A Randomized Phase II Dose-Response Exercise Trial among Colon Cancer Survivors: Purpose, Study Design, Methods, and Recruitment Results

PubMed Central

Brown, Justin C.; Troxel, Andrea B.; Ky, Bonnie; Damjanov, Nevena; Zemel, Babette S.; Rickels, Michael R.; Rhim, Andrew D.; Rustgi, Anil K.; Courneya, Kerry S.; Schmitz, Kathryn H.

2016-01-01

Background Observational studies indicate that higher volumes of physical activity are associated with improved disease outcomes among colon cancer survivors. The aim of this report is to describe the purpose, study design, methods, and recruitment results of the COURAGE trial, a National Cancer Institute (NCI) sponsored, phase II, randomized, dose-response exercise trial among colon cancer survivors. Methods/Results The primary objective of the COURAGE trial is to quantify the feasibility, safety, and physiologic effects of low-dose (150 min·wk−1) and high-dose (300 min·wk−1) moderate-intensity aerobic exercise compared to usual-care control group over six months. The exercise groups are provided with in-home treadmills and heart rate monitors. Between January and July 2015, 1,433 letters were mailed using a population-based state cancer registry; 126 colon cancer survivors inquired about participation, and 39 were randomized onto the study protocol. Age was associated with inquiry about study participation (P<0.001) and randomization onto the study protocol (P<0.001). No other demographic, clinical, or geographic characteristics were associated with study inquiry or randomization. The final trial participant was randomized in August 2015. Six month endpoint data collection was completed in February 2016. Discussion The recruitment of colon cancer survivors into an exercise trial is feasible. The findings from this trial will inform key design aspects for future phase 2 and phase 3 randomized controlled trials to examine the efficacy of exercise to improve clinical outcomes among colon cancer survivors. PMID:26970181

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

PubMed

Sandilands, Euan A; Cameron, Sharon; Paterson, Frances; Donaldson, Sam; Briody, Lesley; Crowe, Jane; Donnelly, Julie; Thompson, Adrian; Johnston, Neil R; Mackenzie, Ivor; Uren, Neal; Goddard, Jane; Webb, David J; Megson, Ian L; Bateman, Nicholas; Eddleston, Michael

2012-02-03

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

Chlorambucil for the treatment of patients with chronic lymphocytic leukemia (CLL) - a systematic review and meta-analysis of randomized trials.

PubMed

Vidal, Liat; Gurion, Ronit; Ram, Ron; Raanani, Pia; Bairey, Osnat; Robak, Tadeusz; Gafter-Gvili, Anat; Shpilberg, Ofer

2016-09-01

Randomized clinical trials that compared chlorambucil to different regimens, for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) do not support an overall survival (OS) benefit. To assess the efficacy and safety of chlorambucil as frontline treatment, we conducted a systematic review and meta-analysis of randomized controlled trials. OS was the primary outcome. Meta-analysis of 18 trials that compared purine analogs, alkylators, alemtuzumab and ibrutinib to chlorambucil demonstrated no OS benefit for therapy without chlorambucil over chlorambucil (pooled HR 0.99, 95% CI 0.91-1.08; 4133 patients). PFS was longer with purine analogs compared with chlorambucil with an increased risk of infection. The risk of secondary malignancies was not increased with chlorambucil. In conclusion, our study showed that chlorambucil is an acceptable chemotherapy backbone for unfit patients with CLL. Purine analogs should be preferred in fit younger patients because of longer PFS. Future trials should focus on unfit patients who are underrepresented in clinical trials.

A Bayesian comparative effectiveness trial in action: developing a platform for multisite study adaptive randomization.

PubMed

Brown, Alexandra R; Gajewski, Byron J; Aaronson, Lauren S; Mudaranthakam, Dinesh Pal; Hunt, Suzanne L; Berry, Scott M; Quintana, Melanie; Pasnoor, Mamatha; Dimachkie, Mazen M; Jawdat, Omar; Herbelin, Laura; Barohn, Richard J

2016-08-31

In the last few decades, the number of trials using Bayesian methods has grown rapidly. Publications prior to 1990 included only three clinical trials that used Bayesian methods, but that number quickly jumped to 19 in the 1990s and to 99 from 2000 to 2012. While this literature provides many examples of Bayesian Adaptive Designs (BAD), none of the papers that are available walks the reader through the detailed process of conducting a BAD. This paper fills that gap by describing the BAD process used for one comparative effectiveness trial (Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations) that can be generalized for use by others. A BAD was chosen with efficiency in mind. Response-adaptive randomization allows the potential for substantially smaller sample sizes, and can provide faster conclusions about which treatment or treatments are most effective. An Internet-based electronic data capture tool, which features a randomization module, facilitated data capture across study sites and an in-house computation software program was developed to implement the response-adaptive randomization. A process for adapting randomization with minimal interruption to study sites was developed. A new randomization table can be generated quickly and can be seamlessly integrated in the data capture tool with minimal interruption to study sites. This manuscript is the first to detail the technical process used to evaluate a multisite comparative effectiveness trial using adaptive randomization. An important opportunity for the application of Bayesian trials is in comparative effectiveness trials. The specific case study presented in this paper can be used as a model for conducting future clinical trials using a combination of statistical software and a web-based application. ClinicalTrials.gov Identifier: NCT02260388 , registered on 6 October 2014.

Patient representatives' views on patient information in clinical cancer trials.

PubMed

Dellson, Pia; Nilbert, Mef; Carlsson, Christina

2016-02-01

Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed consent is possible to provide. We explored patient representatives' views and perceptions on the written trial information used in clinical cancer trials. Written patient information leaflets used in four clinical trials for colorectal cancer were used for the study. The trials included phase I-III trials, randomized and non-randomized trials that evaluated chemotherapy/targeted therapy in the neoadjuvant, adjuvant and palliative settings. Data were collected through focus groups and were analysed using inductive content analysis. Two major themes emerged: emotional responses and cognitive responses. Subthemes related to the former included individual preferences and perceptions of effect, while subthemes related to the latter were comprehensibility and layout. Based on these observations the patient representatives provided suggestions for improvement, which largely included development of future simplified and more attractive informed consent forms. The emotional and cognitive responses to written patient information reported by patient representatives provides a basis for revised formats in future trials and add to the body of information that support use of plain language, structured text and illustrations to improve the informed consent process and thereby patient enrolment into clinical trials.

A Randomized trial of an Asthma Internet Self-management Intervention (RAISIN): study protocol for a randomized controlled trial.

PubMed

Morrison, Deborah; Wyke, Sally; Thomson, Neil C; McConnachie, Alex; Agur, Karolina; Saunderson, Kathryn; Chaudhuri, Rekha; Mair, Frances S

2014-05-24

The financial costs associated with asthma care continue to increase while care remains suboptimal. Promoting optimal self-management, including the use of asthma action plans, along with regular health professional review has been shown to be an effective strategy and is recommended in asthma guidelines internationally. Despite evidence of benefit, guided self-management remains underused, however the potential for online resources to promote self-management behaviors is gaining increasing recognition. The aim of this paper is to describe the protocol for a pilot evaluation of a website 'Living well with asthma' which has been developed with the aim of promoting self-management behaviors shown to improve outcomes. The study is a parallel randomized controlled trial, where adults with asthma are randomly assigned to either access to the website for 12 weeks, or usual asthma care for 12 weeks (followed by access to the website if desired). Individuals are included if they are over 16-years-old, have a diagnosis of asthma with an Asthma Control Questionnaire (ACQ) score of greater than, or equal to 1, and have access to the internet. Primary outcomes for this evaluation include recruitment and retention rates, changes at 12 weeks from baseline for both ACQ and Asthma Quality of Life Questionnaire (AQLQ) scores, and quantitative data describing website usage (number of times logged on, length of time logged on, number of times individual pages looked at, and for how long). Secondary outcomes include clinical outcomes (medication use, health services use, lung function) and patient reported outcomes (including adherence, patient activation measures, and health status). Piloting of complex interventions is considered best practice and will maximise the potential of any future large-scale randomized controlled trial to successfully recruit and be able to report on necessary outcomes. Here we will provide results across a range of outcomes which will provide estimates of efficacy to inform the design of a future full-scale randomized controlled trial of the 'Living well with asthma' website. This trial is registered with Current Controlled Trials ISRCTN78556552 on 18/06/13.

Testing the potential paradoxes in "retrocausal" phenomena

NASA Astrophysics Data System (ADS)

Jolij, Jacob; Bierman, Dick J.

2017-05-01

Discussions with regard to potential paradoxes arising from "retrocausal" phenomena have been purely theoretical because so far no empirical effects had been established that allowed for empirical exploration of these potential paradoxes. In this article we describe three human experiments that showed clear "retrocausal" effects. In these neuropsychological, so-called, face-detection experiments, consisting of hundreds of trials per participant, we use brain signals to predict an upcoming random stimulus. The binary random decision, corresponding to showing a noisy cartoon face or showing only noise on a display with equal probability is taken after the brain signals have been measured. The prediction accuracy ranges from 50.5-56.5% for the 3 experiments where chance performance would be 50%. The prediction algorithm is based on a template constructed out of all the pre-stimulus brain signals obtained in other trials of that particular participant. This approach thus controls for individual difference in brain functioning. Subsequently we describe an experiment based upon these findings where the predictive information is used in part of the trials to determine the stimulus rather than randomly select that stimulus. In those trials we analyze what the brain signals tell us what the future stimulus would be and then we reverse the actual future that is presented on the display. This is a `bilking' condition. We analyze what the consequence of the introduction of this bilking condition is on the accuracy of the remaining (normal) trials and, following a suggestion inferred from Thorne et al, we also check what the effect is on the random decision to either bilk or not bilk the specific trial. The bilking experiment is in progress and the results so far do not allow for conclusions and are presented only as an illustration.

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

PubMed Central

2012-01-01

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

Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial.

PubMed

Fröbert, Ole; Götberg, Matthias; Angerås, Oskar; Jonasson, Lena; Erlinge, David; Engstrøm, Thomas; Persson, Jonas; Jensen, Svend E; Omerovic, Elmir; James, Stefan K; Lagerqvist, Bo; Nilsson, Johan; Kåregren, Amra; Moer, Rasmus; Yang, Cao; Agus, David B; Erglis, Andrejs; Jensen, Lisette O; Jakobsen, Lars; Christiansen, Evald H; Pernow, John

2017-07-01

Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI. The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all-cause death, a new AMI, or stent thrombosis at 1 year. The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Customizing chemotherapy in non-small cell lung cancer: the promise is still unmet

PubMed Central

2015-01-01

A combination of cytotoxic agents with cis-platin remains the cornerstone of treatment for the vast majority of patients with non-small cell lung cancer (NSCLC). Molecular analysis of the primary may lead better prognostication and eventually in more accurate therapeutic approaches. Data from retrospective analysis of randomized trials as well as large patients’ series have suggested that chemotherapy may be customized upon molecular-genetic analysis of the tumor cells. The Spanish Lung Cancer Group (SLCG) in collaboration with French lung Cancer Group (FLCG) had conduct randomized, phase III, biomarkers-driven trial and supported simultaneously a randomized phase II trial in collaborating centers in China. Despite the evidence from the preclinical data and the results from the retrospective studies, the results of these trials published recently in Annals of Oncology were in favor of ‘standard approach’. The present commentary tries to give some explanation for the disappointing results, provide potential solution for the future trials and explain why the vision of customizing treatment is still alive. PMID:26629440

Endoscopic vs. Surgical Interventions for Painful Chronic Pancreatitis: What is Needed for Future Clinical Trials

PubMed Central

Windsor, John A; Reddy, Nageshwar D

2017-01-01

The treatment of painful chronic pancreatitis remains controversial. The available evidence from two randomized controlled trials favor surgical intervention, whereas an endotherapy-first approach is widely practiced. Chronic pancreatitis is complex disease with different genetic and environmental factors, different pain mechanisms and different treatment modalities including medical, endoscopic, and surgical. The widely practiced step-up approach remains unproven. In designing future clinical trials there are some important pre-requisites including a more comprehensive pain assessment tool, the optimization of conservative medical treatment and interventional techniques. Consideration should be given to the need of a control arm and the optimal timing of intervention. Pending better designed studies, the practical way forward is to identify subgroups of patients who clearly warrant endotherapy or surgery first, and to design the future clinical trials for the remainder. PMID:28079861

Surrogate and Intermediate Endpoints in Randomized Trials: What's the Goal?

PubMed

Korn, Edward L; Freidlin, Boris

2018-05-15

Establishing trial-level surrogacy of an intermediate endpoint for predicting survival benefit in future trials is extremely challenging because of the extrapolations required, but there are other useful drug development and patient management applications of intermediate endpoints. Clin Cancer Res; 24(10); 2239-40. ©2018 AACR See related article by Mushti et al., p. 2268 . ©2018 American Association for Cancer Research.

A novel cognitive behaviour therapy for bipolar disorders (Think Effectively About Mood Swings or TEAMS): study protocol for a randomized controlled trial.

PubMed

Mansell, Warren; Tai, Sara; Clark, Alexandra; Akgonul, Savas; Dunn, Graham; Davies, Linda; Law, Heather; Morriss, Richard; Tinning, Neil; Morrison, Anthony P

2014-10-24

Existing psychological therapies for bipolar disorders have been found to have mixed results, with a consensus that they provide a significant, but modest, effect on clinical outcomes. Typically, these approaches have focused on promoting strategies to prevent future relapse. An alternative treatment approach, termed 'Think Effectively About Mood Swings' (TEAMS) addresses current symptoms, including subclinical hypomania, depression and anxiety, and promotes long-term recovery. Following the publication of a theoretical model, a range of research studies testing the model and a case series have demonstrated positive results. The current study reports the protocol of a feasibility randomized controlled trial to inform a future multi-centre trial. A target number of 84 patients with a diagnosis of bipolar I or II disorder, or bipolar disorder not-otherwise-specified are screened, allocated to a baseline assessment and randomized to either 16 sessions of TEAMS therapy plus treatment-as-usual (TAU) or TAU. Patients complete self-report inventories of depression, anxiety, recovery status and bipolar cognitions targeted by TEAMS. Assessments of diagnosis, bipolar symptoms, medication, access to services and quality of life are conducted by assessors blind to treatment condition at 3, 6, 12 and 18 months post-randomization. The main aim is to evaluate recruitment and retention of participants into both arms of the study, as well as adherence to therapy, to determine feasibility and acceptability. It is predicted that TEAMS plus TAU will reduce self-reported depression in comparison to TAU alone at six months post-randomization. The secondary hypotheses are that TEAMS will reduce the severity of hypomanic symptoms and anxiety, reduce bipolar cognitions, improve social functioning and promote recovery compared to TAU alone at post-treatment and follow-up. The study also incorporates semi-structured interviews about the experiences of previous treatment and the experience of TEAMS therapy that will be subject to qualitative analyses to inform future developments of the approach. The design will provide preliminary evidence of efficacy, feasibility, acceptability, uptake, attrition and barriers to treatment to design a definitive trial of this novel intervention compared to treatment as usual. This trial was registered with Current Controlled Trials (ISRCTN83928726) on registered 25 July 2014.

Disappointment and adherence among parents of newborns allocated to the control group: a qualitative study of a randomized clinical trial.

PubMed

Meinich Petersen, Sandra; Zoffmann, Vibeke; Kjærgaard, Jesper; Graff Stensballe, Lone; Graff Steensballe, Lone; Greisen, Gorm

2014-04-15

When a child participates in a clinical trial, informed consent has to be given by the parents. Parental motives for participation are complex, but the hope of getting a new and better treatment for the child is important. We wondered how parents react when their child is allocated to the control group of a randomized controlled trial, and how it will affect their future engagement in the trial. We included parents of newborns randomized to the control arm in the Danish Calmette study at Rigshospitalet in Copenhagen. The Calmette study is a randomized clinical trial investigating the non-specific effects of early BCG-vaccine to healthy neonates. Randomization is performed immediately after birth and parents are not blinded to the allocation. We set up a semi-structured focus group with six parents from four families. Afterwards we telephone-interviewed another 19 mothers to achieve saturation. Thematic analysis was used to identify themes across the data sets. The parents reported good understanding of the randomization process. Their most common reaction to allocation was disappointment, though relief was also seen. A model of reactions to being allocated to the control group was developed based on the participants' different positions along two continuities from 'Our participation in trial is not important' to 'Our participation in trial is important', and 'Vaccine not important to us' to 'Vaccine important to us'. Four very disappointed families had thought of getting the vaccine elsewhere, and one had actually had their child vaccinated. All parents involved in the focus group and the telephone interviews wanted to participate in the follow-ups planned for the Calmette study. This study identified an almost universal experience of disappointment among parents of newborns who were randomized to the control group, but also a broad expression of understanding and accepting the idea of randomization. The trial staff might use the model of reactions in understanding the parents' disappointment and in this way support their motives for participation. A generalized version might be applicable across randomized controlled trials at large. The Calmette study is registered in EudraCT (https://eudract.ema.europa.eu/) with trial number 2010-021979-85.

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.

An Evaluation of the Effectiveness of Recruitment Methods: The Staying Well after Depression Randomized Controlled Trial

PubMed Central

Krusche, Adele; Rudolf von Rohr, Isabelle; Muse, Kate; Duggan, Danielle; Crane, Catherine; Williams, J. Mark G.

2014-01-01

Background Randomized controlled trials (RCTs) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies. However, researchers conducting RCTs commonly report difficulties recruiting an adequate sample within planned timescales. In an effort to overcome recruitment difficulties, researchers often are forced to expand their recruitment criteria or extend the recruitment phase, thus increasing costs and delaying publication of results. Research investigating the effectiveness of recruitment strategies is limited and trials often fail to report sufficient details about the recruitment sources and resources utilised. Purpose We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression. Methods We describe eight recruitment methods utilised and two further sources not initiated by the research team and examine their efficacy in terms of (i) the return, including the number of potential participants who contacted the trial and the number who were randomized into the trial, (ii) cost-effectiveness, comprising direct financial cost and manpower for initial contacts and randomized participants, and (iii) comparison of sociodemographic characteristics of individuals recruited from different sources. Results Poster advertising, web-based advertising and mental health worker referrals were the cheapest methods per randomized participant; however, the ratio of randomized participants to initial contacts differed markedly per source. Advertising online, via posters and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were randomized into the trial. Advertising across many sources (saturation) was found to be important. Limitations It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other populations, such as those currently unwell, or in other geographical locations. Recruitment source was unavailable for participants who could not be reached after the initial contact. Thus, it is possible that the efficiency of certain methods of recruitment was poorer than estimated. Efficacy and costs of other recruitment initiatives, such as providing travel expenses to the in-person eligibility assessment and making follow-up telephone calls to candidates who contacted the recruitment team but could not be screened promptly, were not analysed. Conclusions Website advertising resulted in the highest number of randomized participants and was the second cheapest method of recruiting. Future research should evaluate the effectiveness of recruitment strategies for other samples to contribute to a comprehensive base of knowledge for future RCTs. PMID:24686105

An evaluation of the effectiveness of recruitment methods: the staying well after depression randomized controlled trial.

PubMed

Krusche, Adele; Rudolf von Rohr, Isabelle; Muse, Kate; Duggan, Danielle; Crane, Catherine; Williams, J Mark G

2014-04-01

Randomized controlled trials (RCTs) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies. However, researchers conducting RCTs commonly report difficulties in recruiting an adequate sample within planned timescales. In an effort to overcome recruitment difficulties, researchers often are forced to expand their recruitment criteria or extend the recruitment phase, thus increasing costs and delaying publication of results. Research investigating the effectiveness of recruitment strategies is limited, and trials often fail to report sufficient details about the recruitment sources and resources utilized. We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression. We describe eight recruitment methods utilized and two further sources not initiated by the research team and examine their efficacy in terms of (1) the return, including the number of potential participants who contacted the trial and the number who were randomized into the trial; (2) cost-effectiveness, comprising direct financial cost and manpower for initial contacts and randomized participants; and (3) comparison of sociodemographic characteristics of individuals recruited from different sources. Poster advertising, web-based advertising, and mental health worker referrals were the cheapest methods per randomized participant; however, the ratio of randomized participants to initial contacts differed markedly per source. Advertising online, via posters, and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were randomized into the trial. Advertising across many sources (saturation) was found to be important. It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other populations, such as those currently unwell, or in other geographical locations. Recruitment source was unavailable for participants who could not be reached after the initial contact. Thus, it is possible that the efficiency of certain methods of recruitment was poorer than estimated. Efficacy and costs of other recruitment initiatives, such as providing travel expenses to the in-person eligibility assessment and making follow-up telephone calls to candidates who contacted the recruitment team but could not be screened promptly, were not analysed. Website advertising resulted in the highest number of randomized participants and was the second cheapest method of recruiting. Future research should evaluate the effectiveness of recruitment strategies for other samples to contribute to a comprehensive base of knowledge for future RCTs.

Assessment of the Reporting Quality of Placebo-controlled Randomized Trials on the Treatment of Type 2 Diabetes With Traditional Chinese Medicine in Mainland China: A PRISMA-Compliant Systematic Review.

PubMed

Zhao, Xiyan; Zhen, Zhong; Guo, Jing; Zhao, Tianyu; Ye, Ru; Guo, Yu; Chen, Hongdong; Lian, Fengmei; Tong, Xiaolin

2016-01-01

Placebo-controlled randomized trials are often used to evaluate the absolute effect of new treatments and are considered gold standard for clinical trials. No studies, however, have yet been conducted evaluating the reporting quality of placebo-controlled randomized trials. The current study aims to assess the reporting quality of placebo-controlled randomized trials on treatment of diabetes with Traditional Chinese Medicine (TCM) in Mainland China and to provide recommendations for improvements.China National Knowledge Infrastructure database, Wanfang database, China Biology Medicine database, and VIP database were searched for placebo-controlled randomized trials on treatment of diabetes with TCM. Review, animal experiment, and randomized controlled trials without placebo control were excluded. According to Consolidated Standards of Reporting Trials (CONSORT) 2010 checklists items, each item was given a yes or no depending on whether it was reported or not.A total of 68 articles were included. The reporting percentage in each article ranged from 24.3% to 73%, and 30.9% articles reported more than 50% of the items. Seven of the 37 items were reported more than 90% of the items, whereas 7 items were not mentioned at all. The average reporting for "title and abstract," "introduction," "methods," "results," "discussion," and "other information" was 43.4%, 78.7%, 40.1%, 49.9%, 71.1%, and 17.2%, respectively. The percentage of each section had increased after 2010. In addition, the reporting of multiple study centers, funding, placebo species, informed consent forms, and ethical approvals were 14.7%, 50%, 36.85%, 33.8%, and 4.4%, respectively.Although a scoring system was created according to the CONSORT 2010 checklist, it was not designed as an assessment tool. According to CONSORT 2010, the reporting quality of placebo-controlled randomized trials on the treatment of diabetes with TCM improved after 2010. Future improvements, however, are still needed, particularly in methods sections.

Renal denervation for the management of resistant hypertension

PubMed Central

Patel, Hitesh C; Hayward, Carl; Vassiliou, Vassilis; Patel, Ketna; Howard, James P; Di Mario, Carlo

2015-01-01

Renal sympathetic denervation (RSD) as a therapy for patients with resistant hypertension has attracted great interest. The majority of studies in this field have demonstrated impressive reductions in blood pressure (BP). However, these trials were not randomized or sham-controlled and hence, the findings may have been overinflated due to trial biases. SYMPLICITY HTN-3 was the first randomized controlled trial to use a blinded sham-control and ambulatory BP monitoring. A surprise to many was that this study was neutral. Possible reasons for this neutrality include the fact that RSD may not be effective at lowering BP in man, RSD was not performed adequately due to limited operator experience, patients’ adherence with their anti-hypertensive drugs may have changed during the trial period, and perhaps the intervention only works in certain subgroups that are yet to be identified. Future studies seeking to demonstrate efficacy of RSD should be designed as randomized blinded sham-controlled trials. The efficacy of RSD is in doubt, but many feel that its safety has been established through the thousands of patients in whom the procedure has been performed. Over 90% of these data, however, are for the Symplicity™ system and rarely extend beyond 12 months of follow-up. Long-term safety cannot be assumed with RSD and nor should it be assumed that if one catheter system is safe then all are. We hope that in the near future, with the benefit of well-designed clinical trials, the role of renal denervation in the management of hypertension will be established. PMID:26672761

A randomized controlled trial to evaluate the feasibility of the Wii Fit for improving walking in older adults with lower limb amputation.

PubMed

Imam, Bita; Miller, William C; Finlayson, Heather; Eng, Janice J; Jarus, Tal

2017-01-01

To assess the feasibility of Wii.n.Walk for improving walking capacity in older adults with lower limb amputation. A parallel, evaluator-blind randomized controlled feasibility trial. Community-living. Individuals who were ⩾50 years old with a unilateral lower limb amputation. Wii.n.Walk consisted of Wii Fit training, 3x/week (40 minute sessions), for 4 weeks. Training started in the clinic in groups of 3 and graduated to unsupervised home training. Control group were trained using cognitive games. Feasibility indicators: trial process (recruitment, retention, participants' perceived benefit from the Wii.n.Walk intervention measured by exit questionnaire), resources (adherence), management (participant processing, blinding), and treatment (adverse event, and Cohen's d effect size and variance). Primary clinical outcome: walking capacity measured using the 2 Minute Walk Test at baseline, end of treatment, and 3-week retention. Of 28 randomized participants, 24 completed the trial (12/arm). Median (range) age was 62.0 (50-78) years. Mean (SD) score for perceived benefit from the Wii.n.Walk intervention was 38.9/45 (6.8). Adherence was 83.4%. The effect sizes for the 2 Minute Walk Test were 0.5 (end of treatment) and 0.6 (3-week retention) based on intention to treat with imputed data; and 0.9 (end of treatment) and 1.2 (3-week retention) based on per protocol analysis. The required sample size for a future larger RCT was deemed to be 72 (36 per arm). The results suggested the feasibility of the Wii.n.Walk with a medium effect size for improving walking capacity. Future larger randomized controlled trials investigating efficacy are warranted.

Impact of Probiotics on Necrotizing Enterocolitis

PubMed Central

Underwood, Mark A.

2016-01-01

A large number of randomized placebo-controlled clinical trials and cohort studies have demonstrated a decrease in the incidence of necrotizing enterocolitis with administration of probiotic microbes. These studies have prompted many neonatologists to adopt routine prophylactic administration of probiotics while others await more definitive studies and/or probiotic products with demonstrated purity and stable numbers of live organisms. Cross-contamination and inadequate sample size limit the value of further traditional placebo-controlled randomized controlled trials. Key areas for future research include mechanisms of protection, optimum probiotic species or strains (or combinations thereof) and duration of treatment, interactions between diet and the administered probiotic, and the influence of genetic polymorphisms in the mother and infant on probiotic response. Next generation probiotics selected based on bacterial genetics rather than ease of production and large cluster-randomized clinical trials hold great promise for NEC prevention. PMID:27836423

Value of information: interim analysis of a randomized, controlled trial of goal-directed hemodynamic treatment for aged patients.

PubMed

Bartha, Erzsebet; Davidson, Thomas; Brodtkorb, Thor-Henrik; Carlsson, Per; Kalman, Sigridur

2013-07-09

A randomized, controlled trial, intended to include 460 patients, is currently studying peroperative goal-directed hemodynamic treatment (GDHT) of aged hip-fracture patients. Interim efficacy analysis performed on the first 100 patients was statistically uncertain; thus, the trial is continuing in accordance with the trial protocol. This raised the present investigation's main question: Is it reasonable to continue to fund the trial to decrease uncertainty? To answer this question, a previously developed probabilistic cost-effectiveness model was used. That model depicts (1) a choice between routine fluid treatment and GDHT, given uncertainty of current evidence and (2) the monetary value of further data collection to decrease uncertainty. This monetary value, that is, the expected value of perfect information (EVPI), could be used to compare future research costs. Thus, the primary aim of the present investigation was to analyze EVPI of an ongoing trial with interim efficacy observed. A previously developed probabilistic decision analytic cost-effectiveness model was employed to compare the routine fluid treatment to GDHT. Results from the interim analysis, published trials, the meta-analysis, and the registry data were used as model inputs. EVPI was predicted using (1) combined uncertainty of model inputs; (2) threshold value of society's willingness to pay for one, quality-adjusted life-year; and (3) estimated number of future patients exposed to choice between GDHT and routine fluid treatment during the expected lifetime of GDHT. If a decision to use GDHT were based on cost-effectiveness, then the decision would have a substantial degree of uncertainty. Assuming a 5-year lifetime of GDHT in clinical practice, the number of patients who would be subject to future decisions was 30,400. EVPI per patient would be €204 at a €20,000 threshold value of society's willingness to pay for one quality-adjusted life-year. Given a future population of 30,400 individuals, total EVPI would be €6.19 million. If future trial costs are below EVPI, further data collection is potentially cost-effective. When applying a cost-effectiveness model, statements such as 'further research is needed' are replaced with 'further research is cost-effective and 'further funding of a trial is justified'. ClinicalTrials.gov NCT01141894.

Reading and assessing reports of treatment studies in oncology.

PubMed

Simon, R

2000-04-01

Rapid advances in tumor biology, immunology, genomics, and technology give physicians great hopes for providing patients with better chances in the struggle against cancer. The pace of progress will be slowed, however, if we do not have clear answers regarding which treatments work and do not work. Such answers come from carefully designed, randomized, clinical trials. Such trials require infrastructure, commitment, cooperation, time, and money, and they provide little fame. They are, however, an invaluable contribution of the medical profession to their patients, to their next generation of colleagues, and to future patients. Randomized clinical trials that answer important medical questions definitively should be supported, participated in, and demanded by surgeons and oncologists.

Mindfulness-Based Cognitive Therapy: Further Issues in Current Evidence and Future Research

ERIC Educational Resources Information Center

Williams, J. Mark G.; Russell, Ian; Russell, Daphne

2008-01-01

The authors respond to the article by H. F. Coelho, P. H. Canter, and E. Ernst (2007), which reviewed the current status of mindfulness-based cognitive therapy (MBCT). First, they clarify the randomization procedures in the 2 main MBCT trials. Second, they report posttreatment and follow-up data to show that trial participants allocated to…

Diabetes in pregnancy outcomes: a systematic review and proposed codification of definitions.

PubMed

Feig, Denice S; Corcoy, Rosa; Jensen, Dorte Moller; Kautzky-Willer, Alexandra; Nolan, Christopher J; Oats, Jeremy J N; Sacks, David A; Caimari, Francisca; McIntyre, H David

2015-10-01

Rising rates of diabetes in pregnancy have led to an escalation in research in this area. As in any area of clinical research, definitions of outcomes vary from study to study, making it difficult to compare research findings and draw conclusions. Our aim was to compile and create a repository of definitions, which could then be used universally. A systematic review of the literature was performed on published and ongoing randomized controlled trials in the area of diabetes in pregnancy between 01 Jan 2000 and 01 Jun 2012. Other sources included the World Health Organization and Academic Society Statements. The advice of experts was sought when appropriate definitions were lacking. Among the published randomized controlled trials on diabetes and pregnancy, 171 abstracts were retrieved, 64 full texts were reviewed and 53 were included. Among the ongoing randomized controlled trials published in ClinicalTrials.gov, 90 protocols were retrieved and 25 were finally included. The definitions from these were assembled and the final maternal definitions and foetal definitions were agreed upon by consensus. It is our hope that the definitions we have provided (i) will be widely used in the reporting of future studies in the area of diabetes in pregnancy, that they will (ii) facilitate future systematic reviews and formal meta analyses and (iii) ultimately improve outcomes for mothers and babies. Copyright © 2015 John Wiley & Sons, Ltd.

Design and analysis of group-randomized trials in cancer: A review of current practices.

PubMed

Murray, David M; Pals, Sherri L; George, Stephanie M; Kuzmichev, Andrey; Lai, Gabriel Y; Lee, Jocelyn A; Myles, Ranell L; Nelson, Shakira M

2018-06-01

The purpose of this paper is to summarize current practices for the design and analysis of group-randomized trials involving cancer-related risk factors or outcomes and to offer recommendations to improve future trials. We searched for group-randomized trials involving cancer-related risk factors or outcomes that were published or online in peer-reviewed journals in 2011-15. During 2016-17, in Bethesda MD, we reviewed 123 articles from 76 journals to characterize their design and their methods for sample size estimation and data analysis. Only 66 (53.7%) of the articles reported appropriate methods for sample size estimation. Only 63 (51.2%) reported exclusively appropriate methods for analysis. These findings suggest that many investigators do not adequately attend to the methodological challenges inherent in group-randomized trials. These practices can lead to underpowered studies, to an inflated type 1 error rate, and to inferences that mislead readers. Investigators should work with biostatisticians or other methodologists familiar with these issues. Funders and editors should ensure careful methodological review of applications and manuscripts. Reviewers should ensure that studies are properly planned and analyzed. These steps are needed to improve the rigor and reproducibility of group-randomized trials. The Office of Disease Prevention (ODP) at the National Institutes of Health (NIH) has taken several steps to address these issues. ODP offers an online course on the design and analysis of group-randomized trials. ODP is working to increase the number of methodologists who serve on grant review panels. ODP has developed standard language for the Application Guide and the Review Criteria to draw investigators' attention to these issues. Finally, ODP has created a new Research Methods Resources website to help investigators, reviewers, and NIH staff better understand these issues. Published by Elsevier Inc.

The macular degeneration and aging study: Design and research protocol of a randomized trial for a psychosocial intervention with macular degeneration patients.

PubMed

Sörensen, Silvia; White, Katherine; Mak, Wingyun; Zanibbi, Katherine; Tang, Wan; O'Hearn, Amanda; Hegel, Mark T

2015-05-01

Age-related Macular Degeneration (AMD) is the leading cause of irreversible and predictable blindness among older adults with serious physical and mental health consequences. Visual impairment is associated with negative future outlook and depression and has serious consequences for older adults' quality of life and, by way of depression, on long-term survival. Psychosocial interventions have the potential to alleviate and prevent depression symptoms among older AMD patients. We describe the protocol of the Macular Degeneration and Aging Study, a randomized clinical trial of a psychosocial Preventive Problem-Solving Intervention. The intervention is aimed at enhancing well-being and future planning among older adults with macular degeneration by increasing preparation for future care. Adequate randomization and therapeutic fidelity were achieved. Current retention rates were acceptable, given the vulnerability of the population. Acceptability (adherence and satisfaction) was high. Given the high public health significance and impact on quality of life among older adults with vision loss, this protocol contributes a valid test of a promising intervention for maintaining mental and physical health in this population. Copyright © 2015 Elsevier Inc. All rights reserved.

Post-trial follow-up methodology in large randomized controlled trials: a systematic review protocol.

PubMed

Llewellyn-Bennett, Rebecca; Bowman, Louise; Bulbulia, Richard

2016-12-15

Clinical trials typically have a relatively short follow-up period, and may both underestimate potential benefits of treatments investigated, and fail to detect hazards, which can take much longer to emerge. Prolonged follow-up of trial participants after the end of the scheduled trial period can provide important information on both efficacy and safety outcomes. This protocol describes a systematic review to qualitatively compare methods of post-trial follow-up used in large randomized controlled trials. A systematic search of electronic databases and clinical trial registries will use a predefined search strategy. All large (more than 1000 adult participants) randomized controlled trials will be evaluated. Two reviewers will screen and extract data according to this protocol with the aim of 95% concordance of papers checked and discrepancies will be resolved by a third reviewer. Trial methods, participant retention rates and prevalence of missing data will be recorded and compared. The potential for bias will be evaluated using the Cochrane Risk of Bias tool (applied to the methods used during the in-trial period) with the aim of investigating whether the quality of the post-trial follow-up methodology might be predicted by the quality of the methods used for the original trial. Post-trial follow-up can provide valuable information about the long-term benefits and hazards of medical interventions. However, it can be logistically challenging and costly. The aim of this systematic review is to describe how trial participants have been followed-up post-trial in order to inform future post-trial follow-up designs. Not applicable for PROSPERO registration.

Parent-Child Interaction Therapy with Physically Abusive Parents: Efficacy for Reducing Future Abuse Reports

ERIC Educational Resources Information Center

Chaffin, Mark; Silovsky, Jane F.; Funderburk, Beverly; Valle, Linda Anne; Brestan, Elizabeth V.; Balachova, Tatiana; Jackson, Shelli; Lensgraf, Jay; Bonner, Barbara L.

2004-01-01

A randomized trial was conducted to test the efficacy and sufficiency of parent-child interaction therapy (PCIT) in preventing re-reports of physical abuse among abusive parents. Physically abusive parents (N=110) were randomly assigned to one of three intervention conditions: (a) PCIT, (b) PCIT plus individualized enhanced services, or (c) a…

Measurement Error Correction Formula for Cluster-Level Group Differences in Cluster Randomized and Observational Studies

ERIC Educational Resources Information Center

Cho, Sun-Joo; Preacher, Kristopher J.

2016-01-01

Multilevel modeling (MLM) is frequently used to detect cluster-level group differences in cluster randomized trial and observational studies. Group differences on the outcomes (posttest scores) are detected by controlling for the covariate (pretest scores) as a proxy variable for unobserved factors that predict future attributes. The pretest and…

Clinical trials with rasagiline: evidence for short-term and long-term effects.

PubMed

Siderowf, Andrew; Stern, Matthew

2006-05-23

Rasagiline (N-propargyl-1 (R)-aminoindan) is a selective, potent irreversible inhibitor of MAO-B that possesses neuroprotective and anti-apoptotic properties in a variety of in vitro and in vivo animal models relevant to Parkinson's disease (PD). Several randomized controlled clinical trials have demonstrated the safety and efficacy of rasagiline as monotherapy in PD and as adjunctive therapy for patients receiving levodopa. In addition, the 1-year randomized, delayed-start analysis of the TEMPO study suggests that rasagiline may slow the rate of progression of PD. The randomized delayed-start paradigm has potential to differentiate short-term symptomatic effects from long-term effects of anti-parkinsonian agents. In the future, long-term trials to examine the potential disease-modifying effects of rasagiline, which incorporate biological markers as well as clinical endpoints, may further elucidate the role of rasagiline in the treatment of both early and advanced PD.

How Important Is ‘Accuracy’ of Surrogate Decision-Making for Research Participation?

PubMed Central

Kim, Scott Y. H.; Kim, H. Myra; Ryan, Kerry A.; Appelbaum, Paul S.; Knopman, David S.; Damschroder, Laura; De Vries, Raymond

2013-01-01

Background There is a longstanding concern about the accuracy of surrogate consent in representing the health care and research preferences of those who lose their ability to decide for themselves. We sought informed, deliberative views of the older general public (≥50 years old) regarding their willingness to participate in dementia research and to grant leeway to future surrogates to choose an option contrary to their stated wishes. Methodology/Principal Findings 503 persons aged 50+ recruited by random digit dialing were randomly assigned to one of three groups: deliberation, education, or control. The deliberation group attended an all-day education/peer deliberation session; the education group received written information only. Participants were surveyed at baseline, after the deliberation session (or equivalent time), and one month after the session, regarding their willingness to participate in dementia research and to give leeway to surrogates, regarding studies of varying risk-benefit profiles (a lumbar puncture study, a drug randomized controlled trial, a vaccine randomized controlled trial, and an early phase gene transfer trial). At baseline, 48% (gene transfer scenario) to 92% (drug RCT) were willing to participate in future dementia research. A majority of respondents (57–71% depending on scenario) were willing to give leeway to future surrogate decision-makers. Democratic deliberation increased willingness to participate in all scenarios, to grant leeway in 3 of 4 scenarios (lumbar puncture, vaccine, and gene transfer), and to enroll loved ones in research in all scenarios. On average, respondents were more willing to volunteer themselves for research than to enroll their loved ones. Conclusions/Significance Most people were willing to grant leeway to their surrogates, and this willingness was either sustained or increased after democratic deliberation, suggesting that the attitude toward leeway is a reliable opinion. Eliciting a person’s current preferences about future research participation should also involve eliciting his or her leeway preferences. PMID:23382969

Executive summary of the joint position paper on renal denervation of the Cardiovascular and Interventional Radiological Society of Europe and the European Society of Hypertension.

PubMed

Moss, Jonathan G; Belli, Anna-Maria; Coca, Antonio; Lee, Michael; Mancia, Giuseppe; Peregrin, Jan H; Redon, Josep; Reekers, Jim A; Tsioufis, Costas; Vorwerk, Dierk; Schmieder, Roland E

2016-12-01

Renal denervation (RDN) was reported as a novel exciting treatment for resistant hypertension in 2009. An initial randomized trial supported its efficacy and the technique gained rapid acceptance across the globe. However, a subsequent large blinded, sham arm randomized trial conducted in the USA (to gain Food and Drug Administration approval) failed to achieve its primary efficacy end point in reducing office blood pressure at 6 months. Published in 2014 this trial received both widespread praise and criticism. RDN has effectively stopped out with clinical trials pending further evidence. This joint consensus document representing the European Society of Hypertension and the Cardiovascular and Radiological Society of Europe attempts to distill the current evidence and provide future direction and guidance.

Sample Size Calculations for Micro-randomized Trials in mHealth

PubMed Central

Liao, Peng; Klasnja, Predrag; Tewari, Ambuj; Murphy, Susan A.

2015-01-01

The use and development of mobile interventions are experiencing rapid growth. In “just-in-time” mobile interventions, treatments are provided via a mobile device and they are intended to help an individual make healthy decisions “in the moment,” and thus have a proximal, near future impact. Currently the development of mobile interventions is proceeding at a much faster pace than that of associated data science methods. A first step toward developing data-based methods is to provide an experimental design for testing the proximal effects of these just-in-time treatments. In this paper, we propose a “micro-randomized” trial design for this purpose. In a micro-randomized trial, treatments are sequentially randomized throughout the conduct of the study, with the result that each participant may be randomized at the 100s or 1000s of occasions at which a treatment might be provided. Further, we develop a test statistic for assessing the proximal effect of a treatment as well as an associated sample size calculator. We conduct simulation evaluations of the sample size calculator in various settings. Rules of thumb that might be used in designing a micro-randomized trial are discussed. This work is motivated by our collaboration on the HeartSteps mobile application designed to increase physical activity. PMID:26707831

Prophylactic antibiotics for manual removal of retained placenta in vaginal birth.

PubMed

Chongsomchai, Chompilas; Lumbiganon, Pisake; Laopaiboon, Malinee

2014-10-20

Retained placenta is a potentially life-threatening condition because of its association with postpartum hemorrhage. Manual removal of placenta increases the likelihood of bacterial contamination in the uterine cavity. To compare the effectiveness and side-effects of routine antibiotic use for manual removal of placenta in vaginal birth in women who received antibiotic prophylaxis and those who did not and to identify the appropriate regimen of antibiotic prophylaxis for this procedure. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2014). All randomized controlled trials comparing antibiotic prophylaxis and placebo or non antibiotic use to prevent endometritis after manual removal of placenta in vaginal birth. There are no included trials. In future updates, if we identify eligible trials, two review authors will independently assess trial quality and extract data No studies that met the inclusion criteria were identified. There are no randomized controlled trials to evaluate the effectiveness of antibiotic prophylaxis to prevent endometritis after manual removal of placenta in vaginal birth.

Effectiveness guidance document (EGD) for Chinese medicine trials: a consensus document

PubMed Central

2014-01-01

Background There is a need for more Comparative Effectiveness Research (CER) on Chinese medicine (CM) to inform clinical and policy decision-making. This document aims to provide consensus advice for the design of CER trials on CM for researchers. It broadly aims to ensure more adequate design and optimal use of resources in generating evidence for CM to inform stakeholder decision-making. Methods The Effectiveness Guidance Document (EGD) development was based on multiple consensus procedures (survey, written Delphi rounds, interactive consensus workshop, international expert review). To balance aspects of internal and external validity, multiple stakeholders, including patients, clinicians, researchers and payers were involved in creating this document. Results Recommendations were developed for “using available data” and “future clinical studies”. The recommendations for future trials focus on randomized trials and cover the following areas: designing CER studies, treatments, expertise and setting, outcomes, study design and statistical analyses, economic evaluation, and publication. Conclusion The present EGD provides the first systematic methodological guidance for future CER trials on CM and can be applied to single or multi-component treatments. While CONSORT statements provide guidelines for reporting studies, EGDs provide recommendations for the design of future studies and can contribute to a more strategic use of limited research resources, as well as greater consistency in trial design. PMID:24885146

Movement-Pattern Training to Improve Function in People With Chronic Hip Joint Pain: A Feasibility Randomized Clinical Trial.

PubMed

Harris-Hayes, Marcie; Czuppon, Sylvia; Van Dillen, Linda R; Steger-May, Karen; Sahrmann, Shirley; Schootman, Mario; Salsich, Gretchen B; Clohisy, John C; Mueller, Michael J

2016-06-01

Study Design Feasibility randomized clinical trial. Background Rehabilitation may be an appropriate treatment strategy for patients with chronic hip joint pain; however, the evidence related to the effectiveness of rehabilitation is limited. Objectives To assess feasibility of performing a randomized clinical trial to investigate the effectiveness of movement-pattern training (MPT) to improve function in people with chronic hip joint pain. Methods Thirty-five patients with chronic hip joint pain were randomized into a treatment (MPT) group or a control (wait-list) group. The MPT program included 6 one-hour supervised sessions and incorporated (1) task-specific training for basic functional tasks and symptom-provoking tasks, and (2) strengthening of hip musculature. The wait-list group received no treatment. Primary outcomes for feasibility were patient retention and adherence. Secondary outcomes to assess treatment effects were patient-reported function (Hip disability and Osteoarthritis Outcome Score), lower extremity kinematics, and hip muscle strength. Results Retention rates did not differ between the MPT (89%) and wait-list groups (94%, P = 1.0). Sixteen of the 18 patients (89%) in the MPT group attended at least 80% of the treatment sessions. For the home exercise program, 89% of patients reported performing their home program at least once per day. Secondary outcomes support the rationale for conduct of a superiority randomized clinical trial. Conclusion Based on retention and adherence rates, a larger randomized clinical trial appears feasible and warranted to assess treatment effects more precisely. Data from this feasibility study will inform our future clinical trial. Level of Evidence Therapy, level 2b-. J Orthop Sports Phys Ther 2016;46(6):452-461. Epub 26 Apr 2016. doi:10.2519/jospt.2016.6279.

Methodological issues associated with clinical trials in epilepsy.

PubMed

Ferlazzo, Edoardo; Sueri, Chiara; Gasparini, Sara; Russo, Emilio; Cianci, Vittoria; Ascoli, Michele; De Sarro, Giovambattista; Aguglia, Umberto

2017-10-01

despite methodological advances in epilepsy clinical trials, the proportion of patients reaching seizure-freedom has not substantially changed over the years. We review the main methodological limitations of current trials, the possible strategies to overcome these limits, and the issues that need to be addressed in next future. Area covered: references were identified by PubMed search until March 2017 and unpublished literature was searched on ClinicalTrials.gov. Add-on trials mainly involve refractory epilepsy subjects, reducing overall response to the investigational drug. The inclusion of subjects with earlier disease from less developed countries has partially allowed overcoming this limitation, but has introduced more random variability of results. Monotherapy trials rise methodological, economical, and ethical concerns with different regulatory requirements in European Union and in the United States of America. Newer trial designs, such as futility trials or 'time-to-event' design, have been implemented. Moreover, both add-on and monotherapy trials results might be affected by patient's ability to recognize and record seizures, and by randomness of seizures occurrence over time. Possible strategies to achieve more reliable outcomes are detailed. Expert commentary: clinical trial methodology needs to be optimized to better address regulatory agencies requirements and to encounter both patients' and clinicians' needs.

A randomized trial of enhanced HIV risk-reduction and vaccine trial education interventions among HIV-negative, high-risk women who use noninjection drugs: the UNITY study.

PubMed

Koblin, Beryl A; Bonner, Sebastian; Hoover, Donald R; Xu, Guozhen; Lucy, Debbie; Fortin, Princess; Putnam, Sara; Latka, Mary H

2010-03-01

Limited data are available on interventions to reduce sexual risk behaviors and increase knowledge of HIV vaccine trial concepts in high-risk populations eligible to participate in HIV vaccine efficacy trials. The UNITY Study was a 2-arm randomized trial to determine the efficacy of enhanced HIV risk-reduction and vaccine trial education interventions to reduce the occurrence of unprotected vaginal sex acts and increase HIV vaccine trial knowledge among 311 HIV-negative noninjection drug using women. The enhanced vaccine education intervention using pictures along with application vignettes and enhanced risk-reduction counseling consisting of 3 one-on-one counseling sessions were compared with standard conditions. Follow-up visits at 1 week and 1, 6, and 12 months after randomization included HIV testing and assessment of outcomes. During follow-up, the percent of women reporting sexual risk behaviors declined significantly but did not differ significantly by study arm. Knowledge of HIV vaccine trial concepts significantly increased but did not significantly differ by study arm. Concepts about HIV vaccine trials not adequately addressed by either condition included those related to testing a vaccine for both efficacy and safety, guarantees about participation in future vaccine trials, assurances of safety, medical care, and assumptions about any protective effect of a test vaccine. Further research is needed to boost educational efforts and strengthen risk-reduction counseling among high-risk noninjection drug using women.

[Randomized, controlled clinical trials with observational follow-up investigations for evaluating efficacy of antihyperglycaemic treatment. II. Features of and lessons from the follow-up investigations].

PubMed

Jermendy, György

2018-04-01

Although the outcomes of the follow-up investigation period of the randomized clinical studies for evaluating the efficacy of a treatment or an antidiabetic drug may be confounded or potentially biased by several factors, the results are widely accepted by the diabetes community. In line with the theory of metabolic memory or metabolic legacy, early and intensive antihyperglycaemic treatment should be provided for all diabetic patients as this strategy can result in beneficial effects even in the long run. The recent cardiovascular safety trials with new, innovative antidiabetic drugs differ in several aspects from the former efficacy studies. Ten cardiovascular safety trials were completed so far enabling to define their unique and common features. It can be anticipated that the era of randomized, controlled efficacy studies with observational follow-up investigations came to an end in diabetes research. Nowadays, cardiovascular safety trials are in the focus of clinical research in diabetology and results of several ongoing studies are expected with interest in the near future. Orv Hetil. 2018; 159(16): 615-619.

Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor.

