Method for appraising model validity of randomised controlled trials of homeopathic treatment: multi-rater concordance study

PubMed Central

2012-01-01

Background A method for assessing the model validity of randomised controlled trials of homeopathy is needed. To date, only conventional standards for assessing intrinsic bias (internal validity) of trials have been invoked, with little recognition of the special characteristics of homeopathy. We aimed to identify relevant judgmental domains to use in assessing the model validity of homeopathic treatment (MVHT). We define MVHT as the extent to which a homeopathic intervention and the main measure of its outcome, as implemented in a randomised controlled trial (RCT), reflect 'state-of-the-art' homeopathic practice. Methods Using an iterative process, an international group of experts developed a set of six judgmental domains, with associated descriptive criteria. The domains address: (I) the rationale for the choice of the particular homeopathic intervention; (II) the homeopathic principles reflected in the intervention; (III) the extent of homeopathic practitioner input; (IV) the nature of the main outcome measure; (V) the capability of the main outcome measure to detect change; (VI) the length of follow-up to the endpoint of the study. Six papers reporting RCTs of homeopathy of varying design were randomly selected from the literature. A standard form was used to record each assessor's independent response per domain, using the optional verdicts 'Yes', 'Unclear', 'No'. Concordance among the eight verdicts per domain, across all six papers, was evaluated using the kappa (κ) statistic. Results The six judgmental domains enabled MVHT to be assessed with 'fair' to 'almost perfect' concordance in each case. For the six RCTs examined, the method allowed MVHT to be classified overall as 'acceptable' in three, 'unclear' in two, and 'inadequate' in one. Conclusion Future systematic reviews of RCTs in homeopathy should adopt the MVHT method as part of a complete appraisal of trial validity. PMID:22510227

Analysis and interpretation of cost data in randomised controlled trials: review of published studies

PubMed Central

Barber, Julie A; Thompson, Simon G

1998-01-01

Objective To review critically the statistical methods used for health economic evaluations in randomised controlled trials where an estimate of cost is available for each patient in the study. Design Survey of published randomised trials including an economic evaluation with cost values suitable for statistical analysis; 45 such trials published in 1995 were identified from Medline. Main outcome measures The use of statistical methods for cost data was assessed in terms of the descriptive statistics reported, use of statistical inference, and whether the reported conclusions were justified. Results Although all 45 trials reviewed apparently had cost data for each patient, only 9 (20%) reported adequate measures of variability for these data and only 25 (56%) gave results of statistical tests or a measure of precision for the comparison of costs between the randomised groups. Only 16 (36%) of the articles gave conclusions which were justified on the basis of results presented in the paper. No paper reported sample size calculations for costs. Conclusions The analysis and interpretation of cost data from published trials reveal a lack of statistical awareness. Strong and potentially misleading conclusions about the relative costs of alternative therapies have often been reported in the absence of supporting statistical evidence. Improvements in the analysis and reporting of health economic assessments are urgently required. Health economic guidelines need to be revised to incorporate more detailed statistical advice. Key messagesHealth economic evaluations required for important healthcare policy decisions are often carried out in randomised controlled trialsA review of such published economic evaluations assessed whether statistical methods for cost outcomes have been appropriately used and interpretedFew publications presented adequate descriptive information for costs or performed appropriate statistical analysesIn at least two thirds of the papers, the main conclusions regarding costs were not justifiedThe analysis and reporting of health economic assessments within randomised controlled trials urgently need improving PMID:9794854

An optimised patient information sheet did not significantly increase recruitment or retention in a falls prevention study: an embedded randomised recruitment trial.

PubMed

Cockayne, Sarah; Fairhurst, Caroline; Adamson, Joy; Hewitt, Catherine; Hull, Robin; Hicks, Kate; Keenan, Anne-Maree; Lamb, Sarah E; Green, Lorraine; McIntosh, Caroline; Menz, Hylton B; Redmond, Anthony C; Rodgers, Sara; Torgerson, David J; Vernon, Wesley; Watson, Judith; Knapp, Peter; Rick, Jo; Bower, Peter; Eldridge, Sandra; Madurasinghe, Vichithranie W; Graffy, Jonathan

2017-03-28

Randomised controlled trials are generally regarded as the 'gold standard' experimental design to determine the effectiveness of an intervention. Unfortunately, many trials either fail to recruit sufficient numbers of participants, or recruitment takes longer than anticipated. The current embedded trial evaluates the effectiveness of optimised patient information sheets on recruitment of participants in a falls prevention trial. A three-arm, embedded randomised methodology trial was conducted within the National Institute for Health Research-funded REducing Falls with ORthoses and a Multifaceted podiatry intervention (REFORM) cohort randomised controlled trial. Routine National Health Service podiatry patients over the age of 65 were randomised to receive either the control patient information sheet (PIS) for the host trial or one of two optimised versions, a bespoke user-tested PIS or a template-developed PIS. The primary outcome was the proportion of patients in each group who went on to be randomised to the host trial. Six thousand and nine hundred patients were randomised 1:1:1 into the embedded trial. A total of 193 (2.8%) went on to be randomised into the main REFORM trial (control n = 62, template-developed n = 68; bespoke user-tested n = 63). Information sheet allocation did not improve recruitment to the trial (odds ratios for the three pairwise comparisons: template vs control 1.10 (95% CI 0.77-1.56, p = 0.60); user-tested vs control 1.01 (95% CI 0.71-1.45, p = 0.94); and user-tested vs template 0.92 (95% CI 0.65-1.31, p = 0.65)). This embedded methodology trial has demonstrated limited evidence as to the benefit of using optimised information materials on recruitment and retention rates in the REFORM study. International Standard Randomised Controlled Trials Number registry, ISRCTN68240461 . Registered on 01 July 2011.

Automated blood glucose control in type 1 diabetes: A review of progress and challenges.

PubMed

Bertachi, Arthur; Ramkissoon, Charrise M; Bondia, Jorge; Vehí, Josep

2018-03-01

Since the 2000s, research teams worldwide have been working to develop closed-loop (CL) systems able to automatically control blood glucose (BG) levels in patients with type 1 diabetes. This emerging technology is known as artificial pancreas (AP), and its first commercial version just arrived in the market. The main objective of this paper is to present an extensive review of the clinical trials conducted since 2011, which tested various implementations of the AP for different durations under varying conditions. A comprehensive table that contains key information from the selected publications is provided, and the main challenges in AP development and the mitigation strategies used are discussed. The development timelines for different AP systems are also included, highlighting the main evolutions over the clinical trials for each system. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

A systematic review of reboxetine for treating patients with attention deficit hyperactivity disorder.

PubMed

Ghanizadeh, Ahmad

2015-05-01

No published systematic review has ever assessed the efficacy and safety of reboxetine for treating of patients with attention deficit hyperactivity disorder (ADHD). This systematic review aimed to review the available evidence regarding the efficacy of reboxetine for treating ADHD. The databases of Pubmed/Medline, Google scholar, SCOPUS and Web of Science were searched using the Keywords: "reboxetine", "ADHD" and "attention deficit hyperactivity disorder". The reference lists of the included studies were screened to find any possible other relevant articles. All the non-controlled and controlled clinical trials were included. The current evidence mainly consists of un-controlled studies, such as case series. Only three of 33 studies were controlled clinical trials. They are from single sites and included a sub-sample of patients with ADHD. Non-controlled studies and controlled trials support the promising effect of reboxetine for treating ADHD in a sub-sample of patients that are without co-morbid psychiatric disorder and mental retardation. Reboxetine is tolerated well. However, more controlled trials are needed to reach any firm conclusion.

Time to publication for publicly funded clinical trials in Australia: an observational study.

PubMed

Strand, Linn Beate; Clarke, Philip; Graves, Nicholas; Barnett, Adrian G

2017-03-22

To examine the length of time between receiving funding and publishing the protocol and main paper for randomised controlled trials. An observational study using survival analysis. Publicly funded health and medical research in Australia. Randomised controlled trials funded by the National Health and Medical Research Council of Australia between 2008 and 2010. Time from funding to the protocol paper and main results paper. Multiple variable survival models examining whether study characteristics predicted publication times. We found 77 studies with a total funding of $A59 million. The median time to publication of the protocol paper was 6.4 years after funding (95% CI 4.1 to 8.1). The proportion with a published protocol paper 8 years after funding was 0.61 (95% CI 0.48 to 0.74). The median time to publication of the main results paper was 7.1 years after funding (95% CI 6.3 to 7.6). The proportion with a published main results paper 8 years after funding was 0.72 (95% CI 0.56 to 0.87). The HRs for how study characteristics might influence timing were generally close to one with narrow CIs, the notable exception was that a longer study length lengthened the time to the main paper (HR=0.62 per extra study year, 95% CI 0.43 to 0.89). Despite the widespread registration of clinical trials, there remain serious concerns of trial results not being published or being published with a long delay. We have found that these same concerns apply to protocol papers, which should be publishable soon after funding. Funding agencies could set a target of publishing the protocol paper within 18 months of funding. 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/.

Risperidone in the treatment of behavioral disorders associated with autism in children and adolescents

PubMed Central

Canitano, Roberto; Scandurra, Valeria

2008-01-01

This is a review of the clinical trials investigating the efficacy and safety of risperidone in the treatment of children with autistic spectrum disorders (ASD). The main clinical characteristics are impairment in social skills, communication difficulties, repetitive movements and behaviors, including stereotypies. Pharmacotherapy is mainly directed at the so-called target symptoms, ie, behavioral disorders and the various kinds of repetitions associated with ASD. According to the available data, risperidone seems to be moderately efficacious and safe for treating behavioral disorders. 4 double blind controlled trial. 3 reanalysis studies, and 12 open studies have documented the role of risperidone in children with ASD. Controlled studies have been thoroughly considered in this review. PMID:19043516

Clinical trials of homoeopathy.

PubMed Central

Kleijnen, J; Knipschild, P; ter Riet, G

1991-01-01

OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials. PMID:1825800

Evaluation of a novel vital sign device to reduce maternal mortality and morbidity in low-resource settings: a mixed method feasibility study for the CRADLE-3 trial.

PubMed

Vousden, Nicola; Lawley, Elodie; Nathan, Hannah L; Seed, Paul T; Brown, Adrian; Muchengwa, Tafadzwa; Charantimath, Umesh; Bellad, Mrutyunjaya; Gidiri, Muchabayiwa Francis; Goudar, Shivaprasad; Chappell, Lucy C; Sandall, Jane; Shennan, Andrew H

2018-04-27

The CRADLE-3 trial is a stepped-wedge randomised controlled trial aiming to reduce maternal mortality and morbidity by implementing a novel vital sign device (CRADLE Vital Sign Alert) and training package into routine maternity care in 10 low-income sites. The MRC Guidance on complex interventions proposes that interventions and implementation strategies be shaped by early phase piloting and development work. We present the findings of a three-month mixed-methodology feasibility study for this trial, describe how this was informed by the MRC guidance and the study design was refined. The fidelity, dose, feasibility and acceptability of implementation and training materials were assessed in three representative non-trial sites (Zimbabwe, Ethiopia, India) using multiple-choice questionnaires, evaluation of clinical management (action log), healthcare provider (HCP) semi-structured interviews and focus groups 4-10 weeks after implementation. Simultaneously, the 10 sites included in the main trial (eight countries) collected primary outcome data to inform the power calculation and randomisation allocation and assess the feasibility of data collection. The package was implemented with high fidelity (85% of HCP trained, n = 204). The questionnaires indicated a good understanding of device use with 75% of participants scoring > 75% (n = 97; 90% of those distributed). Action logs were inconsistently completed but indicated that the majority of HCP responded appropriately to abnormal results. From 18 HCP interviews and two focus groups it was widely reported that the intervention improved capacity to make clinical decisions, escalate care and make appropriate referrals. Nine of the ten main trial sites achieved ethical approval for pilot data collection. Intensive care was an inconsistent marker of morbidity and stroke an infrequent outcome and therefore they were removed from the main trial composite outcome. Tools and methods of data collection were optimized and event rates used to inform randomisation. This feasibility study demonstrates that the components of the intervention were acceptable, methods of implementing were successful and the main trial design would be feasible. Qualitative work identified key moderators that informed the main trial process evaluation. Changes to the training package, implementation strategy, study design and processes were identified to refine the implementation in the main trial. ISRCTN41244132 ; Registered 24/11/2015.

Assessment of contamination and misclassification biases in a randomized controlled trial of a social network peer education intervention to reduce HIV risk behaviors among drug users and risk partners in Philadelphia, PA and Chiang Mai, Thailand

PubMed Central

Simmons, Nicole; Donnell, Deborah; Ou, San-san; Celentano, David D.; Aramrattana, Apinun; Davis-Vogel, Annet; Metzger, David; Latkin, Carl

2015-01-01

Context Controlled trials of educational interventions are susceptible to contamination. Objectives To test a contamination measure based on recall of terms. Main study A randomized controlled trial of a social network peer education intervention among 1,123 injection drug users and risk partners in Philadelphia, PA and Chiang Mai, Thailand. Methods We assessed the recall of test, negative and positive control terms by intervention and control arm participants and compared the relative odds (OR) of recall of test vs. negative control terms between study arms. Results The contamination measure showed good discriminant ability only among participants from Chiang Mai. In Philadelphia there was no evidence of contamination and little evidence of diffusion. In Chiang Mai there was evidence of diffusion and contamination of 4 of 5 terms tested. Conclusions Network structure and peer education in Chiang Mai likely led to contamination. Recall of intervention materials can be a useful method to detect contamination in trials of educational interventions. PMID:25935214

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

PubMed

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

2015-10-15

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

Zhen gan xi feng decoction, a traditional chinese herbal formula, for the treatment of essential hypertension: a systematic review of randomized controlled trials.

PubMed

Xiong, Xingjiang; Yang, Xiaochen; Feng, Bo; Liu, Wei; Duan, Lian; Gao, Ao; Li, Haixia; Ma, Jizheng; Du, Xinliang; Li, Nan; Wang, Pengqian; Su, Kelei; Chu, Fuyong; Zhang, Guohao; Li, Xiaoke; Wang, Jie

2013-01-01

Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use.

Implementation of an educational intervention to improve hand washing in primary schools: process evaluation within a randomised controlled trial.

PubMed

Chittleborough, Catherine R; Nicholson, Alexandra L; Young, Elaine; Bell, Sarah; Campbell, Rona

2013-08-15

Process evaluations are useful for understanding how interventions are implemented in trial settings. This is important for interpreting main trial results and indicating how the intervention might function beyond the trial. The purpose of this study was to examine the reach, dose, fidelity, acceptability, and sustainability of the implementation of an educational hand washing intervention in primary schools, and to explore views regarding acceptability and sustainability of the intervention. Process evaluation within a cluster randomised controlled trial, including focus groups with pupils aged 6 to 11, semi-structured interviews with teachers and external staff who coordinated the intervention delivery, and school reports and direct observations of the intervention delivery. The educational package was delivered in 61.4% of schools (85.2% of intervention schools, 37.8% of control schools following completion of the trial). Teachers and pupils reacted positively to the intervention, although concerns were raised about the age-appropriateness of the resources. Teachers adapted the resources to suit their school setting and pupils. Staff coordinating the intervention delivery had limited capacity to follow up and respond to schools. The hand washing intervention was acceptable to schools, but its reach outside of a randomised trial, evidenced in the low proportion of schools in the control arm who received it after the trial had ended, suggests that the model of delivery may not be sustainable. ISRCTN: ISRCTN93576146.

Effectiveness of Workplace Weight Management Interventions: a Systematic Review.

PubMed

Weerasekara, Yasoma Kumari; Roberts, Susan B; Kahn, Mira A; LaVertu, Amy E; Hoffman, Ben; Das, Sai Krupa

2016-06-01

A systematic review was conducted of randomized trials of workplace weight management interventions, including trials with dietary, physical activity, environmental, behavioral, and incentive-based components. Main outcomes were defined as change in weight-related measures. Keywords related to weight management and workplace interventions were used to search relevant databases, and 23 eligible studies were reviewed in detail using a data extraction form and quality assessment checklist. The trials were conducted mainly in the USA and Europe, with four additional countries represented. Interventions were mostly multicomponent and were implemented in both sexes and in a range of employment categories. Intervention effectiveness appeared unrelated to region of the world and was highest in 6-12-month trials. The results ranged widely from clinically significant 8.8-kg weight loss in one trial to less effective than the control treatment in others. Some workplace interventions achieve clinically significant benefits, and further studies are needed to replicate those results in wider sociocultural and geographical contexts.

‘Putting Life in Years’ (PLINY) telephone friendship groups research study: pilot randomised controlled trial

PubMed Central

2014-01-01

Background Loneliness in older people is associated with poor health-related quality of life (HRQoL). We undertook a parallel-group randomised controlled trial to evaluate the effectiveness and cost-effectiveness of telephone befriending for the maintenance of HRQoL in older people. An internal pilot tested the feasibility of the trial and intervention. Methods Participants aged >74 years, with good cognitive function, living independently in one UK city were recruited through general practices and other sources, then randomised to: (1) 6 weeks of short one-to-one telephone calls, followed by 12 weeks of group telephone calls with up to six participants, led by a trained volunteer facilitator; or (2) a control group. The main trial required the recruitment of 248 participants in a 1-year accrual window, of whom 124 were to receive telephone befriending. The pilot specified three success criteria which had to be met in order to progress the main trial to completion: recruitment of 68 participants in 95 days; retention of 80% participants at 6 months; successful delivery of telephone befriending by local franchise of national charity. The primary clinical outcome was the Short Form (36) Health Instrument (SF-36) Mental Health (MH) dimension score collected by telephone 6 months following randomisation. Results We informed 9,579 older people about the study. Seventy consenting participants were randomised to the pilot in 95 days, with 56 (80%) providing valid primary outcome data (26 intervention, 30 control). Twenty-four participants randomly allocated to the research arm actually received telephone befriending due to poor recruitment and retention of volunteer facilitators. The trial was closed early as a result. The mean 6-month SF-36 MH scores were 78 (SD 18) and 71 (SD 21) for the intervention and control groups, respectively (mean difference, 7; 95% CI, -3 to 16). Conclusions Recruitment and retention of participants to a definitive trial with a recruitment window of 1 year is feasible. For the voluntary sector to recruit sufficient volunteers to match demand for telephone befriending created by trial recruitment would require the study to be run in more than one major population centre, and/or involve dedicated management of volunteers. Trial registration ISRCTN28645428. PMID:24758530

Effect of virtual reality training on laparoscopic surgery: randomised controlled trial

PubMed Central

Soerensen, Jette L; Grantcharov, Teodor P; Dalsgaard, Torur; Schouenborg, Lars; Ottosen, Christian; Schroeder, Torben V; Ottesen, Bent S

2009-01-01

Objective To assess the effect of virtual reality training on an actual laparoscopic operation. Design Prospective randomised controlled and blinded trial. Setting Seven gynaecological departments in the Zeeland region of Denmark. Participants 24 first and second year registrars specialising in gynaecology and obstetrics. Interventions Proficiency based virtual reality simulator training in laparoscopic salpingectomy and standard clinical education (controls). Main outcome measure The main outcome measure was technical performance assessed by two independent observers blinded to trainee and training status using a previously validated general and task specific rating scale. The secondary outcome measure was operation time in minutes. Results The simulator trained group (n=11) reached a median total score of 33 points (interquartile range 32-36 points), equivalent to the experience gained after 20-50 laparoscopic procedures, whereas the control group (n=10) reached a median total score of 23 (22-27) points, equivalent to the experience gained from fewer than five procedures (P<0.001). The median total operation time in the simulator trained group was 12 minutes (interquartile range 10-14 minutes) and in the control group was 24 (20-29) minutes (P<0.001). The observers’ inter-rater agreement was 0.79. Conclusion Skills in laparoscopic surgery can be increased in a clinically relevant manner using proficiency based virtual reality simulator training. The performance level of novices was increased to that of intermediately experienced laparoscopists and operation time was halved. Simulator training should be considered before trainees carry out laparoscopic procedures. Trial registration ClinicalTrials.gov NCT00311792. PMID:19443914

Benefits and challenges of using the cohort multiple randomised controlled trial design for testing an intervention for depression.

PubMed

Viksveen, Petter; Relton, Clare; Nicholl, Jon

2017-07-06

Trials which test the effectiveness of interventions compared with the status quo frequently encounter challenges. The cohort multiple randomised controlled trial (cmRCT) design is an innovative approach to the design and conduct of pragmatic trials which seeks to address some of these challenges. In this article, we report our experiences with the first completed randomised controlled trial (RCT) using the cmRCT design. This trial-the Depression in South Yorkshire (DEPSY) trial-involved comparison of treatment as usual (TAU) with TAU plus the offer of an intervention for people with self-reported long-term moderate to severe depression. In the trial, we used an existing large population-based cohort: the Yorkshire Health Study. We discuss our experiences with recruitment, attrition, crossover, data analysis, generalisability of results, and cost. The main challenges in using the cmRCT design were the high crossover to the control group and the lower questionnaire response rate among patients who refused the offer of treatment. However, the design did help facilitate efficient and complete recruitment of the trial population as well as analysable data that were generalisable to the population of interest. Attrition rates were also smaller than those reported in other depression trials. This first completed full trial using the cmRCT design testing an intervention for self-reported depression was associated with a number of important benefits. Further research is required to compare the acceptability and cost effectiveness of standard pragmatic RCT design with the cmRCT design. ISRCTN registry: ISRCTN02484593 . Registered on 7 Jan 2013.

Effect of Weight Loss with or without Exercise on Inflammatory Markers and Adipokines in Postmenopausal Women: The SHAPE-2 Trial, A Randomized Controlled Trial.

PubMed

van Gemert, Willemijn A; May, Anne M; Schuit, Albertine J; Oosterhof, Blanche Y M; Peeters, Petra H; Monninkhof, Evelyn M

2016-05-01

We investigated the effect of equivalent weight loss, by a hypocaloric diet or mainly exercise, on inflammatory markers and adipokines in overweight postmenopausal women. Women were randomized to a diet (n = 97), mainly exercise (n = 98), or control group (n = 48). Goal of both interventions was to lose 5 to 6 kg bodyweight by a hypocaloric diet or an exercise program (4 hours/week) combined with a small caloric intake restriction. Outcomes after 16 weeks included serum high-sensitive C-reactive protein (hsCRP), IL6, adiponectin, and leptin. Both intervention groups achieved the target weight loss. Controls remained weight stable. Compared with control, hsCRP decreased with mainly exercise [treatment effect ratio (TER) = 0.64] and borderline statistically significant with diet (TER = 0.77). There was a suggestively larger effect of exercise, directly compared with diet (TER = 0.83). Leptin decreased with both interventions: mainly exercise (TER = 0.55) and diet (TER = 0.59), versus control. Effects attenuated and lost significance after adjusting for change in body fat percentage, and to a lesser extent when adjusting for fitness. No effects were seen on IL6 and adiponectin. A 16-week randomized intervention inducing comparable weight loss by a hypocaloric diet or mainly exercise, resulted in favorable effects on serum hsCRP and leptin. We found a possible more beneficial effect on hsCRP with mainly exercise versus diet. These effects of exercise were established by changes in body fat percentage and physical fitness. A modest amount of weight loss in postmenopausal women reduces hsCRP and leptin levels which might be associated with a lower breast cancer risk. Cancer Epidemiol Biomarkers Prev; 25(5); 799-806. ©2016 AACR. ©2016 American Association for Cancer Research.

A school-based program implemented by community providers previously trained for the prevention of eating and weight-related problems in secondary-school adolescents: the MABIC study protocol.

PubMed

Sánchez-Carracedo, David; López-Guimerà, Gemma; Fauquet, Jordi; Barrada, Juan Ramón; Pàmias, Montserrat; Puntí, Joaquim; Querol, Mireia; Trepat, Esther

2013-10-12

The prevention of eating disorders and disordered eating are increasingly recognized as public health priorities. Challenges in this field included moving from efficacy to effectiveness and developing an integrated approach to the prevention of a broad spectrum of eating and weight-related problems. A previous efficacy trial indicated that a universal disordered eating prevention program, based on the social cognitive model, media literacy educational approach and cognitive dissonance theory, reduced risk factors for disordered eating, but it is unclear whether this program has effects under more real-world conditions. The main aim of this effectiveness trial protocol is to test whether this program has effects when incorporating an integrated approach to prevention and when previously-trained community providers implement the intervention. The research design involved a multi-center non-randomized controlled trial with baseline, post and 1-year follow-up measures. Six schools from the city of Sabadell (close to Barcelona) participated in the intervention group, and eleven schools from four towns neighboring Sabadell participated in the control group. A total of 174 girls and 180 boys in the intervention group, and 484 girls and 490 boys in the control group were registered in class lists prior to baseline. A total of 18 community providers, secondary-school class tutors, nurses from the Catalan Government's Health and School Program, and health promotion technicians from Sabadell City Council were trained and delivered the program. Shared risk factors of eating and weight-related problems were assessed as main measures. It will be vital for progress in disordered eating prevention to conduct effectiveness trials, which test whether interventions are effective when delivered by community providers under ecologically valid conditions, as opposed to tightly controlled research trials. The MABIC project will provide new contributions in this transition from efficacy to effectiveness and new data about progress in the integrated approach to prevention. Pending the results, the effectiveness trial meets the effectiveness standards set down by the Society for Prevention Research. This study will provide new evidence to improve and enhance disordered eating prevention programs. Current Controlled Trials ISRCTN47682626.

Circle of Security–Parenting: A randomized controlled trial in Head Start

PubMed Central

CASSIDY, JUDE; BRETT, BONNIE E.; GROSS, JACQUELYN T.; STERN, JESSICA A.; MARTIN, DAVID R.; MOHR, JONATHAN J.; WOODHOUSE, SUSAN S.

2017-01-01

Although evidence shows that attachment insecurity and disorganization increase risk for the development of psychopathology (Fearon, Bakermans-Kranenburg, van IJzendoorn, Lapsley, & Roisman, 2010; Groh, Roisman, van IJzendoorn, Bakermans-Kranenburg, & Fearon, 2012), implementation challenges have precluded dissemination of attachment interventions on the broad scale at which they are needed. The Circle of Security–Parenting Intervention (COS-P; Cooper, Hoffman, & Powell, 2009), designed with broad implementation in mind, addresses this gap by training community service providers to use a manualized, video-based program to help caregivers provide a secure base and a safe haven for their children. The present study is a randomized controlled trial of COS-P in a low-income sample of Head Start enrolled children and their mothers. Mothers (N = 141; 75 intervention, 66 waitlist control) completed a baseline assessment and returned with their children after the 10-week intervention for the outcome assessment, which included the Strange Situation. Intent to treat analyses revealed a main effect for maternal response to child distress, with mothers assigned to COS-P reporting fewer unsupportive (but not more supportive) responses to distress than control group mothers, and a main effect for one dimension of child executive functioning (inhibitory control but not cognitive flexibility when maternal age and marital status were controlled), with intervention group children showing greater control. There were, however, no main effects of intervention for child attachment or behavior problems. Exploratory follow-up analyses suggested intervention effects were moderated by maternal attachment style or depressive symptoms, with moderated intervention effects emerging for child attachment security and disorganization, but not avoidance; for inhibitory control but not cognitive flexibility; and for child internalizing but not externalizing behavior problems. This initial randomized controlled trial of the efficacy of COS-P sets the stage for further exploration of “what works for whom” in attachment intervention. PMID:28401843

Implementation of an educational intervention to improve hand washing in primary schools: process evaluation within a randomised controlled trial

PubMed Central

2013-01-01

Background Process evaluations are useful for understanding how interventions are implemented in trial settings. This is important for interpreting main trial results and indicating how the intervention might function beyond the trial. The purpose of this study was to examine the reach, dose, fidelity, acceptability, and sustainability of the implementation of an educational hand washing intervention in primary schools, and to explore views regarding acceptability and sustainability of the intervention. Methods Process evaluation within a cluster randomised controlled trial, including focus groups with pupils aged 6 to 11, semi-structured interviews with teachers and external staff who coordinated the intervention delivery, and school reports and direct observations of the intervention delivery. Results The educational package was delivered in 61.4% of schools (85.2% of intervention schools, 37.8% of control schools following completion of the trial). Teachers and pupils reacted positively to the intervention, although concerns were raised about the age-appropriateness of the resources. Teachers adapted the resources to suit their school setting and pupils. Staff coordinating the intervention delivery had limited capacity to follow up and respond to schools. Conclusions The hand washing intervention was acceptable to schools, but its reach outside of a randomised trial, evidenced in the low proportion of schools in the control arm who received it after the trial had ended, suggests that the model of delivery may not be sustainable. Trial registration ISRCTN: ISRCTN93576146 PMID:23947388

TOPPITS: Trial Of Proton Pump Inhibitors in Throat Symptoms. Study protocol for a randomised controlled trial.

PubMed

Watson, Gillian; O'Hara, James; Carding, Paul; Lecouturier, Jan; Stocken, Deborah; Fouweather, Tony; Wilson, Janet

2016-04-01

Persistent throat symptoms and Extra Oesophageal Reflux (EOR) are among the commonest reasons for attendance at a secondary care throat or voice clinic. There is a growing trend to treat throat symptom patients with proton pump inhibitors (PPIs) to suppress stomach acid, but most controlled studies fail to demonstrate a significant benefit of PPI over placebo. In addition, patient views on PPI use vary widely. A UK multi-centre, randomised, controlled trial for adults with persistent throat symptoms to compare the effectiveness of treatment with the proton pump inhibitor (PPI) lansoprazole versus placebo. The trial includes a six-month internal pilot, during which three sites will recruit 30 participants in total, to assess the practicality of the trial and assess the study procedures and willingness of the patient population to participate. If the pilot is successful, three additional sites will be opened to recruitment, and a further 302 participants recruited across the six main trial sites. Further trial sites may be opened, as necessary. The main trial will continue for a further 18 months. Participants will be followed up for 12 months from randomisation, throughout which both primary and secondary outcome data will be collected. The primary outcome is change in Reflux Symptom Index (RSI) score, the 'area standard' for this type of assessment, after 16 weeks (four months) of treatment. Secondary outcomes are RSI changes at 12 months after randomisation, Quality of Life assessment at four and 12 months, laryngeal mucosal changes, assessments of compliance and side effects, and patient-reported satisfaction. TOPPITS is designed to evaluate the relative effectiveness of treatment with a proton pump inhibitor versus placebo in patients with persistent throat symptoms. This will provide valuable information to clinicians and GPs regarding the treatment and management of care for these patients, on changes in symptoms, and in Quality of Life, over time. ISRCTN38578686 . Registered 17 April 2014.

Dependability of results in conference abstracts of randomized controlled trials in ophthalmology and author financial conflicts of interest as a factor associated with full publication.

PubMed

Saldanha, Ian J; Scherer, Roberta W; Rodriguez-Barraquer, Isabel; Jampel, Henry D; Dickersin, Kay

2016-04-26

Discrepancies between information in conference abstracts and full publications describing the same randomized controlled trial have been reported. The association between author conflicts of interest and the publication of randomized controlled trials is unclear. The objective of this study was to use randomized controlled trials in ophthalmology to evaluate (1) the agreement in the reported main outcome results by comparing abstracts and corresponding publications and (2) the association between the author conflicts of interest and publication of the results presented in the abstracts. We considered abstracts describing results of randomized controlled trials presented at the 2001-2004 Association for Research in Vision and Ophthalmology conferences as eligible for our study. Through electronic searching and by emailing abstract authors, we identified the earliest publication (journal article) containing results of each abstract's main outcome through November 2013. We categorized the discordance between the main outcome results in the abstract and its paired publication as qualitative (a difference in the direction of the estimated effect) or as quantitative. We used the Association for Research in Vision and Ophthalmology categories for conflicts of interest: financial interest, employee of business with interest, consultant to business with interest, inventor/developer with patent, and receiving ≥ 1 gift from industry in the past year. We calculated the relative risks (RRs) of publication associated with the categories of conflicts of interest for abstracts with results that were statistically significant, not statistically significant, or not reported. We included 513 abstracts, 230 (44.8 %) of which reached publication. Among the 86 pairs with the same main outcome domain at the same time point, 47 pairs (54.7 %) had discordant results: qualitative discordance in 7 pairs and quantitative discordance in 40 pairs. Quantitative discordance was indicated as < 10, 10-20, > 20 %, and unclear in 14, 5, 14, and 7 pairs, respectively. First authors reporting of one or more conflicts of interest was associated with a greater likelihood of publication (RR = 1.31; 95 % CI = 1.04 to 1.64) and a shorter time-to-publication (log-rank p = 0.026). First author conflicts of interests that were associated with publication were financial support (RR = 1.50; 95 % CI = 1.19 to 1.90) and one or more gifts (RR = 1.42; 95 % CI = 1.05 to 1.92). The association between conflicts of interest and publication remained, irrespective of the statistical significance of the results. More than half the abstract/publication pairs exhibited some amount of discordance in the main outcome results, calling into question the dependability of conference abstracts. Regardless of the main outcome results, the conflicts of interests of the abstract's first author were associated with publication.

What motivates Parkinson's disease patients to enter clinical trials?

PubMed

Valadas, Anabela; Coelho, Miguel; Mestre, Tiago; Guedes, Leonor Correia; Finisterra, Maria; Noronha, Ana; Rosa, Mário M; Sampaio, Cristina; Ferreira, Joaquim J

2011-11-01

Limited data is available regarding motivations and concerns of Parkinson's disease (PD) patients when participating in clinical trials (CTs). Knowledge of these factors may improve the recruitment and quality of future trials. To assess the motivations and concerns of PD patients concerning participation in CTs and to evaluate the extent to which patients understand informed consent materials and placebo effect concept. Cross-sectional study in PD patients enrolled in CTs between 2002 and 2007. Two questionnaires designed for placebo-controlled and active-controlled studies were mailed to patients. From the 93/127 replied questionnaires (response rate: 73.2%) 91 were evaluable. Fifty-nine percent of the participants were women with a mean age of 66.8 years. The main reasons for participating in CTs were to help the advance of science (63.7%), to gain access to a better treatment (56.0%), and to benefit others (51.6%). Risk of adverse events (49.5%) and negative effects of treatment (35.2%) were the major concerns. Ninety percent reported they had understood the informed consent. Of 80 patients included in placebo-controlled studies, 63.9% understood the placebo effect concept. Globally, 66% of patients would participate in another CT and 41.6% in a placebo-controlled trial. The main motivations of PD patients to participate in CTs were the benefit to the patient himself and to others. The major concern was safety. PD patients understood the informed consent, but more educational efforts must be made to explain the placebo effect. Most PD patients were very positive toward CTs and would participate in another trial. Copyright © 2011 Elsevier Ltd. All rights reserved.

The effectiveness and cost-evaluation of manual therapy and physical therapy in patients with sub-acute and chronic non specific neck pain. Rationale and design of a Randomized Controlled Trial (RCT)

PubMed Central

2010-01-01

Background Manual Therapy applied to patients with non specific neck pain has been investigated several times. In the Netherlands, manual therapy as applied according to the Utrecht School of Manual Therapy (MTU) has not been the subject of a randomized controlled trial. MTU differs in diagnoses and treatment from other forms of manual therapy. Methods/Design This is a single blind randomized controlled trial in patients with sub-acute and chronic non specific neck pain. Patients with neck complaints existing for two weeks (minimum) till one year (maximum) will participate in the trial. 180 participants will be recruited in thirteen primary health care centres in the Netherlands. The experimental group will be treated with MTU during a six week period. The control group will be treated with physical therapy (standard care, mainly active exercise therapy), also for a period of six weeks. Primary outcomes are Global Perceived Effect (GPE) and functional status (Neck Disability Index (NDI-DV)). Secondary outcomes are neck pain (Numeric Rating Scale (NRS)), Eurocol, costs and quality of life (SF36). Discussion This paper presents details on the rationale of MTU, design, methods and operational aspects of the trial. Trial registration ClinicalTrials.gov Identifier: NCT00713843 PMID:20096136

Assessing delay and lag in sagittal trunk control using a tracking task.

PubMed

Reeves, N Peter; Luis, Abraham; Chan, Elizabeth C; Sal Y Rosas, Victor G; Tanaka, Martin L

2018-05-17

Slower trunk muscle responses are linked to back pain and injury. Unfortunately, clinical assessments of spine function do not objectively evaluate this important attribute, which reflects speed of trunk control. Speed of trunk control can be parsed into two components: (1) delay, the time it takes to initiate a movement, and (2) lag, the time it takes to execute a movement once initiated. The goal of this study is to demonstrate a new approach to assess delay and lag in trunk control using a simple tracking task. Ten healthy subjects performed four blocks of six trials of trunk tracking in the sagittal plane. Delay and lag were estimated by modeling trunk control for predictable and unpredictable (control mode) trunk movements in flexion and extension (control direction) at movement amplitudes of 2°, 4°, and 6° (control amplitude). The main effect of control mode, direction, and amplitude of movement were compared between trial blocks to assess secondary influencers (e.g., fatigue). Only control mode was consistent across trial blocks with predictable movements being faster than unpredictable for both delay and lag. Control direction and amplitude effects on delay and lag were consistent across the first two trial blocks and less consistent in later blocks. Given the heterogeneity in the presentation of back pain, clinical assessment of trunk control should include different control modes, directions, and amplitudes. To reduce testing time and the influence of fatigue, we recommend six trials to assess trunk control. Copyright © 2018 Elsevier Ltd. All rights reserved.

'Putting Life in Years' (PLINY) telephone friendship groups research study: pilot randomised controlled trial.

PubMed

Mountain, Gail A; Hind, Daniel; Gossage-Worrall, Rebecca; Walters, Stephen J; Duncan, Rosie; Newbould, Louise; Rex, Saleema; Jones, Carys; Bowling, Ann; Cattan, Mima; Cairns, Angela; Cooper, Cindy; Edwards, Rhiannon Tudor; Goyder, Elizabeth C

2014-04-24

Loneliness in older people is associated with poor health-related quality of life (HRQoL). We undertook a parallel-group randomised controlled trial to evaluate the effectiveness and cost-effectiveness of telephone befriending for the maintenance of HRQoL in older people. An internal pilot tested the feasibility of the trial and intervention. Participants aged >74 years, with good cognitive function, living independently in one UK city were recruited through general practices and other sources, then randomised to: (1) 6 weeks of short one-to-one telephone calls, followed by 12 weeks of group telephone calls with up to six participants, led by a trained volunteer facilitator; or (2) a control group. The main trial required the recruitment of 248 participants in a 1-year accrual window, of whom 124 were to receive telephone befriending. The pilot specified three success criteria which had to be met in order to progress the main trial to completion: recruitment of 68 participants in 95 days; retention of 80% participants at 6 months; successful delivery of telephone befriending by local franchise of national charity. The primary clinical outcome was the Short Form (36) Health Instrument (SF-36) Mental Health (MH) dimension score collected by telephone 6 months following randomisation. We informed 9,579 older people about the study. Seventy consenting participants were randomised to the pilot in 95 days, with 56 (80%) providing valid primary outcome data (26 intervention, 30 control). Twenty-four participants randomly allocated to the research arm actually received telephone befriending due to poor recruitment and retention of volunteer facilitators. The trial was closed early as a result. The mean 6-month SF-36 MH scores were 78 (SD 18) and 71 (SD 21) for the intervention and control groups, respectively (mean difference, 7; 95% CI, -3 to 16). Recruitment and retention of participants to a definitive trial with a recruitment window of 1 year is feasible. For the voluntary sector to recruit sufficient volunteers to match demand for telephone befriending created by trial recruitment would require the study to be run in more than one major population centre, and/or involve dedicated management of volunteers. ISRCTN28645428.

A school-based program implemented by community providers previously trained for the prevention of eating and weight-related problems in secondary-school adolescents: the MABIC study protocol

PubMed Central

2013-01-01

Background The prevention of eating disorders and disordered eating are increasingly recognized as public health priorities. Challenges in this field included moving from efficacy to effectiveness and developing an integrated approach to the prevention of a broad spectrum of eating and weight-related problems. A previous efficacy trial indicated that a universal disordered eating prevention program, based on the social cognitive model, media literacy educational approach and cognitive dissonance theory, reduced risk factors for disordered eating, but it is unclear whether this program has effects under more real-world conditions. The main aim of this effectiveness trial protocol is to test whether this program has effects when incorporating an integrated approach to prevention and when previously-trained community providers implement the intervention. Methods/design The research design involved a multi-center non-randomized controlled trial with baseline, post and 1-year follow-up measures. Six schools from the city of Sabadell (close to Barcelona) participated in the intervention group, and eleven schools from four towns neighboring Sabadell participated in the control group. A total of 174 girls and 180 boys in the intervention group, and 484 girls and 490 boys in the control group were registered in class lists prior to baseline. A total of 18 community providers, secondary-school class tutors, nurses from the Catalan Government’s Health and School Program, and health promotion technicians from Sabadell City Council were trained and delivered the program. Shared risk factors of eating and weight-related problems were assessed as main measures. Discussion It will be vital for progress in disordered eating prevention to conduct effectiveness trials, which test whether interventions are effective when delivered by community providers under ecologically valid conditions, as opposed to tightly controlled research trials. The MABIC project will provide new contributions in this transition from efficacy to effectiveness and new data about progress in the integrated approach to prevention. Pending the results, the effectiveness trial meets the effectiveness standards set down by the Society for Prevention Research. This study will provide new evidence to improve and enhance disordered eating prevention programs. Trial registration Current Controlled Trials ISRCTN47682626 PMID:24118981

A Design to Investigate the Feasibility and Effects of Partnered Ballroom Dancing on People With Parkinson Disease: Randomized Controlled Trial Protocol

PubMed Central

Roberts, Lisa; Pickering, Ruth; Roberts, Helen Clare; Wiles, Rose; Kunkel, Dorit; Hulbert, Sophia; Robison, Judy; Fitton, Carolyn

2014-01-01

Background Self-help and physical leisure activities has become increasingly important in the maintenance of safe and functional mobility among an increasingly elderly population. Preventing the cycle of deterioration, falling, inactivity, dependency, and secondary complications in people with Parkinson disease (PD) is a priority. Research has shown that people with PD are interested in dance and although the few existing trials are small, initial proof of principle trials from the United States have demonstrated beneficial effects on balance control, gait, and activity levels. To our knowledge, there has been no research into long-term effects, cost effectiveness, the influence on spinal posture and turning, or the personal insights of dance participants. Objective The purpose of this study was to determine the methodological feasibility of conducting a definitive phase III trial to evaluate the benefits of dance in people with PD. We will build on the proof of principle trials by addressing gaps in knowledge, focusing on areas of greatest methodological uncertainty; the choice of dances and intensity of the program; for the main trial, the availability of partners, the suitability of the currently envisaged primary outcomes, balance and spinal posture; and the key costs of delivering and participating in a dance program to inform economic evaluation. Methods Fifty participants (mild-to-moderate condition) will be randomized to the control (usual care) or experimental (dance plus usual care) groups at a ratio of 15:35. Dance will be taught by professional teachers in a dance center in the South of England. Each participant in the experimental group will dance with his or her spouse, a friend, or a partner from a bank of volunteers. A blinded assessor will complete clinical measures and self-reported ability at baseline, and at 3 and 6 months after randomization. A qualitative study of a subgroup of participants and partners will examine user’s views about the appropriateness and acceptability of the intervention, assessment protocol, and general trial procedures. Procedures for an economic evaluation of dance for health care will be developed for the main trial. Results Recruitment began in January 2013 and the last participant is expected to complete the trial follow-up in June 2014. Conclusions Findings from our study may provide novel insights into the way people with PD become involved in dance, their views and opinions, and the suitability of our primary and secondary outcomes. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 63088686; http://www.controlled-trials.com/ISRCTN63088686/63088686 (Archived by WebCite at http://www.webcitation.org/6QYyjehP7). PMID:25051989

Cost effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes: economic analysis alongside randomised controlled trial (UKPDS 41)

PubMed Central

Gray, Alastair; Raikou, Maria; McGuire, Alistair; Fenn, Paul; Stevens, Richard; Cull, Carole; Stratton, Irene; Adler, Amanda; Holman, Rury; Turner, Robert

2000-01-01

Objective To estimate the cost effectiveness of conventional versus intensive blood glucose control in patients with type 2 diabetes. Design Incremental cost effectiveness analysis alongside randomised controlled trial. Setting 23 UK hospital clinic based study centres. Participants 3867 patients with newly diagnosed type 2 diabetes (mean age 53 years). Interventions Conventional (primarily diet) glucose control policy versus intensive control policy with a sulphonylurea or insulin. Main outcome measures Incremental cost per event-free year gained within the trial period. Results Intensive glucose control increased trial treatment costs by £695 (95% confidence interval £555 to £836) per patient but reduced the cost of complications by £957 (£233 to £1681) compared with conventional management. If standard practice visit patterns were assumed rather than trial conditions, the incremental cost of intensive management was £478 (−£275 to £1232) per patient. The within trial event-free time gained in the intensive group was 0.60 (0.12 to 1.10) years and the lifetime gain 1.14 (0.69 to 1.61) years. The incremental cost per event-free year gained was £1166 (costs and effects discounted at 6% a year) and £563 (costs discounted at 6% a year and effects not discounted). Conclusions Intensive blood glucose control in patients with type 2 diabetes significantly increased treatment costs but substantially reduced the cost of complications and increased the time free of complications. PMID:10818026

Interventions for the prevention of nutritional rickets in term born children.

PubMed

Lerch, C; Meissner, T

2007-10-17

Nutritional rickets is a disease of growing children leading to bone deformities, bone pain, convulsions or delayed motor development. Today, high-incidence of nutritional rickets is mainly found in low-income countries. To assess the effects of various interventions on the prevention of nutritional rickets in term born children. Studies were obtained from computerised searches of The Cochrane Library, MEDLINE, EMBASE, LILACS and reference lists of relevant articles. We contacted authors of studies or reviews to obtain further studies. Studies were included if they were randomised controlled clinical trials, controlled clinical trials or prospective cohort studies comparing any intervention for the prevention of nutritional rickets in term born children with placebo or no intervention. Minimum duration of the intervention was three months for children under 12 months or six months for children over 12 months. Two authors independently extracted data and assessed study quality. Authors of studies were contacted to obtain missing information. Four studies enrolled approximately 1700 participants. Trials lasted between nine months to two years. Three studies were randomised controlled trials, two of which showed a cluster randomised design; one trial probably was a controlled trial with researcher controlled group assignment. In children up to three years of age in Turkey, Vitamin D compared to no intervention showed a relative risk of 0.04 (95% confidence interval (CI) 0 to 0.71). Despite a marked non-compliance, a Chinese trial in children up to three years of age comparing a combined intervention of supplementation of vitamin D, calcium and nutritional counseling showed a relative risk of 0.76 (95% CI 0.61 to 0.95) compared to no intervention. In two studies conducted in older children in China and in France no rickets occurred in both the intervention and control group. There a only few studies on the prevention of nutritional rickets in term born children. Until new data become available, it appears sound to offer preventive measures (vitamin D or calcium) to groups of high risk, like infants and toddlers; children living in Africa, Asia or the Middle East or migrated children from these regions into areas where rickets is not frequent. Due to a marked clinical heterogeneity and the scarcity of data, the main and adverse effects of preventive measures against nutritional rickets should be investigated in different countries, different age groups and in children of different ethnic origin.

A brief history of placebos and clinical trials in psychiatry.

PubMed

Shorter, Edward

2011-04-01

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

Randomised controlled trials of veterinary homeopathy: characterising the peer-reviewed research literature for systematic review.

PubMed

Mathie, Robert T; Hacke, Daniela; Clausen, Jürgen

2012-10-01

Systematic review of the research evidence in veterinary homeopathy has never previously been carried out. This paper presents the search methods, together with categorised lists of retrieved records, that enable us to identify the literature that is acceptable for future systematic review of randomised controlled trials (RCTs) in veterinary homeopathy. All randomised and controlled trials of homeopathic intervention (prophylaxis and/or treatment of disease, in any species except man) were appraised according to pre-specified criteria. The following databases were systematically searched from their inception up to and including March 2011: AMED; Carstens-Stiftung Homeopathic Veterinary Clinical Research (HomVetCR) database; CINAHL; Cochrane Central Register of Controlled Trials; Embase; Hom-Inform; LILACS; PubMed; Science Citation Index; Scopus. One hundred and fifty records were retrieved; 38 satisfied the acceptance criteria (substantive report of a clinical treatment or prophylaxis trial in veterinary homeopathic medicine randomised and controlled and published in a peer-reviewed journal), and were thus eligible for future planned systematic review. Approximately half of the rejected records were theses. Seven species and 27 different species-specific medical conditions were represented in the 38 papers. Similar numbers of papers reported trials of treatment and prophylaxis (n=21 and n=17 respectively) and were controlled against placebo or other than placebo (n=18, n=20 respectively). Most research focused on non-individualised homeopathy (n=35 papers) compared with individualised homeopathy (n=3). The results provide a complete and clarified view of the RCT literature in veterinary homeopathy. We will systematically review the 38 substantive peer-reviewed journal articles under the main headings: treatment trials; prophylaxis trials. Copyright © 2012 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Preventing substance misuse: study protocol for a randomised controlled trial of the Strengthening Families Programme 10–14 UK (SFP 10–14 UK)

PubMed Central

2014-01-01

Background Prevention of alcohol, drug and tobacco misuse by young people is a key public health priority. There is a need to develop the evidence base through rigorous evaluations of innovative approaches to substance misuse prevention. The Strengthening Families Programme 10–14 is a universal family-based alcohol, drugs and tobacco prevention programme, which has achieved promising results in US trials, and which now requires cross-cultural assessment. This paper therefore describes the protocol for a randomised controlled trial of the UK version of the Strengthening Families Programme 10–14 (SFP 10–14 UK). Methods/Design The trial comprises a pragmatic cluster randomised controlled effectiveness trial with families as the unit of randomisation, with embedded process and economic evaluations. Participating families will be randomised to one of two treatment groups - usual care with full access to existing services (control group), or usual care plus SFP 10–14 UK (intervention group). The trial has two primary outcomes - the number of occasions that young people report having drunk alcohol in the last 30 days, and drunkenness during the last 30 days, both dichotomised as ‘never’ and ‘1-2 times or more’. The main follow-up is at 2 years past baseline, and short-term and intermediate outcomes are also measured at 9 and 15 months. Discussion The results from this trial will provide evidence on the effectiveness and cost-effectiveness of an innovative universal family-based substance misuse prevention programme in a UK context. Trial registration Current Controlled Trials ISRCTN63550893. PMID:24438460

A randomized, placebo-controlled trial of patient education for acute low back pain (PREVENT Trial): statistical analysis plan.

PubMed

Traeger, Adrian C; Skinner, Ian W; Hübscher, Markus; Lee, Hopin; Moseley, G Lorimer; Nicholas, Michael K; Henschke, Nicholas; Refshauge, Kathryn M; Blyth, Fiona M; Main, Chris J; Hush, Julia M; Pearce, Garry; Lo, Serigne; McAuley, James H

Statistical analysis plans increase the transparency of decisions made in the analysis of clinical trial results. The purpose of this paper is to detail the planned analyses for the PREVENT trial, a randomized, placebo-controlled trial of patient education for acute low back pain. We report the pre-specified principles, methods, and procedures to be adhered to in the main analysis of the PREVENT trial data. The primary outcome analysis will be based on Mixed Models for Repeated Measures (MMRM), which can test treatment effects at specific time points, and the assumptions of this analysis are outlined. We also outline the treatment of secondary outcomes and planned sensitivity analyses. We provide decisions regarding the treatment of missing data, handling of descriptive and process measure data, and blinded review procedures. Making public the pre-specified statistical analysis plan for the PREVENT trial minimizes the potential for bias in the analysis of trial data, and in the interpretation and reporting of trial results. ACTRN12612001180808 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612001180808). Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Zhen Gan Xi Feng Decoction, a Traditional Chinese Herbal Formula, for the Treatment of Essential Hypertension: A Systematic Review of Randomized Controlled Trials

PubMed Central

Xiong, Xingjiang; Yang, Xiaochen; Feng, Bo; Liu, Wei; Duan, Lian; Gao, Ao; Li, Haixia; Ma, Jizheng; Du, Xinliang; Li, Nan; Wang, Pengqian; Su, Kelei; Chu, Fuyong; Zhang, Guohao; Li, Xiaoke; Wang, Jie

2013-01-01

Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use. PMID:23573163

A Preliminary Study of the Effectiveness of Chinese Therapeutic Food on Regulating Female Reproductive Hormones

PubMed Central

Fu, Lulu; Xu, Hong

2011-01-01

This study investigated the effectiveness of Chinese therapeutic food on female reproductive hormones in a double-blind, placebo-controlled clinical trial. Chinese kiwi fruit extract (Hong En No. 1) was provided for Australian peri-menopausal women for one month. Chinese medical assessment and urinary 2-hydroxyestrone (2-OHE) and 16alpha-hydroxyestrone (16alpha-OHE) tests were conducted. Twenty-six urinary samples (pre and post-trial) which met the requirement of testing were analysed, the ratio 2-OHE:16alpha-OHE of pre-trial (1.18 ± 0.34) and post-trial (0.97 ± 0.29) in the control group (n = 6) decreased but showed no significant change, this ratio of pre-trial (1.44 ± 0.16) and post-trial (1.65 ± 0.21) in the treatment group (n = 7) indicated an improvement (P = 0.066), which results in beneficial hormone regulation. The Chinese medicine assessment indicated that the patterns of disharmony mainly include Liver Qi stagnation and Liver-Kidney Yin deficiency patterns. No significant change observed in the control group, significant score reduction of the patterns of disharmony was achieved at post-trial in the treatment group, which indicates an improvement of general health condition. PMID:21614163

The Effect of Aging on the Dynamics of Reactive and Proactive Cognitive Control of Response Interference

PubMed Central

Xiang, Ling; Zhang, Baoqiang; Wang, Baoxi; Jiang, Jun; Zhang, Fenghua; Hu, Zhujing

2016-01-01

A prime-target interference task was used to investigate the effects of cognitive aging on reactive and proactive control after eliminating frequency confounds and feature repetitions from the cognitive control measures. We used distributional analyses to explore the dynamics of the two control functions by distinguishing the strength of incorrect response capture and the efficiency of suppression control. For reactive control, within-trial conflict control and between-trial conflict adaption were analyzed. The statistical analysis showed that there were no reliable between-trial conflict adaption effects for either young or older adults. For within-trial conflict control, the results revealed that older adults showed larger interference effects on mean RT and mean accuracy. Distributional analyses showed that the decline mainly stemmed from inefficient suppression rather than from stronger incorrect responses. For proactive control, older adults showed comparable proactive conflict resolution to young adults on mean RT and mean accuracy. Distributional analyses showed that older adults were as effective as younger adults in adjusting their responses based on congruency proportion information to minimize automatic response capture and actively suppress the direct response activation. The results suggest that older adults were less proficient at suppressing interference after conflict was detected but can anticipate and prevent inference in response to congruency proportion manipulation. These results challenge earlier views that older adults have selective deficits in proactive control but intact reactive control. PMID:27847482

The Effect of Aging on the Dynamics of Reactive and Proactive Cognitive Control of Response Interference.

PubMed

Xiang, Ling; Zhang, Baoqiang; Wang, Baoxi; Jiang, Jun; Zhang, Fenghua; Hu, Zhujing

2016-01-01

A prime-target interference task was used to investigate the effects of cognitive aging on reactive and proactive control after eliminating frequency confounds and feature repetitions from the cognitive control measures. We used distributional analyses to explore the dynamics of the two control functions by distinguishing the strength of incorrect response capture and the efficiency of suppression control. For reactive control, within-trial conflict control and between-trial conflict adaption were analyzed. The statistical analysis showed that there were no reliable between-trial conflict adaption effects for either young or older adults. For within-trial conflict control, the results revealed that older adults showed larger interference effects on mean RT and mean accuracy. Distributional analyses showed that the decline mainly stemmed from inefficient suppression rather than from stronger incorrect responses. For proactive control, older adults showed comparable proactive conflict resolution to young adults on mean RT and mean accuracy. Distributional analyses showed that older adults were as effective as younger adults in adjusting their responses based on congruency proportion information to minimize automatic response capture and actively suppress the direct response activation. The results suggest that older adults were less proficient at suppressing interference after conflict was detected but can anticipate and prevent inference in response to congruency proportion manipulation. These results challenge earlier views that older adults have selective deficits in proactive control but intact reactive control.

Analyses of group sequential clinical trials.

PubMed

Koepcke, W

1989-12-01

In the first part of this article the methodology of group sequential plans is reviewed. After introducing the basic definition of such plans the main properties are shown. At the end of this section three different plans (Pocock, O'Brien-Fleming, Koepcke) are compared. In the second part of the article some unresolved issues and recent developments in the application of group sequential methods to long-term controlled clinical trials are discussed. These include deviation from the assumptions, life table methods, multiple-arm clinical trials, multiple outcome measures, and confidence intervals.

Protocol for a pilot randomised controlled trial of an intervention to increase the use of traffic light food labelling in UK shoppers (the FLICC trial).

PubMed

Scarborough, Peter; Hodgkins, Charo; Raats, Monique M; Harrington, Richard A; Cowburn, Gill; Dean, Moira; Doherty, Aiden; Foster, Charlie; Juszczak, Edmund; Matthews, Anne; Mizdrak, Anja; Mhurchu, Cliona Ni; Shepherd, Richard; Tiomotijevic, Lada; Winstone, Naomi; Rayner, Mike

2015-01-01

Traffic light labelling of foods-a system that incorporates a colour-coded assessment of the level of total fat, saturated fat, sugar and salt on the front of packaged foods-has been recommended by the UK Government and is currently in use or being phased in by many UK manufacturers and retailers. This paper describes a protocol for a pilot randomised controlled trial of an intervention designed to increase the use of traffic light labelling during real-life food purchase decisions. The objectives of this two-arm randomised controlled pilot trial are to assess recruitment, retention and data completion rates, to generate potential effect size estimates to inform sample size calculations for the main trial and to assess the feasibility of conducting such a trial. Participants will be recruited by email from a loyalty card database of a UK supermarket chain. Eligible participants will be over 18 and regular shoppers who frequently purchase ready meals or pizzas. The intervention is informed by a review of previous interventions encouraging the use of nutrition labelling and the broader behaviour change literature. It is designed to impact on mechanisms affecting belief and behavioural intention formation as well as those associated with planning and goal setting and the adoption and maintenance of the behaviour of interest, namely traffic light label use during purchases of ready meals and pizzas. Data will be collected using electronic sales data via supermarket loyalty cards and web-based questionnaires and will be used to estimate the effect of the intervention on the nutrition profile of purchased ready meals and pizzas and the behavioural mechanisms associated with label use. Data collection will take place over 48 weeks. A process evaluation including semi-structured interviews and web analytics will be conducted to assess feasibility of a full trial. The design of the pilot trial allows for efficient recruitment and data collection. The intervention could be generalised to a wider population if shown to be feasible in the main trial. ISRCTN: ISRCTN19316955.

Screening versus routine practice in detection of atrial fibrillation in patients aged 65 or over: cluster randomised controlled trial

PubMed Central

Fitzmaurice, David A; Jowett, Sue; Mant, Jonathon; Murray, Ellen T; Holder, Roger; Raftery, J P; Bryan, S; Davies, Michael; Lip, Gregory Y H; Allan, T F

2007-01-01

Objectives To assess whether screening improves the detection of atrial fibrillation (cluster randomisation) and to compare systematic and opportunistic screening. Design Multicentred cluster randomised controlled trial, with subsidiary trial embedded within the intervention arm. Setting 50 primary care centres in England, with further individual randomisation of patients in the intervention practices. Participants 14 802 patients aged 65 or over in 25 intervention and 25 control practices. Interventions Patients in intervention practices were randomly allocated to systematic screening (invitation for electrocardiography) or opportunistic screening (pulse taking and invitation for electrocardiography if the pulse was irregular). Screening took place over 12 months in each practice from October 2001 to February 2003. No active screening took place in control practices. Main outcome measure Newly identified atrial fibrillation. Results The detection rate of new cases of atrial fibrillation was 1.63% a year in the intervention practices and 1.04% in control practices (difference 0.59%, 95% confidence interval 0.20% to 0.98%). Systematic and opportunistic screening detected similar numbers of new cases (1.62% v 1.64%, difference 0.02%, −0.5% to 0.5%). Conclusion Active screening for atrial fibrillation detects additional cases over current practice. The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse taking with follow-up electrocardiography. Trial registration Current Controlled Trials ISRCTN19633732. PMID:17673732

The effects of laughter therapy on mood state and self-esteem in cancer patients undergoing radiation therapy: a randomized controlled trial.

PubMed

Kim, So Hee; Kook, Jeong Ran; Kwon, Moonjung; Son, Myeong Ha; Ahn, Seung Do; Kim, Yeon Hee

2015-04-01

To investigate whether laughter therapy lowers total mood disturbance scores and improves self-esteem scores in patients with cancer. Randomized controlled trial in a radio-oncology outpatient setting. Sixty-two patients were enrolled and randomly assigned to the experimental group (n=33) or the wait list control group (n=29). Three laughter therapy sessions lasting 60 minutes each. Mood state and self-esteem. The intention-to-treat analysis revealed a significant main effect of group: Experimental group participants reported a 14.12-point reduction in total mood disturbance, while the wait list control group showed a 1.21-point reduction (p=0.001). The per-protocol analysis showed a significant main effect of group: The experimental group reported a 18.86-point decrease in total mood disturbance, while controls showed a 0.19-point reduction (p<0.001). The self-esteem of experimental group was significantly greater than that of the wait list control group (p=0.044). These results indicate that laughter therapy can improve mood state and self-esteem and can be a beneficial, noninvasive intervention for patients with cancer in clinical settings.

Early mortality of alcoholic hepatitis: a review of data from placebo-controlled clinical trials.

PubMed

Yu, Chao-Hui; Xu, Cheng-Fu; Ye, Hua; Li, Lan; Li, You-Ming

2010-05-21

To investigate the early mortality of placebo-treated alcoholic hepatitis patients. Mortality data about alcoholic hepatitis patients who participated in randomized placebo-controlled trials were searched from PubMed, EMBASE, and Cochrane Library, extracted and analyzed. A total of 661 placebo-treated patients in 19 trials were included. The overall mortality rate was 34.19% with a median observation time of 160 d (range 21-720 d). Hepatic failure, gastrointestinal bleeding and infection were the three main causes of death, accounting for 55.47%, 21.17% and 7.30% of all deaths, respectively. One-month mortality data about 324 placebo-treated alcoholic hepatitis patients in 10 trials were reported with a pooled mortality rate of 20.37%. The one-month mortality rate of patients with moderate to severe alcoholic hepatitis tended to be higher than that of general patients (22.69% vs 10.93%, P < 0.05), whereas no significant difference was observed between the patients from North America or Europe (22.43% vs 18.45%, P > 0.05), neither any difference was found between the studies published before and after 1990 (18.18% vs 21.88%, P > 0.05). Alcoholic hepatitis is a severe liver disease with a high mortality rate, and hepatic failure, gastrointestinal bleeding and infection are the three main causes of death.

Participant recruitment to FiCTION, a primary dental care trial - survey of facilitators and barriers.

PubMed

Keightley, A; Clarkson, J; Maguire, A; Speed, C; Innes, N

2014-11-01

To identify reasons behind a lower than expected participant recruitment rate within the FiCTION trial, a multi-centre paediatric primary dental care randomised controlled trial (RCT). An online survey, based on a previously published tool, consisting of both quantitative and qualitative responses, completed by staff in dental practices recruiting to FiCTION. Ratings from quantitative responses were aggregated to give overall scores for factors related to participant recruitment. Qualitative responses were independently grouped into themes. Thirty-nine anonymous responses were received. Main facilitators related to the support received from the central research team and importance of the research question. The main barriers related to low child eligibility rates and the integration of trial processes within routine workloads. These findings have directed strategies for enhancing participant recruitment at existing practices and informed recruitment of further practices. The results help provide a profile of the features required of practices to successfully screen and recruit participants. Future trials in this setting should consider the level of interest in the research question within practices, and ensure trial processes are as streamlined as possible. Research teams should actively support practices with participant recruitment and maintain enthusiasm among the entire practice team.

Statistical analyses in Swedish randomised trials on mammography screening and in other randomised trials on cancer screening: a systematic review

PubMed Central

Boniol, Mathieu; Smans, Michel; Sullivan, Richard; Boyle, Peter

2015-01-01

Objectives We compared calculations of relative risks of cancer death in Swedish mammography trials and in other cancer screening trials. Participants Men and women from 30 to 74 years of age. Setting Randomised trials on cancer screening. Design For each trial, we identified the intervention period, when screening was offered to screening groups and not to control groups, and the post-intervention period, when screening (or absence of screening) was the same in screening and control groups. We then examined which cancer deaths had been used for the computation of relative risk of cancer death. Main outcome measures Relative risk of cancer death. Results In 17 non-breast screening trials, deaths due to cancers diagnosed during the intervention and post-intervention periods were used for relative risk calculations. In the five Swedish trials, relative risk calculations used deaths due to breast cancers found during intervention periods, but deaths due to breast cancer found at first screening of control groups were added to these groups. After reallocation of the added breast cancer deaths to post-intervention periods of control groups, relative risks of 0.86 (0.76; 0.97) were obtained for cancers found during intervention periods and 0.83 (0.71; 0.97) for cancers found during post-intervention periods, indicating constant reduction in the risk of breast cancer death during follow-up, irrespective of screening. Conclusions The use of unconventional statistical methods in Swedish trials has led to overestimation of risk reduction in breast cancer death attributable to mammography screening. The constant risk reduction observed in screening groups was probably due to the trial design that optimised awareness and medical management of women allocated to screening groups. PMID:26152677

Effectiveness of a Smoking Cessation Intervention in Dutch Pharmacies and General Practices

ERIC Educational Resources Information Center

Hoving, Ciska; Mudde, Aart N.; Dijk, Froukje; de Vries, Hein

2010-01-01

Purpose: The purpose of this paper is to test the effectiveness of a computer-tailored smoking cessation intervention, distributed through 75 Dutch general practices (GP) and 65 pharmacies (PH) in a randomised control trial. Design/methodology/approach: Respondents receive a tailored letter or a thank you letter (control condition). Main outcome…

Evidence based general practice: a retrospective study of interventions in one training practice.

PubMed Central

Gill, P.; Dowell, A. C.; Neal, R. D.; Smith, N.; Heywood, P.; Wilson, A. E.

1996-01-01

OBJECTIVES--To estimate the proportion of interventions in general practice that are based on evidence from clinical trials and to assess the appropriateness of such an evaluation. DESIGN--Retrospective review of case notes. SETTING--One suburban training general practice. SUBJECTS--122 consecutive doctor-patient consultations over two days. MAIN OUTCOME MEASURES--Proportions of interventions based on randomised controlled trials (from literature search with Medline, pharmaceutical databases, and standard textbooks), on convincing non-experimental evidence, and without substantial evidence. RESULTS--21 of the 122 consultations recorded were excluded due to insufficient data; 31 of the interventions were based on randomised controlled trial evidence and 51 based on convincing non-experimental evidence. Hence 82/101 (81%) of interventions were based on evidence meeting our criteria. CONCLUSIONS--Most interventions within general practice are based on evidence from clinical trials, but the methods used in such trials may not be the most appropriate to apply to this setting. PMID:8608291

Beneficiaries' perceptions and reported use of unconditional cash transfers intended to prevent acute malnutrition in children in poor rural communities in Burkina Faso: qualitative results from the MAM'Out randomized controlled trial.

PubMed

Tonguet-Papucci, Audrey; Houngbe, Freddy; Lompo, Palamanga; Yameogo, Wambi Maurice Evariste; Huneau, Jean-François; Ait Aissa, Myriam; Kolsteren, Patrick

2017-05-30

Acute malnutrition is a public health issue worldwide, and particularly in the Eastern region of Burkina Faso. Following a needs assessment, unconditional seasonal, multiannual cash transfers were implemented as a safety net to prevent childhood undernutrition. The objectives of this study were to explore the types of purchases made by beneficiaries of this cash transfer program and to understand the perceived effects of and changes induced by regular cash transfers in the daily lives of women, and at the household and community level. The design of this study was a two-arm cluster randomized controlled trial. Qualitative data were collected each month during the cash transfer period for two years, leading to a total of more than 300 interviews and focus group discussions with various participants: beneficiary mothers, heads of households, mothers-in-law, co-wives, key members of the community, and participants of the control group. The two main types of expenses reported were food and health care for the child and the whole family. The program was also associated with positive perceived changes at the household level, mainly related to gender equality and improvement of women's status, and has promoted an increase in dignity and social integration of the poorest at the community level through cash sharing. Unexpected effects of this program included some women planning new pregnancies and some individuals not expecting the transfers to end. Although the transfers were unconditional, the cash was mainly used to improve the children's and households' food security and health, which correspond to two main underlying causes of undernutrition. Therefore, spending mainly in these areas can help to prevent undernutrition in children. ClinicalTrials.gov , identifier: NCT01866124 , registered May 7, 2013.

Pilot study for a trial of ursodeoxycholic acid and/or early delivery for obstetric cholestasis

PubMed Central

Gurung, Vinita; Williamson, Catherine; Chappell, Lucy; Chambers, Jenny; Briley, Annette; Pipkin, Fiona Broughton; Thornton, Jim

2009-01-01

Background Obstetric cholestasis (OC) is a serious problem in pregnancy. It affects about 4500 women per year in the UK. Affected women develop itching and occasionally jaundice. More importantly, the condition is associated with premature delivery, fetal distress and is believed to be an important cause of stillbirth. However, even now, there is no clear evidence as to whether the most popular treatment, a drug called ursodeoxycholic acid is beneficial to the baby, or even if it is safe in pregnancy. Nor do we know whether planned early delivery of the baby at 37–38 weeks, another popular treatment, does more good than harm. A randomised trial to evaluate both ursodeoxycholic acid and timed delivery is needed but will be complicated and expensive. We plan a preliminary study, Pilot study for a trial of ursodeoxycholic acid and/or early delivery for obstetric cholestasis (Acronym PITCH- Pregnancy Intervention Trial in Cholestasis) trial, to evaluate the feasibility of a larger trial. The trial is funded by the NHS Research for Patient Benefit (RfPB) Programme. Methods PITCH is a multi-centre, double blinded, randomised, controlled, factorial design trial. The trial is being run in six UK centres and women with obstetric cholestasis will be recruited for eighteen months. In this pilot trial we aim to collect data to finalise the design for the main trial. This will include measuring trial recruitment rate, including recruitment to each factorial comparison separately. We will also measure the spectrum of disease among recruits and non-recruits and compliance with the four possible treatment allocations. We will use these data to design the main trial. Discussion The ultimate aim of the main trial is to enable clinicians to manage this condition more effectively. If it transpires that ursodeoxycholic acid and early delivery are both safe and effective then steps will be taken to ensure that all women with OC who could benefit from them receives this treatment. Conversely, if one or both the treatments turn out to be ineffective or even harmful, they will be stopped and researchers will work at developing other modes of treatment. Trial registration number ISRCTN37730443 PMID:19445704

The home as an appropriate setting for women undertaking cervical ripening before the induction of labour.

PubMed

Reid, Margaret; Lorimer, Karen; Norman, Jane E; Bollapragada, Shrikant S; Norrie, John

2011-02-01

to explore women's experiences of cervical ripening using isosorbide mononitrate (IMN) in the home as part of the main randomised controlled trial. qualitative study with semi-structured interviews carried out at three weeks post partum. Interview transcripts were analysed to identify recurrent themes, focusing on why women became involved in the study, their views about both the self-medication and the home setting, and whether they would repeat the experience. the home. twenty women enrolled in the main randomised controlled trial. the study is part of a double-blind randomised controlled trial with 350 patients investigating whether a nitric oxide donor (IMN) used in cervical ripening improves the process of induction of labour. women liked the opportunity to remain at home during the cervical ripening process. Timing and setting were central issues; women hoped that it would hasten labour, while the home was seen as a setting offering freedom, security and reassurance, as opposed to the hospital, seen as constraining. Two women reported problems with IMN but the remainder reported that they would repeat the experience. women were very positive about the opportunity to undertake cervical ripening at home. It is important to explore this setting further for appropriate interventions. Copyright © 2009 Elsevier Ltd. All rights reserved.

The ethics of placebo-controlled trials: a comparison of inert and active placebo controls.

PubMed

Edward, Sarah J L; Stevens, Andrew J; Braunholtz, David A; Lilford, Richard J; Swift, Teresa

2005-05-01

Because of the recent and controversial example of sham surgery for the evaluation of fetal tissue transplants for Parkinson's disease, there is renewed interest in the ethics of using "active" placebos in surgical trials, where otherwise there are no inert procedures available, and in pharmacological trials, where there are inert substances, but where patients may guess to which arm they have been allocated. This paper seeks to clarify the ethical arguments surrounding the use of active placebos in trials, and to set up a notation for assessing the ethics of trials more generally. We first establish an framework by which ethics committees can analyze such trials. We examine (1) the scientific value of the research; (2) the expected risks and benefits to individual patients, and (3) the voluntary nature of consent. We then contrast the implications of this framework for inert and active placebo-controlled trials, respectively. In particular, we analyze their relative expected utility using three main utility factors, namely, treatment effects, placebo effects, and altruism. We conclude that, when the intervention is already widely available, active placebo trials rely more heavily on altruism than do inert placebo trials and, when the intervention is restricted, this excess reliance may not be needed. What our analysis provides is the explicit justification for the apparent caution of Institutional Review Boards or ethics committees when reviewing sham operations, especially when the expected harm is not trivial and the risk of exploitation is high.

Rare cancers: Challenges & issues.

PubMed

Pillai, Raveendran K; Jayasree, K

2017-01-01

Rare cancers account for about 22 per cent of all cancers diagnosed worldwide, disproportionately affecting some demographic groups, with an occurrence of less than 6 per 100,000 individuals annually. Many rare cancers in adults, adolescents and children are not curable, and patients and care providers have little option to take therapeutic decisions. The epidemiology of rare cancers is a challenging area of study but is inadequately addressed. Despite efforts mainly in some European nations, a few improvements have been observed in the management of rare cancers. Reasons for this obvious stagnation are multifactorial and are mainly inherent to logistical difficulties in carrying out clinical trials in very small patient populations, hesitation of the pharmaceutical industry to spend in small markets and complexity in creating adequate information for the development of cost-effective drugs. Rare cancers also face specific challenges that include late and incorrect diagnosis, lack of clinical expertise and lack of research interest and development of new therapies. The utilization of nationally representative study findings for the patients' evaluation may possibly offer chances to find out pathogenesis and prevalence, and this will eventually lead to control and prevention. Currently, advancing targeted therapies offer a great opportunity for the better management of rare cancers. Conducting clinical trials with small patient population, innovative clinical trial approach, prevailing controlling obstacles for international cooperation and financial support for research are the present challenges for rare cancers. The International Rare Cancers Initiative functions as a main platform for achieving new international clinical trials in rare tumours. This review delineates the current challenges and issues in the interpretation, management and research scenarios of rare cancers.

Rare cancers: Challenges & issues

PubMed Central

Pillai, Raveendran K.; Jayasree, K.

2017-01-01

Rare cancers account for about 22 per cent of all cancers diagnosed worldwide, disproportionately affecting some demographic groups, with an occurrence of less than 6 per 100,000 individuals annually. Many rare cancers in adults, adolescents and children are not curable, and patients and care providers have little option to take therapeutic decisions. The epidemiology of rare cancers is a challenging area of study but is inadequately addressed. Despite efforts mainly in some European nations, a few improvements have been observed in the management of rare cancers. Reasons for this obvious stagnation are multifactorial and are mainly inherent to logistical difficulties in carrying out clinical trials in very small patient populations, hesitation of the pharmaceutical industry to spend in small markets and complexity in creating adequate information for the development of cost-effective drugs. Rare cancers also face specific challenges that include late and incorrect diagnosis, lack of clinical expertise and lack of research interest and development of new therapies. The utilization of nationally representative study findings for the patients’ evaluation may possibly offer chances to find out pathogenesis and prevalence, and this will eventually lead to control and prevention. Currently, advancing targeted therapies offer a great opportunity for the better management of rare cancers. Conducting clinical trials with small patient population, innovative clinical trial approach, prevailing controlling obstacles for international cooperation and financial support for research are the present challenges for rare cancers. The International Rare Cancers Initiative functions as a main platform for achieving new international clinical trials in rare tumours. This review delineates the current challenges and issues in the interpretation, management and research scenarios of rare cancers. PMID:28574010

New-generation stents compared with coronary bypass surgery for unprotected left main disease: A word of caution.

PubMed

Benedetto, Umberto; Taggart, David P; Sousa-Uva, Miguel; Biondi-Zoccai, Giuseppe; Di Franco, Antonino; Ohmes, Lucas B; Rahouma, Mohamed; Kamel, Mohamed; Caputo, Massimo; Girardi, Leonard N; Angelini, Gianni D; Gaudino, Mario

2018-05-01

With the advent of bare metal stents and drug-eluting stents, percutaneous coronary intervention has emerged as an alternative to coronary artery bypass grafting surgery for unprotected left main disease. However, whether the evolution of stents technology has translated into better results after percutaneous coronary intervention remains unclear. We aimed to compare coronary artery bypass grafting with stents of different generations for left main disease by performing a Bayesian network meta-analysis of available randomized controlled trials. All randomized controlled trials with at least 1 arm randomized to percutaneous coronary intervention with stents or coronary artery bypass grafting for left main disease were included. Bare metal stents and drug-eluting stents of first- and second-generation were compared with coronary artery bypass grafting. Poisson methods and Bayesian framework were used to compute the head-to-head incidence rate ratio and 95% credible intervals. Primary end points were the composite of death/myocardial infarction/stroke and repeat revascularization. Nine randomized controlled trials were included in the final analysis. Six trials compared percutaneous coronary intervention with coronary artery bypass grafting (n = 4654), and 3 trials compared different types of stents (n = 1360). Follow-up ranged from 6 months to 5 years. Second-generation drug-eluting stents (incidence rate ratio, 1.3; 95% credible interval, 1.1-1.6), but not bare metal stents (incidence rate ratio, 0.63; 95% credible interval, 0.27-1.4), and first-generation drug-eluting stents (incidence rate ratio, 0.85; 95% credible interval, 0.65-1.1) were associated with a significantly increased risk of death/myocardial infarction/stroke when compared with coronary artery bypass grafting. When compared with coronary artery bypass grafting, the highest risk of repeat revascularization was observed for bare metal stents (hazard ratio, 5.1; 95% confidence interval, 2.1-14), whereas first-generation drug-eluting stents (incidence rate ratio, 1.8; 95% confidence interval, 1.4-2.4) and second-generation drug-eluting stents (incidence rate ratio, 1.8; 95% confidence interval, 1.4-2.4) were comparable. The introduction of new-generation drug-eluting stents did not translate into better outcomes for percutaneous coronary intervention when compared with coronary artery bypass grafting. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

A systematic review of randomized clinical trials published in Malaria Journal between 2008 and 2013.

PubMed

Martínez-Alonso, E; Ramos, J M

2016-06-01

Randomized controlled trials (RCT) are a key component in clinical research and they provide the highest quality clinical results. The objective of this study was to describe the main characteristics of RCTs published in Malaria Journal, including research topics, study population and design, funding sources and collaboration between institutions. This may help researchers and funders define future research priorities in this field. A retrospective analysis was performed on the RCTs published in Malaria Journal between January 1, 2008 and December 31, 2013. A key-word search by "Randomized controlled trial" or "Random*" was carried out in PubMed. RCT indexed to MEDLINE were selected for the analysis. A total of 108 published articles containing RCTs were analysed. Treatment of uncomplicated Plasmodium falciparum malaria (n=45, 41.6%), especially the efficacy and safety of antimalarial drugs, and malaria prevention (n=34, 31.5%) were the two main research topics. The majority of trials were conducted in Africa (62.2%) and Asia (27%) and received external funding (private, 42.3% and/or public, 38.6%). Paediatric population was the primary study group (n=63, 58.3%), followed by adults (n=29, 26.9%). Pregnant women (n=7) and geriatric population (n=1) remain underrepresented. Nearly 75% of trials were conducted in individual subjects and 25% in groups of subjects (cluster RCTs). A considerable collaboration between researchers and institutions is noteworthy. RCTs published in Malaria Journal address a wide range of research topics. Paediatric trials conducted in Africa and Asia are frequently performed, and a significant worldwide collaboration to fight against malaria has been identified.

Impact of a web-based tool (WebCONSORT) to improve the reporting of randomised trials: results of a randomised controlled trial.

PubMed

Hopewell, Sally; Boutron, Isabelle; Altman, Douglas G; Barbour, Ginny; Moher, David; Montori, Victor; Schriger, David; Cook, Jonathan; Gerry, Stephen; Omar, Omar; Dutton, Peter; Roberts, Corran; Frangou, Eleni; Clifton, Lei; Chiocchia, Virginia; Rombach, Ines; Wartolowska, Karolina; Ravaud, Philippe

2016-11-28

The CONSORT Statement is an evidence-informed guideline for reporting randomised controlled trials. A number of extensions have been developed that specify additional information to report for more complex trials. The aim of this study was to evaluate the impact of using a simple web-based tool (WebCONSORT, which incorporates a number of different CONSORT extensions) on the completeness of reporting of randomised trials published in biomedical publications. We conducted a parallel group randomised trial. Journals which endorsed the CONSORT Statement (i.e. referred to it in the Instruction to Authors) but do not actively implement it (i.e. require authors to submit a completed CONSORT checklist) were invited to participate. Authors of randomised trials were requested by the editor to use the web-based tool at the manuscript revision stage. Authors registering to use the tool were randomised (centralised computer generated) to WebCONSORT or control. In the WebCONSORT group, they had access to a tool allowing them to combine the different CONSORT extensions relevant to their trial and generate a customised checklist and flow diagram that they must submit to the editor. In the control group, authors had only access to a CONSORT flow diagram generator. Authors, journal editors, and outcome assessors were blinded to the allocation. The primary outcome was the proportion of CONSORT items (main and extensions) reported in each article post revision. A total of 46 journals actively recruited authors into the trial (25 March 2013 to 22 September 2015); 324 author manuscripts were randomised (WebCONSORT n = 166; control n = 158), of which 197 were reports of randomised trials (n = 94; n = 103). Over a third (39%; n = 127) of registered manuscripts were excluded from the analysis, mainly because the reported study was not a randomised trial. Of those included in the analysis, the most common CONSORT extensions selected were non-pharmacologic (n = 43; n = 50), pragmatic (n = 20; n = 16) and cluster (n = 10; n = 9). In a quarter of manuscripts, authors either wrongly selected an extension or failed to select the right extension when registering their manuscript on the WebCONSORT study site. Overall, there was no important difference in the overall mean score between WebCONSORT (mean score 0.51) and control (0.47) in the proportion of CONSORT and CONSORT extension items reported pertaining to a given study (mean difference, 0.04; 95% CI -0.02 to 0.10). This study failed to show a beneficial effect of a customised web-based CONSORT checklist to help authors prepare more complete trial reports. However, the exclusion of a large number of inappropriately registered manuscripts meant we had less precision than anticipated to detect a difference. Better education is needed, earlier in the publication process, for both authors and journal editorial staff on when and how to implement CONSORT and, in particular, CONSORT-related extensions. ClinicalTrials.gov: NCT01891448 [registered 24 May 2013].

A Brief History of Placebos and Clinical Trials in Psychiatry

PubMed Central

Shorter, Edward

2013-01-01

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

Efficacy of group psychotherapy for social anxiety disorder: A meta-analysis of randomized-controlled trials.

PubMed

Barkowski, Sarah; Schwartze, Dominique; Strauss, Bernhard; Burlingame, Gary M; Barth, Jürgen; Rosendahl, Jenny

2016-04-01

Group psychotherapy for social anxiety disorder (SAD) is an established treatment supported by findings from primary studies and earlier meta-analyses. However, a comprehensive summary of the recent evidence is still pending. This meta-analysis investigates the efficacy of group psychotherapy for adult patients with SAD. A literature search identified 36 randomized-controlled trials examining 2171 patients. Available studies used mainly cognitive-behavioral group therapies (CBGT); therefore, quantitative analyses were done for CBGT. Medium to large positive effects emerged for wait list-controlled trials for specific symptomatology: g=0.84, 95% CI [0.72; 0.97] and general psychopathology: g=0.62, 95% CI [0.36; 0.89]. Group psychotherapy was also superior to common factor control conditions in alleviating symptoms of SAD, but not in improving general psychopathology. No differences appeared for direct comparisons of group psychotherapy and individual psychotherapy or pharmacotherapy. Hence, group psychotherapy for SAD is an efficacious treatment, equivalent to other treatment formats. Copyright © 2016 Elsevier Ltd. All rights reserved.

A randomized controlled trial on errorless learning in goal management training: study rationale and protocol

PubMed Central

2013-01-01

Background Many brain-injured patients referred for outpatient rehabilitation have executive deficits, notably difficulties with planning, problem-solving and goal directed behaviour. Goal Management Training (GMT) has proven to be an efficacious cognitive treatment for these problems. GMT entails learning and applying an algorithm, in which daily tasks are subdivided into multiple steps. Main aim of the present study is to examine whether using an errorless learning approach (preventing the occurrence of errors during the acquisition phase of learning) contributes to the efficacy of Goal Management Training in the performance of complex daily tasks. Methods/Design The study is a double blind randomized controlled trial, in which the efficacy of Goal Management Training with an errorless learning approach will be compared with conventional Goal Management Training, based on trial and error learning. In both conditions 32 patients with acquired brain injury of mixed etiology will be examined. Main outcome measure will be the performance on two individually chosen everyday-tasks before and after treatment, using a standardized observation scale and goal attainment scaling. Discussion This is the first study that introduces errorless learning in Goal Management Training. It is expected that the GMT-errorless learning approach will improve the execution of complex daily tasks in brain-injured patients with executive deficits. The study can contribute to a better treatment of executive deficits in cognitive rehabilitation. Trial registration (Dutch Trial Register): http://NTR3567 PMID:23786651

The impact of insecticide-treated school uniforms on dengue infections in school-aged children: study protocol for a randomised controlled trial in Thailand

PubMed Central

2012-01-01

Background There is an urgent need to protect children against dengue since this age group is particularly sensitive to the disease. Since dengue vectors are active mainly during the day, a potential target for control should be schools where children spend a considerable amount of their day. School uniforms are the cultural norm in most developing countries, worn throughout the day. We hypothesise that insecticide-treated school uniforms will reduce the incidence of dengue infection in school-aged children. Our objective is to determine the impact of impregnated school uniforms on dengue incidence. Methods A randomised controlled trial will be conducted in eastern Thailand in a group of schools with approximately 2,000 students aged 7–18 years. Pre-fabricated school uniforms will be commercially treated to ensure consistent, high-quality insecticide impregnation with permethrin. A double-blind, randomised, crossover trial at the school level will cover two dengue transmission seasons. Discussion Practical issues and plans concerning intervention implementation, evaluation, analysing and interpreting the data, and possible policy implications arising from the trial are discussed. Trial registration clinicaltrial.gov. Registration number: NCT01563640 PMID:23153360

Different Patterns of Walking and Postprandial Triglycerides in Older Women

PubMed Central

KASHIWABARA, KYOKO; KIDOKORO, TETSUHIRO; YANAOKA, TAKUMA; BURNS, STEPHEN F.; STENSEL, DAVID J.; MIYASHITA, MASASHI

2018-01-01

ABSTRACT Purpose Although a single bout of continuous exercise (≥30 min) reduces postprandial triglyceride (TG), little evidence is available regarding the effect of multiple short (≤10 min) bouts of exercise on postprandial TG in individuals at increased risk for cardiovascular diseases. This study compared the effects of different patterns of walking on postprandial TG in postmenopausal, older women with hypertriglyceridemia. Methods Twelve inactive women (mean age ± SD, 71 ± 5 yr) with hypertriglyceridemia (fasting TG ≥1.70 mmol·L−1) completed three, 1-d laboratory-based trials in a random order: 1) control, 2) continuous walking, and 3) multiple short bouts of walking. On the control trial, participants sat in a chair for 8 h. For the walking trials, participants walked briskly in either one 30-min bout in the morning (0900–0930 h) or twenty 90-s bouts over 8 h. Except for walking, both exercise trials mimicked the control trial. In each trial, participants consumed a standardized breakfast (0800 h) and lunch (1100 h). Venous blood samples were collected in the fasted state and at 2, 4, 6, and 8 h after breakfast. Results The serum TG incremental area under the curve was 35% and 33% lower on the continuous and multiple short bouts of walking trials than that on the control trial (8.2 ± 3.1 vs 8.5 ± 5.4 vs 12.7 ± 5.8 mmol per 8 h·L−1, respectively; main effect of trial: effect size = 0.459, P = 0.001). Conclusions Accumulating walking in short bouts limits postprandial TG in at-risk, inactive older women with fasting hypertriglyceridemia. PMID:28857839

Efficacy vs effectiveness trial results of an indicated "model" substance abuse program: implications for public health.

PubMed

Hallfors, Denise; Cho, Hyunsan; Sanchez, Victoria; Khatapoush, Shereen; Kim, Hyung Min; Bauer, Daniel

2006-12-01

The US Department of Education requires schools to choose substance abuse and violence prevention programs that meet standards of effectiveness. The Substance Abuse and Mental Health Services Agency certifies "model" programs that meet this standard. We compared findings from a large, multisite effectiveness trial of 1 model program to its efficacy trial findings, upon which the certification was based. 1370 high-risk youths were randomized to experimental or control groups across 9 high schools in 2 large urban school districts. We used intent-to-treat and on-treatment approaches to examine baseline equivalence, attrition, and group differences in outcomes at the end of the program and at a 6-month follow-up. Positive efficacy trial findings were not replicated in the effectiveness trial. All main effects were either null or worse for the experimental than for the control group. These findings suggest that small efficacy trials conducted by developers provide insufficient evidence of effectiveness. Federal agencies and public health scientists must work together to raise the standards of evidence and ensure that data from new trials are incorporated into ongoing assessments of program effects.

Industry sponsorship bias in research findings: a network meta-analysis of LDL cholesterol reduction in randomised trials of statins

PubMed Central

Dias, Sofia; Ades, A E

2014-01-01

Objective To explore the risk of industry sponsorship bias in a systematically identified set of placebo controlled and active comparator trials of statins. Design Systematic review and network meta-analysis. Eligibility Open label and double blind randomised controlled trials comparing one statin with another at any dose or with control (placebo, diet, or usual care) for adults with, or at risk of developing, cardiovascular disease. Only trials that lasted longer than four weeks with more than 50 participants per trial arm were included. Two investigators assessed study eligibility. Data sources Bibliographic databases and reference lists of relevant articles published between 1 January 1985 and 10 March 2013. Data extraction One investigator extracted data and another confirmed accuracy. Main outcome measure Mean absolute change from baseline concentration of low density lipoprotein (LDL) cholesterol. Data synthesis Study level outcomes from randomised trials were combined using random effects network meta-analyses. Results We included 183 randomised controlled trials of statins, 103 of which were two-armed or multi-armed active comparator trials. When all of the existing randomised evidence was synthesised in network meta-analyses, there were clear differences in the LDL cholesterol lowering effects of individual statins at different doses. In general, higher doses resulted in higher reductions in baseline LDL cholesterol levels. Of a total of 146 industry sponsored trials, 64 were placebo controlled (43.8%). The corresponding number for the non-industry sponsored trials was 16 (43.2%). Of the 35 unique comparisons available in 37 non-industry sponsored trials, 31 were also available in industry sponsored trials. There were no systematic differences in magnitude between the LDL cholesterol lowering effects of individual statins observed in industry sponsored versus non-industry sponsored trials. In industry sponsored trials, the mean change from baseline LDL cholesterol level was on average 1.77 mg/dL (95% credible interval −11.12 to 7.66) lower than the change observed in non-industry sponsored trials. There was no detectable inconsistency in the evidence network. Conclusions Our analysis shows that the findings obtained from industry sponsored statin trials seem similar in magnitude as those in non-industry sources. There are actual differences in the effectiveness of individual statins at various doses that explain previously observed discrepancies between industry and non-industry sponsored trials. PMID:25281681

Effectiveness of exercise intervention and health promotion on cardiovascular risk factors in middle-aged men: a protocol of a randomized controlled trial.

PubMed

From, Svetlana; Liira, Helena; Leppävuori, Jenni; Remes-Lyly, Taina; Tikkanen, Heikki; Pitkälä, Kaisu

2013-02-11

Although cardiovascular disease has decreased, there is still potential for prevention as obesity and diabetes increase. Exercise has a positive effect on many cardiovascular risk factors, and it can significantly reduce the components of metabolic syndrome. The main challenge with exercise in primary care is how to succeed in motivating the patients at risk to change and increase their exercise habits. The objective of this study is to modify the cardiovascular risk in middle-aged men, either through a health promotion intervention alone or combined with an exercise intervention. During a two-year period we recruit 300 men aged from 35 to 45 years with elevated cardiovascular risk (> two traditional risk factors). The men are randomized into three arms: 1) a health promotion intervention alone, 2) both health promotion and exercise intervention, or 3) control with usual community care and delayed health promotion (these men receive the intervention after one year). The main outcome measures will be the existence of metabolic syndrome and physical activity frequency (times per week). The participants are assessed at baseline, and at 3, 6, and 12 months. The follow-up of the study will last 12 months. This pragmatic trial in primary health care aimed to assess the effect of a health promotion programme with or without exercise intervention on cardiovascular risk and physical activity in middle-aged men. The results of this study may help to plan the primary care interventions to further reduce cardiovascular mortality.The study was registered at the Controlled Trials ( http://www.controlled-trials.com). ISRCTN80672011. The study received ethics approval from the Coordinating Ethics Committee at Helsinki University Hospital on 8 June 2009 (ref: 4/13/03/00/09).

