end of the program. These include the 2-min Walk Test, Grip Strength, Duke Activity Status Index, and the Timed Up-and-Go Test, as well as wearing a pedometer for one week. Throughout the 16-week exercise program, and at 12 weeks after, we will record patients' exercise using the Godin Leisure-time Exercise Questionnaire. Patients will also keep a diary of the exercise that they do at home on non-dialysis days. Qualitative interviews, conducted at baseline, 8, and 16 weeks, will explore the impact of Fit for Dialysis on the knowledge/attitudes of patients, family caregivers, and nephrology staff regarding exercise for wellness, and in what ways the film is effective in educating, motivating, or sustaining patient exercise during dialysis, at home, and in the community. This research will determine for whom Fit for Dialysis is effective, why, and under what conditions. If Fit for Dialysis is proven beneficial to patients, nephrology staff and family caregivers, research-based film as a model to support exercise promotion and adherence could be used to support the National Kidney Foundation's guideline recommendation (NKF-KDOQI) that exercise be incorporated into the care and treatment of dialysis patients. NCT02754271 (ClinicalTrials.gov), retroactively registered on April 21, 2016.

The Acute Effect of Methylphenidate in Brazilian Male Children and Adolescents with ADHD: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Szobot, C. M.; Ketzer, C.; Parente, M. A.; Biederman, J.; Rohde, L. A.

2004-01-01

Objective: To evaluate the acute efficacy of methylphenidate (MPH) in Brazilian male children and adolescents with ADHD. Method: In a 4-day, double-blind, placebo-controlled, randomized, fix dose escalating, parallel-group trial, 36 ADHD children and adolescents were allocated to two groups: MPH (n = 19) and placebo (n = 17). Participants were…

Evaluating perceptual integration: uniting response-time- and accuracy-based methodologies.

PubMed

Eidels, Ami; Townsend, James T; Hughes, Howard C; Perry, Lacey A

2015-02-01

This investigation brings together a response-time system identification methodology (e.g., Townsend & Wenger Psychonomic Bulletin & Review 11, 391-418, 2004a) and an accuracy methodology, intended to assess models of integration across stimulus dimensions (features, modalities, etc.) that were proposed by Shaw and colleagues (e.g., Mulligan & Shaw Perception & Psychophysics 28, 471-478, 1980). The goal was to theoretically examine these separate strategies and to apply them conjointly to the same set of participants. The empirical phases were carried out within an extension of an established experimental design called the double factorial paradigm (e.g., Townsend & Nozawa Journal of Mathematical Psychology 39, 321-359, 1995). That paradigm, based on response times, permits assessments of architecture (parallel vs. serial processing), stopping rule (exhaustive vs. minimum time), and workload capacity, all within the same blocks of trials. The paradigm introduced by Shaw and colleagues uses a statistic formally analogous to that of the double factorial paradigm, but based on accuracy rather than response times. We demonstrate that the accuracy measure cannot discriminate between parallel and serial processing. Nonetheless, the class of models supported by the accuracy data possesses a suitable interpretation within the same set of models supported by the response-time data. The supported model, consistent across individuals, is parallel and has limited capacity, with the participants employing the appropriate stopping rule for the experimental setting.

Design Sketches For Optical Crossbar Switches Intended For Large-Scale Parallel Processing Applications

NASA Astrophysics Data System (ADS)

Hartmann, Alfred; Redfield, Steve

1989-04-01

This paper discusses design of large-scale (1000x 1000) optical crossbar switching networks for use in parallel processing supercom-puters. Alternative design sketches for an optical crossbar switching network are presented using free-space optical transmission with either a beam spreading/masking model or a beam steering model for internodal communications. The performances of alternative multiple access channel communications protocol-unslotted and slotted ALOHA and carrier sense multiple access (CSMA)-are compared with the performance of the classic arbitrated bus crossbar of conventional electronic parallel computing. These comparisons indicate an almost inverse relationship between ease of implementation and speed of operation. Practical issues of optical system design are addressed, and an optically addressed, composite spatial light modulator design is presented for fabrication to arbitrarily large scale. The wide range of switch architecture, communications protocol, optical systems design, device fabrication, and system performance problems presented by these design sketches poses a serious challenge to practical exploitation of highly parallel optical interconnects in advanced computer designs.

National Combustion Code: Parallel Implementation and Performance

NASA Technical Reports Server (NTRS)

Quealy, A.; Ryder, R.; Norris, A.; Liu, N.-S.

2000-01-01

The National Combustion Code (NCC) is being developed by an industry-government team for the design and analysis of combustion systems. CORSAIR-CCD is the current baseline reacting flow solver for NCC. This is a parallel, unstructured grid code which uses a distributed memory, message passing model for its parallel implementation. The focus of the present effort has been to improve the performance of the NCC flow solver to meet combustor designer requirements for model accuracy and analysis turnaround time. Improving the performance of this code contributes significantly to the overall reduction in time and cost of the combustor design cycle. This paper describes the parallel implementation of the NCC flow solver and summarizes its current parallel performance on an SGI Origin 2000. Earlier parallel performance results on an IBM SP-2 are also included. The performance improvements which have enabled a turnaround of less than 15 hours for a 1.3 million element fully reacting combustion simulation are described.

A non-pharmacologic approach to address challenging behaviors of Veterans with dementia: description of the tailored activity program-VA randomized trial

PubMed Central

2013-01-01

Background Behavioral symptoms accompanying dementia are associated with increased health care costs, reduced quality of life and daily functioning, heightened family caregiver burden, and nursing home placement. Standard care typically involves pharmacologic agents, but these are, at best, modestly effective, carry serious risks, including mortality, and do not address behavioral symptoms families consider most distressful and which may prompt nursing home placement. Given dementia’s devastating effects and the absence of an imminent cure, the Veterans Administration has supported the development and testing of new approaches to manage challenging behaviors at home. Methods/Design The Tailored Activity Program – Veterans Administration is a Phase III efficacy trial designed to reduce behavioral symptoms in Veterans with dementia living with their caregivers in the community. The study uses a randomized two-group parallel design with 160 diverse Veterans and caregivers. The experimental group receives a transformative patient-centric intervention designed to reduce the burden of behavioral symptoms in Veterans with dementia. An occupational therapist conducts an assessment to identify a Veteran’s preserved capabilities, deficit areas, previous roles, habits, and interests to develop activities tailored to the Veteran. Family caregivers are then trained to incorporate activities into daily care. The attention-control group receives bi-monthly telephone contact where education on topics relevant to dementia is provided to caregivers. Key outcomes include reduced frequency and severity of behavioral symptoms using the 12-item Neuropsychiatric Inventory (primary endpoint), reduced caregiver burden, enhanced skill acquisition, efficacy using activities, and time spent providing care at 4 months; and long-term effects (8 months) on the Veteran’s quality of life and frequency and severity of behavioral symptoms, and caregiver use of activities. The programs’ impact of Veterans Administration cost is also examined. Study precision will be increased through face-to-face research team trainings with procedural manuals and review of audio-taped interviews and intervention sessions. Discussion The Tailored Activity Program – Veterans Administration is designed to improve the quality of life of Veterans with dementia and lessen the burden of care on caregivers. Activities are tailored to reflect the Veteran’s preserved capabilities and interests to enhance active engagement, while not taxing areas of cognition that are most impaired. Trial registration ClinicalTrials.gov, NCT01357564 PMID:24060106

A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers: methodological issues in a feasibility study

PubMed Central

2012-01-01

Background Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown. Methods Attrition (dropouts) and compliance with treatment were assessed in a 25-week randomized, placebo controlled, crossover, feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers. Each treatment lasted 4 weeks with 2 weeks of washout in between. Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions. The interventions consisted of packets of green tea, black tea, caffeinated water, or placebo. Participants were assigned to each treatment for four weeks, and were instructed to drink five packets per day while on the treatment. Dropout from the trial and compliance (consumption of ≥ 85% of the prescribed treatment packets) are the main outcome measures reported. Results There was a high rate of dropout (51%) from the study, and the rates were significantly higher among smokers (64%) than non-smokers (36%). Among participants who completed the study the rate of compliance was 72%. The highest rates of dropouts occurred between the first and second treatment visits in both smokers (38% dropout) and non-smokers (18% dropout). Throughout the study smokers were more likely to dropout than non-smokers. Black tea treatment was associated with the highest rates of dropout among smokers (37%), but was associated with the lowest rate of dropout among non-smokers (4%). Conclusions In a study conducted to test the feasibility of a four-treatment crossover tea trial, a high rate of dropout among smokers and non-smokers was observed. Multi-arm crossover tea trials might pose a higher burden on participants and research is needed to improve adherence and treatment compliance in such trials. Trial registration number ISRCTN70410203 PMID:22800470

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.

A Robust and Scalable Software Library for Parallel Adaptive Refinement on Unstructured Meshes

NASA Technical Reports Server (NTRS)

Lou, John Z.; Norton, Charles D.; Cwik, Thomas A.

1999-01-01

The design and implementation of Pyramid, a software library for performing parallel adaptive mesh refinement (PAMR) on unstructured meshes, is described. This software library can be easily used in a variety of unstructured parallel computational applications, including parallel finite element, parallel finite volume, and parallel visualization applications using triangular or tetrahedral meshes. The library contains a suite of well-designed and efficiently implemented modules that perform operations in a typical PAMR process. Among these are mesh quality control during successive parallel adaptive refinement (typically guided by a local-error estimator), parallel load-balancing, and parallel mesh partitioning using the ParMeTiS partitioner. The Pyramid library is implemented in Fortran 90 with an interface to the Message-Passing Interface (MPI) library, supporting code efficiency, modularity, and portability. An EM waveguide filter application, adaptively refined using the Pyramid library, is illustrated.

An application of analyzing the trajectories of two disorders: A parallel piecewise growth model of substance use and attention-deficit/hyperactivity disorder.

PubMed

Mamey, Mary Rose; Barbosa-Leiker, Celestina; McPherson, Sterling; Burns, G Leonard; Parks, Craig; Roll, John

2015-12-01

Researchers often want to examine 2 comorbid conditions simultaneously. One strategy to do so is through the use of parallel latent growth curve modeling (LGCM). This statistical technique allows for the simultaneous evaluation of 2 disorders to determine the explanations and predictors of change over time. Additionally, a piecewise model can help identify whether there are more than 2 growth processes within each disorder (e.g., during a clinical trial). A parallel piecewise LGCM was applied to self-reported attention-deficit/hyperactivity disorder (ADHD) and self-reported substance use symptoms in 303 adolescents enrolled in cognitive-behavioral therapy treatment for a substance use disorder and receiving either oral-methylphenidate or placebo for ADHD across 16 weeks. Assessing these 2 disorders concurrently allowed us to determine whether elevated levels of 1 disorder predicted elevated levels or increased risk of the other disorder. First, a piecewise growth model measured ADHD and substance use separately. Next, a parallel piecewise LGCM was used to estimate the regressions across disorders to determine whether higher scores at baseline of the disorders (i.e., ADHD or substance use disorder) predicted rates of change in the related disorder. Finally, treatment was added to the model to predict change. While the analyses revealed no significant relationships across disorders, this study explains and applies a parallel piecewise growth model to examine the developmental processes of comorbid conditions over the course of a clinical trial. Strengths of piecewise and parallel LGCMs for other addictions researchers interested in examining dual processes over time are discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis.

PubMed

Thomas, Peter W; Thomas, Sarah; Kersten, Paula; Jones, Rosemary; Nock, Alison; Slingsby, Vicky; Green, Colin; Baker, Roger; Galvin, Kate; Hillier, Charles

2010-06-16

Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Current Controlled Trials ISRCTN76517470.

Bath additives for the treatment of childhood eczema (BATHE): protocol for multicentre parallel group randomised trial

PubMed Central

Santer, Miriam; Rumsby, Kate; Ridd, Matthew J; Francis, Nick A; Stuart, Beth; Chorozoglou, Maria; Wood, Wendy; Roberts, Amanda; Thomas, Kim S; Williams, Hywel C; Little, Paul

2015-01-01

Introduction Bath emollients are widely prescribed for childhood eczema, yet evidence of their benefits over direct application of emollients is lacking. Objectives To determine the clinical and cost-effectiveness of adding bath emollient to the standard management of eczema in children Methods and analysis Design: Pragmatic open 2-armed parallel group randomised controlled trial. Setting: General practitioner (GP) practices in England and Wales. Participants: Children aged over 12 months and less than 12 years with eczema, excluding inactive or very mild eczema (5 or less on Nottingham Eczema Severity Scale). Interventions: Children will be randomised to either bath emollients plus standard eczema care or standard eczema care only. Outcome measures: Primary outcome is long-term eczema severity, measured by the Patient-Oriented Eczema Measure (POEM) repeated weekly for 16 weeks. Secondary outcomes include: number of eczema exacerbations resulting in healthcare consultations over 1 year; eczema severity over 1 year; disease-specific and generic quality of life; medication use and healthcare resource use; cost-effectiveness. Aiming to detect a mean difference between groups of 2.0 (SD 7.0) in weekly POEM scores over 16 weeks (significance 0.05, power 0.9), allowing for 20% loss to follow-up, gives a total sample size of 423 children. We will use repeated measures analysis of covariance, or a mixed model, to analyse weekly POEM scores. We will control for possible confounders, including baseline eczema severity and child's age. Cost-effectiveness analysis will be carried out from a National Health Service (NHS) perspective. Ethics and dissemination This protocol was approved by Newcastle and North Tyneside 1 NRES committee 14/NE/0098. Follow-up will be completed in 2017. Findings will be disseminated to participants and carers, the public, dermatology and primary care journals, guideline developers and decision-makers. Trial registration number ISRCTN84102309. PMID:26525422

A parallel-group, randomised controlled trial of a multimedia, self-directed, coping skills training intervention for patients with cancer and their partners: design and rationale.

PubMed

Lambert, Sylvie D; Girgis, Afaf; McElduff, Patrick; Turner, Jane; Levesque, Janelle V; Kayser, Karen; Mihalopoulos, Cathrine; Shih, Sophy T F; Barker, Daniel

2013-01-01

Coping skills training interventions have been found to be efficacious in helping both patients and their partners manage the physical and emotional challenges they face following a cancer diagnosis. However, many of these interventions are costly and not sustainable. To overcome these issues, a self-directed format is increasingly used. The efficacy of self-directed interventions for patients has been supported; however, no study has reported on the outcomes for their partners. This study will test the efficacy of Coping-Together-a multimedia, self-directed, coping skills training intervention for patients with cancer and their partners. The proposed three-group, parallel, randomised controlled trial will recruit patients diagnosed in the past 4 months with breast, prostate, colorectal cancer or melanoma through their treating clinician. Patients and their partners will be randomised to (1) a minimal ethical care (MEC) condition-selected Cancer Council New South Wales booklets and a brochure for the Cancer Council Helpline, (2) Coping-Together generic-MEC materials, the six Coping-Together booklets and DVD, the Cancer Council Queensland relaxation audio CD and login to the Coping-Together website or (3) Coping-Together tailored-MEC materials, the Coping-Together DVD, the login to the website and only those Coping-Together booklet sections that pertain to their direct concerns. Anxiety (primary outcome), distress, depression, dyadic adjustment, quality of life, illness or caregiving appraisal, self-efficacy and dyadic and individual coping will be assessed before receiving the study material (ie, baseline) and again at 3, 6 and 12 months postbaseline. Intention-to-treat and per protocol analysis will be conducted. This study has been approved by the relevant local area health and University ethics committees. Study findings will be disseminated not only through peer-reviewed publications and conference presentations but also through educational outreach visits, publication of lay research summaries in consumer newsletters and publications targeting clinicians. Australian New Zealand Clinical Trials Registry ACTRN12613000491763 (03/05/2013).

Design of a massively parallel computer using bit serial processing elements

NASA Technical Reports Server (NTRS)

Aburdene, Maurice F.; Khouri, Kamal S.; Piatt, Jason E.; Zheng, Jianqing

1995-01-01

A 1-bit serial processor designed for a parallel computer architecture is described. This processor is used to develop a massively parallel computational engine, with a single instruction-multiple data (SIMD) architecture. The computer is simulated and tested to verify its operation and to measure its performance for further development.

Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods.

PubMed

McClellan, Jon; Sikich, Linmarie; Findling, Robert L; Frazier, Jean A; Vitiello, Benedetto; Hlastala, Stefanie A; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E; Ritz, Louise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

2007-08-01

The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

Capacity-building and clinical competence in infectious disease in Uganda: a mixed-design study with pre/post and cluster-randomized trial components.

PubMed

Weaver, Marcia R; Crozier, Ian; Eleku, Simon; Makanga, Gyaviira; Mpanga Sebuyira, Lydia; Nyakake, Janepher; Thompson, MaryLou; Willis, Kelly

2012-01-01

Best practices for training mid-level practitioners (MLPs) to improve global health-services are not well-characterized. Two hypotheses were: 1) Integrated Management of Infectious Disease (IMID) training would improve clinical competence as tested with a single arm, pre-post design, and 2) on-site support (OSS) would yield additional improvements as tested with a cluster-randomized trial. Thirty-six Ugandan health facilities (randomized 1∶1 to parallel OSS and control arms) enrolled two MLPs each. All MLPs participated in IMID (3-week core course, two 1-week boost sessions, distance learning). After the 3-week course, OSS-arm trainees participated in monthly OSS. Twelve written case scenarios tested clinical competencies in HIV/AIDS, tuberculosis, malaria, and other infectious diseases. Each participant completed different randomly-assigned blocks of four scenarios before IMID (t0), after 3-week course (t1), and after second boost course (t2, 24 weeks after t1). Scoring guides were harmonized with IMID content and Ugandan national policy. Score analyses used a linear mixed-effects model. The primary outcome measure was longitudinal change in scenario scores. Scores were available for 856 scenarios. Mean correct scores at t0, t1, and t2 were 39.3%, 49.1%, and 49.6%, respectively. Mean score increases (95% CI, p-value) for t0-t1 (pre-post period) and t1-t2 (parallel-arm period) were 12.1 ((9.6, 14.6), p<0.001) and -0.6 ((-3.1, +1.9), p = 0.647) percent for OSS arm and 7.5 ((5.0, 10.0), p<0.001) and 1.6 ((-1.0, +4.1), p = 0.225) for control arm. The estimated mean difference in t1 to t2 score change, comparing arm A (participated in OSS) vs. arm B was -2.2 ((-5.8, +1.4), p = 0.237). From t0-t2, mean scores increased for all 12 scenarios. Clinical competence increased significantly after a 3-week core course; improvement persisted for 24 weeks. No additional impact of OSS was observed. Data on clinical practice, facility-level performance and health outcomes will complete assessment of overall impact of IMID and OSS. ClinicalTrials.gov NCT01190540.

mHealth Intervention to Improve Diabetes Risk Behaviors in India: A Prospective, Parallel Group Cohort Study.

PubMed

Pfammatter, Angela; Spring, Bonnie; Saligram, Nalini; Davé, Raj; Gowda, Arun; Blais, Linelle; Arora, Monika; Ranjani, Harish; Ganda, Om; Hedeker, Donald; Reddy, Sethu; Ramalingam, Sandhya

2016-08-05

In low/middle income countries like India, diabetes is prevalent and health care access limited. Most adults have a mobile phone, creating potential for mHealth interventions to improve public health. To examine the feasibility and initial evidence of effectiveness of mDiabetes, a text messaging program to improve diabetes risk behaviors, a global nonprofit organization (Arogya World) implemented mDiabetes among one million Indian adults. A prospective, parallel cohort design was applied to examine whether mDiabetes improved fruit, vegetable, and fat intakes and exercise. Intervention participants were randomly selected from the one million Nokia subscribers who elected to opt in to mDiabetes. Control group participants were randomly selected from non-Nokia mobile phone subscribers. mDiabetes participants received 56 text messages in their choice of 12 languages over 6 months; control participants received no contact. Messages were designed to motivate improvement in diabetes risk behaviors and increase awareness about the causes and complications of diabetes. Participant health behaviors (exercise and fruit, vegetable, and fat intake) were assessed between 2012 and 2013 via telephone surveys by blinded assessors at baseline and 6 months later. Data were cleaned and analyzed in 2014 and 2015. 982 participants in the intervention group and 943 in the control group consented to take the phone survey at baselne. At the end of the 6-month period, 611 (62.22%) in the intervention and 632 (67.02%) in the control group completed the follow-up telephone survey. Participants receiving texts demonstrated greater improvement in a health behavior composite score over 6 months, compared with those who received no messages F(1, 1238) = 30.181, P<.001, 95% CI, 0.251-0.531. Fewer intervention participants demonstrated health behavior decline compared with controls. Improved fruit, vegetable, and fat consumption (P<.01) but not exercise were observed in those receiving messages, as compared with controls. A text messaging intervention was feasible and showed initial evidence of effectiveness in improving diabetes-related health behaviors, demonstrating the potential to facilitate population-level behavior change in a low/middle income country. Australian New Zealand Clinical Trials Registry (ACTRN): 12615000423516; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367946&isReview=true (Archived by WebCite at http://www.webcitation.org/6j5ptaJgF).

Preventing relapse in recurrent depression using mindfulness-based cognitive therapy, antidepressant medication or the combination: trial design and protocol of the MOMENT study

PubMed Central

2012-01-01

Background Depression is a common psychiatric disorder characterized by a high rate of relapse and recurrence. The most commonly used strategy to prevent relapse/recurrence is maintenance treatment with antidepressant medication (mADM). Recently, it has been shown that Mindfulness-Based Cognitive Therapy (MBCT) is at least as effective as mADM in reducing the relapse/recurrence risk. However, it is not yet known whether combination treatment of MBCT and mADM is more effective than either of these treatments alone. Given the fact that most patients have a preference for either mADM or for MBCT, the aim of the present study is to answer the following questions. First, what is the effectiveness of MBCT in addition to mADM? Second, how large is the risk of relapse/recurrence in patients withdrawing from mADM after participating in MBCT, compared to those who continue to use mADM after MBCT? Methods/design Two parallel-group, multi-center randomized controlled trials are conducted. Adult patients with a history of depression (3 or more episodes), currently either in full or partial remission and currently treated with mADM (6 months or longer) are recruited. In the first trial, we compare mADM on its own with mADM plus MBCT. In the second trial, we compare MBCT on its own, including tapering of mADM, with mADM plus MBCT. Follow-up assessments are administered at 3-month intervals for 15 months. Primary outcome is relapse/recurrence. Secondary outcomes are time to, duration and severity of relapse/recurrence, quality of life, personality, several process variables, and incremental cost-effectiveness ratio. Discussion Taking into account patient preferences, this study will provide information about a) the clinical and cost-effectiveness of mADM only compared with mADM plus MBCT, in patients with a preference for mADM, and b) the clinical and cost-effectiveness of withdrawing from mADM after MBCT, compared with mADM plus MBCT, in patients with a preference for MBCT. Trial registration ClinicalTrials.gov: NCT00928980 PMID:22925198

Effects of Anma massage therapy (Japanese massage) for gynecological cancer survivors: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Cancer patients and survivors regularly feel anxious about cancer recurrence or death, even after the conclusion of medical treatment, and they are often highly physiologically and psychologically stressed. Massage therapy is one of the most widely used complementary and alternative therapies used in the hope of alleviating such stress and physical and psychological complaints and to improve health-related quality of life. This randomized phase III, two-armed, parallel group, clinical trial was designed after obtaining positive findings in a preliminary study. The primary objective is to verify the effects of continuous Japanese massage therapy, referred to as Anma therapy, for cancer survivors. The secondary objective is to confirm the immediate effects of a single Anma massage session for cancer survivors. Methods/Design Sixty cancer survivors older than 20 years of age who have had histologically confirmed uterine cervical, endometrial, ovarian, fallopian tube or peritoneal cancer in the past, but with no recurrence for more than 3 years since receiving standard medical treatment, are being recruited by gynecologists in medical facilities. In the coordinating office, they are randomly allocated to two groups (n = 30 each): an Anma massage group receiving a 40-min Anma massage session once weekly over a 2-month intervention period (total of eight Anma massage sessions) and a control group being followed by medical doctors and receiving no Anma massage sessions. The primary end point is the severity of physical subjective symptoms that cancer survivors report in daily life, assessed using a Visual Analogue Scale. Secondary end points are urine and saliva analyses, psychological condition and health-related quality-of-life scores as determined on the basis of a self-report questionnaire. Discussion Using the evidence-based findings of this trial, medical professionals should be able to explain the benefits conferred by Anma massage to cancer survivors and provide higher-quality information to better inform patients regarding their decisions about whether to receive such therapy. Trial registration This trial is registered with the UMIN Clinical Trials Registry as UMIN000009097. PMID:23883162

Comparison of tai chi vs. strength training for fall prevention among female cancer survivors: study protocol for the GET FIT trial

PubMed Central

2012-01-01

Background Women with cancer are significantly more likely to fall than women without cancer placing them at higher risk of fall-related fractures, other injuries and disability. Currently, no evidence-based fall prevention strategies exist that specifically target female cancer survivors. The purpose of the GET FIT (Group Exercise Training for Functional Improvement after Treatment) trial is to compare the efficacy of two distinct types of exercise, tai chi versus strength training, to prevent falls in women who have completed treatment for cancer. The specific aims of this study are to: 1) Determine and compare the efficacy of both tai chi training and strength training to reduce falls in older female cancer survivors, 2) Determine the mechanism(s) by which tai chi and strength training each reduces falls and, 3) Determine whether or not the benefits of each intervention last after structured training stops. Methods/Design We will conduct a three-group, single-blind, parallel design, randomized controlled trial in women, aged 50–75 years old, who have completed chemotherapy for cancer comparing 1) tai chi 2) strength training and 3) a placebo control group of seated stretching exercise. Women will participate in supervised study programs twice per week for six months and will be followed for an additional six months after formal training stops. The primary outcome in this study is falls, which will be prospectively tracked by monthly self-report. Secondary outcomes are maximal leg strength measured by isokinetic dynamometry, postural stability measured by computerized dynamic posturography and physical function measured by the Physical Performance Battery, all measured at baseline, 3, 6 and 12 months. The sample for this trial (N=429, assuming 25% attrition) will provide adequate statistical power to detect at least a 47% reduction in the fall rate over 1 year by being in either of the 2 exercise groups versus the control group. Discussion The GET FIT trial will provide important new knowledge about preventing falls using accessible and implementable exercise interventions for women following chemotherapy for cancer. ClinicalTrials.gov NCT01635413 PMID:23217054

Concurrent Collections (CnC): A new approach to parallel programming

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

Knobe, Kathleen

2010-05-07

A common approach in designing parallel languages is to provide some high level handles to manipulate the use of the parallel platform. This exposes some aspects of the target platform, for example, shared vs. distributed memory. It may expose some but not all types of parallelism, for example, data parallelism but not task parallelism. This approach must find a balance between the desire to provide a simple view for the domain expert and provide sufficient power for tuning. This is hard for any given architecture and harder if the language is to apply to a range of architectures. Either simplicitymore » or power is lost. Instead of viewing the language design problem as one of providing the programmer with high level handles, we view the problem as one of designing an interface. On one side of this interface is the programmer (domain expert) who knows the application but needs no knowledge of any aspects of the platform. On the other side of the interface is the performance expert (programmer or program) who demands maximal flexibility for optimizing the mapping to a wide range of target platforms (parallel / serial, shared / distributed, homogeneous / heterogeneous, etc.) but needs no knowledge of the domain. Concurrent Collections (CnC) is based on this separation of concerns. The talk will present CnC and its benefits. About the speaker. Kathleen Knobe has focused throughout her career on parallelism especially compiler technology, runtime system design and language design. She worked at Compass (aka Massachusetts Computer Associates) from 1980 to 1991 designing compilers for a wide range of parallel platforms for Thinking Machines, MasPar, Alliant, Numerix, and several government projects. In 1991 she decided to finish her education. After graduating from MIT in 1997, she joined Digital Equipment’s Cambridge Research Lab (CRL). She stayed through the DEC/Compaq/HP mergers and when CRL was acquired and absorbed by Intel. She currently works in the Software and Services Group / Technology Pathfinding and Innovation.« less

Concurrent Collections (CnC): A new approach to parallel programming

ScienceCinema

Knobe, Kathleen

2018-04-16

A common approach in designing parallel languages is to provide some high level handles to manipulate the use of the parallel platform. This exposes some aspects of the target platform, for example, shared vs. distributed memory. It may expose some but not all types of parallelism, for example, data parallelism but not task parallelism. This approach must find a balance between the desire to provide a simple view for the domain expert and provide sufficient power for tuning. This is hard for any given architecture and harder if the language is to apply to a range of architectures. Either simplicity or power is lost. Instead of viewing the language design problem as one of providing the programmer with high level handles, we view the problem as one of designing an interface. On one side of this interface is the programmer (domain expert) who knows the application but needs no knowledge of any aspects of the platform. On the other side of the interface is the performance expert (programmer or program) who demands maximal flexibility for optimizing the mapping to a wide range of target platforms (parallel / serial, shared / distributed, homogeneous / heterogeneous, etc.) but needs no knowledge of the domain. Concurrent Collections (CnC) is based on this separation of concerns. The talk will present CnC and its benefits. About the speaker. Kathleen Knobe has focused throughout her career on parallelism especially compiler technology, runtime system design and language design. She worked at Compass (aka Massachusetts Computer Associates) from 1980 to 1991 designing compilers for a wide range of parallel platforms for Thinking Machines, MasPar, Alliant, Numerix, and several government projects. In 1991 she decided to finish her education. After graduating from MIT in 1997, she joined Digital Equipment’s Cambridge Research Lab (CRL). She stayed through the DEC/Compaq/HP mergers and when CRL was acquired and absorbed by Intel. She currently works in the Software and Services Group / Technology Pathfinding and Innovation.

Precompetitive Data Sharing as a Catalyst to Address Unmet Needs in Parkinson’s Disease 1

PubMed Central

Stephenson, Diane; Hu, Michele T.; Romero, Klaus; Breen, Kieran; Burn, David; Ben-Shlomo, Yoav; Bhattaram, Atul; Isaac, Maria; Venuto, Charles; Kubota, Ken; Little, Max A.; Friend, Stephen; Lovestone, Simon; Morris, Huw R.; Grosset, Donald; Sutherland, Margaret; Gallacher, John; Williams-Gray, Caroline; Bain, Lisa J.; Avilés, Enrique; Marek, Ken; Toga, Arthur W.; Stark, Yafit; Forrest Gordon, Mark; Ford, Steve

2015-01-01

Abstract Parkinson’s disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson’s UK and co-organized by Critical Path Institute’s (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success. Government agencies included EMA, FDA, NINDS/NIH and IMI (Innovative Medicines Initiative). Emerging discoveries in new biomarkers and genetic endophenotypes are contributing to our understanding of the underlying pathophysiology of PD. In parallel there is growing recognition that early intervention will be key for successful treatments aimed at disease modification. At present, there is a lack of a comprehensive understanding of disease progression and the many factors that contribute to disease progression heterogeneity. Novel therapeutic targets and trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination are required. The integration of robust clinical data sets is viewed as a powerful approach to hasten medical discovery and therapies, as is being realized across diverse disease conditions employing big data analytics for healthcare. The application of lessons learned from parallel efforts is critical to identify barriers and enable a viable path forward. A roadmap is presented for a regulatory, academic, industry and advocacy driven integrated initiative that aims to facilitate and streamline new drug trials and registrations in Parkinson’s disease. PMID:26406139

Efficacy and safety of combined treatment of miniscalpel acupuncture and non-steroidal anti-inflammatory drugs: an assessor-blinded randomized controlled pilot study.

PubMed

Jun, Seungah; Lee, Jung Hee; Gong, Han Mi; Chung, Yeon-Joong; Kim, Ju-Ran; Park, Chung A; Choi, Seong Hun; Lee, Geon-Mok; Lee, Hyun-Jong; Kim, Jae Soo

2018-01-12

Chronic neck pain is a common musculoskeletal disease during the lifespan of an individual. With an increase in dependence on computer technology, the prevalence of chronic neck pain is expected to rise and this can lead to socioeconomic problems. We have designed the current pilot study to evaluate the efficacy and safety of miniscalpel acupuncture treatment combined with non-steroidal anti-inflammatory drugs (NSAIDs) in patients with chronic neck pain. This seven-week clinical trial has been designed as an assessor-blinded, randomized controlled trial with three parallel arms. Thirty-six patients will be recruited and randomly allocated to three treatment groups: miniscalpel acupuncture treatment; NSAIDs; and miniscalpel acupuncture treatment combined with NSAIDs. Patients in the miniscalpel acupuncture and combined treatment groups will receive three sessions of miniscalpel acupuncture over a three-week period. Patients in the NSAIDs and combined treatment groups will receive zaltoprofen (one oral tablet, three times a day for three weeks). Primary and secondary outcomes will be measured at weeks 0 (baseline), 1, 2, 3 (primary end point), and 7 (four weeks after treatment completion) using the visual analogue scale and the Neck Disability Index, EuroQol 5-dimension questionnaire, and Patients' Global Impression of Change scale, respectively. Adverse events will also be recorded. This pilot study will provide a basic foundation for a future large-scale trial as well as information about the feasibility of miniscalpel acupuncture treatment combined with NSAIDs for chronic neck pain. Korean Clinical Research Information Service registry, KCT0002258 . Registered on 9 March 2017.

Outcome of patients after lower limb fracture with partial weight bearing postoperatively treated with or without anti-gravity treadmill (alter G®) during six weeks of rehabilitation - a protocol of a prospective randomized trial.