PubMed

Selvarajah, Dinesh; Gandhi, Rajiv; Emery, Celia J; Tesfaye, Solomon

2010-01-01

To assess the efficacy of Sativex, a cannabis-based medicinal extract, as adjuvant treatment in painful diabetic peripheral neuropathy (DPN). In this randomized controlled trial, 30 subjects with painful DPN received daily Sativex or placebo. The primary outcome measure was change in mean daily pain scores, and secondary outcome measures included quality-of-life assessments. There was significant improvement in pain scores in both groups, but mean change between groups was not significant. There were no significant differences in secondary outcome measures. Patients with depression had significantly greater baseline pain scores that improved regardless of intervention. This first-ever trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful DPN. Depression was a major confounder and may have important implications for future trials on painful DPN.

Commentary: Randomized controlled trials in autism spectrum disorder: state of the field and challenges for the future.

PubMed

Simonoff, Emily

2018-04-01

This issue of the Journal includes two articles summarizing the evidence from clinical trials aimed at improving symptoms of autism. French and Kennedy (Journal of Child Psychology and Psychiatry, 2018, xx, xxxx) systematically review randomized controlled trials (RCTs) aimed at an "early intervention" and focus on trials including children with or at risk of autism under age 6 years. Although no type of intervention were excluded from their review, none of the included 48 RCTs employed pharmacological modalities and the overwhelming majority tested psychological/behavioural interventions aimed at modifying aspects of observed behaviours that are abnormal in children with autism. Using the standard Cochrane tool for evaluating risk of bias, French and Kennedy conclude that many RCTs are of low quality, which throws into question the reliance that should be placed on the findings. © 2018 Association for Child and Adolescent Mental Health.

Randomized Placebo-Controlled Double-Blind Clinical Trial of Cannabis-Based Medicinal Product (Sativex) in Painful Diabetic Neuropathy

PubMed Central

Selvarajah, Dinesh; Gandhi, Rajiv; Emery, Celia J.; Tesfaye, Solomon

2010-01-01

OBJECTIVE To assess the efficacy of Sativex, a cannabis-based medicinal extract, as adjuvant treatment in painful diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS In this randomized controlled trial, 30 subjects with painful DPN received daily Sativex or placebo. The primary outcome measure was change in mean daily pain scores, and secondary outcome measures included quality-of-life assessments. RESULTS There was significant improvement in pain scores in both groups, but mean change between groups was not significant. There were no significant differences in secondary outcome measures. Patients with depression had significantly greater baseline pain scores that improved regardless of intervention. CONCLUSIONS This first-ever trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful DPN. Depression was a major confounder and may have important implications for future trials on painful DPN. PMID:19808912

A stepped wedge, cluster-randomized trial of a household UV-disinfection and safe storage drinking water intervention in rural Baja California Sur, Mexico.

PubMed

Gruber, Joshua S; Reygadas, Fermin; Arnold, Benjamin F; Ray, Isha; Nelson, Kara; Colford, John M

2013-08-01

In collaboration with a local non-profit organization, this study evaluated the expansion of a program that promoted and installed Mesita Azul, an ultraviolet-disinfection system designed to treat household drinking water in rural Mexico. We conducted a 15-month, cluster-randomized stepped wedge trial by randomizing the order in which 24 communities (444 households) received the intervention. We measured primary outcomes (water contamination and diarrhea) during seven household visits. The intervention increased the percentage of households with access to treated and safely stored drinking water (23-62%), and reduced the percentage of households with Escherichia coli contaminated drinking water (risk difference (RD): -19% [95% CI: -27%, -14%]). No significant reduction in diarrhea was observed (RD: -0.1% [95% CI: -1.1%, 0.9%]). We conclude that household water quality improvements measured in this study justify future promotion of the Mesita Azul, and that future studies to measure its health impact would be valuable if conducted in populations with higher diarrhea prevalence.

A Stepped Wedge, Cluster-Randomized Trial of a Household UV-Disinfection and Safe Storage Drinking Water Intervention in Rural Baja California Sur, Mexico

PubMed Central

Gruber, Joshua S.; Reygadas, Fermin; Arnold, Benjamin F.; Ray, Isha; Nelson, Kara; Colford, John M.

2013-01-01

In collaboration with a local non-profit organization, this study evaluated the expansion of a program that promoted and installed Mesita Azul, an ultraviolet-disinfection system designed to treat household drinking water in rural Mexico. We conducted a 15-month, cluster-randomized stepped wedge trial by randomizing the order in which 24 communities (444 households) received the intervention. We measured primary outcomes (water contamination and diarrhea) during seven household visits. The intervention increased the percentage of households with access to treated and safely stored drinking water (23–62%), and reduced the percentage of households with Escherichia coli contaminated drinking water (risk difference (RD): −19% [95% CI: −27%, −14%]). No significant reduction in diarrhea was observed (RD: −0.1% [95% CI: −1.1%, 0.9%]). We conclude that household water quality improvements measured in this study justify future promotion of the Mesita Azul, and that future studies to measure its health impact would be valuable if conducted in populations with higher diarrhea prevalence. PMID:23732255

The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine.

PubMed

Vassy, Jason L; Lautenbach, Denise M; McLaughlin, Heather M; Kong, Sek Won; Christensen, Kurt D; Krier, Joel; Kohane, Isaac S; Feuerman, Lindsay Z; Blumenthal-Barby, Jennifer; Roberts, J Scott; Lehmann, Lisa Soleymani; Ho, Carolyn Y; Ubel, Peter A; MacRae, Calum A; Seidman, Christine E; Murray, Michael F; McGuire, Amy L; Rehm, Heidi L; Green, Robert C

2014-03-20

Whole genome sequencing (WGS) is already being used in certain clinical and research settings, but its impact on patient well-being, health-care utilization, and clinical decision-making remains largely unstudied. It is also unknown how best to communicate sequencing results to physicians and patients to improve health. We describe the design of the MedSeq Project: the first randomized trials of WGS in clinical care. This pair of randomized controlled trials compares WGS to standard of care in two clinical contexts: (a) disease-specific genomic medicine in a cardiomyopathy clinic and (b) general genomic medicine in primary care. We are recruiting 8 to 12 cardiologists, 8 to 12 primary care physicians, and approximately 200 of their patients. Patient participants in both the cardiology and primary care trials are randomly assigned to receive a family history assessment with or without WGS. Our laboratory delivers a genome report to physician participants that balances the needs to enhance understandability of genomic information and to convey its complexity. We provide an educational curriculum for physician participants and offer them a hotline to genetics professionals for guidance in interpreting and managing their patients' genome reports. Using varied data sources, including surveys, semi-structured interviews, and review of clinical data, we measure the attitudes, behaviors and outcomes of physician and patient participants at multiple time points before and after the disclosure of these results. The impact of emerging sequencing technologies on patient care is unclear. We have designed a process of interpreting WGS results and delivering them to physicians in a way that anticipates how we envision genomic medicine will evolve in the near future. That is, our WGS report provides clinically relevant information while communicating the complexity and uncertainty of WGS results to physicians and, through physicians, to their patients. This project will not only illuminate the impact of integrating genomic medicine into the clinical care of patients but also inform the design of future studies. ClinicalTrials.gov identifier NCT01736566.

Safety and efficacy of pharmacologic thromboprophylaxis following blunt head injury: a systematic review.

PubMed

Reeves, Fairleigh; Batty, Lachlan; Pitt, Veronica; Chau, Marisa; Pattuwage, Loyal; Gruen, Russell L

2013-10-01

Patients with blunt head injury are at high risk of venous thromboembolism. However, pharmacologic thromboprophylaxis (PTP) may cause progression of intracranial hemorrhage, and clinicians must often weigh up the risks and benefits. This review aimed to determine whether adding PTP to mechanical prophylaxis confers net benefit or harm and the optimal timing, dose, and agent for PTP in patients with blunt head injury. We searched MEDLINE, EMBASE, The Cochrane Library Central Register of Controlled Trials (CENTRAL), and www.clinicaltrials.gov on April 24, 2013, to identify controlled studies and ongoing trials that assessed the efficacy or safety of thromboprophylaxis interventions in the early management of head-injured patients. Studies were classified based on types of interventions and comparisons, and the quality of included studies was assessed using Cochrane risk-of-bias tool and the Newcastle-Ottawa Quality Assessment Scale. We intended to undertake a meta-analysis if studies were sufficiently similar. Sixteen studies met the inclusion criteria, including four randomized controlled trials. At least two randomized controlled trials were at high risk of bias owing to inadequate randomization and concealment of allocation, and observational studies were potentially confounded by substantial differences between comparison groups. Heterogeneity of included studies precluded meta-analysis. Results were mixed, with some studies supporting and others refuting addition of PTP to mechanical interventions. Little evidence was available about dose or choice of agent. The safety and efficacy of early PTP in patients without early progression of hemorrhage is unclear. There is currently insufficient evidence to guide thromboprophylaxis in patients with blunt head injury. Standardized definitions and outcome measurements would facilitate comparison of outcomes across future studies. Studies in mixed populations should report head-injured specific subgroup data. Future randomized controlled trials should investigate the efficacy and safety of early pharmacologic prophylaxis in addition to mechanical intervention. Systematic review, level IV.

Is a comparative clinical trial for breast cancer tumor markers to monitor disease recurrence warranted? A value of information analysis

PubMed Central

Thariani, Rahber; Henry, Norah Lynn; Ramsey, Scott D; Blough, David K; Barlow, Bill; Gralow, Julie R; Veenstra, David L

2014-01-01

Background Breast cancer tumor markers are used by some clinicians to screen for disease recurrence risk. Since there is limited evidence of benefit, additional research may be warranted. Aim To assess the potential value of a randomized clinical trial of breast tumor marker testing in routine follow-up of high-risk, stage II–III breast cancer survivors. Materials & methods We developed a decision-analytic model of tumor marker testing plus standard surveillance every 3–6 months for 5 years. The expected value of sample information was calculated using probabilistic simulations and was a function of: the probability of selecting the optimal monitoring strategy with current versus future information; the impact of choosing the nonoptimal strategy; and the size of the population affected. Results The value of information for a randomized clinical trial involving 9000 women was US$214 million compared with a cost of US$30–60 million to conduct such a trial. The probability of making an alternate, nonoptimal decision and choosing testing versus no testing was 32% with current versus future information from the trial. The impact of a nonoptimal decision was US$2150 and size of population impacted over 10 years was 308,000. The value of improved information on overall survival was US$105 million, quality of life US$37 million and test performance US$71 million. Conclusion Conducting a randomized clinical trial of breast cancer tumor markers appears to offer a good societal return on investment. Retrospective analyses to assess test performance and evaluation of patient quality of life using tumor markers may also offer valuable areas of research. However, alternative investments may offer even better returns in investments and, as such, the trial concept deserves further study as part of an overall research-portfolio evaluation. PMID:24236631

Using simulation pedagogy to teach clinical education skills: A randomized trial.

PubMed

Holdsworth, Clare; Skinner, Elizabeth H; Delany, Clare M

2016-05-01

Supervision of students is a key role of senior physiotherapy clinicians in teaching hospitals. The objective of this study was to test the effect of simulated learning environments (SLE) on educators' self-efficacy in student supervision skills. A pilot prospective randomized controlled trial with concealed allocation was conducted. Clinical educators were randomized to intervention (SLE) or control groups. SLE participants completed two 3-hour workshops, which included simulated clinical teaching scenarios, and facilitated debrief. Standard Education (StEd) participants completed two online learning modules. Change in educator clinical supervision self-efficacy (SE) and student perceptions of supervisor skill were calculated. Between-group comparisons of SE change scores were analyzed with independent t-tests to account for potential baseline differences in education experience. Eighteen educators (n = 18) were recruited (SLE [n = 10], StEd [n = 8]). Significant improvements in SE change scores were seen in SLE participants compared to control participants in three domains of self-efficacy: (1) talking to students about supervision and learning styles (p = 0.01); (2) adapting teaching styles for students' individual needs (p = 0.02); and (3) identifying strategies for future practice while supervising students (p = 0.02). This is the first study investigating SLE for teaching skills of clinical education. SLE improved educators' self-efficacy in three domains of clinical education. Sample size limited the interpretation of student ratings of educator supervision skills. Future studies using SLE would benefit from future large multicenter trials evaluating its effect on educators' teaching skills, student learning outcomes, and subsequent effects on patient care and health outcomes.

A randomized controlled trial of group Stepping Stones Triple P: a mixed-disability trial.

PubMed

Roux, Gemma; Sofronoff, Kate; Sanders, Matthew

2013-09-01

Stepping Stones Triple P (SSTP) is a parenting program designed for families of a child with a disability. The current study involved a randomized controlled trial of Group Stepping Stones Triple P (GSSTP) for a mixed-disability group. Participants were 52 families of children diagnosed with an Autism Spectrum Disorder, Down syndrome, Cerebral Palsy, or an intellectual disability. The results demonstrated significant improvements in parent-reported child behavior, parenting styles, parental satisfaction, and conflict about parenting. Results among participants were similar despite children's differing impairments. The intervention effect was maintained at 6-month follow-up. The results indicate that GSSTP is a promising intervention for a mixed-disability group. Limitations of the study, along with areas for future research, are also discussed. © FPI, Inc.

How to Measure Motivational Interviewing Fidelity in Randomized Controlled Trials: Practical Recommendations.

PubMed

Jelsma, Judith G M; Mertens, Vera-Christina; Forsberg, Lisa; Forsberg, Lars

2015-07-01

Many randomized controlled trials in which motivational interviewing (MI) is a key intervention make no provision for the assessment of treatment fidelity. This methodological shortcoming makes it impossible to distinguish between high- and low-quality MI interventions, and, consequently, to know whether MI provision has contributed to any intervention effects. This article makes some practical recommendations for the collection, selection, coding and reporting of MI fidelity data, as measured using the Motivational Interviewing Treatment Integrity Code. We hope that researchers will consider these recommendations and include MI fidelity measures in future studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Neighborhood Effects in a Behavioral Randomized Controlled Trial

PubMed Central

Pruitt, Sandi L.; Leonard, Tammy; Murdoch, James; Hughes, Amy; McQueen, Amy; Gupta, Samir

2015-01-01

Randomized controlled trials (RCTs) of interventions intended to modify health behaviors may be influenced by neighborhood effects which can impede unbiased estimation of intervention effects. Examining a RCT designed to increase colorectal cancer (CRC) screening (N=5,628), we found statistically significant neighborhood effects: average CRC test use among neighboring study participants was significantly and positively associated with individual patient’s CRC test use. This potentially important spatially-varying covariate has not previously been considered in a RCT. Our results suggest that future RCTs of health behavior interventions should assess potential social interactions between participants, which may cause intervention arm contamination and may bias effect size estimation. PMID:25456014

Establishing Evidence-Based Indications for Proton Therapy: An Overview of Current Clinical Trials

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

Mishra, Mark V., E-mail: mmishra@umm.edu; Aggarwal, Sameer; Bentzen, Soren M.

Purpose: To review and assess ongoing proton beam therapy (PBT) clinical trials and to identify major gaps. Methods and Materials: Active PBT clinical trials were identified from (clinicaltrials.gov) and the World Health Organization International Clinical Trials Platform Registry. Data on clinical trial disease site, age group, projected patient enrollment, expected start and end dates, study type, and funding source were extracted. Results: A total of 122 active PBT clinical trials were identified, with target enrollment of >42,000 patients worldwide. Ninety-six trials (79%), with a median planned sample size of 68, were classified as interventional studies. Observational studies accounted for 21% ofmore » trials but 71% (n=29,852) of planned patient enrollment. The most common PBT clinical trials focus on gastrointestinal tract tumors (21%, n=26), tumors of the central nervous system (15%, n=18), and prostate cancer (12%, n=15). Five active studies (lung, esophagus, head and neck, prostate, breast) will randomize patients between protons and photons, and 3 will randomize patients between protons and carbon ion therapy. Conclusions: The PBT clinical trial portfolio is expanding rapidly. Although the majority of ongoing studies are interventional, the majority of patients will be accrued to observational studies. Future efforts should focus on strategies to encourage optimal patient enrollment and retention, with an emphasis on randomized, controlled trials, which will require support from third-party payers. Results of ongoing PBT studies should be evaluated in terms of comparative effectiveness, as well as incremental effectiveness and value offered by PBT in comparison with conventional radiation modalities.« less

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.

Whose data set is it anyway? Sharing raw data from randomized trials.

PubMed

Vickers, Andrew J

2006-05-16

Sharing of raw research data is common in many areas of medical research, genomics being perhaps the most well-known example. In the clinical trial community investigators routinely refuse to share raw data from a randomized trial without giving a reason. Data sharing benefits numerous research-related activities: reproducing analyses; testing secondary hypotheses; developing and evaluating novel statistical methods; teaching; aiding design of future trials; meta-analysis; and, possibly, preventing error, fraud and selective reporting. Clinical trialists, however, sometimes appear overly concerned with being scooped and with misrepresentation of their work. Both possibilities can be avoided with simple measures such as inclusion of the original trialists as co-authors on any publication resulting from data sharing. Moreover, if we treat any data set as belonging to the patients who comprise it, rather than the investigators, such concerns fall away. Technological developments, particularly the Internet, have made data sharing generally a trivial logistical problem. Data sharing should come to be seen as an inherent part of conducting a randomized trial, similar to the way in which we consider ethical review and publication of study results. Journals and funding bodies should insist that trialists make raw data available, for example, by publishing data on the Web. If the clinical trial community continues to fail with respect to data sharing, we will only strengthen the public perception that we do clinical trials to benefit ourselves, not our patients.

Debate Regarding Oseltamivir Use for Seasonal and Pandemic Influenza

PubMed Central

Kelly, Heath

2016-01-01

A debate about the market-leading influenza antiviral medication, oseltamivir, which initially focused on treatment for generally mild illness, has been expanded to question the wisdom of stockpiling for use in future influenza pandemics. Although randomized controlled trial evidence confirms that oseltamivir will reduce symptom duration by 17–25 hours among otherwise healthy adolescents and adults with community-managed disease, no randomized controlled trials have examined the effectiveness of oseltamivir against more serious outcomes. Observational studies, although criticized on methodologic grounds, suggest that oseltamivir given early can reduce the risk for death by half among persons hospitalized with confirmed infection caused by influenza A(H1N1)pdm09 and influenza A(H5N1) viruses. However, available randomized controlled trial data may not be able to capture the effect of oseltamivir use among hospitalized patients with severe disease. We assert that data on outpatients with relatively mild disease should not form the basis for policies on the management of more severe disease. PMID:27191818

Combined Cognitive-Strategy and Task-Specific Training Affects Cognition and Upper-Extremity Function in Subacute Stroke: An Exploratory Randomized Controlled Trial

PubMed Central

Polatajko, Helene; Baum, Carolyn; Rios, Jorge; Cirone, Dianne; Doherty, Meghan; McEwen, Sara

2016-01-01

The purpose of this study was to estimate the effect of Cognitive Orientation to Daily Occupational Performance (CO–OP) compared with usual occupational therapy on upper-extremity movement, cognitive flexibility, and stroke impact in people less than 3 mo after stroke. An exploratory, single-blind randomized controlled trial was conducted with people referred to outpatient occupational therapy services at two rehabilitation centers. Arm movement was measured with the Action Research Arm Test, cognitive flexibility with the Delis–Kaplan Executive Function System Trail Making subtest, and stroke impact with subscales of the Stroke Impact Scale. A total of 35 participants were randomized, and 26 completed the intervention. CO–OP demonstrated measurable effects over usual care on all measures. These data provide early support for the use of CO–OP to improve performance and remediate cognitive and arm movement impairments after stroke over usual care; however, future study is warranted to confirm the effects observed in this trial. PMID:26943113

‘Help for Hay Fever’, a goal-focused intervention for people with intermittent allergic rhinitis, delivered in Scottish community pharmacies: study protocol for a pilot cluster randomized controlled trial

PubMed Central

2013-01-01

Background Despite the availability of evidence-based guidelines for managing allergic rhinitis in primary care, management of the condition in the United Kingdom (UK) remains sub-optimal. Its high prevalence and negative effects on quality of life, school performance, productivity and co-morbid respiratory conditions (in particular, asthma), and high health and societal costs, make this a priority for developing novel models of care. Recent Australian research demonstrated the potential of a community pharmacy-based ‘goal-focused’ intervention to help people with intermittent allergic rhinitis to self-manage their condition better, reduce symptom severity and improve quality of life. In this pilot study we will assess the transferability of the goal-focused intervention to a UK context, the suitability of the intervention materials, procedures and outcome measures and collect data to inform a future definitive UK randomized controlled trial (RCT). Methods/Design A pilot cluster RCT with associated preliminary economic analysis and embedded qualitative evaluation. The pilot trial will take place in two Scottish Health Board areas: Grampian and Greater Glasgow & Clyde. Twelve community pharmacies will be randomly assigned to intervention or usual care group. Each will recruit 12 customers seeking advice or treatment for intermittent allergic rhinitis. Pharmacy staff in intervention pharmacies will support recruited customers in developing strategies for setting and achieving goals that aim to avoid/minimize triggers for, and eliminate/minimize symptoms of allergic rhinitis. Customers recruited in non-intervention pharmacies will receive usual care. The co-primary outcome measures, selected to inform a sample size calculation for a future RCT, are: community pharmacy and customer recruitment and completion rates; and effect size of change in the validated mini-Rhinoconjunctivitis Quality of Life Questionnaire between baseline, one-week and six-weeks post-intervention. Secondary outcome measures relate to changes in symptom severity, productivity, medication adherence and self-efficacy. Quantitative data about accrual, retention and economic measures, and qualitative data about participants’ experiences during the trial will be collected to inform the future RCT. Discussion This work will lay the foundations for a definitive RCT of a community pharmacy-based ‘goal-focused’ self-management intervention for people with intermittent allergic rhinitis. Results of the pilot trial are expected to be available in April 2013. Trial registration Current Controlled Trials ISRCTN43606442 PMID:23856015

DESIGNING PHARMACEUTICAL TRIALS FOR SARCOPENIA IN FRAIL OLDER ADULTS: EU/US TASK FORCE RECOMMENDATIONS

PubMed Central

VELLAS, B.; PAHOR, M.; MANINI, T.; ROOKS, D.; GURALNIK, J.M.; MORLEY, J.; STUDENSKI, S.; EVANS, W.; ASBRAND, C.; FARIELLO, R.; PEREIRA, S.; ROLLAND, Y.; VAN KAN, G. ABELLAN; CESARI, M.; CHUMLEA, WM.C.; FIELDING, R.

2014-01-01

An international task force of academic and industry leaders in sarcopenia research met on December 5, 2012 in Orlando, Florida to develop guidelines for designing and executing randomized clinical trials of sarcopenia treatments. The Task Force reviewed results from previous trials in related disease areas to extract lessons relevant to future sarcopenia trials, including practical issues regarding the design and conduct of trials in elderly populations, the definition of appropriate target populations, and the selection of screening tools, outcome measures, and biomarkers. They discussed regulatory issues, the challenges posed by trials of different types of interventions, and the need for standardization and harmonization. The Task Force concluded with recommendations for advancing the field toward better clinical trials. PMID:23933872

Bioengineered Temporomandibular Joint Disk Implants: Study Protocol for a Two-Phase Exploratory Randomized Preclinical Pilot Trial in 18 Black Merino Sheep (TEMPOJIMS)

PubMed Central

Monje, Florencio Gil; González-García, Raúl; Little, Christopher B; Mónico, Lisete; Pinho, Mário; Santos, Fábio Abade; Carrapiço, Belmira; Gonçalves, Sandra Cavaco; Morouço, Pedro; Alves, Nuno; Moura, Carla; Wang, Yadong; Jeffries, Eric; Gao, Jin; Sousa, Rita; Neto, Lia Lucas; Caldeira, Daniel; Salvado, Francisco

2017-01-01

Background Preclinical trials are essential to test efficacious options to substitute the temporomandibular joint (TMJ) disk. The contemporary absence of an ideal treatment for patients with severe TMJ disorders can be related to difficulties concerning the appropriate study design to conduct preclinical trials in the TMJ field. These difficulties can be associated with the use of heterogeneous animal models, the use of the contralateral TMJ as control, the absence of rigorous randomized controlled preclinical trials with blinded outcomes assessors, and difficulties involving multidisciplinary teams. Objective This study aims to develop a new, reproducible, and effective study design for preclinical research in the TMJ domain, obtaining rigorous data related to (1) identify the impact of bilateral discectomy in black Merino sheep, (2) identify the impact of bilateral discopexy in black Merino sheep, and (3) identify the impact of three different bioengineering TMJ discs in black Merino sheep. Methods A two-phase exploratory randomized controlled preclinical trial with blinded outcomes is proposed. In the first phase, nine sheep are randomized into three different surgical bilateral procedures: bilateral discectomy, bilateral discopexy, and sham surgery. In the second phase, nine sheep are randomized to bilaterally test three different TMJ bioengineering disk implants. The primary outcome is the histological gradation of TMJ. Secondary outcomes are imaging changes, absolute masticatory time, ruminant time per cycle, ruminant kinetics, ruminant area, and sheep weight. Results Previous preclinical studies in this field have used the contralateral unoperated side as a control, different animal models ranging from mice to a canine model, with nonrandomized, nonblinded and uncontrolled study designs and limited outcomes measures. The main goal of this exploratory preclinical protocol is to set a new standard for future preclinical trials in oromaxillofacial surgery, particularly in the TMJ field, by proposing a rigorous design in black Merino sheep. The authors also intend to test the feasibility of pilot outcomes. The authors expect to increase the quality of further studies in this field and to progress in future treatment options for patients undergoing surgery for TMJ disk replacement. Conclusions The study has commenced, but it is too early to provide results or conclusions. PMID:28254733

Association Splitting: A randomized controlled trial of a new method to reduce craving among inpatients with alcohol dependence.

PubMed

Schneider, Brooke C; Moritz, Steffen; Hottenrott, Birgit; Reimer, Jens; Andreou, Christina; Jelinek, Lena

2016-04-30

Association Splitting, a novel cognitive intervention, was tested in patients with alcohol dependence as an add-on intervention in an initial randomized controlled trial. Preliminary support for Association Splitting has been found in patients with obsessive-compulsive disorder, as well as in an online pilot study of patients with alcohol use disorders. The present variant sought to reduce craving by strengthening neutral associations with alcohol-related stimuli, thus, altering cognitive networks. Eighty-four inpatients with verified diagnoses of alcohol dependence, who were currently undergoing inpatient treatment, were randomly assigned to Association Splitting or Exercise Therapy. Craving was measured at baseline, 4-week follow-up, and six months later with the Obsessive-Compulsive Drinking Scale (primary outcome) and the Alcohol Craving Questionnaire. There was no advantage for Association Splitting after three treatment sessions relative to Exercise Therapy. Among Association Splitting participants, 51.9% endorsed a subjective decline in craving and 88.9% indicated that they would use Association Splitting in the future. Despite high acceptance, an additional benefit of Association Splitting beyond standard inpatient treatment was not found. Given that participants were concurrently undergoing inpatient treatment and Association Splitting has previously shown moderate effects, modification of the study design may improve the potential to detect significant effects in future trials. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A randomized trial of enhanced HIV risk reduction and vaccine trial education interventions among HIV-negative, high-risk women who use non-injection drugs: The UNITY Study

PubMed Central

Koblin, Beryl A.; Bonner, Sebastian; Hoover, Donald R.; Xu, Guozhen; Lucy, Debbie; Fortin, Princess; Putnam, Sara; Latka, Mary H.

2014-01-01

Background Limited data are available on interventions to reduce sexual risk behaviors and increase knowledge of HIV vaccine trial concepts in high risk populations eligible to participate in HIV vaccine efficacy trials. Methods The UNITY Study was a two-arm randomized trial to determine the efficacy of enhanced HIV risk reduction and vaccine trial education interventions to reduce the occurrence of unprotected vaginal sex acts and increase HIV vaccine trial knowledge among 311 HIV-negative non-injection drug using women. The enhanced vaccine education intervention using pictures along with application vignettes and enhanced risk reduction counseling consisting of three one-on-one counseling sessions were compared to standard conditions. Follow-up visits at one week and one, six and twelve months after randomization included HIV testing and assessment of outcomes. Results During follow up, the percent of women reporting sexual risk behaviors declined significantly, but did not differ significantly by study arm. Knowledge of HIV vaccine trial concepts significantly increased but did not significantly differ by study arm. Concepts about HIV vaccine trials not adequately addressed by either condition included those related to testing a vaccine for both efficacy and safety, guarantees about participation in future vaccine trials, assurances of safety, medical care, and assumptions about any protective effect of a test vaccine. Conclusions Further research is needed to boost educational efforts and strengthen risk reduction counseling among high-risk non-injection drug using women. PMID:20190585

Changing Health Behaviors to Improve Health Outcomes after Angioplasty: A Randomized Trial of Net Present Value versus Future Value Risk Communication

ERIC Educational Resources Information Center

Charlson, M. E.; Peterson, J. C.; Boutin-Foster, C.; Briggs, W. M.; Ogedegbe, G. G.; McCulloch, C. E.; Hollenberg, J.; Wong, C.; Allegrante, J. P.

2008-01-01

Patients who have undergone angioplasty experience difficulty modifying at-risk behaviors for subsequent cardiac events. The purpose of this study was to test whether an innovative approach to framing of risk, based on "net present value" economic theory, would be more effective in behavioral intervention than the standard "future value approach"…

A 12-week interdisciplinary rehabilitation trial in patients with gliomas - a feasibility study.

PubMed

Hansen, Anders; Søgaard, Karen; Minet, Lisbeth Rosenbek; Jarden, Jens Ole

2018-06-01

This report aims to assess the safety and feasibility of using an interdisciplinary rehabilitation intervention for a future randomized controlled trial in patients with gliomas in the initial treatment phase. We conducted an outpatient two-part rehabilitation intervention that involved six weeks of therapeutic supervised training (part one) and six weeks of unsupervised training in a local gym following a training protocol (part two). Predefined feasibility objectives of safety (100%), consent rate (>80%), drop-out (<20%), adherence (>80%) and patient satisfaction (>80%) was achieved at part one. However, the failure to meet predefined feasibility objectives of drop-out, adherence and patient satisfaction of the unsupervised intervention at part two have led to a protocol revision for a future randomized controlled trial. This study demonstrates that an intensive rehabilitation intervention of physical therapy and occupational therapy in the initial treatment phase of patients with gliomas whose Karnofsky performance status is ≥70 is safe and feasible, if relevant inclusion criteria and precautionary screening are made. With the revised protocol, we are confident that the foundation for conducting a successful randomized controlled trial among these vulnerable patients has been established. Implications for rehabilitation Brain tumors constitute some of the most challenging cancer diagnoses presenting for rehabilitation intervention. Patients with gliomas experiences limitations in physical functioning, cognition, and emotional wellbeing. In a relatively small sample this study shows that supervised physical- and occupational therapy in patients with gliomas is safe and feasible in the initial treatment phase. Patients with gliomas can potentially improve functioning through interdisciplinary rehabilitation.

Outcomes Research in Cardiovascular Imaging

PubMed Central

Douglas, Pamela S.; Taylor, Allen; Bild, Diane; Bonow, Robert; Greenland, Philip; Lauer, Michael; Peacock, Frank; Udelson, James

2009-01-01

In July of 2008, the National Heart, Lung, and Blood Institute convened experts in noninvasive cardiovascular imaging, outcomes research, statistics, and clinical trials to develop recommendations for future randomized controlled trials of the use of imaging in: 1) screening the asymptomatic patient for coronary artery disease; 2) assessment of patients with stable angina; 3) identification of acute coronary syndromes in the emergency room; and 4) assessment of heart failure patients with chronic coronary artery disease with reduced left ventricular ejection fraction. This study highlights several possible trial designs for each clinical situation. PMID:19560655

A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics.

PubMed

Jones, L A T; Lammertse, D P; Charlifue, S B; Kirshblum, S C; Apple, D F; Ragnarsson, K T; Poonian, D; Betz, R R; Knoller, N; Heary, R F; Choudhri, T F; Jenkins, A L; Falci, S P; Snyder, D A

2010-11-01

Post hoc analysis from a randomized controlled cellular therapy trial in acute, complete spinal cord injury (SCI). Description and quantitative review of study logistics, referral patterns, current practice patterns and subject demographics. Subjects were recruited to one of six international study centers. Data are presented from 1816 patients pre-screened, 75 participants screened and 50 randomized. Of the 1816 patients pre-screened, 53.7% did not meet initial study criteria, primarily due to an injury outside the time window (14 days) or failure to meet neurological criteria (complete SCI between C5 motor/C4 sensory and T11). MRIs were obtained on 339 patients; 51.0% were ineligible based on imaging criteria. Of the 75 participants enrolled, 25 failed screening (SF), leaving 50 randomized. The primary reason for SF was based on the neurological exam (51.9%), followed by failure to meet MRI criteria (22.2%). Of the 50 randomized subjects, there were no significant differences in demographics in the active versus control arms. In those participants for whom data was available, 93.8% (45 of 48) of randomized participants received steroids before study entry, whereas 94.0% (47 of 50) had spine surgery before study enrollment. The 'funnel effect' (large numbers of potentially eligible participants with a small number enrolled) impacts all trials, but was particularly challenging in this trial due to eligibility criteria and logistics. Data collected may provide information on current practice patterns and the issues encountered and addressed may facilitate design of future trials.

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.

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

PubMed Central

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

2016-01-01

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

[Recent and upcoming randomized trials for left atrial appendage occlusion : Need for a definite assessment of the situation].

PubMed

Skurk, Carsten; Hartung, Johannes Jakob; Landmesser, Ulf

2017-12-01

Atrial fibrillation (AF) is the most common arrhythmia affecting more than 1.6 million patients in Germany. Based on demographic developments, an the number is expected to increase. Embolic strokes in AF patients are particularly severe, and individualized new oral anticoagulant (NOAC) therapy reduces the incidence of stroke in these patients by approximately 70%. Besides vitamin K antagonists, the NOACs rivaroxaban, dabigatran, apixaban, and edoxaban have been introduced into clinical practice; however, major bleeding still occurs at a rate of 2-3% per year. Moreover, randomized studies and real-life registries suggest that >20% of patients with AF and an indication for anticoagulation cannot tolerate chronic oral anticoagulant therapy. Therefore, an alternative method for stroke prevention in AF patients has been developed, i. e., catheter-based exclusion of the left atrial appendage (LAA), a location that is prone for thrombus formation in these patients. The randomized trials of catheter-based LAA occlusion have compared this interventional therapy with vitamin K antagonists. In the future, however, LAA exclusion needs to be compared with NOAC therapy. Moreover, percutaneous LAA exclusion in clinical practice is mostly offered to patients ineligible for long-term oral anticoagulation or with high bleeding risk. However, no controlled, randomized trial data exist for this patient population. These data are needed for appropriate clinical judgment and optimal clinical management. Ongoing studies and scientific questions that are important to define the future for catheter-based LAA closure are discussed in this review.

Lessons learned from a practice-based, multi-site intervention study with nurse participants

PubMed Central

Friese, Christopher R.; Mendelsohn-Victor, Kari; Ginex, Pamela; McMahon, Carol M.; Fauer, Alex J.; McCullagh, Marjorie C.

2016-01-01

Purpose To identify challenges and solutions to the efficient conduct of a multi-site, practice-based randomized controlled trial to improve nurses’ adherence to personal protective equipment use in ambulatory oncology settings. Design The Drug Exposure Feedback and Education for Nurses’ Safety (DEFENS) study is a clustered, randomized, controlled trial. Participating sites are randomized to web-based feedback on hazardous drug exposures in the sites plus tailored messages to address barriers versus a control intervention of a web-based continuing education video. Approach The study principal investigator, the study coordinator, and two site leaders identified challenges to study implementation and potential solutions, plus potential methods to prevent logistical challenges in future studies. Findings Noteworthy challenges included variation in human subjects protection policies, grants and contracts budgeting, infrastructure for nursing-led research, and information technology variation. Successful strategies included scheduled web conferences, site-based study champions, site visits by the principal investigator, and centrally-based document preparation. Strategies to improve efficiency in future studies include early and continued engagement with contract personnel in sites, and proposed changes to the common rule concerning human subjects. The DEFENS study successfully recruited 393 nurses across 12 sites. To date, 369 have completed surveys and 174 nurses have viewed educational materials. Conclusions Multi-site studies of nursing personnel are rare and challenging to existing infrastructure. These barriers can be overcome with strong engagement and planning. Clinical Relevance Leadership engagement, onsite staff support, and continuous communication can facilitate successful recruitment to a workplace-based randomized, controlled behavioral trial. PMID:28098951

Hospital recruitment for a pragmatic cluster-randomized clinical trial: Lessons learned from the COMPASS study.

PubMed

Johnson, Anna M; Jones, Sara B; Duncan, Pamela W; Bushnell, Cheryl D; Coleman, Sylvia W; Mettam, Laurie H; Kucharska-Newton, Anna M; Sissine, Mysha E; Rosamond, Wayne D

2018-01-26

Pragmatic randomized clinical trials are essential to determine the effectiveness of interventions in "real-world" clinical practice. These trials frequently use a cluster-randomized methodology, with randomization at the site level. Despite policymakers' increased interest in supporting pragmatic randomized clinical trials, no studies to date have reported on the unique recruitment challenges faced by cluster-randomized pragmatic trials. We investigated key challenges and successful strategies for hospital recruitment in the Comprehensive Post-Acute Stroke Services (COMPASS) study. The COMPASS study is designed to compare the effectiveness of the COMPASS model versus usual care in improving functional outcomes, reducing the numbers of hospital readmissions, and reducing caregiver strain for patients discharged home after stroke or transient ischemic attack. This model integrates early supported discharge planning with transitional care management, including nurse-led follow-up phone calls after 2, 30, and 60 days and an in-person clinic visit at 7-14 days involving a functional assessment and neurological examination. We present descriptive statistics of the characteristics of successfully recruited hospitals compared with all eligible hospitals, reasons for non-participation, and effective recruitment strategies. We successfully recruited 41 (43%) of 95 eligible North Carolina hospitals. Leading, non-exclusive reasons for non-participation included: insufficient staff or financial resources (n = 33, 61%), lack of health system support (n = 16, 30%), and lack of support of individual decision-makers (n = 11, 20%). Successful recruitment strategies included: building and nurturing relationships, engaging team members and community partners with a diverse skill mix, identifying gatekeepers, finding mutually beneficial solutions, having a central institutional review board, sharing published pilot data, and integrating contracts and review board administrators. Although we incorporated strategies based on the best available evidence at the outset of the study, hospital recruitment required three times as much time and considerably more staff than anticipated. To reach our goal, we tailored strategies to individuals, hospitals, and health systems. Successful recruitment of a sufficient number and representative mix of hospitals requires considerable preparation, planning, and flexibility. Strategies presented here may assist future trial organizers in implementing cluster-randomized pragmatic trials. Clinicaltrials.gov, NCT02588664 . Registered on 23 October 2015.

Advances in heroin addiction treatment with traditional Chinese medicine: a systematic review of recent Chinese language journals.

PubMed

Jordan, James B; Tu, Xiang

2008-01-01

The aim of this review is to critically examine the clinical trial research on Traditional Chinese Medicine (TCM) as an intervention in treating heroin addiction in People's Republic of China. This review examines Chinese-language-only publications for the patent medicines: Shenfu Tuodu, Fukang Pian, and Shifu Sheng. Other compound medicines will be reviewed in future publications. A systematic review of the literature was conducted in Western and Chinese databases. Most trials were excluded because they did not declare randomization and had poor methodology or reporting. The majority of clinical evidence in the random controlled trials demonstrates good evidence for TCM patent medicines in heroin addiction treatment. When compared to typical Western medications, TCMs demonstrate fewer side-effects, in addition to equal measures of treatment efficacy and safety.

Do Bayesian adaptive trials offer advantages for comparative effectiveness research? Protocol for the RE-ADAPT study

PubMed Central

Luce, Bryan R; Broglio, Kristine R; Ishak, K Jack; Mullins, C Daniel; Vanness, David J; Fleurence, Rachael; Saunders, Elijah; Davis, Barry R

2013-01-01

Background Randomized clinical trials, particularly for comparative effectiveness research (CER), are frequently criticized for being overly restrictive or untimely for health-care decision making. Purpose Our prospectively designed REsearch in ADAptive methods for Pragmatic Trials (RE-ADAPT) study is a ‘proof of concept’ to stimulate investment in Bayesian adaptive designs for future CER trials. Methods We will assess whether Bayesian adaptive designs offer potential efficiencies in CER by simulating a re-execution of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study using actual data from ALLHAT. Results We prospectively define seven alternate designs consisting of various combinations of arm dropping, adaptive randomization, and early stopping and describe how these designs will be compared to the original ALLHAT design. We identify the one particular design that would have been executed, which incorporates early stopping and information-based adaptive randomization. Limitations While the simulation realistically emulates patient enrollment, interim analyses, and adaptive changes to design, it cannot incorporate key features like the involvement of data monitoring committee in making decisions about adaptive changes. Conclusion This article describes our analytic approach for RE-ADAPT. The next stage of the project is to conduct the re-execution analyses using the seven prespecified designs and the original ALLHAT data. PMID:23983160

Transanal hemorrhoidal dearterialization with mucopexy versus open hemorrhoidectomy in the treatment of hemorrhoids: a meta-analysis of randomized control trials.

PubMed

Xu, L; Chen, H; Lin, G; Ge, Q; Qi, H; He, X

2016-12-01

The aim of this study was to analyse the outcomes of transanal hemorrhoidal dearterialization with mucopexy (THDm) versus open hemorrhoidectomy (OH) in the management of hemorrhoids. Randomized controlled trials in English were found by searching PubMed, Web of science, EMBASE, and the Cochrane Library database. Trials that compared THDm with OH were identified. Data were extracted independently for each study, and a meta-analysis was performed using fixed and random effects models. Four trials, including 316 patients, met the inclusion criteria. No statistically significant differences were noted in either total complications or postoperative bleeding, incontinence, recurrent prolapse, and urinary retention rate. Operative time was significantly longer for THDm with Doppler guidance than for THDm without Doppler guidance. Patients returned to normal activities faster after THDm than after OH. No statistically significant differences between THDm and OH were noted with regard to recurrence and reoperation rates. Our meta-analysis shows that THDm and OH are equally effective and can be attempted for the management of hemorrhoids. However, for THDm with Doppler guidance, more instruments and a longer operative time are required. Future large-scale, high-quality, multicenter trials with long-term outcomes are needed to prove these results and determine whether Doppler guidance in THD is truly necessary or not.

A randomized controlled trial of the effectiveness of a pre-recruitment primer letter to increase participation in a study of colorectal screening and surveillance.

PubMed

Paul, Christine; Courtney, Ryan; Sanson-Fisher, Rob; Carey, Mariko; Hill, David; Simmons, Jody; Rose, Shiho

2014-04-01

Recruiting cancer patients is a barrier often encountered in research trials. However, very few randomized trials explore strategies to improve participation rates. The purpose of this study was to evaluate the effectiveness of a pre-recruitment primer letter to recruit persons diagnosed with colorectal cancer for a research trial. Potentially eligible participants were identified by the Victorian Cancer Registry. A total of 1,062 participants were randomized to receive either a mailed explanatory primer letter designed to encourage research participation, or no primer letter. Two weeks after the intervention, the Victorian Cancer Registry sought permission from patients to release their contact details to researchers. Those who agreed were contacted and invited to the study. Pre-recruitment encouragement was not effective at increasing recruitment, with no significant differences demonstrated between experimental groups. Overall, 40% (n = 425) consented to participate, 25% (n = 243) refused and 35% (n = 394) did not respond. While this study demonstrated disappointing outcomes, pre-recruitment letters should not be ruled out as an approach altogether. Rather, future research should explore whether other factors to increase motivation, such as intensity and timing, are feasible and acceptable for contacting cancer patients. Australian and New Zealand Clinical Trials Registry, ACTRN12609000628246.

The Quality of Reporting of Abstracts in Physical Therapy Literature is Suboptimal: Cross-Sectional, Bibliographic Analysis.

PubMed

Richter, Randy R; Sebelski, Chris A; Austin, Tricia M

2016-09-01

The quality of abstract reporting in physical therapy literature is unknown. The purpose of this study was to provide baseline data for judging the future impact of the 2010 Consolidated Standards of Reporting Trials statement specifically referencing the 2008 Consolidated Standards of Reporting Trials statement for reporting of abstracts of randomized controlled trials across and between a broad sample and a core sample of physical therapy literature. A cross-sectional, bibliographic analysis was conducted. Abstracts of randomized controlled trials from 2009 were retrieved from PubMed, PEDro, and CENTRAL. Eligibility was determined using PEDro criteria. For outcomes measures, items from the Consolidated Standards of Reporting Trials statement for abstract reporting were used for assessment. Raters were not blinded to citation details. Using a computer-generated set of random numbers, 150 abstracts from 112 journals comprised the broad sample. A total of 53 abstracts comprised the core sample. Fourteen of 20 Consolidated Standards of Reporting Trials items for both samples were reported in less than 50% of the abstracts. Significantly more abstracts in the core sample reported (% difference core - broad; 95% confidence interval) title (28.4%; 12.9%-41.2%), blinding (15.2%; 1.6%-29.8%), setting (47.6%; 32.4%-59.4%), and confidence intervals (13.1%; 5.0%-25.1%). These findings provide baseline data for determining if continuing efforts to improve abstract reporting are heeded.

Design and challenges for a randomized, multi-site clinical trial comparing the use of service dogs and emotional support dogs in Veterans with post-traumatic stress disorder (PTSD).

PubMed

Saunders, Gabrielle H; Biswas, Kousick; Serpi, Tracey; McGovern, Stephanie; Groer, Shirley; Stock, Eileen M; Magruder, Kathryn M; Storzbach, Daniel; Skelton, Kelly; Abrams, Thad; McCranie, Mark; Richerson, Joan; Dorn, Patricia A; Huang, Grant D; Fallon, Michael T

2017-11-01

Posttraumatic stress disorder (PTSD) is a leading cause of impairments in quality of life and functioning among Veterans. Service dogs have been promoted as an effective adjunctive intervention for PTSD, however published research is limited and design and implementation flaws in published studies limit validated conclusions. This paper describes the rationale for the study design, a detailed methodological description, and implementation challenges of a multisite randomized clinical trial examining the impact of service dogs on the on the functioning and quality of life of Veterans with PTSD. Trial design considerations prioritized participant and intervention (dog) safety, selection of an intervention comparison group that would optimize enrollment in all treatment arms, pragmatic methods to ensure healthy well-trained dogs, and the selection of outcomes for achieving scientific and clinical validity in a Veteran PTSD population. Since there is no blueprint for conducting a randomized clinical trial examining the impact of dogs on PTSD of this size and scope, it is our primary intent that the successful completion of this trial will set a benchmark for future trial design and scientific rigor, as well as guiding researchers aiming to better understand the role that dogs can have in the management of Veterans experiencing mental health conditions such as PTSD. Published by Elsevier Inc.

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.

Meta-analysis of randomized clinical trials in the era of individual patient data sharing.

PubMed

Kawahara, Takuya; Fukuda, Musashi; Oba, Koji; Sakamoto, Junichi; Buyse, Marc

2018-06-01

Individual patient data (IPD) meta-analysis is considered to be a gold standard when the results of several randomized trials are combined. Recent initiatives on sharing IPD from clinical trials offer unprecedented opportunities for using such data in IPD meta-analyses. First, we discuss the evidence generated and the benefits obtained by a long-established prospective IPD meta-analysis in early breast cancer. Next, we discuss a data-sharing system that has been adopted by several pharmaceutical sponsors. We review a number of retrospective IPD meta-analyses that have already been proposed using this data-sharing system. Finally, we discuss the role of data sharing in IPD meta-analysis in the future. Treatment effects can be more reliably estimated in both types of IPD meta-analyses than with summary statistics extracted from published papers. Specifically, with rich covariate information available on each patient, prognostic and predictive factors can be identified or confirmed. Also, when several endpoints are available, surrogate endpoints can be assessed statistically. Although there are difficulties in conducting, analyzing, and interpreting retrospective IPD meta-analysis utilizing the currently available data-sharing systems, data sharing will play an important role in IPD meta-analysis in the future.

Neighborhood effects in a behavioral randomized controlled trial.

PubMed

Pruitt, Sandi L; Leonard, Tammy; Murdoch, James; Hughes, Amy; McQueen, Amy; Gupta, Samir

2014-11-01

Randomized controlled trials (RCTs) of interventions intended to modify health behaviors may be influenced by neighborhood effects which can impede unbiased estimation of intervention effects. Examining a RCT designed to increase colorectal cancer (CRC) screening (N=5628), we found statistically significant neighborhood effects: average CRC test use among neighboring study participants was significantly and positively associated with individual patient's CRC test use. This potentially important spatially-varying covariate has not previously been considered in a RCT. Our results suggest that future RCTs of health behavior interventions should assess potential social interactions between participants, which may cause intervention arm contamination and may bias effect size estimation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.

PubMed

Kreimer, Aimée R; Herrero, Rolando; Sampson, Joshua N; Porras, Carolina; Lowy, Douglas R; Schiller, John T; Schiffman, Mark; Rodriguez, Ana Cecilia; Chanock, Stephen; Jimenez, Silvia; Schussler, John; Gail, Mitchell H; Safaeian, Mahboobeh; Kemp, Troy J; Cortes, Bernal; Pinto, Ligia A; Hildesheim, Allan; Gonzalez, Paula

2018-01-20

The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose. Published by Elsevier Ltd.

Prevention of nosocomial infections in critically ill patients with lactoferrin (PREVAIL study): study protocol for a randomized controlled trial.

PubMed

Muscedere, John; Maslove, David; Boyd, John Gordon; O'Callaghan, Nicole; Lamontagne, Francois; Reynolds, Steven; Albert, Martin; Hall, Rick; McGolrick, Danielle; Jiang, Xuran; Day, Andrew G

2016-09-29

Nosocomial infections remain an important source of morbidity, mortality, and increased health care costs in hospitalized patients. This is particularly problematic in intensive care units (ICUs) because of increased patient vulnerability due to the underlying severity of illness and increased susceptibility from utilization of invasive therapeutic and monitoring devices. Lactoferrin (LF) and the products of its breakdown have multiple biological effects, which make its utilization of interest for the prevention of nosocomial infections in the critically ill. This is a phase II randomized, multicenter, double-blinded trial to determine the effect of LF on antibiotic-free days in mechanically ventilated, critically ill, adult patients in the ICU. Eligible, consenting patients will be randomized to receive either LF or placebo. The treating clinician will remain blinded to allocation during the study; blinding will be maintained by using opaque syringes and containers. The primary outcome will be antibiotic-free days, defined as the number of days alive and free of antibiotics 28 days after randomization. Secondary outcomes will include: antibiotic utilization, adjudicated diagnosis of nosocomial infection (longer than 72 h of admission to ICU), hospital and ICU length of stay, change in organ function after randomization, hospital and 90-day mortality, incidence of tracheal colonization, changes in gastrointestinal permeability, and immune function. Outcomes to inform the conduct of a larger definitive trial will also be evaluated, including feasibility as determined by recruitment rates and protocol adherence. The results from this study are expected to provide insight into a potential novel therapeutic use for LF in critically ill adult patients. Further, analysis of study outcomes will inform a future, large-scale phase III randomized controlled trial powered on clinically important outcomes related to the use of LF. The trial was registered at www.ClinicalTrials.gov on 18 November 2013. NCT01996579 .