Dry needling in a manual physiotherapy and therapeutic exercise protocol for patients with chronic mechanical shoulder pain of unspecific origin: a protocol for a randomized control trial.

PubMed

Tejera-Falcón, Emma; Toledo-Martel, Nuria Del Carmen; Sosa-Medina, Francisco Manuel; Santana-González, Fátima; Quintana-de la Fe, Miriam Del Pino; Gallego-Izquierdo, Tomás; Pecos-Martín, Daniel

2017-09-18

Shoulder pain of musculoskeletal origin is the main cause of upper limb pain of non-traumatic origin. Despite being one of the most common reasons for consultation, there is no established protocol for treatment due to the complexity of its etiology. However, it has been shown that the presence of myofascial trigger points on the shoulder muscles is a common condition associated with patients suffering from shoulder pain. This protocol has been created which describes the design of a randomized controlled trial to evaluate the effectiveness of the inclusion of dry needling (DN) within a protocol of manual physiotherapy and therapeutic exercise in the treatment of chronic shoulder pain of unspecific origin. Thirty-six participants aged 18-65 years will be recruited having mechanical chronic shoulder pain on unspecific origin and meeting the inclusion criteria. These will be randomized to one of two interventions, (i) DN, manual physiotherapy and therapeutic exercise or (ii) sham DN, manual physiotherapy and therapeutic exercise. The protocol will cover 6 weeks of treatment, with a 6-month follow-up. Our main outcome measure will be the Visual Analogue Scale for pain. This is the first study to combine the use of DN, manual physiotherapy and an exercise program with a 6-month follow-up, thus becoming a new contribution to the treatment of chronic shoulder pain, while new lines of research may be established to help determine the effects of DN on chronic shoulder pain and the frequency and proper dosage. International Standard Randomized Controlled Trial Number Register: ISRCTN30604244 ( http://www.controlled-trials.com ) 29 June 2016.

Appetite, appetite hormone and energy intake responses to two consecutive days of aerobic exercise in healthy young men.

PubMed

Douglas, Jessica A; King, James A; McFarlane, Ewan; Baker, Luke; Bradley, Chloe; Crouch, Nicole; Hill, David; Stensel, David J

2015-09-01

Single bouts of exercise do not cause compensatory changes in appetite, food intake or appetite regulatory hormones on the day that exercise is performed. It remains possible that such changes occur over an extended period or in response to a higher level of energy expenditure. This study sought to test this possibility by examining appetite, food intake and appetite regulatory hormones (acylated ghrelin, total peptide-YY, leptin and insulin) over two days, with acute bouts of exercise performed on each morning. Within a controlled laboratory setting, 15 healthy males completed two, 2-day long (09:00-16:00) experimental trials (exercise and control) in a randomised order. On the exercise trial participants performed 60 min of continuous moderate-high intensity treadmill running (day one: 70.1 ± 2.5% VO2peak, day two: 70.0 ± 3.2% VO2max (mean ± SD)) at the beginning of days one and two. Across each day appetite perceptions were assessed using visual analogue scales and appetite regulatory hormones were measured from venous blood samples. Ad libitum energy and macronutrient intakes were determined from meals provided two and six hours into each day and from a snack bag provided in-between trial days. Exercise elicited a high level of energy expenditure (total = 7566 ± 635 kJ across the two days) but did not produce compensatory changes in appetite or energy intake over two days (control: 29,217 ± 4006 kJ; exercise: 28,532 ± 3899 kJ, P > 0.050). Two-way repeated measures ANOVA did not reveal any main effects for acylated ghrelin or leptin (all P > 0.050). However a significant main effect of trial (P = 0.029) for PYY indicated higher concentrations on the exercise vs. control trial. These findings suggest that across a two day period, high volume exercise does not stimulate compensatory appetite regulatory changes. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effectiveness of exercise intervention and health promotion on cardiovascular risk factors in middle-aged men: a protocol of a randomized controlled trial

PubMed Central

2013-01-01

Background Although cardiovascular disease has decreased, there is still potential for prevention as obesity and diabetes increase. Exercise has a positive effect on many cardiovascular risk factors, and it can significantly reduce the components of metabolic syndrome. The main challenge with exercise in primary care is how to succeed in motivating the patients at risk to change and increase their exercise habits. The objective of this study is to modify the cardiovascular risk in middle-aged men, either through a health promotion intervention alone or combined with an exercise intervention. Methods/design During a two-year period we recruit 300 men aged from 35 to 45 years with elevated cardiovascular risk (> two traditional risk factors). The men are randomized into three arms: 1) a health promotion intervention alone, 2) both health promotion and exercise intervention, or 3) control with usual community care and delayed health promotion (these men receive the intervention after one year). The main outcome measures will be the existence of metabolic syndrome and physical activity frequency (times per week). The participants are assessed at baseline, and at 3, 6, and 12 months. The follow-up of the study will last 12 months. Discussion This pragmatic trial in primary health care aimed to assess the effect of a health promotion programme with or without exercise intervention on cardiovascular risk and physical activity in middle-aged men. The results of this study may help to plan the primary care interventions to further reduce cardiovascular mortality. The study was registered at the Controlled Trials ( http://www.controlled-trials.com). Trial number: ISRCTN80672011. The study received ethics approval from the Coordinating Ethics Committee at Helsinki University Hospital on 8 June 2009 (ref: 4/13/03/00/09). PMID:23398957

Aerial Prefeeding Followed by Ground Based Toxic Baiting for More Efficient and Acceptable Poisoning of Invasive Small Mammalian Pests

PubMed Central

Morgan, David; Warburton, Bruce; Nugent, Graham

2015-01-01

Introduced brushtail possums (Trichosurus vulpecula) and rat species (Rattus spp.) are major vertebrate pests in New Zealand, with impacts on conservation and agriculture being managed largely through poisoning operations. Aerial distribution of baits containing sodium fluoroacetate (1080) has been refined to maximise cost effectiveness and minimise environmental impact, but this method is strongly opposed by some as it is perceived as being indiscriminate. Although ground based control enables precise placement of baits, operations are often more than twice as costly as aerial control, mainly due to the high labour costs. We investigated a new approach to ground based control that combined aerial distribution of non-toxic ‘prefeed’ baits followed by sparse distribution of toxic baits at regular intervals along the GPS tracked prefeeding flight paths. This approach was tested in two field trials in which both 1080 baits and cholecalciferol baits were used in separate areas. Effectiveness of the approach, assessed primarily using ‘chewcards’, was compared with that of scheduled aerial 1080 operations that were conducted in outlying areas of both trials. Contractors carrying out ground based control were able to follow the GPS tracks of aerial prefeeding flight lines very accurately, and with 1080 baits achieved very high levels of kill of possums and rats similar to those achieved by aerial 1080 baiting. Cholecalciferol was less effective in the first trial, but by doubling the amount of cholecalciferol bait used in the second trial, few possums or rats survived. By measuring the time taken to complete ground baiting from GPS tracks, we predicted that the method (using 1080 baits) would be similarly cost effective to aerial 1080 operations for controlling possums and rats, and considerably less expensive than typical current costs of ground based control. The main limitations to the use of the method will be access to, and size of, the operational site, along with topography and vegetation density. PMID:26218095

Combining long-lasting insecticidal nets and indoor residual spraying for malaria prevention in Ethiopia: study protocol for a cluster randomized controlled trial.

PubMed

Deressa, Wakgari; Loha, Eskindir; Balkew, Meshesha; Hailu, Alemayehu; Gari, Taye; Kenea, Oljira; Overgaard, Hans J; Gebremichael, Teshome; Robberstad, Bjarne; Lindtjørn, Bernt

2016-01-12

Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the main malaria prevention interventions in Ethiopia. There is conflicting evidence that the combined application of both interventions is better than either LLINs or IRS used alone. This trial aims to investigate whether the combination of LLINs (PermaNet 2.0, Vestergaard Frandsen, Lausanne, Switzerland) with IRS using propoxur will enhance the protective benefits and cost-effectiveness of the interventions against malaria and its effect on mosquito behavior, as compared to each intervention alone. This 2 x 2 factorial cluster randomized controlled trial is being carried out in the Adami Tullu district in south-central Ethiopia for about 116 weeks from September 2014 to December 2016. The trial is based on four arms: LLINs + IRS, LLINs alone, IRS alone and control. Villages (or clusters) will be the unit of randomization. The sample size includes 44 clusters per arm, with each cluster comprised of approximately 35 households (about 175 people). Prior to intervention, all households in the LLINs + IRS and LLINs alone arms will be provided with LLINs free of charge. Households in the LLINs + IRS and IRS alone arms will be sprayed with carbamate propoxur once a year just before the main malaria transmission season throughout the investigation. The primary outcome of this trial will be a malaria incidence based on the results of the rapid diagnostic tests in patients with a fever or history of fever attending health posts by passive case detection. Community-based surveys will be conducted each year to assess anemia among children 5-59 months old. In addition, community-based malaria prevalence surveys will be conducted each year on a representative sample of households during the main transmission season. The cost-effectiveness of the interventions and entomological studies will be simultaneously conducted. Analysis will be based on an intention-to-treat principle. This trial aims to provide evidence on the combined use of LLINs and IRS for malaria prevention by answering the following research questions: Can the combined use of LLINs and IRS significantly reduce the incidence of malaria compared with the use of either LLINs or IRS alone? And is the reduced incidence justifiable compared to the added costs? Will the combined use of LLINs and IRS reduce vector density, infection, longevity and the entomological inoculation rate? These data are crucial in order to maximize the impact of vector control interventions on the morbidity and mortality of malaria. PACTR201411000882128 (8 September 2014).

Complementary and alternative medicine for the treatment of type 2 diabetes

PubMed Central

Nahas, Richard; Moher, Matthew

2009-01-01

ABSTRACT OBJECTIVE To review clinical evidence supporting complementary and alternative medicine interventions for improving glycemic control in type 2 diabetes mellitus. QUALITY OF EVIDENCE MEDLINE and EMBASE were searched from January 1966 to August 2008 using the term type 2 diabetes in combination with each of the following terms for specific therapies selected by the authors: cinnamon, fenugreek, gymnema, green tea, fibre, momordica, chromium, and vanadium. Only human clinical trials were selected for review. MAIN MESSAGE Chromium reduced glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels in a large meta-analysis. Gymnema sylvestre reduced HbA1c levels in 2 small open-label trials. Cinnamon improved FBG but its effects on HbA1c are unknown. Bitter melon had no effect in 2 small trials. Fibre had no consistent effect on HbA1c or FBG in 12 small trials. Green tea reduced FBG levels in 1 of 3 small trials. Fenugreek reduced FBG in 1 of 3 small trials. Vanadium reduced FBG in small, uncontrolled trials. There were no trials evaluating microvascular or macrovascular complications or other clinical end points. CONCLUSION Chromium, and possibly gymnema, appears to improve glycemic control. Fibre, green tea, and fenugreek have other benefits but there is little evidence that they substantially improve glycemic control. Further research on bitter melon and cinnamon is warranted. There is no complementary and alternative medicine research addressing microvascular or macrovascular clinical outcomes. PMID:19509199

Current randomized control trials, observational studies and meta analysis in off-pump coronary surgery.

PubMed

Parissis, Haralabos; Lau, Man Chi; Parissis, Mondrian; Lampridis, Savvas; Graham, Victoria; Al-Saudi, Reza; Mhandu, Peter

2015-12-17

The off-pump literature is divided into three eras: the "early phase" with results favouring off-pump surgery supported with randomized control trials (RCTs) mainly from Bristol, UK; an "intermediate phase" dominated by the results of the ROOBY trial and finally a more "contemporary phase" whereby the off/on-pump argument is unsettled. Although the literature has failed to project an overall superiority of off-pump versus on-pump surgery, nevertheless, small randomized control trials and large meta-analysis studies are concluding that the incidence of a stroke is less than 1 % when an aortic off-pump techniques (especially the non-touch technique) are advocated in patients with diseased ascending aorta. Furthermore, off-pump combined with hybrid procedures may lead to a reduction of adverse outcome in the aged high-risk population with concomitant poor left ventricular function and co-morbidities.The current review attempts to bring an insight onto the last ten years knowledge on the on/off-pump debate, with an aim to draw some clear conclusions in order to allow practitioners to reflect on the subject.

The impact of insecticide-treated school uniforms on dengue infections in school-aged children: study protocol for a randomised controlled trial in Thailand.

PubMed

Wilder-Smith, Annelies; Byass, Peter; Olanratmanee, Phanthip; Maskhao, Pongsri; Sringernyuang, Luechai; Logan, James G; Lindsay, Steve W; Banks, Sarah; Gubler, Duane; Louis, Valérie R; Tozan, Yesim; Kittayapong, Pattamaporn

2012-11-15

There is an urgent need to protect children against dengue since this age group is particularly sensitive to the disease. Since dengue vectors are active mainly during the day, a potential target for control should be schools where children spend a considerable amount of their day. School uniforms are the cultural norm in most developing countries, worn throughout the day. We hypothesise that insecticide-treated school uniforms will reduce the incidence of dengue infection in school-aged children. Our objective is to determine the impact of impregnated school uniforms on dengue incidence. A randomised controlled trial will be conducted in eastern Thailand in a group of schools with approximately 2,000 students aged 7-18 years. Pre-fabricated school uniforms will be commercially treated to ensure consistent, high-quality insecticide impregnation with permethrin. A double-blind, randomised, crossover trial at the school level will cover two dengue transmission seasons. Practical issues and plans concerning intervention implementation, evaluation, analysing and interpreting the data, and possible policy implications arising from the trial are discussed. clinicaltrial.gov. NCT01563640.

The NAtional randomised controlled Trial of Tonsillectomy IN Adults (NATTINA): a clinical and cost-effectiveness study: study protocol for a randomised control trial.

PubMed

Rubie, Isabel; Haighton, Catherine; O'Hara, James; Rousseau, Nikki; Steen, Nick; Stocken, Deborah D; Sullivan, Frank; Vale, Luke; Wilkes, Scott; Wilson, Janet

2015-06-06

The role of tonsillectomy in the management of adult tonsillitis remains uncertain and UK regional variation in tonsillectomy rates persists. Patients, doctors and health policy makers wish to know the costs and benefits of tonsillectomy against conservative management and whether therapy can be better targeted to maximise benefits and minimise risks of surgery, hence maximising cost-effective use of resources. NATTINA incorporates the first attempt to map current NHS referral criteria against other metrics of tonsil disease severity. A UK multi-centre, randomised, controlled trial for adults with recurrent tonsillitis to compare the clinical and cost-effectiveness of tonsillectomy versus conservative management. An initial feasibility study comprises qualitative interviews to investigate the practicality of the protocol, including willingness to randomise and be randomised. Approximately 20 otolaryngology staff, 10 GPs and 15 ENT patients will be recruited over 5 months in all 9 proposed main trial participating sites. A 6-month internal pilot will then recruit 72 patients across 6 of the 9 sites. Participants will be adults with recurrent acute tonsillitis referred by a GP to secondary care. Randomisation between tonsillectomy and conservative management will be according to a blocked allocation method in a 1:1 ratio stratified by centre and baseline disease severity. If the pilot is successful, the main trial will recruit a further 528 patients over 18 months in all 9 participating sites. All participants will be followed up for a total of 24 months, throughout which both primary and secondary outcome data will be collected. The primary outcome is the number of sore throat days experienced over the 24-month follow-up. The pilot and main trials include an embedded qualitative process evaluation. NATTINA is designed to evaluate the relative effectiveness and efficiency of tonsillectomy versus conservative management in patients with recurrent sore throat who are eligible for surgery. Most adult tonsil disease and surgery has an impact on economically active age groups, with individual and societal costs through loss of earnings and productivity. Avoidance of unnecessary operations and prioritisation of those individuals likely to gain most from tonsillectomy would reduce costs to the NHS and society. ISRCTN55284102, Date of Registration: 4 August 2014.

Recruitment of older adults to three preventative lifestyle improvement studies.

PubMed

Chatters, Robin; Newbould, Louise; Sprange, Kirsty; Hind, Daniel; Mountain, Gail; Shortland, Katy; Powell, Lauren; Gossage-Worrall, Rebecca; Chater, Tim; Keetharuth, Anju; Lee, Ellen; Woods, Bob

2018-02-20

Recruiting isolated older adults to clinical trials is complex, time-consuming and difficult. Previous studies have suggested querying existing databases to identify appropriate potential participants. We aim to compare recruitment techniques (general practitioner (GP) mail-outs, community engagement and clinician referrals) used in three randomised controlled trial (RCT) studies assessing the feasibility or effectiveness of two preventative interventions in isolated older adults (the Lifestyle Matters and Putting Life In Years interventions). During the three studies (the Lifestyle Matters feasibility study, the Lifestyle Matters RCT, the Putting Life In Years RCT) data were collected about how participants were recruited. The number of letters sent by GP surgeries for each study was recorded. In the Lifestyle Matters RCT, we qualitatively interviewed participants and intervention facilitators at 6 months post randomisation to seek their thoughts on the recruitment process. Referrals were planned to be the main source of recruitment in the Lifestyle Matters feasibility study, but due to a lack of engagement from district nurses, community engagement was the main source of recruitment. District nurse referrals and community engagement were also utilised in the Lifestyle Matters and Putting Life In Years RCTs; both mechanisms yielded few participants. GP mail-outs were the main source of recruitment in both the RCTs, but of those contacted, recruiting yield was low (< 3%). Facilitators of the Lifestyle Matters intervention questioned whether the most appropriate individuals had been recruited. Participants recommended that direct contact with health professionals would be the most beneficial way to recruit. Recruitment to the Lifestyle Matters RCT did not mirror recruitment to the feasibility study of the same intervention. Direct district nurse referrals were not effective at recruiting participants. The majority of participants were recruited via GP mail-outs, which may have led to isolated individuals not being recruited to the trials. Further research is required into alternative recruitment techniques, including respondent-driven sampling plus mechanisms which will promote health care professionals to recruit vulnerable populations to research. International Standard Randomised Controlled Trial Registry, ID: ISRCTN28645428 (Putting Life In Years RCT). Registered on 11 April 2012; International Standard Randomised Controlled Trial Registry, ID: ISRCTN67209155 (Lifestyle Matters RCT). Registered on 22 March 2012; ClinicalTrials.gov , ID: NCT03054311 (Lifestyle Matters feasibility study). Registered retrospectively on 19 January 2017.

Randomised factorial mixed method pilot study of aerobic and resistance exercise in haemodialysis patients: DIALY-SIZE!

PubMed Central

Thompson, Stephanie; Klarenbach, Scott; Molzahn, Anita; Lloyd, Anita; Gabrys, Iwona; Haykowsky, Mark; Tonelli, Marcello

2016-01-01

Objectives For people with end-stage renal disease requiring haemodialysis, exercise can improve aspects of quality of life (QoL). However, the relative benefits and risks of different types of exercise in this population are unknown. Therefore, this pilot study aimed to evaluate the feasibility of a main study evaluating the efficacy of cycling and resistance exercise each performed during the haemodialysis treatment on QoL. Methods In this factorial (2×2) pilot trial, 31 haemodialysis patients were randomised to cycling, resistance, cycling and resistance, or an attention control. Feasibility was defined a priori by criteria on recruitment, fidelity to the protocol and patient response to the intervention. To better understand feasibility, we conducted interviews with dialysis unit staff and trial participants. As secondary outcomes, we estimated the main effect of cycling and weights each compared with control on QoL, physical function and strength. Findings We exceeded the target accrual of 28 participants over 12 weeks. Irrespective of exercise group allocation, adherence was high; of the 1038 training sessions offered, 87% were initiated and over 80% of exercise sessions were performed as per protocol. Progression based on perceived exertion, individual instruction and interactions with the kinesiologist facilitated acceptability across exercise groups. Using an attention control, measures of contamination and attrition were low. Important barriers to unit staff readiness for the intervention were initial safety and workflow concerns, unit workload and onerous data collection. Secondary outcomes were not statistically significant. Adverse events were low and did not increase with a higher volume of exercise. Conclusions The main study is feasible with minor modifications. In addition to practical assistance, involvement from unit staff could increase patient participation and improve trial implementation. Strategies to increase acceptability of the intervention for staff include improving workflow integration and using a prestudy demonstration phase to introduce the intervention. Trial registration number NCT02234232. Results PMID:27601500

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

PubMed

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

2013-12-17

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

Internet trials: participant experiences and perspectives.

PubMed

Mathieu, Erin; Barratt, Alexandra; Carter, Stacy M; Jamtvedt, Gro

2012-10-23

Use of the Internet to conduct randomised controlled trials is increasing, and provides potential to increase equity of access to medical research, increase the generalisability of trial results and decrease the costs involved in conducting large scale trials. Several studies have compared response rates, completeness of data, and reliability of surveys using the Internet and traditional methods, but very little is known about participants' attitudes towards Internet-based randomised trials or their experience of participating in an Internet-based trial. To obtain insights into the experiences and perspectives of participants in an Internet-based randomised controlled trial, their attitudes to the use of the Internet to conduct medical research, and their intentions regarding future participation in Internet research. All English speaking participants in a recently completed Internet randomised controlled trial were invited to participate in an online survey. 1246 invitations were emailed. 416 participants completed the survey between May and October 2009 (33% response rate). Reasons given for participating in the Internet RCT fell into 4 main areas: personal interest in the research question and outcome, ease of participation, an appreciation of the importance of research and altruistic reasons. Participants' comments and reflections on their experience of participating in a fully online trial were positive and less than half of participants would have participated in the trial had it been conducted using other means of data collection. However participants identified trade-offs between the benefits and downsides of participating in Internet-based trials. The main trade-off was between flexibility and convenience - a perceived benefit - and a lack connectedness and understanding - a perceived disadvantage. The other tradeoffs were in the areas of: ease or difficulty in use of the Internet; security, privacy and confidentiality issues; perceived benefits and disadvantages for researchers; technical aspects of using the Internet; and the impact of Internet data collection on information quality. Overall, more advantages were noted by participants, consistent with their preference for this mode of research over others. The majority of participants (69%) would prefer to participate in Internet-based research compared to other modes of data collection in the future. Participants in our survey would prefer to participate in Internet-based trials in the future compared to other ways of conducting trials. From the participants' perspective, participating in Internet-based trials involves trade-offs. The central trade-off is between flexibility and convenience - a perceived benefit - and lack of connectedness and understanding - a perceived disadvantage. Strategies to maintain the convenience of the Internet while increasing opportunities for participants to feel supported, well-informed and well-understood would seem likely to increase the acceptability of Internet-based trials.

Internet trials: participant experiences and perspectives

PubMed Central

2012-01-01

Background Use of the Internet to conduct randomised controlled trials is increasing, and provides potential to increase equity of access to medical research, increase the generalisability of trial results and decrease the costs involved in conducting large scale trials. Several studies have compared response rates, completeness of data, and reliability of surveys using the Internet and traditional methods, but very little is known about participants’ attitudes towards Internet-based randomised trials or their experience of participating in an Internet-based trial. Objective To obtain insights into the experiences and perspectives of participants in an Internet-based randomised controlled trial, their attitudes to the use of the Internet to conduct medical research, and their intentions regarding future participation in Internet research. Methods All English speaking participants in a recently completed Internet randomised controlled trial were invited to participate in an online survey. Results 1246 invitations were emailed. 416 participants completed the survey between May and October 2009 (33% response rate). Reasons given for participating in the Internet RCT fell into 4 main areas: personal interest in the research question and outcome, ease of participation, an appreciation of the importance of research and altruistic reasons. Participants’ comments and reflections on their experience of participating in a fully online trial were positive and less than half of participants would have participated in the trial had it been conducted using other means of data collection. However participants identified trade-offs between the benefits and downsides of participating in Internet-based trials. The main trade-off was between flexibility and convenience – a perceived benefit – and a lack connectedness and understanding – a perceived disadvantage. The other tradeoffs were in the areas of: ease or difficulty in use of the Internet; security, privacy and confidentiality issues; perceived benefits and disadvantages for researchers; technical aspects of using the Internet; and the impact of Internet data collection on information quality. Overall, more advantages were noted by participants, consistent with their preference for this mode of research over others. The majority of participants (69%) would prefer to participate in Internet-based research compared to other modes of data collection in the future. Conclusion Participants in our survey would prefer to participate in Internet-based trials in the future compared to other ways of conducting trials. From the participants’ perspective, participating in Internet-based trials involves trade-offs. The central trade-off is between flexibility and convenience – a perceived benefit – and lack of connectedness and understanding – a perceived disadvantage. Strategies to maintain the convenience of the Internet while increasing opportunities for participants to feel supported, well-informed and well-understood would seem likely to increase the acceptability of Internet-based trials. PMID:23092116

Telehealthcare for chronic obstructive pulmonary disease: Cochrane Review and meta-analysis

PubMed Central

McLean, Susannah; Nurmatov, Ulugbek; Liu, Joseph LY; Pagliari, Claudia; Car, Josip; Sheikh, Aziz

2012-01-01

Background Chronic obstructive pulmonary disease (COPD) is common. Telehealthcare, involving personalised health care over a distance, is seen as having the potential to improve care for people with COPD. Aim To systematically review the effectiveness of telehealthcare interventions in COPD to improve clinical and process outcomes. Design and setting Cochrane Systematic Review of randomised controlled trials. Methods The study involved searching the Cochrane Airways Group Register of Trials, which is derived from the Cochrane Central Register of Controlled Trials, MEDLINE®, embase™, and CINAHL®, as well as searching registers of ongoing and unpublished trials. Randomised controlled trials comparing a telehealthcare intervention with a control intervention in people with a clinical diagnosis of COPD were identified. The main outcomes of interest were quality of life and risk of emergency department visit, hospitalisation, and death. Two authors independently selected trials for inclusion and extracted data. Study quality was assessed using the Cochrane Collaboration’s risk of bias method. Meta-analysis was undertaken using fixed effect and/or random effects modelling. Results Ten randomised controlled trials were included. Telehealthcare did not improve COPD quality of life: mean difference –6.57 (95% confidence interval [CI] = –13.62 to 0.48). However, there was a significant reduction in the odds ratios (ORs) of emergency department attendance (OR = 0.27; 95% CI = 0.11 to 0.66) and hospitalisation (OR = 0.46; 95% CI = 0.33 to 0.65). There was a non-significant change in the OR of death (OR = 1.05; 95% CI = 0.63 to 1.75). Conclusion In COPD, telehealthcare interventions can significantly reduce the risk of emergency department attendance and hospitalisation, but has little effect on the risk of death. PMID:23211177

[Mirror therapy in hemiplegic patient].

PubMed

Lisalde-Rodríguez, María Elena; Garcia-Fernández, José Antonio

2016-01-01

Mirror therapy is a relatively new intervention, every time more used and with easy access for the rehabilitation treatment of stroke patient. The patient moves the unaffected limb in front of a mirror watching the reflection of that move as if he was moving de affected limb. To analyze the effectiveness of mirror therapy in the sensorimotor function, hemineglect and activities of daily living of stroke patients. We defined a strategy of bibliography search in Medline, EMBASE, PEDro y Cochrane Central Register of Controlled Trials (CENTRAL) looking for randomised controlled trials (RCT) conducted with hemiplegic patients considering mirror therapy as the main rehabilitation intervention. Seven trials met the inclusion criteria with medium-high methodological quality. Most of them evaluate the mirror therapy effect on motor outcomes showing significant improvements. Three of this RCTs evaluate the effect of mirror therapy on the hemineglect with positive result. A combination of mirror therapy with conventional rehabilitation obtained significant improvements mainly in motor function but not that much on sensory function and functional performance. About the effect of mirror therapy on hemineglect, there are significant improvements but supported only with a few RCTs with small sample sizes producing promising but inconclusive results.

Differentiating closed-loop cortical intention from rest: building an asynchronous electrocorticographic BCI

NASA Astrophysics Data System (ADS)

Williams, Jordan J.; Rouse, Adam G.; Thongpang, Sanitta; Williams, Justin C.; Moran, Daniel W.

2013-08-01

Objective. Recent experiments have shown that electrocorticography (ECoG) can provide robust control signals for a brain-computer interface (BCI). Strategies that attempt to adapt a BCI control algorithm by learning from past trials often assume that the subject is attending to each training trial. Likewise, automatic disabling of movement control would be desirable during resting periods when random brain fluctuations might cause unintended movements of a device. To this end, our goal was to identify ECoG differences that arise between periods of active BCI use and rest. Approach. We examined spectral differences in multi-channel, epidural micro-ECoG signals recorded from non-human primates when rest periods were interleaved between blocks of an active BCI control task. Main Results. Post-hoc analyses demonstrated that these states can be decoded accurately on both a trial-by-trial and real-time basis, and this discriminability remains robust over a period of weeks. In addition, high gamma frequencies showed greater modulation with desired movement direction, while lower frequency components demonstrated greater amplitude differences between task and rest periods, suggesting possible specialized BCI roles for these frequencies. Significance. The results presented here provide valuable insight into the neurophysiology of BCI control as well as important considerations toward the design of an asynchronous BCI system.

The association of funding source on effect size in randomized controlled trials: 2013-2015 - a cross-sectional survey and meta-analysis.

PubMed

Falk Delgado, Alberto; Falk Delgado, Anna

2017-03-14

Trials financed by for-profit organizations have been associated with favorable outcomes of new treatments, although the effect size of funding source impact on outcome is unknown. The aim of this study was to estimate the effect size for a favorable outcome in randomized controlled trials (RCTs), stratified by funding source, that have been published in general medical journals. Parallel-group RCTs published in The Lancet, New England Journal of Medicine, and JAMA between 2013 and 2015 were identified. RCTs with binary primary endpoints were included. The primary outcome was the OR of patients' having a favorable outcome in the intervention group compared with the control group. The OR of a favorable outcome in each trial was calculated by the number of positive events that occurred in the intervention and control groups. A meta-analytic technique with random effects model was used to calculate summary OR. Data were stratified by funding source as for-profit, mixed, and nonprofit. Prespecified sensitivity, subgroup, and metaregression analyses were performed. Five hundred nine trials were included. The OR for a favorable outcome in for-profit-funded RCTs was 1.92 (95% CI 1.72-2.14), which was higher than mixed source-funded RCTs (OR 1.34, 95% CI 1.25-1.43) and nonprofit-funded RCTs (OR 1.32, 95% CI 1.26-1.39). The OR for a favorable outcome was higher for both clinical and surrogate endpoints in for-profit-funded trials than in RCTs with other funding sources. Excluding drug trials lowered the OR for a favorable outcome in for-profit-funded RCTs. The OR for a favorable surrogate outcome in drug trials was higher in for-profit-funded trials than in nonprofit-funded trials. For-profit-funded RCTs have a higher OR for a favorable outcome than nonprofit- and mixed source-funded RCTs. This difference is associated mainly with the use of surrogate endpoints in for-profit-financed drug trials.

Randomized Trial of a Web-Based Intervention to Address Barriers to Clinical Trials.

PubMed

Meropol, Neal J; Wong, Yu-Ning; Albrecht, Terrance; Manne, Sharon; Miller, Suzanne M; Flamm, Anne Lederman; Benson, Al Bowen; Buzaglo, Joanne; Collins, Michael; Egleston, Brian; Fleisher, Linda; Katz, Michael; Kinzy, Tyler G; Liu, Tasnuva M; Margevicius, Seunghee; Miller, Dawn M; Poole, David; Roach, Nancy; Ross, Eric; Schluchter, Mark D

2016-02-10

Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option. A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient's barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials. Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone. These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was more effective than NCI text in improving knowledge and reducing attitudinal barriers. © 2015 by American Society of Clinical Oncology.

Interventions for preventing and treating hyperthyroidism in pregnancy

PubMed Central

Earl, Rachel; Crowther, Caroline A; Middleton, Philippa

2014-01-01

Background Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption. Objectives To assess the effects of interventions for preventing or treating hyperthyroidism in pregnant women. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 July 2010). Selection criteria We intended to include randomised controlled trials comparing antithyroid treatments in pregnant women with hyperthyroidism. Data collection and analysis Two review authors would have assessed trial eligibility and risk of bias, and extracted data. Main results No trials were located. Authors’ conclusions As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid drugs for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil. PMID:20824882

CONSORT item reporting quality in the top ten ranked journals of critical care medicine in 2011: a retrospective analysis.

PubMed

Stevanovic, Ana; Schmitz, Sabine; Rossaint, Rolf; Schürholz, Tobias; Coburn, Mark

2015-01-01

Reporting randomised controlled trials is a key element in order to disseminate research findings. The CONSORT statement was introduced to improve the reporting quality. We assessed the adherence to the CONSORT statement of randomised controlled trials published 2011 in the top ten ranked journals of critical care medicine (ISI Web of Knowledge 2011, Thomson Reuters, London UK). Design. We performed a retrospective cross sectional data analysis. Setting. This study was executed at the University Hospital of RWTH, Aachen. Participants. We selected the following top ten listed journals according to ISI Web of Knowledge (Thomson Reuters, London, UK) critical care medicine ranking in the year 2011: American Journal of Respiratory and Critical Care Medicine, Critical Care Medicine, Intensive Care Medicine, CHEST, Critical Care, Journal of Neurotrauma, Resuscitation, Pediatric Critical Care Medicine, Shock and Minerva Anestesiologica. Main outcome measures. We screened the online table of contents of each included journal, to identify the randomised controlled trials. The adherence to the items of the CONSORT Checklist in each trial was evaluated. Additionally we correlated the citation frequency of the articles and the impact factor of the respective journal with the amount of reported items per trial. We analysed 119 randomised controlled trials and found, 15 years after the implementation of the CONSORT statement, that a median of 61,1% of the checklist-items were reported. Only 55.5% of the articles were identified as randomised trials in their titles. The citation frequency of the trials correlated significantly (rs = 0,433; p<0,001 and r = 0,331; p<0,001) to the CONSORT statement adherence. The impact factor showed also a significant correlation to the CONSORT adherence (r = 0,386; p<0,001). The reporting quality of randomised controlled trials in the field of critical care medicine remains poor and needs considerable improvement.

Randomised controlled feasibility trial of a web-based weight management intervention with nurse support for obese patients in primary care

PubMed Central

2014-01-01

Background There is a need for cost-effective weight management interventions that primary care can deliver to reduce the morbidity caused by obesity. Automated web-based interventions might provide a solution, but evidence suggests that they may be ineffective without additional human support. The main aim of this study was to carry out a feasibility trial of a web-based weight management intervention in primary care, comparing different levels of nurse support, to determine the optimal combination of web-based and personal support to be tested in a full trial. Methods This was an individually randomised four arm parallel non-blinded trial, recruiting obese patients in primary care. Following online registration, patients were randomly allocated by the automated intervention to either usual care, the web-based intervention only, or the web-based intervention with either basic nurse support (3 sessions in 3 months) or regular nurse support (7 sessions in 6 months). The main outcome measure (intended as the primary outcome for the main trial) was weight loss in kg at 12 months. As this was a feasibility trial no statistical analyses were carried out, but we present means, confidence intervals and effect sizes for weight loss in each group, uptake and retention, and completion of intervention components and outcome measures. Results All randomised patients were included in the weight loss analyses (using Last Observation Carried Forward). At 12 months mean weight loss was: usual care group (n = 43) 2.44 kg; web-based only group (n = 45) 2.30 kg; basic nurse support group (n = 44) 4.31 kg; regular nurse support group (n = 47) 2.50 kg. Intervention effect sizes compared with usual care were: d = 0.01 web-based; d = 0.34 basic nurse support; d = 0.02 regular nurse support. Two practices deviated from protocol by providing considerable weight management support to their usual care patients. Conclusions This study demonstrated the feasibility of delivering a web-based weight management intervention supported by practice nurses in primary care, and suggests that the combination of the web-based intervention with basic nurse support could provide an effective solution to weight management support in a primary care context. Trial registration Current Controlled Trials ISRCTN31685626. PMID:24886516

A cluster randomised controlled trial evaluating an incentive-based outdoor physical activity programme to increase outdoor time and prevent myopia in children.

PubMed

Ngo, Cheryl S; Pan, Chen-Wei; Finkelstein, Eric A; Lee, Chun-Fan; Wong, Inez B; Ong, Julia; Ang, Marcus; Wong, Tien-Yin; Saw, Seang-Mei

2014-05-01

To evaluate an incentive-based intervention to increase time spent outdoors among children in a 9-month cluster randomised controlled trial. Two hundred and eighty-five children aged 6-12 years of age were randomised to the intervention (n = 147) or control arm (n = 138) in the Family incentive trial (FIT). The FIT intervention comprised of targeted education on myopia and good eye care habits, structured weekend outdoor activities and incentives for children to increase their daily steps via pedometers. The main outcome measure was outdoor time, measured by the WHO questionnaire and a 1-week diary. Interim analysis at 6 months showed a significant increase in mean outdoor time per week in the intervention arm (14.75 h week(-1) ) compared to the control arm (12.40 h week(-1) ) as measured by the questionnaire (p = 0.04). However, greater outdoor time was not statistically significant at the end of the trial (15.95 h week(-1) vs 14.34 h in the control group (p = 0.29). There was an increase in outdoor time for children in the incentive-based physical activity outdoor program after 6 months but not at the end of the trial. Further larger school trials with better compliance with the intervention and longer duration could be conducted to evaluate clinical outcomes such as myopic shifts. © 2014 The Authors Ophthalmic & Physiological Optics © 2014 The College of Optometrists.

[Phase II clinical trial of nedaplatin in advanced non-small cell lung cancer].

PubMed

Xu, Rui-hua; Guan, Zhong-zhen; Jiang, Wen-qi; Huang, He; Hu, Xiao-hua; Xie, Wei-min; Li, Xing-gen; Liu, Ya-li; Pan, Liang-xi; Dai, Ai-di; Zhuang, Wu; Zhang, Chun; Ma, Zhi-yong; Wang, Jian-hua

2002-12-01

The aim of this study was to observe the efficacy and the side effects of nedaplatin in treatment of non-small cell lung cancer (NSCLC). This is a multi-center phase II clinical trial. The previously chemotherapy treated patients with NSCLC were administrated nedaplatin alone. Nedaplatin was given at 100 mg/m2, i.v., repeated every 3 weeks. The chemonaive patients with NSCLC were randomized to two groups. The combination trial group was given with nedaplatin + vindesine regimen, and the combination control group with cisplatin + vindesine. Of 138 patients, 16 were in the nedaplatin single drug group; 60 were in the combination trial group; and 62 were in the combination control group. All of the 16 cases in the single drug group, which were treated with platinum previously, achieved 12.5% of response rate. And the combination trial group and control group had a very similar response rate, which were 26.7% versus 25.8%, respectively. The incidence rates of neutropenia and anemia were similar in the two groups. But the incidence rate of thrombocytopenia was higher in the trial group than that in the control group. Nedaplatin has a possibility to result in mild nausea/vomiting. Nedaplatin is an effective platinum drug in the treatment of NSCLC, not only for no previously chemotherapy patients, but also for those patients resistant to cisplatin/carboplatin. Nedaplatin has a good clinical tolerance. And the main adverse reaction was myelosuppression, especially thrombocytopenia.

Effects of acute exercise on postprandial triglyceride response after a high fat meal in overweight black and white adolescents

PubMed Central

Lee, SoJung; Burns, Stephen F.; White, David; Kuk, Jennifer L.; Arslanian, Silva

2014-01-01

Objective We examined the effects of acute exercise on postprandial triglyceride (TG) metabolism following a high fat meal in overweight black vs. white adolescents. Design and Subjects Twenty-one black and 17 white adolescents (12-18 yrs, BMI >85th percentile) were evaluated twice, during control versus exercise trials, 1-4 weeks apart, in a counterbalanced randomized design. In the control trial, participants performed no exercise on day 1. In the exercise trial, participants performed a single bout of 60 min exercise (50% VO2peak) on a cycle ergometer on day 1. On day 2 of both trials, participants consumed a high-fat breakfast (70% calories from fat) and blood was sampled for TG concentration in the fasted state and for 6 hrs postprandially. Results There was a significant main effect of condition on postprandial peak TG concentration (P=0.01) and TG-area under the curve (AUC) (P=0.003), suggesting that independent of race, peak TG and TG-AUC was lower in the exercise trial vs. control trial. Including Tanner stage, gender, total fat (kg) and VAT as independent variables, stepwise multiple regression analyses revealed that in whites, VAT was the strongest (P<0.05) predictor of postprandial TG-AUC explaining 56% and 25% of the variances in TG-AUC in the control and exercise trials, respectively. In blacks, VAT was not associated with postprandial TG-AUC independent of trial. Conclusion A single bout of aerobic exercise preceding a high fat meal is beneficial to reduce postprandial TG concentrations in overweight white adolescents to a greater extent than black adolescents, particularly those with increased visceral adiposity. PMID:23507997

Effects of acute exercise on postprandial triglyceride response after a high-fat meal in overweight black and white adolescents.

PubMed

Lee, S; Burns, S F; White, D; Kuk, J L; Arslanian, S

2013-07-01

We examined the effects of acute exercise on postprandial triglyceride (TG) metabolism following a high-fat meal in overweight black vs white adolescents. Twenty-one black and 17 white adolescents (12-18 yrs, body mass index 85th percentile) were evaluated twice, during control versus exercise trials, 1-4 weeks apart, in a counterbalanced randomized design. In the control trial, participants performed no exercise on day 1. In the exercise trial, participants performed a single bout of 60-min exercise (50% VO2 peak) on a cycle ergometer on day 1. On day 2 of both trials, participants consumed a high-fat breakfast (70% calories from fat) and blood was sampled for TG concentration in the fasted state and for 6 h postprandially. There was a significant main effect of condition on postprandial peak TG concentration (P=0.01) and TG area under the curve (AUC) (P=0.003), suggesting that independent of race, peak TG and TG-AUC was lower in the exercise trial vs control trial. Including Tanner stage, gender, total fat (kg) and visceral adipose tissue (VAT) as independent variables, stepwise multiple regression analyses revealed that in whites, VAT was the strongest (P<0.05) predictor of postprandial TG-AUC, explaining 56 and 25% of the variances in TG-AUC in the control and exercise trials, respectively. In blacks, VAT was not associated with postprandial TG-AUC, independent of trial. A single bout of aerobic exercise preceding a high-fat meal is beneficial to reduce postprandial TG concentrations in overweight white adolescents to a greater extent than black adolescents, particularly those with increased visceral adiposity.

Appetite and Energy Intake Responses to Acute Energy Deficits in Females versus Males

PubMed Central

ALAJMI, NAWAL; DEIGHTON, KEVIN; KING, JAMES A.; REISCHAK-OLIVEIRA, ALVARO; WASSE, LUCY K.; JONES, JENNY; BATTERHAM, RACHEL L.; STENSEL, DAVID J.

2016-01-01

ABSTRACT Purpose To explore whether compensatory responses to acute energy deficits induced by exercise or diet differ by sex. Methods In experiment one, 12 healthy women completed three 9-h trials (control, exercise-induced (Ex-Def) and food restriction–induced energy deficit (Food-Def)) with identical energy deficits being imposed in the Ex-Def (90-min run, ∼70% of V˙O2max) and Food-Def trials. In experiment two, 10 men and 10 women completed two 7-h trials (control and exercise). Sixty minutes of running (∼70% of V˙O2max) was performed at the beginning of the exercise trial. The participants rested throughout the remainder of the exercise trial and during the control trial. Appetite ratings, plasma concentrations of gut hormones, and ad libitum energy intake were assessed during main trials. Results In experiment one, an energy deficit of approximately 3500 kJ induced via food restriction increased appetite and food intake. These changes corresponded with heightened concentrations of plasma acylated ghrelin and lower peptide YY3–36. None of these compensatory responses were apparent when an equivalent energy deficit was induced by exercise. In experiment two, appetite ratings and plasma acylated ghrelin concentrations were lower in exercise than in control, but energy intake did not differ between trials. The appetite, acylated ghrelin, and energy intake response to exercise did not differ between men and women. Conclusions Women exhibit compensatory appetite, gut hormone, and food intake responses to acute energy restriction but not in response to an acute bout of exercise. Additionally, men and women seem to exhibit similar acylated ghrelin and PYY3–36 responses to exercise-induced energy deficits. These findings advance understanding regarding the interaction between exercise and energy homeostasis in women. PMID:26465216

Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin’s lymphoma: a systematic review

PubMed Central

Herbst, Christine; Rehan, Fareed A.; Brillant, Corinne; Bohlius, Julia; Skoetz, Nicole; Schulz, Holger; Monsef, Ina; Specht, Lena; Engert, Andreas

2010-01-01

Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin’s lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication. We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin’s lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were hazard ratios for OS and tumor control as well as relative risks for complete response (CR). Meta-analyses were performed using RevMan5. Five randomized controlled trials involving 1,245 patients were included. The hazard ratio (HR) was 0.41 (95% confidence interval (CI) 0.25 to 0.66) for tumor control and 0.40 (95% CI 0.27 to 0.59) for OS for patients receiving CMT compared to chemotherapy alone. CR rates were similar between treatment groups. In sensitivity analyses another 6 trials were included that did not fulfill the inclusion criteria of our protocol but were considered relevant to the topic. These trials underlined the results of the main analysis. In conclusion, adding radiotherapy to chemotherapy improves tumor control and OS in patients with early stage Hodgkin’s lymphoma. PMID:19951972

A Double-Blind, Randomized Pilot Trial of Chromium Picolinate for Overweight Individuals with Binge-Eating Disorder: Effects on Glucose Regulation.

PubMed

Sala, Margarita; Breithaupt, Lauren; Bulik, Cynthia M; Hamer, Robert M; La Via, Maria C; Brownley, Kimberly A

2017-03-04

Chromium treatment has been shown to improve glucose regulation in some populations. The purpose of this study was to evaluate whether chromium picolinate (CrPic) supplementation improves glucose regulation in overweight individuals with binge-eating disorder (BED). In this double-blinded randomized pilot trial, participants (N = 24) were randomized to high (HIGH, 1000 mcg/day, n = 8) or moderate (MOD, 600 mcg/day, n = 9) dose of CrPic or placebo (PL, n = 7) for 6 months. Participants completed an oral glucose tolerance test (OGTT) at baseline, 3 months, and 6 months. Fixed effects models were used to estimate mean change in glucose area under the curve (AUC), insulin AUC , and insulin sensitivity index (ISI). Results revealed a significant group and time interaction (p < 0.04) for glucose AUC , with glucose AUC increasing significantly in the PL group (p < 0.02) but decreasing significantly in the MOD group (p < 0.03) at 6 months. Insulin AUC increased significantly over time (main effect, p < 0.02), whereas ISI decreased significantly over time (main effect, p < 0.03). As anticipated, a moderate dose of CrPic was associated with improved glycemic control, whereas PL was associated with decreased glycemic control. It was unexpected that the improved glycemic control seen in the MOD dose group was not seen in the HIGH dose group. However, although participants randomized to the HIGH dose group did not have improved glycemic control, they had better glycemic control than participants randomized to the PL group. These findings support the need for larger trials.

Effectiveness of policy to provide breastfeeding groups (BIG) for pregnant and breastfeeding mothers in primary care: cluster randomised controlled trial

PubMed Central

Britten, Jane; Prescott, Gordon J; Tappin, David; Ludbrook, Anne; Godden, David J

2009-01-01

Objective To assess the clinical effectiveness and cost effectiveness of a policy to provide breastfeeding groups for pregnant and breastfeeding women. Design Cluster randomised controlled trial with prospective mixed method embedded case studies to evaluate implementation processes. Setting Primary care in Scotland. Participants Pregnant women, breastfeeding mothers, and babies registered with 14 of 66 eligible clusters of general practices (localities) in Scotland that routinely collect breastfeeding outcome data. Intervention Localities set up new breastfeeding groups to provide population coverage; control localities did not change group activity. Main outcome measures Primary outcome: any breast feeding at 6-8 weeks from routinely collected data for two pre-trial years and two trial years. Secondary outcomes: any breast feeding at birth, 5-7 days, and 8-9 months; maternal satisfaction. Results Between 1 February 2005 and 31 January 2007, 9747 birth records existed for intervention localities and 9111 for control localities. The number of breastfeeding groups increased from 10 to 27 in intervention localities, where 1310 women attended, and remained at 10 groups in control localities. No significant differences in breastfeeding outcomes were found. Any breast feeding at 6-8 weeks declined from 27% to 26% in intervention localities and increased from 29% to 30% in control localities (P=0.08, adjusted for pre-trial rate). Any breast feeding at 6-8 weeks increased from 38% to 39% in localities not participating in the trial. Women who attended breastfeeding groups were older (P<0.001) than women initiating breast feeding who did not attend and had higher income (P=0.02) than women in the control localities who attended postnatal groups. The locality cost was £13 400 (€14 410; $20 144) a year. Conclusion A policy for providing breastfeeding groups in relatively deprived areas of Scotland did not improve breastfeeding rates at 6-8 weeks. The costs of running groups would be similar to the costs of visiting women at home. Trial registration Current Controlled Trials ISRCTN44857041. PMID:19181729

First-line treatment for advanced ovarian cancer: paclitaxel, platinum and the evidence

PubMed Central

Sandercock, J; Parmar, M K B; Torri, V; Qian, W

2002-01-01

Four large randomised trials of paclitaxel in combination with platinum against a platinum-based control treatment have now been published in full, representing around 88% (3588 out of 4057) of patients randomised into the eight known trials of this question. There is substantial heterogeneity in the results of these four trials. Four main explanations for this heterogeneity have been proposed: differences in the extent and timing of ‘crossover’ to taxanes in the control groups; differences in the types of patient included; differences in the effectiveness of the research regimens used; differences in the effectiveness of the control regimens used. In this study we examine whether any of these explanations is consistent with the pattern of results seen in these trials. Each explanation suggests that a particular characteristic of each trial was responsible for the results observed. For each explanation the trials were split into groups according to that characteristic, in order to partition the total heterogeneity into that seen ‘within’ and ‘between’ groups of trials. If a particular explanation was consistent with the pattern of results, we would expect to see relatively little heterogeneity within each group of trial results viewed in this way, with most of the heterogeneity being between groups which are dissimilar with respect to the key characteristic. Heterogeneity ‘within’ and ‘between’ groups was formally compared using the F-ratio. If any explanation appeared to be consistent with the results of the trials, it was considered whether the explanation was also consistent with other evidence available about these regimens. Only one explanation appeared to be consistent with the pattern of results seen in these trials, and that was differences in effectiveness of the control arms used in these trials. This suggests that the very positive results in favour of paclitaxel/cisplatin seen in two of the trials may have been due to the use of a suboptimal control arm. There is no direct evidence about the relative effectiveness of the control arms used in these trials, but indirect evidence is consistent with the conclusion that the cyclophosphamide/cisplatin regimen used in two of the trials may be less effective than the control regimens used in the other trials. Specific concerns about the choice of a cyclophosphamide/cisplatin control arm in the first of these trials to report were raised before the results of the other trials were known, i.e. before any heterogeneity had been observed. Further investigation of this question would be useful. In the meantime, given all of the randomised evidence on the efficacy and toxicity associated with the regimens used in these trials, we conclude that single agent carboplatin is a safe and effective first-line treatment for women with advanced ovarian cancer. British Journal of Cancer (2002) 87, 815–824. doi:10.1038/sj.bjc.6600567 www.bjcancer.com © 2002 Cancer Research UK PMID:12373593

A randomized controlled trial of pre-conception treatment for periodontal disease to improve periodontal status during pregnancy and birth outcomes.

PubMed

Jiang, Hong; Xiong, Xu; Su, Yi; Zhang, Yiming; Wu, Hongqiao; Jiang, Zhijun; Qian, Xu

2013-12-09

Evidence has suggested that periodontal disease is associated with an increased risk of various adverse pregnancy and birth outcomes. However, several large clinical randomized controlled trials failed to demonstrate periodontal therapy during pregnancy reduced the incidence of adverse pregnancy and birth outcomes. It has been suggested that the pre-conception period may be an optimal period for periodontal disease treatment rather than during pregnancy. To date, no randomized controlled trial (RCT) has examined if treating periodontal disease before pregnancy reduces adverse birth outcomes. This study aims to examine if the pre-conception treatment of periodontal disease will lead to improved periodontal status during late pregnancy and subsequent birth outcomes. A sample of 470 (235 in each arm of the study) pre-conception women who plan to conceive within one year and with periodontal disease will be recruited for the study. All participants will be randomly allocated to the intervention or control group. The intervention group will receive free therapy including dental scaling and root planning (the standard therapy), supragingival prophylaxis, and oral hygiene education. The control group will only receive supragingival prophylaxis and oral hygiene education. Women will be followed throughout their pregnancy and then to childbirth. The main outcomes include periodontal disease status in late pregnancy and birth outcomes measured such as mean birth weight (grams), and mean gestational age (weeks). Periodontal disease will be diagnosed through a dental examination by measuring probing depth, clinical attachment loss and percentage of bleeding on probing (BOP) between gestational age of 32 and 36 weeks. Local and systemic inflammatory mediators are also included as main outcomes. This will be the first RCT to test whether treating periodontal disease among pre-conception women reduces periodontal disease during pregnancy and prevents adverse birth outcomes. If the effect of pre-pregnancy periodontal treatment is confirmed, this intervention could be recommended for application in low- or middle-income countries to improve both oral health and maternal and child health. This trial is registered with Chinese Clinical Trial Registry (ChiCTR): ChiCTR-TRC-12001913.

The effect of static scanning and mobility training on mobility in people with hemianopia after stroke: A randomized controlled trial comparing standardized versus non-standardized treatment protocols

PubMed Central

2011-01-01

Background Visual loss following stroke impacts significantly on activities of daily living and is an independent risk factor for becoming dependent. Routinely, allied health clinicians provide training for visual field loss, mainly with eye movement based therapy. The effectiveness of the compensatory approach to rehabilitation remains inconclusive largely due to difficulty in validating functional outcome with the varied type and dosage of therapy received by an individual patient. This study aims to determine which treatment is more effective, a standardized approach or individualized therapy in patients with homonymous hemianopia post stroke. Methods/Design This study is a double-blind randomized controlled, multicenter trial. A standardised scanning rehabilitation program (Neuro Vision Technology (NVT) program) of 7 weeks at 3 times per week, is compared to individualized therapy recommended by clinicians. Discussion The results of the trial will provide information that could potentially inform the allocation of resources in visual rehabilitation post stroke. Trial Registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000494033 PMID:21767413

Mechanisms of Corneal Pain and Implications for Postoperative Pain After Laser Correction of Refractive Errors.

PubMed

Garcia, Renato; de Andrade, Daniel C; Teixeira, Manoel J; Nozaki, Siro S; Bechara, Samir J

2016-05-01

The cornea is the target of most surgeries for refractive disorders, as myopia. It is estimated that almost 1 million patients undergo corneal refractive surgery each year in the United States. Refractive surgery includes photorefractive keratectomy (PRK) that produces intense postoperative pain. This review presents the main pain mechanisms behind PRK-related pain and the available therapeutic options for its management. Data sources included literature of cornea anatomy, treatment of PRK postoperative pain, mechanisms of corneal pain, in 3 electronic databases: Pubmed, Scopus, and Web of Science. Only double-blinded controlled trials on pain control after PRK were selected to show the endpoints, treatment, and control strategies. A total of 18 double-blind, controlled trials were identified. These studies have shown the use of topical nonsteroidal anti-inflammatory drugs, topical steroidal anti-inflammatory drugs, systemic analgesics, cold balanced saline solution, topical anesthetic, gabapentin, and morphine to treat postoperative pain in PRK. The percentage of responders has seldom been reported, and few studies allow for the formal calculation of the number necessary to treat. Postoperative intense pain after PRK laser surgery remains the main challenge to its widespread use for the correction of refractive errors.

Experiment on a novel user input for computer interface utilizing tongue input for the severely disabled.

PubMed

Kencana, Andy Prima; Heng, John

2008-11-01

This paper introduces a novel passive tongue control and tracking device. The device is intended to be used by the severely disabled or quadriplegic person. The main focus of this device when compared to the other existing tongue tracking devices is that the sensor employed is passive which means it requires no powered electrical sensor to be inserted into the user's mouth and hence no trailing wires. This haptic interface device employs the use of inductive sensors to track the position of the user's tongue. The device is able perform two main PC functions that of the keyboard and mouse function. The results show that this device allows the severely disabled person to have some control in his environment, such as to turn on and off or control daily electrical devices or appliances; or to be used as a viable PC Human Computer Interface (HCI) by tongue control. The operating principle and set-up of such a novel passive tongue HCI has been established with successful laboratory trials and experiments. Further clinical trials will be required to test out the device on disabled persons before it is ready for future commercial development.

A Cluster-Randomized Trial of Restorative Practices: An Illustration to Spur High-Quality Research and Evaluation.

PubMed

Acosta, Joie D; Chinman, Matthew; Ebener, Patricia; Phillips, Andrea; Xenakis, Lea; Malone, Patrick S

2016-01-01

Restorative Practices in schools lack rigorous evaluation studies. As an example of rigorous school-based research, this paper describes the first randomized control trial of restorative practices to date, the Study of Restorative Practices. It is a 5-year, cluster-randomized controlled trial (RCT) of the Restorative Practices Intervention (RPI) in 14 middle schools in Maine to assess whether RPI impacts both positive developmental outcomes and problem behaviors and whether the effects persist during the transition from middle to high school. The two-year RPI intervention began in the 2014-2015 school year. The study's rationale and theoretical concerns are discussed along with methodological concerns including teacher professional development. The theoretical rationale and description of the methods from this study may be useful to others conducting rigorous research and evaluation in this area.

Double-blind trials in hyperbaric medicine: A narrative review on past experiences and considerations in designing sham hyperbaric treatment.

PubMed

Lansdorp, C A; van Hulst, Rob A

2018-06-01

Background Hyperbaric oxygen therapy, which consists of breathing 100% oxygen under a higher atmospheric pressure than normal, is utilized worldwide in the treatment of several diseases. With the growing demand for evidence-based research, hyperbaric oxygen therapy has been criticized for delivering too little high-quality research, mainly in the form of randomized controlled trials. While not always indispensable, the addition of a sham-controlled group to such a trial can contribute to the quality of the research. However, the design of a sham (hyperbaric) treatment is associated with several considerations regarding adequate blinding and the use of pressure and oxygen. This narrative review discusses information on the sham profile and the blinding and safety of double-blind trials in hyperbaric medicine, irrespective of the indication for treatment. Methods MEDLINE, Embase and CENTRAL were searched for sham-controlled trials on hyperbaric oxygen therapy. The control treatment was considered sham if patients were blinded to their allocation and treatment took place in a hyperbaric chamber, with no restrictions regarding pressurization, oxygen levels or indication. Studies involving children or only one session of hyperbaric oxygen were excluded. Information on (the choice of) treatment profile, blinding measures, patient's perception regarding allocation and safety issues was extracted from eligible studies. Results A total of 42 eligible trials were included. The main strategies for sham treatment were (1) use of a lower pressure than that of the hyperbaric oxygen group, while breathing 21% oxygen; (2) use of the same pressure as the hyperbaric oxygen group, while breathing an adjusted percentage of oxygen; and (3) use of the same pressure as the hyperbaric oxygen group, while breathing 21% oxygen. The advantages and disadvantages of each strategy are discussed using the information provided by the trials. Conclusion Based on this review, using a lower pressure than the hyperbaric oxygen group while breathing 21% oxygen best matches the inertness of the placebo. Although studies show that use of a lower pressure does allow adequate blinding, this is associated with more practical issues than with the other strategies. The choice of which sham profile to use requires careful consideration; moreover, to ensure proper performance, a clear and detailed protocol is also required.

Comparison of Antibiotic Therapy and Appendectomy for Acute Uncomplicated Appendicitis in Children

PubMed Central

Huang, Libin; Yin, Yuan; Yang, Lie; Wang, Cun; Zhou, Zongguang

2017-01-01

Importance Antibiotic therapy for acute uncomplicated appendicitis is effective in adult patients, but its application in pediatric patients remains controversial. Objective To compare the safety and efficacy of antibiotic treatment vs appendectomy as the primary therapy for acute uncomplicated appendicitis in pediatric patients. Data Sources The PubMed, MEDLINE, EMBASE, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched through April 17, 2016. The search was limited to studies published in English. Search terms included appendicitis, antibiotics, appendectomy, randomized controlled trial, controlled clinical trial, randomized, placebo, drug therapy, randomly, and trial. Study Selection Randomized clinical trials and prospective clinical controlled trials comparing antibiotic therapy with appendectomy for acute uncomplicated appendicitis in pediatric patients (aged 5-18 years) were included in the meta-analysis. The outcomes included at least 2 of the following terms: success rate of antibiotic treatment and appendectomy, complications, readmissions, length of stay, total cost, and disability days. Data Extraction and Synthesis Data were independently extracted by 2 reviewers. The quality of the included studies was examined in accordance with the Cochrane guidelines and the Newcastle-Ottawa criteria. Data were pooled using a logistic fixed-effects model, and the subgroup pooled risk ratio with or without appendicolith was estimated. Main Outcomes and Measures The primary outcome was the success rate of treatment. The hypothesis was formulated before data collection. Results A total of 527 articles were screened. In 5 unique studies, 404 unique patients with uncomplicated appendicitis (aged 5-15 years) were enrolled. Nonoperative treatment was successful in 152 of 168 patients (90.5%), with a Mantel-Haenszel fixed-effects risk ratio of 8.92 (95% CI, 2.67-29.79; heterogeneity, P = .99; I2 = 0%). Subgroup analysis showed that the risk for treatment failure in patients with appendicolith increased, with a Mantel-Haenszel fixed-effects risk ratio of 10.43 (95% CI, 1.46-74.26; heterogeneity, P = .91; I2 = 0%). Conclusions and Relevance This meta-analysis shows that antibiotics as the initial treatment for pediatric patients with uncomplicated appendicitis may be feasible and effective without increasing the risk for complications. However, the failure rate, mainly caused by the presence of appendicolith, is higher than for appendectomy. Surgery is preferably suggested for uncomplicated appendicitis with appendicolith. PMID:28346589

Surgery for post-vitrectomy cataract

PubMed Central

Do, Diana V; Gichuhi, Stephen; Vedula, Satyanarayana S; Hawkins, Barbara S

2014-01-01

Background Cataract formation or acceleration can occur after intraocular surgery, especially following vitrectomy, a surgical technique for removing the vitreous which is used in the treatment of disorders that affect the posterior segment of the eye. The underlying problem that led to vitrectomy may limit the benefit from cataract surgery. Objectives The objective of this review was to evaluate the effectiveness and safety of surgery for post-vitrectomy cataract with respect to visual acuity, quality of life, and other outcomes. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 4), Ovid MEDLINE, Ovid MEDLINE in-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily Update, Ovid OLDMED-LINE (January 1946 to May 2013), EMBASE (January 1980 to May 2013, Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to May 2013), PubMed (January 1946 to May 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrial.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 22 May 2013. Selection criteria We planned to include randomized and quasi-randomized controlled trials comparing cataract surgery with no surgery in adult patients who developed cataract following vitrectomy. Data collection and analysis Two authors screened the search results independently according to the standard methodological procedures expected by The Cochrane Collaboration. Main results We found no randomized or quasi-randomized controlled trials comparing cataract surgery with no cataract surgery for patients who developed cataracts following vitrectomy surgery. Authors' conclusions There is no evidence from randomized or quasi-randomized controlled trials on which to base clinical recommendations for surgery for post-vitrectomy cataract. There is a clear need for randomized controlled trials to address this evidence gap. Such trials should stratify participants by their age, the retinal disorder leading to vitrectomy, and the status of the underlying disease process in the contralateral eye. Outcomes assessed in such trials may include gain of vision on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, quality of life, and adverse events such as posterior capsular rupture. Both short-term (six-month) and long-term (one-year or two-year) outcomes should be examined. PMID:24357418

Streamlining cardiovascular clinical trials to improve efficiency and generalisability.

PubMed

Zannad, Faiez; Pfeffer, Marc A; Bhatt, Deepak L; Bonds, Denise E; Borer, Jeffrey S; Calvo-Rojas, Gonzalo; Fiore, Louis; Lund, Lars H; Madigan, David; Maggioni, Aldo Pietro; Meyers, Catherine M; Rosenberg, Yves; Simon, Tabassome; Stough, Wendy Gattis; Zalewski, Andrew; Zariffa, Nevine; Temple, Robert

2017-08-01

Controlled trials provide the most valid determination of the efficacy and safety of an intervention, but large cardiovascular clinical trials have become extremely costly and complex, making it difficult to study many important clinical questions. A critical question, and the main objective of this review, is how trials might be simplified while maintaining randomisation to preserve scientific integrity and unbiased efficacy assessments. Experience with alternative approaches is accumulating, specifically with registry-based randomised controlled trials that make use of data already collected. This approach addresses bias concerns while still capitalising on the benefits and efficiencies of a registry. Several completed or ongoing trials illustrate the feasibility of using registry-based controlled trials to answer important questions relevant to daily clinical practice. Randomised trials within healthcare organisation databases may also represent streamlined solutions for some types of investigations, although data quality (endpoint assessment) is likely to be a greater concern in those settings. These approaches are not without challenges, and issues pertaining to informed consent, blinding, data quality and regulatory standards remain to be fully explored. Collaboration among stakeholders is necessary to achieve standards for data management and analysis, to validate large data sources for use in randomised trials, and to re-evaluate ethical standards to encourage research while also ensuring that patients are protected. The rapidly evolving efforts to streamline cardiovascular clinical trials have the potential to lead to major advances in promoting better care and outcomes for patients with cardiovascular disease. © 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.

Interventions for hyperthyroidism pre-pregnancy and during pregnancy.

PubMed

Earl, Rachel; Crowther, Caroline A; Middleton, Philippa

2013-11-19

Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption. To identify interventions used in the management of hyperthyroidism pre-pregnancy or during pregnancy and to ascertain the impact of these interventions on important maternal, fetal, neonatal and childhood outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013). We planned to include randomised controlled trials, quasi-randomised controlled trials, and cluster-randomised trials comparing antithyroid interventions for hyperthyroidism pre-pregnancy or during pregnancy with another intervention or no intervention (placebo or no treatment). Two review authors assessed trial eligibility and planned to assess trial quality and extract the data independently. No trials were included in the review. As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid interventions for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil.

Why is recruitment to trials difficult? An investigation into recruitment difficulties in an RCT of supported employment in patients with severe mental illness

PubMed Central

Howard, Louise; de Salis, Isabel; Tomlin, Zelda; Thornicroft, Graham; Donovan, Jenny

2009-01-01

Background Under-recruitment to randomised controlled trials (RCTs) is often problematic and there may be particular difficulties in recruiting patients with severe mental illness. Aim To evaluate reasons for under-recruitment in an RCT of patients with severe mental illness Methods Qualitative study during the recruitment phase of an RCT of supported employment. Trial staff and recruiting clinicians were interviewed. Data were analyzed thematically using constant comparative techniques. Results Recruitment rates were low. Five main reasons for recruitment difficulties were found. These included: (i) misconceptions about trials, (ii) lack of equipoise, (iii) misunderstanding of the trial arms, (iv) variable interpretations of eligibility criteria, (v) paternalism. Conclusion Reasons for recruitment difficulties in trials involving patients with severe mental illness include issues that occur in trials in general, but others are more specific to these patients. Clinician and patient involvement in the study design may improve recruitment in future similar trials. PMID:18718555

Ethics of clinical trials in Nigeria.

PubMed

Okonta, Patrick I

2014-05-01

The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria.

Ethics of clinical trials in Nigeria

PubMed Central

Okonta, Patrick I.

2014-01-01

The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria. PMID:25013247

Treating neurocysticercosis medically: a systematic review of randomized, controlled trials.

PubMed

Salinas, R; Counsell, C; Prasad, K; Gelband, H; Garner, P

1999-11-01

To summarize the evidence from randomized controlled trials on the effects of cysticidal therapy used for treating human cysticercosis. Published and unpublished studies in any language identified through MEDLINE (1966 - June 1999) specialized databases, abstracts, proceedings and contact with experts were analysed. Those which compared, using randomized or quasi-randomized methods, any cysticidal drug with placebo or symptomatic therapy were entered in the study. Data were extracted independently by two reviewers and trial quality assessed. Meta-analysis using fixed effects models calculated provided there was no significant heterogeneity, expressed as relative risk. Four trials met the inclusion criteria, treating intraparenchymatous neurocysticercosis with either albendazole or praziquantel compared to placebo or no treatment. In the two trials reporting clinical outcomes, treatment was not associated with a reduction in the risk of seizures, although numbers were small (RR 0.95, 95% CI 0.59-1.51). Four trials reported radiological outcomes, and cysticidal treatment was associated with a lower risk of cyst persistence of scans taken within six months of start of treatment (RR 0.83, 95% CI 0.70-0.99). Subsidiary analysis assuming different outcomes in patients lost to follow-up did not alter the findings of the main analysis. There is insufficient evidence to determine whether cysticidal therapy is of any clinical benefit to patients with neurocysticercosis. The review does not exclude the possibility that more patients remain seizure-free when treated with cysticidal drugs. Further testing through placebo-controlled trials is required.

Theory-based self-management educational interventions on patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Zhao, Fang-Fang; Suhonen, Riitta; Koskinen, Sanna; Leino-Kilpi, Helena

2017-04-01

To synthesize the effects of theory-based self-management educational interventions on patients with type 2 diabetes (T2DM) in randomized controlled trials. Type 2 diabetes is a common chronic disease causing complications that put a heavy burden on society and reduce the quality of life of patients. Good self-management of diabetes can prevent complications and improve the quality of life of T2DM patients. Systematic review with meta-analysis of randomized controlled trials following Cochrane methods. A literature search was carried out in the MEDLINE, EMBASE, CINAHL, PSYCINFO, and Web of Science databases (1980-April 2015). The risk of bias of these eligible studies was assessed independently by two authors using the Cochrane Collaboration's tool. The Publication bias of the main outcomes was examined. Statistical heterogeneity and random-effects model were used for meta-analysis. Twenty studies with 5802 participants met the inclusion criteria. The interventions in the studies were based on one or more theories which mostly belong to mid-range theories. The pooled main outcomes by random-effects model showed significant improvements in HbA1c, self-efficacy, and diabetes knowledge, but not in BMI. As for quality of life, no conclusions can be drawn as the pooled outcome became the opposite with reduced heterogeneity after one study was excluded. No significant publication bias was found in the main outcomes. To get theory-based interventions to produce more effects, the role of patients should be more involved and stronger and the education team should be trained beyond the primary preparation for the self-management education program. © 2016 John Wiley & Sons Ltd.

Sulforaphane Treatment of Children with Autism Spectrum Disorder

DTIC Science & Technology

2017-07-01

the course of the study . To date, the Pilot trial of 10 children has been completed, and 36 out of the target 50 children for the Main trial have... study will enroll 50 children with moderate to severe autism, between 3 and 12 years old, in a randomized, double-blind, placebo-controlled phase-2... children were unable to cooperate, and because in some cases study participants took the study drug in the morning and then went to school for the

A randomized double-blind trial of two low dose combined oral contraceptives.

PubMed

Bounds, W; Vessey, M; Wiggins, P

1979-04-01

Fifty-five women using Loestrin-20 (20 microgram ethinyl oestradiol and 1 mg norethisterone acetate) as an oral contraceptive have been compared with a like number using Microgynon-30 (30 microgram ethinyl oestradiol and 150 microgram levonorgestrel) in a randomized, double-blind trial. Despite the small sample size, the main finding in the trial is clear-cut; Loestrin-20 provides poor cycle control and is thus less acceptable as an oral contraceptive than Microgynon-30. Although there is also a suggestion that Loestrin-20 may be less effective than Microgynon-30, the difference in the accidental pregnancy rates is not statistically significant.

Treatment of Common Cold Patients with the Shi-Cha Capsule: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Dose-Escalation Trial

PubMed Central

Chang, Jing; Dong, Shou-Jin; She, Bin; Zhang, Rui-Ming; Meng, Mao-Bin; Xu, Yan-Ling; Wan, Li-Ling; Shi, Ke-Hua; Pan, Jun-Hun; Mao, Bing

2012-01-01

This study was designed to determine the therapeutic efficacy and safety of the Shi-cha capsule, a Chinese herbal formula, in the treatment of patients with wind-cold type common cold. In our multi-center, prospective, double-blind, randomized, placebo-controlled, dose-escalation trial, patients with wind-cold type common cold received 0.6 g of Shi-cha capsule plus 0.6 g placebo (group A), 1.2 g of Shi-cha capsule (group B), or 1.2 g placebo (group C), three times daily for 3 days and followed up to 10 days. The primary end point was all symptom duration. The secondary end points were main symptom duration, minor symptom duration, the changes in cumulative symptom score, main symptom score, and minor symptom score 4 days after the treatment, as well as adverse events. A total of 377 patients were recruited and 360 met the inclusive criteria; 120 patients constituted each treatment group. Compared with patients in group C, patients in groups A and B had significant improvement in the all symptom duration, main symptom duration, minor symptom duration, as well as change from baseline of cumulative symptom score, main symptom score, and minor symptom score at day 4. The symptom durations and scores showed slight superiority of group B over group A, although these differences were not statistically significant. There were no differences in adverse events. The Shi-cha capsule is efficacious and safe for the treatment of patients with wind-cold type common cold. Larger trials are required to fully assess the benefits and safety of this treatment for common cold. PMID:23346193

Prevention of illicit drug use through a school-based program: results of a longitudinal, cluster-randomized controlled trial.

PubMed

Guo, Jong-Long; Lee, Tzu-Chi; Liao, Jung-Yu; Huang, Chiu-Mieh

2015-03-01

To evaluate the long-term effects of an illicit drug use prevention program for adolescents that integrates life skills into the theory of planned behavior. We conducted a cluster-randomized trial in which 24 participating schools were randomized to either an intervention group (12 schools, n = 1,176 students) or a control group (12 schools, n = 915 students). Participants were grade 7 students. The intervention comprised a main intervention of 10 sessions and two booster interventions. Booster 1 (four sessions) and booster 2 (two sessions) were performed at 6 months and 12 months, respectively, after completion of the main intervention. Assessments were made at baseline, after the main intervention, and after each booster session using specific questionnaires for measuring participants' attitudes, subjective norms, perceived behavioral control, and life skills. Retention rates were 71.9% (845/1,176) in the intervention group and 90.7% (830/915) in the control group after the 12-month follow-up. A significantly lower proportion of intervention group participants reported illicit drug use after the first and second booster sessions compared with control group participants (.1% vs. 1.7% and .2% vs. 1.7%, respectively; both p < .05). Attitudes, subjective norms, perceived behavioral control, life skills, and behavioral intention scores of the intervention group were significantly higher than those of control group after the first and second booster sessions (all p < .001), suggesting that intervention group students tended to avoid drug use. A drug use prevention program integrating life skills into the theory of planned behavior may be effective for reducing illicit drug use and improving planned behavior-related constructs in adolescents. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Child language interventions in public health: a systematic literature review.

PubMed

De Cesaro, Bruna Campos; Gurgel, Léia Gonçalves; Nunes, Gabriela Pisoni Canedo; Reppold, Caroline Tozzi

2013-01-01

Systematically review the literature on interventions in children's language in primary health care. One searched the electronic databases (January 1980 to March 2013) MEDLINE (accessed by PubMed), Scopus, Lilacs and Scielo. The search terms used were "child language", "primary health care", "randomized controlled trial" and "intervention studies" (in English, Portuguese and Spanish). There were included any randomized controlled trials that addressed the issues child language and primary health care. The analysis was based on the type of language intervention conducted in primary health care. Seven studies were included and used intervention strategies such as interactive video, guidance for parents and group therapy. Individuals of both genders were included in the seven studies. The age of the children participant in the samples of the articles included in this review ranged from zero to 11 years. These seven studies used approaches that included only parents, parents and children or just children. The mainly intervention in language on primary health care, used in randomized controlled trials, involved the use of interactional video. Several professionals, beyond speech and language therapist, been inserted in the language interventions on primary health care, demonstrating the importance of interdisciplinary work. None of the articles mentioned aspects related to hearing. There was scarcity of randomized controlled trials that address on language and public health, either in Brazil or internationally.

Association between berries intake and cardiovascular diseases risk factors: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials.

PubMed

Luís, Ângelo; Domingues, Fernanda; Pereira, Luísa

2018-02-21

The main goal of this work was to clarify the effects of the consumption of berries on cardiovascular disease (CVD) risk factors by performing a systematic review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, followed by a meta-analysis and a trial sequential analysis (TSA) of randomized controlled trials (RCTs). The electronic search was conducted in PubMed, Scopus, SciELO, Web of Science and Cochrane Library between April and June 2016. To be included, RCTs had to report 1 or more of the following outcomes: total cholesterol (TC), HDL-cholesterol (HDL), LDL-cholesterol (LDL), triglycerides (TG), blood pressure (BP), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM), intercellular adhesion molecule-1 (ICAM), glucose, insulin, apolipoprotein A-I (Apo A-I) or apolipoprotein B (Apo B). It was observed that the intake of berries reduces TC, LDL, TG, and BP while increasing the level of HDL, suggesting a beneficial effect on the control of CVDs' risk factors. Thus, the intake of berries as nutraceuticals or functional foods could be suggested for the prevention and control of CVDs.

Cognitive control during a spatial Stroop task: Comparing conflict monitoring and prediction of response-outcome theories.

PubMed

Pires, Luís; Leitão, José; Guerrini, Chiara; Simões, Mário R

2017-07-03

Cognitive control allows information processing and behaviour to vary adaptively from moment to moment depending on current goals. Two of the most prominent theories that have been proposed to account for the processing of cognitive control are the Conflict Monitoring Theory (CMT) and the Prediction of Response-Outcome Theory (PRO). According to both theories, the implementation of cognitive control during a trial in a conflict task reflects processing events that occurred in the preceding trial. Both CMT and PRO advocate that the detection of conflict situations leads to the recruitment of cognitive control, but they differ regarding the processing underpinnings of cognitive control during conflict resolution. CMT proposes that conflict between alternative responses is resolved by enhancing the task's relevant dimension, reducing interference from the task's irrelevant dimension(s). This control setup promotes conflict adaptation in the subsequent trial. PRO proposes that conflict is resolved by means of a cost-effectiveness analysis that identifies and suppresses action plans linked to the less appropriate responses, facilitating conflict resolution in the subsequent trial. To adjudicate between these alternatives, we manipulated contingencies pertaining to two-trial sequences (n-1; n), namely, the congruency between task relevant/irrelevant dimensions in trial n-1 and response repetition in trial n. A spatial Stroop task was used, in which task-relevant and irrelevant information were integrated within the same stimulus. In this task, participants were required to attend to the direction of an arrow while ignoring its position. The arrow's direction and position could be congruent (C) or incongruent (IC). In one experiment, trials in which the participant was required to respond according to the position of a circle (PO; position only trials), occupying the sequential position n, were the focus of the analyses. Three experiments were conducted manipulating the trials' sequence structure. In Experiment 1, we studied a low control/low conflict condition (cC trials), and two high control/low conflict conditions (icC with and without response repetition). In Experiment 2, we studied two low control/no conflict conditions (cPO with and without response repetition) and two high control/no conflict conditions (icPO with and without response repetition). In Experiment 3, we studied a high control/high conflict condition (icIC) and two low control/high conflict conditions (cIC with and without response repetition). Overall, our findings are in agreement with previous studies in which both bottom-up processing, linked to response and stimulus position repetition, and top-down processing, linked to cognitive control, were shown to contribute to sequence effects in conflict tasks. Specifically, our observations mainly support PRO's account of conflict resolution, in which the intervention of top-down processing is substantially more complex than in CMT's account. Copyright © 2017 Elsevier B.V. All rights reserved.

Interventions targeted at women to encourage the uptake of cervical screening

PubMed Central

Everett, Thomas; Bryant, Andrew; Griffin, Michelle F; Martin-Hirsch, Pierre PL; Forbes, Carol A; Jepson, Ruth G

2014-01-01

Background World-wide, cervical cancer is the second most common cancer in women. Increasing the uptake of screening, alongside increasing informed choice is of great importance in controlling this disease through prevention and early detection. Objectives To assess the effectiveness of interventions aimed at women, to increase the uptake, including informed uptake, of cervical cancer screening. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Issue 1, 2009. MEDLINE, EMBASE and LILACS databases up to March 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) of interventions to increase uptake/informed uptake of cervical cancer screening. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. Main results Thirty-eight trials met our inclusion criteria. These trials assessed the effectiveness of invitational and educational interventions, counselling, risk factor assessment and procedural interventions. Heterogeneity between trials limited statistical pooling of data. Overall, however, invitations appear to be effective methods of increasing uptake. In addition, there is limited evidence to support the use of educational materials. Secondary outcomes including cost data were incompletely documented so evidence was limited. Most trials were at moderate risk of bias. Informed uptake of cervical screening was not reported in any trials. Authors’ conclusions There is evidence to support the use of invitation letters to increase the uptake of cervical screening. There is limited evidence to support educational interventions but it is unclear what format is most effective. The majority of the studies are from developed countries and so the relevance to developing countries is unclear. PMID:21563135

Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre, randomised controlled trial: design and methodology.

PubMed

Gazzard, Gus; Konstantakopoulou, Evgenia; Garway-Heath, David; Barton, Keith; Wormald, Richard; Morris, Stephen; Hunter, Rachael; Rubin, Gary; Buszewicz, Marta; Ambler, Gareth; Bunce, Catey

2018-05-01

The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open-angle glaucoma (POAG) or ocular hypertension (OHT). The LiGHT Trial is a prospective, unmasked, multicentre, pragmatic, randomised controlled trial. 718 previously untreated patients with POAG or OHT were recruited at six collaborating centres in the UK between 2012 and 2014. The trial comprises two treatment arms: initial SLT followed by conventional medical therapy as required, and medical therapy without laser therapy. Randomisation was provided online by a web-based randomisation service. Participants will be monitored for 3 years, according to routine clinical practice. The target intraocular pressure (IOP) was set at baseline according to an algorithm, based on disease severity and lifetime risk of loss of vision at recruitment, and subsequently adjusted on the basis of IOP control, optic disc and visual field. The primary outcome measure is health-related quality of life (HRQL) (EQ-5D five-level). Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, Glaucoma Quality of Life, objective measures of pathway effectiveness, visual function and safety profiles and concordance. A single main analysis will be performed at the end of the trial on an intention-to-treat basis. The LiGHT Trial is a multicentre, pragmatic, randomised clinical trial that will provide valuable data on the relative HRQL, clinical effectiveness and cost-effectiveness of SLT and topical IOP-lowering medication. ISRCTN32038223, 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.

Multimodal manual therapy vs. pharmacological care for management of tension type headache: A meta-analysis of randomized trials.

PubMed

Mesa-Jiménez, Juan A; Lozano-López, Cristina; Angulo-Díaz-Parreño, Santiago; Rodríguez-Fernández, Ángel L; De-la-Hoz-Aizpurua, Jose L; Fernández-de-Las-Peñas, Cesar

2015-12-01

Manual therapies are generally requested by patients with tension type headache. To compare the efficacy of multimodal manual therapy vs. pharmacological care for the management of tension type headache pain by conducting a meta-analysis of randomized controlled trials. PubMed, MEDLINE, EMBASE, AMED, CINAHL, EBSCO, Cochrane Database of Systematic Reviews, Cochrane Collaboration Trials Register, PEDro and SCOPUS were searched from their inception until June 2014. All randomized controlled trials comparing any manual therapy vs. medication care for treating tension type headache adults were included. Data were extracted and methodological quality assessed independently by two reviewers. We pooled headache frequency as the main outcome and also intensity and duration. The weighted mean difference between manual therapy and pharmacological care was used to determine effect sizes. Five randomized controlled trials met our inclusion criteria and were included in the meta-analysis. Pooled analyses found that manual therapies were more effective than pharmacological care in reducing frequency (weighted mean difference -0.8036, 95% confidence interval -1.66 to -0.44; three trials), intensity (weighted mean difference -0.5974, 95% confidence interval -0.8875 to -0.3073; five trials) and duration (weighted mean difference -0.5558, 95% confidence interval -0.9124 to -0.1992; three trials) of the headache immediately after treatment. No differences were found at longer follow-up for headache intensity (weighted mean difference -0.3498, 95% confidence interval -1.106 to 0.407; three trials). Manual therapies were associated with moderate effectiveness at short term, but similar effectiveness at longer follow-up for reducing headache frequency, intensity and duration in tension type headache than pharmacological medical drug care. However, due to the heterogeneity of the interventions, these results should be considered with caution at this stage. © International Headache Society 2015.

Why all randomised controlled trials produce biased results.

PubMed

Krauss, Alexander

2018-06-01

Randomised controlled trials (RCTs) are commonly viewed as the best research method to inform public health and social policy. Usually they are thought of as providing the most rigorous evidence of a treatment's effectiveness without strong assumptions, biases and limitations. This is the first study to examine that hypothesis by assessing the 10 most cited RCT studies worldwide. These 10 RCT studies with the highest number of citations in any journal (up to June 2016) were identified by searching Scopus (the largest database of peer-reviewed journals). This study shows that these world-leading RCTs that have influenced policy produce biased results by illustrating that participants' background traits that affect outcomes are often poorly distributed between trial groups, that the trials often neglect alternative factors contributing to their main reported outcome and, among many other issues, that the trials are often only partially blinded or unblinded. The study here also identifies a number of novel and important assumptions, biases and limitations not yet thoroughly discussed in existing studies that arise when designing, implementing and analysing trials. Researchers and policymakers need to become better aware of the broader set of assumptions, biases and limitations in trials. Journals need to also begin requiring researchers to outline them in their studies. We need to furthermore better use RCTs together with other research methods. Key messages RCTs face a range of strong assumptions, biases and limitations that have not yet all been thoroughly discussed in the literature. This study assesses the 10 most cited RCTs worldwide and shows that trials inevitably produce bias. Trials involve complex processes - from randomising, blinding and controlling, to implementing treatments, monitoring participants etc. - that require many decisions and steps at different levels that bring their own assumptions and degree of bias to results.

The Walking Interventions Through Texting (WalkIT) Trial: Rationale, Design, and Protocol for a Factorial Randomized Controlled Trial of Adaptive Interventions for Overweight and Obese, Inactive Adults.

PubMed

Hurley, Jane C; Hollingshead, Kevin E; Todd, Michael; Jarrett, Catherine L; Tucker, Wesley J; Angadi, Siddhartha S; Adams, Marc A

2015-09-11

Walking is a widely accepted and frequently targeted health promotion approach to increase physical activity (PA). Interventions to increase PA have produced only small improvements. Stronger and more potent behavioral intervention components are needed to increase time spent in PA, improve cardiometabolic risk markers, and optimize health. Our aim is to present the rationale and methods from the WalkIT Trial, a 4-month factorial randomized controlled trial (RCT) in inactive, overweight/obese adults. The main purpose of the study was to evaluate whether intensive adaptive components result in greater improvements to adults' PA compared to the static intervention components. Participants enrolled in a 2x2 factorial RCT and were assigned to one of four semi-automated, text message-based walking interventions. Experimental components included adaptive versus static steps/day goals, and immediate versus delayed reinforcement. Principles of percentile shaping and behavioral economics were used to operationalize experimental components. A Fitbit Zip measured the main outcome: participants' daily physical activity (steps and cadence) over the 4-month duration of the study. Secondary outcomes included self-reported PA, psychosocial outcomes, aerobic fitness, and cardiorespiratory risk factors assessed pre/post in a laboratory setting. Participants were recruited through email listservs and websites affiliated with the university campus, community businesses and local government, social groups, and social media advertising. This study has completed data collection as of December 2014, but data cleaning and preliminary analyses are still in progress. We expect to complete analysis of the main outcomes in late 2015 to early 2016. The Walking Interventions through Texting (WalkIT) Trial will further the understanding of theory-based intervention components to increase the PA of men and women who are healthy, insufficiently active and are overweight or obese. WalkIT is one of the first studies focusing on the individual components of combined goal setting and reward structures in a factorial design to increase walking. The trial is expected to produce results useful to future research interventions and perhaps industry initiatives, primarily focused on mHealth, goal setting, and those looking to promote behavior change through performance-based incentives. ClinicalTrials.gov NCT02053259; https://clinicaltrials.gov/ct2/show/NCT02053259 (Archived by WebCite at http://www.webcitation.org/6b65xLvmg).

The clinical and cost-effectiveness of brief advice for excessive alcohol consumption among people attending sexual health clinics: a randomised controlled trial

PubMed Central

Crawford, Mike J; Sanatinia, Rahil; Barrett, Barbara; Byford, Sarah; Dean, Madeleine; Green, John; Jones, Rachael; Leurent, Baptiste; Sweeting, Michael J; Touquet, Robin; Greene, Linda; Tyrer, Peter; Ward, Helen; Lingford-Hughes, Anne

2015-01-01

Objectives To examine the clinical and cost-effectiveness of brief advice for excessive alcohol consumption among people who attend sexual health clinics. Methods Two-arm, parallel group, assessor blind, pragmatic, randomised controlled trial. 802 people aged 19 years or over who attended one of three sexual health clinics and were drinking excessively were randomised to either brief advice or control treatment. Brief advice consisted of feedback on alcohol and health, written information and an offer of an appointment with an Alcohol Health Worker. Control participants received a leaflet on health and lifestyle. The primary outcome was mean weekly alcohol consumption during the previous 90 days measured 6 months after randomisation. The main secondary outcome was unprotected sex during this period. Results Among the 402 randomised to brief advice, 397 (99%) received it. The adjusted mean difference in alcohol consumption at 6 months was −2.33 units per week (95% CI −4.69 to 0.03, p=0.053) among those in the active compared to the control arm of the trial. Unprotected sex was reported by 154 (53%) of those who received brief advice, and 178 (59%) controls (adjusted OR=0.89, 95% CI 0.63 to 1.25, p=0.496). There were no significant differences in costs between study groups at 6 months. Conclusions Introduction of universal screening and brief advice for excessive alcohol use among people attending sexual health clinics does not result in clinically important reductions in alcohol consumption or provide a cost-effective use of resources. Trial registration number Current Controlled Trials ISRCTN 99963322. PMID:24936090

Does Supplementation with Omega-3 PUFAs Add to the Prevention of Cardiovascular Disease?

PubMed

Rizos, Evangelos C; Elisaf, Moses S

2017-06-01

Omega-3 fatty acids are increasingly used for the protection of cardiovascular disease. The main but not the sole mechanism of action is the reduction of triglyceride levels. In this review, we summarize the effect of omega-3 supplements on all-cause and cardiovascular mortality, myocardial infarction, and stroke from the relevant randomized controlled trials. Twenty-one randomized controlled trials assessed omega-3 supplementation on mortality and cardiovascular-related outcomes. From these studies, as well as from the relevant meta-analyses, we found that omega-3 supplements do not exert a consistent benefit for cardiovascular protection. There is uncertainty of a clear profit from omega-3 supplementation in cardiovascular disease.

Clinical Impact Research – how to choose experimental or observational intervention study?

PubMed Central

Malmivaara, Antti

2016-01-01

Abstract Background: Interventions directed to individuals by health and social care systems should increase health and welfare of patients and customers. Aims: This paper aims to present and define a new concept Clinical Impact Research (CIR) and suggest which study design, either randomized controlled trial (RCT) (experimental) or benchmarking controlled trial (BCT) (observational) is recommendable and to consider the feasibility, validity, and generalizability issues in CIR. Methods: The new concept is based on a narrative review of the literature and on author’s idea that in intervention studies, there is a need to cover comprehensively all the main impact categories and their respective outcomes. The considerations on how to choose the most appropriate study design (RCT or BCT) were based on previous methodological studies on RCTs and BCTs and on author’s previous work on the concepts benchmarking controlled trial and system impact research (SIR). Results: The CIR covers all studies aiming to assess the impact for health and welfare of any health (and integrated social) care or public health intervention directed to an individual. The impact categories are accessibility, quality, equality, effectiveness, safety, and efficiency. Impact is the main concept, and within each impact category, both generic- and context-specific outcome measures are needed. CIR uses RCTs and BCTs. Conclusions: CIR should be given a high priority in medical, health care, and health economic research. Clinicians and leaders at all levels of health care can exploit the evidence from CIR. Key messagesThe new concept of Clinical Impact Research (CIR) is defined as a research field aiming to assess what are the impacts of healthcare and public health interventions targeted to patients or individuals.The term impact refers to all effects caused by the interventions, with particular emphasis on accessibility, quality, equality, effectiveness, safety, and efficiency. CIR uses two study designs: randomized controlled trials (RCTs) (experimental) and benchmarking controlled trials (BCTs) (observational). Suggestions on how to choose between RCT and BCT as the most suitable study design are presented.Simple way of determining the study question in CIR based on the PICO (patient, intervention, control intervention, outcome) framework is presented.CIR creates the scientific basis for clinical decisions. Clinicians and leaders at all levels of health care and those working for public health can use the evidence from CIR for the benefit of patients and the population. PMID:27494394

Clinical Impact Research - how to choose experimental or observational intervention study?