PubMed

Henkelmann, Ralf; Schneider, Sebastian; Müller, Daniel; Gahr, Ralf; Josten, Christoph; Böhme, Jörg

2017-03-14

Partial or complete immobilization leads to different adjustment processes like higher risk of muscle atrophy or a decrease of general performance. The present study is designed to prove efficacy of the anti-gravity treadmill (alter G®) compared to a standard rehabilitation protocol in patients with tibial plateau (group 1)or ankle fractures (group 2) with six weeks of partial weight bearing of 20 kg. This prospective randomized study will include a total of 60 patients for each group according to predefined inclusion and exclusion criteria. 1:1 randomization will be performed centrally via fax supported by the Clinical Trial Centre Leipzig (ZKS Leipzig). Patients in the treatment arm will be treated with an anti-gravity treadmill (alter G®) instead of physiotherapy. The protocol is designed parallel to standard physiotherapy with a frequency of two to three times of training with the treadmill per week with duration of 20 min for six weeks. Up to date no published randomized controlled trial with an anti-gravity treadmill is available. The findings of this study can help to modify rehabilitation of patients with partial weight bearing due to their injury or postoperative protocol. It will deliver interesting results if an anti-gravity treadmill is useful in rehabilitation in those patients. Further ongoing studies will identify different indications for an anti-gravity treadmill. Thus, in connection with those studies, a more valid statement regarding safety and efficacy is possible. NCT02790229 registered on May 29, 2016.

Protocol: the effect of 12 weeks of Tai Chi practice on anxiety in healthy but stressed people compared to exercise and wait-list comparison groups: a randomized controlled trial.

PubMed

Zheng, Shuai; Lal, Sara; Meier, Peter; Sibbritt, David; Zaslawski, Chris

2014-06-01

Stress is a major problem in today's fast-paced society and can lead to serious psychosomatic complications. The ancient Chinese mind-body exercise of Tai Chi may provide an alternative and self-sustaining option to pharmaceutical medication for stressed individuals to improve their coping mechanisms. The protocol of this study is designed to evaluate whether Tai Chi practice is equivalent to standard exercise and whether the Tai Chi group is superior to a wait-list control group in improving stress coping levels. This study is a 6-week, three-arm, parallel, randomized, clinical trial designed to evaluate Tai Chi practice against standard exercise and a Tai Chi group against a nonactive control group over a period of 6 weeks with a 6-week follow-up. A total of 72 healthy adult participants (aged 18-60 years) who are either Tai Chi naïve or have not practiced Tai Chi in the past 12 months will be randomized into a Tai Chi group (n = 24), an exercise group (n = 24) or a wait-list group (n = 24). The primary outcome measure will be the State Trait Anxiety Inventory with secondary outcome measures being the Perceived Stress Scale 14, heart rate variability, blood pressure, Short Form 36 and a visual analog scale. The protocol is reported using the appropriate Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) items. Copyright © 2014. Published by Elsevier B.V.

Parallel integer sorting with medium and fine-scale parallelism

NASA Technical Reports Server (NTRS)

Dagum, Leonardo

1993-01-01

Two new parallel integer sorting algorithms, queue-sort and barrel-sort, are presented and analyzed in detail. These algorithms do not have optimal parallel complexity, yet they show very good performance in practice. Queue-sort designed for fine-scale parallel architectures which allow the queueing of multiple messages to the same destination. Barrel-sort is designed for medium-scale parallel architectures with a high message passing overhead. The performance results from the implementation of queue-sort on a Connection Machine CM-2 and barrel-sort on a 128 processor iPSC/860 are given. The two implementations are found to be comparable in performance but not as good as a fully vectorized bucket sort on the Cray YMP.

Whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults.

PubMed

Costello, Joseph T; Baker, Philip R A; Minett, Geoffrey M; Bieuzen, Francois; Stewart, Ian B; Bleakley, Chris

2015-09-18

Recovery strategies are often used with the intention of preventing or minimising muscle soreness after exercise. Whole-body cryotherapy, which involves a single or repeated exposure(s) to extremely cold dry air (below -100 °C) in a specialised chamber or cabin for two to four minutes per exposure, is currently being advocated as an effective intervention to reduce muscle soreness after exercise. To assess the effects (benefits and harms) of whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, the British Nursing Index and the Physiotherapy Evidence Database. We also searched the reference lists of articles, trial registers and conference proceedings, handsearched journals and contacted experts.The searches were run in August 2015. We aimed to include randomised and quasi-randomised trials that compared the use of whole-body cryotherapy (WBC) versus a passive or control intervention (rest, no treatment or placebo treatment) or active interventions including cold or contrast water immersion, active recovery and infrared therapy for preventing or treating muscle soreness after exercise in adults. We also aimed to include randomised trials that compared different durations or dosages of WBC. Our prespecified primary outcomes were muscle soreness, subjective recovery (e.g. tiredness, well-being) and adverse effects. Two review authors independently screened search results, selected studies, assessed risk of bias and extracted and cross-checked data. Where appropriate, we pooled results of comparable trials. The random-effects model was used for pooling where there was substantial heterogeneity. We assessed the quality of the evidence using GRADE. Four laboratory-based randomised controlled trials were included. These reported results for 64 physically active predominantly young adults (mean age 23 years). All but four participants were male. Two trials were parallel group trials (44 participants) and two were cross-over trials (20 participants). The trials were heterogeneous, including the type, temperature, duration and frequency of WBC, and the type of preceding exercise. None of the trials reported active surveillance of predefined adverse events. All four trials had design features that carried a high risk of bias, potentially limiting the reliability of their findings. The evidence for all outcomes was classified as 'very low' quality based on the GRADE criteria.Two comparisons were tested: WBC versus control (rest or no WBC), tested in four studies; and WBC versus far-infrared therapy, also tested in one study. No studies compared WBC with other active interventions, such as cold water immersion, or different types and applications of WBC.All four trials compared WBC with rest or no WBC. There was very low quality evidence for lower self-reported muscle soreness (pain at rest) scores after WBC at 1 hour (standardised mean difference (SMD) -0.77, 95% confidence interval (CI) -1.42 to -0.12; 20 participants, 2 cross-over trials); 24 hours (SMD -0.57, 95% CI -1.48 to 0.33) and 48 hours (SMD -0.58, 95% CI -1.37 to 0.21), both with 38 participants, 2 cross-over studies, 1 parallel group study; and 72 hours (SMD -0.65, 95% CI -2.54 to 1.24; 29 participants, 1 cross-over study, 1 parallel group study). Of note is that the 95% CIs also included either no between-group differences or a benefit in favour of the control group. One small cross-over trial (9 participants) found no difference in tiredness but better well-being after WBC at 24 hours post exercise. There was no report of adverse events.One small cross-over trial involving nine well-trained runners provided very low quality evidence of lower levels of muscle soreness after WBC, when compared with infrared therapy, at 1 hour follow-up, but not at 24 or 48 hours. The same trial found no difference in well-being but less tiredness after WBC at 24 hours post exercise. There was no report of adverse events. There is insufficient evidence to determine whether whole-body cryotherapy (WBC) reduces self-reported muscle soreness, or improves subjective recovery, after exercise compared with passive rest or no WBC in physically active young adult males. There is no evidence on the use of this intervention in females or elite athletes. The lack of evidence on adverse events is important given that the exposure to extreme temperature presents a potential hazard. Further high-quality, well-reported research in this area is required and must provide detailed reporting of adverse events.

Efficacy and safety of CP-945,598, a selective cannabinoid CB1 receptor antagonist, on weight loss and maintenance.

PubMed

Aronne, Louis J; Finer, Nick; Hollander, Priscilla A; England, Richard D; Klioze, Solomon S; Chew, Robert D; Fountaine, Robert J; Powell, Coralie M; Obourn, John D

2011-07-01

Three double-blind, placebo-controlled, three-parallel-group, multicenter phase 3 trials were conducted to assess the efficacy and safety of CP-945,598 for weight loss and weight-loss maintenance. Two trials were designed to be 2 years in duration (in obese and overweight patients) and one as a 1-year study (in obese and overweight patients with type 2 diabetes). However, the 2-year trials and the CP-945,598 development program were terminated before completion due to changing regulatory perspectives of CB1 receptor-related drugs. In total, 1,253 and 2,536 participants in the two 2-year multinational and North American studies were randomized to 10-mg CP-945,598 (n = 360; 718); 20-mg CP-945,598 (n = 534, 1,084) and placebo (n = 359, 734), respectively; and 975 participants were randomized to 10-mg CP-945,598 (n = 318); 20-mg CP-945,598 (n = 320); and placebo (n = 337) in the 1-year multinational diabetes trial. Baseline demographics were similar between treatment groups within each trial. One year of treatment with CP-945,598 resulted in a dose-related mean percentage reduction from baseline body-weight in all trials. A significant proportion of all participants also achieved 5% and 10% weight loss after 1 year. In participants with mainly well-controlled type 2 diabetes, the combination of lifestyle and CP-945,598 induced substantial improvements in glycemic control. The most frequent adverse events (AEs) for CP-945,598 were: diarrhea, nausea, nasopharyngitis, and headache. Self-reported experiences of anxiety and suicidal thoughts were higher with CP-945,598 than placebo, as were the incidence of depression and depressed mood. However, the reported increases in psychiatric symptoms were not consistently dose dependent.

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

Guided Internet-based versus face-to-face clinical care in the management of tinnitus: study protocol for a multi-centre randomised controlled trial.

PubMed

Beukes, Eldré W; Baguley, David M; Allen, Peter M; Manchaiah, Vinaya; Andersson, Gerhard

2017-04-21

Innovative strategies are required to improve access to evidence-based tinnitus interventions. A guided Internet-based cognitive behavioural therapy (iCBT) intervention for tinnitus was therefore developed for a U.K. Initial clinical trials indicated efficacy of iCBT at reducing tinnitus severity and associated comorbidities such as insomnia and depression. The aim of this phase III randomised controlled trial is to compare this new iCBT intervention with an established intervention, namely face-to-face clinical care for tinnitus. This will be a multi-centre study undertaken across three hospitals in the East of England. The design is a randomised, two-arm, parallel-group, non-inferiority trial with a 2-month follow-up. The experimental group will receive the guided iCBT intervention, whereas the active control group will receive the usual face-to-face clinical care. An independent researcher will randomly assign participants, using a computer-generated randomisation schedule, after stratification for tinnitus severity. There will be 46 participants in each group. The primary assessment measure will be the Tinnitus Functional Index. Data analysis will establish whether non-inferiority is achieved using a pre-defined non-inferiority margin. This protocol outlines phase III of a clinical trial comparing a new iCBT with established face-to-face care for tinnitus. If guided iCBT for tinnitus proves to be as effective as the usual tinnitus care, it may be a viable additional management route for individuals with tinnitus. This could increase access to evidence-based effective tinnitus care and reduce the pressures on existing health care systems. ClinicalTrials.gov identifier: NCT02665975 . Registered on 22 January 2016.

MYPLAN -mobile phone application to manage crisis of persons at risk of suicide: study protocol for a randomized controlled trial.

PubMed

Andreasson, Kate; Krogh, Jesper; Bech, Per; Frandsen, Hanne; Buus, Niels; Stanley, Barbara; Kerkhof, Ad; Nordentoft, Merete; Erlangsen, Annette

2017-04-11

Persons with a past episode of self-harm or severe suicidal ideation are at elevated risk of self-harm as well as dying by suicide. It is well established that suicidal ideation fluctuates over time. Previous studies have shown that a personal safety plan can assist in providing support, when a person experiences suicide ideation, and help seeking professional assistance if needed. The aim of the trial is to determine whether a newly developed safety mobile app is more effective in reducing suicide ideation and other symptoms, compared to a safety plan on paper. The trial is designed as a two-arm, observer-blinded, parallel-group randomized clinical superiority trial, where participants will either receive: (1) Experimental intervention: the safety plan provided as the app MyPlan, or (2) Treatment as Usual: the safety plan in the original paper format. Based on a power calculation, a total of 546 participants, 273 in each arm will be included. They will be recruited from Danish Suicide Prevention Clinics. Both groups will receive standard psychosocial therapeutic care, up to 8-10 sessions of supportive psychotherapy. Primary outcome will be reduction in suicide ideation after 12 months. Follow-up interviews will be conducted at 3, 6, 9, and 12 months after date of inclusion. A safety plan is a mandatory part of the treatment in the Suicide Prevention Clinics in Demark. There are no studies investigating the effectiveness of a safety plan app compared to a safety plan on paper on reducing suicide ideation in patients with suicide ideation and suicidal behavior. The trial will gain new knowledge of whether modern technology can augment the effects of traditional personalized safety planning. ClinicalTrials.gov, NCT02877316 . Registered on 19 August 2016.

Wrist-ankle acupuncture (WAA) for primary dysmenorrhea (PD) of young females: study protocol for a randomized controlled trial.

PubMed

Chen, Yingfan; Tian, Sinan; Tian, Jing; Shu, Shi

2017-08-22

Primary dysmenorrhea (PD) is one of the most common health complaints all over the world, specifically among young females. Acupuncture has been employed to relieve the pain-based symptoms and to avoid the side effects of conventional medication, and wrist-ankle acupuncture (WAA) has confirmed analgesic efficacy for various types of pain. The aim of this study is to evaluate the immediate analgesia effect of WAA on PD of young females. This study will carry out a randomized parallel controlled single-blind trial to observe the immediate analgesia effect of WAA in PD of young females. Sixty participants who meet inclusion criteria will be recruited from September 2016 to September 2017 in Changhai hospital of China. They are randomly assigned to WAA therapy or sham acupuncture groups (30 patients for each group), and then receive real or sham acupuncture treatment, respectively. In this trial, the primary outcome measure is simple form of McGill pain questionnaire (SF-MPQ), while expectation and treatment credibility scale (ETCS), safety assessment, the COX menstrual symptom scale (CMSS), questionnaire about the feeling of being punctured are included in the secondary outcomes. This trial will be the first study protocol designed to evaluate the immediate analgesia effect of WAA in PD of young females. The strengths in methodology, including rigorous randomized, sham-controlled, participants-blinded and assessors-blinded, will guarantee the quality of this study. WAA doesn't require any needling sensation, so non-penetrating sham acupuncture can serve as an effective placebo intervention in this trial. Chinese Clinical Trial Registry (identifier: ChiCTR-IOR-16008546 ; registration date: 27 May 2016).

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.

Improving coronary heart disease self-management using mobile technologies (Text4Heart): a randomised controlled trial protocol.

PubMed

Dale, Leila Pfaeffli; Whittaker, Robyn; Jiang, Yannan; Stewart, Ralph; Rolleston, Anna; Maddison, Ralph

2014-03-04

Cardiac rehabilitation (CR) is a secondary prevention program that offers education and support to assist patients with coronary heart disease (CHD) make lifestyle changes. Despite the benefits of CR, attendance at centre-based sessions remains low. Mobile technology (mHealth) has potential to reach more patients by delivering CR directly to mobile phones, thus providing an alternative to centre-based CR. The aim of this trial is to evaluate if a mHealth comprehensive CR program can improve adherence to healthy lifestyle behaviours (for example, physically active, fruit and vegetable intake, not smoking, low alcohol consumption) over and above usual CR services in New Zealand adults diagnosed with CHD. A two-arm, parallel, randomised controlled trial will be conducted at two Auckland hospitals in New Zealand. One hundred twenty participants will be randomised to receive a 24-week evidence- and theory-based personalised text message program and access to a supporting website in addition to usual CR care or usual CR care alone (control). The primary outcome is the proportion of participants adhering to healthy behaviours at 6 months, measured using a composite health behaviour score. Secondary outcomes include overall cardiovascular disease risk, body composition, illness perceptions, self-efficacy, hospital anxiety/depression and medication adherence. This study is one of the first to examine an mHealth-delivered comprehensive CR program. Strengths of the trial include quality research design and in-depth description of the intervention to aid replication. If effective, the trial has potential to augment standard CR practices and to be used as a model for other disease prevention or self-management programs. Australian New Zealand Clinical Trials Registry: ACTRN12613000901707.

The effectiveness of neuro-music therapy according to the Heidelberg model compared to a single session of educational counseling as treatment for tinnitus: a controlled trial.

PubMed

Argstatter, Heike; Grapp, Miriam; Hutter, Elisabeth; Plinkert, Peter K; Bolay, Hans-Volker

2015-03-01

Tinnitus is a very common symptom, yet the quest for an effective treatment is challenging. Results from several clinical trials support the notion that neuro-music therapy is an effective means to reduce tinnitus distress with short duration and long lasting effect. However, until now, the effectiveness has not been tested in a controlled trial against an active comparator. The trial was designed as two-center, parallel intervention group controlled study with two intervention groups: Counseling (50minute individualized personal instruction) or neuro-music therapy (counseling plus eight 50-minute sessions of individualized music therapy). Data of n=290 patients suffering from chronic tinnitus were analyzed. Outcome measure was the change in Tinnitus Questionnaire Total Scores (TQ) from baseline (admission) to end of treatment. Both treatment groups achieved a statistically relevant reduction in TQ scores, though 66% of patients in the music therapy group attained a clinically meaningful improvement compared to 33% in the counseling group. A binary logistic regression revealed two variables significantly influencing therapy outcome: initial tinnitus score and type of therapy with an OR for the music therapy compared to the counseling of 4.34 (CI 2.33-8.09). Counseling is an appropriate treatment option with well above chance of improvement. The neuro-music therapy outperformed the counseling. This treatment targets the tinnitus sound itself, is short in duration, intrinsically motivating and easy to operate and thus presents a possible complement to the therapeutic spectrum in chronic tinnitus. The trial was registered at the ClinicalTrials.gov registry (ID: NCT01845155). Copyright © 2014 Elsevier Inc. All rights reserved.

Design considerations for parallel graphics libraries

NASA Technical Reports Server (NTRS)

Crockett, Thomas W.

1994-01-01

Applications which run on parallel supercomputers are often characterized by massive datasets. Converting these vast collections of numbers to visual form has proven to be a powerful aid to comprehension. For a variety of reasons, it may be desirable to provide this visual feedback at runtime. One way to accomplish this is to exploit the available parallelism to perform graphics operations in place. In order to do this, we need appropriate parallel rendering algorithms and library interfaces. This paper provides a tutorial introduction to some of the issues which arise in designing parallel graphics libraries and their underlying rendering algorithms. The focus is on polygon rendering for distributed memory message-passing systems. We illustrate our discussion with examples from PGL, a parallel graphics library which has been developed on the Intel family of parallel systems.

Designing Feature and Data Parallel Stochastic Coordinate Descent Method forMatrix and Tensor Factorization

DTIC Science & Technology

2016-05-11

AFRL-AFOSR-JP-TR-2016-0046 Designing Feature and Data Parallel Stochastic Coordinate Descent Method for Matrix and Tensor Factorization U Kang Korea...maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or   any other aspect...Designing Feature and Data Parallel Stochastic Coordinate Descent Method for Matrix and Tensor Factorization 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA2386

Type synthesis for 4-DOF parallel press mechanism using GF set theory

NASA Astrophysics Data System (ADS)

He, Jun; Gao, Feng; Meng, Xiangdun; Guo, Weizhong

2015-07-01

Parallel mechanisms is used in the large capacity servo press to avoid the over-constraint of the traditional redundant actuation. Currently, the researches mainly focus on the performance analysis for some specific parallel press mechanisms. However, the type synthesis and evaluation of parallel press mechanisms is seldom studied, especially for the four degrees of freedom(DOF) press mechanisms. The type synthesis of 4-DOF parallel press mechanisms is carried out based on the generalized function(GF) set theory. Five design criteria of 4-DOF parallel press mechanisms are firstly proposed. The general procedure of type synthesis of parallel press mechanisms is obtained, which includes number synthesis, symmetrical synthesis of constraint GF sets, decomposition of motion GF sets and design of limbs. Nine combinations of constraint GF sets of 4-DOF parallel press mechanisms, ten combinations of GF sets of active limbs, and eleven combinations of GF sets of passive limbs are synthesized. Thirty-eight kinds of press mechanisms are presented and then different structures of kinematic limbs are designed. Finally, the geometrical constraint complexity( GCC), kinematic pair complexity( KPC), and type complexity( TC) are proposed to evaluate the press types and the optimal press type is achieved. The general methodologies of type synthesis and evaluation for parallel press mechanism are suggested.

Design of on-board parallel computer on nano-satellite

NASA Astrophysics Data System (ADS)

You, Zheng; Tian, Hexiang; Yu, Shijie; Meng, Li

2007-11-01

This paper provides one scheme of the on-board parallel computer system designed for the Nano-satellite. Based on the development request that the Nano-satellite should have a small volume, low weight, low power cost, and intelligence, this scheme gets rid of the traditional one-computer system and dual-computer system with endeavor to improve the dependability, capability and intelligence simultaneously. According to the method of integration design, it employs the parallel computer system with shared memory as the main structure, connects the telemetric system, attitude control system, and the payload system by the intelligent bus, designs the management which can deal with the static tasks and dynamic task-scheduling, protect and recover the on-site status and so forth in light of the parallel algorithms, and establishes the fault diagnosis, restoration and system restructure mechanism. It accomplishes an on-board parallel computer system with high dependability, capability and intelligence, a flexible management on hardware resources, an excellent software system, and a high ability in extension, which satisfies with the conception and the tendency of the integration electronic design sufficiently.

Electroacupuncture for poststroke spasticity (EAPSS): protocol for a randomised controlled trial

PubMed Central

Cai, Yiyi; Ouyang, Wenwei; Li, Jianmin; Nong, Wenheng; Zhang, Anthony Lin

2018-01-01

Introduction Spasticity is a common complication of stroke. Current therapies for poststroke spasticity (PSS) have been reported to be associated with high costs, lack of long-term benefit and unwanted adverse events (AEs). Electroacupuncture (EA) has been used for PSS, however, its efficacy and safety is yet to be confirmed by high-quality clinical studies. This study is designed to evaluate the add-on effects and safety profile of EA when used in combination with usual care (UC). Methods and analysis This study is a parallel group randomised controlled trial. A total of 136 participants will be included and randomly assigned to either the treatment group (EA plus UC) or the control group (UC alone). Prior to the main trial, a pilot study involving 30 participants will be conducted to assess the feasibility of the trial protocol. EA will be administered by registered acupuncturists for 20min to 30 min, three times per week for 4 weeks. The primary outcome measure (Modified Ashworth Scale) and secondary outcome measures (Fugl-Meyer Assessment and Barthel Index) will be evaluated at baseline, the end of treatment (week 4) and the end of follow-up (week 8). AEs will be monitored, recorded and reported, and their causality will be explored. Ethics and dissemination Ethics approval was obtained from the ethics committees of Guangdong Provincial Hospital of Chinese Medicine and RMIT University in December 2016. The results will be disseminated in a peer-reviewed journal, and PhD theses and might be presented at international conferences. Trial registration number ChiCTR-IOR-16010283; Pre-results. PMID:29487073

Electroacupuncture for insomnia disorder: study protocol for a randomized controlled trial.

PubMed

Kim, Sung-Phil; Kim, Joo-Hee; Kim, Bo-Kyung; Kim, Hyeong-Jun; Jung, In Chul; Cho, Jung Hyo; Kim, Jung-Eun; Kim, Mi-Kyung; Kwon, O-Jin; Kim, Ae-Ran; Park, Hyo-Ju; Seo, Bok-Nam

2017-04-13

Insomnia is a common sleep disorder that affects many adults either transiently or chronically. The societal cost of insomnia is on the rise, while long-term use of current drug treatments can involve adverse effects. Recently, electroacupuncture (EA) has been used to treat various conditions including insomnia. The objective of this study is to provide scientific evidence for the effect and safety of using EA to treat insomnia. In this multicentre, assessor-blind, three-arm, parallel-design, randomised controlled trial, 150 participants will be assigned to the EA group, the sham EA (SEA) group, or the usual care group. The EA and SEA groups will receive the specific treatments 2-3 times a week for 4 weeks, for a total of 10 sessions, whereas the usual care group will not receive EA and will continue with usual care during the same time period. The primary outcome measure will be changes in the Insomnia Severity Index 5 weeks after randomisation. The secondary outcomes will include the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, a sleep diary, the EuroQoL-5 dimension questionnaire, the levels of melatonin and cortisol, and the Patient Global Impression of Change. Safety will be assessed at each visit. The results of this multicentre randomised controlled trial will contribute to provide rigorous clinical evidence for the effects and safety of EA for insomnia disorder. Korean Clinical Trial Registry, CRIS, KCT0001685 . Registered on 2 November 2015 (retrospectively registered). Date of enrolment of the first participant to the trial 13 October 2015.

Study protocol for a randomised controlled trial of cognitive processing therapy for post-traumatic stress disorder among Japanese patients: the Safety, Power, Intimacy, Esteem, Trust (SPINET) study

PubMed Central

Ito, Masaya; Horikoshi, Masaru; Resick, Patricia A; Katayanagi, Akiko; Miyamae, Mitsuhiro; Takagishi, Yuriko; Takebayashi, Yoshitake; Kanie, Ayako; Hirabayashi, Naotsugu; Furukawa, Toshiaki A

2017-01-01

Introduction Cognitive processing therapy (CPT) is widely regarded as a safe and effective first-line treatment for individuals with post-traumatic stress disorder (PTSD); however, no comparative studies have been conducted to examine the treatment outcomes in an Asian population. The aim of the present trial is to investigate the efficacy of CPT (individual format) as a treatment for PTSD in a population of Japanese patients. Methods and analysis A 16-week, single-centre, assessor-masked, randomised, parallel-group superiority trial has been designed to compare the efficacy of CPT in conjunction with treatment as usual (mostly pharmacotherapy and clinical monitoring) versus treatment as usual alone. The Clinician-Administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) will be our primary outcome measure of the post-traumatic stress symptoms at 17 weeks, whereas the PTSD Checklist for DSM-5 and determination of the operationally defined responder status will be used to assess the secondary outcomes. An estimated sample size of 29 participants in each group will be required to detect an expected effect size of 1.4 (95% CI 0.85 to 1.95). Ethics and dissemination The institutional review board at the National Center of Neurology and Psychiatry in Japan approved this study. The results of this clinical trial will be presented at conferences and disseminated through publication in a peer-reviewed journal. Trial registration number UMIN000021670 (registered on 1 April 2016). PMID:28667201

Spatially parallel processing of within-dimension conjunctions.

PubMed

Linnell, K J; Humphreys, G W

2001-01-01

Within-dimension conjunction search for red-green targets amongst red-blue, and blue-green, nontargets is extremely inefficient (Wolfe et al, 1990 Journal of Experimental Psychology: Human Perception and Performance 16 879-892). We tested whether pairs of red-green conjunction targets can nevertheless be processed spatially in parallel. Participants made speeded detection responses whenever a red-green target was present. Across trials where a second identical target was present, the distribution of detection times was compatible with the assumption that targets were processed in parallel (Miller, 1982 Cognitive Psychology 14 247-279). We show that this was not an artifact of response-competition or feature-based processing. We suggest that within-dimension conjunctions can be processed spatially in parallel. Visual search for such items may be inefficient owing to within-dimension grouping between items.

CFD Analysis and Design Optimization Using Parallel Computers

NASA Technical Reports Server (NTRS)

Martinelli, Luigi; Alonso, Juan Jose; Jameson, Antony; Reuther, James

1997-01-01

A versatile and efficient multi-block method is presented for the simulation of both steady and unsteady flow, as well as aerodynamic design optimization of complete aircraft configurations. The compressible Euler and Reynolds Averaged Navier-Stokes (RANS) equations are discretized using a high resolution scheme on body-fitted structured meshes. An efficient multigrid implicit scheme is implemented for time-accurate flow calculations. Optimum aerodynamic shape design is achieved at very low cost using an adjoint formulation. The method is implemented on parallel computing systems using the MPI message passing interface standard to ensure portability. The results demonstrate that, by combining highly efficient algorithms with parallel computing, it is possible to perform detailed steady and unsteady analysis as well as automatic design for complex configurations using the present generation of parallel computers.

ProperCAD: A portable object-oriented parallel environment for VLSI CAD

NASA Technical Reports Server (NTRS)

Ramkumar, Balkrishna; Banerjee, Prithviraj

1993-01-01

Most parallel algorithms for VLSI CAD proposed to date have one important drawback: they work efficiently only on machines that they were designed for. As a result, algorithms designed to date are dependent on the architecture for which they are developed and do not port easily to other parallel architectures. A new project under way to address this problem is described. A Portable object-oriented parallel environment for CAD algorithms (ProperCAD) is being developed. The objectives of this research are (1) to develop new parallel algorithms that run in a portable object-oriented environment (CAD algorithms using a general purpose platform for portable parallel programming called CARM is being developed and a C++ environment that is truly object-oriented and specialized for CAD applications is also being developed); and (2) to design the parallel algorithms around a good sequential algorithm with a well-defined parallel-sequential interface (permitting the parallel algorithm to benefit from future developments in sequential algorithms). One CAD application that has been implemented as part of the ProperCAD project, flat VLSI circuit extraction, is described. The algorithm, its implementation, and its performance on a range of parallel machines are discussed in detail. It currently runs on an Encore Multimax, a Sequent Symmetry, Intel iPSC/2 and i860 hypercubes, a NCUBE 2 hypercube, and a network of Sun Sparc workstations. Performance data for other applications that were developed are provided: namely test pattern generation for sequential circuits, parallel logic synthesis, and standard cell placement.

The exploitation of "Exploitation" in the tenofovir prep trial in Cameroon: Lessons learned from media coverage of an HIV prevention trial.

PubMed

Mack, Natasha; Robinson, Elizabeth T; MacQueen, Kathleen M; Moffett, Jill; Johnson, Laura M

2010-06-01

media coverage influences how clinical trials are perceived internationally and in communities where trials occur, affecting recruitment, retention, and political support for research. We conducted a discourse analysis of news coverage from 2004-2005 of a trial in Cameroon on oral PrEP for HIV prevention, to identify messages, communication techniques, and sources of messages that were amplified via media. We identified two parallel discourses: one on ethical concerns about the Cameroon trial, and a second, more general "science exploitation" discourse concerned with the potential for trials with vulnerable participant populations to be conducted unethically, benefiting only wealthy populations. Researchers should overtly address exploitation as an integral, ongoing component of research, particularly where historical or cultural conditions set the stage for controversy to emerge.

What makes a good home-based nocturnal seizure detector? A value sensitive design.

PubMed

van Andel, Judith; Leijten, Frans; van Delden, Hans; van Thiel, Ghislaine

2015-01-01

A device for the in-home detection of nocturnal seizures is currently being developed in the Netherlands, to improve care for patients with severe epilepsy. It is recognized that the design of medical technology is not value neutral: perspectives of users and developers are influential in design, and design choices influence these perspectives. However, during development processes, these influences are generally ignored and value-related choices remain implicit and poorly argued for. In the development process of the seizure detector we aimed to take values of all stakeholders into consideration. Therefore, we performed a parallel ethics study, using "value sensitive design." Analysis of stakeholder communication (in meetings and e-mail messages) identified five important values, namely, health, trust, autonomy, accessibility, and reliability. Stakeholders were then asked to give feedback on the choice of these values and how they should be interpreted. In a next step, the values were related to design choices relevant for the device, and then the consequences (risks and benefits) of these choices were investigated. Currently the process of design and testing of the device is still ongoing. The device will be validated in a trial in which the identified consequences of design choices are measured as secondary endpoints. Value sensitive design methodology is feasible for the development of new medical technology and can help designers substantiate the choices in their design.

Charon Toolkit for Parallel, Implicit Structured-Grid Computations: Functional Design

NASA Technical Reports Server (NTRS)

VanderWijngaart, Rob F.; Kutler, Paul (Technical Monitor)

1997-01-01

In a previous report the design concepts of Charon were presented. Charon is a toolkit that aids engineers in developing scientific programs for structured-grid applications to be run on MIMD parallel computers. It constitutes an augmentation of the general-purpose MPI-based message-passing layer, and provides the user with a hierarchy of tools for rapid prototyping and validation of parallel programs, and subsequent piecemeal performance tuning. Here we describe the implementation of the domain decomposition tools used for creating data distributions across sets of processors. We also present the hierarchy of parallelization tools that allows smooth translation of legacy code (or a serial design) into a parallel program. Along with the actual tool descriptions, we will present the considerations that led to the particular design choices. Many of these are motivated by the requirement that Charon must be useful within the traditional computational environments of Fortran 77 and C. Only the Fortran 77 syntax will be presented in this report.

A benefit-finding intervention for family caregivers of persons with Alzheimer disease: study protocol of a randomized controlled trial

PubMed Central

2012-01-01

Background Caregivers of relatives with Alzheimer’s disease are highly stressed and at risk for physical and psychiatric conditions. Interventions are usually focused on providing caregivers with knowledge of dementia, skills, and/or support, to help them cope with the stress. This model, though true to a certain extent, ignores how caregiver stress is construed in the first place. Besides burden, caregivers also report rewards, uplifts, and gains, such as a sense of purpose and personal growth. Finding benefits through positive reappraisal may offset the effect of caregiving on caregiver outcomes. Design Two randomized controlled trials are planned. They are essentially the same except that Trial 1 is a cluster trial (that is, randomization based on groups of participants) whereas in Trial 2, randomization is based on individuals. Participants are randomized into three groups - benefit finding, psychoeducation, and simplified psychoeducation. Participants in each group receive a total of approximately 12 hours of training either in group or individually at home. Booster sessions are provided at around 14 months after the initial treatment. The primary outcomes are caregiver stress (subjective burden, role overload, and cortisol), perceived benefits, subjective health, psychological well-being, and depression. The secondary outcomes are caregiver coping, and behavioral problems and functional impairment of the care-recipient. Outcome measures are obtained at baseline, post-treatment (2 months), and 6, 12, 18 and 30 months. Discussion The emphasis on benefits, rather than losses and difficulties, provides a new dimension to the way interventions for caregivers can be conceptualized and delivered. By focusing on the positive, caregivers may be empowered to sustain caregiving efforts in the long term despite the day-to-day challenges. The two parallel trials will provide an assessment of whether the effectiveness of the intervention depends on the mode of delivery. Trial registration Chinese Clinical Trial Registry (http://www.chictr.org/en/) identifier number ChiCTR-TRC-10000881. PMID:22747914

Supercomputing on massively parallel bit-serial architectures

NASA Technical Reports Server (NTRS)

Iobst, Ken

1985-01-01

Research on the Goodyear Massively Parallel Processor (MPP) suggests that high-level parallel languages are practical and can be designed with powerful new semantics that allow algorithms to be efficiently mapped to the real machines. For the MPP these semantics include parallel/associative array selection for both dense and sparse matrices, variable precision arithmetic to trade accuracy for speed, micro-pipelined train broadcast, and conditional branching at the processing element (PE) control unit level. The preliminary design of a FORTRAN-like parallel language for the MPP has been completed and is being used to write programs to perform sparse matrix array selection, min/max search, matrix multiplication, Gaussian elimination on single bit arrays and other generic algorithms. A description is given of the MPP design. Features of the system and its operation are illustrated in the form of charts and diagrams.