Glutamine Randomized Studies in Early Life: The Unsolved Riddle of Experimental and Clinical Studies

PubMed Central

Briassouli, Efrossini; Briassoulis, George

2012-01-01

Glutamine may have benefits during immaturity or critical illness in early life but its effects on outcome end hardpoints are controversial. Our aim was to review randomized studies on glutamine supplementation in pups, infants, and children examining whether glutamine affects outcome. Experimental work has proposed various mechanisms of glutamine action but none of the randomized studies in early life showed any effect on mortality and only a few showed some effect on inflammatory response, organ function, and a trend for infection control. Although apparently safe in animal models (pups), premature infants, and critically ill children, glutamine supplementation does not reduce mortality or late onset sepsis, and its routine use cannot be recommended in these sensitive populations. Large prospectively stratified trials are needed to better define the crucial interrelations of “glutamine-heat shock proteins-stress response” in critical illness and to identify the specific subgroups of premature neonates and critically ill infants or children who may have a greater need for glutamine and who may eventually benefit from its supplementation. The methodological problems noted in the reviewed randomized experimental and clinical trials should be seriously considered in any future well-designed large blinded randomized controlled trial involving glutamine supplementation in critical illness. PMID:23019424

Feasibility of Extracting Key Elements from ClinicalTrials.gov to Support Clinicians' Patient Care Decisions.

PubMed

Kim, Heejun; Bian, Jiantao; Mostafa, Javed; Jonnalagadda, Siddhartha; Del Fiol, Guilherme

2016-01-01

Motivation: Clinicians need up-to-date evidence from high quality clinical trials to support clinical decisions. However, applying evidence from the primary literature requires significant effort. Objective: To examine the feasibility of automatically extracting key clinical trial information from ClinicalTrials.gov. Methods: We assessed the coverage of ClinicalTrials.gov for high quality clinical studies that are indexed in PubMed. Using 140 random ClinicalTrials.gov records, we developed and tested rules for the automatic extraction of key information. Results: The rate of high quality clinical trial registration in ClinicalTrials.gov increased from 0.2% in 2005 to 17% in 2015. Trials reporting results increased from 3% in 2005 to 19% in 2015. The accuracy of the automatic extraction algorithm for 10 trial attributes was 90% on average. Future research is needed to improve the algorithm accuracy and to design information displays to optimally present trial information to clinicians.

Aromatherapy for treatment of hypertension: a systematic review.

PubMed

Hur, Myung-Haeng; Lee, Myeong Soo; Kim, Chan; Ernst, Edzard

2012-02-01

The objective of this review is to systematically review the evidence for the effectiveness of aromatherapy in the treatment of high blood pressure. Twelve databases were searched from their inception through December 2009. Controlled trials testing aromatherapy in patients with hypertension of any origin that assessed blood pressure were considered. The selection of studies, data extraction and validations were performed independently by two reviewers. One randomized clinical trial (RCT) and four non-randomized controlled clinical trials (CCTs) met our inclusion criteria. The one RCT included tested the effects of aromatherapy as compared with placebo and showed significant reduction of systolic blood pressure and diastolic blood pressure. All of the four CCTs showed favourable effects of aromatherapy. However, all of the CCTs also had a high risk of bias. The existing trial evidence does not show convincingly that aromatherapy is effective for hypertension. Future studies should be of high quality with a particular emphasis on designing an adequate control intervention. © 2010 Blackwell Publishing Ltd.

Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial.

PubMed

Mackay, Alan; Burford, Anna; Molinari, Valeria; Jones, David T W; Izquierdo, Elisa; Brouwer-Visser, Jurriaan; Giangaspero, Felice; Haberler, Christine; Pietsch, Torsten; Jacques, Thomas S; Figarella-Branger, Dominique; Rodriguez, Daniel; Morgan, Paul S; Raman, Pichai; Waanders, Angela J; Resnick, Adam C; Massimino, Maura; Garrè, Maria Luisa; Smith, Helen; Capper, David; Pfister, Stefan M; Würdinger, Thomas; Tam, Rachel; Garcia, Josep; Thakur, Meghna Das; Vassal, Gilles; Grill, Jacques; Jaspan, Tim; Varlet, Pascale; Jones, Chris

2018-05-14

The HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8 + tumor-infiltrating lymphocytes, and longer survival with the addition of BEV. Histone H3 subgroups (hemispheric G34R/V and midline K27M) had a worse outcome and were immune cold. Future clinical trials will need to take into account the diversity represented by the term "HGG" in the pediatric population. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

'Help for Hay Fever', a goal-focused intervention for people with intermittent allergic rhinitis, delivered in Scottish community pharmacies: study protocol for a pilot cluster randomized controlled trial.

PubMed

Porteous, Terry; Wyke, Sally; Smith, Sarah; Bond, Christine; Francis, Jill; Lee, Amanda J; Lowrie, Richard; Scotland, Graham; Sheikh, Aziz; Thomas, Mike; Smith, Lorraine

2013-07-15

Despite the availability of evidence-based guidelines for managing allergic rhinitis in primary care, management of the condition in the United Kingdom (UK) remains sub-optimal. Its high prevalence and negative effects on quality of life, school performance, productivity and co-morbid respiratory conditions (in particular, asthma), and high health and societal costs, make this a priority for developing novel models of care. Recent Australian research demonstrated the potential of a community pharmacy-based 'goal-focused' intervention to help people with intermittent allergic rhinitis to self-manage their condition better, reduce symptom severity and improve quality of life. In this pilot study we will assess the transferability of the goal-focused intervention to a UK context, the suitability of the intervention materials, procedures and outcome measures and collect data to inform a future definitive UK randomized controlled trial (RCT). A pilot cluster RCT with associated preliminary economic analysis and embedded qualitative evaluation. The pilot trial will take place in two Scottish Health Board areas: Grampian and Greater Glasgow & Clyde. Twelve community pharmacies will be randomly assigned to intervention or usual care group. Each will recruit 12 customers seeking advice or treatment for intermittent allergic rhinitis. Pharmacy staff in intervention pharmacies will support recruited customers in developing strategies for setting and achieving goals that aim to avoid/minimize triggers for, and eliminate/minimize symptoms of allergic rhinitis. Customers recruited in non-intervention pharmacies will receive usual care. The co-primary outcome measures, selected to inform a sample size calculation for a future RCT, are: community pharmacy and customer recruitment and completion rates; and effect size of change in the validated mini-Rhinoconjunctivitis Quality of Life Questionnaire between baseline, one-week and six-weeks post-intervention. Secondary outcome measures relate to changes in symptom severity, productivity, medication adherence and self-efficacy. Quantitative data about accrual, retention and economic measures, and qualitative data about participants' experiences during the trial will be collected to inform the future RCT. This work will lay the foundations for a definitive RCT of a community pharmacy-based 'goal-focused' self-management intervention for people with intermittent allergic rhinitis. Results of the pilot trial are expected to be available in April 2013. Current Controlled Trials ISRCTN43606442.

A response adaptive randomization platform trial for efficient evaluation of Ebola virus treatments: A model for pandemic response.

PubMed

Berry, Scott M; Petzold, Elizabeth A; Dull, Peter; Thielman, Nathan M; Cunningham, Coleen K; Corey, G Ralph; McClain, Micah T; Hoover, David L; Russell, James; Griffiss, J McLeod; Woods, Christopher W

2016-02-01

The outbreak of Ebola virus disease in West Africa is the largest ever recorded. Numerous treatment alternatives for Ebola have been considered, including widely available repurposed drugs, but initiation of enrollment into clinical trials has been limited. The proposed trial is an adaptive platform design. Multiple agents and combinations will be investigated simultaneously. Additionally, new agents may enter the trial as they become available, and failing agents may be removed. In order to accommodate the many possible agents and combinations, a critical feature of this design is the use of response adaptive randomization to assign treatment regimens. As the trial progresses, the randomization ratio evolves to favor the arms that are performing better, making the design also suitable for all-cause pandemic preparedness planning. The study was approved by US and Sierra Leone ethics committees, and reviewed by the US Food and Drug Administration. Additionally, data management, drug supply lines, and local sites were prepared. However, in response to the declining epidemic seen in February 2015, the trial was not initiated. Sierra Leone remains ready to rapidly activate the protocol as an emergency response trial in the event of a resurgence of Ebola. (ClinicalTrials.gov Identifier: NCT02380625.) In summary, we have designed a single controlled trial capable of efficiently identifying highly effective or failing regimens among a rapidly evolving list of proposed therapeutic alternatives for Ebola virus disease and to treat the patients within the trial effectively based on accruing data. Provision of these regimens, if found safe and effective, would have a major impact on future epidemics by providing effective treatment options. © The Author(s) 2016.

A Systematic Review of Randomized Controlled Trials Examining Psychological Interventions for Needle-related Procedural Pain and Distress in Children and Adolescents: An Abbreviated Cochrane Review*

PubMed Central

Chambers, Christine T.; McGrath, Patrick J.; Kisely, Stephen

2008-01-01

Objective To report the results of a systematic review of randomized controlled trials (RCTs) of psychological interventions for children and adolescents undergoing needle-related procedures. Methods A variety of cognitive-behavioral psychological interventions for managing procedural pain and distress in children and adolescents between 2 and 19 years of age were examined. Outcome measures included pain and distress as assessed by self-report, observer report, behavioral/observational measures, and physiological correlates. Results Twenty-eight trials met the criteria for inclusion in the review and provided the data necessary for pooling the results. Together, the trials included 1,039 participants in treatment conditions and 951 in control conditions. The largest effect sizes for treatment improvement over control conditions were found for distraction, combined cognitive-behavioral interventions, and hypnosis, with promising but limited evidence for several other psychological interventions. Conclusions Recommendations for conducting future RCTs are provided, and particular attention to the quality of trial design and reporting is highlighted. PMID:18387963

Presence of music while eating: Effects on energy intake, eating rate and appetite sensations.

PubMed

Mamalaki, Eirini; Zachari, Konstantina; Karfopoulou, Eleni; Zervas, Efthimios; Yannakoulia, Mary

2017-01-01

The role of music in energy and dietary intake of humans is poorly understood. The purpose of the present laboratory study was to examine the effect of background music, its presence and its intensity, on energy intake, eating rate and appetite feelings. The study had a randomized crossover design. Twenty-six normal weight and overweight/obese men participated in random order in three trials: the control trial (no music was playing), the 60dB and the 90dB music trials, while an ad libitum lunch was consumed. Visual analogue scales for hunger, fullness/satiety, as well as desire to eat were administered to the participants. Energy intake at the ad libitum lunch did not differ between trials, even when covariates were taken into account. There were no statistically significant differences between trials on meal characteristics, such as meal duration, number of servings, number of bites eaten and on appetite indices. Future studies are needed to replicate these results and investigate the effect of different types of music and/or sound. Copyright © 2016 Elsevier Inc. All rights reserved.

Intensive gestational glycemic management and childhood obesity: a systematic review and meta-analysis.

PubMed

Guillemette, L; Durksen, A; Rabbani, R; Zarychanski, R; Abou-Setta, A M; Duhamel, T A; McGavock, J M; Wicklow, B

2017-07-01

Hyperglycemia in pregnancy is associated with increased risk of offspring childhood obesity. Treatment reduces macrosomia; however, it is unclear if this effect translates into a reduced risk of childhood obesity. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy and safety of intensive glycemic management in pregnancy in preventing childhood obesity. We searched MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov up to February 2016 and conference abstracts from 2010 to 2015. Two reviewers independently identified randomized controlled trials evaluating intensive glycemic management interventions for hyperglycemia in pregnancy and included four of the 383 citations initially identified. Two reviewers independently extracted study data and evaluated internal validity of the studies using the Cochrane Collaboration's Risk of Bias tool. Data were pooled using random-effects models. Statistical heterogeneity was quantified using the I 2 test. The primary outcome was age- and sex-adjusted childhood obesity. Secondary outcomes included childhood weight and waist circumference and maternal hypoglycemia during the trial (safety outcome). The four eligible trials (n=767 children) similarly used lifestyle and insulin to manage gestational hyperglycemia, but only two measured offspring obesity and waist circumference and could be pooled for these outcomes. We found no association between intensive gestational glucose management and childhood obesity at 7-10 years of age (relative risk 0.89, 95% confidence interval (CI) 0.65 to 1.22; two trials; n=568 children). Waist circumference also did not differ between treatment and control arms (mean difference, -2.68 cm; 95% CI, -8.17 to 2.81 cm; two trials; n=568 children). Intensive gestational glycemic management is not associated with reduced childhood obesity in offspring, but randomized data is scarce. Long-term follow-up of trials should be prioritized and comprehensive measures of childhood metabolic risk should be considered as outcomes in future trials.

'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).

Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial

PubMed Central

Wali, Ramesh K.; Bianchi, Laura; Kupfer, Sonia; De La Cruz, Mart; Jovanovic, Borko; Weber, Christopher; Goldberg, Michael J.; Rodriguez, L. M.; Bergan, Raymond; Rubin, David; Tull, Mary Beth; Richmond, Ellen; Parker, Beth; Khan, Seema

2018-01-01

Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data may provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention. Trial registration: ClinicalTrials.gov NCT00828984 PMID:29617381

Methods to Limit Attrition in Longitudinal Comparative Effectiveness Trials: Lessons from the Lithium Use for Bipolar Disorder (LiTMUS) Study

PubMed Central

Sylvia, Louisa G.; Reilly-Harrington, Noreen A.; Leon, Andrew C.; Kansky, Christine I.; Ketter, Terence A.; Calabrese, Joseph R.; Thase, Michael E.; Bowden, Charles L.; Friedman, Edward S.; Ostacher, Michael J.; Iosifescu, Dan V.; Severe, Joanne; Nierenberg, Andrew A.

2013-01-01

Background High attrition rates which occur frequently in longitudinal clinical trials of interventions for bipolar disorder limit the interpretation of results. Purpose The aim of this article is to present design approaches that limited attrition in the Lithium Use for Bipolar Disorder (LiTMUS) Study. Methods LiTMUS was a 6-month randomized, longitudinal multi-site comparative effectiveness trial that examined bipolar participants who were at least mildly ill. Participants were randomized to either low to moderate doses of lithium or no lithium, in addition to other treatments needed for mood stabilization administered in a guideline-informed, empirically supported, and personalized fashion (N=283). Results Components of the study design that may have contributed to the low attrition rate of the study included use of: (1) an intent-to-treat design; (2) a randomized adjunctive single-blind design; (3) participant reimbursement; (4) intent-to-attend the next study visit (includes a discussion of attendance obstacles when intention is low); (5) quality care with limited participant burden; and (6) target windows for study visits. Limitations Site differences and the effectiveness and tolerability data have not been analyzed yet. Conclusions These components of the LiTMUS study design may have reduced the probability of attrition which would inform the design of future randomized clinical effectiveness trials. PMID:22076437

Training balance with opto-kinetic stimuli in the home: a randomized controlled feasibility study in people with pure cerebellar disease.

PubMed

Bunn, Lisa M; Marsden, Jonathan F; Giunti, Paola; Day, Brian L

2015-02-01

To investigate the feasibility of a randomized controlled trial of a home-based balance intervention for people with cerebellar ataxia. A randomized controlled trial design. Intervention and assessment took place in the home environment. A total of 12 people with spinocerebellar ataxia type 6 were randomized into a therapy or control group. Both groups received identical assessments at baseline, four and eight weeks. Therapy group participants undertook balance exercises in front of optokinetic stimuli during weeks 4-8, while control group participants received no intervention. Test-retest reliability was analysed from outcome measures collected twice at baseline and four weeks later. Feasibility issues were evaluated using daily diaries and end trial exit interviews. The home-based training intervention with opto-kinetic stimuli was feasible for people with pure ataxia, with one drop-out. Test-retest reliability is strong (intraclass correlation coefficient >0.7) for selected outcome measures evaluating balance at impairment and activity levels. Some measures reveal trends towards improvement for those in the therapy group. Sample size estimations indicate that Bal-SARA scores could detect a clinically significant change of 0.8 points in this functional balance score if 80 people per group were analysed in future trials. Home-based targeted training of functional balance for people with pure cerebellar ataxia is feasible and the outcome measures employed are reliable. © The Author(s) 2014.

Sleep Promotion Program for Improving Sleep Behaviors in Adolescents: A Randomized Controlled Pilot Study

PubMed Central

John, Bindu; Bellipady, Sumanth Shetty; Bhat, Shrinivasa Undaru

2016-01-01

Aims. The purpose of this pilot trial was to determine the efficacy of sleep promotion program to adapt it for the use of adolescents studying in various schools of Mangalore, India, and evaluate the feasibility issues before conducting a randomized controlled trial in a larger sample of adolescents. Methods. A randomized controlled trial design with stratified random sampling method was used. Fifty-eight adolescents were selected (mean age: 14.02 ± 2.15 years; intervention group, n = 34; control group, n = 24). Self-report questionnaires, including sociodemographic questionnaire with some additional questions on sleep and activities, Sleep Hygiene Index, Pittsburgh Sleep Quality Index, The Cleveland Adolescent Sleepiness Questionnaire, and PedsQL™ Present Functioning Visual Analogue Scale, were used. Results. Insufficient weekday-weekend sleep duration with increasing age of adolescents was observed. The program revealed a significant effect in the experimental group over the control group in overall sleep quality, sleep onset latency, sleep duration, daytime sleepiness, and emotional and overall distress. No significant effect was observed in sleep hygiene and other sleep parameters. All target variables showed significant correlations with each other. Conclusion. The intervention holds a promise for improving the sleep behaviors in healthy adolescents. However, the effect of the sleep promotion program treatment has yet to be proven through a future research. This trial is registered with ISRCTN13083118. PMID:27088040

The effects of Bifidobacterium animalis ssp. lactis B94 on gastrointestinal wellness in adults with Prader-Willi syndrome: study protocol for a randomized controlled trial.

PubMed

Alyousif, Zainab; Miller, Jennifer L; Sandoval, Mariana Y; MacPherson, Chad W; Nagulesapillai, Varuni; Dahl, Wendy J

2018-04-27

Constipation is a frequent problem in adults with Prader-Willi syndrome. Certain probiotics have been shown to improve transit and gastrointestinal symptoms of adults with functional constipation. The aim of this study is to determine the effect of daily consumption of Bifidobacterium animalis ssp. lactis B94 (B. lactis B94) on stool frequency, stool form, and gastrointestinal symptoms in adults with Prader-Willi syndrome. Adults with Prader-Willi syndrome (18-75 years old, n = 36) will be recruited and enrolled in a 20-week, randomized, double-blind, placebo-controlled, crossover study. Study subjects will be randomized to B. lactis B94 or placebo each for a 4-week period, preceded by a 4-week baseline and followed by 4-week washouts. Subjects will complete daily records of stool frequency and stool form (a proxy of transit time). Dietary intake data also will be collected. Stools, one in each period, will be collected for exploratory microbiota analyses. To our knowledge, this is the first randomized controlled trial evaluating the effectiveness of B. lactis in adults with Prader-Willi syndrome. The results of this study will provide evidence of efficacy for future clinical trials in patient populations with constipation. ClinicalTrials.gov ( NCT03277157 ). Registered on 08 September 2017.

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial.

PubMed

Bucur, Roxana C; Reid, Lauren S; Hamilton, Celeste J; Cummings, Steven R; Jamal, Sophie A

2013-09-08

Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. This will be an open-label randomized, controlled trial conducted at Women's College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the 'multiple comparisons with the best' approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies. Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures. ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742.

A systematic review of randomized trials of mind-body interventions for PTSD.

PubMed

Niles, Barbara L; Mori, DeAnna L; Polizzi, Craig; Pless Kaiser, Anica; Weinstein, Elizabeth S; Gershkovich, Marina; Wang, Chenchen

2018-05-10

To systematically review outcomes from randomized controlled trials (RCTs) of mind-body treatments for PTSD. Inclusion criteria based on guidelines for assessing risk of bias were used to evaluate articles identified through electronic literature searches. Twenty-two RCTs met inclusion standards. In most of the nine mindfulness and six yoga studies, significant between-group effects were found indicating moderate to large effect size advantages for these treatments. In all seven relaxation RCT's, relaxation was used as a control condition and five studies reported significant between-group differences on relevant PTSD outcomes in favor of the target treatments. However, there were large within-group symptom improvements in the relaxation condition for the majority of studies. Although many studies are limited by methodologic weaknesses, recent studies have increased rigor and, in aggregate, the results for mindfulness, yoga, and relaxation are promising. Recommendations for design of future mind-body trials are offered. © 2018 Wiley Periodicals, Inc.

Statistical lessons learned for designing cluster randomized pragmatic clinical trials from the NIH Health Care Systems Collaboratory Biostatistics and Design Core.

PubMed

Cook, Andrea J; Delong, Elizabeth; Murray, David M; Vollmer, William M; Heagerty, Patrick J

2016-10-01

Pragmatic clinical trials embedded within health care systems provide an important opportunity to evaluate new interventions and treatments. Networks have recently been developed to support practical and efficient studies. Pragmatic trials will lead to improvements in how we deliver health care and promise to more rapidly translate research findings into practice. The National Institutes of Health (NIH) Health Care Systems Collaboratory was formed to conduct pragmatic clinical trials and to cultivate collaboration across research areas and disciplines to develop best practices for future studies. Through a two-stage grant process including a pilot phase (UH2) and a main trial phase (UH3), investigators across the Collaboratory had the opportunity to work together to improve all aspects of these trials before they were launched and to address new issues that arose during implementation. Seven Cores were created to address the various considerations, including Electronic Health Records; Phenotypes, Data Standards, and Data Quality; Biostatistics and Design Core; Patient-Reported Outcomes; Health Care Systems Interactions; Regulatory/Ethics; and Stakeholder Engagement. The goal of this article is to summarize the Biostatistics and Design Core's lessons learned during the initial pilot phase with seven pragmatic clinical trials conducted between 2012 and 2014. Methodological issues arose from the five cluster-randomized trials, also called group-randomized trials, including consideration of crossover and stepped wedge designs. We outlined general themes and challenges and proposed solutions from the pilot phase including topics such as study design, unit of randomization, sample size, and statistical analysis. Our findings are applicable to other pragmatic clinical trials conducted within health care systems. Pragmatic clinical trials using the UH2/UH3 funding mechanism provide an opportunity to ensure that all relevant design issues have been fully considered in order to reliably and efficiently evaluate new interventions and treatments. The integrity and generalizability of trial results can only be ensured if rigorous designs and appropriate analysis choices are an essential part of their research protocols. © The Author(s) 2016.

Review of methodological challenges in comparing the effectiveness of neoadjuvant chemotherapy versus primary debulking surgery for advanced ovarian cancer in the United States.

PubMed

Cole, Ashley L; Austin, Anna E; Hickson, Ryan P; Dixon, Matthew S; Barber, Emma L

2018-05-11

Randomized trials outside the U.S. have found non-inferior survival for neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) for advanced ovarian cancer (AOC). However, these trials reported lower overall survival and lower rates of optimal debulking than U.S. studies, leading to questions about generalizability to U.S. practice, where aggressive debulking is more common. Consequently, comparative effectiveness in the U.S. remains controversial. We reviewed U.S. comparative effectiveness studies of NACT versus PDS for AOC. Here we describe methodological challenges, compare results to trials outside the U.S., and make suggestions for future research. We identified U.S. studies published in 2010 or later that evaluated the comparative effectiveness of NACT versus PDS on survival in AOC through a PubMed search. Two independent reviewers abstracted data from eligible articles. Nine of 230 articles were eligible for review. Methodological challenges included unmeasured confounders, heterogeneous treatment effects, treatment variations over time, and inconsistent measurement of treatment and survival. Whereas some limitations were unavoidable, several limitations noted across studies were avoidable, including conditioning on mediating factors and immortal time introduced by measuring survival beginning from diagnosis. Without trials in the U.S., non-randomized studies are an important source of evidence for the ideal treatment for AOC. However, several methodological challenges exist when assessing the comparative effectiveness of NACT versus PDS in a non-randomized setting. Future observational studies must ensure that treatment is consistent throughout the study period and that treatment groups are comparable. Rapidly-evolving oncology data networks may allow for identification of treatment intent and other important confounders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Intraclass correlation estimates for cancer screening outcomes: estimates and applications in the design of group-randomized cancer screening studies.

PubMed

Hade, Erinn M; Murray, David M; Pennell, Michael L; Rhoda, Dale; Paskett, Electra D; Champion, Victoria L; Crabtree, Benjamin F; Dietrich, Allen; Dignan, Mark B; Farmer, Melissa; Fenton, Joshua J; Flocke, Susan; Hiatt, Robert A; Hudson, Shawna V; Mitchell, Michael; Monahan, Patrick; Shariff-Marco, Salma; Slone, Stacey L; Stange, Kurt; Stewart, Susan L; Strickland, Pamela A Ohman

2010-01-01

Screening has become one of our best tools for early detection and prevention of cancer. The group-randomized trial is the most rigorous experimental design for evaluating multilevel interventions. However, identifying the proper sample size for a group-randomized trial requires reliable estimates of intraclass correlation (ICC) for screening outcomes, which are not available to researchers. We present crude and adjusted ICC estimates for cancer screening outcomes for various levels of aggregation (physician, clinic, and county) and provide an example of how these ICC estimates may be used in the design of a future trial. Investigators working in the area of cancer screening were contacted and asked to provide crude and adjusted ICC estimates using the analysis of variance method estimator. Of the 29 investigators identified, estimates were obtained from 10 investigators who had relevant data. ICC estimates were calculated from 13 different studies, with more than half of the studies collecting information on colorectal screening. In the majority of cases, ICC estimates could be adjusted for age, education, and other demographic characteristics, leading to a reduction in the ICC. ICC estimates varied considerably by cancer site and level of aggregation of the groups. Previously, only two articles had published ICCs for cancer screening outcomes. We have complied more than 130 crude and adjusted ICC estimates covering breast, cervical, colon, and prostate screening and have detailed them by level of aggregation, screening measure, and study characteristics. We have also demonstrated their use in planning a future trial and the need for the evaluation of the proposed interval estimator for binary outcomes under conditions typically seen in GRTs.

Acceptability of Home-Assessment Post Medical Abortion and Medical Abortion in a Low-Resource Setting in Rajasthan, India. Secondary Outcome Analysis of a Non-Inferiority Randomized Controlled Trial

PubMed Central

Paul, Mandira; Iyengar, Kirti; Essén, Birgitta; Gemzell-Danielsson, Kristina; Iyengar, Sharad D.; Bring, Johan; Soni, Sunita; Klingberg-Allvin, Marie

2015-01-01

Background Studies evaluating acceptability of simplified follow-up after medical abortion have focused on high-resource or urban settings where telephones, road connections, and modes of transport are available and where women have formal education. Objective To investigate women’s acceptability of home-assessment of abortion and whether acceptability of medical abortion differs by in-clinic or home-assessment of abortion outcome in a low-resource setting in India. Design Secondary outcome of a randomised, controlled, non-inferiority trial. Setting Outpatient primary health care clinics in rural and urban Rajasthan, India. Population Women were eligible if they sought abortion with a gestation up to 9 weeks, lived within defined study area and agreed to follow-up. Women were ineligible if they had known contraindications to medical abortion, haemoglobin < 85mg/l and were below 18 years. Methods Abortion outcome assessment through routine clinic follow-up by a doctor was compared with home-assessment using a low-sensitivity pregnancy test and a pictorial instruction sheet. A computerized random number generator generated the randomisation sequence (1:1) in blocks of six. Research assistants randomly allocated eligible women who opted for medical abortion (mifepristone and misoprostol), using opaque sealed envelopes. Blinding during outcome assessment was not possible. Main Outcome Measures Women’s acceptability of home-assessment was measured as future preference of follow-up. Overall satisfaction, expectations, and comparison with previous abortion experiences were compared between study groups. Results 731 women were randomized to the clinic follow-up group (n = 353) or home-assessment group (n = 378). 623 (85%) women were successfully followed up, of those 597 (96%) were satisfied and 592 (95%) found the abortion better or as expected, with no difference between study groups. The majority, 355 (57%) women, preferred home-assessment in the event of a future abortion. Significantly more women, 284 (82%), in the home-assessment group preferred home-assessment in the future, as compared with 188 (70%) of women in the clinic follow-up group, who preferred clinic follow-up in the future (p < 0.001). Conclusion Home-assessment is highly acceptable among women in low-resource, and rural, settings. The choice to follow-up an early medical abortion according to women’s preference should be offered to foster women’s reproductive autonomy. Trial Registration ClinicalTrials.gov NCT01827995 PMID:26327217

Impact of the National Institutes of Health Focal Segmental Glomerulosclerosis (NIH FSGS) clinical trial on the treatment of steroid-resistant FSGS.

PubMed

Canetta, Pietro A; Radhakrishnan, Jai

2013-03-01

Idiopathic focal segmental glomerulosclerosis (FSGS) is among the most common, morbid and treatment-resistant conditions faced by nephrologists. While glucocorticoids have traditionally been the mainstay of initial treatment, they induce remission in only a minority of patients. A variety of other immunosuppressants have been utilized against steroid-resistant FSGS, but few have been rigorously examined in well-controlled trials. Recently, the results were published from a National Institutes of Health (NIH)-sponsored multicenter randomized trial comparing cyclosporine (CSA) with a combination of mycophenolate mofetil (MMF) and pulse dexamethasone (DEX) for the treatment of steroid-resistant FSGS. No difference in treatment effectiveness was shown between the two groups, and adverse effects were comparable. This was the largest randomized trial ever undertaken in FSGS, but it was unfortunately underpowered to show clinically relevant differences in response rates. This shortcoming, along with particularities of the study population and outcome measures, makes it challenging to draw definitive conclusions from the trial results. Despite these limitations, the trial does provide valuable insights into treatment strategies for FSGS and offers important lessons for planning future research.

A critical review of clinical trials in systemic lupus erythematosus

PubMed Central

Mahieu, Mary A.; Strand, Vibeke; Simon, Lee S.; Lipsky, Peter E.; Ramsey-Goldman, Rosalind

2016-01-01

One challenge in caring for patients with systemic lupus erythematosus (SLE) is a paucity of approved therapeutics for treatment of the diverse disease manifestations. In the last 60 years, only one drug, belimumab, has been approved for SLE treatment. Critical evaluation of investigator initiated and pharma-sponsored randomized controlled trials (RCTs) highlights barriers to successful drug development in SLE, including disease heterogeneity, inadequate trial size or duration, insufficient dose finding before initiation of large trials, handling of background medications, and choice of primary endpoint. Herein we examine lessons learned from landmark SLE RCTs and subsequent advances in trial design, as well as discuss efforts to address limitations in current SLE outcome measures that will improve detection of true therapeutic responses in future RCTs. PMID:27497257

Emerging innovations in clinical trial design.

PubMed

Berry, D A

2016-01-01

Designs of clinical trials have changed little since the advent of randomization in the 1940s. Modern innovations in designs are being driven by the increasing recognition in clinical research that diseases are heterogeneous and patients who apparently have the same disease require different therapies. This article describes some innovations in clinical trial design across therapeutic areas but with a focus on oncology. No one knows what the future holds for clinical trial design but the status quo of large trials that pretend the patient population is homogeneous is not sustainable, either economically or scientifically/medically. No one knows what the eventual business model and regulatory model will be, but they will be very different from today's. © 2015 American Society for Clinical Pharmacology and Therapeutics.

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.

A randomized clinical trial aimed at preventing poor psychosocial and glycemic outcomes in teens with type 1 diabetes (T1D)

PubMed Central

Weissberg-Benchell, Jill; Rausch, Joseph; Iturralde, Esti; Jedraszko, Aneta; Hood, Korey

2016-01-01

Adolescents with type 1 diabetes have an increased risk for a variety of emotional and behavioral challenges as well as negative diabetes outcomes. This study was designed to compare the effectiveness of a depression-prevention, resilience promotion program with an advanced diabetes education program. Each program consisted of 9 group-based sessions. There were 264 adolescents enrolled in this multi-site randomized clinical trial. The primary outcomes were depressive symptoms and glycemic control; secondary outcomes included resilience skills, diabetes management and adherence, and diabetes-specific distress. The goal of the present paper is to describe the study design, the intervention, and the baseline characteristics of the sample. Preliminary data suggests that enrollment, randomization and retention were successful. Longitudinal follow-up and examination of mechanisms of action as they relate to psychosocial and glycemic outcomes will be explored in the future. PMID:27267154

The Effect of the Time of Injection of Intrathecal Analgesia on the Length of Early and Advanced Labor

DTIC Science & Technology

2000-01-03

drug combinations. Intrathecal Analgesia 36 Future Studies Recommendations for future studies include a prospective randomized clinical trial to examine...second stages of labor because of the variations in client population and in clinical practice. Friedman (1978) Intrathecal Analgesia 7 however, does...that the administration of morphine into the subarchnoid space of rats produced potent analgesia (Wang, 1977). These effects were then clinically applied

Bayes to the Rescue: Continuous Positive Airway Pressure Has Less Mortality Than High-Flow Oxygen.

PubMed

Modesto I Alapont, Vicent; Khemani, Robinder G; Medina, Alberto; Del Villar Guerra, Pablo; Molina Cambra, Alfred

2017-02-01

The merits of high-flow nasal cannula oxygen versus bubble continuous positive airway pressure are debated in children with pneumonia, with suggestions that randomized controlled trials are needed. In light of a previous randomized controlled trial showing a trend for lower mortality with bubble continuous positive airway pressure, we sought to determine the probability that a new randomized controlled trial would find high-flow nasal cannula oxygen superior to bubble continuous positive airway pressure through a "robust" Bayesian analysis. Sample data were extracted from the trial by Chisti et al, and requisite to "robust" Bayesian analysis, we specified three prior distributions to represent clinically meaningful assumptions. These priors (reference, pessimistic, and optimistic) were used to generate three scenarios to represent the range of possible hypotheses. 1) "Reference": we believe bubble continuous positive airway pressure and high-flow nasal cannula oxygen are equally effective with the same uninformative reference priors; 2) "Sceptic on high-flow nasal cannula oxygen": we believe that bubble continuous positive airway pressure is better than high-flow nasal cannula oxygen (bubble continuous positive airway pressure has an optimistic prior and high-flow nasal cannula oxygen has a pessimistic prior); and 3) "Enthusiastic on high-flow nasal cannula oxygen": we believe that high-flow nasal cannula oxygen is better than bubble continuous positive airway pressure (high-flow nasal cannula oxygen has an optimistic prior and bubble continuous positive airway pressure has a pessimistic prior). Finally, posterior empiric Bayesian distributions were obtained through 100,000 Markov Chain Monte Carlo simulations. In all three scenarios, there was a high probability for more death from high-flow nasal cannula oxygen compared with bubble continuous positive airway pressure (reference, 0.98; sceptic on high-flow nasal cannula oxygen, 0.982; enthusiastic on high-flow nasal cannula oxygen, 0.742). The posterior 95% credible interval on the difference in mortality identified a future randomized controlled trial would be extremely unlikely to find a mortality benefit for high-flow nasal cannula oxygen over bubble continuous positive airway pressure, regardless of the scenario. Interpreting these findings using the "range of practical equivalence" framework would recommend rejecting the hypothesis that high-flow nasal cannula oxygen is superior to bubble continuous positive airway pressure for these children. For children younger than 5 years with pneumonia, high-flow nasal cannula oxygen has higher mortality than bubble continuous positive airway pressure. A future randomized controlled trial in this population is unlikely to find high-flow nasal cannula oxygen superior to bubble continuous positive airway pressure.

Understanding the patient perspective on research access to national health records databases for conduct of randomized registry trials.

PubMed

Avram, Robert; Marquis-Gravel, Guillaume; Simard, François; Pacheco, Christine; Couture, Étienne; Tremblay-Gravel, Maxime; Desplantie, Olivier; Malhamé, Isabelle; Bibas, Lior; Mansour, Samer; Parent, Marie-Claude; Farand, Paul; Harvey, Luc; Lessard, Marie-Gabrielle; Ly, Hung; Liu, Geoffrey; Hay, Annette E; Marc Jolicoeur, E

2018-07-01

Use of health administrative databases is proposed for screening and monitoring of participants in randomized registry trials. However, access to these databases raises privacy concerns. We assessed patient's preferences regarding use of personal information to link their research records with national health databases, as part of a hypothetical randomized registry trial. Cardiology patients were invited to complete an anonymous self-reported survey that ascertained preferences related to the concept of accessing government health databases for research, the type of personal identifiers to be shared and the type of follow-up preferred as participants in a hypothetical trial. A total of 590 responders completed the survey (90% response rate), the majority of which were Caucasians (90.4%), male (70.0%) with a median age of 65years (interquartile range, 8). The majority responders (80.3%) would grant researchers access to health administrative databases for screening and follow-up. To this end, responders endorsed the recording of their personal identifiers by researchers for future record linkage, including their name (90%), and health insurance number (83.9%), but fewer responders agreed with the recording of their social security number (61.4%, p<0.05 with date of birth as reference). Prior participation in a trial predicted agreement for granting researchers access to the administrative databases (OR: 1.69, 95% confidence interval: 1.03-2.90; p=0.04). The majority of Cardiology patients surveyed were supportive of use of their personal identifiers to access administrative health databases and conduct long-term monitoring in the context of a randomized registry trial. Copyright © 2018 Elsevier Ireland Ltd. All rights reserved.

Efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (rTMS) versus electroconvulsive therapy (ECT) for major depression: a systematic review and meta-analysis of randomized trials.

PubMed

Berlim, Marcelo T; Van den Eynde, Frederique; Daskalakis, Zafiris J

2013-07-01

Clinical trials comparing the efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) and electroconvulsive therapy (ECT) for treating major depression (MD) have yielded conflicting results. As this may have been the result of limited statistical power, we have carried out this meta-analysis to examine this issue. We searched the literature for randomized trials on head-to-head comparisons between HF-rTMS and ECT from January 1995 through September 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and SCOPUS. The main outcome measures were remission rates, pre-post changes in depression ratings, as well as overall dropout rates at study end. We used a random-effects model, Odds Ratios (OR), Number Needed to Treat (NNT), and Hedges' g effect sizes. Data were obtained from 7 randomized trials, totalling 294 subjects with MD. After an average of 15.2 HF-rTMS and 8.2 ECT sessions, 33.6% (38/113) and 52% (53/102) of subjects were classified as remitters (OR = 0.46; p = 0.04), respectively. The associated NNT for remission was 6 and favoured ECT. Also, reduction of depressive symptomatology was significantly more pronounced in the ECT group (Hedges' g = -0.93; p = 0.007). No differences on dropout rates for HF-rTMS and ECT groups were found. In conclusion, ECT seems to be more effective than HF-rTMS for treating MD, although they did not differ in terms of dropout rates. Nevertheless, future comparative trials with larger sample sizes and better matching at baseline, longer follow-ups and more intense stimulation protocols are warranted. © 2013 Wiley Periodicals, Inc.

Use of nonintrusive sensor-based information and communication technology for real-world evidence for clinical trials in dementia.

PubMed

Teipel, Stefan; König, Alexandra; Hoey, Jesse; Kaye, Jeff; Krüger, Frank; Robillard, Julie M; Kirste, Thomas; Babiloni, Claudio

2018-06-21

Cognitive function is an important end point of treatments in dementia clinical trials. Measuring cognitive function by standardized tests, however, is biased toward highly constrained environments (such as hospitals) in selected samples. Patient-powered real-world evidence using information and communication technology devices, including environmental and wearable sensors, may help to overcome these limitations. This position paper describes current and novel information and communication technology devices and algorithms to monitor behavior and function in people with prodromal and manifest stages of dementia continuously, and discusses clinical, technological, ethical, regulatory, and user-centered requirements for collecting real-world evidence in future randomized controlled trials. Challenges of data safety, quality, and privacy and regulatory requirements need to be addressed by future smart sensor technologies. When these requirements are satisfied, these technologies will provide access to truly user relevant outcomes and broader cohorts of participants than currently sampled in clinical trials. Copyright © 2018. Published by Elsevier Inc.

A randomized controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (The seAFOod Polyp Prevention Trial): study protocol for a randomized controlled trial.

PubMed

Hull, Mark A; Sandell, Anna C; Montgomery, Alan A; Logan, Richard F A; Clifford, Gayle M; Rees, Colin J; Loadman, Paul M; Whitham, Diane

2013-07-29

The naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials. The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2×2 factorial 'efficacy' study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55-73 year-old patients, who have been identified as 'high risk' (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and 'advanced') per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as 'intermediate risk' for future surveillance. Exploratory end-points include levels of bioactive lipid mediators such as ω-3 PUFAs, resolvin E1 and PGE-M in plasma, urine, erythrocytes and rectal mucosa in order to gain insights into the mechanism(s) of action of EPA and aspirin, alone and in combination, as well as to discover predictive biomarkers of chemopreventive efficacy. The recruitment target is 904 patients. Current Controlled Trials ISRCTN05926847.

Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial.

PubMed

Wali, Ramesh K; Bianchi, Laura; Kupfer, Sonia; De La Cruz, Mart; Jovanovic, Borko; Weber, Christopher; Goldberg, Michael J; Rodriguez, L M; Bergan, Raymond; Rubin, David; Tull, Mary Beth; Richmond, Ellen; Parker, Beth; Khan, Seema; Roy, Hemant K

2018-01-01

Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data may provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention. ClinicalTrials.gov NCT00828984.

Calcium/Vitamin D Supplementation and Coronary Artery Calcification

PubMed Central

Manson, JoAnn E.; Allison, Matthew A.; Carr, J. Jeffrey; Langer, Robert D.; Cochrane, Barbara B.; Hendrix, Susan L.; Hsia, Judith; Hunt, Julie R.; Lewis, Cora E.; Margolis, Karen L.; Robinson, Jennifer G.; Rodabough, Rebecca J.; Thomas, Asha M.

2010-01-01

Objectives Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. The relationship between calcium plus vitamin D supplementation and coronary artery calcium (CAC) has not been previously assessed in a randomized trial setting. We compared coronary artery calcium scores among women randomized to calcium/vitamin D supplementation versus placebo following trial completion. Methods In an ancillary substudy of women randomized to calcium carbonate (1000 mg of elemental calcium daily) plus vitamin D3 (400 IU daily) versus placebo, nested within the Women’s Health Initiative trial of estrogen among women with hysterectomy, we measured CAC with cardiac computed tomography in 754 women aged 50–59 years at randomization. Imaging for CAC was performed at 28 of 40 centers following a mean of 7 years of treatment and scans were read centrally. Coronary artery calcium scores were measured by a central reading center with masking to randomization assignments. Results Post-trial CAC measurements were similar in women randomized to calcium/vitamin D supplementation (calcium/D) and those receiving placebo. The mean CAC score was 91.6 for calcium/D and 100.5 for placebo (rank test p-value=0.74). After adjustment for coronary risk factors, multivariate odds ratios for increasing CAC score cutpoints (CAC >0, ≥10, and ≥100) for calcium/D vs placebo were 0.92 (95% confidence interval, 0.64–1.34), 1.29 (0.88–1.87), and 0.90 (0.56–1.44), respectively. Corresponding odds ratios among women with >50% adherence to study pills and for higher levels of CAC (>300), were similar. Conclusions Treatment with moderate doses of calcium plus vitamin D3 did not appear to alter coronary artery calcified plaque burden among postmenopausal women. PMID:20551849

The role of vitamin D in the prevention of late-life depression.

PubMed

Okereke, Olivia I; Singh, Ankura

2016-07-01

In this article, we review current evidence regarding potential benefits of vitamin D for improving mood and reducing depression risk in older adults. We summarize gaps in knowledge and describe future efforts that may clarify the role of vitamin D in late-life depression prevention. MEDLINE and PsychINFO databases were searched for all articles on vitamin D and mood that had been published up to and including May 2015. Observational studies and randomized trials with 50 or more participants were included. We excluded studies that involved only younger adults and/or exclusively involved persons with current depression. Twenty observational (cross-sectional and prospective) studies and 10 randomized trials (nine were randomized placebo-controlled trials [RCTs]; one was a randomized blinded comparison trial) were reviewed. Inverse associations of vitamin D blood level or vitamin D intake with depression were found in 13 observational studies; three identified prospective relations. Results from all but one of the RCTs showed no statistically significant differences in depression outcomes between vitamin D and placebo groups. Observational studies were mostly cross-sectional and frequently lacked adequate control of confounding. RCTs often featured low treatment doses, suboptimal post-intervention changes in biochemical levels of vitamin D, and/or short trial durations. Vitamin D level-mood associations were observed in most, but not all, observational studies; results indicated that vitamin D deficiency may be a risk factor for late-life depression. However, additional data from well-designed RCTs are required to determine the impact of vitamin D in late-life depression prevention. Copyright © 2016 Elsevier B.V. All rights reserved.

Cognitive enhancement treatments for bipolar disorder: A systematic review and methodological recommendations.

PubMed

Miskowiak, Kamilla W; Carvalho, André F; Vieta, Eduard; Kessing, Lars V

2016-10-01

Cognitive dysfunction is an emerging treatment target in bipolar disorder (BD). Several trials have assessed the efficacy of novel pharmacological and psychological treatments on cognition in BD but the findings are contradictory and unclear. A systematic search following the PRISMA guidelines was conducted on PubMed and PsychInfo. Eligible articles reported randomized, controlled or open-label trials investigating pharmacological or psychological treatments targeting cognitive dysfunction in BD. The quality of the identified randomized controlled trials (RCTs) was evaluated with the Cochrane Collaboration's Risk of Bias tool. We identified 19 eligible studies of which 13 were RCTs and six were open-label or non-randomized studies. The findings regarding efficacy on cognition were overall disappointing or preliminary, possibly due to several methodological challenges. For the RCTs, the risk of bias was high in nine cases, unclear in one case and low in three cases. Key reasons for the high risk of bias were lack of details on the randomization process, suboptimal handling of missing data and lack of a priori priority between cognition outcomes. Other challenges were the lack of consensus on whether and how to screen for cognitive impairment and on how to assess efficacy on cognition. In conclusion, methodological problems are likely to impede the success rates of cognition trials in BD. We recommend adherence to the CONSORT guidelines for RCTs, screening for cognitive impairment before inclusion of trial participants and selection of one primary cognition outcome. Future implementation of a 'neurocircuitry-based' biomarker model to evaluate neural target engagement is warranted. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Planning Future Clinical Trials for Machado-Joseph Disease.

PubMed

Saute, Jonas Alex Morales; Jardim, Laura Bannach

2018-01-01

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is an autosomal dominant multiple neurological systems degenerative disorder caused by a CAG repeat expansion at ATXN3 gene. Only a few treatments were evaluated in randomized clinical trials (RCT) in SCA3/MJD patients, with a lack of evidence for both disease-modifying and symptomatic therapies. The present chapter discuss in detail major methodological issues for planning future RCT for SCA3/MJD. There are several potential therapies for SCA3/MJD with encouraging preclinical results. Route of treatment, dosage titration and potential therapy biomarkers might differ among candidate drugs; however, the core study design and protocol will be mostly the same. RCT against placebo group is the best study design to test a disease-modifying therapy; the same cannot be stated for some symptomatic treatments. Main outcomes for future RCT are clinical scales: the Scale for the Assessment and Rating of ataxia (SARA) is currently the instrument of choice to prove efficacy of disease-modifying or symptomatic treatments against ataxia, the most important disease feature. Ataxia quantitative scales or its composite scores can be used as primary outcomes to provide preliminary evidence of efficacy in phase 2 RCT, due to a greater sensitivity to change. Details regarding eligibility criteria, randomization, sample size estimation, duration and type of analysis for both disease modifying and symptomatic treatment trials, were also discussed. Finally, a section anticipates the methodological issues for testing novel drugs when an effective treatment is already available. We conclude emphasizing four points, the first being the need of RCT for a number of different aims in the care of SCA3/MJD. Due to large sample sizes needed to warrant power, RCT for disease-modifying therapies should be multicenter enterprises. There is an urge need for surrogate markers validated for several drug classes. Finally, engagement of at risk or presymptomatic individuals in future trials will enable major advances on treatment research for SCA3/MJD.

Challenges to recruitment and retention of African Americans in the gene-environment trial of response to dietary interventions (GET READI) for heart health

PubMed Central

Kennedy, Betty M.; Harsha, David W.; Bookman, Ebony B.; Hill, Yolanda R.; Rankinen, Tuomo; Rodarte, Ruben Q.; Murla, Connie D.

2011-01-01

In this paper, challenges to recruiting African Americans specifically for a dietary feeding trial are examined, learning experiences gained and suggestions to overcome these challenges in future trials are discussed. A total of 333 individuals were randomized in the trial and 234 (167 sibling pairs and 67 parents/siblings) completed the dietary intervention and required DNA blood sampling for genetic analysis. The trial used multiple strategies for recruitment. Hand distributed letters and flyers through mass distribution at various churches resulted in the largest number (n = 153, 46%) of African Americans in the trial. Word of mouth accounted for the second largest number (n = 120, 36%) and included prior study participants. These two recruitment sources represented 82% (n = 273) of the total number of individuals randomized in GET READI. The remaining 18% (n = 60) consisted of a combination of sources including printed message on check stubs, newspaper articles, radio and TV appearances, screening events and presentations. Though challenging, the recruitment efforts for GET READI produced a significant number of African American participants despite the inability to complete the trial as planned because of low recruitment yields. Nevertheless, the recruitment process produced substantial numbers that successfully completed all study requirements. PMID:21865154

Designing Comparative Effectiveness Trials of Surgical Ablation for Atrial Fibrillation: Experience of the Cardiothoracic Surgical Trials Network

PubMed Central

Gillinov, A. Marc; Argenziano, Michael; Blackstone, Eugene H.; Iribarne, Alexander; DeRose, Joseph J.; Ailawadi, Gorav; Russo, Mark J.; Ascheim, Deborah D.; Parides, Michael K.; Rodriguez, Evelio; Bouchard, Denis; Taddei-Peters, Wendy C.; Geller, Nancy L.; Acker, Michael A.; Gelijns, Annetine C.