PubMed

Malmivaara, Antti

2016-11-01

Interventions directed to individuals by health and social care systems should increase health and welfare of patients and customers. This paper aims to present and define a new concept Clinical Impact Research (CIR) and suggest which study design, either randomized controlled trial (RCT) (experimental) or benchmarking controlled trial (BCT) (observational) is recommendable and to consider the feasibility, validity, and generalizability issues in CIR. The new concept is based on a narrative review of the literature and on author's idea that in intervention studies, there is a need to cover comprehensively all the main impact categories and their respective outcomes. The considerations on how to choose the most appropriate study design (RCT or BCT) were based on previous methodological studies on RCTs and BCTs and on author's previous work on the concepts benchmarking controlled trial and system impact research (SIR). The CIR covers all studies aiming to assess the impact for health and welfare of any health (and integrated social) care or public health intervention directed to an individual. The impact categories are accessibility, quality, equality, effectiveness, safety, and efficiency. Impact is the main concept, and within each impact category, both generic- and context-specific outcome measures are needed. CIR uses RCTs and BCTs. CIR should be given a high priority in medical, health care, and health economic research. Clinicians and leaders at all levels of health care can exploit the evidence from CIR. Key messages The new concept of Clinical Impact Research (CIR) is defined as a research field aiming to assess what are the impacts of healthcare and public health interventions targeted to patients or individuals. The term impact refers to all effects caused by the interventions, with particular emphasis on accessibility, quality, equality, effectiveness, safety, and efficiency. CIR uses two study designs: randomized controlled trials (RCTs) (experimental) and benchmarking controlled trials (BCTs) (observational). Suggestions on how to choose between RCT and BCT as the most suitable study design are presented. Simple way of determining the study question in CIR based on the PICO (patient, intervention, control intervention, outcome) framework is presented. CIR creates the scientific basis for clinical decisions. Clinicians and leaders at all levels of health care and those working for public health can use the evidence from CIR for the benefit of patients and the population.

Multifaceted intervention to decrease the rate of severe postpartum haemorrhage: the PITHAGORE6 cluster-randomised controlled trial

PubMed Central

Deneux-Tharaux, Catherine; Dupont, Corinne; Colin, C.; Rabilloud, Muriel; Touzet, S.; Lansac, Jacques; Harvey, Thierry; Tessier, Véronique; Chauleur, C.; Pennehouat, G.; Morin, X.; Bouvier-Colle, Marie-Hélène; Rudigoz, René

2010-01-01

Objective Decreasing the prevalence of severe postpartum haemorrhages (PPH) is a major obstetrical challenge. These are often considered to be associated with substandard initial care. Strategies to increase the appropriateness of early management of PPH must be assessed. We tested the hypothesis that a multifaceted intervention aimed at increasing the translation into practice of a protocol for early management of PPH, would reduce the incidence of severe PPH. Design Cluster-randomised trial Population 106 maternity units in 6 French regions Methods Maternity units were randomly assigned to receive the intervention, or to have the protocol passively disseminated. The intervention combined outreach visits to discuss the protocol in each local context, reminders, and peer reviews of severe cases, and was implemented in each maternity hospital by a team pairing an obstetrician and a midwife. Main outcome measures The primary outcome was the incidence of severe PPH, defined as a composite of one or more of: transfusion, embolisation, surgical procedure, transfer to intensive care, peripartum haemoglobin delta of 4 g/dl or more, death. The main secondary outcomes were PPH management practices. Results The mean rate of severe PPH was 1.64% (SD0.80) in the intervention units and 1.65% (SD0.96) in control units; difference not significant. Some elements of PPH management were applied more frequently in intervention units –help from senior staff (p=0.005)-, or tended to – second line pharmacological treatment (p=0.06), timely blood test (p=0.09). Conclusion This educational intervention did not affect the rate of severe PPH as compared to control units, although it improved some practices. Trial registration: ClinicalTrials.gov NCT 00344929 PMID:20573150

Authors of clinical trials reported individual and financial conflicts of interest more frequently than institutional and nonfinancial ones: a methodological survey.

PubMed

Hakoum, Maram B; Jouni, Nahla; Abou-Jaoude, Eliane A; Hasbani, Divina Justina; Abou-Jaoude, Elias A; Lopes, Luciane Cruz; Khaldieh, Mariam; Hammoud, Mira Z; Al-Gibbawi, Mounir; Anouti, Sirine; Guyatt, Gordon; Akl, Elie A

2017-07-01

Conflicts of interest (COIs) are increasingly recognized as important to disclose and manage in health research. The objective of this study was to assess the reporting of both financial and nonfinancial COI by authors of randomized controlled trials published in a representative sample of clinical journals. We searched Ovid Medline and included a random sample of 200 randomized controlled trials published in 2015 in one of the 119 Core Clinical Journals. We classified COI using a comprehensive framework that includes the following: individual COIs (financial, professional, scholarly, advocatory, personal) and institutional COIs (financial, professional, scholarly, and advocatory). We conducted descriptive and regression analyses. Of the 200 randomized controlled trials, 188 (94%) reported authors' COI disclosures that were available in the main document (92%) and as International Committee of Medical Journal Editors forms accessible online (12%). Of the 188 trials, 57% had at least one author reporting at least one COI; in all these trials, at least one author reported financial COI. Institutional COIs (11%) and nonfinancial COIs (4%) were less commonly reported. References to COI disclosure statements for editors (1%) and medical writers (0%) were seldom present. Regression analyses showed positive associations between reporting individual financial COI and higher journal impact factor (odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.02-1.10), larger number of authors (OR = 1.10, 95% CI 1.02-1.20), affiliation with an institution from a high-income country (OR = 16.75, 95% CI 3.38-82.87), and trials reporting on pharmacological interventions (OR = 2.28, 95% CI 1.13-4.62). More than half of published randomized controlled trials report that at least one author has a COI. Trial authors report financial COIs more often than nonfinancial COIs and individual COIs more frequently than institutional COIs. Copyright © 2017 Elsevier Inc. All rights reserved.

School-based intervention to improve the mental health of low-income, secondary school students in Santiago, Chile (YPSA): study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Depression is common and can have devastating effects on the life of adolescents. Psychological interventions are the first-line for treating or preventing depression among adolescents. This proposal aims to evaluate a school-based, universal psychological intervention to reduce depressive symptoms among student's aged 13-14 attending municipal state secondary schools in Santiago, Chile. Study design This is a cluster randomised controlled trial with schools as the main clusters. We compared this intervention with a control group in a study involving 22 schools, 66 classes and approximately 2,600 students. Students in the active schools attended 11 weekly and 3 booster sessions of an intervention based on cognitive-behavioural models. The control schools received their usual but enhanced counselling sessions currently included in their curriculum. Mean depression scores and indicators of levels of functioning were assessed at 3 and 12 months after the completion of the intervention in order to assess the effectiveness of the intervention. Direct and indirect costs were measured in both groups to assess the cost-effectiveness of this intervention. Discussion As far as we are aware this is the first cluster randomised controlled trial of a school intervention for depression among adolescents outside the Western world. Trial Registration ISRCTN19466209 PMID:21333015

Figures in clinical trial reports: current practice & scope for improvement.

PubMed

Pocock, Stuart J; Travison, Thomas G; Wruck, Lisa M

2007-11-19

Most clinical trial publications include figures, but there is little guidance on what results should be displayed as figures and how. To evaluate the current use of figures in Trial reports, and to make constructive suggestions for future practice. We surveyed all 77 reports of randomised controlled trials in five general medical journals during November 2006 to January 2007. The numbers and types of figures were determined, and then each Figure was assessed for its style, content, clarity and suitability. As a consequence, guidelines are developed for presenting figures, both in general and for each specific common type of Figure. Most trial reports contained one to three figures, mean 2.3 per article. The four main types were flow diagram, Kaplan Meier plot, Forest plot (for subgroup analyses) and repeated measures over time: these accounted for 92% of all figures published. For each type of figure there is a considerable diversity of practice in both style and content which we illustrate with selected examples of both good and bad practice. Some pointers on what to do, and what to avoid, are derived from our critical evaluation of these articles' use of figures. There is considerable scope for authors to improve their use of figures in clinical trial reports, as regards which figures to choose, their style of presentation and labelling, and their specific content. Particular improvements are needed for the four main types of figures commonly used.

Design and challenges of a randomized controlled trial for reducing risk factors of metabolic syndrome in Mexican women through water intake

PubMed Central

Hernández-Cordero, Sonia; González-Castell, Dinorah; Rodríguez-Ramírez, Sonia; Villanueva-Borbolla, María Ángeles; Unar, Mishel; Barquera, Simón; de Cossío, Teresita González; Rivera-Dommarco, Juan; Popkin, Barry M

2014-01-01

Objective To describe the design, methods, and challenges encountered during a randomized clinical trial aimed to promote water intake for reducing risks of metabolic syndrome in Mexican women. Materials and methods In a randomized clinical trial in Cuernavaca, Mexico, overweight and obese (body mass index [BMI] ≥ 25 < 39) women, 18 – < 45 years old with an intake of sugar-sweetened beverages ≥ 250 kilocalories per day (kcal/day) were randomly allocated to the water and education provision group (n = 120) or the education provision only group (n = 120). Results We screened 1 756 women. The main difficulties encountered were identifying participants with the recruitment criteria, delivering water to participants, and the time demanded from the study participants. Conclusions The trial’s main challenges were difficulties surrounding recruitment, delivery of the intervention, and the time demanded from the study participants. Modifications were effectively implemented without jeopardizing the original protocol. PMID:24715012

A Cluster-Randomized Trial of Restorative Practices: An Illustration to Spur High-Quality Research and Evaluation

PubMed Central

Acosta, Joie D.; Chinman, Matthew; Ebener, Patricia; Phillips, Andrea; Xenakis, Lea; Malone, Patrick S.

2017-01-01

Restorative Practices in schools lack rigorous evaluation studies. As an example of rigorous school-based research, this paper describes the first randomized control trial of restorative practices to date, the Study of Restorative Practices. It is a 5-year, cluster-randomized controlled trial (RCT) of the Restorative Practices Intervention (RPI) in 14 middle schools in Maine to assess whether RPI impacts both positive developmental outcomes and problem behaviors and whether the effects persist during the transition from middle to high school. The two-year RPI intervention began in the 2014–2015 school year. The study’s rationale and theoretical concerns are discussed along with methodological concerns including teacher professional development. The theoretical rationale and description of the methods from this study may be useful to others conducting rigorous research and evaluation in this area. PMID:28936104

78 FR 37228 - Cooperative Agreement To Support the Western Center for Food Safety

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-20

... Davis main campus and experimental stations provide invaluable access to one of the leading food... sites for experimental trials is instrumental to FDA receiving the most current scientifically validated... facilitate industry compliance with preventive control standards. Information gleaned from this research has...

EDUCORE project: a clinical trial, randomised by clusters, to assess the effect of a visual learning method on blood pressure control in the primary healthcare setting

PubMed Central

2010-01-01

Background High blood pressure (HBP) is a major risk factor for cardiovascular disease (CVD). European hypertension and cardiology societies as well as expert committees on CVD prevention recommend stratifying cardiovascular risk using the SCORE method, the modification of lifestyles to prevent CVD, and achieving good control over risk factors. The EDUCORE (Education and Coronary Risk Evaluation) project aims to determine whether the use of a cardiovascular risk visual learning method - the EDUCORE method - is more effective than normal clinical practice in improving the control of blood pressure within one year in patients with poorly controlled hypertension but no background of CVD; Methods/Design This work describes a protocol for a clinical trial, randomised by clusters and involving 22 primary healthcare clinics, to test the effectiveness of the EDUCORE method. The number of patients required was 736, all between 40 and 65 years of age (n = 368 in the EDUCORE and control groups), all of whom had been diagnosed with HBP at least one year ago, and all of whom had poorly controlled hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic ≥ 90 mmHg). All personnel taking part were explained the trial and trained in its methodology. The EDUCORE method contemplates the visualisation of low risk SCORE scores using images embodying different stages of a high risk action, plus the receipt of a pamphlet explaining how to better maintain cardiac health. The main outcome variable was the control of blood pressure; secondary outcome variables included the SCORE score, therapeutic compliance, quality of life, and total cholesterol level. All outcome variables were measured at the beginning of the experimental period and again at 6 and 12 months. Information on sex, age, educational level, physical activity, body mass index, consumption of medications, change of treatment and blood analysis results was also recorded; Discussion The EDUCORE method could provide a simple, inexpensive means of improving blood pressure control, and perhaps other health problems, in the primary healthcare setting; Trial registration The trial was registered with ClinicalTrials.gov, number NCT01155973 [http://ClinicalTrials.gov]. PMID:20673325

Impact of Free Glasses and a Teacher Incentive on Children's Use of Eyeglasses: A Cluster-Randomized Controlled Trial.

PubMed

Yi, Hongmei; Zhang, Haiqing; Ma, Xiaochen; Zhang, Linxiu; Wang, Xiuqin; Jin, Ling; Naidoo, Kovin; Minto, Hasan; Zou, Haidong; Lu, Lina; Rozelle, Scott; Congdon, Nathan

2015-11-01

To study the effect of free glasses combined with teacher incentives on in-school glasses wear among Chinese urban migrant children. Cluster-randomized controlled trial. Children with visual acuity (VA) ≤6/12 in either eye owing to refractive error in 94 randomly chosen primary schools underwent randomization by school to receive free glasses, education on their use, and a teacher incentive (Intervention), or glasses prescriptions only (Control). Intervention group teachers received a tablet computer if ≥80% of children given glasses wore them during unannounced visits 6 weeks and 6 months (main outcome) after intervention. Among 4376 children, 728 (16.7%, mean age 10.9 years, 51.0% boys) met enrollment criteria and were randomly allocated, 358 (49.2%, 47 schools) to Intervention and 370 (50.8%, 47 schools) to Control. Among these, 693 children (95.2%) completed the study and underwent analysis. Spectacle wear was significantly higher at 6 months among Intervention children (Observed [main outcome]: 68.3% vs 23.9%, adjusted odds ratio [OR] = 11.5, 95% confidence interval [CI] 5.91-22.5, P < .001; Self-reported: 90.6% vs 32.1%, OR = 43.7, 95% CI = 21.7-88.5, P < .001). Other predictors of observed wear at 6 months included baseline spectacle wear (P < .001), uncorrected VA <6/18 (P = .01), and parental spectacle wear (P = .02). The 6-month observed wear rate was only 41% among similar-aged children provided free glasses in our previous trial without teacher incentives. Free spectacles and teacher incentives maintain classroom wear in the large majority of children needing glasses over a school year. Low wear among Control children demonstrates the need for interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

Insecticide treated curtains and residual insecticide treatment to control Aedes aegypti: An acceptability study in Santiago de Cuba.

PubMed

Pérez, Dennis; Van der Stuyft, Patrick; Toledo, María Eugenia; Ceballos, Enrique; Fabré, Francisco; Lefèvre, Pierre

2018-01-01

Within the context of a field trial conducted by the Cuban vector control program (AaCP), we assessed acceptability of insecticide-treated curtains (ITCs) and residual insecticide treatment (RIT) with deltamethrin by the community. We also assessed the potential influence of interviewees' risk perceptions for getting dengue and disease severity. We embedded a qualitative study using in-depth interviews in a cluster randomized trial (CRT) testing the effectiveness of ITCs and RIT in Santiago de Cuba. In-depth interviews (N = 38) were conducted four and twelve months after deployment of the tools with people who accepted the tools, who stopped using them and who did not accept the tools. Data analysis was deductive. Main reasons for accepting ITCs at the start of the trial were perceived efficacy and not being harmful to health. Constraints linked to manufacturer instructions were the main reason for not using ITCs. People stopped using the ITCs due to perceived allergy, toxicity and low efficacy. Few heads of households refused RIT despite the noting reasons for rejection, such as allergy, health hazard and toxicity. Positive opinions of the vector control program influenced acceptability of both tools. However, frequent insecticide fogging as part of routine AaCP vector control actions diminished perceived efficacy of both tools and, therefore, acceptability. Fifty percent of interviewees did feel at risk for getting dengue and considered dengue a severe disease. However, this did not appear to influence acceptability of ITCs or RIT. Acceptability of ITCs and RIT was linked to acceptability of AaCP routine vector control activities. However, uptake and use were not always an indication of acceptability. Factors leading to acceptability may be best identified using qualitative methods, but more research is needed on the concept of acceptability and its measurement.

Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in Obese Older Patients with Heart Failure and Preserved Ejection Fraction A Randomized, Controlled Trial

PubMed Central

Kitzman, Dalane W.; Brubaker, Peter; Morgan, Timothy; Haykowsky, Mark; Hundley, Gregory; Kraus, William E.; Eggebeen, Joel; Nicklas, Barbara J.

2016-01-01

Importance More than 80% of patients with heart failure with preserved ejection fraction (HFPEF), the most common form of HF among older persons, are overweight/obese. Exercise intolerance is the primary symptom of chronic HFPEF and a major determinant of reduced quality-of-life (QOL). Objective To determine whether caloric restriction (Diet), or aerobic exercise training (Exercise), improves exercise capacity and QOL in obese older HFPEF patients. Design Randomized, attention-controlled, 2x2 factorial trial conducted from February 2009 November 2014. Setting Urban academic medical center. Participants 100 older (67±5 years) obese (BMI=39.3±5.6kg/m2) women (n=81) and men (n=19) with chronic, stable HFPEF enrolled from 577 patients initially screened (366 excluded by inclusion / exclusion criteria, 31 for other reasons, 80 declined participation). Twenty-six participants were randomized to Exercise alone, 24 to Diet alone, 25 to Diet+Exercise, and 25 to Control; 92 completed the trial. Interventions 20 weeks of Diet and/or Exercise; Attention Control consisted of telephone calls every 2 weeks. Main Outcomes and Measures Exercise capacity measured as peak oxygen consumption (VO2, ml/kg/min; primary outcome) and QOL measured by the Minnesota Living with HF Questionnaire (MLHF) total score (co-primary outcome; score range: 0–105, higher scores indicate worse HF-related QOL). Results By main effects analysis, peak VO2 was increased significantly by both interventions: Exercise main effect 1.2 ml/kg/min (95%CI: 0.7,1.7; p<0.001); Diet main effect 1.3 ml/kg/min (95%CI: 0.8,1.8; p<0.001). The combination of Exercise+Diet was additive (complementary) for peak VO2 (joint effect 2.5 ml/kg/min). The change in MLHF total score was non-significant with Exercise (main effect −1 unit; 95%CI: −8,5; p=0.70) and with Diet (main effect −6 units; 95%CI: −12,1; p=0.078). The change in peak VO2 was positively correlated with the change in percent lean body mass (r=0.32; p=0.003) and the change in thigh muscle/intermuscular fat ratio (r=0.27; p=0.02). There were no study-related serious adverse events. Exercise attendance was 84±14%; Diet compliance was 99±1%. Body weight decreased by 7±1 kg (7%) in Diet, 4±1 kg (3%) in Exercise, 11±1 kg (10%) in Exercise+Diet, and 1±1 kg (1%) in Control. Conclusion and Relevance Among obese older patients with clinically stable heart failure and preserved ejection fraction, caloric restriction diet or aerobic exercise training increased peak oxygen consumption, and the effects may be additive. Neither intervention had a significant effect on quality of life as measured by the Minnesota Living with Heart Failure Questionnaire, Clinical Trial Registration Clinicaltrials.gov, NCT00959660; https://clinicaltrials.gov/ct2/show/NCT00959660 PMID:26746456

Debt Counselling for Depression in Primary Care: an adaptive randomised controlled pilot trial (DeCoDer study).

PubMed

Gabbay, Mark B; Ring, Adele; Byng, Richard; Anderson, Pippa; Taylor, Rod S; Matthews, Caryn; Harris, Tirril; Berry, Vashti; Byrne, Paula; Carter, Elliot; Clarke, Pam; Cocking, Laura; Edwards, Suzanne; Emsley, Richard; Fornasiero, Mauro; Frith, Lucy; Harris, Shaun; Huxley, Peter; Jones, Siw; Kinderman, Peter; King, Michael; Kosnes, Liv; Marshall, Daniel; Mercer, Dave; May, Carl; Nolan, Debbie; Phillips, Ceri; Rawcliffe, Tim; Sardani, Alexandra V; Shaw, Elizabeth; Thompson, Sam; Vickery, Jane; Wainman, Brian; Warner, Mark

2017-06-01

Depression and debt are common in the UK. Debt Counselling for Depression in Primary Care: an adaptive randomised controlled pilot trial (DeCoDer) aimed to assess the clinical effectiveness and cost-effectiveness of the addition of a primary care debt counselling advice service to usual care for patients with depression and debt. However, the study was terminated early during the internal pilot trial phase because of recruitment delays. This report describes the rationale, methods and findings of the pilot study, and implications for future research. The overarching aim of the internal pilot was to identify and resolve problems, thereby assessing the feasibility of the main trial. The specific objectives were to confirm methods for practice recruitment and the ability to recruit patients via the proposed approaches; to determine the acceptability of the study interventions and outcome measures; to assess contamination; to confirm the randomisation method for main trial and the level of participant attrition; and to check the robustness of data collection systems. An adaptive, parallel, two-group multicentre randomised controlled pilot trial with a nested mixed-methods process and economic evaluation. Both individual- and cluster (general practice)-level were was used in the pilot phase to assign participants to intervention or control groups. General practices in England and Wales. Individuals were included who were aged ≥ 18 years, scored ≥ 14 on the Beck Depression Inventory II and self-identified as having debt worries. The main exclusion criteria were being actively suicidal or psychotic and/or severely depressed and unresponsive to treatment; having a severe addiction to alcohol/illicit drugs; being unable/unwilling to give written informed consent; currently participating in other research including follow-up phases; having received Citizens Advice Bureau (CAB) debt advice in the past year; and not wanting debt advice via a general practice. The participants in the intervention group were given debt advice provided by the CAB and shared biopsychosocial assessment, in addition to treatment as usual (TAU) and two debt advice leaflets. The participants in the control group were given advice leaflets provided by the general practitioner and TAU only. (1) Outcomes of the pilot trial - the proportion of eligible patients who consented, the number of participants recruited compared with target, assessment of contamination, and assessment of patient satisfaction with intervention and outcome measures. (2) Participant outcomes - primary - Beck Depression Inventory II; secondary - psychological well-being, health and social care utilisation, service satisfaction, substance misuse, record of priority/non-priority debts, life events and difficulties, and explanatory measures. Outcomes were assessed at baseline (pre-randomisation) and at 4 months post randomisation. Other data sources - qualitative interviews were conducted with participants, clinicians and CAB advisors. Of the 238 expressions of interest screened, 61 participants (26%) were recruited and randomised (32 in the intervention group and 29 in the control group). All participants provided baseline outcomes and 52 provided the primary outcome at 4 months' follow-up (14.7% dropout). Seventeen participants allocated to the intervention saw a CAB advisor. Descriptive statistics are reported for participants with complete outcomes at baseline and 4 months' follow-up. Our qualitative findings suggest that the relationship between debt and depression is complex, and the impact of each on the other is compounded by other psychological, social and contextual influences. As a result of low recruitment, this trial was terminated at the internal pilot phase and was too small for inferential statistical analysis. We recommend ways to reduce this risk when conducting complex trials among vulnerable populations recruited in community settings. These cover trial design, the design and delivery of interventions, recruitment strategies and support for sites. Current Controlled Trials ISRCTN79705874. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 35. See the NIHR Journals Library website for further project information. Mark Gabbay and Adele Ring are part-funded by NIHR Collaborations for Leadership in Applied Health Research and Care (CLAHRC) North West Coast and Richard Byng and Rod S Taylor, Vashti Berry and Elizabeth Shaw part-funded by NIHR CLAHRC South West Peninsula.

[How to adapt to the requirements of "clinical value-oriented drug innovation" for pharmaceutical research in application process of new traditional Chinese medicine].

PubMed

Jin, Fang

2017-05-01

On August 9, 2015, the State Council promulgated the "Opinions of the State Council on the reform of drug and medical device review and approval system" (Guofa 2015 No. 44), and established the "clinical value-oriented drug innovation" model to encourage the research and development of new drugs. Following that, China Food and Drug Administration (CFDA) promulgated the "Notice on several policies for drug registration review and approval" (2015 No. 230 ) on November 11, 2015, clearly specifying that CFDA would "implement one-time approval for clinical trials application of the new drugs, and no longer take a phased declaration, review and approval system; for the new drugs that apply for clinical trials, mainly review the scientific natureof the clinical protocols and the risk control of the new drugs to guarantee the safety of subjects". Accordingly, the evaluation ideas and forms of new drug registration have also been adjusted greatly. For example, issues like the rationality of the drug manufacturing process, whether the scale can reflect the stability of the process, whether the preparation process is sufficient, and whether the choice of dosage form is reasonable are no longer the focus of evaluation before clinical trials. Issues regarding whether the preparation process design is reasonable, whether the effective components can be transferred to the preparation to a maximum extent, whether the process parameters determined in small and middle pilot trials can adapt to the requirements of mass production, no longer act as the reasons for refusing the clinical trials. The corresponding risks shall be borne by the applicant as the subject of liability. The focus in registration evaluation is mainly transferred to how to ensure the consistence of quality between clinical trial samples and the samples already available on market by guaranteeing stable sources of drug raw materials and stable quality of medicines as well as control of the whole preparation process. These issues run through the whole process of new drug development, but also have different focuses in different stages. According to the "Measures on communicating about drug research and development and technical review" (2016 No. 94) (On Trial) issued by CFDA on June 2, 2016, the applicants may communicate with the drug evaluation center in different phases in the process of new drugs registration in respects of medicine material problems, technological problems, and quality control of the preparations. In this paper, the transformation of Chinese medicine research model was described mainly in the following aspects: how to control the quality of medicines from origins, technology design of the preparation and technology process research, and how to establish whole-process quality system. The paper also reflects the concept that the quality of new Chinese drugs research and development comes from design. Copyright© by the Chinese Pharmaceutical Association.

Vector and reservoir control for preventing leishmaniasis

PubMed Central

González, Urbà; Pinart, Mariona; Sinclair, David; Firooz, Alireza; Enk, Claes; Vélez, Ivan D; Esterhuizen, Tonya M; Tristan, Mario; Alvar, Jorge

2015-01-01

Background Leishmaniasis is caused by the Leishmania parasite, and transmitted by infected phlebotomine sandflies. Of the two distinct clinical syndromes, cutaneous leishmaniasis (CL) affects the skin and mucous membranes, and visceral leishmaniasis (VL) affects internal organs. Approaches to prevent transmission include vector control by reducing human contact with infected sandflies, and reservoir control, by reducing the number of infected animals. Objectives To assess the effects of vector and reservoir control interventions for cutaneous and for visceral leishmaniasis. Search methods We searched the following databases to 13 January 2015: Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS and WHOLIS, Web of Science, and RePORTER. We also searched trials registers for ongoing trials. Selection criteria Randomized controlled trials (RCTs) evaluating the effects of vector and reservoir control interventions in leishmaniasis-endemic regions. Data collection and analysis Two review authors independently searched for trials and extracted data from included RCTs. We resolved any disagreements by discussion with a third review author. We assessed the quality of the evidence using the GRADE approach. Main results We included 14 RCTs that evaluated a range of interventions across different settings. The study methods were generally poorly described, and consequently all included trials were judged to be at high or unclear risk of selection and reporting bias. Only seven trials reported clinical outcome data which limits our ability to make broad generalizations to different epidemiological settings and cultures. Cutaneous leishmaniasis One four-arm RCT from Afghanistan compared indoor residual spraying (IRS), insecticide-treated bednets (ITNs), and insecticide-treated bedsheets, with no intervention. Over 15 months follow-up, all three insecticide-based interventions had a lower incidence of CL than the control area (IRS: risk ratio (RR) 0.61, 95% confidence interval (CI) 0.38 to 0.97, 2892 participants, moderate quality evidence; ITNs: RR 0.32, 95% CI 0.18 to 0.56, 2954 participants, low quality evidence; ITS: RR 0.34, 95% CI 0.20 to 0.57, 2784 participants, low quality evidence). No difference was detected between the three interventions (low quality evidence). One additional trial of ITNs from Iran was underpowered to show a difference. Insecticide treated curtains were compared with no intervention in one RCT from Venezuela, where there were no CL episodes in the intervention areas over 12 months follow-up compared to 142 in control areas (RR 0.00, 95% CI 0.00 to 0.49, one trial, 2938 participants, low quality evidence). Personal protection using insecticide treated clothing was evaluated by two RCTs in soldiers, but the trials were underpowered to reliably detect effects on the incidence of CL (RR 0.40, 95% CI 0.13 to 1.20, two trials, 558 participants, low quality evidence). Visceral leishmaniasis In a single RCT of ITNs versus no intervention from India and Nepal, the incidence of VL was low in both groups and no difference was detected (RR 0.99, 95% CI 0.46 to 2.15, one trial, 19,810 participants, moderate quality evidence). Two trials from Brazil evaluated the effects of culling infected dogs compared to no intervention or IRS. Although they report a reduction in seroconversion over 18 months follow-up, they did not measure or report effects on clinical disease. Authors' conclusions Using insecticides to reduce phlebotomine sandfly numbers may be effective at reducing the incidence of CL, but there is insufficient evidence from trials to know whether it is better to spray the internal walls of houses or to treat bednets, curtains, bedsheets or clothing. PLAIN LANGUAGE SUMMARY Vector and reservoir control for preventing leishmaniasis This review summarises trials evaluating different measures to prevent leishmaniasis. After searching for relevant trials up to January 2015, we included 14 randomized controlled trials. What is vector and reservoir control and how might they prevent leishmaniasis? Leishmaniasis is a group of infectious diseases caused by Leishmania parasites, which are transmitted between humans and animals by the bite of infected phlebotomine sandflies. There are two main clinical diseases: cutaneous leishmaniasis (CL), where parasites infect the skin, and visceral leishmaniasis (VL), where they infect the internal organs. Leishmaniasis could be prevented by reducing human contact with infected phlebotomine sandflies (the vector), or by reducing the number of infected animals (the reservoir). What the research says? Cutaneous leishmaniasis Using insecticides to reduce the number of sandflies may be effective at reducing the number of new cases of cutaneous leishmaniasis (low quality evidence). However, there is not enough evidence to know whether it is better to use insecticides to spray the internal walls of houses, or use insecticide treated bednets, bedsheets, or curtains. Personal protection using insecticide treated clothing was also evaluated in two small trials in soldiers, but the trials were too small to know whether this was effective (low quality evidence). Visceral leishmaniasis Insecticide treated nets may not be effective at preventing visceral leishmaniasis but this has only been tested in a single trial from India and Nepal (low quality evidence). Although culling dogs is sometimes discussed as a potential way to reduce visceral leishmaniasis, this has not been tested in trials measuring clinical disease. PMID:26246011

Perception of young adults with sickle cell disease or sickle cell trait about participation in the CHOICES randomized controlled trial.

PubMed

Hershberger, Patricia E; Gallo, Agatha M; Molokie, Robert; Thompson, Alexis A; Suarez, Marie L; Yao, Yingwei; Wilkie, Diana J

2016-06-01

To gain an in-depth understanding of the perceptions of young adults with sickle cell disease and sickle cell trait about parenthood and participating in the CHOICES randomized controlled trial that used computer-based, educational programmes. In the USA, there is insufficient education to assure that all young adults with sickle cell disease or sickle cell trait understand genetic inheritance risks and reproductive options to make informed reproductive decisions. To address this educational need, we developed a computer-based, multimedia program (CHOICES) and reformatted usual care into a computer-based (e-Book) program. We then conducted a two-year randomized controlled trial that included a qualitative component that would deepen understanding of young adults' perceptions of parenthood and use of computer-based, educational programmes. A qualitative descriptive approach completed after a randomized controlled trial. Sixty-eight men and women of childbearing age participated in semi-structured interviews at the completion of the randomized controlled trial from 2012-2013. Thematic content analysis guided the qualitative description. Three main themes were identified: (1) increasing knowledge and new ways of thinking and behaving; (2) rethinking parenting plans; and (3) appraising the program design and delivery. Most participants reported increased knowledge and rethinking of their parenting plans and were supportive of computer-based learning. Some participants expressed difficulty in determining individual transmission risks. Participants perceived the computer programs as beneficial to their learning. Future development of an Internet-based educational programme is warranted, with emphasis on providing tailored education or memory boosters about individual transmission risks. © 2015 John Wiley & Sons Ltd.

Interrupted time-series analysis yielded an effect estimate concordant with the cluster-randomized controlled trial result.

PubMed

Fretheim, Atle; Soumerai, Stephen B; Zhang, Fang; Oxman, Andrew D; Ross-Degnan, Dennis

2013-08-01

We reanalyzed the data from a cluster-randomized controlled trial (C-RCT) of a quality improvement intervention for prescribing antihypertensive medication. Our objective was to estimate the effectiveness of the intervention using both interrupted time-series (ITS) and RCT methods, and to compare the findings. We first conducted an ITS analysis using data only from the intervention arm of the trial because our main objective was to compare the findings from an ITS analysis with the findings from the C-RCT. We used segmented regression methods to estimate changes in level or slope coincident with the intervention, controlling for baseline trend. We analyzed the C-RCT data using generalized estimating equations. Last, we estimated the intervention effect by including data from both study groups and by conducting a controlled ITS analysis of the difference between the slope and level changes in the intervention and control groups. The estimates of absolute change resulting from the intervention were ITS analysis, 11.5% (95% confidence interval [CI]: 9.5, 13.5); C-RCT, 9.0% (95% CI: 4.9, 13.1); and the controlled ITS analysis, 14.0% (95% CI: 8.6, 19.4). ITS analysis can provide an effect estimate that is concordant with the results of a cluster-randomized trial. A broader range of comparisons from other RCTs would help to determine whether these are generalizable results. Copyright © 2013 Elsevier Inc. All rights reserved.

The use of autologous platelet-rich plasma in the orthopedic setting.

PubMed

Cohn, Claudia S; Lockhart, Evelyn; McCullough, J Jeffrey

2015-07-01

Autologous platelet-rich plasma (aPRP) is widely used with orthopedic patients to help treat injuries to tendons, cartilage, ligaments, and muscle. A comprehensive review of the literature was conducted to evaluate aPRP's efficacy and compare available methods. In addition, the production and administration of aPRP were explored. A literature search was performed. Randomized controlled clinical trials (RCTs) in orthopedic procedures on adult patients were included and assessed for methodologic quality. The main outcomes were pain relief, increase in function, structural integrity, and "healing" based on various validated scales. Twelve RCTs and one controlled cohort were included (four lateral epicondylitis, two chronic Achilles tendinopathy, two anterior cruciate ligament injury, and five rotator cuff injuries). Four trials reported some benefit from aPRP versus controls while eight trials found no benefit from aPRP applications versus control. One study had too many patients withdraw from the control arm for acceptable data interpretation. All protocols used a different aPRP formulation or method of delivery or application. Despite its popularity, there are no standardized criteria that define aPRP. Different techniques yield wide variability in terms of platelet count and concentration. These variations make it difficult to compare clinical trials that use aPRP or draw conclusions concerning its clinical efficacy in orthopedic procedures. Blood bankers have experience in the production of standardized blood components. This expertise may be used to develop and implement protocols for the production and administration of aPRP, as well as quality control measures. © 2015 AABB.

How informed is declared altruism in clinical trials? A qualitative interview study of patient decision-making about the QUEST trials (Quality of Life after Mastectomy and Breast Reconstruction).

PubMed

Bidad, Natalie; MacDonald, Lindsay; Winters, Zoë E; Edwards, Sarah J L; Emson, Marie; Griffin, Clare L; Bliss, Judith; Horne, Rob

2016-09-02

Randomised controlled trials (RCTs) often fail to recruit sufficient participants, despite altruism being cited as their motivation. Previous investigations of factors influencing participation decisions have been methodologically limited. This study evaluated how women weigh up different motivations after initially expressing altruism, and explored their understanding of a trial and its alternatives. The trial was the 'Quality of Life after Mastectomy and Breast Reconstruction' (QUEST) trial. Thirty-nine women participated in qualitative interviews 1 month post-surgery. Twenty-seven women (10 trial decliners and 17 acceptors) who spontaneously mentioned 'altruism' were selected for thematic analysis. Verbatim transcripts were coded independently by two researchers. Participants' motivations to accept or decline randomisation were cross-referenced with their understanding of the QUEST trials and the process of randomisation. The seven emerging themes were: (1) altruism expressed by acceptors and decliners; (2) overriding personal needs in decliners; (3) pure altruism in acceptors; (4) 'hypothetical altruism' amongst acceptors; (5) weak altruism amongst acceptors; (6) conditional altruism amongst acceptors; and (7) sense of duty to participate. Poor understanding of the trial rationale and its implications was also evident. Altruism was a motivating factor for participation in the QUEST randomised controlled trials where the main outcomes comprised quality of life and allocated treatments comprised established surgical procedures. Women's decisions were influenced by their understanding of the trial. Both acceptors and decliners of the trial expressed 'altruism', but most acceptors lacked an obvious treatment preference, hoped for personal benefits regarding a treatment allocation, or did not articulate complete understanding of the trial. QUEST A, ISRCTN38846532 ; Date assigned 6 January 2010. QUEST B, ISRCTN92581226 ; Date assigned 6 January 2010.

An Intervention with Mineral Water Decreases Cardiometabolic Risk Biomarkers. A Crossover, Randomised, Controlled Trial with Two Mineral Waters in Moderately Hypercholesterolaemic Adults.

PubMed

Toxqui, Laura; Vaquero, M Pilar

2016-06-28

Water intake is essential for health maintenance and disease prevention. The effects of an intervention with two mineral waters, sodium-bicarbonated mineral water (BW) or control mineral water low in mineral content (CW), on cardiometabolic risk biomarkers were studied. In a randomised-controlled crossover-trial, sixty-four moderately hypercholesterolaemic adults were randomly assigned to consume 1 L/day of either BW (sodium, 1 g/L; bicarbonate, 2 g/L) or CW with the main meals for eight weeks, separated by an eight-week washout period. Blood lipids, lipid oxidation, glucose, insulin, aldosterone, urine pH, urinary electrolytes, blood pressure, body weight, fluid intake, energy, and nutrients from total diet and beverages were determined. Total cholesterol, LDL cholesterol, and glucose decreased (p < 0.01), oxidised LDL tended to decrease (p = 0.073), and apolipoprotein B increased during the intervention, without water type effect. Energy and carbohydrates from beverages decreased since soft drinks and fruit juice consumptions decreased throughout the trial. BW increased urinary pH (p = 0.006) and reduced calcium/creatinine excretion (p = 0.011). Urinary potassium/creatinine decreased with both waters. Consumption of 1 L/day of mineral water with the main meals reduces cardiometabolic risk biomarkers, likely to be attributed to a replacement of soft drinks by water. In addition, BW does not affect blood pressure and exerts a moderate alkalizing effect in the body.

The Walking Interventions Through Texting (WalkIT) Trial: Rationale, Design, and Protocol for a Factorial Randomized Controlled Trial of Adaptive Interventions for Overweight and Obese, Inactive Adults

PubMed Central

Hurley, Jane C; Hollingshead, Kevin E; Todd, Michael; Jarrett, Catherine L; Tucker, Wesley J; Angadi, Siddhartha S

2015-01-01

Background Walking is a widely accepted and frequently targeted health promotion approach to increase physical activity (PA). Interventions to increase PA have produced only small improvements. Stronger and more potent behavioral intervention components are needed to increase time spent in PA, improve cardiometabolic risk markers, and optimize health. Objective Our aim is to present the rationale and methods from the WalkIT Trial, a 4-month factorial randomized controlled trial (RCT) in inactive, overweight/obese adults. The main purpose of the study was to evaluate whether intensive adaptive components result in greater improvements to adults’ PA compared to the static intervention components. Methods Participants enrolled in a 2x2 factorial RCT and were assigned to one of four semi-automated, text message–based walking interventions. Experimental components included adaptive versus static steps/day goals, and immediate versus delayed reinforcement. Principles of percentile shaping and behavioral economics were used to operationalize experimental components. A Fitbit Zip measured the main outcome: participants’ daily physical activity (steps and cadence) over the 4-month duration of the study. Secondary outcomes included self-reported PA, psychosocial outcomes, aerobic fitness, and cardiorespiratory risk factors assessed pre/post in a laboratory setting. Participants were recruited through email listservs and websites affiliated with the university campus, community businesses and local government, social groups, and social media advertising. Results This study has completed data collection as of December 2014, but data cleaning and preliminary analyses are still in progress. We expect to complete analysis of the main outcomes in late 2015 to early 2016. Conclusions The Walking Interventions through Texting (WalkIT) Trial will further the understanding of theory-based intervention components to increase the PA of men and women who are healthy, insufficiently active and are overweight or obese. WalkIT is one of the first studies focusing on the individual components of combined goal setting and reward structures in a factorial design to increase walking. The trial is expected to produce results useful to future research interventions and perhaps industry initiatives, primarily focused on mHealth, goal setting, and those looking to promote behavior change through performance-based incentives. Trial Registration ClinicalTrials.gov NCT02053259; https://clinicaltrials.gov/ct2/show/NCT02053259 (Archived by WebCite at http://www.webcitation.org/6b65xLvmg). PMID:26362511

The effects of mindfulness eating and yoga exercise on blood sugar levels of pregnant women with gestational diabetes mellitus.

PubMed

Youngwanichsetha, Sununta; Phumdoung, Sasitorn; Ingkathawornwong, Thitiporn

2014-11-01

This randomized controlled trial was carried out to investigate the effect of mindfulness eating and yoga exercise on blood sugar levels among pregnant Thai women with GDM. Interventions promoting achievement of good glycemic control result in desired pregnancy outcomes. Little is known about the health benefits of mindfulness eating and yoga exercise on blood sugar levels among pregnant with GDM. A randomized controlled trial was carried out. Main outcome measures were capillary fasting plasma glucose, 2-h postprandial blood glucose, and hemoglobin A1c. The intervention group showed significantly reduced fasting plasma glucose, 2-h postprandial blood glucose, and glycosylated hemoglobin (HbA1c) in the intervention group (p<0.05). Mindfulness eating and yoga exercise had health benefits on glycemic control in pregnant women with GDM. It should be recommended in clinical and community health services. Copyright © 2014 Elsevier Inc. All rights reserved.

Home-based neurologic music therapy for arm hemiparesis following stroke: results from a pilot, feasibility randomized controlled trial

PubMed Central

Street, Alexander J; Magee, Wendy L; Bateman, Andrew; Parker, Michael; Odell-Miller, Helen; Fachner, Jorg

2017-01-01

Objective: To assess the feasibility of a randomized controlled trial to evaluate music therapy as a home-based intervention for arm hemiparesis in stroke. Design: A pilot feasibility randomized controlled trial, with cross-over design. Randomization by statistician using computer-generated, random numbers concealed in opaque envelopes. Setting: Participants’ homes across Cambridgeshire, UK. Subjects: Eleven people with stroke and arm hemiparesis, 3–60 months post stroke, following discharge from community rehabilitation. Interventions: Each participant engaged in therapeutic instrumental music performance in 12 individual clinical contacts, twice weekly for six weeks. Main measures: Feasibility was estimated by recruitment from three community stroke teams over a 12-month period, attrition rates, completion of treatment and successful data collection. Structured interviews were conducted pre and post intervention to establish participant tolerance and preference. Action Research Arm Test and Nine-hole Peg Test data were collected at weeks 1, 6, 9, 15 and 18, pre and post intervention by a blinded assessor. Results: A total of 11 of 14 invited participants were recruited (intervention n = 6, waitlist n = 5). In total, 10 completed treatment and data collection. Conclusion: It cannot be concluded whether a larger trial would be feasible due to unavailable data regarding a number of eligible patients screened. Adherence to treatment, retention and interview responses might suggest that the intervention was motivating for participants. Trial registration: ClinicalTrials.gov identifier NCT 02310438. PMID:28643570

Hyperbaric Oxygen Therapy Can Diminish Fibromyalgia Syndrome – Prospective Clinical Trial

PubMed Central

Efrati, Shai; Golan, Haim; Bechor, Yair; Faran, Yifat; Daphna-Tekoah, Shir; Sekler, Gal; Fishlev, Gregori; Ablin, Jacob N.; Bergan, Jacob; Volkov, Olga; Friedman, Mony; Ben-Jacob, Eshel; Buskila, Dan

2015-01-01

Background Fibromyalgia Syndrome (FMS) is a persistent and debilitating disorder estimated to impair the quality of life of 2–4% of the population, with 9:1 female-to-male incidence ratio. FMS is an important representative example of central nervous system sensitization and is associated with abnormal brain activity. Key symptoms include chronic widespread pain, allodynia and diffuse tenderness, along with fatigue and sleep disturbance. The syndrome is still elusive and refractory. The goal of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on symptoms and brain activity in FMS. Methods and Findings A prospective, active control, crossover clinical trial. Patients were randomly assigned to treated and crossover groups: The treated group patients were evaluated at baseline and after HBOT. Patients in the crossover-control group were evaluated three times: baseline, after a control period of no treatment, and after HBOT. Evaluations consisted of physical examination, including tender point count and pain threshold, extensive evaluation of quality of life, and single photon emission computed tomography (SPECT) imaging for evaluation of brain activity. The HBOT protocol comprised 40 sessions, 5 days/week, 90 minutes, 100% oxygen at 2ATA. Sixty female patients were included, aged 21–67 years and diagnosed with FMS at least 2 years earlier. HBOT in both groups led to significant amelioration of all FMS symptoms, with significant improvement in life quality. Analysis of SPECT imaging revealed rectification of the abnormal brain activity: decrease of the hyperactivity mainly in the posterior region and elevation of the reduced activity mainly in frontal areas. No improvement in any of the parameters was observed following the control period. Conclusions The study provides evidence that HBOT can improve the symptoms and life quality of FMS patients. Moreover, it shows that HBOT can induce neuroplasticity and significantly rectify abnormal brain activity in pain related areas of FMS patients. Trial Registration ClinicalTrials.gov NCT01827683 PMID:26010952

The Swedish six-community alcohol and drug prevention trial: effects on youth drinking.

PubMed

Hallgren, Mats; Andréasson, Sven

2013-09-01

Local communities are increasingly targeted for alcohol and drug prevention campaigns. This study describes some of the key findings from the Swedish six-community alcohol and drug prevention trial (2003-2007) and lessons learned following an evaluation of the trial's effectiveness. The paper focuses mainly on changes in youth drinking and related harms. This was a pre- to post-intervention effect study comparing six trial communities that received added training and technical support with six control communities where regular prevention efforts were supported by national alcohol and drug action plans. A repeated, cross-sectional survey of 8092 youths aged 15-19 years assessed changes in alcohol consumption, binge drinking, perceived alcohol availability, access to alcohol via parents and adult attitudes towards the supply of alcohol to youths. National registry data were used to assess changes in hospital admissions due to alcohol intoxication. Overall, there were few significant improvements in the six trial communities compared with the control communities. The absence of program effects was largely attributable to the selection of strategies (in particular, school and parental programs) lacking evidence of effectiveness in reducing alcohol consumption at the aggregate level. Prevention programs based on efficacy studies need to be tested in community-based effectiveness trials before being disseminated. © 2013 Australasian Professional Society on Alcohol and other Drugs.

Effects of intravenous magnesium in suspected acute myocardial infarction: overview of randomised trials.

PubMed Central

Teo, K K; Yusuf, S; Collins, R; Held, P H; Peto, R

1991-01-01

OBJECTIVE--To investigate the effect of intravenous magnesium on mortality in suspected acute myocardial infarction. DESIGN--Systematic overview of all available randomised trials in which patients were allocated to receive either intravenous magnesium or otherwise similar treatment without magnesium. SETTING--Coronary care units of several hospitals. PATIENTS--1301 patients in seven randomised trials. MAIN OUTCOME MEASURE--Short term mortality. RESULTS--Considering the seven trials collectively there were 25 (3.8%) deaths among 657 patients allocated to receive magnesium and 53 (8.2%) deaths among 644 patients allocated control, generally during hospital follow up. This represents a 55% reduction in the odds of death (p less than 0.001) with 95% confidence intervals ranging from about one third to about two thirds. 70 of 648 patients allocated magnesium compared with 109 of 641 controls had serious ventricular arrhythmias, suggesting that magnesium reduces the incidence, though the definition varied among trials. Other adverse effects were rare in the limited number of patients for whom this data were available. CONCLUSION--Despite the limited number of patients randomised this overview suggests that intravenous magnesium therapy may reduce mortality in patients with acute myocardial infarction. Further large scale trials to confirm (or refute) these findings are desirable. PMID:1838289

The Cost Implications of Less Tight Versus Tight Control of Hypertension in Pregnancy (CHIPS Trial).

PubMed

Ahmed, Rashid J; Gafni, Amiram; Hutton, Eileen K; Hu, Zheng Jing; Pullenayegum, Eleanor; von Dadelszen, Peter; Rey, Evelyne; Ross, Susan; Asztalos, Elizabeth; Murphy, Kellie E; Menzies, Jennifer; Sanchez, J Johanna; Ganzevoort, Wessel; Helewa, Michael; Lee, Shoo K; Lee, Terry; Logan, Alexander G; Moutquin, Jean-Marie; Singer, Joel; Thornton, Jim G; Welch, Ross; Magee, Laura A

2016-10-01

The CHIPS randomized controlled trial (Control of Hypertension in Pregnancy Study) found no difference in the primary perinatal or secondary maternal outcomes between planned "less tight" (target diastolic 100 mm Hg) and "tight" (target diastolic 85 mm Hg) blood pressure management strategies among women with chronic or gestational hypertension. This study examined which of these management strategies is more or less costly from a third-party payer perspective. A total of 981 women with singleton pregnancies and nonsevere, nonproteinuric chronic or gestational hypertension were randomized at 14 to 33 weeks to less tight or tight control. Resources used were collected from 94 centers in 15 countries and costed as if the trial took place in each of 3 Canadian provinces as a cost-sensitivity analysis. Eleven hospital ward and 24 health service costs were obtained from a similar trial and provincial government health insurance schedules of medical benefits. The mean total cost per woman-infant dyad was higher in less tight versus tight control, but the difference in mean total cost (DM) was not statistically significant in any province: Ontario ($30 191.62 versus $24 469.06; DM $5723, 95% confidence interval, -$296 to $12 272; P=0.0725); British Columbia ($30 593.69 versus $24 776.51; DM $5817; 95% confidence interval, -$385 to $12 349; P=0.0725); or Alberta ($31 510.72 versus $25 510.49; DM $6000.23; 95% confidence interval, -$154 to $12 781; P=0.0637). Tight control may benefit women without increasing risk to neonates (as shown in the main CHIPS trial), without additional (and possibly lower) cost to the healthcare system. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01192412. © 2016 The Authors.

Some physiotherapy treatments may relieve menstrual pain in women with primary dysmenorrhea: a systematic review.

PubMed

Kannan, Priya; Claydon, Leica Sarah

2014-03-01

In women with primary dysmenorrhoea, what is the effect of physiotherapeutic interventions compared to control (either no treatment or placebo/sham) on pain and quality of life? Systematic review of randomised trials with meta-analysis. Women with primary dysmenorrhea. Any form of physiotherapy treatment. The primary outcome was menstrual pain intensity and the secondary outcome was quality of life. The search yielded 222 citations. Of these, 11 were eligible randomised trials and were included in the review. Meta-analysis revealed statistically significant reductions in pain severity on a 0-10 scale from acupuncture (weighted mean difference 2.3, 95% CI 1.6 to 2.9) and acupressure (weighted mean difference 1.4, 95% CI 0.8 to 1.9), when compared to a control group receiving no treatment. However, these are likely to be placebo effects because when the control groups in acupuncture/acupressure trials received a sham instead of no treatment, pain severity did not significantly differ between the groups. Significant reductions in pain intensity on a 0-10 scale were noted in individual trials of heat (by 1.8, 95% CI 0.9 to 2.7), transcutaneous electrical nerve stimulation (2.3, 95% CI 0.03 to 4.2), and yoga (3.2, 95% CI 2.2 to 4.2). Meta-analysis of two trials of spinal manipulation showed no significant reduction in pain. None of the included studies measured quality of life. Physiotherapists could consider using heat, transcutaneous electrical nerve stimulation, and yoga in the management of primary dysmenorrhea. While benefits were also identified for acupuncture and acupressure in no-treatment controlled trials, the absence of significant effects in sham-controlled trials suggests these effects are mainly attributable to placebo effects. Copyright © 2014 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

One-stage or two-stage revision surgery for prosthetic hip joint infection--the INFORM trial: a study protocol for a randomised controlled trial.

PubMed

Strange, Simon; Whitehouse, Michael R; Beswick, Andrew D; Board, Tim; Burston, Amanda; Burston, Ben; Carroll, Fran E; Dieppe, Paul; Garfield, Kirsty; Gooberman-Hill, Rachael; Jones, Stephen; Kunutsor, Setor; Lane, Athene; Lenguerrand, Erik; MacGowan, Alasdair; Moore, Andrew; Noble, Sian; Simon, Joanne; Stockley, Ian; Taylor, Adrian H; Toms, Andrew; Webb, Jason; Whittaker, John-Paul; Wilson, Matthew; Wylde, Vikki; Blom, Ashley W

2016-02-17

Periprosthetic joint infection (PJI) affects approximately 1% of patients following total hip replacement (THR) and often results in severe physical and emotional suffering. Current surgical treatment options are debridement, antibiotics and implant retention; revision THR; excision of the joint and amputation. Revision surgery can be done as either a one-stage or two-stage operation. Both types of surgery are well-established practice in the NHS and result in similar rates of re-infection, but little is known about the impact of these treatments from the patient's perspective. The main aim of this randomised controlled trial is to determine whether there is a difference in patient-reported outcome measures 18 months after randomisation for one-stage or two-stage revision surgery. INFORM (INFection ORthopaedic Management) is an open, two-arm, multi-centre, randomised, superiority trial. We aim to randomise 148 patients with eligible PJI of the hip from approximately seven secondary care NHS orthopaedic units from across England and Wales. Patients will be randomised via a web-based system to receive either a one-stage revision or a two-stage revision THR. Blinding is not possible due to the nature of the intervention. All patients will be followed up for 18 months. The primary outcome is the WOMAC Index, which assesses hip pain, function and stiffness, collected by questionnaire at 18 months. Secondary outcomes include the following: cost-effectiveness, complications, re-infection rates, objective hip function assessment and quality of life. A nested qualitative study will explore patients' and surgeons' experiences, including their views about trial participation and randomisation. INFORM is the first ever randomised trial to compare two widely accepted surgical interventions for the treatment of PJI: one-stage and two-stage revision THR. The results of the trial will benefit patients in the future as the main focus is on patient-reported outcomes: pain, function and wellbeing in the long term. Patients state that these outcomes are more important than those that are clinically derived (such as re-infection) and have been commonly used in previous non-randomised studies. Results from the INFORM trial will also benefit clinicians and NHS managers by enabling the comparison of these key interventions in terms of patients' complication rates, health and social resource use and their overall cost-effectiveness. Current controlled trials ISRCTN10956306 (registered on 29 January 2015); UKCRN ID 18159.

Gut microbiota and probiotics: Focus on diabetes mellitus.

PubMed

Bordalo Tonucci, Livia; Dos Santos, Karina Maria Olbrich; De Luces Fortes Ferreira, Celia Lucia; Ribeiro, Sonia Machado Rocha; De Oliveira, Leandro Licursi; Martino, Hercia Stampini Duarte

2017-07-24

The characterization of gut microbiota has become an important area of research in several clinical conditions, including type 2 diabetes (T2DM). Changes in the composition and/or metabolic activity of the gut microbiota can contribute to human health. Thus, this review discusses the effects of probiotics and gut microbiota on metabolic control in these individuals. Relevant studies were obtained from electronic databases such as PubMed/Medline and ISI Web of Science. The main probiotics used in these studies belonged to the genera Lactobacillus and Bifidobacterium. The authors found seven randomized placebo-controlled clinical trials and 13 experimental studies directly related to the effect of probiotics on metabolic control in the context of T2DM. The hypothesis that gut microbiota plays a role in the development of diabetes indicates an important beginning, and the potential of probiotics to prevent and reduce the severity of T2DM is better observed in animal studies. In clinical trials, the use of probiotics in glycemic control presented conflicting results, and only few studies have attempted to evaluate factors that justify metabolic changes, such as markers of oxidative stress, inflammation, and incretins. Thus, further research is needed to assess the effects of probiotics in the metabolism of diabetic individuals, as well as the main mechanisms involved in this complex relationship.

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

PubMed Central

2010-01-01

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

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

PubMed Central

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

2016-01-01

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

Distance to health services affects local-level vaccine efficacy for pneumococcal conjugate vaccine (PCV) among rural Filipino children.

PubMed

Root, Elisabeth Dowling; Lucero, Marilla; Nohynek, Hanna; Anthamatten, Peter; Thomas, Deborah S K; Tallo, Veronica; Tanskanen, Antti; Quiambao, Beatriz P; Puumalainen, Taneli; Lupisan, Socorro P; Ruutu, Petri; Ladesma, Erma; Williams, Gail M; Riley, Ian; Simões, Eric A F

2014-03-04

Pneumococcal conjugate vaccines (PCVs) have demonstrated efficacy against childhood pneumococcal disease in several regions globally. We demonstrate how spatial epidemiological analysis of a PCV trial can assist in developing vaccination strategies that target specific geographic subpopulations at greater risk for pneumococcal pneumonia. We conducted a secondary analysis of a randomized, placebo-controlled, double-blind vaccine trial that examined the efficacy of an 11-valent PCV among children less than 2 y of age in Bohol, Philippines. Trial data were linked to the residential location of each participant using a geographic information system. We use spatial interpolation methods to create smoothed surface maps of vaccination rates and local-level vaccine efficacy across the study area. We then measure the relationship between distance to the main study hospital and local-level vaccine efficacy, controlling for ecological factors, using spatial autoregressive models with spatial autoregressive disturbances. We find a significant amount of spatial variation in vaccination rates across the study area. For the primary study endpoint vaccine efficacy increased with distance from the main study hospital from -14% for children living less than 1.5 km from Bohol Regional Hospital (BRH) to 55% for children living greater than 8.5 km from BRH. Spatial regression models indicated that after adjustment for ecological factors, distance to the main study hospital was positively related to vaccine efficacy, increasing at a rate of 4.5% per kilometer distance. Because areas with poor access to care have significantly higher VE, targeted vaccination of children in these areas might allow for a more effective implementation of global programs.

Test of a non-physical barrier consisting of light, sound, and bubble screen to block upstream movement of sea lamprey in an experimental raceway

USGS Publications Warehouse

Miehls, Scott M.; Johnson, Nicholas S.; Hrodey, Pete J.

2017-01-01

Control of the invasive Sea Lamprey Petromyzon marinus is critical for management of commercial and recreational fisheries in the Laurentian Great Lakes. Use of physical barriers to block Sea Lampreys from spawning habitat is a major component of the control program. However, the resulting interruption of natural streamflow and blockage of nontarget species present substantial challenges. Development of an effective nonphysical barrier would aid the control of Sea Lampreys by eliminating their access to spawning locations while maintaining natural streamflow. We tested the effect of a nonphysical barrier consisting of strobe lights, low-frequency sound, and a bubble screen on the movement of Sea Lampreys in an experimental raceway designed as a two-choice maze with a single main channel fed by two identical inflow channels (one control and one blocked). Sea Lampreys were more likely to move upstream during trials when the strobe light and low-frequency sound were active compared with control trials and trials using the bubble screen alone. For those Sea Lampreys that did move upstream to the confluence of inflow channels, no combination of stimuli or any individual stimulus significantly influenced the likelihood that Sea Lampreys would enter the blocked inflow channel, enter the control channel, or return downstream.

Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria.

PubMed

Bukirwa, Hasifa; Unnikrishnan, B; Kramer, Christine V; Sinclair, David; Nair, Suma; Tharyan, Prathap

2014-03-04

The World Health Organization (WHO) recommends that people with uncomplicated Plasmodium falciparum malaria are treated using Artemisinin-based Combination Therapy (ACT). ACT combines three-days of a short-acting artemisinin derivative with a longer-acting antimalarial which has a different mode of action. Pyronaridine has been reported as an effective antimalarial over two decades of use in parts of Asia, and is currently being evaluated as a partner drug for artesunate. To evaluate the efficacy and safety of artesunate-pyronaridine compared to alternative ACTs for treating people with uncomplicated P. falciparum malaria. We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; ClinicalTrials.gov; the metaRegister of Controlled Trials (mRCT); and the WHO International Clinical Trials Search Portal up to 16 January 2014. We searched reference lists and conference abstracts, and contacted experts for information about ongoing and unpublished trials. Randomized controlled trials of artesunate-pyronaridine versus other ACTs in adults and children with uncomplicated P. falciparum malaria.For the safety analysis, we also included adverse events data from trials comparing any treatment regimen containing pyronaridine with regimens not containing pyronaridine. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We combined dichotomous data using risk ratios (RR) and continuous data using mean differences (MD), and presented all results with a 95% confidence interval (CI). We used the GRADE approach to assess the quality of evidence. We included six randomized controlled trials enrolling 3718 children and adults. Artesunate-pyronaridine versus artemether-lumefantrineIn two multicentre trials, enrolling mainly older children and adults from west and south-central Africa, both artesunate-pyronaridine and artemether-lumefantrine had fewer than 5% PCR adjusted treatment failures during 42 days of follow-up, with no differences between groups (two trials, 1472 participants, low quality evidence). There were fewer new infections during the first 28 days in those given artesunate-pyronaridine (PCR-unadjusted treatment failure: RR 0.60, 95% CI 0.40 to 0.90, two trials, 1720 participants, moderate quality evidence), but no difference was detected over the whole 42 day follow-up (two trials, 1691 participants, moderate quality evidence). Artesunate-pyronaridine versus artesunate plus mefloquineIn one multicentre trial, enrolling mainly older children and adults from South East Asia, both artesunate-pyronaridine and artesunate plus mefloquine had fewer than 5% PCR adjusted treatment failures during 28 days follow-up (one trial, 1187 participants, moderate quality evidence). PCR-adjusted treatment failures were 6% by day 42 for these treated with artesunate-pyronaridine, and 4% for those with artesunate-mefloquine (RR 1.64, 95% CI 0.89 to 3.00, one trial, 1116 participants, low quality evidence). Again, there were fewer new infections during the first 28 days in those given artesunate-pyronaridine (PCR-unadjusted treatment failure: RR 0.35, 95% CI 0.17 to 0.73, one trial, 1720 participants, moderate quality evidence), but no differences were detected over the whole 42 days (one trial, 1146 participants, low quality evidence). Adverse effectsSerious adverse events were uncommon in these trials, with no difference detected between artesunate-pyronaridine and comparator ACTs. The analysis of liver function tests showed biochemical elevation were four times more frequent with artesunate-pyronaridine than with the other antimalarials (RR 4.17, 95% CI 1.38 to 12.62, four trials, 3523 participants, moderate quality evidence). Artesunate-pyronaridine performed well in these trials compared to artemether-lumefantrine and artesunate plus mefloquine, with PCR-adjusted treatment failure at day 28 below the 5% standard set by the WHO. Further efficacy and safety studies in African and Asian children are required to clarify whether this combination is an option for first-line treatment.

Feasibility and effectiveness of a low cost campaign on antibiotic prescribing in Italy: community level, controlled, non-randomised trial.

PubMed

Formoso, Giulio; Paltrinieri, Barbara; Marata, Anna Maria; Gagliotti, Carlo; Pan, Angelo; Moro, Maria Luisa; Capelli, Oreste; Magrini, Nicola

2013-09-12

To test the hypothesis that a multifaceted, local public campaign could be feasible and influence antibiotic prescribing for outpatients. Community level, controlled, non-randomised trial. Provinces of Modena and Parma in Emilia-Romagna, northern Italy, November 2011 to February 2012. 1,150,000 residents of Modena and Parma (intervention group) and 3,250,000 residents in provinces in the same region but where no campaign had been implemented (control group). Campaign materials (mainly posters, brochures, and advertisements on local media, plus a newsletter on local antibiotic resistance targeted at doctors and pharmacists). General practitioners and paediatricians in the intervention area participated in designing the campaign messages. Primary outcome was the average change in prescribing rates of antibiotics for outpatient in five months, measured as defined daily doses per 1000 inhabitants/day, using health districts as the unit of analysis. Antibiotic prescribing was reduced in the intervention area compared with control area (-4.3%, 95% confidence interval -7.1% to -1.5%). This result was robust to "sensitivity analysis" modifying the baseline period from two months (main analysis) to one month. A higher decrease was observed for penicillins resistant to β lactamase and a lower decrease for penicillins susceptible to β lactamase, consistent with the content of the newsletter on antibiotic resistance directed at health professionals. The decrease in expenditure on antibiotics was not statistically significant in a district level analysis with a two month baseline period (main analysis), but was statistically significant in sensitivity analyses using either a one month baseline period or a more powered doctor level analysis. Knowledge and attitudes of the target population about the correct use of antibiotics did not differ between the intervention and control areas. A local low cost information campaign targeted at citizens, combined with a newsletter on local antibiotic resistance targeted at doctors and pharmacists, was associated with significantly decreased total rates of antibiotic prescribing but did not affect the population's knowledge and attitudes about antibiotic resistance. ClinicalTrials.gov NCT01604096.

Palliative radiotherapy in addition to self-expanding metal stent for improving dysphagia and survival in advanced oesophageal cancer (ROCS: Radiotherapy after Oesophageal Cancer Stenting): study protocol for a randomized controlled trial.

PubMed

Adamson, Douglas; Blazeby, Jane; Nelson, Annmarie; Hurt, Chris; Nixon, Lisette; Fitzgibbon, Jim; Crosby, Tom; Staffurth, John; Evans, Mim; Kelly, Noreen Hopewell; Cohen, David; Griffiths, Gareth; Byrne, Anthony

2014-10-22

The single most distressing symptom for patients with advanced esophageal cancer is dysphagia. Amongst the more effective treatments for relief of dysphagia is insertion of a self-expanding metal stent (SEMS). It is possible that the addition of a palliative dose of external beam radiotherapy may prolong the relief of dysphagia and provide additional survival benefit. The ROCS trial will assess the effect of adding palliative radiotherapy after esophageal stent insertion. The study is a randomized multicenter phase III trial, with an internal pilot phase, comparing stent alone versus stent plus palliative radiotherapy in patients with incurable esophageal cancer. Eligible participants are those with advanced esophageal cancer who are in need of stent insertion for primary management of dysphagia. Radiotherapy will be administered as 20 Gray (Gy) in five fractions over one week or 30 Gy in 10 fractions over two weeks, within four weeks of stent insertion. The internal pilot will assess rates and methods of recruitment; pre-agreed criteria will determine progression to the main trial. In total, 496 patients will be randomized in a 1:1 ratio with follow up until death. The primary outcome is time to progression of patient-reported dysphagia. Secondary outcomes include survival, toxicity, health resource utilization, and quality of life. An embedded qualitative study will explore the feasibility of patient recruitment by examining patients' motivations for involvement and their experiences of consent and recruitment, including reasons for not consenting. It will also explore patients' experiences of each trial arm. The ROCS study will be a challenging trial studying palliation in patients with a poor prognosis. The internal pilot design will optimize methods for recruitment and data collection to ensure that the main trial is completed on time. As a pragmatic trial, study strengths include collection of all follow-up data in the usual place of care, and a focus on patient-reported, rather than disease-orientated, outcomes. Exploration of patient experience and health economic analyses will be integral to the assessment of benefit for patients and the NHS. The trial was registered with Current Controlled Trials (registration number: ISRCTN12376468) on 10 July 2012.

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

PubMed Central

2011-01-01

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

Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial

PubMed Central

Aga, Anna-Birgitte; Olsen, Inge Christoffer; Lillegraven, Siri; Hammer, Hilde B; Uhlig, Till; Fremstad, Hallvard; Madland, Tor Magne; Lexberg, Åse Stavland; Haukeland, Hilde; Rødevand, Erik; Høili, Christian; Stray, Hilde; Noraas, Anne; Hansen, Inger Johanne Widding; Bakland, Gunnstein; Nordberg, Lena Bugge; van der Heijde, Désirée; Kvien, Tore K

2016-01-01

Objective To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy. Design Multicentre, open label, two arm, parallel group, randomised controlled strategy trial. Setting Ten rheumatology departments and one specialist centre in Norway, from September 2010 to September 2015. Participants 238 patients were recruited between September 2010 and April 2013, of which 230 (141 (61%) female) received the allocated intervention and were analysed for the primary outcome. The main inclusion criteria were age 18-75 years, fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis, disease modifying anti-rheumatic drug naivety with indication for disease modifying drug therapy, and time from first patient reported swollen joint less than two years. Patients with abnormal kidney or liver function or major comorbidities were excluded. Interventions 122 patients were randomised to an ultrasound tight control strategy targeting clinical and imaging remission, and 116 patients were randomised to a conventional tight control strategy targeting clinical remission. Patients in both arms were treated according to the same disease modifying anti-rheumatic drug escalation strategy, with 13 visits over two years. Main outcome measures The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints, and non-progression of radiographic joint damage. Secondary outcomes included measures of disease activity, radiographic progression, functioning, quality of life, and adverse events. All participants who attended at least one follow-up visit were included in the full analysis set. Results 26 (22%) of the 118 analysed patients in the ultrasound tight control arm and 21 (19%) of the 112 analysed patients in the clinical tight control arm reached the primary endpoint (mean difference 3.3%, 95% confidence interval −7.1% to 13.7%). Secondary endpoints (disease activity, physical function, and joint damage) were similar between the two groups. Six (5%) patients in the ultrasound tight control arm and seven (6%) patients in the conventional arm had serious adverse events. Conclusions The systematic use of ultrasound in the follow-up of patients with early rheumatoid arthritis treated according to current recommendations is not justified on the basis of the ARCTIC results. The findings highlight the need for randomised trials assessing the clinical application of medical technology. Trial registration Clinical trials NCT01205854. PMID:27530741

Development and Evaluation of a Pedagogical Tool to Improve Understanding of a Quality Checklist: A Randomised Controlled Trial

PubMed Central

Fourcade, Lola; Boutron, Isabelle; Moher, David; Ronceray, Lucie; Baron, Gabriel; Ravaud, Philippe

2007-01-01

Objective: The aim of this study was to develop and evaluate a pedagogical tool to enhance the understanding of a checklist that evaluates reports of nonpharmacological trials (CLEAR NPT). Design: Paired randomised controlled trial. Participants: Clinicians and systematic reviewers. Interventions: We developed an Internet-based computer learning system (ICLS). This pedagogical tool used many examples from published randomised controlled trials to demonstrate the main coding difficulties encountered when using this checklist. Randomised participants received either a specific Web-based training with the ICLS (intervention group) or no specific training. Outcome measures: The primary outcome was the rate of correct answers compared to a criterion standard for coding a report of randomised controlled trials with the CLEAR NPT. Results: Between April and June 2006, 78 participants were randomly assigned to receive training with the ICLS (39) or no training (39). Participants trained by the ICLS did not differ from the control group in performance on the CLEAR NPT. The mean paired difference and corresponding 95% confidence interval was 0.5 (−5.1 to 6.1). The rate of correct answers did not differ between the two groups regardless of the CLEAR NPT item. Combining both groups, the rate of correct answers was high or items related to allocation sequence (79.5%), description of the intervention (82.0%), blinding of patients (79.5%), and follow-up schedule (83.3%). The rate of correct answers was low for items related to allocation concealment (46.1%), co-interventions (30.3%), blinding of outcome assessors (53.8%), specific measures to avoid ascertainment bias (28.6%), and intention-to-treat analysis (60.2%). Conclusions: Although we showed no difference in effect between the intervention and control groups, our results highlight the gap in knowledge and urgency for education on important aspects of trial conduct. PMID:17479163

The Cost Implications of Less Tight Versus Tight Control of Hypertension in Pregnancy (CHIPS Trial)

PubMed Central

Ahmed, Rashid J.; Gafni, Amiram; Hu, Zheng Jing; Pullenayegum, Eleanor; von Dadelszen, Peter; Rey, Evelyne; Ross, Susan; Asztalos, Elizabeth; Murphy, Kellie E.; Menzies, Jennifer; Sanchez, J. Johanna; Ganzevoort, Wessel; Helewa, Michael; Lee, Shoo K.; Lee, Terry; Logan, Alexander G.; Moutquin, Jean-Marie; Singer, Joel; Thornton, Jim G.; Welch, Ross; Magee, Laura A.

2016-01-01

The CHIPS randomized controlled trial (Control of Hypertension in Pregnancy Study) found no difference in the primary perinatal or secondary maternal outcomes between planned “less tight” (target diastolic 100 mm Hg) and “tight” (target diastolic 85 mm Hg) blood pressure management strategies among women with chronic or gestational hypertension. This study examined which of these management strategies is more or less costly from a third-party payer perspective. A total of 981 women with singleton pregnancies and nonsevere, nonproteinuric chronic or gestational hypertension were randomized at 14 to 33 weeks to less tight or tight control. Resources used were collected from 94 centers in 15 countries and costed as if the trial took place in each of 3 Canadian provinces as a cost-sensitivity analysis. Eleven hospital ward and 24 health service costs were obtained from a similar trial and provincial government health insurance schedules of medical benefits. The mean total cost per woman–infant dyad was higher in less tight versus tight control, but the difference in mean total cost (DM) was not statistically significant in any province: Ontario ($30 191.62 versus $24 469.06; DM $5723, 95% confidence interval, −$296 to $12 272; P=0.0725); British Columbia ($30 593.69 versus $24 776.51; DM $5817; 95% confidence interval, −$385 to $12 349; P=0.0725); or Alberta ($31 510.72 versus $25 510.49; DM $6000.23; 95% confidence interval, −$154 to $12 781; P=0.0637). Tight control may benefit women without increasing risk to neonates (as shown in the main CHIPS trial), without additional (and possibly lower) cost to the healthcare system. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01192412. PMID:27550914

RApid Primary care Initiation of Drug treatment for Transient Ischaemic Attack (RAPID-TIA): study protocol for a pilot randomised controlled trial.

PubMed

Edwards, Duncan; Fletcher, Kate; Deller, Rachel; McManus, Richard; Lasserson, Daniel; Giles, Matthew; Sims, Don; Norrie, John; McGuire, Graham; Cohn, Simon; Whittle, Fiona; Hobbs, Vikki; Weir, Christopher; Mant, Jonathan

2013-07-02

People who have a transient ischaemic attack (TIA) or minor stroke are at high risk of a recurrent stroke, particularly in the first week after the event. Early initiation of secondary prevention drugs is associated with an 80% reduction in risk of stroke recurrence. This raises the question as to whether these drugs should be given before being seen by a specialist--that is, in primary care or in the emergency department. The aims of the RAPID-TIA pilot trial are to determine the feasibility of a randomised controlled trial, to analyse cost effectiveness and to ask: Should general practitioners and emergency doctors (primary care physicians) initiate secondary preventative measures in addition to aspirin in people they see with suspected TIA or minor stroke at the time of referral to a specialist? This is a pilot randomised controlled trial with a sub-study of accuracy of primary care physician diagnosis of TIA. In the pilot trial, we aim to recruit 100 patients from 30 general practices (including out-of-hours general practice centres) and 1 emergency department whom the primary care physician diagnoses with TIA or minor stroke and randomly assign them to usual care (that is, initiation of aspirin and referral to a TIA clinic) or usual care plus additional early initiation of secondary prevention drugs (a blood-pressure lowering protocol, simvastatin 40 mg and dipyridamole 200 mg m/r bd). The primary outcome of the main study will be the number of strokes at 90 days. The diagnostic accuracy sub-study will include these 100 patients and an additional 70 patients in whom the primary care physician thinks the diagnosis of TIA is possible, rather than probable. For the pilot trial, we will report recruitment rate, follow-up rate, a preliminary estimate of the primary event rate and occurrence of any adverse events. For the diagnostic study, we will calculate sensitivity and specificity of primary care physician diagnosis using the final TIA clinic diagnosis as the reference standard. This pilot study will be used to estimate key parameters that are needed to design the main study and to estimate the accuracy of primary care diagnosis of TIA. The planned follow-on trial will have important implications for the initial management of people with suspected TIA. ISRCTN62019087.

Echinacea for preventing and treating the common cold

PubMed Central

Karsch-Völk, Marlies; Barrett, Bruce; Kiefer, David; Bauer, Rudolf; Ardjomand-Woelkart, Karin; Linde, Klaus

2014-01-01

Background Echinacea plant preparations (family Asteraceae) are widely used in Europe and North America for common colds. Most consumers and physicians are not aware that products available under the term Echinacea differ appreciably in their composition, mainly due to the use of variable plant material, extraction methods and the addition of other components. Objectives To assess whether there is evidence that Echinacea preparations are effective and safe compared to placebo in the prevention and treatment of the common cold. Search methods We searched CENTRAL 2013, Issue 5, MEDLINE (1946 to May week 5, 2013), EMBASE (1991 to June 2013), CINAHL (1981 to June 2013), AMED (1985 to February 2012), LILACS (1981 to June 2013), Web of Science (1955 to June 2013), CAMBASE (no time limits), the Centre for Complementary Medicine Research (1988 to September 2007), WHO ICTRP and clinicaltrials.gov (last searched 5 June 2013), screened references and asked experts in the field about published and unpublished studies. Selection criteria Randomized controlled trials (RCTs) comparing mono-preparations of Echinacea with placebo. Data collection and analysis At least two review authors independently assessed eligibility and trial quality and extracted data. The primary efficacy outcome was the number of individuals with at least one cold in prevention trials and the duration of colds in treatment trials. For all included trials the primary safety and acceptability outcome was the number of participants dropping out due to adverse events. We assessed trial quality using the Cochrane ’Risk of bias’ tool. Main results Twenty-four double-blind trials with 4631 participants including a total of 33 comparisons of Echinacea preparations and placebo met the inclusion criteria. A variety of different Echinacea preparations based on different species and parts of plant were used. Evidence from seven trials was available for preparations based on the aerial parts of Echinacea purpurea. Ten trials were considered to have a low risk of bias, six to have an unclear risk of bias and eight to have a high risk of bias. Ten trials with 13 comparisons investigated prevention and 15 trials with 20 comparisons investigated treatment of colds (one trial addressed both prevention and treatment). Due to the strong clinical heterogeneity of the studies we refrained from pooling for the main analysis. None of the 12 prevention comparisons reporting the number of patients with at least one cold episode found a statistically significant difference. However a post hoc pooling of their results, suggests a relative risk reduction of 10% to 20%. Of the seven treatment trials reporting data on the duration of colds, only one showed a significant effect of Echinacea over placebo. The number of patients dropping out or reporting adverse effects did not differ significantly between treatment and control groups in prevention and treatment trials. However, in prevention trials there was a trend towards a larger number of patients dropping out due to adverse events in the treatment groups. Authors’ conclusions Echinacea products have not here been shown to provide benefits for treating colds, although, it is possible there is a weak benefit from some Echinacea products: the results of individual prophylaxis trials consistently show positive (if non-significant) trends, although potential effects are of questionable clinical relevance. PMID:24554461

Nonresponse bias in randomized controlled experiments in criminology: Putting the Queensland Community Engagement Trial (QCET) under a microscope.

PubMed

Antrobus, Emma; Elffers, Henk; White, Gentry; Mazerolle, Lorraine

2013-01-01

The goal of this article is to examine whether or not the results of the Queensland Community Engagement Trial (QCET)-a randomized controlled trial that tested the impact of procedural justice policing on citizen attitudes toward police-were affected by different types of nonresponse bias. We use two methods (Cochrane and Elffers methods) to explore nonresponse bias: First, we assess the impact of the low response rate by examining the effects of nonresponse group differences between the experimental and control conditions and pooled variance under different scenarios. Second, we assess the degree to which item response rates are influenced by the control and experimental conditions. Our analysis of the QCET data suggests that our substantive findings are not influenced by the low response rate in the trial. The results are robust even under extreme conditions, and statistical significance of the results would only be compromised in cases where the pooled variance was much larger for the nonresponse group and the difference between experimental and control conditions was greatly diminished. We also find that there were no biases in the item response rates across the experimental and control conditions. RCTs that involve field survey responses-like QCET-are potentially compromised by low response rates and how item response rates might be influenced by the control or experimental conditions. Our results show that the QCET results were not sensitive to the overall low response rate across the experimental and control conditions and the item response rates were not significantly different across the experimental and control groups. Overall, our analysis suggests that the results of QCET are robust and any biases in the survey responses do not significantly influence the main experimental findings.

Efficacy and safety profile evaluation of acarbose alone and in association with other antidiabetic drugs: a systematic review.

PubMed

Derosa, Giuseppe; Maffioli, Pamela

2012-06-01

Epidemiologic studies have revealed that postprandial hyperglycemia significantly contributes to high glycated hemoglobin concentrations and could be linked to the development of chronic diabetic complications. The purpose of our review was to evaluate the clinical efficacy and safety profile of treatment with acarbose alone and combined with other antidiabetic drugs. A systematic search strategy was developed to identify randomized controlled trials included in MEDLINE and the Cochrane Register of Controlled Trials. The terms acarbose, α-glucosidase inhibitors, type 2 diabetes, adverse events, combination therapy, and postprandial glucose were incorporated into an electronic search strategy that included the Dickersin filter for randomized controlled trials. To qualify for inclusion, clinical trials had to be randomized trials comparing treatment with acarbose at any dosage with any other antidiabetic drug in patients with type 2 diabetes mellitus or impaired glucose tolerance. Eligible trials had to present results on glycemic control or adverse events. Trial participants needed to be affected by type 2 diabetes mellitus or have impaired glucose tolerance, and the intervention had to include acarbose at any dosage as monotherapy or combined with other antidiabetic drugs. A validated 3-item scale was used to evaluate the overall reporting quality of the trials selected for inclusion in the present review. Nineteen trials were included. Treatment with acarbose significantly reduced glycated hemoglobin levels when given as monotherapy and as an add-on to other antidiabetic drug treatment (P < 0.0001). Acarbose treatment was effective in patients with uncontrolled type 2 diabetes and in patients with apparently good metabolic control owing to its positive effect on postprandial hyperglycemia (P < 0.0001). Treatment with acarbose seemed to improve the lipid profile (P < 0.05), reduce circulating levels of cell adhesion molecules (P < 0.05), reduce intima-media thickness progression (P = 0.01), and reverse impaired glucose tolerance to normal glucose tolerance (P < 0.0001). When current therapy is not adequate to obtain glycemic control, acarbose could be an option as monotherapy and as an add-on to other antidiabetic drug treatment, especially when postprandial hyperglycemia is the main concern. Long-term studies are needed to determine whether the effects observed with acarbose use are maintained over the years. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

A Review of Marital Intimacy-Enhancing Interventions among Married Individuals

PubMed Central

Kardan-Souraki, Maryam; Hamzehgardeshi, Zeinab; Asadpour, Ismail; Mohammadpour, Reza Ali; Khani, Soghra

2016-01-01

Background: Lack of intimacy is currently the main concern rather than main concern of the experts in psychology and counseling. It is considered as one of the most important causes for divorce and as such to improve marital intimacy a great number of interventions have been proposed in the literature. Intimacy training and counseling make the couples take effective and successful steps to increase marital intimacy. No study has reviewed the interventions promoting marital intimacy after marriage. Thus, this review study aimed to classify the articles investigating the impact of interventional programs on marital intimacy after marriage. Search Methods: In April 2015, we performed a general search in Google Scholar search engines, and then we did an advanced search the databases of Science Direct, ProQuest, SID, Magiran, Irandoc, Pubmed, Scopus, Cochrane Library, and Psych info; Cumulative Index to Nursing and Allied Health Literature (CINAHL). Also, lists of the references of the relevant articles were reviewed for additional citations. Using Medical Subject Headings (MESH) keywords: Intervention (Clinical Trials, Non-Randomized Controlled Trials, Randomized Controlled Trials, Education), intimacy, marital (Marriage) and selected related articles to the study objective were from 1995 to April 2015. Clinical trials that evaluated one or more behavioral interventions to improve marital intimacy were reviewed in the study. Main Results: 39 trials met the inclusion criteria. Eleven interventions had follow-up, and 28 interventions lacked follow-up. The quality evidence for 22 interventions was low, for 15 interventions moderate, and for one intervention was considered high. Findings from studies were categorized in 11 categories as the intimacy promoting interventions in dimensions of emotional, psychological, physical, sexual, temporal, communicational, social and recreational, aesthetic, spiritual, intellectual intimacy, and total intimacy. Authors’ Conclusions: Improving and promoting communication, problem solving, self-disclosure and empathic response skills and sexual education and counseling in the form of cognitive-behavioral techniques and based on religious and cultural context of each society, an effective step can be taken to enhance marital intimacy and strengthen family bonds and stability. Health care providers should consider which interventions are appropriate to the couple characteristics and their relationships. PMID:27045400

A randomised controlled non-inferiority trial of primary care-based facilitated access to an alcohol reduction website (EFAR Spain): the study protocol

PubMed Central

López-Pelayo, Hugo; Wallace, Paul; Segura, Lidia; Miquel, Laia; Díaz, Estela; Teixidó, Lidia; Baena, Begoña; Struzzo, Pierliugio; Palacio-Vieira, Jorge; Casajuana, Cristina; Colom, Joan; Gual, Antoni

2014-01-01

Introduction Early identification (EI) and brief interventions (BIs) for risky drinkers are effective tools in primary care. Lack of time in daily practice has been identified as one of the main barriers to implementation of BI. There is growing evidence that facilitated access by primary healthcare professionals (PHCPs) to a web-based BI can be a time-saving alternative to standard face-to-face BIs, but there is as yet no evidence about the effectiveness of this approach relative to conventional BI. The main aim of this study is to test non-inferiority of facilitation to a web-based BI for risky drinkers delivered by PHCP against face-to-face BI. Method and analysis A randomised controlled non-inferiority trial comparing both interventions will be performed in primary care health centres in Catalonia, Spain. Unselected adult patients attending participating centres will be given a leaflet inviting them to log on to a website to complete the Alcohol Use Disorders Identification Test (AUDIT-C) alcohol screening questionnaire. Participants with positive results will be requested online to complete a trial module including consent, baseline assessment and randomisation to either face-to-face BI by the practitioner or BI via the alcohol reduction website. Follow-up assessment of risky drinking will be undertaken online at 3 months and 1 year using the full AUDIT and D5-EQD5 scale. Proportions of risky drinkers in each group will be calculated and non-inferiority assessed against a specified margin of 10%. Assuming reduction of 30% of risky drinkers receiving standard intervention, 1000 patients will be required to give 90% power to reject the null hypothesis. Ethics and dissemination The protocol was approved by the Ethics Commmittee of IDIAP Jordi Gol i Gurina P14/028. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations. Trial registration number ClinicalTrials.gov NCT02082990. PMID:25552616

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

Treatment of diverticular disease of the colon and prevention of acute diverticulitis: a systematic review.

PubMed

Maconi, Giovanni; Barbara, Giovanni; Bosetti, Cristina; Cuomo, Rosario; Annibale, Bruno

2011-10-01

Diverticular disease of the colon is a common disorder, characterized by recurrent symptoms and complications such as diverticulitis, requiring hospital admissions and surgery. This study aimed to systematically review the evidence for medical therapy of diverticular disease in reducing symptoms and preventing acute diverticulitis. MEDLINE and Embase databases (1966 to February 2010). The studies selected were prospective clinical trials on uncomplicated diverticular disease of the colon. Four investigators independently reviewed articles, extracted data, and assessed study quality according to standardized criteria. The main outcomes measured were improvement in symptoms, complete remission of symptoms, and prevention of acute diverticulitis. We identified 31 studies, including 6 placebo-controlled trials. The methodological quality of these studies was suboptimal. Only 10 trials provided a detailed description of the patient history, 8 assessed symptoms by the use of a validated questionnaire, and 14 appropriately defined inclusion and exclusion criteria. Only one long-term double-blind placebo-controlled study was identified. This reported a significant improvement in symptoms and greater prevalence of symptom-free patients at 1 year with fiber plus rifaximin in comparison with fiber alone. The efficacy of treatment in preventing acute diverticulitis was evaluated in 11 randomized trials. Four trials compared rifaximin plus fiber vs fiber alone and failed to show a significant difference between treatments. However, cumulative data from these trials revealed a significant benefit following rifaximin and fiber (1-year rate of acute diverticulitis: 11/970 (1.1%) vs 20/690 (2.9%); P = .012), but with a number needed to treat of 57, to prevent an attack of acute diverticulitis. : Heterogeneity of the study design, patients' characteristics, regimens and combination of studied treatment, and outcome reporting precluded the pooling of results and limited interpretation. The treatment for diverticular disease relies mainly on data from uncontrolled studies. Treatment showed some evidence of improvement in symptoms, but its role in the prevention of acute diverticulitis remains to be defined.

Earlier versus later continuous Kangaroo Mother Care (KMC) for stable low-birth-weight infants: a randomized controlled trial.

PubMed

Nagai, S; Andrianarimanana, D; Rabesandratana, N; Yonemoto, N; Nakayama, T; Mori, R

2010-06-01

The aim of this study was to examine the effectiveness of earlier continuous Kangaroo Mother Care (KMC) for relatively stable low-birth-weight (LBW) infants in a resource-limited country. A randomized controlled trial was performed in LBW infants at a referral hospital in Madagascar. Earlier continuous KMC (intervention) was begun as soon as possible, within 24 h postbirth, and later continuous KMC (control: conventional care) was begun after complete stabilization (generally after 24 h postbirth). Main outcome measure was mortality during the first 28 days postbirth. This trial was registered with ClinicalTrials.gov, NCT00531492. A total of 73 infants (intervention 37, control 36) were included. Earlier continuous KMC had higher but no statistically different mortality in the first 28 days postbirth (1 vs. 2; risk ratio, 1.95; 95% CIs, 0.18-20.53; p = 1.00). There were no differences in incidence of morbidities. Body weight loss from birth to 24 h postbirth was significantly less in earlier KMC infants compared with later KMC infants. (-34.81 g vs. -73.97 g; mean difference, 39.16 g; 95% CIs, 10.30-68.03; p = 0.01; adjusted p = 0.02). Adverse events and duration of hospitalization were not different between the two groups. Further evaluations of earlier continuous KMC including measurement of KMC dose, are needed in resource-limited countries.

Is reflexology an effective intervention? A systematic review of randomised controlled trials.

PubMed

Ernst, Edzard

2009-09-07

To evaluate the evidence for and against the effectiveness of reflexology for treating any medical condition. Six electronic databases were searched from their inception to February 2009 to identify all relevant randomised controlled trials (RCTs). No language restrictions were applied. RCTs of reflexology delivered by trained reflexologists to patients with specific medical conditions. Condition studied, study design and controls, primary outcome measures, follow-up, and main results were extracted. 18 RCTs met all the inclusion criteria. The studies examined a range of conditions: anovulation, asthma, back pain, dementia, diabetes, cancer, foot oedema in pregnancy, headache, irritable bowel syndrome, menopause, multiple sclerosis, the postoperative state and premenstrual syndrome. There were > 1 studies for asthma, the postoperative state, cancer palliation and multiple sclerosis. Five RCTs yielded positive results. Methodological quality was evaluated using the Jadad scale. The methodological quality was often poor, and sample sizes were generally low. Most higher-quality trials did not generate positive findings. The best evidence available to date does not demonstrate convincingly that reflexology is an effective treatment for any medical condition.

N of 1, two contemporary arm, randomised controlled clinical trial for bilateral epicondylitis: a new study design

PubMed Central

Fante, Claudia Del; Perotti, Cesare; Pavesi, Claudio Francesco; Coscia, Davide; Scotti, Valeria; Tinelli, Carmine

2011-01-01

Objective To investigate the use of a novel study design in analysis of bilateral elbow pain. Design N of 1, two contemporary arm, open label, randomised controlled clinical trial. Setting A clinical epidemiologist at a university hospital in Pavia, Italy. Participants Two elbows with epicondylitis. Interventions Autologous platelet lysate versus “wait and see” strategy. Main outcome measures Visual analogue scale for pain on elbow extension and resisted wrist extension. Results Over six months’ follow-up, the patient experienced bilateral improvement in pain, but higher in the treated arm, with a drop in visual analogue scale for pain from 28 to 4 for right (control) arm (drop of 24 points) and from 67 to 10.5 for left (treated) arm (drop of 56.5 points). Conclusions Platelet lysate might (or might not) work. Competing interests and lack of blinding might be relevant issues in the interpretation of trial results. However, the new study design can be applied to a number of conditions such as bilateral sport or trauma injuries, bilateral otitis, or any condition affecting chiral organs or limbs. PMID:22187187

The size of a pilot study for a clinical trial should be calculated in relation to considerations of precision and efficiency.

PubMed

Sim, Julius; Lewis, Martyn

2012-03-01

To investigate methods to determine the size of a pilot study to inform a power calculation for a randomized controlled trial (RCT) using an interval/ratio outcome measure. Calculations based on confidence intervals (CIs) for the sample standard deviation (SD). Based on CIs for the sample SD, methods are demonstrated whereby (1) the observed SD can be adjusted to secure the desired level of statistical power in the main study with a specified level of confidence; (2) the sample for the main study, if calculated using the observed SD, can be adjusted, again to obtain the desired level of statistical power in the main study; (3) the power of the main study can be calculated for the situation in which the SD in the pilot study proves to be an underestimate of the true SD; and (4) an "efficient" pilot size can be determined to minimize the combined size of the pilot and main RCT. Trialists should calculate the appropriate size of a pilot study, just as they should the size of the main RCT, taking into account the twin needs to demonstrate efficiency in terms of recruitment and to produce precise estimates of treatment effect. Copyright © 2012 Elsevier Inc. All rights reserved.

The unbearable lightness of technocratic efforts at dengue control.