Process optimization using combinatorial design principles: parallel synthesis and design of experiment methods.

PubMed

Gooding, Owen W

2004-06-01

The use of parallel synthesis techniques with statistical design of experiment (DoE) methods is a powerful combination for the optimization of chemical processes. Advances in parallel synthesis equipment and easy to use software for statistical DoE have fueled a growing acceptance of these techniques in the pharmaceutical industry. As drug candidate structures become more complex at the same time that development timelines are compressed, these enabling technologies promise to become more important in the future.

Modeling and simulation to support dose selection and clinical development of SC-75416, a selective COX-2 inhibitor for the treatment of acute and chronic pain.

PubMed

Kowalski, K G; Olson, S; Remmers, A E; Hutmacher, M M

2008-06-01

Pharmacokinetic/pharmacodynamic (PK/PD) models were developed and clinical trial simulations were conducted to recommend a study design to test the hypothesis that a dose of SC-75416, a selective cyclooxygenase-2 inhibitor, can be identified that achieves superior pain relief (PR) compared to 400 mg ibuprofen in a post-oral surgery pain model. PK/PD models were developed for SC-75416, rofecoxib, valdecoxib, and ibuprofen relating plasma concentrations to PR scores using a nonlinear logistic-normal model. Clinical trial simulations conducted using these models suggested that 360 mg SC-75416 could achieve superior PR compared to 400 mg ibuprofen. A placebo- and positive-controlled parallel-group post-oral surgery pain study was conducted evaluating placebo, 60, 180, and 360 mg SC-75416 oral solution, and 400 mg ibuprofen. The study results confirmed the hypothesis that 360 mg SC-75416 achieved superior PR relative to 400 mg ibuprofen (DeltaTOTPAR6=3.3, P<0.05) and demonstrated the predictive performance of the PK/PD models.

Treatment of lymphangiomas with OK-432 (Picibanil) sclerotherapy: a prospective multi-institutional trial.

PubMed

Giguère, Chantal M; Bauman, Nancy M; Sato, Yutaka; Burke, Diane K; Greinwald, John H; Pransky, Seth; Kelley, Peggy; Georgeson, Keith; Smith, Richard J H

2002-10-01

To describe and to determine the robustness of our study evaluating the efficacy of OK-432 (Picibanil) as a therapeutic modality for lymphangiomas. Prospective, randomized trial and parallel-case series at 13 US tertiary care referral centers. Thirty patients diagnosed as having lymphangioma. Ages in 25 ranged from 6 months to 18 years. Twenty-nine had lesions located in the head-and-neck area. Every patient received a 4-dose injection series of OK-432 scheduled 6 to 8 weeks apart unless a contraindication existed or a complete response was observed before completion of all injections. A control group was observed for 6 months. Successful outcome of therapy was defined as a complete or a substantial (>60%) reduction in lymphangioma size as determined by calculated lesion volumes on computed tomographic or magnetic resonance imaging scans. Overall, 19 (86%) of the 22 patients with predominantly macrocystic lymphangiomas had a successful outcome. OK-432 should be efficacious in the treatment of lymphangiomas. Our study design is well structured to clearly define the role of this treatment agent.

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.

Slice-selective RF pulses for in vivo B1+ inhomogeneity mitigation at 7 tesla using parallel RF excitation with a 16-element coil.

PubMed

Setsompop, Kawin; Alagappan, Vijayanand; Gagoski, Borjan; Witzel, Thomas; Polimeni, Jonathan; Potthast, Andreas; Hebrank, Franz; Fontius, Ulrich; Schmitt, Franz; Wald, Lawrence L; Adalsteinsson, Elfar

2008-12-01

Slice-selective RF waveforms that mitigate severe B1+ inhomogeneity at 7 Tesla using parallel excitation were designed and validated in a water phantom and human studies on six subjects using a 16-element degenerate stripline array coil driven with a butler matrix to utilize the eight most favorable birdcage modes. The parallel RF waveform design applied magnitude least-squares (MLS) criteria with an optimized k-space excitation trajectory to significantly improve profile uniformity compared to conventional least-squares (LS) designs. Parallel excitation RF pulses designed to excite a uniform in-plane flip angle (FA) with slice selection in the z-direction were demonstrated and compared with conventional sinc-pulse excitation and RF shimming. In all cases, the parallel RF excitation significantly mitigated the effects of inhomogeneous B1+ on the excitation FA. The optimized parallel RF pulses for human B1+ mitigation were only 67% longer than a conventional sinc-based excitation, but significantly outperformed RF shimming. For example the standard deviations (SDs) of the in-plane FA (averaged over six human studies) were 16.7% for conventional sinc excitation, 13.3% for RF shimming, and 7.6% for parallel excitation. This work demonstrates that excitations with parallel RF systems can provide slice selection with spatially uniform FAs at high field strengths with only a small pulse-duration penalty. (c) 2008 Wiley-Liss, Inc.

Evaluation of the clinical benefit of an electromagnetic navigation system for CT-guided interventional radiology procedures in the thoraco-abdominal region compared with conventional CT guidance (CTNAV II): study protocol for a randomised controlled trial.

PubMed

Rouchy, R C; Moreau-Gaudry, A; Chipon, E; Aubry, S; Pazart, L; Lapuyade, B; Durand, M; Hajjam, M; Pottier, S; Renard, B; Logier, R; Orry, X; Cherifi, A; Quehen, E; Kervio, G; Favelle, O; Patat, F; De Kerviler, E; Hughes, C; Medici, M; Ghelfi, J; Mounier, A; Bricault, I

2017-07-06

Interventional radiology includes a range of minimally invasive image-guided diagnostic and therapeutic procedures that have become routine clinical practice. Each procedure involves a percutaneous needle insertion, often guided using computed tomography (CT) because of its availability and usability. However, procedures remain complicated, in particular when an obstacle must be avoided, meaning that an oblique trajectory is required. Navigation systems track the operator's instruments, meaning the position and progression of the instruments are visualised in real time on the patient's images. A novel electromagnetic navigation system for CT-guided interventional procedures (IMACTIS-CT®) has been developed, and a previous clinical trial demonstrated improved needle placement accuracy in navigation-assisted procedures. In the present trial, we are evaluating the clinical benefit of the navigation system during the needle insertion step of CT-guided procedures in the thoraco-abdominal region. This study is designed as an open, multicentre, prospective, randomised, controlled interventional clinical trial and is structured as a standard two-arm, parallel-design, individually randomised trial. A maximum of 500 patients will be enrolled. In the experimental arm (navigation system), the procedures are carried out using navigation assistance, and in the active comparator arm (CT), the procedures are carried out with conventional CT guidance. The randomisation is stratified by centre and by the expected difficulty of the procedure. The primary outcome of the trial is a combined criterion to assess the safety (number of serious adverse events), efficacy (number of targets reached) and performance (number of control scans acquired) of navigation-assisted, CT-guided procedures as evaluated by a blinded radiologist and confirmed by an expert committee in case of discordance. The secondary outcomes are (1) the duration of the procedure, (2) the satisfaction of the operator and (3) the irradiation dose delivered, with (4) subgroup analysis according to the expected difficulty of the procedure, as well as an evaluation of (5) the usability of the device. This trial addresses the lack of published high-level evidence studies in which navigation-assisted CT-guided interventional procedures are evaluated. This trial is important because it addresses the problems associated with conventional CT guidance and is particularly relevant because the number of interventional radiology procedures carried out in routine clinical practice is increasing. ClinicalTrials.gov identifier: NCT01896219 . Registered on 5 July 2013.

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

Integrated Task and Data Parallel Programming

NASA Technical Reports Server (NTRS)

Grimshaw, A. S.

1998-01-01

This research investigates the combination of task and data parallel language constructs within a single programming language. There are an number of applications that exhibit properties which would be well served by such an integrated language. Examples include global climate models, aircraft design problems, and multidisciplinary design optimization problems. Our approach incorporates data parallel language constructs into an existing, object oriented, task parallel language. The language will support creation and manipulation of parallel classes and objects of both types (task parallel and data parallel). Ultimately, the language will allow data parallel and task parallel classes to be used either as building blocks or managers of parallel objects of either type, thus allowing the development of single and multi-paradigm parallel applications. 1995 Research Accomplishments In February I presented a paper at Frontiers 1995 describing the design of the data parallel language subset. During the spring I wrote and defended my dissertation proposal. Since that time I have developed a runtime model for the language subset. I have begun implementing the model and hand-coding simple examples which demonstrate the language subset. I have identified an astrophysical fluid flow application which will validate the data parallel language subset. 1996 Research Agenda Milestones for the coming year include implementing a significant portion of the data parallel language subset over the Legion system. Using simple hand-coded methods, I plan to demonstrate (1) concurrent task and data parallel objects and (2) task parallel objects managing both task and data parallel objects. My next steps will focus on constructing a compiler and implementing the fluid flow application with the language. Concurrently, I will conduct a search for a real-world application exhibiting both task and data parallelism within the same program. Additional 1995 Activities During the fall I collaborated with Andrew Grimshaw and Adam Ferrari to write a book chapter which will be included in Parallel Processing in C++ edited by Gregory Wilson. I also finished two courses, Compilers and Advanced Compilers, in 1995. These courses complete my class requirements at the University of Virginia. I have only my dissertation research and defense to complete.

Omega 3/6 Fatty Acids for Reading in Children: A Randomized, Double-Blind, Placebo-Controlled Trial in 9-Year-Old Mainstream Schoolchildren in Sweden

ERIC Educational Resources Information Center

Johnson, Mats; Fransson, Gunnar; Östlund, Sven; Areskoug, Björn; Gillberg, Christopher

2017-01-01

Background: Previous research has shown positive effects of Omega 3/6 fatty acids in children with inattention and reading difficulties. We aimed to investigate if Omega 3/6 improved reading ability in mainstream schoolchildren. Methods: We performed a 3-month parallel, randomized, double-blind, placebo-controlled trial followed by 3-month active…

Acupuncture for sequelae of Bell's palsy: a randomized controlled trial protocol

PubMed Central

2011-01-01

Objective Incomplete recovery from facial palsy has a long-term impact on the quality of life, and medical options for the sequelae of Bell's palsy are limited. Invasive treatments and physiotherapy have been employed to relieve symptoms, but there is limited clinical evidence for their effectiveness. Acupuncture is widely used on Bell's palsy patients in East Asia, but there is insufficient evidence for its effectiveness on Bell's palsy sequelae. The objective is to evaluate the efficacy and safety of acupuncture in patients with sequelae of Bell's palsy. Method/Design This study consists of a randomized controlled trial with two parallel arms: an acupuncture group and a waitlist group. The acupuncture group will receive acupuncture treatment three times per week for a total of 24 sessions over 8 weeks. Participants in the waitlist group will not receive any acupuncture treatments during this 8 week period, but they will participate in the evaluations of symptoms at the start of the study, at 5 weeks and at 8 weeks after randomization, at which point the same treatment as the acupuncture group will be provided. The primary outcome will be analyzed by the change in the Facial Disability Index (FDI) from baseline to week eight. The secondary outcome measures will include FDI from baseline to week five, House-Brackmann Grade, lip mobility, and stiffness scales. Trial registration Current Controlled-Trials ISRCTN43104115; registration date: 06 July 2010; the date of the first patient's randomization: 04 August 2010 PMID:21388554

Short message service text messaging was feasible as a tool for data collection in a trial of treatment for irritable bowel syndrome.

PubMed

Brabyn, Sally; Adamson, Joy; MacPherson, Hugh; Tilbrook, Helen; Torgerson, David J

2014-09-01

To examine the feasibility of collecting data relating to irritable bowel syndrome (IBS), symptoms by short message service (SMS) text and explore the data to assess its usefulness. In a randomized parallel group design substudy, 59 consenting participants recruited from primary care to a trial of acupuncture for IBS (ISRCTN 08827905) were randomized to receive a one-question SMS message at either 9:30 am or at 6:30 pm for 7 days: "On a scale of 0-9, with 0 being no symptoms and 9 being the worst symptoms you could have, how would you score your IBS symptoms now? Please text back a single number." Of the total messages, 59% (n = 203) were answered within 15 minutes, 73.4% (n = 254) within 1 hour, and 97% (n = 334) within 10 hours. Response rates to evening texts were higher (93.5% vs. 87.6% P = 0.05) and response times shorter though not significantly (median: 0 vs. 5 hours; P = 0.12). There was no difference in mean scores, and morning symptoms varied more. Mean scores correlated significantly with IBS trial primary outcome measure, the IBS symptom severity score, and secondary outcome measures. Among IBS trial participants, data collection by SMS is feasible and acceptable, and there is potential for deriving meaningful data from the scores. Copyright © 2014 Elsevier Inc. All rights reserved.

Nitrates for stable angina: a systematic review and meta-analysis of randomized clinical trials.

PubMed

Wei, Jiafu; Wu, Taixiang; Yang, Qing; Chen, Mao; Ni, Juan; Huang, Dejia

2011-01-07

To assess the effect (harms and benefits) of nitrates for stable angina. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Randomized controlled trials with both parallel and crossover design were included. The following outcome measures were evaluated: number of angina attacks weekly and nitroglycerin consumption, quality of life, total exercise duration, time to onset of angina and time to 1 mm ST depression. Fifty-one trials with 3595 patients meeting inclusion criteria were analyzed. Both intermittent and continuous regimens of nitrates lengthened exercise duration significantly by 31 and 53 s respectively. The number of angina attacks was significantly reduced by 2.89 episodes weekly for continuous administration and 1.5 episodes weekly for intermittent administration. With intermittent administration, increased dose provided with 21 s more length of exercise duration. With continuous administration, exercise duration was pronged more in low-dose group. Quality of life was not improved by continuous application of GTN patches and was similar between continuous and intermittent groups. In addition, 51.6% patients receiving nitrates complained with headache. Long-term administration of nitrates was beneficial for angina prophylaxis and improved exercise performance but might be ineffective for improving quality of life. With continuous regimen, low-dose nitrates were more effective than high-dose ones for improving exercise performance. By contrast, with intermittent regimen, high-dose nitrates were more effective. In addition, intermittent administration could bring zero-hour effect. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The Aspirin Regimens in Essential Thrombocythemia (ARES) phase II randomized trial design: Implementation of the serum thromboxane B2 assay as an evaluation tool of different aspirin dosing regimens in the clinical setting.

PubMed

De Stefano, Valerio; Rocca, Bianca; Tosetto, Alberto; Soldati, Denise; Petrucci, Giovanna; Beggiato, Eloise; Bertozzi, Irene; Betti, Silvia; Carli, Giuseppe; Carpenedo, Monica; Cattaneo, Daniele; Cavalca, Viviana; Dragani, Alfredo; Elli, Elena; Finazzi, Guido; Iurlo, Alessandra; Lanzarone, Giuseppe; Lissandrini, Laura; Palandri, Francesca; Paoli, Chiara; Rambaldi, Alessandro; Ranalli, Paola; Randi, Maria Luigia; Ricco, Alessandra; Rossi, Elena; Ruggeri, Marco; Specchia, Giorgina; Timillero, Andrea; Turnu, Linda; Vianelli, Nicola; Vannucchi, Alessandro M; Rodeghiero, Francesco; Patrono, Carlo

2018-06-01

Once-daily (od), low-dose aspirin (75-100 mg) is recommended to reduce the thrombotic risk of patients with essential thrombocytemia (ET). This practice is based on data extrapolated from other high-risk patients and an aspirin trial in polycythemia vera, with the assumption of similar aspirin pharmacodynamics in the two settings. However, the pharmacodynamics of low-dose aspirin is impaired in ET, reflecting accelerated renewal of platelet cyclooxygenase (COX)-1. ARES is a parallel-arm, placebo-controlled, randomized, dose-finding, phase II trial enrolling 300 ET patients to address two main questions. First, whether twice or three times 100 mg aspirin daily dosing is superior to the standard od regimen in inhibiting platelet thromboxane (TX)A 2 production, without inhibiting vascular prostacyclin biosynthesis. Second, whether long-term persistence of superior biochemical efficacy can be safely maintained with multiple vs. single dosing aspirin regimen. Considering that the primary study end point is serum TXB 2 , a surrogate biomarker of clinical efficacy, a preliminary exercise of reproducibility and validation of this biomarker across all the 11 participating centers was implemented. The results of this preliminary phase demonstrate the importance of controlling reproducibility of biomarkers in multicenter trials and the feasibility of using serum TXB 2 as a reliable end point for dose-finding studies of novel aspirin regimens.

Specific treatment of problems of the spine (STOPS): design of a randomised controlled trial comparing specific physiotherapy versus advice for people with subacute low back disorders

PubMed Central

2011-01-01

Background Low back disorders are a common and costly cause of pain and activity limitation in adults. Few treatment options have demonstrated clinically meaningful benefits apart from advice which is recommended in all international guidelines. Clinical heterogeneity of participants in clinical trials is hypothesised as reducing the likelihood of demonstrating treatment effects, and sampling of more homogenous subgroups is recommended. We propose five subgroups that allow the delivery of specific physiotherapy treatment targeting the pathoanatomical, neurophysiological and psychosocial components of low back disorders. The aim of this article is to describe the methodology of a randomised controlled trial comparing specific physiotherapy treatment to advice for people classified into five subacute low back disorder subgroups. Methods/Design A multi-centre parallel group randomised controlled trial is proposed. A minimum of 250 participants with subacute (6 weeks to 6 months) low back pain and/or referred leg pain will be classified into one of five subgroups and then randomly allocated to receive either physiotherapy advice (2 sessions over 10 weeks) or specific physiotherapy treatment (10 sessions over 10 weeks) tailored according to the subgroup of the participant. Outcomes will be assessed at 5 weeks, 10 weeks, 6 months and 12 months following randomisation. Primary outcomes will be activity limitation measured with a modified Oswestry Disability Index as well as leg and back pain intensity measured on separate 0-10 Numerical Rating Scales. Secondary outcomes will include a 7-point global rating of change scale, satisfaction with physiotherapy treatment, satisfaction with treatment results, the Sciatica Frequency and Bothersomeness Scale, quality of life (EuroQol-5D), interference with work, and psychosocial risk factors (Orebro Musculoskeletal Pain Questionnaire). Adverse events and co-interventions will also be measured. Data will be analysed according to intention to treat principles, using linear mixed models for continuous outcomes, Mann Whitney U tests for ordinal outcomes, and Chi-square, risk ratios and risk differences for dichotomous outcomes. Discussion This trial will determine the difference in outcomes between specific physiotherapy treatment tailored to each of the five subgroups versus advice which is recommended in guidelines as a suitable treatment for most people with a low back disorder. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609000834257. PMID:21599941

Acupuncture for menopausal vasomotor symptoms: study protocol for a randomised controlled trial

PubMed Central

2014-01-01

Background Hot flushes and night sweats (vasomotor symptoms) are common menopausal symptoms, often causing distress, sleep deprivation and reduced quality of life. Although hormone replacement therapy is an effective treatment, there are concerns about serious adverse events. Non-hormonal pharmacological therapies are less effective and can also cause adverse effects. Complementary therapies, including acupuncture, are commonly used for menopausal vasomotor symptoms. While the evidence for the effectiveness of acupuncture in treating vasomotor symptoms is inconclusive, acupuncture has a low risk of adverse effects, and two small studies suggest it may be more effective than non-insertive sham acupuncture. Our objective is to assess the efficacy of needle acupuncture in improving hot flush severity and frequency in menopausal women. Our current study design is informed by methods tested in a pilot study. Methods/design This is a stratified, parallel, randomised sham-controlled trial with equal allocation of participants to two trial groups. We are recruiting 360 menopausal women experiencing a minimum average of seven moderate hot flushes a day over a seven-day period and who meet diagnostic criteria for the Traditional Chinese Medicine diagnosis of Kidney Yin deficiency. Exclusion criteria include breast cancer, surgical menopause, and current hormone replacement therapy use. Eligible women are randomised to receive either true needle acupuncture or sham acupuncture with non-insertive (blunt) needles for ten treatments over eight weeks. Participants are blinded to treatment allocation. Interventions are provided by Chinese medicine acupuncturists who have received specific training on trial procedures. The primary outcome measure is hot flush score, assessed using the validated Hot Flush Diary. Secondary outcome measures include health-related quality of life, anxiety and depression symptoms, credibility of the sham treatment, expectancy and beliefs about acupuncture, and adverse events. Participants will be analysed in the groups in which they were randomised using an intention-to-treat analysis strategy. Discussion Results from this trial will significantly add to the current body of evidence on the role of acupuncture for vasomotor symptoms. If found to be effective and safe, acupuncture will be a valuable additional treatment option for women who experience menopausal vasomotor symptoms. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12611000393954 11/02/2009. PMID:24925094

Evidence-based care of older people with suspected cognitive impairment in general practice: protocol for the IRIS cluster randomised trial.

PubMed

McKenzie, Joanne E; French, Simon D; O'Connor, Denise A; Mortimer, Duncan S; Browning, Colette J; Russell, Grant M; Grimshaw, Jeremy M; Eccles, Martin P; Francis, Jill J; Michie, Susan; Murphy, Kerry; Kossenas, Fiona; Green, Sally E

2013-08-19

Dementia is a common and complex condition. Evidence-based guidelines for the management of people with dementia in general practice exist; however, detection, diagnosis and disclosure of dementia have been identified as potential evidence-practice gaps. Interventions to implement guidelines into practice have had varying success. The use of theory in designing implementation interventions has been limited, but is advocated because of its potential to yield more effective interventions and aid understanding of factors modifying the magnitude of intervention effects across trials. This protocol describes methods of a randomised trial that tests a theory-informed implementation intervention that, if effective, may provide benefits for patients with dementia and their carers. This trial aims to estimate the effectiveness of a theory-informed intervention to increase GPs' (in Victoria, Australia) adherence to a clinical guideline for the detection, diagnosis, and management of dementia in general practice, compared with providing GPs with a printed copy of the guideline. Primary objectives include testing if the intervention is effective in increasing the percentage of patients with suspected cognitive impairment who receive care consistent with two key guideline recommendations: receipt of a i) formal cognitive assessment, and ii) depression assessment using a validated scale (primary outcomes for the trial). The design is a parallel cluster randomised trial, with clusters being general practices. We aim to recruit 60 practices per group. Practices will be randomised to the intervention and control groups using restricted randomisation. Patients meeting the inclusion criteria, and GPs' detection and diagnosis behaviours directed toward these patients, will be identified and measured via an electronic search of the medical records nine months after the start of the intervention. Practitioners in the control group will receive a printed copy of the guideline. In addition to receipt of the printed guideline, practitioners in the intervention group will be invited to participate in an interactive, opinion leader-led, educational face-to-face workshop. The theory-informed intervention aims to address identified barriers to and enablers of implementation of recommendations. Researchers responsible for identifying the cohort of patients with suspected cognitive impairment, and their detection and diagnosis outcomes, will be blind to group allocation. Australian New Zealand Clinical Trials Registry: ACTRN12611001032943 (date registered 28 September, 2011).

The NKF-NUS hemodialysis trial protocol - a randomized controlled trial to determine the effectiveness of a self management intervention for hemodialysis patients

PubMed Central

2011-01-01

Background Poor adherence to treatment is common in patients on hemodialysis which may increase risk for poor clinical outcomes and mortality. Self management interventions have been shown to be effective in improving compliance in other chronic populations. The aim of this trial is to evaluate the effectiveness of a recently developed group based self management intervention for hemodialysis patients compared to standard care. Methods/Design This is a multicentre parallel arm block randomized controlled trial (RCT) of a four session group self management intervention for hemodialysis patients delivered by health care professionals compared to standard care. A total of 176 consenting adults maintained on hemodialysis for a minimum of 6 months will be randomized to receive the self management intervention or standard care. Primary outcomes are biochemical markers of clinical status and adherence. Secondary outcomes include general health related quality of life, disease-specific quality of life, mood, self efficacy and self-reported adherence. Outcomes will be measured at baseline, immediately post-intervention and at 3 and 9 months post-intervention by an independent assessor and analysed on intention to treat principles with linear mixed-effects models across all time points. A qualitative component will examine which aspects of program participants found particularly useful and any barriers to change. Discussion The NKF-NUS intervention builds upon previous research emphasizing the importance of empowering patients in taking control of their treatment management. The trial design addresses weaknesses of previous research by use of an adequate sample size to detect clinically significant changes in biochemical markers, recruitment of a sufficiently large representative sample, a theory based intervention and careful assessment of both clinical and psychological endpoints at various follow up points. Inclusion of multiple dependent variables allows us to assess the broader impact on the intervention including both hard end points as well as patient reported outcomes. This program, if found to be effective, has the potential to be implemented within the existing renal services delivery model in Singapore, particularly as this is being delivered by health care professionals already working with hemodialysis patients in these settings who are specifically trained in facilitating self management in renal patients. Trial registration Current Controlled Trials ISRTN31434033 PMID:21272382

Improving quality of care and long-term health outcomes through continuity of care with the use of an electronic or paper patient-held portable health file (COMMUNICATE): study protocol for a randomized controlled trial.

PubMed

Lassere, Marissa Nichole; Baker, Sue; Parle, Andrew; Sara, Anthony; Johnson, Kent Robert

2015-06-04

The advantages of patient-held portable health files (PHF) and personal health records (PHR), paper or electronic, are said to include improved health-care provider continuity-of-care and patient empowerment in maintaining health. Top-down approaches are favored by public sector government and health managers. Bottom-up approaches include systems developed directly by health-care providers, consumers and industry, implemented locally on devices carried by patient-consumers or shared via web-based portals. These allow individuals to access, manage and share their health information, and that of others for whom they are authorized, in a private, secure and confidential environment. Few medical record technologies have been evaluated in randomized trials to determine whether there are important clinical benefits of these interventions. The COMMUNICATE trial will assess the acceptability and long-term clinical outcomes of an electronic and paper patient-held PHF. This is a 48-month, open-label pragmatic, superiority, parallel-group design randomized controlled trial. Subjects (n = 792) will be randomized in a 1:1:1 ratio to each of the trial arms: the electronic PHF added to usual care, the paper PHF added to usual care and usual care alone (no PHF). Inclusion criteria include those 60 years or older living independently in the community, but who have two or more chronic medical conditions that require prescription medication and regular care by at least three medical practitioners (general and specialist care). The primary objective is whether use of a PHF compared to usual care reduces a combined endpoint of deaths, overnight hospitalizations and blindly adjudicated serious out-of-hospital events. All primary analyses will be undertaken masked to randomized arm allocation using intention-to-treat principles. Secondary outcomes include quality of life and health literacy improvements. Lack of blinding creates potential for bias in trial conduct and ascertainment of clinical outcomes. Mechanisms are provided to reduce bias, including balanced study contact with all participants, a blinded adjudication committee determining which out-of-hospital events are serious and endpoints that are objective (overnight hospitalizations and mortality). The PRECIS tool provides a summary of the trial's design on the Pragmatic-Explanatory Continuum. Registered with Clinicaltrials.gov (identifier: NCT01082978) on 8 March 2010.

Small incision lenticule extraction (SMILE) versus laser in-situ keratomileusis (LASIK): study protocol for a randomized, non-inferiority trial

PubMed Central

2012-01-01

Background Small incision lenticule extraction or SMILE is a novel form of ‘flapless’ corneal refractive surgery that was adapted from refractive lenticule extraction (ReLEx). SMILE uses only one femtosecond laser to complete the refractive surgery, potentially reducing surgical time, side effects, and cost. If successful, SMILE could potentially replace the current, widely practiced laser in-situ keratomileusis or LASIK. The aim of this study is to evaluate whether SMILE is non-inferior to LASIK in terms of refractive outcomes at 3 months post-operatively. Methods/Design Single tertiary center, parallel group, single-masked, paired-eye design, non-inferiority, randomized controlled trial. Participants who are eligible for LASIK will be enrolled for study after informed consent. Each participant will be randomized to receive SMILE and LASIK in each eye. Our primary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (>21 years old) with myopia (> −3.00 diopter (D)) at a tertiary eye center in terms of refractive predictability at 3 months post-operatively. Our secondary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (>21 years old) with myopia (> −3.00 D) at a tertiary eye center in terms of other refractive outcomes (efficacy, safety, higher-order aberrations) at 3 months post-operatively. Our primary outcome is refractive predictability, which is one of several standard refractive outcomes, defined as the proportion of eyes achieving a postoperative spherical equivalent (SE) within ±0.50 D of the intended target. Randomization will be performed using random allocation sequence generated by a computer with no blocks or restrictions, and implemented by concealing the number-coded surgery within sealed envelopes until just before the procedure. In this single-masked trial, subjects and their caregivers will be masked to the assigned treatment in each eye. Discussion This novel trial will provide information on whether SMILE has comparable, if not superior, refractive outcomes compared to the established LASIK for myopia, thus providing evidence for translation into clinical practice. Trial registration Clinicaltrials.gov NCT01216475. PMID:22647480

Feasibility of a multi-modal exercise program on cognition in older adults with Type 2 diabetes - a pilot randomised controlled trial.

PubMed

Callisaya, M L; Daly, R M; Sharman, J E; Bruce, D; Davis, T M E; Greenaway, T; Nolan, M; Beare, R; Schultz, M G; Phan, T; Blizzard, L C; Srikanth, V K

2017-10-16

Type 2 Diabetes (T2D) is associated with increased risk of dementia. We aimed to determine the feasibility of a randomised controlled trial (RCT) examining the efficacy of exercise on cognition and brain structure in people with T2D. A 6-month pilot parallel RCT of a progressive aerobic- and resistance-training program versus a gentle movement control group in people with T2D aged 50-75 years (n = 50) at the University of Tasmania, Australia. Assessors were blinded to group allocation. Brain volume (total, white matter, hippocampus), cortical thickness and white matter microstructure (fractional anisotrophy and mean diffusivity) were measured using magnetic resonance imaging, and cognition using a battery of neuropsychological tests. Study design was assessed by any changes (during the pilot or recommended) to the protocol, recruitment by numbers screened and time to enrol 50 participants; randomisation by similarity of characteristics in groups at baseline, adherence by exercise class attendance; safety by number and description of adverse events and retention by numbers withdrawn. The mean age of participants was 66.2 (SD 4.9) years and 48% were women. There were no changes to the design during the study. A total of 114 people were screened for eligibility, with 50 participants with T2D enrolled over 8 months. Forty-seven participants (94%) completed the study (23 of 24 controls; 24 of 26 in the intervention group). Baseline characteristics were reasonably balanced between groups. Exercise class attendance was 79% for the intervention and 75% for the control group. There were 6 serious adverse events assessed as not or unlikely to be due to the intervention. Effect sizes for each outcome variable are provided. This study supports the feasibility of a large scale RCT to test the benefits of multi-modal exercise to prevent cognitive decline in people with T2D. Design changes to the future trial are provided. ANZCTR 12614000222640 ; Registered 3/3/2014; First participant enrolled 26/6/2014, study screening commenced 1/9/2014; Australian and New Zealand Clinical Trial Registry.

Increasing the quantity and quality of searching for current best evidence to answer clinical questions: protocol and intervention design of the MacPLUS FS Factorial Randomized Controlled Trials.

PubMed

Agoritsas, Thomas; Iserman, Emma; Hobson, Nicholas; Cohen, Natasha; Cohen, Adam; Roshanov, Pavel S; Perez, Miguel; Cotoi, Chris; Parrish, Rick; Pullenayegum, Eleanor; Wilczynski, Nancy L; Iorio, Alfonso; Haynes, R Brian

2014-09-20

Finding current best evidence for clinical decisions remains challenging. With 3,000 new studies published every day, no single evidence-based resource provides all answers or is sufficiently updated. McMaster Premium LiteratUre Service--Federated Search (MacPLUS FS) addresses this issue by looking in multiple high quality resources simultaneously and displaying results in a one-page pyramid with the most clinically useful at the top. Yet, additional logistical and educational barriers need to be addressed to enhance point-of-care evidence retrieval. This trial seeks to test three innovative interventions, among clinicians registered to MacPLUS FS, to increase the quantity and quality of searching for current best evidence to answer clinical questions. In a user-centered approach, we designed three interventions embedded in MacPLUS FS: (A) a web-based Clinical Question Recorder; (B) an Evidence Retrieval Coach composed of eight short educational videos; (C) an Audit, Feedback and Gamification approach to evidence retrieval, based on the allocation of 'badges' and 'reputation scores.' We will conduct a randomized factorial controlled trial among all the 904 eligible medical doctors currently registered to MacPLUS FS at the hospitals affiliated with McMaster University, Canada. Postgraduate trainees (n=429) and clinical faculty/staff (n=475) will be randomized to each of the three following interventions in a factorial design (AxBxC). Utilization will be continuously recorded through clinicians’ accounts that track logins and usage, down to the level of individual keystrokes. The primary outcome is the rate of searches per month per user during the six months of follow-up. Secondary outcomes, measured through the validated Impact Assessment Method questionnaire, include: utility of answers found (meeting clinicians’ information needs), use (application in practice), and perceived usefulness on patient outcomes. Built on effective models for the point-of-care teaching, these interventions approach evidence retrieval as a clinical skill. If effective, they may offer the opportunity to enhance it for a large audience, at low cost, providing better access to relevant evidence across many top EBM resources in parallel. ClinicalTrials.Gov NCT02038439.