2013-01-01

Background Since the introduction of the cut-and-sew Cox-Maze procedure for atrial fibrillation (AF) there has been substantial innovation in techniques for ablation. Use of alternate energy sources for ablation simplified the procedure and has resulted in dramatic increase in the number of AF patients treated by surgical ablation. Despite its increasingly widespread adoption, there is lack of rigorous clinical evidence to establish this as an effective clinical therapy. Methods and Results This paper describes a comparative effectiveness randomized trial, supported by the Cardiothoracic Surgical Trials Network, of surgical ablation with left atrial appendage (LAA) closure versus LAA closure alone in patients with persistent and longstanding persistent AF undergoing mitral valve surgery. Nested within this trial, is a further randomized comparison of 2 different lesions sets: pulmonary vein isolation and full Maze lesion set. This paper addresses trial design challenges, including how to best characterize the target population, operationalize freedom from AF as a primary endpoint, account for the impact of anti-arrhythmic drugs, and measure and analyze secondary endpoints, such as post-operative AF load. Conclusions This paper concludes by discussing how insights that emerge from this trial may affect surgical practice and guide future research in this area. PMID:21616507

Oncosurgical Management of Liver Limited Stage IV Colorectal Cancer: Preliminary Data and Protocol for a Randomized Controlled Trial.

PubMed

Sutton, Paul; Vimalachandran, Dale; Poston, Graeme; Fenwick, Stephen; Malik, Hassan

2018-05-09

Colorectal cancer is the fourth commonest cancer and second commonest cause of cancer-related death in the United Kingdom. Almost 15% of patients have metastases on presentation. An increasing number of surgical strategies and better neoadjuvant treatment options are responsible for more patients undergoing resection of liver metastases, with prolonged survival in a select group of patients who present with synchronous disease. It is clear that the optimal strategy for the management of these patients remains unclear, and there is certainly a complete absence of Level 1 evidence in the literature. The objective of this study is to undertake preliminary work and devise an outline trial protocol to inform the future development of clinical studies to investigate the management of patients with liver limited stage IV colorectal cancer. We have undertaken some preliminary work and begun the process of designing a randomized controlled trial and present a draft trial protocol here. This study is at the protocol development stage only, and as such no results are available. There is no funding in place for this study, and no anticipated start date. We have presented preliminary work and an outline trial protocol which we anticipate will inform the future development of clinical studies to investigate the management of patients with liver limited stage IV colorectal cancer. We do not believe that the trial we have designed will answer the most significant clinical questions, nor that it is feasible to be delivered within the United Kingdom's National Health Service at this current time. ©Paul Sutton, Dale Vimalachandran, Graeme Poston, Stephen Fenwick, Hassan Malik. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 09.05.2018.

Randomized controlled trial of a web-based indoor tanning intervention: Acceptability and preliminary outcomes.

PubMed

Stapleton, Jerod L; Manne, Sharon L; Darabos, Katie; Greene, Kathryn; Ray, Anne E; Turner, Amber L; Coups, Elliot J

2015-12-01

This article describes the acceptability and preliminary behavioral outcomes of a pilot randomized control trial of a web-based indoor tanning intervention for young adult women. The intervention targets indoor tanning users' perceptions of the benefits and value of tanning and addresses the role of body image-related constructs in indoor tanning. Participants were 186 young adult women who reported indoor tanning at least once in the past 12 months. The study design was a 2-arm randomized controlled trial with pre- and postintervention assessments and random assignment to an intervention or control condition. Intervention acceptability was assessed by obtaining participants' evaluation of the intervention. Regression analyses were used to test for intervention condition differences in preliminary behavioral outcomes measured at 6 weeks postintervention. Participants provided favorable evaluations of the intervention on several dimensions and a highly positive overall rating. Intervention participants were more likely to report abstaining from indoor tanning and indicated a lower likelihood of using indoor tanning in the future compared with control participants on the postintervention assessment. No differences were found for sunburns. The results of this pilot randomized controlled trial provide evidence that the indoor tanning intervention is acceptable to participants and may encourage cessation of indoor tanning behavior. The findings provide preliminary support for an indoor tanning intervention that engages tanners to challenge their beliefs about the benefits of indoor tanning. The use of a web-based indoor tanning intervention is unique and provides strong potential for dissemination. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Effects of music therapy on intravitreal injections: a randomized clinical trial.

PubMed

Chen, Xuejing; Seth, Rajeev K; Rao, Veena S; Huang, John J; Adelman, Ron A

2012-08-01

To investigate the effects of music therapy on anxiety, perceived pain, and satisfaction in patients undergoing intravitreal injections in the outpatient setting. This is a randomized clinical trial. Seventy-three patients were recruited from the retina clinic at 1 institution and randomized into a music therapy (n=37) or control (n=36) group. Prior to injection, patients completed the state portion of the Spielberger State Trait Anxiety Inventory (STAI-S). The music therapy group listened to classical music through computer speakers while waiting for and during the injection. The control group underwent the injection in the same setting without music. Afterward, all patients completed another STAI-S and a satisfaction and pain questionnaire. The main outcome measures were objective anxiety derived from STAI-S scores and subjective pain and anxiety from the post procedure questionnaire. The music therapy group had a greater decrease in anxiety than the control group (P=0.0480). Overall, 73% of all patients requested music for future injections (P=0.0001). The music therapy group (84%) requested music in future injections more frequently than the control group (61%) (P=0.0377). Both groups reported similar levels of pain (P=0.5879). Classical music before and during intravitreal injections decreases anxiety in patients without decreasing pain. Most patients desire to have music during future injections. Music therapy is a low-cost, easy, safe intervention that reduces anxiety during intravitreal injections in the outpatient setting.

The Effectiveness and Cost-Effectiveness of Spinal Cord Stimulation for Refractory Angina (RASCAL Study): A Pilot Randomized Controlled Trial.

PubMed

Eldabe, Sam; Thomson, Simon; Duarte, Rui; Brookes, Morag; deBelder, Mark; Raphael, Jon; Davies, Ed; Taylor, Rod

2016-01-01

Patients with "refractory angina" (RA) unsuitable for coronary revascularization experience high levels of hospitalization and poor health-related quality of life. Randomized trials have shown spinal cord stimulation (SCS) to be a promising treatment for chronic stable angina and RA; however, none has compared SCS with usual care (UC). The aim of this pilot study was to address the key uncertainties of conducting a definitive multicenter trial to assess the clinical and cost-effectiveness of SCS in RA patients, i.e., recruitment and retention of patients, burden of outcome measures, our ability to standardize UC in a UK NHS setting. RA patients deemed suitable were randomized in a 1:1 ratio to SCS plus UC (SCS group) or UC alone (UC group). We sought to assess: recruitment, uptake, and retention of patients; feasibility and acceptability of SCS treatment; the feasibility and acceptability of standardizing UC; and the feasibility and acceptability of the proposed trial outcome measures. Patient outcomes were assessed at baseline (prerandomization) and three and six months postrandomization. We failed to meet our planned recruitment target (45 patients) and randomized 29 patients (15 SCS group, 14 UC group) over a 42-month period across four sites. None of the study participants chose to withdraw following consent and randomization. With exception of two deaths, all completed evaluation at baseline and follow-up. Although the study was not formally powered to compare outcomes between groups, we saw a trend toward larger improvements in both primary and secondary outcomes in the SCS group. While patient recruitment was found to be challenging, levels of participant retention, outcome completion, and acceptability of SCS therapy were high. A number of lessons are presented in order to take forward a future definitive pragmatic randomized trial. © 2015 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.

Online distribution channel increases article usage on Mendeley: a randomized controlled trial.

PubMed

Kudlow, Paul; Cockerill, Matthew; Toccalino, Danielle; Dziadyk, Devin Bissky; Rutledge, Alan; Shachak, Aviv; McIntyre, Roger S; Ravindran, Arun; Eysenbach, Gunther

2017-01-01

Prior research shows that article reader counts (i.e. saves) on the online reference manager, Mendeley, correlate to future citations. There are currently no evidenced-based distribution strategies that have been shown to increase article saves on Mendeley. We conducted a 4-week randomized controlled trial to examine how promotion of article links in a novel online cross-publisher distribution channel (TrendMD) affect article saves on Mendeley. Four hundred articles published in the Journal of Medical Internet Research were randomized to either the TrendMD arm ( n  = 200) or the control arm ( n  = 200) of the study. Our primary outcome compares the 4-week mean Mendeley saves of articles randomized to TrendMD versus control. Articles randomized to TrendMD showed a 77% increase in article saves on Mendeley relative to control. The difference in mean Mendeley saves for TrendMD articles versus control was 2.7, 95% CI (2.63, 2.77), and statistically significant ( p  < 0.01). There was a positive correlation between pageviews driven by TrendMD and article saves on Mendeley (Spearman's rho r  = 0.60). This is the first randomized controlled trial to show how an online cross-publisher distribution channel (TrendMD) enhances article saves on Mendeley. While replication and further study are needed, these data suggest that cross-publisher article recommendations via TrendMD may enhance citations of scholarly articles.

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. Methods and design This will be an open-label randomized, controlled trial conducted at Women’s College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the ‘multiple comparisons with the best’ approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies. Discussion Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures. Trial registration ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742. PMID:24010992

Physical Activity Outcomes of Nurse-Delivered Lifestyle Interventions.

PubMed

Richards, Elizabeth A; Cai, Yun

2016-02-01

Promotion of physical activity has been a public health priority for decades. Over two million home healthcare nurses are at the front line to deliver effective health education and health promotion interventions in the United States. The purpose of this systematic review is to examine the effectiveness of nurse-delivered lifestyle physical interventions on physical activity outcomes conducted in home settings. Computerized database and ancestry search strategies located distinct intervention trials between 1990 and 2015. A total of eight quantitative studies were reviewed. Four of the eight studies were randomized control trials and four studies used an uncontrolled pretest-posttest design. The eight studies represented a total of 1,221 participants with mean ages from 43 to 81. Study sample sizes ranged from 16 to 504. Seven of the eight studies demonstrated modest effect of nurse-delivered home-based interventions on physical activity behaviors. Home-based physical activity promotion was most often incorporated into secondary prevention of postacute diseases, chronic disease management, or disease prevention/health promotion. Findings indicate that nurse-delivered home-based physical activity promotion show overall effectiveness in general adult populations. Possible effective intervention domains were also discussed in this review to guide future home-based health promotion. More large randomized controlled trials with longer study/follow-up periods and studies with cost-effectiveness data are warranted in future research.

Quality of reporting of modern randomized controlled trials in medical oncology: a systematic review.

PubMed

Péron, Julien; Pond, Gregory R; Gan, Hui K; Chen, Eric X; Almufti, Roula; Maillet, Denis; You, Benoit

2012-07-03

The Consolidated Standards of Reporting Trials (CONSORT) guidelines were developed in the mid-1990s for the explicit purpose of improving clinical trial reporting. However, there is little information regarding the adherence to CONSORT guidelines of recent publications of randomized controlled trials (RCTs) in oncology. All phase III RCTs published between 2005 and 2009 were reviewed using an 18-point overall quality score for reporting based on the 2001 CONSORT statement. Multivariable linear regression was used to identify features associated with improved reporting quality. To provide baseline data for future evaluations of reporting quality, RCTs were also assessed according to the 2010 revised CONSORT statement. All statistical tests were two-sided. A total of 357 RCTs were reviewed. The mean 2001 overall quality score was 13.4 on a scale of 0-18, whereas the mean 2010 overall quality score was 19.3 on a scale of 0-27. The overall RCT reporting quality score improved by 0.21 points per year from 2005 to 2009. Poorly reported items included method used to generate the random allocation (adequately reported in 29% of trials), whether and how blinding was applied (41%), method of allocation concealment (51%), and participant flow (59%). High impact factor (IF, P = .003), recent publication date (P = .008), and geographic origin of RCTs (P = .003) were independent factors statistically significantly associated with higher reporting quality in a multivariable regression model. Sample size, tumor type, and positivity of trial results were not associated with higher reporting quality, whereas funding source and treatment type had a borderline statistically significant impact. The results show that numerous items remained unreported for many trials. Thus, given the potential impact of poorly reported trials, oncology journals should require even stricter adherence to the CONSORT guidelines.

A randomized controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (The seAFOod Polyp Prevention Trial): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background The naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials. Design The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2 × 2 factorial ‘efficacy’ study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55–73 year-old patients, who have been identified as ‘high risk’ (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and ‘advanced’) per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as ‘intermediate risk’ for future surveillance. Exploratory end-points include levels of bioactive lipid mediators such as ω-3 PUFAs, resolvin E1 and PGE-M in plasma, urine, erythrocytes and rectal mucosa in order to gain insights into the mechanism(s) of action of EPA and aspirin, alone and in combination, as well as to discover predictive biomarkers of chemopreventive efficacy. The recruitment target is 904 patients. Trial Registration Current Controlled Trials ISRCTN05926847 PMID:23895505

Feasibility of Extracting Key Elements from ClinicalTrials.gov to Support Clinicians’ Patient Care Decisions

PubMed Central

Kim, Heejun; Bian, Jiantao; Mostafa, Javed; Jonnalagadda, Siddhartha; Del Fiol, Guilherme

2016-01-01

Motivation: Clinicians need up-to-date evidence from high quality clinical trials to support clinical decisions. However, applying evidence from the primary literature requires significant effort. Objective: To examine the feasibility of automatically extracting key clinical trial information from ClinicalTrials.gov. Methods: We assessed the coverage of ClinicalTrials.gov for high quality clinical studies that are indexed in PubMed. Using 140 random ClinicalTrials.gov records, we developed and tested rules for the automatic extraction of key information. Results: The rate of high quality clinical trial registration in ClinicalTrials.gov increased from 0.2% in 2005 to 17% in 2015. Trials reporting results increased from 3% in 2005 to 19% in 2015. The accuracy of the automatic extraction algorithm for 10 trial attributes was 90% on average. Future research is needed to improve the algorithm accuracy and to design information displays to optimally present trial information to clinicians. PMID:28269867

Determinants of high and low attendance to diet and exercise interventions among overweight and obese older adults. Results from the arthritis, diet, and activity promotion trial.

PubMed

van Gool, Coen H; Penninx, Brenda W J H; Kempen, Gertrudis I J M; Miller, Gary D; van Eijk, Jacques Th M; Pahor, Marco; Messier, Stephen P

2006-06-01

Determinants of adherence to lifestyle regimens are ill understood. Attendance to intervention sessions is crucial for patients to acquire knowledge and skills regarding the core elements of an intervention. Therefore, we explored demographic, health-related, and social determinants of high and low attendance to diet and exercise sessions among overweight and obese patients with knee osteoarthritis (> or = 60 years; N = 206). The Arthritis, Diet, and Activity Promotion Trial was an 18-month randomized controlled trial on the effectiveness of dietary weight loss and exercise interventions. We conducted chi-square and t-tests, and logistic regression analyses on categories of short- and long-term attendance to intervention sessions. Over the 18-month duration of the study, 60.7% (+/- 28.5) of diet sessions, and 53.2% (+/- 29.0) of exercise sessions were attended. Not being married, low social participation, and single intervention randomization predicted high attendance to diet sessions during months 1-4. Exercising at home, and single intervention randomization predicted high attendance to exercise sessions during months 5-18. High attendance to sessions early in the intervention was a significant determinant of high session attendance thereafter. Offering people a choice where to exercise, and stimulating early intervention session attendance can be effective in improving long-term attendance to both interventions. Several determinants we found may be amenable to change to enhance intervention adherence of future randomized controlled trials involving dietary weight loss and/or physical exercise.

Prevention of Mental Health Disorders Using Internet- and Mobile-Based Interventions: A Narrative Review and Recommendations for Future Research

PubMed Central

Ebert, David Daniel; Cuijpers, Pim; Muñoz, Ricardo F.; Baumeister, Harald

2017-01-01

Although psychological interventions might have a tremendous potential for the prevention of mental health disorders (MHD), their current impact on the reduction of disease burden is questionable. Possible reasons include that it is not practical to deliver those interventions to the community en masse due to limited health care resources and the limited availability of evidence-based interventions and clinicians in routine practice, especially in rural areas. Therefore, new approaches are needed to maximize the impact of psychological preventive interventions. Limitations of traditional prevention programs could potentially be overcome by providing Internet- and mobile-based interventions (IMIs). This relatively new medium for promoting mental health and preventing MHD introduces a fresh array of possibilities, including the provision of evidence-based psychological interventions that are free from the restraints of travel and time and allow reaching participants for whom traditional opportunities are not an option. This article provides an introduction to the subject and narratively reviews the available evidence for the effectiveness of IMIs with regard to the prevention of MHD onsets. The number of randomized controlled trials that have been conducted to date is very limited and so far it is not possible to draw definite conclusions about the potential of IMIs for the prevention of MHD for specific disorders. Only for the indicated prevention of depression there is consistent evidence across four different randomized trial trials. The only trial on the prevention of general anxiety did not result in positive findings in terms of eating disorders (EDs), effects were only found in post hoc subgroup analyses, indicating that it might be possible to prevent ED onset for subpopulations of people at risk of developing EDs. Future studies need to identify those subpopulations likely to profit from preventive. Disorders not examined so far include substance use disorders, bipolar disorders, stress-related disorders, phobic disorders and panic disorder, obsessive–compulsive disorder, impulse-control disorders, somatic symptom disorder, and insomnia. In summary, there is a need for more rigorously conducted large scale randomized controlled trials using standard clinical diagnostic instruments for the selection of participants without MHD at baseline and the assessment of MHD onset. Subsequently, we discuss future directions for the field in order to fully exploit the potential of IMI for the prevention of MHD. PMID:28848454

Prevention of Mental Health Disorders Using Internet- and Mobile-Based Interventions: A Narrative Review and Recommendations for Future Research.

PubMed

Ebert, David Daniel; Cuijpers, Pim; Muñoz, Ricardo F; Baumeister, Harald

2017-01-01

Although psychological interventions might have a tremendous potential for the prevention of mental health disorders (MHD), their current impact on the reduction of disease burden is questionable. Possible reasons include that it is not practical to deliver those interventions to the community en masse due to limited health care resources and the limited availability of evidence-based interventions and clinicians in routine practice, especially in rural areas. Therefore, new approaches are needed to maximize the impact of psychological preventive interventions. Limitations of traditional prevention programs could potentially be overcome by providing Internet- and mobile-based interventions (IMIs). This relatively new medium for promoting mental health and preventing MHD introduces a fresh array of possibilities, including the provision of evidence-based psychological interventions that are free from the restraints of travel and time and allow reaching participants for whom traditional opportunities are not an option. This article provides an introduction to the subject and narratively reviews the available evidence for the effectiveness of IMIs with regard to the prevention of MHD onsets. The number of randomized controlled trials that have been conducted to date is very limited and so far it is not possible to draw definite conclusions about the potential of IMIs for the prevention of MHD for specific disorders. Only for the indicated prevention of depression there is consistent evidence across four different randomized trial trials. The only trial on the prevention of general anxiety did not result in positive findings in terms of eating disorders (EDs), effects were only found in post hoc subgroup analyses, indicating that it might be possible to prevent ED onset for subpopulations of people at risk of developing EDs. Future studies need to identify those subpopulations likely to profit from preventive. Disorders not examined so far include substance use disorders, bipolar disorders, stress-related disorders, phobic disorders and panic disorder, obsessive-compulsive disorder, impulse-control disorders, somatic symptom disorder, and insomnia. In summary, there is a need for more rigorously conducted large scale randomized controlled trials using standard clinical diagnostic instruments for the selection of participants without MHD at baseline and the assessment of MHD onset. Subsequently, we discuss future directions for the field in order to fully exploit the potential of IMI for the prevention of MHD.

Outcomes following vaginal prolapse repair and mid urethral sling (OPUS) trial--design and methods.

PubMed

Wei, John; Nygaard, Ingrid; Richter, Holly; Brown, Morton; Barber, Matthew; Xiao Xu; Kenton, Kimberly; Nager, Charles; Schaffer, Joseph; Visco, Anthony; Weber, Anne

2009-04-01

The primary aims of this trial are to determine whether the use of a concomitant prophylactic anti-incontinence procedure may prevent stress urinary incontinence symptom development in women undergoing vaginal prolapse surgery and to evaluate the cost-effectiveness of this prophylactic approach. To present the rationale and design of a randomized controlled surgical trial (RCT), the Outcomes following vaginal Prolapse repair and mid Urethral Sling (OPUS) Trial highlighting the challenges in the design and implementation. The challenges of implementing this surgical trial combined with a cost-effectiveness study and patient preference group are discussed including the study design, ethical issues regarding use of sham incision, maintaining the masking of study staff, and pragmatic difficulties encountered in the collection of cost data. The trial is conducted by the NICHD-funded Pelvic Floor Disorders Network. The ongoing OPUS trial started enrollment in May 2007 with a planned accrual of 350. The use of sham incision was generally well accepted but the collection of cost data using conventional billing forms was found to potentially unmask key study personnel. This necessitated changes in the study forms and planned timing for collection of cost data. To date, the enrollment to the patient preference group has been lower than the limit established by the protocol suggesting a willingness on the part of women to participate in the randomization. Given the invasive nature of surgical intervention trials, potential participants may be reluctant to accept random assignment, potentially impacting generalizability. Findings from the OPUS trial will provide important information that will help surgeons to better counsel women on the benefits and risks of concomitant prophylactic anti-incontinence procedure at the time of vaginal surgery for prolapse. The implementation of the OPUS trial has necessitated that investigators consider ethical issues up front, remain flexible with regards to data collection and be constantly aware of unanticipated opportunities for unmasking. Future surgical trials should be aware of potential challenges in maintaining masking and collection of cost-related information.

STAR*D: helping to close the gap between science and practice.

PubMed

Shern, David L; Moran, Hazel

2009-11-01

Practical clinical trials, such as STAR*D (Sequenced Treatment Alternatives to Relieve Depression), extend the traditional randomized controlled trial to real-world settings. Consumers and clinicians should be encouraged by STAR*D's 70% remission rate and should realize that for many participants remission required medication switching and augmentation. Policy makers should recognize the importance of easy access to a full range of treatments. Researchers should be sobered by the high attrition rate and the 30% of participants who did not achieve remission. Although more such practical trials are needed, future work must more meaningfully involve consumers in design, analysis, and interpretation.

Rationale, conduct, and outcome using hypofractionated radiotherapy in prostate cancer

PubMed Central

Ritter, Mark

2008-01-01

Hypofractionated radiation therapy for prostate cancer has become of increasing interest with the recognition of a potential improvement in therapeutic ratio with treatments delivered in larger-sized fractions. In addition, the associated reduction in fraction number produces attractive cost and patient convenience advantages as well. A still limited but growing number of hypofractionation trials have reported acceptable short-term levels of toxicity and biochemical control, but most have insufficient follow-up to assure the long-term safety and efficacy of this approach. This situation will improve as many currently active trials mature, particularly several high value randomized trials. In contrast, extreme hypofractionation, with schedules delivering only on the order of 5 fractions, is truly in its infancy for prostate cancer, with extremely limited tolerance and efficacy information currently available. Several uncertainties in the radiobiology of hypofractionation mitigate for an organized, cautious investigational approach. The fractionation response (α/β ratio) of prostate cancers and, for that matter, late responding normal tissues, has yet to be rigorously defined. Additionally, the linear quadratic (LQ) model used in the design of hypofractionation schedules is subject to its own uncertainties, particularly with respect to the upper limit of fraction sizes for which it remains valid. Contemporary dose escalated radiation therapy is already highly effective, making it imperative that ongoing and future studies of hypofractionation be carried out in carefully designed, randomized clinical trials. Clinical validation permitting, the adaptation of hypofractionation as a standard of care could profoundly influence future management of localized prostate cancer. PMID:18725112

Understanding health economic analysis in critical care: insights from recent randomized controlled trials.

PubMed

Sud, Sachin; Cuthbertson, Brian H

2011-10-01

The article reviews the methods of health economic analysis (HEA) in clinical trials of critically ill patients. Emphasis is placed on the usefulness of HEA in the context of positive and 'no effect' studies, with recent examples. The need to control costs and promote effective spending in caring for the critically ill has garnered considerable attention due to the high cost of critical illness. Many clinical trials focus on short-term mortality, ignoring costs and quality of life, and fail to change clinical practice or promote efficient use of resources. Incorporating HEA into clinical trials is a possible solution. Such studies have shown some interventions, although expensive, provide good value, whereas others should be withdrawn from clinical practice. Incorporating HEA into randomized controlled trials (RCTs) requires careful attention to collect all relevant costs. Decision trees, modeling assumptions and methods for collecting costs and measuring outcomes should be planned and published beforehand to minimize bias. Costs and cost-effectiveness are potentially useful outcomes in RCTs of critically ill patients. Future RCTs should incorporate parallel HEA to provide both economic outcomes, which are important to the community, alongside patient-centered outcomes, which are important to individuals.

The Risk of Bias in Randomized Trials in General Dentistry Journals.

PubMed

Hinton, Stephanie; Beyari, Mohammed M; Madden, Kim; Lamfon, Hanadi A

2015-01-01

The use of a randomized controlled trial (RCT) research design is considered the gold standard for conducting evidence-based clinical research. In this present study, we aimed to assess the quality of RCTs in dentistry and create a general foundation for evidence-based dentistry on which to perform subsequent RCTs. We conducted a systematic assessment of bias of RCTs in seven general dentistry journals published between January 2011 and March 2012. We extracted study characteristics in duplicate and assessed each trial's quality using the Cochrane Risk of Bias tool. We compared risk of bias across studies graphically. Among 1,755 studies across seven journals, we identified 67 RCTs. Many included studies were conducted in Europe (39%), with an average sample size of 358 participants. These studies included 52% female participants and the maximum follow-up period was 13 years. Overall, we found a high percentage of unclear risk of bias among included RCTs, indicating poor quality of reporting within the included studies. An overall high proportion of trials with an "unclear risk of bias" suggests the need for better quality of reporting in dentistry. As such, key concepts in dental research and future trials should focus on high-quality reporting.

Chelation therapy to treat atherosclerosis, particularly in diabetes: is it time to reconsider?

PubMed

Lamas, Gervasio A; Ergui, Ian

2016-08-01

Case reports and case series have suggested a possible beneficial effect of chelation therapy in patients with atherosclerotic disease. Small randomized trials conducted in patients with angina or peripheral artery disease, however, were not sufficiently powered to provide conclusive evidence on clinical outcomes. The Trial to Assess Chelation Therapy (TACT) was the first randomized trial adequately powered to detect the effects of chelation therapy on clinical endpoints. We discuss results and future research. Expert commentary: Chelation reduced adverse cardiovascular events in a post myocardial infarction (MI) population. Patients with diabetes demonstrated even greater benefit, with a number needed to treat of 6.5 patients to prevent a cardiac event over 5 years, with a 41% relative reduction in risk of a cardiac event (p = 0.0002). These results led to the revision of the ACC/AHA guideline recommendations for chelation therapy, changing its classification from class III to class IIb. TACT2, a replicative trial, will assess the effects of chelation therapy on cardiovascular outcomes in diabetic patients with a prior myocardial infarction. We are seeking participating sites for TACT2.

Progression-free survival as primary endpoint in randomized clinical trials of targeted agents for advanced renal cell carcinoma. Correlation with overall survival, benchmarking and power analysis.

PubMed

Bria, Emilio; Massari, Francesco; Maines, Francesca; Pilotto, Sara; Bonomi, Maria; Porta, Camillo; Bracarda, Sergio; Heng, Daniel; Santini, Daniele; Sperduti, Isabella; Giannarelli, Diana; Cognetti, Francesco; Tortora, Giampaolo; Milella, Michele

2015-01-01

A correlation, power and benchmarking analysis between progression-free and overall survival (PFS, OS) of randomized trials with targeted agents or immunotherapy for advanced renal cell carcinoma (RCC) was performed to provide a practical tool for clinical trial design. For 1st-line of treatment, a significant correlation was observed between 6-month PFS and 12-month OS, between 3-month PFS and 9-month OS and between the distributions of the cumulative PFS and OS estimates. According to the regression equation derived for 1st-line targeted agents, 7859, 2873, 712, and 190 patients would be required to determine a 3%, 5%, 10% and 20% PFS advantage at 6 months, corresponding to an absolute increase in 12-month OS rates of 2%, 3%, 6% and 11%, respectively. These data support PFS as a reliable endpoint for advanced RCC receiving up-front therapies. Benchmarking and power analyses, on the basis of the updated survival expectations, may represent practical tools for future trial' design. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Methodological Overview of an African American Couple-Based HIV/STD Prevention Trial

PubMed Central

2010-01-01

Objective To provide an overview of the NIMH Multisite HIV/STD Prevention Trial for African American Couples conducted in four urban areas: Atlanta, Los Angeles, New York, and Philadelphia. The rationale, study design methods, proposed data analyses, and study management are described. Design This is a two arm randomized Trial, implementing a modified randomized block design, to evaluate the efficacy of a couples based intervention designed for HIV serodiscordant African American couples. Methods The study phases consisted of formative work, pilot studies, and a randomized clinical trial. The sample is 535 HIV serodiscordant heterosexual African American couples. There are two theoretically derived behavioral interventions with eight group and individual sessions: the Eban HIV/STD Risk Reduction Intervention (treatment) versus the Eban Health Promotion Intervention (control). The treatment intervention was couples based and focused on HIV/STD risk reduction while the control was individual based and focused on health promotion. The two study conditions were structurally similar in length and types of activities. At baseline, participants completed an Audio Computer-assisted Self Interview (ACASI) interview as well as interviewer-administered questionnaire, and provided biological specimens to assess for STDs. Similar follow-up assessments were conducted immediately after the intervention, at 6 months, and at 12 months. Results The Trial results will be analyzed across the four sites by randomization assignment. Generalized estimating equations (GEE) and mixed effects modeling (MEM) are planned to test: (1) the effects of the intervention on STD incidence and condom use as well as on mediator variables of these outcomes, and (2) whether the effects of the intervention differ depending on key moderator variables (e.g., gender of the HIV-seropositive partners, length of relationship, psychological distress, sexual abuse history, and substance abuse history). Conclusions The lessons learned from the design and conduct of this clinical trial provide guidelines for future couples based clinical trials in HIV/STD risk reduction and can be generalized to other couples based behavioral interventions. PMID:18724188

78 FR 66008 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-04

... developing recommendations, future research and program needs concerning home- testing for MSM. Specific Aims... Manhunt and Adam4Adam. This study also has a qualitative component that aims to examine the experiences of participants in the randomized control trial (RCT). Participants for the qualitative data collection will be...

Promoting "Healthy Futures" to Reduce Risk Behaviors in Urban Youth: A Randomized Controlled Trial.

PubMed

Lindstrom Johnson, Sarah; Jones, Vanya; Cheng, Tina L

2015-09-01

There is increasing evidence of the interconnection between educational and health outcomes. Unfortunately wide disparities exist by both socioeconomic status and race/ethnicity in educational and vocational success. This study sought to promote urban youths' career readiness as a way to reduce involvement in risk behaviors. Two hundred primarily African-American youth (ages 14-21) were recruited from a pediatric primary care clinic. Youth randomized to the intervention received three motivational interviewing sessions focused around expectations and planning for the future. Baseline and 6-month follow-up assessments included measures of career readiness and risk behavior involvement (i.e., physical fighting, alcohol and marijuana use). At 6-months, youth randomized to the intervention condition showed increased confidence in their ability to perform the behaviors needed to reach their college/career goals. Additionally, youth randomized to the intervention arm showed decreased fighting behavior (adjusted rate ratio: .27) and marijuana use (adjusted rate ratio: .61). Assisting urban youth in thinking and planning about their future holds promise as a way to reduce their involvement in risk behaviors. This study also demonstrated that motivational interviewing could be used to promote positive behaviors (i.e., career readiness).

Rationale and design of a randomized controlled trial of the effect of retinol and vitamin D supplementation on treatment in active pulmonary tuberculosis patients with diabetes

PubMed Central

2013-01-01

Background The association between pulmonary tuberculosis (PTB) and diabetes mellitus (DM) has been previously attracted much attention. Diabetes alters immunity to tuberculosis, leading to more frequent treatment failure in TB patients with DM. Moreover, TB and DM often coincide with micronutrients deficiencies, such as retinol and vitamin D, which are especially important to immunity of the body and may influence pancreas β-cell function. However, the effects of retinol and vitamin D supplementation in active TB patients with diabetes on treatment outcomes, immune and nutrition state are still uncertain. We are conducting a randomized controlled trial of vitamin A and/or D in active PTB patients with DM in a network of 4 TB treatment clinics to determine whether the supplementation could improve the outcome in the patients. Methods/design This is a 2×2 factorial trial. We plan to enroll 400 active PTB patients with DM, and randomize them to VA (2000 IU daily retinol); VD (400 IU daily cholecalciferol); VAD (2000 IU daily retinol plus 400 IU cholecalciferol) or control (placebo) group. Our primary outcome measure is the efficacy of anti-tuberculosis treatment and ameliorating of glucose metabolism, and the secondary outcome measure being immune and nutrition status of the subjects. Of the first 37 subjects enrolled: 8 have been randomized to VA, 10 to VD, 9 to VAD and 10 to control. To date, the sample is 97.3% Han Chinese and 91.9% female. The average fasting plasma glucose level is 12.19 mmol/L. Discussion This paper describes the design and rationale of a randomized clinical trial comparing VA and/or VD supplementation to active pulmonary TB patients with DM. Our trial will allow rigorous evaluation of the efficacy of the supplementation to active TB and DM therapy for improving clinical outcomes and immunological condition. This detailed description of trial methodology can serve as a template for the development of future treatment scheme for active TB patient with DM. Trial registration ChiCTR-TRC-12002546 PMID:23442225

What's in a title? An assessment of whether randomized controlled trial in a title means that it is one.

PubMed

Koletsi, Despina; Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2012-06-01

In this study, we aimed to investigate whether studies published in orthodontic journals and titled as randomized clinical trials are truly randomized clinical trials. A second objective was to explore the association of journal type and other publication characteristics on correct classification. American Journal of Orthodontics and Dentofacial Orthopedics, European Journal of Orthodontics, Angle Orthodontist, Journal of Orthodontics, Orthodontics and Craniofacial Research, World Journal of Orthodontics, Australian Orthodontic Journal, and Journal of Orofacial Orthopedics were hand searched for clinical trials labeled in the title as randomized from 1979 to July 2011. The data were analyzed by using descriptive statistics, and univariable and multivariable examinations of statistical associations via ordinal logistic regression modeling (proportional odds model). One hundred twelve trials were identified. Of the included trials, 33 (29.5%) were randomized clinical trials, 52 (46.4%) had an unclear status, and 27 (24.1%) were not randomized clinical trials. In the multivariable analysis among the included journal types, year of publication, number of authors, multicenter trial, and involvement of statistician were significant predictors of correctly classifying a study as a randomized clinical trial vs unclear and not a randomized clinical trial. From 112 clinical trials in the orthodontic literature labeled as randomized clinical trials, only 29.5% were identified as randomized clinical trials based on clear descriptions of appropriate random number generation and allocation concealment. The type of journal, involvement of a statistician, multicenter trials, greater numbers of authors, and publication year were associated with correct clinical trial classification. This study indicates the need of clear and accurate reporting of clinical trials and the need for educating investigators on randomized clinical trial methodology. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Participant recruitment and retention in longitudinal preconception randomized trials: lessons learnt from the Calcium And Pre-eclampsia (CAP) trial.

PubMed

Lawrie, Theresa A; Betrán, Ana Pilar; Singata-Madliki, Mandisa; Ciganda, Alvaro; Hofmeyr, G Justus; Belizán, José M; Purnat, Tina Dannemann; Manyame, Sarah; Parker, Catherine; Cormick, Gabriela

2017-10-26

The preconception period has the potential to influence pregnancy outcomes and randomized controlled trials (RCTs) are needed to evaluate a variety of potentially beneficial preconception interventions. However, RCTs commencing before pregnancy have significant participant recruitment and retention challenges. The Calcium And Pre-eclampsia trial (CAP trial) is a World Health Organization multi-country RCT of calcium supplementation commenced before pregnancy to prevent recurrent pre-eclampsia in which non-pregnant participants are recruited and followed up until childbirth. This sub-study explores recruitment methods and preconception retention of participants of the CAP trial to inform future trials. Recruiters at the study sites in Argentina, South Africa and Zimbabwe completed post-recruitment phase questionnaires on recruitment methods used. Qualitative data from these questionnaires and quantitative data on pre-pregnancy trial visit attendance and pregnancy rates up to September 2016 are reported in this paper. RStudio (Version 0.99.903 https://www.rstudio.org ) statistical software was used for summary statistics. Between July 2011 and 8 September 2016, 1354 women with previous pre-eclampsia were recruited. Recruitment took 2 years longer than expected and was facilitated mainly through medical record/register and maternity ward/clinic-based strategies. Recruiters highlighted difficulties associated with inadequate medical records, redundant patient contact details, and follow-up of temporarily ineligible women as some of the challenges faced. Whilst the attendance rates at pre-pregnancy visits were high (78% or more), visits often occurred later than scheduled. Forty-five percent of participants became pregnant (614/1354), 33.5% (454/1354) within 1 year of randomization. In preconception trials, both retrospective and prospective methods are useful for recruiting eligible women with certain conditions. However, these are time-consuming in low-resource settings with suboptimal medical records and other challenges. Trial planners should ensure that trial budgets cover sufficient on-site researchers with pre-trial training, and should consider using mobile phone and web-based electronic tools to optimize recruitment and retention. This should lead to greater efficiency and shorter trial durations. Pan-African Clinical Trials Registry, Registration Number: PACTR201105000267371 . The trial was registered on 6 December 2016.

Efficacy of Platelet-Rich Fibrin After Mandibular Third Molar Extraction: A Systematic Review and Meta-Analysis.

PubMed

Al-Hamed, Faez Saleh; Tawfik, Mohamed Abdel-Monem; Abdelfadil, Ehab; Al-Saleh, Mohammed A Q

2017-06-01

To assess the effect of platelet-rich fibrin (PRF) on the healing process of the alveolar socket after surgical extraction of the mandibular third molars. PubMed, the Cochrane Central Register of Controlled Trials, Scopus, and relevant journals were searched using a combination of specific keywords ("platelet-rich fibrin," "oral surgery," and "third molar"). The final search was conducted on November 2, 2015. Randomized controlled clinical trials, as well as controlled clinical trials, aimed at comparing the effect of PRF versus natural healing after extraction of mandibular third molars were included. Five randomized controlled trials and one controlled clinical trial were included. There were 335 extractions (168 with PRF and 167 controls) in 183 participants. Considerable heterogeneity in study characteristics, outcome variables, and estimated scales was observed. Positive results were generally recorded for pain, trismus, swelling, periodontal pocket depth, soft tissue healing, and incidence of localized osteitis, but not in all studies. However, no meta-analysis could be conducted for such variables because of the different measurement scales used. The qualitative and meta-analysis results showed no significant improvement in bone healing with PRF-treated sockets compared with the naturally healing sockets. Within the limitations of the available evidence, PRF seems to have no beneficial role in bone healing after extraction of the mandibular third molars. Future standardized randomized controlled clinical trials are required to estimate the effect of PRF on socket regeneration. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Managing Multi-Center Recruitment in the PLCO Cancer Screening Trial.

PubMed

Gohagan, John K; Broski, Karen; Gren, Lisa H; Fouad, Mona N; Higgins, Darlene; Lappe, Karen; Ogden, Sheryl; Shambaugh, Vicki; Pinsky, Paul F; O'Brien, Barbara; Yurgalevich, Susan; Riley, Tom; Wright, Patrick; Prorok, Philip C

2015-01-01

There were significant recruitment challenges specific to the PLCO Cancer Screening Trial. Large numbers of participants were to be randomized from ten catchment areas nationwide within time and budgetary constraints. The eligible population was elderly and had to meet health and behavioral thresholds. Informed consent was required to participate and be randomized to screening for three cancers at periodic clinic visits or to a usual care arm that included no clinical visits. Consenting required special efforts to fully explain the trial and its potential scientific benefit to future patients with potentially no benefits but possible harms to PLCO participants. Participation would include continued follow-up for at least 13 years after randomization. Strong collaborative investments were required by the NCI and screening centers (SCs) to assure timely recruitment and appropriate racial participation. A trial-wide pilot phase tested recruitment and protocol follow through at SCs and produced a vanguard population of 11,406 participants. NCI announced the trial nationally in advance of the pilot and followed with an even more intense collaborative role with SCs for the main phase to facilitate trial-wide efficient and timely recruitment. Special efforts to enhance recruitment in the main phase included centralized and local monitoring of progress, cross-linking SCs to share experiences in problem solving, centralized training, substantial additional funding dedicated to recruitment and retention, including specialized programs for minority recruitment, obtaining national endorsement by the American Cancer Society, launching satellite recruitment and screening centers, including minority focused satellites, and adding a new SC dedicated to minority recruitment.

PRagmatic trial Of Video Education in Nursing homes: The design and rationale for a pragmatic cluster randomized trial in the nursing home setting.

PubMed

Mor, Vincent; Volandes, Angelo E; Gutman, Roee; Gatsonis, Constantine; Mitchell, Susan L

2017-04-01

Background/Aims Nursing homes are complex healthcare systems serving an increasingly sick population. Nursing homes must engage patients in advance care planning, but do so inconsistently. Video decision support tools improved advance care planning in small randomized controlled trials. Pragmatic trials are increasingly employed in health services research, although not commonly in the nursing home setting to which they are well-suited. This report presents the design and rationale for a pragmatic cluster randomized controlled trial that evaluated the "real world" application of an Advance Care Planning Video Program in two large US nursing home healthcare systems. Methods PRagmatic trial Of Video Education in Nursing homes was conducted in 360 nursing homes (N = 119 intervention/N = 241 control) owned by two healthcare systems. Over an 18-month implementation period, intervention facilities were instructed to offer the Advance Care Planning Video Program to all patients. Control facilities employed usual advance care planning practices. Patient characteristics and outcomes were ascertained from Medicare Claims, Minimum Data Set assessments, and facility electronic medical record data. Intervention adherence was measured using a Video Status Report embedded into electronic medical record systems. The primary outcome was the number of hospitalizations/person-day alive among long-stay patients with advanced dementia or cardiopulmonary disease. The rationale for the approaches to facility randomization and recruitment, intervention implementation, population selection, data acquisition, regulatory issues, and statistical analyses are discussed. Results The large number of well-characterized candidate facilities enabled several unique design features including stratification on historical hospitalization rates, randomization prior to recruitment, and 2:1 control to intervention facilities ratio. Strong endorsement from corporate leadership made randomization prior to recruitment feasible with 100% participation of facilities randomized to the intervention arm. Critical regulatory issues included minimal risk determination, waiver of informed consent, and determination that nursing home providers were not engaged in human subjects research. Intervention training and implementation were initiated on 5 January 2016 using corporate infrastructures for new program roll-out guided by standardized training elements designed by the research team. Video Status Reports in facilities' electronic medical records permitted "real-time" adherence monitoring and corrective actions. The Centers for Medicare and Medicaid Services Virtual Research Data Center allowed for rapid outcomes ascertainment. Conclusion We must rigorously evaluate interventions to deliver more patient-focused care to an increasingly frail nursing home population. Video decision support is a practical approach to improve advance care planning. PRagmatic trial Of Video Education in Nursing homes has the potential to promote goal-directed care among millions of older Americans in nursing homes and establish a methodology for future pragmatic randomized controlled trials in this complex healthcare setting.

Nitrofurantoin vs other prophylactic agents in reducing recurrent urinary tract infections in adult women: a systematic review and meta-analysis.

PubMed

Price, Jameca Renee; Guran, Larissa A; Gregory, W Thomas; McDonagh, Marian S

2016-11-01

The clinical and financial burden from bladder infections is significant. Daily antibiotic use is the recommended strategy for recurrent urinary tract infection prevention. Increasing antibiotic resistance rates, however, require immediate identification of innovative alternative prophylactic therapies. This systematic review aims to provide guidance on gaps in evidence to guide future research. The objective of this review was to provide current pooled estimates of randomized control trials comparing the effects of nitrofurantoin vs other agents in reducing recurrent urinary tract infections in adult, nonpregnant women and assess relative adverse side effects. Data sources included the following: MEDLINE, Jan. 1, 1946, to Jan. 31, 2015; Cochrane Central Register of Controlled Trials the Cochrane Database of Systematic Reviews, and web sites of the National Institute for Clinical Excellence, and the National Guideline Clearinghouse from 2000 to 2015. Randomized control trials of women with recurrent urinary tract infections comparing nitrofurantoin with any other treatment were included. A protocol for the study was developed a priori. Published guidance was followed for assessment of study quality. All meta-analyses were performed using random-effects models with Stats Direct Software. Dual review was used for all decisions and data abstraction. Twelve randomized control trials involving 1063 patients were included. One study that had a serious flaw was rated poor in quality, one study rated good, and the remainder fair. No significant differences in prophylactic antibiotic treatment with nitrofurantoin and norfloxacin, trimethoprim, sulfamethoxazole/trimethoprim, methamine hippurate, estriol, or cefaclor were found in clinical or microbiological cure in adult nonpregnant women with recurrent urinary tract infections (9 randomized control trials, 673 patients, relative risk ratio, 1.06; 95% confidence interval, 0.89-1.27; I 2 , 65%; and 12 randomized control trials, 1063 patients, relative risk ratio, 1.06; 95% confidence interval, 0.90-1.26; I 2 , 76%, respectively). Duration of prophylaxis also did not have a significant impact on outcomes. There was a statistically significant difference in overall adverse effects, with nitrofurantoin resulting in greater risk than other prophylactic treatments (10 randomized control trials, 948 patients, relative risk ratio, 2.17; 95% confidence interval, 1.34-3.50; I 2 , 61%). Overall, the majority of nitrofurantoin adverse effects were gastrointestinal, with a significant difference for withdrawals (12 randomized control trials, 1063 patients, relative risk ratio, 2.14; 95% confidence interval, 1.28-3.56; I 2 , 8%). Nitrofurantoin had similar efficacy but a greater risk of adverse events than other prophylactic treatments. Balancing the risks of adverse events, particularly gastrointestinal symptoms, with potential benefits of decreasing collateral ecological damage should be considered if selecting nitrofurantoin. Copyright © 2016 Elsevier Inc. All rights reserved.

Testing an alternate informed consent process.

PubMed

Yates, Bernice C; Dodendorf, Diane; Lane, Judy; LaFramboise, Louise; Pozehl, Bunny; Duncan, Kathleen; Knodel, Kendra

2009-01-01

One of the main problems in conducting clinical trials is low participation rate due to potential participants' misunderstanding of the rationale for the clinical trial or perceptions of loss of control over treatment decisions. The objective of this study was to test an alternate informed consent process in cardiac rehabilitation participants that involved the use of a multimedia flip chart to describe a future randomized clinical trial and then asked, hypothetically, if they would participate in the future trial. An attractive and inviting visual presentation of the study was created in the form of a 23-page flip chart that included 24 color photographs displaying information about the purpose of the study, similarities and differences between the two treatment groups, and the data collection process. We tested the flip chart in 35 cardiac rehabilitation participants. Participants were asked if they would participate in this future study on two occasions: immediately after the description of the flip chart and 24 hours later, after reading through the informed consent document. Participants were also asked their perceptions of the flip chart and consent process. Of the 35 participants surveyed, 19 (54%) indicated that they would participate in the future study. No participant changed his or her decision 24 hours later after reading the full consent form. The participation rate improved 145% over that of an earlier feasibility study where the recruitment rate was 22%. Most participants stated that the flip chart was helpful and informative and that the photographs were effective in communicating the purpose of the study. Participation rates could be enhanced in future clinical trials by using a visual presentation to explain and describe the study as part of the informed consent process. More research is needed to test alternate methods of obtaining informed consent.

Influence of Prior Heart Failure Hospitalization on Cardiovascular Events in Patients with Reduced and Preserved Ejection Fraction

PubMed Central

Bello, Natalie A.; Claggett, Brian; Desai, Akshay S.; McMurray, John J.V.; Granger, Christopher B.; Yusuf, Salim; Swedberg, Karl; Pfeffer, Marc A.; Solomon, Scott D.

2014-01-01

Background Hospitalization for acute heart failure (HF) is associated with high rates of subsequent mortality and readmission. We assessed the influence of the time interval between prior HF hospitalization and randomization in the CHARM trials on clinical outcomes in patients with both reduced and preserved ejection fraction. Methods and Results CHARM enrolled 7,599 patients with NYHA class II-IV heart failure, of whom 5,426 had a history of prior HF hospitalization. Cox proportional hazards regression models were utilized to assess the association between time from prior HF hospitalization and randomization and the primary outcome of cardiovascular death or unplanned admission to hospital for the management of worsening HF over a median of 36.6 months. For patients with HF and reduced (HFrEF) or preserved (HFpEF) ejection fraction, rates of CV mortality and HF hospitalization were higher among patients with prior HF hospitalization than those without. The risk for mortality and hospitalization varied inversely with the time interval between hospitalization and randomization. Rates were higher for HFrEF patients within each category. Event rates for those with HFpEF and a HF hospitalization in the 6 months prior to randomization were comparable to the rate in HFrEF patients with no prior HF hospitalization. Conclusions Rates of CV death or HF hospitalization are greatest in those who have been previously hospitalized for HF. Independent of EF, rates of death and readmission decline as time from HF hospitalization to trial enrollment increased. Recent HF hospitalization identifies a high risk population for future clinical trials in HFrEF and HFpEF. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00634400. PMID:24874200

Rationale and Design of the "Safety and Efficacy of the Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) Trial:" A Double-Blind, Randomized, Placebo-Controlled Study to Determine the Effect of Combined Diuretic Therapy (Loop Diuretics With Thiazide-Type Diuretics) Among Patients With Decompensated Heart Failure.