PubMed

Toledo, Maria E; Baly, Alberto; Vanlerberghe, Veerle; Rodríguez, Maritza; Benitez, Juan R; Duvergel, Jacinto; Van der Stuyft, Patrick

2008-05-01

To identify key elements that should provide an added value and assure sustainable effects of the deployment of technical tools for Aedes aegypti control. An observational study was conducted between April 2001 and March 2002 in 30 blocks (1574 houses) in the central zone of Guantanamo city. A trial that combined two complementary technical interventions, the distribution of new ground level water tanks and the intensive use of insecticide, was nested in May 2001. Another 30 blocks (1535 houses) were selected as control area. We assessed community perceptions and household risk behaviour at baseline and after 9 months, and measured the trial's impact through entomological indices. Perceived self efficacy to solve A. aegypti infestation and prevent dengue was not modified. We found no changes in behaviour. In the study area the container indices decreased significantly from 0.7% before to 0.1% 1 month after the intervention. Six months later, they had increased to 2.7% and uncovered new water tanks constituted 75.9% of all breeding sites. Over the 9 months after the trial the average monthly house indices were similar in the study and control areas. A technical approach and lack of community involvement in the trial's implementation were the main causes of these short-lived results. Top-down deployment of technical tools without active involvement of the community has a temporary effect and does not lead to the behavioural changes necessary for sustainable A. aegypti control.

Adaptation to recent conflict in the classical color-word Stroop-task mainly involves facilitation of processing of task-relevant information.

PubMed

Purmann, Sascha; Pollmann, Stefan

2015-01-01

To process information selectively and to continuously fine-tune selectivity of information processing are important abilities for successful goal-directed behavior. One phenomenon thought to represent this fine-tuning are conflict adaptation effects in interference tasks, i.e., reduction of interference after an incompatible trial and when incompatible trials are frequent. The neurocognitive mechanisms of these effects are currently only partly understood and results from brainimaging studies so far are mixed. In our study we validate and extend recent findings by examining adaption to recent conflict in the classical Stroop task using functional magnetic resonance imaging. Consistent with previous research we found increased activity in a fronto-parietal network comprising the medial prefrontal cortex, ventro-lateral prefrontal cortex, and posterior parietal cortex when contrasting incompatible with compatible trials. These areas have been associated with attentional processes and might reflect increased cognitive conflict and resolution thereof during incompatible trials. While carefully controlling for non-attentional sequential effects we found smaller Stroop interference after an incompatible trial (conflict adaptation effect). These behavioral conflict adaptation effects were accompanied by changes in activity in visual color-selective areas (V4, V4α), while there was no modulation by previous trial compatibility in a visual word-selective area (VWFA). Our results provide further evidence for the notion, that adaptation to recent conflict seems to be based mainly on enhancement of processing of the task-relevant information.

Figures in clinical trial reports: current practice & scope for improvement

PubMed Central

Pocock, Stuart J; Travison, Thomas G; Wruck, Lisa M

2007-01-01

Background Most clinical trial publications include figures, but there is little guidance on what results should be displayed as figures and how. Purpose To evaluate the current use of figures in Trial reports, and to make constructive suggestions for future practice. Methods We surveyed all 77 reports of randomised controlled trials in five general medical journals during November 2006 to January 2007. The numbers and types of figures were determined, and then each Figure was assessed for its style, content, clarity and suitability. As a consequence, guidelines are developed for presenting figures, both in general and for each specific common type of Figure. Results Most trial reports contained one to three figures, mean 2.3 per article. The four main types were flow diagram, Kaplan Meier plot, Forest plot (for subgroup analyses) and repeated measures over time: these accounted for 92% of all figures published. For each type of figure there is a considerable diversity of practice in both style and content which we illustrate with selected examples of both good and bad practice. Some pointers on what to do, and what to avoid, are derived from our critical evaluation of these articles' use of figures. Conclusion There is considerable scope for authors to improve their use of figures in clinical trial reports, as regards which figures to choose, their style of presentation and labelling, and their specific content. Particular improvements are needed for the four main types of figures commonly used. PMID:18021449

Testing moderation in network meta-analysis with individual participant data

PubMed Central

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

2016-01-01

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

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.

Planned hospital birth versus planned home birth

PubMed Central

Olsen, Ole; Clausen, Jette A

2014-01-01

Background Observational studies of increasingly better quality and in different settings suggest that planned home birth in many places can be as safe as planned hospital birth and with less intervention and fewer complications. This is an update of a Cochrane review first published in 1998. Objectives To assess the effects of planned hospital birth compared with planned home birth in selected low-risk women, assisted by an experienced midwife with collaborative medical back up in case transfer should be necessary. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 March 2012) and contacted editors and authors involved with possible trials. Selection criteria Randomised controlled trials comparing planned hospital birth with planned home birth in low-risk women as described in the objectives. Data collection and analysis The two review authors as independently as possible assessed trial quality and extracted data. We contacted study authors for additional information. Main results Two trials met the inclusion criteria but only one trial involving 11 women provided some outcome data and was included. The evidence from this trial was of moderate quality and too small to allow conclusions to be drawn. Authors’ conclusions There is no strong evidence from randomised trials to favour either planned hospital birth or planned home birth for low-risk pregnant women. However, the trials show that women living in areas where they are not well informed about home birth may welcome ethically well-designed trials that would ensure an informed choice. As the quality of evidence in favour of home birth from observational studies seems to be steadily increasing, it might be as important to prepare a regularly updated systematic review including observational studies as described in the Cochrane Handbook for Systematic Reviews of Interventions as to attempt to set up new randomised controlled trials. PMID:22972043

Time-Lag Bias in Trials of Pediatric Antidepressants: A Systematic Review and Meta-Analysis

PubMed Central

Reyes, Magdalena M.; Panza, Kaitlyn E.; Martin, Andrés; Bloch, Michael H.

2013-01-01

Objective To determine if there is evidence of a time-lag bias in the publication of pediatric antidepressant trials. Method We conducted a meta-analysis of published and unpublished randomized, placebo-controlled trials of serotonin reuptake inhibitors (SRIs) in subjects less than 18 years old with major depressive disorder. Our main outcomes were (1) time to publication of positive versus negative trials, and (2) proportion of treatment responders in trials with standard (< 3 years after study completion) versus delayed publication. Results We identified 15 randomized, placebo-controlled trials of SRIs for pediatric depression. Trials with negative findings had a significantly longer time to publication (median years ± standard deviation = 4.2 ±1.9) than trials with positive findings (2.2 ±0.9; log-rank χ2 = 4.35, p = 0.037). The estimated efficacy in trials with standard publication time (number needed to treat = 7, 95% CI: 5 – 11) was significantly greater than those with delayed publication (17, 95% CI: 9 – ∞; χ2 = 4.98, p = 0.025). The inflation-adjusted impact factor of journals for published trials with positive (15.33 ±11.01) and negative results (7.54 ±7.90) did not statistically differ (t = 1.4, df = 10, p = 0.17). Conclusions Despite a small number of trials of SRIs for pediatric antidepressants we found a significant evidence of time-lag bias in the publication of findings. This time-lag bias altered the perceived efficacy of pediatric antidepressants in the medical literature. Time-lag bias is not unique to child psychiatry and reflects a larger problem in scientific publishing. PMID:21156271

Remedial after-school support classes offered in rural Gambia (The SCORE trial): study protocol for a cluster randomized controlled trial.

PubMed

Boone, Peter; Camara, Alpha; Eble, Alex; Elbourne, Diana; Fernandes, Samory; Frost, Chris; Jayanty, Chitra; Lenin, Maitri; Silva, Ana Filipa

2015-12-16

Low education levels are endemic in much of the developing world, particularly in rural areas where traditional government-provided public services often have difficulty reaching beneficiaries. Providing trained para-teachers to teach regular after-school remedial education classes has been shown to improve literacy and numeracy in children of primary school age residing in such areas in India. This trial investigates whether such an intervention can also be effective in a West African setting with similarly low learning levels and difficult geographic access. cluster-randomized controlled trial. Clusters: villages or groups of villages with 15-300 households and at least 15 eligible children in the Lower River and North Bank Regions of The Gambia. children born between 1 September 2007 and 31 August 2009 planning to enter the first grade, for the first time, in the 2015-2016 school year in eligible villages. We anticipate enrolling approximately 150 clusters of villages with approximately 6000 children as participants. a program providing remedial after-school lessons, focusing on literacy and numeracy, 5 to 6 days a week for 3 years to eligible children, based on the intervention evaluated in the Support To Rural India's Public Education System (STRIPES) trial (PLoS ONE 8(7):e65775). both the intervention and control groups will receive small bundles of useful materials during annual data collection as recompense for their time. If the education intervention is shown to be cost-effective at raising learning levels, it is expected that the control group villages will receive the intervention for several years after the trial results are available. the primary outcome of the trial is a composite mathematics and language test score. Secondary outcomes include school attendance, enrollment, performance on nationally administered exams, parents' spending on education, spillover learning to siblings and family members, and school-related time use of parents and children. Subgroup analyses of the primary outcome will also be carried out based on ethnic group, gender, distance from the main highway, parents' education level, and school type. The trial will run by independent research and implementation teams and supervised by a Trial Steering Committee. Along with the overall impact of the intervention, we will conduct a cost-effectiveness analysis. There are no major ethical issues for this study. Current controlled trials ISRCTN12500245 . 1 May 2015.

First step in managing bulimia nervosa: controlled trial of therapeutic manual.

PubMed Central

Treasure, J.; Schmidt, U.; Troop, N.; Tiller, J.; Todd, G.; Keilen, M.; Dodge, E.

1994-01-01

OBJECTIVE--To test the short term efficacy of a self directed treatment manual for bulimia nervosa. DESIGN--Randomised controlled trial of the manual against cognitive behavioural therapy and a waiting list. SETTING--Tertiary referral centre. SUBJECTS--81 consecutive referrals presenting with bulimia nervosa or atypical bulimia nervosa. MAIN OUTCOME MEASURES--Frequency of binge eating, vomiting, and other behaviours to control weight as well as abstinence from these behaviours. RESULTS--Cognitive behavioural treatment produced a significant reduction in the frequency of binge eating, vomiting, and other behaviours to control weight. The manual significantly reduced frequency of binge eating and weight control behaviours other than vomiting, and there was no change in the group on the waiting list. Full remission was achieved in five (24%) of the group assigned to cognitive behavioural treatment, nine (22%) of the group who used the manual, and two (11%) of the group on the waiting list. CONCLUSIONS--A self directed treatment manual may be a useful first intervention in the treatment of bulimia nervosa. PMID:8142791

Do u smoke after txt? Results of a randomised trial of smoking cessation using mobile phone text messaging

PubMed Central

Rodgers, A; Corbett, T; Bramley, D; Riddell, T; Wills, M; Lin, R; Jones, M

2005-01-01

Objectives: To determine the effectiveness of a mobile phone text messaging smoking cessation programme. Design: Randomised controlled trial Setting: New Zealand Participants: 1705 smokers from throughout New Zealand who wanted to quit, were aged over 15 years, and owned a mobile phone were randomised to an intervention group that received regular, personalised text messages providing smoking cessation advice, support, and distraction, or to a control group. All participants received a free month of text messaging; starting for the intervention group on their quit day to assist with quitting, and starting for the control group at six months to encourage follow up. Follow up data were available for 1624 (95%) at six weeks and 1265 (74%) at six months. Main outcome measures: The main trial outcome was current non-smoking (that is, not smoking in the past week) six weeks after randomisation. Secondary outcomes included current non-smoking at 12 and 26 weeks. Results: More participants had quit at six weeks in the intervention compared to the control group: 239 (28%) v 109 (13%), relative risk 2.20 (95% confidence interval 1.79 to 2.70), p < 0.0001. This treatment effect was consistent across subgroups defined by age, sex, income level, or geographic location (p homogeneity > 0.2). The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests. Reported quit rates remained high at six months, but there was some uncertainty about between group differences because of incomplete follow up. Conclusions: This programme offers potential for a new way to help young smokers to quit, being affordable, personalised, age appropriate, and not location dependent. Future research should test these findings in different settings, and provide further assessment of long term quit rates. PMID:16046689

Evaluation of the COPING parent online universal programme: study protocol for a pilot randomised controlled trial

PubMed Central

Owen, Dawn Adele; Griffith, Nia; Hutchings, Judy

2017-01-01

Trial sponsor Bangor University, Brigantia Building, College Road, Bangor, LL57 2AS, UK Introduction The COPING parent online universal programme is a web-based parenting intervention for parents of children aged 3-8 years with an interest in positive parenting. The programme focuses on strengthening parent-child relationships and encouraging positive child behaviour. This trial will evaluate whether the intervention is effective in increasing the use of positive parenting strategies outlined in the programme using parent report and blind observation measures. Methods and analysis This is a pilot randomised controlled trial with intervention and wait-list control conditions. The intervention is a 10-week online parenting programme to promote positive parent-child relations by teaching core social learning theory principles that encourage positive child behaviour, primarily through the use of praise and rewards. Health visitors and school nurses will circulate a recruitment poster to parents of children aged 3–8 years on their current caseloads. Recruitment posters will also be distributed via local primary schools and nurseries. Parents recruited to the trial will be randomised on a 2:1 ratio to intervention or wait-list control conditions (stratified according to child gender and age). The primary outcome measure is positive parenting as measured by a behavioural observation of parent-child interactions using the Dyadic Parent-Child Interaction Coding System. Secondary outcomes include parent report of child behaviour, and self-reported parental sense of competence, parenting behaviour and parental mental health. Data will be collected at baseline and 3 months later (postintervention) for all participants and 6 months postbaseline for the intervention group only. Analysis of covariance will be the main statistical method used. Ethics and dissemination The trial has received ethical approval from the NHS Betsi Cadwaladr University Health Board Ethics Committee (REC) and the School of Psychology, Bangor University REC (15/WA/0463). Publication of all outcomes will be in peer-reviewed journals and conference presentations. Trial registration number Current Controlled Trials ISRCTN89370147 (5 May 2016). PMID:28446523

Adolescents’ use of purpose built shade in secondary schools: cluster randomised controlled trial

PubMed Central

White, Vanessa; Wakefield, Melanie A; Jamsen, Kris M; White, Victoria; Livingston, Patricia M; English, Dallas R; Simpson, Julie A

2009-01-01

Objective To examine whether students use or avoid newly shaded areas created by shade sails installed at schools. Design Cluster randomised controlled trial with secondary schools as the unit of randomisation. Setting 51 secondary schools with limited available shade, in Australia, assessed over two spring and summer terms. Participants Students outside at lunch times. Intervention Purpose built shade sails were installed in winter 2005 at full sun study sites to increase available shade for students in the school grounds. Main outcome measure Mean number of students using the primary study sites during weekly observations at lunch time. Results Over the study period the mean change in students using the primary study site from pre-test to post-test was 2.63 (95% confidence interval 0.87 to 4.39) students in intervention schools and −0.03 (−1.16 to 1.09) students in control schools. The difference in mean change between groups was 2.67 (0.65 to 4.68) students (P=0.011). Conclusions Students used rather than avoided newly shaded areas provided by purpose built shade sails at secondary schools in this trial, suggesting a practical means of reducing adolescents’ exposure to ultraviolet radiation. Trial registration Exempt. PMID:19223344

Hydrotherapy as a recovery strategy after exercise: a pragmatic controlled trial

PubMed Central

2013-01-01

Background Our aim was to evaluate the recovery effects of hydrotherapy after aerobic exercise in cardiovascular, performance and perceived fatigue. Methods A pragmatic controlled repeated measures; single-blind trial was conducted. Thirty-four recreational sportspeople visited a Sport-Centre and were assigned to a Hydrotherapy group (experimental) or rest in a bed (control) after completing a spinning session. Main outcomes measures including blood pressure, heart rate, handgrip strength, vertical jump, self-perceived fatigue, and body temperature were assessed at baseline, immediately post-exercise and post-recovery. The hypothesis of interest was the session*time interaction. Results The analysis revealed significant session*time interactions for diastolic blood pressure (P=0.031), heart rate (P=0.041), self perceived fatigue (P=0.046), and body temperature (P=0.001); but not for vertical jump (P=0.437), handgrip (P=0.845) or systolic blood pressure (P=0.266). Post-hoc analysis revealed that hydrotherapy resulted in recovered heart rate and diastolic blood pressure similar to baseline values after the spinning session. Further, hydrotherapy resulted in decreased self-perceived fatigue after the spinning session. Conclusions Our results support that hydrotherapy is an adequate strategy to facilitate cardiovascular recovers and perceived fatigue, but not strength, after spinning exercise. Trial registration ClinicalTrials.gov Identifier: NCT01765387 PMID:23866725

Physical activity and resting pulse rate in older adults: findings from a randomized controlled trial

USDA-ARS?s Scientific Manuscript database

Background: Elevated resting pulse rate (RPR) is a well-recognized risk factor for adverse outcomes. Epidemiological evidence supports the beneficial effects of regular exercise for lowering RPR, but studies are mainly confined to persons younger than 65 years. We set out to evaluate the utility of ...

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

PubMed

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

2016-07-10

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

Can research assessments themselves cause bias in behaviour change trials? A systematic review of evidence from solomon 4-group studies.

PubMed

McCambridge, Jim; Butor-Bhavsar, Kaanan; Witton, John; Elbourne, Diana

2011-01-01

The possible effects of research assessments on participant behaviour have attracted research interest, especially in studies with behavioural interventions and/or outcomes. Assessments may introduce bias in randomised controlled trials by altering receptivity to intervention in experimental groups and differentially impacting on the behaviour of control groups. In a Solomon 4-group design, participants are randomly allocated to one of four arms: (1) assessed experimental group; (2) unassessed experimental group (3) assessed control group; or (4) unassessed control group. This design provides a test of the internal validity of effect sizes obtained in conventional two-group trials by controlling for the effects of baseline assessment, and assessing interactions between the intervention and baseline assessment. The aim of this systematic review is to evaluate evidence from Solomon 4-group studies with behavioural outcomes that baseline research assessments themselves can introduce bias into trials. Electronic databases were searched, supplemented by citation searching. Studies were eligible if they reported appropriately analysed results in peer-reviewed journals and used Solomon 4-group designs in non-laboratory settings with behavioural outcome measures and sample sizes of 20 per group or greater. Ten studies from a range of applied areas were included. There was inconsistent evidence of main effects of assessment, sparse evidence of interactions with behavioural interventions, and a lack of convincing data in relation to the research question for this review. There were too few high quality completed studies to infer conclusively that biases stemming from baseline research assessments do or do not exist. There is, therefore a need for new rigorous Solomon 4-group studies that are purposively designed to evaluate the potential for research assessments to cause bias in behaviour change trials.

Impact of the European Clinical Trials Directive on academic clinical research.

PubMed

Baeyens, A J

2004-01-01

With the adoption of the Clinical Trials Directive it was Europe's intention to make the performance of multi-national clinical trials in Europe easier through the harmonization of the regulatory procedures. As the Directive was mainly conceived to facilitate the performance of multi-national clinical trials to develop new drugs, it is to be determined to what extent academic clinical trials will be concerned by the Directive and more importantly what will be its impact on daily academic clinical research. Contrary to several national regulations the scope of the Directive is very large only excluding non-interventional trials. This implies that most of the academic clinical trials will be concerned by the Directive. Besides the handling of the regulatory procedures in the different countries, issues related to insurance, labeling requirements and provision of the investigational medical products will expose the academic sponsor to additional administrative and financial challenges that will have to be handled appropriately, as the academic sponsors will be controlled by Inspectors regarding their compliance with the new regulations to come.

Community involvement in dengue vector control: cluster randomised trial

PubMed Central

Toledo, M E; Rodríguez, M; Gomez, D; Baly, A; Benitez, J R; Van der Stuyft, P

2009-01-01

Objective To assess the effectiveness of an integrated community based environmental management strategy to control Aedes aegypti, the vector of dengue, compared with a routine strategy. Design Cluster randomised trial. Setting Guantanamo, Cuba. Participants 32 circumscriptions (around 2000 inhabitants each). Interventions The circumscriptions were randomly allocated to control clusters (n=16) comprising routine Aedes control programme (entomological surveillance, source reduction, selective adulticiding, and health education) and to intervention clusters (n=16) comprising the routine Aedes control programme combined with a community based environmental management approach. Main outcome measures The primary outcome was levels of Aedes infestation: house index (number of houses positive for at least one container with immature stages of Ae aegypti per 100 inspected houses), Breteau index (number of containers positive for immature stages of Ae aegypti per 100 inspected houses), and the pupae per inhabitant statistic (number of Ae aegypti pupae per inhabitant). Results All clusters were subjected to the intended intervention; all completed the study protocol up to February 2006 and all were included in the analysis. At baseline the Aedes infestation levels were comparable between intervention and control clusters: house index 0.25% v 0.20%, pupae per inhabitant 0.44×10−3 v 0.29×10−3. At the end of the intervention these indices were significantly lower in the intervention clusters: rate ratio for house indices 0.49 (95% confidence interval 0.27 to 0.88) and rate ratio for pupae per inhabitant 0.27 (0.09 to 0.76). Conclusion A community based environmental management embedded in a routine control programme was effective at reducing levels of Aedes infestation. Trial registration Current Controlled Trials ISRCTN88405796. PMID:19509031

Effect of tailored on-road driving lessons on driving safety in older adults: A randomised controlled trial.

PubMed

Anstey, Kaarin J; Eramudugolla, Ranmalee; Kiely, Kim M; Price, Jasmine

2018-06-01

We evaluated the effectiveness of individually tailored driving lessons compared with a road rules refresher course for improving older driver safety. Two arm parallel randomised controlled trial, involving current drivers aged 65 and older (Mean age 72.0, 47.4% male) residing in Canberra, Australia. The intervention group (n = 28) received a two-hour class-based road rules refresher course, and two one-hour driving lessons tailored to improve poor driving skills and habits identified in a baseline on-road assessment. The control group (n = 29) received the road rules refresher course only. Tests of cognitive performance, and on-road driving were conducted at baseline and at 12-weeks. Main outcome measure was the Driver safety rating (DSR) on the on-road driving test. The number of Critical Errors made during the on-road was also recorded. 55 drivers completed the trial (intervention group: 27, control group: 28). Both groups showed reduction in dangerous/hazardous driver errors that required instructor intervention. From baseline to follow-up there was a greater reduction in the number of critical errors made by the intervention group relative to the control group (IRR = 0.53, SE = 0.1, p = .008). The intervention group improved on the DSR more than the control group (intervention mean change = 1.07 SD = 2.00, control group mean change = 0.32 SD = 1.61). The intervention group had 64% remediation of unsafe driving, where drivers who achieved a score of 'fail' at baseline, 'passed' at follow-up. The control group had 25% remediation. Tailored driving lessons reduced the critical driving errors made by older adults. Longer term follow-up and larger trials are required. Copyright © 2018 Elsevier Ltd. All rights reserved.

A novel school-based intervention to improve nutrition knowledge in children: cluster randomised controlled trial

PubMed Central

2010-01-01

Background Improving nutrition knowledge among children may help them to make healthier food choices. The aim of this study was to assess the effectiveness and acceptability of a novel educational intervention to increase nutrition knowledge among primary school children. Methods We developed a card game 'Top Grub' and a 'healthy eating' curriculum for use in primary schools. Thirty-eight state primary schools comprising 2519 children in years 5 and 6 (aged 9-11 years) were recruited in a pragmatic cluster randomised controlled trial. The main outcome measures were change in nutrition knowledge scores, attitudes to healthy eating and acceptability of the intervention by children and teachers. Results Twelve intervention and 13 control schools (comprising 1133 children) completed the trial. The main reason for non-completion was time pressure of the school curriculum. Mean total nutrition knowledge score increased by 1.1 in intervention (baseline to follow-up: 28.3 to 29.2) and 0.3 in control schools (27.3 to 27.6). Total nutrition knowledge score at follow-up, adjusted for baseline score, deprivation, and school size, was higher in intervention than in control schools (mean difference = 1.1; 95% CI: 0.05 to 2.16; p = 0.042). At follow-up, more children in the intervention schools said they 'are currently eating a healthy diet' (39.6%) or 'would try to eat a healthy diet' (35.7%) than in control schools (34.4% and 31.7% respectively; chi-square test p < 0.001). Most children (75.5%) enjoyed playing the game and teachers considered it a useful resource. Conclusions The 'Top Grub' card game facilitated the enjoyable delivery of nutrition education in a sample of UK primary school age children. Further studies should determine whether improvements in nutrition knowledge are sustained and lead to changes in dietary behaviour. PMID:20219104

School-based intervention to improve the mental health of low-income, secondary school students in Santiago, Chile (YPSA): study protocol for a randomized controlled trial.

PubMed

Araya, Ricardo; Montgomery, Alan A; Fritsch, Rosemarie; Gunnell, David; Stallard, Paul; Noble, Sian; Martinez, Vania; Barroilhet, Sergio; Vohringer, Paul; Guajardo, Viviana; Cova, Felix; Gaete, Jorge; Gomez, Alejandro; Rojas, Graciela

2011-02-19

Depression is common and can have devastating effects on the life of adolescents. Psychological interventions are the first-line for treating or preventing depression among adolescents. This proposal aims to evaluate a school-based, universal psychological intervention to reduce depressive symptoms among student's aged 13-14 attending municipal state secondary schools in Santiago, Chile. This is a cluster randomised controlled trial with schools as the main clusters. We compared this intervention with a control group in a study involving 22 schools, 66 classes and approximately 2,600 students. Students in the active schools attended 11 weekly and 3 booster sessions of an intervention based on cognitive-behavioural models. The control schools received their usual but enhanced counselling sessions currently included in their curriculum. Mean depression scores and indicators of levels of functioning were assessed at 3 and 12 months after the completion of the intervention in order to assess the effectiveness of the intervention. Direct and indirect costs were measured in both groups to assess the cost-effectiveness of this intervention. As far as we are aware this is the first cluster randomised controlled trial of a school intervention for depression among adolescents outside the Western world. ISRCTN19466209.

Sample size determinations for group-based randomized clinical trials with different levels of data hierarchy between experimental and control arms.

PubMed

Heo, Moonseong; Litwin, Alain H; Blackstock, Oni; Kim, Namhee; Arnsten, Julia H

2017-02-01

We derived sample size formulae for detecting main effects in group-based randomized clinical trials with different levels of data hierarchy between experimental and control arms. Such designs are necessary when experimental interventions need to be administered to groups of subjects whereas control conditions need to be administered to individual subjects. This type of trial, often referred to as a partially nested or partially clustered design, has been implemented for management of chronic diseases such as diabetes and is beginning to emerge more commonly in wider clinical settings. Depending on the research setting, the level of hierarchy of data structure for the experimental arm can be three or two, whereas that for the control arm is two or one. Such different levels of data hierarchy assume correlation structures of outcomes that are different between arms, regardless of whether research settings require two or three level data structure for the experimental arm. Therefore, the different correlations should be taken into account for statistical modeling and for sample size determinations. To this end, we considered mixed-effects linear models with different correlation structures between experimental and control arms to theoretically derive and empirically validate the sample size formulae with simulation studies.

Cryotherapy following total knee replacement.

PubMed

Adie, Sam; Kwan, Amy; Naylor, Justine M; Harris, Ian A; Mittal, Rajat

2012-09-12

Total knee replacement (TKR) is a common intervention for patients with end-stage osteoarthritis of the knee. Post-surgical management may include cryotherapy. However, the effectiveness of cryotherapy is unclear. To evaluate the acute (within 48 hours) application of cryotherapy following TKR on pain, blood loss and function. We searched the Cochrane Database of Systematic Reviews, CENTRAL, DARE, HTA Database, MEDLINE, EMBASE, CINAHL, PEDro and Web of Science on 15th March 2012. Randomised controlled trials or controlled clinical trials in which the experimental group received any form of cryotherapy, and was compared to any control group following TKR indicated for osteoarthritis. Two reviewers independently selected trials for inclusion. Disagreements were discussed and resolved involving a third reviewer if required. Data were then extracted and the risk of bias of trials assessed. Main outcomes were blood loss, visual analogue score (VAS) pain, adverse events, knee range of motion, transfusion rate and knee function. Secondary outcomes were analgesia use, knee swelling, length of hospital stay, quality of life and activity level. Effects of interventions were estimated as mean differences (MD), standardised mean differences (SMD) or given as risk ratios (RR), with 95% confidence intervals (CI). Meta-analyses were performed using the inverse variance method and pooled using random effects. Eleven randomised trials and one controlled clinical trial involving 809 participants met the inclusion criteria. There is very low quality evidence from 10 trials (666 participants) that cryotherapy has a small benefit on blood loss (SMD -0.46, 95% CI, -0.84 to -0.08), equivalent to 225mL less blood loss in cryotherapy group (95% CI, 39 to 410mL). This benefit may not be clinically significant. There was very low quality evidence from four trials (322 participants) that cryotherapy improved visual analogue score pain at 48 hours (MD = -1.32 points on a 10 point scale, 95% CI, -2.37 to -0.27), but not at 24 or 72 hours. This benefit may not be clinically significant. There was no difference between groups in adverse events (RR = 0.98, 95% CI, 0.28 to 3.47). There is low quality evidence from two trials (107 participants) for improved range of motion at discharge (MD 11.39 degrees of additional flexion, 95% CI 4.13 to 18.66), but this benefit may not be clinically significant. There was no difference between groups in transfusion rate (RR 2.13, 95% CI 0.04 to 109.63), and knee function was not measured in any trial. No significant benefit were found for analgesia use, swelling or length of stay. Outcomes measuring quality of life or activity level were not reported. Potential benefits of cryotherapy on blood loss, postoperative pain, and range of motion may be too small to justify its use, and the quality of the evidence was very low or low for all main outcomes. This needs to be balanced against potential inconveniences and expenses of using cryotherapy. Well designed randomised trials are required to improve the quality of the evidence.

Efficacy and safety of Lian-Ju-Gan-Mao capsules for treating the common cold with wind-heat syndrome: study protocol for a randomized controlled trial.

PubMed

Wang, Shengjun; Jiang, Hongli; Yu, Qin; She, Bin; Mao, Bing

2017-01-05

The common cold is a common and frequent respiratory disease mainly caused by viral infection of the upper respiratory tract. Chinese herbal medicine has been increasingly prescribed to treat the common cold; however, there is a lack of evidence to support the wide utility of this regimen. This protocol describes an ongoing phase II randomized controlled clinical trial, based on the theory of traditional Chinese medicine (TCM), with the objective of evaluating the efficacy and safety of Lian-Ju-Gan-Mao capsules (LJGMC), a Chinese patent medicine, compared with placebo in patients suffering from the common cold with wind-heat syndrome (CCWHS). This is a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial. A total of 240 patients will be recruited and randomly assigned to a high-dose group, medium-dose group, low-dose group, and placebo-matched group in a 1:1:1:1 ratio. The treatment course is 3 consecutive days, with a 5-day follow-up. The primary outcome is time to all symptoms' clearance. Secondary outcomes include time to the disappearance of primary symptoms and each secondary symptom, time to fever relief, time to fever clearance, and change in TCM symptom and sign scores. This trial is a well-designed study according to principles and regulations issued by the China Food and Drug Administration (CFDA). The results will provide high-quality evidence on the efficacy and safety of LJGMC in treating CCWHS and help to optimize the dose for the next phase III clinical trial. Moreover, the protocol presents a detailed and practical methodology for future clinical trials of drugs developed based on TCM. Chinese Clinical Trial Registry, ChiCTR-IPR-15006504 . Registered on 4 June 2015.

RApid Primary care Initiation of Drug treatment for Transient Ischaemic Attack (RAPID−TIA): study protocol for a pilot randomised controlled trial

PubMed Central

2013-01-01

Background People who have a transient ischaemic attack (TIA) or minor stroke are at high risk of a recurrent stroke, particularly in the first week after the event. Early initiation of secondary prevention drugs is associated with an 80% reduction in risk of stroke recurrence. This raises the question as to whether these drugs should be given before being seen by a specialist – that is, in primary care or in the emergency department. The aims of the RAPID-TIA pilot trial are to determine the feasibility of a randomised controlled trial, to analyse cost effectiveness and to ask: Should general practitioners and emergency doctors (primary care physicians) initiate secondary preventative measures in addition to aspirin in people they see with suspected TIA or minor stroke at the time of referral to a specialist? Methods/Design This is a pilot randomised controlled trial with a sub-study of accuracy of primary care physician diagnosis of TIA. In the pilot trial, we aim to recruit 100 patients from 30 general practices (including out-of-hours general practice centres) and 1 emergency department whom the primary care physician diagnoses with TIA or minor stroke and randomly assign them to usual care (that is, initiation of aspirin and referral to a TIA clinic) or usual care plus additional early initiation of secondary prevention drugs (a blood-pressure lowering protocol, simvastatin 40 mg and dipyridamole 200 mg m/r bd). The primary outcome of the main study will be the number of strokes at 90 days. The diagnostic accuracy sub-study will include these 100 patients and an additional 70 patients in whom the primary care physician thinks the diagnosis of TIA is possible, rather than probable. For the pilot trial, we will report recruitment rate, follow-up rate, a preliminary estimate of the primary event rate and occurrence of any adverse events. For the diagnostic study, we will calculate sensitivity and specificity of primary care physician diagnosis using the final TIA clinic diagnosis as the reference standard. Discussion This pilot study will be used to estimate key parameters that are needed to design the main study and to estimate the accuracy of primary care diagnosis of TIA. The planned follow-on trial will have important implications for the initial management of people with suspected TIA. Trial registration ISRCTN62019087 PMID:23819476

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

PubMed

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

2014-01-01

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

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

PubMed Central

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

2014-01-01

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

Effectiveness and cost effectiveness of counselling in primary care.

PubMed

Bower, P; Rowland, N; Mellor, C l; Heywood, P; Godfrey, C; Hardy, R

2002-01-01

Counsellors are prevalent in primary care settings. However, there are concerns about the clinical and cost-effectiveness of the treatments they provide, compared with alternatives such as usual care from the general practitioner, medication or other psychological therapies. To assess the effectiveness and cost effectiveness of counselling in primary care by reviewing cost and outcome data in randomised controlled trials, controlled clinical trials and controlled patient preference trials of counselling interventions in primary care, for patients with psychological and psychosocial problems considered suitable for counselling. The original search strategy included electronic searching of databases (including the CCDAN Register of RCTs and CCTs) along with handsearching of a specialist journal. Published and unpublished sources (clinical trials, books, dissertations, agency reports etc.) were searched, and their reference lists scanned to uncover further controlled trials. Contact was made with subject experts and CCDAN members in order to uncover further trials. For the updated review, searches were restricted to those databases judged to be high yield in the first version of the review: MEDLINE, EMBASE, PSYCLIT and CINAHL, the Cochrane Controlled Trials register and the CCDAN trials register. All controlled trials comparing counselling in primary care with other treatments for patients with psychological and psychosocial problems considered suitable for counselling. Trials completed before the end of June 2001 were included in the review. Data were extracted using a standardised data extraction sheet. The relevant data were entered into the Review Manager software. Trials were quality rated, using CCDAN criteria, to assess the extent to which their design and conduct were likely to have prevented systematic error. Continuous measures of outcome were combined using standardised mean differences. An overall effect size was calculated for each outcome with 95% confidence intervals. Continuous data from different measuring instruments were transformed into a standard effect size by dividing mean values by standard deviations. In view of the diversity of counselling services in primary care (the range of treatments, patients and practitioners) tests of heterogeneity were done to assess the feasibility of aggregating measures of outcome from trials. Sensitivity analyses were undertaken to test the robustness of the results. Seven trials were included in the review. The main analyses showed significantly greater clinical effectiveness in the counselling group compared with 'usual care' in the short-term (standardised mean difference -0.28, 95% CI -0.43 to -0.13, n=772, 6 trials) but not the long-term (standardised mean difference -0.09, 95% CI -0.27 to 0.10, n=475, 4 trials). Levels of satisfaction with counselling were high. Four studies reported similar total costs associated with counselling and usual care over the long-term. However, the economic analyses were likely to be underpowered. Counselling is associated with modest improvement in short-term outcome compared to 'usual care', but provides no additional advantages in the long-term. Patients are satisfied with counselling, and it may not be associated with increased costs.

Suicide prevention after traumatic brain injury: a randomized controlled trial of a program for the psychological treatment of hopelessness.

PubMed

Simpson, Grahame K; Tate, Robyn L; Whiting, Diane L; Cotter, Rachel E

2011-01-01

To evaluate the efficacy of a psychological treatment to reduce moderate to severe hopelessness after severe traumatic brain injury (TBI). Randomized controlled trial. Participants were aged between 18 and 65 years, experienced posttraumatic amnesia more than 1day and moderate to severe hopelessness (Beck Hopelessness Scale [BHS]) and/or suicide ideation. Intervention comprised a 20-hour manualized group cognitive behavior therapy program. Participants were randomly allocated using concealed allocation (treatment n = 8; wait-list n = 9); all remained in their allocated group. Outcome variables were collected by assessors blind to group allocation. No between-groups differences were observed on demographic, injury, cognitive, and psychosocial variables at baseline (time 1). A significant group-by-time interaction was found for BHS in the treatment group (F1,15 = 13.20, P = .002), reflecting a reduction in mean BHS scores between time 1 and time 2 (posttreatment) with no main effects for group or time. At 3-month follow-up (time 3), the treatment gains were maintained or improved for 75% (6/8) of participants. Secondary outcome variables (suicide ideation, depression, social problem solving, self-esteem, hopefulness) displayed no significant group-by-time interactions or main effects. This trial provides initial evidence for the efficacy of a psychological intervention in reducing hopelessness among long-term survivors with severe TBI.

Health research ethics in malaria vector trials in Africa

PubMed Central

2010-01-01

Malaria mosquito research in Africa as elsewhere is just over a century old. Early trials for development of mosquito control tools were driven by colonial enterprises and war efforts; they were, therefore, tested in military or colonial settings. The failure of those tools and environmental concerns, coupled with the desperate need for integrated malaria control strategies, has necessitated the development of new malaria mosquito control tools, which are to be tested on humans, their environment and mosquito habitats. Ethical concerns start with phase 2 trials, which pose limited ethical dilemmas. Phase 3 trials, which are undertaken on vulnerable civilian populations, pose ethical dilemmas ranging from individual to community concerns. It is argued that such trials must abide by established ethical principles especially safety, which is mainly enshrined in the principle of non-maleficence. As there is total lack of experience with many of the promising candidate tools (eg genetically modified mosquitoes, entomopathogenic fungi, and biocontrol agents), great caution must be exercised before they are introduced in the field. Since malaria vector trials, especially phase 3 are intrusive and in large populations, individual and community respect is mandatory, and must give great priority to community engagement. It is concluded that new tools must be safe, beneficial, efficacious, effective, and acceptable to large populations in the short and long-term, and that research benefits should be equitably distributed to all who bear the brunt of the research burdens. It is further concluded that individual and institutional capacity strengthening should be provided, in order to undertake essential research, carry out scientific and ethical review, and establish competent regulatory frameworks. PMID:21144083

INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?): study protocol for a mixed methods study to assess the feasibility of a future randomised controlled trial of the clinical utility of invasive urodynamic testing

PubMed Central

2011-01-01

Background Urinary incontinence is an important health problem to the individual sufferer and to health services. Stress and stress predominant mixed urinary incontinence are increasingly managed by surgery due to advances in surgical techniques. Despite the lack of evidence for its clinical utility, most clinicians undertake invasive urodynamic testing (IUT) to confirm a functional diagnosis of urodynamic stress incontinence before offering surgery for this condition. IUT is expensive, embarrassing and uncomfortable for women and carries a small risk. Recent systematic reviews have confirmed the lack of high quality evidence of effectiveness. The aim of this pilot study is to test the feasibility of a future definitive randomised control trial that would address whether IUT alters treatment decisions and treatment outcome in these women and would test its clinical and cost effectiveness. Methods/design This is a mixed methods pragmatic multicentre feasibility pilot study with four components:- (a) A multicentre, external pilot randomised trial comparing basic clinical assessment with non-invasive tests and IUT. The outcome measures are rates of recruitment, randomisation and data completion. Data will be used to estimate sample size necessary for the definitive trial. (b) Qualitative interviews of a purposively sampled sub-set of women eligible for the pilot trial will explore willingness to participate, be randomised and their overall trial experience. (c) A national survey of clinicians to determine their views of IUT in this context, the main outcome being their willingness to randomise patients into the definitive trial. (d) Qualitative interviews of a purposively sampled group of these clinicians will explore whether and how they use IUT to inform their decisions. Discussion The pilot trial will provide evidence of feasibility and acceptability and therefore inform the decision whether to proceed to the definitive trial. Results will inform the design and conduct of the definitive trial and ensure its effectiveness in achieving its research aim. Trial registration number Current Controlled Trials ISRCTN71327395 assigned 7th June 2010. PMID:21733166

Strategic modulation of cognitive control.

PubMed

Lungu, Ovidiu V; Liu, Tao; Waechter, Tobias; Willingham, Daniel T; Ashe, James

2007-08-01

The neural substrate of cognitive control is thought to comprise an evaluative component located in the anterior cingulate cortex (ACC) and an executive component in the prefrontal cortex (PFC). The control mechanism itself is mainly local, triggered by response conflict (monitored by the ACC) and involving the allocation of executive resources (recruited by the PFC) in a trial-to-trial fashion. However, another way to achieve control would be to use a strategic mechanism based on long-term prediction of upcoming events and on a chronic response strategy that ignores local features of the task. In the current study, we showed that such a strategic control mechanism was based on a functional dissociation or complementary relationship between the ACC and the PFC. When information in the environment was available to make predictions about upcoming stimuli, local task features (e.g., response conflict) were no longer used as a control signal. We suggest that having separate control mechanisms based on local or global task features allows humans to be persistent in pursuing their goals, yet flexible enough to adapt to changes in the environment.

Brain research to ameliorate impaired neurodevelopment--home-based intervention trial (BRAIN-HIT).

PubMed

Wallander, Jan L; McClure, Elizabeth; Biasini, Fred; Goudar, Shivaprasad S; Pasha, Omrana; Chomba, Elwyn; Shearer, Darlene; Wright, Linda; Thorsten, Vanessa; Chakraborty, Hrishikesh; Dhaded, Sangappa M; Mahantshetti, Niranjana S; Bellad, Roopa M; Abbasi, Zahid; Carlo, Waldemar

2010-04-30

This randomized controlled trial aims to evaluate the effects of an early developmental intervention program on the development of young children in low- and low-middle-income countries who are at risk for neurodevelopmental disability because of birth asphyxia. A group of children without perinatal complications are evaluated in the same protocol to compare the effects of early developmental intervention in healthy infants in the same communities. Birth asphyxia is the leading specific cause of neonatal mortality in low- and low-middle-income countries and is also the main cause of neonatal and long-term morbidity including mental retardation, cerebral palsy, and other neurodevelopmental disorders. Mortality and morbidity from birth asphyxia disproportionately affect more infants in low- and low-middle-income countries, particularly those from the lowest socioeconomic groups. There is evidence that relatively inexpensive programs of early developmental intervention, delivered during home visit by parent trainers, are capable of improving neurodevelopment in infants following brain insult due to birth asphyxia. This trial is a block-randomized controlled trial that has enrolled 174 children with birth asphyxia and 257 without perinatal complications, comparing early developmental intervention plus health and safety counseling to the control intervention receiving health and safety counseling only, in sites in India, Pakistan, and Zambia. The interventions are delivered in home visits every two weeks by parent trainers from 2 weeks after birth until age 36 months. The primary outcome of the trial is cognitive development, and secondary outcomes include social-emotional and motor development. Child, parent, and family characteristics and number of home visits completed are evaluated as moderating factors. The trial is supervised by a trial steering committee, and an independent data monitoring committee monitors the trial. Findings from this trial have the potential to inform about strategies for reducing neurodevelopmental disabilities in at-risk young children in low and middle income countries.

Short-acting insulin analogues versus regular human insulin for adults with type 1 diabetes mellitus.

PubMed

Fullerton, Birgit; Siebenhofer, Andrea; Jeitler, Klaus; Horvath, Karl; Semlitsch, Thomas; Berghold, Andrea; Plank, Johannes; Pieber, Thomas R; Gerlach, Ferdinand M

2016-06-30

Short-acting insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. To assess the effects of short-acting insulin analogues versus regular human insulin in adults with type 1 diabetes. We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared short-acting insulin analogues with regular human insulins in the treatment of adults with type 1 diabetes who were not pregnant. Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results.The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the insulin analogue, insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable.We also found no clear evidence for a substantial effect of insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Our analysis suggests only a minor benefit of short-acting insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of short acting insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

Programs for the Prevention of Youth Depression: Evaluation of Efficacy, Effectiveness, and Readiness for Dissemination

PubMed Central

Brunwasser, Steven M.; Garber, Judy

2015-01-01

Objective To evaluate the current state of evidence of the effectiveness of depression prevention programs for youth, assess the degree to which current evidence supports broad implementation, and outline additional steps needed to close the gap between effectiveness and dissemination. Method We used the Society for Prevention Research’s Standards of Evidence (Flay et al., 2005) to evaluate the degree to which existing depression prevention programs have established intervention efficacy, effectiveness, and readiness for dissemination. We reviewed all depression prevention programs for youth that have been evaluated in at least two published, randomized controlled trials in which the intervention was compared to a no-intervention control group. A total of 37 studies evaluating 11 different programs were reviewed with regard to depressive symptoms and diagnoses post intervention and at follow-up (at least 6 months). Results Eight programs demonstrated significant main effects on depressive symptoms relative to controls in multiple RCTs; five programs had at least one trial with significant main effects present at least one year post-intervention. Two programs demonstrated efficacy for both depressive symptoms and depressive episodes across multiple independent trials. Regarding effectiveness, six programs had at least one study showing significant effects when delivered by endogenous service providers; four programs had significant effects in studies conducted independently of the program developers. Conclusions Several programs have demonstrated promise in terms of efficacy, but no depression prevention program for children or adolescents as yet has garnered sufficient evidence of effectiveness under real-world conditions to warrant widespread dissemination at this time. PMID:25933173

Effects of Gyejibongnyeong-hwan on dysmenorrhea caused by blood stagnation: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Gyejibongnyeong-hwan (GJBNH) is one of the most popular Korean medicine formulas for menstrual pain of dysmenorrhea. The concept of blood stagnation in Korean medicine is considered the main factor of causing abdominal pain, or cramps, during menstrual periods. To treat the symptoms, GJBNH is used to fluidify the stagnated blood and induce the blood flow to be smooth, reducing pain as the result. The purpose of this trial is to identify the efficacy of GJBNH in dysmenorrhea caused by blood stagnation. Methods This study is a multi-centre, randomised, double-blind, controlled trial with two parallel arms: the group taking GJBNH and the group taking placebo. 100 patients (women from age 18 to 35) will be enrolled to the trial. Through randomization 50 patients will be in experiment arm, and the other 50 patients will be in control arm. At the second visit (baseline), all participants who were already screened that they fulfil both the inclusion and the exclusion criteria will be randomised into two groups. Each group will take the intervention three times per day during two menstrual cycles. After the treatment for two cycles, each patient will be followed up during their 3rd, 4th and 5th menstrual cycles. From the screening (Visit 1) through the second follow-up (Visit 6) the entire process will take 25 weeks. Discussion This trial will provide evidence for the effectiveness of GJBNH in treating periodical pain due to dysmenorrhea that is caused by blood stagnation. The primary outcome between the two groups will be measured by changes in the Visual Analogue Score (VAS) of pain. The secondary outcome will be measured by the Blood Stagnation Scale, the Short-form McGill questionnaire and the COX menstrual symptom scale. Analysis of covariance (ANCOVA) and repeated measured ANOVA will be used to analyze the data analysis. Trial registration Current Controlled Trials: ISRCTN30426947 PMID:22217258

Cognitive Behavioral Treatment for Recurrent Binge Eating in Adolescent Girls: A Pilot Trial

PubMed Central

DeBar, Lynn L.; Wilson, G. Terence; Yarborough, Bobbi Jo; Burns, Beryl; Oyler, Barbara; Hildebrandt, Tom; Clarke, Gregory N.; Dickerson, John; Striegel, Ruth H.

2013-01-01

There is a need for treatment interventions to address the high prevalence of disordered eating throughout adolescence and early adulthood. We developed an adolescent-specific manualized CBT protocol to treat female adolescents with recurrent binge eating and tested its efficacy in a small, pilot randomized controlled trial. We present lessons learned in recruiting adolescents, a description of our treatment approach, acceptability of the treatment for teens and parents, as well as results from the pilot trial. Participants in the CBT group had significantly fewer posttreatment eating binges than those in a treatment as usual/delayed treatment (TAU-DT) control group; 100% of CBT participants were abstinent at follow-up. Our results provide preliminary support for the efficacy of this adolescent adaptation of evidence-based CBT for recurrent binge eating. The large, robust effect size estimate observed for the main outcome (NNT=2) places this among the larger effects observed for any mental health intervention. PMID:23645978

Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial

PubMed Central

Moll, Etelka; Bossuyt, Patrick M M; Korevaar, Johanna C; Lambalk, Cornelis B; van der Veen, Fulco

2006-01-01

Objective To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome. Design Randomised clinical trial. Setting Multicentre trial in 20 Dutch hospitals. Participants 228 women with polycystic ovary syndrome. Interventions Clomifene citrate plus metformin or clomifene citrate plus placebo. Main outcome measure The primary outcome measure was ovulation. Secondary outcome measures were ongoing pregnancy, spontaneous abortion, and clomifene resistance. Results 111 women were allocated to clomifene citrate plus metformin (metformin group) and 114 women were allocated to clomifene citrate plus placebo (placebo group). The ovulation rate in the metformin group was 64% compared with 72% in the placebo group, a non-significant difference (risk difference - 8%, 95% confidence interval - 20% to 4%). There were no significant differences in either rate of ongoing pregnancy (40% v 46%; - 6%, - 20% to 7%) or rate of spontaneous abortion (12% v 11%; 1%, - 7% to 10%). A significantly larger proportion of women in the metformin group discontinued treatment because of side effects (16% v 5%; 11%, 5% to 16%). Conclusion Metformin is not an effective addition to clomifene citrate as the primary method of inducing ovulation in women with polycystic ovary syndrome. Trial registration Current Controlled Trials ISRCTN55906981 [controlled-trials.com]. PMID:16769748

Therapeutic advances in multiple system atrophy and progressive supranuclear palsy.

PubMed

Poewe, Werner; Mahlknecht, Philipp; Krismer, Florian

2015-09-15

Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are relentlessly progressive neurodegenerative diseases leading to severe disability and ultimately death within less than 10 y. Despite increasing efforts in basic and clinical research, effective therapies for these atypical parkinsonian disorders are lacking. Although earlier small clinical studies in MSA and PSP mainly focused on symptomatic treatment, advances in the understanding of the molecular underpinnings of these diseases and in the search for biomarkers have paved the way for the first large and well-designed clinical trials aiming at disease modification. Targets of intervention in these trials have included α-synuclein inclusion pathology in the case of MSA and tau-related mechanisms in PSP. Since 2013, four large randomized, placebo-controlled, double-blind disease-modification trials have been completed and published, using rasagiline (MSA), rifampicin (MSA), tideglusib (PSP), or davunetide (PSP). All of these failed to demonstrate signal efficacy with regard to the primary outcome measures. In addition, two randomized, placebo-controlled, double-blind trials have studied the efficacy of droxidopa in the symptomatic treatment of neurogenic orthostatic hypotension, including patients with MSA, with positive results in one trial. This review summarizes the design and the outcomes of these and other smaller trials published since 2013 and attempts to highlight priority areas of future therapeutic research in MSA and PSP. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.

6-PACK programme to decrease fall injuries in acute hospitals: cluster randomised controlled trial

PubMed Central

Morello, Renata T; Wolfe, Rory; Brand, Caroline A; Haines, Terry P; Hill, Keith D; Brauer, Sandra G; Botti, Mari; Cumming, Robert G; Livingston, Patricia M; Sherrington, Catherine; Zavarsek, Silva; Lindley, Richard I; Kamar, Jeannette

2016-01-01

Objective To evaluate the effect of the 6-PACK programme on falls and fall injuries in acute wards. Design Cluster randomised controlled trial. Setting Six Australian hospitals. Participants All patients admitted to 24 acute wards during the trial period. Interventions Participating wards were randomly assigned to receive either the nurse led 6-PACK programme or usual care over 12 months. The 6-PACK programme included a fall risk tool and individualised use of one or more of six interventions: “falls alert” sign, supervision of patients in the bathroom, ensuring patients’ walking aids are within reach, a toileting regimen, use of a low-low bed, and use of a bed/chair alarm. Main outcome measures The co-primary outcomes were falls and fall injuries per 1000 occupied bed days. Results During the trial, 46 245 admissions to 16 medical and eight surgical wards occurred. As many people were admitted more than once, this represented 31 411 individual patients. Patients’ characteristics and length of stay were similar for intervention and control wards. Use of 6-PACK programme components was higher on intervention wards than on control wards (incidence rate ratio 3.05, 95% confidence interval 2.14 to 4.34; P<0.001). In all, 1831 falls and 613 fall injuries occurred, and the rates of falls (incidence rate ratio 1.04, 0.78 to 1.37; P=0.796) and fall injuries (0.96, 0.72 to 1.27; P=0.766) were similar in intervention and control wards. Conclusions Positive changes in falls prevention practice occurred following the introduction of the 6-PACK programme. However, no difference was seen in falls or fall injuries between groups. High quality evidence showing the effectiveness of falls prevention interventions in acute wards remains absent. Novel solutions to the problem of in-hospital falls are urgently needed. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12611000332921. PMID:26813674

Nonoperative versus operative treatment for thoracolumbar burst fractures without neurologic deficit: a meta-analysis.

PubMed

Gnanenthiran, Sonali R; Adie, Sam; Harris, Ian A

2012-02-01

Decision-making regarding nonoperative versus operative treatment of patients with thoracolumbar burst fractures in the absence of neurologic deficits is controversial. Lack of evidence-based practice may result in patients being treated inappropriately and being exposed to unnecessary adverse consequences. Using meta-analysis, we therefore compared pain (VAS) and function (Roland Morris Disability Questionnaire) in patients with thoracolumbar burst fractures without neurologic deficit treated nonoperatively and operatively. Secondary outcomes included return to work, radiographic progression of kyphosis, radiographic progression of spinal canal stenosis, complications, cost, and length of hospitalization. We searched MEDLINE, EMBASE(®), and the Cochrane Central Register of Controlled Trials for 'thoracic fractures', 'lumbar fractures', 'non-operative', 'operative' and 'controlled clinical trials'. We established five criteria for inclusion. Data extraction and quality assessment were in accordance with Cochrane Collaboration guidelines. The main analyses were performed on individual patient data from randomized controlled trials. Sensitivity analyses were performed on VAS pain, Roland Morris Disability Questionnaire score, kyphosis, and return to work, including data from nonrandomized controlled trials and using fixed effects meta-analysis. We identified four trials, including two randomized controlled trials consisting of 79 patients (41 with operative treatment and 38 with nonoperative treatment). The mean followups ranged from 24 to 118 months. We found no between-group differences in baseline pain, kyphosis, and Roland Morris Disability Questionnaire scores. At last followup, there were no between-group differences in pain, Roland Morris Disability Questionnaire scores, and return to work rates. We found an improvement in kyphosis ranging from means of 12.8º to 11º in the operative group, but surgery was associated with higher complication rates and costs. Operative management of thoracolumbar burst fractures without neurologic deficit may improve residual kyphosis, but does not appear to improve pain or function at an average of 4 years after injury and is associated with higher complication rates and costs. Level II, therapeutic study. See the Guidelines for Authors for a complete description of level of evidence.

Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials

PubMed Central

Forman, David; Hunt, Richard H; Yuan, Yuhong; Moayyedi, Paul

2014-01-01

Objectives To determine whether searching for Helicobacter pylori and treating with eradication therapy leads to a reduction in incidence of gastric cancer among healthy asymptomatic infected individuals. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, and the Cochrane central register of controlled trials were searched through to December 2013. Conference proceedings between 2001 and 2013 were hand searched. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions. Eligibility criteria for selecting studies Randomised controlled trials examining the effect of at least seven days of eradication therapy on subsequent occurrence of gastric cancer in adults who tested positive for Helicobacter pylori but otherwise healthy and asymptomatic were eligible. The control arm had to receive placebo or no treatment. Subjects had to be followed for ≥2 years. Main outcome measures Primary outcome, defined a priori, was the effect of eradication therapy on the subsequent occurrence of gastric cancer expressed as a relative risk of gastric cancer with 95% confidence intervals. Results The search strategy identified 1560 citations, of which six individual randomised controlled trials were eligible. Fifty one (1.6%) gastric cancers occurred among 3294 individuals who received eradication therapy versus 76 (2.4%) in 3203 control subjects (relative risk 0.66, 95% confidence interval 0.46 to 0.95), with no heterogeneity between studies (I2=0%, P=0.60). If the benefit of eradication therapy was assumed to persist lifelong the number needed to treat was as low as 15 for Chinese men and as high as 245 for US women. Conclusions These data provide limited, moderate quality evidence that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations. PMID:24846275

Alternative treatments for adults with attention-deficit hyperactivity disorder (ADHD).

PubMed

Arnold, L E

2001-06-01

A previous review of alternative treatments (Tx) of ADHD--those other than psychoactive medication and behavioral/psychosocial Tx--was supplemented with an additional literature search focused on adults with ADHD. Twenty-four alternative Tx were identified, ranging in scientific documentation from discrediting controlled studies through mere hypotheses to positive controlled double-blind clinical trials. Many of them are applicable only to a specific subgroup. Although oligoantigenic (few-foods) diets have convincing double-blind evidence of efficacy for a properly selected subgroup of children, they do not appear promising for adults. Enzyme-potentiated desensitization, relaxation/EMG biofeedback, and deleading also have controlled evidence of efficacy. Iron supplementation, magnesium supplementation, Chinese herbals, EEG biofeedback, massage, meditation, mirror feedback, channel-specific perceptual training, and vestibular stimulation all have promising prospective pilot data, many of these tests reasonably controlled. Single-vitamin megadosage has some intriguing pilot trial data. Zinc supplementation is hypothetically supported by systematic case-control data, but no systematic clinical trial. Laser acupuncture has promising unpublished pilot data and may be more applicable to adults than children. Essential fatty acid supplementation has promising systematic case-control data, but clinical trials are equivocal. RDA vitamin supplementation, non-Chinese herbals, homeopathic remedies, and antifungal therapy have no systematic data in ADHD. Megadose multivitamin combinations are probably ineffective for most patients and are possibly dangerous. Simple sugar restriction seems ineffective. Amino acid supplementation is mildly effective in the short term, but not beyond 2-3 months. Thyroid treatment is effective in the presence of documented thyroid abnormality. Some alternative Tx of ADHD are effective or probably effective, but mainly for certain patients. In some cases, they are the Tx of choice, and initial evaluation should consider the relevant etiologies. A few have failed to prove effective in controlled trials. Most need research to determine whether they are effective and/or to define the applicable subgroup. Some of them, although not safer than standard Tx, may be preferable for an etiologic subgroup.

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

Acupuncture for the prevention of tension-type headache

PubMed Central

Linde, Klaus; Allais, Gianni; Brinkhaus, Benno; Fei, Yutong; Mehring, Michael; Shin, Byung-Cheul; Vickers, Andrew; White, Adrian R

2016-01-01

Background Acupuncture is often used for prevention of tension-type headache but its effectiveness is still controversial. This is an update of our Cochrane review originally published in Issue 1, 2009 of The Cochrane Library. Objectives To investigate whether acupuncture is a) more effective than no prophylactic treatment/routine care only; b) more effective than ‘sham’ (placebo) acupuncture; and c) as effective as other interventions in reducing headache frequency in adults with episodic or chronic tension-type headache. Search methods We searched CENTRAL, MEDLINE, EMBASE and AMED to 19 January 2016. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform to 10 February 2016 for ongoing and unpublished trials. Selection criteria We included randomised trials with a post-randomisation observation period of at least eight weeks, which compared the clinical effects of an acupuncture intervention with a control (treatment of acute headaches only or routine care), a sham acupuncture intervention or another prophylactic intervention in adults with episodic or chronic tension-type headache. Data collection and analysis Two review authors checked eligibility; extracted information on participants, interventions, methods and results; and assessed study risk of bias and the quality of the acupuncture intervention. The main efficacy outcome measure was response (at least 50% reduction of headache frequency) after completion of treatment (three to four months after randomisation). To assess safety/acceptability we extracted the number of participants dropping out due to adverse effects and the number of participants reporting adverse effects. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Main results Twelve trials (11 included in the previous version and one newly identified) with 2349 participants (median 56, range 10 to 1265) met the inclusion criteria. Acupuncture was compared with routine care or treatment of acute headaches only in two large trials (1265 and 207 participants), but they had quite different baseline headache frequency and management in the control groups. Neither trial was blinded but trial quality was otherwise high (low risk of bias). While effect size estimates of the two trials differed considerably, the proportion of participants experiencing at least 50% reduction of headache frequency was much higher in groups receiving acupuncture than in control groups (moderate quality evidence; trial 1: 302/629 (48%) versus 121/636 (19%); risk ratio (RR) 2.5; 95% confidence interval (CI) 2.1 to 3.0; trial 2: 60/132 (45%) versus 3/75 (4%); RR 11; 95% CI 3.7 to 35). Long-term effects (beyond four months) were not investigated. Acupuncture was compared with sham acupuncture in seven trials of moderate to high quality (low risk of bias); five large studies provided data for one or more meta-analyses. Among participants receiving acupuncture, 205 of 391 (51%) had at least 50% reduction of headache frequency compared to 133 of 312 (43%) in the sham group after treatment (RR 1.3; 95% CI 1.09 to 1.5; four trials; moderate quality evidence). Results six months after randomisation were similar. Withdrawals were low: 1 of 420 participants receiving acupuncture dropped out due to adverse effects and 0 of 343 receiving sham (six trials; low quality evidence). Three trials reported the number of participants reporting adverse effects: 29 of 174 (17%) with acupuncture versus 12 of 103 with sham (12%; odds ratio (OR) 1.3; 95% CI 0.60 to 2.7; low quality evidence). Acupuncture was compared with physiotherapy, massage or exercise in four trials of low to moderate quality (high risk of bias); study findings were inadequately reported. No trial found a significant superiority of acupuncture and for some outcomes the results slightly favoured the comparison therapy. None of these trials reported the number of participants dropping out due to adverse effects or the number of participants reporting adverse effects. Overall, the quality of the evidence assessed using GRADE was moderate or low, downgraded mainly due to a lack of blinding and variable effect sizes. Authors’ conclusions The available results suggest that acupuncture is effective for treating frequent episodic or chronic tension-type headaches, but further trials - particularly comparing acupuncture with other treatment options - are needed. PMID:27092807

The Efficacy and Safety of Shen Guo Lao Nian Granule for Common Cold of Qi-Deficiency Syndrome: Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase II Clinical Trial

PubMed Central

Fu, Juanjuan; Ding, Hong; Yang, Haimiao; Huang, Yuhong

2017-01-01

Background Common cold is one of the most frequently occurring illnesses in primary healthcare services and represents considerable disease burden. Common cold of Qi-deficiency syndrome (CCQDS) is an important but less addressed traditional Chinese medicine (TCM) pattern. We designed a protocol to explore the efficacy, safety, and optimal dose of Shen Guo Lao Nian Granule (SGLNG) for treating CCQDS. Methods/Design This is a multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. A total of 240 eligible patients will be recruited from five centers. Patients are randomly assigned to high-dose group, middle-dose group, low-dose group, or control group in a 1 : 1 : 1 : 1 ratio. All drugs are required to be taken 3 times daily for 5 days with a 5-day follow-up period. Primary outcomes are duration of all symptoms, total score reduction on Jackson's scale, and TCM symptoms scale. Secondary outcomes include every single TCM symptom duration and score reduction, TCM main symptoms disappearance rate, curative effects, and comparison between Jackson's scale and TCM symptom scale. Ethics and Trial Registration This study protocol was approved by the Ethics Committee of Clinical Trials and Biomedicine of West China Hospital of Sichuan University (number IRB-2014-12) and registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-15006349). PMID:29430253

Explaining physical activity levels from a self-efficacy perspective: the physical activity counseling trial.

PubMed

Blanchard, Chris M; Fortier, Michelle; Sweet, Shane; O'Sullivan, Tracey; Hogg, William; Reid, Robert D; Sigal, Ronald J

2007-01-01

The Physical Activity Counseling (PAC) trial compared the effects of a 13-week primary care physical activity (PA) intervention that incorporated a PA counselor into a health care practice compared to a control condition on PA over a 25-week period and showed group differences in PA were present at 6 and 13 weeks. The main purpose was to examine the mediating effect of 6-week task and barrier self-efficacy on the intervention versus control group/13-week PA relationships. A secondary purpose was to determine whether task and barrier self-efficacy were significantly related to PA throughout the trial for both groups. Participants were primarily sedentary individuals who received a 2- to 4-min PA intervention from their primary care provider, after which they were randomly assigned to the intervention (n = 61) or control condition (n = 59). Self-reported PA and task (barrier) self-efficacy measures were obtained during (i.e., baseline, 6 and 13 weeks) and after (i.e., 19 and 25 weeks) the intervention in both groups. Six-week task and barrier self-efficacy had a small mediating effect. Furthermore, barrier self-efficacy had a significant relationship with PA throughout the trial, whereas the relationship between task self-efficacy and PA became significantly weaker as the trial progressed. PAC interventions among primarily sedentary individuals should be partly based on barrier and task self-efficacy. However, the stability of the task self-efficacy/PA relationship needs further examination.

A qualitative case study of telehealth for in-home monitoring to support the management of type 2 diabetes.

PubMed

Carlisle, Karen; Warren, Robin

2013-10-01

The present study formed part of a randomised controlled trial of telehealth for in-home monitoring to support people with poorly controlled type 2 diabetes. We explored the experiences of patients and healthcare practitioners, and their perceptions of the telehealth model of care used in the trial. In addition to their usual diabetes care, participants receive diabetes care from a diabetes educator nurse via an in-home broadband communication device. On average, each patient participated in 14 videoconferences with a diabetes care coordinator during the 12-month trial period. Qualitative data was collected from two general practices and included semi-structured interviews and document review of patient clinical notes. A total of 12 people were interviewed: 8 health practitioners and 4 patients. Patients and health practitioners expressed a high level of satisfaction with the model of care provided. Patients also reported positive health and social outcomes as a result of being involved in the trial and indicated that in the main they had achieved their goals and were happy with their progress over the 12-month period. Analysis of interviews revealed three broad elements associated with the implementation of telehealth: interpersonal factors, operational problems and the wider health system context within which the general practices and trial team were operating. The findings suggest that adopting telehealth in the management of type 2 diabetes can lead to improved diabetes control, but more support is required to ensure sustainability and widespread implementation.

Distance to health services affects local-level vaccine efficacy for pneumococcal conjugate vaccine (PCV) among rural Filipino children

PubMed Central

Root, Elisabeth Dowling; Lucero, Marilla; Nohynek, Hanna; Anthamatten, Peter; Thomas, Deborah S. K.; Tallo, Veronica; Tanskanen, Antti; Quiambao, Beatriz P.; Puumalainen, Taneli; Lupisan, Socorro P.; Ruutu, Petri; Ladesma, Erma; Williams, Gail M.; Riley, Ian; Simões, Eric A. F.

2014-01-01

Pneumococcal conjugate vaccines (PCVs) have demonstrated efficacy against childhood pneumococcal disease in several regions globally. We demonstrate how spatial epidemiological analysis of a PCV trial can assist in developing vaccination strategies that target specific geographic subpopulations at greater risk for pneumococcal pneumonia. We conducted a secondary analysis of a randomized, placebo-controlled, double-blind vaccine trial that examined the efficacy of an 11-valent PCV among children less than 2 y of age in Bohol, Philippines. Trial data were linked to the residential location of each participant using a geographic information system. We use spatial interpolation methods to create smoothed surface maps of vaccination rates and local-level vaccine efficacy across the study area. We then measure the relationship between distance to the main study hospital and local-level vaccine efficacy, controlling for ecological factors, using spatial autoregressive models with spatial autoregressive disturbances. We find a significant amount of spatial variation in vaccination rates across the study area. For the primary study endpoint vaccine efficacy increased with distance from the main study hospital from −14% for children living less than 1.5 km from Bohol Regional Hospital (BRH) to 55% for children living greater than 8.5 km from BRH. Spatial regression models indicated that after adjustment for ecological factors, distance to the main study hospital was positively related to vaccine efficacy, increasing at a rate of 4.5% per kilometer distance. Because areas with poor access to care have significantly higher VE, targeted vaccination of children in these areas might allow for a more effective implementation of global programs. PMID:24550454

Effects of Computer-Aided Interlimb Force Coupling Training on Paretic Hand and Arm Motor Control following Chronic Stroke: A Randomized Controlled Trial

PubMed Central

Lin, Chueh-Ho; Chou, Li-Wei; Luo, Hong-Ji; Tsai, Po-Yi; Lieu, Fu-Kong; Chiang, Shang-Lin; Sung, Wen-Hsu

2015-01-01

Objective We investigated the training effects of interlimb force coupling training on paretic upper extremity outcomes in patients with chronic stroke and analyzed the relationship between motor recovery of the paretic hand, arm and functional performances on paretic upper limb. Design A randomized controlled trial with outcome assessment at baseline and after 4 weeks of intervention. Setting Taipei Veterans General Hospital, National Yang-Ming University. Participants Thirty-three subjects with chronic stroke were recruited and randomly assigned to training (n = 16) and control groups (n = 17). Interventions The computer-aided interlimb force coupling training task with visual feedback included different grip force generation methods on both hands. Main Outcome Measures The Barthel Index (BI), the upper extremity motor control Fugl-Meyer Assessment (FMA-UE), the Motor Assessment Score (MAS), and the Wolf Motor Function Test (WMFT). All assessments were executed by a blinded evaluator, and data management and statistical analysis were also conducted by a blinded researcher. Results The training group demonstrated greater improvement on the FMA-UE (p<.001), WMFT (p<.001), MAS (p = .004) and BI (p = .037) than the control group after 4 weeks of intervention. In addition, a moderate correlation was found between the improvement of scores for hand scales of the FMA and other portions of the FMA UE (r = .528, p = .018) or MAS (r = .596, p = .015) in the training group. Conclusion Computer-aided interlimb force coupling training improves the motor recovery of a paretic hand, and facilitates motor control and enhances functional performance in the paretic upper extremity of people with chronic stroke. Trial Registration ClinicalTrials.gov NCT02247674. PMID:26193492

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

PubMed Central

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

2011-01-01

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

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Córdoba, Juan; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2015-02-25

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index on 2 October 2014. We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. Based on the combined Cochrane Hepato-Biliary Group score, we classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics.

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2017-05-18

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded and Conference Proceedings Citation Index - Science, and LILACS (May 2017). We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. We classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics.

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Córdoba, Juan; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2015-09-17

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index (August 2015). We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. We classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics.

Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a double-blind, placebo-controlled trial.

PubMed

Wullt, Marlene; Hagslätt, Marie-Louise Johansson; Odenholt, Inga

2003-01-01

A double-blind, placebo-controlled trial was performed to analyse the ability of Lactobacillus plantarum 299v to prevent further recurrent episodes of Clostridium difficile-associated diarrhoea (RCDAD). Recurrence of clinical symptoms (main outcome) was seen in 4 of 11 patients who received metronidazole in combination with L. plantarum 299v and in 6 of 9 treated with metronidazole in combination with placebo. The lactobacilli treatment had no side-effects. Although the small sample size does not allow any conclusion to be drawn concerning the efficacy of L. plantarum in patients with RCDAD, these results may contribute to the ongoing discussion about the benefits of probiotics in patients with RCDAD and encourage the performance of larger multicentre studies.

The Camino Verde intervention in Nicaragua, 2004-2012.

PubMed

Arosteguí, Jorge; Ledogar, Robert J; Coloma, Josefina; Hernández-Alvarez, Carlos; Suazo-Laguna, Harold; Cárcamo, Alvaro; Reyes, Rosa María; Belli, Alejandro; Andersson, Neil; Harris, Eva

2017-05-30

Camino Verde (the Green Way) is an evidence-based community mobilisation tool for prevention of dengue and other mosquito-borne viral diseases. Its effectiveness was demonstrated in a cluster-randomised controlled trial conducted in 2010-2013 in Nicaragua and Mexico. The Nicaraguan arm of the trial was preceded, from 2004 to 2008, by a feasibility study that provided valuable lessons and trained facilitators for the trial itself. Here, guided by the Template for Intervention Description and Replication (TIDieR), we describe the Camino Verde intervention in Nicaragua, presenting its rationale, its time and location, activities, materials used, the main actors, modes of delivery, how it was tailored to encourage community engagement, modifications made from the feasibility study to the trial itself, and how fidelity to the process originally designed was maintained. We also present information on costs and discuss the place of this study within the literature on implementation science. ISRCTN27581154 .

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

Group art therapy as an adjunctive treatment for people with schizophrenia: multicentre pragmatic randomised trial

PubMed Central

Killaspy, Helen; Barnes, Thomas R E; Barrett, Barbara; Byford, Sarah; Clayton, Katie; Dinsmore, John; Floyd, Siobhan; Hoadley, Angela; Johnson, Tony; Kalaitzaki, Eleftheria; King, Michael; Leurent, Baptiste; Maratos, Anna; O’Neill, Francis A; Osborn, David P; Patterson, Sue; Soteriou, Tony; Tyrer, Peter; Waller, Diane

2012-01-01

Objectives To evaluate the clinical effectiveness of group art therapy for people with schizophrenia and to test whether any benefits exceed those of an active control treatment. Design Three arm, rater blinded, pragmatic, randomised controlled trial. Setting Secondary care services across 15 sites in the United Kingdom. Participants 417 people aged 18 or over, who had a diagnosis of schizophrenia and provided written informed consent to take part in the study. Interventions Participants, stratified by site, were randomised to 12 months of weekly group art therapy plus standard care, 12 months of weekly activity groups plus standard care, or standard care alone. Art therapy and activity groups had up to eight members and lasted for 90 minutes. In art therapy, members were given access to a range of art materials and encouraged to use these to express themselves freely. Members of activity groups were offered various activities that did not involve use of art or craft materials and were encouraged to collectively select those they wanted to pursue. Main outcome measures The primary outcomes were global functioning, measured using the global assessment of functioning scale, and mental health symptoms, measured using the positive and negative syndrome scale, 24 months after randomisation. Main secondary outcomes were levels of group attendance, social functioning, and satisfaction with care at 12 and 24 months. Results 417 participants were assigned to either art therapy (n=140), activity groups (n=140), or standard care alone (n=137). Primary outcomes between the three study arms did not differ. The adjusted mean difference between art therapy and standard care at 24 months on the global assessment of functioning scale was −0.9 (95% confidence interval −3.8 to 2.1), and on the positive and negative syndrome scale was 0.7 (−3.1 to 4.6). Secondary outcomes did not differ between those referred to art therapy or those referred to standard care at 12 or 24 months. Conclusions Referring people with established schizophrenia to group art therapy as delivered in this trial did not improve global functioning, mental health, or other health related outcomes. Trial registration Current Controlled Trials ISRCTN46150447. PMID:22374932

Multisite effectiveness trials of treatments for substance abuse and co-occurring problems: have we chosen the best designs?

PubMed

Nunes, Edward V; Ball, Samuel; Booth, Robert; Brigham, Gregory; Calsyn, Donald A; Carroll, Kathleen; Feaster, Daniel J; Hien, Denise; Hubbard, Robert L; Ling, Walter; Petry, Nancy M; Rotrosen, John; Selzer, Jeffrey; Stitzer, Maxine; Tross, Susan; Wakim, Paul; Winhusen, Theresa; Woody, George

2010-06-01

Multisite effectiveness trials such as those carried out in the National Drug Abuse Treatment Clinical Trials Network (CTN) are a critical step in the development and dissemination of evidence-based treatments because they address how such treatments perform in real-world clinical settings. As Brigham et al. summarized in a recent article (G. S. Brigham, D. J. Feaster, P. G. Wakim, & C. L. Dempsey C. L., 2009), several possible experimental designs may be chosen for such effectiveness trials. These include (a) a new treatment intervention (Tx) is compared to an existing mode of community based treatment as usual (TAU): Tx versus TAU; (b) a new intervention is added to TAU and compared to TAU alone: Tx + TAU versus TAU; or (c) a new intervention is added to TAU and compared to a control condition added to TAU: Tx + TAU versus control + TAU. Each of these designs addresses a different question and has different potential strengths and weaknesses. As of December 2009, the primary outcome paper had been published for 16 of the multisite randomized clinical trials conducted in the CTN, testing various treatments for drug abuse, HIV risk behavior, or related problems. This paper systematically examines, for each of the completed trials, the experimental design type chosen and its original rationale, the main findings of the trial, and the strengths and weaknesses of the design in hindsight. Based on this review, recommendations are generated to inform the design of future effectiveness trials on treatments for substance abuse, HIV risk, and other behavioral health problems.

Fluoride gel effective at reducing caries in children.

PubMed

Richards, Derek

2015-12-01

Data Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline , Embase, CINAHL, LILACS, ProQuest Dissertations and Theses, the Web of Science Conference Proceedings, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Randomised or quasi-randomised controlled trials comparing topically applied fluoride gel with placebo or no treatment in children up to 16 years were considered. Studies had to be at least one year in duration with a frequency of application of at least once a year with blind outcome assessment. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces in both permanent and primary teeth (D(M)FS and d(e/m)fs). At least two reviewers extracted data and assessed risk of bias. The primary measure of effect was the prevented fraction (PF). Where data could be pooled random-effects meta-analyses were conducted. Potential sources of heterogeneity were examined in random-effects meta-regression analyses. Twenty-eight trials involving 9140 children and adolescents were included. Most of the studies (20) were at high risk of bias, with eight at unclear risk of bias. Twenty-five trials (8479 participants) provided data for meta-analysis on permanent teeth, with a D(M)FS pooled prevented fraction (PF) estimate of 28% (95% CI; 19-36%; P < 0.0001; with substantial heterogeneity (P < 0.0001; I(2) = 82%); moderate quality evidence). Subgroup and metaregression analyses suggested no significant association between estimates of D(M)FS prevented fractions and the prespecified trial characteristics. However, the effect of fluoride gel varied according to the type of control group used, with D(M)FS PF on average being 17% (95% CI 3% to 31%; P = 0.018) higher in non-placebo-controlled trials (the reduction in caries was 38% (95% CI 24% to 52%; P < 0.0001, 2808 participants) for the ten trials with no treatment as control group, and 21% (95% CI 15% to 28%; P < 0.0001, 5671 participants) for the 15 placebo-controlled trials.A funnel plot of the 25 trials in the D(M)FS PF meta-analysis indicated a relationship between prevented fraction and study precision, with an apparent lack of small studies with statistically significant large effects.For primary teeth the d(e/m)fs pooled prevented fraction estimate for the three trials (1254 participants) = 20% (95%CI; 1% - 38%; P = 0.04; with no heterogeneity (P = 0.54; I(2) = 0%); low quality evidence).There was limited reporting of adverse events. Only two trials reported information on acute toxicity signs and symptoms during the application of the gel (risk difference 0.01, 95% CI -0.01 to 0.02; P = 0.36; with no heterogeneity (P = 36; I(2) = 0%); 490 participants; very low quality evidence). None of the trials reported information on tooth staining, mucosal irritation or allergic reaction. The conclusions of this updated review remain the same as those when it was first published. There is moderate quality evidence of a large caries-inhibiting effect of fluoride gel in the permanent dentition. Information concerning the caries-preventive effect of fluoride gel on the primary dentition, which also shows a large effect, is based on low quality evidence from only three placebo-controlled trials. There is little information on adverse effects or on acceptability of treatment. Future trials should include assessment of potential adverse effects.

A Randomized Controlled Trial of Two Syntactic Treatment Procedures With Cantonese-Speaking, School-Age Children With Language Disorders.

PubMed

To, Carol K S; Lui, Hoi Ming; Li, Xin Xin; Lam, Gary Y H

2015-08-01

In this study, we aimed to evaluate the efficacy of sentence-combining (SC) and narrative-based (NAR) intervention approaches to syntax intervention using a randomized-controlled-trial design. Fifty-two Cantonese-speaking, school-age children with language impairment were assigned randomly to either the SC or the NAR treatment arm. Seven children did not receive treatment as assigned. Intervention in both arms targeted the same complex syntactical structures. The SC group focused on sentence combination training, whereas the NAR group made use of narratives in which the target structures were embedded. Pretest and posttest performances measured using a standardized language assessment were subjected to analyses of covariance mixed-effect-model analyses of variance. Children in both treatment arms demonstrated significant growth after 4 months of intervention. The main effect between treatment arms and time was not significant after controlling the pretest performance, suggesting that both treatment approaches showed similar effects. The main effect of time was significant. This study provided evidence to support language intervention in the school years in Cantonese-speaking children. However, neither approach was shown to be more efficacious than the other. Future researchers could examine the effects of a longer treatment period and include functional outcome measures.

Corticosteroids for Bell's palsy (idiopathic facial paralysis).

PubMed

Salinas, Rodrigo A; Alvarez, Gonzalo; Daly, Fergus; Ferreira, Joaquim

2010-03-17

Inflammation and oedema of the facial nerve are implicated in causing Bell's palsy. Corticosteroids have a potent anti-inflammatory action which should minimise nerve damage. The objective of this review was to assess the effect of corticosteroid therapy in Bell's palsy. We searched the Cochrane Neuromuscular Disease Group Trials Specialized Register (9 December 2008) for randomised trials, as well as MEDLINE (January 1966 to December 2008), EMBASE (January 1980 to December 2008) and LILACS (9 December 2008). We contacted known experts in the field to identify additional published or unpublished trials. Randomised trials comparing different routes of administration and dosage schemes of corticosteroid or adrenocorticotrophic hormone therapy versus a control group where no therapy considered effective for this condition was administered, unless it was also given in a similar way to the experimental group. Two authors independently assessed eligibility, trial quality, and extracted the data. Eight trials with a total of 1569 participants were included. Allocation concealment was appropriate in six trials, and the data reported allowed an intention-to-treat analysis in four, while unpublished data from the fifth and sixth trials were provided by the authors. The data included in the main outcome of this meta-analysis were collected from seven trials with a total of 1507 participants. Overall 175/754 (23%) of the participants allocated to corticosteroids had incomplete recovery of facial motor function six months or more after randomisation, significantly less than 245/753 (33%) in the control group (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.61 to 0.83). There was, also, a significant reduction in motor synkinesis during follow-up in those receiving corticosteroids (RR 0.6, 95% CI 0.44 to 0.81). The reduction in the proportion of patients with cosmetically disabling sequelae six months after randomisation, however, was not significant (RR 0.97, 95% CI 0.44 to 2.15). The trial not included in the primary outcome of this meta-analysis showed a non-significant difference in outcomes between the arms. The available evidence from randomised controlled trials shows significant benefit from treating Bell's palsy with corticosteroids.

A Systematic Review of Interventions Aimed at Reducing Binge Drinking among College Students

ERIC Educational Resources Information Center

Bridges, Ledetra S.; Sharma, Manoj

2015-01-01

The purpose of this article was to systematically review the interventions aimed at reducing binge drinking in college students. A total of 18 interventions published between 2010 and 2015 were evaluated in this review. Two main study designs were used by these interventions: randomized controlled trials (RCTs) and quasi-experimental designs, with…

Modular Cognitive Behavioral Therapy for Youth Anxiety Disorders: A Partial Effectiveness Test in Schools

ERIC Educational Resources Information Center

Chiu, Angela Wai Mon

2010-01-01

The current study used a programmatic dissemination model as a guiding framework for testing an evidence-supported treatment (EST) for child anxiety disorders in the school setting. The main goal of the project was to conduct the first of a planned series of partial-effectiveness tests (group-design randomized controlled trials) evaluating the…

Placebo effects in trials evaluating 12 selected minimally invasive interventions: a systematic review and meta-analysis

PubMed Central

Holtedahl, Robin; Brox, Jens Ivar; Tjomsland, Ole

2015-01-01

Objectives To analyse the impact of placebo effects on outcome in trials of selected minimally invasive procedures and to assess reported adverse events in both trial arms. Design A systematic review and meta-analysis. Data sources and study selection We searched MEDLINE and Cochrane library to identify systematic reviews of musculoskeletal, neurological and cardiac conditions published between January 2009 and January 2014 comparing selected minimally invasive with placebo (sham) procedures. We searched MEDLINE for additional randomised controlled trials published between January 2000 and January 2014. Data synthesis Effect sizes (ES) in the active and placebo arms in the trials’ primary and pooled secondary end points were calculated. Linear regression was used to analyse the association between end points in the active and sham groups. Reported adverse events in both trial arms were registered. Results We included 21 trials involving 2519 adult participants. For primary end points, there was a large clinical effect (ES≥0.8) after active treatment in 12 trials and after sham procedures in 11 trials. For secondary end points, 7 and 5 trials showed a large clinical effect. Three trials showed a moderate difference in ES between active treatment and sham on primary end points (ES ≥0.5) but no trials reported a large difference. No trials showed large or moderate differences in ES on pooled secondary end points. Regression analysis of end points in active treatment and sham arms estimated an R2 of 0.78 for primary and 0.84 for secondary end points. Adverse events after sham were in most cases minor and of short duration. Conclusions The generally small differences in ES between active treatment and sham suggest that non-specific mechanisms, including placebo, are major predictors of the observed effects. Adverse events related to sham procedures were mainly minor and short-lived. Ethical arguments frequently raised against sham-controlled trials were generally not substantiated. PMID:25636794

Clinical trial design and dissemination: comprehensive analysis of clinicaltrials.gov and PubMed data since 2005

PubMed Central

Davies, Mark; Hingorani, Aroon D; Hunter, Jackie

2018-01-01

Abstract Objective To investigate the distribution, design characteristics, and dissemination of clinical trials by funding organisation and medical specialty. Design Cross sectional descriptive analysis. Data sources Trial protocol information from clinicaltrials.gov, metadata of journal articles in which trial results were published (PubMed), and quality metrics of associated journals from SCImago Journal and Country Rank database. Selection criteria All 45 620 clinical trials evaluating small molecule therapeutics, biological drugs, adjuvants, and vaccines, completed after January 2006 and before July 2015, including randomised controlled trials and non-randomised studies across all clinical phases. Results Industry was more likely than non-profit funders to fund large international randomised controlled trials, although methodological differences have been decreasing with time. Among 27 835 completed efficacy trials (phase II-IV), 15 084 (54.2%) had disclosed their findings publicly. Industry was more likely than non-profit trial funders to disseminate trial results (59.3% (10 444/17 627) v 45.3% (4555/10 066)), and large drug companies had higher disclosure rates than small ones (66.7% (7681/11 508) v 45.2% (2763/6119)). Trials funded by the National Institutes of Health (NIH) were disseminated more often than those of other non-profit institutions (60.0% (1451/2417) v 40.6% (3104/7649)). Results of studies funded by large drug companies and NIH were more likely to appear on clinicaltrials.gov than were those from non-profit funders, which were published mainly as journal articles. Trials reporting the use of randomisation were more likely than non-randomised studies to be published in a journal article (6895/19 711 (34.9%) v 1408/7748 (18.2%)), and journal publication rates varied across disease areas, ranging from 42% for autoimmune diseases to 20% for oncology. Conclusions Trial design and dissemination of results vary substantially depending on the type and size of funding institution as well as the disease area under study. PMID:29875212

Effect of Industry Sponsorship on Dental Restorative Trials.

PubMed

Schwendicke, F; Tu, Y-K; Blunck, U; Paris, S; Göstemeyer, G

2016-01-01

Industry sponsorship was found to potentially introduce bias into clinical trials. We assessed the effects of industry sponsorship on the design, comparator choice, and findings of randomized controlled trials on dental restorative materials. A systematic review was performed via MEDLINE, CENTRAL, and EMBASE. Randomized trials on dental restorative and adhesive materials published 2005 to 2015 were included. The design of sponsored and nonsponsored trials was compared statistically (risk of bias, treatment indication, setting, transferability, sample size). Comparator choice and network geometry of sponsored and nonsponsored trials were assessed via network analysis. Material performance rankings in different trial types were estimated via Bayesian network meta-analysis. Overall, 114 studies were included (15,321 restorations in 5,232 patients). We found 21 and 41 (18% and 36%) trials being clearly or possibly industry sponsored, respectively. Trial design of sponsored and nonsponsored trials did not significantly differ for most assessed items. Sponsored trials evaluated restorations of load-bearing cavities significantly more often than nonsponsored trials, had longer follow-up periods, and showed significantly increased risk of detection bias. Regardless of sponsorship status, comparisons were mainly performed within material classes. The proportion of trials comparing against gold standard restorative or adhesive materials did not differ between trial types. If ranked for performance according to the need to re-treat (best: least re-treatments), most material combinations were ranked similarly in sponsored and nonsponsored trials. The effect of industry sponsorship on dental restorative trials seems limited. © International & American Associations for Dental Research 2015.

Systematic Review of the Effectiveness of Physical Therapy Modalities in Women With Provoked Vestibulodynia.

PubMed

Morin, Mélanie; Carroll, Marie-Soleil; Bergeron, Sophie

2017-07-01

Pelvic floor muscle physical therapy is recommended in clinical guidelines for women with provoked vestibulodynia (PVD). Including isolated or combined treatment modalities, physical therapy is viewed as an effective first-line intervention, yet no systematic review concerning the effectiveness of physical therapy has been conducted. To systematically appraise the current literature on the effectiveness of physical therapy modalities for decreasing pain during intercourse and improving sexual function in women with PVD. A systematic literature search using PubMed, Scopus, CINHAL, and PEDro was conducted until October 2016. Moreover, a manual search from reference lists of included articles was performed. Ongoing trials also were reviewed using clinicaltrial.gov and ISRCTNregistry. Randomized controlled trials, prospective and retrospective cohorts, and case reports evaluating the effect of isolated or combined physical therapy modalities in women with PVD were included in the review. Main outcome measures were pain during intercourse, sexual function, and patient's perceived improvement. The literature search resulted in 43 eligible studies including 7 randomized controlled trials, 20 prospective studies, 5 retrospective studies, 6 case reports, and 6 study protocols. Most studies had a high risk of bias mainly associated with the lack of a comparison group. Another common bias was related to insufficient sample size, non-validated outcomes, non-standardized intervention, and use of other ongoing treatment. The vast majority of studies showed that physical therapy modalities such as biofeedback, dilators, electrical stimulation, education, multimodal physical therapy, and multidisciplinary approaches were effective for decreasing pain during intercourse and improving sexual function. The positive findings for the effectiveness of physical therapy modalities in women with PVD should be investigated further in robust and well-designed randomized controlled trials. Morin M, Carroll M-S, Bergeron S. Systematic Review of the Effectiveness of Physical Therapy Modalities in Women With Provoked Vestibulodynia. Sex Med Rev 2017;5:295-322. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Self-controlled video feedback on tactical skills for soccer teams results in more active involvement of players.

PubMed

van Maarseveen, Mariëtte J J; Oudejans, Raôul R D; Savelsbergh, Geert J P

2018-02-01

Many studies have shown that self-controlled feedback is beneficial for learning motor tasks, and that learners prefer to receive feedback after supposedly good trials. However, to date all studies conducted on self-controlled learning have used individual tasks and mainly relatively simple skills. Therefore, the aim of this study was to examine self-controlled feedback on tactical skills in small-sided soccer games. Highly talented youth soccer players were assigned to a self-control or yoked group and received video feedback on their offensive performance in 3 vs. 2 small-sided games. The results showed that the self-control group requested feedback mostly after good trials, that is, after they scored a goal. In addition, the perceived performance of the self-control group was higher on feedback than on no-feedback trials. Analyses of the conversations around the video feedback revealed that the players and coach discussed good and poor elements of performance and how to improve it. Although the coach had a major role in these conversations, the players of the self-control group spoke more and showed more initiative compared to the yoked group. The results revealed no significant beneficial effect of self-controlled feedback on performance as judged by the coach. Overall, the findings suggest that in such a complex situation as small-sided soccer games, self-controlled feedback is used both to confirm correct performance elements and to determine and correct errors, and that self-controlled learning stimulates the involvement of the learner in the learning process. Copyright © 2017 Elsevier B.V. All rights reserved.

[Achievements and problems of modern trials of antihypertensive drugs].

PubMed

Kobalava, Zh D; Kotovskaia, Iu V

2011-01-01

Most important value of lowering of substantially elevated arterial pressure (AP) for improvement of outcomes in patients with arterial hypertension (AH) was convincingly confirmed by large truly placebo controlled randomized clinical trials (RCT) with the use of mainly diuretics, and/or beta-adrenoblockers in the 60-80ths. Later comparative RCT confirmed equal antihypertensive efficacy of 5 main drug classes relative to AP level in brachial artery. In this review we discuss merit of auxiliary class-specific properties of antihypertensive agents potentially affecting prognosis besides AP lowering. We also discuss problems related to decline of significance of quantitative criteria of AH and consideration of AP level in general context of cardiovascular risk; problems of external validity of RCT; extrapolation of RCT results obtained in patients with complicated AH and very high cardiovascular risk on young patients with uncomplicated AH; significance of hard and surrogate end points.

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.

A mixed methods study to assess the feasibility of a randomised controlled trial of invasive urodynamic testing versus clinical assessment and non-invasive tests prior to surgery for stress urinary incontinence in women: the INVESTIGATE-I study.