Heated humidification versus heat and moisture exchangers for ventilated adults and children.

PubMed

Kelly, Margaret; Gillies, Donna; Todd, David A; Lockwood, Catherine

2010-10-01

Humidification by artificial means must be provided when the upper airway is bypassed during mechanical ventilation. Heated humidification (HH) and heat and moisture exchangers (HMEs) are the most commonly used types of artificial humidification in this situation. To determine whether HHs or HMES are more effective in preventing mortality and other complications in people who are mechanically ventilated. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 4) and MEDLINE, EMBASE and CINAHL (January, 2010) to identify relevant randomized controlled trials. We included randomized controlled trials comparing HMEs to HHs in mechanically ventilated adults and children. We included randomized crossover studies. We assessed the quality of each study and extracted the relevant data. Where appropriate, results from relevant studies were meta-analyzed for individual outcomes. We included 33 trials with 2833 participants; 25 studies were parallel group design (n = 2710) and 8 crossover design (n = 123). Only 3 included studies reported data for infants or children. There was no overall effect on artificial airway occlusion, mortality, pneumonia, or respiratory complications; however, the PaCO(2) and minute ventilation were increased when HMEs were compared to HHs and body temperature was lower. The cost of HMEs was lower in all studies that reported this outcome. There was some evidence that hydrophobic HMEs may reduce the risk of pneumonia and that blockages of artificial airways may be increased with the use of HMEs in certain subgroups of patients. There is little evidence of an overall difference between HMEs and HHs. However, hydrophobic HMEs may reduce the risk of pneumonia and the use of an HMEs may increase artificial airway occlusion in certain subgroups of patients. Therefore, HMEs may not be suitable for patients with limited respiratory reserve or prone to airway blockage. Further research is needed relating to hydrophobic versus hygroscopic HMEs and the use of HMEs in the pediatric and neonatal populations. As the design of HMEs evolves, evaluation of new generation HMEs will also need to be undertaken.

The postcard intervention against depression among community-dwelling older adults: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Depression in older adults deteriorates quality of life and increases morbidity, mortality, and medical expenses. Medicine and social policy should work together to decrease this burden. Existing prevention studies are often based on time-consuming psychotherapies, which therefore are not feasible for a wide application at the community level. Postcard interventions have been shown to be effective for patients after hospitalization for major depression, drug overdose, or self-harm. This paper describes the protocol of a pragmatic, randomized controlled trial designed to examine the efficacy of a postcard intervention for depression among community-dwelling individuals aged 65 years or older. Methods/Design This is a pragmatic, non-blinded, parallel comparison, randomized controlled trial using Zelen’s design in a community setting. Participants will include community-dwelling older adults (aged 65 years or older) with limited social support (indicated by eating meals alone) and with symptoms of depression (scoring 4 or higher on the 15-item Geriatric Depression Scale (GDS)). The intervention will consist of sending postcards with handwritten messages and seasonal reports from a historical city to participants once a month for eight consecutive months. Self-addressed, stamped envelopes will be enclosed to facilitate non-obligatory replies. Primary outcomes will be changes in the GDS scores that are administered to all elderly inhabitants of the community every year as part of annual health checks. Secondary outcomes include quality of life as measured by a visual analogue scale, and self-rated basic and advanced activities of daily living. We will also examine the subjective sense of effectiveness of the intervention, recollection of the number of intervention mailings received, and the number of mailed replies as the index of the acceptability of the postcard intervention. The time × group interaction for two consecutive years will be analyzed using a generalized linear mixed model. To detect an effect size of 0.5 at alpha error of 0.05 and statistical power of 0.80, 63 participants per group are required. Based on an estimated consent and dropout rate of 70%, a total of 180 subjects will be recruited. Trial registration UMIN000010529 PMID:23837527

Effects and feasibility of a standardised orientation and mobility training in using an identification cane for older adults with low vision: design of a randomised controlled trial.

PubMed

Zijlstra, G A R; van Rens, G H M B; Scherder, E J A; Brouwer, D M; van der Velde, J; Verstraten, P F J; Kempen, G I J M

2009-08-27

Orientation and mobility training (O&M-training) in using an identification cane, also called symbol cane, is provided to people with low vision to facilitate independent participation in the community. In The Netherlands this training is mainly practice-based because a standardised and validly evaluated O&M-training in using the identification cane is lacking. Recently a standardised O&M-training in using the identification cane was developed. This training consists of two face-to-face sessions and one telephone session during which, in addition to usual care, the client's needs regarding mobility are prioritised, and cognitive restructuring techniques, action planning and contracting are applied to facilitate the use of the cane. This paper presents the design of a randomised controlled trial aimed to evaluate this standardised O&M-training in using the identification cane in older adults with low vision. A parallel group randomised controlled trial was designed to compare the standardised O&M-training with usual care, i.e. the O&M-training commonly provided by the mobility trainer. Community-dwelling older people who ask for support at a rehabilitation centre for people with visual impairment and who are likely to receive an O&M-training in using the identification cane are included in the trial (N = 190). The primary outcomes of the effect evaluation are ADL self care and visual functioning with respect to distance activities and mobility. Secondary outcomes include quality of life, feelings of anxiety, symptoms of depression, fear of falling, and falls history. Data for the effect evaluation are collected by means of telephone interviews at baseline, and at 5 and 17 weeks after the start of the O&M-training. In addition to an effect evaluation, a process evaluation to study the feasibility of the O&M-training is carried out. The screening procedure for eligible participants started in November 2007 and will continue until October 2009. Preliminary findings regarding the evaluation are expected in the course of 2010. If the standardised O&M-training is more effective than the current O&M-training or, in case of equal effectiveness, is considered more feasible, the training will be embedded in the Dutch national instruction for mobility trainers. ClinicalTrials.gov NCT00946062.

Variable-Complexity Multidisciplinary Optimization on Parallel Computers

NASA Technical Reports Server (NTRS)

Grossman, Bernard; Mason, William H.; Watson, Layne T.; Haftka, Raphael T.

1998-01-01

This report covers work conducted under grant NAG1-1562 for the NASA High Performance Computing and Communications Program (HPCCP) from December 7, 1993, to December 31, 1997. The objective of the research was to develop new multidisciplinary design optimization (MDO) techniques which exploit parallel computing to reduce the computational burden of aircraft MDO. The design of the High-Speed Civil Transport (HSCT) air-craft was selected as a test case to demonstrate the utility of our MDO methods. The three major tasks of this research grant included: development of parallel multipoint approximation methods for the aerodynamic design of the HSCT, use of parallel multipoint approximation methods for structural optimization of the HSCT, mathematical and algorithmic development including support in the integration of parallel computation for items (1) and (2). These tasks have been accomplished with the development of a response surface methodology that incorporates multi-fidelity models. For the aerodynamic design we were able to optimize with up to 20 design variables using hundreds of expensive Euler analyses together with thousands of inexpensive linear theory simulations. We have thereby demonstrated the application of CFD to a large aerodynamic design problem. For the predicting structural weight we were able to combine hundreds of structural optimizations of refined finite element models with thousands of optimizations based on coarse models. Computations have been carried out on the Intel Paragon with up to 128 nodes. The parallel computation allowed us to perform combined aerodynamic-structural optimization using state of the art models of a complex aircraft configurations.

The need to balance merits and limitations from different disciplines when considering the stepped wedge cluster randomized trial design.

PubMed

de Hoop, Esther; van der Tweel, Ingeborg; van der Graaf, Rieke; Moons, Karel G M; van Delden, Johannes J M; Reitsma, Johannes B; Koffijberg, Hendrik

2015-10-30

Various papers have addressed pros and cons of the stepped wedge cluster randomized trial design (SWD). However, some issues have not or only limitedly been addressed. Our aim was to provide a comprehensive overview of all merits and limitations of the SWD to assist researchers, reviewers and medical ethics committees when deciding on the appropriateness of the SWD for a particular study. We performed an initial search to identify articles with a methodological focus on the SWD, and categorized and discussed all reported advantages and disadvantages of the SWD. Additional aspects were identified during multidisciplinary meetings in which ethicists, biostatisticians, clinical epidemiologists and health economists participated. All aspects of the SWD were compared to the parallel group cluster randomized design. We categorized the merits and limitations of the SWD to distinct phases in the design and conduct of such studies, highlighting that their impact may vary depending on the context of the study or that benefits may be offset by drawbacks across study phases. Furthermore, a real-life illustration is provided. New aspects are identified within all disciplines. Examples of newly identified aspects of an SWD are: the possibility to measure a treatment effect in each cluster to examine the (in)consistency in effects across clusters, the detrimental effect of lower than expected inclusion rates, deviation from the ordinary informed consent process and the question whether studies using the SWD are likely to have sufficient social value. Discussions are provided on e.g. clinical equipoise, social value, health economical decision making, number of study arms, and interim analyses. Deciding on the use of the SWD involves aspects and considerations from different disciplines not all of which have been discussed before. Pros and cons of this design should be balanced in comparison to other feasible design options as to choose the optimal design for a particular intervention study.

Design of a dataway processor for a parallel image signal processing system

NASA Astrophysics Data System (ADS)

Nomura, Mitsuru; Fujii, Tetsuro; Ono, Sadayasu

1995-04-01

Recently, demands for high-speed signal processing have been increasing especially in the field of image data compression, computer graphics, and medical imaging. To achieve sufficient power for real-time image processing, we have been developing parallel signal-processing systems. This paper describes a communication processor called 'dataway processor' designed for a new scalable parallel signal-processing system. The processor has six high-speed communication links (Dataways), a data-packet routing controller, a RISC CORE, and a DMA controller. Each communication link operates at 8-bit parallel in a full duplex mode at 50 MHz. Moreover, data routing, DMA, and CORE operations are processed in parallel. Therefore, sufficient throughput is available for high-speed digital video signals. The processor is designed in a top- down fashion using a CAD system called 'PARTHENON.' The hardware is fabricated using 0.5-micrometers CMOS technology, and its hardware is about 200 K gates.

Xyce parallel electronic simulator users guide, version 6.1

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

Keiter, Eric R; Mei, Ting; Russo, Thomas V.

This manual describes the use of the Xyce Parallel Electronic Simulator. Xyce has been designed as a SPICE-compatible, high-performance analog circuit simulator, and has been written to support the simulation needs of the Sandia National Laboratories electrical designers. This development has focused on improving capability over the current state-of-the-art in the following areas; Capability to solve extremely large circuit problems by supporting large-scale parallel computing platforms (up to thousands of processors). This includes support for most popular parallel and serial computers; A differential-algebraic-equation (DAE) formulation, which better isolates the device model package from solver algorithms. This allows one to developmore » new types of analysis without requiring the implementation of analysis-specific device models; Device models that are specifically tailored to meet Sandia's needs, including some radiationaware devices (for Sandia users only); and Object-oriented code design and implementation using modern coding practices. Xyce is a parallel code in the most general sense of the phrase-a message passing parallel implementation-which allows it to run efficiently a wide range of computing platforms. These include serial, shared-memory and distributed-memory parallel platforms. Attention has been paid to the specific nature of circuit-simulation problems to ensure that optimal parallel efficiency is achieved as the number of processors grows.« less

Xyce parallel electronic simulator users' guide, Version 6.0.1.

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

Keiter, Eric R; Mei, Ting; Russo, Thomas V.

This manual describes the use of the Xyce Parallel Electronic Simulator. Xyce has been designed as a SPICE-compatible, high-performance analog circuit simulator, and has been written to support the simulation needs of the Sandia National Laboratories electrical designers. This development has focused on improving capability over the current state-of-the-art in the following areas: Capability to solve extremely large circuit problems by supporting large-scale parallel computing platforms (up to thousands of processors). This includes support for most popular parallel and serial computers. A differential-algebraic-equation (DAE) formulation, which better isolates the device model package from solver algorithms. This allows one to developmore » new types of analysis without requiring the implementation of analysis-specific device models. Device models that are specifically tailored to meet Sandias needs, including some radiationaware devices (for Sandia users only). Object-oriented code design and implementation using modern coding practices. Xyce is a parallel code in the most general sense of the phrase a message passing parallel implementation which allows it to run efficiently a wide range of computing platforms. These include serial, shared-memory and distributed-memory parallel platforms. Attention has been paid to the specific nature of circuit-simulation problems to ensure that optimal parallel efficiency is achieved as the number of processors grows.« less

Xyce parallel electronic simulator users guide, version 6.0.

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

Keiter, Eric R; Mei, Ting; Russo, Thomas V.

This manual describes the use of the Xyce Parallel Electronic Simulator. Xyce has been designed as a SPICE-compatible, high-performance analog circuit simulator, and has been written to support the simulation needs of the Sandia National Laboratories electrical designers. This development has focused on improving capability over the current state-of-the-art in the following areas: Capability to solve extremely large circuit problems by supporting large-scale parallel computing platforms (up to thousands of processors). This includes support for most popular parallel and serial computers. A differential-algebraic-equation (DAE) formulation, which better isolates the device model package from solver algorithms. This allows one to developmore » new types of analysis without requiring the implementation of analysis-specific device models. Device models that are specifically tailored to meet Sandias needs, including some radiationaware devices (for Sandia users only). Object-oriented code design and implementation using modern coding practices. Xyce is a parallel code in the most general sense of the phrase a message passing parallel implementation which allows it to run efficiently a wide range of computing platforms. These include serial, shared-memory and distributed-memory parallel platforms. Attention has been paid to the specific nature of circuit-simulation problems to ensure that optimal parallel efficiency is achieved as the number of processors grows.« less

PELE web server: atomistic study of biomolecular systems at your fingertips.

PubMed

Madadkar-Sobhani, Armin; Guallar, Victor

2013-07-01

PELE, Protein Energy Landscape Exploration, our novel technology based on protein structure prediction algorithms and a Monte Carlo sampling, is capable of modelling the all-atom protein-ligand dynamical interactions in an efficient and fast manner, with two orders of magnitude reduced computational cost when compared with traditional molecular dynamics techniques. PELE's heuristic approach generates trial moves based on protein and ligand perturbations followed by side chain sampling and global/local minimization. The collection of accepted steps forms a stochastic trajectory. Furthermore, several processors may be run in parallel towards a collective goal or defining several independent trajectories; the whole procedure has been parallelized using the Message Passing Interface. Here, we introduce the PELE web server, designed to make the whole process of running simulations easier and more practical by minimizing input file demand, providing user-friendly interface and producing abstract outputs (e.g. interactive graphs and tables). The web server has been implemented in C++ using Wt (http://www.webtoolkit.eu) and MySQL (http://www.mysql.com). The PELE web server, accessible at http://pele.bsc.es, is free and open to all users with no login requirement.

Effect of a Mobile Phone Intervention on Quitting Smoking in a Young Adult Population of Smokers: Randomized Controlled Trial Study Protocol

PubMed Central

Struik, Laura Louise; Hammond, David; Guindon, G Emmanuel; Norman, Cameron D; Whittaker, Robyn; Burns, Catherine M; Grindrod, Kelly A; Brown, K Stephen

2015-01-01

Background Tobacco use remains the number one cause of preventable chronic disease and death in developed countries worldwide. In North America, smoking rates are highest among young adults. Despite that the majority of young adult smokers indicate wanting to quit, smoking rates among this age demographic have yet to decline. Helping young adults quit smoking continues to be a public health priority. Digital mobile technology presents a promising medium for reaching this population with smoking cessation interventions, especially because young adults are the heaviest users of this technology. Objective The primary aim of this trial is to determine the effectiveness of an evidence-informed mobile phone app for smoking cessation, Crush the Crave, on reducing smoking prevalence among young adult smokers. Methods A parallel randomized controlled trial (RCT) with two arms will be conducted in Canada to evaluate Crush the Crave. In total, 1354 young adult smokers (19 to 29 years old) will be randomized to receive the evidence-informed mobile phone app, Crush the Crave, or an evidence-based self-help guide known as “On the Road to Quitting” (control) for a period of 6 months. The primary outcome measure is a 30-day point prevalence of abstinence at the 6-month follow-up. Secondary outcomes include a 7-day point prevalence of abstinence, number of quit attempts, reduction in consumption of cigarettes, self-efficacy, satisfaction, app utilization metrics, and use of smoking cessation services. A cost-effectiveness analysis is included. Results This trial is currently open for recruitment. The anticipated completion date for the study is April 2016. Conclusions This randomized controlled trial will provide the evidence to move forward on decision making regarding the inclusion of technology-based mobile phone interventions as part of existing smoking cessation efforts made by health care providers. Evidence from the trial will also inform the development of future apps, provide a deeper understanding of the factors that drive change in smoking behavior using an app, and improve the design of cessation apps. This trial is among the first to assess the effect of a comprehensive and evidence-informed mHealth smoking cessation app on a large sample of young adult smokers. Strengths of the trial include the high-quality research design and in-depth assessment of the implementation of the intervention. If effective, the trial has the potential to demonstrate that including mHealth technology as a population-based intervention strategy can cost-effectively reach a greater proportion of the population and help young adult smokers to quit. Trial Registration ClinicalTrials.gov NCT01983150; http://clinicaltrials.gov/ct2/show/NCT01983150 (Archived by WebCite at http://www.webcitation.org/6VGyc0W0i). PMID:25599695

Globally optimal trial design for local decision making.

PubMed

Eckermann, Simon; Willan, Andrew R

2009-02-01

Value of information methods allows decision makers to identify efficient trial design following a principle of maximizing the expected value to decision makers of information from potential trial designs relative to their expected cost. However, in health technology assessment (HTA) the restrictive assumption has been made that, prospectively, there is only expected value of sample information from research commissioned within jurisdiction. This paper extends the framework for optimal trial design and decision making within jurisdiction to allow for optimal trial design across jurisdictions. This is illustrated in identifying an optimal trial design for decision making across the US, the UK and Australia for early versus late external cephalic version for pregnant women presenting in the breech position. The expected net gain from locally optimal trial designs of US$0.72M is shown to increase to US$1.14M with a globally optimal trial design. In general, the proposed method of globally optimal trial design improves on optimal trial design within jurisdictions by: (i) reflecting the global value of non-rival information; (ii) allowing optimal allocation of trial sample across jurisdictions; (iii) avoiding market failure associated with free-rider effects, sub-optimal spreading of fixed costs and heterogeneity of trial information with multiple trials. Copyright (c) 2008 John Wiley & Sons, Ltd.

A design methodology for portable software on parallel computers

NASA Technical Reports Server (NTRS)

Nicol, David M.; Miller, Keith W.; Chrisman, Dan A.

1993-01-01

This final report for research that was supported by grant number NAG-1-995 documents our progress in addressing two difficulties in parallel programming. The first difficulty is developing software that will execute quickly on a parallel computer. The second difficulty is transporting software between dissimilar parallel computers. In general, we expect that more hardware-specific information will be included in software designs for parallel computers than in designs for sequential computers. This inclusion is an instance of portability being sacrificed for high performance. New parallel computers are being introduced frequently. Trying to keep one's software on the current high performance hardware, a software developer almost continually faces yet another expensive software transportation. The problem of the proposed research is to create a design methodology that helps designers to more precisely control both portability and hardware-specific programming details. The proposed research emphasizes programming for scientific applications. We completed our study of the parallelizability of a subsystem of the NASA Earth Radiation Budget Experiment (ERBE) data processing system. This work is summarized in section two. A more detailed description is provided in Appendix A ('Programming Practices to Support Eventual Parallelism'). Mr. Chrisman, a graduate student, wrote and successfully defended a Ph.D. dissertation proposal which describes our research associated with the issues of software portability and high performance. The list of research tasks are specified in the proposal. The proposal 'A Design Methodology for Portable Software on Parallel Computers' is summarized in section three and is provided in its entirety in Appendix B. We are currently studying a proposed subsystem of the NASA Clouds and the Earth's Radiant Energy System (CERES) data processing system. This software is the proof-of-concept for the Ph.D. dissertation. We have implemented and measured the performance of a portion of this subsystem on the Intel iPSC/2 parallel computer. These results are provided in section four. Our future work is summarized in section five, our acknowledgements are stated in section six, and references for published papers associated with NAG-1-995 are provided in section seven.

Effectiveness of adjuvant radiotherapy in patients with oropharyngeal and floor of mouth squamous cell carcinoma and concomitant histological verification of singular ipsilateral cervical lymph node metastasis (pN1-state)--a prospective multicenter randomized controlled clinical trial using a comprehensive cohort design.

PubMed

Moergel, Maximilian; Jahn-Eimermacher, Antje; Krummenauer, Frank; Reichert, Torsten E; Wagner, Wilfried; Wendt, Thomas G; Werner, Jochen A; Al-Nawas, Bilal

2009-12-23

Modern radiotherapy plays an important role in therapy of advanced head and neck carcinomas. However, no clinical studies have been published addressing the effectiveness of postoperative radiotherapy in patients with small tumor (pT1, pT2) and concomitant ipsilateral metastasis of a single lymph node (pN1), which would provide a basis for a general treatment recommendation. The present study is a non-blinded, prospective, multi-center randomized controlled trial (RCT). As the primary clinical endpoint, overall-survival in patients receiving postoperative radiation therapy vs. patients without adjuvant therapy following curative intended surgery is compared. The aim of the study is to enroll 560 adult males and females for 1:1 randomization to one of the two treatment arms (irradiation/no irradiation). Since patients with small tumor (T1/T2) but singular lymph node metastasis are rare and the amount of patients consenting to randomization is not predictable in advance, all patients rejecting randomization will be treated as preferred and enrolled in a prospective observational study (comprehensive cohort design) after giving informed consent. This observational part of the trial will be performed with maximum consistency to the treatment and observation protocol of the RCT. Because the impact of patient preference for a certain treatment option is not calculable, parallel design of RCT and observational study may provide a maximum of evidence and efficacy for evaluation of treatment outcome. Secondary clinical endpoints are as follows: incidence and time to tumor relapse (locoregional relapse, lymph node involvement and distant metastatic spread), Quality of life as reported by EORTC (QLQ-C30 with H&N 35 module), and time from operation to orofacial rehabilitation. All tumors represent a homogeneous clinical state and therefore additional investigation of protein expression levels within resection specimen may serve for establishment of surrogate parameters of patient outcome. The inherent challenges of a rare clinical condition (pN1) and two substantially different therapy arms would limit the practicality of a classical randomized study. The concept of a Comprehensive Cohort Design combines the preference of a randomized study, with the option of careful data interpretation within an observational study. ClinicalTrials.gov: NCT00964977.

Characterizing parallel file-access patterns on a large-scale multiprocessor

NASA Technical Reports Server (NTRS)

Purakayastha, A.; Ellis, Carla; Kotz, David; Nieuwejaar, Nils; Best, Michael L.

1995-01-01

High-performance parallel file systems are needed to satisfy tremendous I/O requirements of parallel scientific applications. The design of such high-performance parallel file systems depends on a comprehensive understanding of the expected workload, but so far there have been very few usage studies of multiprocessor file systems. This paper is part of the CHARISMA project, which intends to fill this void by measuring real file-system workloads on various production parallel machines. In particular, we present results from the CM-5 at the National Center for Supercomputing Applications. Our results are unique because we collect information about nearly every individual I/O request from the mix of jobs running on the machine. Analysis of the traces leads to various recommendations for parallel file-system design.

Assessment of the radioanatomic positioning of the osteoarthritic knee in serial radiographs: comparison of three acquisition techniques.

PubMed

Le Graverand, M-P H; Mazzuca, S; Lassere, M; Guermazi, A; Pickering, E; Brandt, K; Peterfy, C; Cline, G; Nevitt, M; Woodworth, T; Conaghan, P; Vignon, E

2006-01-01

Recent studies using various standardized radiographic acquisition techniques have demonstrated the necessity of reproducible radioanatomic alignment of the knee to assure precise measurements of medial tibiofemoral joint space width (JSW). The objective of the present study was to characterize the longitudinal performance of several acquisition techniques with respect to long-term reproducibility of positioning of the knee, and the impact of changes in positioning on the rate and variability of joint space narrowing (JSN). Eighty subjects were randomly selected from each of three cohorts followed in recent studies of the radiographic progression of knee osteoarthritis (OA): the Health ABC study (paired fixed-flexion [FF] radiographs taken at a 36-month interval); the Glucosamine Arthritis Intervention Trial (GAIT) (paired metatarsophalangeal [MTP] radiographs obtained at a 12-month interval), and a randomized clinical trial of doxycycline (fluoroscopically assisted semiflexed anteroposterior (AP) radiographs taken at a 16-month interval). Manual measurements were obtained from each radiograph to represent markers of radioanatomic positioning of the knee (alignment of the medial tibial plateau and X-ray beam, knee rotation, femorotibial angle) and to evaluate minimum JSW (mJSW) in the medial tibiofemoral compartment. The effects on the mean annualized rate of JSN and on the variability of that rate of highly reproduced vs variable positioning of the knee in serial radiographs were evaluated. Parallel or near-parallel alignment was achieved significantly more frequently with the fluoroscopically guided positioning used in the semiflexed AP protocol than with either the non-fluoroscopic FF or MTP protocol (68% vs 14% for both FF and MTP protocols when measured at the midpoint of the medial compartment; 75% vs 26% and 34% for the FF and MTP protocols, respectively, when measured at the site of mJSW; P<0.001 for each). Knee rotation was reproduced more frequently in semiflexed AP radiographs than in FF radiographs (66% vs 45%, P<0.01). In contrast, the FF technique yielded a greater proportion of paired radiographs in which the femorotibial angle was accurately reproduced than the semiflexed AP or MTP protocol (78% vs 59% and 56%, respectively, P<0.01 for each). Notably, only paired radiographs with parallel or near-parallel alignment exhibited a mean rate of JSN (+/-SD) in the OA knee that was more rapid and less variable than that measured in all knees (0.186+/-0.274 mm/year, standardized response to mean [SRM]=0.68 vs 0.128+/-0.291 mm/year, SRM=0.44). This study confirms the importance of parallel radioanatomic alignment of the anterior and posterior margins of the medial tibial plateau in detecting JSN in subjects with knee OA. The use of radiographic methods that assure parallel alignment during serial X-ray examinations will permit the design of more efficient studies of biomarkers of OA progression and of structure modification in knee OA.

National Combustion Code Parallel Performance Enhancements

NASA Technical Reports Server (NTRS)

Quealy, Angela; Benyo, Theresa (Technical Monitor)

2002-01-01

The National Combustion Code (NCC) is being developed by an industry-government team for the design and analysis of combustion systems. The unstructured grid, reacting flow code uses a distributed memory, message passing model for its parallel implementation. The focus of the present effort has been to improve the performance of the NCC code to meet combustor designer requirements for model accuracy and analysis turnaround time. Improving the performance of this code contributes significantly to the overall reduction in time and cost of the combustor design cycle. This report describes recent parallel processing modifications to NCC that have improved the parallel scalability of the code, enabling a two hour turnaround for a 1.3 million element fully reacting combustion simulation on an SGI Origin 2000.

Effects of protein supplements consumed with meals, versus between meals, on resistance training-induced body composition changes in adults: a systematic review.

PubMed

Hudson, Joshua L; Bergia, Robert E; Campbell, Wayne W

2018-06-01

The impact of timing the consumption of protein supplements in relation to meals on resistance training-induced changes in body composition has not been evaluated systematically. The aim of this systematic review was to assess the effect of consuming protein supplements with meals, vs between meals, on resistance training-induced body composition changes in adults. Studies published up to 2017 were identified with the PubMed, Scopus, Cochrane, and CINAHL databases. Two researchers independently screened 2077 abstracts for eligible randomized controlled trials of parallel design that prescribed a protein supplement and measured changes in body composition for a period of 6 weeks or more. In total, 34 randomized controlled trials with 59 intervention groups were included and qualitatively assessed. Of the intervention groups designated as consuming protein supplements with meals (n = 16) vs between meals (n = 43), 56% vs 72% showed an increase in body mass, 94% vs 90% showed an increase in lean mass, 87% vs 59% showed a reduction in fat mass, and 100% vs 84% showed an increase in the ratio of lean mass to fat mass over time, respectively. Concurrently with resistance training, consuming protein supplements with meals, rather than between meals, may more effectively promote weight control and reduce fat mass without influencing improvements in lean mass.

A Web-Based Intervention to Reduce Indoor Tanning Motivations In Adolescents: A Randomized Controlled Trial

PubMed Central

Hillhouse, Joel; Turrisi, Rob; Scaglione, Nichole M.; Cleveland, Michael J.; Baker, Katie; Florence, L. Carter

2016-01-01

Youthful indoor tanning as few as ten sessions can increase the risk of melanoma by 2 to 4 times with each additional session adding another 2% to the risk. Recent research estimates that indoor tanning can be linked to approximately 450,000 cases of skin cancer annually in the United States, Europe, and Australia. Despite these risks, indoor tanning remains popular with adolescents. This study tested the efficacy of a web-based skin cancer prevention intervention designed to reduce indoor tanning motivations in adolescent females. A nationally representative sample of 443 female teens were enrolled from an online panel into a two-arm, parallel group design, randomized controlled trial. Treatment participants received an appearance-focused intervention grounded in established health behavior change models. Controls viewed a teen alcohol prevention website. Outcome variables included willingness and intentions to indoor tan, willingness to sunless tan and measures of indoor tanning attitudes and beliefs. The intervention decreased willingness and intentions to indoor tan and increased sunless tanning willingness relative to controls. We also examined indirect mechanisms of change through intervening variables (e.g., indoor tanning attitudes, norms, positive and negative expectancies) using the product of coefficients approach. The web-based intervention demonstrated efficacy in changing adolescent indoor tanning motivations and improving their orientation toward healthier alternatives. Results from the intervening variable analyses give guidance to future adolescent skin cancer prevention interventions. PMID:27549602

A Web-Based Intervention to Reduce Indoor Tanning Motivations in Adolescents: a Randomized Controlled Trial.

PubMed

Hillhouse, Joel; Turrisi, Rob; Scaglione, Nichole M; Cleveland, Michael J; Baker, Katie; Florence, L Carter

2017-02-01

Youthful indoor tanning as few as ten sessions can increase the risk of melanoma by two to four times with each additional session adding another 2 % to the risk. Recent research estimates that indoor tanning can be linked to approximately 450,000 cases of skin cancer annually in the USA, Europe, and Australia. Despite these risks, indoor tanning remains popular with adolescents. This study tested the efficacy of a web-based skin cancer prevention intervention designed to reduce indoor tanning motivations in adolescent females. A nationally representative sample of 443 female teens was enrolled from an online panel into a two-arm, parallel group design, randomized controlled trial. Treatment participants received an appearance-focused intervention grounded in established health behavior change models. Controls viewed a teen alcohol prevention website. Outcome variables included willingness and intentions to indoor tan, willingness to sunless tan, and measures of indoor tanning attitudes and beliefs. The intervention decreased willingness and intentions to indoor tan and increased sunless tanning willingness relative to controls. We also examined indirect mechanisms of change through intervening variables (e.g., indoor tanning attitudes, norms, positive and negative expectancies) using the product of coefficient approach. The web-based intervention demonstrated efficacy in changing adolescent indoor tanning motivations and improving their orientation toward healthier alternatives. Results from the intervening variable analyses give guidance to future adolescent skin cancer prevention interventions.

The Effects of Iron and/or Zinc Supplementation on Maternal Reports of Sleep in Infants from Nepal and Zanzibar

PubMed Central

Kordas, Katarzyna; Siegel, Emily H.; Olney, Deanna K.; Katz, Joanne; Tielsch, James M.; Kariger, Patricia K.; Khalfan, Sabra S.; LeClerq, Steven C.; Khatry, Subarna K.; Stoltzfus, Rebecca J.

2009-01-01

Background There is some evidence that sleep patterns may be affected by iron deficiency anemia but the role of iron in sleep has not been tested in a randomized iron supplementation trial. Objective We investigated the effect of iron supplementation on maternal reports of sleep in infants in 2 randomized, placebo-controlled trials from Pemba Island, Zanzibar, and Nepal. Design In both studies, which had parallel designs and were carried out in years 2002 to 2003, infants received iron–folic acid with or without zinc daily for 12 months, and assessments of development were made every 3 months for the duration of the study. Eight hundred seventy-seven Pemban (12.5 ± 4.0 months old) and 567 Nepali (10.8 ± 4.0 months) infants participated. Maternal reports of sleep patterns (napping frequency and duration, nighttime sleep duration, frequency of night waking) were collected. Results Mean Hb concentration was 9.2 ± 1.1 for Pemban and 10.1 ± 1.2 g/dL for Nepali infants. Approximately, one-third of the children were stunted. Supplemental iron was consistently associated with longer night and total sleep duration. The effects of zinc supplementation also included longer sleep duration. Conclusions Micronutrient supplementation in infants at high risk for iron deficiency and iron deficiency anemia was related to increased night sleep duration and less night waking. PMID:19322104

A Parallel Genetic Algorithm for Automated Electronic Circuit Design

NASA Technical Reports Server (NTRS)

Lohn, Jason D.; Colombano, Silvano P.; Haith, Gary L.; Stassinopoulos, Dimitris; Norvig, Peter (Technical Monitor)

2000-01-01

We describe a parallel genetic algorithm (GA) that automatically generates circuit designs using evolutionary search. A circuit-construction programming language is introduced and we show how evolution can generate practical analog circuit designs. Our system allows circuit size (number of devices), circuit topology, and device values to be evolved. We present experimental results as applied to analog filter and amplifier design tasks.

The life cycles of six multi-center adaptive clinical trials focused on neurological emergencies developed for the Advancing Regulatory Science initiative of the National Institutes of Health and US Food and Drug Administration: Case studies from the Adaptive Designs Accelerating Promising Treatments Into Trials Project.