PubMed

Trullàs, Joan Carles; Morales-Rull, José Luís; Casado, Jesús; Freitas Ramírez, Adriana; Manzano, Luís; Formiga, Francesc

2016-07-01

Fluid overload refractory to loop diuretic therapy can complicate acute or chronic heart failure (HF) management. The Safety and Efficacy of the Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) trial (Clinicaltrials.gov identifier NCT01647932) will test the hypothesis that blocking distal tubule sodium reabsorption with hydrochlorothiazide can antagonize the renal adaptation to chronic loop diuretic therapy and improve diuretic resistance. CLOROTIC is a randomized, placebo-controlled, double-blind, multicenter study. Three hundred and four patients with decompensated HF will be randomly assigned to receive hydrochlorothiazide or placebo in addition to a furosemide regimen. The main inclusion criteria are: age ≥18 years, history of chronic HF (irrespective of etiology and/or ejection fraction), admission for acute decompensation, and previous treatment with an oral loop diuretic for at least 1 month before randomization. The 2 coprimary endpoints are changes in body weight and changes in patient-reported dyspnea during hospital admission. Morbidity, mortality, and safety aspects will also be addressed. CLOROTIC is the first large-scale trial to evaluate whether the addition of a thiazide diuretic (hydrochlorothiazide) to a loop diuretic (furosemide) is a safe and effective strategy for improving congestive symptoms resulting from HF. This trial will provide important information and will therefore have a major impact on treatment strategies and future trials in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial.

PubMed

Kasner, Scott E; Lavados, Pablo; Sharma, Mukul; Wang, Yongjun; Wang, Yilong; Dávalos, Antoni; Shamalov, Nikolay; Cunha, Luis; Lindgren, Arne; Mikulik, Robert; Arauz, Antonio; Lang, Wilfried; Czlonkowska, Anna; Eckstein, Jens; Gagliardi, Rubens; Amarenco, Pierre; Ameriso, Sebastián F; Tatlisumak, Turgut; Veltkamp, Roland; Hankey, Graeme J; Toni, Danilo S; Bereczki, Daniel; Uchiyama, Shinichiro; Ntaios, George; Yoon, Byung-Woo; Brouns, Raf; DeVries Basson, M M; Endres, Matthias; Muir, Keith; Bornstein, Natan; Ozturk, Serefnur; O'Donnell, Martin; Mundl, Hardi; Pater, Calin; Weitz, Jeffrey; Peacock, W Frank; Swaminathan, Balakumar; Kirsch, Bodo; Berkowitz, Scott D; Peters, Gary; Pare, Guillaume; Themeles, Ellison; Shoamanesh, Ashkan; Connolly, Stuart J; Hart, Robert G

2018-06-01

The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Using the MEDiPORT humanoid robot to reduce procedural pain and distress in children with cancer: A pilot randomized controlled trial.

PubMed

Jibb, Lindsay A; Birnie, Kathryn A; Nathan, Paul C; Beran, Tanya N; Hum, Vanessa; Victor, J Charles; Stinson, Jennifer N

2018-06-12

Subcutaneous port needle insertions are painful and distressing for children with cancer. The interactive MEDiPORT robot has been programmed to implement psychological strategies to decrease pain and distress during this procedure. This study assessed the feasibility of a future MEDiPORT trial. The secondary aim was to determine the preliminary effectiveness of MEDiPORT in reducing child pain and distress during subcutaneous port accesses. This 5-month pilot randomized controlled trial used a web-based service to randomize 4- to 9-year-olds with cancer to the MEDiPORT cognitive-behavioral arm (robot using evidence-based cognitive-behavioral interventions) or active distraction arm (robot dancing and singing) while a nurse conducted a needle insertion. We assessed accrual and retention; technical difficulties; outcome measure completion by children, parents, and nurses; time taken to complete the study and clinical procedure; and child-, parent-, and nurse-rated acceptability. Descriptive analyses, with exploratory inferential testing of child pain and distress data, were used to address study aims. Forty children were randomized across study arms. Most (85%) eligible children participated and no children withdrew. Technical difficulties were more common in the cognitive-behavioral arm. Completion times for the study and needle insertion were acceptable and >96% of outcome measure items were completed. Overall, MEDiPORT and the study were acceptable to participants. There was no difference in pain between arms, but distress during the procedure was less pronounced in the active distraction arm. The MEDiPORT study appears feasible to implement as an adequately-powered effectiveness-assessing trial following modifications to the intervention and study protocol. ClinicalTrials.gov NCT02611739. © 2018 Wiley Periodicals, Inc.

Impact of vitamin D supplementation on the outcome of tuberculosis treatment: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Xia, Jingyan; Shi, Liyun; Zhao, Lifang; Xu, Feng

2014-01-01

Vitamin D supplementation is believed to be beneficial in the treatment of patients with tuberculosis (TB), however, results from clinical trials have been inconclusive. We performed a systematic literature search across MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Springer, EBSCO, ProQuest, HighWire Press, and Web of Science, published as of December 2013. We individually inspected citations and extracted data independently. We estimated pooled risk ratios (RR) and 95% confidence intervals (CI) using random-effect models. We also assessed risk of bias using the Jadad scale and the quality of the evidence using GRADE. We included all randomized controlled trials comparing vitamin D with or without standard TB therapy or placebo. A total of five studies were analyzed in our meta analysis covering 841 newly-diagnosed TB cases. Patients receiving vitamin D supplementation had a 39% reduced risk of sputum smear or culture positive after six weeks of anti-TB treatment than those in the control group, although this is not statistically significant (pooled RR 0.61, 95% CI 0.24 to 1.56, P = 0.30). Apart from an increased serum vitamin D level in the supplement group after eight weeks of treatment there was no evidence of any additional adverse effects related to vitamin D. The meta analysis results indicate that vitamin D supplementation does not seem to have any beneficial effect in the treatment of TB. Future rigorous randomized controlled trials are needed to explore whether the supplementation of vitamin D could shorten treatment duration and to confirm whether the polymorphisms of vitamin D receptor have any potentially beneficial effect.

'On Your Feet to Earn Your Seat', a habit-based intervention to reduce sedentary behaviour in older adults: study protocol for a randomized controlled trial.

PubMed

Gardner, Benjamin; Thuné-Boyle, Ingela; Iliffe, Steve; Fox, Kenneth R; Jefferis, Barbara J; Hamer, Mark; Tyler, Nick; Wardle, Jane

2014-09-20

Many older adults are both highly sedentary (that is, spend considerable amounts of time sitting) and physically inactive (that is, do little physical activity). This protocol describes an exploratory trial of a theory-based behaviour change intervention in the form of a booklet outlining simple activities ('tips') designed both to reduce sedentary behaviour and to increase physical activity in older adults. The intervention is based on the 'habit formation' model, which proposes that consistent repetition leads to behaviour becoming automatic, sustaining activity gains over time. The intervention is being developed iteratively, in line with Medical Research Council complex intervention guidelines. Selection of activity tips was informed by semi-structured interviews and focus groups with older adults, and input from a multidisciplinary expert panel. An ongoing preliminary field test of acceptability among 25 older adults will inform further refinement. An exploratory randomized controlled trial will be conducted within a primary care setting, comparing the tips booklet with a control fact sheet. Retired, inactive and sedentary adults (n = 120) aged 60 to 74 years, with no physical impairments precluding light physical activity, will be recruited from general practices in north London, UK. The primary outcomes are recruitment and attrition rates. Secondary outcomes are changes in behaviour, habit, health and wellbeing over 12 weeks. Data will be used to inform study procedures for a future, larger-scale definitive randomized controlled trial. Current Controlled Trials ISRCTN47901994.

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

PubMed

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

2017-08-01

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

Effectiveness of Chinese massage therapy (Tui Na) for chronic low back pain: study protocol for a randomized controlled trial.

PubMed

Yang, Mingxiao; Feng, Yue; Pei, Hong; Deng, Shufang; Wang, Minyu; Xiao, Xianjun; Zheng, Hui; Lai, Zhenhong; Chen, Jiao; Li, Xiang; He, Xiaoguo; Liang, Fanrong

2014-10-29

Low back pain is a common, disabling musculoskeletal disorder in both developing and developed countries. Although often recommended, the potential efficacy of massage therapy in general, and Chinese massage (tuina) in particular, for relief of chronic low back pain (CLBP) has not been fully established due to inadequate sample sizes, low methodological quality, and subclinical dosing regimens of trials to date. Thus, the purpose of this randomized controlled trial (RCT) is to evaluate the comparative effectiveness of tuina massage therapy versus conventional analgesics for CLBP. The present study is a single center, two-arm, open-label RCT. A total of 150 eligible CLBP patients will be randomly assigned to either a tuina treatment group or a conventional drug control group in a 1:1 ratio. Patients in the tuina group receive a 20 minutes, 4-step treatment protocol which includes both structural and relaxation massage, administered in 20 sessions over a period of 4 weeks. Patients in the conventional drug control group are instructed to take a specific daily dose of ibuprofen. The primary outcome measure is the change from baseline back pain and function, measured by Roland-Morris Disability Questionnaire, at two months. Secondary outcome measures include the visual analogue scale, Japanese orthopedic association score (JOAS), and McGill pain questionnaire. The design and methodological rigor of this trial will allow for collection of valuable data to evaluate the efficacy of a specific tuina protocol for treating CLBP. This trial will therefore contribute to providing a solid foundation for clinical treatment of CLBP, as well as future research in massage therapy. This trial was registered with ClinicalTrials.gov of the National Institute of Health on 22 October 2013 (http://NCT01973010).

Effectiveness of electroacupuncture for polycystic ovary syndrome: study protocol for a randomized controlled trial.

PubMed

Chen, Jiao; Feng, Shuwei; Zeng, Jiuzhi; Wu, Xi; Yang, Mingxiao; Tang, Hongzhi; Fan, Huaying; Yang, Jie; Liang, Fanrong

2016-05-21

Whether electroacupuncture is effective for patients with polycystic ovary syndrome is still inconclusive. Therefore, this study aims to evaluate the add-on effects of electroacupuncture to conventional drugs for the treatment of polycystic ovary syndrome. This study is a two-center, open-labeled, randomized, controlled trial. A total of 116 eligible patients with polycystic ovary syndrome will be randomly allocated in a 1:1 ratio to the electroacupuncture plus clomiphene citrate group or to the clomiphene citrate group. Participants in the electroacupuncture plus clomiphene citrate group will receive electroacupuncture treatment in addition to clomiphene citrate capsules, whereas participants in the clomiphene citrate group will be prescribed clomiphene citrate capsules only. Electroacupuncture treatment will be performed from the fifth day of menstruation or withdrawal bleeding until the next menstruation, in three sessions per week for three menstrual cycles. The primary outcome is the ovulation rate. The secondary outcomes include the dominant follicle rate, mean number of dominant follicles, endometrial thickness, time point of ovulation, follicular size before ovulation, luteinizing hormone, estradiol level, and pregnancy rate. The measuring points for outcomes will be baseline and the completion of treatment. Any adverse events occurring during the trial process will be recorded. In addition, a quality-monitoring group independent from the research team will be set up to control the quality of the trial. The design and methodological rigor of this trial will allow for the collection of valuable data to evaluate the effectiveness of electroacupuncture for treating polycystic ovary syndrome. Therefore, this trial will contribute reliable evidence for use in clinical decision-making in acupuncture therapy of polycystic ovary syndrome as well as to future research in acupuncture for polycystic ovary syndrome. Chinese Clinical Trial Registry, ChiCTR-IOR-15007358 , registered on 26 October 2015.

Clinical trials attitudes and practices of Latino physicians.

PubMed

Ramirez, Amelie G; Wildes, Kimberly; Talavera, Greg; Nápoles-Springer, Anna; Gallion, Kipling; Pérez-Stable, Eliseo J

2008-07-01

Ethnic differences in physicians' attitudes and behaviors related to clinical trials might partially account for disparities in clinical trial participation among Latino patients. Literature regarding Latino physicians' clinical trials attitudes and practices, in comparison to White physicians, was lacking. Cross-sectional data from randomly selected physicians (N=695), stratified by ethnicity, were analyzed to test associations of ethnicity with physicians' participation in and attitudes toward referral of patients to clinical trials. Chi-square analyses showed significant (p<0.05) associations of physician race/ethnicity and clinical trials involvement, type of trial for which the physician is likely to recommend a patient, belief in scientific value, and factors that would influence recommendation for a patient to participate. Multivariate analyses resulted in several significant (p<0.05) predictors of clinical trials outcomes, including physician race/ethnicity. Latino physicians were significantly less involved in clinical trials than White physicians and found less scientific value in them, highlighting areas for future education and intervention.

The patient perspective on remote monitoring of patients with an implantable cardioverter defibrillator: Narrative review and future directions.

PubMed

Timmermans, Ivy; Meine, Matias; Zitron, Edgar; Widdershoven, Jos; Kimman, Geert; Prevot, Sébastien; Rauwolf, Thomas; Anselme, Frédéric; Szendey, Istvan; Romero Roldán, Javier; Mabo, Philippe; Schaer, Beat; Denollet, Johan; Versteeg, Henneke

2017-07-01

Studies have shown that remote patient monitoring (RPM) of implantable cardioverter defibrillators (ICDs) is at least comparable to in-clinic follow-up with regard to clinical outcomes and might be cost-effective, yet RPM is not standard clinical practice within Europe. Better insight into the patient perspective on RPM may aid in its acceptance, implementation, and reimbursement. This narrative review (1) summarizes existing evidence on the impact of RPM on patient-reported outcomes and (2) discusses future directions in examining the patient perspective. Literature review indicated that only five randomized trials on RPM in ICD patients included patient-reported outcomes, with inconclusive results. Observational studies show a trend toward good patient satisfaction and acceptation of RPM. Yet, results should be interpreted with caution due to a number of limitations including a potential selection bias, use of generic/nonvalidated questionnaires, relatively short follow-up durations, and a lack of subgroup identification. Although RPM seems to be safe, effective, timely, and efficient, the patient perspective has received little attention so far. The scarce evidence on patient-reported outcomes in RPM studies seems to be positive, but future trials with a follow-up of ≥12 months and validated patient-reported outcome measures are needed. The REMOTE-CIED study from our group is the first prospective randomized controlled trial primarily designed to examine the patient perspective on RPM, and is powered to identify characteristics associated with RPM satisfaction and benefit. Results are expected in 2018 and will add valuable information to the current evidence. © 2017 Wiley Periodicals, Inc.

A preliminary investigation on the efficacy of N-acetyl cysteine for mania or hypomania.

PubMed

Magalhães, Pedro Vieira da Silva; Dean, Olivia M; Bush, Ashley I; Copolov, David L; Malhi, Gin S; Kohlmann, Kristy; Jeavons, Susan; Schapkaitz, Ian; Anderson-Hunt, Murray; Berk, Michael

2013-06-01

Oxidative imbalance has emerged as a treatment target in bipolar disorder. As very limited data are available on the clinical use of antioxidants for mania, we report here results from a post hoc and exploratory subgroup analysis of a randomized, placebo-controlled trial of N-acetyl cysteine (NAC). This was a placebo-controlled, randomized, clinical trial assessing the effect of NAC over 24 weeks in mania or hypomania. Symptomatic and functional outcomes were collected over the study period. Fifteen participants were available for this report; two participants in each group failed to complete all assessments. Within-group analyses pointed to an improvement in the NAC group on manic symptoms and worsening in the placebo group on depressive symptoms at endpoint. Although the sample size was small, these results indicated within-group efficacy for this glutathione precursor as compared to placebo. Future trials specifically designed to demonstrate the efficacy of NAC in mania are needed.

Influences of Deqi on Immediate Analgesia Effect of Needling SP6 (Sanyinjiao) in Patients with Primary Dysmenorrhea in Cold and Dampness Stagnation Pattern: Study Protocol for a Randomized Controlled Trial

PubMed Central

Liu, Yu-qi; Zhang, Peng; Xie, Jie-ping; Ma, Liang-xiao; Yuan, Hong-wen; Li, Jing; Lin, Chi; Wang, Pei; Yang, Guo-yan; Zhu, Jiang

2015-01-01

Deqi, according to traditional Chinese medicine, is a specific needle sensation during the retention of needles at certain acupoints and is considered to be necessary to produce therapeutic effects from acupuncture. Although some modern researches have showed that Deqi is essential for producing acupuncture analgesia and anesthesia, the data are not enough. It is a paper of a multicenter, randomized controlled study protocol, to evaluate the influences of Deqi on acupuncture SP6 in Cold and Dampness Stagnation pattern primary dysmenorrhea patients, in terms of reducing pain and anxiety, and to find out the relationship between Deqi and the temperature changes at SP6 (Sanyinjiao) and CV4 (Guanyuan). The results of this trial will be helpful to explain the role of Deqi in acupuncture analgesia and may provide a new objective index for measuring Deqi in the future study. This trial is registered with ChiCTR-TRC-13003086. PMID:26294921

Anal Cancer: An Examination of Radiotherapy Strategies

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

Glynne-Jones, Rob; Lim, Faye

2011-04-01

The Radiation Therapy Oncology Group 9811, ACCORD-03, and ACT II Phase III trials in anal cancer showed no benefit for cisplatin-based induction and maintenance chemotherapy, or radiation dose-escalation >59 Gy. This review examines the efficacy and toxicity of chemoradiation (CRT) in anal cancer, and discusses potential alternative radiotherapy strategies. The evidence for the review was compiled from randomized and nonrandomized trials of radiation therapy and CRT. A total of 103 retrospective/observational studies, 4 Phase I/II studies, 16 Phase II prospective studies, 2 randomized Phase II studies, and 6 Phase III trials of radiotherapy or chemoradiation were identified. There are nomore » meta-analyses based on individual patient data. A 'one-size-fits-all' approach for all stages of anal cancer is inappropriate. Early T1 tumors are probably currently overtreated, whereas T3/T4 lesions might merit escalation of treatment. Intensity-modulated radiotherapy or the integration of biological therapy may play a role in future.« less

Taxonomy for colorectal cancer screening promotion: Lessons from recent randomized controlled trials.

PubMed

Ritvo, Paul; Myers, Ronald E; Serenity, Mardie; Gupta, Samir; Inadomi, John M; Green, Beverly B; Jerant, Anthony; Tinmouth, Jill; Paszat, Lawrence; Pirbaglou, Meysam; Rabeneck, Linda

2017-08-01

To derive a taxonomy for colorectal cancer screening that advances Randomized Controlled Trials (RCTs) and screening uptake. Detailed publication review, multiple interviews with principal investigators (PIs) and collaboration with PIs as co-authors produced a CRCS intervention taxonomy. Semi-structured interview questions with PIs (Drs. Inadomi, Myers, Green, Gupta, Jerant and Ritvo) yielded details about trial conduct. Interview comparisons led to an iterative process informing serial interviews until a consensus was obtained on final taxonomy structure. These taxonomy headings (Engagement Sponsor, Population Targeted, Alternative Screening Tests, Delivery Methods, and Support for Test Performance (EPADS)) were used to compare studies. Exemplary insights emphasized: 1) direct test delivery to patients; 2) linguistic-ethnic matching of staff to minority subjects; and 3) authorization of navigators to schedule or refer for colonoscopies and/or distribute stool blood tests during screening promotion. PIs of key RCTs (2012-2015) derived a CRCS taxonomy useful in detailed examination of CRCS promotion and design of future RCTs. Copyright © 2017 Elsevier Inc. All rights reserved.

Qualitative exploration of a smoking cessation trial for people living with HIV in South Africa.

PubMed

Krishnan, Nandita; Gittelsohn, Joel; Ross, Alexandra; Elf, Jessica; Chon, Sandy; Niaura, Raymond; Martinson, Neil; Golub, Jonathan E

2017-06-16

In South Africa, people living with HIV (PLWH) have a high prevalence of smoking, which undermines the beneficial effects of antiretroviral therapy (ART). However, little is known about barriers to smoking cessation and what interventions work for PLWH in this setting. A randomized trial comparing intensive anti-smoking counseling versus counseling and nicotine replacement therapy (NRT) was recently concluded in Klerksdorp, South Africa. In a post-trial follow-up, 23 in-depth interviews with patients and one focus group discussion with counselors from the trial were conducted. A codebook was developed and codes were applied to the transcripts, which were analyzed using a thematic analysis. Barriers at the economic, social/interpersonal, and individual levels induced stress, which hindered smoking cessation. Economic stressors included unemployment and poverty. Social or interpersonal stressors were lack of social support for quitting smoking and lack of social support due to having HIV. Individual stressors were traumatic life events. Alcohol was used to cope with stress and frequently co-occurred with smoking. Managing cravings was a barrier unrelated to stress. Participants proposed income and employment opportunities, group counseling and more frequent counseling as solutions to address stressors at different levels. NRT was helpful to mitigate cravings. Future smoking cessation interventions need to target barriers at multiple levels. Increasing the supply and duration of NRT may increase its effectiveness. Other behavioral approaches such as group counseling or peer counseling could hold promise in this setting but need to be tested for efficacy through randomized controlled trials. To our knowledge, this is the first qualitative study examining barriers to smoking cessation for people living with HIV in South Africa. Smoking is highly prevalent among people with HIV in South Africa and cessation interventions are urgently needed. A better understanding of barriers to smoking cessation that people with HIV face will lead to the development of contextually appropriate interventions. This study also provides feedback on interventions from a recently concluded smoking cessation randomized trial and will help guide the design of future smoking cessation trials. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Designing clinical trials of interventions for mobility disability: results from the lifestyle interventions and independence for elders pilot (LIFE-P) trial.

PubMed

Espeland, Mark A; Gill, Thomas M; Guralnik, Jack; Miller, Michael E; Fielding, Roger; Newman, Anne B; Pahor, Marco

2007-11-01

Clinical trials to assess interventions for mobility disability are critically needed; however, data for efficiently designing such trials are lacking. Results are described from a pilot clinical trial in which 424 volunteers aged 70-89 years were randomly assigned to one of two interventions-physical activity or a healthy aging education program-and followed for a planned minimum of 12 months. We evaluated the longitudinal distributions of four standardized outcomes to contrast how they may serve as primary outcomes of future clinical trials: ability to walk 400 meters, ability to walk 4 meters in < or =10 seconds, a physical performance battery, and a questionnaire focused on physical function. Changes in all four outcomes were interrelated over time. The ability to walk 400 meters as a dichotomous outcome provided the smallest sample size projections (i.e., appeared to be the most efficient outcome). It loaded most heavily on the underlying latent variable in structural equation modeling with a weight of 80%. A 4-year trial based on the outcome of the 400-meter walk is projected to require N = 962-2234 to detect an intervention effect of 30%-20% with 90% power. Future clinical trials of interventions designed to influence mobility disability may have greater efficiency if they adopt the ability to complete a 400-meter walk as their primary outcome.

Prophylaxis of Radiation-Induced Nausea and Vomiting Using 5-Hydroxytryptamine-3 Serotonin Receptor Antagonists: A Systematic Review of Randomized Trials

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

Salvo, Nadia; Doble, Brett; Khan, Luluel

Purpose: To systematically review the effectiveness and safety of 5-hydroxytryptamine-3 receptor antagonists (5-HT3 RAs) compared with other antiemetic medication or placebo for prophylaxis of radiation-induced nausea and vomiting. Methods and Materials: We searched the following electronic databases: MEDLINE, Embase, the Cochrane Central Register of Controlled Clinical Trials, and Web of Science. We also hand-searched reference lists of included studies. Randomized, controlled trials that compared a 5-HT3 RA with another antiemetic medication or placebo for preventing radiation-induced nausea and vomiting were included. We excluded studies recruiting patients receiving concomitant chemotherapy. When appropriate, meta-analysis was conducted using Review Manager (v5) software. Relativemore » risks were calculated using inverse variance as the statistical method under a random-effects model. We assessed the quality of evidence by outcome using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: Eligibility screening of 47 articles resulted in 9 included in the review. The overall methodologic quality was moderate. Meta-analysis of 5-HT3 RAs vs. placebo showed significant benefit for 5-HT3 RAs (relative risk [RR] 0.70; 95% confidence interval [CI] 0.57-0.86 for emesis; RR 0.84, 95% CI 0.73-0.96 for nausea). Meta-analysis comparing 5-HT3 RAs vs. metoclopramide showed a significant benefit of the 5-HT3 RAs for emetic control (RR 0.27, 95% CI 0.15-0.47). Conclusion: 5-Hydroxytryptamine-3 RAs are superior to placebo and other antiemetics for prevention of emesis, but little benefit was identified for nausea prevention. 5-Hydroxytryptamine-3 RAs are suggested for prevention of emesis. Limited evidence was found regarding delayed emesis, adverse events, quality of life, or need for rescue medication. Future randomized, controlled trials should evaluate different 5-HT3 antiemetics and new agents with novel mechanisms of action such at the NK{sub 1} receptor antagonists to determine the most effective drug. Delayed nausea and vomiting should be a focus of future study, perhaps concentrating on the palliative cancer population.« less

Systematic review on randomized controlled clinical trials of acupuncture therapy for neurovascular headache.

PubMed

Zhao, Lei; Guo, Yi; Wang, Wei; Yan, Li-juan

2011-08-01

To evaluate the effectiveness of acupuncture as a treatment for neurovascular headache and to analyze the current situation related to acupuncture treatment. PubMed database (1966-2010), EMBASE database (1986-2010), Cochrane Library (Issue 1, 2010), Chinese Biomedical Literature Database (1979-2010), China HowNet Knowledge Database (1979-2010), VIP Journals Database (1989-2010), and Wanfang database (1998-2010) were retrieved. Randomized or quasi-randomized controlled studies were included. The priority was given to high-quality randomized, controlled trials. Statistical outcome indicators were measured using RevMan 5.0.20 software. A total of 16 articles and 1 535 cases were included. Meta-analysis showed a significant difference between the acupuncture therapy and Western medicine therapy [combined RR (random efficacy model)=1.46, 95% CI (1.21, 1.75), Z=3.96, P<0.0001], indicating an obvious superior effect of the acupuncture therapy; significant difference also existed between the comprehensive acupuncture therapy and acupuncture therapy alone [combined RR (fixed efficacy model)=3.35, 95% CI (1.92, 5.82), Z=4.28, P<0.0001], indicating that acupuncture combined with other therapies, such as points injection, scalp acupuncture, auricular acupuncture, etc., were superior to the conventional body acupuncture therapy alone. The inclusion of limited clinical studies had verified the efficacy of acupuncture in the treatment of neurovascular headache. Although acupuncture or its combined therapies provides certain advantages, most clinical studies are of small sample sizes. Large sample size, randomized, controlled trials are needed in the future for more definitive results.

OPTIM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma.

PubMed

Kaufman, Howard L; Bines, Steven D

2010-06-01

There are few effective treatment options available for patients with advanced melanoma. An oncolytic herpes simplex virus type 1 encoding granulocyte macrophage colony-stimulating factor (GM-CSF; Oncovex(GM-CSF)) for direct injection into accessible melanoma lesions resulted in a 28% objective response rate in a Phase II clinical trial. Responding patients demonstrated regression of both injected and noninjected lesions highlighting the dual mechanism of action of Oncovex(GM-CSF) that includes both a direct oncolytic effect in injected tumors and a secondary immune-mediated anti-tumor effect on noninjected tumors. Based on these preliminary results a prospective, randomized Phase III clinical trial in patients with unresectable Stage IIIb or c and Stage IV melanoma has been initiated. The rationale, study design, end points and future development of the Oncovex(GM-CSF) Pivotal Trial in Melanoma (OPTIM) trial are discussed in this article.

Randomized trials published in some Chinese journals: how many are randomized?

PubMed

Wu, Taixiang; Li, Youping; Bian, Zhaoxiang; Liu, Guanjian; Moher, David

2009-07-02

The approximately 1100 medical journals now active in China are publishing a rapidly increasing number of research reports, including many studies identified by their authors as randomized controlled trials. It has been noticed that these reports mostly present positive results, and their quality and authenticity have consequently been called into question. We investigated the adequacy of randomization of clinical trials published in recent years in China to determine how many of them met acceptable standards for allocating participants to treatment groups. The China National Knowledge Infrastructure electronic database was searched for reports of randomized controlled trials on 20 common diseases published from January 1994 to June 2005. From this sample, a subset of trials that appeared to have used randomization methods was selected. Twenty-one investigators trained in the relevant knowledge, communication skills and quality control issues interviewed the original authors of these trials about the participant randomization methods and related quality-control features of their trials. From an initial sample of 37,313 articles identified in the China National Knowledge Infrastructure database, we found 3137 apparent randomized controlled trials. Of these, 1452 were studies of conventional medicine (published in 411 journals) and 1685 were studies of traditional Chinese medicine (published in 352 journals). Interviews with the authors of 2235 of these reports revealed that only 207 studies adhered to accepted methodology for randomization and could on those grounds be deemed authentic randomized controlled trials (6.8%, 95% confidence interval 5.9-7.7). There was no statistically significant difference in the rate of authenticity between randomized controlled trials of traditional interventions and those of conventional interventions. Randomized controlled trials conducted at hospitals affiliated to medical universities were more likely to be authentic than trials conducted at level 3 and level 2 hospitals (relative risk 1.58, 95% confidence interval 1.18-2.13, and relative risk 14.42, 95% confidence interval 9.40-22.10, respectively). The likelihood of authenticity was higher in level 3 hospitals than in level 2 hospitals (relative risk 9.32, 95% confidence interval 5.83-14.89). All randomized controlled trials of pre-market drug clinical trial were authentic by our criteria. Of the trials conducted at university-affiliated hospitals, 56.3% were authentic (95% confidence interval 32.0-81.0). Most reports of randomized controlled trials published in some Chinese journals lacked an adequate description of randomization. Similarly, most so called 'randomized controlled trials' were not real randomized controlled trials owing to a lack of adequate understanding on the part of the authors of rigorous clinical trial design. All randomized controlled trials of pre-market drug clinical trial included in this research were authentic. Randomized controlled trials conducted by authors in high level hospitals, especially in hospitals affiliated to medical universities had a higher rate of authenticity. That so many non-randomized controlled trials were published as randomized controlled trials reflected the fact that peer review needs to be improved and a good practice guide for peer review including how to identify the authenticity of the study urgently needs to be developed.

Randomized trials published in some Chinese journals: how many are randomized?

PubMed Central

Wu, Taixiang; Li, Youping; Bian, Zhaoxiang; Liu, Guanjian; Moher, David

2009-01-01

Background The approximately 1100 medical journals now active in China are publishing a rapidly increasing number of research reports, including many studies identified by their authors as randomized controlled trials. It has been noticed that these reports mostly present positive results, and their quality and authenticity have consequently been called into question. We investigated the adequacy of randomization of clinical trials published in recent years in China to determine how many of them met acceptable standards for allocating participants to treatment groups. Methods The China National Knowledge Infrastructure electronic database was searched for reports of randomized controlled trials on 20 common diseases published from January 1994 to June 2005. From this sample, a subset of trials that appeared to have used randomization methods was selected. Twenty-one investigators trained in the relevant knowledge, communication skills and quality control issues interviewed the original authors of these trials about the participant randomization methods and related quality-control features of their trials. Results From an initial sample of 37,313 articles identified in the China National Knowledge Infrastructure database, we found 3137 apparent randomized controlled trials. Of these, 1452 were studies of conventional medicine (published in 411 journals) and 1685 were studies of traditional Chinese medicine (published in 352 journals). Interviews with the authors of 2235 of these reports revealed that only 207 studies adhered to accepted methodology for randomization and could on those grounds be deemed authentic randomized controlled trials (6.8%, 95% confidence interval 5.9–7.7). There was no statistically significant difference in the rate of authenticity between randomized controlled trials of traditional interventions and those of conventional interventions. Randomized controlled trials conducted at hospitals affiliated to medical universities were more likely to be authentic than trials conducted at level 3 and level 2 hospitals (relative risk 1.58, 95% confidence interval 1.18–2.13, and relative risk 14.42, 95% confidence interval 9.40–22.10, respectively). The likelihood of authenticity was higher in level 3 hospitals than in level 2 hospitals (relative risk 9.32, 95% confidence interval 5.83–14.89). All randomized controlled trials of pre-market drug clinical trial were authentic by our criteria. Of the trials conducted at university-affiliated hospitals, 56.3% were authentic (95% confidence interval 32.0–81.0). Conclusion Most reports of randomized controlled trials published in some Chinese journals lacked an adequate description of randomization. Similarly, most so called 'randomized controlled trials' were not real randomized controlled trials owing toa lack of adequate understanding on the part of the authors of rigorous clinical trial design. All randomized controlled trials of pre-market drug clinical trial included in this research were authentic. Randomized controlled trials conducted by authors in high level hospitals, especially in hospitals affiliated to medical universities had a higher rate of authenticity. That so many non-randomized controlled trials were published as randomized controlled trials reflected the fact that peer review needs to be improved and a good practice guide for peer review including how to identify the authenticity of the study urgently needs to be developed. PMID:19573242

Achieving definitive results in long-chain polyunsaturated fatty acid supplementation trials of term infants: factors for consideration.

PubMed

Meldrum, Suzanne J; Smith, Michael A; Prescott, Susan L; Hird, Kathryn; Simmer, Karen

2011-04-01

Numerous randomized controlled trials (RCTs) have been undertaken to determine whether supplementation with long-chain polyunsaturated fatty acids (LCPUFAs) in infancy would improve the developmental outcomes of term infants. The results of such trials have been thoroughly reviewed with no definitive conclusion as to the efficacy of LCPUFA supplementation. A number of reasons for the lack of conclusive findings in this area have been proposed. This review examines such factors with the aim of determining whether an optimal method of investigation for RCTs of LCPUFA supplementation in term infants can be ascertained from previous research. While more research is required to completely inform a method that is likely to achieve definitive results, the findings of this literature review indicate future trials should investigate the effects of sex, genetic polymorphisms, the specific effects of LCPUFAs, and the optimal tests for neurodevelopmental assessment. The current literature indicates a docosahexaenoic acid dose of 0.32%, supplementation from birth to 12 months, and a total sample size of at least 286 (143 per group) should be included in the methodology of future trials. © 2011 International Life Sciences Institute.

A randomized-control trial for the teachers' diploma programme on psychosocial care, support and protection in Zambian government primary schools.

PubMed

Kaljee, Linda; Zhang, Liying; Langhaug, Lisa; Munjile, Kelvin; Tembo, Stephen; Menon, Anitha; Stanton, Bonita; Li, Xiaoming; Malungo, Jacob

2017-04-01

Orphaned and vulnerable children (OVC) experience poverty, stigma, and abuse resulting in poor physical, emotional, and psychological outcomes. The Teachers' Diploma Programme on Psychosocial Care, Support, and Protection is a child-centered 15-month long-distance learning program focused on providing teachers with the knowledge and skills to enhance their school environments, foster psychosocial support, and facilitate school-community relationships. A randomized controlled trial was implemented in 2013-2014. Both teachers (n=325) and students (n=1378) were assessed at baseline and 15-months post-intervention from randomly assigned primary schools in Lusaka and Eastern Provinces, Zambia. Multilevel linear mixed models (MLM) indicate positive significant changes for intervention teachers on outcomes related to self-care, teaching resources, safety, social support, and gender equity. Positive outcomes for intervention students related to future orientation, respect, support, safety, sexual abuse, and bullying. Outcomes support the hypothesis that teachers and students benefit from a program designed to enhance teachers' psychosocial skills and knowledge.

Positive effect of an autologous platelet concentrate in lateral epicondylitis in a double-blind randomized controlled trial: platelet-rich plasma versus corticosteroid injection with a 1-year follow-up.

PubMed

Peerbooms, Joost C; Sluimer, Jordi; Bruijn, Daniël J; Gosens, Taco

2010-02-01

Platelet-rich plasma (PRP) has shown to be a general stimulation for repair. Purpose To determine the effectiveness of PRP compared with corticosteroid injections in patients with chronic lateral epicondylitis. Randomized controlled trial; Level of evidence, 1. The trial was conducted in 2 teaching hospitals in the Netherlands. One hundred patients with chronic lateral epicondylitis were randomly assigned in the PRP group (n = 51) or the corticosteroid group (n = 49). A central computer system carried out randomization and allocation to the trial group. Patients were randomized to receive either a corticosteroid injection or an autologous platelet concentrate injection through a peppering technique. The primary analysis included visual analog scores and DASH Outcome Measure scores (DASH: Disabilities of the Arm, Shoulder, and Hand). Successful treatment was defined as more than a 25% reduction in visual analog score or DASH score without a reintervention after 1 year. The results showed that, according to the visual analog scores, 24 of the 49 patients (49%) in the corticosteroid group and 37 of the 51 patients (73%) in the PRP group were successful, which was significantly different (P <.001). Furthermore, according to the DASH scores, 25 of the 49 patients (51%) in the corticosteroid group and 37 of the 51 patients (73%) in the PRP group were successful, which was also significantly different (P = .005). The corticosteroid group was better initially and then declined, whereas the PRP group progressively improved. Treatment of patients with chronic lateral epicondylitis with PRP reduces pain and significantly increases function, exceeding the effect of corticosteroid injection. Future decisions for application of the PRP for lateral epicondylitis should be confirmed by further follow-up from this trial and should take into account possible costs and harms as well as benefits.

Field evaluation of a random forest activity classifier for wrist-worn accelerometer data.

PubMed

Pavey, Toby G; Gilson, Nicholas D; Gomersall, Sjaan R; Clark, Bronwyn; Trost, Stewart G

2017-01-01

Wrist-worn accelerometers are convenient to wear and associated with greater wear-time compliance. Previous work has generally relied on choreographed activity trials to train and test classification models. However, validity in free-living contexts is starting to emerge. Study aims were: (1) train and test a random forest activity classifier for wrist accelerometer data; and (2) determine if models trained on laboratory data perform well under free-living conditions. Twenty-one participants (mean age=27.6±6.2) completed seven lab-based activity trials and a 24h free-living trial (N=16). Participants wore a GENEActiv monitor on the non-dominant wrist. Classification models recognising four activity classes (sedentary, stationary+, walking, and running) were trained using time and frequency domain features extracted from 10-s non-overlapping windows. Model performance was evaluated using leave-one-out-cross-validation. Models were implemented using the randomForest package within R. Classifier accuracy during the 24h free living trial was evaluated by calculating agreement with concurrently worn activPAL monitors. Overall classification accuracy for the random forest algorithm was 92.7%. Recognition accuracy for sedentary, stationary+, walking, and running was 80.1%, 95.7%, 91.7%, and 93.7%, respectively for the laboratory protocol. Agreement with the activPAL data (stepping vs. non-stepping) during the 24h free-living trial was excellent and, on average, exceeded 90%. The ICC for stepping time was 0.92 (95% CI=0.75-0.97). However, sensitivity and positive predictive values were modest. Mean bias was 10.3min/d (95% LOA=-46.0 to 25.4min/d). The random forest classifier for wrist accelerometer data yielded accurate group-level predictions under controlled conditions, but was less accurate at identifying stepping verse non-stepping behaviour in free living conditions Future studies should conduct more rigorous field-based evaluations using observation as a criterion measure. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection.

PubMed

Nell, Andre S; D'lom, Eva; Bouic, Patrick; Sabaté, Montserrat; Bosser, Ramon; Picas, Jordi; Amat, Mercè; Churchyard, Gavin; Cardona, Pere-Joan

2014-01-01

To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection. Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination. Each subject received two vaccine administrations, 28 Days apart. Five patients withdrew and 90 patients completed the study. Assessment of safety showed no deaths during study. Two subjects had serious adverse events one had a retinal detachment while taking INH and was not randomized and the other had a severe local injection site abscess on each arm and was hospitalized; causality was assessed as very likely and by the end of the study the outcome had resolved. All the patients except 5 (21%) patients of the placebo group (3 HIV+ and 2 HIV-) reported at least one adverse event (AE) during the study. The most frequently occurring AEs among RUTI recipients were (% in HIV+/-): injection site reactions [erythema (91/92), induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis (20/5)]. These events were mostly mild and well tolerated. Overall, a polyantigenic response was observed, which differed by HIV- status. The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation. This Phase II clinical trial demonstrates reasonable tolerability of RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being variable among groups, allows us considering one single injection of one of the highest doses in future trials, preceded by an extended safety clinical phase. ClinicalTrials.gov NCT01136161.

Design challenges in transdiagnostic psychotherapy research: Comparing Transdiagnostic Behavior Therapy (TBT) to existing evidence-based psychotherapy in veterans with affective disorders.

PubMed

Gros, Daniel F

2015-07-01

To address the limitations of disorder-specific approaches, newer transdiagnostic approaches to psychotherapy have been developed to provide a single treatment that is capable of addressing several, related disorders. However, the recruitment of multiple diagnoses presents many challenges to the traditional design of psychotherapy randomized controlled trials (RCTs). The goal of the manuscript is to present the challenges and rationale for designing a RCT for transdiagnostic treatment to inform and aid in the development of future investigations. A recently funded and ongoing RCT for Transdiagnostic Behavior Therapy (TBT) is used as an example to discuss the related design challenges. The TBT study involves the recruitment of 96 veteran participants with any of the following eight principal diagnoses: posttraumatic stress disorder, panic disorder, social anxiety disorder, obsessive compulsive disorder, generalized anxiety disorder, specific phobia, major depressive disorder, or persistent depressive disorder. Within the TBT study, participants will complete a semi-structured diagnostic interview and a series of transdiagnostic self-report measures to determine eligibility and assess baseline symptomatology. Qualifying participants will be randomized to TBT or control psychotherapy. Additional assessments will be completed at post-treatment and 6-month follow-up. Due to the transdiagnostic nature of the sample, adjustments to the recruitment and randomization procedures, selection of measures, selection of control psychotherapy, and analysis plan were required. These adjustments have implications to future trials on transdiagnostic psychotherapy protocols as well as future research in line with the transdiagnostic focus of the National Institute of Mental Health's Research Domain Criteria (RDoC) funding strategy. Published by Elsevier Inc.

Mobile access to virtual randomization for investigator-initiated trials.

PubMed

Deserno, Thomas M; Keszei, András P

2017-08-01

Background/aims Randomization is indispensable in clinical trials in order to provide unbiased treatment allocation and a valid statistical inference. Improper handling of allocation lists can be avoided using central systems, for example, human-based services. However, central systems are unaffordable for investigator-initiated trials and might be inaccessible from some places, where study subjects need allocations. We propose mobile access to virtual randomization, where the randomization lists are non-existent and the appropriate allocation is computed on demand. Methods The core of the system architecture is an electronic data capture system or a clinical trial management system, which is extended by an R interface connecting the R server using the Java R Interface. Mobile devices communicate via the representational state transfer web services. Furthermore, a simple web-based setup allows configuring the appropriate statistics by non-statisticians. Our comprehensive R script supports simple randomization, restricted randomization using a random allocation rule, block randomization, and stratified randomization for un-blinded, single-blinded, and double-blinded trials. For each trial, the electronic data capture system or the clinical trial management system stores the randomization parameters and the subject assignments. Results Apps are provided for iOS and Android and subjects are randomized using smartphones. After logging onto the system, the user selects the trial and the subject, and the allocation number and treatment arm are displayed instantaneously and stored in the core system. So far, 156 subjects have been allocated from mobile devices serving five investigator-initiated trials. Conclusion Transforming pre-printed allocation lists into virtual ones ensures the correct conduct of trials and guarantees a strictly sequential processing in all trial sites. Covering 88% of all randomization models that are used in recent trials, virtual randomization becomes available for investigator-initiated trials and potentially for large multi-center trials.

Clinical studies in restorative dentistry: New directions and new demands.

PubMed

Opdam, N J M; Collares, K; Hickel, R; Bayne, S C; Loomans, B A; Cenci, M S; Lynch, C D; Correa, M B; Demarco, F; Schwendicke, F; Wilson, N H F

2018-01-01

Clinical research of restorative materials is confounded by problems of study designs, length of trials, type of information collected, and costs for trials, despite increasing numbers and considerable development of trials during the past 50 years. This opinion paper aims to discuss advantages and disadvantages of different study designs and outcomes for evaluating survival of dental restorations and to make recommendations for future study designs. Advantages and disadvantages of randomized trials, prospective and retrospective longitudinal studies, practice-based, pragmatic and cohort studies are addressed and discussed. The recommendations of the paper are that clinical trials should have rational control groups, include confounders such as patient risk factors in the data and analysis and should use outcome parameters relevant for profession and patients. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Quality assurance audit: a prospective non-randomised trial of chemotherapy and radiotherapy for osteolymphoma (TROG 99.04/ALLG LY02).

PubMed

Christie, D; Le, T; Watling, K; Cornes, D; O'Brien, P; Hitchins, R

2009-04-01

A quality assurance (QA) audit of the Trans Tasman Radiation Oncology Group and Australasian Lymphoma and Leukaemia Group trial (TROG 99.04/ALLG LY02) began after accrual of 25 patients. The trial is a prospective non-randomized study of standard treatment for osteolymphoma. Data relating to informed consent, eligibility, chemotherapy and radiotherapy were reviewed. The audit showed a relatively low level of major variations from the protocol, with an overall rate of 3.6%. As this trial has accrued slowly over a long period, the concept of QA has also developed. Amendments were made to the protocol accordingly. In the future, QA procedures should be predetermined, conducted rapidly in real time, and appropriately funded in order to be relevant to the ongoing conduct of the trial.

The role of Imaging and Radiation Oncology Core for precision medicine era of clinical trial

PubMed Central

Rosen, Mark

2017-01-01

Imaging and Radiation Oncology Core (IROC) services have been established for the quality assurance (QA) of imaging and radiotherapy (RT) for NCI’s Clinical Trial Network (NCTN) for any trials that contain imaging or RT. The randomized clinical trial is the gold standard for evidence-based medicine. QA ensures data quality, preventing noise from inferior treatments obscuring clinical trial outcome. QA is also found to be cost-effective. IROC has made great progress in multi-institution standardization and is expected to lead QA standardization, QA science in imaging and RT and to advance quality data analysis with big data in the future. The QA in the era of precision medicine is of paramount importance, when individualized decision making may depend on the quality and accuracy of RT and imaging. PMID:29218265

A novel application of the Intent to Attend assessment to reduce bias due to missing data in a randomized controlled clinical trial

PubMed Central

Rabideau, Dustin J; Nierenberg, Andrew A; Sylvia, Louisa G; Friedman, Edward S.; Bowden, Charles L.; Thase, Michael E.; Ketter, Terence; Ostacher, Michael J.; Reilly-Harrington, Noreen; Iosifescu, Dan V.; Calabrese, Joseph R.; Leon, Andrew C.; Schoenfeld, David A

2014-01-01

Background Missing data are unavoidable in most randomized controlled clinical trials, especially when measurements are taken repeatedly. If strong assumptions about the missing data are not accurate, crude statistical analyses are biased and can lead to false inferences. Furthermore, if we fail to measure all predictors of missing data, we may not be able to model the missing data process sufficiently. In longitudinal randomized trials, measuring a patient's intent to attend future study visits may help to address both of these problems. Leon et al. developed and included the Intent to Attend assessment in the Lithium Treatment—Moderate dose Use Study (LiTMUS), aiming to remove bias due to missing data from the primary study hypothesis [1]. Purpose The purpose of this study is to assess the performance of the Intent to Attend assessment with regard to its use in a sensitivity analysis of missing data. Methods We fit marginal models to assess whether a patient's self-rated intent predicted actual study adherence. We applied inverse probability of attrition weighting (IPAW) coupled with patient intent to assess whether there existed treatment group differences in response over time. We compared the IPAW results to those obtained using other methods. Results Patient-rated intent predicted missed study visits, even when adjusting for other predictors of missing data. On average, the hazard of retention increased by 19% for every one-point increase in intent. We also found that more severe mania, male gender, and a previously missed visit predicted subsequent absence. Although we found no difference in response between the randomized treatment groups, IPAW increased the estimated group difference over time. Limitations LiTMUS was designed to limit missed study visits, which may have attenuated the effects of adjusting for missing data. Additionally, IPAW can be less efficient and less powerful than maximum likelihood or Bayesian estimators, given that the parametric model is well-specified. Conclusions In LiTMUS, the Intent to Attend assessment predicted missed study visits. This item was incorporated into our IPAW models and helped reduce bias due to informative missing data. This analysis should both encourage and facilitate future use of the Intent to Attend assessment along with IPAW to address missing data in a randomized trial. PMID:24872362

Prophylactic intra-peritoneal drain placement following pancreaticoduodenectomy: A systematic review and meta-analysis

PubMed Central

Wang, Yi-Chao; Szatmary, Peter; Zhu, Jing-Qiang; Xiong, Jun-Jie; Huang, Wei; Gomatos, Ilias; Nunes, Quentin M; Sutton, Robert; Liu, Xu-Bao

2015-01-01

AIM: To conduct a meta-analysis comparing outcomes after pancreaticoduodenectomy (PD) with or without prophylactic drainage. METHODS: Relevant comparative randomized and non-randomized studies were systemically searched based on specific inclusion and exclusion criteria. Postoperative outcomes were compared between patients with and those without routine drainage. Pooled odds ratios (OR) with 95%CI were calculated using either fixed effects or random effects models. RESULTS: One randomized controlled trial and four non-randomized comparative studies recruiting 1728 patients were analyzed. Patients without prophylactic drainage after PD had significantly higher mortality (OR = 2.32, 95%CI: 1.11-4.85; P = 0.02), despite the fact that they were associated with fewer overall complications (OR = 0.62, 95%CI: 0.48-0.82; P = 0.00), major complications (OR = 0.75, 95%CI: 0.60-0.93; P = 0.01) and readmissions (OR = 0.77, 95%CI: 0.60-0.98; P = 0.04). There were no significant differences in the rates of pancreatic fistula, intra-abdominal abscesses, postpancreatectomy hemorrhage, biliary fistula, delayed gastric emptying, reoperation or radiologic-guided drains between the two groups. CONCLUSION: Indiscriminate abandonment of intra-abdominal drainage following PD is associated with greater mortality, but lower complication rates. Future randomized trials should compare routine vs selective drainage. PMID:25741162

Effects of horticultural therapy on elderly' health: protocol of a randomized controlled trial.

PubMed

Chan, Hui Yu; Ho, Roger Chun-Man; Mahendran, Rathi; Ng, Kheng Siang; Tam, Wilson Wai-San; Rawtaer, Iris; Tan, Chay Hoon; Larbi, Anis; Feng, Lei; Sia, Angelia; Ng, Maxel Kian-Wee; Gan, Goh Lee; Kua, Ee Heok

2017-08-29

Due to a rapidly ageing population in the world, it is increasingly pertinent to promote successful ageing strategies which are cost-effective, easily accessible, and more likely to be acceptable to the elderly. Past research associates exposure to natural environments and horticultural therapy (HT) with positive psychological, social and physical health benefits. This Randomized Controlled Trial (RCT) is designed to evaluate the efficacy of HT in promoting Asian elderly' mental health, cognitive functioning and physical health. 70 elderly participants aged 60 to 85 years old will be randomized to participate in either the active horticultural therapy group or be in the waitlist control. Sessions will be weekly for 12 weeks, and monthly for 3 months. Mental health will be assessed through self-reports of depressive and anxiety symptomatology, life satisfaction, social connectedness and psychological well-being, collaborated with immunological markers. Outcome measures of cognitive functioning and physical health include neuropsychological tests of cognitive function and basic health screening. Outcomes will be assessed at baseline, 3 months and 6 months post-intervention. This RCT comprehensively investigates the efficacy of a non-invasive intervention, HT, in enhancing mental health, cognitive functioning and physical health. The results have tremendous potential for supporting future successful ageing programs and applicability to larger populations. ClinicalTrials.gov NCT02495194 . Trial registration date: July 13, 2015. Retrospectively registered.