PubMed

Hilton, Paul; Armstrong, Natalie; Brennand, Catherine; Howel, Denise; Shen, Jing; Bryant, Andrew; Tincello, Douglas G; Lucas, Malcolm G; Buckley, Brian S; Chapple, Christopher R; Homer, Tara; Vale, Luke; McColl, Elaine

2015-09-08

The position of invasive urodynamic testing (IUT) in diagnostic pathways for urinary incontinence is unclear, and systematic reviews have called for further trials evaluating clinical utility. The objective of this study was to inform the decision whether to proceed to a definitive randomised trial of IUT compared to clinical assessment with non-invasive tests, prior to surgery in women with stress urinary incontinence (SUI) or stress-predominant mixed urinary incontinence (MUI). A mixed methods study comprising a pragmatic multicentre randomised pilot trial, a qualitative face-to face interview study with patients eligible for the trial, an exploratory economic evaluation including value of information study, a survey of clinicians' views about IUT, and qualitative telephone interviews with purposively sampled survey respondents. Only the first and second of these elements are reported here. Trial participants were randomised to either clinical assessment with non-invasive tests (control arm) or clinical assessment with non-invasive tests plus IUT (intervention arm). The main outcome measures of these feasibility studies were confirmation that units can identify and recruit eligible women, acceptability of investigation strategies and data collection tools, and acquisition of outcome data to determine the sample size for a definitive trial. The primary outcome proposed for a definitive trial was ICIQ-FLUTS (total score) 6 months after surgery or the start of nonsurgical treatment. Of 284 eligible women, 222 (78%) were recruited, 165/219 (75%) returned questionnaires at baseline, and 125/200 returned them (63%) at follow-up. Most women underwent surgery; management plans were changed in 19 (19%) participants following IUT. Participants interviewed were positive about the trial and the associated documentation. All elements of a definitive trial were rehearsed. Such a trial would require between 232 and 922 participants, depending on the target difference in the primary outcome. We identified possible modifications to our protocol for application in a definitive trial including clarity over inclusion/exclusions, screening processes, reduction in secondary outcomes, and modification to patient questionnaire booklets and bladder diaries. A definitive trial of IUT versus clinical assessment prior to surgery for SUI or stress predominant MUI is feasible and remains relevant. Current Controlled Trials: ISRCTN 71327395, registered 7 June 2010.

Cognitive-behaviour therapy for post-traumatic stress in schizophrenia. A randomized controlled trial.

PubMed

Steel, C; Hardy, A; Smith, B; Wykes, T; Rose, S; Enright, S; Hardcastle, M; Landau, S; Baksh, M F; Gottlieb, J D; Rose, D; Mueser, K T

2017-01-01

There is limited evidence for effective interventions in the treatment of post-traumatic stress symptoms within individuals diagnosed with schizophrenia. Clinicians have concerns about using exposure treatments with this patient group. The current trial was designed to evaluate a 16-session cognitive restructuring programme, without direct exposure, for the treatment of post-traumatic stress symptoms specifically within individuals diagnosed with schizophrenia. A multicentre randomized controlled single-blinded trial with assessments at 0 months, 6 months (post-treatment) and 12 months (follow-up) was conducted. A total of 61 participants diagnosed with schizophrenia and exhibiting post-traumatic stress symptoms were recruited. Those randomized to treatment were offered up to 16 sessions of cognitive-behaviour therapy (CBT, including psychoeducation, breathing training and cognitive restructuring) over a 6-month period, with the control group offered routine clinical services. The main outcome was blind rating of post-traumatic stress symptoms using the Clinician Administered PTSD Scale for Schizophrenia. Secondary outcomes were psychotic symptoms as measured by the Positive and Negative Symptom Scale and the Psychotic Symptom Rating Scale. Both the treatment and control groups experienced a significant decrease in post-traumatic stress symptoms over time but there was no effect of the addition of CBT on either the primary or secondary outcomes. The current trial did not demonstrate any effect in favour of CBT. Cognitive restructuring programmes may require further adaptation to promote emotional processing of traumatic memories within people diagnosed with a psychotic disorder.

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

PubMed Central

2010-01-01

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

Feed forward and feedback control for over-ground locomotion in anaesthetized cats

NASA Astrophysics Data System (ADS)

Mazurek, K. A.; Holinski, B. J.; Everaert, D. G.; Stein, R. B.; Etienne-Cummings, R.; Mushahwar, V. K.

2012-04-01

The biological central pattern generator (CPG) integrates open and closed loop control to produce over-ground walking. The goal of this study was to develop a physiologically based algorithm capable of mimicking the biological system to control multiple joints in the lower extremities for producing over-ground walking. The algorithm used state-based models of the step cycle each of which produced different stimulation patterns. Two configurations were implemented to restore over-ground walking in five adult anaesthetized cats using intramuscular stimulation (IMS) of the main hip, knee and ankle flexor and extensor muscles in the hind limbs. An open loop controller relied only on intrinsic timing while a hybrid-CPG controller added sensory feedback from force plates (representing limb loading), and accelerometers and gyroscopes (representing limb position). Stimulation applied to hind limb muscles caused extension or flexion in the hips, knees and ankles. A total of 113 walking trials were obtained across all experiments. Of these, 74 were successful in which the cats traversed 75% of the 3.5 m over-ground walkway. In these trials, the average peak step length decreased from 24.9 ± 8.4 to 21.8 ± 7.5 (normalized units) and the median number of steps per trial increased from 7 (Q1 = 6, Q3 = 9) to 9 (8, 11) with the hybrid-CPG controller. Moreover, within these trials, the hybrid-CPG controller produced more successful steps (step length ≤ 20 cm ground reaction force ≥ 12.5% body weight) than the open loop controller: 372 of 544 steps (68%) versus 65 of 134 steps (49%), respectively. This supports our previous preliminary findings, and affirms that physiologically based hybrid-CPG approaches produce more successful stepping than open loop controllers. The algorithm provides the foundation for a neural prosthetic controller and a framework to implement more detailed control of locomotion in the future.

Feed forward and feedback control for over-ground locomotion in anaesthetized cats

PubMed Central

Mazurek, K A; Holinski, B J; Everaert, D G; Stein, R B; Etienne-Cummings, R; Mushahwar, V K

2012-01-01

The biological central pattern generator (CPG) integrates open and closed loop control to produce over-ground walking. The goal of this study was to develop a physiologically based algorithm capable of mimicking the biological system to control multiple joints in the lower extremities for producing over-ground walking. The algorithm used state-based models of the step cycle each of which produced different stimulation patterns. Two configurations were implemented to restore over-ground walking in five adult anaesthetized cats using intramuscular stimulation (IMS) of the main hip, knee and ankle flexor and extensor muscles in the hind limbs. An open loop controller relied only on intrinsic timing while a hybrid-CPG controller added sensory feedback from force plates (representing limb loading), and accelerometers and gyroscopes (representing limb position). Stimulation applied to hind limb muscles caused extension or flexion in the hips, knees and ankles. A total of 113 walking trials were obtained across all experiments. Of these, 74 were successful in which the cats traversed 75% of the 3.5 m over-ground walkway. In these trials, the average peak step length decreased from 24.9 ± 8.4 to 21.8 ± 7.5 (normalized units) and the median number of steps per trial increased from 7 (Q1=6, Q3 = 9) to 9 (8, 11) with the hybrid-CPG controller. Moreover, these trials, the hybrid-CPG controller produced more successful steps (step length ≤ 20 cm; ground reaction force ≥ 12.5% body weight) than the open loop controller: 372 of 544 steps (68%) versus 65 of 134 steps (49%), respectively. This supports our previous preliminary findings, and affirms that physiologically based hybrid-CPG approaches produce more successful stepping than open loop controllers. The algorithm provides the foundation for a neural prosthetic controller and a framework to implement more detailed control of locomotion in the future. PMID:22328615

Impact and Costs of Incentives to Reduce Attrition in Online Trials: Two Randomized Controlled Trials

PubMed Central

Murray, Elizabeth; Kalaitzaki, Eleftheria; White, Ian R; McCambridge, Jim; Thompson, Simon G; Wallace, Paul; Godfrey, Christine

2011-01-01

Background Attrition from follow-up is a major methodological challenge in randomized trials. Incentives are known to improve response rates in cross-sectional postal and online surveys, yet few studies have investigated whether they can reduce attrition from follow-up in online trials, which are particularly vulnerable to low follow-up rates. Objectives Our objective was to determine the impact of incentives on follow-up rates in an online trial. Methods Two randomized controlled trials were embedded in a large online trial of a Web-based intervention to reduce alcohol consumption (the Down Your Drink randomized controlled trial, DYD-RCT). Participants were those in the DYD pilot trial eligible for 3-month follow-up (study 1) and those eligible for 12-month follow-up in the DYD main trial (study 2). Participants in both studies were randomly allocated to receive an offer of an incentive or to receive no offer of an incentive. In study 1, participants in the incentive arm were randomly offered a £5 Amazon.co.uk gift voucher, a £5 charity donation to Cancer Research UK, or entry in a prize draw for £250. In study 2, participants in the incentive arm were offered a £10 Amazon.co.uk gift voucher. The primary outcome was the proportion of participants who completed follow-up questionnaires in the incentive arm(s) compared with the no incentive arm. Results In study 1 (n = 1226), there was no significant difference in response rates between those participants offered an incentive (175/615, 29%) and those with no offer (162/611, 27%) (difference = 2%, 95% confidence interval [CI] –3% to 7%). There was no significant difference in response rates among the three different incentives offered. In study 2 (n = 2591), response rates were 9% higher in the group offered an incentive (476/1296, 37%) than in the group not offered an incentive (364/1295, 28%) (difference = 9%, 95% CI 5% to 12%, P < .001). The incremental cost per extra successful follow-up in the incentive arm was £110 in study 1 and £52 in study 2. Conclusion Whereas an offer of a £10 Amazon.co.uk gift voucher can increase follow-up rates in online trials, an offer of a lower incentive may not. The marginal costs involved require careful consideration. Trial registration ISRCTN31070347; http://www.controlled-trials.com/ISRCTN31070347 (Archived by WebCite at http://www.webcitation.org/5wgr5pl3s) PMID:21371988

Effectiveness and cost-effectiveness of a universal parenting skills programme in deprived communities: multicentre randomised controlled trial

PubMed Central

Simkiss, D E; Snooks, H A; Stallard, N; Kimani, P K; Sewell, B; Fitzsimmons, D; Anthony, R; Winstanley, S; Wilson, L; Phillips, C J; Stewart-Brown, S

2013-01-01

Objective To evaluate the effectiveness and cost utility of a universally provided early years parenting programme. Design Multicentre randomised controlled trial with cost-effectiveness analysis. Setting Early years centres in four deprived areas of South Wales. Participants Families with children aged between 2 and 4 years. 286 families were recruited and randomly allocated to the intervention or waiting list control. Intervention The Family Links Nurturing Programme (FLNP), a 10-week course with weekly 2 h facilitated group sessions. Main outcome measures Negative and supportive parenting, child and parental well-being and costs assessed before the intervention, following the course (3 months) and at 9 months using standardised measures. Results There were no significant differences in primary or secondary outcomes between trial arms at 3 or 9 months. With ‘+’ indicating improvement, difference in change in negative parenting score at 9 months was +0.90 (95%CI −1.90 to 3.69); in supportive parenting, +0.17 (95%CI −0.61 to 0.94); and 12 of the 17 secondary outcomes showed a non-significant positive effect in the FLNP arm. Based on changes in parental well-being (SF-12), the cost per quality-adjusted life year (QALY) gained was estimated to be £34 913 (range 21 485–46 578) over 5 years and £18 954 (range 11 664–25 287) over 10 years. Probability of cost per QALY gained below £30 000 was 47% at 5 years and 57% at 10 years. Attendance was low: 34% of intervention families attended no sessions (n=48); only 47% completed the course (n=68). Also, 19% of control families attended a parenting programme before 9-month follow-up. Conclusions Our trial has not found evidence of clinical or cost utility for the FLNP in a universal setting. However, low levels of exposure and contamination mean that uncertainty remains. Trial registration The trial is registered with Current Controlled Trials ISRCTN13919732. PMID:23906953

Effectiveness of medicines review with web-based pharmaceutical treatment algorithms in reducing potentially inappropriate prescribing in older people in primary care: a cluster randomized trial (OPTI-SCRIPT study protocol).

PubMed

Clyne, Barbara; Bradley, Marie C; Smith, Susan M; Hughes, Carmel M; Motterlini, Nicola; Clear, Daniel; McDonnell, Ronan; Williams, David; Fahey, Tom

2013-03-13

Potentially inappropriate prescribing in older people is common in primary care and can result in increased morbidity, adverse drug events, hospitalizations and mortality. In Ireland, 36% of those aged 70 years or over received at least one potentially inappropriate medication, with an associated expenditure of over €45 million.The main objective of this study is to determine the effectiveness and acceptability of a complex, multifaceted intervention in reducing the level of potentially inappropriate prescribing in primary care. This study is a pragmatic cluster randomized controlled trial, conducted in primary care (OPTI-SCRIPT trial), involving 22 practices (clusters) and 220 patients. Practices will be allocated to intervention or control arms using minimization, with intervention participants receiving a complex multifaceted intervention incorporating academic detailing, medicines review with web-based pharmaceutical treatment algorithms that provide recommended alternative treatment options, and tailored patient information leaflets. Control practices will deliver usual care and receive simple patient-level feedback on potentially inappropriate prescribing. Routinely collected national prescribing data will also be analyzed for nonparticipating practices, acting as a contemporary national control. The primary outcomes are the proportion of participant patients with potentially inappropriate prescribing and the mean number of potentially inappropriate prescriptions per patient. In addition, economic and qualitative evaluations will be conducted. This study will establish the effectiveness of a multifaceted intervention in reducing potentially inappropriate prescribing in older people in Irish primary care that is generalizable to countries with similar prescribing challenges. Current controlled trials ISRCTN41694007.

Mosquito larval source management for controlling malaria

PubMed Central

Tusting, Lucy S; Thwing, Julie; Sinclair, David; Fillinger, Ulrike; Gimnig, John; Bonner, Kimberly E; Bottomley, Christian; Lindsay, Steven W

2015-01-01

Background Malaria is an important cause of illness and death in people living in many parts of the world, especially sub-Saharan Africa. Long-lasting insecticide treated bed nets (LLINs) and indoor residual spraying (IRS) reduce malaria transmission by targeting the adult mosquito vector and are key components of malaria control programmes. However, mosquito numbers may also be reduced by larval source management (LSM), which targets mosquito larvae as they mature in aquatic habitats. This is conducted by permanently or temporarily reducing the availability of larval habitats (habitat modification and habitat manipulation), or by adding substances to standing water that either kill or inhibit the development of larvae (larviciding). Objectives To evaluate the effectiveness of mosquito LSM for preventing malaria. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CABS Abstracts; and LILACS up to 24 October 2012. We handsearched the Tropical Diseases Bulletin from 1900 to 2010, the archives of the World Health Organization (up to 11 February 2011), and the literature database of the Armed Forces Pest Management Board (up to 2 March 2011). We also contacted colleagues in the field for relevant articles. Selection criteria We included cluster randomized controlled trials (cluster-RCTs), controlled before-and-after trials with at least one year of baseline data, and randomized cross-over trials that compared LSM with no LSM for malaria control. We excluded trials that evaluated biological control of anopheline mosquitoes with larvivorous fish. Data collection and analysis At least two authors assessed each trial for eligibility. We extracted data and at least two authors independently determined the risk of bias in the included studies. We resolved all disagreements through discussion with a third author. We analyzed the data using Review Manager 5 software. Main results We included 13 studies; four cluster-RCTs, eight controlled before-and-after trials, and one randomized cross-over trial. The included studies evaluated habitat modification (one study), habitat modification with larviciding (two studies), habitat manipulation (one study), habitat manipulation plus larviciding (two studies), or larviciding alone (seven studies) in a wide variety of habitats and countries. Malaria incidence In two cluster-RCTs undertaken in Sri Lanka, larviciding of abandoned mines, streams, irrigation ditches, and rice paddies reduced malaria incidence by around three-quarters compared to the control (RR 0.26, 95% CI 0.22 to 0.31, 20,124 participants, two trials, moderate quality evidence). In three controlled before-and-after trials in urban and rural India and rural Kenya, results were inconsistent (98,233 participants, three trials, very low quality evidence). In one trial in urban India, the removal of domestic water containers together with weekly larviciding of canals and stagnant pools reduced malaria incidence by three quarters. In one trial in rural India and one trial in rural Kenya, malaria incidence was higher at baseline in intervention areas than in controls. However dam construction in India, and larviciding of streams and swamps in Kenya, reduced malaria incidence to levels similar to the control areas. In one additional randomized cross-over trial in the flood plains of the Gambia River, where larval habitats were extensive and ill-defined, larviciding by ground teams did not result in a statistically significant reduction in malaria incidence (2039 participants, one trial). Parasite prevalence In one cluster-RCT from Sri Lanka, larviciding reduced parasite prevalence by almost 90% (RR 0.11, 95% CI 0.05 to 0.22, 2963 participants, one trial, moderate quality evidence). In five controlled before-and-after trials in Greece, India, the Philippines, and Tanzania, LSM resulted in an average reduction in parasite prevalence of around two-thirds (RR 0.32, 95% CI 0.19 to 0.55, 8041 participants, five trials, moderate quality evidence). The interventions in these five trials included dam construction to reduce larval habitats, flushing of streams, removal of domestic water containers, and larviciding. In the randomized cross-over trial in the flood plains of the Gambia River, larviciding by ground teams did not significantly reduce parasite prevalence (2039 participants, one trial). Authors’ conclusions In Africa and Asia, LSM is another policy option, alongside LLINs and IRS, for reducing malaria morbidity in both urban and rural areas where a sufficient proportion of larval habitats can be targeted. Further research is needed to evaluate whether LSM is appropriate or feasible in parts of rural Africa where larval habitats are more extensive. PMID:23986463

Methods of dietary and nutritional assessment and intervention and other methods in the Multiple Risk Factor Intervention Trial.

PubMed

Dolecek, T A; Stamler, J; Caggiula, A W; Tillotson, J L; Buzzard, I M

1997-01-01

Various dietary assessment instruments were used in the Multiple Risk Factor Intervention Trial (MRFIT), either to assist with the special intervention program or to assess trial outcomes. For the latter purpose, the 24-h recall was the main method and was selected with the understanding that the single recall collected at baseline and at most annual visits--considered by itself--would be useful mainly for assessing groups rather than individuals. Major components of the data collection and analysis system developed for the 24-h recall included central training and certification of nutritionists, a central nutrient coding system, and a food grouping system to assist interventionists in using recall data for counseling. Several additional nutritional assessment methods were used for men in the special intervention group only to assist them in attaining the dietary goals. These goals consisted chiefly of reduced intake of saturated fat and cholesterol and a modest increase in intake of polyunsaturated fat; total fat intake was also decreased, primarily for control of energy intake. Short-term success at attainment of these nutritional goals was evaluated by means of 3-d food records collected before the intervention and after the initial 10-wk intensive intervention period. The MRFIT nutrient goals, which became more vigorous at certain points in the trial, were translated into food patterns. Adherence to these food patterns was also assessed by scoring of 3-d records and by subjective evaluation by nutritionists throughout the trial. Methods of collecting other trial data are also described in this chapter.

Insecticide treated curtains and residual insecticide treatment to control Aedes aegypti: An acceptability study in Santiago de Cuba

PubMed Central

Van der Stuyft, Patrick; Toledo, María Eugenia; Ceballos, Enrique; Fabré, Francisco; Lefèvre, Pierre

2018-01-01

Background Within the context of a field trial conducted by the Cuban vector control program (AaCP), we assessed acceptability of insecticide-treated curtains (ITCs) and residual insecticide treatment (RIT) with deltamethrin by the community. We also assessed the potential influence of interviewees’ risk perceptions for getting dengue and disease severity. Methodology/principal findings We embedded a qualitative study using in-depth interviews in a cluster randomized trial (CRT) testing the effectiveness of ITCs and RIT in Santiago de Cuba. In-depth interviews (N = 38) were conducted four and twelve months after deployment of the tools with people who accepted the tools, who stopped using them and who did not accept the tools. Data analysis was deductive. Main reasons for accepting ITCs at the start of the trial were perceived efficacy and not being harmful to health. Constraints linked to manufacturer instructions were the main reason for not using ITCs. People stopped using the ITCs due to perceived allergy, toxicity and low efficacy. Few heads of households refused RIT despite the noting reasons for rejection, such as allergy, health hazard and toxicity. Positive opinions of the vector control program influenced acceptability of both tools. However, frequent insecticide fogging as part of routine AaCP vector control actions diminished perceived efficacy of both tools and, therefore, acceptability. Fifty percent of interviewees did feel at risk for getting dengue and considered dengue a severe disease. However, this did not appear to influence acceptability of ITCs or RIT. Conclusion/significance Acceptability of ITCs and RIT was linked to acceptability of AaCP routine vector control activities. However, uptake and use were not always an indication of acceptability. Factors leading to acceptability may be best identified using qualitative methods, but more research is needed on the concept of acceptability and its measurement. PMID:29293501

Cluster randomised feasibility trial to improve the Control of Hypertension In Rural India (CHIRI): a study protocol

PubMed Central

Riddell, Michaela A; Joshi, Rohina; Oldenburg, Brian; Chow, Clara; Thankappan, K R; Mahal, Ajay; Thomas, Nihal; Srikanth, Velandai K; Evans, Roger G; Kalyanram, Kartik; Kartik, Kamakshi; Maulik, Pallab K; Arabshahi, Simin; Varma, R P; Guggilla, Rama K; Suresh, Oduru; Mini, G K; D'Esposito, Fabrizio; Sathish, Thirunavukkarasu; Alim, Mohammed

2016-01-01

Introduction Hypertension is emerging in rural populations of India. Barriers to diagnosis and treatment of hypertension may differ regionally according to economic development. Our main objectives are to estimate the prevalence, awareness, treatment and control of hypertension in 3 diverse regions of rural India; identify barriers to diagnosis and treatment in each setting and evaluate the feasibility of a community-based intervention to improve control of hypertension. Methods and analysis This study includes 4 main activities: (1) assessment of risk factors, quality of life, socioeconomic position and barriers to changes in lifestyle behaviours in ∼14 500 participants; (2) focus group discussions with individuals with hypertension and indepth interviews with healthcare providers, to identify barriers to control of hypertension; (3) use of a medicines-availability survey to determine the availability, affordability and accessibility of medicines and (4) trial of an intervention provided by Accredited Social Health Activists (ASHAs), comprising group-based education and support for individuals with hypertension to self-manage blood pressure. Wards/villages/hamlets of a larger Mandal are identified as the primary sampling unit (PSU). PSUs are then randomly selected for inclusion in the cross-sectional survey, with further randomisation to intervention or control. Changes in knowledge of hypertension and risk factors, and clinical and anthropometric measures, are assessed. Evaluation of the intervention by participants provides insight into perceptions of education and support of self-management delivered by the ASHAs. Ethics and dissemination Approval for the overall study was obtained from the Health Ministry's Screening Committee, Ministry of Health and Family Welfare (India), institutional review boards at each site and Monash University. In addition to publication in peer-reviewed articles, results will be shared with federal, state and local government health officers, local healthcare providers and communities. Trial registration number CTRI/2016/02/006678; Pre-results. PMID:27855099

Combined exercise is more effective than aerobic exercise in the improvement of fall risk factors: a randomized controlled trial in community-dwelling older men.

PubMed

Sousa, Nelson; Mendes, Romeu; Silva, André; Oliveira, José

2017-04-01

To compare the long-term effects of two community-based exercise programs on fall risk factors, such as balance, postural control, mobility and leg strength, in community-dwelling older men. Single-blinded randomized controlled trial, comparing three groups, with follow-ups at eight, 16, 24 and 32 weeks. Older men independent-living residing in Maia city, Portugal. A total of 66 older men (aged 69.0 ±4.9 years) were randomly assigned to an aerobic exercise group ( n = 22), a combined aerobic and resistance exercise group ( n = 22) or a control group ( n = 22). Both community-based exercise programs consisted of three sessions each week for 32 consecutive weeks and were planned for moderate-to-vigorous intensity. The control group had no exercise intervention. Main outcomes were measured by the Timed Up and Go Test, functional reach test, 30-second chair stand test and 6-minute walk test, on five different occasions. Repeated measures of analysis of covariance revealed significant main effects between time × group interaction in all outcomes over time (Timed Up and Go Test: p < 0.001; functional reach test: p = 0.002; 30-second chair stand: p = 0.001; 6-minute walk test: p < 0.001). Both exercise groups reported improvements; however, better performance was identified in the combined aerobic and resistance exercise group compared with the aerobic exercise group (-20.3% vs. -9.1% on the Timed Up and Go Test, +27.5% vs. +10.9% on the functional reach test, +20.8% vs. +7.3% on 30-second chair stand, +10.9% vs. +3.5% on 6-minute walk test). Adding resistance exercise to aerobic exercise improves factors associated with an increased risk of falls. However, both exercise regimes, combined or aerobic alone, are more effective than no exercise in the reduction of fall risk factors. ClinicalTrials.org #NCT01874132.

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

PubMed

Fuglsang, Anders

2015-05-01

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

Neuroreflexotherapy for non-specific low-back pain.

PubMed

Urrútia, G; Burton, A K; Morral, A; Bonfill, X; Zanoli, G

2004-01-01

Among the wide range of therapeutic alternatives proposed for the management of low-back pain (LBP), a less widely used technique from Spain, called neuroreflexotherapy (NRT) has claimed to show very favourable results, mainly in patients with chronic low-back pain. The aim of this review was to systematically assess the effectiveness of NRT for the treatment of non-specific LBP in adult patients, aged 16 to 65 years. A secondary objective was to compare NRT with other conventional interventions. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE to October 1, 2002. Only randomised controlled trials (RCTs) of NRT for the treatment of patients with a clinical diagnosis of non-specific LBP were included. Two reviewers independently selected trials and extracted data using pre-designed forms. Because the outcome variables were not assessed in a homogenous way, it was not possible to pool the results to obtain an estimate of global effect, as initially planned. Three RCT were included, with a total of 125 subjects randomised to the control groups and 148 subjects receiving active NRT. Neuroreflexotherapy was the same in all three trials, while the control groups received sham-NRT in two trials and standard care in one. Two trials studied patients with chronic LBP, the third studied patients with a mix of chronic and sub-acute LBP. Clinical outcomes were measured in the short-term (15 to 60 days) in all three trials; in one trial, resource utilization was measured after one year. Individuals who received active NRT showed statistically significantly better outcomes than the control groups for measures of pain, degree of mobility, disability, medication use, consumption of resources and costs. No significant differences were observed for quality of life measures. Side effects were more frequently reported in the control groups during short-term follow-up, with no major side effects reported by those receiving active NRT. NRT appears to be a safe and effective intervention for the treatment of chronic non-specific LBP. The efficacy is less clear for sub-acute LBP. However, these results are limited to three trials conducted by a small number of specifically trained and experienced clinicians, in a limited geographical location. No data are available on the ease and time-frame needed to achieve that level of expertise. RCTs by other practitioners, in other locations, that replicate the effects reported in this review are needed before recommending a broader practice.

Recruitment and retention of participants in randomised controlled trials: a review of trials funded and published by the United Kingdom Health Technology Assessment Programme

PubMed Central

Bonacho dos Anjos Henriques-Cadby, Inês; Bortolami, Oscar; Flight, Laura; Hind, Daniel; Knox, Christopher; Nadin, Ben; Rothwell, Joanne; Surtees, Michael; Julious, Steven A

2017-01-01

Background Substantial amounts of public funds are invested in health research worldwide. Publicly funded randomised controlled trials (RCTs) often recruit participants at a slower than anticipated rate. Many trials fail to reach their planned sample size within the envisaged trial timescale and trial funding envelope. Objectives To review the consent, recruitment and retention rates for single and multicentre randomised control trials funded and published by the UK's National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme. Data sources and study selection HTA reports of individually randomised single or multicentre RCTs published from the start of 2004 to the end of April 2016 were reviewed. Data extraction Information was extracted, relating to the trial characteristics, sample size, recruitment and retention by two independent reviewers. Main outcome measures Target sample size and whether it was achieved; recruitment rates (number of participants recruited per centre per month) and retention rates (randomised participants retained and assessed with valid primary outcome data). Results This review identified 151 individually RCTs from 787 NIHR HTA reports. The final recruitment target sample size was achieved in 56% (85/151) of the RCTs and more than 80% of the final target sample size was achieved for 79% of the RCTs (119/151). The median recruitment rate (participants per centre per month) was found to be 0.92 (IQR 0.43–2.79) and the median retention rate (proportion of participants with valid primary outcome data at follow-up) was estimated at 89% (IQR 79–97%). Conclusions There is considerable variation in the consent, recruitment and retention rates in publicly funded RCTs. Investigators should bear this in mind at the planning stage of their study and not be overly optimistic about their recruitment projections. PMID:28320800

Study protocol of a multicentre randomised controlled trial of self-help cognitive behaviour therapy for working women with menopausal symptoms (MENOS@Work).

PubMed

Hunter, Myra S; Hardy, Claire; Norton, Sam; Griffiths, Amanda

2016-10-01

Hot flushes and night sweats (HFNS) - the main symptoms of the menopause transition - can reduce quality of life and are particularly difficult to manage at work. A cognitive behaviour therapy (CBT) intervention has been developed specifically for HFNS that is theoretically based and shown to reduce significantly the impact of HFNS in several randomised controlled trials (RCTs). Self-help CBT has been found to be as effective as group CBT for these symptoms, but these interventions are not widely available in the workplace. This paper describes the protocol of an RCT aiming to assess the efficacy of CBT for menopausal symptoms implemented in the workplace, with a nested qualitative study to examine acceptability and feasibility. One hundred menopausal working women, aged 45-60 years, experiencing bothersome HFNS for two months will be recruited from several (2-10) large organisations into a multicentre randomised controlled trial. Women will be randomly assigned to either treatment (a self-help CBT intervention lasting 4 weeks) or to a no treatment-wait control condition (NTWC), following a screening interview, consent, and completion of a baseline questionnaire. All participants will complete follow-up questionnaires at 6 weeks and 20 weeks post-randomisation. The primary outcome is the rating of HFNS; secondary measures include HFNS frequency, mood, quality of life, attitudes to menopause, HFNS beliefs and behaviours, work absence and presenteeism, job satisfaction, job stress, job performance, disclosure to managers and turnover intention. Adherence, acceptability and feasibility will be assessed at 20 weeks post-randomisation in questionnaires and qualitative interviews. Upon trial completion, the control group will also be offered the intervention. This is the first randomised controlled trial of a self-management intervention tailored for working women who have troublesome menopausal symptoms. Clin.Gov NCT02623374. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Percutaneous Coronary Intervention of Left Main Disease: Pre- and Post-EXCEL (Evaluation of XIENCE Everolimus Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) and NOBLE (Nordic-Baltic-British Left Main Revascularization Study) Era.

PubMed

Park, Duk-Woo; Park, Seung-Jung

2017-06-01

For nearly half a century, coronary artery bypass grafting has been the standard treatment for patients with obstructive left main coronary artery (LMCA) disease. However, there has been considerable evolution in the field of percutaneous coronary intervention, and especially, percutaneous coronary intervention for LMCA disease has been rapidly expanded with adoption of drug-eluting stents. Some, but not all randomized trials, have shown that percutaneous coronary intervention with drug-eluting stents might be a suitable alternative for selected patients with LMCA disease instead of bypass surgery. However, none of previous trials involving early-generation drug-eluting stents was sufficiently powered and comparative trials using contemporary drug-eluting stents were limited. Recently, primary results of 2 new trials of EXCEL (Evaluation of XIENCE Everolimus Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) and NOBLE (Nordic-Baltic-British Left Main Revascularization Study) were reported. However, these trials showed conflicting results, which might pose uncertainty on the optimal revascularization strategy for LMCA disease. In this article, with the incorporation of a key review on evolution of LMCA treatment, we summarize the similarity or disparity of the EXCEL and NOBLE trials, focus on how they relate to previous trials in the field, and finally speculate on how the treatment strategy may be changed or recommended for LMCA treatment. © 2017 American Heart Association, Inc.

Increasing walking among older people: A test of behaviour change techniques using factorial randomised N-of-1 trials

PubMed Central

Nyman, Samuel R.; Goodwin, Kelly; Kwasnicka, Dominika; Callaway, Andrew

2016-01-01

Objective: Evaluations of techniques to promote physical activity usually adopt a randomised controlled trial (RCT). Such designs inform how a technique performs on average but cannot be used for treatment of individuals. Our objective was to conduct the first N-of-1 RCTs of behaviour change techniques with older people and test the effectiveness of the techniques for increasing walking within individuals. Design: Eight adults aged 60–87 were randomised to a 2 (goal-setting vs. active control) × 2 (self-monitoring vs. active control) factorial RCT over 62 days. The time series data were analysed for each single case using linear regressions. Main outcome measures: Walking was objectively measured using pedometers. Results: Compared to control days, goal-setting increased walking in 4 out of 8 individuals and self-monitoring increased walking in 7 out of 8 individuals. While the probability for self-monitoring to be effective in 7 out of 8 participants was beyond chance (p = .03), no intervention effect was significant for individual participants. Two participants had a significant but small linear decrease in walking over time. Conclusion: We demonstrate the utility of N-of-1 trials for advancing scientific enquiry of behaviour change and in practice for increasing older people’s physical activity. PMID:26387689

A randomised study of ilio-inguinal nerve blocks following inguinal hernia repair: a stopped randomised controlled trial.

PubMed

Walker, Stuart; Orlikowski, Chris

2008-02-01

Local anaesthetic use for post-operative pain control is widely used following open inguinal hernia repair but this is not without risk. The aim of this study was to compare ilio-inguinal nerve block and wound irrigation in patients undergoing open inguinal hernia repair under general anaesthetic in a randomised, double blind, placebo controlled trial. Adult patients admitted for unilateral primary open mesh repair of an inguinal hernia were recruited. The patients received a standard general anaesthetic. Prior to skin incision, an ilio-inguinal injection was performed by the anaesthetist with either ropivicaine or normal saline. Prior to closure of the wound, the wound was irrigated with either ropivicaine or normal saline. Post-operatively, all patients received fentynal patient controlled analgesia and regular oral analgesia. Pain scores and visual analogue scores were recorded until discharge. Patients were then contacted by telephone at 24h, 48h, 2weeks and 4weeks post-operatively and asked a standard series of questions, mainly related to post-operative pain. After 12 patients had been recruited the trial was stopped as 5 of the 8 patients who received an ilio-inguinal nerve block suffered a neurological complication. Ilio-inguinal nerve block with ropivicaine should be avoided.

Understanding influences on teachers' uptake and use of behaviour management strategies within the STARS trial: process evaluation protocol for a randomised controlled trial.

PubMed

Hansford, Lorraine; Sharkey, Siobhan; Edwards, Vanessa; Ukoumunne, Obioha; Byford, Sarah; Norwich, Brahm; Logan, Stuart; Ford, Tamsin

2015-02-10

The 'Supporting Teachers And childRen in Schools' (STARS) study is a cluster randomised controlled trial evaluating the Incredible Years Teacher Classroom Management (TCM) programme as a public health intervention. TCM is a 6 day training course delivered to groups of 8-12 teachers. The STARS trial will investigate whether TCM can improve children's behaviour, attainment and wellbeing, reduce teachers' stress and improve their self-efficacy. This protocol describes the methodology of the process evaluation embedded within the main trial, which aims to examine the uptake and implementation of TCM strategies within the classroom plus the wider school environment and improve the understanding of outcomes. The STARS trial will work with eighty teachers of children aged 4-9 years from eighty schools. Teachers will be randomised to attend the TCM course (intervention arm) or to "teach as normal" (control arm) and attend the course a year later. The process evaluation will use quantitative and qualitative approaches to assess fidelity to model, as well as explore headteachers' and teachers' experiences of TCM and investigate school factors that influence the translation of skills learnt to practice. Four of the eight groups of teachers (n = 40) will be invited to participate in focus groups within one month of completing the TCM course, and again a year later, while 45 of the 80 headteachers will be invited to take part in telephone interviews. Standardised checklists will be completed by group leaders and each training session will be videotaped to assess fidelity to model. Teachers will also complete standardised session evaluations. This study will provide important information about whether the Teacher Classroom Management course influences child and teacher mental health and well-being in both the short and long term. The process evaluation will provide valuable insights into factors that may facilitate or impede any impact. The trial has been registered with ISCTRN (Controlled Trials Ltd) and assigned an ISRCTN number ISRCTN84130388 . Date assigned: 15 May 2012.

Efficacy of Ambroxol lozenges for pharyngitis: a meta-analysis

PubMed Central

2014-01-01

Background Ambroxol has a local anaesthetic action and is marketed for pain relief for sore throat. The objective is to examine the efficacy and safety of ambroxol for the relief of pain associated with acute uncomplicated sore throat. Methods A systematic review of the literature and meta-analysis. Selection criteria consisted of randomized controlled trials which compared ambroxol to placebo or any other treatment for sore throat. Two reviewers independently assessed for relevance, inclusion, and risk of bias. Weighted mean differences (WMDs) were calculated and are reported with corresponding 95% confidence intervals (CIs). Results and conclusion From 14 potentially relevant citations, five trials reported in three publications met the inclusion criteria, three of them were published twice. Ambroxol lozenges were compared in different dosages (5–30 mg) with mint flavoured lozenges and once with benzocaine. Main outcome was a ratio of pain reduction measured repeatedly over 3 h compared to baseline on 6-item verbal rating scale. A total of 1.772 adult patients participated in the trials. Pain intensity decreased in both study arms. A meta-analysis of the 5 controlled trials resulted in a difference in pain reduction compared to placebo of -0.11 (95% CI [-0.15, -0.07]; p < 0.0001) favouring ambroxol 20 mg. Quality of reporting of the studies was low. Ambroxol is slightly more effective in relieving pain in acute sore throat than mint flavoured lozenges over a period of 3 h. However, the additional benefits of ambroxol beyond three hours, remain unclear given that more than 50% of patients using mint flavoured lozenges for pain relief reported good or very good efficacy after 1 day compared to 69% with ambroxol. Ambroxol is a safe option for individual patients with mainly local symptoms asking for treatment. PMID:24621446

Efficacy of Ambroxol lozenges for pharyngitis: a meta-analysis.

PubMed

Chenot, Jean-François; Weber, Peter; Friede, Tim

2014-03-13

Ambroxol has a local anaesthetic action and is marketed for pain relief for sore throat. The objective is to examine the efficacy and safety of ambroxol for the relief of pain associated with acute uncomplicated sore throat. A systematic review of the literature and meta-analysis. Selection criteria consisted of randomized controlled trials which compared ambroxol to placebo or any other treatment for sore throat. Two reviewers independently assessed for relevance, inclusion, and risk of bias. Weighted mean differences (WMDs) were calculated and are reported with corresponding 95% confidence intervals (CIs). From 14 potentially relevant citations, five trials reported in three publications met the inclusion criteria, three of them were published twice. Ambroxol lozenges were compared in different dosages (5-30 mg) with mint flavoured lozenges and once with benzocaine. Main outcome was a ratio of pain reduction measured repeatedly over 3 h compared to baseline on 6-item verbal rating scale. A total of 1.772 adult patients participated in the trials. Pain intensity decreased in both study arms. A meta-analysis of the 5 controlled trials resulted in a difference in pain reduction compared to placebo of -0.11 (95% CI [-0.15, -0.07]; p < 0.0001) favouring ambroxol 20 mg. Quality of reporting of the studies was low. Ambroxol is slightly more effective in relieving pain in acute sore throat than mint flavoured lozenges over a period of 3 h. However, the additional benefits of ambroxol beyond three hours, remain unclear given that more than 50% of patients using mint flavoured lozenges for pain relief reported good or very good efficacy after 1 day compared to 69% with ambroxol. Ambroxol is a safe option for individual patients with mainly local symptoms asking for treatment.

FFR-guided multivessel stenting reduces urgent revascularization compared with infarct-related artery only stenting in ST-elevation myocardial infarction: A meta-analysis of randomized controlled trials.

PubMed

Gupta, Ankur; Bajaj, Navkaranbir S; Arora, Pankaj; Arora, Garima; Qamar, Arman; Bhatt, Deepak L

2018-02-01

Randomized controlled trials (RCTs) have shown fractional flow reserve-guided (FFR) multivessel stenting to be superior to infarct-related artery (IRA) only stenting in patients with ST-elevation myocardial infarction (STEMI) and multivessel disease. This effect was mainly driven by a reduction in overall repeat revascularization. However, the ability to assess the effect of this strategy on urgent revascularization or reinfarction was underpowered in individual trials. We searched Pubmed, EMBASE, Cochrane CENTRAL, and Web of Science for RCTs of FFR-guided multivessel stenting versus IRA-only stenting in STEMI with multivessel disease. The outcomes of interest were death, reinfarction, urgent, and non-urgent repeat revascularization. Risk ratios (RR) were pooled using the DerSimonian and Laird random-effects model. After review of 786 citations, 2 RCTs were included. The pooled results demonstrated a significant reduction in the composite of death, reinfarction, or revascularization in the FFR-guided multivessel stenting group versus IRA-only stenting group (RR [95%, Confidence Interval]: 0.49 [0.33-0.72], p<0.001). This risk reduction was driven mainly by a reduction in repeat revascularization, both urgent (0.41 [0.24-0.71], p=0.002) and non-urgent revascularization (0.31 [0.19-0.50], p<0.001). Pooled RR for reinfarction was lower in the FFR-guided strategy, but was not statistically significant (0.71[0.39-1.31], p=0.28). This systematic review and meta-analysis suggests that a strategy of FFR-guided multivessel stenting in STEMI patients reduces not only overall repeat revascularization but also urgent revascularization. The effect on reinfarction needs to be evaluated in larger trials. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Instructor feedback versus no instructor feedback on performance in a laparoscopic virtual reality simulator: a randomized educational trial

PubMed Central

2012-01-01

Abstract Background Several studies have found a positive effect on the learning curve as well as the improvement of basic psychomotor skills in the operating room after virtual reality training. Despite this, the majority of surgical and gynecological departments encounter hurdles when implementing this form of training. This is mainly due to lack of knowledge concerning the time and human resources needed to train novice surgeons to an adequate level. The purpose of this trial is to investigate the impact of instructor feedback regarding time, repetitions and self-perception when training complex operational tasks on a virtual reality simulator. Methods/Design The study population consists of medical students on their 4th to 6th year without prior laparoscopic experience. The study is conducted in a skills laboratory at a centralized university hospital. Based on a sample size estimation 98 participants will be randomized to an intervention group or a control group. Both groups have to achieve a predefined proficiency level when conducting a laparoscopic salpingectomy using a surgical virtual reality simulator. The intervention group receives standardized instructor feedback of 10 to 12 min a maximum of three times. The control group receives no instructor feedback. Both groups receive the automated feedback generated by the virtual reality simulator. The study follows the CONSORT Statement for randomized trials. Main outcome measures are time and repetitions to reach the predefined proficiency level on the simulator. We include focus on potential sex differences, computer gaming experience and self-perception. Discussion The findings will contribute to a better understanding of optimal training methods in surgical education. Trial Registration NCT01497782 PMID:22373062

The effect of walking and vitamin B supplementation on quality of life in community-dwelling adults with mild cognitive impairment: a randomized, controlled trial

PubMed Central

van Uffelen, Jannique G. Z.; Hopman-Rock, Marijke; van Mechelen, Willem

2007-01-01

Objectives To examine the effect of walking and vitamin B supplementation on quality-of-life (QoL) in community-dwelling adults with mild cognitive impairment. Methods One year, double-blind, placebo-controlled trial. Participants were randomized to: (1) twice-weekly, group-based, moderate-intensity walking program (n = 77) or a light-intensity placebo activity program (n = 75); and (2) daily vitamin B pills containing 5 mg folic acid, 0.4 mg B12, 50 mg B6 (n = 78) or placebo pills (n = 74). QoL was measured at baseline, after six and 12 months using the population-specific Dementia Quality-of-Life (D-QoL) to assess overall QoL and the generic Short-Form 12 mental and physical component scales (SF12-MCS and SF12-PCS) to assess health-related QoL. Results Baseline levels of QoL were relatively high. Modified intention-to-treat analyses revealed no positive main intervention effect of walking or vitamin supplementation. In both men and women, ratings of D-QoL-belonging and D-QoL-positive affect subscales improved with 0.003 (P = 0.04) and 0.002 points (P = 0.06) with each percent increase in attendance to the walking program. Only in men, SF12-MCS increased with 0.03 points with each percent increase in attendance (P = 0.08). Conclusion Several small but significant improvements in QoL were observed with increasing attendance to the walking program. No effect of vitamin B supplementation was observed. Trial Registration International Standard Randomized Controlled Trial Number Register, 19227688, http://www.controlled-trials.com/isrctn/. PMID:17616840

GestationaL Obesity Weight management: Implementation of National Guidelines (GLOWING): a pilot cluster randomised controlled trial of a guideline implementation intervention for the management of maternal obesity by midwives.

PubMed

Heslehurst, Nicola; Rankin, Judith; McParlin, Catherine; Sniehotta, Falko F; Howel, Denise; Rice, Stephen; McColl, Elaine

2018-01-01

Weight management in pregnancy guidelines exist, although dissemination alone is an ineffective means of implementation. Midwives identify the need for support to overcome complex barriers to practice. An evaluation of an intervention to support midwives' guideline implementation would require a large-scale cluster randomised controlled trial. A pilot study is necessary to explore the feasibility of delivery and evaluation prior to a definitive trial. The GestationaL Obesity Weight management: Implementation of National Guidelines (GLOWING) trial aims to test whether it is feasible and acceptable to deliver a behaviour change intervention to support midwives' implementation of weight management guidelines. GLOWING is a multi-centre parallel group pilot cluster randomised controlled trial comparing the delivery of a behaviour change intervention for midwives versus usual practice. Four NHS Trusts (clusters) will be randomised to intervention and control arms, stratified by size of maternity services. The intervention uses social cognitive theory and consists of face-to-face midwifery training plus information resources for routine practice. The main outcomes are whether the intervention and trial procedures are feasible and acceptable to participants and the feasibility of recruitment and data collection for a definitive trial. Target recruitment involves all eligible midwives in the intervention arm recruited to receive the intervention, 30 midwives and pregnant women per arm for baseline and outcome questionnaire data collection and 20 midwives and women to provide qualitative data. All quantitative and qualitative analyses will be descriptive with the purpose of informing the development of the definitive trial. This pilot study has been developed to support community midwives' implementation of guidelines. Community midwives have been selected as they usually carry out the booking appointment which includes measuring and discussing maternal body mass index. A cluster design is the gold standard in implementation research as there would be a high risk of contamination if randomisation was at individual midwife level: community midwives usually work in locality-based teams, interact on a daily basis, and share care of pregnant women. The results of the pilot trial will be used to further develop and refine GLOWING prior to a definitive trial to evaluate effectiveness and cost-effectiveness. ISRCTN46869894; retrospectively registered 25th May 2016.

[Thinking on designation of sham acupuncture in clinical research].

PubMed

Pan, Li-Jia; Chen, Bo; Zhao, Xue; Guo, Yi

2014-01-01

Randomized controlled trials (RCT) is the source of the raw data of evidence-based medicine. Blind method is adopted in most of the high-quality RCT. Sham acupuncture is the main form of blinded in acupuncture clinical trial. In order to improve the quality of acupuncture clinical trail, based on the necessity of sham acupuncture in clinical research, the current situation as well as the existing problems of sham acupuncture, suggestions were put forward from the aspects of new way and new designation method which can be adopted as reference, and factors which have to be considered during the process of implementing. Various subjective and objective factors involving in the process of trial should be considered, and used of the current international standards, try to be quantification, and carry out strict quality monitoring.

Ultrasonographic evaluation of urinary tract morbidity in school-aged and preschool-aged children infected with Schistosoma haematobium and its evolution after praziquantel treatment: A randomized controlled trial.

PubMed

Barda, Beatrice; Coulibaly, Jean T; Hatz, Christoph; Keiser, Jennifer

2017-02-01

Schistosoma haematobium infections are responsible for significant urinary tract (UT) complications. Schistosomiasis control programs aim to reduce morbidity, yet the extent of morbidity in preschool-aged children and the impact of treatment on morbidity reduction are not well studied. Our study was embedded in a randomized, placebo-controlled, single-blind trial in Côte d'Ivoire, which evaluated the efficacy and safety of three doses (20, 40 and 60 mg/kg) of praziquantel in school-aged (SAC) and preschool-aged (PSAC) children infected with S. haematobium. Enrolled children were invited to participate in an ultrasound examination prior and six months after treatment. At these time points 3 urine samples were collected for parasitological and clinical examinations. 162 PSAC and 141 SAC participated in the ultrasound examination at baseline, of which 128 PSAC and 122 SAC were present at follow-up. At baseline 43% (70/162) of PSAC had UT morbidity, mostly at bladder level and 7% had hydronephrosis. 67% (94/141) of SAC revealed mainly moderate UT pathology, 4% presented pseudopolyps on the bladder wall, and 6% had pyelectasis. At follow up, 45% of PSAC and 58% of SAC were S. haematobium positive, mostly harboring light infection intensities (41% and 51%, respectively). Microhematuria was present in 33% of PSAC and 42% of SAC and leukocyturia in 53% and 40% of PSAC and SAC, respectively. 50% (64/128) of PSAC and 58% (71/122) of SAC presented urinary tract morbidity, which was mainly mild. A significant correlation (p<0.05) was observed between praziquantel treatment and reversal of S. haematobium induced morbidity. Progression of UT pathology decreased with increasing praziquantel dosages. A worsening of morbidity was observed among children in the placebo group. Bladder morbidity is widespread among PSAC. Praziquantel treatment is significantly associated with the reversal of S. haematobium induced morbidity, which underscores the importance of preventive chemotherapy programs. These programs should be expanded to PSAC to prevent or decrease the prevalence of morbidity in young children. This trial is registered as an International Standard Randomized Controlled Trial, number ISRCTN15280205.

Quality of Life after Diet or Exercise-Induced Weight Loss in Overweight to Obese Postmenopausal Women: The SHAPE-2 Randomised Controlled Trial.

PubMed

van Gemert, Willemijn A M; van der Palen, Job; Monninkhof, Evelyn M; Rozeboom, Anouk; Peters, Roelof; Wittink, Harriet; Schuit, Albertine J; Peeters, Petra H

2015-01-01

This study investigates the effect of a modest weight loss either by a calorie restricted diet or mainly by increased physical exercise on health related quality of life (HRQoL) in overweight-to-obese and inactive postmenopausal women. We hypothesize that HRQoL improves with weight loss, and that exercise-induced weight loss is more effective for this than diet-induced weight loss. The SHAPE-2 trial was primarily designed to evaluate any additional effect of weight loss by exercise compared with a comparable amount of weight loss by diet on biomarkers relevant for breast cancer risk. In the present analysis we focus on HRQoL. We randomly assigned 243 eligible women to a diet (n = 97), exercise (n = 98), or control group (n = 48). Both interventions aimed for 5-6 kg weight loss. HRQoL was measured at baseline and after 16 weeks by the SF-36 questionnaire. Data of 214 women were available for analysis. Weight loss was 4.9 kg (6.1%) and 5.5 kg (6.9%) with diet and exercise, respectively. Scores of the SF-36 domain 'health change' increased significantly by 8.8 points (95% CI 1.6;16.1) with diet, and by 20.5 points (95% CI 13.2;27.7) with exercise when compared with control. Direct comparison of diet and exercise showed a statistically significantly stronger improvement with exercise. Both intervention groups showed a tendency towards improvements in most other domains, which were more pronounced in the exercise group, but not statistically different from control or each other. In a randomized trial in overweight-to-obese and inactive postmenopausal women a comparable 6%-7% weight loss was achieved by diet-only or mainly by exercise and showed improvements in physical and mental HRQoL domains, but results were not statistically significant in either the diet or exercise group. However, a modest weight loss does lead to a positive change in self-perceived health status. This effect was significantly larger with exercise-induced weight loss than with comparable diet-induced weight loss. ClinicalTrials.gov NCT01511276.

How does visual manipulation affect obstacle avoidance strategies used by athletes?

PubMed

Bijman, M P; Fisher, J J; Vallis, L A

2016-01-01

Research examining our ability to avoid obstacles in our path has stressed the importance of visual input. The aim of this study was to determine if athletes playing varsity-level field sports, who rely on visual input to guide motor behaviour, are more able to guide their foot over obstacles compared to recreational individuals. While wearing kinematic markers, eight varsity athletes and eight age-matched controls (aged 18-25) walked along a walkway and stepped over stationary obstacles (180° motion arc). Visual input was manipulated using PLATO visual goggles three or two steps pre-obstacle crossing and compared to trials where vision was given throughout. A main effect between groups for peak trail toe elevation was shown with greater values generated by the controls for all crossing conditions during full vision trials only. This may be interpreted as athletes not perceiving this obstacle as an increased threat to their postural stability. Collectively, findings suggest the athletic group is able to transfer their abilities to non-specific conditions during full vision trials; however, varsity-level athletes were equally reliant on visual cues for these visually guided stepping tasks as their performance was similar to the controls when vision is removed.

Social Norms and Financial Incentives to Promote Employees’ Healthy Food Choices: A Randomized Controlled Trial

PubMed Central

Thorndike, Anne N.; Riis, Jason; Levy, Douglas E.

2016-01-01

Population-level strategies to improve healthy food choices are needed for obesity prevention. We conducted a randomized controlled trial of 2,672 employees at Massachusetts General Hospital who were regular customers of the hospital cafeteria with all items labeled green (healthy), yellow (less healthy), or red (unhealthy) to determine if social norm (peer-comparison) feedback with or without financial incentives increased employees’ healthy food choices. Participants were randomized in 2012 to three arms: 1) monthly letter with social norm feedback about healthy food purchases, comparing employee to “all” and to “healthiest” customers (feedback-only); 2) monthly letter with social norm feedback plus small financial incentive for increasing green purchases (feedback-incentive); or 3) no contact (control). The main outcome was change in proportion of green-labeled purchases at end of 3-month intervention. Post-hoc analyses examined linear trends. At baseline, the proportion of green-labeled purchases (50%) did not differ between arms. At end of the 3-month intervention, the percentage increase in green-labeled purchases was larger in the feedback-incentive arm compared to control (2.2% vs. 0.1%, P=0.03), but the two intervention arms were not different. The rate of increase in green-labeled purchases was higher in both feedback-only (P=0.04) and feedback-incentive arms (P=0.004) compared to control. At end of a 3-month wash-out, there were no differences between control and intervention arms. Social norms plus small financial incentives increased employees’ healthy food choices over the short-term. Future research will be needed to assess the impact of this relatively low-cost intervention on employees’ food choices and weight over the long-term. Trial Registration: Clinical Trials.gov NCT01604499 PMID:26827617

Improving Motor Control in Walking: A Randomized Clinical Trial in Older Adults with Subclinical Walking Difficulty

PubMed Central

Brach, Jennifer S.; Lowry, Kristin; Perera, Subashan; Hornyak, Victoria; Wert, David; Studenski, Stephanie A.; VanSwearingen, Jessie M.

2016-01-01

Objective The objective was to test the proposed mechanism of action of a task-specific motor learning intervention by examining its effect on measures of the motor control of gait. Design Single blinded randomized clinical trial. Setting University research laboratory. Participants Forty older adults 65 years of age and older, with gait speed >1.0 m/s and impaired motor skill (Figure of 8 walk time > 8 secs). Interventions The two interventions included a task-oriented motor learning and a standard exercise program. Both interventions lasted 12 weeks, with twice weekly one hour physical therapist supervised sessions. Main Outcome Measures Two measure of the motor control of gait, gait variability and smoothness of walking, were assessed pre and post intervention by assessors masked to treatment arm. Results Of 40 randomized subjects; 38 completed the trial (mean age 77.1±6.0 years). Motor control group improved more than standard group in double support time variability (0.13 vs. 0.05 m/s; adjusted difference, AD=0.006, p=0.03). Smoothness of walking in the anterior/posterior direction improved more in motor control than standard for all conditions (usual: AD=0.53, p=0.05; narrow: AD=0.56, p=0.01; dual task: AD=0.57, p=0.04). Conclusions Among older adults with subclinical walking difficulty, there is initial evidence that task-oriented motor learning exercise results in gains in the motor control of walking, while standard exercise does not. Task-oriented motor learning exercise is a promising intervention for improving timing and coordination deficits related to mobility difficulties in older adults, and needs to be evaluated in a definitive larger trial. PMID:25448244

Post-traumatic stress disorder in the context of terrorism and other civil conflict in Northern Ireland: randomised controlled trial

PubMed Central

Gillespie, Kate; Clark, David M

2007-01-01

Objective To evaluate the effectiveness of cognitive therapy for post-traumatic stress disorder related to terrorism and other civil conflict in Northern Ireland. Design Randomised controlled trial. Setting Community treatment centre, Northern Ireland. Participants 58 consecutive patients with chronic post-traumatic stress disorder (median 5.2 years, range 3 months to 32 years) mostly resulting from multiple traumas linked to terrorism and other civil conflict. Interventions Immediate cognitive therapy compared with a waiting list control condition for 12 weeks followed by treatment. Treatment comprised a mean of 5.9 sessions during 12 weeks and 2.0 sessions thereafter. Main outcome measures Primary outcome measures were patients' scores for post-traumatic stress disorder (post-traumatic stress diagnostic scale) and depression (Beck depression inventory). The secondary outcome measure was scores for occupational and social functioning (work related disability, social disability, and family related disability) on the Sheehan disability scale. Results At 12 weeks after randomisation, immediate cognitive therapy was associated with significantly greater improvement than the waiting list control group in the symptoms of post-traumatic stress disorder (mean difference 9.6, 95% confidence interval 3.6 to 15.6), depression (mean difference 10.1, 4.8 to 15.3), and self reported occupational and social functioning (mean difference 1.3, 0.3 to 2.5). Effect sizes from before to after treatment were large: post-traumatic stress disorder 1.25, depression 1.05, and occupational and social functioning 1.17. No change was observed in the control group. Conclusion Cognitive therapy is an effective treatment for post-traumatic stress disorder related to terrorism and other civil conflict. Trial registration Current Controlled Trials ISRCTN16228473. PMID:17495988

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/.

Corticosteroids for neurocysticercosis: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Cuello-García, Carlos A; Roldán-Benítez, Yetiani M; Pérez-Gaxiola, Giordano; Villarreal-Careaga, Jorge

2013-08-01

Neurocysticercosis is an infection of the central nervous system by the larval stage of Taenia solium. It is a major cause of epileptic seizures in low- and middle-income countries. Corticosteroids are frequently used to reduce inflammation and perilesional edema. We aimed to evaluate their efficacy for reducing the rate of seizures and lesion persistence in imaging studies. We searched randomized controlled trials in Medline, Central, EMBASE, LILACS, and the gray literature without language restrictions. We assessed eligibility, extracted data, and assessed the risk of bias in the included studies. The main outcomes included seizure recurrence and lesion persistence on imaging studies at 6-12 months of follow-up. Risk ratios (RR) were used for evaluating the main outcomes. Thirteen studies involving 1373 participants were included. The quality of the evidence was deemed low to very low. Corticosteroids alone versus placebo/no drug (five trials) reduced the rate of seizure recurrence at 6-12 months (RR 0.46, 95% confidence interval (CI) 0.27-0.77; 426 participants) and the persistence of lesions in imaging studies (RR 0.63, 95% CI 0.43-0.92; 417 participants). No differences were noted in other comparisons, including the use of corticosteroids and albendazole combined. Corticosteroids plus albendazole increased the risk of abdominal pain, rash, and headaches (odds ratio 8.73, 95% CI 2.09-36.5; 116 participants, one trial). Although the evidence suggest corticosteroids can reduce the rate of seizure recurrence and speed up resolution of lesions at 6-12 months of follow-up, there remains uncertainty on the effect estimate due to a high risk of methodological and publication bias. More adequately performed randomized trials that evaluate the use of anthelmintics, corticosteroids, and both combined against placebo are needed. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Trends in research involving human beings in Brazil.

PubMed

Silva, Ricardo Eccard da; Novaes, Maria Rita Carvalho; Pastor, Elza Martínez; Barragan, Elena; Amato, Angélica Amorim

2015-02-01

Developing countries have experienced a dramatic increase in the number of clinical studies in the last decades. The aim of this study was to describe 1) the number of clinical trials submitted to the Brazilian Health Surveillance Agency (Agência Nacional de Vigilância Sanitária, Anvisa) from 2007 to 2012 and the number of human-subject research projects approved by research ethics committees (RECs) and the National Research Ethics Committee (Comissão Nacional de Ética em Pesquisa, CONEP) in Brazil from 2007 to 2011 and 2) the diseases most frequently studied in Brazilian states in clinical trials approved in the country from 2009 to 2012, based on information from an Anvisa databank. Two databases were used: 1) the National Information System on Research Ethics Involving Human Beings (Sistema Nacional de Informação Sobre Ética em Pesquisa envolvendo Seres Humanos, SISNEP) and 2) Anvisa's Clinical Research Control System (Sistema de Controle de Pesquisa Clínica, SCPC). Data from the SCPC indicated an increase of 32.7% in the number of clinical trials submitted to Anvisa, and data from the SISNEP showed an increase of 69.9% in those approved by RECs and CONEP (from 18 160 in 2007 to 30 860 in 2011). Type 2 diabetes (26.0%) and breast cancer (20.5%)-related to the main causes of mortality in Brazil-were the two most frequently studied diseases. The so-called “neglected diseases,” such as dengue fever, were among the least studied diseases in approved clinical trials, despite their significant impact on social, economic, and health indicators in Brazil. Overall, the data indicated 1) a clear trend toward more research involving human beings in Brazil, 2) good correspondence between diseases most studied in clinical trials approved by Anvisa and the main causes of death in Brazil, and 3) a low level of attention to neglected diseases, an issue that should be considered in setting future research priorities, given their socioeconomic and health effects.

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.

Treatment effects of Ginkgo biloba extract EGb 761® on the spectrum of behavioral and psychological symptoms of dementia: meta-analysis of randomized controlled trials.

PubMed

Savaskan, Egemen; Mueller, Heiko; Hoerr, Robert; von Gunten, Armin; Gauthier, Serge

2018-03-01

ABSTRACTBackground:In randomized controlled trials, Ginkgo biloba extract EGb 761® has been found to be effective in the treatment of behavioral and psychological symptoms of dementia (BPSD). To assess the effects of EGb 761® on specific BPSD, we analyzed data from all randomized, placebo-controlled, at least 20-week, trials of EGb 761® enrolling patients with dementia (probable Alzheimer's disease (AD), probable vascular dementia or probable AD with cerebrovascular disease) who had clinically significant BPSD (Neuropsychiatric Inventory (NPI) total score at least 6). Data were pooled and joint analyses of NPI single item composite and caregiver distress scores were performed by meta-analysis with a fixed effects model. Four trials involving 1628 patients (EGb 761®, 814; placebo, 814) were identified; treatment duration was 22 or 24 weeks; the daily dose of EGb 761® was 240 mg in all trials. Pooled analyses including data from the full analysis sets of all trials (EGb 761®, 796 patients; placebo, 802 patients) revealed significant superiority of EGb 761® over placebo in total scores and 10 single symptom scores. Regarding caregiver distress scores, EGb 761®-treated patients improved significantly more than those receiving placebo in all symptoms except delusions, hallucinations, and elation/euphoria. The benefit of EGb 761® mainly consists of improvement in symptoms present at baseline, but the incidence of some symptoms was also decreased. Twenty two- to twenty four-week treatment with Ginkgo biloba extract EGb 761® improved BPSD (except psychotic-like features) and caregiver distress caused by such symptoms.

Behavioural, educational and respiratory outcomes of antenatal betamethasone for term caesarean section (ASTECS trial)

PubMed Central

Stutchfield, Peter Roy; Whitaker, Rhiannon; Gliddon, Angela E; Hobson, Lucie; Kotecha, Sailesh; Doull, Iolo J M

2013-01-01

Objectives To determine whether antenatal betamethasone prior to elective term caesarean section (CS) affects long term behavioural, cognitive or developmental outcome, and whether the risk of asthma or atopic disease is reduced. Design A questionnaire based follow-up of a multicentre randomised controlled trial (Antenatal Steroids for Term Elective Caesarean Section, BMJ 2005). Setting Four UK study centres from the original trial. Participants 862 participants from the four largest recruiting centres, 92% of the original study. 824 (96%) were traced and 799 (93%) were successfully contacted. Fifty-one percent (407/799) completed and returned the questionnaire. The children were aged 8–15 years (median 12.2 years, 52% girls). 386 gave consent to contact schools with 352 (91%) reports received. Main outcome measures Questionnaires including a strengths and difficulties questionnaire, International Study of Asthma and Allergies in Childhood, general health and school performance. Results There were no significant differences between children whose mothers received betamethasone and controls for the mean total strengths and difficulties questionnaire scores and subscores for hyperactivity, emotional symptoms, prosocial behaviour, conduct or peer problems. 25 (12%) children whose mothers received betamethasone had reported learning difficulties compared with 27 (14%) control children. The proportion of children who achieved standard assessment tests KS2 exams level 4 or above for mathematics, English or science was similar as were the rates of ever reported wheeze (30% vs 30%), asthma (24% vs 21%), eczema (34% vs 37%) and hay fever (25% vs 27%). Conclusions Antenatal betamethasone did not result in any adverse outcomes or reduction in asthma or atopy. It should be considered for elective CS at 37–38 weeks of gestation. Trial registration: Original trial was preregistration, the trial publication is BMJ. 2005 Sep 24;331(7518):662. PMID:23424017

Umbilical cord mesenchyme stem cell local intramuscular injection for treatment of uterine niche: Protocol for a prospective, randomized, double-blinded, placebo-controlled clinical trial.

PubMed

Fan, Dazhi; Wu, Shuzhen; Ye, Shaoxin; Wang, Wen; Guo, Xiaoling; Liu, Zhengping

2017-11-01

Uterine niche is defined as a triangular anechoic structure at the site of the scar or a gap in the myometrium at the site of a previous caesarean section. The main clinical manifestations are postmenstrual spotting and intrauterine infection, which may seriously affect the daily life of nonpregnant women. Trials have shown an excellent safety and efficacy for the potential of mesenchymal stem cells (MSCs) as a therapeutic option for scar reconstruction. Therefore, this study is designed to investigate the safety and efficacy of using MSCs in the treatment for the uterine niche. This phase II clinical trial is a single-center, prospective, randomized, double-blind, placebo-controlled with 2 arms. One hundred twenty primiparous participants will be randomly (1:1 ratio) assigned to receive direct intramuscular injection of MSCs (a dose of 1*10 cells in 1 mL of 0.9% saline) (MSCs group) or an identical-appearing 1 mL of 0.9% saline (placebo-controlled group) near the uterine incision. The primary outcome of this trial is to evaluate the proportion of participants at 6 months who is found uterine niche in the uterus by transvaginal utrasonography. Adverse events will be documented in a case report form. The study will be conducted at the Department of Obstetric of Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan. This trial is the first investigation of the potential for therapeutic use of MSCs for the management of uterine niche after cesarean delivery. This protocol will help to determine the efficacy and safety of MSCs treatment in uterine niche and bridge the gap with regards to the current preclinical and clinical evidence. NCT02968459 (Clinical Trials.gov: http://clinicaltrials.gov/).

A randomised controlled trial of six weeks of home enteral nutrition versus standard care after oesophagectomy or total gastrectomy for cancer: report on a pilot and feasibility study.

PubMed

Bowrey, David J; Baker, Melanie; Halliday, Vanessa; Thomas, Anne L; Pulikottil-Jacob, Ruth; Smith, Karen; Morris, Tom; Ring, Arne

2015-11-21

Poor nutrition in the first months after oesophago-gastric resection is a contributing factor to the reduced quality of life seen in these patients. The aim of this pilot and feasibility study was to ascertain the feasibility of conducting a multi-centre randomised controlled trial to evaluate routine home enteral nutrition in these patients. Patients undergoing oesophagectomy or total gastrectomy were randomised to either six weeks of home feeding through a jejunostomy (intervention), or treatment as usual (control). Intervention comprised overnight feeding, providing 50 % of energy and protein requirements, in addition to usual oral intake. Primary outcome measures were recruitment and retention rates at six weeks and six months. Nutritional intake, nutritional parameters, quality of life and healthcare costs were also collected. Interviews were conducted with a sample of participants, to ascertain patient and carer experiences. Fifty-four of 112 (48 %) eligible patients participated in the study over the 20 months. Study retention at six weeks was 41/54 patients (76 %) and at six months was 36/54 (67 %). At six weeks, participants in the control group had lost on average 3.9 kg more than participants in the intervention group (95 % confidence interval [CI] 1.6 to 6.2). These differences remained evident at three months (mean difference 2.5 kg, 95 % CI -0.5 to 5.6) and at six months (mean difference 2.5 kg, 95 % CI -1.2 to 6.1). The mean values observed in the intervention group for mid arm circumference, mid arm muscle circumference, triceps skin fold thickness and right hand grip strength were greater than for the control group at all post hospital discharge time points. The economic evaluation suggested that it was feasible to collect resource use and EQ-5D data for a full cost-effectiveness analysis. Thematic analysis of 15 interviews identified three main themes related to the intervention and the trial: 1) a positive experience, 2) the reasons for taking part, and 3) uncertainty of the study process. This study demonstrated that home enteral feeding by jejunostomy was feasible, safe and acceptable to patients and their carers. Whether home enteral feeding as 'usual practice' is a cost-effective therapy would require confirmation in an appropriately powered, multi-centre study. UK Clinical Research Network ID 12447 (main trial, first registered 30 May 2012); UK Clinical Research Network ID 13361 (qualitative substudy, first registered 30 May 2012); ClinicalTrials.gov NCT01870817 (first registered 28 May 2013).

CHAMP: Cognitive behaviour therapy for health anxiety in medical patients, a randomised controlled trial

PubMed Central

2011-01-01

Background Abnormal health anxiety, also called hypochondriasis, has been successfully treated by cognitive behaviour therapy (CBT) in patients recruited from primary care, but only one pilot trial has been carried out among those attending secondary medical clinics where health anxiety is likely to be more common and have a greater impact on services. The CHAMP study extends this work to examine both the clinical and cost effectiveness of CBT in this population. Method/Design The study is a randomized controlled trial with two parallel arms and equal randomization of 466 eligible patients (assuming a 20% drop-out) to an active treatment group of 5-10 sessions of cognitive behaviour therapy and to a control group. The aim at baseline, after completion of all assessments but before randomization, was to give a standard simple explanation of the nature of health anxiety for all participants. Subsequently the control group was to receive whatever care might usually be available in the clinics, which is normally a combination of clinical assessment, appropriate tests and reassurance. Those allocated to the active treatment group were planned to receive between 5 and 10 sessions of an adapted form of cognitive behaviour therapy based on the Salkovskis/Warwick model, in which a set of treatment strategies are chosen aimed at helping patients understand the factors that drive and maintain health anxiety. The therapy was planned to be given by graduate research workers, nurses or other health professionals trained for this intervention whom would also have their competence assessed independently during the course of treatment. The primary outcome is reduction in health anxiety symptoms after one year and the main secondary outcome is the cost of care after two years. Discussion This represents the first trial of adapted cognitive behaviour therapy in health anxiety that is large enough to test not only the clinical benefits of treatment but also whether the cost of treatment is offset by savings from reduced use of other health services in comparison to the control group. Cognitive behaviour therapy for Health Anxiety in Medical Patients (CHAMP) Trial registration Current Controlled Trials ISRCTN14565822 PMID:21672205

Oddball and incongruity effects during Stroop task performance: a comparative fMRI study on selective attention.

PubMed

Melcher, Tobias; Gruber, Oliver

2006-11-22

The aim of this fMRI study was to investigate and compare the neural mechanisms of selective attention during two different operationalizations of competition between task-relevant and task-irrelevant information: Stroop-incongruity and oddballs. For this purpose, we employed a Stroop-like oddball task in which subjects responded to the font size of presented word stimuli. Stroop-incongruity was created by (response-)incongruent word information while oddballs comprised low-frequency events in a task-irrelevant, unattended dimension. Thereby, in order to elucidate the influence of processing domain from which competition emanates, oddball conditions were created in two different attribute dimensions, color and word meaning. Either oddball condition was expected to evoke an orienting response, which participants would have to override in order to maintain adequate performance. Incongruent Stroop trials were expected to produce Stroop-interference so that subjects would have to override the predominant tendency to read and respond to word meaning. All competition conditions exhibited significantly prolonged reaction times compared to control trials, demonstrating that our experimental manipulation was indeed effective. fMRI data analyses delineated two discriminative components of competition: one component mainly related to motor preparation and another, primarily attentional component. Regarding the first, Stroop-interference increased activation mainly in regions implicated in motor control or response preparation. Regarding the second, Word-oddballs increased activation in a frontoparietal "attention network". Furthermore, Word-oddballs and Color-oddballs exhibited striking activation overlap mainly in prefrontal regions but also in posterior processing areas. Here, the data emphasized a prominent role of posterior lateral PFC in implementing top-down attentional control.

Strategies for informed sample size reduction in adaptive controlled clinical trials

NASA Astrophysics Data System (ADS)

Arandjelović, Ognjen

2017-12-01

Clinical trial adaptation refers to any adjustment of the trial protocol after the onset of the trial. The main goal is to make the process of introducing new medical interventions to patients more efficient. The principal challenge, which is an outstanding research problem, is to be found in the question of how adaptation should be performed so as to minimize the chance of distorting the outcome of the trial. In this paper, we propose a novel method for achieving this. Unlike most of the previously published work, our approach focuses on trial adaptation by sample size adjustment, i.e. by reducing the number of trial participants in a statistically informed manner. Our key idea is to select the sample subset for removal in a manner which minimizes the associated loss of information. We formalize this notion and describe three algorithms which approach the problem in different ways, respectively, using (i) repeated random draws, (ii) a genetic algorithm, and (iii) what we term pair-wise sample compatibilities. Experiments on simulated data demonstrate the effectiveness of all three approaches, with a consistently superior performance exhibited by the pair-wise sample compatibilities-based method.

Corticosteroids for ocular toxoplasmosis

PubMed Central

Jasper, Smitha; Vedula, Satyanarayana S; John, Sheeja S; Horo, Saban; Sepah, Yasir J; Nguyen, Quan Dong

2014-01-01

Background Ocular infestation with Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea and consequently lead to complications such as glaucoma, cataract, and posterior synechiae. Objectives The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids for ocular toxoplasmosis. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to October 2012), EMBASE (January 1980 to October 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2012), 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 searched the reference lists of included studies for any additional studies not identified by the electronic searches. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 October 2012. Selection criteria We planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with active ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, or different doses or times of initiation of corticosteroids. Data collection and analysis Two authors independently screened titles and abstracts retrieved from the electronic searches. We retrieved full-text articles of studies categorized as ‘unsure’ or ‘include’ after review of the abstracts. Two authors independently reviewed each full-text article. Discrepancies were resolved through discussion. Main results The electronic searches retrieved 368 titles and abstracts. We reviewed 20 full-text articles. We identified no trials eligible for inclusion in this systematic review. Authors' conclusions Although research has identified wide variation in practices regarding use of corticosteroids, our systematic review did not identify evidence from randomized controlled trials for the role of corticosteroids in the management of ocular toxoplasmosis. Several questions remain unanswered by well-conducted randomized trials in this context, including whether use of corticosteroids is more effective than use of anti-parasitic therapy alone, when corticosteroids should be initiated in the treatment regimen (early versus late course of treatment), and which dosage and duration of steroid use is best. These questions are easily amenable to research using a randomized controlled design and they are ethical due to the absence of evidence to support or discourage use of corticosteroids for this condition. The question of foremost importance, however, is whether they should be used as adjunct therapy (that is, additional) to anti-parasitic agents. PMID:23633342

[Randomized controlled trial on the effectiveness of Corpitolinol 60 in the prevention of pressure sores in patients undergoing surgery].

PubMed

Chiari, Paolo; Giorgi, Sabina; Ugolini, Daniela; Montanari, Morena; Giudanella, Pietro; Gramantieri, Antonella; Collesi, Franca; Pau, Michelina; Smaldone, Maddalena; Matarasso, Maddalena; Mazzini, Cinzia; Russo, Francesca; Gazineo, Domenica; Fontana, Mirella; Taddia, Patrizia

2012-01-01

Randomized controlled trial on the effectiveness of Corpitolinol 60 in the prevention of pressure sores in surgical patients. The risk of pressure sores in surgical patients is widely recognised. The Corpitolinol 60 (Sanyréne®) applied on compressed areas seems to reduce the risk of pressure sores. To assess the efficacy of Corpitolinol 60 in preventing pressure sores in the operatory theatre. The open label randomized clinical trial was conducted in 5 operating theatres of Northen Italy. Patients were randomized to receive Corpitolinol 60 in areas undergoing compression. Experimental group and controls were treated with usual measures for preventing pressure sores. The lesions were staged according to NPUAP up to 24 hours after surgery. Three-hundred-one patients were randomized (155 in the Sanyréne® group and 143 controls). The main variables predictive of pressure sores risk (ASA class, sex, age, duration of the surgery, and BMI) were comparable across groups. At the end of the surgery 71 patients (23.8%) in the experimental group and 47 controls (30.8%) had a pressure sore (p 0.006; RR 1.81 IC95% 1.17-2.79). Twelve and 24 hours after surgery the differences between groups were not significant. The aim of reducing pressure sores was not reached for patients treated with Corpitolinol 60.

Personalized upper limb training combined with anodal-tDCS for sensorimotor recovery in spastic hemiparesis: study protocol for a randomized controlled trial.

PubMed

Levin, Mindy F; Baniña, Melanie C; Frenkel-Toledo, Silvi; Berman, Sigal; Soroker, Nachum; Solomon, John M; Liebermann, Dario G

2018-01-04

Recovery of voluntary movement is a main rehabilitation goal. Efforts to identify effective upper limb (UL) interventions after stroke have been unsatisfactory. This study includes personalized impairment-based UL reaching training in virtual reality (VR) combined with non-invasive brain stimulation to enhance motor learning. The approach is guided by limiting reaching training to the angular zone in which active control is preserved ("active control zone") after identification of a "spasticity zone". Anodal transcranial direct current stimulation (a-tDCS) is used to facilitate activation of the affected hemisphere and enhance inter-hemispheric balance. The purpose of the study is to investigate the effectiveness of personalized reaching training, with and without a-tDCS, to increase the range of active elbow control and improve UL function. This single-blind randomized controlled trial will take place at four academic rehabilitation centers in Canada, India and Israel. The intervention involves 10 days of personalized VR reaching training with both groups receiving the same intensity of treatment. Participants with sub-acute stroke aged 25 to 80 years with elbow spasticity will be randomized to one of three groups: personalized training (reaching within individually determined active control zones) with a-tDCS (group 1) or sham-tDCS (group 2), or non-personalized training (reaching regardless of active control zones) with a-tDCS (group 3). A baseline assessment will be performed at randomization and two follow-up assessments will occur at the end of the intervention and at 1 month post intervention. Main outcomes are elbow-flexor spatial threshold and ratio of spasticity zone to full elbow-extension range. Secondary outcomes include the Modified Ashworth Scale, Fugl-Meyer Assessment, Streamlined Wolf Motor Function Test and UL kinematics during a standardized reach-to-grasp task. This study will provide evidence on the effectiveness of personalized treatment on spasticity and UL motor ability and feasibility of using low-cost interventions in low-to-middle-income countries. ClinicalTrials.gov, ID: NCT02725853 . Initially registered on 12 January 2016.

Revascularization for Left Main and Multivessel Coronary Artery Disease: Current Status and Future Prospects after the EXCEL and NOBLE Trials

PubMed Central

2018-01-01

Revascularization of severe left main and multivessel coronary artery disease has been shown to improve survival in both stable ischemic heart disease and acute coronary syndrome. While revascularization with coronary artery bypass surgery for these disease entities carries class I recommendation in most current guidelines, recent trials has shown potential comparable survival and cardiovascular outcomes between percutaneous and surgical interventions in patients with less complex coronary anatomy. Despite the conflicting results observed in the most recent left main revascularization trials, Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease (EXCEL) and Nordic-Baltic-British left main revascularization (NOBLE), both treatment strategies remain important for the management of left main disease (LMD) and multivessel disease (MVD) reflecting on the importance of heart team discussion. This review is focused on revascularization of LMD and MVD in patients who are not presenting with ST-segment elevation myocardial infarction, encompassing the evidence from historic and contemporary trials which shaped up current practices. This review discusses the heart team approach to guide decision making, including special populations that are not represented in clinical trials. PMID:29856140

Revascularization for Left Main and Multivessel Coronary Artery Disease: Current Status and Future Prospects after the EXCEL and NOBLE Trials.

PubMed

Al-Hijji, Mohammed; El Sabbagh, Abdallah; Holmes, David R

2018-06-01

Revascularization of severe left main and multivessel coronary artery disease has been shown to improve survival in both stable ischemic heart disease and acute coronary syndrome. While revascularization with coronary artery bypass surgery for these disease entities carries class I recommendation in most current guidelines, recent trials has shown potential comparable survival and cardiovascular outcomes between percutaneous and surgical interventions in patients with less complex coronary anatomy. Despite the conflicting results observed in the most recent left main revascularization trials, Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease (EXCEL) and Nordic-Baltic-British left main revascularization (NOBLE), both treatment strategies remain important for the management of left main disease (LMD) and multivessel disease (MVD) reflecting on the importance of heart team discussion. This review is focused on revascularization of LMD and MVD in patients who are not presenting with ST-segment elevation myocardial infarction, encompassing the evidence from historic and contemporary trials which shaped up current practices. This review discusses the heart team approach to guide decision making, including special populations that are not represented in clinical trials. Copyright © 2018. The Korean Society of Cardiology.

Efficacy of a web- and text messaging-based intervention to reduce problem drinking in young people: study protocol of a cluster-randomised controlled trial.

PubMed

Haug, Severin; Kowatsch, Tobias; Castro, Raquel Paz; Filler, Andreas; Schaub, Michael P

2014-08-07

Problem drinking, particularly risky single-occasion drinking is widespread among adolescents and young adults in most Western countries. Mobile phone text messaging allows a proactive and cost-effective delivery of short messages at any time and place and allows the delivery of individualised information at times when young people typically drink alcohol. The main objective of the planned study is to test the efficacy of a combined web- and text messaging-based intervention to reduce problem drinking in young people with heterogeneous educational level. A two-arm cluster-randomised controlled trial with one follow-up assessment after 6 months will be conducted to test the efficacy of the intervention in comparison to assessment only. The fully-automated intervention program will provide an online feedback based on the social norms approach as well as individually tailored mobile phone text messages to stimulate (1) positive outcome expectations to drink within low-risk limits, (2) self-efficacy to resist alcohol and (3) planning processes to translate intentions to resist alcohol into action. Program participants will receive up to two weekly text messages over a time period of 3 months. Study participants will be 934 students from approximately 93 upper secondary and vocational schools in Switzerland. Main outcome criterion will be risky single-occasion drinking in the past 30 days preceding the follow-up assessment. This is the first study testing the efficacy of a combined web- and text messaging-based intervention to reduce problem drinking in young people. Given that this intervention approach proves to be effective, it could be easily implemented in various settings, and it could reach large numbers of young people in a cost-effective way. Current Controlled Trials ISRCTN59944705.

Interventions for improving patients' trust in doctors and groups of doctors.

PubMed

Rolfe, Alix; Cash-Gibson, Lucinda; Car, Josip; Sheikh, Aziz; McKinstry, Brian

2014-03-04

Trust is a fundamental component of the patient-doctor relationship and is associated with increased satisfaction, adherence to treatment, and continuity of care. Our 2006 review found little evidence that interventions improve patients' trust in their doctor; therefore an updated search was required to find out if there is further evidence of the effects of interventions that may improve trust in doctors or groups of doctors. To update our earlier review assessing the effects of interventions intended to improve patients' trust in doctors or a group of doctors. In 2003 we searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE, Health Star, PsycINFO, CINAHL, LILACS, African Trials Register, African Health Anthology, Dissertation Abstracts International and the bibliographies of studies selected for inclusion. We also contacted researchers active in the field. We updated and re-ran the searches on available original databases (Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library issue 2, 2013), MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), CINAHL (Ebsco)) as well as Proquest Dissertations and Current Contents for the period 2003 to 18 March 2013. Randomised controlled trials (RCTs), quasi-randomised controlled trials, controlled before and after studies, and interrupted time series of interventions (informative, educational, behavioural, organisational) directed at doctors or patients (or carers) where trust was assessed as a primary or secondary outcome. Two review authors independently extracted data and assessed the risk of bias of included studies. Where mentioned, we extracted data on adverse effects. We synthesised data narratively. We included 10 randomised controlled trials (including 7 new trials) involving 11,063 patients. These studies were all undertaken in North America, and all but two involved primary care.  As expected, there was considerable heterogeneity between the studies.  Interventions were of three main types; three employed additional physician training, four were education for patients and three provided additional information about doctors in terms of financial incentives or consulting style. Additionally, several different measures of trust were employed.The studies gave conflicting results. Trials showing a small but statistically-significant increase in trust included: a trial of physician disclosure of financial incentives; a trial of providing choice of physician based on concordance between patient and physician beliefs about care; a trial of group visits for new inductees into a Health Maintenance Organisation; a trial of training oncologists in communication skills; and a trial of group visits for diabetic patients. However, trust was not affected in a subsequent larger trial of group visits for uninsured people with diabetes, nor with a decision aid for helping choose statins, another trial of disclosure of financial incentives or specifically training doctors to increase trust or cultural competence. There was no evidence of harm from any of the studies. Overall, there remains insufficient evidence to conclude that any intervention may increase or decrease trust in doctors. This may be due in part to the sensitivity of trust instruments, and a ceiling effect, as trust in doctors is generally high. It may be that current measures of trust are insufficiently sensitive. Further trials are required to explore the impact of doctors' specific training or the use of a patient-centred or decision-sharing approach on patients' trust, especially in the areas of healthcare provider choice, and induction into healthcare organisation. International trials would be of particular benefit. The review was constrained by the lack of consistency between trust measurements, timeframes and populations.

Examining Variation in the Impact of School-Wide Positive Behavioral Interventions and Supports: Findings from a Randomized Controlled Effectiveness Trial

ERIC Educational Resources Information Center

Bradshaw, Catherine P.; Waasdorp, Tracy E.; Leaf, Philip J.

2015-01-01

School-Wide Positive Behavioral Interventions and Supports (SWPBIS; Sugai & Horner, 2006) is currently implemented in over 20,000 schools across the country with the goal of preventing disruptive behavior problems and enhancing the school climate. While previous studies have indicated significant main effects of SWPBIS on student outcomes, the…

Does Patient Time Spent Viewing Computer-Tailored Colorectal Cancer Screening Materials Predict Patient-Reported Discussion of Screening with Providers?

ERIC Educational Resources Information Center

Sanders, Mechelle; Fiscella, Kevin; Veazie, Peter; Dolan, James G.; Jerant, Anthony

2016-01-01

The main aim is to examine whether patients' viewing time on information about colorectal cancer (CRC) screening before a primary care physician (PCP) visit is associated with discussion of screening options during the visit. We analyzed data from a multi-center randomized controlled trial of a tailored interactive multimedia computer program…

Intravenous tranexamic acid for hyperacute primary intracerebral hemorrhage: Protocol for a randomized, placebo-controlled trial.

PubMed

Sprigg, Nikola; Robson, Katie; Bath, Philip; Dineen, Robert; Roberts, Ian; Robinson, Tom; Roffe, Christine; Werring, David; Al-Shahi Salman, Rustam; Pocock, Stuart; Duley, Lelia; England, Tim; Whynes, David; Ciccone, Alfonso; Laska, Ann Charlotte; Christensen, Hanne; Ozturk, Serefnur; Collins, Ronan; Bereczki, Daniel; Egea-Guerrero, Juan Jose; Law, Zhe Kang; Czlonkowska, Anna; Seiffge, David; Beredzie, Maia

2016-08-01

Outcome after intracerebral hemorrhage remains poor. Tranexamic acid is easy to administer, readily available, inexpensive, and effective in other hemorrhagic conditions. This randomized trial aims to test the hypothesis that intravenous tranexamic acid given within 8 h of spontaneous intracerebral hemorrhage reduces death or dependency. Phase III prospective double-blind randomized placebo-controlled trial. Participants within 8 h of spontaneous intracerebral hemorrhage are randomized to receive either intravenous tranexamic acid 1 g 10 min bolus followed by 1 g 8 h infusion, or placebo. A trial of 2000 participants (300 from start-up phase and 1700 from main phase) will have 90% power to detect an ordinal shift of the modified Rankin Scale with odds ratio 0.79. The primary outcome is death or dependency measured by ordinal shift analysis of the 7 level mRS at day 90. Secondary outcomes are neurological impairment at day 7 and disability, quality of life, cognition, and mood at day 90. Safety outcomes are death, serious adverse events, thromboembolic events, and seizures. Cost outcomes are length of stay in hospital, readmission, and institutionalization. This pragmatic trial is assessing efficacy of tranexamic acid after spontaneous intracerebral hemorrhage. Recruitment started in 2013; as of 15th January 2016 1355 participants have been enrolled, from 95 centers in seven countries. Recruitment is due to end in 2017. TICH-2 Trial is registered as ISRCTN93732214. © 2016 World Stroke Organization.

Methodological and ethical aspects of randomized controlled clinical trials in minors with malignant diseases.

PubMed

Rothenberger, Lillian G; Henschel, Andreas Dirk; Schrey, Dominik; Becker, Andreas; Boos, Joachim

2011-10-01

Due to the new European regulations for pediatric medications, future clinical trials will include an increasing number of minors. It is therefore important to reconsider and evaluate recent methodological and ethical aspects of clinical trials in minors. The following questions were investigated: How are randomized controlled clinical trials (RCTs) performed in practice? Do investigators take into consideration biomedical ethical principles, explicated for example by Beauchamp and Childress, when planning and conducting a trial? The study was conducted in a descriptive manner. A systematic, algorithm-guided search focusing on RCTs in minors with malignant diseases was carried out in PubMed. One-thousand-nine-hundred-sixty-two publications from 2001 to 2005 were randomized in sequence. The first 1,000 publications were screened according to a priori defined inclusion criteria. One hundred seventy-five publications met the criteria and were reviewed using the SIGN methodological checklist (2004), the CONSORT Statement (2001, section Methods, items 3-12) and indicators for ethical aspects. Seventeen publications were checked by two raters. Information on randomization and blinding was often equivocal. The publications were mainly rated positive for the criteria of the SIGN checklist, and mostly rated negative for the additional items of the CONSORT Statement. Regarding the ethical principles, only few contributions were found in the publications. Inter-rater reliability was good. In the publications analyzed, we found only limited information concerning methods and reflections on ethical principles of the trials. Improvements are thus necessary and possible. We suggest how such trials and their respective publications can be optimized for these aspects. Copyright © 2011 Wiley-Liss, Inc.

Multicentre randomized controlled trial comparing ferric(III)carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients.

PubMed

Borstlap, W A A; Buskens, C J; Tytgat, K M A J; Tuynman, J B; Consten, E C J; Tolboom, R C; Heuff, G; van Geloven, N; van Wagensveld, B A; C A Wientjes, C A; Gerhards, M F; de Castro, S M M; Jansen, J; van der Ven, A W H; van der Zaag, E; Omloo, J M; van Westreenen, H L; Winter, D C; Kennelly, R P; Dijkgraaf, M G W; Tanis, P J; Bemelman, W A

2015-06-28

At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer. In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland. This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity. ClincalTrials.gov: NCT02243735 .

Off-pump versus On-pump Coronary Artery Bypass Grafting in Frail Patients: Study Protocol for the FRAGILE Multicenter Randomized Controlled Trial.

PubMed

Mejía, Omar Asdrúbal Vilca; Sá, Michel Pompeu Barros Oliveira; Deininger, Maurilio Onofre; Dallan, Luís Roberto Palma; Segalote, Rodrigo Coelho; Oliveira, Marco Antonio Praça de; Atik, Fernando Antibas; Santos, Magaly Arrais Dos; Silva, Pedro Gabriel Melo de Barros E; Milani, Rodrigo Mussi; Hueb, Alexandre Ciappina; Monteiro, Rosangela; Lima, Ricardo Carvalho; Lisboa, Luiz Augusto Ferreira; Dallan, Luís Alberto Oliveira; Puskas, John; Jatene, Fabio Biscegli

2017-01-01

Advances in modern medicine have led to people living longer and healthier lives. Frailty is an emerging concept in medicine yet to be explored as a risk factor in cardiac surgery. When it comes to CABG surgery, randomized controlled clinical trials have primarily focused on low-risk (ROOBY, CORONARY), elevated-risk (GOPCABE) or high-risk patients (BBS), but not on frail patients. Therefore, we believe that off-pump CABG could be an important technique in patients with limited functional capacity to respond to surgical stress. In this study, the authors introduce the new national, multicenter, randomized, controlled trial "FRAGILE", to be developed in the main cardiac surgery centers of Brazil, to clarify the potential benefit of off-pump CABG in frail patients. FRAGILE is a two-arm, parallel-group, multicentre, individually randomized (1:1) controlled trial which will enroll 630 patients with blinded outcome assessment (at 30 days, 6 months, 1 year, 2 years and 3 years), which aims to compare adverse cardiac and cerebrovascular events after off-pump versus on-pump CABG in pre-frail and frail patients. Primary outcomes will be all-cause mortality, acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome/cardiogenic shock, stroke, and coronary reintervention. Secondary outcomes will be major adverse cardiac and cerebrovascular events, operative time, mechanical ventilation time, hyperdynamic shock, new onset of atrial fibrillation, renal replacement therapy, reoperation for bleeding, pneumonia, length of stay in intensive care unit, length of stay in hospital, number of units of blood transfused, graft patency, rate of complete revascularization, neurobehavioral outcomes after cardiac surgery, quality of life after cardiac surgery and costs. FRAGILE trial will determine whether off-pump CABG is superior to conventional on-pump CABG in the surgical treatment of pre-frail and frail patients. ClinicalTrials.gov, ID: NCT02338947. Registered on August 29th 2014; last updated on March 21st 2016.