PubMed

Guetterman, Timothy C; Fetters, Michael D; Mawocha, Samkeliso; Legocki, Laurie J; Barsan, William G; Lewis, Roger J; Berry, Donald A; Meurer, William J

2017-01-01

Clinical trials are complicated, expensive, time-consuming, and frequently do not lead to discoveries that improve the health of patients with disease. Adaptive clinical trials have emerged as a methodology to provide more flexibility in design elements to better answer scientific questions regarding whether new treatments are efficacious. Limited observational data exist that describe the complex process of designing adaptive clinical trials. To address these issues, the Adaptive Designs Accelerating Promising Treatments Into Trials project developed six, tailored, flexible, adaptive, phase-III clinical trials for neurological emergencies, and investigators prospectively monitored and observed the processes. The objective of this work is to describe the adaptive design development process, the final design, and the current status of the adaptive trial designs that were developed. To observe and reflect upon the trial development process, we employed a rich, mixed methods evaluation that combined quantitative data from visual analog scale to assess attitudes about adaptive trials, along with in-depth qualitative data about the development process gathered from observations. The Adaptive Designs Accelerating Promising Treatments Into Trials team developed six adaptive clinical trial designs. Across the six designs, 53 attitude surveys were completed at baseline and after the trial planning process completed. Compared to baseline, the participants believed significantly more strongly that the adaptive designs would be accepted by National Institutes of Health review panels and non-researcher clinicians. In addition, after the trial planning process, the participants more strongly believed that the adaptive design would meet the scientific and medical goals of the studies. Introducing the adaptive design at early conceptualization proved critical to successful adoption and implementation of that trial. Involving key stakeholders from several scientific domains early in the process appears to be associated with improved attitudes towards adaptive designs over the life cycle of clinical trial development.

NAT2 genotype guided regimen reduces isoniazid-induced liver injury and early treatment failure in the 6-month four-drug standard treatment of tuberculosis: a randomized controlled trial for pharmacogenetics-based therapy.

PubMed

Azuma, Junichi; Ohno, Masako; Kubota, Ryuji; Yokota, Soichiro; Nagai, Takayuki; Tsuyuguchi, Kazunari; Okuda, Yasuhisa; Takashima, Tetsuya; Kamimura, Sayaka; Fujio, Yasushi; Kawase, Ichiro

2013-05-01

This study is a pharmacogenetic clinical trial designed to clarify whether the N-acetyltransferase 2 gene (NAT2) genotype-guided dosing of isoniazid improves the tolerability and efficacy of the 6-month four-drug standard regimen for newly diagnosed pulmonary tuberculosis. In a multicenter, parallel, randomized, and controlled trial with a PROBE design, patients were assigned to either conventional standard treatment (STD-treatment: approx. 5 mg/kg of isoniazid for all) or NAT2 genotype-guided treatment (PGx-treatment: approx. 7.5 mg/kg for patients homozygous for NAT2 4: rapid acetylators; 5 mg/kg, patients heterozygous for NAT2 4: intermediate acetylators; 2.5 mg/kg, patients without NAT2 4: slow acetylators). The primary outcome included incidences of 1) isoniazid-related liver injury (INH-DILI) during the first 8 weeks of therapy, and 2) early treatment failure as indicated by a persistent positive culture or no improvement in chest radiographs at the 8th week. One hundred and seventy-two Japanese patients (slow acetylators, 9.3 %; rapid acetylators, 53.5 %) were enrolled in this trial. In the intention-to-treat (ITT) analysis, INH-DILI occurred in 78 % of the slow acetylators in the STD-treatment, while none of the slow acetylators in the PGx-treatment experienced either INH-DILI or early treatment failure. Among the rapid acetylators, early treatment failure was observed with a significantly lower incidence rate in the PGx-treatment than in the STD-treatment (15.0 % vs. 38 %). Thus, the NAT2 genotype-guided regimen resulted in much lower incidences of unfavorable events, INH-DILI or early treatment failure, than the conventional standard regimen. Our results clearly indicate a great potential of the NAT2 genotype-guided dosing stratification of isoniazid in chemotherapy for tuberculosis.

Attrition during a randomized controlled trial of reduced nicotine content cigarettes as a proxy for understanding acceptability of nicotine product standards

PubMed Central

Mercincavage, Melissa; Wileyto, E. Paul; Saddleson, Megan L.; Lochbuehler, Kirsten; Donny, Eric C.; Strasser, Andrew A.

2017-01-01

Aims To determine (1) if nicotine content affects study attrition – a potential behavioral measure of acceptability – in a trial that required compliance with three levels of reduced nicotine content (RNC) cigarettes, and (2) if attrition is associated with subjective and behavioral responses to RNC cigarettes. Design Secondary analysis of a 35-day, parallel design, open-label, randomized controlled trial. After a 5-day baseline period, participants were randomized to smoke for three, 10-day periods: their preferred brand (control group), or RNC cigarettes with three nicotine levels in a within-subject, stepdown (1 group: high-moderate-low) or non-stepdown (5 groups: high-low-moderate, low-moderate-high, low-high-moderate, moderate-low-high, moderate-high-low) fashion. Setting A single site in Philadelphia, Pennsylvania, USA. Participants 246 non-treatment-seeking daily smokers (M age = 39.52, CPD = 20.95, 68.3% White) were recruited from October 2007 to June 2013. Measurements The primary outcome was attrition. Key predictors were nicotine content transition and study period. Exploratory predictors were taste and strength subjective ratings, total puff volume, and carbon monoxide (CO) boost. Covariates included: age, gender, race, education, and nicotine dependence. Findings Overall attrition was 31.3% (n = 77): 24.1% of the control and 25.0% of the stepdown RNC cigarette groups dropped out vs. 44.6% of non-stepdown groups (p = 0.006). Compared with controls, attrition odds were 4.5 and 4.7 times greater among smokers transitioning from preferred and the highest RNC cigarettes to the lowest RNC cigarettes, respectively (p’s = .001 and .003). Providing more favorable initial taste ratings of study cigarettes decreased attrition odds by 2% (p = .012). Conclusions The majority of participants completed a 35-day trial of varying levels of reduced nicotine content cigarettes. Participant drop-out was greater for cigarettes with lower nicotine content and less in smokers reporting more favorable subjective ratings of the cigarettes. PMID:28107596

Information and Risk Modification Trial (INFORM): design of a randomised controlled trial of communicating different types of information about coronary heart disease risk, alongside lifestyle advice, to achieve change in health-related behaviour.

PubMed

Silarova, Barbora; Lucas, Joanne; Butterworth, Adam S; Di Angelantonio, Emanuele; Girling, Christine; Lawrence, Kathryn; Mackintosh, Stuart; Moore, Carmel; Payne, Rupert A; Sharp, Stephen J; Shefer, Guy; Tolkien, Zoe; Usher-Smith, Juliet; Walker, Matthew; Danesh, John; Griffin, Simon

2015-09-07

Cardiovascular disease (CVD) remains the leading cause of death globally. Primary prevention of CVD requires cost-effective strategies to identify individuals at high risk in order to help target preventive interventions. An integral part of this approach is the use of CVD risk scores. Limitations in previous studies have prevented reliable inference about the potential advantages and the potential harms of using CVD risk scores as part of preventive strategies. We aim to evaluate short-term effects of providing different types of information about coronary heart disease (CHD) risk, alongside lifestyle advice, on health-related behaviours. In a parallel-group, open randomised trial, we are allocating 932 male and female blood donors with no previous history of CVD aged 40-84 years in England to either no intervention (control group) or to one of three active intervention groups: i) lifestyle advice only; ii) lifestyle advice plus information on estimated 10-year CHD risk based on phenotypic characteristics; and iii) lifestyle advice plus information on estimated 10-year CHD risk based on phenotypic and genetic characteristics. The primary outcome is change in objectively measured physical activity. Secondary outcomes include: objectively measured dietary behaviours; cardiovascular risk factors; current medication and healthcare usage; perceived risk; cognitive evaluation of provision of CHD risk scores; and psychological outcomes. The follow-up assessment takes place 12 weeks after randomisation. The experiences, attitudes and concerns of a subset of participants will be also studied using individual interviews and focus groups. The INFORM study has been designed to provide robust findings about the short-term effects of providing different types of information on estimated 10-year CHD risk and lifestyle advice on health-related behaviours. Current Controlled Trials ISRCTN17721237 . Registered 12 January 2015.

Improving psychotropic drug prescription in nursing home patients with dementia: design of a cluster randomized controlled trial

PubMed Central

2013-01-01

Background Neuropsychiatric symptoms are highly prevalent in nursing home patients with dementia. Despite modest effectiveness and considerable side effects, psychotropic drugs are frequently prescribed for these neuropsychiatric symptoms. This raises questions whether psychotropic drugs are appropriately prescribed. The aim of the PROPER (PRescription Optimization of Psychotropic drugs in Elderly nuRsing home patients with dementia) II study is to investigate the efficacy of an intervention for improving the appropriateness of psychotropic drug prescription in nursing home patients with dementia. Methods/design The PROPER II study is a multi-center cluster randomized controlled, pragmatic trial using parallel groups. It has a duration of eighteen months and four six-monthly assessments. Six nursing homes will participate in the intervention and six will continue care as usual. The nursing homes will be located throughout the Netherlands, each participating with two dementia special care units with an average of fifteen patients per unit, resulting in 360 patients. The intervention consists of a structured and repeated multidisciplinary medication review supported by education and continuous evaluation. It is conducted by pharmacists, physicians, and nurses and consists of three components: 1) preparation and education, 2) conduct, and 3) evaluation/guidance. The primary outcome is the proportion of patients with appropriate psychotropic drug use. Secondary outcomes are the overall frequency of psychotropic drug use, neuropsychiatric symptoms, quality of life, activities of daily living, psychotropic drug side effects and adverse events (including cognition, comorbidity, and mortality). Besides, a process analysis on the intervention will be carried out. Discussion This study is expected to improve the appropriateness of psychotropic drug prescription for neuropsychiatric symptoms in nursing home patients with dementia by introducing a structured and repeated multidisciplinary medication review supported by education and continuous evaluation. Trial registration Netherlands Trial Registry (NTR): NTR3569. PMID:24180295

Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE): A Cluster-Randomized Pragmatic Trial of a Multifactorial Fall Injury Prevention Strategy: Design and Methods.

PubMed

Bhasin, Shalender; Gill, Thomas M; Reuben, David B; Latham, Nancy K; Gurwitz, Jerry H; Dykes, Patricia; McMahon, Siobhan; Storer, Thomas W; Duncan, Pamela W; Ganz, David A; Basaria, Shehzad; Miller, Michael E; Travison, Thomas G; Greene, Erich J; Dziura, James; Esserman, Denise; Allore, Heather; Carnie, Martha B; Fagan, Maureen; Hanson, Catherine; Baker, Dorothy; Greenspan, Susan L; Alexander, Neil; Ko, Fred; Siu, Albert L; Volpi, Elena; Wu, Albert W; Rich, Jeremy; Waring, Stephen C; Wallace, Robert; Casteel, Carri; Magaziner, Jay; Charpentier, Peter; Lu, Charles; Araujo, Katy; Rajeevan, Haseena; Margolis, Scott; Eder, Richard; McGloin, Joanne M; Skokos, Eleni; Wiggins, Jocelyn; Garber, Lawrence; Clauser, Steven B; Correa-De-Araujo, Rosaly; Peduzzi, Peter

2017-10-14

Fall injuries are a major cause of morbidity and mortality among older adults. We describe the design of a pragmatic trial to compare the effectiveness of an evidence-based, patient-centered multifactorial fall injury prevention strategy to an enhanced usual care. Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) is a 40-month cluster-randomized, parallel-group, superiority, pragmatic trial being conducted at 86 primary care practices in 10 healthcare systems across USA. The 86 practices were randomized to intervention or control group using covariate-based constrained randomization, stratified by healthcare system. Participants are community-living persons, ≥70 years, at increased risk for serious fall injuries. The intervention is a co-management model in which a nurse Falls Care Manager performs multifactorial risk assessments, develops individualized care plans, which include surveillance, follow-up evaluation, and intervention strategies. Control group receives enhanced usual care, with clinicians and patients receiving evidence-based information on falls prevention. Primary outcome is serious fall injuries, operationalized as those leading to medical attention (non-vertebral fractures, joint dislocation, head injury, lacerations, and other major sequelae). Secondary outcomes include all fall injuries, all falls, and well-being (concern for falling; anxiety and depressive symptoms; physical function and disability). Target sample size was 5,322 participants to provide 90% power to detect 20% reduction in primary outcome rate relative to control. Trial enrolled 5451 subjects in 20 months. Intervention and follow-up are ongoing. The findings of the STRIDE study will have important clinical and policy implications for the prevention of fall injuries in older adults. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial.

PubMed

Liu, Zongjun; Shen, Li; Huang, Weijian; Zhao, Xianxian; Fang, Weiyi; Wang, Changqian; Yin, Zhaofang; Wang, Jianan; Fu, Guosheng; Liu, Xuebo; Jiang, Jianjun; Zhang, Zhihui; Li, Jingbo; Lu, Yingmin; Ge, Junbo

2017-09-01

Available data show that approximately 8%-18% of patients with primary hypertension will develop resistant hypertension. In recent years, catheter-based renal denervation (RDN) has emerged as a potential treatment option for resistant hypertension. A number of observational studies and randomised controlled trials among non-Chinese patients have demonstrated its potential safety and efficacy. This is a multicentre, randomised, open-label, parallel-group, active controlled trial that will investigate the efficacy and safety of a 5F saline-irrigated radiofrequency ablation (RFA) used for RDN in the treatment of Chinese patients with resistant hypertension. A total of 254 patients who have failed pharmacological therapy will be enrolled. Eligible subjects will be randomised in a 1:1 ratio to undergo RDN using the RFA plus antihypertensive medication or to receive treatment with antihypertensive medication alone. The primary outcome measure is the change in 24 hours average ambulatory systolic blood pressure from baseline to 3 months, comparing the RDN-plus-medication group with the medication-alone group. Important secondary endpoints include the change in office blood pressure from baseline to 6 months after randomisation. Safety endpoints such as changes in renal function will also be evaluated. The full analysis set, according to the intent-to-treat principle, will be established as the primary analysis population. All participants will provide informed consent; the study protocol has been approved by the Independent Ethics Committee for each site. This study is designed to investigate the efficacy and safety of RDN using a 5F saline microirrigated RFA. Findings will be shared with participating hospitals, policymakers and the academic community to promote the clinical management of resistant hypertension in China. ClinicalTrials.gov ID: NCT02900729; 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.

Evaluation of a practice team-supported exposure training for patients with panic disorder with or without agoraphobia in primary care - study protocol of a cluster randomised controlled superiority trial

PubMed Central

2014-01-01

Background Panic disorder and agoraphobia are debilitating and frequently comorbid anxiety disorders. A large number of patients with these conditions are treated by general practitioners in primary care. Cognitive behavioural exposure exercises have been shown to be effective in reducing anxiety symptoms. Practice team-based case management can improve clinical outcomes for patients with chronic diseases in primary care. The present study compares a practice team-supported, self-managed exposure programme for patients with panic disorder with or without agoraphobia in small general practices to usual care in terms of clinical efficacy and cost-effectiveness. Methods/Design This is a cluster randomised controlled superiority trial with a two-arm parallel group design. General practices represent the units of randomisation. General practitioners recruit adult patients with panic disorder with or without agoraphobia according to the International Classification of Diseases, version 10 (ICD-10). In the intervention group, patients receive cognitive behaviour therapy-oriented psychoeducation and instructions to self-managed exposure exercises in four manual-based appointments with the general practitioner. A trained health care assistant from the practice team delivers case management and is continuously monitoring symptoms and treatment progress in ten protocol-based telephone contacts with patients. In the control group, patients receive usual care from general practitioners. Outcomes are measured at baseline (T0), at follow-up after six months (T1), and at follow-up after twelve months (T2). The primary outcome is clinical severity of anxiety of patients as measured by the Beck Anxiety Inventory (BAI). To detect a standardised effect size of 0.35 at T1, 222 patients from 37 general practices are included in each group. Secondary outcomes include anxiety-related clinical parameters and health-economic costs. Trial registration Current Controlled Trials [http://ISCRTN64669297] PMID:24708672

The long-term effect of minimalist shoes on running performance and injury: design of a randomised controlled trial.

PubMed

Fuller, Joel T; Thewlis, Dominic; Tsiros, Margarita D; Brown, Nicholas A T; Buckley, Jonathan D

2015-08-21

The outcome of the effects of transitioning to minimalist running shoes is a topic of interest for runners and scientists. However, few studies have investigated the longer term effects of running in minimalist shoes. The purpose of this randomised controlled trial (RCT) is to investigate the effects of a 26 week transition to minimalist shoes on running performance and injury risk in trained runners unaccustomed to minimalist footwear. A randomised parallel intervention design will be used. Seventy-six trained male runners will be recruited. To be eligible, runners must be aged 18-40 years, run with a habitual rearfoot footfall pattern, train with conventional shoes and have no prior experience with minimalist shoes. Runners will complete a standardised transition to either minimalist or control shoes and undergo assessments at baseline, 6 and 26 weeks. 5 km time-trial performance (5TT), running economy, running biomechanics, triceps surae muscle strength and lower limb bone mineral density will be assessed at each time point. Pain and injury will be recorded weekly. Training will be standardised during the first 6 weeks. Primary statistical analysis will compare 5TT between shoe groups at the 6-week time point and injury incidence across the entire 26-week study period. This RCT has been approved by the Human Research Ethics Committee of the University of South Australia. Participants will be required to provide their written informed consent prior to participation in the study. Study findings will be disseminated in the form of journal publications and conference presentations after completion of planned data analysis. This RCT has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000642785). 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.

Chiropractic and self-care for back-related leg pain: design of a randomized clinical trial

PubMed Central

2011-01-01

Background Back-related leg pain (BRLP) is a common variation of low back pain (LBP), with lifetime prevalence estimates as high as 40%. Often disabling, BRLP accounts for greater work loss, recurrences, and higher costs than uncomplicated LBP and more often leads to surgery with a lifetime incidence of 10% for those with severe BRLP, compared to 1-2% for those with LBP. In the US, half of those with back-related conditions seek CAM treatments, the most common of which is chiropractic care. While there is preliminary evidence suggesting chiropractic spinal manipulative therapy is beneficial for patients with BRLP, there is insufficient evidence currently available to assess the effectiveness of this care. Methods/Design This study is a two-site, prospective, parallel group, observer-blinded randomized clinical trial (RCT). A total of 192 study patients will be recruited from the Twin Cities, MN (n = 122) and Quad Cities area in Iowa and Illinois (n = 70) to the research clinics at WHCCS and PCCR, respectively. It compares two interventions: chiropractic spinal manipulative therapy (SMT) plus home exercise program (HEP) to HEP alone (minimal intervention comparison) for patients with subacute or chronic back-related leg pain. Discussion Back-related leg pain (BRLP) is a costly and often disabling variation of the ubiquitous back pain conditions. As health care costs continue to climb, the search for effective treatments with few side-effects is critical. While SMT is the most commonly sought CAM treatment for LBP sufferers, there is only a small, albeit promising, body of research to support its use for patients with BRLP. This study seeks to fill a critical gap in the LBP literature by performing the first full scale RCT assessing chiropractic SMT for patients with sub-acute or chronic BRLP using important patient-oriented and objective biomechanical outcome measures. Trial Registration ClinicalTrials.gov NCT00494065 PMID:21426558

Using Bayesian Adaptive Trial Designs for Comparative Effectiveness Research: A Virtual Trial Execution.

PubMed

Luce, Bryan R; Connor, Jason T; Broglio, Kristine R; Mullins, C Daniel; Ishak, K Jack; Saunders, Elijah; Davis, Barry R

2016-09-20

Bayesian and adaptive clinical trial designs offer the potential for more efficient processes that result in lower sample sizes and shorter trial durations than traditional designs. To explore the use and potential benefits of Bayesian adaptive clinical trial designs in comparative effectiveness research. Virtual execution of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) as if it had been done according to a Bayesian adaptive trial design. Comparative effectiveness trial of antihypertensive medications. Patient data sampled from the more than 42 000 patients enrolled in ALLHAT with publicly available data. Number of patients randomly assigned between groups, trial duration, observed numbers of events, and overall trial results and conclusions. The Bayesian adaptive approach and original design yielded similar overall trial conclusions. The Bayesian adaptive trial randomly assigned more patients to the better-performing group and would probably have ended slightly earlier. This virtual trial execution required limited resampling of ALLHAT patients for inclusion in RE-ADAPT (REsearch in ADAptive methods for Pragmatic Trials). Involvement of a data monitoring committee and other trial logistics were not considered. In a comparative effectiveness research trial, Bayesian adaptive trial designs are a feasible approach and potentially generate earlier results and allocate more patients to better-performing groups. National Heart, Lung, and Blood Institute.

ARTS III/Parallel Processor Design Study

DOT National Transportation Integrated Search

1975-04-01

It was the purpose of this design study to investigate the feasibility, suitability, and cost-effectiveness of augmenting the ARTS III failsafe/failsoft multiprocessor system with a form of parallel processor to accomodate a large growth in air traff...

Practical characteristics of adaptive design in phase 2 and 3 clinical trials.

PubMed

Sato, A; Shimura, M; Gosho, M

2018-04-01

Adaptive design methods are expected to be ethical, reflect real medical practice, increase the likelihood of research and development success and reduce the allocation of patients into ineffective treatment groups by the early termination of clinical trials. However, the comprehensive details regarding which types of clinical trials will include adaptive designs remain unclear. We examined the practical characteristics of adaptive design used in clinical trials. We conducted a literature search of adaptive design clinical trials published from 2012 to 2015 using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, with common search terms related to adaptive design. We systematically assessed the types and characteristics of adaptive designs and disease areas employed in the adaptive design trials. Our survey identified 245 adaptive design clinical trials. The number of trials by the publication year increased from 2012 to 2013 and did not greatly change afterwards. The most frequently used adaptive design was group sequential design (n = 222, 90.6%), especially for neoplasm or cardiovascular disease trials. Among the other types of adaptive design, adaptive dose/treatment group selection (n = 21, 8.6%) and adaptive sample-size adjustment (n = 19, 7.8%) were frequently used. The adaptive randomization (n = 8, 3.3%) and adaptive seamless design (n = 6, 2.4%) were less frequent. Adaptive dose/treatment group selection and adaptive sample-size adjustment were frequently used (up to 23%) in "certain infectious and parasitic diseases," "diseases of nervous system," and "mental and behavioural disorders" in comparison with "neoplasms" (<6.6%). For "mental and behavioural disorders," adaptive randomization was used in two trials of eight trials in total (25%). Group sequential design and adaptive sample-size adjustment were used frequently in phase 3 trials or in trials where study phase was not specified, whereas the other types of adaptive designs were used more in phase 2 trials. Approximately 82% (202 of 245 trials) resulted in early termination at the interim analysis. Among the 202 trials, 132 (54% of 245 trials) had fewer randomized patients than initially planned. This result supports the motive to use adaptive design to make study durations shorter and include a smaller number of subjects. We found that adaptive designs have been applied to clinical trials in various therapeutic areas and interventions. The applications were frequently reported in neoplasm or cardiovascular clinical trials. The adaptive dose/treatment group selection and sample-size adjustment are increasingly common, and these adaptations generally follow the Food and Drug Administration's (FDA's) recommendations. © 2017 John Wiley & Sons Ltd.

A randomised controlled trial of an intervention to facilitate the implementation of healthy eating and physical activity policies and practices in childcare services

PubMed Central

Jones, Jannah; Wolfenden, Luke; Wyse, Rebecca; Finch, Meghan; Yoong, Sze Lin; Dodds, Pennie; Pond, Nicole; Gillham, Karen; Freund, Megan; McElduff, Patrick; Wye, Paula; Wiggers, John

2014-01-01

Introduction Childhood overweight and obesity tracks into adulthood, increasing the risk of developing future chronic disease. Implementing initiatives promoting healthy eating and physical activity in childcare settings has been identified as a priority to prevent excessive child weight gain. Despite this, few trials have been conducted to assess the effectiveness of interventions to support population-wide implementation of such initiatives. The aim of this study is to assess the effectiveness of a multicomponent intervention in increasing the implementation of healthy eating and physical activity policies and practices by centre-based childcare services. Methods and analysis The study will employ a parallel group randomised controlled trial design. A sample of 128 childcare services in the Hunter region of New South Wales, Australia, will be recruited to participate in the trial. 64 services will be randomly allocated to a 12-month implementation intervention. The remaining 64 services will be allocated to a usual care control group. The intervention will consist of a number of strategies to facilitate childcare service implementation of healthy eating and physical activity policies and practices. Intervention strategies will include implementation support staff, securing executive support, consensus processes, staff training, academic detailing visits, performance monitoring and feedback, tools and resources, and a communications strategy. The primary outcome of the trial will be the prevalence of services implementing all healthy eating and physical activity policies and practices targeted by the intervention. To assess the effectiveness of the intervention, telephone surveys with nominated supervisors and room leaders of childcare services will be conducted at baseline and immediately postintervention. Ethics and dissemination The study was approved by the Hunter New England Human Research Ethics Committee and the University of Newcastle Human Research Ethics Committee. Study findings will be disseminated widely through peer-reviewed publications and conference presentations. Trial registration number Australian Clinical Trials Registry ACTRN12612000927820. PMID:24742978

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol.

PubMed

Sandilands, Euan A; Cameron, Sharon; Paterson, Frances; Donaldson, Sam; Briody, Lesley; Crowe, Jane; Donnelly, Julie; Thompson, Adrian; Johnston, Neil R; Mackenzie, Ivor; Uren, Neal; Goddard, Jane; Webb, David J; Megson, Ian L; Bateman, Nicholas; Eddleston, Michael

2012-02-03

Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.

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.

Unraveling the molecular genetics of head and neck cancer through genome-wide approaches

PubMed Central

Riaz, Nadeem; Morris, Luc G.; Lee, William; Chan, Timothy A.

2014-01-01

The past decade has seen an unprecedented increase in our understanding of the biology and etiology of head and neck squamous cell carcinomas (HNSCC). Genome-wide sequencing projects have identified a number of recurrently mutated genes, including unexpected alterations in the NOTCH pathway and chromatin related genes. Gene-expression profiling has identified 4 distinct genetic subtypes which show some parallels to lung squamous cell carcinoma biology. The identification of the human papilloma virus as one causative agent in a subset of oropharyngeal cancers and their association with a favorable prognosis has opened up avenues for new therapeutic strategies. The expanding knowledge of the underlying molecular abnormalities in this once very poorly understood cancer should allow for increasingly rational clinical trial design and improved patient outcomes. PMID:25642447

Will dapivirine redeem the promises of anti-HIV microbicides? Overview of product design and clinical testing.

PubMed

das Neves, José; Martins, João Pedro; Sarmento, Bruno

2016-08-01

Microbicides are being developed in order to prevent sexual transmission of HIV. Dapivirine, a non-nucleoside reverse transcriptase inhibitor, is one of the leading drug candidates in the field, currently being tested in various dosage forms, namely vaginal rings, gels, and films. In particular, a ring allowing sustained drug release for 1month is in an advanced stage of clinical testing. Two parallel phase III clinical trials are underway in sub-Saharan Africa and results are expected to be released in early 2016. This article overviews the development of dapivirine and its multiple products as potential microbicides, with particular emphasis being placed on clinical evaluation. Also, critical aspects regarding regulatory approval, manufacturing, distribution, and access are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Trials with errors--preserving the integrity of clinical trials.

PubMed

Guyer, R L

2000-01-01

The crucial final test of medical research is the clinical trial, which determines whether a drug or discovery really is an effective therapy. All people who participate in clinical trials--researchers, sponsors, volunteers, analysts, reviewers, overseers, others--have opportunities to strengthen or weaken the integrity of the trial system by their behavior. Medical research is now officially married to business, and "profitable" connotes something different to each partner. Only if research and business can profit in parallel will the alliance succeed. Every person who is involved in the medical research business faces temptations and must choose how to react. Each has power and must choose how to wield it. Several centuries before this marriage, the Englishman Izaak Walton noted that "Health is...a blessing that money cannot buy."

Dose-response relationship between light exposure and cycling performance.

PubMed

Knaier, R; Meister, S; Aeschbacher, T; Gemperle, D; Rossmeissl, A; Cajochen, C; Schmidt-Trucksäss, A

2016-07-01

Light has a stimulating effect on physical performance if scheduled according to the chronotype, but dose-dependent effects on performance have not yet been examined. Three groups of healthy men (25.1 ± 3.1 years) were exposed to light for different durations in a parallel group design before a 40-min time-trial. In each group, subjects were exposed to either bright light (BL, 4420 lx) or moderate light (ML, 230 lx) in a randomized order in a crossover design. The durations of light exposure were 120 min prior to and during exercise (2HEX; n = 16), 60 min prior to and during exercise (1HEX; n = 10), or only for 60 min prior to exercise (1H; n = 15). Total work performed during the time-trial in kJ in the 2HEX group was significantly higher in the BL setting (527 kJ) than in ML (512 kJ) (P = 0.002), but not in 1HEX (BL: 485 kJ; ML: 498 kJ) or 1H (BL: 519 kJ; ML: 514 kJ) (P = 0.770; P = 0.485). There was a significant (P = 0.006) positive dose-response relationship between the duration of light exposure and the work performed over the three doses of light exposure. A long duration light exposure is an effective tool to increase total work in a medium length time-trial in subjects normalized for their individual chronotype. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Randomised controlled study in the primary healthcare sector to investigate the effectiveness and safety of auriculotherapy for the treatment of uncomplicated chronic rachialgia: a study protocol

PubMed Central

Vas, Jorge; Aguilar, Inmaculada; Campos, M Ángeles; Méndez, Camila; Perea-Milla, Emilio; Modesto, Manuela; Caro, Paloma; Martos, Francisco; García-Ruiz, Antonio J

2008-01-01

Background Uncomplicated chronic rachialgia is a highly prevalent complaint, and one for which therapeutic results are contradictory. The aim of the present study is to evaluate the effectiveness and safety of treatment with auriculopressure, in the primary healthcare sector, carried out by trained healthcare professionals via a 30-hour course. Methods/Design The design consists of a multi-centre randomized controlled trial, with placebo, with two parallel groups, and including an economic evaluation. Patients with chronic uncomplicated rachialgia, whose GP is considering referral for auriculopressure sensory stimulation, are eligible for inclusion. Sampling will be by consecutive selection, and randomised allocation to one of the two study arms will be determined using a centralised method, following a 1:1 plan (true auriculopressure; placebo auriculopressure). The implants (true and placebo) will be replaced once weekly, and the treatment will have a duration of 8 weeks. The primary outcome measure will be the change in pain intensity, measured on a visual analogue scale (VAS) of 100 mm, at 9 weeks after beginning the treatment. A follow up study will be performed at 6 months after beginning treatment. An assessment will also be made of the changes measured in the Spanish version of the McGill Pain Questionnaire, of the changes in the Lattinen test, and of the changes in quality of life (SF-12). Also planned is an analysis of cost-effectiveness and also, if necessary, a cost-benefit analysis. Discussion This study will contribute to developing evidence on the use of auriculotherapy using Semen vaccariae [wang bu liu xing] for the treatment of uncomplicated chronic rachialgia. Trial registration Current Controlled Trials ISRCTN01897462. PMID:18601750

Family, Community and Clinic Collaboration to Treat Overweight and Obese Children: Stanford GOALS -- a Randomized Controlled Trial of a Three-Year, Multi-Component, Multi-Level, Multi-Setting Intervention

PubMed Central

Robinson, Thomas N.; Matheson, Donna; Desai, Manisha; Wilson, Darrell M.; Weintraub, Dana L.; Haskell, William L.; McClain, Arianna; McClure, Samuel; Banda, Jorge; Sanders, Lee M.; Haydel, K. Farish; Killen, Joel D.

2013-01-01

Objective To test the effects of a three-year, community-based, multi-component, multi-level, multi-setting (MMM) approach for treating overweight and obese children. Design Two-arm, parallel group, randomized controlled trial with measures at baseline, 12, 24, and 36 months after randomization. Participants Seven through eleven year old, overweight and obese children (BMI ≥ 85th percentile) and their parents/caregivers recruited from community locations in low-income, primarily Latino neighborhoods in Northern California. Interventions Families are randomized to the MMM intervention versus a community health education active-placebo comparison intervention. Interventions last for three years for each participant. The MMM intervention includes a community-based after school team sports program designed specifically for overweight and obese children, a home-based family intervention to reduce screen time, alter the home food/eating environment, and promote self-regulatory skills for eating and activity behavior change, and a primary care behavioral counseling intervention linked to the community and home interventions. The active-placebo comparison intervention includes semi-annual health education home visits, monthly health education newsletters for children and for parents/guardians, and a series of community-based health education events for families. Main Outcome Measure Body mass index trajectory over the three-year study. Secondary outcome measures include waist circumference, triceps skinfold thickness, accelerometer-measured physical activity, 24-hour dietary recalls, screen time and other sedentary behaviors, blood pressure, fasting lipids, glucose, insulin, hemoglobin A1c, C-reactive protein, alanine aminotransferase, and psychosocial measures. Conclusions The Stanford GOALS trial is testing the efficacy of a novel community-based multi-component, multi-level, multi-setting treatment for childhood overweight and obesity in low-income, Latino families. PMID:24028942

Design of the effect of adaptive servo-ventilation on survival and cardiovascular hospital admissions in patients with heart failure and sleep apnoea: the ADVENT-HF trial.