Supplementation of omega 3 fatty acids may improve hyperactivity, lethargy, and stereotypy in children with autism spectrum disorders: a meta-analysis of randomized controlled trials

PubMed Central

Cheng, Yu-Shian; Tseng, Ping-Tao; Chen, Yen-Wen; Stubbs, Brendon; Yang, Wei-Chieh; Chen, Tien-Yu; Wu, Ching-Kuan; Lin, Pao-Yen

2017-01-01

Aim Deficiency of omega 3 fatty acids may be linked to autism spectrum disorder (ASD). Evidence about the potential therapeutic effects of supplementation of omega 3 fatty acids is lacking in ASD patients. Methods We searched major electronic databases from inception to June 21, 2017, for randomized clinical trials, which compared treatment outcomes between supplementation of omega 3 fatty acids and placebo in patients with ASD. An exploratory random-effects meta-analysis of the included studies was undertaken. Results and conclusion Six trials were included (n=194). Meta-analysis showed that supplementation of omega 3 fatty acids improved hyperactivity (difference in means =−2.692, 95% confidence interval [CI] =−5.364 to −0.020, P=0.048, studies =4, n=109), lethargy (difference in means =−1.969, 95% CI =−3.566 to −0.372, P=0.016, studies =4, n=109), and stereotypy (difference in means =−1.071, 95% CI =−2.114 to −0.029, P=0.044, studies =4, n=109). No significant differences emerged between supplementation of omega 3 fatty acids and placebo in global assessment of functioning (n=169) or social responsiveness (n=97). Our preliminary meta-analysis suggests that supplementation of omega 3 fatty acids may improve hyperactivity, lethargy, and stereotypy in ASD patients. However, the number of studies was limited and the overall effects were small, precluding definitive conclusions. Future large-scale randomized clinical trials are needed to confirm or refute our findings. PMID:29042783

Effects of Massage on Blood Pressure in Patients With Hypertension and Prehypertension: A Meta-analysis of Randomized Controlled Trials.

PubMed

Liao, I-Chen; Chen, Shiah-Lian; Wang, Mei-Yeh; Tsai, Pei-Shan

2016-01-01

Massage may help reduce blood pressure; previous studies on the effect of massage on blood pressure have presented conflicting findings. In addition, no systematic review is available. The aim of this study was to evaluate the evidence concerning the effect of massage on blood pressure in patients with hypertension or prehypertension. A search was performed on electronic database records up to October 31, 2013, based on the following medical subject headings or keywords: hypertension, massage, chiropractic, manipulation, and blood pressure. The methodological quality of randomized controlled trials was assessed based on the Cochrane collaboration tool. A meta-analysis was performed to evaluate the effect of massage on hypertension. The study selection, data extraction, and validation were performed independently by 2 reviewers. Nine randomized controlled trials met our inclusion criteria. The results of this study show that massage contributes to significantly enhanced reduction in both systolic blood pressure (SBP) (mean difference, -7.39 mm Hg) and diastolic blood pressure (DBP) (mean difference, -5.04 mm Hg) as compared with control treatments in patients with hypertension and prehypertension. The effect size (Hedges g) for SBP and DBP was -0.728 (95% confidence interval, -1.182 to -0.274; P = .002) and -0.334 (95% confidence interval, -0.560 to -0.107; P = .004), respectively. This systematic review found a medium effect of massage on SBP and a small effect on DBP in patients with hypertension or prehypertension. High-quality randomized controlled trials are urgently required to confirm these results, although the findings of this study can be used to guide future research.

Subgroup analysis of telehealthcare for patients with chronic obstructive pulmonary disease: the cluster-randomized Danish Telecare North Trial

PubMed Central

Witt Udsen, Flemming; Lilholt, Pernille H; Hejlesen, Ole K; Ehlers, Lars H

2017-01-01

Purpose Results from the Danish cluster-randomized trial of telehealthcare to 1,225 patients with chronic obstructive pulmonary disease (COPD), the Danish Telecare North Trial, concluded that the telehealthcare solution was unlikely to be cost-effective, by applying international willingness-to-pay threshold values. The purpose of this article was to assess potential sources of variation across subgroups, which could explain overall cost-effectiveness results or be utilized in future economic studies in telehealthcare research. Methods First, the cost-structures and cost-effectiveness across COPD severities were analyzed. Second, five additional subgroup analyses were conducted, focusing on differences in cost-effectiveness across a set of comorbidities, age-groups, genders, resource patterns (resource use in the social care sector prior to randomization), and delivery sites. All subgroups were investigated post hoc. In analyzing cost-effectiveness, two separate linear mixed-effects models with treatment-by-covariate interactions were applied: one for quality-adjusted life-year (QALY) gain and one for total healthcare and social sector costs. Probabilistic sensitivity analysis was used for each subgroup result in order to quantify the uncertainty around the cost-effectiveness results. Results The study concludes that, across the COPD severities, patients with severe COPD (GOLD 3 classification) are likely to be the most cost-effective group. This is primarily due to lower hospital-admission and primary-care costs. Telehealthcare for patients younger than 60 years is also more likely to be cost-effective than for older COPD patients. Overall, results indicate that existing resource patterns of patients and variations in delivery-site practices might have a strong influence on cost-effectiveness, possibly stronger than the included health or sociodemographic sources of heterogeneity. Conclusion Future research should focus more on sources of heterogeneity found in the implementation context and the way telehealthcare is adopted (eg, by integrating formative evaluation into cost-effectiveness analyses). Trial registration Clinicaltrials.gov, NCT01984840. PMID:28740411

Ongoing positive effect of platelet-rich plasma versus corticosteroid injection in lateral epicondylitis: a double-blind randomized controlled trial with 2-year follow-up.

PubMed

Gosens, Taco; Peerbooms, Joost C; van Laar, Wilbert; den Oudsten, Brenda L

2011-06-01

Platelet-rich plasma (PRP) has been shown to be a general stimulation for repair and 1-year results showed promising success percentages. This trial was undertaken to determine the effectiveness of PRP compared with corticosteroid injections in patients with chronic lateral epicondylitis with a 2-year follow-up. Randomized controlled trial; Level of evidence, 1. The trial was conducted in 2 Dutch teaching hospitals. One hundred patients with chronic lateral epicondylitis were randomly assigned to a leukocyte-enriched PRP group (n = 51) or the corticosteroid group (n = 49). Randomization and allocation to the trial group were carried out by a central computer system. Patients received either a corticosteroid injection or an autologous platelet concentrate injection through a peppering needling technique. The primary analysis included visual analog scale (VAS) pain scores and Disabilities of the Arm, Shoulder and Hand (DASH) outcome scores. The PRP group was more often successfully treated than the corticosteroid group (P < .0001). Success was defined as a reduction of 25% on VAS or DASH scores without a reintervention after 2 years. When baseline VAS and DASH scores were compared with the scores at 2-year follow-up, both groups significantly improved across time (intention-to-treat principle). However, the DASH scores of the corticosteroid group returned to baseline levels, while those of the PRP group significantly improved (as-treated principle). There were no complications related to the use of PRP. Treatment of patients with chronic lateral epicondylitis with PRP reduces pain and increases function significantly, exceeding the effect of corticosteroid injection even after a follow-up of 2 years. Future decisions for application of PRP for lateral epicondylitis should be confirmed by further follow-up from this trial and should take into account possible costs and harms as well as benefits.

The effects of mental practice in neurological rehabilitation; a systematic review and meta-analysis

PubMed Central

Braun, Susy; Kleynen, Melanie; van Heel, Tessa; Kruithof, Nena; Wade, Derick; Beurskens, Anna

2013-01-01

Objective: To investigate the beneficial and adverse effects of a mental practice intervention on activities, cognition, and emotion in patients after stroke, patients with Parkinson's disease or multiple sclerosis. Methods: Electronic databases PubMed/Medline, PEDro, Science Direct, Cochrane Library, PsycINFO, Rehadat, Embase, and Picarta were searched until June 2012. Fourteen randomized controlled trials in stroke and two randomized controlled trials in Parkinson's disease were included, representing 491 patients (421 with stroke). No randomized controlled trials in multiple sclerosis were identified. The methodologic quality of the included trials was assessed with the Amsterdam-Maastricht-Consensus-List (AMCL). Information on study characteristics and outcomes was summarized and evidence for effects described. Data from individual studies in stroke with same outcome measures were pooled. Results: The included 16 randomized controlled trials were heterogeneous and methodologic quality varied. Ten trials reported significant effects in favor of mental practice in patients with stroke (n = 9) and Parkinson's disease (n = 1). In six studies mental practice had similar effects as therapy as usual (n = 5 in stroke and n = 1 in Parkinson's disease). Of six performed meta-analyses with identical measures in stroke studies only two showed significant effects of mental practice: short-term improvement of arm-hand-ability (ARAT: SMD 0.62; 95% CI: 0.05 to 1.19) and improvement of performance of activities (NRS: SMD 0.9; 95% CI: 0.04 to 1.77). Five studies found effects on cognition (e.g., effects on attention, plan actions in unfamiliar surroundings) and four reported observed side-effects, both positive (e.g., might increase motivation and arousal and reduce depression) and negative (e.g., diminished concentration, irritation). Conclusions: Mental practice might have positive effects on performance of activities in patients with neurological diseases, but this review reports less positive results than earlier published ones. Strengths and limitations of past studies are pointed out. Methodologic recommendations for future studies are given. PMID:23935572

Rationale and design of a randomized controlled trial of the effect of retinol and vitamin D supplementation on treatment in active pulmonary tuberculosis patients with diabetes.

PubMed

Wang, Qiuzhen; Ma, Aiguo; Bygbjerg, Ib Christian; Han, Xiuxia; Liu, Yufeng; Zhao, Shanliang; Cai, Jing

2013-02-26

The association between pulmonary tuberculosis (PTB) and diabetes mellitus (DM) has been previously attracted much attention. Diabetes alters immunity to tuberculosis, leading to more frequent treatment failure in TB patients with DM. Moreover, TB and DM often coincide with micronutrients deficiencies, such as retinol and vitamin D, which are especially important to immunity of the body and may influence pancreas β-cell function. However, the effects of retinol and vitamin D supplementation in active TB patients with diabetes on treatment outcomes, immune and nutrition state are still uncertain. We are conducting a randomized controlled trial of vitamin A and/or D in active PTB patients with DM in a network of 4 TB treatment clinics to determine whether the supplementation could improve the outcome in the patients. This is a 2×2 factorial trial. We plan to enroll 400 active PTB patients with DM, and randomize them to VA (2000 IU daily retinol); VD (400 IU daily cholecalciferol); VAD (2000 IU daily retinol plus 400 IU cholecalciferol) or control (placebo) group. Our primary outcome measure is the efficacy of anti-tuberculosis treatment and ameliorating of glucose metabolism, and the secondary outcome measure being immune and nutrition status of the subjects. Of the first 37 subjects enrolled: 8 have been randomized to VA, 10 to VD, 9 to VAD and 10 to control. To date, the sample is 97.3% Han Chinese and 91.9% female. The average fasting plasma glucose level is 12.19 mmol/L. This paper describes the design and rationale of a randomized clinical trial comparing VA and/or VD supplementation to active pulmonary TB patients with DM. Our trial will allow rigorous evaluation of the efficacy of the supplementation to active TB and DM therapy for improving clinical outcomes and immunological condition. This detailed description of trial methodology can serve as a template for the development of future treatment scheme for active TB patient with DM. ChiCTR-TRC-12002546.

Safety, Tolerability, and Immunogenicity of the Novel Antituberculous Vaccine RUTI: Randomized, Placebo-Controlled Phase II Clinical Trial in Patients with Latent Tuberculosis Infection

PubMed Central

Nell, Andre S.; D’lom, Eva; Bouic, Patrick; Sabaté, Montserrat; Bosser, Ramon; Picas, Jordi; Amat, Mercè; Churchyard, Gavin; Cardona, Pere-Joan

2014-01-01

Objectives To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection. Methods and Findings Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination. Each subject received two vaccine administrations, 28 Days apart. Five patients withdrew and 90 patients completed the study. Assessment of safety showed no deaths during study. Two subjects had serious adverse events one had a retinal detachment while taking INH and was not randomized and the other had a severe local injection site abscess on each arm and was hospitalized; causality was assessed as very likely and by the end of the study the outcome had resolved. All the patients except 5 (21%) patients of the placebo group (3 HIV+ and 2 HIV−) reported at least one adverse event (AE) during the study. The most frequently occurring AEs among RUTI recipients were (% in HIV+/−): injection site reactions [erythema (91/92), induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis (20/5)]. These events were mostly mild and well tolerated. Overall, a polyantigenic response was observed, which differed by HIV− status. The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation. Conclusion This Phase II clinical trial demonstrates reasonable tolerability of RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being variable among groups, allows us considering one single injection of one of the highest doses in future trials, preceded by an extended safety clinical phase. Trial Registration ClinicalTrials.gov NCT01136161 PMID:24586912

Efficacy and safety of secukinumab administration by autoinjector in patients with psoriatic arthritis: results from a randomized, placebo-controlled trial (FUTURE 3).

PubMed

Nash, Peter; Mease, Philip J; McInnes, Iain B; Rahman, Proton; Ritchlin, Christopher T; Blanco, Ricardo; Dokoupilova, Eva; Andersson, Mats; Kajekar, Radhika; Mpofu, Shephard; Pricop, Luminita

2018-03-15

The study aimed to assess 52-week efficacy and safety of secukinumab self-administration by autoinjector in patients with active psoriatic arthritis (PsA) in the FUTURE 3 study ( ClinicalTrials.gov NCT01989468). Patients (≥ 18 years of age; N = 414) with active PsA were randomized 1:1:1 to subcutaneous (s.c.) secukinumab 300 mg, 150 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and every 4 weeks thereafter. Per clinical response, placebo-treated patients were re-randomized to s.c. secukinumab 300 or 150 mg at week 16 (nonresponders) or week 24 (responders) and stratified at randomization by prior anti-tumor necrosis factor (TNF) therapy (anti-TNF-naïve, 68.1%; intolerant/inadequate response (anti-TNF-IR), 31.9%). The primary endpoint was the proportion of patients achieving at least 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24. Autoinjector usability was evaluated by Self-Injection Assessment Questionnaire (SIAQ). Overall, 92.1% (300 mg), 91.3% (150 mg), and 93.4% (placebo) of patients completed 24 weeks, and 84.9% (300 mg) and 79.7% (150 mg) completed 52 weeks. In the overall population (combined anti-TNF-naïve and anti-TNF-IR), ACR20 response rate at week 24 was significantly higher in secukinumab groups (300 mg, 48.2% (p < 0.0001); 150 mg, 42% (p < 0.0001); placebo, 16.1%) and was sustained through 52 weeks. SIAQ results showed that more than 93% of patients were satisfied/very satisfied with autoinjector usage. Secukinumab was well tolerated with no new or unexpected safety signals reported. Secukinumab provided sustained improvements in signs and symptoms in active PsA patients through 52 weeks. High acceptability of autoinjector was observed. The safety profile was consistent with that reported previously. ClinicalTrials.gov NCT01989468 . Registered 21 November 2013. EudraCT 2013-004002-25 . Registered 17 December 2013.

Surrogate endpoints for overall survival in metastatic melanoma: a meta-analysis of randomised controlled trials

PubMed Central

Flaherty, Keith T; Hennig, Michael; Lee, Sandra J; Ascierto, Paolo A; Dummer, Reinhard; Eggermont, Alexander M M; Hauschild, Axel; Kefford, Richard; Kirkwood, John M; Long, Georgina V; Lorigan, Paul; Mackensen, Andreas; McArthur, Grant; O'Day, Steven; Patel, Poulam M; Robert, Caroline; Schadendorf, Dirk

2015-01-01

Summary Background Recent phase 3 trials have shown an overall survival benefit in metastatic melanoma. We aimed to assess whether progression-free survival (PFS) could be regarded as a reliable surrogate for overall survival through a meta-analysis of randomised trials. Methods We systematically reviewed randomised trials comparing treatment regimens in metastatic melanoma that included dacarbazine as the control arm, and which reported both PFS and overall survival with a standard hazard ratio (HR). We correlated HRs for overall survival and PFS, weighted by sample size or by precision of the HR estimate, assuming fixed and random effects. We did sensitivity analyses according to presence of crossover, trial size, and dacarbazine dose. Findings After screening 1649 reports and meeting abstracts published before Sept 8, 2013, we identified 12 eligible randomised trials that enrolled 4416 patients with metastatic melanoma. Irrespective of weighting strategy, we noted a strong correlation between the treatment effects for PFS and overall survival, which seemed independent of treatment type. Pearson correlation coefficients were 0.71 (95% CI 0.29–0.90) with a random-effects assumption, 0.85 (0.59–0.95) with a fixed-effects assumption, and 0.89 (0.68–0.97) with sample-size weighting. For nine trials without crossover, the correlation coefficient was 0.96 (0.81–0.99), which decreased to 0.93 (0.74–0.98) when two additional trials with less than 50% crossover were included. Inclusion of mature follow-up data after at least 50% crossover (in vemurafenib and dabrafenib phase 3 trials) weakened the PFS to overall survival correlation (0.55, 0.03–0.84). Inclusion of trials with no or little crossover with the random-effects assumption yielded a conservative statement of the PFS to overall survival correlation of 0.85 (0.51–0.96). Interpretation PFS can be regarded as a robust surrogate for overall survival in dacarbazine-controlled randomised trials of metastatic melanoma; we postulate that this association will hold as treatment standards evolve and are adopted as the control arm in future trials. Funding None. PMID:24485879

Independent data monitoring committees: Preparing a path for the future

PubMed Central

Hess, Connie N.; Roe, Matthew T.; Gibson, C. Michael; Temple, Robert J.; Pencina, Michael J.; Zarin, Deborah A.; Anstrom, Kevin J.; Alexander, John H.; Sherman, Rachel E.; Fiedorek, Fred T.; Mahaffey, Kenneth W.; Lee, Kerry L.; Chow, Shein-Chung; Armstrong, Paul W.; Califf, Robert M.

2014-01-01

Independent data monitoring committees (IDMCs) were introduced to monitor patient safety and study conduct in randomized clinical trials (RCTs), but certain challenges regarding the utilization of IDMCs have developed. First, the roles and responsibilities of IDMCs are expanding, perhaps due to increasing trial complexity and heterogeneity regarding medical, ethical, legal, regulatory, and financial issues. Second, no standard for IDMC operating procedures exists, and there is uncertainty about who should determine standards and whether standards should vary with trial size and design. Third, considerable variability in communication pathways exist across IDMC interfaces with regulatory agencies, academic coordinating centers, and sponsors. Finally, there has been a substantial increase in the number of RCTs using IDMCs, yet there is no set of qualifications to help guide the training and development of the next generation of IDMC members. Recently, an expert panel of representatives from government, industry, and academia assembled at the Duke Clinical Research Institute to address these challenges and to develop recommendations for the future utilization of IDMCs in RCTs. PMID:25066551

Running injuries in novice runners enrolled in different training interventions: a pilot randomized controlled trial.

PubMed

Baltich, J; Emery, C A; Whittaker, J L; Nigg, B M

2017-11-01

The purpose of this trial was to evaluate injury risk in novice runners participating in different strength training interventions. This was a pilot randomized controlled trial. Novice runners (n = 129, 18-60 years old, <2 years recent running experience) were block randomized to one of three groups: a "resistance" strength training group, a "functional" strength training group, or a stretching "control" group. The primary outcome was running related injury. The number of participants with complaints and the injury rate (IR = no. injuries/1000 running hours) were quantified for each intervention group. For the first 8 weeks, participants were instructed to complete their training intervention three to five times a week. The remaining 4 months was a maintenance period. NCT01900262. A total of 52 of the 129 (40%) novice runners experienced at least one running related injury: 21 in the functional strength training program, 16 in the resistance strength training program and 15 in the control stretching program. Injury rates did not differ between study groups [IR = 32.9 (95% CI 20.8, 49.3) in the functional group, IR = 31.6 (95% CI 18.4, 50.5) in the resistance group, and IR = 26.7 (95% CI 15.2, 43.2)] in the control group. Although this was a pilot assessment, home-based strength training did not appear to alter injury rates compared to stretching. Future studies should consider methods to minimize participant drop out to allow for the assessment of injury risk. Injury risk in novice runners based on this pilot study will inform the development of future larger studies investigating the impact of injury prevention interventions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Randomization in clinical trials in orthodontics: its significance in research design and methods to achieve it.

PubMed

Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2011-12-01

Randomization is a key step in reducing selection bias during the treatment allocation phase in randomized clinical trials. The process of randomization follows specific steps, which include generation of the randomization list, allocation concealment, and implementation of randomization. The phenomenon in the dental and orthodontic literature of characterizing treatment allocation as random is frequent; however, often the randomization procedures followed are not appropriate. Randomization methods assign, at random, treatment to the trial arms without foreknowledge of allocation by either the participants or the investigators thus reducing selection bias. Randomization entails generation of random allocation, allocation concealment, and the actual methodology of implementing treatment allocation randomly and unpredictably. Most popular randomization methods include some form of restricted and/or stratified randomization. This article introduces the reasons, which make randomization an integral part of solid clinical trial methodology, and presents the main randomization schemes applicable to clinical trials in orthodontics.

Moxibustion for the treatment of chemotherapy-induced leukopenia: a systematic review of randomized clinical trials.

PubMed

Choi, Tae-Young; Lee, Myeong Soo; Ernst, Edzard

2015-06-01

The purpose of this study is to assess the efficacy of moxibustion as a treatment of chemotherapy-induced leukopenia. Twelve databases were searched from their inception through June 2014, without a language restriction. Randomized clinical trials (RCTs) were included if moxibustion was used as the sole treatment or as a part of a combination therapy with conventional drugs for leukopenia induced by chemotherapy. Cochrane criteria were used to assess the risk of bias. Six RCTs with a total of 681 patients met our inclusion criteria. All of the included RCTs were associated with a high risk of bias. The trials included patients with various types of cancer receiving ongoing chemotherapy or after chemotherapy. The results of two RCTs suggested the effectiveness of moxibustion combined with chemotherapy vs. chemotherapy alone. In four RCTs, moxibustion was more effective than conventional drug therapy. Six RCTs showed that moxibustion was more effective than various types of control interventions in increasing white blood cell counts. There is low level of evidence based on these six trials that demonstrates the superiority of moxibustion over drug therapies in the treatment of chemotherapy-induced leukopenia. However, the number of trials, the total sample size, and the methodological quality are too low to draw firm conclusions. Future RCTs appear to be warranted.

Do brief motivational interventions reduce drinking game frequency in mandated students? An analysis of data from two randomized controlled trials.

PubMed

Fernandez, Anne C; Yurasek, Ali M; Merrill, Jennifer E; Miller, Mary Beth; Zamboanga, Byron L; Carey, Kate B; Borsari, Brian

2017-02-01

College students frequently engage in drinking games (DGs) and experience a variety of consequences as a result. It is currently unknown whether brief motivational interventions (BMIs) that provide feedback on DG participation can reduce this high risk behavior. This study examined outcome data from 2 randomized clinical trials to examine whether BMIs facilitate change in DG frequency and how these changes may occur. Mandated college students (Trial 1, N = 198, 46% female; Trial 2, N = 412; 32% female) were randomized to BMI or comparison control conditions. Hierarchical linear modeling (HLM) was used to compare the BMI and comparison groups to determine whether the BMI reduced DG participation over time. Percent change talk (PCT) during the discussion of DG during the session was examined as a predictor of change in DG frequency, and gender was examined as a moderator of treatment effects. Controlling for regular drinking frequency, participants who received a BMI did not significantly reduce their DG frequency relative to the comparison group in either sample, and the BMI was equally ineffective at reducing DG behavior for men and women. DG-related PCT during the BMI was associated with lower DG frequency at the second follow-up in both trials. In Trial 1, PCT during the BMI was associated with less steep increases in DG frequency across the course of all follow-ups. Effects of PCT on DG behavior were not moderated by gender. Findings did not support hypothesized reductions in DG participation following a BMI. Future research should explore whether targeted DG-specific interventions could reduce DG participation and the role of in-session client language in facilitating such change. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Neurofeedback for Attention-Deficit/Hyperactivity Disorder: Meta-Analysis of Clinical and Neuropsychological Outcomes From Randomized Controlled Trials.

PubMed

Cortese, Samuele; Ferrin, Maite; Brandeis, Daniel; Holtmann, Martin; Aggensteiner, Pascal; Daley, David; Santosh, Paramala; Simonoff, Emily; Stevenson, Jim; Stringaris, Argyris; Sonuga-Barke, Edmund J S

2016-06-01

We performed meta-analyses of randomized controlled trials to examine the effects of neurofeedback on attention-deficit/hyperactivity disorder (ADHD) symptoms and neuropsychological deficits in children and adolescents with ADHD. We searched PubMed, Ovid, Web of Science, ERIC, and CINAHAL through August 30, 2015. Random-effects models were employed. Studies were evaluated with the Cochrane Risk of Bias tool. We included 13 trials (520 participants with ADHD). Significant effects were found on ADHD symptoms rated by assessors most proximal to the treatment setting, that is, the least blinded outcome measure (standardized mean difference [SMD]: ADHD total symptoms = 0.35, 95% CI = 0.11-0.59; inattention = 0.36, 95% CI = 0.09-0.63; hyperactivity/impulsivity = 0.26, 95% CI = 0.08-0.43). Effects were not significant when probably blinded ratings were the outcome or in trials with active/sham controls. Results were similar when only frequency band training trials, the most common neurofeedback approach, were analyzed separately. Effects on laboratory measures of inhibition (SMD = 0.30, 95% CI = -0.10 to 0.70) and attention (SMD = 0.13, 95% CI = -0.09 to 0.36) were not significant. Only 4 studies directly assessed whether learning occurred after neurofeedback training. The risk of bias was unclear for many Cochrane Risk of Bias domains in most studies. Evidence from well-controlled trials with probably blinded outcomes currently fails to support neurofeedback as an effective treatment for ADHD. Future efforts should focus on implementing standard neurofeedback protocols, ensuring learning, and optimizing clinically relevant transfer. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Fixation using alternative implants for the treatment of hip fractures (FAITH): design and rationale for a multi-centre randomized trial comparing sliding hip screws and cancellous screws on revision surgery rates and quality of life in the treatment of femoral neck fractures.

PubMed

2014-06-26

Hip fractures are a common type of fragility fracture that afflict 293,000 Americans (over 5,000 per week) and 35,000 Canadians (over 670 per week) annually. Despite the large population impact the optimal fixation technique for low energy femoral neck fractures remains controversial. The primary objective of the FAITH study is to assess the impact of cancellous screw fixation versus sliding hip screws on rates of revision surgery at 24 months in individuals with femoral neck fractures. The secondary objective is to determine the impact on health-related quality of life, functional outcomes, health state utilities, fracture healing, mortality and fracture-related adverse events. FAITH is a multi-centre, multi-national randomized controlled trial utilizing minimization to determine patient allocation. Surgeons in North America, Europe, Australia, and Asia will recruit a total of at least 1,000 patients with low-energy femoral neck fractures. Using central randomization, patients will be allocated to receive surgical treatment with cancellous screws or a sliding hip screw. Patient outcomes will be assessed at one week (baseline), 10 weeks, 6, 12, 18, and 24 months post initial fixation. We will independently adjudicate revision surgery and complications within 24 months of the initial fixation. Outcome analysis will be performed using a Cox proportional hazards model and likelihood ratio test. This study represents major international efforts to definitively resolve the treatment of low-energy femoral neck fractures. This trial will not only change current Orthopaedic practice, but will also set a benchmark for the conduct of future Orthopaedic trials. The FAITH trial is registered at ClinicalTrials.gov (Identifier NCT00761813).

Do Brief Motivational Interventions Reduce Drinking Game Frequency in Mandated Students? An analysis of data from two randomized controlled trials

PubMed Central

Fernandez, Anne C.; Yurasek, Allison M.; Merrill, Jennifer E.; Miller, Mary Beth; Zamboanga, Byron L.; Carey, Kate B.; Borsari, Brian

2016-01-01

Purpose College students frequently engage in drinking games (DG) and experience a variety of consequences as a result. It is currently unknown whether brief motivational interventions (BMI) that provide feedback on DG participation can reduce this high risk behavior. This study examined outcome data from two randomized clinical trials to examine whether BMIs facilitate change in DG frequency and how these changes may occur. Methods Mandated college students (Trial 1, N = 198, 46% female; Trial 2, N = 412; 32% female) were randomized to BMI or comparison control conditions. Hierarchical linear modeling (HLM) was used to compare the BMI and comparison groups to determine whether the BMI reduced DG participation over time. Percent change talk (PCT) during the discussion of DG during the session was examined as a predictor of change in DG frequency, and gender was examined as a moderator of treatment effects. Results Controlling for regular drinking frequency, participants who received a BMI did not significantly reduce their DG frequency relative to the comparison group in either sample, and the BMI was equally ineffective at reducing DG behavior for men and women. DG-related PCT during the BMI was associated with lower DG frequency at the second follow-up in both Trials. In Trial 1, PCT during the BMI was associated with less steep increases in DG frequency across the course of all follow-ups. Effects of PCT on DG behavior were not moderated by gender. Conclusions Findings did not support hypothesized reductions in DG participation following a BMI. Future research should explore whether targeted DG-specific interventions could reduce DG participation and the role of in-session client language in facilitating such change. PMID:27936818

A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression

PubMed Central

Romijn, Amy R; Rucklidge, Julia J; Kuijer, Roeline G; Frampton, Chris

2017-01-01

Objectives: This trial investigated whether probiotics improved mood, stress and anxiety in a sample selected for low mood. We also tested whether the presence or severity of irritable bowel syndrome symptoms, and levels of proinflammatory cytokines, brain-derived neurotrophic factor and other blood markers, would predict or impact treatment response. Method: Seventy-nine participants (10 dropouts) not currently taking psychotropic medications with at least moderate scores on self-report mood measures were randomly allocated to receive either a probiotic preparation (containing Lactobacillus helveticus and Bifidobacterium longum) or a matched placebo, in a double-blind trial for 8 weeks. Data were analysed as intent-to-treat. Results: No significant difference was found between the probiotic and placebo groups on any psychological outcome measure (Cohen’s d range = 0.07–0.16) or any blood-based biomarker. At end-point, 9 (23%) of those in the probiotic group showed a ⩾60% change on the Montgomery–Åsberg Depression Rating Scale (responders), compared to 10 (26%) of those in the placebo group (χ12=0.107, p = ns). Baseline vitamin D level was found to moderate treatment effect on several outcome measures. Dry mouth and sleep disruption were reported more frequently in the placebo group. Conclusions: This study found no evidence that the probiotic formulation is effective in treating low mood, or in moderating the levels of inflammatory and other biomarkers. The lack of observed effect on mood symptoms may be due to the severity, chronicity or treatment resistance of the sample; recruiting an antidepressant-naive sample experiencing mild, acute symptoms of low mood, may well yield a different result. Future studies taking a preventative approach or using probiotics as an adjuvant treatment may also be more effective. Vitamin D levels should be monitored in future studies in the area. The results of this trial are preliminary; future studies in the area should not be discouraged. PMID:28068788

A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression.

PubMed

Romijn, Amy R; Rucklidge, Julia J; Kuijer, Roeline G; Frampton, Chris

2017-08-01

This trial investigated whether probiotics improved mood, stress and anxiety in a sample selected for low mood. We also tested whether the presence or severity of irritable bowel syndrome symptoms, and levels of proinflammatory cytokines, brain-derived neurotrophic factor and other blood markers, would predict or impact treatment response. Seventy-nine participants (10 dropouts) not currently taking psychotropic medications with at least moderate scores on self-report mood measures were randomly allocated to receive either a probiotic preparation (containing Lactobacillus helveticus and Bifidobacterium longum) or a matched placebo, in a double-blind trial for 8 weeks. Data were analysed as intent-to-treat. No significant difference was found between the probiotic and placebo groups on any psychological outcome measure (Cohen's d range = 0.07-0.16) or any blood-based biomarker. At end-point, 9 (23%) of those in the probiotic group showed a ⩾60% change on the Montgomery-Åsberg Depression Rating Scale (responders), compared to 10 (26%) of those in the placebo group ([Formula: see text], p = ns). Baseline vitamin D level was found to moderate treatment effect on several outcome measures. Dry mouth and sleep disruption were reported more frequently in the placebo group. This study found no evidence that the probiotic formulation is effective in treating low mood, or in moderating the levels of inflammatory and other biomarkers. The lack of observed effect on mood symptoms may be due to the severity, chronicity or treatment resistance of the sample; recruiting an antidepressant-naive sample experiencing mild, acute symptoms of low mood, may well yield a different result. Future studies taking a preventative approach or using probiotics as an adjuvant treatment may also be more effective. Vitamin D levels should be monitored in future studies in the area. The results of this trial are preliminary; future studies in the area should not be discouraged.

Extrapolating Survival from Randomized Trials Using External Data: A Review of Methods

PubMed Central

Jackson, Christopher; Stevens, John; Ren, Shijie; Latimer, Nick; Bojke, Laura; Manca, Andrea; Sharples, Linda

2016-01-01

This article describes methods used to estimate parameters governing long-term survival, or times to other events, for health economic models. Specifically, the focus is on methods that combine shorter-term individual-level survival data from randomized trials with longer-term external data, thus using the longer-term data to aid extrapolation of the short-term data. This requires assumptions about how trends in survival for each treatment arm will continue after the follow-up period of the trial. Furthermore, using external data requires assumptions about how survival differs between the populations represented by the trial and external data. Study reports from a national health technology assessment program in the United Kingdom were searched, and the findings were combined with “pearl-growing” searches of the academic literature. We categorized the methods that have been used according to the assumptions they made about how the hazards of death vary between the external and internal data and through time, and we discuss the appropriateness of the assumptions in different circumstances. Modeling choices, parameter estimation, and characterization of uncertainty are discussed, and some suggestions for future research priorities in this area are given. PMID:27005519

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

PubMed Central

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

2017-01-01

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

Systematic instruction for individuals with acquired brain injury: Results of a randomized controlled trial

PubMed Central

Powell, Laurie Ehlhardt; Glang, Ann; Ettel, Deborah; Todis, Bonnie; Sohlberg, McKay; Albin, Richard

2012-01-01

The goal of this study was to experimentally evaluate systematic instruction compared with trial-and-error learning (conventional instruction) applied to assistive technology for cognition (ATC), in a double blind, pretest-posttest, randomized controlled trial. Twenty-nine persons with moderate-severe cognitive impairments due to acquired brain injury (15 in systematic instruction group; 14 in conventional instruction) completed the study. Both groups received 12, 45-minute individual training sessions targeting selected skills on the Palm Tungsten E2 personal digital assistant (PDA). A criterion-based assessment of PDA skills was used to evaluate accuracy, fluency/efficiency, maintenance, and generalization of skills. There were no significant differences between groups at immediate posttest with regard to accuracy and fluency. However, significant differences emerged at 30-day follow-up in favor of systematic instruction. Furthermore, systematic instruction participants performed significantly better at immediate posttest generalizing trained PDA skills when interacting with people other than the instructor. These results demonstrate that systematic instruction applied to ATC results in better skill maintenance and generalization than trial-and-error learning for individuals with moderate-severe cognitive impairments due to acquired brain injury. Implications, study limitations, and directions for future research are discussed. PMID:22264146

Research design features and patient characteristics associated with the outcome of antidepressant clinical trials.

PubMed

Khan, Arif; Kolts, Russell L; Thase, Michael E; Krishnan, K Ranga Rama; Brown, Walter

2004-11-01

The authors examined which, if any, research design features and patient characteristics would significantly differ between successful and unsuccessful antidepressant trials. Clinical trial data were reviewed for nine antidepressants approved by the Food and Drug Administration between 1985 and 2000. From the antidepressant research programs on these medications, 52 clinical trials were included in the study. The authors evaluated trial design features, patient characteristics, and difference in response between placebo and antidepressant. Nine trial design features and patient characteristics were present in the research programs for all nine of the antidepressants. The severity of depressive symptoms before patient randomization, the dosing schedule (flexible versus fixed), the number of treatment arms, and the percentage of female patients were significantly associated with the difference in response to antidepressant and placebo. The duration of the antidepressant trial, number of patients per treatment arm, number of sites, and mean age of the patients were similar in successful trials (with a greater antidepressant-placebo difference) and less successful trials (with a smaller antidepressant-placebo difference). These findings may help in the design of future antidepressant trials.

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.

Blastocyst culture using single versus sequential media in clinical IVF: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Sfontouris, Ioannis A; Martins, Wellington P; Nastri, Carolina O; Viana, Iara G R; Navarro, Paula A; Raine-Fenning, Nick; van der Poel, Sheryl; Rienzi, Laura; Racowsky, Catherine

2016-10-01

The purpose of this study was to undertake a review of the available evidence comparing the use of a single medium versus sequential media for embryo culture to the blastocyst stage in clinical IVF. We searched the Cochrane Central, PubMed, Scopus, ClinicalTrials.gov, Current Controlled Trials and WHO International Clinical Trials Registry Platform to identify randomized controlled trials comparing single versus sequential media for blastocyst culture and ongoing pregnancy rate. Included studies randomized either oocytes/zygotes or women. Eligible oocyte/zygote studies were analyzed to assess the risk difference (RD) and 95 % confidence intervals (CI) between the two media systems; eligible woman-based studies were analyzed to assess the risk ratio (RR) and 95 % CI for clinical pregnancy rate. No differences were observed between single and sequential media for either ongoing pregnancy per randomized woman (relative risk (RR) = 0.9, 95 % CI = 0.7 to 1.3, two studies including 246 women, I 2  = 0 %) or clinical pregnancy per randomized woman (RR = 1.0, 95 % CI = 0.7 to 1.4, one study including 100 women); or miscarriage per clinical pregnancy: RR = 1.3, 95 % CI = 0.4 to 4.3, two studies including 246 participants, I 2  = 0 %). Single media use was associated with an increase blastocyst formation per randomized oocyte/zygote (relative distribution (RD) = +0.06, 95 % CI = +0.01 to +0.12, ten studies including 7455 oocytes/zygotes, I 2  = 83 %) but not top/high blastocyst formation (RD = +0.05, 95 % CI = -0.01 to +0.11, five studies including 3879 oocytes/zygotes, I 2  = 93 %). The overall quality of the evidence was very low for all these four outcomes. Although using a single medium for extended culture has some practical advantages and blastocyst formation rates appear to be higher, there is insufficient evidence to recommend either sequential or single-step media as being superior for the culture of embryos to days 5/6. Future studies comparing these two media systems in well-designed trials should be performed.

New approaches to trials in glomerulonephritis.

PubMed

Craig, Jonathan C; Tong, Allison; Strippoli, Giovanni F M

2017-01-01

Randomized controlled trials are required to reliably identify interventions to improve the outcomes for people with glomerulonephritis (GN). Unfortunately, although easier, observational studies are inherently unreliable even though the findings of both study designs agree most of the time. Currently there are ∼790 trials in GN, but suboptimal design and reporting, together with small sample sizes, mean that they may not be reliable for decision making. If the history is somewhat bleak, the future looks bright, with recent initiatives to improve the quality, size and relevance of clinical trials in nephrology, including greater patient engagement, trial networks, core outcome sets, registry-based trials and adaptive designs. Given the current state of the evidence informing the care of people with GN, disruptive technologies and pervasive culture change is required to ensure that the potential of trials to improve the health of people with this complex condition is to be realized. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Thrombus Aspiration in ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration.

PubMed

Jolly, Sanjit S; James, Stefan; Džavík, Vladimír; Cairns, John A; Mahmoud, Karim D; Zijlstra, Felix; Yusuf, Salim; Olivecrona, Goran K; Renlund, Henrik; Gao, Peggy; Lagerqvist, Bo; Alazzoni, Ashraf; Kedev, Sasko; Stankovic, Goran; Meeks, Brandi; Frøbert, Ole

2017-01-10

Thrombus aspiration during percutaneous coronary intervention (PCI) for the treatment of ST-segment-elevation myocardial infarction (STEMI) has been widely used; however, recent trials have questioned its value and safety. In this meta-analysis, we, the trial investigators, aimed to pool the individual patient data from these trials to determine the benefits and risks of thrombus aspiration during PCI in patients with ST-segment-elevation myocardial infarction. Included were large (n≥1000), randomized, controlled trials comparing manual thrombectomy and PCI alone in patients with ST-segment-elevation myocardial infarction. Individual patient data were provided by the leadership of each trial. The prespecified primary efficacy outcome was cardiovascular mortality within 30 days, and the primary safety outcome was stroke or transient ischemic attack within 30 days. The 3 eligible randomized trials (TAPAS [Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction], TASTE [Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia], and TOTAL [Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI]) enrolled 19 047 patients, of whom 18 306 underwent PCI and were included in the primary analysis. Cardiovascular death at 30 days occurred in 221 of 9155 patients (2.4%) randomized to thrombus aspiration and 262 of 9151 (2.9%) randomized to PCI alone (hazard ratio, 0.84; 95% confidence interval, 0.70-1.01; P=0.06). Stroke or transient ischemic attack occurred in 66 (0.8%) randomized to thrombus aspiration and 46 (0.5%) randomized to PCI alone (odds ratio, 1.43; 95% confidence interval, 0.98-2.10; P=0.06). There were no significant differences in recurrent myocardial infarction, stent thrombosis, heart failure, or target vessel revascularization. In the subgroup with high thrombus burden (TIMI [Thrombolysis in Myocardial Infarction] thrombus grade ≥3), thrombus aspiration was associated with fewer cardiovascular deaths (170 [2.5%] versus 205 [3.1%]; hazard ratio, 0.80; 95% confidence interval, 0.65-0.98; P=0.03) and with more strokes or transient ischemic attacks (55 [0.9%] versus 34 [0.5%]; odds ratio, 1.56; 95% confidence interval, 1.02-2.42, P=0.04). However, the interaction P values were 0.32 and 0.34, respectively. Routine thrombus aspiration during PCI for ST-segment-elevation myocardial infarction did not improve clinical outcomes. In the high thrombus burden group, the trends toward reduced cardiovascular death and increased stroke or transient ischemic attack provide a rationale for future trials of improved thrombus aspiration technologies in this high-risk subgroup. URLs: http://www.ClinicalTrials.gov http://www.crd.york.ac.uk/prospero/. Unique identifiers: NCT02552407 and CRD42015025936. © 2016 American Heart Association, Inc.

Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639].

PubMed

Gasparovic, Hrvoje; Petricevic, Mate; Kopjar, Tomislav; Djuric, Zeljko; Svetina, Lucija; Biocina, Bojan

2012-08-25

Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive. The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events. Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology) as well as bleeding events will be recorded. This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management. This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639).

Future directions in treatment of brain metastases

PubMed Central

Barani, Igor J.; Larson, David A.; Berger, Mitchel S.

2013-01-01

Background: Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. Methods: A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. Results: The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Conclusions: Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT. PMID:23717793

Future directions in treatment of brain metastases.

PubMed

Barani, Igor J; Larson, David A; Berger, Mitchel S

2013-01-01

Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT.

Composite outcomes in randomized clinical trials: arguments for and against.

PubMed

Ross, Sue

2007-02-01

Composite outcomes that combine a number of individual outcomes (such as types of morbidity) are frequently used as primary outcomes in obstetrical trials. The main argument for their use is to ensure that trials can answer important clinical questions in a timely fashion, without needing huge sample sizes. Arguments against their use are that composite outcomes may be difficult to use and interpret, leading to errors in sample size estimation, possible contradictory trial results, and difficulty in interpreting findings. Such problems may reduce the credibility of the research, and may impact on the implementation of findings. Composite outcomes are an attractive solution to help to overcome the problem of limited available resources for clinical trials. However, future studies should carefully consider both the advantages and disadvantages before using composite outcomes. Rigorous development and reporting of composite outcomes is essential if the research is to be useful.

The Efficacy of a Home-School Intervention for Preschoolers with Challenging Behaviors: A Randomized Controlled Trial of Preschool First Step to Success

ERIC Educational Resources Information Center

Feil, Edward G.; Frey, Andy; Walker, Hill M.; Small, Jason W.; Seeley, John R.; Golly, Annemieke; Forness, Steven R.

2014-01-01

The field of early intervention is currently faced with the challenge of reducing the prevalence of antisocial behavior in children. Longitudinal outcomes research indicates that increased antisocial behavior and impairments in social competence skills during the preschool years often serve as harbingers of future adjustment problems in a number…

Future aspects of cellular and molecular research in clinical voice treatment aspects of optical coherence tomography

NASA Astrophysics Data System (ADS)

Pedersen, Mette; Mahmood, Sanila

2015-02-01

Focus is upon our clinical experience in a prospective cohort study on cure of dystonia where the mode of treatment was fexofenadine tablets and local budesonide inhaler in the larynx, and in a randomized controlled trial of lifestyle change related to acid provocation of food and habits in laryngopharyngeal reflux (LPR). The advanced high-speed films is one new tool, another being optical coherence tomography (OCT), which should be used in the future in randomized controlled trials. We are focusing on OCT of the swallowing process in the oesophagaus and larynx as well as the vocal fold function. It can be shown on OCT how the layer of the vocal folds develop, possibly corresponding to hormonal and paediatric development. The arytenoid area in the larynx should also be focused upon with OCT in pathology. The thyroid function is related to voice and the swallowing function, both hormonally and pathoanatomically. We know too little about voice and thyroid hormones in an updated way as well as the outer anatomic supporting muscular structure of the larynx, related to thyroid immune degeneration and cysts. Also, here OCT analyses might be of value.

Methodological quality of randomized trials published in the Journal of the American Podiatric Medical Association, 1999-2013.

PubMed

Landorf, Karl B; Menz, Hylton B; Armstrong, David G; Herbert, Robert D

2015-07-01

Randomized trials must be of high methodological quality to yield credible, actionable findings. The main aim of this project was to evaluate whether there has been an improvement in the methodological quality of randomized trials published in the Journal of the American Podiatric Medical Association (JAPMA). Randomized trials published in JAPMA during a 15-year period (January 1999 to December 2013) were evaluated. The methodological quality of randomized trials was evaluated using the PEDro scale (scores range from 0 to 10, with 0 being lowest quality). Linear regression was used to assess changes in methodological quality over time. A total of 1,143 articles were published in JAPMA between January 1999 and December 2013. Of these, 44 articles were reports of randomized trials. Although the number of randomized trials published each year increased, there was only minimal improvement in their methodological quality (mean rate of improvement = 0.01 points per year). The methodological quality of the trials studied was typically moderate, with a mean ± SD PEDro score of 5.1 ± 1.5. Although there were a few high-quality randomized trials published in the journal, most (84.1%) scored between 3 and 6. Although there has been an increase in the number of randomized trials published in JAPMA, there is substantial opportunity for improvement in the methodological quality of trials published in the journal. Researchers seeking to publish reports of randomized trials should seek to meet current best-practice standards in the conduct and reporting of their trials.

Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: A combined analysis of two randomized controlled trials

PubMed Central

Wolsk, Helene M.; Chawes, Bo L.; Litonjua, Augusto A.; Hollis, Bruce W.; Waage, Johannes; Stokholm, Jakob; Bønnelykke, Klaus; Bisgaard, Hans

2017-01-01

Background We recently published two independent randomized controlled trials of vitamin D supplementation during pregnancy, both indicating a >20% reduced risk of asthma/recurrent wheeze in the offspring by 3 years of age. However, neither reached statistical significance. Objective To perform a combined analysis of the two trials and investigate whether maternal 25-hydroxy-vitamin D (25(OH)D) level at trial entry modified the intervention effect. Methods VDAART (N = 806) and COPSAC2010. (N = 581) randomized pregnant women to daily high-dose vitamin D3 (4,000 IU/d and 2,400 IU/d, respectively) or placebo. All women also received a prenatal vitamin containing 400 IU/d vitamin D3. The primary outcome was asthma/recurrent wheeze from 0-3yrs. Secondary end-points were specific IgE, total IgE, eczema and lower respiratory tract infections (LRTI). We conducted random effects combined analyses of the treatment effect, individual patient data (IPD) meta-analyses, and analyses stratified by 25(OH)D level at study entry. Results The analysis showed a 25% reduced risk of asthma/recurrent wheeze at 0-3yrs: adjusted odds ratio (aOR) = 0.74 (95% CI, 0.57–0.96), p = 0.02. The effect was strongest among women with 25(OH)D level ≥30ng/ml at study entry: aOR = 0.54 (0.33–0.88), p = 0.01, whereas no significant effect was observed among women with 25(OH)D level <30ng/ml at study entry: aOR = 0.84 (0.62–1.15), p = 0.25. The IPD meta-analyses showed similar results. There was no effect on the secondary end-points. Conclusions This combined analysis shows that vitamin D supplementation during pregnancy results in a significant reduced risk of asthma/recurrent wheeze in the offspring, especially among women with 25(OH)D level ≥ 30 ng/ml at randomization, where the risk was almost halved. Future studies should examine the possibility of raising 25(OH)D levels to at least 30 ng/ml early in pregnancy or using higher doses than used in our studies. Trial registration COPSAC2010: ClinicalTrials.gov NCT00856947; VDAART: ClinicalTrials.gov NCT00920621 PMID:29077711

Rhodiola rosea therapy for major depressive disorder: a study protocol for a randomized, double-blind, placebo- controlled trial

PubMed Central

Mao, Jun J; Li, Qing S.; Soeller, Irene; Xie, Sharon X; Amsterdam, Jay D.

2014-01-01

Background Rhodiola rosea (R. rosea), a botanical of both western and traditional Chinese medicine, has been used as a folk remedy for improving stamina and reducing stress. However, few controlled clinical trials have examined the safety and efficacy of R. rosea for the treatment of major depressive disorder (MDD). This study seeks to evaluate the safety and efficacy of R. rosea in a 12-week, randomized, double-blind, placebo-controlled, parallel group study design. Methods / Design Subjects with MDD not receiving antidepressant therapy will be randomized to either R. rosea extract 340–1,360 mg daily; sertraline 50–200 mg daily, or placebo for 12 weeks. The primary outcome measure will be change over time in the mean 17-item Hamilton Depression Rating score. Secondary outcome measures will include safety and quality of life ratings. Statistical procedures will include mixed-effects models to assess efficacy for primary and secondary outcomes. Discussion This study will provide valuable preliminary information on the safety and efficacy data of R. rosea versus conventional antidepressant therapy of MDD. It will also inform additional hypotheses and study design of future, fully powered, phase III clinical trials with R. rosea to determine its safety and efficacy in MDD. PMID:25610752

Chronic obstructive pulmonary disease self-management activation research trial (COPD-SMART): results of recruitment and baseline patient characteristics.