Evaluation of Safety and Efficacy of Qinming8631 DR Implantable Cardiac Pacemaker in Chinese Patients: A Prospective, Multicenter, Randomized Controlled Trial of the First Domestically Developed Pacemaker of China.

PubMed

Xiang, Mei-Xiang; Wang, Dong-Qi; Xu, Jing; Zhang, Zheng; Hu, Jian-Xin; Wang, Dong-Mei; Gu, Xiang; Liu, He-Ping; Guo, Tao; Yang, Xiang-Jun; Ling, Feng; Lin, Jia-Feng; Cai, Shang-Lang; Zhu, Guo-Bin; Wang, Jian-An

2016-11-20

High cost of imported pacemakers is a main obstacle for Chinese patients suffering from bradyarrhythmia, and a domestically developed pacemaker will help lower the burden. This study aimed to evaluate the safety and efficacy of Qinming8631 DR (Qinming Medical, Baoji, China), the first domestically developed dual-chamber pacemaker of China, compared with a commercially available pacemaker Talos DR (Biotronik, Berlin, Germany) in Chinese patients. A prospective randomized trial was conducted at 14 centers in China. Participants were randomized into trial (Qinming8631 DR) and control (Talos DR) groups. Parameters of the pacing systems were collected immediately after device implantation and during follow-ups. The effective pacing rate at 6-month follow-up was recorded as the primary end point. Electrical properties, magnet response, single- and double-pole polarity conversion, rate response function, and adverse events of the pacing system were analyzed. The Cochran-Mantel-Haenszel Chi-square test, paired t-test, and Wilcoxon signed-rank test were used for measuring primary qualitative outcomes and comparing normally and abnormally distributed measurement data. A total of 225 patients with a diagnosis of bradyarrhythmia and eligible for this study were randomly enrolled into the trial (n = 113) and control (n = 112) groups. They underwent successful pacemaker implantation with acceptable postoperative pacing threshold and sensitivity. Effective pacing rates of trial and control groups were comparable both in the full analysis set and the per protocol set (81.4% vs. 79.5%, P = 0.712 and 95.4% vs. 89.5%, P = 0.143, respectively). In both data sets, noninferiority of the trial group was above the predefined noninferiority limit(-9.5%). This study established the noninferiority of Qinming8631 DR to Talos DR. The safety and efficacy of Qinming8631 DR pacemaker were comparable to those of Talos DR in treating patients with cardiac bradyarrhythmia.

Barriers towards the publication of academic drug trials. Follow-up of trials approved by the Danish Medicines Agency.

PubMed

Berendt, Louise; Petersen, Lene Grejs; Bach, Karin Friis; Poulsen, Henrik Enghusen; Dalhoff, Kim

2017-01-01

To characterize and quantify barriers towards the publication of academic drug trials. We identified academic drug trials approved during a 3-year period (2004-2007) by the Danish Medicines Agency. We conducted a survey among the trial sponsors to describe the rates of initiation, completion, and publication, and the reasons for the failure to reach each of these milestones. Information on size and methodological characteristics of the trials was extracted from the EudraCT database, a prospective register of all approved clinical drug trials submitted to European medicines agencies since 2004. A total of 181 academic drug trials were eligible for inclusion, 139 of which participated in our survey (response rate: 77%). Follow-up time ranged from 5.1 to 7.9 years. Most trials were randomized controlled trials (73%, 95% CI 65-81%). Initiation and completion rates were 92% (95% CI: 88-97%) and 93% (95% CI: 89-97%) respectively. The publication rate of completed trials was 73% (95% CI: 62-79%). RCTs were published faster than non-RCTs (quartile time to publication 2.9 vs. 3.1 years, p = 0.0412). Many academic drug trials are left unpublished. Main barriers towards publication were related to the process from completion to publication. Hence, there is much to gain by facilitating the process from analysis to publication. Research institutions and funders should actively influence this process, e.g. by requiring the publication of trial results within a given time after completion.

Hypnosis for pain management during labour and childbirth.

PubMed

Madden, Kelly; Middleton, Philippa; Cyna, Allan M; Matthewson, Mandy; Jones, Leanne

2016-05-19

This review is one in a series of Cochrane reviews investigating pain management for childbirth. These reviews all contribute to an overview of systematic reviews of pain management for women in labour, and share a generic protocol. This review updates an earlier version of the review of the same title. To examine the effectiveness and safety of hypnosis for pain management during labour and childbirth. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2015) and the reference lists of primary studies and review articles. Randomised controlled trials (RCTs) and quasi-RCTS comparing preparation for labour using hypnosis and/or use of hypnosis during labour, with or without concurrent use of pharmacological or non-pharmacological pain relief methods versus placebo, no treatment or any analgesic drug or technique. Two review authors independently extracted data and assessed trial quality. Where possible we contacted study authors seeking additional information about data and methodology. We included nine trials randomising a total of 2954 women. The risk of bias in trials was variable, there were several well-designed large trials and some trials where little was reported about trial design. Although eight of the nine trials assessed antenatal hypnotherapy, there were considerable differences between these trials in timing and technique. One trial provided hypnotherapy during labour. In this updated review we compared hypnosis interventions with all control groups (main comparison) and also with specific control conditions: standard care (nine RCTs), supportive counselling (two RCTs) and relaxation training (two RCTs).In the main comparison, women in the hypnosis group were less likely to use pharmacological pain relief or analgesia than those in the control groups, (average risk ratio (RR) 0.73, 95% CI 0.57 to 0.94, eight studies, 2916 women; very low-quality evidence; random-effects model). There were no clear differences between women in the hypnosis group and those in the control groups for most of the other primary outcomes. There were no clear differences for sense of coping with labour (MD 0.22, 95% CI -0.14 to 0.58, one study, 420 women; low-quality evidence) or spontaneous vaginal birth (average RR 1.12, 95% CI 0.96 to 1.32, six studies, 2361 women; low-quality evidence; random-effects model). There were no clear differences for satisfaction with pain relief (measured on a seven-point scale two weeks postnatally) for women in the hypnosis group who also received pethidine (MD 0.41, 95% CI -0.45 to 1.27; one study, 72 women), Entonox (MD 0.19, 95% CI -0.19 to 0.57; one study, 357 women), self-hypnosis (MD 0.28, 95% CI -0.32 to 0.88; one study, 160 women), or epidural (MD -0.03, 95% CI -0.40 to 0.34; one study, 127 women), but a slight benefit in favour of hypnosis was seen for women who received water immersion (MD 0.52, 95% CI 0.04 to 1.00; one study, 174 women (all low-quality evidence). There were no clear differences for satisfaction with pain relief when it was measured as the number of women who reported they had adequate pain relief (risk ratio (RR) 1.06, 95% confidence interval (CI) 0.94 to 1.20, one study, 264 women; low-quality evidence). It should be noted that for pharmacological pain relief and spontaneous vaginal birth, there was evidence of considerable statistical heterogeneity, which could not be fully explained by subgroup analysis.For this review's secondary outcomes, no clear differences were found between women in the hypnosis group and women in the control groups for most outcomes where data were available. There was mixed evidence regarding benefits for women in the hypnosis group compared with all control groups for pain intensity, satisfaction with childbirth experience and postnatal depression. For each of these outcomes, data from more than one trial were available for analysis but could not be combined due to differences in measurement methods. There was evidence that fewer women in the hypnosis group stayed in hospital for more than two days after the birth but this finding was based on one small study (RR 0.11, 95% CI 0.02 to 0.83). No clear differences between women in the hypnosis group and the control groups were found for the other secondary outcomes where data were available.In the comparisons of hypnosis with specific types of control conditions: standard care, supportive counselling and relaxation training, there were no clear differences found between women in the hypnosis group and those in the standard care control groups or the relaxation control groups for the primary outcomes. Compared with the women in the supportive counselling control group, women in the hypnosis group were less likely to use pharmacological analgesia (average RR 0.48, 95% CI 0.32 to 0.73, two studies, 562 women). They were also more likely to have a spontaneous vaginal birth (RR 2.42, 95% CI 1.43 to 4.07), although this finding was based on the results of one small study. Overall these new comparisons displayed much less statistical heterogeneity than the comparison including all control groups. There are still only a relatively small number of studies assessing the use of hypnosis for labour and childbirth. Hypnosis may reduce the overall use of analgesia during labour, but not epidural use. No clear differences were found between women in the hypnosis group and those in the control groups for satisfaction with pain relief, sense of coping with labour or spontaneous vaginal birth. Not enough evidence currently exists regarding satisfaction with pain relief or sense of coping with labour and we would encourage any future research to prioritise the measurement of these outcomes. The evidence for the main comparison was assessed using GRADE as being of low quality for all the primary outcomes with downgrading decisions due to concerns regarding inconsistency of the evidence, limitations in design and imprecision. Further research is needed in the form of large, well-designed randomised controlled trials to assess whether hypnosis is of value for pain management during labour and childbirth.

Permissive hypotension in bleeding trauma patients: helpful or not and when?

PubMed

Gourgiotis, Stavros; Gemenetzis, George; Kocher, Hemant M; Aloizos, Stavros; Salemis, Nikolaos S; Grammenos, Stylianos

2013-12-01

Severity of hemorrhage and rate of bleeding are fundamental factors in the outcomes of trauma. Intravenous administration of fluid is the basic treatment to maintain blood pressure until bleeding is controlled. The main guideline, used almost worldwide, Advanced Trauma Life Support, established by the American College of Surgeons in 1976, calls for aggressive administration of intravenous fluids, primarily crystalloid solutions. Several other guidelines, such as Prehospital Trauma Life Support, Trauma Evaluation and Management, and Advanced Trauma Operative Management, are applied according to a patient's current condition. However, the ideal strategy remains unclear. With permissive hypotension, also known as hypotensive resuscitation, fluid administration is less aggressive. The available models of permissive hypotension are based on hypotheses in hypovolemic physiology and restricted clinical trials in animals. Before these models can be used in patients, randomized, controlled clinical trials are necessary.

Poor reporting of scientific leadership information in clinical trial registers.

PubMed

Sekeres, Melanie; Gold, Jennifer L; Chan, An-Wen; Lexchin, Joel; Moher, David; Van Laethem, Marleen L P; Maskalyk, James; Ferris, Lorraine; Taback, Nathan; Rochon, Paula A

2008-02-20

In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The objective is to examine the proportion of registered clinical trials providing valid scientific leadership information. We reviewed clinical trial entries listing Canadian investigators in the two largest international and public trial registers, the International Standard Randomized Controlled Trial Number (ISRCTN) register, and ClinicalTrials.gov. The main outcome measures were the proportion of clinical trials reporting valid contact information for the trials' Principal Investigator (PI)/Co-ordinating Investigator/Study Chair/Site PI, and trial e-mail contact address, stratified by funding source, recruiting status, and register. A total of 1388 entries (142 from ISRCTN and 1246 from ClinicalTrials.gov) comprised our sample. We found non-compliance with mandatory registration requirements regarding scientific leadership and trial contact information. Non-industry and partial industry funded trials were significantly more likely to identify the individual responsible for scientific leadership (OR = 259, 95% CI: 95-701) and to provide a contact e-mail address (OR = 9.6, 95% CI: 6.6-14) than were solely industry funded trials. Despite the requirements set by WHO and ICMJE, data on scientific leadership and contact e-mail addresses are frequently omitted from clinical trials registered in the two leading public clinical trial registers. To promote accountability and transparency in clinical trials research, public clinical trials registers should ensure adequate monitoring of trial registration to ensure completion of mandatory contact information fields identifying scientific leadership.

Dacron® vs. PTFE as bypass materials in peripheral vascular surgery – systematic review and meta-analysis

PubMed Central

Roll, Stephanie; Müller-Nordhorn, Jacqueline; Keil, Thomas; Scholz, Hans; Eidt, Daniela; Greiner, Wolfgang; Willich, Stefan N

2008-01-01

Background In peripheral vascular bypass surgery different synthetic materials are available for bypass grafting. It is unclear which of the two commonly used materials, polytetrafluoroethylene (PTFE) or polyester (Dacron®) grafts, is to be preferred. Thus, the aim of this meta-analysis and systematic review was to compare the effectiveness of these two prosthetic bypass materials (Dacron® and PTFE). Methods We performed a systematic literature search in MEDLINE, Cochrane-Library – CENTRAL, EMBASE and other databases for relevant publications in English and German published between 1999 and 2008. Only randomized controlled trials were considered for inclusion. We assessed the methodological quality by means of standardized checklists. Primary patency was used as the main endpoint. Random-effect meta-analysis as well as pooling data in life table format was performed to combine study results. Results Nine randomized controlled trials (RCT) were included. Two trials showed statistically significant differences in primary patency, one favouring Dacron® and one favouring PTFE grafts, while 7 trials did not show statistically significant differences between the two materials. Meta-analysis on the comparison of PTFE vs. Dacron® grafts yielded no differences with regard to primary patency rates (hazard ratio 1.04 (95% confidence interval [0.85;1.28]), no significant heterogeneity (p = 0.32, I2 = 14%)). Similarly, there were no significant differences with regard to secondary patency rates. Conclusion Systematic evaluation and meta-analysis of randomized controlled trials comparing Dacron® and PTFE as bypass materials for peripheral vascular surgery showed no evidence of an advantage of one synthetic material over the other. PMID:19099583

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

Does a functional activity programme improve function, quality of life, and falls for residents in long term care? Cluster randomised controlled trial

PubMed Central

Peri, Kathy; Robinson, Elizabeth; Wilkinson, Tim; von Randow, Martin; Kiata, Liz; Parsons, John; Latham, Nancy; Parsons, Matthew; Willingale, Jane; Brown, Paul; Arroll, Bruce

2008-01-01

Objective To assess the effectiveness of an activity programme in improving function, quality of life, and falls in older people in residential care. Design Cluster randomised controlled trial with one year follow-up. Setting 41 low level dependency residential care homes in New Zealand. Participants 682 people aged 65 years or over. Interventions 330 residents were offered a goal setting and individualised activities of daily living activity programme by a gerontology nurse, reinforced by usual healthcare assistants; 352 residents received social visits. Main outcome measures Function (late life function and disability instruments, elderly mobility scale, FICSIT-4 balance test, timed up and go test), quality of life (life satisfaction index, EuroQol), and falls (time to fall over 12 months). Secondary outcomes were depressive symptoms and hospital admissions. Results 473 (70%) participants completed the trial. The programme had no impact overall. However, in contrast to residents with impaired cognition (no differences between intervention and control group), those with normal cognition in the intervention group may have maintained overall function (late life function and disability instrument total function, P=0.024) and lower limb function (late life function and disability instrument basic lower extremity, P=0.015). In residents with cognitive impairment, the likelihood of depression increased in the intervention group. No other outcomes differed between groups. Conclusion A programme of functional rehabilitation had minimal impact for elderly people in residential care with normal cognition but was not beneficial for those with poor cognition. Trial registration Australian Clinical Trials Register ACTRN12605000667617. PMID:18845605

A low cost virtual reality system for home based rehabilitation of the arm following stroke: a randomised controlled feasibility trial

PubMed Central

Standen, PJ; Threapleton, K; Richardson, A; Connell, L; Brown, DJ; Battersby, S; Platts, F; Burton, A

2016-01-01

Objective: To assess the feasibility of conducting a randomised controlled trial of a home-based virtual reality system for rehabilitation of the arm following stroke. Design: Two group feasibility randomised controlled trial of intervention versus usual care. Setting: Patients’ homes. Participants: Patients aged 18 or over, with residual arm dysfunction following stroke and no longer receiving any other intensive rehabilitation. Interventions: Eight weeks’ use of a low cost home-based virtual reality system employing infra-red capture to translate the position of the hand into game play or usual care. Main measures: The primary objective was to collect information on the feasibility of a trial, including recruitment, collection of outcome measures and staff support required. Patients were assessed at three time points using the Wolf Motor Function Test, Nine-Hole Peg Test, Motor Activity Log and Nottingham Extended Activities of Daily Living. Results: Over 15 months only 47 people were referred to the team. Twenty seven were randomised and 18 (67%) of those completed final outcome measures. Sample size calculation based on data from the Wolf Motor Function Test indicated a requirement for 38 per group. There was a significantly greater change from baseline in the intervention group on midpoint Wolf Grip strength and two subscales of the final Motor Activity Log. Training in the use of the equipment took a median of 230 minutes per patient. Conclusions: To achieve the required sample size, a definitive home-based trial would require additional strategies to boost recruitment rates and adequate resources for patient support. PMID:27029939

Timing luteal support in ART: a systematic review F & S 19112 revision non-highlighted

PubMed Central

Connell, Matthew T.; Szatkowski, Jennifer M.; Terry, Nancy; DeCherney, Alan H.; Propst, Anthony M.; Hill, Micah J.

2015-01-01

Objective To summarize the available published randomized controlled trial data regarding timing of progesterone supplementation during the luteal phase of patients undergoing ART. Design A systematic review. Setting Not applicable. Patient(s) Undergoing in vitro fertilization. Intervention(s) Different starting times of progesterone for luteal support. Main Outcome Measure(s) Clinical pregnancy and live birth. Results Five randomized controlled trials were identified that met inclusion criteria with a total of 872 patients. A planned meta-analysis was not performed due to a high degree of clinical heterogeneity in regards to the timing, dose, and route of progesterone. Two studies compared progesterone initiated before oocyte retrieval versus the day of oocyte retrieval and pregnancy rates were 5–12% higher when starting progesterone on the day of oocyte retrieval. One study compared starting progesterone on post retrieval day 6 versus day 3, reporting a 16% decrease in pregnancy in the day 6 group. Trials comparing progesterone start times on the day of oocyte retrieval versus two or three days post retrieval showed no significant differences in pregnancy. Conclusions There appears to be a window for progesterone start time between the evening of oocyte retrieval and day 3 after oocyte retrieval. While some studies have suggested a potential benefit in delaying vaginal progesterone start time to 2 days after oocyte retrieval, this review could not find randomized controlled trials to adequately assess this. Further randomized clinical trials are needed to better define progesterone start time for luteal support after ART. PMID:25638420

Findings of the Chronic Obstructive Pulmonary Disease-Sitting and Exacerbations Trial (COPD-SEAT) in Reducing Sedentary Time Using Wearable and Mobile Technologies With Educational Support: Randomized Controlled Feasibility Trial.

PubMed

Orme, Mark W; Weedon, Amie E; Saukko, Paula M; Esliger, Dale W; Morgan, Mike D; Steiner, Michael C; Downey, John W; Sherar, Lauren B; Singh, Sally J

2018-04-11

Targeting sedentary time post exacerbation may be more relevant than targeting structured exercise for individuals with chronic obstructive pulmonary disease. Focusing interventions on sitting less and moving more after an exacerbation may act as a stepping stone to increase uptake to pulmonary rehabilitation. The aim of this paper was to conduct a randomized trial examining trial feasibility and the acceptability of an education and self-monitoring intervention using wearable technology to reduce sedentary behavior for individuals with chronic obstructive pulmonary disease admitted to hospital for an acute exacerbation. Participants were recruited and randomized in hospital into 3 groups, with the intervention lasting 2 weeks post discharge. The Education group received verbal and written information about reducing their time in sedentary behavior, sitting face-to-face with a study researcher. The Education+Feedback group received the same education component along with real-time feedback on their sitting time, stand-ups, and steps at home through a waist-worn inclinometer linked to an app. Patients were shown how to use the technology by the same study researcher. The inclinometer also provided vibration prompts to encourage movement at patient-defined intervals of time. Patients and health care professionals involved in chronic obstructive pulmonary disease exacerbation care were interviewed to investigate trial feasibility and acceptability of trial design and methods. Main quantitative outcomes of trial feasibility were eligibility, uptake, and retention, and for acceptability, were behavioral responses to the vibration prompts. In total, 111 patients were approached with 33 patients recruited (11 Control, 10 Education, and 12 Education+Feedback). Retention at 2-week follow-up was 52% (17/33; n=6 for Control, n=3 for Education, and n=8 for Education+Feedback). No study-related adverse events occurred. Collectively, patients responded to 106 out of 325 vibration prompts from the waist-worn inclinometer (32.62%). Within 5 min of the prompt, 41% of responses occurred, with patients standing for a mean 1.4 (SD 0.8) min and walking for 0.4 (SD 0.3) min (21, SD 11, steps). Interviews indicated that being unwell and overwhelmed after an exacerbation was the main reason for not engaging with the intervention. Health care staff considered reducing sedentary behavior potentially attractive for patients but suggested starting the intervention as an inpatient. Although the data support that it was feasible to conduct the trial, modifications are needed to improve participant retention. The intervention was acceptable to most patients and health care professionals. International Standard Randomized Controlled Trial Number (ISRCTN) 13790881; http://www.isrctn.com/ISRCTN13790881 (Archived by WebCite at http://www.webcitation.org/6xmnRGjFf). ©Mark W Orme, Amie E Weedon, Paula M Saukko, Dale W Esliger, Mike D Morgan, Michael C Steiner, John W Downey, Lauren B Sherar, Sally J Singh. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 11.04.2018.

Reporting of statistically significant results at ClinicalTrials.gov for completed superiority randomized controlled trials.

PubMed

Dechartres, Agnes; Bond, Elizabeth G; Scheer, Jordan; Riveros, Carolina; Atal, Ignacio; Ravaud, Philippe

2016-11-30

Publication bias and other reporting bias have been well documented for journal articles, but no study has evaluated the nature of results posted at ClinicalTrials.gov. We aimed to assess how many randomized controlled trials (RCTs) with results posted at ClinicalTrials.gov report statistically significant results and whether the proportion of trials with significant results differs when no treatment effect estimate or p-value is posted. We searched ClinicalTrials.gov in June 2015 for all studies with results posted. We included completed RCTs with a superiority hypothesis and considered results for the first primary outcome with results posted. For each trial, we assessed whether a treatment effect estimate and/or p-value was reported at ClinicalTrials.gov and if yes, whether results were statistically significant. If no treatment effect estimate or p-value was reported, we calculated the treatment effect and corresponding p-value using results per arm posted at ClinicalTrials.gov when sufficient data were reported. From the 17,536 studies with results posted at ClinicalTrials.gov, we identified 2823 completed phase 3 or 4 randomized trials with a superiority hypothesis. Of these, 1400 (50%) reported a treatment effect estimate and/or p-value. Results were statistically significant for 844 trials (60%), with a median p-value of 0.01 (Q1-Q3: 0.001-0.26). For the 1423 trials with no treatment effect estimate or p-value posted, we could calculate the treatment effect and corresponding p-value using results reported per arm for 929 (65%). For 494 trials (35%), p-values could not be calculated mainly because of insufficient reporting, censored data, or repeated measurements over time. For the 929 trials we could calculate p-values, we found statistically significant results for 342 (37%), with a median p-value of 0.19 (Q1-Q3: 0.005-0.59). Half of the trials with results posted at ClinicalTrials.gov reported a treatment effect estimate and/or p-value, with significant results for 60% of these. p-values could be calculated from results reported per arm at ClinicalTrials.gov for only 65% of the other trials. The proportion of significant results was much lower for these trials, which suggests a selective posting of treatment effect estimates and/or p-values when results are statistically significant.

Combined N-of-1 trials to investigate mexiletine in non-dystrophic myotonia using a Bayesian approach; study rationale and protocol.

PubMed

Stunnenberg, Bas C; Woertman, Willem; Raaphorst, Joost; Statland, Jeffrey M; Griggs, Robert C; Timmermans, Janneke; Saris, Christiaan G; Schouwenberg, Bas J; Groenewoud, Hans M; Stegeman, Dick F; van Engelen, Baziel G M; Drost, Gea; van der Wilt, Gert Jan

2015-03-25

To obtain evidence for the clinical and cost-effectiveness of treatments for patients with rare diseases is a challenge. Non-dystrophic myotonia (NDM) is a group of inherited, rare muscle diseases characterized by muscle stiffness. The reimbursement of mexiletine, the expert opinion drug for NDM, has been discontinued in some countries due to a lack of independent randomized controlled trials (RCTs). It remains unclear however, which concessions can be accepted towards the level 1 evidence needed for coverage decisions, in rare diseases. Considering the large number of rare diseases with a lack of treatment evidence, more experience with innovative trial designs is needed. Both NDM and mexiletine are well suited for an N-of-1 trial design. A Bayesian approach allows for the combination of N-of-1 trials, which enables the assessment of outcomes on the patient and group level simultaneously. We will combine 30 individual, double-blind, randomized, placebo-controlled N-of-1 trials of mexiletine (600 mg daily) vs. placebo in genetically confirmed NDM patients using hierarchical Bayesian modeling. Our results will be compared and combined with the main results of an international cross-over RCT (mexiletine vs. placebo in NDM) published in 2012 that will be used as an informative prior. Similar criteria of eligibility, treatment regimen, end-points and measurement instruments are employed as used in the international cross-over RCT. The treatment of patients with NDM with mexiletine offers a unique opportunity to compare outcomes and efficiency of novel N-of-1 trial-based designs and conventional approaches in producing evidence of clinical and cost-effectiveness of treatments for patients with rare diseases. ClinicalTrials.gov Identifier: NCT02045667.

Effect of cocoa on blood pressure.

PubMed

Ried, Karin; Fakler, Peter; Stocks, Nigel P

2017-04-25

High blood pressure is an important risk factor for cardiovascular disease, contributing to about 50% of cardiovascular events worldwide and 37% of cardiovascular-related deaths in Western populations. Epidemiological studies suggest that cocoa-rich products reduce the risk of cardiovascular disease. Flavanols found in cocoa have been shown to increase the formation of endothelial nitric oxide which promotes vasodilation and therefore blood pressure reduction. Here we update previous meta-analyses on the effect of cocoa on blood pressure. To assess the effects on blood pressure of chocolate or cocoa products versus low-flavanol products or placebo in adults with or without hypertension when consumed for two weeks or longer. This is an updated version of the review initially published in 2012. In this updated version, we searched the following electronic databases from inception to November 2016: Cochrane Hypertension Group Specialised Register, CENTRAL, MEDLINE and Embase. We also searched international trial registries, and the reference lists of review articles and included trials. Randomised controlled trials (RCTs) investigating the effects of chocolate or cocoa products on systolic and diastolic blood pressure in adults for a minimum of two weeks duration. Two review authors independently extracted data and assessed the risks of bias in each trial. We conducted random-effects meta-analyses on the included studies using Review Manager 5. We explored heterogeneity with subgroup analyses by baseline blood pressure, flavanol content of control group, blinding, age and duration. Sensitivity analyses explored the influence of unusual study design. Thirty-five trials (including 40 treatment comparisons) met the inclusion criteria. Of these, we added 17 trials (20 treatment comparisons) to the 18 trials (20 treatment comparisons) in the previous version of this updated review.Trials provided participants with 30 to 1218 mg of flavanols (mean = 670 mg) in 1.4 to 105 grams of cocoa products per day in the active intervention group. The control group received either a flavanol-free product (n = 26 treatment comparisons) or a low-flavanol-containing cocoa powder (range 6.4 to 88 mg flavanols (mean = 55 mg, 13 treatment comparisons; 259 mg, 1 trial).Meta-analyses of the 40 treatment comparisons involving 1804 mainly healthy participants revealed a small but statistically significant blood pressure-reducing effect of flavanol-rich cocoa products compared with control in trials of two to 18 weeks duration (mean nine weeks):Mean difference systolic blood pressure (SBP) (95% confidence interval (CI): -1.76 (-3.09 to -0.43) mmHg, P = 0.009, n = 40 treatment comparisons, 1804 participants;Mean difference diastolic blood pressure (DBP) (95% CI): -1.76 (-2.57 to -0.94) mmHg, P < 0.001, n = 39 treatment comparisons, 1772 participants.Baseline blood pressure may play a role in the effect of cocoa on blood pressure. While systolic blood pressure was reduced significantly by 4 mmHg in hypertensive people (n = 9 treatment comparisons, 401 participants), and tended to be lowered in prehypertensive people (n= 8 treatment comparisons, 340 participants), there was no significant difference in normotensive people (n = 23 treatment comparisons, 1063 participants); however, the test for subgroup differences was of borderline significance (P = 0.08; I 2 = 60%), requiring further research to confirm the findings.Subgroup meta-analysis by blinding suggested a trend towards greater blood pressure reduction in unblinded trials compared to double-blinded trials, albeit statistically not significant. Further research is needed to confirm whether participant expectation may influence blood pressure results. Subgroup analysis by type of control (flavanol-free versus low-flavanol control) did not reveal a significant difference.Whether the age of participants plays a role in the effect of cocoa on blood pressure, with younger participants responding with greater blood pressure reduction, needs to be further investigated.Sensitivity analysis excluding trials with authors employed by trials sponsoring industry (33 trials, 1482 participants) revealed a small reduction in effect size, indicating some reporting bias.Due to the remaining heterogeneity, which we could not explain in terms of blinding, flavanol content of the control groups, age of participants, or study duration, we downgraded the quality of the evidence from high to moderate.Results of subgroup analyses should be interpreted with caution and need to be confirmed or refuted in trials using direct randomised comparisons.Generally, cocoa products were highly tolerable, with adverse effects including gastrointestinal complaints and nausea being reported by 1% of participants in the active cocoa intervention group and 0.4% of participants in the control groups (moderate-quality evidence). This review provides moderate-quality evidence that flavanol-rich chocolate and cocoa products cause a small (2 mmHg) blood pressure-lowering effect in mainly healthy adults in the short term.These findings are limited by the heterogeneity between trials, which could not be explained by prespecified subgroup analyses, including blinding, flavanol content of the control groups, age of participants, or study duration. However, baseline blood pressure may play a role in the effect of cocoa on blood pressure; subgroup analysis of trials with (pre)hypertensive participants revealed a greater blood pressure-reducing effect of cocoa compared to normotensive participants with borderline significance.Long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events and to assess potential adverse effects associated with chronic ingestion of cocoa products.

Variations in reporting of outcomes in randomized trials on diet and physical activity in pregnancy: A systematic review.

PubMed

Rogozińska, Ewelina; Marlin, Nadine; Yang, Fen; Dodd, Jodie M; Guelfi, Kym; Teede, Helena; Surita, Fernanda; Jensen, Dorte M; Geiker, Nina R W; Astrup, Arne; Yeo, SeonAe; Kinnunen, Tarja I; Stafne, Signe N; Cecatti, Jose G; Bogaerts, Annick; Hauner, Hans; Mol, Ben W; Scudeller, Tânia T; Vinter, Christina A; Renault, Kristina M; Devlieger, Roland; Thangaratinam, Shakila; Khan, Khalid S

2017-07-01

Trials on diet and physical activity in pregnancy report on various outcomes. We aimed to assess the variations in outcomes reported and their quality in trials on lifestyle interventions in pregnancy. We searched major databases without language restrictions for randomized controlled trials on diet and physical activity-based interventions in pregnancy up to March 2015. Two independent reviewers undertook study selection and data extraction. We estimated the percentage of papers reporting 'critically important' and 'important' outcomes. We defined the quality of reporting as a proportion using a six-item questionnaire. Regression analysis was used to identify factors affecting this quality. Sixty-six randomized controlled trials were published in 78 papers (66 main, 12 secondary). Gestational diabetes (57.6%, 38/66), preterm birth (48.5%, 32/66) and cesarian section (60.6%, 40/66), were the commonly reported 'critically important' outcomes. Gestational weight gain (84.5%, 56/66) and birth weight (87.9%, 58/66) were reported in most papers, although not considered critically important. The median quality of reporting was 0.60 (interquartile range 0.25, 0.83) for a maximum score of one. Study and journal characteristics did not affect quality. Many studies on lifestyle interventions in pregnancy do not report critically important outcomes, highlighting the need for core outcome set development. © 2017 Japan Society of Obstetrics and Gynecology.

A systematic review of the effects of acupuncture on xerostomia and hyposalivation.

PubMed

Assy, Zainab; Brand, Henk S

2018-02-13

Saliva is fundamental to our oral health and our well-being. Many factors can impair saliva secretion, such as adverse effects of prescribed medication, auto-immune diseases (for example Sjögren's syndrome) and radiotherapy for head and neck cancers. Several studies have suggested a positive effect of acupuncture on oral dryness. Pubmed and Web of Science were electronically searched. Reference lists of the included studies and relevant reviews were manually searched. Studies that met the inclusion criteria were systematically evaluated. Two reviewers assessed each of the included studies to confirm eligibility and assessing the risk of bias. Ten randomized controlled trials investigating the effect of acupuncture were included. Five trials compared acupuncture to sham/placebo acupuncture. Four trials compared acupuncture to oral hygiene/usual care. Only one clinical trial used oral care sessions as control group. For all the included studies, the quality for all the main outcomes has been assessed as low. Although some publications suggest a positive effect of acupuncture on either salivary flow rate or subjective dry mouth feeling, the studies are inconclusive about the potential effects of acupuncture. Insufficient evidence is available to conclude whether acupuncture is an evidence-based treatment option for xerostomia/hyposalivation. Further well-designed, larger, double blinded trials are required to determine the potential benefit of acupuncture. Sample size calculations should be performed before before initiating these studies.

Prevention of generalized anxiety disorder using a web intervention, iChill: randomized controlled trial.

PubMed

Christensen, Helen; Batterham, Philip; Mackinnon, Andrew; Griffiths, Kathleen M; Kalia Hehir, Kanupriya; Kenardy, Justin; Gosling, John; Bennett, Kylie

2014-09-02

Generalized Anxiety Disorder (GAD) is a high prevalence, chronic disorder. Web-based interventions are acceptable, engaging, and can be delivered at scale. Few randomized controlled trials evaluate the effectiveness of prevention programs for anxiety, or the factors that improve effectiveness and engagement. The intent of the study was to evaluate the effectiveness of a Web-based program in preventing GAD symptoms in young adults, and to determine the role of telephone and email reminders. A 5-arm randomized controlled trial with 558 Internet users in the community, recruited via the Australian Electoral Roll, was conducted with 6- and 12-month follow-up. Five interventions were offered over a 10-week period. Group 1 (Active website) received a combined intervention of psycho-education, Internet-delivered Cognitive Behavioral Therapy (ICBT) for anxiety, physical activity promotion, and relaxation. Group 2 (Active website with telephone) received the identical Web program plus weekly telephone reminder calls. Group 3 (Active website with email) received the identical Web program plus weekly email reminders. Group 4 (Control) received a placebo website. Group 5 (Control with telephone) received the placebo website plus telephone calls. Main outcome measures were severity of anxiety symptoms as measured by the GAD 7-item scale (GAD-7) (at post-test, 6, and 12 months). Secondary measures were GAD caseness, measured by the Mini International Neuropsychiatric Interview (MINI) at 6 months, Centre for Epidemiologic Studies-Depression scale (CES-D), Anxiety Sensitivity Index (ASI), Penn State Worry Questionnaire (PSWQ), and Days out of Role. GAD-7 symptoms reduced over post-test, 6-month, and 12-month follow-up. There were no significant differences between Group 4 (Control) and Groups 1 (Active website), 2 (Active website with telephone), 3 (Active website with email), or 5 (Control with telephone) at any follow-up. A total of 16 cases of GAD were identified at 6 months, comprising 6.7% (11/165) from the Active groups (1, 2, 3) and 4.5% (5/110) from the Control groups (4, 5), a difference that was not significant. CES-D, ASI, and PSWQ scores were significantly lower for the active website with email reminders at post-test, relative to the control website condition. Indicated prevention of GAD was not effective in reducing anxiety levels, measured by GAD-7. There were significant secondary effects for anxiety sensitivity, worry, and depression. Challenges for indicated prevention trials are discussed. International Standard Randomized Controlled Trial Number (ISRCTN): 76298775; http://www.controlled-trials.com/ISRCTN76298775 (Archived by WebCite at http://www.webcitation.org/6S9aB5MAq).

The effect of family-based multidisciplinary cognitive behavioral treatment in children with obesity: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background The prevalence of childhood obesity has increased rapidly during the last three decades in the Netherlands. It is assumed that mainly environmental factors have contributed to this trend. Parental overweight and low social economic status are risk factors for childhood obesity. Childhood obesity affects self-esteem and has negative consequences on cognitive and social development. Obese children tend to become obese adults, which increases the risk for developing cardiovascular complications, type 2 diabetes mellitus, and psychosocial problems. Additionally, the secretion of several gastrointestinal hormones, responsible for appetite and food intake, is impaired in obese subjects. Weight reduction through lifestyle changes in order to change health risks is, until now, suggested as the preferred treatment for childhood obesity. The objective of this study is the effect evaluation of a family-based cognitive behavioral multidisciplinary lifestyle treatment. The intervention aims to establish long-term weight reduction and stabilization, reduction of obesity-related health consequences and improvement of self-image by change of lifestyle and learning cognitive behavioral techniques. Study design/Methods In this randomized clinical trial newly presented children with obesity (8-17 years old) are divided, by randomization, in an intervention and control group, both consisting of 40 obese children. The intervention is carried out in groups of 8-11 children, and consists of respectively 7 and 5 separate group meetings for the children and their parents and 1 joint group meeting of 2 ½ hours. Main topics are education on nutrition, self-control techniques, social skills, physical activity and improvement of self-esteem. The control group is given advice on physical activity and nutrition. For normal data comparison, data were collected of 40 normal-weight children, 8-17 years old. Discussion Because of the increasing prevalence of childhood obesity and the impact on the individual as well as on society, prevention and treatment of obesity in children is of great importance. For evaluation of short- and long-term effects of the treatment, measurements are taken before and after 3 months of treatment, and after 12 and 24 months follow-up. During these visits clinical and biochemical data are determined, cardiovascular fitness tests are performed and quality of life questionnaires are completed. Trial registration International Standard Randomised Controlled Trial Number Register ISRCTN36146436 PMID:21548919

Investigational opioid antagonists for treating opioid-induced bowel dysfunction.

PubMed

Mozaffari, Shilan; Nikfar, Shekoufeh; Abdollahi, Mohammad

2018-03-01

Opioids have been highlighted for their role in pain relief among cancer and non-cancer patients. Novel agents have been investigated to reduce opioid-induced constipation (OIC) as the main adverse effect that may lead to treatment discontinuation. Development of peripherally acting mu-opioid receptor antagonists (PAMORA) has resulted in a novel approach to preserve the efficacy of pain control along with less OIC. Areas covered: Clinical evidence for investigational PAMORAs was reviewed and clinical trials on investigational agents to reduce OIC were included. TD-1211 is currently being evaluated in Phase II clinical trial. Oxycodone-naltrexone and ADL-5945 went through Phase III clinical trials, but have been discontinued. Expert opinion: There is a substantial need to develop agents with specific pharmacokinetic properties to meet the needs of patients with underlying diseases. Holding the efficacy of a medicine with the highest selectivity on targeted receptors and the least adverse effects is the main approach in upcoming investigations to improve patients' quality of life (QoL). Novel agents to reduce opioid-induced bowel dysfunction (OIBD) that do not reverse peripherally mediated pain analgesia are of great interest. Direct comparison of available agents in this field is lacking in the literature.

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

PubMed

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

2011-11-23

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

Vaccines for preventing malaria (blood-stage).

PubMed

Graves, P; Gelband, H

2006-10-18

A malaria vaccine is needed because of the heavy burden of mortality and morbidity due to this disease. This review describes the results of trials of blood (asexual)-stage vaccines. Several are under development, but only one (MSP/RESA, also known as Combination B) has been tested in randomized controlled trials. To assess the effect of blood-stage malaria vaccines in preventing infection, disease, and death. In March 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and the Science Citation Index. We also searched conference proceedings and reference lists of articles, and contacted organizations and researchers in the field. Randomized controlled trials comparing blood-stage vaccines (other than SPf66) against P. falciparum, P. vivax, P. malariae, or P. ovale with placebo, control vaccine, or routine antimalarial control measures in people of any age receiving a challenge malaria infection. Both authors independently assessed trial quality and extracted data. Results for dichotomous data were expressed as relative risks (RR) with 95% confidence intervals (CI). Five trials of MSP/RESA vaccine with 217 participants were included; all five reported on safety, and two on efficacy. No severe or systemic adverse effects were reported at doses of 13 to 15 microg of each antigen (39 to 45 microg total). One small efficacy trial with 17 non-immune participants with blood-stage parasites showed no reduction or delay in parasite growth rates after artificial challenge. In the second efficacy trial in 120 children aged five to nine years in Papua New Guinea, episodes of clinical malaria were not reduced, but MSP/RESA significantly reduced parasite density only in children who had not been pretreated with an antimalarial drug (sulfadoxine-pyrimethamine). Infections with the 3D7 parasite subtype of MSP2 (the variant included in the vaccine) were reduced (RR 0.38, 95% CI 0.26 to 0.57; 719 participants) while those with the other main subtype, FC27, were not (720 participants). The MSP/RESA (Combination B) vaccine shows promise as a way to reduce the severity of malaria episodes, but the effect of the vaccine is MSP2 variant-specific. Pretreatment for malaria during a vaccine trial makes the results difficult to interpret, particularly with the relatively small sample sizes of early trials. The results show that blood-stage vaccines may play a role and merit further development.

Brief intervention to reduce risky drinking in pregnancy: study protocol for a randomized controlled trial.

PubMed

Wilson, Graeme B; McGovern, Ruth; Antony, Grace; Cassidy, Paul; Deverill, Mark; Graybill, Erin; Gilvarry, Eilish; Hodgson, Moira; Kaner, Eileen F S; Laing, Kirsty; McColl, Elaine; Newbury-Birch, Dorothy; Rankin, Judith

2012-09-24

Risky drinking in pregnancy by UK women is likely to result in many alcohol-exposed pregnancies. Studies from the USA suggest that brief intervention has promise for alcohol risk reduction in antenatal care. However, further research is needed to establish whether this evidence from the USA is applicable to the UK. This pilot study aims to investigate whether pregnant women can be recruited and retained in a randomized controlled trial of brief intervention aimed at reducing risky drinking in women receiving antenatal care. The trial will rehearse the parallel-group, non-blinded design and procedures of a subsequent definitive trial. Over 8 months, women aged 18 years and over (target number 2,742) attending their booking appointment with a community midwife (n = 31) in north-east England will be screened for alcohol consumption using the consumption questions of the Alcohol Use Disorders Identification Test (AUDIT-C). Those screening positive, without a history of substance use or alcohol dependence, with no pregnancy complication, and able to give informed consent, will be invited to participate in the trial (target number 120). Midwives will be randomized in a 1:1 ratio to deliver either treatment as usual (control) or structured brief advice and referral for a 20-minute motivational interviewing session with an alcohol health worker (intervention). As well as demographic and health information, baseline measures will include two 7-day time line follow-back questionnaires and the EuroQoL EQ-5D-3 L questionnaire. Measures will be repeated in telephone follow-ups in the third trimester and at 6 months post-partum, when a questionnaire on use of National Health Service and social care resources will also be completed. Information on pregnancy outcomes and stillbirths will be accessed from central health service records before the follow-ups. Primary outcomes will be rates of eligibility, recruitment, intervention delivery, and retention in the study population, to inform power calculations for a definitive trial. The health-economics component will establish how cost-effectiveness will be assessed, and examine which data on health service resource use should be collected in a main trial. Participants' views on instruments and procedures will be sought to confirm their acceptability. The study will produce a full trial protocol with robust sample-size calculations to extend evidence on effectiveness of screening and brief intervention. Current Controlled Trials ISRCTN43218782.

Effect of cocoa on blood pressure.

PubMed

Ried, Karin; Sullivan, Thomas R; Fakler, Peter; Frank, Oliver R; Stocks, Nigel P

2012-08-15

High blood pressure is an important risk factor for cardiovascular disease attributing to about 50% of cardiovascular events worldwide and 37% of cardiovascular related deaths in Western populations. Epidemiological studies suggest that cocoa rich products reduce the risk of cardiovascular disease. Flavanols found in cocoa have been shown to increase the formation of endothelial nitric oxide which promotes vasodilation and therefore blood pressure reduction. Previous meta-analyses have shown that cocoa-rich foods may reduce blood pressure. Recently additional trials had conflicting results. To determine the effect of flavanol-rich chocolate or cocoa products on blood pressure in people with or without hypertension. We searched the following electronic databases from inception to November 2011: Cochrane Hypertension Group Specialised Register, CENTRAL, MEDLINE and EMBASE. In addition we searched international trial registries, and the reference lists of review articles and included trials. Randomised controlled trials (RCT) investigating the effects of chocolate or cocoa products on systolic and diastolic blood pressure in adults for a minimum of two weeks duration. Two authors independently extracted data and assessed the risk of bias in each trial in consultation with a third author. Random effects meta-analyses on all studies fitting the inclusion criteria were conducted using Review Manager version 5.1 and Stata version 12. Heterogeneity was explored by subgroup analyses and univariate meta-regression analysis of several variables including dosage of flavanol content (total or monomers) in chocolate or cocoa products, blinding, baseline blood pressure, theobromine content, sugar content, body-mass-index (BMI), duration and age. Twenty studies met the inclusion criteria. Meta-analyses of the 20 studies involving 856 mainly healthy participants revealed a statistically significant blood pressure reducing effect of flavanol-rich cocoa products compared with control in short-term trials of 2-18 weeks duration: Mean difference SBP (95%CI): -2.77 (-4.72, -0.82) mm Hg, p=0.005, n=20; mean difference DBP (95%CI): - 2.20 (-3.46, -0.93) mm Hg, p=0.006, n=19 available for DBP.Trials provided participants with 30-1080 mg of flavanols (mean=545.5 mg) in 3.6-105 g of cocoa products per day in the active intervention group. In half of the trials (n=10) the active group consumed 500-750 mg of flavanols per day. The control group received either a flavanol-free product (n=12) or a low-flavanol containing cocoa powder (6.4 and 41 mg flavanols, n=8). Subgroup meta-analysis of trials with a flavanol-free control group revealed a significant blood pressure reducing effect, in contrast to trials using a low-flavanol product in the control group. This analysis may have been confounded by trial duration and the level of blinding of participants.Trial duration was short (mean 4.4 weeks, range 2-8 weeks, n=19, and one trial of 18 weeks). A significant blood pressure reducing effect was evident in trials of 2 weeks duration (n=9), but not in trials of >2 weeks duration (n=11). It is important to note that seven out of the nine trials (78%) of 2 weeks duration also had a flavanol-free control group. Therefore, subgroup analysis by duration might be confounded by flavanol dosage used in the control groups, and the level of blinding of participants.Adverse effects including gastrointestinal complaints and distaste of the trial product were reported by 5% of patients in the active cocoa intervention group and 1% of patients in the control groups. Flavanol-rich chocolate and cocoa products may have a small but statistically significant effect in lowering blood pressure by 2-3 mm Hg in the short term.Our findings are limited by the heterogeneity between trials, which was explored by univariate meta-regression and subgroup analyses. Subgroup meta-analysis of trials using a flavanol-free control group revealed a significant blood pressure reducing effect of cocoa, whereas analysis of trials using a low-flavanol control product did not. While it appears that shorter trials of 2 weeks duration were more effective, analysis may be confounded by type of control and unblinding of participants, as the majority of 2-week trials also used a flavanol-free control and unblinding of participants. Results of these and other subgroup analyses based on, for example, age of participants, should be interpreted with caution and need to be confirmed or refuted in trials using direct randomized comparison.Long-term trials investigating the effect of cocoa products are needed to determine whether or not blood pressure is reduced on a chronic basis by daily ingestion of cocoa. Furthermore, long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events and to assess potential adverse effects associated with chronic ingestion of cocoa products.

Motivation by potential gains and losses affects control processes via different mechanisms in the attentional network.

PubMed

Paschke, Lena M; Walter, Henrik; Steimke, Rosa; Ludwig, Vera U; Gaschler, Robert; Schubert, Torsten; Stelzel, Christine

2015-05-01

Attentional control in demanding cognitive tasks can be improved by manipulating the motivational state. Motivation to obtain gains and motivation to avoid losses both usually result in faster reaction times and stronger activation in relevant brain areas such as the prefrontal cortex, but little is known about differences in the underlying neurocognitive mechanisms of these types of motivation in an attentional control context. In the present functional magnetic resonance imaging (fMRI) study, we tested whether potential gain and loss as motivating incentives lead to overlapping or distinct neural effects in the attentional network, and whether one of these conditions is more effective than the other. A Flanker task with word stimuli as targets and distracters was performed by 115 healthy participants. Using a mixed blocked and event-related design allowed us to investigate transient and sustained motivation-related effects. Participants could either gain money (potential gain) or avoid losing money (potential loss) in different task blocks. Participants showed a congruency effect with increased reaction times for incongruent compared to congruent trials. Potential gain led to generally faster responses compared to the neutral condition and to stronger improvements than potential loss. Potential loss also led to shorter response times compared to the neutral condition, but participants improved mainly during incongruent and not during congruent trials. The event-related fMRI data revealed a main effect of congruency with increased activity in the left inferior frontal gyrus (IFG) and inferior frontal junction area (IFJ), the pre-supplementary motor area (pre-SMA), bilateral insula, intraparietal sulcus (IPS) and visual word form area (VWFA). While potential gain led to increased activity in a cluster of the IFJ and the VWFA only during incongruent trials, potential loss was linked to activity increases in these regions during incongruent and congruent trials. The block analysis revealed greater activity in gain and loss blocks compared to the neutral condition in most of these regions but no differences in the direct comparison of gain and loss blocks. These findings show that potential monetary gain and loss rely on different mechanisms: Gain was more effective in reducing the reaction time compared to potential loss. Brain data indicate that in the gain context attentional control is executed specifically in incongruent trials, whereas the loss context induces an unspecific increase of attentional control. These findings extend previous studies by providing evidence for diverging neural mechanisms for the effects of different types of motivation on attentional control, specifying the underlying activity patterns in task- and stimulus-related regions. Copyright © 2015 Elsevier Inc. All rights reserved.

Interventions for promoting smoking cessation during pregnancy

PubMed Central

Lumley, Judith; Chamberlain, Catherine; Dowswell, Therese; Oliver, Sandy; Oakley, Laura; Watson, Lyndsey

2014-01-01

Background Tobacco smoking in pregnancy remains one of the few preventable factors associated with complications in pregnancy, low birthweight, preterm birth and has serious long-term health implications for women and babies. Smoking in pregnancy is decreasing in high-income countries and increasing in low- to middle-income countries and is strongly associated with poverty, low educational attainment, poor social support and psychological illness. Objectives To assess the effects of smoking cessation interventions during pregnancy on smoking behaviour and perinatal health outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (June 2008), the Cochrane Tobacco Addiction Group’s Trials Register (June 2008), EMBASE, PsycLIT, and CINAHL (all from January 2003 to June 2008). We contacted trial authors to locate additional unpublished data. Selection criteria Randomised controlled trials where smoking cessation during pregnancy was a primary aim of the intervention. Data collection and analysis Trials were identified and data extracted by one person and checked by a second. Subgroup analysis was conducted to assess the effect of risk of trial bias, intensity of the intervention and main intervention strategy used. Main results Seventy-two trials are included. Fifty-six randomised controlled trials (over 20,000 pregnant women) and nine cluster-randomised trials (over 5000 pregnant women) provided data on smoking cessation outcomes. There was a significant reduction in smoking in late pregnancy following interventions (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.93 to 0.96), an absolute difference of six in 100 women who stopped smoking during pregnancy. However, there is significant heterogeneity in the combined data (I2 > 60%). In the trials with the lowest risk of bias, the interventions had less effect (RR 0.97, 95% CI 0.94 to 0.99), and lower heterogeneity (I2 = 36%). Eight trials of smoking relapse prevention (over 1000 women) showed no statistically significant reduction in relapse. Smoking cessation interventions reduced low birthweight (RR 0.83, 95% CI 0.73 to 0.95) and preterm birth (RR 0.86, 95% CI 0.74 to 0.98), and there was a 53.91g (95% CI 10.44 g to 95.38 g) increase in mean birthweight. There were no statistically significant differences in neonatal intensive care unit admissions, very low birthweight, stillbirths, perinatal or neonatal mortality but these analyses had very limited power. Authors’ conclusions Smoking cessation interventions in pregnancy reduce the proportion of women who continue to smoke in late pregnancy, and reduce low birthweight and preterm birth. Smoking cessation interventions in pregnancy need to be implemented in all maternity care settings. Given the difficulty many pregnant women addicted to tobacco have quitting during pregnancy, population-based measures to reduce smoking and social inequalities should be supported. PMID:19588322

Listening to Relaxing Music Improves Physiological Responses in Premature Infants: A Randomized Controlled Trial.

PubMed

Caparros-Gonzalez, Rafael A; de la Torre-Luque, Alejandro; Diaz-Piedra, Carolina; Vico, Francisco J; Buela-Casal, Gualberto

2018-02-01

Premature infants are exposed to high levels of noise in the neonatal intensive care unit (NICU). This study evaluated the effect of a relaxing music therapy intervention composed by artificial intelligence on respiratory rate, systolic and diastolic blood pressure, and heart rate. A double-blind, randomized, controlled trial was conducted in the NICUs of 2 general public hospitals in Andalusia, Spain. Participants were 17 healthy premature infants, randomly allocated to the intervention group or the control group (silence) at a 1:1 ratio. To be included in the study, the subjects were to be 32 to 36 weeks of gestation at birth (M= 32.33; SD = 1.79) and passed a hearing screening test satisfactorily. The intervention lasted 20 minutes, 3 times a day for 3 consecutive days, while infants were in the incubator. Infants' heart rate, respiratory rate, and blood pressure were assessed before and after each intervention session. After each session, the respiratory rate decreased in the experimental group (main between-groups effect (F1,13 = 6.73, P = .022, ηpartial = 0.34). Across the sessions, the heart rate increased in the control group (main between-groups effect, F1,11 = 5.09, P = .045, ηpartial = 0.32). Future studies can use this music intervention to assess its potential effects in premature infants. Nurses can apply the relaxing music intervention presented in this study to ameliorate the impact of the stressful environment on premature infants.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of rehabilitation interventions for osteoarthritis.

PubMed

Fitzgerald, G K; Hinman, R S; Zeni, J; Risberg, M A; Snyder-Mackler, L; Bennell, K L

2015-05-01

A Task Force of the Osteoarthritis Research Society International (OARSI) has previously published a set of guidelines for the conduct of clinical trials in osteoarthritis (OA) of the hip and knee. Limited material available on clinical trials of rehabilitation in people with OA has prompted OARSI to establish a separate Task Force to elaborate guidelines encompassing special issues relating to rehabilitation of OA. The Task Force identified three main categories of rehabilitation clinical trials. The categories included non-operative rehabilitation trials, post-operative rehabilitation trials, and trials examining the effectiveness of devices (e.g., assistive devices, bracing, physical agents, electrical stimulation, etc.) that are used in rehabilitation of people with OA. In addition, the Task Force identified two main categories of outcomes in rehabilitation clinical trials, which include outcomes related to symptoms and function, and outcomes related to disease modification. The guidelines for rehabilitation clinical trials provided in this report encompass these main categories. The report provides guidelines for conducting and reporting on randomized clinical trials. The topics include considerations for entering patients into trials, issues related to conducting trials, considerations for selecting outcome measures, and recommendations for statistical analyses and reporting of results. The focus of the report is on rehabilitation trials for hip, knee and hand OA, however, we believe the content is broad enough that it could be applied to rehabilitation trials for other regions as well. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Menstruation and the Cycle of Poverty: A Cluster Quasi-Randomised Control Trial of Sanitary Pad and Puberty Education Provision in Uganda.

PubMed

Montgomery, Paul; Hennegan, Julie; Dolan, Catherine; Wu, Maryalice; Steinfield, Laurel; Scott, Linda

2016-01-01

Poor menstrual knowledge and access to sanitary products have been proposed as barriers to menstrual health and school attendance. In response, interventions targeting these needs have seen increasing implementation in public and private sectors. However, there has been limited assessment of their effectiveness. Assess the impact of providing reusable sanitary pads and puberty education on girls' school attendance and psychosocial wellbeing outcomes. A cluster quasi-randomised controlled trial was conducted across 8 schools, including 1124 girls, in rural Uganda. Schools were allocated to one of four conditions: the provision of puberty education alone; reusable sanitary pads alone; puberty education and reusable sanitary pads; and a control (no intervention). The primary outcome was school attendance. Secondary outcomes reflected psychosocial wellbeing. At follow-up, school attendance had worsened for girls across all conditions. Per-protocol analysis revealed that this decline was significantly greater for those in the control condition d = 0.52 (95%CI 0.26-0.77), with those in control schools having a 17.1% (95%CI: 8.7-25.5) greater drop in attendance than those in any intervention school. There were no differences between the intervention conditions. High rates of school drop-out and transfer meant the trial suffered from substantial participant drop-out. Intention-to-treat analyses using two different imputation strategies were consistent with the main results, with mean differences of 5.2% attendance in best-case and 24.5% in worst-case imputations. Results were robust to adjustments for clustering. There was no impact of the interventions on girls' self-reported shame or insecurity during menstruation. Results of the trial support the hypothesised positive impact of providing sanitary pads or puberty education for girls' school attendance in a developing country context. Findings must be interpreted with caution in light of poor participant retention, intervention fidelity, and the attendance measures used. Pan African Clinical Trials Registry PACTR201503001044408.

Altered orientation of spatial attention in depersonalization disorder.

PubMed

Adler, Julia; Beutel, Manfred E; Knebel, Achim; Berti, Stefan; Unterrainer, Josef; Michal, Matthias

2014-05-15

Difficulties with concentration are frequent complaints of patients with depersonalization disorder (DPD). Standard neuropsychological tests suggested alterations of the attentional and perceptual systems. To investigate this, the well-validated Spatial Cueing paradigm was used with two different tasks, consisting either in the detection or in the discrimination of visual stimuli. At the start of each trial a cue indicated either the correct (valid) or the incorrect (invalid) position of the upcoming stimulus or was uninformative (neutral). Only under the condition of increased task difficulty (discrimination task) differences between DPD patients and controls were observed. DPD patients showed a smaller total attention directing effect (RT in valid vs. invalid trials) compared to healthy controls only in the discrimination condition. RT costs (i.e., prolonged RT in neutral vs. invalid trials) mainly accounted for this difference. These results indicate that DPD is associated with altered attentional mechanisms, especially with a stronger responsiveness to unexpected events. From an evolutionary perspective this may be advantageous in a dangerous environment, in daily life it may be experienced as high distractibility. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Epidemiology and control of east coast fever in Zambia. A field trial with traditionally managed Sanga cattle.

PubMed

Minjauw, B; Otte, M J; James, A D

1998-06-29

The main objective of the reported field trial was to compare different East Coast Fever (ECF) control strategies for their efficacy, effect on cattle productivity and cost-effectiveness. Five strategies were tested in groups of traditionally managed Sanga cattle over a period of 2.5 years. Two groups were under intensive tick control, one group immunized by the infection and treatment method and the other non-immunized. Two groups were under no tick control, one group immunized and the other non-immunized (the control group). The fifth group was under strategic tick control and was immunized against ECF. All ECF control methods tested significantly reduced mortality, but no marked differences to the control group were seen in other production parameters. No difference in mortality was observed between animals protected from ECF by immunization or by tick control. The most cost-effective method of controlling the disease was by immunization. A financial analysis showed that under the prevailing conditions the break-even price for immunization ranged from US$21.5 to US$25.7 depending of the proportion of reactors. The carrier state induced by immunization did not lead to a persistent high incidence of ECF in non-immunized animals using the same grazing area.

Effectiveness of health education intervention in improving knowledge, attitude, and practices regarding Tuberculosis among HIV patients in General Hospital Minna, Nigeria – A randomized control trial

PubMed Central

Bisallah, Chindo Ibrahim; Lye, Munn-Sann; Mohd Sidik, Sherina; Ibrahim, Normala; Iliyasu, Zubairu; Onyilo, Michael Ochigbo

2018-01-01

Introduction The risk of development of active TB in HIV-infected individuals is 20–37 times higher than those that are HIV negative. Poor knowledge of TB amongst people living with HIV has been associated with high transmission. Objectives To determine the effectiveness of a new health education intervention module in improving knowledge, attitude, and practice (KAP) regarding tuberculosis among HIV patients in General Hospital Minna, Nigeria. Methods A randomized control trial was carried out from July 2015 to June 2017. A random number generating program was used to allocate 226 respondents into 2 groups. The intervention group received health education regarding tuberculosis using the developed module. The control group received the normal services provided for HIV patients. Data were collected from December 2015 to September 2016 at baseline, immediate post intervention, three, six and nine months. The outcome measures were knowledge, attitude, and practice. Results There was no significant difference with respect to socio-demographic characteristics, KAP of the respondents in the intervention and control group at baseline. However, there was significant improvement in knowledge in the intervention group compared to the control group, group main effect (F = (1,218) = 665.889, p = 0.001, partial ἠ2 = 0.753, d = 5.4); time (F = (3.605, 218) = 52.046, p = 0.001, partial ἠ2 = 0.193, d = 1.52) and interaction between group with time (F = (3.605, 218) = 34.028, p = 0.001, partial ἠ2 = 0.135, d = 1.23). Likewise, there was significant improvement in attitude, group main effect (p = 0.001, d = 1.26) and time (p = 0.001, p, d = 0.65). Similarly, there was improvement in practice, group main effect, time, and interaction of group with time (p < 0.05). Conclusion The health education intervention program was effective in improving KAP regarding tuberculosis among HIV patients. PMID:29470530

Effectiveness of health education intervention in improving knowledge, attitude, and practices regarding Tuberculosis among HIV patients in General Hospital Minna, Nigeria - A randomized control trial.

PubMed

Bisallah, Chindo Ibrahim; Rampal, Lekhraj; Lye, Munn-Sann; Mohd Sidik, Sherina; Ibrahim, Normala; Iliyasu, Zubairu; Onyilo, Michael Ochigbo

2018-01-01

The risk of development of active TB in HIV-infected individuals is 20-37 times higher than those that are HIV negative. Poor knowledge of TB amongst people living with HIV has been associated with high transmission. To determine the effectiveness of a new health education intervention module in improving knowledge, attitude, and practice (KAP) regarding tuberculosis among HIV patients in General Hospital Minna, Nigeria. A randomized control trial was carried out from July 2015 to June 2017. A random number generating program was used to allocate 226 respondents into 2 groups. The intervention group received health education regarding tuberculosis using the developed module. The control group received the normal services provided for HIV patients. Data were collected from December 2015 to September 2016 at baseline, immediate post intervention, three, six and nine months. The outcome measures were knowledge, attitude, and practice. There was no significant difference with respect to socio-demographic characteristics, KAP of the respondents in the intervention and control group at baseline. However, there was significant improvement in knowledge in the intervention group compared to the control group, group main effect (F = (1,218) = 665.889, p = 0.001, partial ἠ2 = 0.753, d = 5.4); time (F = (3.605, 218) = 52.046, p = 0.001, partial ἠ2 = 0.193, d = 1.52) and interaction between group with time (F = (3.605, 218) = 34.028, p = 0.001, partial ἠ2 = 0.135, d = 1.23). Likewise, there was significant improvement in attitude, group main effect (p = 0.001, d = 1.26) and time (p = 0.001, p, d = 0.65). Similarly, there was improvement in practice, group main effect, time, and interaction of group with time (p < 0.05). The health education intervention program was effective in improving KAP regarding tuberculosis among HIV patients.

Cluster randomised controlled trial to examine medical mask use as source control for people with respiratory illness

PubMed Central

MacIntyre, Chandini Raina; Zhang, Yi; Chughtai, Abrar Ahmad; Seale, Holly; Zhang, Daitao; Chu, Yanhui; Zhang, Haiyan; Rahman, Bayzidur; Wang, Quanyi

2016-01-01

Rationale Medical masks are commonly used by sick individuals with influenza-like illness (ILI) to prevent spread of infections to others, but clinical efficacy data are absent. Objective Determine whether medical mask use by sick individuals with ILI protects well contacts from related respiratory infections. Setting 6 major hospitals in 2 districts of Beijing, China. Design Cluster randomised controlled trial. Participants 245 index cases with ILI. Intervention Index cases with ILI were randomly allocated to medical mask (n=123) and control arms (n=122). Since 43 index cases in the control arm also used a mask during the study period, an as-treated post hoc analysis was performed by comparing outcomes among household members of index cases who used a mask (mask group) with household members of index cases who did not use a mask (no-mask group). Main outcome measure Primary outcomes measured in household members were clinical respiratory illness, ILI and laboratory-confirmed viral respiratory infection. Results In an intention-to-treat analysis, rates of clinical respiratory illness (relative risk (RR) 0.61, 95% CI 0.18 to 2.13), ILI (RR 0.32, 95% CI 0.03 to 3.13) and laboratory-confirmed viral infections (RR 0.97, 95% CI 0.06 to 15.54) were consistently lower in the mask arm compared with control, although not statistically significant. A post hoc comparison between the mask versus no-mask groups showed a protective effect against clinical respiratory illness, but not against ILI and laboratory-confirmed viral respiratory infections. Conclusions The study indicates a potential benefit of medical masks for source control, but is limited by small sample size and low secondary attack rates. Larger trials are needed to confirm efficacy of medical masks as source control. Trial registration number ACTRN12613000852752; Results. PMID:28039289

From assessment to improvement of elderly care in general practice using decision support to increase adherence to ACOVE quality indicators: study protocol for randomized control trial

PubMed Central

2014-01-01

Background Previous efforts such as Assessing Care of Vulnerable Elders (ACOVE) provide quality indicators for assessing the care of elderly patients, but thus far little has been done to leverage this knowledge to improve care for these patients. We describe a clinical decision support system to improve general practitioner (GP) adherence to ACOVE quality indicators and a protocol for investigating impact on GPs’ adherence to the rules. Design We propose two randomized controlled trials among a group of Dutch GP teams on adherence to ACOVE quality indicators. In both trials a clinical decision support system provides un-intrusive feedback appearing as a color-coded, dynamically updated, list of items needing attention. The first trial pertains to real-time automatically verifiable rules. The second trial concerns non-automatically verifiable rules (adherence cannot be established by the clinical decision support system itself, but the GPs report whether they will adhere to the rules). In both trials we will randomize teams of GPs caring for the same patients into two groups, A and B. For the automatically verifiable rules, group A GPs receive support only for a specific inter-related subset of rules, and group B GPs receive support only for the remainder of the rules. For non-automatically verifiable rules, group A GPs receive feedback framed as actions with positive consequences, and group B GPs receive feedback framed as inaction with negative consequences. GPs indicate whether they adhere to non-automatically verifiable rules. In both trials, the main outcome measure is mean adherence, automatically derived or self-reported, to the rules. Discussion We relied on active end-user involvement in selecting the rules to support, and on a model for providing feedback displayed as color-coded real-time messages concerning the patient visiting the GP at that time, without interrupting the GP’s workflow with pop-ups. While these aspects are believed to increase clinical decision support system acceptance and its impact on adherence to the selected clinical rules, systems with these properties have not yet been evaluated. Trial registration Controlled Trials NTR3566 PMID:24642339

Effects of mineralocorticoid receptor antagonists in patients with hypertension and diabetes mellitus: a systematic review and meta-analysis.

PubMed

Takahashi, S; Katada, J; Daida, H; Kitamura, F; Yokoyama, K

2016-09-01

Blood pressure (BP) control is important to ameliorate cardiovascular events in patients with diabetes mellitus (DM). However, achieving the target BP with a single drug is often difficult. The objective of this study was to evaluate the antihypertensive effects of mineralocorticoid receptor antagonists (MRAs) as add-on therapy to renin-angiotensin system (RAS) inhibitor(s) in patients with hypertension and DM. Studies were searched through October 2014 in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. Randomized, controlled trials or prospective, observational studies regarding concomitant administration of MRA and RAS inhibitor(s) in patients with DM were included. Articles were excluded if the mean systolic BP (SBP) was <130 mm Hg before randomization for interventional studies or at baseline for prospective cohort studies. We identified nine eligible studies (486 patients): five randomized placebo-controlled trials; three randomized active drug-controlled trials; and one single-arm observational study. The mean differences in office SBP and diastolic BP (DBP) between the MRA and placebo groups were -9.4 (95% confidence interval (CI) -12.9 to -5.9) and -3.8 (95% CI, -5.5 to -2.2) mm Hg, respectively. Subgroup analysis results for study type, age, baseline office SBP and follow-up duration were similar to those of the main analysis. MRA mildly increased serum potassium (0.4 mEq l(-1); 95% CI, 0.3-0.5 mEq l(-1)). A consistent reduction of albuminuria across these studies was also demonstrated. MRA further reduced SBP and DBP in patients with hypertension and DM already taking RAS inhibitors. Serum potassium levels should be monitored to prevent hyperkalemia.

Implementing core NICE guidelines for osteoarthritis in primary care with a model consultation (MOSAICS): a cluster randomised controlled trial.

PubMed

Dziedzic, K S; Healey, E L; Porcheret, M; Afolabi, E K; Lewis, M; Morden, A; Jinks, C; McHugh, G A; Ryan, S; Finney, A; Main, C; Edwards, J J; Paskins, Z; Pushpa-Rajah, A; Hay, E M

2018-01-01

To determine the effectiveness of a model osteoarthritis consultation, compared with usual care, on physical function and uptake of National Institute for Health and Care Excellence (NICE) osteoarthritis recommendations, in adults ≥45 years consulting with peripheral joint pain in UK general practice. Two-arm cluster-randomised controlled trial with baseline health survey. Eight general practices in England. 525 adults ≥45 years consulting for peripheral joint pain, amongst 28,443 population survey recipients. Four intervention practices delivered the model osteoarthritis consultation to patients consulting with peripheral joint pain; four control practices continued usual care. The primary clinical outcome of the trial was the SF-12 physical component score (PCS) at 6 months; the main secondary outcome was uptake of NICE core recommendations by 6 months, measured by osteoarthritis quality indicators. A Linear Mixed Model was used to analyse clinical outcome data (SF-12 PCS). Differences in quality indicator outcomes were assessed using logistic regression. 525 eligible participants were enrolled (mean age 67.3 years, SD 10.5; 59.6% female): 288 from intervention and 237 from control practices. There were no statistically significant differences in SF-12 PCS: mean difference at the 6-month primary endpoint was -0.37 (95% CI -2.32, 1.57). Uptake of core NICE recommendations by 6 months was statistically significantly higher in the intervention arm compared with control: e.g., increased written exercise information, 20.5% (7.9, 28.3). Whilst uptake of core NICE recommendations was increased, there was no evidence of benefit of this intervention, as delivered in this pragmatic randomised trial, on the primary outcome of physical functioning at 6 months. ISRCTN06984617. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impact of age-related macular degeneration on object searches in realistic panoramic scenes.

PubMed

Thibaut, Miguel; Tran, Thi-Ha-Chau; Szaffarczyk, Sebastien; Boucart, Muriel

2018-05-01

This study investigated whether realistic immersive conditions with dynamic indoor scenes presented on a large, hemispheric panoramic screen covering 180° of the visual field improved the visual search abilities of participants with age-related macular degeneration (AMD). Twenty-one participants with AMD, 16 age-matched controls and 16 young observers were included. Realistic indoor scenes were presented on a panoramic five metre diameter screen. Twelve different objects were used as targets. The participants were asked to search for a target object, shown on paper before each trial, within a room composed of various objects. A joystick was used for navigation within the scene views. A target object was present in 24 trials and absent in 24 trials. The percentage of correct detection of the target, the percentage of false alarms (that is, the detection of the target when it was absent), the number of scene views explored and the search time were measured. The search time was slower for participants with AMD than for the age-matched controls, who in turn were slower than the young participants. The participants with AMD were able to accomplish the task with a performance of 75 per cent correct detections. This was slightly lower than older controls (79.2 per cent) while young controls were at ceiling (91.7 per cent). Errors were mainly due to false alarms resulting from confusion between the target object and another object present in the scene in the target-absent trials. The outcomes of the present study indicate that, under realistic conditions, although slower than age-matched, normally sighted controls, participants with AMD were able to accomplish visual searches of objects with high accuracy. © 2017 Optometry Australia.

Supported self-management for patients with COPD who have recently been discharged from hospital: a systematic review and meta-analysis

PubMed Central

Majothi, Saimma; Jolly, Kate; Heneghan, Nicola R; Price, Malcolm J; Riley, Richard D; Turner, Alice M; Bayliss, Susan E; Moore, David J; Singh, Sally J; Adab, Peymané; Fitzmaurice, David A; Jordan, Rachel E

2015-01-01

Purpose Although many hospitals promote self-management to chronic obstructive pulmonary disease (COPD) patients post discharge from hospital, the clinical effectiveness of this is unknown. We undertook a systematic review of the evidence as part of a Health Technology Assessment review. Methods A comprehensive search strategy with no language restrictions was conducted across relevant databases from inception to May 2012. Randomized controlled trials of patients with COPD, recently discharged from hospital after an acute exacerbation and comparing a self-management intervention with control, usual care or other intervention were included. Study selection, data extraction, and risk of bias assessment were undertaken by two reviewers independently. Results Of 13,559 citations, 836 full texts were reviewed with nine randomized controlled trials finally included in quantitative syntheses. Interventions were heterogeneous. Five trials assessed highly supported multi-component interventions and four trials were less supported with fewer contacts with health care professionals and mainly home-based interventions. Total sample size was 1,466 (range 33–464 per trial) with length of follow-up 2–12 months. Trials varied in quality; poor patient follow-up and poor reporting was common. No evidence of effect in favor of self-management support was observed for all-cause mortality (pooled hazard ratio =1.07; 95% confidence interval [0.74 to 1.55]; I2=0.0%, [n=5 trials]). No clear evidence of effect on all-cause hospital admissions was observed (hazard ratio 0.88 [0.61, 1.27] I2=66.0%). Improvements in St George’s Respiratory Questionnaire score were seen in favor of self-management interventions (mean difference =3.84 [1.29 to 6.40]; I2=14.6%), although patient follow-up rates were low. Conclusion There is insufficient evidence to support self-management interventions post-discharge. There is a need for good quality primary research to identify effective approaches. PMID:25995625

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.

[Health services research the example of atopic dermatitis].

PubMed

Schmitt, J

2011-03-01

Within the past years, health services research projects have analyzed critically the management of atopic eczema (AE) in routine care, quantified the utility of controlling severe AE, and introduced an international standardization of core outcome measures for AE. With a prevalence of 16%, AE is the most frequent chronic condition at all among children and adolescents seeking medical care. Despite lower prevalence in adults, about 60% of patients with AE in routine care are adults. There is a clinically relevant comorbidity of AE and psychiatric conditions. Independent of patient's age and physician's medical discipline topical corticosteroids dominate outpatient treatment of AE. However, there is considerable heterogeneity in the management of AE between treating physicians. Despite a lack of clinical trials, systemic corticosteroids are most frequently prescribed for severe AE. In contrast, cyclosporine only plays a minor role in routine care of severe AE although its efficacy is well-documented in trials. This observation stimulated a head-to-head trial that indicated superiority of cyclosporine over prednisolone for severe adult AE. The control of severe AE has high priority from the perspective of the general population and from the patients' perspective. Competence of the treating physician, disease severity and patient's competence to adjust treatment to disease activity are the main determinants of patient satisfaction. Aiming for a better comparability of clinical trials and better translation of trial evidence into clinical practice, we conducted a Delphi exercise including clinical experts from 11 countries, editors of international dermatological journals, regulatory agencies, and patient representatives. The preliminary core set of outcome domains for eczema trials as defined by the panel included symptoms, physician-assessed clinical signs, and a measurement for long-term control of flares. Symptoms such as itching should be regularly assessed in clinical practice. The presented studies indicate that health services research not only describes and critically analyzes the effectiveness of routine clinical care, but is also translational research in that it may stimulate clinical trials and generate new, clinically relevant hypotheses for experimental studies.

Positive and cost-effectiveness effect of spa therapy on the resumption of occupational and non-occupational activities in women in breast cancer remission: a French multicentre randomised controlled trial.

PubMed

Mourgues, Charline; Gerbaud, Laurent; Leger, Stéphanie; Auclair, Candy; Peyrol, Fleur; Blanquet, Marie; Kwiatkowski, Fabrice; Leger-Enreille, Anne; Bignon, Yves-Jean

2014-10-01

The main aim was to assess the effects of a spa treatment on the resumption of occupational and non-occupational activities and the abilities of women in breast cancer remission. A cost-effectiveness analysis (CEA) was also performed. A multicentre randomised controlled trial was carried out between 2008 and 2010 in the University Hospital of Auvergne and two private hospitals in Clermont-Ferrand, France. Eligible patients were women in complete breast cancer remission without contraindication for physical activities or cognitive disorders and a body mass index between 18.5 and 40 kg/m(2). The intervention group underwent spa treatment combined with consultation with dietician whereas the control underwent consultations with the dietician only. Of the 181 patients randomised, 92 and 89 were included in the intervention and the control groups, respectively. The CEA involved 90 patients, 42 from the intervention group and 48 from the control group. The main results showed a higher rate of resumption of occupational activities in the intervention group (p = 0.0025) and a positive effect of the intervention on the women's ability to perform occupational activities 12 months after the beginning of the study (p = 0.0014), and on their ability to perform family activities (p = 0.033). The stay in a thermal centre was cost-effective at 12 months. Spa treatment is a cost-effective strategy to improve resumption of occupational and non-occupational activities and the abilities of women in breast cancer remission. Copyright © 2014 Elsevier Ltd. All rights reserved.

Interventions to increase immunisation coverage among children 12–23 months of age in India through participatory learning and community engagement: pilot study for a cluster randomised trial

PubMed Central

Johri, Mira; Chandra, Dinesh; Koné, Georges K; Dudeja, Sakshi; Sylvestre, Marie-Pierre; Sharma, Jitendar K; Pahwa, Smriti

2015-01-01

Objective With the aim of conducting a future cluster randomised trial to assess intervention impact on child vaccination coverage, we designed a pilot study to assess feasibility and aid in refining methods for the larger study. Trial design Cluster-randomised design with a 1:1 allocation ratio. Methods Clusters were 12 villages in rural Uttar Pradesh. All women residing in a selected village who were mothers of a child 0–23 months of age were eligible; participants were chosen at random. Over 4 months, intervention group (IG) villages received: (1) home visits by volunteers; (2) community mobilisation events to promote immunisation. Control group (CG) villages received community mobilisation to promote nutrition. A toll-free number for immunisation was offered to all IG and CG village residents. Primary outcomes were ex-ante criteria for feasibility of the main study related to processes for recruitment and randomisation (50% of villages would agree to participate and accept randomisation; 30 women could be recruited in 70% of villages), and retention of participants (50% of women retained from baseline to endline). Clusters were assigned to IG or CG using a computer-generated randomisation schedule. Neither participants nor those delivering interventions were blinded, but those assessing outcomes were blinded to group assignment. Results All villages contacted agreed to participate and accepted randomisation. 36 women were recruited per village; 432 participants were randomised (IG n=216; CG n=216). No clusters were lost to follow-up. The main analysis included 86% (373/432) of participants, 90% (195/216) from the IG and 82% (178/216) from the CG. Conclusions Criteria related to feasibility were satisfied, giving us confidence that we can successfully conduct a larger cluster randomised trial. Methodological lessons will inform design of the main study. Trial registration number ISRCTN16703097 PMID:26384721

Spinal cord stimulation for chronic pain.

PubMed

Mailis-Gagnon, A; Furlan, A D; Sandoval, J A; Taylor, R

2004-01-01

Spinal cord stimulation (SCS) is a form of therapy used to treat certain types of chronic pain. It involves an electrical generator that delivers pulses to a targeted spinal cord area. The leads can be implanted by laminectomy or percutaneously and the source of power is supplied by an implanted battery or by an external radio-frequency transmitter. The exact mechanism of action of SCS is poorly understood. To assess the efficacy and effectiveness of spinal cord stimulation in relieving certain kinds of pain, as well as the complications and adverse effects of this procedure. We searched MEDLINE and EMBASE to September 2003; the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2003); textbooks and reference lists in retrieved articles. We also contacted experts in the field of pain and the main manufacturer of the stimulators. We included trials with a control group, either randomized controlled trials (RCTs) or non-randomized controlled clinical trials (CCTs), that assessed spinal cord stimulation for chronic pain. Two independent reviewers selected the studies, assessed study quality and extracted the data. One of the assessors of methodological quality was blinded to authors, dates and journals. The data were analysed using qualitative methods (best evidence synthesis). Two RCTs (81 patients in total) met our inclusion criteria. One was judged as being of high quality (score of 3 on Jadad scale) and the other of low quality (score of 1 on Jadad scale). One trial included patients with Complex Regional Pain Syndrome Type I (reflex sympathetic dystrophy) and the other patients with Failed Back Surgery Syndrome. The follow-up periods varied from 6 to 12 months. Both studies reported that SCS was effective, however, meta-analysis was not undertaken because of the small number of patients and the heterogeneity of the study population. Although there is limited evidence in favour of SCS for Failed Back Surgery Syndrome and Complex Regional Pain Syndrome Type I, more trials are needed to confirm whether SCS is an effective treatment for certain types of chronic pain. In addition, there needs to be a debate about trial designs that will provide the best evidence for assessing this type of intervention.

Impact of Personalised Feedback about Physical Activity on Change in Objectively Measured Physical Activity (the FAB Study): A Randomised Controlled Trial

PubMed Central

Godino, Job G.; Watkinson, Clare; Corder, Kirsten; Marteau, Theresa M.; Sutton, Stephen; Sharp, Stephen J.; Griffin, Simon J.; van Sluijs, Esther M. F.

2013-01-01

Background Low levels of physical activity are a major public health concern, and interventions to promote physical activity have had limited success. Whether or not personalised feedback about physical activity following objective measurement motivates behaviour change has yet to be rigorously examined. Methods And Findings: In a parallel group, open randomised controlled trial, 466 healthy adults aged 32 to 54 years were recruited from the ongoing population-based Fenland Study (Cambridgeshire, UK). Participants were randomised to receive either no feedback until the end of the trial (control group, n=120) or one of three different types of feedback: simple, visual, or contextualised (intervention groups, n=346). The primary outcome was physical activity (physical activity energy expenditure (PAEE) in kJ/kg/day and average body acceleration (ACC) in m/s2) measured objectively using a combined heart rate monitor and accelerometer (Actiheart®). The main secondary outcomes included self-reported physical activity, intention to increase physical activity, and awareness of physical activity (the agreement between self-rated and objectively measured physical activity). At 8 weeks, 391 (83.9%) participants had complete physical activity data. The intervention had no effect on objectively measured physical activity (PAEE: β=-0.92, 95% CI=-3.50 to 1.66, p=0.48 and ACC: β=0.01, 95% CI=-0.00 to 0.02, p=0.21), self-reported physical activity (β=-0.39, 95% CI=-1.59 to 0.81), or intention to increase physical activity (β=-0.05, 95% CI=-0.22 to 0.11). However, it was associated with an increase in awareness of physical activity (OR=1.74, 95% CI=1.05 to 2.89). Results did not differ according to the type of feedback. Conclusions Personalised feedback about physical activity following objective measurement increased awareness but did not result in changes in physical activity in the short term. Measurement and feedback may have a role in promoting behaviour change but are ineffective on their own. Trial Registration Current Controlled Trials ISRCTN92551397 http://www.controlled-trials.com/ISRCTN92551397 PMID:24066178

The effects of using cognitive behavioural therapy to improve sleep for patients with delusions and hallucinations (the BEST study): study protocol for a randomized controlled trial.

PubMed

Freeman, Daniel; Startup, Helen; Myers, Elissa; Harvey, Allison; Geddes, John; Yu, Ly-Mee; Zaiwalla, Zenobia; Luengo-Fernandez, Ramon; Foster, Russell; Lister, Rachel

2013-07-11

Patients with psychosis frequently report difficulties getting or staying asleep (insomnia). Dissatisfaction with sleep is high. Insomnia should be treated in this group, but typically it is not even assessed. Importantly, recent evidence indicates that insomnia triggers and exacerbates delusions and hallucinations. The clinical implication is that if the insomnia is treated then the psychotic symptoms will significantly lessen. In a case series with 15 patients with persecutory delusions resistant to previous treatment this is exactly what we found: cognitive behavioural therapy for insomnia (CBT-I) led to large reductions in both the insomnia and delusions. The clear next step is a pilot randomized controlled test. The clinical aim is to test whether CBT-I can reduce both insomnia and psychotic symptoms. The trial will inform decisions for a definitive large-scale evaluation. We will carry out a randomized controlled trial (the Better Sleep Trial, or the BEST study) with 60 patients with distressing delusions or hallucinations in the context of a schizophrenia spectrum diagnosis. Half of the participants will be randomized to receive CBT-I, in addition to their standard treatment, for up to eight sessions over 12 weeks. The other half will continue with treatment as usual. Blind assessments will take place at 0 weeks, 12 weeks (post-treatment) and 24 weeks (follow-up). The primary outcome hypotheses are that CBT-I added to treatment as usual will improve sleep, delusions and hallucinations compared with only treatment as usual. All main analyses will be carried out at the end of the last follow-up assessments and will be based on the intention-to-treat principle. The trial is funded by the NHS National Institute for Health Research (NIHR) Research for Patient Benefit Programme. Data collection will be complete by the end of 2014. This will be the first controlled test of CBT-I for patients with delusions and hallucinations. It will provide significant evidence for an easily administered intervention that is likely to prove very popular with patients experiencing the difficult-to-treat problems of delusions and hallucinations. Current Controlled Trials ISRCTN 33695128.

Menstruation and the Cycle of Poverty: A Cluster Quasi-Randomised Control Trial of Sanitary Pad and Puberty Education Provision in Uganda

PubMed Central

Montgomery, Paul; Hennegan, Julie; Dolan, Catherine; Wu, Maryalice; Steinfield, Laurel; Scott, Linda

2016-01-01

Background Poor menstrual knowledge and access to sanitary products have been proposed as barriers to menstrual health and school attendance. In response, interventions targeting these needs have seen increasing implementation in public and private sectors. However, there has been limited assessment of their effectiveness. Objectives Assess the impact of providing reusable sanitary pads and puberty education on girls’ school attendance and psychosocial wellbeing outcomes. Methods A cluster quasi-randomised controlled trial was conducted across 8 schools, including 1124 girls, in rural Uganda. Schools were allocated to one of four conditions: the provision of puberty education alone; reusable sanitary pads alone; puberty education and reusable sanitary pads; and a control (no intervention). The primary outcome was school attendance. Secondary outcomes reflected psychosocial wellbeing. Results At follow-up, school attendance had worsened for girls across all conditions. Per-protocol analysis revealed that this decline was significantly greater for those in the control condition d = 0.52 (95%CI 0.26–0.77), with those in control schools having a 17.1% (95%CI: 8.7–25.5) greater drop in attendance than those in any intervention school. There were no differences between the intervention conditions. High rates of school drop-out and transfer meant the trial suffered from substantial participant drop-out. Intention-to-treat analyses using two different imputation strategies were consistent with the main results, with mean differences of 5.2% attendance in best-case and 24.5% in worst-case imputations. Results were robust to adjustments for clustering. There was no impact of the interventions on girls’ self-reported shame or insecurity during menstruation. Conclusion Results of the trial support the hypothesised positive impact of providing sanitary pads or puberty education for girls’ school attendance in a developing country context. Findings must be interpreted with caution in light of poor participant retention, intervention fidelity, and the attendance measures used. Trial Registration Pan African Clinical Trials Registry PACTR201503001044408 PMID:28002415

[Optimizing the managment of patients with diabetes mellitus: selected clinical trials from the 2004 Congress of the American Diabetes Association].

PubMed

Scheen, A J; Radermecker, R P; Philips, J C

2004-06-01

The 64th scientific congress of the American Diabetes Association had a special session devoted to the presentation of the results from three clinical trials: 1) the first multicentre international trial of pancreatic islet transplantation according to the so-called Edmonton protocol with the primary endpoint of restoring insulin independence in type 1 diabetic patients; 2) three pivotal studies of 30 weeks testing both the efficacy and safety of exenatide (exendin-4), a new insulin secretagogue that is a long-acting analogue of glucagon-like peptide-1, in patients with type 2 diabetes treated with either metformin, or a sulfonylurea, or a metformin-sulfonylurea combination; and 3) the "Collaborative AtoRvastatin Diabetes Study" (CARDS), a placebo-controlled primary prevention trial of cardiovascular complications using atorvastatin 10 mg in 2 838 at risk patients with type 2 diabetes. The main results and conclusions of these trials are briefly presented as they open new perspectives in the management of patients with type 1 or type 2 diabetes mellitus.

Effects of scapulohumeral rehabilitation protocol on trunk control recovery in patients with subacute stroke: A pilot randomized controlled trial.

PubMed

Dell'Uomo, Daniela; Morone, Giovanni; Centrella, Antonio; Paolucci, Stefano; Caltagirone, Carlo; Grasso, Maria Grazia; Traballesi, Marco; Iosa, Marco

2017-01-01

Despite upper limb rehabilitation is widely investigated in patients with stroke, the effects of scapulohumeral rehabilitation on trunk stabillization are mainly unknown. To test the effects of scapulohumeral rehabilitation protocol on trunk control recovery in patients with subacute stroke. A pilot randomized controlled trial with two groups of 14 patients each one performing 20 minutes per day, 5 days a week, for 6 weeks in add on to standard therapy. Experimental group performed a specific scapulohumeral rehabilitation protocol aiming to improve trunk competencies whereas control group performed conventional arm rehabilitation. Clinical scale tests and accelerometric evaluations were performed pre- and post-treatment. Experimental groups showed better scores at discharge at Trunk impairment Scale (p < 0.001), Barthel Index (p = 0.024), Trunk Control Test (p = 0.002), Sitting Balance Scale (p = 0.002), but neither at Fugl-Meyer Scale (p = 0.194) nor Modified Ashworth Scale (p = 0.114). Accelerometric analysis showed higher stability of trunk for experimental group especially during static and dynamic items. The recovery of scapulohumeral functions also acts on trunk stabilization post-stroke.

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

PubMed Central

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

1999-01-01

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

[The informed consent in international clinical trials including developing countries].

PubMed

Montenegro Surís, Alexander; Monreal Agüero, Magda Elaine

2008-01-01

The informed consent procedure has been one of the most important controversies of ethical debates about clinical trials in developing countries. In this essay we present our recommendations about important aspects to consider in the informed consent procedure for clinical trials in developing countries. We performed a full publications review identified by MEDLINE using these terms combinations: informed consent, developing countries, less developed countries and clinical trials. To protect volunteers in less developed countries should be valuated the importance of the community in the informed consent proceeding. The signing and dating of the informed consent form is not always the best procedure to document the informed consent. The informed consent form should be written by local translators. Alternative medias of communications could be needed for communicatios of the information to volunteers. Comparing with developed countries the informed consent proceeding in clinical trials in developing countries frequently require additional efforts. The developing of pragmatic researches is needed to implement informed consent proceedings assuring subjects voluntarily in each developing country. The main aspects to define in each clinical trial for each country are the influence of the community, the effective communication of the information, the documentation of the informed consent and local authority's control.

Interventions for preventing and treating hyperthyroidism in pregnancy.

PubMed

Earl, Rachel; Crowther, Caroline A; Middleton, Philippa

2010-09-08

Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption. To assess the effects of interventions for preventing or treating hyperthyroidism in pregnant women. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 July 2010). We intended to include randomised controlled trials comparing antithyroid treatments in pregnant women with hyperthyroidism. Two review authors would have assessed trial eligibility and risk of bias, and extracted data. No trials were located. As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid drugs for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil.

[Methods of pushing at vaginal delivery and pelvi-perineal consequences. Review].

PubMed

Ratier, N; Balenbois, E; Letouzey, V; Marès, P; de Tayrac, R

2015-03-01

The main objective of that review was to evaluate the pelvi-perineal consequences of the different methods of pushing at vaginal delivery. A review on PubMed, the Cochrane Library and EM-Premium was performed from 1984 to 2014. Among 29 manuscripts analysed, only nine randomised controlled trials (including one meta-analysis of three trials) comparing Valsalva and spontaneous pushing were selected. A 10 th study, secondary analysis of a randomized controlled trial comparing different methods of perineal protection (warm compresses, massage and manual protection), was also selected. Two trials have shown that spontaneous pushing reduces the risk of perineal tears, but studies were heterogeneous and discordant results do not allowed definitive conclusions. Results on the duration of the second stage of labour are conflicting. The method of pushing does not seem to affect the rate of episiotomy, instrumental delivery and cesarean section. Maternal satisfaction seems to be better after spontaneous pushing. It seems that there is no negative effect of spontaneous pushing on neonate well-being, and one study has shown a significant improvement of prenatal fetal parameters during the expulsive phase. According to current knowledge, both techniques of pushing during the expulsive phase at delivery seem comparable in terms of duration, risk of perineal tears and neonatal outcome. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The effect of vitamin B12 supplementation in Nepalese infants on growth and development: study protocol for a randomized controlled trial.