PubMed

Lyons, Owen D; Floras, John S; Logan, Alexander G; Beanlands, Robert; Cantolla, Joaquin Durán; Fitzpatrick, Michael; Fleetham, John; John Kimoff, R; Leung, Richard S T; Lorenzi Filho, Geraldo; Mayer, Pierre; Mielniczuk, Lisa; Morrison, Debra L; Ryan, Clodagh M; Series, Frederic; Tomlinson, George A; Woo, Anna; Arzt, Michael; Parthasarathy, Sairam; Redolfi, Stefania; Kasai, Takatoshi; Parati, Gianfranco; Delgado, Diego H; Bradley, T Douglas

2017-04-01

Both types of sleep-disordered breathing (SDB), obstructive and central sleep apnoea (OSA and CSA, respectively), are common in patients with heart failure and reduced ejection fraction (HFrEF). In such patients, SDB is associated with increased cardiovascular morbidity and mortality but it remains uncertain whether treating SDB by adaptive servo-ventilation (ASV) in such patients reduces morbidity and mortality. ADVENT-HF is designed to assess the effects of treating SDB with ASV on morbidity and mortality in patients with HFrEF. ADVENT-HF is a multicentre, multinational, randomized, parallel-group, open-label trial with blinded assessment of endpoints of standard medical therapy for HFrEF alone vs. with the addition of ASV in patients with HFrEF and SDB. Patients with a history of HFrEF undergo echocardiography and polysomnography. Those with a left ventricular ejection fraction ≤45% and SDB (apnoea-hypopnoea index ≥15) are eligible. SDB is stratified into OSA with ≥50% of events obstructive or CSA with >50% of events central. Those with OSA must not have excessive daytime sleepiness (Epworth score of ≤10). Patients are then randomized to receive or not receive ASV. The primary outcome is the composite of all-cause mortality, cardiovascular hospital admissions, new-onset atrial fibrillation requiring anti-coagulation but not hospitalization, and delivery of an appropriate discharge from an implantable cardioverter-defibrillator not resulting in hospitalization during a maximum follow-up time of 5 years. The ADVENT-HF trial will help to determine whether treating SDB by ASV in patients with HFrEF improves morbidity and mortality. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Primary prevention of stroke and cardiovascular disease in the community (PREVENTS): Methodology of a health wellness coaching intervention to reduce stroke and cardiovascular disease risk, a randomized clinical trial.

PubMed

Mahon, Susan; Krishnamurthi, Rita; Vandal, Alain; Witt, Emma; Barker-Collo, Suzanne; Parmar, Priya; Theadom, Alice; Barber, Alan; Arroll, Bruce; Rush, Elaine; Elder, Hinemoa; Dyer, Jesse; Feigin, Valery

2018-02-01

Rationale Stroke is a major cause of death and disability worldwide, yet 80% of strokes can be prevented through modifications of risk factors and lifestyle and by medication. While management strategies for primary stroke prevention in high cardiovascular disease risk individuals are well established, they are underutilized and existing practice of primary stroke prevention are inadequate. Behavioral interventions are emerging as highly promising strategies to improve cardiovascular disease risk factor management. Health Wellness Coaching is an innovative, patient-focused and cost-effective, multidimensional psychological intervention designed to motivate participants to adhere to recommended medication and lifestyle changes and has been shown to improve health and enhance well-being. Aims and/or hypothesis To determine the effectiveness of Health Wellness Coaching for primary stroke prevention in an ethnically diverse sample including Māori, Pacific Island, New Zealand European and Asian participants. Design A parallel, prospective, randomized, open-treatment, single-blinded end-point trial. Participants include 320 adults with absolute five-year cardiovascular disease risk ≥ 10%, calculated using the PREDICT web-based clinical tool. Randomization will be to Health Wellness Coaching or usual care groups. Participants randomized to Health Wellness Coaching will receive 15 coaching sessions over nine months. Study outcomes A substantial relative risk reduction of five-year cardiovascular disease risk at nine months post-randomization, which is defined as 10% relative risk reduction among those at moderate five-year cardiovascular disease risk (10-15%) and 25% among those at high risk (>15%). Discussion This clinical trial will determine whether Health Wellness Coaching is an effective intervention for reducing modifiable risk factors, and hence decrease the risk of stroke and cardiovascular disease.

Adult Congenital Heart Disease-Coping And REsilience (ACHD-CARE): Rationale and methodology of a pilot randomized controlled trial.

PubMed

Kovacs, Adrienne H; Bandyopadhyay, Mimi; Grace, Sherry L; Kentner, Amanda C; Nolan, Robert P; Silversides, Candice K; Irvine, M Jane

2015-11-01

One-third of North American adults with congenital heart disease (CHD) have diagnosable mood or anxiety disorders and most do not receive mental health treatment. There are no published interventions targeting the psychosocial needs of patients with CHD of any age. We describe the development of a group psychosocial intervention aimed at improving the psychosocial functioning, quality of life, and resilience of adults with CHD and the design of a study protocol to determine the feasibility of a potential full-scale randomized controlled trial (RCT). Drawing upon our quantitative and qualitative research, we developed the Adult CHD-Coping And REsilience (ACHD-CARE) intervention and designed a feasibility study that included a 2-parallel arm non-blinded pilot RCT. Eligible participants (CHD, age ≥ 18 years, no planned surgery, symptoms suggestive of a mood and/or anxiety disorder) were randomized to the ACHD-CARE intervention or Usual Care (1:1 allocation ratio). The group intervention was delivered during eight 90-minute weekly sessions. Feasibility will be assessed in the following domains: (i) process (e.g. recruitment and retention), (ii) resources, (iii) management, (iv) scientific outcomes, and (v) intervention acceptability. This study underscores the importance of carefully developing and testing the feasibility of psychosocial interventions in medical populations before moving to full-scale clinical trials. At study conclusion, we will be poised to make one of three determinations for a full-scale RCT: (1) feasible, (2) feasible with modifications, or (3) not feasible. This study will guide the future evaluation and provision of psychosocial treatment for adults with CHD. Copyright © 2015. Published by Elsevier Inc.

Multidisciplinary Optimization Methods for Aircraft Preliminary Design

NASA Technical Reports Server (NTRS)

Kroo, Ilan; Altus, Steve; Braun, Robert; Gage, Peter; Sobieski, Ian

1994-01-01

This paper describes a research program aimed at improved methods for multidisciplinary design and optimization of large-scale aeronautical systems. The research involves new approaches to system decomposition, interdisciplinary communication, and methods of exploiting coarse-grained parallelism for analysis and optimization. A new architecture, that involves a tight coupling between optimization and analysis, is intended to improve efficiency while simplifying the structure of multidisciplinary, computation-intensive design problems involving many analysis disciplines and perhaps hundreds of design variables. Work in two areas is described here: system decomposition using compatibility constraints to simplify the analysis structure and take advantage of coarse-grained parallelism; and collaborative optimization, a decomposition of the optimization process to permit parallel design and to simplify interdisciplinary communication requirements.

Xyce parallel electronic simulator : users' guide.

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

Mei, Ting; Rankin, Eric Lamont; Thornquist, Heidi K.

2011-05-01

This manual describes the use of the Xyce Parallel Electronic Simulator. Xyce has been designed as a SPICE-compatible, high-performance analog circuit simulator, and has been written to support the simulation needs of the Sandia National Laboratories electrical designers. This development has focused on improving capability over the current state-of-the-art in the following areas: (1) Capability to solve extremely large circuit problems by supporting large-scale parallel computing platforms (up to thousands of processors). Note that this includes support for most popular parallel and serial computers; (2) Improved performance for all numerical kernels (e.g., time integrator, nonlinear and linear solvers) through state-of-the-artmore » algorithms and novel techniques. (3) Device models which are specifically tailored to meet Sandia's needs, including some radiation-aware devices (for Sandia users only); and (4) Object-oriented code design and implementation using modern coding practices that ensure that the Xyce Parallel Electronic Simulator will be maintainable and extensible far into the future. Xyce is a parallel code in the most general sense of the phrase - a message passing parallel implementation - which allows it to run efficiently on the widest possible number of computing platforms. These include serial, shared-memory and distributed-memory parallel as well as heterogeneous platforms. Careful attention has been paid to the specific nature of circuit-simulation problems to ensure that optimal parallel efficiency is achieved as the number of processors grows. The development of Xyce provides a platform for computational research and development aimed specifically at the needs of the Laboratory. With Xyce, Sandia has an 'in-house' capability with which both new electrical (e.g., device model development) and algorithmic (e.g., faster time-integration methods, parallel solver algorithms) research and development can be performed. As a result, Xyce is a unique electrical simulation capability, designed to meet the unique needs of the laboratory.« less

Rationale, Design, and Baseline Characteristics of the Utopia Trial for Preventing Diabetic Atherosclerosis Using an SGLT2 Inhibitor: A Prospective, Randomized, Open-Label, Parallel-Group Comparative Study.

PubMed

Katakami, Naoto; Mita, Tomoya; Yoshii, Hidenori; Shiraiwa, Toshihiko; Yasuda, Tetsuyuki; Okada, Yosuke; Umayahara, Yutaka; Kaneto, Hideaki; Osonoi, Takeshi; Yamamoto, Tsunehiko; Kuribayashi, Nobuichi; Maeda, Kazuhisa; Yokoyama, Hiroki; Kosugi, Keisuke; Ohtoshi, Kentaro; Hayashi, Isao; Sumitani, Satoru; Tsugawa, Mamiko; Ohashi, Makoto; Taki, Hideki; Nakamura, Tadashi; Kawashima, Satoshi; Sato, Yasunori; Watada, Hirotaka; Shimomura, Iichiro

2017-10-01

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are anti-diabetic agents that improve glycemic control with a low risk of hypoglycemia and ameliorate a variety of cardiovascular risk factors. The aim of the ongoing study described herein is to investigate the preventive effects of tofogliflozin, a potent and selective SGLT2 inhibitor, on the progression of atherosclerosis in subjects with type 2 diabetes (T2DM) using carotid intima-media thickness (IMT), an established marker of cardiovascular disease (CVD), as a marker. The Study of Using Tofogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, blinded-endpoint, multicenter, and parallel-group comparative study. The aim was to recruit a total of 340 subjects with T2DM but no history of apparent CVD at 24 clinical sites and randomly allocate these to a tofogliflozin treatment group or a conventional treatment group using drugs other than SGLT2 inhibitors. As primary outcomes, changes in mean and maximum IMT of the common carotid artery during a 104-week treatment period will be measured by carotid echography. Secondary outcomes include changes in glycemic control, parameters related to β-cell function and diabetic nephropathy, the occurrence of CVD and adverse events, and biochemical measurements reflecting vascular function. This is the first study to address the effects of SGLT2 inhibitors on the progression of carotid IMT in subjects with T2DM without a history of CVD. The results will be available in the very near future, and these findings are expected to provide clinical data that will be helpful in the prevention of diabetic atherosclerosis and subsequent CVD. Kowa Co., Ltd. UMIN000017607.

The impact of a mobile application-based treatment for urinary incontinence in adult women: Design of a mixed-methods randomized controlled trial in a primary care setting.

PubMed

Loohuis, Anne M M; Wessels, Nienke J; Jellema, Petra; Vermeulen, Karin M; Slieker-Ten Hove, Marijke C; van Gemert-Pijnen, Julia E W C; Berger, Marjolein Y; Dekker, Janny H; Blanker, Marco H

2018-02-02

We aim to assess whether a purpose-developed mobile application (app) is non-inferior regarding effectiveness and cost-effective when used to treat women with urinary incontinence (UI), as compared to care as usual in Dutch primary care. Additionally, we will explore the expectations and experiences of patients and care providers regarding app usage. A mixed-methods study will be performed, combining a pragmatic, randomized-controlled, non-inferiority trial with an extensive process evaluation. Women aged ≥18 years, suffering from UI ≥ 2 times per week and with access to a smartphone or tablet are eligible to participate. The primary outcome will be the change in UI symptom scores at 4 months after randomization, as assessed by the International Consultation on Incontinence Modular Questionnaire UI Short Form. Secondary outcomes will be the change in UI symptom scores at 12 months, as well as the patient-reported global impression of improvement, quality of life, change in sexual functioning, UI episodes per day, and costs at 4 and 12 months. In parallel, we will perform an extensive process evaluation to assess the expectations and experiences of patients and care providers regarding app usage, making use of interviews, focus group sessions, and log data analysis. This study will assess both the effectiveness and cost-effectiveness of app-based treatment for UI. The combination with the process evaluation, which will be performed in parallel, should also give valuable insights into the contextual factors that influence the effectiveness of such a treatment. © 2018 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.

Prospective Randomized Phase II Parallel Study of Vinorelbine Maintenance Therapy versus Best Supportive Care in Advanced Non-Small Cell Lung Cancer.

PubMed

Khosravi, Adnan; Esfahani-Monfared, Zahra; Seifi, Sharareh; Khodadad, Kian

2017-01-01

Maintenance strategy has been used to improve survival in non-small cell lung cancer (NSCLC). We investigated whether switch maintenance therapy with vinorelbine improved progression free survival (PFS) after first-line chemotherapy with gemcitabine plus carboplatin. In this single blind, parallel, phase 2, randomized trial, patients with NSCLC pathology, age >18 years, Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-2, and advanced stage (IIIB and IV) were treated with up to 6 cycles of gemcitabine 1250 mg/m 2 (day 1 and 8) plus carboplatin AUC 5 (day 1) every 3 weeks. Patients who did not show progression after first-line chemotherapy were randomly assigned to receive switch maintenance with vinorelbine (25 mg/m 2 , day 1, 15) or the best supportive care until disease progression. A total of 100 patients were registered, of whom 34 had a non-progressive response to first-line chemotherapy and randomly received maintenance vinorelbine (n=19) or best supportive care (n=15). The hazard ratio of PFS in the vinorelbine group relative to the best supportive care group was 1.097 (95% confidence interval = 0.479-2.510; P-value =0.827). There was no significant difference between the overall survival for the two groups (P=0.068). Switch maintenance strategies are beneficial, but defining the right candidates for treatment is a problem. Moreover, the trial designs do not always reflect the real-world considerations. Switch maintenance therapy with vinorelbine, though had tolerable toxicity, did not improve PFS in patients with NSCLC. Therefore, other agents should be considered in this setting.

Parallel coding of conjunctions in visual search.

PubMed

Found, A

1998-10-01

Two experiments investigated whether the conjunctive nature of nontarget items influenced search for a conjunction target. Each experiment consisted of two conditions. In both conditions, the target item was a red bar tilted to the right, among white tilted bars and vertical red bars. As well as color and orientation, display items also differed in terms of size. Size was irrelevant to search in that the size of the target varied randomly from trial to trial. In one condition, the size of items correlated with the other attributes of display items (e.g., all red items were big and all white items were small). In the other condition, the size of items varied randomly (i.e., some red items were small and some were big, and some white items were big and some were small). Search was more efficient in the size-correlated condition, consistent with the parallel coding of conjunctions in visual search.

Affect school and script analysis versus basic body awareness therapy in the treatment of psychological symptoms in patients with diabetes and high HbA1c concentrations: two study protocols for two randomized controlled trials.

PubMed

Melin, Eva O; Svensson, Ralph; Gustavsson, Sven-Åke; Winberg, Agneta; Denward-Olah, Ewa; Landin-Olsson, Mona; Thulesius, Hans O

2016-04-27

Depression is linked with alexithymia, anxiety, high HbA1c concentrations, disturbances of cortisol secretion, increased prevalence of diabetes complications and all-cause mortality. The psycho-educational method 'affect school with script analysis' and the mind-body therapy 'basic body awareness treatment' will be trialled in patients with diabetes, high HbA1c concentrations and psychological symptoms. The primary outcome measure is change in symptoms of depression. Secondary outcome measures are changes in HbA1c concentrations, midnight salivary cortisol concentration, symptoms of alexithymia, anxiety, self-image measures, use of antidepressants, incidence of diabetes complications and mortality. Two studies will be performed. Study I is an open-labeled parallel-group study with a two-arm randomized controlled trial design. Patients are randomized to either affect school with script analysis or to basic body awareness treatment. According to power calculations, 64 persons are required in each intervention arm at the last follow-up session. Patients with type 1 or type 2 diabetes were recruited from one hospital diabetes outpatient clinic in 2009. The trial will be completed in 2016. Study II is a multicentre open-labeled parallel-group three-arm randomized controlled trial. Patients will be randomized to affect school with script analysis, to basic body awareness treatment, or to treatment as usual. Power calculations show that 70 persons are required in each arm at the last follow-up session. Patients with type 2 diabetes will be recruited from primary care. This study will start in 2016 and finish in 2023. For both studies, the inclusion criteria are: HbA1c concentration ≥62.5 mmol/mol; depression, alexithymia, anxiety or a negative self-image; age 18-59 years; and diabetes duration ≥1 year. The exclusion criteria are pregnancy, severe comorbidities, cognitive deficiencies or inadequate Swedish. Depression, anxiety, alexithymia and self-image are assessed using self-report instruments. HbA1c concentration, midnight salivary cortisol concentration, blood pressure, serum lipid concentrations and anthropometrics are measured. Data are collected from computerized medical records and the Swedish national diabetes and causes of death registers. Whether the "affect school with script analysis" will reduce psychological symptoms, increase emotional awareness and improve diabetes related factors will be tried, and compared to "basic body awareness treatment" and treatment as usual. ClinicalTrials.gov: NCT01714986.

Electropalatography for articulation disorders associated with cleft palate.

PubMed

Lee, Alice S-Y; Law, James; Gibbon, Fiona E

2009-07-08

Cleft palate is the most common congenital deformity of the face. It could affect speech acquisition, resulting in articulation errors that could persist into adulthood. Electropalatography (EPG) has been used in speech therapy with individuals who have articulation problems that are unresponsive to "standard treatment" procedures. To determine the effectiveness of speech intervention using electropalatography (EPG) for treating articulation errors in individuals with repaired cleft palate. The following databases were searched: CENTRAL 2008 (Issue1), MEDLINE 1966 to March 2008, EMBASE 1974 to March 2008, CINAHL 1982 to March 2008, PsycINFO 1967 to March 2008 and eight other databases. We handsearched Clinical Linguistics and Phonetics (1987 to 2008, Issue 2), Cleft Palate Journal/ Cleft Palate-Craniofacial Journal (1980 to 2008, Issue 1), and the International Journal of Language and Communication Disorders (1980 to 2008, Issue 1). We searched the EPG bibliography (Gibbon 2007). We reviewed reference lists of relevant articles and approached researchers to identify other possible published and unpublished studies. Randomised controlled studies comparing EPG intervention to no treatment, delayed treatment, "standard treatment", or alternative treatment techniques for managing articulation problems associated with cleft palate in children or adults. One author searched the titles and abstracts and assessed trial quality. A second author checked judgements; disagreement was resolved through discussion. Three authors were available to examine any potential trials for possible inclusion in the review. One trial using parallel design met the inclusion criteria of this review; no meta-analysis was performed. The study reported that fewer therapy sessions were needed to achieve the treatment goals for the EPG therapy and frication display method (N = 2), followed by EPG therapy (N = 2) and "standard treatment" (N = 2). The included trial was a small-scaled study and there were serious limitations in the design and methodology (e.g. allocation concealment was unclear, blinding of outcome assessor(s) was not ensured, few quantitative outcome measures were used, and the results were not reported as planned). Therefore, the current evidence supporting the efficacy of EPG is not strong and there remains a need for high-quality randomised controlled trials to be undertaken in this area.

Protocol for a pilot randomised controlled clinical trial to compare the effectiveness of a graduated three layer straight tubular bandaging system when compared to a standard short stretch compression bandaging system in the management of people with venous ulceration: 3VSS2008

PubMed Central

2010-01-01

Background The incidence of venous ulceration is rising with the increasing age of the general population. Venous ulceration represents the most prevalent form of difficult to heal wounds and these problematic wounds require a significant amount of health care resources for treatment. Based on current knowledge multi-layer high compression system is described as the gold standard for treating venous ulcers. However, to date, despite our advances in venous ulcer therapy, no convincing low cost compression therapy studies have been conducted and there are no clear differences in the effectiveness of different types of high compression. Methods/Design The trial is designed as a pilot multicentre open label parallel group randomised trial. Male and female participants aged greater than 18 years with a venous ulcer confirmed by clinical assessment will be randomised to either the intervention compression bandage which consists of graduated lengths of 3 layers of elastic tubular compression bandage or to the short stretch inelastic compression bandage (control). The primary objective is to assess the percentage wound reduction from baseline compared to week 12 following randomisation. Randomisation will be allocated via a web based central independent randomisation service (nQuery v7) and stratified by study centre and wound size ≤ 10 cm2 or >10 cm2. Neither participants nor study staff will be blinded to treatment. Outcome assessments will be undertaken by an assessor who is blinded to the randomisation process. Discussion The aim of this study is to evaluate the efficacy and safety of two compression bandages; graduated three layer straight tubular bandaging (3L) when compared to standard short stretch (SS) compression bandaging in healing venous ulcers in patients with chronic venous ulceration. The trial investigates the differences in clinical outcomes of two currently accepted ways of treating people with venous ulcers. This study will help answer the question whether the 3L compression system or the SS compression system is associated with better outcomes. Trial Registration ACTRN12608000599370 PMID:20214822

Occupational rehabilitation programs for musculoskeletal pain and common mental health disorders: study protocol of a randomized controlled trial

PubMed Central

2014-01-01

Background Long-term sick leave has considerably negative impact on the individual and society. Hence, the need to identify effective occupational rehabilitation programs is pressing. In Norway, group based occupational rehabilitation programs merging patients with different diagnoses have existed for many years, but no rigorous evaluation has been performed. The described randomized controlled trial aims primarily to compare two structured multicomponent inpatient rehabilitation programs, differing in length and content, with a comparative cognitive intervention. Secondarily the two inpatient programs will be compared with each other, and with a usual care reference group. Methods/design The study is designed as a randomized controlled trial with parallel groups. The Social Security Office performs monthly extractions of sick listed individuals aged 18–60 years, on sick leave 2–12 months, with sick leave status 50% - 100% due to musculoskeletal, mental or unspecific disorders. Sick-listed persons are randomized twice: 1) to receive one of two invitations to participate in the study or not receive an invitation, where the latter “untouched” control group will be monitored for future sick leave in the National Social Security Register, and 2) after inclusion, to a Long or Short inpatient multicomponent rehabilitation program (depending on which invitation was sent) or an outpatient cognitive behavioral therapy group comparative program. The Long program consists of 3 ½ weeks with full rehabilitation days. The Short program consists of 4 + 4 full days, separated by two weeks, in which a workplace visit will be performed if desirable. Three areas of rehabilitation are targeted: mental training, physical training and work-related problem solving. The primary outcome is number of sick leave days. Secondary outcomes include time until full sustainable return to work, health related quality of life, health related behavior, functional status, somatic and mental health, and perceptions of work. In addition, health economic evaluation will be performed, and the implementation of the interventions, expectations and experiences of users and service providers will be investigated with different qualitative methods. Trial registration ClinicalTrials.gov: NCT01926574. PMID:24735616

A randomised controlled trial of a complex intervention to reduce children’s exposure to secondhand smoke in the home

PubMed Central

Thorley, Rebecca; Jones, Laura; Opazo Breton, Magdalena; Cook, Juliette; McNeill, Ann; Britton, John; Coleman, Tim; Lewis, Sarah

2018-01-01

Objectives Exposing children to secondhand tobacco smoke (SHS) causes significant harm and occurs predominantly through smoking by caregivers in the family home. We report a trial of a complex intervention designed to reduce secondhand smoke exposure of children whose primary caregiver feels unable or unwilling to quit smoking. Design An open-label, parallel, randomised controlled trial. Setting Deprived communities in Nottingham City and County, England Participants Caregivers resident in Nottingham City and County in England who were at least 18 years old, the main caregiver of a child aged under 5 years living in their household, and reported that they were smoking tobacco inside their home. Interventions We compared a complex intervention combining personalised feedback on home air quality, behavioural support and nicotine replacement therapy for temporary abstinence with usual care. Main outcomes The primary outcome was change in air quality in the home, measured as average 16–24  hours levels of particulate matter of  < 2.5  µm diameter (PM2.5), between baseline and 12 weeks. Secondary outcomes included changes in maximum PM2.5, proportion of time PM2.5 exceeded WHO recommended levels of maximum exposure of 25  µg/mg3, child salivary cotinine, caregivers’ cigarette consumption, nicotine dependence, determination to stop smoking, quit attempts and quitting altogether during the intervention. Results Arithmetic mean PM2.5 decreased significantly more (by 35.2 %; 95%  CI 12.7% to 51.9 %) in intervention than in usual care households, as did the proportion of time PM2.5 exceeded 25  µg/mg3, child salivary cotinine concentrations, caregivers’ cigarette consumption in the home, nicotine dependence, determination to quit and likelihood of having made a quit attempt. Conclusions By reducing exposure to SHS in the homes of children who live with smokers unable or unwilling to quit, this intervention offers huge potential to reduce children’s’ tobacco-related harm. Trial registration number ISRCTN81701383. This trial was funded by the UK National Institute for Health Research (NIHR): RP-PG-0608-10020 PMID:28432210

Efficacy of cryotherapy plus topical Juniperus excelsa M. Bieb cream versus cryotherapy plus placebo in the treatment of Old World cutaneous leishmaniasis: A triple-blind randomized controlled clinical trial

PubMed Central

Parvizi, Mohammad Mahdi; Moein, Mahmoodreza; Hatam, Gholamreza; Nimrouzi, Majid; Hassanzadeh, Jafar; Hamidizadeh, Nasrin; Khorrami, Hamid Reza; Zarshenas, Mohammad Mehdi

2017-01-01

Background Cutaneous leishmaniasis is one of the highly prevalent endemic diseases in the Middle East and North Africa. Many treatment modalities have been recommended for this condition but success rates remain limited. Herbal remedies have also been used for treatment but evidence-based clinical trials with these products are sparse. In-vitro and in-vivo studies have shown the anti-leishmanial and curative effects of extract of fruits and leaves of Juniperus excelsa (J. excelsa). The aim of this study was to determine the efficacy of topical J. excelsa M. Bieb extract as an adjuvant to cryotherapy for the treatment of human CL. Materials and methods This study was designed as a two-arm triple-blind randomized placebo-controlled clinical trial using a parallel design. Seventy-two patients with clinical diagnosis of CL confirmed by leishmania smears were allocated to receive either a topical formulation of leaf of J. excelsa extract (group A) or placebo (group B) for 3 months. Both groups received cryotherapy as baseline standard treatment. Patients were evaluated before and weekly after the intervention was initiated until complete cure. Results Overall, 82% of patients in group A, experienced complete cure and 9% of them had partial cure. On the other hand, 34% in group B reported complete cure, while 14% of them had partial cure at the end of treatment protocol with a significant difference between the two groups (P< 0.001). The mean duration to healing of the lesions in patients who received J. excelsa extract was statistically significantly shorter than the placebo group (p = 0.04). No significant side effect was seen in the J. excelsa extract group except for mild to moderate local irritation after a few weeks in a few numbers of patients. Conclusion The results of this study showed that topical J. excelsa extract can be used as an adjuvant treatment modality in addition to cryotherapy for accelerating the time to cure in addition to increasing the complete cure rate in CL. Trial registration ClinicalTrials.gov IRCT2015082523753N1 PMID:28981503

Testing the activitystat hypothesis: a randomised controlled trial protocol

PubMed Central

2012-01-01

Background The activitystat hypothesis proposes that when physical activity or energy expenditure is increased or decreased in one domain, there will be a compensatory change in another domain to maintain an overall, stable level of physical activity or energy expenditure. To date, there has been no experimental study primarily designed to test the activitystat hypothesis in adults. The aim of this trial is to determine the effect of two different imposed exercise loads on total daily energy expenditure and physical activity levels. Methods This study will be a randomised, multi-arm, parallel controlled trial. Insufficiently active adults (as determined by the Active Australia survey) aged 18–60 years old will be recruited for this study (n=146). Participants must also satisfy the Sports Medicine Australia Pre-Exercise Screening System and must weigh less than 150 kg. Participants will be randomly assigned to one of three groups using a computer-generated allocation sequence. Participants in the Moderate exercise group will receive an additional 150 minutes of moderate to vigorous physical activity per week for six weeks, and those in the Extensive exercise group will receive an additional 300 minutes of moderate to vigorous physical activity per week for six weeks. Exercise targets will be accumulated through both group and individual exercise sessions monitored by heart rate telemetry. Control participants will not be given any instructions regarding lifestyle. The primary outcome measures are activity energy expenditure (doubly labeled water) and physical activity (accelerometry). Secondary measures will include resting metabolic rate via indirect calorimetry, use of time, maximal oxygen consumption and several anthropometric and physiological measures. Outcome measures will be conducted at baseline (zero weeks), mid- and end-intervention (three and six weeks) with three (12 weeks) and six month (24 week) follow-up. All assessors will be blinded to group allocation. Discussion This protocol has been specifically designed to test the activitystat hypothesis while taking into account the key conceptual and methodological considerations of testing a biologically regulated homeostatic feedback loop. Results of this study will be an important addition to the growing literature and debate concerning the possible existence of an activitystat. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12610000248066 PMID:23043381

A novel community-based study to address disparities in hypertension and colorectal cancer: a study protocol for a randomized control trial

PubMed Central

2013-01-01

Background Black men have the greatest burden of premature death and disability from hypertension (HTN) in the United States, and the highest incidence and mortality from colorectal cancer (CRC). While several clinical trials have reported beneficial effects of lifestyle changes on blood pressure (BP) reduction, and improved CRC screening with patient navigation (PN), the effectiveness of these approaches in community-based settings remains understudied, particularly among Black men. Methods/design MISTER B is a two-parallel-arm randomized controlled trial that will compare the effect of a motivational interviewing tailored lifestyle intervention (MINT) versus a culturally targeted PN intervention on improvement of BP and CRC screening among black men aged ≥50 with uncontrolled HTN who are eligible for CRC screening. Approximately 480 self-identified black men will be randomly assigned to one of the two study conditions. This innovative research design allows each intervention to serve as the control for the other. Specifically, the MINT arm is the control condition for the PN arm, and vice-versa. This novel, simultaneous testing of two community-based interventions in a randomized fashion is an economical and yet rigorous strategy that also enhances the acceptability of the project. Participants will be recruited during scheduled screening events at barbershops in New York City. Trained research assistants will conduct the lifestyle intervention, while trained community health workers will deliver the PN intervention. The primary outcomes will be 1) within-patient change in systolic and diastolic BP from baseline to six months and 2) CRC screening rates at six months. Discussion This innovative study will provide a unique opportunity to test two interventions for two health disparities simultaneously in community-based settings. Our study is one of the first to test culturally targeted patient navigation for CRC screening among black men in barbershops. Thus, our study has the potential to improve the reach of hypertension control and cancer prevention efforts within a high-risk population that is under-represented in primary care settings. Trial registration ClinicalTrials.gov, NCT01092078 PMID:24011142

Mentalization-based treatment in groups for adolescents with borderline personality disorder (BPD) or subthreshold BPD versus treatment as usual (M-GAB): study protocol for a randomized controlled trial.

PubMed

Beck, Emma; Bo, Sune; Gondan, Matthias; Poulsen, Stig; Pedersen, Liselotte; Pedersen, Jesper; Simonsen, Erik

2016-07-12

Evidence-based outpatient psychotherapeutic programs are first-line treatment of borderline personality disorder (BPD). Early and effective treatment of BPD is crucial to the prevention of its individual, psychosocial, and economic consequences. However, in spite of recent advantages in diagnosing adolescent BPD, there is a lack of cost-effective evidence-based treatment programs for adolescents. Mentalization-based treatment is an evidence-based program for BPD, originally developed for adults. We will investigate whether a specifically designed mentalization-based treatment in groups is an efficacious treatment for adolescents with BPD or subthreshold BPD compared to treatment as usual. The trial is a four-center, two-armed, parallel-group, assessor-blinded randomized clinical superiority trial. One hundred twelve patients aged 14 to 17 referred to Child and Adolescent Psychiatric Clinics in Region Zealand are randomized to 1 year of either mentalization-based treatment in groups or treatment as usual. Patients will be included if they meet at least four DSM-5 criteria for BPD. The primary outcome is self-reported borderline features at discharge. Secondary outcomes will include self-harm, depression, BPD criteria, externalizing and internalizing symptoms, and social functioning, together with parental reports on borderline features, externalizing and internalizing symptoms. Measures of attachment and mentalization will be included as mediational variables. Follow-up assessment will take place at 3 and 12 months after end of treatment. This is the first randomized controlled trial to test the efficacy of a group-based mentalization-based treatment for adolescents with BPD or subthreshold BPD. If the results confirm our hypothesis, this trial will add to the treatment options of cost-effective treatment of adolescent BPD. Clinicaltrials.gov NCT02068326 , February 19, 2014.

Medicoeconomic analysis of lobectomy using thoracoscopy versus thoracotomy for lung cancer: a study protocol for a multicentre randomised controlled trial (Lungsco01)

PubMed Central

Pagès, Pierre-Benoit; Abou Hanna, Halim; Bertaux, Anne-Claire; Serge Aho, Ludwig Serge; Magdaleinat, Pierre; Baste, Jean-Marc; Filaire, Marc; de Latour, Richard; Assouad, Jalal; Tronc, François; Jayle, Christophe; Mouroux, Jérome; Thomas, Pascal-Alexandre; Falcoz, Pierre-Emmanuel; Marty-Ané, Charles-Henri; Bernard, Alain

2017-01-01

Introduction In the last decade, video-assisted thoracoscopic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC) has had a major effect on thoracic surgery. Retrospective series have reported benefits of VATS when compared with open thoracotomy in terms of postoperative pain, postoperative complications and length of hospital stay. However, no large randomised control trial has been conducted to assess the reality of the potential benefits of VATS lobectomy or its medicoeconomic impact. Methods and analysis The French National Institute of Health funded Lungsco01 to determine whether VATS for lobectomy is superior to open thoracotomy for the treatment of NSCLC in terms of economic cost to society. This trial will also include an analysis of postoperative outcomes, the length of hospital stay, the quality of life, long-term survival and locoregional recurrence. The study design is a two-arm parallel randomised controlled trial comparing VATS lobectomy with lobectomy using thoracotomy for the treatment of NSCLC. Patients will be eligible if they have proven or suspected lung cancer which could be treated by lobectomy. Patients will be randomised via an independent service. All patients will be monitored according to standard thoracic surgical practices. All patients will be evaluated at day 1, day 30, month 3, month 6, month 12 and then every year for 2 years thereafter. The recruitment target is 600 patients. Ethics and dissemination The protocol has been approved by the French National Research Ethics Committee (CPP Est I: 09/06/2015) and the French Medicines Agency (09/06/2015). Results will be presented at national and international meetings and conferences and published in peer-reviewed journals. Trial registration number NCT02502318. PMID:28619764

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.