PubMed

Russo, Rennie; Coultas, David; Ashmore, Jamile; Peoples, Jennifer; Sloan, John; Jackson, Bradford E; Uhm, Minyong; Singh, Karan P; Blair, Steven N; Bae, Sejong

2015-03-01

To describe the recruitment methods, study participation rate, and baseline characteristics of a representative sample of outpatients with COPD eligible for pulmonary rehabilitation participating in a trial of a lifestyle behavioral intervention to increase physical activity. A patient registry was developed for recruitment using an administrative database from primary care and specialty clinics of an academic medical center in northeast Texas for a parallel group randomized trial. The registry was comprised of 5582 patients and over the course of the 30 month recruitment period 325 patients were enrolled for an overall study participation rate of 35.1%. After a 6-week COPD self-management education period provided to all enrolled patients, 305 patients were randomized into either usual care (UC; n=156) or the physical activity self-management intervention (PASM; n=149). There were no clinically significant differences in demographics, clinical characteristics, or health status indicators between the randomized groups. The results of this recruitment process demonstrate the successful use of a patient registry for enrolling a representative sample of outpatients eligible for pulmonary rehabilitation with COPD from primary and specialty care. Moreover, this approach to patient recruitment provides a model for future studies utilizing administrative databases and electronic health records. Published by Elsevier Inc.

Commercial programs' online weight loss claims as compared to results from randomized controlled trials

PubMed Central

Vakil, Rachit M.; Chaudhry, Zoobia W.; Doshi, Ruchi S.; Clark, Jeanne M.; Gudzune, Kimberly A.

2017-01-01

Objective To characterize weight-loss claims and disclaimers present on websites for commercial weight-loss programs and compare them to results from published randomized controlled trials (RCT). Methods We performed a content analysis of all homepages and testimonials available on the websites of 24 randomly selected programs. Two team members independently reviewed each page and abstracted information from text and images to capture relevant content including demographics, weight loss, and disclaimers. We performed a systematic review to evaluate the efficacy of these programs by searching MEDLINE and Cochrane Database of Systematic Reviews, and abstracted mean weight change from each included RCT. Results Overall, the amount of weight loss portrayed in the testimonials was extreme across all programs examined (range median weight loss 10.7 to 49.5 kg). Only 10 out of the 24 programs had eligible RCTs. Median weight losses reported in testimonials exceeded that achieved by trial participants. Most programs with RCTs (78%) provided disclaimers stating that the testimonial's results were non-typical and/or giving a range of typical weight loss. Conclusion Weight loss claims within testimonials were higher than results from RCTs. Future studies should examine whether commercial programs' advertising practices influence patients' expectations or satisfaction with modest weight loss results. PMID:28865085

Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke--a randomized, double-blind, placebo-controlled trial.

PubMed

Lokk, J; Salman Roghani, R; Delbari, A

2011-04-01

Amphetamine-like drugs are reported to enhance motor recovery and activities of daily living (ADL) in stroke rehabilitation, but results from trials with humans are inconclusive. This study is aimed at investigating whether levodopa (LD) and/or methylphenidate (MPH) in combination with physiotherapy could improve functional motor recovery and ADL in patients with stroke. A randomized, double-blind, placebo-controlled trial with ischemic stroke patients randomly allocated to one of four treatment groups of either MPH, LD or MPH+LD or placebo combined with physiotherapy was performed. Motor function, ADL, and stroke severity were assessed by Fugl-Meyer (FM), Barthel index (BI), and National Institute of Health Stroke Scale (NIHSS) at baseline, 15, 90, and 180 days respectively. All participants showed recovery of motor function and ADL during treatment and at 6-month follow-up. There were slightly but significant differences in BI and NIHSS compared to placebo at the 6-month follow-up. Ischemic chronic stroke patients having MPH and/or LD in combination with physiotherapy showed a slight ADL and stroke severity improvement over time. Future studies should address the issue of the optimal therapeutic window and dosage of medications to identify those patients who would benefit most. © 2010 John Wiley & Sons A/S.

Current Evidence on Auricular Therapy for Chemotherapy-Induced Nausea and Vomiting in Cancer Patients: A Systematic Review of Randomized Controlled Trials

PubMed Central

Molassiotis, Alexander; Wang, Tao; Suen, Lorna K. P.

2014-01-01

Auricular therapy (AT) has been historically viewed as a convenient approach adjunct to pharmacological therapy for cancer patients with chemotherapy-induced nausea and vomiting (CINV). The aim of this study was to assess the evidence of the therapeutic effect of AT for CINV management in cancer patients. Relevant randomized controlled trials were retrieved from 12 electronic databases without language restrictions. Meanwhile, manual search was conducted for Chinese journals on complementary medicine published within the last five years, and the reference lists of included studies were also checked to identify any possible eligible studies. Twenty-one studies with 1713 participants were included. The effect rate of AT for managing acute CINV ranged from 44.44% to 93.33% in the intervention groups and 15% to 91.67% in the control groups. For delayed CINV, it was 62.96% to 100% and 25% to 100%, respectively. AT seems to be a promising approach in managing CINV. However, the level of evidence was low and the definite effect cannot be concluded as there were significant methodological flaws identified in the analyzed studies. The implications drawn from the 21 studies put some clues for future practice in this area including the need to conduct more rigorously designed randomized controlled trials. PMID:25525445

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

PubMed

Andrews, Peter J D

2010-03-01

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

Designing Clinical Trials of Interventions for Mobility Disability: Results from the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) Trial

PubMed Central

Espeland, Mark A.; Gill, Thomas M.; Guralnik, Jack; Miller, Michael E.; Fielding, Roger; Newman, Anne B.; Pahor, Marco

2008-01-01

Background Clinical trials to assess interventions for mobility disability are critically needed; however, data for efficiently designing such trials are lacking. Methods Results are described from a pilot clinical trial in which 424 volunteers aged 70–89 years were randomly assigned to one of two interventions -- physical activity or a healthy aging education program -- and followed for a planned minimum of 12 months. We evaluated the longitudinal distributions of four standardized outcomes to contrast how they may serve as primary outcomes of future clinical trials: ability to walk 400 meters, ability to walk 4 meters in ≤10 seconds, a physical performance battery, and a questionnaire focused on physical function. Results Changes in all four outcomes were inter-related over time. The ability to walk 400 meters as a dichotomous outcome provided the smallest sample size projections (i.e. appeared to be the most efficient outcome). It loaded most heavily on the underlying latent variable in structural equation modeling with a weight of 80%. A four-year trial based on the outcome of 400 meter walk is projected to require N = 962 to 2,234 to detect an intervention effect of 30% to 20% with 90% power. Conclusions Future clinical trials of interventions designed to influence mobility disability may have greater efficiency if they adopt the ability to complete a 400 meter walk as their primary outcome. PMID:18000143

Physical activity measurements affected participants' behavior in a randomized controlled trial.

PubMed

van Sluijs, Esther M F; van Poppel, Mireille N M; Twisk, Jos W R; van Mechelen, Willem

2006-04-01

Assessing levels and determinants of physical activity as outcome measurements might have an independent effect on participant's physical activity behavior. The objective is to study this effect in a randomized controlled trial (RCT) promoting regular physical activity in Dutch general practice. Using a Solomon four-group design, participants were randomized twice. After randomization to a control or intervention-condition at general practice level (N = 29), participants were randomized to a group participating in measurements at baseline, 2 and 6 months (3M-group, N = 361), or a group only participating in measurements at 6 months (1M-group, N = 356). Outcome measures assessed at 6 months included: level of physical activity (self-reported and objectively measured with accelerometry), meeting ACSM/CDC guideline for regular physical activity, stage of change, and determinants of physical activity. Follow-up data on 635 participants (89%) was collected. Statistically significant measurement effects were found for meeting the ACSM/CDC guideline (self-reported), self-efficacy for resisting relapse, knowledge, and on awareness. Other outcome measures showed positive trends, except stages of change. Measurements of physical activity affect participant's physical activity behavior, possibly triggered by a raised awareness about their own physical activity level. Implications for future research are discussed, as well as methodologic limitations of the study design.

Comparing the effect of a decision aid plus patient navigation with usual care on colorectal cancer screening completion in vulnerable populations: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Screening can reduce colorectal cancer (CRC) incidence and mortality. However, screening is underutilized in vulnerable patient populations, particularly among Latinos. Patient-directed decision aids can increase CRC screening knowledge, self-efficacy, and intent; however, their effect on actual screening test completion tends to be modest. This is probably because decision aids do not address some of the patient-specific barriers that prevent successful completion of CRC screening in these populations. These individual barriers might be addressed though patient navigation interventions. This study will test a combined decision aid and patient navigator intervention on screening completion in diverse populations of vulnerable primary care patients. Methods/Design We will conduct a multisite, randomized controlled trial with patient-level randomization. Planned enrollment is 300 patients aged 50 to 75 years at average CRC risk presenting for appointments at two primary clinics in North Carolina and New Mexico. Intervention participants will view a video decision aid immediately before the clinic visit. The 14 to 16 minute video presents information about fecal occult blood tests and colonoscopy and will be viewed on a portable computer tablet in English or Spanish. Clinic-based patient navigators are bilingual and bicultural and will provide both face-to-face and telephone-based navigation. Control participants will view an unrelated food safety video and receive usual care. The primary outcome is completion of a CRC screening test at six months. Planned subgroup analyses include examining intervention effectiveness in Latinos, who will be oversampled. Secondarily, the trial will evaluate the intervention effects on knowledge of CRC screening, self-efficacy, intent, and patient-provider communication. The study will also examine whether patient ethnicity, acculturation, language preference, or health insurance status moderate the intervention effect on CRC screening. Discussion This pragmatic randomized controlled trial will test a combined decision aid and patient navigator intervention targeting CRC screening completion. Findings from this trial may inform future interventions and implementation policies designed to promote CRC screening in vulnerable patient populations and to reduce screening disparities. Clinical trial registration ClinicalTrials.gov NCT02054598. PMID:25004983

Telemedicine Provides Non-Inferior Research Informed Consent for Remote Study Enrollment: A Randomized Controlled Trial

PubMed Central

Bobb, Morgan R.; Van Heukelom, Paul G.; Faine, Brett A.; Ahmed, Azeemuddin; Messerly, Jeffrey T.; Bell, Gregory; Harland, Karisa K.; Simon, Christian; Mohr, Nicholas M.

2016-01-01

Objective Telemedicine networks are beginning to provide an avenue for conducting emergency medicine research, but using telemedicine to recruit participants for clinical trials has not been validated. The goal of this consent study is to determine whether patient comprehension of telemedicine-enabled research informed consent is non-inferior to standard face-to-face research informed consent. Methods A prospective, open-label randomized controlled trial was performed in a 60,000-visit Midwestern academic Emergency Department (ED) to test whether telemedicine-enabled research informed consent provided non-inferior comprehension compared with standard consent. This study was conducted as part of a parent clinical trial evaluating the effectiveness of oral chlorhexidine gluconate 0.12% in preventing hospital-acquired pneumonia among adult ED patients with expected hospital admission. Prior to being recruited into the study, potential participants were randomized in a 1:1 allocation ratio to consent by telemedicine versus standard face-to-face consent. Telemedicine connectivity was provided using a commercially available interface (REACH platform, Vidyo Inc., Hackensack, NJ) to an emergency physician located in another part of the ED. Comprehension of research consent (primary outcome) was measured using the modified Quality of Informed Consent (QuIC) instrument, a validated tool for measuring research informed consent comprehension. Parent trial accrual rate and qualitative survey data were secondary outcomes. Results One-hundred thirty-one patients were randomized (n = 64, telemedicine), and 101 QuIC surveys were completed. Comprehension of research informed consent using telemedicine was not inferior to face-to-face consent (QuIC scores 74.4 ± 8.1 vs. 74.4 ± 6.9 on a 100-point scale, p = 0.999). Subjective understanding of consent (p=0.194) and parent trial study accrual rates (56% vs. 69%, p = 0.142) were similar. Conclusion Telemedicine is non-inferior to face-to-face consent for delivering research informed consent, with no detected differences in comprehension and patient-reported understanding. This consent study will inform design of future telemedicine-enabled clinical trials. PMID:26990899

Revisiting sample size: are big trials the answer?

PubMed

Lurati Buse, Giovanna A L; Botto, Fernando; Devereaux, P J

2012-07-18

The superiority of the evidence generated in randomized controlled trials over observational data is not only conditional to randomization. Randomized controlled trials require proper design and implementation to provide a reliable effect estimate. Adequate random sequence generation, allocation implementation, analyses based on the intention-to-treat principle, and sufficient power are crucial to the quality of a randomized controlled trial. Power, or the probability of the trial to detect a difference when a real difference between treatments exists, strongly depends on sample size. The quality of orthopaedic randomized controlled trials is frequently threatened by a limited sample size. This paper reviews basic concepts and pitfalls in sample-size estimation and focuses on the importance of large trials in the generation of valid evidence.

Study protocol of a multicenter randomized controlled trial of mindfulness training to reduce burnout and promote quality of life in police officers: the POLICE study.

PubMed

Trombka, Marcelo; Demarzo, Marcelo; Bacas, Daniel Campos; Antonio, Sonia Beira; Cicuto, Karen; Salvo, Vera; Claudino, Felipe Cesar Almeida; Ribeiro, Letícia; Christopher, Michael; Garcia-Campayo, Javier; Rocha, Neusa Sica

2018-05-25

Police officers experience a high degree of chronic stress. Policing ranks among the highest professions in terms of disease and accident rates. Mental health is particularly impacted, evidenced by elevated rates of burnout, anxiety and depression, and poorer quality of life than the general public. Mindfulness training has been shown to reduce stress, anxiety, burnout and promote quality of life in a variety of settings, although its efficacy in this context has yet to be systematically evaluated. Therefore, this trial will investigate the efficacy of a mindfulness-based intervention versus a waitlist control in improving quality of life and reducing negative mental health symptoms in police officers. This multicenter randomized controlled trial has three assessment points: baseline, post-intervention, and six-month follow-up. Active police officers (n = 160) will be randomized to Mindfulness-Based Health Promotion (MBHP) or waitlist control group at two Brazilian major cities: Porto Alegre and São Paulo. The primary outcomes are burnout symptoms and quality of life. Consistent with the MBHP conceptual model, assessed secondary outcomes include perceived stress, anxiety and depression symptoms, and the potential mechanisms of resilience, mindfulness, decentering, self-compassion, spirituality, and religiosity. Findings from this study will inform and guide future research, practice, and policy regarding police offer health and quality of life in Brazil and globally. ClinicalTrials.gov NCT03114605 . Retrospectively registered on March 21, 2017.

Enhanced Recovery After Surgery (ERAS®) in Individuals with Diabetes: A Systematic Review.

PubMed

Albalawi, Zaina; Laffin, Michael; Gramlich, Leah; Senior, Peter; McAlister, Finlay A

2017-08-01

Prevalence of diabetes in surgical patients is 10-40%. It is well recognized that they have higher rates of complications, and longer stays in hospital compared to patients without diabetes. Enhanced recovery after surgery (ERAS) is an evidence-based multimodal surgical care pathway that improves postoperative complications and length of stay in patients without diabetes. This review evaluates the evidence on whether individuals with diabetes would benefit from ERAS implementation. MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE searched with no language restrictions applied. Conference proceedings and bibliographies were reviewed. Experts in the field were contacted, and www.clinicaltrials.gov searched for ongoing trials. Randomized controlled trials (RCT) looking at individuals with diabetes undergoing surgery randomized to ERAS ® or conventional care. Non-randomized controlled trials, controlled before-after studies, interrupted time series, and cohort studies with concurrent controls were also considered. Two authors independently screened studies. The electronic search yielded 437 references. After removing duplicates, 376 were screened for eligibility. Conference proceedings and bibliographies identified additional references. Searching www.clinicaltrials.gov yielded 59 references. Contacting experts in the field identified no further studies. Fourteen full articles were assessed and subsequently excluded for the following reasons: used an intervention other than ERAS ® , did not include patients with diabetes, or used an uncontrolled observational design. To date, the effects of ERAS ® on patients with diabetes have not been rigorously evaluated. This review highlights the lack of evidence in this area and provides guidance on design for future studies.

Probiotic supplementation can positively affect anxiety and depressive symptoms: a systematic review of randomized controlled trials.

PubMed

Pirbaglou, Meysam; Katz, Joel; de Souza, Russell J; Stearns, Jennifer C; Motamed, Mehras; Ritvo, Paul

2016-09-01

Gastrointestinal microbiota, consisting of microbial communities in the gastrointestinal tract, play an important role in digestive, metabolic, and immune functioning. Preclinical studies on rodents have linked behavioral and neurochemical changes in the central nervous system with deficits or alterations in these bacterial communities. Moreover, probiotic supplementation in rodents has been shown to markedly change behavior, with correlated changes in central neurochemistry. While such studies have documented behavioral and mood-related supplementation effects, the significance of these effects in humans, especially in relation to anxiety and depression symptoms, are relatively unknown. Thus, the purpose of this paper was to systematically evaluate current literature on the impact of probiotic supplementation on anxiety and depression symptoms in humans. To this end, multiple databases, including Medline, PsycINFO, PubMed, Scopus, and Web of Science were searched for randomized controlled trials published between January 1990 and January 2016. Search results led to a total of 10 randomized controlled trials (4 in clinically diagnosed and 6 in non-clinical samples) that provided limited support for the use of some probiotics in reducing human anxiety and depression. Despite methodological limitations of the included trials and the complex nature of gut-brain interactions, results suggest the detection of apparent psychological benefits from probiotic supplementation. Nevertheless a better understanding of developmental, modulatory, and metagenomic influences on the GI microbiota, specifically as they relate to mood and mental health, represent strong priorities for future research in this area. Copyright © 2016 Elsevier Inc. All rights reserved.

Randomized controlled trial of parent-enhanced CBT compared with individual CBT for obsessive-compulsive disorder in young people.

PubMed

Reynolds, Shirley A; Clark, Sarah; Smith, Holly; Langdon, Peter E; Payne, Ruth; Bowers, Gemma; Norton, Elisabeth; McIlwham, Harriet

2013-12-01

Obsessive-compulsive disorder (OCD) in young people can be effectively treated with Cognitive Behavior Therapy (CBT). Practice guidelines in the United Kingdom recommend that CBT be delivered with parental or family involvement; however, there is no evidence from randomized trials that this enhances effectiveness. The aim of this trial was to assess if CBT with high parental involvement was more effective than CBT with low parental involvement (individual CBT) in reducing symptoms of OCD. Fifty young people ages 12-17 years with OCD were randomly allocated to individual CBT or parent-enhanced CBT. In parent-enhanced CBT parents attended all treatment sessions; in individual CBT, parents attended only Sessions 1, 7, and the final session. Participants received up to 14 sessions of CBT. Data were analyzed using intent-to-treat and per-protocol methods. The primary outcome measure was the Children's Yale-Brown Obsessive Compulsion Scale (Scahill et al., 1997). Both forms of CBT significantly reduced symptoms of OCD and anxiety. Change in OCD symptoms was maintained at 6 months. Per-protocol analysis suggested that parent-enhanced CBT may be associated with significantly larger reductions in anxiety symptoms. High and low parental involvement in CBT for OCD in young people were both effective, and there was no evidence that 1 method of delivery was superior on the primary outcome measure. However, this study was small. Future trials should be adequately powered and examine interactions with the age of the young person and comorbid anxiety disorders.

Update on PEG-interferon α-2b as adjuvant therapy in melanoma.

PubMed

Di Trolio, Rossella; Simeone, Ester; Di Lorenzo, Giuseppe; Grimaldi, Antonio Maria; Romano, Anna; Ayala, Fabrizio; Caracò, Corrado; Mozzillo, Nicola; Ascierto, Paolo A

2012-09-01

Based on the results of European Organization for Research and Treatment of Cancer (EORTC) 18991 trial, the US Food and Drug Administration (FDA) approved PEG-interferon α-2b (PEG-IFN) (Sylatron) as adjuvant therapy for high-risk melanoma. The EORTC 18991 trial was an open-label study of resectable stage III melanoma with 1,256 patients who were randomized to observation-alone or to treatment with PEG-IFN for up to 5 years. The median recurrence-free survival of the treatment groups was significantly longer, while overall survival, a secondary endpoint, was not significantly different between the two groups. This review, after a short summary of interferon α-2b trials, critically analyzes the EORTC18991 trial, as well as the subgroup results and future perspectives for this stage of disease.

A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease.

PubMed

Mente, Andrew; de Koning, Lawrence; Shannon, Harry S; Anand, Sonia S

2009-04-13

Although a wealth of literature links dietary factors and coronary heart disease (CHD), the strength of the evidence supporting valid associations has not been evaluated systematically in a single investigation. We conducted a systematic search of MEDLINE for prospective cohort studies or randomized trials investigating dietary exposures in relation to CHD. We used the Bradford Hill guidelines to derive a causation score based on 4 criteria (strength, consistency, temporality, and coherence) for each dietary exposure in cohort studies and examined for consistency with the findings of randomized trials. Strong evidence supports valid associations (4 criteria satisfied) of protective factors, including intake of vegetables, nuts, and "Mediterranean" and high-quality dietary patterns with CHD, and associations of harmful factors, including intake of trans-fatty acids and foods with a high glycemic index or load. Among studies of higher methodologic quality, there was also strong evidence for monounsaturated fatty acids and "prudent" and "western" dietary patterns. Moderate evidence (3 criteria) of associations exists for intake of fish, marine omega-3 fatty acids, folate, whole grains, dietary vitamins E and C, beta carotene, alcohol, fruit, and fiber. Insufficient evidence (< or =2 criteria) of association is present for intake of supplementary vitamin E and ascorbic acid (vitamin C); saturated and polyunsaturated fatty acids; total fat; alpha-linolenic acid; meat; eggs; and milk. Among the dietary exposures with strong evidence of causation from cohort studies, only a Mediterranean dietary pattern is related to CHD in randomized trials. The evidence supports a valid association of a limited number of dietary factors and dietary patterns with CHD. Future evaluation of dietary patterns, including their nutrient and food components, in cohort studies and randomized trials is recommended.

A Meta-Analysis of D-Cycloserine in Exposure-Based Treatment: Moderators of Treatment Efficacy, Response, and Diagnostic Remission

PubMed Central

McGuire, Joseph F.; Wu, Monica S.; Piacentini, John; McCracken, James T.; Storch, Eric A.

2018-01-01

Objective This meta-analysis examined treatment efficacy, treatment response, and diagnostic remission effect sizes (ES) and moderators of d-cycloserine (DCS) augmented exposure treatment in randomized controlled trials (RCTs) of individuals with anxiety disorders, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). Data Sources and Study Selection Using search terms d-cycloserine AND randomized controlled trial, PubMED (1965-May 2015), PsycInfo, and Scopus were searched for randomized placebo-controlled trials of DCS-augmented exposure therapy for anxiety disorders, OCD, and PTSD. Data Extraction Clinical variables and ES were extracted from 20 RCTs (957 participants). A random effects model calculated the ES for treatment efficacy, treatment response, and diagnostic remission using standardized rating scales. Subgroup analyses and meta-regression examined potential moderators. Results A small non-significant benefit of DCS augmentation compared to placebo augmentation was identified across treatment efficacy (g=0.15), response (RR=1.08), and remission (RR=1.109), with a moderately significant effect for anxiety disorders specifically (g=0.33, p=.03). At initial follow-up assessments, a small non-significant ES of DCS augmentation compared to placebo was found for treatment efficacy (g=0.21), response (RR=1.06), and remission (RR=1.12). Specific treatment moderators (e.g., comorbidity, medication status, gender, publication year) were found across conditions for both acute treatment and initial follow-up assessments. Conclusions DCS does not universally enhance treatment outcomes, but demonstrates promise for anxiety disorders. Distinct treatment moderators may account for discrepant findings across RCTs and disorders. Future trials may be strengthened by accounting for identified moderators in their design, with ongoing research needed on the mechanisms of DCS to tailor treatment protocols and maximize its benefit. PMID:27314661

A novel early intervention for preschool depression: findings from a pilot randomized controlled trial.

PubMed

Luby, Joan; Lenze, Shannon; Tillman, Rebecca

2012-03-01

Validation for depression in preschool children has been established; however, to date no empirical investigations of interventions for the early onset disorder have been conducted. Based on this and the modest efficacy of available treatments for childhood depression, the need for novel early interventions has been emphasized. Large effect sizes (ES) for preschool psychotherapies for several Axis I disorders suggest that earlier intervention in depression may also be promising. Therefore, a novel form of treatment for preschool depression, Parent-Child Interaction Therapy Emotion Development (PCIT-ED) was developed and tested. A preliminary randomized controlled trial (RCT) was conducted comparing PCIT-ED to psycho-education in depressed 3- to 7-year-olds and their caregivers. A total of 54 patients met symptom criteria for DSM-IV major depressive disorder and were randomized, 19 patients completed the active treatment (n = 8 dropouts) and 10 completed psycho-education (n = 17 dropouts). Both groups showed significant improvement in several domains, with PCIT-ED showing significance in a greater number of domains. An intent-to-treat analysis suggested that PCIT-ED was significantly more effective than psycho-education on executive functioning (p = .011, ES = 0.12) and emotion recognition skills (p = .002, ES = 0.83). The RCT proved feasible and suggests an individual control condition should be used in future trials to minimize differential dropout. These pilot data, although limited by power, suggest that PCIT-ED may be a promising early intervention for depression. Larger scale randomized controlled trials of PCIT-ED for depressed preschoolers are now warranted. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.

Effects of Exercise Training on Cardiorespiratory Fitness and Biomarkers of Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Lin, Xiaochen; Zhang, Xi; Guo, Jianjun; Roberts, Christian K; McKenzie, Steve; Wu, Wen-Chih; Liu, Simin; Song, Yiqing

2015-06-26

Guidelines recommend exercise for cardiovascular health, although evidence from trials linking exercise to cardiovascular health through intermediate biomarkers remains inconsistent. We performed a meta-analysis of randomized controlled trials to quantify the impact of exercise on cardiorespiratory fitness and a variety of conventional and novel cardiometabolic biomarkers in adults without cardiovascular disease. Two researchers selected 160 randomized controlled trials (7487 participants) based on literature searches of Medline, Embase, and Cochrane Central (January 1965 to March 2014). Data were extracted using a standardized protocol. A random-effects meta-analysis and systematic review was conducted to evaluate the effects of exercise interventions on cardiorespiratory fitness and circulating biomarkers. Exercise significantly raised absolute and relative cardiorespiratory fitness. Lipid profiles were improved in exercise groups, with lower levels of triglycerides and higher levels of high-density lipoprotein cholesterol and apolipoprotein A1. Lower levels of fasting insulin, homeostatic model assessment-insulin resistance, and glycosylated hemoglobin A1c were found in exercise groups. Compared with controls, exercise groups had higher levels of interleukin-18 and lower levels of leptin, fibrinogen, and angiotensin II. In addition, we found that the exercise effects were modified by age, sex, and health status such that people aged <50 years, men, and people with type 2 diabetes, hypertension, dyslipidemia, or metabolic syndrome appeared to benefit more. This meta-analysis showed that exercise significantly improved cardiorespiratory fitness and some cardiometabolic biomarkers. The effects of exercise were modified by age, sex, and health status. Findings from this study have significant implications for future design of targeted lifestyle interventions. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Effects of Exercise Training on Cardiorespiratory Fitness and Biomarkers of Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Lin, Xiaochen; Zhang, Xi; Guo, Jianjun; Roberts, Christian K; McKenzie, Steve; Wu, Wen-Chih; Liu, Simin; Song, Yiqing

2015-01-01

Background Guidelines recommend exercise for cardiovascular health, although evidence from trials linking exercise to cardiovascular health through intermediate biomarkers remains inconsistent. We performed a meta-analysis of randomized controlled trials to quantify the impact of exercise on cardiorespiratory fitness and a variety of conventional and novel cardiometabolic biomarkers in adults without cardiovascular disease. Methods and Results Two researchers selected 160 randomized controlled trials (7487 participants) based on literature searches of Medline, Embase, and Cochrane Central (January 1965 to March 2014). Data were extracted using a standardized protocol. A random-effects meta-analysis and systematic review was conducted to evaluate the effects of exercise interventions on cardiorespiratory fitness and circulating biomarkers. Exercise significantly raised absolute and relative cardiorespiratory fitness. Lipid profiles were improved in exercise groups, with lower levels of triglycerides and higher levels of high-density lipoprotein cholesterol and apolipoprotein A1. Lower levels of fasting insulin, homeostatic model assessment–insulin resistance, and glycosylated hemoglobin A1c were found in exercise groups. Compared with controls, exercise groups had higher levels of interleukin-18 and lower levels of leptin, fibrinogen, and angiotensin II. In addition, we found that the exercise effects were modified by age, sex, and health status such that people aged <50 years, men, and people with type 2 diabetes, hypertension, dyslipidemia, or metabolic syndrome appeared to benefit more. Conclusions This meta-analysis showed that exercise significantly improved cardiorespiratory fitness and some cardiometabolic biomarkers. The effects of exercise were modified by age, sex, and health status. Findings from this study have significant implications for future design of targeted lifestyle interventions. PMID:26116691

Sexual risk reduction among non-injection drug users: report of a randomized controlled trial.

PubMed

Castor, Delivette; Pilowsky, Daniel J; Hadden, Bernadette; Fuller, Crystal; Ompad, Danielle C; de Leon, Cora L; Neils, Greg; Hoepner, Lori; Andrews, Howard F; Latkin, Carl; Hoover, Donald R

2010-01-01

We conducted a randomized controlled trial of a sexual risk-reduction intervention targeting non-injection drug users (NIDUs) and members of their drug-use/sexual networks (N=270). The intervention was based primarily on the social-influencing approach, and was delivered in four sessions. Sexual risk behaviors were examined at baseline, and 3, 6, 9, and 12 months after the completion of the intervention using the vaginal equivalent episodes (VEE), a weighted sexual risk behavior index. VEE scores decreased in both the active and control conditions in the first six months post-intervention and continued to decline in the control group. However, in the active condition, VEE scores increased after the nine-month assessment and approached baseline levels by the 12-month assessment. There was no evidence of significant differences in high-risk sexual behaviors between the intervention and control conditions. Future studies are needed to improve behavioral interventions in this population.

Improving guideline concordance in multidisciplinary teams: preliminary results of a cluster-randomized trial evaluating the effect of a web-based audit and feedback intervention with outreach visits

PubMed Central

van Engen-Verheul, Mariëtte M.; Gude, Wouter T.; van der Veer, Sabine N.; Kemps, Hareld M.C.; Jaspers, Monique M.W.; de Keizer, Nicolette F.; Peek, Niels

2015-01-01

Despite their widespread use, audit and feedback (A&F) interventions show variable effectiveness on improving professional performance. Based on known facilitators of successful A&F interventions, we developed a web-based A&F intervention with indicator-based performance feedback, benchmark information, action planning and outreach visits. The goal of the intervention was to engage with multidisciplinary teams to overcome barriers to guideline concordance and to improve overall team performance in the field of cardiac rehabilitation (CR). To assess its effectiveness we conducted a cluster-randomized trial in 18 CR clinics (14,847 patients) already working with computerized decision support (CDS). Our preliminary results showed no increase in concordance with guideline recommendations regarding prescription of CR therapies. Future analyses will investigate whether our intervention did improve team performance on other quality indicators. PMID:26958310

A pilot randomized trial teaching mindfulness-based stress reduction to traumatized youth in foster care.

PubMed

Jee, Sandra H; Couderc, Jean-Philippe; Swanson, Dena; Gallegos, Autumn; Hilliard, Cammie; Blumkin, Aaron; Cunningham, Kendall; Heinert, Sara

2015-08-01

This article presents a pilot project implementing a mindfulness-based stress reduction program among traumatized youth in foster and kinship care over 10 weeks. Forty-two youth participated in this randomized controlled trial that used a mixed-methods (quantitative, qualitative, and physiologic) evaluation. Youth self-report measuring mental health problems, mindfulness, and stress were lower than anticipated, and the relatively short time-frame to teach these skills to traumatized youth may not have been sufficient to capture significant changes in stress as measured by electrocardiograms. Main themes from qualitative data included expressed competence in managing ongoing stress, enhanced self-awareness, and new strategies to manage stress. We share our experiences and recommendations for future research and practice, including focusing efforts on younger youth, and using community-based participatory research principles to promote engagement and co-learning. CLINICALTRIALS.GOV: Protocol Registration System ID NCT01708291. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of an Empirically Based Preventive Intervention for Depression in Preadolescent African American Girls.

PubMed

Duffy, Sophia; Brown, Tasha M; Katsonga-Phiri, Tiamo; Bouris, Alida; Grant, Kathryn E; Keenan, Kate

2016-05-01

We describe the development, feasibility, and acceptability of a novel preventive intervention for depression in African American girls living in urban poverty. Our approach targeted individual and interpersonal vulnerabilities that have been shown to confer risk for depression in samples of African American girls living in low-income, urban settings, including suppression of negative emotion and lack of assertiveness with peers, memory for positive emotion, active coping, and family connection. Focus groups and an open trial were conducted to refine the goals and mechanisms for skill building. A randomized controlled trial (RCT) of the new program (Cities Mother-Daughter Project) was conducted with 3rd-5th grade students from Chicago Public Schools (CPS). Three cycles of screening, randomization, and deployment were conducted to assess feasibility, satisfaction, and usability. Results indicate that feasibility was weak; whereas, satisfaction and usability were high. Future directions for testing efficacy are discussed.

Evidence-Based Parenting Interventions to Promote Secure Attachment

PubMed Central

Wright, Barry; Edginton, Elizabeth

2016-01-01

Various interventions are used in clinical practice to address insecure or disorganized attachment patterns and attachment disorders. The most common of these are parenting interventions, but not all have a robust empirical evidence base. We undertook a systematic review of randomized trials comparing a parenting intervention with a control, where these used a validated attachment instrument, in order to evaluate the clinical and cost-effectiveness of interventions aiming to improve attachment in children with severe attachment problems (mean age <13 years). This article aims to inform clinicians about the parenting interventions included in our systematic review that were clinically effective in promoting secure attachment. For completeness, we also briefly discuss other interventions without randomized controlled trial evidence, identified in Patient Public Involvement workshops and expert groups at the point our review was completed as being used or recommended. We outline the key implications of our findings for clinical practice and future research. PMID:27583298

Rigorous control conditions diminish treatment effects in weight loss randomized controlled trials

PubMed Central

Dawson, John A.; Kaiser, Kathryn A.; Affuso, Olivia; Cutter, Gary R.; Allison, David B.

2015-01-01

Background It has not been established whether control conditions with large weight losses (WLs) diminish expected treatment effects in WL or prevention of weight gain (PWG) randomized controlled trials (RCTs). Subjects/Methods We performed a meta-analysis of 239 WL/PWG RCTs that include a control group and at least one treatment group. A maximum likelihood meta-analysis framework is used in order to model and understand the relationship between treatment effects and control group outcomes. Results Under the informed model, an increase in control group WL of one kilogram corresponds with an expected shrinkage of the treatment effect by 0.309 kg [95% CI (−0.480, −0.138), p = 0.00081]; this result is robust against violations of the model assumptions. Conclusions We find that control conditions with large weight losses diminish expected treatment effects. Our investigation may be helpful to clinicians as they design future WL/PWG studies. PMID:26449419

HIV Prevention for Adults With Criminal Justice Involvement: A Systematic Review of HIV Risk-Reduction Interventions in Incarceration and Community Settings

PubMed Central

Dumont, Dora; Operario, Don

2014-01-01

We summarized and appraised evidence regarding HIV prevention interventions for adults with criminal justice involvement. We included randomized and quasi-randomized controlled trials that evaluated an HIV prevention intervention, enrolled participants with histories of criminal justice involvement, and reported biological or behavioral outcomes. We used Cochrane methods to screen 32 271 citations from 16 databases and gray literature. We included 37 trials enrolling n = 12 629 participants. Interventions were 27 psychosocial, 7 opioid substitution therapy, and 3 HIV-testing programs. Eleven programs significantly reduced sexual risk taking, 4 reduced injection drug risks, and 4 increased testing. Numerous interventions may reduce HIV-related risks among adults with criminal justice involvement. Future research should consider process evaluations, programs involving partners or families, and interventions integrating biomedical, psychosocial, and structural approaches. PMID:25211725

Reporting of symptoms in randomized controlled trials of atopic eczema treatments: a systematic review.

PubMed

Gerbens, L A A; Chalmers, J R; Rogers, N K; Nankervis, H; Spuls, P I

2016-10-01

'Symptoms' is a core outcome domain for atopic eczema (AE) trials, agreed by consensus as part of the Harmonising Outcome Measures for Eczema (HOME) initiative. To standardize and validate the core domain symptoms and symptom instruments for AE trials the HOME roadmap is followed. Its first step is to establish if and how symptoms have been measured in published AE treatment trials. Therefore the Global Resource for Eczema Trials database was used to collect all randomized controlled trials (RCTs) of treatments for AE between January 2000 and April 2014. Study selection and data extraction were performed by three reviewers independently. We identified the use of symptoms in 295 of 378 trials (78%). Symptoms as a primary end point were applied by 147 RCTs (50%). Seventeen different symptoms were measured, but mostly itch and sleep loss. Symptoms were assessed by only 37% of trials by a stand-alone symptom measurement. Overall 63% of RCTs used a composite instrument, and 30 different instruments were identified. The Scoring Atopic Dermatitis (SCORAD) index was the most commonly applied, but only 23% of RCTs reported the SCORAD symptom score separately. This systematic review demonstrates that symptoms, most frequently itch and sleep loss, are commonly reported in AE treatment trials, but are measured using many different instruments. Often symptoms are evaluated as part of a composite instrument, and currently it is not possible to extract symptoms-only data from most published studies. Future trials should report symptom scores to permit meta-analysis of the core outcomes. © 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

"Congratulations, you have been randomized into the control group!(?)": issues to consider when recruiting schools for matched-pair randomized control trials of prevention programs.

PubMed

Ji, Peter; DuBois, David L; Flay, Brian R; Brechling, Vanessa

2008-03-01

Recruiting schools into a matched-pair randomized control trial (MP-RCT) to evaluate the efficacy of a school-level prevention program presents challenges for researchers. We considered which of 2 procedures would be most effective for recruiting schools into the study and assigning them to conditions. In 1 procedure (recruit and match/randomize), we would recruit schools and match them prior to randomization, and in the other (match/randomize and recruitment), we would match schools and randomize them prior to recruitment. We considered how each procedure impacted the randomization process and our ability to recruit schools into the study. After implementing the selected procedure, the equivalence of both treatment and control group schools and the participating and nonparticipating schools on school demographic variables was evaluated. We decided on the recruit and match/randomize procedure because we thought it would provide the opportunity to build rapport with the schools and prepare them for the randomization process, thereby increasing the likelihood that they would accept their randomly assigned conditions. Neither the treatment and control group schools nor the participating and nonparticipating schools exhibited statistically significant differences from each other on any of the school demographic variables. Recruitment of schools prior to matching and randomization in an MP-RCT may facilitate the recruitment of schools and thus enhance both the statistical power and the representativeness of study findings. Future research would benefit from the consideration of a broader range of variables (eg, readiness to implement a comprehensive prevention program) both in matching schools and in evaluating their representativeness to nonparticipating schools.

The Role of Melatonin in the Treatment of Primary Headache Disorders

PubMed Central

Gelfand, Amy A.; Goadsby, Peter J.

2016-01-01

Objective To provide a summary of knowledge about the use of melatonin in the treatment of primary headache disorders. Background Melatonin is secreted by the pineal gland; its production is regulated by the hypothalamus and increases during periods of darkness. Methods We undertook a narrative review of the literature on the role of melatonin in the treatment of primary headache disorders. Results There are randomized placebo-controlled trials examining melatonin for preventive treatment of migraine and cluster headache. For cluster headache, melatonin 10 mg was superior to placebo. For migraine, a randomized placebo-controlled trial of melatonin 3 mg (immediate release) was positive, though an underpowered trial of melatonin 2 mg (sustained release) was negative. Uncontrolled studies, case series, and case reports cover melatonin’s role in treating tension-type headache, hypnic headache, hemicrania continua, SUNCT/SUNA and primary stabbing headache. Conclusions Melatonin may be effective in treating several primary headache disorders, particularly cluster headache and migraine. Future research should focus on elucidating the underlying mechanisms of benefit of melatonin in different headache disorders, as well as clarifying optimal dosing and formulation. PMID:27316772

Intraarticular cortisone injection for osteoarthritis of the hip. Is it effective? Is it safe?

PubMed

Kruse, David W

2008-12-01

Osteoarthritis of the hip is a significant source of morbidity in the elderly. Treatment guidelines are available for the management of hip osteoarthritis, but these do not address the application of intraarticular corticosteroid injection. The intraarticular injection of corticosteroid is used in the management of other large joint osteoarthritic diseases and is well studied in the knee, however, this data cannot be used to make sound clinical decisions regarding its use for hip osteoarthritis. There are also concerns regarding the safety of this modality. Review of the published literature reveals that there are eight trials examining the efficacy of intraarticular corticosteroid injection for hip osteoarthritis and of these only four are randomized controlled trials. In general, the available literature demonstrates a short-term reduction of pain with corticosteroid injection and is indicated for patients refractory to non-pharmacologic or analgesic and NSAID therapy. The use of radiologic-guidance is recommended and, with proper sterile technique, the risk of adverse outcomes is very low. Future randomized controlled trials are needed to further examine the efficacy and safety of intraarticular corticosteroid injection for hip osteoarthritis.

Clinical Trials of Blood Pressure Lowering and Antihypertensive Medication: Is Cognitive Measurement State-of-the-Art?

PubMed

Elias, Merrill F; Torres, Rachael V; Davey, Adam

2018-05-07

Randomized controlled trials of blood pressure (BP) lowering and antihypertensive medication use on cognitive outcomes have often been disappointing, reporting mixed findings and small effect sizes. We evaluate the extent to which cognitive assessment protocols used in these trials approach state-of-the-art. Overall, we find that a primary focus on cognition and the systematic selection of cognitive outcomes across trials take a backseat to other trial goals. Twelve trials investigating change in cognitive functioning were examined and none met criteria for state-of-the-art assessment, including use of at least 4 tests indexing 2 cognitive domains. Four trials investigating incident dementia were also examined. Each trial used state-of-the-art diagnostic criteria to assess dementia, although follow-up periods were relatively short, with only 2 trials lasting for at least 3 years. Weaknesses in each trial may act to obscure or weaken the positive effects of BP lowering on cognitive functioning. Improving trial designs in terms of cognitive outcomes selected and length of follow-up periods employed could lead to more promising findings. We offer logical steps to achieve state-of-the-art assessment protocols, with examples, in hopes of improving future trials.

Control groups in recent septic shock trials: a systematic review.

PubMed

Pettilä, Ville; Hjortrup, Peter Buhl; Jakob, Stephan M; Wilkman, Erika; Perner, Anders; Takala, Jukka

2016-12-01

The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2-17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care. Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.

Interventions to improve hemodialysis adherence: a systematic review of randomized-controlled trials.

PubMed

Matteson, Michelle L; Russell, Cynthia

2010-10-01

Over 485,000 people in the United States have chronic kidney disease, a progressive kidney disease that may lead to hemodialysis. Hemodialysis involves a complex regimen of treatment, medication, fluid, and diet management. In 2005, over 312,000 patients were undergoing hemodialysis in the United States. Dialysis nonadherence rates range from 8.5% to 86%. Dialysis therapy treatment nonadherence, including treatment, medication, fluid, and diet nonadherence, significantly increases the risk of morbidity and mortality. The purpose of this paper is to systematically review randomized-controlled trial intervention studies designed to increase treatment, medication, fluid, and diet adherence in adult hemodialysis patients. A search of Cumulative Index of Nursing and Allied Health Literature (CINAHL) (1982 to May 2008), MEDLINE (1950 to May 2008), PsycINFO (1806 to May 2008), and all Evidence-Based Medicine (EBM) Reviews (Cochran DSR, ACP Journal Club, DARE, and CCTR) was conducted to identify randomized-controlled studies that tested the efficacy of interventions to improve adherence in adult hemodialysis patients. Eight randomized-controlled trials met criteria for inclusion. Six of the 8 studies found statistically significant improvement in adherence with the intervention. Of these 6 intervention studies, all studies had a cognitive component, with 3 studies utilizing cognitive/behavioral intervention strategies. Based on this systematic review, interventions utilizing a cognitive or cognitive/behavioral component appear to show the most promise for future study. © 2010 The Authors. Hemodialysis International © 2010 International Society for Hemodialysis.

Impact of Exposure to Electronic Cigarette Advertising on Susceptibility and Trial of Electronic Cigarettes and Cigarettes in US Young Adults: A Randomized Controlled Trial.

PubMed

Villanti, Andrea C; Rath, Jessica M; Williams, Valerie F; Pearson, Jennifer L; Richardson, Amanda; Abrams, David B; Niaura, Raymond S; Vallone, Donna M

2016-05-01

This study assessed the impact of brief exposure to four electronic cigarette (e-cigarette) print advertisements (ads) on perceptions, intention, and subsequent use of e-cigarettes and cigarettes in US young adults. A randomized controlled trial was conducted in a national sample of young adults from an online panel survey in 2013. Participants were randomized to ad exposure or control. Curiosity, intentions, and perceptions regarding e-cigarettes were assessed post-exposure and e-cigarette and cigarette use at 6-month follow-up. Analyses were conducted in 2014. Approximately 6% of young adults who had never used an e-cigarette at baseline tried an e-cigarette at 6-month follow-up, half of whom were current cigarette smokers at baseline. Compared to the control group, ad exposure was associated with greater curiosity to try an e-cigarette (18.3% exposed vs. 11.3% unexposed, AOR = 1.63, 95% CI = 1.18, 2.26) among never e-cigarette users and greater likelihood of e-cigarette trial at follow-up (3.6% exposed vs. 1.2% unexposed, AOR = 2.85; 95% CI = 1.07, 7.61) among never users of cigarettes and e-cigarettes. Exploratory analyses did not find an association between ad exposure and cigarette trial or past 30-day use among never users, nor cigarette use among smokers over time. Curiosity mediated the relationship between ad exposure and e-cigarette trial among e-cigarette never users. Exposure to e-cigarette ads may enhance curiosity and limited trial of e-cigarettes in never users. Future studies are needed to examine the net effect of curiosity and trial of e-cigarettes on longer-term patterns of tobacco use. This randomized trial provides the first evidence of the effect of e-cigarette advertising on a behavioral outcome in young adults. Compared to the control group, ad exposure was associated with greater curiosity to try an e-cigarette among never e-cigarette users and greater likelihood of e-cigarette trial at follow-up in a small number of never e-cigarette users and greater likelihood of e-cigarette trial at follow-up among never users of cigarettes and e-cigarettes. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Comparing cluster-level dynamic treatment regimens using sequential, multiple assignment, randomized trials: Regression estimation and sample size considerations.

PubMed

NeCamp, Timothy; Kilbourne, Amy; Almirall, Daniel

2017-08-01

Cluster-level dynamic treatment regimens can be used to guide sequential treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level. In a cluster-level dynamic treatment regimen, the treatment is potentially adapted and re-adapted over time based on changes in the cluster that could be impacted by prior intervention, including aggregate measures of the individuals or patients that compose it. Cluster-randomized sequential multiple assignment randomized trials can be used to answer multiple open questions preventing scientists from developing high-quality cluster-level dynamic treatment regimens. In a cluster-randomized sequential multiple assignment randomized trial, sequential randomizations occur at the cluster level and outcomes are observed at the individual level. This manuscript makes two contributions to the design and analysis of cluster-randomized sequential multiple assignment randomized trials. First, a weighted least squares regression approach is proposed for comparing the mean of a patient-level outcome between the cluster-level dynamic treatment regimens embedded in a sequential multiple assignment randomized trial. The regression approach facilitates the use of baseline covariates which is often critical in the analysis of cluster-level trials. Second, sample size calculators are derived for two common cluster-randomized sequential multiple assignment randomized trial designs for use when the primary aim is a between-dynamic treatment regimen comparison of the mean of a continuous patient-level outcome. The methods are motivated by the Adaptive Implementation of Effective Programs Trial which is, to our knowledge, the first-ever cluster-randomized sequential multiple assignment randomized trial in psychiatry.

The Effects of Interactive and Passive Distraction on Cold Pressor Pain in Preschool-aged Children

PubMed Central

Dahlquist, Lynnda M.; Wohlheiter, Karen

2011-01-01

Objective Using a mixed model design, this study examined the effects of interactive versus passive distraction on healthy preschool-aged children’s cold pressor pain tolerance. Methods Sixty-one children aged 3–5 years were randomly assigned to one of the following: interactive distraction, passive distraction, or no distraction control. Participants underwent a baseline cold pressor trial followed by interactive distraction trial, passive distraction trial, or second baseline trial. One or two additional trials followed. Children originally assigned to distraction received the alternate distraction intervention. Controls participated in both interactive and passive distraction trials in counterbalanced order. Results Participants showed significantly higher pain tolerance during both interactive and passive distraction relative to baseline. The two distraction conditions did not differ. Conclusions Interactive and passive video game distraction appear to be effective for preschool-aged children during laboratory pain exposure. Future studies should examine whether more extensive training would enhance effects of interactive video game distraction. PMID:21278378

The Missing Pieces in Reporting of Randomized Controlled Trials of External Beam Radiation Therapy Dose Escalation for Prostate Cancer.