PubMed

Strand, Tor A; Ulak, Manjeswori; Chandyo, Ram K; Kvestad, Ingrid; Hysing, Mari; Shrestha, Merina; Basnet, Sudha; Ranjitkar, Suman; Shrestha, Laxman; Shrestha, Prakash S

2017-04-21

Vitamin B 12 deficiency is one of the most common micronutrient deficiencies and is associated with poor cognitive development and growth. Vitamin B 12 is crucial for normal cell division and differentiation, and it is necessary for the development and myelination of the central nervous system. The aim of the present study is to measure the effect of daily supplementation of vitamin B 12 on the neurodevelopment and growth of young children in Nepal. We are conducting an individually randomized, double-blind, placebo-controlled trial with 600 marginally stunted children 6-11 months old (length for age less than -1 z-score). Children are randomized to receive a lipid-based paste containing vitamin B 12 or placebo daily for 12 months. The main outcomes are changes in growth (z-scores) and in neurodevelopment measured by the Bayley Scales of Infant and Toddler Development, Third Edition, from baseline until the end of the study. If vitamin B 12 supplementation benefits early child development and growth, this will have consequences for dietary recommendations for malnourished children worldwide. ClinicalTrials.gov Identifier: NCT02272842 . Registered on 21 October 2014. Universal Trial Number: U1111-1161-5187. Registered on 8 September 2014.

Factors influencing adherence with therapeutic sunlight exposure in older people in intermediate care facilities.

PubMed

Durvasula, Seeta; Sambrook, Philip N; Cameron, Ian D

2012-01-01

The purpose of this study was to investigate the factors influencing low adherence with therapeutic sunlight exposure in a randomized controlled trial conducted with older people living in intermediate care facilities. The study involved participants in the FREEDOM (Falls Risk Epidemiology: Effect of vitamin D on skeletal Outcomes and other Measures) study, a randomized controlled trial of therapeutic sun exposure to reduce falls in older people in intermediate care facilities. Semi-structured interviews were conducted with thirty participants in the FREEDOM trial, and with ten sunlight officers who were employed to facilitate the sun exposure. Two focus groups involving 10 participants in the FREEDOM trial were also held at the end of the intervention period. Common themes were derived from the interview and focus group transcripts. The study showed that the perceived health benefits did not influence adherence with the sun exposure. Factors such as socializing with others and being outdoors were more important in encouraging attendance. The main barriers to adherence included the perceived inflexibility and regimentation of daily attendance, clash with other activities, unsuitable timing and heat discomfort. This study showed that providing greater flexibility and autonomy to older people in how and when they receive sun exposure is likely to improve adherence. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The role of sensorimotor processes in social group contagion.

PubMed

Cracco, Emiel; Brass, Marcel

2018-06-01

Although it is well known that action observation triggers an imitative response, not much is known about how these responses develop as a function of group size. Research on social contagion suggests that imitative tendencies initially increase but then stabilize as groups become larger. However, these findings have mainly been explained in terms of interpretative processes. Across seven experiments (N = 322), the current study investigated the contribution of sensorimotor processes to social group contagion by looking at the relation between group size and automatic imitation in a task that involved minimal interpretation. The results of Experiments 1-2 revealed that automatic imitation increased with group size according to an asymptotic curve on congruent trials but a linear curve on incongruent trials. The results of Experiments 3-7 showed that the asymptote on congruent trials disappeared when no control was needed, namely in the absence of incongruent trials. This suggests that the asymptote in the relation between group size and automatic imitation can be explained in terms of strategic control mechanisms that aim to prevent unintended imitative responses. The findings of the current study are in close correspondence with previous research in the social domain and as such support the hypothesis that sensorimotor processes contribute to the relation between group size and social contagion. Copyright © 2018 Elsevier Inc. All rights reserved.

Calcium and Vitamin D Supplementation and Loss of Bone Mineral Density in Women Undergoing Breast Cancer Therapy

PubMed Central

Datta, Mridul; Schwartz, Gary G.

2013-01-01

An unintended consequence of breast cancer therapies is an increased risk of osteoporosis due to accelerated bone loss. We conducted a systematic review of calcium and/or vitamin D (Ca±D) supplementation trials for maintaining bone mineral density (BMD) in women with breast cancer using the “before-after” data from the Ca±D supplemented comparison group of trials evaluating the effect of drugs such as bisphosphonates on BMD. Whether Ca±D supplements increase BMD in women undergoing breast cancer therapy has never been tested against an unsupplemented control group. However, results from 16 trials indicate that the Ca±D doses tested (500-1500 mg calcium; 200-1000 IU vitamin D) were inadequate to prevent BMD loss in these women. Cardiovascular disease is the main cause of mortality in women with breast cancer. Because calcium supplements may increase cardiovascular disease risk, future trials should evaluate the safety and efficacy of Ca±D supplementation in women undergoing breast cancer therapy. PMID:23932583

An overview of 37 randomised trials of blood pressure lowering agents among 270,000 individuals. World Health Organization-International Society of Hypertension Blood Pressure Lowering Treatment Trialists' Collaboration.

PubMed

Neal, B; MacMahon, S

1999-01-01

Overviews (meta-analyses) of the major ongoing randomized trials of blood pressure lowering drugs will be conducted to determine the effects of: first, newer versus older classes of blood pressure lowering drugs in patients with hypertension; and second, blood pressure lowering treatments versus untreated or less treated control conditions in patient groups at high risk of cardiovascular events. The principal study outcomes are stroke, coronary heart disease, total cardiovascular events and total cardiovascular deaths. The overviews have been prospectively designed and will be conducted on individual patient data. The analyses will be conducted as a collaboration between the principal investigators of participating trials involving about 270,000 patients. Full data should be available in 2003, with the first round of analyses performed in 1999-2000. The combination of trial results should provide good statistical power to detect even modest differences between the effects on the main study outcomes.

Sub-Network Access Control Technology Demonstrator: Software Design of the Network Management System

DTIC Science & Technology

2002-08-01

Canadian Operational Fleet. Requirements The proposed network management solution must provide the normal monitoring and configuration mechanisms generally...Joint Warrior Inter- operability Demonstrations (JWID) m and the Communication System Network Inter- Operability (CSNI) Navy Network Trials. In short...management functional area normally includes two main functions: fault isolation and diagnosis, and restoration of the system . In short, an operator

CADASIL: Treatment and Management Options.

PubMed

Bersano, Anna; Bedini, Gloria; Oskam, Joshua; Mariotti, Caterina; Taroni, Franco; Baratta, Silvia; Parati, Eugenio Agostino

2017-09-01

CADASIL is a life-threatening and disabling disease. Despite the progress achieved so far, no therapies able to limit the disease progression have been found and only empiric treatments can be employed to relieve the main disease symptoms. Further in vivo studies as well as data aggregation and multi-centre controlled clinical trials are needed to confirm the emerging findings in order to identify evidence-based therapies for CADASIL.

Effectiveness of olive oil for the prevention of pressure ulcers caused in immobilized patients within the scope of primary health care: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Pressure ulcers are considered an important issue, mainly affecting immobilized older patients. These pressure ulcers increase the care burden for the professional health service staff as well as pharmaceutical expenditure. There are a number of studies on the effectiveness of different products used for the prevention of pressure ulcers; however, most of these studies were carried out at a hospital level, basically using hyperoxygenated fatty acids (HOFA). There are no studies focused specifically on the use of olive-oil-based products and therefore this research is intended to find the most cost-effective treatment and achieve an alternative treatment. Methods/design The main objective is to assess the effectiveness of olive oil, comparing it with HOFA, to treat immobilized patients at home who are at risk of pressure ulcers. As a secondary objective, the cost-effectiveness balance of this new application with regard to the HOFA will be assessed. The study is designed as a noninferiority, triple-blinded, parallel, multi-center, randomized clinical trial. The scope of the study is the population attending primary health centers in Andalucía (Spain) in the regional areas of Malaga, Granada, Seville, and Cadiz. Immobilized patients at risk of pressure ulcers will be targeted. The target group will be treated by application of an olive-oil-based formula whereas the control group will be treated by application of HOFA to the control group. The follow-up period will be 16 weeks. The main variable will be the presence of pressure ulcers in the patient. Secondary variables include sociodemographic and clinical information, caregiver information, and whether technical support exists. Statistical analysis will include the Kolmogorov-Smirnov test, symmetry and kurtosis analysis, bivariate analysis using the Student’s t and chi-squared tests as well as the Wilcoxon and the Man-Whitney U tests, ANOVA and multivariate logistic regression analysis. Discussion The regular use of olive-oil-based formulas should be effective in preventing pressure ulcers in immobilized patients, thus leading to a more cost-effective product and an alternative treatment. Trial registration Clinicaltrials.gov identifier: NCT01595347. PMID:24152576

Clinical trial design and dissemination: comprehensive analysis of clinicaltrials.gov and PubMed data since 2005.

PubMed

Zwierzyna, Magdalena; Davies, Mark; Hingorani, Aroon D; Hunter, Jackie

2018-06-06

To investigate the distribution, design characteristics, and dissemination of clinical trials by funding organisation and medical specialty. Cross sectional descriptive analysis. Trial protocol information from clinicaltrials.gov, metadata of journal articles in which trial results were published (PubMed), and quality metrics of associated journals from SCImago Journal and Country Rank database. All 45 620 clinical trials evaluating small molecule therapeutics, biological drugs, adjuvants, and vaccines, completed after January 2006 and before July 2015, including randomised controlled trials and non-randomised studies across all clinical phases. Industry was more likely than non-profit funders to fund large international randomised controlled trials, although methodological differences have been decreasing with time. Among 27 835 completed efficacy trials (phase II-IV), 15 084 (54.2%) had disclosed their findings publicly. Industry was more likely than non-profit trial funders to disseminate trial results (59.3% (10 444/17 627) v 45.3% (4555/10 066)), and large drug companies had higher disclosure rates than small ones (66.7% (7681/11 508) v 45.2% (2763/6119)). Trials funded by the National Institutes of Health (NIH) were disseminated more often than those of other non-profit institutions (60.0% (1451/2417) v 40.6% (3104/7649)). Results of studies funded by large drug companies and NIH were more likely to appear on clinicaltrials.gov than were those from non-profit funders, which were published mainly as journal articles. Trials reporting the use of randomisation were more likely than non-randomised studies to be published in a journal article (6895/19 711 (34.9%) v 1408/7748 (18.2%)), and journal publication rates varied across disease areas, ranging from 42% for autoimmune diseases to 20% for oncology. Trial design and dissemination of results vary substantially depending on the type and size of funding institution as well as the disease area under study. 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.

Massage Therapy in Children with Asthma: A Systematic Review and Meta-Analysis.

PubMed

Wu, Ji; Yang, Xi-Wen; Zhang, Ming

2017-01-01

To systematically evaluate the efficacy of massage, a traditional treatment method of traditional Chinese medicine on children with asthma. Literatures from 5 databases using the date ranging from 1 January, 1990, to 13 December, 2016, were reviewed, which were all randomized controlled trials evaluating the efficacy on children with asthma and effect on lung function mainly by massage therapy. 14 researches with 1299 patients were included in the meta-analysis. Compared with control group, a better efficacy was found in treatment group, which focused on massage therapy. Compared with control group, there was remarkable increase on FEV1 as well as PEF in treatment group. All studies have shown that massage therapy has a significantly positive effect on children with asthma, improves the pulmonary function parameters of large airway, reduces the plasma concentrations of PAF and prostaglandin, and increases the levels of PAF-AH and DP1; therefore, it greatly improves pulmonary function. However, the limited research designs of included studies lead to high risk of bias. More randomized controlled trials with better methodological quality are needed to further confirm the effectiveness of massage.

Preventing childhood obesity by reducing consumption of carbonated drinks: cluster randomised controlled trial

PubMed Central

James, Janet; Thomas, Peter; Cavan, David; Kerr, David

2004-01-01

Objective To determine if a school based educational programme aimed at reducing consumption of carbonated drinks can prevent excessive weight gain in children. Design Cluster randomised controlled trial. Setting Six primary schools in southwest England. Participants 644 children aged 7-11 years. Intervention Focused educational programme on nutrition over one school year. Main outcome measures Drink consumption and number of overweight and obese children. Results Consumption of carbonated drinks over three days decreased by 0.6 glasses (average glass size 250 ml) in the intervention group but increased by 0.2 glasses in the control group (mean difference 0.7, 95% confidence interval 0.1 to 1.3). At 12 months the percentage of overweight and obese children increased in the control group by 7.5%, compared with a decrease in the intervention group of 0.2% (mean difference 7.7%, 2.2% to 13.1%). Conclusion A targeted, school based education programme produced a modest reduction in the number of carbonated drinks consumed, which was associated with a reduction in the number of overweight and obese children. PMID:15107313

Effectiveness of Mechanical Debridement Combined With Adjunctive Therapies for Nonsurgical Treatment of Periimplantitis: A Systematic Review.

PubMed

de Almeida, Juliano Milanezi; Matheus, Henrique Rinaldi; Rodrigues Gusman, David Jonathan; Faleiros, Paula Lazilha; Januário de Araújo, Nathália; Noronha Novaes, Vivian Cristina

2017-02-01

This study aimed to perform a systematic review of the effectiveness of nonsurgical treatment associated with different adjuvant therapies on periimplantitis. Different individuals, following a research process, performed a network research of controlled and randomized controlled clinical trials on PubMed, Embase/MEDLINE, with 20 years' time constraint and the last search in January 2016. From 108 articles found by the first search, they analyzed 10 full texts, and in none did they find a standard control group. When compared, mechanical therapies combined with adjuvant therapy decreased prevalence of periimplant ratios; however, some groups showed unsatisfactory results, mainly related to the probing depth and bleeding index. When comparing debridement with other nonsurgical therapies (Er:YAG, Vector, air abrasive with amino acid glycine powder), increased periimplant levels were noticed in the test and control groups, although in different periods. Despite the improvement in the periimplant indices, there is no sufficient evidence to score the best results or even to choose the best association for nonsurgical treatment of periimplantitis; hence, more trials are necessary to answer this question.

Biochemical verification of the self-reported smoking status of screened male smokers of the Dutch-Belgian randomized controlled lung cancer screening trial.

PubMed

van der Aalst, Carlijn M; de Koning, Harry J

2016-04-01

Smoking is the main cause of lung cancer, so data linked to smoking behaviour are important in lung cancer screening trials. However, self-reporting data concerning smoking behaviour are mainly used. The aim of this study was to biochemically determine the validity and reliability of self-reported smoking status among smokers at high risk for developing lung cancer participating in the Dutch-Belgian lung cancer screening (NELSON) trial. For this sub study, a random sample of 475 men was selected who were scheduled for the fourth screening round in the NELSON trial. They were asked to complete a short questionnaire to verify the smoking behaviour for the previous seven days and a blood sample was collected to measure the cotinine level. The validity (sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV)) and reliability (Kappa) of the self-reported smoking status compared to the cotinine level (as golden standard) were determined. Both a completed questionnaire as well as a cotinine level were available for 199 (41.9%) participants. Based on these data, Se and Sp were respectively 98% (95%-Confidence Interval (CI): 91-99) and 98% (95%-CI: 93-100). PPV and NPV were 98% and 96% and Kappa was 0.96. In conclusion, the validity of the self-reported smoking status turned out to be reliable amongst men at high risk for developing lung cancer who participate in the NELSON lung cancer screening trial. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Intelligent Control System and Experiments for an Unmanned Wave Glider.

PubMed

Liao, Yulei; Wang, Leifeng; Li, Yiming; Li, Ye; Jiang, Quanquan

2016-01-01

The control system designing of Unmanned Wave Glider (UWG) is challenging since the control system is weak maneuvering, large time-lag and large disturbance, which is difficult to establish accurate mathematical model. Meanwhile, to complete marine environment monitoring in long time scale and large spatial scale autonomously, UWG asks high requirements of intelligence and reliability. This paper focuses on the "Ocean Rambler" UWG. First, the intelligent control system architecture is designed based on the cerebrum basic function combination zone theory and hierarchic control method. The hardware and software designing of the embedded motion control system are mainly discussed. A motion control system based on rational behavior model of four layers is proposed. Then, combining with the line-of sight method(LOS), a self-adapting PID guidance law is proposed to compensate the steady state error in path following of UWG caused by marine environment disturbance especially current. Based on S-surface control method, an improved S-surface heading controller is proposed to solve the heading control problem of the weak maneuvering carrier under large disturbance. Finally, the simulation experiments were carried out and the UWG completed autonomous path following and marine environment monitoring in sea trials. The simulation experiments and sea trial results prove that the proposed intelligent control system, guidance law, controller have favorable control performance, and the feasibility and reliability of the designed intelligent control system of UWG are verified.

The Intelligent Control System and Experiments for an Unmanned Wave Glider

PubMed Central

Liao, Yulei; Wang, Leifeng; Li, Yiming; Li, Ye; Jiang, Quanquan

2016-01-01

The control system designing of Unmanned Wave Glider (UWG) is challenging since the control system is weak maneuvering, large time-lag and large disturbance, which is difficult to establish accurate mathematical model. Meanwhile, to complete marine environment monitoring in long time scale and large spatial scale autonomously, UWG asks high requirements of intelligence and reliability. This paper focuses on the “Ocean Rambler” UWG. First, the intelligent control system architecture is designed based on the cerebrum basic function combination zone theory and hierarchic control method. The hardware and software designing of the embedded motion control system are mainly discussed. A motion control system based on rational behavior model of four layers is proposed. Then, combining with the line-of sight method(LOS), a self-adapting PID guidance law is proposed to compensate the steady state error in path following of UWG caused by marine environment disturbance especially current. Based on S-surface control method, an improved S-surface heading controller is proposed to solve the heading control problem of the weak maneuvering carrier under large disturbance. Finally, the simulation experiments were carried out and the UWG completed autonomous path following and marine environment monitoring in sea trials. The simulation experiments and sea trial results prove that the proposed intelligent control system, guidance law, controller have favorable control performance, and the feasibility and reliability of the designed intelligent control system of UWG are verified. PMID:28005956

Effect of Oral Magnesium Oxide Supplementation on Cisplatin-Induced Hypomagnesemia in Cancer Patients: A Randomized Controlled Trial

PubMed Central

ZARIF YEGANEH, Maryam; VAKILI, Masoud; SHAHRIARI-AHMADI, Ali; NOJOMI, Marzieh

2016-01-01

Background: Hypomagnesaemia is one of the main side effects of cisplatin-based chemotherapy regimens in cancer patients. The aim of the current investigation was to evaluate the effect of oral magnesium oxide (MgO) supplementation on cisplatin-induced hypomagnesemia. Methods: This parallel-randomized controlled, open label trial was conducted in a hospital of Iran University of Medical Sciences in Tehran between December 2009 and May 2011. Participants were 69 adult patients with newly diagnosed non- leukemia neoplasms candidate for starting cisplatin-based chemotherapy. Oral MgO supplement according to cisplatin dose (500 mg MgO per 50 mg/m2 of cisplatin) as 2–3 divided daily doses was started after completion of each chemotherapy cycle and continued to the next cycle for the intervention group. Patients in the control group did not receive any supplementation. Serum magnesium (Mg) was measured before each chemotherapy cycle. The main outcome was measuring serum Mg change and hypomagnesaemia rate during chemotherapy treatment. Results: Sixty-two participants (31 intervention- 31 controls) enrolled into the study. Serum Mg levels showed significant difference between the two groups (P=0.01). There was a significant decrease in serum Mg of the control group (P=0.001). At the end of follow-up period prevalence of hypomagnesaemia in the intervention group was 10.7% versus 23.1% in the control group. Conclusion: Continuously oral supplementation with MgO according to cisplatin dose (500 mg MgO per 50 mg/m2 cisplatin) as 2–3 divided daily doses at rest days between chemotherapy cycles reduces the decline in serum Mg levels and also the prevalence of hypomagnesaemia in cancer patients. PMID:27057522

Efficacy of resin infiltration of proximal caries in primary molars: 1-year follow-up of a split-mouth randomized controlled clinical trial.

PubMed

Ammari, Michelle Mikhael; Jorge, R C; Souza, I P R; Soviero, V M

2018-04-01

The main purpose of this split month, randomized, controlled clinical trial was evaluate the efficacy of caries infiltration in controlling the progression of non-cavitated proximal lesions in primary molars. Anxiety and time required for the caries infiltration was also evaluated. Fifty healthy children, 5 to 9 years, presenting two primary molars with proximal caries lesions (1/2 of the enamel or outer 1/3 of dentin), were included. Lesions were randomly allocated to the test group (fluoridated toothpaste + flossing + infiltration) or to the control group (fluoridated toothpaste + flossing). Caries risk was based on the Cariogram model. The main outcome after 1-year radiographic follow up was assessed by an independent blinded examiner A facial image scale (FIS) was applied to assess dental anxiety and time required to perform the infiltration was recorded. Of the sample, 92.9% corresponded to high or medium caries risk. In 42 patients (1-year follow up), caries progression was observed in 11.9% (5/42) of the test lesions compared with 33.3% (14/42) of the control lesions (p < 0.05). Five control and three test lesions progressed to the middle 1/3 of dentin and were restored. No side effects were observed. Anxiety was both low before and after the treatment, and mean time required for the infiltration was 11.29 min (± 1.16 min). Caries infiltration of proximal caries lesions in primary molars is significantly more efficacious than standard therapy alone (fluoride toothpaste + flossing). Caries infiltration is an applicable and well-accepted method be used in children, representing a promising micro-invasive approach.

HYPERTENSION IMPROVEMENT PROJECT (HIP): RANDOMIZED TRIAL OF QUALITY IMPROVEMENT FOR PHYSICIANS AND LIFESTYLE MODIFICATION FOR PATIENTS

PubMed Central

Svetkey, Laura P.; Pollak, Kathryn I.; Yancy, William S.; Dolor, Rowena J.; Batch, Bryan C.; Samsa, Greg; Matchar, David B.; Lin, Pao-Hwa

2009-01-01

Despite widely publicized hypertension treatment guidelines for physicians and lifestyle recommendations for patients, blood pressure control rates remain low. In community-based primary care clinics, we performed a nested, 2×2 randomized, controlled trial of physician intervention vs. control and/or patient intervention vs. control. Physician Intervention included internet-based training, self-monitoring, and quarterly feedback reports. Patient Intervention included 20 weekly group sessions followed by 12 monthly phone counseling contacts, and focused on weight loss, DASH dietary pattern, exercise, and reduced sodium intake. The primary outcome was change in systolic blood pressure at 6 months. Eight primary care practices (32 physicians) were randomized to Physician Intervention or Control. Within those practices, 574 patients were randomized to Patient Intervention or Control. Patients’ mean age was 60 years, 61% female, 37% African American. BP data were available for 91% of patients at 6 months. The main effect of Physician Intervention on systolic blood pressure at 6 months, adjusted for baseline pressure, was 0.3 mmHg (95% CI −1.5 to 2.2; p = 0.72). The main effect of the Patient Intervention was −2.6 mmHg (95% CI −4.4, −0.7; p = 0.01). The interaction of the 2 interventions was significant (p = 0.03); the largest impact was observed with the combination of Physician and Patient Intervention (−9.7 ± 12.7 mmHg). Differences between treatment groups did not persist at 18 months. Combined physician and patient intervention lowers blood pressure; future research should focus on enhancing effectiveness and sustainability of these interventions. PMID:19920081

Associations of Adiposity and Aerobic Fitness with Executive Function and Math Performance in Danish Adolescents.

PubMed

Huang, Tao; Tarp, Jakob; Domazet, Sidsel Louise; Thorsen, Anne Kær; Froberg, Karsten; Andersen, Lars Bo; Bugge, Anna

2015-10-01

To examine the associations of adiposity and aerobic fitness with executive function and math performance in Danish adolescents. Cross-sectional analyses were conducted with data on 525 adolescents attending sixth and seventh grades from 14 schools in the 5 main regions of Denmark. A modified Eriksen flanker task was used to assess inhibitory control, a key aspect of executive function. Academic performance was assessed by a customized math test. Aerobic fitness was assessed by an intermittent shuttle-run test (Andersen test). Body mass index (BMI) was negatively associated with accuracy on incongruent trials during the flanker task (P = .005). A higher BMI was associated with a larger accuracy interference score (P = .01). Similarly, waist circumference (WC) was negatively associated with accuracy on incongruent trials (P = .008). A higher WC was associated with a larger reaction time (RT) interference score (P = .02) and accuracy interference score (P = .009). Higher aerobic fitness was associated with a faster RT on congruent trials (P = .009) and incongruent trials (P = .003). Higher aerobic fitness was associated with a smaller RT interference score (P = .04). Aerobic fitness was positively associated with math score (P < .001). BMI and WC were not associated with math score (P > .05). These results suggest that aerobic fitness is positively associated with both inhibitory control and math performance in adolescents. Adiposity is negatively associated with inhibitory control in adolescents. Adiposity is not associated with math performance. Copyright © 2015 Elsevier Inc. All rights reserved.

Critical period of weed control in aerobic rice.

PubMed

Anwar, M P; Juraimi, A S; Samedani, B; Puteh, A; Man, A

2012-01-01

Critical period of weed control is the foundation of integrated weed management and, hence, can be considered the first step to design weed control strategy. To determine critical period of weed control of aerobic rice, field trials were conducted during 2010/2011 at Universiti Putra Malaysia. A quantitative series of treatments comprising two components, (a) increasing duration of weed interference and (b) increasing length of weed-free period, were imposed. Critical period was determined through Logistic and Gompertz equations. Critical period varied between seasons; in main season, it started earlier and lasted longer, as compared to off-season. The onset of the critical period was found relatively stable between seasons, while the end was more variable. Critical period was determined as 7-49 days after seeding in off-season and 7-53 days in main season to achieve 95% of weed-free yield, and 23-40 days in off-season and 21-43 days in main season to achieve 90% of weed-free yield. Since 5% yield loss level is not practical from economic view point, a 10% yield loss may be considered excellent from economic view point. Therefore, aerobic rice should be kept weed-free during 21-43 days for better yield and higher economic return.

Surgery for congenital choanal atresia.

PubMed

Cedin, Antonio C; Atallah, Alvaro N; Andriolo, Régis B; Cruz, Oswaldo L; Pignatari, Shirley N

2012-02-15

Congenital choanal atresia is a rare abnormality characterized by unilateral or bilateral lack of patency of the posterior end of the nasal cavity. With an incidence of 1:5000 to 1:8000 births, it is twice as prevalent in females as it is in males. Surgical procedures aim to provide adequate functional choanal patency and a low rate of restenosis, avoid harm to any structure in development, enable shorter surgery and hospitalization times, and minimize morbidity and mortality. To evaluate the effectiveness and safety of the available surgical techniques for the treatment of congenital choanal atresia in patients with unilateral and bilateral atresia. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the search was 31 January 2011. We planned to include parallel randomized or quasi-randomized controlled trials testing surgical approaches for the treatment of congenital atresia (irrespective of gender and age) that evaluated normal/adequate respiratory function (self reported or preserved nasal airway) and restenosis as the main primary outcomes. We did not consider reoperation and non-congenital atresia (e.g. traumatic, iatrogenic atresias) for inclusion. Three review authors independently assessed the titles and abstracts of the identified articles to determine potential relevance. For dichotomous and continuous variables, we planned to calculate risk ratios (relative risks; RR) and mean differences (MD) with 95% confidence intervals (CI), respectively. We planned to use the random-effects model since we were expecting substantial clinical and methodological heterogeneity. No randomized controlled trials were identified. From the 120 reports retrieved using our search strategy, 46 primary studies had the potential to be included since they had tested surgical approaches for choanal atresia. However, we excluded all of them during the final selection process because their study designs did not meet our inclusion criteria. There is no definitive evidence, based on randomized controlled trials, to demonstrate the potential advantages and disadvantages of any specific surgical technique for patients with choanal atresia. Specialists should unify their efforts in multicenter randomized controlled trials that test the effectiveness and safety of different surgical techniques in patients with choanal atresia.

The effects of using cognitive behavioural therapy to improve sleep for patients with delusions and hallucinations (the BEST study): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Patients with psychosis frequently report difficulties getting or staying asleep (insomnia). Dissatisfaction with sleep is high. Insomnia should be treated in this group, but typically it is not even assessed. Importantly, recent evidence indicates that insomnia triggers and exacerbates delusions and hallucinations. The clinical implication is that if the insomnia is treated then the psychotic symptoms will significantly lessen. In a case series with 15 patients with persecutory delusions resistant to previous treatment this is exactly what we found: cognitive behavioural therapy for insomnia (CBT-I) led to large reductions in both the insomnia and delusions. The clear next step is a pilot randomized controlled test. The clinical aim is to test whether CBT-I can reduce both insomnia and psychotic symptoms. The trial will inform decisions for a definitive large-scale evaluation. Methods/design We will carry out a randomized controlled trial (the Better Sleep Trial, or the BEST study) with 60 patients with distressing delusions or hallucinations in the context of a schizophrenia spectrum diagnosis. Half of the participants will be randomized to receive CBT-I, in addition to their standard treatment, for up to eight sessions over 12 weeks. The other half will continue with treatment as usual. Blind assessments will take place at 0 weeks, 12 weeks (post-treatment) and 24 weeks (follow-up). The primary outcome hypotheses are that CBT-I added to treatment as usual will improve sleep, delusions and hallucinations compared with only treatment as usual. All main analyses will be carried out at the end of the last follow-up assessments and will be based on the intention-to-treat principle. The trial is funded by the NHS National Institute for Health Research (NIHR) Research for Patient Benefit Programme. Data collection will be complete by the end of 2014. Discussion This will be the first controlled test of CBT-I for patients with delusions and hallucinations. It will provide significant evidence for an easily administered intervention that is likely to prove very popular with patients experiencing the difficult-to-treat problems of delusions and hallucinations. Trial registration Current Controlled Trials ISRCTN 33695128 PMID:23845104

A comparison of Kneipp hydrotherapy with conventional physiotherapy in the treatment of osteoarthritis: a pilot trial.

PubMed

Schencking, Martin; Wilm, Stefan; Redaelli, Marcus

2013-01-01

An increasingly aging population implies an increasing prevalence of osteoarthritis (OA) of hip or knee. It has been ascertained that unspecific hydrotherapy of OA according to Sebastian Kneipp not only improves the range of mobility but also reduces pain significantly and increases the quality of life of the patients affected. The main aim of this pilot study was to determine the effects of hydrotherapy in comparison to conventional physiotherapy, and to analyze the feasibility of the study design under clinical circumstances. The study design is a prospective randomized controlled three-arm clinical pilot trial, carried out at a specialist clinic for integrative medicine. Thirty patients diagnosed with symptomatic OA of hip or knee and radiologic findings were randomly assigned to one of two intervention groups and a control group: hydrotherapy (group 1), physiotherapy (group 2), and both physiotherapy and hydrotherapy (group 3, control group) of the affected joint. pain intensity of the affected joint in the course of inpatient treatment; secondary outcome: health-related quality of life, joint-specific pain and mobility in the course of the study. Concerning the main outcome, intervention group 1 showed most beneficial effects in the course of inpatient treatment, followed by groups 3 and 2, and also the indirect flexion ability of hip or knee together with the general patient mobility through the "timed up and go" test were mainly improved within group 1 followed by groups 3 and 2. The results of this pilot study demonstrate beneficial effects of hydrotherapy. The study design is feasible. For statistically significant evidence and a robust conclusion of efficacy of Kneipp's hydrotherapy, a larger sample size is necessary. NCT 00950326.

Lateral Wedge Insoles as a Conservative Treatment for Pain in Patients With Medial Knee Osteoarthritis

PubMed Central

Parkes, Matthew J.; Maricar, Nasimah; Lunt, Mark; LaValley, Michael P.; Jones, Richard K.; Segal, Neil A.; Takahashi-Narita, Kayoko; Felson, David T.

2015-01-01

IMPORTANCE There is no consensus regarding the efficacy of lateral wedge insoles as a treatment for pain in medial knee osteoarthritis. OBJECTIVE To evaluate whether lateral wedge insoles reduce pain in patients with medial knee osteoarthritis compared with an appropriate control. DATA SOURCES Databases searched include the Cochrane Central Register of Controlled Trials, EMBASE, AMED, MEDLINE, CINAHL Plus, ScienceDirect, SCOPUS, Web of Science, and BIOSIS from inception to May 2013, with no limits on study date or language. The metaRegister of Controlled Trials and the NHS Evidence website were also searched. STUDY SELECTION Included were randomized trials comparing shoe-based treatments (lateral heel wedge insoles or shoes with variable stiffness soles) aimed at reducing medial knee load, with a neutral or no wedge control condition in patients with painful medial knee osteoarthritis. Studies must have included patient-reported pain as an outcome. DATA EXTRACTION AND SYNTHESIS Trial data were extracted independently by 2 researchers using a standardized form. Risk of bias was assessed using the Cochrane Risk of Bias tool by 2 observers. Eligible studies were pooled using a random-effects approach. MAIN OUTCOME AND MEASURES Change in self-reported knee pain at follow-up. RESULTS Twelve trials met inclusion criteria with a total of 885 participants of whom 502 received lateral wedge treatment. The pooled standardized mean difference (SMD) suggested a favorable association with lateral wedges compared with control (SMD, −0.47; 95% CI, −0.80 to −0.14); however, substantial heterogeneity was present (I2 = 82.7%). This effect size represents an effect of −2.12 points on the 20-point Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale. Larger trials with a lower risk of bias suggested a null association. Meta-regression analyses showed that higher effect sizes (unstandardized β, 1.07 [95% CI, 0.28 to 1.87] for trials using a no treatment control) were seen in trials using a no wedge treatment control group (n = 4 trials; SMD, −1.20 [95% CI, −2.09 to −0.30]) and lower effect sizes (unstandardized β, 0.26 [95% CI, 0.002 to 0.52] for each bias category deemed low risk) when the study method was deemed at low risk of bias. Among trials in which the control treatment was a neutral insole (n = 7), lateral wedges showed no association (SMD, −0.03 [95% CI, −0.18 to 0.12] on WOMAC; this represents an effect of −0.12 points), and results showed little heterogeneity (I2 = 7.1%). CONCLUSIONS AND RELEVANCE Although meta-analytic pooling of all studies showed a statistically significant association between use of lateral wedges and lower pain in medial knee osteoarthritis, restriction of studies to those using a neutral insole comparator did not show a significant or clinically important association. These findings do not support the use of lateral wedges for this indication. PMID:23989797

Massage therapy for children with autism spectrum disorders: a systematic review.

PubMed

Lee, Myeong Soo; Kim, Jong-In; Ernst, Edzard

2011-03-01

We aimed to assess the effectiveness of massage as a treatment option for autism. We searched the following electronic databases using the time of their inception through March 2010: MEDLINE, AMED, CINAHL, EMBASE, PsycINFO, Health Technology Assessment, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Psychology and Behavioral Sciences Collection, 6 Korean medical databases (KSI, DBpia, KISTEP, RISS, KoreaMed, and National Digital Library), China Academic Journal (through China National Knowledge Infrastructure), and 3 Japanese medical databases (Journal@rchive, Science Links Japan, and Japan Science & Technology link). The search phrase used was "(massage OR touch OR acupressure) AND (autistic OR autism OR Asperger's syndrome OR pervasive developmental disorder)." The references in all located articles were also searched. No language restrictions were imposed. Prospective controlled clinical studies of any type of massage therapy for autistic patients were included. Trials in which massage was part of a complex intervention were also included. Case studies, case series, qualitative studies, uncontrolled trials, studies that failed to provide detailed results, and trials that compared one type of massage with another were excluded. All articles were read by 2 independent reviewers (M.S.L. and J-I.K.), who extracted data from the articles according to predefined criteria. Risk of bias was assessed using the Cochrane classification. Of 132 articles, only 6 studies met our inclusion criteria. One randomized clinical trial found that massage plus conventional language therapy was superior to conventional language therapy alone for symptom severity (P < .05) and communication attitude (P < .01). Two randomized clinical trials reported a significant benefit of massage for sensory profile (P < .01), adaptive behavior (P < .05), and language and social abilities (P < .01) as compared with a special education program. The fourth randomized clinical trial showed beneficial effects of massage for social communication (P < .05). Two nonrandomized controlled clinical trials suggested that massage therapy is effective. However, all of the included trials have high risk of bias. The main limitations of the included studies were small sample sizes, predefined primary outcome measures, inadequate control for nonspecific effects, and a lack of power calculations or adequate follow-up. Limited evidence exists for the effectiveness of massage as a symptomatic treatment of autism. Because the risk of bias was high, firm conclusions cannot be drawn. Future, more rigorous randomized clinical trials seem to be warranted. © Copyright 2011 Physicians Postgraduate Press, Inc.

Worksite Environmental Interventions for Obesity Prevention and Control: Evidence from Group Randomized Trials.

PubMed

Fernandez, Isabel Diana; Becerra, Adan; Chin, Nancy P

2014-06-01

Worksites provide multiple advantages to prevent and treat obesity and to test environmental interventions to tackle its multiple causal factors. We present a literature review of group-randomized and non-randomized trials that tested worksite environmental, multiple component interventions for obesity prevention and control paying particular attention to the conduct of formative research prior to intervention development. The evidence on environmental interventions on measures of obesity appears to be strong since most of the studies have a low (4/8) and unclear (2/8) risk of bias. Among the studies reviewed whose potential risk of bias was low, the magnitude of the effect was modest and sometimes in the unexpected direction. None of the four studies describing an explicit formative research stage with clear integration of findings into the intervention was able to demonstrate an effect on the main outcome of interest. We present alternative explanation for the findings and recommendations for future research.

Evidence-based pharmacological treatment of substance use disorders and pathological gambling.

PubMed

van den Brink, Wim

2012-03-01

This review summarizes our current knowledge of the pharmacological treatment of substance use disorders and pathological gambling using data mainly from randomized controlled trials and meta-analyses regarding these randomized controlled trials. The review is restricted to the selection of first and second line pharmacological treatments for smoking, alcohol dependence, opioid dependence, cocaine dependence, cannabis dependence and pathological gambling. It is concluded that great progress has been made in the last three decades and that currently evidence-based pharmacological treatments are available for smoking cessation, alcohol and opioid dependence and pathological gambling. At the same time a series of existing and new pharmacological compounds are being tested in cocaine and cannabis dependence. The review concludes with a summary of additional strategies to increase the effect size of already available pharmacological interventions, including polypharmacy, combining pharmacotherapy with psychotherapy and psychosocial support, and improved patient-treatment matching.

Cognitive rigidity in unipolar depression and obsessive compulsive disorder: examination of task switching, Stroop, working memory updating and post-conflict adaptation.

PubMed

Meiran, Nachshon; Diamond, Gary M; Toder, Doron; Nemets, Boris

2011-01-30

Obsessive compulsive disorder (OCD) and depressive rumination are both characterized by cognitive rigidity. We examined the performance of 17 patients (9 suffering from unipolar depression [UD] without OCD, and 8 suffering from OCD without UD), and 17 control participants matched on age, gender, language and education, on a battery covering the four main executive functions. Results indicated that, across both disorders, patients required more trials to adjust to single-task conditions after experiencing task switching, reflecting slow disengagement from switching mode, and showed abnormal post-conflict adaptation of processing mode following high conflict Stroop trials in comparison to controls. Rumination, which was elevated in UD and not in OCD, was associated with poor working memory updating and less task preparation. The results show that OCD and UD are associated with similar cognitive rigidity in the presently tested paradigms. Copyright © 2010 Elsevier Ltd. All rights reserved.

Massage therapy decreases pain and perceived fatigue after long-distance Ironman triathlon: a randomised trial.

PubMed

Nunes, Guilherme S; Bender, Paula Urio; de Menezes, Fábio Sprada; Yamashitafuji, Igor; Vargas, Valentine Zimermann; Wageck, Bruna

2016-04-01

Can massage therapy reduce pain and perceived fatigue in the quadriceps of athletes after a long-distance triathlon race (Ironman)? Randomised, controlled trial with concealed allocation, intention-to-treat analysis and blinded outcome assessors. Seventy-four triathlon athletes who completed an entire Ironman triathlon race and whose main complaint was pain in the anterior portion of the thigh. The experimental group received massage to the quadriceps, which was aimed at recovery after competition, and the control group rested in sitting. The outcomes were pain and perceived fatigue, which were reported using a visual analogue scale, and pressure pain threshold at three points over the quadriceps muscle, which was assessed using digital pressure algometry. The experimental group had significantly lower scores than the control group on the visual analogue scale for pain (MD -7 mm, 95% CI -13 to -1) and for perceived fatigue (MD -15 mm, 95% CI -21 to -9). There were no significant between-group differences for the pressure pain threshold at any of the assessment points. Massage therapy was more effective than no intervention on the post-race recovery from pain and perceived fatigue in long-distance triathlon athletes. Brazilian Registry of Clinical Trials, RBR-4n2sxr. Copyright © 2016 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Risk factors for proper oral language development in children: a systematic literature review.

PubMed

Gurgel, Léia Gonçalves; Vidor, Deisi Cristina Gollo Marques; Joly, Maria Cristina Rodrigues Azevedo; Reppold, Caroline Tozzi

2014-01-01

To conduct a systematic review of literature production related to risk factors for proper oral language development in children. We used the terms "child language," "risk factors," and "randomized controlled trial" in MEDLINE (accessed via PubMed), Lilacs, SciELO, and The Cochrane Library from January 1980 to February 2014. Randomized controlled trials involving the study of some risk factors related to child language were included. Works with individuals who were not from the age group 0-12 years and presented no reliable definition of risk factors were excluded. The research findings were classified according to their theme and categorized methodological aspects. We observed the lack of a standardized list of risk factors for language available for health professionals. The main risk factor mentioned was family dynamics, followed by interaction with parents, immediate social environment, and encouragement given to the child in the first years of life. It was also observed that organic hazards such as brain injury, persistent otitis media, and cardiac surgery, besides the type of food and parental counseling, may be related to language disorders. More randomized controlled trials involving the evaluation of risk factors for child language and the creation of further studies involving children above 6 years of age and males are needed.

Hydrotherapy as a recovery strategy after exercise: a pragmatic controlled trial.

PubMed

Cuesta-Vargas, Antonio I; Travé-Mesa, Alvaro; Vera-Cabrera, Alberto; Cruz-Terrón, Dario; Castro-Sánchez, Adelaida M; Fernández-de-las-Peñas, Cesar; Arroyo-Morales, Manuel

2013-07-18

Our aim was to evaluate the recovery effects of hydrotherapy after aerobic exercise in cardiovascular, performance and perceived fatigue. A pragmatic controlled repeated measures; single-blind trial was conducted. Thirty-four recreational sportspeople visited a Sport-Centre and were assigned to a Hydrotherapy group (experimental) or rest in a bed (control) after completing a spinning session. Main outcomes measures including blood pressure, heart rate, handgrip strength, vertical jump, self-perceived fatigue, and body temperature were assessed at baseline, immediately post-exercise and post-recovery. The hypothesis of interest was the session*time interaction. The analysis revealed significant session*time interactions for diastolic blood pressure (P=0.031), heart rate (P=0.041), self perceived fatigue (P=0.046), and body temperature (P=0.001); but not for vertical jump (P=0.437), handgrip (P=0.845) or systolic blood pressure (P=0.266). Post-hoc analysis revealed that hydrotherapy resulted in recovered heart rate and diastolic blood pressure similar to baseline values after the spinning session. Further, hydrotherapy resulted in decreased self-perceived fatigue after the spinning session. Our results support that hydrotherapy is an adequate strategy to facilitate cardiovascular recovers and perceived fatigue, but not strength, after spinning exercise. ClinicalTrials.gov Identifier: NCT01765387.

Barriers to the sustainability of an intervention designed to improve patient engagement within NHS mental health rehabilitation units: a qualitative study nested within a randomised controlled trial.

PubMed

Lean, Melanie; Leavey, Gerard; Killaspy, Helen; Green, Nicholas; Harrison, Isobel; Cook, Sarah; Craig, Thomas; Holloway, Frank; Arbuthnott, Maurice; King, Michael

2015-09-02

We undertook a cluster randomised controlled trial to assess the effectiveness of a staff training intervention to improve patient engagement in activities in inpatient mental health rehabilitation units. Concurrently, we undertook a qualitative study to investigate the experiences of staff within the intervention units and the contextual issues that may have influenced the effectiveness of the intervention. We conducted focus groups with staff working in the inpatient units that received the intervention, sampled using a maximum variation strategy. The intervention was accepted by staff. However, the skills gained, and changes to the unit's processes and structures that were agreed with the intervention team were not sustained after they left. The main reasons for this were a) external factors (economic recession, resource limitations); b) organisation level factors (lack of senior staff support; competing priorities); c) limitations of the intervention itself (length of intensive training period; reinforcement of skills). This study illustrates some of the inter-related factors which operate at different levels within and outside of NHS organisations that may impact on the success of complex interventions. These factors need to be considered when designing interventions to ensure adequate buy-in from senior staff. Current Controlled Trials ISRCTN25898179 (Registered 23 April 2010).

Individual differences in the efficacy of a short theory of mind intervention for children with autism spectrum disorder: a randomized controlled trial.

PubMed

Hoddenbach, Elske; Koot, Hans M; Clifford, Pamela; Gevers, Carolien; Clauser, Cassandra; Boer, Frits; Begeer, Sander

2012-11-09

Having a 'theory of mind', or having the ability to attribute mental states to oneself or others, is considered one of the most central domains of impairment among children with an autism spectrum disorder (ASD). Many interventions focus on improving theory of mind skills in children with ASD. Nonetheless, the empirical evidence for the effect of these interventions is limited. The main goal of this study is to examine the effectiveness of a short theory of mind intervention for children with ASD. A second objective is to determine which subgroups within the autism spectrum profit most from the intervention. This study is a randomized controlled trial. One hundred children with ASD, aged 7 to 12 years will be randomly assigned to an intervention or a waiting list control group. Outcome measures include the completion of theory of mind and emotion understanding tasks, and parent and teacher questionnaires on children's social skills. Follow-up data for the intervention group will be collected 6 months after the interventions. This study evaluates the efficacy of a theory of mind intervention for children with ASD. Hypotheses, strengths, and limitations of the study are discussed. Netherlands Trial Register NTR2327.

Task-Based Mirror Therapy Augmenting Motor Recovery in Poststroke Hemiparesis: A Randomized Controlled Trial.

PubMed

Arya, Kamal Narayan; Pandian, Shanta; Kumar, Dharmendra; Puri, Vinod

2015-08-01

To establish the effect of the task-based mirror therapy (TBMT) on the upper limb recovery in stroke. A pilot, randomized, controlled, assessor-blinded trial was conducted in a rehabilitation institute. A convenience sample of 33 poststroke (mean duration, 12.5 months) hemiparetic subjects was randomized into 2 groups (experimental, 17; control, 16). The subjects were allocated to receive either TBMT or standard motor rehabilitation-40 sessions (5/week) for a period of 8 weeks. The TBMT group received movements using various goal-directed tasks and a mirror box. The movements were performed by the less-affected side superimposed on the affected side. The main outcome measures were Brunnstrom recovery stage (BRS) and Fugl-Meyer assessment (FMA)-FMA of upper extremity (FMA-UE), including upper arm (FMA-UA) and wrist-hand (FMA-WH). The TBMT group exhibited highly significant improvement on mean scores of FMA-WH (P < .001) and FMA-UE (P < .001) at postassessment in comparison to the control group. Furthermore, there was a 12% increase in the number of subjects at BRS stage 5 (out of synergy movement) in the experimental group as compared to a 0% rise at the same stage in the control group. This pilot trial confirmed the role of TBMT in improving the wrist-hand motor recovery in poststroke hemiparesis. MT using tasks may be used as an adjunct in stroke rehabilitation. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Wheeze as an Adverse Event in Pediatric Vaccine and Drug Randomized Controlled Trials: A Systematic Review

PubMed Central

Marangu, Diana; Kovacs, Stephanie; Walson, Judd; Bonhoeffer, Jan; Ortiz, Justin R.; John-Stewart, Grace; Horne, David J.

2016-01-01

Introduction Wheeze is an important sign indicating a potentially severe adverse event in vaccine and drug trials, particularly in children. However, there are currently no consensus definitions of wheeze or associated respiratory compromise in randomized controlled trials (RCTs). Objective To identify definitions and severity grading scales of wheeze as an adverse event in vaccine and drug RCTs enrolling children <5 years and to determine their diagnostic performance based on sensitivity, specificity and inter-observer agreement. Methods We performed a systematic review of electronic databases and reference lists with restrictions for trial settings, English language and publication date ≥ 1970. Wheeze definitions and severity grading were abstracted and ranked by a diagnostic certainty score based on sensitivity, specificity and inter-observer agreement. Results Of 1,205 articles identified using our broad search terms, we identified 58 eligible trials conducted in 38 countries, mainly in high-income settings. Vaccines made up the majority (90%) of interventions, particularly influenza vaccines (65%). Only 15 trials provided explicit definitions of wheeze. Of 24 studies that described severity, 11 described wheeze severity in the context of an explicit wheeze definition. The remaining 13 studies described wheeze severity where wheeze was defined as part of a respiratory illness or a wheeze equivalent. Wheeze descriptions were elicited from caregiver reports (14%), physical examination by a health worker (45%) or a combination (41%). There were 21/58 studies in which wheeze definitions included combined caregiver report and healthcare worker assessment. The use of these two methods appeared to have the highest combined sensitivity and specificity. Conclusion Standardized wheeze definitions and severity grading scales for use in pediatric vaccine or drug trials are lacking. Standardized definitions of wheeze are needed for assessment of possible adverse events as new vaccines and drugs are evaluated. PMID:26319071

Task-related enhancement in corticomotor excitability during haptic sensing with the contra- or ipsilateral hand in young and senior adults.

PubMed

Master, Sabah; Tremblay, François

2012-03-14

Haptic sensing with the fingers represents a unique class of manipulative actions, engaging motor, somatosensory and associative areas of the cortex while requiring only minimal forces and relatively simple movement patterns. Using transcranial magnetic stimulation (TMS), we investigated task-related changes in motor evoked potential (MEP) amplitude associated with unimanual haptic sensing in two related experiments. In Experiment I, we contrasted changes in the excitability of the hemisphere controlling the task hand in young and old adults under two trial conditions, i.e. when participants either touched a fine grating (smooth trials) or touched a coarse grating to detect its groove orientation (grating trials). In Experiment II, the same contrast between tasks was performed but with TMS applied over the hemisphere controlling the resting hand, while also addressing hemispheric (right vs. left) and age differences. In Experiment I, a main effect of trial type on MEP amplitude was detected (p = 0.001), MEPs in the task hand being ~50% larger during grating than smooth trials. No interaction with age was detected. Similar results were found for Experiment II, trial type having a large effect on MEP amplitude in the resting hand (p < 0.001) owing to selective increase in MEP size (~2.6 times greater) for grating trials. No interactions with age or side (right vs. left) were detected. Collectively, these results indicate that adding a haptic component to a simple unilateral finger action can elicit robust corticomotor facilitation not only in the working hemisphere but also in the opposite hemisphere. The fact that this facilitation seems well preserved with age, when task difficulty is adjusted, has some potential clinical implications.

PLUTO trial protocol: percutaneous shunting for lower urinary tract obstruction randomised controlled trial.

PubMed

Kilby, Mark; Khan, Khalid; Morris, Katie; Daniels, Jane; Gray, Richard; Magill, Laura; Martin, Bill; Thompson, Peter; Alfirevic, Zarko; Kenny, Simon; Bower, Sarah; Sturgiss, Stephen; Anumba, Dilly; Mason, Gerald; Tydeman, Graham; Soothill, Peter; Brackley, Karen; Loughna, Pamela; Cameron, Alan; Kumar, Sailesh; Bullen, Phil

2007-07-01

The primary objective is to determine whether intrauterine vesicoamniotic shunting for fetal bladder outflow obstruction, compared with conservative, noninterventional care, improves prenatal and perinatal mortality and renal function. The secondary objectives are to determine if shunting for fetal bladder outflow obstruction improves perinatal morbidity, to determine if improvement in outcomes is related to prognostic assessment at diagnosis and, if possible, derive a prognostic risk index and to determine the safety and long-term efficacy of shunting. A multicentre randomised controlled trial (RCT). Fetal medicine units. Pregnant women with singleton, male fetus with isolated lower urinary tract obstruction (LUTO). Following ultrasound diagnosis of LUTO in a male fetus and exclusion of other structural and chromosomal anomalies, participation in the trial will be discussed with the mother and written information given. Consent for participation in the trial will be taken and the mother randomised via the internet to either insertion of a vesicoamniotic shunt or expectant management. During pregnancy, both groups will be followed with regular ultrasound scans looking at viability, renal measurements and amniotic fluid volume. Following delivery, babies will be followed up by paediatric nephrologists/urologists at 4-6 weeks, 12 months and 3 and 5 years to assess renal function via serum creatinine, renal ultrasound and need for dialysis/transplant. The main outcome measures will be perinatal mortality rates and renal function at 4-6 weeks and 12 months measured via serum creatinine, renal ultrasound and need for dialysis/transplant. Wellbeing of Women. ESTIMATED COMPLETION DATE: September 2010. TRIAL ALGORITHM: [flowchart: see text].

Cost-effectiveness of multidisciplinary management of Tinnitus at a specialized Tinnitus centre

PubMed Central

Cima, Rilana; Joore, Manuela; Maes, Iris; Scheyen, Dyon; Refaie, Amr El; Baguley, David M; Vlaeyen, Johan WS; Anteunis, Lucien

2009-01-01

Background Tinnitus is a common chronic health condition that affects 10% to 20% of the general population. Among severe sufferers it causes disability in various areas. As a result of the tinnitus, quality of life is often impaired. At present there is no cure or uniformly effective treatment, leading to fragmentized and costly tinnitus care. Evidence suggests that a comprehensive multidisciplinary approach in treating tinnitus is effective. The main objective of this study is to examine the effectiveness, costs, and cost-effectiveness of a comprehensive treatment provided by a specialized tinnitus center versus usual care. This paper describes the study protocol. Methods/Design In a randomized controlled clinical trial 198 tinnitus patients will be randomly assigned to a specialized tinnitus care group or a usual care group. Adult tinnitus sufferers referred to the audiological centre are eligible. Included patients will be followed for 12 months. Primary outcome measure is generic quality of life (measured with the Health Utilities Index Mark III). Secondary outcomes are severity of tinnitus, general distress, tinnitus cognitions, tinnitus specific fear, and costs. Based on health state utility outcome data the number of patients to include is 198. Economic evaluation will be performed from a societal perspective. Discussion This is, to our knowledge, the first randomized controlled trial that evaluates a comprehensive treatment of tinnitus and includes a full economic evaluation from a societal perspective. If this intervention proves to be effective and cost-effective, implementation of this intervention is considered and anticipated. Trial Registration The trial has been registered at ClinicalTrial.gov. The trial registration number is NCT00733044 PMID:19210767

The Design of Clinical Trials in Portal Hypertension.

PubMed

Abraldes, Juan G; Garcia-Tsao, Guadalupe

2017-02-01

Portal hypertension (PH) is the main consequence of cirrhosis and is responsible for the majority of its complications. Gastroesophageal varices and variceal hemorrhage are direct consequences of PH; therefore, most clinical trials in PH have been directed toward treating or preventing variceal hemorrhage. However, varices and variceal hemorrhage are not isolated events; they must be considered in the context of the presence (or absence) of other complications of cirrhosis/PH. Cirrhosis progresses across different stages, each with a different prognosis and pathophysiology and hence different therapeutic targets. In this review, the authors discuss the design of proof-of-concept studies for the assessment of new drugs for the treatment of PH, that are mainly based on the drug's ability to reduce the hepatic venous pressure gradient. They further discuss the design of studies with clinical endpoints in the context of each stage of cirrhosis, specifically targets of therapy, optimal therapies in the control arm, risk stratification, and primary outcome. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Deliberate self harm: systematic review of efficacy of psychosocial and pharmacological treatments in preventing repetition

PubMed Central

Hawton, Keith; Arensman, Ella; Townsend, Ellen; Bremner, Sandy; Feldman, Eleanor; Goldney, Robert; Gunnell, David; Hazell, Philip; van Heeringen, Kees; House, Allan; Owens, David; Sakinofsky, Isaac; Träskman-Bendz, Lil

1998-01-01

Objective: To identify and synthesise the findings from all randomised controlled trials that have examined the effectiveness of treatments of patients who have deliberately harmed themselves. Design: Systematic review of randomised controlled trials of psychosocial and physical treatments. Studies categorised according to type of treatment. When there was more than one investigation in a particular category a summary odds ratio was estimated with the Mantel-Haenszel method. Setting: Randomised trials available in electronic databases in 1996, in the Cochrane Controlled Trials Register in 1997, and from hand searching of journals to 1997. Subjects: Patients who had deliberately harmed themselves shortly before entry into the trials with information on repetition of behaviour. The included trials comprised 2452 randomised participants with outcome data. Main outcome measure: Repetition of self harm. Results: 20 trials reported repetition of self harm as an outcome variable, classified into 10 categories. Summary odds ratio (all for comparison with standard aftercare) indicated reduced repetition for problem solving therapy (0.73; 95% confidence interval 0.45 to 1.18) and for provision of an emergency contact card in addition to standard care (0.45; 0.19 to 1.07). The summary odds ratios were 0.83 (0.61 to 1.14) for trials of intensive aftercare plus outreach and 1.19 (0.53 to 2.67) for antidepressant treatment compared with placebo. Significantly reduced rates of further self harm were observed for depot flupenthixol versus placebo in multiple repeaters (0.09; 0.02 to 0.50) and for dialectical behaviour therapy versus standard aftercare (0.24; 0.06 to 0.93). Conclusion: There remains considerable uncertainty about which forms of psychosocial and physical treatments of patients who harm themselves are most effective. Further larger trials of treatments are needed. Key messages A systematic review of the effectiveness of psychosocial and drug treatments of patients who deliberately harm themselves identified 20 randomised controlled trials in which repetition of self harm was reported as an outcome Promising results were found for problem solving therapy, provision of a card to allow patients to make emergency contact with services, depot flupenthixol for recurrent self harm, and long term psychological therapy for female patients with borderline personality disorder and recurrent self harm Assertive outreach can help to keep patients in treatment Nearly all the trials included too few patients to detect clinically significant differences in repetition of self harm, and even synthesis of results by meta-analysis did not have the power to detect such differences There is an urgent need for large trials of promising therapies for this substantial clinical population PMID:9703526

Physiotherapy Post Lumbar Discectomy: Prospective Feasibility and Pilot Randomised Controlled Trial

PubMed Central

Rushton, Alison; Goodwin, Peter C.

2015-01-01

Objectives To evaluate: acceptability and feasibility of trial procedures; distribution of scores on the Roland Morris Disability Questionnaire (RMDQ, planned primary outcome); and efficient working of trial components. Design and Setting A feasibility and external pilot randomised controlled trial (ISRCTN33808269, assigned 10/12/2012) was conducted across 2 UK secondary care outpatient physiotherapy departments associated with regional spinal surgery centres. Participants Consecutive consenting patients aged >18 years; post primary, single level, lumbar discectomy. Interventions Participants were randomised to either 1:1 physiotherapy outpatient management including patient leaflet, or patient leaflet alone. Main Outcome Measures Blinded assessments were made at 4 weeks post surgery (baseline) and 12 weeks post baseline (proposed primary end point). Secondary outcomes included: Global Perceived Effect, back/leg pain, straight leg raise, return to work/function, quality of life, fear avoidance, range of movement, medication, re-operation. Results At discharge, 110 (44%) eligible patients gave consent to be contacted. 59 (54%) patients were recruited. Loss to follow up was 39% at 12 weeks, with one site contributing 83% losses. Mean (SD) RMDQ was 10.07 (5.58) leaflet and 10.52 (5.94) physiotherapy/leaflet at baseline; and 5.37 (4.91) leaflet and 5.53 (4.49) physiotherapy/leaflet at 12 weeks. 5.1% zero scores at 12 weeks illustrated no floor effect. Sensitivity to change was assessed at 12 weeks with mean (SD) change -4.53 (6.41), 95%CI -7.61 to -1.44 for leaflet; and -6.18 (5.59), 95%CI -9.01 to -3.30 for physiotherapy/leaflet. RMDQ mean difference (95%CI) between change from baseline to twelve weeks was 1.65(-2.46 to 5.75). Mean difference (95%CI) between groups at 12 weeks was -0.16 (-3.36 to 3.04). Participant adherence with treatment was good. No adverse events were reported. Conclusions Both interventions were acceptable, and it is promising that they both demonstrated a trend in reducing disability in this population. A randomised controlled trial, using a different trial design, is needed to ascertain the effectiveness of combining the interventions into a stepped care intervention and comparing to a no intervention arm. Findings will guide design changes for an adequately powered randomised controlled trial, using RMDQ as the primary outcome. Trial Registration ISRCTN registry 33808269 PMID:26562660

Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease

PubMed Central

Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Hambleton, Ian R; Cho, Gavin

2016-01-01

Background Sickle cell disease is a genetic haemoglobin disorder, which can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Sickle cell disease is one of the most common severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. The two most common chronic chest complications due to sickle cell disease are pulmonary hypertension and chronic sickle lung disease. These complications can lead to morbidity (such as reduced exercise tolerance) and increased mortality. This is an update of a Cochrane review first published in 2011 and updated in 2014. Objectives We wanted to determine whether trials involving people with sickle cell disease that compare regular long-term blood transfusion regimens with standard care, hydroxycarbamide (hydroxyurea) any other drug treatment show differences in the following: mortality associated with chronic chest complications; severity of established chronic chest complications; development and progression of chronic chest complications; serious adverse events. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register. Date of the last search: 25 April 2016. We also searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 26 January 2016), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 26 January 2016. Selection criteria We included randomised controlled trials of people of any age with one of four common sickle cell disease genotypes, i.e. Hb SS, Sß0, SC, or Sß+ that compared regular red blood cell transfusion regimens (either simple or exchange transfusions) to hydroxycarbamide, any other drug treatment, or to standard care that were aimed at reducing the development or progression of chronic chest complications (chronic sickle lung and pulmonary hypertension). Data collection and analysis We used the standard methodological procedures expected by Cochrane. Main results No studies matching the selection criteria were found. Authors’ conclusions There is a need for randomised controlled trials looking at the role of long-term transfusion therapy in pulmonary hypertension and chronic sickle lung disease. Due to the chronic nature of the conditions, such trials should aim to use a combination of objective and subjective measures to assess participants repeatedly before and after the intervention. PMID:27198469

The Efficacy of a Web-Based Screening and Brief Intervention for Reducing Alcohol Consumption Among Japanese Problem Drinkers: Protocol for a Single-Blind Randomized Controlled Trial.

PubMed

Hamamura, Toshitaka; Suganuma, Shinichiro; Takano, Ayumi; Matsumoto, Toshihiko; Shimoyama, Haruhiko

2018-05-30

The literature shows that computer-delivered interventions with personalized normative feedback can reduce problem drinking for up to 6 months in the West. Meanwhile, no studies have been conducted to examine the effects of such interventions among Japanese problem drinkers. Possible moderators associated with effectiveness of the intervention need to be also explored. The purpose of this study is to conduct a trial and examine the efficacy of a brief intervention with personal normative feedback and psychoeducation on several measures of alcohol consumption among Japanese problem drinkers. Additionally, this study will examine whether the level of alcohol use disorder and beliefs about the physical and psychological outcomes of drinking moderate the effect of the intervention on outcome measures. This study will conduct a single-blind, 2-armed randomized controlled trial. Japanese adults with an Alcohol Use Disorder Identification Test score of 8 or higher will be enrolled in the trial. Participants allocated to the intervention group will receive the intervention immediately after the baseline measurements, and participants allocated to the waitlist group will receive the intervention at the end of the trial. Outcome measures include drinking quantity, drinking frequency, and alcohol-related consequences. Follow-up assessment will take place at 1 month, 2 months, and 6 months following the baseline measurement. The authors will not know the group allocation during trial. The authors will plan to collect a sample of 600 participants. Mixed-effect analyses of variance will be used to examine the main effects of condition, the main effects of time, and the interaction effects between condition and time on outcome variables. Enrollment for the trial began on January 6, 2018 and data are expected to be available by August 2018. This study will contribute to the literature by demonstrating the efficacy of Web-based screenings and brief interventions among Japanese problem drinkers and indicating several possible moderators between the intervention and outcomes. This type of Web-based brief intervention has the possibility of being implemented in Japanese schools and workplaces as a prevention tool. UMIN Clinical Trials Registry R000034388; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi? recptno=R000034388 (Archived by WebCite at http://www.webcitation.org/6xmOoTfTI). RR1-10.2196/10650. ©Toshitaka Hamamura, Shinichiro Suganuma, Ayumi Takano, Toshihiko Matsumoto, Haruhiko Shimoyama. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 30.05.2018.

Randomized controlled drug trials on very elderly subjects: descriptive and methodological analysis of trials published between 1990 and 2002 and comparison with trials on adults.

PubMed

Le Quintrec, Jean-Laurent; Bussy, Caroline; Golmard, Jean-Louis; Hervé, Christian; Baulon, Alain; Piette, François

2005-03-01

Very elderly subjects (VES; aged 80 years or older) constitute a special population as they frequently present multiple diseases (polypathology). Results from trials on general adult populations therefore cannot be extrapolated to VES. We performed a census of randomized controlled trials (RCT) on VES published between 1990 and 2002, and carried out a descriptive and methodological analysis of these RCT/VES, comparing them with matched RCT on general adult populations (control RCT, RCT/C). We searched for RCT/VES in two international databases (EMBASE and MEDLINE) and then manually. RCT/C were matched to RCT/VES for disease area and year of publication. The methodological quality of each RCT was assessed with Chalmers' scale. We identified 84 RCT/VES, 63 of which were conclusive and 21, inconclusive. Subjects were institutionalized in 48 RCT, and community dwelling in 11 RCT (unspecified in 25 RCT). Efficacy was the main criterion in 75 RCT; tolerance in 9 RCT. Twenty-six RCT were published by geriatrics journals, and 58 by general medical journals. The RCT/VES covered most of the disease areas of geriatrics. The 84 RCT/VES had a mean methodological quality score of 0.578 +/- 0.157. The matched 84 RCT/C had a mean methodological quality score of 0.592 +/- 0.116 (p = .466). The methodological quality score of RCT/VES increased with the number of included subjects (p = .004) and the year of publication (p = .001). The methodological quality of RCT/VES is equivalent to that of RCT in general adult populations. Nevertheless, RCT/VES remain very scarce, and neglect certain diseases. RCT/VES and the inclusion of very elderly subjects in RCT on adults should be strongly encouraged.

Levosimendan for Perioperative Cardioprotection: Myth or Reality?

PubMed

Santillo, Elpidio; Migale, Monica; Massini, Carlo; Incalzi, Raffaele Antonelli

2018-03-21

Levosimendan is a calcium sensitizer drug causing increased contractility in the myocardium and vasodilation in the vascular system. It is mainly used for the therapy of acute decompensated heart failure. Several studies on animals and humans provided evidence of the cardioprotective properties of levosimendan including preconditioning and anti-apoptotic. In view of these favorable effects, levosimendan has been tested in patients undergoing cardiac surgery for the prevention or treatment of low cardiac output syndrome. However, initial positive results from small studies have not been confirmed in three recent large trials. To summarize levosimendan mechanisms of action and clinical use and to review available evidence on its perioperative use in cardiac surgery setting. We searched two electronic medical databases for randomized controlled trials studying levosimendan in cardiac surgery patients, ranging from January 2000 to August 2017. Meta-analyses, consensus documents and retrospective studies were also reviewed. In the selected interval of time, 54 studies on the use of levosimendan in heart surgery have been performed. Early small size studies and meta-analyses have suggested that perioperative levosimendan infusion could diminish mortality and other adverse outcomes (i.e. intensive care unit stay and need for inotropic support). Instead, three recent large randomized controlled trials (LEVO-CTS, CHEETAH and LICORN) showed no significant survival benefits from levosimendan. However, in LEVO-CTS trial, prophylactic levosimendan administration significantly reduced the incidence of low cardiac output syndrome. Based on most recent randomized controlled trials, levosimendan, although effective for the treatment of acute heart failure, can't be recommended as standard therapy for the management of heart surgery patients. Further studies are needed to clarify whether selected subgroups of heart surgery patients may benefit from perioperative levosimendan infusion. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

What is the evidence for rest, ice, compression, and elevation therapy in the treatment of ankle sprains in adults?

PubMed

van den Bekerom, Michel P J; Struijs, Peter A A; Blankevoort, Leendert; Welling, Lieke; van Dijk, C Niek; Kerkhoffs, Gino M M J

2012-01-01

Ankle sprains are common problems in acute medical care. The variation in treatment observed for the acutely injured lateral ankle ligament complex in the first week after the injury suggests a lack of evidence-based management strategies for this problem. To analyze the effectiveness of applying rest, ice, compression, and elevation (RICE) therapy begun within 72 hours after trauma for patients in the initial period after ankle sprain. Eligible studies were published original randomized or quasi-randomized controlled trials concerning at least 1 of the 4 subtreatments of RICE therapy in the treatment of acute ankle sprains in adults. MEDLINE, Cochrane Clinical Trial Register, CINAHL, and EMBASE. The lists of references of retrieved publications also were checked manually. We extracted relevant data on treatment outcome (pain, swelling, ankle mobility or range of motion, return to sports, return to work, complications, and patient satisfaction) and assessed the quality of included studies. If feasible, the results of comparable studies were pooled using fixed- or random-effects models. After deduction of the overlaps among the different databases, evaluation of the abstracts, and contact with some authors, 24 potentially eligible trials remained. The full texts of these articles were retrieved and thoroughly assessed as described. This resulted in the inclusion of 11 trials involving 868 patients. The main reason for exclusion was that the authors did not describe a well-defined control group without the intervention of interest. Insufficient evidence is available from randomized controlled trials to determine the relative effectiveness of RICE therapy for acute ankle sprains in adults. Treatment decisions must be made on an individual basis, carefully weighing the relative benefits and risks of each option, and must be based on expert opinions and national guidelines.

A cognitive-behavioral intervention for emotion regulation in adults with high-functioning autism spectrum disorders: study protocol for a randomized controlled trial.

PubMed

Kuroda, Miho; Kawakubo, Yuki; Kuwabara, Hitoshi; Yokoyama, Kazuhito; Kano, Yukiko; Kamio, Yoko

2013-07-23

Adults with high-functioning autism spectrum disorders (ASD) have difficulties in social communication; thus, these individuals have trouble understanding the mental states of others. Recent research also suggests that adults with ASD are unable to understand their own mental states, which could lead to difficulties in emotion-regulation. Some studies have reported the efficacy of cognitive-behavioral therapy (CBT) in improving emotion-regulation among children with ASD. The current study will investigate the efficacy of group-based CBT for adults with ASD. The study is a randomized, waitlist controlled, single-blinded trial. The participants will be 60 adults with ASD; 30 will be assigned to a CBT group and 30 to a waitlist control group. Primary outcome measures are the 20-item Toronto Alexithymia Scale, the Coping Inventory for Stressful Situations, the Motion Picture Mind-Reading task, and an ASD questionnaire. The secondary outcome measures are the Center for Epidemiological Studies Depression Scale, the World Health Organization Quality of Life Scale 26-item version, the Global Assessment of Functioning, State-trait Anxiety Inventory, Social Phobia and Anxiety Inventory, and Liebowitz Social Anxiety Scale. All will be administered during the pre- and post-intervention, and 12 week follow-up periods. The CBT group will receive group therapy over an 8 week period (one session per week) with each session lasting approximately 100 minutes. Group therapy will consist of four or five adults with ASD and two psychologists. We will be using visual materials for this program, mainly the Cognitive Affective Training kit. This trial will hopefully indicate the efficacy of group-based CBT for adults with high- functioning ASD. This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry No. UMIN000006236.

Colorectal adenoma recurrence rates among post-polypectomy patients in the placebo-controlled groups of randomized clinical trials: a meta-analysis

PubMed Central

Shi, Xin; Yang, Zhiping; Wu, Qiong; Fan, Daiming

2017-01-01

Background Evidence regarding the benefit of therapy to prevent the post-polypectomy recurrence of colorectal adenoma is limited. Endoscopic recurrence is the main outcome according to an evaluation of trials involving recurrence prevention. Aim To estimate the recurrence rates of post-polypectomy colorectal adenoma in placebo-controlled arms of randomized clinical trials and to identify the prognostic factors influencing these rates. Methods We combined data from all randomized controlled trials evaluating therapies for colorectal adenoma using placebo from 1988 to 2016. The data were combined in a random-effects model. Primary outcomes were endoscopic adenoma and advanced adenoma recurrence of colorectal adenoma. Results The pooled estimates of the adenoma recurrence rates were 37% (95% confidence interval [CI], 33%-41%; range, 33%-52%) at 1 year, 47% (95% CI, 41%-54%; range, 46%-51%) at 2 years, 41% (95% CI, 33%-48%; range, 20%-61%) at 3 years, 48% (95% CI, 38%-57%; range, 37%-53%) at 4 years, and 60% (95% CI, 52%-68%; range, 48%-68%) at 5 years. The pooled estimates of the advanced adenoma recurrence rates were 10% (95% CI, 6%-15%; range, 7%-13%) at 1 year, 12% (95% CI, 8%-16%; range, 3%-19%) at 3 years, 14% (95% CI, 10%-18%; range, 13%-16%) at 4 years, and 14% (95% CI, 10%-19%; range, 9%-21%) at 5 years. Significant heterogeneity among the randomized clinical trials (P < 0.001) was observed for each recurrence rate. Conclusions This meta-analysis confirms the heterogeneity of recurrence rates among post-polypectomy colorectal adenoma patients who received placebo. No single design variable was identified that might explain the heterogeneity. PMID:28977952

Effect of training and lifting equipment for preventing back pain in lifting and handling: systematic review

PubMed Central

2008-01-01

Objectives To determine whether advice and training on working techniques and lifting equipment prevent back pain in jobs that involve heavy lifting. Data sources Medline, Embase, CENTRAL, Cochrane Back Group’s specialised register, CINAHL, Nioshtic, CISdoc, Science Citation Index, and PsychLIT were searched up to September-November 2005. Review methods The primary search focused on randomised controlled trials and the secondary search on cohort studies with a concurrent control group. Interventions aimed to modify techniques for lifting and handling heavy objects or patients and including measurements for back pain, consequent disability, or sick leave as the main outcome were considered for the review. Two authors independently assessed eligibility of the studies and methodological quality of those included. For data synthesis, we summarised the results of studies comparing similar interventions. We used odds ratios and effect sizes to combine the results in a meta-analysis. Finally, we compared the conclusions of the primary and secondary analyses. Results Six randomised trials and five cohort studies met the inclusion criteria. Two randomised trials and all cohort studies were labelled as high quality. Eight studies looked at lifting and moving patients, and three studies were conducted among baggage handlers or postal workers. Those in control groups received no intervention or minimal training, physical exercise, or use of back belts. None of the comparisons in randomised trials (17 720 participants) yielded significant differences. In the secondary analysis, none of the cohort studies (772 participants) had significant results, which supports the results of the randomised trials. Conclusions There is no evidence to support use of advice or training in working techniques with or without lifting equipment for preventing back pain or consequent disability. The findings challenge current widespread practice of advising workers on correct lifting technique. PMID:18244957

Probiotics for Prevention of Atopy and Food Hypersensitivity in Early Childhood: A PRISMA-Compliant Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Zhang, Guo-Qiang; Hu, Hua-Jian; Liu, Chuan-Yang; Zhang, Qiao; Shakya, Shristi; Li, Zhong-Yue

2016-02-01

Most studies investigated probiotics on food hypersensitivity, not on oral food challenge confirmed food allergy in children. The authors systematically reviewed the literature to investigate whether probiotic supplementation prenatally and/or postnatally could reduce the risk of atopy and food hypersensitivity in young children.PubMed, Embase, the Cochrane Central Register of Controlled Trials, and 4 main Chinese literature databases (Wan Fang, VIP, China National Knowledge Infrastructure, and SinoMed) were searched for randomized controlled trials regarding the effect of probiotics on the prevention of allergy in children. The last search was conducted on July 11, 2015.Seventeen trials involving 2947 infants were included. The first follow-up studies were analyzed. Pooled analysis indicated that probiotics administered prenatally and postnatally could reduce the risk of atopy (relative risk [RR] 0.78; 95% confidence interval [CI] 0.66-0.92; I = 0%), especially when administered prenatally to pregnant mother and postnatally to child (RR 0.71; 95% CI 0.57-0.89; I = 0%), and the risk of food hypersensitivity (RR 0.77; 95% CI 0.61-0.98; I = 0%). When probiotics were administered either only prenatally or only postnatally, no effects of probiotics on atopy and food hypersensitivity were observed.Probiotics administered prenatally and postnatally appears to be a feasible way to prevent atopy and food hypersensitivity in young children. The long-term effects of probiotics, however, remain to be defined in the follow-up of existing trials. Still, studies on probiotics and confirmed food allergy, rather than surrogate measure of food hypersensitivity, are warranted.

Reducing Communication Delays and Improving Quality of Care with a Tuberculosis Laboratory Information System in Resource Poor Environments: A Cluster Randomized Controlled Trial

PubMed Central

Blaya, Joaquín A.; Shin, Sonya S.; Yagui, Martin; Contreras, Carmen; Cegielski, Peter; Yale, Gloria; Suarez, Carmen; Asencios, Luis; Bayona, Jaime; Kim, Jihoon; Fraser, Hamish S. F.

2014-01-01

Background Lost, delayed or incorrect laboratory results are associated with delays in initiating treatment. Delays in treatment for Multi-Drug Resistant Tuberculosis (MDR-TB) can worsen patient outcomes and increase transmission. The objective of this study was to evaluate the impact of a laboratory information system in reducing delays and the time for MDR-TB patients to culture convert (stop transmitting). Methods Setting: 78 primary Health Centers (HCs) in Lima, Peru. Participants lived within the catchment area of participating HCs and had at least one MDR-TB risk factor. The study design was a cluster randomized controlled trial with baseline data. The intervention was the e-Chasqui web-based laboratory information system. Main outcome measures were: times to communicate a result; to start or change a patient's treatment; and for that patient to culture convert. Results 1671 patients were enrolled. Intervention HCs took significantly less time to receive drug susceptibility test (DST) (median 11 vs. 17 days, Hazard Ratio 0.67 [0.62–0.72]) and culture (5 vs. 8 days, 0.68 [0.65–0.72]) results. The time to treatment was not significantly different, but patients in intervention HCs took 16 days (20%) less time to culture convert (p = 0.047). Conclusions The eChasqui system reduced the time to communicate results between laboratories and HCs and time to culture conversion. It is now used in over 259 HCs covering 4.1 million people. This is the first randomized controlled trial of a laboratory information system in a developing country for any disease and the only study worldwide to show clinical impact of such a system. Trial Registration ClinicalTrials.gov NCT01201941 PMID:24721980

Patients’ Perspectives of Enrollment in Research Without Consent- The Patients’ Experiences in Emergency Research- ProTECT Study (PEER-ProTECT)

PubMed Central

Dickert, Neal W; Scicluna, Victoria M; Baren, Jill M; Biros, Michelle H; Fleischman, Ross J; Govindarajan, Prasanthi R; Jones, Elizabeth B; Pancioli, Arthur M; Wright, David W; Pentz, Rebecca D

2016-01-01

Objective Research in acute illness often requires an exception from informed consent (EFIC). Few studies have assessed the views of patients enrolled in EFIC trials. This study was designed to assess the views of patients and their surrogates of EFIC enrollment in a randomized, placebo-controlled trial of an investigational agent for traumatic brain injury. Design Interactive interview study. Setting Nested within the Progesterone for the Treatment of Traumatic Brain Injury (ProTECT III) trial, a Phase III randomized controlled trial in acute traumatic brain injury (TBI). Participants Patients and surrogates (for patients incapable of being interviewed) enrolled in ProTECT III under EFIC at 12 sites. Measurements Interviews focused on respondents’ acceptance of EFIC enrollment in ProTECT, use of placebo and randomization, understanding of major study elements, and views regarding regulatory protections. Descriptive statistical analysis was performed; textual data were analyzed thematically. Main Results 85 individuals were interviewed. 84% had positive attitudes toward ProTECT III inclusion. 78% found their inclusion under EFIC acceptable, and 72% found use of EFIC in ProTECT III acceptable in general. Only 2 respondents clearly disagreed with both personal and general EFIC enrollment. The most common concerns (26%) related to absence of consent. 80% and 92% were accepting of placebo use and randomization, respectively. Though there were few black respondents (n=11), they were less accepting of personal EFIC enrollment than white respondents (55% vs 83%, p= 0.0494). Conclusions Acceptance of EFIC in this placebo-controlled trial of an investigational agent was high and exceeded acceptance among community consultation participants. EFIC enrollment appears generally consistent with patients’ preferences. PMID:25574795

Sperm count as a surrogate endpoint for male fertility control.

PubMed

Benda, Norbert; Gerlinger, Christoph

2007-11-30

When assessing the effectiveness of a hormonal method of fertility control in men, the classical approach used for the assessment of hormonal contraceptives in women, by estimating the pregnancy rate or using a life-table analysis for the time to pregnancy, is difficult to apply in a clinical development program. The main reasons are the dissociation of the treated unit, i.e. the man, and the observed unit, i.e. his female partner, the high variability in the frequency of male intercourse, the logistical cost and ethical concerns related to the monitoring of the trial. A reasonable surrogate endpoint of the definite endpoint time to pregnancy is sperm count. In addition to the avoidance of the mentioned problems, trials that compare different treatments are possible with reasonable sample sizes, and study duration can be shorter. However, current products do not suppress sperm production to 100 per cent in all men and the sperm count is only observed with measurement error. Complete azoospermia might not be necessary in order to achieve an acceptable failure rate compared with other forms of male fertility control. Therefore, the use of sperm count as a surrogate endpoint must rely on the results of a previous trial in which both the definitive- and surrogate-endpoint results were assessed. The paper discusses different estimation functions of the mean pregnancy rate (corresponding to the cumulative hazard) that are based on the results of sperm count trial and a previous trial in which both sperm count and time to pregnancy were assessed, as well as the underlying assumptions. Sample size estimations are given for pregnancy rate estimation with a given precision.

Impact of social challenges on gaining employment for veterans with posttraumatic stress disorder: an exploratory moderator analysis.

PubMed

Davis, Lori L; Pilkinton, Patricia; Poddar, Swati; Blansett, Catherine; Toscano, Richard; Parker, Pamela E

2014-06-01

To explore whether psychosocial challenges impact effects of vocational rehabilitation in Veterans with Posttraumatic Stress Disorder (PTSD). A post hoc exploratory analysis of possible moderators of treatment was conducted on outcomes from a randomized, controlled trial of Individual Placement and Support in Veterans with PTSD. When examining groups within each moderator, there was a greater IPS supportive employment benefit in gaining competitive employment for those with inadequate transportation (number needed to treat [NNT] = 1.5) and inadequate housing (NNT = 1.5) compared with the main finding of the pilot study (NNT = 2.07). Compared with the main finding of the pilot study, there was no greater advantage of IPS for those with adequate transportation (NNT = 2.4) or adequate housing (NNT = 2.4). Compared with the main finding in the pilot study, those without a family care burden had a greater benefit from IPS (NNT = 1.4) and those with family care burden had a reduced treatment effect (NNT = 3.3). These results are exploratory and are not intended to guide clinical decision-making, but rather offer a potentially useful strategy in the design of larger trials of IPS.

Does the patient‐held record improve continuity and related outcomes in cancer care: a systematic review

PubMed Central

Gysels, Marjolein; Richardson, Alison; Higginson, Irene J.

2006-01-01

Abstract Objectives  To assess the effectiveness of the patient‐held record (PHR) in cancer care. Background  Patients with cancer may receive care from different services resulting in gaps. A PHR could provide continuity and patient involvement in care. Search strategy  Relevant literature was identified through five electronic databases (Medline, Embase, Cinahl, CCTR and CDSR) and hand searches. Inclusion criteria  Patient‐held records in cancer care with the purpose of improving communication and information exchange between and within different levels of care and to promote continuity of care and patients’ involvement in their own care. Data extraction and synthesis  Data extraction recorded characteristics of intervention, type of study and factors that contributed to methodological quality of individual studies. Data were then contrasted by setting, objectives, population, study design, outcome measures and changes in outcome, including knowledge, satisfaction, anxiety and depression. Methodological quality of randomized control trials and non‐experimental studies were assessed with separate standard grading scales. Main results and conclusions  Seven randomized control trials and six non‐experimental studies were identified. Evaluations of the PHR have reached equivocal findings. Randomized trials found an absence of effect, non‐experimental evaluations shed light on the conditions for its successful use. Most patients welcomed introduction of a PHR. Main problems related to its suitability for different patient groups and the lack of agreement between patients and health professionals regarding its function. Further research is required to determine the conditions under which the PHR can realize its potential as a tool to promote continuity of care and patient participation. PMID:17324196

Instructor feedback versus no instructor feedback on performance in a laparoscopic virtual reality simulator: a randomized educational trial.

PubMed

Oestergaard, Jeanett; Bjerrum, Flemming; Maagaard, Mathilde; Winkel, Per; Larsen, Christian Rifbjerg; Ringsted, Charlotte; Gluud, Christian; Grantcharov, Teodor; Ottesen, Bent; Soerensen, Jette Led

2012-02-28

Several studies have found a positive effect on the learning curve as well as the improvement of basic psychomotor skills in the operating room after virtual reality training. Despite this, the majority of surgical and gynecological departments encounter hurdles when implementing this form of training. This is mainly due to lack of knowledge concerning the time and human resources needed to train novice surgeons to an adequate level. The purpose of this trial is to investigate the impact of instructor feedback regarding time, repetitions and self-perception when training complex operational tasks on a virtual reality simulator. The study population consists of medical students on their 4th to 6th year without prior laparoscopic experience. The study is conducted in a skills laboratory at a centralized university hospital. Based on a sample size estimation 98 participants will be randomized to an intervention group or a control group. Both groups have to achieve a predefined proficiency level when conducting a laparoscopic salpingectomy using a surgical virtual reality simulator. The intervention group receives standardized instructor feedback of 10 to 12 min a maximum of three times. The control group receives no instructor feedback. Both groups receive the automated feedback generated by the virtual reality simulator. The study follows the CONSORT Statement for randomized trials. Main outcome measures are time and repetitions to reach the predefined proficiency level on the simulator. We include focus on potential sex differences, computer gaming experience and self-perception. The findings will contribute to a better understanding of optimal training methods in surgical education. NCT01497782.

European multicentre double-blind placebo-controlled trial of Nilvadipine in mild-to-moderate Alzheimer's disease-the substudy protocols: NILVAD frailty; NILVAD blood and genetic biomarkers; NILVAD cerebrospinal fluid biomarkers; NILVAD cerebral blood flow.

PubMed

Meulenbroek, Olga; O'Dwyer, Sarah; de Jong, Daan; van Spijker, Gerrita; Kennelly, Sean; Cregg, Fiona; Olde Rikkert, Marcel; Abdullah, Laila; Wallin, Anders; Walsh, Cathal; Coen, Robert; Kenny, Rose Anne; Daly, Leslie; Segurado, Ricardo; Borjesson-Hanson, Anne; Crawford, Fiona; Mullan, Michael; Lucca, Ugo; Banzi, Rita; Pasquier, Florence; Breuilh, Laetitia; Riepe, Matthias; Kalman, Janos; Molloy, William; Tsolaki, Magda; Howard, Robert; Adams, Jessica; Gaynor, Siobhan; Lawlor, Brian

2016-07-19

In conjunction with the NILVAD trial, a European Multicentre Double-Blind Placebo Controlled trial of Nilvadipine in Mild-to-Moderate Alzheimer's disease (AD), there are four NILVAD substudies in which eligible NILVAD patients are also invited to participate. The main NILVAD protocol was previously published in BMJ Open (2014). The objectives of the NILVAD substudies are to determine whether frailty, cerebrospinal fluid (CSF), blood biomarker profile and Apolipoprotein E (APOE) status predict response to Nilvadipine, and to investigate the effect of Nilvadipine on cerebral blood flow and blood biomarkers. All participants who fulfil criteria for the main NILVAD study are eligible for participation in the NILVAD substudies. Participation is subject to informed consent and whether the substudy is available at a particular NILVAD study site. Each substudy entails extra measurements during the course of the main NILVAD study. For example, in the blood and genetic biomarkers substudy, extra blood (30 mL) will be collected at week 0, week 13, week 52 and week 78, while in the cerebral blood flow substudy, participants will receive an MRI and transcranial Doppler measurements at week 0, week 26 and week 78. In the CSF substudy, 10 mL CSF is collected at week 0 and week 78. All NILVAD substudies and all subsequent amendments have received ethical approval within each participating country, according to national regulations. Each participant provides written consent to participate. All participants remain anonymised throughout and the results of each substudy will be published in an international peer reviewed journal. EUDRACT 2012-002764-27; 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/

Describing qualitative research undertaken with randomised controlled trials in grant proposals: a documentary analysis.

PubMed

Drabble, Sarah J; O'Cathain, Alicia; Thomas, Kate J; Rudolph, Anne; Hewison, Jenny

2014-02-18

There is growing recognition of the value of conducting qualitative research with trials in health research. It is timely to reflect on how this qualitative research is presented in grant proposals to identify lessons for researchers and research commissioners. As part of a larger study focusing on how to maximise the value of undertaking qualitative research with trials, we undertook a documentary analysis of proposals of funded studies. Using the metaRegister of Controlled Trials (mRCT) database we identified trials funded in the United Kingdom, ongoing between 2001 and 2010, and reporting the use of qualitative research. We requested copies of proposals from lead researchers. We extracted data from the proposals using closed and open questions, analysed using descriptive statistics and content analysis respectively. 2% (89/3812) of trials in the mRCT database described the use of qualitative research undertaken with the trial. From these 89 trials, we received copies of 36 full proposals, of which 32 met our inclusion criteria. 25% used less than a single paragraph to describe the qualitative research. The aims of the qualitative research described in these proposals focused mainly on the intervention or trial conduct. Just over half (56%) of the proposals included an explicit rationale for conducting the qualitative research with the trial, the most frequent being to optimise implementation into clinical practice or to interpret trial findings. Key information about methods, expertise and resources was missing in a large minority of proposals, in particular sample size, type of analysis, and non-personnel resources. 28% specifically stated that qualitative researchers would conduct the qualitative research. Our review of proposals of successfully funded studies identified good practice but also identified limited space given to describing the qualitative research, with an associated lack of attention to the rationale for doing the qualitative research and important methodological details. Acknowledging the space restrictions faced by researchers writing grant proposals, we suggest a starting point for providing practical guidance to help researchers write proposals and research commissioners assess proposals of qualitative research with trials.

Describing qualitative research undertaken with randomised controlled trials in grant proposals: a documentary analysis

PubMed Central

2014-01-01

Background There is growing recognition of the value of conducting qualitative research with trials in health research. It is timely to reflect on how this qualitative research is presented in grant proposals to identify lessons for researchers and research commissioners. As part of a larger study focusing on how to maximise the value of undertaking qualitative research with trials, we undertook a documentary analysis of proposals of funded studies. Methods Using the metaRegister of Controlled Trials (mRCT) database we identified trials funded in the United Kingdom, ongoing between 2001 and 2010, and reporting the use of qualitative research. We requested copies of proposals from lead researchers. We extracted data from the proposals using closed and open questions, analysed using descriptive statistics and content analysis respectively. Results 2% (89/3812) of trials in the mRCT database described the use of qualitative research undertaken with the trial. From these 89 trials, we received copies of 36 full proposals, of which 32 met our inclusion criteria. 25% used less than a single paragraph to describe the qualitative research. The aims of the qualitative research described in these proposals focused mainly on the intervention or trial conduct. Just over half (56%) of the proposals included an explicit rationale for conducting the qualitative research with the trial, the most frequent being to optimise implementation into clinical practice or to interpret trial findings. Key information about methods, expertise and resources was missing in a large minority of proposals, in particular sample size, type of analysis, and non-personnel resources. 28% specifically stated that qualitative researchers would conduct the qualitative research. Conclusions Our review of proposals of successfully funded studies identified good practice but also identified limited space given to describing the qualitative research, with an associated lack of attention to the rationale for doing the qualitative research and important methodological details. Acknowledging the space restrictions faced by researchers writing grant proposals, we suggest a starting point for providing practical guidance to help researchers write proposals and research commissioners assess proposals of qualitative research with trials. PMID:24533771

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

Chemoprophylaxis in Contacts of Patients with Cholera: Systematic Review and Meta-Analysis

PubMed Central

Reveiz, Ludovic; Chapman, Evelina; Ramon-Pardo, Pilar; Koehlmoos, Tracey Perez; Cuervo, Luis Gabriel; Aldighieri, Sylvain; Chambliss, Amy

2011-01-01

Introduction There is a pressing need for effective measures to prevent the spread of cholera. Our systematic review assesses the effects of chemoprophylaxis in preventing cholera among exposed contacts. Methods and Findings We considered published and unpublished reports of studies up to July 2011. For this we searched: PubMed (1966 to July, 2011), Embase (1980 to July 2011), Cochrane Central Register of Controlled Trials (6; 2011), LILACS (1982 to July, 2011), the International Clinical Trials Registry Platform (July 2011) and references of identified publications. We included controlled clinical trials (randomized and non-randomized) in which chemoprophylaxis was used to prevent cholera among patient contacts. The main outcome measures were hospitalization and laboratory diagnosis of cholera in contacts for cholera patients. We assessed the risk of bias. We identified 2638 references and these included 2 randomized trials and 5 controlled trials that added up to a total of 4,154 participants. The risk of bias scored high for most trials. The combined results from two trials found that chemoprophylaxis reduced hospitalization of contacts during the follow-up period by 8–12 days (2826 participants; RR 0.54 95% CI 0.40–0.74;I2 0%). A meta-analysis of five trials found a significant reduction in disease among contacts with at least one positive sample who received chemoprophylaxis during the overall follow-up (range 4–15 days) (1,414 participants; RR 0.35 95% CI 0.18–0.66;I2 74%). A significant reduction in the number of positive samples was also found with chemoprophylaxis (3 CCT; 6,918 samples; RR 0.39 95% CI 0.29–0.51;I2 0%). Conclusion Our findings suggest that chemoprophylaxis has a protective effect among household contacts of people with cholera but the results are based on studies with a high risk of bias. Hence, there is a need for adequate reliable research that allows balancing benefits and harms by evaluating the effects of chemoprophylaxis. PMID:22102873

High variability in results of semen analysis in andrology laboratories in Tuscany (Italy): the experience of an external quality control (EQC) programme.