Effect of acupuncture on insomnia following stroke: study protocol for a randomized controlled trial.

PubMed

Cao, Yan; Yin, Xuan; Soto-Aguilar, Francisca; Liu, Yiping; Yin, Ping; Wu, Junyi; Zhu, Bochang; Li, Wentao; Lao, Lixing; Xu, Shifen

2016-11-16

The incidence, mortality, and prevalence of stroke are high in China. Stroke is commonly associated with insomnia; both insomnia and stroke have been effectively treated with acupuncture for a long time. The aim of this proposed trial is to assess the therapeutic effect of acupuncture on insomnia following stroke. This proposed study is a single-center, single-blinded (patient-assessor-blinded), parallel-group randomized controlled trial. We will randomly assign 60 participants with insomnia following stroke into two groups in a 1:1 ratio. The intervention group will undergo traditional acupuncture that achieves the De-qi sensation, and the control group will receive sham acupuncture without needle insertion. The same acupoints (DU20, DU24, EX-HN3, EX-HN22, HT7, and SP6) will be used in both groups. Treatments will be given to all participants three times a week for the subsequent 4 weeks. The primary outcome will be the Pittsburgh Sleep Quality Index. The secondary outcomes will be: the Insomnia Severity Index; sleep efficacy, sleep awakenings, and total sleep time recorded via actigraphy; the National Institutes of Health Stroke Scale; the Stroke-Specific Quality of Life score; the Hospital Anxiety and Depression Scale. The use of estazolam will be permitted and regulated under certain conditions. Outcomes will be assessed at baseline, 2 weeks after treatment commencement, 4 weeks after treatment commencement, and at the 8-week follow-up. This proposed study will contribute to expanding knowledge about acupuncture treatment for insomnia following stroke. This will be a high-quality randomized controlled trial with strict methodology and few design deficits. It will investigate the effectiveness of acupuncture as an alternative treatment for insomnia following stroke. Chinese Clinical Trial Registry identifier: ChiCTR-IIC-16008382 . Registered on 28 April 2016.

Study protocol: Münster tinnitus randomized controlled clinical trial-2013 based on tailor-made notched music training (TMNMT).

PubMed

Pantev, Christo; Rudack, Claudia; Stein, Alwina; Wunderlich, Robert; Engell, Alva; Lau, Pia; Wollbrink, Andreas; Shaykevich, Alex

2014-03-02

Tinnitus is a result of hyper-activity/hyper-synchrony of auditory neurons coding the tinnitus frequency, which has developed to synchronous mass activity owing the lack of inhibition. We assume that removal of exactly these frequency components from an auditory stimulus will cause the brain to reorganize around tonotopic regions coding the tinnitus frequency. Based on this assumption a novel treatment for tonal tinnitus - tailor-made notched music training (TMNMT) (Proc Natl Acad Sci USA 107:1207-1210, 2010; Ann N Y Acad Sci 1252:253-258, 2012; Frontiers Syst Neurosci 6:50, 2012) has been introduced and will be tested in this clinical trial on a large number of tinnitus patients. A randomized controlled trial (RCT) in parallel group design will be performed in a double-blinded manner. The choice of the intervention we are going to apply is based on two "proof of concept" studies in humans (Proc Natl Acad Sci USA 107:1207-1210, 2010; Ann N Y Acad Sci 1252:253-258, 2012; Frontiers Syst Neurosci 6:50, 2012; PloS One 6(9):e24685, 2011) and on a recent animal study (Front Syst Neurosci 7:21, 2013).The RCT includes 100 participants with chronic, tonal tinnitus who listened to tailor-made notched music (TMNM) for two hours a day for three months. The effect of TMNMT is assessed by the tinnitus handicap questionnaire and visual analogue scales (VAS) measuring perceived tinnitus loudness, distress and handicap. This is the first randomized controlled trial applying TMNMT on a larger number of patients with tonal tinnitus. Our data will verify more securely and reliably the effectiveness of this kind of completely non-invasive and low-cost treatment approach on tonal tinnitus. Current Controlled Trials ISRCTN04840953.

Moxibustion for the treatment of pressure ulcers: study protocol for a pilot, multicentre, randomised controlled trial.

PubMed

Zhang, Qin-hong; Yue, Jin-huan; Li, Chao-ran; Sun, Zhong-ren

2014-12-30

Pressure ulcers are common in the elderly and immobile. Currently, there are few proven effective treatments for pressure ulcers. This trial aims to evaluate the feasibility, efficacy and safety of moxibustion for pressure ulcers. This is a multicentre, two-armed, parallel-design randomised controlled trial (RCT). 30 eligible patients with pressure ulcers will be randomised in a ratio of 1:1 to the treatment group and control group. The participants in the treatment group will undergo indirect moxibustion for 30 min before application of a dressing, one session daily, five sessions weekly for 4 weeks. The patients in the control group will only receive a dressing, applied in the same way as in the treatment group. Both groups will be followed up for 3 months. The primary outcome measures will be wound surface area (WSA) and proportion of ulcers healed within trial period (PUHTP). The secondary outcomes will be the Pressure Ulcer Scale for Healing (PUSH Tool), visual analogue scale (VAS) and adverse events. All outcomes will be evaluated at the beginning of the study, at the end of the second week, at 4 weeks after randomisation and at 1 and 3 months after treatment cessation. This trial has undergone ethical scrutiny and been approved by the ethics review boards of First Affiliated Hospital of Heilongjiang University of Chinese Medicine and Second Affiliated Hospital of Heilongjiang University of Chinese Medicine (Permission number: HZYEYLP2014). The results of this study will provide clinical evidence for the feasibility, efficacy and safety of moxibustion for pressure ulcers. ChiCTR-TRC-13003959. 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.

Rationale and design of the multicenter randomized trial investigating the effects of levosimendan pretreatment in patients with low ejection fraction (≤40 %) undergoing CABG with cardiopulmonary bypass (LICORN study).

PubMed

Caruba, Thibaut; Hourton, Delphine; Sabatier, Brigitte; Rousseau, Dominique; Tibi, Annick; Hoffart-Jourdain, Cécile; Souag, Akim; Freitas, Nelly; Yjjou, Mounia; Almeida, Carla; Gomes, Nathalie; Aucouturier, Pascaline; Djadi-Prat, Juliette; Menasché, Philippe; Chatellier, Gilles; Cholley, Bernard

2016-08-05

Patients with a left ventricular ejection fraction (LVEF) of less than 40 % are at high risk of developing postoperative low cardiac output syndrome (LCOS). Despite actual treatments (inotropic agents and/or mechanical assist devices), the mortality rate of such patients remains very high (13 to 24 %). The LICORN trial aims at assessing the efficacy of a preoperative infusion of levosimendan in reducing postoperative LCOS in patients with poor LVEF undergoing coronary artery bypass grafting (CABG). LICORN study is a multicenter, randomized double-blind, placebo-controlled trial in parallel groups. 340 patients with LVEF ≤40 %, undergoing CABG will be recruited from 13 French hospitals. The study drug will be started after anaesthesia induction and infused over 24 h (0.1 μg/kg/min). The primary outcome (postoperative LCOS) is evaluated using a composite criterion composed of: 1) need for inotropic agents beyond 24 h following discontinuation of the study drug; 2) need for post-operative mechanical assist devices or failure to wean from these techniques when inserted pre-operatively; 3) need for renal replacement therapy. Secondary outcomes include: 1) mortality at Day 28 and Day 180; 2) each item of the composite criterion of the primary outcome; 3) the number of "ventilator-free" days and "out of intensive care unit" days at Day 28. The usefulness of levosimendan in the perioperative period has not yet been documented with a high level of evidence. The LICORN study is the first randomized controlled trial evaluating the clinical value of preoperative levosimendan in high risk cardiac surgical patients undergoing CABG. NCT02184819 (ClinicalTrials.gov).

UK DRAFFT - A randomised controlled trial of percutaneous fixation with kirschner wires versus volar locking-plate fixation in the treatment of adult patients with a dorsally displaced fracture of the distal radius

PubMed Central

2011-01-01

Background Fractures of the distal radius are extremely common injuries in adults. However, the optimal management remains controversial. In general, fractures of the distal radius are treated non-operatively if the bone fragments can be held in anatomical alignment by a plaster cast or orthotic. However, if this is not possible, then operative fixation is required. There are several operative options but the two most common in the UK, are Kirschner-wire fixation (K-wires) and volar plate fixation using fixed-angle screws (locking-plates). The primary aim of this trial is to determine if there is a difference in the Patient-Reported Wrist Evaluation one year following K-wire fixation versus locking-plate fixation for adult patients with a dorsally-displaced fracture of the distal radius. Methods/design All adult patients with an acute, dorsally-displaced fracture of the distal radius, requiring operative fixation are potentially eligible to take part in this study. A total of 390 consenting patients will be randomly allocated to either K-wire fixation or locking-plate fixation. The surgery will be performed in trauma units across the UK using the preferred technique of the treating surgeon. Data regarding wrist function, quality of life, complications and costs will be collected at six weeks and three, six and twelve months following the injury. The primary outcome measure will be wrist function with a parallel economic analysis. Discussion This pragmatic, multi-centre trial is due to deliver results in December 2013. Trial registration Current Controlled Trials ISRCTN31379280 UKCRN portfolio ID 8956 PMID:21914196

Evidence and Clinical Trials.

NASA Astrophysics Data System (ADS)

Goodman, Steven N.

1989-11-01

This dissertation explores the use of a mathematical measure of statistical evidence, the log likelihood ratio, in clinical trials. The methods and thinking behind the use of an evidential measure are contrasted with traditional methods of analyzing data, which depend primarily on a p-value as an estimate of the statistical strength of an observed data pattern. It is contended that neither the behavioral dictates of Neyman-Pearson hypothesis testing methods, nor the coherency dictates of Bayesian methods are realistic models on which to base inference. The use of the likelihood alone is applied to four aspects of trial design or conduct: the calculation of sample size, the monitoring of data, testing for the equivalence of two treatments, and meta-analysis--the combining of results from different trials. Finally, a more general model of statistical inference, using belief functions, is used to see if it is possible to separate the assessment of evidence from our background knowledge. It is shown that traditional and Bayesian methods can be modeled as two ends of a continuum of structured background knowledge, methods which summarize evidence at the point of maximum likelihood assuming no structure, and Bayesian methods assuming complete knowledge. Both schools are seen to be missing a concept of ignorance- -uncommitted belief. This concept provides the key to understanding the problem of sampling to a foregone conclusion and the role of frequency properties in statistical inference. The conclusion is that statistical evidence cannot be defined independently of background knowledge, and that frequency properties of an estimator are an indirect measure of uncommitted belief. Several likelihood summaries need to be used in clinical trials, with the quantitative disparity between summaries being an indirect measure of our ignorance. This conclusion is linked with parallel ideas in the philosophy of science and cognitive psychology.

Developing Substance Use Programming for Person-Oriented Recovery and Treatment (SUPPORT): protocol for a pilot randomized controlled trial.

PubMed

Watson, Dennis P; Ray, Bradley; Robison, Lisa; Xu, Huiping; Edwards, Rhiannon; Salyers, Michelle P; Hill, James; Shue, Sarah

2017-01-01

There is a lack of evidence-based substance use disorder treatment and services targeting returning inmates. Substance Use Programming for Person-Oriented Recovery and Treatment (SUPPORT) is a community-driven, recovery-oriented approach to substance abuse care which has the potential to address this service gap. SUPPORT is modeled after Indiana's Access to Recovery program, which was closed due to lack of federal support despite positive improvements in clients' recovery outcomes. SUPPORT builds on noted limitations of Indiana's Access to Recovery program. The ultimate goal of this project is to establish SUPPORT as an effective and scalable recovery-oriented system of care. A necessary step we must take before launching a large clinical trial is pilot testing the SUPPORT intervention. The pilot will take place at Public Advocates in Community Re-Entry (PACE), nonprofit serving individuals with felony convictions who are located in Marion County, Indiana (Indianapolis). The pilot will follow a basic parallel randomized design to compare clients receiving SUPPORT with clients receiving standard services. A total of 80 clients within 3 months of prison release will be recruited to participate and randomly assigned to one of the two intervention arms. Quantitative measures will be collected at multiple time points to understand SUPPORT's impact on recovery capital and outcomes. We will also collect qualitative data from SUPPORT clients to better understand their program and post-discharge experiences. Successful completion of this pilot will prepare us to conduct a multi-site clinical trial. The ultimate goal of this future work is to develop an evidence-based and scalable approach to treating substance use disorder among persons returning to society after incarceration. ClinicalTrials.gov (Clinical Trials ID: NCT03132753 and Protocol Number: 1511731907). Registered 28 April 2017.

Weight loss referrals for adults in primary care (WRAP): protocol for a multi-centre randomised controlled trial comparing the clinical and cost-effectiveness of primary care referral to a commercial weight loss provider for 12 weeks, referral for 52 weeks, and a brief self-help intervention [ISRCTN82857232

PubMed Central

2014-01-01

Background Recent trials demonstrate the acceptability and short term efficacy of primary care referral to a commercial weight loss provider for weight management. Commissioners now need information on the optimal duration of intervention and the longer term outcomes and cost effectiveness of such treatment to give best value for money. Methods/Design This multicentre, randomised controlled trial with a parallel design will recruit 1200 overweight adults (BMI ≥28 kg/m2) through their primary care provider. They will be randomised in a 2:5:5 allocation to: Brief Intervention, Commercial Programme for 12 weeks, or Commercial Programme for 52 weeks. Participants will be followed up for two years, with assessments at 0, 3, 12 and 24 months. The sequential primary research questions are whether the CP interventions achieve significantly greater weight loss from baseline to 12 months than BI, and whether CP52 achieves significantly greater weight loss from baseline to 12 months than CP12. The primary outcomes will be an intention to treat analysis of between treatment differences in body weight at 12 months. Clinical effectiveness will be also be assessed by measures of weight, fat mass, and blood pressure at each time point and biochemical risk factors at 12 months. Self-report questionnaires will collect data on psychosocial factors associated with adherence, weight-loss and weight-loss maintenance. A within-trial and long-term cost-effectiveness analysis will be conducted from an NHS perspective. Qualitative methods will be used to examine the participant experience. Discussion The current trial compares the clinical and cost effectiveness of referral to a commercial provider with a brief intervention. This trial will specifically examine whether providing longer weight-loss treatment without altering content or intensity (12 months commercial referral vs. 12 weeks) leads to greater weight loss at one year and is sustained at 2 years. It will also evaluate the relative cost-effectiveness of the three interventions. This study has direct implications for primary care practice in the UK and will provide important information to inform the decisions of practitioners and commissioners about service provision. Trial Registration Current Controlled Trials ISRCTN82857232. Date registered: 15/10/2012. PMID:24943673

Parallel Processing at the High School Level.

ERIC Educational Resources Information Center

Sheary, Kathryn Anne

This study investigated the ability of high school students to cognitively understand and implement parallel processing. Data indicates that most parallel processing is being taught at the university level. Instructional modules on C, Linux, and the parallel processing language, P4, were designed to show that high school students are highly…

Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov

PubMed Central

Bothwell, Laura E; Avorn, Jerry; Khan, Nazleen F; Kesselheim, Aaron S

2018-01-01

Objectives This review investigates characteristics of implemented adaptive design clinical trials and provides examples of regulatory experience with such trials. Design Review of adaptive design clinical trials in EMBASE, PubMed, Cochrane Registry of Controlled Clinical Trials, Web of Science and ClinicalTrials.gov. Phase I and seamless Phase I/II trials were excluded. Variables extracted from trials included basic study characteristics, adaptive design features, size and use of independent data monitoring committees (DMCs) and blinded interim analyses. We also examined use of the adaptive trials in new drug submissions to the Food and Drug Administration (FDA) and European Medicines Agency (EMA) and recorded regulators’ experiences with adaptive designs. Results 142 studies met inclusion criteria. There has been a recent growth in publicly reported use of adaptive designs among researchers around the world. The most frequently appearing types of adaptations were seamless Phase II/III (57%), group sequential (21%), biomarker adaptive (20%), and adaptive dose-finding designs (16%). About one-third (32%) of trials reported an independent DMC, while 6% reported blinded interim analysis. We found that 9% of adaptive trials were used for FDA product approval consideration, and 12% were used for EMA product approval consideration. International regulators had mixed experiences with adaptive trials. Many product applications with adaptive trials had extensive correspondence between drug sponsors and regulators regarding the adaptive designs, in some cases with regulators requiring revisions or alterations to research designs. Conclusions Wider use of adaptive designs will necessitate new drug application sponsors to engage with regulatory scientists during planning and conduct of the trials. Investigators need to more consistently report protections intended to preserve confidentiality and minimise potential operational bias during interim analysis. PMID:29440155

Comparison of intra-articular injections of hyaluronic acid and corticosteroid in the treatment of osteoarthritis of the hip in comparison with intra-articular injections of bupivacaine. Design of a prospective, randomized, controlled study with blinding of the patients and outcome assessors.

PubMed

Colen, Sascha; van den Bekerom, Michel P J; Bellemans, Johan; Mulier, Michiel

2010-11-16

Although intra-articular hyaluronic acid is well established as a treatment for osteoarthritis of the knee, its use in hip osteoarthritis is not based on large randomized controlled trials. There is a need for more rigorously designed studies on hip osteoarthritis treatment as this subject is still very much under debate. Randomized, controlled trial with a three-armed, parallel-group design. Approximately 315 patients complying with the inclusion and exclusion criteria will be randomized into one of the following treatment groups: infiltration of the hip joint with hyaluronic acid, with a corticosteroid or with 0.125% bupivacaine.The following outcome measure instruments will be assessed at baseline, i.e. before the intra-articular injection of one of the study products, and then again at six weeks, 3 and 6 months after the initial injection: Pain (100 mm VAS), Harris Hip Score and HOOS, patient assessment of their clinical status (worse, stable or better then at the time of enrollment) and intake of pain rescue medication (number per week). In addition patients will be asked if they have complications/adverse events. The six-month follow-up period for all patients will begin on the date the first injection is administered. This randomized, controlled, three-arm study will hopefully provide robust information on two of the intra-articular treatments used in hip osteoarthritis, in comparison to bupivacaine. NCT01079455.

Effective components of feedback from Routine Outcome Monitoring (ROM) in youth mental health care: study protocol of a three-arm parallel-group randomized controlled trial

PubMed Central

2014-01-01

Background Routine Outcome Monitoring refers to regular measurements of clients’ progress in clinical practice, aiming to evaluate and, if necessary, adapt treatment. Clients fill out questionnaires and clinicians receive feedback about the results. Studies concerning feedback in youth mental health care are rare. The effects of feedback, the importance of specific aspects of feedback, and the mechanisms underlying the effects of feedback are unknown. In the present study, several potentially effective components of feedback from Routine Outcome Monitoring in youth mental health care in the Netherlands are investigated. Methods/Design We will examine three different forms of feedback through a three-arm parallel-group randomized controlled trial. 432 children and adolescents (aged 4 to 17 years) and their parents, who have been referred to mental health care institution Pro Persona, will be randomly assigned to one of three feedback conditions (144 participants per condition). Randomization will be stratified by age of the child or adolescent and by department. All participants fill out questionnaires at the start of treatment, one and a half months after the start of treatment, every three months during treatment, and at the end of treatment. Participants in the second and third feedback conditions fill out an additional questionnaire. In condition 1, clinicians receive basic feedback regarding clients’ symptoms and quality of life. In condition 2, the feedback of condition 1 is extended with feedback regarding possible obstacles to a good outcome and with practical suggestions. In condition 3, the feedback of condition 2 is discussed with a colleague while following a standardized format for case consultation. The primary outcome measure is symptom severity and secondary outcome measures are quality of life, satisfaction with treatment, number of sessions, length of treatment, and rates of dropout. We will also examine the role of being not on track (not responding to treatment). Discussion This study contributes to the identification of effective components of feedback and a better understanding of how feedback functions in real-world clinical practice. If the different feedback components prove to be effective, this can help to support and improve the care for youth. Trial registration Dutch Trial Register NTR4234 PMID:24393491

Predator-induced phenotypic plasticity of shape and behavior: parallel and unique patterns across sexes and species

PubMed Central

Kinnison, Michael T.

2017-01-01

Abstract Phenotypic plasticity is often an adaptation of organisms to cope with temporally or spatially heterogenous landscapes. Like other adaptations, one would predict that different species, populations, or sexes might thus show some degree of parallel evolution of plasticity, in the form of parallel reaction norms, when exposed to analogous environmental gradients. Indeed, one might even expect parallelism of plasticity to repeatedly evolve in multiple traits responding to the same gradient, resulting in integrated parallelism of plasticity. In this study, we experimentally tested for parallel patterns of predator-mediated plasticity of size, shape, and behavior of 2 species and sexes of mosquitofish. Examination of behavioral trials indicated that the 2 species showed unique patterns of behavioral plasticity, whereas the 2 sexes in each species showed parallel responses. Fish shape showed parallel patterns of plasticity for both sexes and species, albeit males showed evidence of unique plasticity related to reproductive anatomy. Moreover, patterns of shape plasticity due to predator exposure were broadly parallel to what has been depicted for predator-mediated population divergence in other studies (slender bodies, expanded caudal regions, ventrally located eyes, and reduced male gonopodia). We did not find evidence of phenotypic plasticity in fish size for either species or sex. Hence, our findings support broadly integrated parallelism of plasticity for sexes within species and less integrated parallelism for species. We interpret these findings with respect to their potential broader implications for the interacting roles of adaptation and constraint in the evolutionary origins of parallelism of plasticity in general. PMID:29491997

Effect of a mobile phone intervention on quitting smoking in a young adult population of smokers: randomized controlled trial study protocol.

PubMed

Baskerville, Neill Bruce; Struik, Laura Louise; Hammond, David; Guindon, G Emmanuel; Norman, Cameron D; Whittaker, Robyn; Burns, Catherine M; Grindrod, Kelly A; Brown, K Stephen

2015-01-19

Tobacco use remains the number one cause of preventable chronic disease and death in developed countries worldwide. In North America, smoking rates are highest among young adults. Despite that the majority of young adult smokers indicate wanting to quit, smoking rates among this age demographic have yet to decline. Helping young adults quit smoking continues to be a public health priority. Digital mobile technology presents a promising medium for reaching this population with smoking cessation interventions, especially because young adults are the heaviest users of this technology. The primary aim of this trial is to determine the effectiveness of an evidence-informed mobile phone app for smoking cessation, Crush the Crave, on reducing smoking prevalence among young adult smokers. A parallel randomized controlled trial (RCT) with two arms will be conducted in Canada to evaluate Crush the Crave. In total, 1354 young adult smokers (19 to 29 years old) will be randomized to receive the evidence-informed mobile phone app, Crush the Crave, or an evidence-based self-help guide known as "On the Road to Quitting" (control) for a period of 6 months. The primary outcome measure is a 30-day point prevalence of abstinence at the 6-month follow-up. Secondary outcomes include a 7-day point prevalence of abstinence, number of quit attempts, reduction in consumption of cigarettes, self-efficacy, satisfaction, app utilization metrics, and use of smoking cessation services. A cost-effectiveness analysis is included. This trial is currently open for recruitment. The anticipated completion date for the study is April 2016. This randomized controlled trial will provide the evidence to move forward on decision making regarding the inclusion of technology-based mobile phone interventions as part of existing smoking cessation efforts made by health care providers. Evidence from the trial will also inform the development of future apps, provide a deeper understanding of the factors that drive change in smoking behavior using an app, and improve the design of cessation apps. This trial is among the first to assess the effect of a comprehensive and evidence-informed mHealth smoking cessation app on a large sample of young adult smokers. Strengths of the trial include the high-quality research design and in-depth assessment of the implementation of the intervention. If effective, the trial has the potential to demonstrate that including mHealth technology as a population-based intervention strategy can cost-effectively reach a greater proportion of the population and help young adult smokers to quit. ClinicalTrials.gov NCT01983150; http://clinicaltrials.gov/ct2/show/NCT01983150 (Archived by WebCite at http://www.webcitation.org/6VGyc0W0i).

78 FR 58318 - Clinical Trial Design for Intravenous Fat Emulsion Products; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-23

...] Clinical Trial Design for Intravenous Fat Emulsion Products; Public Workshop AGENCY: Food and Drug... announcing a 1-day public workshop entitled ``Clinical Trial Design for Intravenous Fat Emulsion Products.'' This workshop will provide a forum to discuss trial design of clinical trials intended to support...

Sequential or parallel decomposed processing of two-digit numbers? Evidence from eye-tracking.

PubMed

Moeller, Korbinian; Fischer, Martin H; Nuerk, Hans-Christoph; Willmes, Klaus

2009-02-01

While reaction time data have shown that decomposed processing of two-digit numbers occurs, there is little evidence about how decomposed processing functions. Poltrock and Schwartz (1984) argued that multi-digit numbers are compared in a sequential digit-by-digit fashion starting at the leftmost digit pair. In contrast, Nuerk and Willmes (2005) favoured parallel processing of the digits constituting a number. These models (i.e., sequential decomposition, parallel decomposition) make different predictions regarding the fixation pattern in a two-digit number magnitude comparison task and can therefore be differentiated by eye fixation data. We tested these models by evaluating participants' eye fixation behaviour while selecting the larger of two numbers. The stimulus set consisted of within-decade comparisons (e.g., 53_57) and between-decade comparisons (e.g., 42_57). The between-decade comparisons were further divided into compatible and incompatible trials (cf. Nuerk, Weger, & Willmes, 2001) and trials with different decade and unit distances. The observed fixation pattern implies that the comparison of two-digit numbers is not executed by sequentially comparing decade and unit digits as proposed by Poltrock and Schwartz (1984) but rather in a decomposed but parallel fashion. Moreover, the present fixation data provide first evidence that digit processing in multi-digit numbers is not a pure bottom-up effect, but is also influenced by top-down factors. Finally, implications for multi-digit number processing beyond the range of two-digit numbers are discussed.

Health trainer-led motivational intervention plus usual care for people under community supervision compared with usual care alone: a study protocol for a parallel-group pilot randomised controlled trial (STRENGTHEN).

PubMed

Thompson, Tom P; Callaghan, Lynne; Hazeldine, Emma; Quinn, Cath; Walker, Samantha; Byng, Richard; Wallace, Gary; Creanor, Siobhan; Green, Colin; Hawton, Annie; Annison, Jill; Sinclair, Julia; Senior, Jane; Taylor, Adrian H

2018-06-04

People with experience of the criminal justice system typically have worse physical and mental health, lower levels of mental well-being and have less healthy lifestyles than the general population. Health trainers have worked with offenders in the community to provide support for lifestyle change, enhance mental well-being and signpost to appropriate services. There has been no rigorous evaluation of the effectiveness and cost-effectiveness of providing such community support. This study aims to determine the feasibility and acceptability of conducting a randomised trial and delivering a health trainer intervention to people receiving community supervision in the UK. A multicentre, parallel, two-group randomised controlled trial recruiting 120 participants with 1:1 individual allocation to receive support from a health trainer and usual care or usual care alone, with mixed methods process evaluation. Participants receive community supervision from an offender manager in either a Community Rehabilitation Company or the National Probation Service. If they have served a custodial sentence, then they have to have been released for at least 2 months. The supervision period must have at least 7 months left at recruitment. Participants are interested in receiving support to change diet, physical activity, alcohol use and smoking and/or improve mental well-being. The primary outcome is mental well-being with secondary outcomes related to smoking, physical activity, alcohol consumption and diet. The primary outcome will inform sample size calculations for a definitive trial. The study has been approved by the Health and Care Research Wales Ethics Committee (REC reference 16/WA/0171). Dissemination will include publication of the intervention development process and findings for the stated outcomes, parallel process evaluation and economic evaluation in peer-reviewed journals. Results will also be disseminated to stakeholders and trial participants. ISRCTN80475744; Pre-results. © 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.

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.

Protocol of randomized control trial for effectiveness of angiotensin receptor blockers on blood pressure control among euvolemic hypertensive hemodialysis patients

PubMed Central

Aftab, Raja Ahsan; Khan, Amer Hayat; Syed Sulaiman, Syed Azhar; Khan, Tahir Mehmood; Adnan, Azreen Syazril

2017-01-01

Abstract Introduction: Volume overload and the renin–aldosterone–angiotensin system (RAAS) are 2 major factors contributing to hypertension (HTN) among hemodialysis (HD) patients. Although volume-dependent components of HTN can be corrected by appropriate volume removal, a proportion of HD patients experience elevated blood pressure (BP) despite achieving euvolemic and ideal dry weight. Method and analysis: A single center, prospective, randomized, parallel design, single-blind trial will be conducted in the Malaysian state of Kelantan among postdialysis euvolemic hypertensive patients that are on regular dialysis at least 3 times a week. The primary outcome of the trial will be to note the effectiveness of losartan (RAAS inhibitor) in reducing systolic BP < 140 mm Hg compared to standard non-RAAS-inhibitor antihypertensive therapy. The secondary outcome will be to look at all causes of mortality. A body composition monitor (BCM) will be used to assess postdialysis volume and dry weight. Postdialysis euvolemic patients that have systolic BP > 140 mm Hg will be randomized using Covariate Adaptive Randomization to standard or treatment arm. Participants in the treatment arm will be given 50 mg of losartan once daily except on dialysis days, whereas the standard arm patients will be prescribed non-RAAS antihypertensive agents. The study participants will be followed for a period of 12 months. A Wilcoxon statistical test will be performed to note the difference in BP from baseline up to 12 months using Statistical Package for the Social Sciences (SPSS) 20. Ethical and trial registration: The study protocols are approved from the Ethical and Research Committee of the Universiti Sains Malaysia (USM/JEPeM/15050173). The trial is registered under the Australia New Zealand Clinical Trial Registry (ACTRN12615001322527). The trial was registered on 2/12/2015 and the 1st patient was enrolled on 10/12/2015. The trial was formally initiated on 16/02/2016. Conclusion: Management of HTN among HD patients requires understanding the primary cause of HTN and treating accordingly. The current trial is an attempt to reduce BP among postdialysis euvolemic but hypertensive patients. PMID:28383400

Vitamin K supplementation for cystic fibrosis.

PubMed

Jagannath, Vanitha A; Fedorowicz, Zbys; Thaker, Vidhu; Chang, Anne B

2011-01-19

Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 15 April 2010. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Two trials (total of 32 participants) were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial; and the other had a cross-over design, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.

Vitamin K supplementation for cystic fibrosis.

PubMed

Jagannath, Vanitha A; Fedorowicz, Zbys; Thaker, Vidhu; Chang, Anne B

2013-04-30

Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 11 October 2012. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Two trials (total of 32 participants) were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial; and the other had a cross-over design, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.

The parallel programming of voluntary and reflexive saccades.

PubMed

Walker, Robin; McSorley, Eugene

2006-06-01

A novel two-step paradigm was used to investigate the parallel programming of consecutive, stimulus-elicited ('reflexive') and endogenous ('voluntary') saccades. The mean latency of voluntary saccades, made following the first reflexive saccades in two-step conditions, was significantly reduced compared to that of voluntary saccades made in the single-step control trials. The latency of the first reflexive saccades was modulated by the requirement to make a second saccade: first saccade latency increased when a second voluntary saccade was required in the opposite direction to the first saccade, and decreased when a second saccade was required in the same direction as the first reflexive saccade. A second experiment confirmed the basic effect and also showed that a second reflexive saccade may be programmed in parallel with a first voluntary saccade. The results support the view that voluntary and reflexive saccades can be programmed in parallel on a common motor map.

Comparing oncology clinical programs by use of innovative designs and expected net present value optimization: Which adaptive approach leads to the best result?

PubMed

Parke, Tom; Marchenko, Olga; Anisimov, Vladimir; Ivanova, Anastasia; Jennison, Christopher; Perevozskaya, Inna; Song, Guochen

2017-01-01

Designing an oncology clinical program is more challenging than designing a single study. The standard approaches have been proven to be not very successful during the last decade; the failure rate of Phase 2 and Phase 3 trials in oncology remains high. Improving a development strategy by applying innovative statistical methods is one of the major objectives of a drug development process. The oncology sub-team on Adaptive Program under the Drug Information Association Adaptive Design Scientific Working Group (DIA ADSWG) evaluated hypothetical oncology programs with two competing treatments and published the work in the Therapeutic Innovation and Regulatory Science journal in January 2014. Five oncology development programs based on different Phase 2 designs, including adaptive designs and a standard two parallel arm Phase 3 design were simulated and compared in terms of the probability of clinical program success and expected net present value (eNPV). In this article, we consider eight Phase2/Phase3 development programs based on selected combinations of five Phase 2 study designs and three Phase 3 study designs. We again used the probability of program success and eNPV to compare simulated programs. For the development strategies, we considered that the eNPV showed robust improvement for each successive strategy, with the highest being for a three-arm response adaptive randomization design in Phase 2 and a group sequential design with 5 analyses in Phase 3.

Fringe Capacitance of a Parallel-Plate Capacitor.

ERIC Educational Resources Information Center

Hale, D. P.