PubMed

Filimberti, E; Degl'Innocenti, S; Borsotti, M; Quercioli, M; Piomboni, P; Natali, I; Fino, M G; Caglieresi, C; Criscuoli, L; Gandini, L; Biggeri, A; Maggi, M; Baldi, E

2013-05-01

We report the results of the first three trials of an external quality control (EQC) programme performed in 71 laboratories executing semen analysis in Tuscany Region (Italy). At the end of the second trial, participants were invited to attend a teaching course illustrating and inviting to adhere to procedures recommended by WHO (V edition). Results of the first three trials of the EQC documented a huge variability in the procedures and the results. The highest variability was found for morphology (CV above 80% for all the trials), followed by count (CV of about 60% for all the trials) and motility (CV below 30% for all the trials). When results of sperm count and morphology were divided according to the used method, mean CV values did not show significant differences. CV for morphology dropped significantly at the third trial for most methods, indicating the usefulness of the teaching course for morphology assessment. Conversely, no differences were observed after the course for motility and for most methods to evaluate count, although CV values were lower at the second and third trial for the laboratories using the Burker cytometer. When results were divided according to tertiles of activity, the lowest mean bias values (difference between each laboratory result and the median value of the results) for count and morphology were observed for laboratories in the third tertile (performing over 200 semen analysis/year). Of interest, mean bias values for concentration dropped significantly at the third trial for low activity laboratories. In conclusion, lack of agreement of results of semen analysis in Tuscany is mainly because of the activity and the experience of the laboratory. Our study points out the importance of participating in EQC programmes and periodical teaching courses as well as the use of WHO recommended standardized procedures to increase precision and to allow the use of WHO reference values. © 2013 American Society of Andrology and European Academy of Andrology.

'Huang Qi Elixir' for proteinuria in patients with diabetic nephropathy: a study protocol for a randomized controlled pilot trial.

PubMed

Tu, Xiang; Liu, Fang; Jordan, James B; Ye, Xue Feng; Fu, Ping; Wang, Fei; Zhong, Sen

2013-07-18

Diabetic nephropathy (DN) is the major complication of diabetes; proteinuria is the hall mark of DN. Currently, the treatment for proteinuria is mainly limited to angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). According to Traditional Chinese Medicine (TCM) theory, Chinese medicinals 'securing essence and tonifying the kidney' may be appropriate for proteinuria. The most promising Chinese medicinals and formulae are introduced in the present study to form a potent formula for DN proteinuria. To make oral administration convenient, the formula will be processed in the form of granules. A randomized, multi-center pilot trial will be conducted. Forty eight participants with DN will be randomly assigned to one of four treatment groups: 1. A granule group, at 10 grams, three times daily (G10 group, n = 12); 2. A granule group, at 20 grams, three times daily (G20 group, n = 12); 3. A decoction group (D group, n = 12); and 4. An irbesartan group (Aprovel group, n = 12).The following outcome measures will be used: the percentage change of the albumin-to-creatinine ratio; and the changes in serum creatinine, glomerular filtration rate, fasting plasma glucose and hemoglobulin from baseline to the end of the trial. It is notable that most published clinical trials which assessed the efficacy of TCM on DN were of poor methodology and, therefore, their results have been invalidated. It is necessary to carry out well-designed clinical trials to provide sound evidence. The present trial is a study with potentially great value, for it will provide the parameters for future randomized, placebo-controlled, clinical trials with large sample sizes. The trial is registered on the Chinese Clinical Trial Registry: ChiCTR-TRC-12002718 (http://www.chictr.org/cn/proj/show.aspx?proj=3820).

Weight reduction for non-alcoholic fatty liver disease.

PubMed

Peng, Lijun; Wang, Jiyao; Li, Feng

2011-06-15

Non-alcoholic fatty liver disease (NAFLD) is becoming a wide spread liver disease. The present recommendations for treatment are not evidence-based. Some of them are various weight reduction measures with diet, exercise, drug, or surgical therapy. To assess the benefits and harms of intended weight reduction for patients with NAFLD. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, PubMed, EMBASE, Science Citation Index Expanded, Chinese Biomedicine Database, and ClinicalTrials.gov until February 2011. We included randomised clinical trials evaluating weight reduction with different measures versus no intervention or placebo in NAFLD patients. We extracted data independently. We calculated the odds ratio (OR) for dichotomous data and calculated the mean difference (MD) for continuous data, both with 95% confidence intervals (CI). The review includes seven trials; five on aspects of lifestyle changes (eg, diet, physical exercise) and two on treatment with a weight reduction drug 'orlistat'. In total, 373 participants were enrolled, and the duration of the trials ranged from 1 month to 1 year. Only one trial on lifestyle programme was judged to be of low risk of bias. We could not perform meta-analyses for the main outcomes as they were either not reported or there were insufficient number of trials for each outcome to be meta-analysed. We could meta-analyse the available data for body weight and body mass index only. Adverse events were poorly reported. The sparse data and high risk of bias preclude us from drawing any definite conclusion on lifestyle programme or orlistat for treatment of NAFLD. Further randomised clinical trials with low risk of bias are needed to test the beneficial and harmful effects of weight reduction for NAFLD patients. The long-term prognosis of development of fibrosis, mortality, and quality of life should be studied.

Clustered randomised controlled trial of two education interventions designed to increase physical activity and well-being of secondary school students: the MOVE Project

PubMed Central

Tymms, Peter B; Curtis, Sarah E; Routen, Ash C; Thomson, Katie H; Bolden, David S; Bock, Susan; Dunn, Christine E; Cooper, Ashley R; Elliott, Julian G; Moore, Helen J; Summerbell, Carolyn D; Tiffin, Paul A; Kasim, Adetayo S

2016-01-01

Objective To assess the effectiveness of 2 interventions in improving the physical activity and well-being of secondary school children. Design A clustered randomised controlled trial; classes, 1 per school, were assigned to 1 of 3 intervention arms or a control group based on a 2×2 factorial design. The interventions were peer-mentoring and participative learning. Year 7 children (aged 11–12) in the peer-mentoring intervention were paired with year 9 children for 6 weekly mentoring meetings. Year 7 children in the participative learning arm took part in 6 weekly geography lessons using personalised physical activity and Global Positioning System (GPS) data. Year 7 children in the combined intervention received both interventions, with the year 9 children only participating in the mentoring sessions. Participants 1494 year 7 students from 60 schools in the North of England took part in the trial. Of these, 43 students opted out of taking part in the evaluation measurements, 2 moved teaching group and 58 changed school. Valid accelerometry outcome data were collected for 892 students from 53 schools; and well-being outcome data were available for 927 students from 52 schools. Main outcome measures The primary outcomes were mean minutes of accelerometer-measured moderate-to-vigorous intensity physical activity per day, and well-being as evaluated by the KIDSCREEN-27 questionnaire. These data were collected 6 weeks after the intervention; a 12-month follow-up is planned. Results No significant effects (main or interaction) were observed for the outcomes. However, small positive differences were found for both outcomes for the participative learning intervention. Conclusions These findings suggest that the 2 school-based interventions did not modify levels of physical activity or well-being within the period monitored. Change in physical activity may require more comprehensive individual behavioural intervention, and/or more system-based efforts to address wider environmental influences such as family, peers, physical environment, transport and educational policy. Trial registration number ISRCTN82956355. PMID:26739729

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

Rogers, Chris A; Welbourn, Richard; Byrne, James; Donovan, Jenny L; Reeves, Barnaby C; Wordsworth, Sarah; Andrews, Robert; Thompson, Janice L; Roderick, Paul; Mahon, David; Noble, Hamish; Kelly, Jamie; Mazza, Graziella; Pike, Katie; Paramasivan, Sangeetha; Blencowe, Natalie; Perkins, Mary; Porter, Tanya; Blazeby, Jane M

2014-02-11

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. 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. 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. Current Controlled Trials ISRCTN00786323.

Effect Size in Efficacy Trials of Women With Decreased Sexual Desire.

PubMed

Pyke, Robert E; Clayton, Anita H

2018-03-22

Regarding hypoactive sexual desire disorder (HSDD) in women, some reviewers judge the effect size small for medications vs placebo, but substantial for cognitive behavior therapy (CBT) or mindfulness meditation training (MMT) vs wait list. However, we lack comparisons of the effect sizes for the active intervention itself, for the control treatment, and for the differential between the two. For efficacy trials of HSDD in women, compare effect sizes for medications (testosterone/testosterone transdermal system, flibanserin, and bremelanotide) and placebo vs effect sizes for psychotherapy and wait-list control. We conducted a literature search for mean changes and SD on main measures of sexual desire and associated distress in trials of medications, CBT, or MMT. Effect size was used as it measures the magnitude of the intervention without confounding by sample size. Cohen d was used to determine effect sizes. For medications, mean (SD) effect size was 1.0 (0.34); for CBT and MMT, 1.0 (0.36); for placebo, 0.55 (0.16); and for wait list, 0.05 (0.26). Recommendations of psychotherapy over medication for treatment of HSDD are premature and not supported by data on effect sizes. Active participation in treatment conveys considerable non-specific benefits. Caregivers should attend to biological and psychosocial elements, and patient preference, to optimize response. Few clinical trials of psychotherapies were substantial in size or utilized adequate control paradigms. Medications and psychotherapies had similar, large effect sizes. Effect size of placebo was moderate. Effect size of wait-list control was very small, about one quarter that of placebo. Thus, a substantial non-specific therapeutic effect is associated with receiving placebo plus active care and evaluation. The difference in effect size between placebo and wait-list controls distorts the value of the subtraction of effect of the control paradigms to estimate intervention effectiveness. Pyke RE, Clayton AH. Effect Size in Efficacy Trials of Women With Decreased Sexual Desire. Sex Med Rev 2018;XX:XXX-XXX. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Effect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM.

PubMed

Penno, G; Chaturvedi, N; Talmud, P J; Cotroneo, P; Manto, A; Nannipieri, M; Luong, L A; Fuller, J H

1998-09-01

We examined whether the ACE gene insertion/deletion (I/D) polymorphism modulates renal disease progression in IDDM and how ACE inhibitors influence this relationship. The EURODIAB Controlled Trial of Lisinopril in IDDM is a multicenter randomized placebo-controlled trial in 530 nonhypertensive, mainly normoalbuminuric IDDM patients aged 20-59 years. Albumin excretion rate (AER) was measured every 6 months for 2 years. Genotype distribution was 15% II, 58% ID, and 27% DD. Between genotypes, there were no differences in baseline characteristics or in changes in blood pressure and glycemic control throughout the trial. There was a significant interaction between the II and DD genotype groups and treatment on change in AER (P = 0.05). Patients with the II genotype showed the fastest rate of AER progression on placebo but had an enhanced response to lisinopril. AER at 2 years (adjusted for baseline AER) was 51.3% lower on lisinopril than placebo in the II genotype patients (95% CI, 15.7 to 71.8; P = 0.01), 14.8% in the ID group (-7.8 to 32.7; P = 0.2), and 7.7% in the DD group (-36.6 to 37.6; P = 0.7). Absolute differences in AER between placebo and lisinopril at 2 years were 8.1, 1.7, and 0.8 microg/min in the II, ID, and DD groups, respectively. The significant beneficial effect of lisinopril on AER in the II group persisted when adjusted for center, blood pressure, and glycemic control, and also for diastolic blood pressure at 1 month into the study. Progression from normoalbuminuria to microalbuminuria (lisinopril versus placebo) was 0.27 (0.03-2.26; P = 0.2) in the II group, and 1.30 (0.33-5.17; P = 0.7) in the DD group (P = 0.6 for interaction). Knowledge of ACE genotype may be of value in determining the likely impact of ACE inhibitor treatment.

Differing antidepressant maintenance methodologies.

PubMed

Safer, Daniel J

2017-10-01

The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate of MDD relapse over time. However, other randomized maintenance trial methodologies merit consideration and comparison. A systematic review of ADM randomized maintenance trials included research reports from multiple databases. Relapse rate was the main effectiveness outcome assessed. Five ADM randomized maintenance methodologies for MDD responders are described and compared for outcome. These effectiveness trials include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs. psychotherapy, and treatment as usual. The placebo-substitution trials for those abruptly switched to placebo resulted in unusually high (46%) rates of relapse over 6-12months, twice the continuing ADM rate. These trials were characterized by selective screening, high attrition, an anxious anticipation of a switch to placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM efficacy responders who entered into 4-12month extension trials experienced relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored randomized trials of adults with multiple prior MDD episodes who were treated with ADM maintenance for 1-2years experienced relapse rates averaging 40%. Placebo substitution trial methodology represents only one approach to assess ADM maintenance. Antidepressant maintenance research for adults with MDD should be evaluated for industry sponsorship, attrition, the impact of the switch to placebo, and major relapse differences in MDD subpopulations. Copyright © 2017. Published by Elsevier Inc.

Rationale, Timeline, Study Design, and Protocol Overview of the Therapeutic Hypothermia After Pediatric Cardiac Arrest Trials

PubMed Central

Moler, Frank W.; Silverstein, Faye S.; Meert, Kathleen L.; Clark, Amy E.; Holubkov, Richard; Browning, Brittan; Slomine, Beth S.; Christensen, James R.; Dean, Michael

2014-01-01

Objective To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Design Multicenter randomized controlled trials. Setting Pediatric intensive care and cardiac ICUs in the United States and Canada. Patients Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent. Interventions Therapeutic hypothermia or therapeutic normothermia. Measurements and Main Results From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015. Conclusions Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials. PMID:23842585

Early screening for Chlamydia trachomatis in young women for primary prevention of pelvic inflammatory disease (i-Predict): study protocol for a randomised controlled trial.

PubMed

Tamarelle, Jeanne; Thiébaut, Anne C M; Sabin, Bénédicte; Bébéar, Cécile; Judlin, Philippe; Fauconnier, Arnaud; Rahib, Delphine; Méaude-Roufai, Layidé; Ravel, Jacques; Morré, Servaas A; de Barbeyrac, Bertille; Delarocque-Astagneau, Elisabeth

2017-11-13

Genital infection with Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection, especially among young women. Mostly asymptomatic, it can lead, if untreated, to pelvic inflammatory disease (PID), tubal factor infertility and ectopic pregnancy. Recent data suggest that Ct infections are not controlled in France and in Europe. The effectiveness of a systematic strategy for Ct screening in under-25 women remains controversial. The main objective of the i-Predict trial (Prevention of Diseases Induced by Chlamydia trachomatis) is to determine whether early screening and treatment of 18- to-24-year-old women for genital Ct infection reduces the incidence of PID over 24 months. This is a randomised prevention trial including 4000 eighteen- to twenty-four-year-old sexually active female students enrolled at five universities. The participants will provide a self-collected vaginal swab sample and fill in an electronic questionnaire at baseline and at 6, 12 and 18 months after recruitment. Vaginal swabs in the intervention arm will be analysed immediately for Ct positivity, and participants will be referred for treatment if they have a positive test result. Vaginal swabs from the control arm will be analysed at the end of the study. All visits to general practitioners, gynaecologists or gynaecology emergency departments for pelvic pain or other gynaecological symptoms will be recorded to evaluate the incidence of PID, and all participants will attend a final visit in a hospital gynaecology department. The primary endpoint measure will be the incidence of PID over 24 months. The outcome status (confirmed, probable or no PID) will be assessed by two independent experts blinded to group assignment and Ct status. This trial is expected to largely contribute to the development of recommendations for Ct screening in young women in France to prevent PID and related complications. It is part of a comprehensive approach to gathering data to facilitate decision-making regarding optimal strategies for Ct infection control. The control group of this randomised trial, following current recommendations, will allow better documentation of the natural history of Ct infection, a prerequisite to evaluating the impact of Ct screening. Characterisation of host immunogenetics will also allow identification of women at risk for complications. ClinicalTrials.gov, NCT02904811 . Registered on September 14, 2016. World Health Organisation International Clinical Trials Registry, NCT02904811. AOM, 15-0063 and P150950. Registered on September 26, 2016. A completed Standard Protocol Items : Recommendations for International Trials (SPIRIT) Checklist is available in additional file 1.

Linked randomised controlled trials of face-to-face and electronic brief intervention methods to prevent alcohol related harm in young people aged 14-17 years presenting to Emergency Departments (SIPS junior).

PubMed

Deluca, Paolo; Coulton, Simon; Alam, M Fasihul; Cohen, David; Donoghue, Kim; Gilvarry, Eilish; Kaner, Eileen; Maconochie, Ian; McArdle, Paul; McGovern, Ruth; Newbury-Birch, Dorothy; Patton, Robert; Phillips, Ceri; Phillips, Thomas; Russell, Ian; Strang, John; Drummond, Colin

2015-04-10

Alcohol is a major global threat to public health. Although the main burden of chronic alcohol-related disease is in adults, its foundations often lie in adolescence. Alcohol consumption and related harm increase steeply from the age of 12 until 20 years. Several trials focusing upon young people have reported significant positive effects of brief interventions on a range of alcohol consumption outcomes. A recent review of reviews also suggests that electronic brief interventions (eBIs) using internet and smartphone technologies may markedly reduce alcohol consumption compared with minimal or no intervention controls. Interventions that target non-drinking youth are known to delay the onset of drinking behaviours. Web based alcohol interventions for adolescents also demonstrate significantly greater reductions in consumption and harm among 'high-risk' drinkers; however changes in risk status at follow-up for non-drinkers or low-risk drinkers have not been assessed in controlled trials of brief alcohol interventions. The study design comprises two linked randomised controlled trials to evaluate the effectiveness and cost-effectiveness of two intervention strategies compared with screening alone. One trial will focus on high-risk adolescent drinkers attending Emergency Departments (Eds) and the other will focus on those identified as low-risk drinkers or abstinent from alcohol but attending the same ED. Our primary (null) hypothesis is similar for both trials: Personalised Feedback and Brief Advice (PFBA) and Personalised Feedback plus electronic Brief Intervention (eBI) are no more effective than screening alone in alcohol consumed at 12 months after randomisation as measured by the Time-Line Follow-Back 28-day version. Our secondary (null) hypothesis relating to economics states that PFBA and eBI are no more cost-effective than screening alone. In total 1,500 participants will be recruited into the trials, 750 high-risk drinkers and 750 low-risk drinkers or abstainers. Participants will be randomised with equal probability, stratified by centre, to either a screening only control group or one of the two interventions: single session of PFBA or eBI. All participants will be eligible to receive treatment as usual in addition to any trial intervention. Individual participants will be followed up at 6 and 12 months after randomisation. The protocol represents an ambitious innovative programme of work addressing alcohol use in the adolescent population. ISRCTN45300218. Registered 5th July 2014.

A Case for Less Intensive Blood Pressure Control: It Matters to Achieve Target Blood Pressure Early and Sustained Below 140/90mmHg.

PubMed

Mariampillai, Julian E; Eskås, Per Anders; Heimark, Sondre; Kjeldsen, Sverre E; Narkiewicz, Krzysztof; Mancia, Giuseppe

Although high blood pressure (BP) is the leading risk factors for cardiovascular (CV) disease, the optimal BP treatment target in order to reduce CV risk is unclear in the aftermath of the SPRINT study. The aim of this review is to assess large, randomized, and controlled trials on BP targets, as well as review selected observational analyses from other large randomized BP trials in order to evaluate the benefit of intense vs. standard BP control. None of the studies, except SPRINT, favored intense BP treatment. Some of the studies suggested favorable effects of lowering treatment target in patients with diabetes or high risk of stroke. In SPRINT, a new BP measurement method was introduced, and the results must be interpreted in light of this. The results of the observational analyses indicated the best preventive effect when achieving early and sustained BP control rather than low targets. In conclusion, today's guidelines' recommended treatment target of <140/90mmHg seems sufficient for most patients. Early and sustained BP control should be the main focus. Copyright © 2016 Elsevier Inc. All rights reserved.

Cost--effectiveness analysis of salpingectomy prior to IVF, based on a randomized controlled trial.

PubMed

Strandell, Annika; Lindhard, Anette; Eckerlund, Ingemar

2005-12-01

In patients with ultrasound-visible hydrosalpinges, salpingectomy prior to IVF increases the chance of a live birth. This study compared the cost-effectiveness of this strategy (intervention) with that of optional salpingectomy after a failed cycle (control). Data from a Scandinavian randomized controlled trial were used to calculate the individual number of treatments and their outcomes. Only patients with ultrasound-visible hydrosalpinges were considered in the main analysis, and a maximum of three fresh cycles were included. The costs for surgical procedures, IVF treatment, medication, complications, management of pregnancy and delivery as well as of early pregnancy losses were calculated from standardized hospital charges. Among the 51 patients in the intervention group, the live birth rate was 60.8% compared with 40.9% in 44 controls. The average cost per patient was 13,943 euro and 12,091 euro, respectively. Thus, the average cost per live birth was 22,823 euro in the intervention group and 29,517 euro in the control group. The incremental cost-effectiveness ratio for adopting the intervention strategy was estimated at 9306 euro. The incremental cost to achieve the higher birth rate of the intervention strategy seems reasonable.

Systematic review and economic evaluation of Helicobacter pylori eradication treatment for non-ulcer dyspepsia

PubMed Central

Moayyedi, Paul; Soo, Shelly; Deeks, Jonathan; Forman, David; Mason, James; Innes, Michael; Delaney, Brendan

2000-01-01

Objectives To evaluate efficacy and cost effectiveness of Helicobacter pylori eradication treatment in patients with non-ulcer dyspepsia infected with H pylori. Design Systematic review of randomised controlled trials comparing H pylori eradication with placebo or another drug treatment. Results were incorporated into a Markov model comparing health service costs and benefits of H pylori eradication with antacid treatment over one year. Data sources Six electronic databases were searched for randomised controlled trials from January 1966 to May 2000. Experts in the field, pharmaceutical companies, and journals were contacted for information on any unpublished trials. Trial reports were reviewed according to predefined eligibility and quality criteria. Main outcome measures Relative risk reduction for remaining dyspeptic symptoms (the same or worse) at 3-12 months. Cost per dyspepsia-free month estimated from Markov model based on estimated relative risk reduction. Results Twelve trials were included in the systematic review, nine of which evaluated dyspepsia at 3-12 months in 2541 patients. H pylori eradication treatment was significantly superior to placebo in treating non-ulcer dyspepsia (relative risk reduction 9% (95% confidence interval 4% to 14%)), one case of dyspepsia being cured for every 15 people treated. H pylori eradication cost £56 per dyspepsia-free month during first year after treatment. Conclusion H pylori eradication may be cost effective treatment for non-ulcer dyspepsia in infected patients but further evidence is needed on decision makers' willingness to pay for relief of dyspepsia. PMID:10987767

Overcoming recruitment challenges in palliative care clinical trials.

PubMed

LeBlanc, Thomas W; Lodato, Jordan E; Currow, David C; Abernethy, Amy P

2013-11-01

Palliative care is increasingly viewed as a necessary component of cancer care, especially for patients with advanced disease. Rigorous clinical trials are thus needed to build the palliative care evidence base, but clinical research-especially participant recruitment-is difficult. Major barriers include (1) patient factors, (2) "gatekeeping," and (3) ethical concerns. Here we discuss an approach to overcoming these barriers, using the Palliative Care Trial (PCT) as a case study. The PCT was a 2 × 2 × 2 factorial randomized controlled trial (RCT) of different service delivery models to improve pain control in the palliative setting. It used a recruitment protocol that fused evidence-based strategies with principles of "social marketing," an approach involving the systematic application of marketing techniques. Main components included (1) an inclusive triage algorithm, (2) information booklets targeting particular stakeholders, (3) a specialized recruitment nurse, and (4) standardization of wording across all study communications. From an eligible pool of 607 patients, the PCT enrolled 461 patients over 26 months. Twenty percent of patients referred to the palliative care service were enrolled (76% of those eligible after screening). Several common barriers were minimized; among those who declined participation, family disinterest was uncommon (5%), as was the perception of burden imposed (4%). Challenges to clinical trial recruitment in palliative care are significant but not insurmountable. A carefully crafted recruitment and retention protocol can be effective. Our experience with designing and deploying a social-marketing-based protocol shows the benefits of such an approach.

Standardized versus Individualized Acupuncture for Chronic Low Back Pain: A Randomized Controlled Trial

PubMed Central

Pach, Daniel; Yang-Strobel, Xiaoli; Lüdtke, Rainer; Icke, Katja; Brinkhaus, Benno; Witt, Claudia M.

2013-01-01

We aimed to compare the effectiveness of standardized and individualized acupuncture treatment in patients with chronic low back pain. A single-center randomized controlled single-blind trial was performed in a general medical practice in Germany run by a Chinese-born medical doctor trained in western and Chinese medicine. One hundred and fifty outpatients with chronic low back pain were randomly allocated to two groups (78 standardized and 72 individualized acupuncture). Patients received either standardized acupuncture or individualized acupuncture. Treatment encompassed between 10 and 15 treatments based on individual symptoms with two treatments per week. The main outcome measure was the area under the curve (AUC) summarizing eight weeks of daily rated pain severity measured with a visual analogue scale (0 mm = no pain, 100 mm = worst imaginable pain). No significant differences between groups were observed for the AUC (individualized acupuncture mean: 1768.7 (95% CI, 1460.4; 2077.1); standardized acupuncture 1482.9 (1177.2; 1788.7); group difference, 285.8 (−33.9; 605.5) P = 0.080). In this single-center trial, individualized acupuncture was not superior to standardized acupuncture for patients suffering from chronic pain. As a next step, a multicenter noninferiority study should be performed to investigate whether standardised acupuncture treatment for chronic low back pain might be applicable in a broader usual care setting. This trial is registered with ClinicalTrials.gov NCT00758017. PMID:24288556

Efficacy of Dragon's blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial

PubMed Central

Namjoyan, Foroogh; Kiashi, Fatemeh; Moosavi, Zahra Beigom; Saffari, Fatemeh; Makhmalzadeh, Behzad Sharif

2015-01-01

The blood-red sap of Dragon's blood has been used in folk medicine for fractures, wounds, inflammation, gastrointestinal disorders, rheumatism, blood circulation dysfunctions, and cancer. Existing in vitro and in vivo bioactivity of this herb on different mechanisms of healing shows strong potential of this sap in wound healing. This clinical trial study was designated to evaluate the wound healing effect of Dragon's blood on human wounds. Sixty patients, between the ages of 14–65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either Dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001). The phenolic compounds and the alkaloid taspine, which exist in Dragon's-blood resin, are probably the main reasons for the wound healing property of this plant. Being natural accessible, safe, and affordable makes Dragon's blood cream, a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of Dragon's blood. PMID:26870678

Efficacy of Dragon's blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial.

PubMed

Namjoyan, Foroogh; Kiashi, Fatemeh; Moosavi, Zahra Beigom; Saffari, Fatemeh; Makhmalzadeh, Behzad Sharif

2016-01-01

The blood-red sap of Dragon's blood has been used in folk medicine for fractures, wounds, inflammation, gastrointestinal disorders, rheumatism, blood circulation dysfunctions, and cancer. Existing in vitro and in vivo bioactivity of this herb on different mechanisms of healing shows strong potential of this sap in wound healing. This clinical trial study was designated to evaluate the wound healing effect of Dragon's blood on human wounds. Sixty patients, between the ages of 14-65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either Dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001). The phenolic compounds and the alkaloid taspine, which exist in Dragon's-blood resin, are probably the main reasons for the wound healing property of this plant. Being natural accessible, safe, and affordable makes Dragon's blood cream, a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of Dragon's blood.

Enhancing biological control of basal stem rot disease (Ganoderma boninense) in oil palm plantations.

PubMed

Susanto, A; Sudharto, P S; Purba, R Y

2005-01-01

Basal Stem Rot (BSR) disease caused by Ganoderma boninense is the most destructive disease in oil palm, especially in Indonesia and Malaysia. The available control measures for BSR disease such as cultural practices and mechanical and chemical treatment have not proved satisfactory due to the fact that Ganoderma has various resting stages such as melanised mycelium, basidiospores and pseudosclerotia. Alternative control measures to overcome the Ganoderma problem are focused on the use of biological control agents and planting resistant material. Present studies conducted at Indonesian Oil Palm Research Institute (IOPRI) are focused on enhancing the use of biological control agents for Ganoderma. These activities include screening biological agents from the oil palm rhizosphere in order to evaluate their effectiveness as biological agents in glasshouse and field trials, testing their antagonistic activities in large scale experiments and eradicating potential disease inoculum with biological agents. Several promising biological agents have been isolated, mainly Trichoderma harzianum, T. viride, Gliocladium viride, Pseudomonas fluorescens, and Bacillus sp. A glasshouse and field trial for Ganoderma control indicated that treatment with T. harzianum and G. viride was superior to Bacillus sp. A large scale trial showed that the disease incidence was lower in a field treated with biological agents than in untreated fields. In a short term programme, research activities at IOPRI are currently focusing on selecting fungi that can completely degrade plant material in order to eradicate inoculum. Digging holes around the palm bole and adding empty fruit bunches have been investigated as ways to stimulate biological agents.

Understanding the Quality Chasm for Hypertension Control in Diabetes: A Structured Review of “Co-maneuvers” Used in Clinical Trials

PubMed Central

Naik, Aanand D.; Issac, Tim T.; Street, Richard L.; Kunik, Mark E.

2010-01-01

Background Observational studies routinely describe a significant gap between rates of blood pressure control in routine diabetes care compared with those achieved in randomized controlled trials (RCTs). Methods We performed a systematic review of the literature to identify co-maneuvers used in RCTs, defined as ancillary activities or agents administered before, during, or immediately after the main agent under investigation (ie, principal maneuver), but not effectively translated to routine diabetes care. We searched multiple databases for RCTs evaluating the efficacy of treatments for hypertension control in adults with type 2 diabetes mellitus. We considered only phase III human studies of interventions that achieved blood pressure control and scrutinized all elements related to the implementation of the principal maneuver in each candidate study. These elements were then sorted into a taxonomy of co-maneuvers. Results Nearly all eligible RCTs used highly consistent groups of co-maneuvers. These typically began with (1) the use of consensual and clearly stated blood pressure goals; (2) frequent visits in which blood pressure levels were measured and compared with predefined goals; and, if the goal was not attained, (3) modifications to the treatment based on a detailed action plan that included communication of adverse events. Patient education, feedback to clinicians, and interventions for medication adherence were not commonly used among eligible trials. Conclusions Clinicians should translate key behavioral co-maneuvers along with clinically proven treatments for hypertension control in diabetes. These co-maneuvers are conceptually similar to collaborative goal setting and action planning interventions used in innovative chronic care programs. PMID:17823464

Anti-TNF therapy for juvenile idiopathic arthritis-related uveitis

PubMed Central

Semeraro, Francesco; Arcidiacono, Barbara; Nascimbeni, Giuseppe; Angi, Martina; Parolini, Barbara; Costagliola, Ciro

2014-01-01

Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds. PMID:24711694

Anti-TNF therapy for juvenile idiopathic arthritis-related uveitis.

PubMed

Semeraro, Francesco; Arcidiacono, Barbara; Nascimbeni, Giuseppe; Angi, Martina; Parolini, Barbara; Costagliola, Ciro

2014-01-01

Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds.

Effects of tailored neck-shoulder pain treatment based on a decision model guided by clinical assessments and standardized functional tests. A study protocol of a randomized controlled trial

PubMed Central

2012-01-01

Background A major problem with rehabilitation interventions for neck pain is that the condition may have multiple causes, thus a single treatment approach is seldom efficient. The present study protocol outlines a single blinded randomised controlled trial evaluating the effect of tailored treatment for neck-shoulder pain. The treatment is based on a decision model guided by standardized clinical assessment and functional tests with cut-off values. Our main hypothesis is that the tailored treatment has better short, intermediate and long-term effects than either non-tailored treatment or treatment-as-usual (TAU) on pain and function. We sub-sequentially hypothesize that tailored and non-tailored treatment both have better effect than TAU. Methods/Design 120 working women with minimum six weeks of nonspecific neck-shoulder pain aged 20–65, are allocated by minimisation with the factors age, duration of pain, pain intensity and disability in to the groups tailored treatment (T), non-tailored treatment (NT) or treatment-as-usual (TAU). Treatment is given to the groups T and NT for 11 weeks (27 sessions evenly distributed). An extensive presentation of the tests and treatment decision model is provided. The main treatment components are manual therapy, cranio-cervical flexion exercise and strength training, EMG-biofeedback training, treatment for cervicogenic headache, neck motor control training. A decision algorithm based on the baseline assessment determines the treatment components given to each participant of T- and NT-groups. Primary outcome measures are physical functioning (Neck Disability Index) and average pain intensity last week (Numeric Rating Scale). Secondary outcomes are general improvement (Patient Global Impression of Change scale), symptoms (Profile Fitness Mapping neck questionnaire), capacity to work in the last 6 weeks (quality and quantity) and pressure pain threshold of m. trapezius. Primary and secondary outcomes will be reported for each group with effect size and its precision. Discussion We have chosen not to include women with psychological ill-health and focus on biomedical aspects of neck pain. Future studies should aim at including psychosocial aspects in a widened treatment decision model. No important adverse events or side-effects are expected. Trial registration Current Controlled Trials registration ISRCTN49348025. PMID:22607546

Effects of a guided web-based smoking cessation program with telephone counseling: a cluster randomized controlled trial.

PubMed

Mehring, Michael; Haag, Max; Linde, Klaus; Wagenpfeil, Stefan; Schneider, Antonius

2014-09-24

Preliminary findings suggest that Web-based interventions may be effective in achieving significant smoking cessation. To date, very few findings are available for primary care patients, and especially for the involvement of general practitioners. Our goal was to examine the short-term effectiveness of a fully automated Web-based coaching program in combination with accompanied telephone counseling in smoking cessation in a primary care setting. The study was an unblinded cluster-randomized trial with an observation period of 12 weeks. Individuals recruited by general practitioners randomized to the intervention group participated in a Web-based coaching program based on education, motivation, exercise guidance, daily short message service (SMS) reminding, weekly feedback through Internet, and active monitoring by general practitioners. All components of the program are fully automated. Participants in the control group received usual care and advice from their practitioner without the Web-based coaching program. The main outcome was the biochemically confirmed smoking status after 12 weeks. We recruited 168 participants (86 intervention group, 82 control group) into the study. For 51 participants from the intervention group and 70 participants from the control group, follow-up data were available both at baseline and 12 weeks. Very few patients (9.8%, 5/51) from the intervention group and from the control group (8.6%, 6/70) successfully managed smoking cessation (OR 0.86, 95% CI 0.25-3.0; P=.816). Similar results were found within the intent-to-treat analysis: 5.8% (5/86) of the intervention group and 7.3% (6/82) of the control group (OR 1.28, 95% CI 0.38-4.36; P=.694). The number of smoked cigarettes per day decreased on average by 9.3 in the intervention group and by 6.6 in the control group (2.7 mean difference; 95% CI -5.33 to -0.58; P=.045). After adjustment for the baseline value, age, gender, and height, this significance decreases (mean difference 2.2; 95% CI -4.7 to 0.3; P=.080). This trial did not show that the tested Web-based intervention was effective for achieving smoking cessation compared to usual care. The limited statistical power and the high drop-out rate may have reduced the study's ability to detect significant differences between the groups. Further randomized controlled trials are needed in larger populations and to investigate the long-term outcome. German Register for Clinical Trials, registration number DRKS00003067; http://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ ID=DRKS00003067 (Archived by WebCite at http://www.webcitation.org/6Sff1YZpx).

A Multicenter, Randomized Controlled Trial of Cerebrospinal Fluid Drainage in Acute Spinal Cord Injury

DTIC Science & Technology

2017-10-01

PRINCIPAL INVESTIGATOR: Nicholas Theodore, MD CONTRACTING ORGANIZATION: Dignity Health San Francisco, CA 94107-1773 REPORT DATE: October 2017...theodore@jhmi.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Dignity Health 8. PERFORMING ORGANIZATION REPORT NUMBER 185...at all three active centers, which include: Barrow Neurological Institute/Dignity Health (the main study site) in Arizona, the University of Arizona

Antenna Linear-Quadratic-Gaussian (LQG) Controllers: Properties, Limits of Performance, and Tuning Procedure

NASA Technical Reports Server (NTRS)

Gawronski, W.

2004-01-01

Wind gusts are the main disturbances that depreciate tracking precision of microwave antennas and radiotelescopes. The linear-quadratic-Gaussian (LQG) controllers - as compared with the proportional-and-integral (PI) controllers significantly improve the tracking precision in wind disturbances. However, their properties have not been satisfactorily understood; consequently, their tuning is a trial-and-error process. A control engineer has two tools to tune an LQG controller: the choice of coordinate system of the controller model and the selection of weights of the LQG performance index. This article analyzes properties of an open- and closed-loop antenna. It shows that the proper choice of coordinates of the open-loop model simplifies the shaping of the closed-loop performance. The closed-loop properties are influenced by the LQG weights. The article shows the impact of the weights on the antenna closed-loop bandwidth, disturbance rejection properties, and antenna acceleration. The bandwidth and the disturbance rejection characterize the antenna performance, while the acceleration represents the performance limit set by the antenna hardware (motors). The article presents the controller tuning procedure, based on the coordinate selection and the weight properties. The procedure rationally shapes the closed-loop performance, as an alternative to the trial-and-error approach.

Randomized Controlled Trial of Expressive Writing and Quality of Life in Men and Women Treated for Colorectal Cancer

PubMed Central

Lepore, Stephen J.; Revenson, Tracey A.; Roberts, Katherine J.; Pranikoff, Julie R.; Davey, Adam

2014-01-01

Objective This randomized trial tested (1) whether a home-based expressive writing (EW) intervention improves quality of life in patients with colorectal cancer and (2) whether the intervention is more beneficial for men or for people who feel constrained in disclosing cancer-related concerns and feelings. Design Patients treated for colorectal cancer were randomized to an EW (n = 101) or control writing (CW; n = 92) group. Assessments were completed at 1 month pre- and post-intervention. Sex and perceived social constraints on disclosure were evaluated as moderators. Main Outcome Measures Primary outcomes were depressive symptoms, sleep problems and quality of life indicators. Results 81% of participants completed all writing assignments. Consistent with hypotheses, relative to the CW group, participants in the EW group expressed more emotion in writing and rated their writings as more meaningful, personal, and emotionally revealing. There were no significant main effects of EW or moderating effects of sex or social constraints on outcomes. Conclusions Although EW is feasible to use with persons who have colorectal cancer, it was not effective as a stand-alone psychotherapeutic intervention. Nor was it more effective for men or for people who felt they could not freely disclose cancer-related concerns and feelings. PMID:25271396

Phenol-enriched olive oils improve HDL antioxidant content in hypercholesterolemic subjects. A randomized, double-blind, cross-over, controlled trial.

PubMed

Farràs, Marta; Fernández-Castillejo, Sara; Rubió, Laura; Arranz, Sara; Catalán, Úrsula; Subirana, Isaac; Romero, Mari-Paz; Castañer, Olga; Pedret, Anna; Blanchart, Gemma; Muñoz-Aguayo, Daniel; Schröder, Helmut; Covas, Maria-Isabel; de la Torre, Rafael; Motilva, Maria-José; Solà, Rosa; Fitó, Montserrat

2018-01-01

At present, high-density lipoprotein (HDL) function is thought to be more relevant than HDL cholesterol quantity. Consumption of olive oil phenolic compounds (PCs) has beneficial effects on HDL-related markers. Enriched food with complementary antioxidants could be a suitable option to obtain additional protective effects. Our aim was to ascertain whether virgin olive oils (VOOs) enriched with (a) their own PC (FVOO) and (b) their own PC plus complementary ones from thyme (FVOOT) could improve HDL status and function. Thirty-three hypercholesterolemic individuals ingested (25 ml/day, 3 weeks) (a) VOO (80 ppm), (b) FVOO (500 ppm) and (c) FVOOT (500 ppm) in a randomized, double-blind, controlled, crossover trial. A rise in HDL antioxidant compounds was observed after both functional olive oil interventions. Nevertheless, α-tocopherol, the main HDL antioxidant, was only augmented after FVOOT versus its baseline. In conclusion, long-term consumption of phenol-enriched olive oils induced a better HDL antioxidant content, the complementary phenol-enriched olive oil being the one which increased the main HDL antioxidant, α-tocopherol. Complementary phenol-enriched olive oil could be a useful dietary tool for improving HDL richness in antioxidants. Copyright © 2017. Published by Elsevier Inc.

Effectiveness, Medication Patterns, and Adverse Events of Traditional Chinese Herbal Patches for Osteoarthritis: A Systematic Review

PubMed Central

Wang, Xuezong; Liu, Ting; Gao, Ningyang; Ding, Daofang; Duan, Tieli; Cao, Yuelong; Zheng, Yuxin

2014-01-01

Objective. The aim of this study is to systematically evaluate the evidence whether traditional Chinese herbal patches (TCHPs) for osteoarthritis (OA) are effective and safe and analyze their medication patterns. Methods. A systematic literature search was performed using all the possible Medical Subject Headings (MeSH) and keywords from January 1979 to July 2013. Both randomized controlled trials (RCTs) and observational studies were included. Estimated effects were analyzed using mean difference (MD) or relative risk (RR) with 95% confidence intervals (CI) and meta-analysis. Results. 86 kinds of TCHPs were identified. RCTs and controlled clinical trials (CCTs) which were mostly of low quality favored TCHPs for local pain and dysfunction relief. TCHPs, compared with diclofenac ointment, had significant effects on global effectiveness rate (RR = 0.50; 95% CI (0.29, 0.87)). Components of formulae were mainly based on the compounds “Xiao Huo Luo Dan” (Minor collateral-freeing pill) and “Du Huo Ji Sheng Tang” (Angelicae Pubescentis and Loranthi decoction). Ten kinds of adverse events (AEs), mainly consisting of itching and/or local skin rashes, were identified after 3-4 weeks of follow-up. Conclusions. TCHPs have certain evidence in improving global effectiveness rate for OA; however, more rigorous studies are warranted to support their use. PMID:24527043

Conflict-specific effects of accessory stimuli on cognitive control in the Stroop task and the Simon task.

PubMed

Soutschek, Alexander; Müller, Hermann J; Schubert, Torsten

2013-01-01

Both the Stroop and the Simon paradigms are often used in research on cognitive control, however, there is evidence that dissociable control processes are involved in these tasks: While conflicts in the Stroop task may be resolved mainly by enhanced task-relevant stimulus processing, conflicts in the Simon task may be resolved rather by suppressing the influence of task-irrelevant information on response selection. In the present study, we show that these control mechanisms interact in different ways with the presentation of accessory stimuli. Accessory stimuli do not affect cognitive control in the Simon task, but they impair the efficiency of cross-trial control processes in the Stroop task. Our findings underline the importance of differentiating between different types of conflicts and mechanisms of cognitive control.

Prevalence and factors associated with use of placebo control groups in randomized controlled trials in psoriasis: a cross-sectional study.

PubMed

Katz, Kenneth A; Karlawish, Jason H; Chiang, David S; Bognet, Rachel A; Propert, Katherine J; Margolis, David J

2006-11-01

The ethics and science of using placebo control groups in clinical trials have been widely debated. Few studies, however, have examined factors associated with choice of control group. Our aim was to assess the prevalence of use of placebo controls in randomized controlled trials in psoriasis and to identify factors associated with use of placebo controls in these trials. This is a cross-sectional study of randomized controlled trials in psoriasis published from January 1, 2001 to December 20, 2005 and indexed in the Cochrane Central Register of Controlled Trials. We extracted data on types of control groups used, design issues (number of patients enrolled, primary end point), disease characteristics (psoriasis type and severity), and extrascientific issues (trial location, funding source, and year of publication). We used bivariable and multivariable logistic regression to determine factors associated with use of a placebo control group. Of 194 citations, 187 were available for review. One hundred thirty-five trials from 134 articles in 38 journals met inclusion criteria. Eighty-three trials (61.5%) enrolling 8171 subjects (41.7%) used active controls only, and 52 trials (38.5%) enrolling 11,406 subjects (58.3%) used placebo controls. Adjusted for trial location and funding source, trials significantly more likely to have used placebo controls included those conducted in the United States (odds ratio [OR], 5.79; 95% confidence interval [CI], 2.45-13.68; P < .001) and those funded by pharmaceutical companies (OR, 2.61; 95% CI, 1.19-5.73; P = .02). Predicted frequencies of placebo use ranged from 77.6% (industry-funded, conducted trials in the United States) to 18.6% (non-industry-funded trials not conducted in the United States). Our searches may not have identified all published trials, and we did not have access to data from unpublished trials. Use of placebo controls has been more common in psoriasis trials conducted in the United States and funded by pharmaceutical companies. The findings suggest that ethical and scientific issues related to choice of control group in psoriasis trials are interpreted markedly differently depending on trial location and funding source.

The effect of massage therapy and/or exercise therapy on subacute or long-lasting neck pain--the Stockholm neck trial (STONE): study protocol for a randomized controlled trial.

PubMed

Skillgate, Eva; Bill, Anne-Sylvie; Côté, Pierre; Viklund, Peter; Peterson, Anna; Holm, Lena W

2015-09-16

Neck pain is a major health problem in populations worldwide and an economic burden in modern societies due to its high prevalence and costs in terms of health care expenditures and lost productivity. Massage and exercise therapy are widely used management options for neck pain. However, there is a lack of scientific evidence regarding their effectiveness for subacute and long-lasting neck pain. This study protocol describes a randomized controlled trial aiming to determine the effect of massage and/or exercise therapy on subacute and long-lasting neck pain over the course of 1 year. A randomized controlled trial in which at least 600 study participants with subacute or long-lasting nonspecific neck pain will be recruited and randomly allocated to one of four treatment arms: massage therapy (A), exercise therapy (B), exercise therapy plus massage therapy (C) and advice to stay active (D). The study has an E-health approach, and study participants are being recruited through advertising with a mix of traditional and online marketing channels. Web-based self-report questionnaires measure the main outcomes at 7, 12, 26 and 52 weeks after inclusion. The primary outcomes are a clinically important improvement in pain intensity and pain-related disability at follow-up, measured with a modified version of the Chronic Pain Questionnaire (CPQ). The secondary outcomes are global improvement, health-related quality of life (EQ-5D), sick leave, drug consumption and healthcare utilization. Adverse events are measured by questionnaires at return visits to the clinic, and automated text messages (SMSes) survey neck pain intensity and pain-related disability every week over one year. The results of this study will provide clinicians and stakeholders much needed knowledge to plan medical care for subacute and long-lasting neck pain disorders. Current Controlled Trials ISRCTN01453590. Date of registration: 3 July 2014.

No reduction in instrumental vaginal births and no increased risk for adverse perineal outcome in nulliparous women giving birth on a birth seat: results of a Swedish randomized controlled trial

PubMed Central

2011-01-01

Background The WHO advises against recumbent or supine position for longer periods during labour and birth and states that caregivers should encourage and support the woman to take the position in which she feels most comfortable. It has been suggested that upright positions may improve childbirth outcomes and reduce the risk for instrumental delivery; however RCTs of interventions to encourage upright positions are scarce. The aim of this study was to test, by means of a randomized controlled trial, the hypothesis that the use of a birthing seat during the second stage of labor, for healthy nulliparous women, decreases the number of instrumentally assisted births and may thus counterbalance any increase in perineal trauma and blood loss. Methods A randomized controlled trial in Sweden where 1002 women were randomized to birth on a birth seat (experimental group) or birth in any other position (control group). Data were collected between November 2006 and July 2009. The primary outcome measurement was the number of instrumental deliveries. Secondary outcome measurements included perineal lacerations, perineal edema, maternal blood loss and hemoglobin. Analysis was by intention to treat. Results The main findings of this study were that birth on the birth seat did not reduce the number of instrumental vaginal births, there was an increase in blood loss between 500 ml and 1000 ml in women who gave birth on the seat but no increase in bleeding over 1000 ml and no increase in perineal lacerations or perineal edema. Conclusions The birth seat did not reduce the number of instrumental vaginal births. The study confirmed an increased blood loss 500 ml - 1000 ml but not over 1000 ml for women giving birth on the seat. Giving birth on a birth seat caused no adverse consequences for perineal outcomes and may even be protective against episiotomies. Trial registration number ClinicalTrials.gov.ID: NCT01182038 PMID:21435238

Is hydroxychloroquine effective in treating primary Sjogren's syndrome: a systematic review and meta-analysis.

PubMed

Wang, Shi-Qin; Zhang, Li-Wei; Wei, Pan; Hua, Hong

2017-05-12

To systematically review and assess the efficacy and safety of hydroxychloroquine (HCQ) for treating primary Sjogren's syndrome (pSS). Five electronic databases (Pubmed, EMBASE, Web of science, Ovid, Cochrane Library) were searched for randomized controlled trials and retrospective or prospective studies published in English that reported the effect of HCQ on pSS. The subjective symptoms (sicca symptoms, fatigue and pain) and the objective indexes (erythrocyte sedimentation rate and Schirmer test) were assessed as main outcome measures. A meta-analysis and descriptive study on the efficacy and safety of HCQ were conducted. The estimate of the effect of HCQ treatment was expressed as a proportion together with 95% confidence interval, and plotted on a forest plot. Four trials with totals of 215 SS patients, including two randomized controlled trials, one double blind crossover trial and one retrospective open-label study, were analyzed in this review. For dry mouth and dry eyes, the effectiveness of HCQ treatment was essentially the same as placebo treatment. For fatigue, the effectiveness of HCQ was lower than placebo. The efficacy of HCQ in treating pain associated with pSS was superior to that of the placebo. There was no significant difference between HCQ-treated groups and controls in terms of Schirmer test results, but HCQ could reduce the erythrocyte sedimentation rate compare with placebo. A descriptive safety assessment showed that gastrointestinal adverse effects were the most common adverse effects associated with HCQ. This systematic review showed that there is no significant difference between HCQ and placebo in the treatment of dry mouth and dry eye in pSS. Well-designed, randomized, controlled trials are needed to provide higher-quality evidence to confirm our findings, and future studies should focus on some other index or extraglandular measures, such as cutaneous manifestations, to further explore the therapeutic effect of HCQ in pSS.

A prospective cluster-randomized trial to implement the Canadian CT Head Rule in emergency departments

PubMed Central

Stiell, Ian G.; Clement, Catherine M.; Grimshaw, Jeremy M.; Brison, Robert J.; Rowe, Brian H.; Lee, Jacques S.; Shah, Amit; Brehaut, Jamie; Holroyd, Brian R.; Schull, Michael J.; McKnight, R. Douglas; Eisenhauer, Mary A.; Dreyer, Jonathan; Letovsky, Eric; Rutledge, Tim; MacPhail, Iain; Ross, Scott; Perry, Jeffrey J.; Ip, Urbain; Lesiuk, Howard; Bennett, Carol; Wells, George A.

2010-01-01

Background The Canadian CT Head Rule was developed to allow physicians to be more selective when ordering computed tomography (CT) imaging for patients with minor head injury. We sought to evaluate the effectiveness of implementing this validated decision rule at multiple emergency departments. Methods We conducted a matched-pair cluster-randomized trial that compared the outcomes of 4531 patients with minor head injury during two 12-month periods (before and after) at hospital emergency departments in Canada, six of which were randomly allocated as intervention sites and six as control sites. At the intervention sites, active strategies, including education, changes to policy and real-time reminders on radiologic requisitions were used to implement the Canadian CT Head Rule. The main outcome measure was referral for CT scan of the head. Results Baseline characteristics of patients were similar when comparing control to intervention sites. At the intervention sites, the proportion of patients referred for CT imaging increased from the “before” period (62.8%) to the “after” period (76.2%) (difference +13.3%, 95% CI 9.7%–17.0%). At the control sites, the proportion of CT imaging usage also increased, from 67.5% to 74.1% (difference +6.7%, 95% CI 2.6%–10.8%). The change in mean imaging rates from the “before” period to the “after” period for intervention versus control hospitals was not significant (p = 0.16). There were no missed brain injuries or adverse outcomes. Interpretation Our knowledge–translation-based trial of the Canadian CT Head Rule did not reduce rates of CT imaging in Canadian emergency departments. Future studies should identify strategies to deal with barriers to implementation of this decision rule and explore more effective approaches to knowledge translation. (ClinicalTrials.gov trial register no. NCT00993252) PMID:20732978

A cluster randomised controlled trial to determine the effect of community mobilisation and advocacy on men’s use of violence in periurban South Africa: study protocol

PubMed Central

Christofides, Nicola J; Hatcher, Abigail M; Pino, Angelica; Rebombo, Dumisani; McBride, Ruari Santiago; Anderson, Althea; Peacock, Dean

2018-01-01

Objective This paper describes the design and methods of a cluster randomised controlled trial (C-RCT) to determine the effectiveness of a community mobilisation intervention that is designed to reduce the perpetration of violence against women (VAW). Methods and analysis A C-RCT of nine intervention and nine control clusters is being carried out in a periurban, semiformal settlement near Johannesburg, South Africa, between 2016 and 2018. A community mobilisation and advocacy intervention, called Sonke CHANGE is being implemented over 18 months. It comprises local advocacy and group activities to engage community members to challenge harmful gender norms and reduce VAW. The intervention is hypothesised to improve equitable masculinities, reduce alcohol use and ultimately, to reduce VAW. Intervention effectiveness will be determined through an audio computer-assisted self-interview questionnaire with behavioural measures among 2600 men aged between 18 and 40 years at baseline, 12 months and 24 months. The primary trial outcome is men’s use of physical and/or sexual VAW. Secondary outcomes include harmful alcohol use, gender attitudes, controlling behaviours, transactional sex and social cohesion. The main analysis will be intention-to-treat based on the randomisation of clusters. A qualitative process evaluation is being conducted alongside the C-RCT. Implementers and men participating in the intervention will be interviewed longitudinally over the period of intervention implementation and observations of the workshops and other intervention activities are being carried out. Ethics and dissemination Ethical approval was obtained from the University of the Witwatersrand Human Research Ethics Committee and procedures comply with ethical recommendations of the United Nations Multi-Country Study on Men and Violence. Dissemination of research findings will take place with local stakeholders and through peer-reviewed publications, with data available on request or after 5 years of trial completion. Trial registration number NCT02823288; Pre-result. PMID:29574438

Rehab-let: touchscreen tablet for self-training impaired dexterity post stroke: study protocol for a pilot randomized controlled trial.

PubMed

Rand, Debbie; Zeilig, Gabi; Kizony, Rachel

2015-06-18

Impaired dexterity of the weaker upper extremity is common post stroke and it is recommended that these individuals practice many repetitions of movement to regain function. However, stroke rehabilitation methods do not achieve the required intensity to be effective. Touchscreen tablet technology may be used as a motivating tool for self-training impaired dexterity of the weaker upper extremity post stroke. Rehab-let is a self-training protocol utilizing game apps on a touchscreen for practicing movement of the weaker upper extremity. We will conduct a pilot randomized controlled trial to assess Rehab-let compared to traditional self-training to improve dexterity of the weaker hand, and to increase self-training time and satisfaction in individuals with subacute stroke. Forty individuals with stroke undergoing subacute rehabilitation will be randomly allocated to Rehab-let or a traditional self-training program using therapeutic aids such as balls, blocks and pegs. All participants will be requested to perform self-training for 60 minutes a day, 5 times a week for 4 weeks. Dexterity assessed by The Nine Hole Peg Test is the main outcome measure. Assessments will be administered pre and post the self-training intervention by assessors blind to the group allocation. The outcomes of this study will inform the design of a fully powered randomized controlled trial to evaluate the effectiveness of Rehab-let. If found to be effective, Rehab-let can be used during subacute rehabilitation to increase treatment intensity and improve dexterity. Potentially, Rehab-let can also be used after discharge and might be ideal for individuals with mild stroke who are often not referred to formal rehabilitation. Current Controlled Trials NCT02136433 registered on 17 September 2014.

Costs and Effects of Abdominal versus Laparoscopic Hysterectomy: Systematic Review of Controlled Trials

PubMed Central

Bijen, Claudia B. M.; Vermeulen, Karin M.; Mourits, Marian J. E.; de Bock, Geertruida H.

2009-01-01

Objective Comparative evaluation of costs and effects of laparoscopic hysterectomy (LH) and abdominal hysterectomy (AH). Data sources Controlled trials from Cochrane Central register of controlled trials, Medline, Embase and prospective trial registers. Selection of studies Twelve (randomized) controlled studies including the search terms costs, laparoscopy, laparotomy and hysterectomy were identified. Methods The type of cost analysis, perspective of cost analyses and separate cost components were assessed. The direct and indirect costs were extracted from the original studies. For the cost estimation, hospital stay and procedure costs were selected as most important cost drivers. As main outcome the major complication rate was taken. Findings Analysis was performed on 2226 patients, of which 1013 (45.5%) in the LH group and 1213 (54.5%) in the AH group. Five studies scored ≥10 points (out of 19) for methodological quality. The reported total direct costs in the LH group ($63,997) were 6.1% higher than the AH group ($60,114). The reported total indirect costs of the LH group ($1,609) were half of the total indirect in the AH group ($3,139). The estimated mean major complication rate in the LH group (14.3%) was lower than in the AH group (15.9%). The estimated total costs in the LH group were $3,884 versus $3,312 in the AH group. The incremental costs for reducing one patient with major complication(s) in the LH group compared to the AH group was $35,750. Conclusions The shorter hospital stay in the LH group compensates for the increased procedure costs, with less morbidity. LH points in the direction of cost effectiveness, however further research is warranted with a broader costs perspective including long term effects as societal benefit, quality of life and survival. PMID:19806210

The Good Schools Toolkit to prevent violence against children in Ugandan primary schools: study protocol for a cluster randomised controlled trial

PubMed Central

2013-01-01

Background We aim to evaluate the effectiveness of the Good School Toolkit, developed by Raising Voices, in preventing violence against children attending school and in improving child mental health and educational outcomes. Methods/design We are conducting a two-arm cluster randomised controlled trial with parallel assignment in Luwero District, Uganda. We will also conduct a qualitative study, a process evaluation and an economic evaluation. A total of 42 schools, representative of Luwero District, Uganda, were allocated to receive the Toolkit plus implementation support, or were allocated to a wait-list control condition. Our main analysis will involve a cross-sectional comparison of the prevalence of past-week violence from school staff as reported by children in intervention and control primary schools at follow-up. At least 60 children per school and all school staff members will be interviewed at follow-up. Data collection involves a combination of mobile phone-based, interviewer-completed questionnaires and paper-and-pen educational tests. Survey instruments include the ISPCAN Child Abuse Screening Tools to assess experiences of violence; the Strengths and Difficulties Questionnaire to measure symptoms of common childhood mental disorders; and word recognition, reading comprehension, spelling, arithmetic and sustained attention tests adapted from an intervention trial in Kenya. Discussion To our knowledge, this is the first study to rigorously investigate the effects of any intervention to prevent violence from school staff to children in primary school in a low-income setting. We hope the results will be informative across the African region and in other settings. Trial registration clinicaltrials.gov NCT01678846 PMID:23883138

Effectiveness of robot-assisted therapy on ankle rehabilitation--a systematic review.

PubMed

Zhang, Mingming; Davies, T Claire; Xie, Shane

2013-03-21

The aim of this study was to provide a systematic review of studies that investigated the effectiveness of robot-assisted therapy on ankle motor and function recovery from musculoskeletal or neurologic ankle injuries. Thirteen electronic databases of articles published from January, 1980 to June, 2012 were searched using keywords 'ankle*', 'robot*', 'rehabilitat*' or 'treat*' and a free search in Google Scholar based on effects of ankle rehabilitation robots was also conducted. References listed in relevant publications were further screened. Eventually, twenty-nine articles were selected for review and they focused on effects of robot-assisted ankle rehabilitation. Twenty-nine studies met the inclusion criteria and a total of 164 patients and 24 healthy subjects participated in these trials. Ankle performance and gait function were the main outcome measures used to assess the therapeutic effects of robot-assisted ankle rehabilitation. The protocols and therapy treatments were varied, which made comparison among different studies difficult or impossible. Few comparative trials were conducted among different devices or control strategies. Moreover, the majority of study designs met levels of evidence that were no higher than American Academy for Cerebral Palsy (CP) and Developmental Medicine (AACPDM) level IV. Only one study used a Randomized Control Trial (RCT) approach with the evidence level being II. All the selected studies showed improvements in terms of ankle performance or gait function after a period of robot-assisted ankle rehabilitation training. The most effective robot-assisted intervention cannot be determined due to the lack of universal evaluation criteria for various devices and control strategies. Future research into the effects of robot-assisted ankle rehabilitation should be carried out based on universal evaluation criteria, which could determine the most effective method of intervention. It is also essential to conduct trials to analyse the differences among different devices or control strategies.

Identifying Items to Assess Methodological Quality in Physical Therapy Trials: A Factor Analysis

PubMed Central

Cummings, Greta G.; Fuentes, Jorge; Saltaji, Humam; Ha, Christine; Chisholm, Annabritt; Pasichnyk, Dion; Rogers, Todd

2014-01-01

Background Numerous tools and individual items have been proposed to assess the methodological quality of randomized controlled trials (RCTs). The frequency of use of these items varies according to health area, which suggests a lack of agreement regarding their relevance to trial quality or risk of bias. Objective The objectives of this study were: (1) to identify the underlying component structure of items and (2) to determine relevant items to evaluate the quality and risk of bias of trials in physical therapy by using an exploratory factor analysis (EFA). Design A methodological research design was used, and an EFA was performed. Methods Randomized controlled trials used for this study were randomly selected from searches of the Cochrane Database of Systematic Reviews. Two reviewers used 45 items gathered from 7 different quality tools to assess the methodological quality of the RCTs. An exploratory factor analysis was conducted using the principal axis factoring (PAF) method followed by varimax rotation. Results Principal axis factoring identified 34 items loaded on 9 common factors: (1) selection bias; (2) performance and detection bias; (3) eligibility, intervention details, and description of outcome measures; (4) psychometric properties of the main outcome; (5) contamination and adherence to treatment; (6) attrition bias; (7) data analysis; (8) sample size; and (9) control and placebo adequacy. Limitation Because of the exploratory nature of the results, a confirmatory factor analysis is needed to validate this model. Conclusions To the authors' knowledge, this is the first factor analysis to explore the underlying component items used to evaluate the methodological quality or risk of bias of RCTs in physical therapy. The items and factors represent a starting point for evaluating the methodological quality and risk of bias in physical therapy trials. Empirical evidence of the association among these items with treatment effects and a confirmatory factor analysis of these results are needed to validate these items. PMID:24786942

Systematic review of randomised controlled trials of strategies to promote adherence to tuberculosis treatment.

PubMed Central

Volmink, J.; Garner, P.

1997-01-01

OBJECTIVE: To determine the effectiveness of strategies to promote adherence to treatment for tuberculosis. IDENTIFICATION: Searches in Medline (1966 to August 1996), the Cochrane trials register (up to October 1996), and LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud) (1982 to September 1996); screening of references in articles on compliance and adherence; contact with experts in research on tuberculosis and adherence. INCLUSION CRITERIA: Randomised or pseudorandomised controlled trials of interventions to promote adherence with curative or preventive treatment for tuberculosis, with at least one measure of adherence. MAIN OUTCOME MEASURE: Relative risks and 95% confidence intervals for estimates of effect for categorical outcomes. RESULTS: Five trials met the inclusion criteria. The relative risk for tested reminder cards sent to patients who defaulted on treatment was 1.2 (95% confidence interval 1.1 to 1.4), for help given to patients by lay health workers 1.4 (1.1 to 1.8), for monetary incentives offered to patients 1.6 (1.3 to 2.0), for health education 1.2 (1.1 to 1.4), for a combination of a patient incentive and health education 2.4 (1.5 to 3.7) or 1.1 (1.0 to 1.2), and for intensive supervision of staff in tuberculosis clinics 1.2 (1.1 to 1.3). There were no completed trials of directly observed treatment. All of the interventions tested improved adherence. On current evidence it is unclear whether health education by itself leads to better adherence to treatment. CONCLUSIONS: Reliable evidence is available to show some specific strategies improve adherence to tuberculosis treatment, and these should be adopted in health systems, depending on their appropriateness to practice circumstances. Further innovations require testing to help find specific approaches that will be useful in low income countries. Randomised controlled trials evaluating the independent effects of directly observed treatment are awaited. PMID:9418086

Identifying items to assess methodological quality in physical therapy trials: a factor analysis.

PubMed

Armijo-Olivo, Susan; Cummings, Greta G; Fuentes, Jorge; Saltaji, Humam; Ha, Christine; Chisholm, Annabritt; Pasichnyk, Dion; Rogers, Todd

2014-09-01

Numerous tools and individual items have been proposed to assess the methodological quality of randomized controlled trials (RCTs). The frequency of use of these items varies according to health area, which suggests a lack of agreement regarding their relevance to trial quality or risk of bias. The objectives of this study were: (1) to identify the underlying component structure of items and (2) to determine relevant items to evaluate the quality and risk of bias of trials in physical therapy by using an exploratory factor analysis (EFA). A methodological research design was used, and an EFA was performed. Randomized controlled trials used for this study were randomly selected from searches of the Cochrane Database of Systematic Reviews. Two reviewers used 45 items gathered from 7 different quality tools to assess the methodological quality of the RCTs. An exploratory factor analysis was conducted using the principal axis factoring (PAF) method followed by varimax rotation. Principal axis factoring identified 34 items loaded on 9 common factors: (1) selection bias; (2) performance and detection bias; (3) eligibility, intervention details, and description of outcome measures; (4) psychometric properties of the main outcome; (5) contamination and adherence to treatment; (6) attrition bias; (7) data analysis; (8) sample size; and (9) control and placebo adequacy. Because of the exploratory nature of the results, a confirmatory factor analysis is needed to validate this model. To the authors' knowledge, this is the first factor analysis to explore the underlying component items used to evaluate the methodological quality or risk of bias of RCTs in physical therapy. The items and factors represent a starting point for evaluating the methodological quality and risk of bias in physical therapy trials. Empirical evidence of the association among these items with treatment effects and a confirmatory factor analysis of these results are needed to validate these items. © 2014 American Physical Therapy Association.

Psycho-educational interventions for children and young people with Type 1 Diabetes in the UK: How effective are they? A systematic review and meta-analysis

PubMed Central

Hesketh, Kathryn R.; Amin, Rakesh; Paes, Veena Mazarello; Viner, Russell M.; Stephenson, Terence

2017-01-01

Aims To synthesise evidence from UK-based randomised trials of psycho-educational interventions in children and young people (CYP) with Type 1 Diabetes (T1D) to inform the evidence-base for adoption of such interventions into the NHS. Methods We searched Medline, Embase, Cochrane, PsycINFO, CINAHL, and Web of Science up to March 2016. Two reviewers independently selected UK-based randomised trials comparing psycho-educational interventions for improving management of T1D for CYP with a control group of usual care or attention control. The main outcome was glycaemic control measured by percentage of glycated haemoglobin (HbA1c); secondary outcomes included psychosocial functioning, diabetes knowledge, adverse and other clinical outcomes. A narrative synthesis and meta-analysis were conducted. Pooled effect sizes of standardised mean difference (SMD) were calculated. Results Ten eligible trials of three educational and seven psycho-educational interventions were identified. Most interventions were delivered by non-psychologists and targeted adolescents with more than one year duration of diabetes. Meta-analysis of nine of these trials (N = 1,838 participants) showed a non-significant reduction in HbA1c attributable to the intervention (pooled SMD = -0.06, 95% CI: -0.21 to 0.09). Psycho-educational interventions aiming to increase children’s self-efficacy had a moderate, beneficial effect (SMD = 0.50, 95% CI: 0.13 to 0.87). No benefits on diabetes knowledge and other indicators of psychosocial functioning were identified. Conclusions There is insufficient evidence to recommend the use of particular psycho-educational programme for CYP with T1D in the UK. Further trials with sufficient power and reporting standards are needed. Future trials could consider active involvement of psychological specialists in the delivery of psychologically informed interventions and implementation of psycho-educational interventions earlier in the course of the disease. Systematic review registration PROSPERO CRD42015010701 PMID:28665946

Increasing students' physical activity during school physical education: rationale and protocol for the SELF-FIT cluster randomized controlled trial.

PubMed

Ha, Amy S; Lonsdale, Chris; Lubans, David R; Ng, Johan Y Y

2017-07-11

The Self-determined Exercise and Learning For FITness (SELF-FIT) is a multi-component school-based intervention based on tenets of self-determination theory. SELF-FIT aims to increase students' moderate-to-vigorous physical activity (MVPA) during physical education lessons, and enhance their autonomous motivation towards fitness activities. Using a cluster randomized controlled trial, we aim to examine the effects of the intervention on students' MVPA during school physical education. Secondary 2 students (approximately aged 14 years) from 26 classes in 26 different schools will be recruited. After baseline assessments, students will be randomized into either the experimental group or wait-list control group using a matched-pair randomization. Teachers allocated to the experimental group will attend two half-day workshops and deliver the SELF-FIT intervention for 8 weeks. The main intervention components include training teachers to teach in more need supportive ways, and conducting fitness exercises using a fitness dice with interchangeable faces. Other motivational components, such as playing music during classes, are also included. The primary outcome of the trial is students' MVPA during PE lessons. Secondary outcomes include students' leisure-time MVPA, perceived need support from teachers, need satisfaction, autonomous motivation towards physical education, intention to engage in physical activity, psychological well-being, and health-related fitness (cardiorespiratory and muscular fitness). Quantitative data will be analyzed using multilevel modeling approaches. Focus group interviews will also be conducted to assess students' perceptions of the intervention. The SELF-FIT intervention has been designed to improve students' health and well-being by using high-intensity activities in classes delivered by teachers who have been trained to be autonomy needs supportive. If successful, scalable interventions based on SELF-FIT could be applied in physical education at large. The trial is registered at the Australia New Zealand Clinical Trial Registry (Trial ID: ACTRN12615000633583 ; date of registration: 18 June 2015).

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

PubMed

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

2016-11-24

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

Palifermin: new drug. Prevention of oral mucositis: inappropriate evaluation.

PubMed

2007-08-01

(1) Patients treated with high-dose chemotherapy combined with total body irradiation (myeloablative therapy) often develop oral mucositis. Prevention is based mainly on sucking ice during chemotherapy. (2) Palifermin is a growth factor marketed for the prevention of severe oral mucositis in adults with malignant haemopathies who are receiving myeloablative therapy followed by peripheral stem cell autografting. (3) Palifermin has not been compared with sucking ice, despite the efficacy of this simple treatment. (4) In a randomised placebo-controlled double-blind trial involving 212 adult patients treated with high-dose chemotherapy and total body irradiation, palifermin reduced the incidence of severe oral mucositis (63% versus 98%) and its duration (about 3 days versus 9 days). The myeloablative regimen used in this trial is not that commonly used in Europe. The efficacy of palifermin during less aggressive regimens, which cause less severe oral mucositis, is not known. (5) The main adverse events noted in clinical trials were erythema and cutaneous oedema. It is not known whether palifermin increases the long-term risk of cancer. (6) Treatment with palifermin is expensive, 4800.00 euros in France); the optimal dosing schedule is not known and the unit dose chosen by the manufacturer is wastefully large. (7) In practice, it remains to be demonstrated that palifermin is more effective than simply sucking ice.

A qualitative process evaluation of a randomised controlled trial of a parenting intervention in community (school) settings for children at risk of attention deficit hyperactivity disorder (ADHD).

PubMed

Taylor, John A; Valentine, Althea Z; Sellman, Edward; Bransby-Adams, Kate; Daley, David; Sayal, Kapil

2015-11-17

Interventions for parents of children experiencing emotional and/or behavioural difficulties can help to improve their children's health, educational and social outcomes. However, the desirability and acceptability of screening and offering such interventions for attention-deficit hyperactivity disorder (ADHD)-type problems are currently unclear. This article is a qualitative process evaluation of a pragmatic cluster randomised controlled trial (Trial registration: ISRCTN87634685; reported elsewhere) to assess the feasibility and acceptability of a school-based parenting intervention programme for parents and teachers of children with high levels of ADHD symptoms. Parents (n = 22) and teaching staff (n = 29) took part in semi-structured group or individual interviews, either by telephone or face-to-face, following the main trial. Interviews were digitally-recorded, transcribed verbatim and subjected to thematic analysis. The parenting intervention was acceptable to parents and teachers, and they were enthusiastic about the need for parenting groups in the school environment and stressed the importance of parent-school collaboration. Parents generally stated a preference for universal recruitment approaches to such programmes whilst teachers described the need to target specific parents. Most parents who took part in the parenting intervention described it favourably and many saw benefits, at least in the short-term. Parents differed in their preferred group size, with some desiring one-to-one sessions and others favouring a larger group. Non-attending parents reported barriers to attendance such as fear of attending in a group, previous use of the programme, work and other commitments. Suggestions to improve the programme included: clearer communication; offering booster sessions; and greater collaboration with teachers. It is feasible to deliver parenting intervention programmes within or near schools. The intervention was acceptable to the majority of parents, thus retention was high, but recruitment was difficult and reaching the parents with the most need was challenging. The findings of the process evaluation identified greater benefits to families than were apparent in the main trial. Recommendations identified by parents and teaching staff may be used to inform service delivery and future research to enhance recruitment to parenting interventions in the school environment.

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

A Review of Marital Intimacy-Enhancing Interventions among Married Individuals.

PubMed

Kardan-Souraki, Maryam; Hamzehgardeshi, Zeinab; Asadpour, Ismail; Mohammadpour, Reza Ali; Khani, Soghra

2016-08-01

Lack of intimacy is currently the main concern rather than main concern of the experts in psychology and counseling. It is considered as one of the most important causes for divorce and as such to improve marital intimacy a great number of interventions have been proposed in the literature. Intimacy training and counseling make the couples take effective and successful steps to increase marital intimacy. No study has reviewed the interventions promoting marital intimacy after marriage. Thus, this review study aimed to classify the articles investigating the impact of interventional programs on marital intimacy after marriage. In April 2015, we performed a general search in Google Scholar search engines, and then we did an advanced search the databases of Science Direct, ProQuest, SID, Magiran, Irandoc, Pubmed, Scopus, Cochrane Library, and Psych info; Cumulative Index to Nursing and Allied Health Literature (CINAHL). Also, lists of the references of the relevant articles were reviewed for additional citations. Using Medical Subject Headings (MESH) keywords: Intervention (Clinical Trials, Non-Randomized Controlled Trials, Randomized Controlled Trials, Education), intimacy, marital (Marriage) and selected related articles to the study objective were from 1995 to April 2015. Clinical trials that evaluated one or more behavioral interventions to improve marital intimacy were reviewed in the study. 39 trials met the inclusion criteria. Eleven interventions had follow-up, and 28 interventions lacked follow-up. The quality evidence for 22 interventions was low, for 15 interventions moderate, and for one intervention was considered high. Findings from studies were categorized in 11 categories as the intimacy promoting interventions in dimensions of emotional, psychological, physical, sexual, temporal, communicational, social and recreational, aesthetic, spiritual, intellectual intimacy, and total intimacy. Improving and promoting communication, problem solving, self-disclosure and empathic response skills and sexual education and counseling in the form of cognitive-behavioral techniques and based on religious and cultural context of each society, an effective step can be taken to enhance marital intimacy and strengthen family bonds and stability. Health care providers should consider which interventions are appropriate to the couple characteristics and their relationships.

Physical activity and adolescents: an exploratory randomized controlled trial investigating the influence of affective and instrumental text messages.

PubMed

Sirriyeh, Reema; Lawton, Rebecca; Ward, Jane

2010-11-01

The present study attempts to develop and pilot the feasibility and efficacy of a novel intervention using affective messages as a strategy to increase physical activity (PA) levels in adolescents. Design An exploratory pilot randomized control trial was used to compare behaviour change over 2 weeks. A modified form of the International Physical Activity Questionnaire was used to assess PA behaviour. A total of 120 adolescents (16-19 years) from 4 sixth forms in West Yorkshire completed the field-based study. Participants were randomly assigned to one of three experimental conditions, or the control condition (N=28). Participants in experimental conditions received 1 short messaging service (SMS) text message per day over the 2 weeks, which included manipulations of either affective beliefs (enjoyable/unenjoyable; N=31), instrumental beliefs (beneficial/harmful; N=30), or a combination of these (N=31). Control participants received one SMS text message per week. Outcomes were measured at baseline and at the end of the 2 week intervention. PA levels increased by the equivalent of 31.5  minutes of moderate (four metabolic equivalent) activity per week during the study. Main effects of condition (p=.049), and current physical activity level (p=.002) were identified, along with a significant interaction between condition and current activity level (p=.006). However, when the sample was split at baseline into active and inactive participants, a main effect of condition remained for inactive participants only (p=.001). Post hoc analysis revealed that inactive participants who received messages targeting affective beliefs increased their activity levels significantly more than the instrumental (p=.012), combined (p=.002), and control groups (p=.018). Strategies based on affective associations may be more effective for increasing PA levels in inactive individuals.

Corticosteroids for Bell's palsy (idiopathic facial paralysis).

PubMed

Madhok, Vishnu B; Gagyor, Ildiko; Daly, Fergus; Somasundara, Dhruvashree; Sullivan, Michael; Gammie, Fiona; Sullivan, Frank

2016-07-18

Inflammation and oedema of the facial nerve are implicated in causing Bell's palsy. Corticosteroids have a potent anti-inflammatory action that should minimise nerve damage. This is an update of a review first published in 2002 and last updated in 2010. To determine the effectiveness and safety of corticosteroid therapy in people with Bell's palsy. On 4 March 2016, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS. We reviewed the bibliographies of the randomised trials and contacted known experts in the field to identify additional published or unpublished trials. We also searched clinical trials registries for ongoing trials. Randomised trials and quasi-randomised trials comparing different routes of administration and dosage schemes of corticosteroid or adrenocorticotrophic hormone therapy versus a control group receiving no therapy considered effective for this condition, unless the same therapy was given in a similar way to the experimental group. We used standard Cochrane methodology. The main outcome of interest was incomplete recovery of facial motor function (i.e. residual facial weakness). Secondary outcomes were cosmetically disabling persistent sequelae, development of motor synkinesis or autonomic dysfunction (i.e. hemifacial spasm, crocodile tears) and adverse effects of corticosteroid therapy manifested during follow-up. We identified seven trials, with 895 evaluable participants for this review. All provided data suitable for the primary outcome meta-analysis. One of the trials was new since the last version of this Cochrane systematic review. Risk of bias in the older, smaller studies included some unclear- or high-risk assessments, whereas we deemed the larger studies at low risk of bias. Overall, 79/452 (17%) participants allocated to corticosteroids had incomplete recovery of facial motor function six months or more after randomisation; significantly fewer than the 125/447 (28%) in the control group (risk ratio (RR) 0.63, 95% confidence interval (CI) 0.50 to 0.80, seven trials, n = 895). The number of people who need to be treated with corticosteroids to avoid one incomplete recovery was 10 (95% CI 6 to 20). The reduction in the proportion of participants with cosmetically disabling sequelae six months after randomisation was very similar in the corticosteroid and placebo groups (RR 0.96, 95% CI 0.40 to 2.29, two trials, n = 75, low-quality evidence). However, there was a significant reduction in motor synkinesis during follow-up in participants receiving corticosteroids (RR 0.64, 95% CI 0.45 to 0.91, three trials, n = 485, moderate-quality evidence). Three studies explicitly recorded the absence of adverse effects attributable to corticosteroids. One trial reported that three participants receiving prednisolone had temporary sleep disturbances and two trials gave a detailed account of adverse effects occurring in 93 participants, all non-serious; the combined analysis of data from these three trials found no significant difference in adverse effect rates between people receiving corticosteroids and people receiving placebo (RR 1.04, 95% CI 0.71 to 1.51, n = 715). The available moderate- to high-quality evidence from randomised controlled trials showed significant benefit from treating Bell's palsy with corticosteroids.

Classroom based cognitive behavioural therapy in reducing symptoms of depression in high risk adolescents: pragmatic cluster randomised controlled trial

PubMed Central

Sayal, Kapil; Phillips, Rhiannon; Taylor, John A; Spears, Melissa; Anderson, Rob; Araya, Ricardo; Lewis, Glyn; Millings, Abigail; Montgomery, Alan A

2012-01-01

Objective To compare the effectiveness of classroom based cognitive behavioural therapy with attention control and usual school provision for adolescents at high risk of depression. Design Three arm parallel cluster randomised controlled trial. Setting Eight UK secondary schools. Participants Adolescents (n=5030) aged 12-16 years in school year groups 8-11. Year groups were randomly assigned on a 1:1:1 ratio to cognitive behavioural therapy, attention control, or usual school provision. Allocation was balanced by school, year, number of students and classes, frequency of lessons, and timetabling. Participants were not blinded to treatment allocation. Interventions Cognitive behavioural therapy, attention control, and usual school provision provided in classes to all eligible participants. Main outcome measures Outcomes were collected by self completed questionnaire administered by researchers. The primary outcome was symptoms of depression assessed at 12 months by the short mood and feelings questionnaire among those identified at baseline as being at high risk of depression. Secondary outcomes included negative thinking, self worth, and anxiety. Analyses were undertaken on an intention to treat basis and accounted for the clustered nature of the design. Results 1064 (21.2%) adolescents were identified at high risk of depression: 392 in the classroom based cognitive behavioural therapy arm, 374 in the attention control arm, and 298 in the usual school provision arm. At 12 months adjusted mean scores on the short mood and feelings questionnaire did not differ for cognitive behavioural therapy versus attention control (−0.63, 95% confidence interval −1.85 to 0.58, P=0.41) or for cognitive behavioural therapy versus usual school provision (0.97, −0.20 to 2.15, P=0.12). Conclusion In adolescents with depressive symptoms, outcomes were similar for attention control, usual school provision, and cognitive behavioural therapy. Classroom based cognitive behavioural therapy programmes may result in increased self awareness and reporting of depressive symptoms but should not be undertaken without further evaluation and research. Trial registration Current Controlled Trials ISRCTN19083628. PMID:23043090

Interventions for increasing fruit and vegetable consumption in children aged 5 years and under

PubMed Central

Wolfenden, Luke; Wyse, Rebecca J; Britton, Ben I; Campbell, Karen J; Hodder, Rebecca K; Stacey, Fiona G; McElduff, Patrick; James, Erica L

2014-01-01

Background Insufficient consumption of fruits and vegetables in childhood increases the risk of future chronic diseases including cardiovascular disease. Objectives To assess the effectiveness, cost-effectiveness and associated adverse events of interventions designed to increase the consumption of fruit and/or vegetables amongst children aged five years and under. Search methods The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 2, 2010, MEDLINE (1950 to 2010 April week 4), EMBASE (1947 to 2010 week 18), CINAHL (up to 12 May 2010), PsycINFO (up to 12 May 2010) and Proquest Dissertations and Theses (up to February 2011) were searched to identify eligible trials, as well as electronic trial registers (also up to February 2011). The reference lists of included trials were reviewed and handsearches of three international nutrition journals were also performed. Authors of all included trials were contacted in order to identify further potentially relevant trials. Selection criteria We included randomised controlled trials (RCTs), including cluster-randomised controlled trials, of any intervention primarily targeting fruit and/or vegetable consumption among children aged five years and under and incorporating a biochemical or dietary assessment of fruit and/or vegetable consumption. Two review authors independently screened the titles and abstracts of identified papers. A third review author with expertise in review methodology resolved any disagreements regarding study eligibility. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias of the included studies. A third reviewer resolved disagreements between review authors. Fixed-effect models were used to perform meta-analysis for the primary review outcomes where a sufficient number of trials with suitable data and homogeneity were identified. Main results Five trials, with 13 trial arms and 3967 participants were included in the review. Two trials examined the impact of specific feeding practices (e.g. repeated food exposure) in increasing child intake of a target vegetable. Two trials assessed the effectiveness of home visiting programs implemented in disadvantaged communities and one trial investigated the effect of a preschool-based intervention in increasing child fruit and vegetable intake. Risk of bias of included studies was low although three of the five trials were judged to be at high risk of performance bias. Meta-analysis of two trials examining repeated food exposure versus a no intervention comparison found no significant difference in target vegetable consumption in the short term (mean difference (MD) 1.37, 95% confidence interval (CI) −2.78 to 5.52). Coupling repeated food exposure with a tangible non-food or social reward, was effective in increasing targeted vegetable consumption in the short term based on one trial. Home visiting programs provided to disadvantaged groups did not significantly increase overall fruit intake in the short term (standardised mean difference (SMD) 0.01, 95% CI −0.09 to 0.11). Similarly, a multi-component preschool-based intervention failed to significantly increase child consumption of vegetables, but did report a small significant increase in mean child consumption of fruit, six months following baseline assessment. None of the trials investigated intervention cost-effectiveness or reported information regarding any adverse events or unintended adverse consequences of the intervention. Authors’ conclusions Despite the importance of encouraging fruit and vegetable consumption among children aged five years and under, this review identified few randomised controlled trials investigating interventions to achieve this. PMID:23152262

Controlled Synthesis of Polyions of Heavy Main-Group Elements in Ionic Liquids

PubMed Central

Groh, Matthias F.; Wolff, Alexander; Grasser, Matthias A.; Ruck, Michael

2016-01-01

Ionic liquids (ILs) have been proven to be valuable reaction media for the synthesis of inorganic materials among an abundance of other applications in different fields of chemistry. Up to now, the syntheses have remained mostly “black boxes”; and researchers have to resort to trial-and-error in order to establish a new synthetic route to a specific compound. This review comprises decisive reaction parameters and techniques for the directed synthesis of polyions of heavy main-group elements (fourth period and beyond) in ILs. Several families of compounds are presented ranging from polyhalides over carbonyl complexes and selenidostannates to homo and heteropolycations. PMID:27598123

Can social dancing prevent falls in older adults? a protocol of the Dance, Aging, Cognition, Economics (DAnCE) fall prevention randomised controlled trial

PubMed Central

2013-01-01

Background Falls are one of the most common health problems among older people and pose a major economic burden on health care systems. Exercise is an accepted stand-alone fall prevention strategy particularly if it is balance training or regular participation in Tai chi. Dance shares the ‘holistic’ approach of practices such as Tai chi. It is a complex sensorimotor rhythmic activity integrating multiple physical, cognitive and social elements. Small-scale randomised controlled trials have indicated that diverse dance styles can improve measures of balance and mobility in older people, but none of these studies has examined the effect of dance on falls or cognition. This study aims to determine whether participation in social dancing: i) reduces the number of falls; and ii) improves cognitive functions associated with fall risk in older people. Methods/design A single-blind, cluster randomised controlled trial of 12 months duration will be conducted. Approximately 450 participants will be recruited from 24 self-care retirement villages that house at least 60 residents each in Sydney, Australia. Village residents without cognitive impairment and obtain medical clearance will be eligible. After comprehensive baseline measurements including physiological and cognitive tests and self-completed questionnaires, villages will be randomised to intervention sites (ballroom or folk dance) or to a wait-listed control using a computer randomisation method that minimises imbalances between villages based on two baseline fall risk measures. Main outcome measures are falls, prospectively measured, and the Trail Making cognitive function test. Cost-effectiveness and cost-utility analyses will be performed. Discussion This study offers a novel approach to balance training for older people. As a community-based approach to fall prevention, dance offers older people an opportunity for greater social engagement, thereby making a major contribution to healthy ageing. Providing diversity in exercise programs targeting seniors recognises the heterogeneity of multicultural populations and may further increase the number of taking part in exercise. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12612000889853 The trial is now in progress with 12 villages already have been randomised. PMID:23675705

Prevention of low back pain and its consequences among nurses’ aides in elderly care: a stepped-wedge multi-faceted cluster-randomized controlled trial

PubMed Central

2013-01-01

Background A high prevalence of low back pain has persisted over the years despite extensive primary prevention initiatives among nurses’ aides. Many single-faceted interventions addressing just one aspect of low back pain have been carried out at workplaces, but with low success rate. This may be due to the multi-factorial origin of low back pain. Participatory ergonomics, cognitive behavioral training and physical training have previously shown promising effects on prevention and rehabilitation of low back pain. Therefore, the main aim of this study is to examine whether a multi-faceted workplace intervention consisting of participatory ergonomics, physical training and cognitive behavioral training can prevent low back pain and its consequences among nurses’ aides. External resources for the participating workplace and a strong commitment from the management and the organization support the intervention. Methods/design To overcome implementation barriers within usual randomized controlled trial designed workplace interventions, this study uses a stepped-wedge cluster-randomized controlled trial design with 4 groups. The intervention is delivered to the groups at random along four successive time periods three months apart. The intervention lasts three months and integrates participatory ergonomics, physical training and cognitive behavioral training tailored to the target group. Local physiotherapists and occupational therapists conduct the intervention after having received standardized training. Primary outcomes are low back pain and its consequences measured monthly by text messages up to three months after initiation of the intervention. Discussion Intervention effectiveness trials for preventing low back pain and its consequences in workplaces with physically demanding work are few, primarily single-faceted, with strict adherence to a traditional randomized controlled trial design that may hamper implementation and compliance, and have mostly been unsuccessful. By using a stepped wedge design, and obtain high management commitment and support we intend to improve implementation and aim to establish the effectiveness of a multi-faceted intervention to prevent low back pain. This study will potentially provide knowledge of prevention of low back pain and its consequences among nurses’ aides. Results are expected to be published in 2015–2016. Trial registration The study is registered as ISRCTN78113519. PMID:24261985

Assessing sex-differences and the effect of timing of vaccination on immunogenicity, reactogenicity and efficacy of vaccines in young children: study protocol for an individual participant data meta-analysis of randomised controlled trials.

PubMed

Voysey, Merryn; Pollard, Andrew J; Perera, Rafael; Fanshawe, Thomas R

2016-07-29

Disease incidence differs between males and females for some infectious or inflammatory diseases. Sex-differences in immune responses to some vaccines have also been observed, mostly to viral vaccines in adults. Little evidence is available on whether sex-differences occur in response to immunisation in infancy even though this is the age group in which most vaccines are administered. Factors other than sex, such as timing or coadministration of other vaccines, can also influence the immune response to vaccination. Individual participant data meta-analysis of randomised controlled trials of vaccines in healthy infants and young children will be conducted. Fully anonymised data from ∼170 randomised controlled trials of vaccines for diphtheria, tetanus, Bordetella pertussis, polio, Haemophilus influenzae type B, hepatitis B, Streptococcus pneumoniae, Neisseria meningitidis, measles, mumps, rubella, varicella and rotavirus will be combined for analysis. Outcomes include measures of immunogenicity (immunoglobulins), reactogenicity, safety and disease-specific clinical efficacy. Data from trials of vaccines containing similar components will be combined in hierarchical models and the effect of sex and timing of vaccinations estimated for each outcome separately. Systematic reviews of published estimates of sex-differences cannot adequately answer questions in this field since such comparisons are never the main purpose of a clinical trial, thus a large degree of reporting bias exists in the published literature. Recent improvements in the widespread availability of individual participant data from randomised controlled trials makes it feasible to conduct extensive individual participant data meta-analyses which were previously impossible, thereby reducing the effect of publication or reporting bias on the understanding of the infant immune response.Preliminary results will be available in 2016 with final results available in 2019. No ethics review is required for secondary analyses of anonymised data. 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/

The paradox of sham therapy and placebo effect in osteopathy

PubMed Central

Cerritelli, Francesco; Verzella, Marco; Cicchitti, Luca; D’Alessandro, Giandomenico; Vanacore, Nicola

2016-01-01

Abstract Background: Placebo, defined as “false treatment,” is a common gold-standard method to assess the validity of a therapy both in pharmacological trials and manual medicine research where placebo is also referred to as “sham therapy.” In the medical literature, guidelines have been proposed on how to conduct robust placebo-controlled trials, but mainly in a drug-based scenario. In contrast, there are not precise guidelines on how to conduct a placebo-controlled in manual medicine trials (particularly osteopathy). The aim of the present systematic review was to report how and what type of sham methods, dosage, operator characteristics, and patient types were used in osteopathic clinical trials and, eventually, assess sham clinical effectiveness. Methods: A systematic Cochrane-based review was conducted by analyzing the osteopathic trials that used both manual and nonmanual placebo control. Searches were conducted on 8 databases from journal inception to December 2015 using a pragmatic literature search approach. Two independent reviewers conducted the study selection and data extraction for each study. The risk of bias was evaluated according to the Cochrane methods. Results: A total of 64 studies were eligible for analysis collecting a total of 5024 participants. More than half (43 studies) used a manual placebo; 9 studies used a nonmanual placebo; and 12 studies used both manual and nonmanual placebo. Data showed lack of reporting sham therapy information across studies. Risk of bias analysis demonstrated a high risk of bias for allocation, blinding of personnel and participants, selective, and other bias. To explore the clinical effects of sham therapies used, a quantitative analysis was planned. However, due to the high heterogeneity of sham approaches used no further analyses were performed. Conclusion: High heterogeneity regarding placebo used between studies, lack of reporting information on placebo methods and within-study variability between sham and real treatment procedures suggest prudence in reading and interpreting study findings in manual osteopathic randomized controlled trials (RCTs). Efforts must be made to promote guidelines to design the most reliable placebo for manual RCTs as a means of increasing the internal validity and improve external validity of findings. PMID:27583913