1978-01-01

Describes an experiment designed to measure the forces between charged parallel plates, and determines the relationship among the effective electrode area, the measured capacitance values, and the electrode spacing of a parallel plate capacitor. (GA)

The life cycles of six multi-center adaptive clinical trials focused on neurological emergencies developed for the Advancing Regulatory Science initiative of the National Institutes of Health and US Food and Drug Administration: Case studies from the Adaptive Designs Accelerating Promising Treatments Into Trials Project

PubMed Central

Guetterman, Timothy C; Fetters, Michael D; Mawocha, Samkeliso; Legocki, Laurie J; Barsan, William G; Lewis, Roger J; Berry, Donald A; Meurer, William J

2017-01-01

Objectives: Clinical trials are complicated, expensive, time-consuming, and frequently do not lead to discoveries that improve the health of patients with disease. Adaptive clinical trials have emerged as a methodology to provide more flexibility in design elements to better answer scientific questions regarding whether new treatments are efficacious. Limited observational data exist that describe the complex process of designing adaptive clinical trials. To address these issues, the Adaptive Designs Accelerating Promising Treatments Into Trials project developed six, tailored, flexible, adaptive, phase-III clinical trials for neurological emergencies, and investigators prospectively monitored and observed the processes. The objective of this work is to describe the adaptive design development process, the final design, and the current status of the adaptive trial designs that were developed. Methods: To observe and reflect upon the trial development process, we employed a rich, mixed methods evaluation that combined quantitative data from visual analog scale to assess attitudes about adaptive trials, along with in-depth qualitative data about the development process gathered from observations. Results: The Adaptive Designs Accelerating Promising Treatments Into Trials team developed six adaptive clinical trial designs. Across the six designs, 53 attitude surveys were completed at baseline and after the trial planning process completed. Compared to baseline, the participants believed significantly more strongly that the adaptive designs would be accepted by National Institutes of Health review panels and non-researcher clinicians. In addition, after the trial planning process, the participants more strongly believed that the adaptive design would meet the scientific and medical goals of the studies. Conclusion: Introducing the adaptive design at early conceptualization proved critical to successful adoption and implementation of that trial. Involving key stakeholders from several scientific domains early in the process appears to be associated with improved attitudes towards adaptive designs over the life cycle of clinical trial development. PMID:29085638

Reinventing clinical trials: a review of innovative biomarker trial designs in cancer therapies.

PubMed

Lin, Ja-An; He, Pei

2015-06-01

Recently, new clinical trial designs involving biomarkers have been studied and proposed in cancer clinical research, in the hope of incorporating the rapid growing basic research into clinical practices. Journal articles related to various biomarkers and their role in cancer clinical trial, articles and books about statistical issues in trial design, and regulatory website, documents, and guidance for submission of targeted cancer therapies. The drug development process involves four phases. The confirmatory Phase III is essential in regulatory approval of a special treatment. Regulatory agency has restrictions on confirmatory trials 'using adaptive designs'. No rule of thumb to pick the most appropriate design for biomarker-related trials. Statistical issues to solve in new designs. Regulatory acceptance of the 'newly proposed trial designs'. Biomarker-related trial designs that can resolve the statistical issues and satisfy the regulatory requirement. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of oxybenzone on PGE2-production in vitro and on plaque and gingivitis in vivo.

PubMed

Jannesson, Lillemor; Birkhed, Dowen; Scherl, Dale; Gaffar, Abdul; Renvert, Stefan

2004-02-01

To study the effect of oxybenzone on prostaglandin E2 (PGE2) production in cell culture and to evaluate the effect of an oxybenzone-containing dentifrice on plaque and gingivitis in a 6-week clinical trial. Human embryo palatal mesenchyme (HEPM) cells were used for testing the inhibition of IL-1beta-stimulated PGE2-production in vitro by different concentrations of oxybenzone. For the in vivo study, a total of 66 individuals with a Quigley & Hein plaque index of at least 1.5 and an Ainamo & Bay gingival index of at least 0.2 were included in a double-blind clinical trial with two cells and a parallel design. Two compositions of fluoride dentifrice were used, one with the addition of 0.5% oxybenzone, and one without. Plaque and gingival index were obtained at three time points: (1) at baseline, (2) after 3 weeks, and (3) after 6 weeks. A dose-dependent inhibition of PGE2-production was found in the HEPM cell culture following oxybenzone exposure. In the clinical trial, a 25% reduction of gingival index was observed in the oxybenzone group (p<0.001) after 6 weeks as compared with 2% for the placebo group. These findings indicate that PGE2-production is reduced by oxybenzone in vitro and that the use of oxybenzone in a dentifrice reduces gingivitis in vivo. Copyright Blackwell Munksgaard, 2004.

Disc extrusions and bulges in nonspecific low back pain and sciatica: Exploratory randomised controlled trial comparing yoga therapy and normal medical treatment.

PubMed

Monro, Robin; Bhardwaj, Abhishek Kumar; Gupta, Ram Kumar; Telles, Shirley; Allen, Beth; Little, Paul

2015-01-01

Previous trials of yoga therapy for nonspecific low back pain (nsLBP) (without sciatica) showed beneficial effects. To test effects of yoga therapy on pain and disability associated with lumbar disc extrusions and bulges. Parallel-group, randomised, controlled trial. Sixty-one adults from rural population, aged 20-45, with nsLBP or sciatica, and disc extrusions or bulges. Randomised to yoga (n=30) and control (n=31). Yoga: 3-month yoga course of group classes and home practice, designed to ensure safety for disc extrusions. normal medical care. OUTCOME MEASURES (3-4 months) Primary: Roland Morris Disability Questionnaire (RMDQ); worst pain in past two weeks. Secondary: Aberdeen Low Back Pain Scale; straight leg raise test; structural changes. Disc projections per case ranged from one bulge or one extrusion to three bulges plus two extrusions. Sixty-two percent had sciatica. Intention-to-treat analysis of the RMDQ data, adjusted for age, sex and baseline RMDQ scores, gave a Yoga Group score 3.29 points lower than Control Group (0.98, 5.61; p=0.006) at 3 months. No other significant differences in the endpoints occurred. No adverse effects of yoga were reported. Yoga therapy can be safe and beneficial for patients with nsLBP or sciatica, accompanied by disc extrusions and bulges.

A pilot randomized controlled trial of D-cycloserine and distributed practice as adjuvants to constraint-induced movement therapy after stroke.

PubMed

Nadeau, Stephen E; Davis, Sandra E; Wu, Samuel S; Dai, Yunfeng; Richards, Lorie G

2014-01-01

Background. Phase III trials of rehabilitation of paresis after stroke have proven the effectiveness of intensive and extended task practice, but they have also shown that many patients do not qualify, because of severity of impairment, and that many of those who are treated are left with clinically significant deficits. Objective. To test the value of 2 potential adjuvants to normal learning processes engaged in constraint-induced movement therapy (CIMT): greater distribution of treatment over time and the coadministration of d-cycloserine, a competitive agonist at the glycine site of the N-methyl-D-aspartate glutamate receptor. Methods. A prospective randomized single-blind parallel-group trial of more versus less condensed therapy (2 vs 10 weeks) and d-cycloserine (50 mg) each treatment day versus placebo (in a 2 × 2 design), as potential adjuvants to 60 hours of CIMT. Results. Twenty-four participants entered the study, and 22 completed it and were assessed at the completion of treatment and 3 months later. Neither greater distribution of treatment nor treatment with d-cycloserine significantly augmented retention of gains achieved with CIMT. Conclusions. Greater distribution of practice and treatment with d-cycloserine do not appear to augment retention of gains achieved with CIMT. However, concentration of CIMT over 2 weeks ("massed practice") appears to confer no advantage either. © The Author(s) 2014.

Enhancing clinical evidence by proactively building quality into clinical trials.

PubMed

Meeker-O'Connell, Ann; Glessner, Coleen; Behm, Mark; Mulinde, Jean; Roach, Nancy; Sweeney, Fergus; Tenaerts, Pamela; Landray, Martin J

2016-08-01

Stakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight. The Clinical Trials Transformation Initiative convened a project to evaluate methods to prospectively build quality into the scientific and operational design of clinical trials ("quality-by-design"), such that trials are feasible to conduct and important errors are prevented rather than remediated. A working group evaluated aspects of trial design and oversight and developed the Clinical Trials Transformation Initiative quality-by-design principles document, outlining a series of factors generally relevant to the reliability of trial conclusions and to patient safety. These principles were then applied and further refined during a series of hands-on workshops to evaluate their utility in facilitating proactive, cross-functional dialogue, and decision-making about trial design and planning. Following these workshops, independent qualitative interviews were conducted with 19 workshop attendees to explore the potential challenges for implementing a quality-by-design approach to clinical trials. The Clinical Trials Transformation Initiative project team subsequently developed recommendations and an online resource guide to support implementation of this approach. The Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of active discussions incorporating the different perspectives within and external to an organization (e.g. clinical investigators, research site staff, and trial participants) in improving trial design. Workshop participants also recognized the value of focusing oversight on those aspects of the trial where errors would have a major impact on participant safety and reliability of results. Applying the Clinical Trials Transformation Initiative quality-by-design recommendations and principles should enable organizations to prioritize the most critical determinants of a trial's quality, identify non-essential activities that can be eliminated to streamline trial conduct and oversight, and formulate appropriate plans to define, avoid, mitigate, monitor, and address important errors. © The Author(s) 2016.

Can emergency medicine research benefit from adaptive design clinical trials?

PubMed

Flight, Laura; Julious, Steven A; Goodacre, Steve

2017-04-01

Adaptive design clinical trials use preplanned interim analyses to determine whether studies should be stopped or modified before recruitment is complete. Emergency medicine trials are well suited to these designs as many have a short time to primary outcome relative to the length of recruitment. We hypothesised that the majority of published emergency medicine trials have the potential to use a simple adaptive trial design. We reviewed clinical trials published in three emergency medicine journals between January 2003 and December 2013. We determined the proportion that used an adaptive design as well as the proportion that could have used a simple adaptive design based on the time to primary outcome and length of recruitment. Only 19 of 188 trials included in the review were considered to have used an adaptive trial design. A total of 154/165 trials that were fixed in design had the potential to use an adaptive design. Currently, there seems to be limited uptake in the use of adaptive trial designs in emergency medicine despite their potential benefits to save time and resources. Failing to take advantage of adaptive designs could be costly to patients and research. It is recommended that where practical and logistical considerations allow, adaptive designs should be used for all emergency medicine clinical trials. 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/.

Learning in Parallel: Using Parallel Corpora to Enhance Written Language Acquisition at the Beginning Level

ERIC Educational Resources Information Center

Bluemel, Brody

2014-01-01

This article illustrates the pedagogical value of incorporating parallel corpora in foreign language education. It explores the development of a Chinese/English parallel corpus designed specifically for pedagogical application. The corpus tool was created to aid language learners in reading comprehension and writing development by making foreign…

Spinal cord injury: promising interventions and realistic goals.

PubMed

McDonald, John W; Becker, Daniel

2003-10-01

Long regarded as impossible, spinal cord repair is approaching the realm of reality as efforts to bridge the gap between bench and bedside point to novel approaches to treatment. It is important to recognize that the research playing field is rapidly changing and that new mechanisms of resource development are required to effectively make the transition from basic science discoveries to effective clinical treatments. This article reviews recent laboratory studies and phase 1 clinical trials in neural and nonneural cell transplantation, stressing that the transition from basic science to clinical applications requires a parallel rather than serial approach, with continuous, two-way feedback to most efficiently translate basic science findings, through evaluation and optimization, to clinical treatments. An example of mobilizing endogenous stem cells for repair is reviewed, with emphasis on the rapid application of basic science to clinical therapy. Successful and efficient transition from basic science to clinical applications requires (1) a parallel rather than a serial approach; (2) development of centers that integrate three spheres of science, translational, transitional, and clinical trials; and (3) development of novel resources to fund the most critically limited step of transitional to clinical trials.

Molecular Monte Carlo Simulations Using Graphics Processing Units: To Waste Recycle or Not?

PubMed

Kim, Jihan; Rodgers, Jocelyn M; Athènes, Manuel; Smit, Berend

2011-10-11

In the waste recycling Monte Carlo (WRMC) algorithm, (1) multiple trial states may be simultaneously generated and utilized during Monte Carlo moves to improve the statistical accuracy of the simulations, suggesting that such an algorithm may be well posed for implementation in parallel on graphics processing units (GPUs). In this paper, we implement two waste recycling Monte Carlo algorithms in CUDA (Compute Unified Device Architecture) using uniformly distributed random trial states and trial states based on displacement random-walk steps, and we test the methods on a methane-zeolite MFI framework system to evaluate their utility. We discuss the specific implementation details of the waste recycling GPU algorithm and compare the methods to other parallel algorithms optimized for the framework system. We analyze the relationship between the statistical accuracy of our simulations and the CUDA block size to determine the efficient allocation of the GPU hardware resources. We make comparisons between the GPU and the serial CPU Monte Carlo implementations to assess speedup over conventional microprocessors. Finally, we apply our optimized GPU algorithms to the important problem of determining free energy landscapes, in this case for molecular motion through the zeolite LTA.

RAPP, a systematic e-assessment of postoperative recovery in patients undergoing day surgery: study protocol for a mixed-methods study design including a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies.

PubMed

Nilsson, U; Jaensson, M; Dahlberg, K; Odencrants, S; Grönlund, Å; Hagberg, L; Eriksson, M

2016-01-13

Day surgery is a well-established practice in many European countries, but only limited information is available regarding postoperative recovery at home though there is a current lack of a standard procedure regarding postoperative follow-up. Furthermore, there is also a need for improvement of modern technology in assessing patient-related outcomes such as mobile applications. This article describes the Recovery Assessment by Phone Points (RAPP) study protocol, a mixed-methods study to evaluate if a systematic e-assessment follow-up in patients undergoing day surgery is cost-effective and improves postoperative recovery, health and quality of life. This study has a mixed-methods study design that includes a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies. 1000 patients >17 years of age who are undergoing day surgery will be randomly assigned to either e-assessed postoperative recovery follow-up daily in 14 days measured via smartphone app including the Swedish web-version of Quality of Recovery (SwQoR) or to standard care (ie, no follow-up). The primary aim is cost-effectiveness. Secondary aims are (A) to explore whether a systematic e-assessment follow-up after day surgery has a positive effect on postoperative recovery, health-related quality of life (QoL) and overall health; (B) to determine whether differences in postoperative recovery have an association with patient characteristic, type of surgery and anaesthesia; (C) to determine whether differences in health literacy have a substantial and distinct effect on postoperative recovery, health and QoL; and (D) to describe day surgery patient and staff experiences with a systematic e-assessment follow-up after day surgery.The primary aim will be measured at 2 weeks postoperatively and secondary outcomes (A-C) at 1 and 2 weeks and (D) at 1 and 4 months. NCT02492191; Pre-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/

Lactic-fermented egg white reduced serum cholesterol concentrations in mildly hypercholesterolemic Japanese men: a double-blind, parallel-arm design.

PubMed

Matsuoka, Ryosuke; Usuda, Mika; Masuda, Yasunobu; Kunou, Masaaki; Utsunomiya, Kazunori

2017-05-30

Lactic-fermented egg white (LE), produced by lactic acid fermentation of egg white, is an easy-to-consume form of egg white. Here we assessed the effect of daily consumption of LE for 8 weeks on serum total cholesterol (TC) levels. The study followed a double-blind, parallel-arm design and included 88 adult men with mild hypercholesterolemia (mean ± standard error) serum TC levels, 229 ± 1.6 mg/dL; range, 204-259 mg/dL). The subjects were randomly divided into three groups, which consumed LE containing 4, 6, or 8 g of protein daily for 8 weeks. Blood samples were collected before starting LE consumption (baseline) and at 4 and 8 weeks to measure serum TC and low-density lipoprotein cholesterol (LDL-C) levels. After 8 weeks of consumption, serum TC levels in the 8 g group decreased by 11.0 ± 3.7 mg/dL, a significant decrease compared to baseline (p < 0.05) and a significantly greater decrease than for the 4 g group (3.1 ± 3.4 mg/dL; p < 0.05). Serum LDL-C levels in the 8 g group decreased by 13.7 ± 3.1 mg/dL, again a significant decrease compared with baseline (p < 0.05) and a significantly greater decrease than that for the 4 g group (2.1 ± 2.9 mg/dL; p < 0.05). Consumption of LE for 8 weeks at a daily dose of 8 g of proteins reduced serum TC and LDL-C levels in men with mild hypercholesterolemia, suggesting this may be effective in helping to prevent arteriosclerotic diseases. This clinical trial was retrospectively registered with the Japan Medical Association Center for Clinical Trials, (JMA-IIA00279; registered on 13/03/2017; https://dbcentre3.jmacct.med.or.jp/JMACTR/App/JMACTRE02_04/JMACTRE02_04.aspx?kbn=3&seqno=6530 ).

Portable parallel stochastic optimization for the design of aeropropulsion components

NASA Technical Reports Server (NTRS)

Sues, Robert H.; Rhodes, G. S.

1994-01-01

This report presents the results of Phase 1 research to develop a methodology for performing large-scale Multi-disciplinary Stochastic Optimization (MSO) for the design of aerospace systems ranging from aeropropulsion components to complete aircraft configurations. The current research recognizes that such design optimization problems are computationally expensive, and require the use of either massively parallel or multiple-processor computers. The methodology also recognizes that many operational and performance parameters are uncertain, and that uncertainty must be considered explicitly to achieve optimum performance and cost. The objective of this Phase 1 research was to initialize the development of an MSO methodology that is portable to a wide variety of hardware platforms, while achieving efficient, large-scale parallelism when multiple processors are available. The first effort in the project was a literature review of available computer hardware, as well as review of portable, parallel programming environments. The first effort was to implement the MSO methodology for a problem using the portable parallel programming language, Parallel Virtual Machine (PVM). The third and final effort was to demonstrate the example on a variety of computers, including a distributed-memory multiprocessor, a distributed-memory network of workstations, and a single-processor workstation. Results indicate the MSO methodology can be well-applied towards large-scale aerospace design problems. Nearly perfect linear speedup was demonstrated for computation of optimization sensitivity coefficients on both a 128-node distributed-memory multiprocessor (the Intel iPSC/860) and a network of workstations (speedups of almost 19 times achieved for 20 workstations). Very high parallel efficiencies (75 percent for 31 processors and 60 percent for 50 processors) were also achieved for computation of aerodynamic influence coefficients on the Intel. Finally, the multi-level parallelization strategy that will be needed for large-scale MSO problems was demonstrated to be highly efficient. The same parallel code instructions were used on both platforms, demonstrating portability. There are many applications for which MSO can be applied, including NASA's High-Speed-Civil Transport, and advanced propulsion systems. The use of MSO will reduce design and development time and testing costs dramatically.

The effect of earthquake on architecture geometry with non-parallel system irregularity configuration

NASA Astrophysics Data System (ADS)

Teddy, Livian; Hardiman, Gagoek; Nuroji; Tudjono, Sri

2017-12-01

Indonesia is an area prone to earthquake that may cause casualties and damage to buildings. The fatalities or the injured are not largely caused by the earthquake, but by building collapse. The collapse of the building is resulted from the building behaviour against the earthquake, and it depends on many factors, such as architectural design, geometry configuration of structural elements in horizontal and vertical plans, earthquake zone, geographical location (distance to earthquake center), soil type, material quality, and construction quality. One of the geometry configurations that may lead to the collapse of the building is irregular configuration of non-parallel system. In accordance with FEMA-451B, irregular configuration in non-parallel system is defined to have existed if the vertical lateral force-retaining elements are neither parallel nor symmetric with main orthogonal axes of the earthquake-retaining axis system. Such configuration may lead to torque, diagonal translation and local damage to buildings. It does not mean that non-parallel irregular configuration should not be formed on architectural design; however the designer must know the consequence of earthquake behaviour against buildings with irregular configuration of non-parallel system. The present research has the objective to identify earthquake behaviour in architectural geometry with irregular configuration of non-parallel system. The present research was quantitative with simulation experimental method. It consisted of 5 models, where architectural data and model structure data were inputted and analyzed using the software SAP2000 in order to find out its performance, and ETAB2015 to determine the eccentricity occurred. The output of the software analysis was tabulated, graphed, compared and analyzed with relevant theories. For areas of strong earthquake zones, avoid designing buildings which wholly form irregular configuration of non-parallel system. If it is inevitable to design a building with building parts containing irregular configuration of non-parallel system, make it more rigid by forming a triangle module, and use the formula.A good collaboration is needed between architects and structural experts in creating earthquake architecture.

Methodological considerations for a randomised controlled trial of podiatry care in rheumatoid arthritis: lessons from an exploratory trial.

PubMed

Turner, Deborah E; Helliwell, Philip S; Woodburn, James

2007-11-06

Whilst evidence exists to support the use of single treatments such as orthoses and footwear, the effectiveness of podiatry-led care as a complex intervention for patients with rheumatoid arthritis (RA) related foot problems is unknown. The aim of this study was to undertake an exploratory randomised controlled parallel arm clinical trial (RheumAFooT) to inform the design and implementation of a definitive trial and to understand the potential benefits of this care. Patients with a definite diagnosis of RA, stable drug management 3 months prior to entry, and a current history of foot problems (pain, deformity, stiffness, skin or nail lesions, or footwear problems) were recruited from a hospital outpatient rheumatology clinic and randomised to receive 12 months of podiatry treatment or no care. The primary outcome was change in foot health status using the impairment/footwear (LFISIF) and activity limitation/participation restriction (LFISAP) subscales of the Leeds Foot Impact Scale. Disease Activity Score (DAS), Health Assessment Questionnaire (HAQ) score and walking speed (m/s) were also recorded. Of the 80 patients identified, 64 patients were eligible to participate in the pilot and 34 were recruited. 16 patients were randomised to receive podiatry led foot care and 18 received no care. Against a backdrop of stable disease (DAS and HAQ scores), there was a statistically significant between group difference in the change in foot health status for foot impairment (LFISIF) but not activity/participation (LFISAP) or function (walking speed) over 12 months. In the podiatry arm, 1 patient declined treatment following randomisation (did not want additional hospital visits) and 3 self-withdrew (lost to follow-up). Patients received an average of 3 consultations for assessment and treatment comprising routine care for skin and nail lesions (n = 3), foot orthoses (n = 9), footwear referral to the orthotist (n = 5), and ultrasound guided intra-articular steroid injection (n = 1). In this exploratory trial patients were difficult to recruit (stable drug management and co-morbid disease) and retain (lack of benefit/additional treatment burden) but overall the intervention was safe (no adverse reactions). Twelve months of podiatry care maintained but did not improve foot health status. These observations are important for the design and implementation of a definitive randomised controlled trial. ISRCTN: 01982076.

Protocol for the New Medicine Service Study: a randomized controlled trial and economic evaluation with qualitative appraisal comparing the effectiveness and cost effectiveness of the New Medicine Service in community pharmacies in England

PubMed Central

2013-01-01

Background Medication non-adherence is considered an important cause of morbidity and mortality in primary care. This study aims to determine the effectiveness, cost effectiveness and acceptability of a complex intervention delivered by community pharmacists, the New Medicine Service (NMS), compared with current practice in reducing non-adherence to, and problems with, newly prescribed medicines for chronic conditions. Methods/design Research subject group: patients aged 14 years and above presenting in a community pharmacy for a newly prescribed medicine for asthma/chronic obstructive pulmonary disease (COPD); hypertension; type 2 diabetes or anticoagulant/antiplatelet agents in two geographical regions in England. Design: parallel group patient-level pragmatic randomized controlled trial. Interventions: patients randomized to either: (i) current practice; or (ii) NMS intervention comprising pharmacist-delivered support for a newly prescribed medicine. Primary outcomes: proportion of adherent patients at six, ten and 26 weeks from the date of presenting their prescriptions at the pharmacy; cost effectiveness of the intervention versus current practice at 10 weeks and 26 weeks; in-depth qualitative understanding of the operationalization of NMS in pharmacies. Secondary outcomes: impact of NMS on: patients’ understanding of their medicines, pharmacovigilance, interprofessional and patient-professional relationships and experiences of service users and stakeholders. Economic analysis: Trial-based economic analysis (cost per extra adherent patient) and long-term modeling of costs and health effects (cost per quality-adjusted-life-year) will be conducted from the perspective of National Health Service (NHS) England, comparing NMS with current practice. Qualitative analysis: a qualitative study of NMS implementation in different community settings, how organizational influences affect NMS delivery, patterns of NMS consultations and experiences of professionals and patients participating in NMS, and patients receiving current practice. Sample size: 250 patients in each treatment arm would provide at least 80% power (two-tailed alpha of 0.05) to demonstrate a reduction in patient-reported non-adherence from 20% to 10% in the NMS arm compared with current practice, assuming a 20% drop-out rate. Discussion At the time of submission of this article, 58 community pharmacies have been recruited and the interventions are being delivered. Analysis has not yet been undertaken. Trial registration Current controlled trials: ISRCTN23560818 Clinical Trials US (clinicaltrials.gov): NCT01635361 PMID:24289059

Do randomized clinical trials with inadequate blinding report enhanced placebo effects for intervention groups and nocebo effects for placebo groups? A protocol for a meta-epidemiological study of PDE-5 inhibitors

PubMed Central

2012-01-01

Background Patients’ expectations of treatment effects may contribute to positive (placebo) and negative (nocebo) outcomes. The effect of patient expectations may be pronounced in subjectively assessed conditions, such as male erectile dysfunction. The aim of this project is to examine the magnitude of expectancy in trials of phosphodiesterase-5 inhibitors. We hypothesize that randomized controlled trials with inadequate blinding will report enhanced placebo effects for intervention groups and nocebo effects for placebo groups, compared with adequately blinded studies. Methods/design We will quantify the magnitude of expectancy by comparing the effect estimates of trials with inadequate and adequate blinding. Blinding will be assessed using four domains from the Cochrane ‘risk-of-bias’ tool: allocation concealment; blinding of patient; caregiver; and outcome assessor. Our secondary aim is to identify factors that can modify expectations, such as prior experience with the intervention and drug side effects. We will perform an electronic search using a combination of controlled vocabulary and free text words in the following databases: MEDLINE, EMBASE, CENTRAL, and a clinical trials register. We will include randomized controlled trials, with either parallel or crossover design, that compare one phosphodiesterase-5 inhibitor with a placebo. The study’s primary aim should be to investigate the efficacy of phosphodiesterase-5 inhibitors for treating male erectile dysfunction. Screening will take place at two levels: abstracts and titles, followed by full text reports. Two reviewers will independently extract data on the primary outcome and assess risk of bias. We will meta-analyze treatment effects, if appropriate, to assess the magnitude of enhanced placebo effects and nocebo effects in intervention and placebo groups, respectively. We will explore possible mediators of placebo and nocebo effects with subgroup and meta-regression analyses. Discussion Treatments may confer significant costs and risk of adverse effects; it is important, therefore, to determine whether the effects of treatments are larger than expectancy alone. If treatment expectations can be used in a non-deceptive way to produce clinically advantageous outcomes, then it may be possible to incorporate such mechanisms into evidence-based healthcare decision-making. PMID:23151403

Minimizing risks and monitoring safety of an antenatal care intervention to mitigate domestic violence among young Indian women: The Dil Mil trial

PubMed Central

2012-01-01

Background Domestic violence - physical, psychological, or sexual abuse perpetrated against women by one or more family members – is highly prevalent in India. However, relatively little research has been conducted on interventions with the potential to mitigate domestic violence and its adverse health consequences, and few resources exist to guide safety planning and monitoring in the context of intervention research. Dil Mil is a promising women’s empowerment-based intervention developed in India that engages with young women (daughters-in-law) and their mothers-in-law to mitigate domestic violence and related adverse health outcomes. This paper describes the design of a randomized controlled trial of Dil Mil in Bengaluru, India, with a focus on strategies used to minimize study-related risks and monitor safety. Methods/design A phase 2 randomized controlled trial using a parallel comparison of the Dil Mil intervention versus standard care will be implemented in three public primary health centers in Bengaluru. Young pregnant women in the first or second trimester of pregnancy will be recruited from antenatal services at study health centers and through community outreach. If eligible and willing, their mother-in-law will also be recruited. Once enrolled, dyads will participate in a baseline interview and then randomized either to the control arm and receive standard care or to the intervention arm and receive standard care plus the Dil Mil intervention. Additional evaluations will be conducted at 3 months and 6 months postpartum. Data will be analyzed to examine the feasibility and safety of the intervention and the effect of the intervention on intermediary outcomes (the empowerment of daughters-in-law and mothers-in-law), incidence of domestic violence among daughters-in-law, and health outcomes including perceived quality of life, psychosocial status and maternal and infant health outcomes. Discussion This study offers approaches that may help guide safety planning and monitoring in other domestic violence intervention trials in similar settings. Moreover, given the staggeringly high prevalence of domestic violence against young women in India (and indeed globally) and the dearth of data on effective interventions, this study is poised to make an important contribution to the evidence-base for domestic violence prevention. Trial registration ClinicalTrials.gov Identifier: NCT01337778 PMID:23116189

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.

Study protocol for iQuit in Practice: a randomised controlled trial to assess the feasibility, acceptability and effectiveness of tailored web- and text-based facilitation of smoking cessation in primary care.

PubMed

Sutton, Stephen; Smith, Susan; Jamison, James; Boase, Sue; Mason, Dan; Prevost, A Toby; Brimicombe, James; Sloan, Melanie; Gilbert, Hazel; Naughton, Felix

2013-04-10

Primary care is an important setting for smoking cessation interventions. There is evidence for the effectiveness of tailored interventions for smoking cessation, and text messaging interventions for smoking cessation show promise. The intervention to be evaluated in this trial consists of two components: (1) a web-based program designed to be used by a practice nurse or other smoking cessation advisor (SCA); the program generates a cessation advice report that is highly tailored to relevant characteristics of the smoker; and (2) a three-month programme of automated tailored text messages sent to the smoker's mobile phone. The objectives of the trial are to assess the acceptability and feasibility of the intervention and to estimate the short-term effectiveness of the intervention in increasing the quit rate compared with usual care alone. The design is a two parallel group randomised controlled trial (RCT). 600 smokers who want to quit will be recruited in up to 30 general practices in the East of England. During a consultation with an SCA, they will be individually randomised by computer program to usual care (Control) or to usual care plus the iQuit system (Intervention). At the four-week follow-up appointment, the SCA will record smoking status and measure carbon monoxide level. There will be two further follow-ups, at eight weeks and six months from randomisation date, by postal questionnaire sent from and returned to the study centre or by telephone interview conducted by a research interviewer. The primary outcome will be self-reported abstinence for at least two weeks at eight weeks. A sample size of 300 per group would give 80% power to detect an increase in quit rate from 20% to 30% (alpha = 0.05, 2-sided test). The main analyses of quit rates will be conducted on an intention-to-treat basis, making the usual assumption that participants lost to follow up are smoking. This trial will focus on acceptability, feasibility and short-term effectiveness. The findings will be used to refine the intervention and to inform the decision to proceed to a pragmatic trial to estimate longer-term effectiveness and cost-effectiveness. ISRCTN56702353.

A CS1 pedagogical approach to parallel thinking

NASA Astrophysics Data System (ADS)

Rague, Brian William

Almost all collegiate programs in Computer Science offer an introductory course in programming primarily devoted to communicating the foundational principles of software design and development. The ACM designates this introduction to computer programming course for first-year students as CS1, during which methodologies for solving problems within a discrete computational context are presented. Logical thinking is highlighted, guided primarily by a sequential approach to algorithm development and made manifest by typically using the latest, commercially successful programming language. In response to the most recent developments in accessible multicore computers, instructors of these introductory classes may wish to include training on how to design workable parallel code. Novel issues arise when programming concurrent applications which can make teaching these concepts to beginning programmers a seemingly formidable task. Student comprehension of design strategies related to parallel systems should be monitored to ensure an effective classroom experience. This research investigated the feasibility of integrating parallel computing concepts into the first-year CS classroom. To quantitatively assess student comprehension of parallel computing, an experimental educational study using a two-factor mixed group design was conducted to evaluate two instructional interventions in addition to a control group: (1) topic lecture only, and (2) topic lecture with laboratory work using a software visualization Parallel Analysis Tool (PAT) specifically designed for this project. A new evaluation instrument developed for this study, the Perceptions of Parallelism Survey (PoPS), was used to measure student learning regarding parallel systems. The results from this educational study show a statistically significant main effect among the repeated measures, implying that student comprehension levels of parallel concepts as measured by the PoPS improve immediately after the delivery of any initial three-week CS1 level module when compared with student comprehension levels just prior to starting the course. Survey results measured during the ninth week of the course reveal that performance levels remained high compared to pre-course performance scores. A second result produced by this study reveals no statistically significant interaction effect between the intervention method and student performance as measured by the evaluation instrument over three separate testing periods. However, visual inspection of survey score trends and the low p-value generated by the interaction analysis (0.062) indicate that further studies may verify improved concept retention levels for the lecture w/PAT group.

Parallel computing works

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

Not Available

An account of the Caltech Concurrent Computation Program (C{sup 3}P), a five year project that focused on answering the question: Can parallel computers be used to do large-scale scientific computations '' As the title indicates, the question is answered in the affirmative, by implementing numerous scientific applications on real parallel computers and doing computations that produced new scientific results. In the process of doing so, C{sup 3}P helped design and build several new computers, designed and implemented basic system software, developed algorithms for frequently used mathematical computations on massively parallel machines, devised performance models and measured the performance of manymore » computers, and created a high performance computing facility based exclusively on parallel computers. While the initial focus of C{sup 3}P was the hypercube architecture developed by C. Seitz, many of the methods developed and lessons learned have been applied successfully on other massively parallel architectures.« less

File concepts for parallel I/O

NASA Technical Reports Server (NTRS)

Crockett, Thomas W.

1989-01-01

The subject of input/output (I/O) was often neglected in the design of parallel computer systems, although for many problems I/O rates will limit the speedup attainable. The I/O problem is addressed by considering the role of files in parallel systems. The notion of parallel files is introduced. Parallel files provide for concurrent access by multiple processes, and utilize parallelism in the I/O system to improve performance. Parallel files can also be used conventionally by sequential programs. A set of standard parallel file organizations is proposed, organizations are suggested, using multiple storage devices. Problem areas are also identified and discussed.