PubMed

Zaorsky, Nicholas G; Egleston, Brian L; Horwitz, Eric M; Dicker, Adam P; Nguyen, Paul L; Showalter, Timothy N; Den, Robert B

2016-08-01

Randomized controlled trials (RCTs) are the most rigorous way of determining whether a cause-effect relation exists between treatment and outcome and for assessing the cost-effectiveness of a treatment. For many patients, cancer is a chronic illness; RCTs evaluating treatments for indolent cancers must evolve to facilitate medical decision-making, as "concrete" patient outcomes (eg, survival) will likely be excellent independent of the intervention, and detecting a difference between trial arms may be impossible. In this commentary, we articulate 9 recommendations that we hope future clinical trialists and funding agencies (including those under the National Cancer Institute) will take into consideration when planning RCTs to help guide subsequent interpretation of results and clinical decision making, based on RCTs of external beam radiation therapy dose escalation for the most common indolent cancer in men, that is, prostate cancer. We recommend routinely reporting: (1) race; (2) medical comorbidities; (3) psychiatric comorbidities; (4) insurance status; (5) education; (6) marital status; (7) income; (8) sexual orientation; and (9) facility-related characteristics (eg, number of centers involved, type of facilities, yearly hospital volumes). We discuss how these factors independently affect patient outcomes and toxicities; future clinicians and governing organizations should consider this information to plan RCTs accordingly (to maximize patient accrual and total n), select appropriate endpoints (eg, toxicity, quality of life, sexual function), actively monitor RCTs, and report results so as to identify the optimal treatment among subpopulations.

Geographic differences in heart failure trials.

PubMed

Ferreira, João Pedro; Girerd, Nicolas; Rossignol, Patrick; Zannad, Faiez

2015-09-01

Randomized controlled trials (RCTs) are essential to develop advances in heart failure (HF). The need for increasing numbers of patients (without substantial cost increase) and generalization of results led to the disappearance of international boundaries in large RCTs. The significant geographic differences in patients' characteristics, outcomes, and, most importantly, treatment effect observed in HF trials have recently been highlighted. Whether the observed regional discrepancies in HF trials are due to trial-specific issues, patient heterogeneity, structural differences in countries, or a complex interaction between factors are the questions we propose to debate in this review. To do so, we will analyse and review data from HF trials conducted in different world regions, from heart failure with preserved ejection fraction (HF-PEF), heart failure with reduced ejection fraction (HF-REF), and acute heart failure (AHF). Finally, we will suggest objective and actionable measures in order to mitigate regional discrepancies in future trials, particularly in HF-PEF where prognostic modifying treatments are urgently needed and in which trials are more prone to selection bias, due to a larger patient heterogeneity. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Impact of different concentrations of an octenidine dihydrochloride mouthwash on salivary bacterial counts: a randomized, placebo-controlled cross-over trial.

PubMed

Lorenz, Katrin; Jockel-Schneider, Yvonne; Petersen, Nicole; Stölzel, Peggy; Petzold, Markus; Vogel, Ulrich; Hoffmann, Thomas; Schlagenhauf, Ulrich; Noack, Barbara

2018-03-02

This bi-centric, placebo-controlled, randomized, evaluator-blinded, incomplete cross-over clinical phase II trial was initialized to identify the most appropriate concentration of octenidine dihydrochloride (OCT) in mouth rinses. Rinses of 0.10, 0.15, and 0.20% OCT were compared to a saline placebo rinse regarding the reduction of salivary bacterial counts (SBCs) in 90 gingivitis patients over 4 days. Changes in plaque (PI) and gingival index (GI), taste perception, and safety issues were evaluated. At baseline, the first OCT (0.10, 0.15, 0.20%) rinse resulted in a decrease of SBC (reduction by 3.63-5.44 log 10 colony forming units [CFU]) compared to placebo (p < 0.001). Differences between OCT concentrations were not verified. After 4 days, the last OCT rinse again resulted in a significant SBC decrease (3.69-4.22 log 10 CFU) compared to placebo (p < 0.001). Overall, SBC reduction between baseline and day 4 was significantly higher in OCT 0.15 and 0.20% groups compared to OCT 0.10% and placebo. Mean GI/PIs were significantly lower in OCT groups than in the placebo group (p < 0.001). Differences in GI/PI between OCT groups were not verified. Adverse effects increased with increasing OCT concentrations. Considering antibacterial efficacy, frequency of adverse events, and user acceptance, 0.10% OCT was identified as the preferred concentration to be used in future clinical trials. Due to its low toxicity and pronounced antibacterial properties, octenidine dihydrochloride (OCT) is a promising candidate for the use in antiseptic mouth rinses. OCT concentrations of 0.10% are recommended for future clinical trials evaluating the plaque-reducing properties of OCT mouth rinses. ( www.clinicaltrials.gov , NCT022138552).

Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial

PubMed Central

2013-01-01

Background Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. Methods/Design This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. Discussion This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine interventions in the future. Trial registration NCT01695850 PMID:24180235

Role of Purified Anthocyanins in Improving Cardiometabolic Risk Factors in Chinese Men and Women with Prediabetes or Early Untreated Diabetes-A Randomized Controlled Trial.

PubMed

Yang, Liping; Ling, Wenhua; Yang, Yan; Chen, Yuming; Tian, Zezhong; Du, Zhicheng; Chen, Jianying; Xie, Yuanling; Liu, Zhaomin; Yang, Lili

2017-10-10

Objective: In vitro and animal studies suggest that purified anthocyanins have favorable effects on metabolic profiles, but clinical trials have reported inconsistent findings. Furthermore, no study has been specifically conducted among individuals with prediabetes. The aim of this study was to investigate whether purified anthocyanins could improve cardiometabolic risk factors in Chinese adults with early untreated hyperglycemia. Research Design and Methods: This was a 12-week randomized, double-blind, placebo-controlled trial. A total of 160 participants aged 40-75 years with prediabetes or early untreated diabetes were randomly allocated to receive either purified anthocyanins (320 mg/day, n = 80) or placebo ( n = 80) of identical appearance. A three-hour oral glucose tolerance test (OGTT) was performed, and cardiometabolic biomarkers (glycated hemoglobin A1c (HbA1c), fasting and postprandial glucose, insulin, C-peptide, and lipids) were measured at baseline and at the end of the trial. Results: A total of 138 subjects completed the protocol. Compared with placebo, purified anthocyanins moderately reduced HbA1c (-0.14%, 95% CI: -0.23~-0.04%; p = 0.005), low-density lipoprotein-c (LDL-c) (-0.2 mmol/L, 95% CI: -0.38~-0.01, p = 0.04), apolipoprotein A-1 (apo A1) (0.09 g/L, 95% CI: 0.02~0.17; p = 0.02), and apolipoprotein B (apo B) (-0.07 g/L, 95% CI: -0.13~-0.01; p = 0.01) according to intention-to-treat analysis. Subgroup analyses suggested that purified anthocyanins were more effective at improving glycemic control, insulin sensitivity, and lipids among patients with elevated metabolic markers. Conclusions: The 12-week randomized controlled trials (RCT) in Chinese adults with prediabetes or early untreated diabetes indicated that purified anthocyanins favorably affected glycemic control and lipid profile. Future studies of a longer duration that explore the dose-response relationship among patients with cardiometabolic disorders are needed to confirm our findings.

Comparative effectiveness and cost-effectiveness of Chuna manual therapy versus conventional usual care for nonacute low back pain: study protocol for a pilot multicenter, pragmatic randomized controlled trial (pCRN study).

PubMed

Shin, Byung-Cheul; Kim, Me-Riong; Cho, Jae-Heung; Jung, Jae-Young; Kim, Koh-Woon; Lee, Jun-Hwan; Nam, Kibong; Lee, Min Ho; Hwang, Eui-Hyoung; Heo, Kwang-Ho; Kim, Namkwen; Ha, In-Hyuk

2017-01-17

While Chuna manual therapy is a Korean manual therapy widely used primarily for low back pain (LBP)-related disorders in Korea, well-designed studies on the comparative effectiveness of Chuna manual therapy are scarce. This study is the protocol for a three-armed, multicenter, pragmatic randomized controlled pilot trial. Sixty severe nonacute LBP patients (pain duration of at least 3 weeks, Numeric Rating Scale (NRS) ≥5) will be recruited at four Korean medicine hospitals. Participants will be randomly allocated to the Chuna group (n = 20), usual care group (n = 20), or Chuna plus usual care group (n = 20) for 6 weeks of treatment. Usual care will consist of orally administered conventional medicine, physical therapy, and back pain care education. The trial will be conducted with outcome assessor and statistician blinding. The primary endpoint will be NRS of LBP at week 7 post randomization. Secondary outcomes include NRS of leg pain, the Oswestry Disability Index (ODI), the Patient Global Impression of Change (PGIC), the Credibility and Expectancy Questionnaire, lumbar range of motion (ROM), the EuroQol-5 Dimension (EQ-5D) health survey, the Health Utility Index III (HUI-III), and economic evaluation and safety data. Post-treatment follow-ups will be conducted at 1, 4, and 10 weeks after conclusion of treatment. This study will assess the comparative effectiveness of Chuna manual therapy compared to conventional usual care. Costs and effectiveness (utility) data will be analyzed for exploratory cost-effectiveness analysis. If this pilot study does not reach a definite conclusion due to its small sample size, these results will be used as preliminary results to calculate sample size for future large-scale clinical trials and contribute in the assessment of feasibility of a full-scale multicenter trial. Clinical Research Information Service (CRIS), KCT0001850 . Registered on 17 March 2016.

Fixation using alternative implants for the treatment of hip fractures (FAITH): design and rationale for a multi-centre randomized trial comparing sliding hip screws and cancellous screws on revision surgery rates and quality of life in the treatment of femoral neck fractures

PubMed Central

2014-01-01

Background Hip fractures are a common type of fragility fracture that afflict 293,000 Americans (over 5,000 per week) and 35,000 Canadians (over 670 per week) annually. Despite the large population impact the optimal fixation technique for low energy femoral neck fractures remains controversial. The primary objective of the FAITH study is to assess the impact of cancellous screw fixation versus sliding hip screws on rates of revision surgery at 24 months in individuals with femoral neck fractures. The secondary objective is to determine the impact on health-related quality of life, functional outcomes, health state utilities, fracture healing, mortality and fracture-related adverse events. Methods/Design FAITH is a multi-centre, multi-national randomized controlled trial utilizing minimization to determine patient allocation. Surgeons in North America, Europe, Australia, and Asia will recruit a total of at least 1,000 patients with low-energy femoral neck fractures. Using central randomization, patients will be allocated to receive surgical treatment with cancellous screws or a sliding hip screw. Patient outcomes will be assessed at one week (baseline), 10 weeks, 6, 12, 18, and 24 months post initial fixation. We will independently adjudicate revision surgery and complications within 24 months of the initial fixation. Outcome analysis will be performed using a Cox proportional hazards model and likelihood ratio test. Discussion This study represents major international efforts to definitively resolve the treatment of low-energy femoral neck fractures. This trial will not only change current Orthopaedic practice, but will also set a benchmark for the conduct of future Orthopaedic trials. Trial registration The FAITH trial is registered at ClinicalTrials.gov (Identifier NCT00761813). PMID:24965132

The cognitive-enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials.

PubMed

Pase, Matthew P; Kean, James; Sarris, Jerome; Neale, Chris; Scholey, Andrew B; Stough, Con

2012-07-01

Traditional knowledge suggests that Bacopa monnieri enhances cognitive performance. Such traditional beliefs have now been scientifically tested through a handful of randomized, controlled human clinical trials. The current systematic review aimed to examine the scientific evidence as to whether Bacopa can enhance cognitive performance in humans. A systematic review of randomized controlled trials is presented. Multiple databases were systematically searched by multiple authors. Relevant trials were objectively assessed for methodological quality. The subjects studied were adult humans without dementia or significant cognitive impairment. B. monnieri, including Bacopa extracts, were administered over long-term supplementation periods. Any validated cognitive test, whether a primary or secondary outcome. Six (6) studies met the final inclusion criteria and were included in review. Trials were all conducted over 12 weeks. Across trials, three different Bacopa extracts were used at dosages of 300-450 mg extract per day. All reviewed trials examined the effects of Bacopa on memory, while other cognitive domains were less well studied. There were no cognitive tests in the areas of auditory perceptual abilities or idea production and only a paucity of research in the domains of reasoning, number facility, and language behavior. Across studies, Bacopa improved performance on 9 of 17 tests in the domain of memory free recall. There was little evidence of enhancement in any other cognitive domains. There is some evidence to suggest that Bacopa improves memory free recall with evidence for enhancement in other cognitive abilities currently lacking perhaps due to inconsistent measures employed by studies across these cognitive domains. Research into the nootropic effects of Bacopa is in its infancy, with research still yet to investigate the effects of Bacopa across all human cognitive abilities. Similarly, future research should examine the nootropic effects of Bacopa at varied dosages and across different extracts.

Multicenter Randomized Controlled Trial on Duration of Therapy for Thrombosis in Children and Young Adults (Kids-DOTT): Pilot/Feasibility Phase Findings

PubMed Central

Goldenberg, N.A.; Abshire, T.; Blatchford, P.J.; Fenton, L.Z.; Halperin, J.L.; Hiatt, W.R.; Kessler, C.M.; Kittelson, J.M.; Manco-Johnson, M.J.; Spyropoulos, A.C.; Steg, P.G.; Stence, N.V.; Turpie, A.G.G.; Schulman, S.

2015-01-01

BACKGROUND Randomized controlled trials (RCTs) in pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. METHODS Kids-DOTT is a multicenter RCT investigating non-inferiority of a 6-week (shortened) vs. 3-month (conventional) duration of anticoagulation in patients <21 years old with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically-relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded endpoint, parallel-cohort RCT design. RESULTS No eligibility violations or randomization errors occurred. Of enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in pre-specified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Inter-observer agreement between local vs. blinded central determination of venous occlusion by imaging at 6 weeks post-diagnosis was strong (κ-statistic=0.75; 95% confidence interval [CI] 0.48–1.0). Primary efficacy and safety event rates were 3.3% (95% CI 0.3–11.5%) and 1.4% (0.03–7.4%). CONCLUSIONS The P/F phase of Kids-DOTT has demonstrated validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention, and endpoint rates to inform the fully-powered RCT. PMID:26118944

Research Review: The Role of Diet in the Treatment of Attention-Deficit/Hyperactivity Disorder--An Appraisal of the Evidence on Efficacy and Recommendations on the Design of Future Studies

ERIC Educational Resources Information Center

Stevenson, Jim; Buitelaar, Jan; Cortese, Samuele; Ferrin, Maite; Konofal, Eric; Lecendreux, Michel; Simonoff, Emily; Wong, Ian C. K.; Sonuga-Barke, Edmund

2014-01-01

Background: The efficacy of three dietary treatments for ADHD has been repeatedly tested in randomized controlled trials (RCTs). These interventions are restricted elimination diets (RED), artificial food colour elimination (AFCE) and supplementation with free fatty acids (SFFA). There have been three systematic reviews and associated…

Hyperbaric oxygen for post-concussive symptoms in United States military service members: a randomized clinical trial.

PubMed

Weaver, Lindell K; Wilson, Steffanie H; Lindblad, Anne S; Churchill, Susan; Deru, Kayla; Price, Robert C; Williams, Chris S; Orrison, William W; Walker, James M; Meehan, Anna; Mirow, Susan

2018-01-01

In prior military randomized trials, participants with persistent symptoms after mild traumatic brain injury (TBI) reported improvement regardless of receiving hyperbaric oxygen (HBO₂) or sham intervention. This study's objectives were to identify outcomes for future efficacy trials and describe changes by intervention. This Phase II, randomized, double-blind, sham-controlled trial enrolled military personnel with mild TBI and persistent post-concussive symptoms. Participants were randomized to receive 40 HBO₂ (1.5 atmospheres absolute (ATA), ⟩99% oxygen, 60 minutes) or sham chamber sessions (1.2 ATA, room air, 60 minutes) over 12 weeks. Participants and evaluators were blinded to allocation. Outcomes assessed at baseline, 13 weeks and six months included symptoms, quality of life, neuropsychological, neurological, electroencephalography, sleep, auditory, vestibular, autonomic, visual, neuroimaging, and laboratory testing. Participants completed 12-month questionnaires. Intention-to-treat results are reported. From 9/11/2012 to 5/19/2014, 71 randomized participants received HBO₂ (n=36) or sham (n=35). At baseline, 35 participants (49%) met post-traumatic stress disorder (PTSD) criteria. By the Neurobehavioral Symptom Inventory, the HBO₂ group had improved 13-week scores (mean change -3.6 points, P=0.03) compared to sham (+3.9 points). In participants with PTSD, change with HBO₂ was more pronounced (-8.6 vs. +4.8 points with sham, P=0.02). PTSD symptoms also improved in the HBO₂ group, and more so in the subgroup with PTSD. Improvements regressed at six and 12 months. Hyperbaric oxygen improved some cognitive processing speed and sleep measures. Participants with PTSD receiving HBO₂ had improved functional balance and reduced vestibular complaints at 13 weeks. By 13 weeks, HBO₂ improved post-concussive and PTSD symptoms, cognitive processing speed, sleep quality, and balance function, most dramatically in those with PTSD. Changes did not persist beyond six months. Several outcomes appeared sensitive to change; additional studies are warranted. Copyright© Undersea and Hyperbaric Medical Society.

The HVTN503/Phambili HIV vaccine trial: a comparison of younger and older participants

PubMed Central

Volk, Jonathan E.; Hessol, Nancy A.; Gray, Glenda E.; Kublin, James G.; Churchyard, Gavin J.; Mlisana, Koleka; Nchabeleng, Maphoshane; Buchbinder, Susan P.; Bekker, Linda-Gail

2014-01-01

By comparing younger to older participants enrolled in a HIV vaccine efficacy trial, we aimed to gain insights into the inclusion of adolescents in future trials. This was a sub-analysis of a multisite HIV vaccine randomized clinical trial in South Africa, conducted January-September, 2007. Motivations for trial enrollment, social harms, adverse events, and loss to follow-up were compared between younger (18-20 years old) and older participants (21-35 years old). Both younger (n=238) and older participants (n=563) were equally likely to report enrolling for altruistic reasons. Younger females were less likely than older participants to join for trial reimbursement (p=0.005), while younger males were more likely to enroll because the vaccine may provide protection from HIV-acquisition (p<0.001). There were no significant differences in the number of social harms reported. Compared to males over 20 years-old, 18-20-year-old females were less likely to experience adverse events (OR=0.1, CI 0.01-0.80) and no more likely to be lost to follow up (OR=0.7, CI 0.39-1.25), while 18-20-year-old males were no more likely to experience adverse events (OR=1.3, CI 0.58-2.83) or loss to follow-up (OR=0.8, CI 0.51-1.41). Our data support the inclusion of younger participants who are at risk for HIV in future HIV vaccine efficacy trials. PMID:24104693

Feasibility of the Enhancing Participation In the Community by improving Wheelchair Skills (EPIC Wheels) program: study protocol for a randomized controlled trial.

PubMed

Giesbrecht, Edward M; Miller, William C; Eng, Janice J; Mitchell, Ian M; Woodgate, Roberta L; Goldsmith, Charles H

2013-10-24

Many older adults rely on a manual wheelchair for mobility but typically receive little, if any, training on how to use their wheelchair effectively and independently. Standardized skill training is an effective intervention, but limited access to clinician trainers is a substantive barrier. Enhancing Participation in the Community by Improving Wheelchair Skills (EPIC Wheels) is a 1-month monitored home training program for improving mobility skills in older novice manual wheelchair users, integrating principles from andragogy and social cognitive theory. The purpose of this study is to determine whether feasibility indicators and primary clinical outcome measures of the EPIC Wheels program are sufficiently robust to justify conducting a subsequent multi-site randomized controlled trial. A 2 × 2 factorial randomized controlled trial at two sites will compare improvement in wheelchair mobility skills between an EPIC Wheels treatment group and a computer-game control group, with additional wheelchair use introduced as a second factor. A total of 40 community-dwelling manual wheelchair users at least 55 years old and living in two Canadian metropolitan cities (n = 20 × 2) will be recruited. Feasibility indicators related to study process, resources, management, and treatment issues will be collected during data collection and at the end of the study period, and evaluated against proposed criteria. Clinical outcome measures will be collected at baseline (pre-randomization) and post-intervention. The primary clinical outcome measure is wheelchair skill capacity, as determined by the Wheelchair Skills Test, version 4.1. Secondary clinical outcome measures include wheelchair skill safety, satisfaction with performance, wheelchair confidence, life-space mobility, divided-attention, and health-related quality of life. The EPIC Wheels training program offers several innovative features. The convenient, portable, economical, and adaptable tablet-based, home program model for wheelchair skills training has great potential for clinical uptake and opportunity for future enhancements. Theory-driven design can foster learning and adherence for older adults. Establishing the feasibility of the study protocol and estimating effect size for the primary clinical outcome measure will be used to develop a multi-site randomized controlled trial to test the guiding hypotheses. Clinical Trials NCT01740635.

Caregiver-Provided Physical Therapy Home Programs for Children with Motor Delay: A Scoping Review.

PubMed

Gorgon, Edward James R

2018-06-01

Caregiver-provided physical therapy home programs (PTHP) play an important role in enhancing motor outcomes in pediatric patient populations. This scoping review systematically mapped clinical trials of caregiver-provided PTHP that were aimed at enhancing motor outcomes in children who have or who are at risk for motor delay, with the purpose of (1) describing trial characteristics; (2) assessing methodologic quality; and (3) examining the reporting of caregiver-related components. Physiotherapy Evidence Database (PEDro), Cochrane CENTRAL, PubMed, Scopus, ScienceDirect, ProQuest Central, CINAHL, LILACS, and OTseeker were searched up to July 31, 2017. Two reviewers independently assessed study eligibility. Randomized or quasi-randomized controlled trials on PTHP administered by parents, other family members, friends, or informal caregivers to children who had or who were at risk for motor delay were included. Two reviewers independently appraised trial quality on the PEDro scale and extracted data. Twenty-four articles representing 17 individual trials were identified. Populations and interventions investigated were heterogeneous. Most of the trials had important research design limitations and methodological issues that could limit usefulness in ascertaining the effectiveness of caregiver-provided PTHP. Few (4 of 17) trials indicated involvement of caregivers in the PTHP planning, assessed how the caregivers learned from the training or instructions provided, or carried out both. Included studies were heterogeneous, and unpublished data were excluded. Although caregiver-provided PTHP are important in addressing motor outcomes in this population, there is a lack of evidence at the level of clinical trials to guide practice. More research is urgently needed to determine the effectiveness of care-giver-provided PTHP. Future studies should address the many important issues identified in this scoping review to improve the usefulness of the trial results.

A randomized trial to investigate the effects of pre-natal and infant nutritional supplementation on infant immune development in rural Gambia: the ENID trial: Early Nutrition and Immune Development.

PubMed

Moore, Sophie E; Fulford, Anthony Jc; Darboe, Momodou K; Jobarteh, Modou Lamin; Jarjou, Landing M; Prentice, Andrew M

2012-10-11

Recent observational research indicates that immune development may be programmed by nutritional exposures early in life. Such findings require replication from trials specifically designed to assess the impact of nutritional intervention during pregnancy on infant immune development. The current trial seeks to establish: (a) which combination of protein-energy (PE) and multiple-micronutrient (MMN) supplements would be most effective; and (b) the most critical periods for intervention in pregnancy and infancy, for optimal immune development in infancy. The ENID Trial is a 2 x 2 x 2 factorial randomized, partially blind trial to assess whether nutritional supplementation to pregnant women (from < 20 weeks gestation to term) and their infants (from 6 to 12 months of age) can enhance infant immune development. Eligible pregnant women from the West Kiang region of The Gambia (pregnancy dated by ultrasound examination) are randomized on entry to 4 intervention groups (Iron-folate (FeFol = standard care), multiple micronutrients (MMN), protein-energy (PE), PE + MMN). Women are visited at home weekly for supplement administration and morbidity assessment and seen at MRC Keneba at 20 and 30 weeks gestation for a detailed antenatal examination, including ultrasound. At delivery, cord blood and placental samples are collected, with detailed infant anthropometry collected within 72 hours. Infants are visited weekly thereafter for a morbidity questionnaire. From 6 to 12 months of age, infants are further randomized to a lipid-based nutritional supplement, with or without additional MMN. The primary outcome measures of this study are thymic development during infancy, and antibody response to vaccination. Measures of cellular markers of immunity will be made in a selected sub-cohort. Subsidiary studies to the main trial will additionally assess the impact of supplementation on infant growth and development to 24 months of age. The proposed trial is designed to test whether nutritional repletion can enhance early immune development and, if so, to help determine the most efficacious form of nutritional support. Where there is evidence of benefit from a specific intervention/combination of interventions, future research should focus on refining the supplements to achieve the optimal, most cost-effective balance of interventions for improved health outcomes.

A Systematic Review of Surgical Randomized Controlled Trials: Part 2. Funding Source, Conflict of Interest, and Sample Size in Plastic Surgery.

PubMed

Voineskos, Sophocles H; Coroneos, Christopher J; Ziolkowski, Natalia I; Kaur, Manraj N; Banfield, Laura; Meade, Maureen O; Chung, Kevin C; Thoma, Achilleas; Bhandari, Mohit

2016-02-01

The authors examined industry support, conflict of interest, and sample size in plastic surgery randomized controlled trials that compared surgical interventions. They hypothesized that industry-funded trials demonstrate statistically significant outcomes more often, and randomized controlled trials with small sample sizes report statistically significant results more frequently. An electronic search identified randomized controlled trials published between 2000 and 2013. Independent reviewers assessed manuscripts and performed data extraction. Funding source, conflict of interest, primary outcome direction, and sample size were examined. Chi-squared and independent-samples t tests were used in the analysis. The search identified 173 randomized controlled trials, of which 100 (58 percent) did not acknowledge funding status. A relationship between funding source and trial outcome direction was not observed. Both funding status and conflict of interest reporting improved over time. Only 24 percent (six of 25) of industry-funded randomized controlled trials reported authors to have independent control of data and manuscript contents. The mean number of patients randomized was 73 per trial (median, 43, minimum, 3, maximum, 936). Small trials were not found to be positive more often than large trials (p = 0.87). Randomized controlled trials with small sample size were common; however, this provides great opportunity for the field to engage in further collaboration and produce larger, more definitive trials. Reporting of trial funding and conflict of interest is historically poor, but it greatly improved over the study period. Underreporting at author and journal levels remains a limitation when assessing the relationship between funding source and trial outcomes. Improved reporting and manuscript control should be goals that both authors and journals can actively achieve.

Implementation and results of an integrated data quality assurance protocol in a randomized controlled trial in Uttar Pradesh, India.

PubMed

Gass, Jonathon D; Misra, Anamika; Yadav, Mahendra Nath Singh; Sana, Fatima; Singh, Chetna; Mankar, Anup; Neal, Brandon J; Fisher-Bowman, Jennifer; Maisonneuve, Jenny; Delaney, Megan Marx; Kumar, Krishan; Singh, Vinay Pratap; Sharma, Narender; Gawande, Atul; Semrau, Katherine; Hirschhorn, Lisa R

2017-09-07

There are few published standards or methodological guidelines for integrating Data Quality Assurance (DQA) protocols into large-scale health systems research trials, especially in resource-limited settings. The BetterBirth Trial is a matched-pair, cluster-randomized controlled trial (RCT) of the BetterBirth Program, which seeks to improve quality of facility-based deliveries and reduce 7-day maternal and neonatal mortality and maternal morbidity in Uttar Pradesh, India. In the trial, over 6300 deliveries were observed and over 153,000 mother-baby pairs across 120 study sites were followed to assess health outcomes. We designed and implemented a robust and integrated DQA system to sustain high-quality data throughout the trial. We designed the Data Quality Monitoring and Improvement System (DQMIS) to reinforce six dimensions of data quality: accuracy, reliability, timeliness, completeness, precision, and integrity. The DQMIS was comprised of five functional components: 1) a monitoring and evaluation team to support the system; 2) a DQA protocol, including data collection audits and targets, rapid data feedback, and supportive supervision; 3) training; 4) standard operating procedures for data collection; and 5) an electronic data collection and reporting system. Routine audits by supervisors included double data entry, simultaneous delivery observations, and review of recorded calls to patients. Data feedback reports identified errors automatically, facilitating supportive supervision through a continuous quality improvement model. The five functional components of the DQMIS successfully reinforced data reliability, timeliness, completeness, precision, and integrity. The DQMIS also resulted in 98.33% accuracy across all data collection activities in the trial. All data collection activities demonstrated improvement in accuracy throughout implementation. Data collectors demonstrated a statistically significant (p = 0.0004) increase in accuracy throughout consecutive audits. The DQMIS was successful, despite an increase from 20 to 130 data collectors. In the absence of widely disseminated data quality methods and standards for large RCT interventions in limited-resource settings, we developed an integrated DQA system, combining auditing, rapid data feedback, and supportive supervision, which ensured high-quality data and could serve as a model for future health systems research trials. Future efforts should focus on standardization of DQA processes for health systems research. ClinicalTrials.gov identifier, NCT02148952 . Registered on 13 February 2014.

Clinical effects of pre-adjusted edgewise orthodontic brackets: a systematic review and meta-analysis.

PubMed

Papageorgiou, Spyridon N; Konstantinidis, Ioannis; Papadopoulou, Konstantina; Jäger, Andreas; Bourauel, Christoph

2014-06-01

Fixed-appliance treatment is a major part of orthodontic treatment, but clinical evidence remains scarce. Objective of this systematic review was to investigate how the therapeutic effects and side-effects of brackets used during the fixed-appliance orthodontic treatment are affected by their characteristics. SEARCH METHODS AND SELECTION CRITERIA: We searched MEDLINE and 18 other databases through April 2012 without restrictions for randomized controlled trials and quasi-randomized controlled trials investigating any bracket characteristic. After duplicate selection and extraction procedures, risk of bias was assessed also in duplicate according to Cochrane guidelines and quality of evidence according to the Grades of Recommendation. Assessment, Development and Evaluation approach. Random-effects meta-analyses, subgroup analyses, and sensitivity analyses were performed with the corresponding 95 per cent confidence intervals (CI) and 95 per cent prediction intervals (PI). We included 25 trials on 1321 patients, with most comparing self-ligated (SL) and conventional brackets. Based on the meta-analyses, the duration of orthodontic treatment was on average 2.01 months longer among patients with SL brackets (95 per cent CI: 0.45 to 3.57). The 95 per cent PIs for a future trial indicated that the difference could be considerable (-1.46 to 5.47 months). Treatment characteristics, outcomes, and side-effects were clinically similar between SL and conventional brackets. For most bracket characteristics, evidence is insufficient. Some meta-analyses included trials with high risk of bias, but sensitivity analyses indicated robustness. Based on existing evidence, no clinical recommendation can be made regarding the bracket material or different ligation modules. For SL brackets, no conclusive benefits could be proven, while their use was associated with longer treatment durations.

Intrathecal Morphine for Laparoscopic Segmental Colonic Resection as Part of an Enhanced Recovery Protocol: A Randomized Controlled Trial.

PubMed

Koning, Mark V; Teunissen, Aart Jan W; van der Harst, Erwin; Ruijgrok, Elisabeth J; Stolker, Robert Jan

2018-02-01

Management of postoperative pain after laparoscopic segmental colonic resections remains controversial. We compared 2 methods of analgesia within an Enhanced Recovery After Surgery (ERAS) program. The goal of the study was to investigate whether administration of intrathecal bupivacaine/morphine would lead to an enhanced recovery. A single-center, randomized, double-blind controlled trial was performed (NL43488.101.13). Patients scheduled for laparoscopic segmental intestinal resections were considered. Exclusion criteria were patients in whom contraindications to spinal anesthesia were present, conversion to open surgery, and gastric and rectal surgery. The intervention group received single-shot intrathecal bupivacaine/morphine (12.5 mg/300 μg), with an altered dose for older patients. The control group received a sham procedure and a bolus of piritramide (0.1 mg/kg). Both groups received standardized general anesthesia and a patient-controlled intravenous analgesia pump as postoperative analgesia. All patients were treated according to an ERAS protocol. A decrease in days to "fit for discharge" was the primary outcome. Fifty-six patients were enrolled. Intervention group patients were fit for discharge earlier (median of 3 vs 4 days, P = 0.044). Furthermore, there was a significant decrease in opioid use and lower pain scores on the first postoperative day in the intervention group. There were no differences in adverse events (except for more pruritus), time to mobilization, fluid administration, or patient satisfaction. This randomized controlled trial shows that intrathecal morphine is a more effective method of postoperative analgesia in laparoscopic surgery than intravenous opioids within an ERAS program. Recovery is faster and less painful with intrathecal morphine. Other studies have confirmed these results, although data on faster recovery are new and require confirmation in future trials. This study was registered at ClinicalTrials.gov, identifier NCT02284282.

Developing Substance Use Programming for Person-Oriented Recovery and Treatment (SUPPORT): protocol for a pilot randomized controlled trial.

PubMed

Watson, Dennis P; Ray, Bradley; Robison, Lisa; Xu, Huiping; Edwards, Rhiannon; Salyers, Michelle P; Hill, James; Shue, Sarah

2017-01-01

There is a lack of evidence-based substance use disorder treatment and services targeting returning inmates. Substance Use Programming for Person-Oriented Recovery and Treatment (SUPPORT) is a community-driven, recovery-oriented approach to substance abuse care which has the potential to address this service gap. SUPPORT is modeled after Indiana's Access to Recovery program, which was closed due to lack of federal support despite positive improvements in clients' recovery outcomes. SUPPORT builds on noted limitations of Indiana's Access to Recovery program. The ultimate goal of this project is to establish SUPPORT as an effective and scalable recovery-oriented system of care. A necessary step we must take before launching a large clinical trial is pilot testing the SUPPORT intervention. The pilot will take place at Public Advocates in Community Re-Entry (PACE), nonprofit serving individuals with felony convictions who are located in Marion County, Indiana (Indianapolis). The pilot will follow a basic parallel randomized design to compare clients receiving SUPPORT with clients receiving standard services. A total of 80 clients within 3 months of prison release will be recruited to participate and randomly assigned to one of the two intervention arms. Quantitative measures will be collected at multiple time points to understand SUPPORT's impact on recovery capital and outcomes. We will also collect qualitative data from SUPPORT clients to better understand their program and post-discharge experiences. Successful completion of this pilot will prepare us to conduct a multi-site clinical trial. The ultimate goal of this future work is to develop an evidence-based and scalable approach to treating substance use disorder among persons returning to society after incarceration. ClinicalTrials.gov (Clinical Trials ID: NCT03132753 and Protocol Number: 1511731907). Registered 28 April 2017.

Renal denervation in heart failure with normal left ventricular ejection fraction. Rationale and design of the DIASTOLE (DenervatIon of the renAl Sympathetic nerves in hearT failure with nOrmal Lv Ejection fraction) trial.

PubMed

Verloop, Willemien L; Beeftink, Martine M A; Nap, Alex; Bots, Michiel L; Velthuis, Birgitta K; Appelman, Yolande E; Cramer, Maarten-Jan; Agema, Willem R P; Scholtens, Asbjorn M; Doevendans, Pieter A; Allaart, Cor P; Voskuil, Michiel

2013-12-01

Aim Increasing evidence suggests an important role for hyperactivation of the sympathetic nervous system (SNS) in the clinical phenomena of heart failure with normal LVEF (HFNEF) and hypertension. Moreover, the level of renal sympathetic activation is directly related to the severity of heart failure. Since percutaneous renal denervation (pRDN) has been shown to be effective in modulating elevated SNS activity in patients with hypertension, it can be hypothesized that pRDN has a positive effect on HFNEF. The DIASTOLE trial will investigate whether renal sympathetic denervation influences parameters of HFNEF. Methods DIASTOLE is a multicentre, randomized controlled trial. Sixty patients, diagnosed with HFNEF and treated for hypertension, will be randomly allocated in a 1:1 ratio to undergo renal denervation on top of medical treatment (n = 30) or to maintain medical treatment alone (n = 30). The primary objective is to investigate the efficacy of pRDN by means of pulsed wave Doppler echocardiographic parameters. Secondary objectives include safety of pRDN and a comparison of changes in the following parameters after pRDN: LV mass, LV volume, LVEF, and left atrial volume as determined by magnetic resonance imaging. Also, MIBG (metaiodobenzylguanidine) uptake and washout, BNP levels, blood pressure, heart rate variability, exercise capacity, and quality of life will be assessed. Perspective DIASTOLE is a randomized controlled trial evaluating renal denervation as a treatment option for HFNEF. The results of the current trial will provide important information regarding the treatment of HFNEF, and therefore may have major impact on future therapeutic strategies. Trail registration NCT01583881.

Early food for future health: a randomized controlled trial evaluating the effect of an eHealth intervention aiming to promote healthy food habits from early childhood.

PubMed

Helle, Christine; Hillesund, Elisabet Rudjord; Omholt, Mona Linge; Øverby, Nina Cecilie

2017-09-20

Childhood overweight and obesity is a global public health challenge. Primary prevention initiatives targeting parents have been called for to encourage a positive feeding environment and healthy eating habits that may lay a good foundation for future health. At the same time, there is a need for interventions which combine accessibility and scalability with cost effectiveness. Today's parents are extensive Internet-users, but only a few randomized controlled trials have investigated the use of Internet to promote healthy eating habits in early childhood. In Early Food for Future Health we have developed and will evaluate an Internet-based tool for parents of children between 6 and 12 months, aiming to increase knowledge about infant nutrition and foster protective feeding behavior. During springtime 2016, parents of children aged between 3 and 5 months were recruited through Norwegian child health centres and announcements on Facebook. After completing the baseline questionnaire, 718 parents were individually randomized to intervention- or control group. The intervention group received monthly emails with links to an age-appropriate web-site when their child was between 6 and 12 months. The control group received ordinary care from the child health centres. The data-collection is ongoing. All participants will be followed up at ages 12 and possibly 24 and 48 months, with questionnaires relating to eating behaviour and feeding practices, food variety and diet quality. Providing guidance and counseling to parents of infants is an important task for health authorities and the public child health services. Early Food for Future health is an intervention focusing on promoting early healthy food-habits which may prevent childhood overweight and obesity. If proven to be effective, Early Food for Future Health can be used by parents and public health nurses for supplementary guidance on feeding practices and diet. This study has the potential to provide greater insight and understanding regarding early parental feeding practices, child eating behavior and the development and efficacy of Internet-based public health interventions. ISRCTN13601567 .

Integrating Comparative Effectiveness Design Elements and Endpoints Into a Phase III, Randomized Clinical Trial (SWOG S1007) Evaluating OncotypeDX-Guided Management for Women With Breast Cancer Involving Lymph Nodes

PubMed Central

Ramsey, Scott D.; Barlow, William E.; Gonzalez-Angulo, Ana M.; Tunis, Sean; Baker, Laurence; Crowley, John; Deverka, Patricia; Veenstra, David; Hortobagyi, Gabriel N.

2012-01-01

Women with breast cancer involving the lymph nodes are typically treated with cytotoxic chemotherapy. Retrospective evaluations of prior studies suggest that the 21-gene test (OncotypeDX®), may allow identification of those who can safely avoid chemotherapy. To better understand the performance of the 21-gene test, the RxPONDER (Rx for Positive Node, Endocrine Responsive breast cancer) study was designed, a multicenter Phase III trial randomizing women with hormone receptor-positive and HER2-negative breast cancer involving 1–3 lymph nodes and a 21-gene assay recurrence score (RS) of 25 or less to endocrine therapy alone versus chemotherapy followed by endocrine therapy. As one of the first large-scale comparative-effectiveness studies in oncology, RxPONDER utilized an external stakeholder group to help inform the design of the trial. Stakeholders met with representatives of SWOG over several months through a structured discussion process. The stakeholder engagement process resulted in several changes being made to the trial design. In addition, stakeholder representatives from the health insurance industry provided guidance regarding a mechanism whereby the costs of OncotypeDX® would be paid by the majority of health insurers as part of the trial. The process may serve as a template for future studies evaluating the comparative effectiveness of genomic tests in oncology, particularly those that are conducted within cooperative clinical trials groups. PMID:23000081

Growth hormone for intestinal adaptation in patients with short bowel syndrome: systematic review and meta-analysis of randomized controlled trials.

PubMed

Guo, Ming-Xiao; Li, You-Sheng; Fan, Lei; Li, Jie-Shou

2011-06-01

The purpose of this systematic review was to assess the efficacy of growth hormone (GH) treatment in patients with short bowel syndrome (SBS). Electronic searches were performed to identify all publications describing randomized controlled trials (RCTs) on the use of GH with or without glutamine for the treatment of patients with SBS. The outcomes of interest were body weight, lean body mass, and intestinal absorption function. Four trials involving 70 patients were included in the review. A meta-analysis of these trials suggested that GH had a positive effect in terms of increased weight (mean difference [MD] = 1.66; 95% CI, 0.69-2.63, P < 0.001), lean body mass (MD = 1.93; 95% CI, 0.97-2.90; P < 0.001), energy absorption (MD = 4.42; 95% CI, 0.26-8.58; P = 0.04), nitrogen absorption (MD = 4.85; 95% CI, 0.20-9.49; P = 0.04), and fat absorption (MD = 5.02; 95% CI, 0.21-9.82; P = 0.04) for patients with SBS. Adverse effects occurred during active treatment in all trials. Only 1 trial included a 12-week follow-up study. The results suggest a possible short-term benefit in terms of body weight, lean body mass, and absorptive capacities; however, no conclusion of long-term efficacy of GH could be obtained. Large-scale, long-term follow-up RCTs are needed to confirm the efficacy and tolerability of GH in the future.

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.

Antiangiogenic Therapy for Glioblastoma: Current Status and Future Prospects

PubMed Central

Batchelor, Tracy T.; Reardon, David A.; de Groot, John F.; Wick, Wolfgang; Weller, Michael

2014-01-01

Glioblastoma is characterized by high expression levels of pro-angiogenic cytokines and microvascular proliferation, highlighting the potential value of treatments targeting angiogenesis. Antiangiogenic treatment likely achieves a beneficial impact through multiple mechanisms of action. Ultimately, however, alternative pro-angiogenic signal transduction pathways are activated leading to the development of resistance, even in tumors that initially respond. The identification of biomarkers or imaging parameters to predict response and to herald resistance is of high priority. Despite promising phase 2 clinical trial results and patient benefit in terms of clinical improvement and longer progression-free survival, an overall survival benefit has not been demonstrated in 4 randomized phase 3 trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin recurrent glioblastoma. However, future studies are warranted: predictive markers may allow appropriate patient enrichment, combination with chemotherapy may ultimately prove successful in improving overall survival, and novel agents targeting multiple pro-angiogenic pathways may prove effective. PMID:25398844

Role of Psychotropic Medications in the Management of Anorexia Nervosa: Rationale, Evidence and Future Prospects

PubMed Central

Frank, Guido K.W.; Shott, Megan E.

2016-01-01

Anorexia nervosa is a severe psychiatric disorder without approved medication intervention. Every class of psychoactive medication has been tried to improve treatment outcome; however, randomized controlled trials have been ambiguous at best and across studies have not shown robust improvements in weight gain and recovery. Here we review the available literature on pharmacological interventions since anorexia nervosa came to greater public recognition in the 1960s. This will include a critical review of why those trials may not have been successful. We further provide a neurobiological background for the disorder and discuss how cognition, learning and emotion-regulating circuits could become treatment targets in the future. Making every effort to develop effective pharmacological treatment options for anorexia nervosa is imperative, as it continues to be a complex psychiatric disorder with high disease burden and mortality. PMID:27106297

Supportive care for men with prostate cancer: why are the trials not working? A systematic review and recommendations for future trials.

PubMed

Moore, Theresa Helen Mazzarello; King, Anna Jyoti Louise; Evans, Maggie; Sharp, Debbie; Persad, Raj; Huntley, Alyson Louise

2015-08-01

Men with prostate cancer are likely to have a long illness and experience psychological distress for which supportive care may be helpful. This systematic review describes the evidence for effectiveness and cost-effectiveness of supportive care for men with prostate cancer, taking into account treatment pathway and components of interventions. MEDLINE, EMBASE, CINAHL, CENTRAL, and Psychinfo were searched from inception--July 2013 for randomized controlled trials and controlled trials. Two authors independently assessed risk of bias and extracted data. Twenty-six studies were included (2740 participants). Interventions were delivered pre and during (n = 12), short-term (n = 8), and longer term (18 months) (n = 5) after primary treatment. No interventions were delivered beyond this time. Few trials recruited ethnic minorities and none recruited men in same sex relationships. Intervention components included information, education, health professional discussion, homework, peer discussion, buddy support, cognitive behavioral therapy, cognitive restructuring, psychoeducation, Reiki and relaxation. Most interventions were delivered for 5-10 weeks. Risk of bias of trials was assessed as unclear for most domains due to lack of information. The majority of trials measuring quality of life and depression found no effect. Relatively few trials measured anxiety, coping skills and self-efficacy, and the majority found no effect. No cost data were available. Trials of supportive care for men with prostate cancer cover a range of interventions but are limited by population diversity, inconsistent measurement and reporting of outcomes, and inability to assess risk of bias. Recommendations on design and conduct of future trials are presented. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Power Calculations for Moderators in Multi-Site Cluster Randomized Trials

ERIC Educational Resources Information Center

Spybrook, Jessaca; Kelcey, Ben; Dong, Nianbo

2016-01-01

Cluster randomized trials (CRTs), or studies in which intact groups of individuals are randomly assigned to a condition, are becoming more common in evaluation studies of educational programs. A specific type of CRT in which clusters are randomly assigned to treatment within blocks or sites, known as multisite cluster randomized trials (MSCRTs),…

Calcium/vitamin D supplementation and coronary artery calcification in the Women's Health Initiative.

PubMed

Manson, JoAnn E; Allison, Matthew A; Carr, J Jeffrey; Langer, Robert D; Cochrane, Barbara B; Hendrix, Susan L; Hsia, Judith; Hunt, Julie R; Lewis, Cora E; Margolis, Karen L; Robinson, Jennifer G; Rodabough, Rebecca J; Thomas, Asha M

2010-07-01

Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. The relationship between calcium plus vitamin D (calcium/D) supplementation and coronary artery calcium (CAC) has not been previously assessed in a randomized trial setting. We compared CAC scores after trial completion between women randomized to calcium/vitamin D supplementation and women randomized to placebo. In an ancillary substudy of women randomized to calcium carbonate (1,000 mg of elemental calcium daily) plus vitamin D3 (400 IU daily) or placebo, nested within the Women's Health Initiative trial of estrogen among women who underwent hysterectomy, we measured CAC with cardiac CT in 754 women aged 50 to 59 years at randomization. Imaging for CAC was performed at 28 of 40 centers after a mean of 7 years of treatment, and scans were read centrally. CAC scores were measured by a central reading center with masking to randomization assignments. Posttrial CAC measurements were similar in women randomized to calcium/D supplementation and those receiving placebo. The mean CAC score was 91.6 for women receiving calcium/D and 100.5 for women receiving placebo (rank test P value = 0.74). After adjustment for coronary risk factors, multivariate odds ratios for increasing CAC score cutpoints (CAC >0, > or =10, and > or =100) for calcium/D versus placebo were 0.92 (95% CI, 0.64-1.34), 1.29 (0.88-1.87), and 0.90 (0.56-1.44), respectively. Corresponding odds ratios among women with a 50% or higher adherence to study pills and for higher levels of CAC (>300) were similar. Treatment with moderate doses of calcium plus vitamin D3 did not seem to alter coronary artery calcified plaque burden among postmenopausal women. Whether higher or lower doses would affect this outcome remains uncertain.

Feasibility of the Enhancing Participation In the Community by improving Wheelchair Skills (EPIC Wheels) program: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Many older adults rely on a manual wheelchair for mobility but typically receive little, if any, training on how to use their wheelchair effectively and independently. Standardized skill training is an effective intervention, but limited access to clinician trainers is a substantive barrier. Enhancing Participation in the Community by Improving Wheelchair Skills (EPIC Wheels) is a 1-month monitored home training program for improving mobility skills in older novice manual wheelchair users, integrating principles from andragogy and social cognitive theory. The purpose of this study is to determine whether feasibility indicators and primary clinical outcome measures of the EPIC Wheels program are sufficiently robust to justify conducting a subsequent multi-site randomized controlled trial. Methods A 2 × 2 factorial randomized controlled trial at two sites will compare improvement in wheelchair mobility skills between an EPIC Wheels treatment group and a computer-game control group, with additional wheelchair use introduced as a second factor. A total of 40 community-dwelling manual wheelchair users at least 55 years old and living in two Canadian metropolitan cities (n = 20 × 2) will be recruited. Feasibility indicators related to study process, resources, management, and treatment issues will be collected during data collection and at the end of the study period, and evaluated against proposed criteria. Clinical outcome measures will be collected at baseline (pre-randomization) and post-intervention. The primary clinical outcome measure is wheelchair skill capacity, as determined by the Wheelchair Skills Test, version 4.1. Secondary clinical outcome measures include wheelchair skill safety, satisfaction with performance, wheelchair confidence, life-space mobility, divided-attention, and health-related quality of life. Discussion The EPIC Wheels training program offers several innovative features. The convenient, portable, economical, and adaptable tablet-based, home program model for wheelchair skills training has great potential for clinical uptake and opportunity for future enhancements. Theory-driven design can foster learning and adherence for older adults. Establishing the feasibility of the study protocol and estimating effect size for the primary clinical outcome measure will be used to develop a multi-site randomized controlled trial to test the guiding hypotheses. Trial registration Clinical Trials NCT01740635. PMID:24156396

Linguistic Strategies for Improving Informed Consent in Clinical Trials Among Low Health Literacy Patients.

PubMed

Krieger, Janice L; Neil, Jordan M; Strekalova, Yulia A; Sarge, Melanie A

2017-03-01

Improving informed consent to participate in randomized clinical trials (RCTs) is a key challenge in cancer communication. The current study examines strategies for enhancing randomization comprehension among patients with diverse levels of health literacy and identifies cognitive and affective predictors of intentions to participate in cancer RCTs. Using a post-test-only experimental design, cancer patients (n = 500) were randomly assigned to receive one of three message conditions for explaining randomization (ie, plain language condition, gambling metaphor, benign metaphor) or a control message. All statistical tests were two-sided. Health literacy was a statistically significant moderator of randomization comprehension (P = .03). Among participants with the lowest levels of health literacy, the benign metaphor resulted in greater comprehension of randomization as compared with plain language (P = .04) and control (P = .004) messages. Among participants with the highest levels of health literacy, the gambling metaphor resulted in greater randomization comprehension as compared with the benign metaphor (P = .04). A serial mediation model showed a statistically significant negative indirect effect of comprehension on behavioral intention through personal relevance of RCTs and anxiety associated with participation in RCTs (P < .001). The effectiveness of metaphors for explaining randomization depends on health literacy, with a benign metaphor being particularly effective for patients at the lower end of the health literacy spectrum. The theoretical model demonstrates the cognitive and affective predictors of behavioral intention to participate in cancer RCTs and offers guidance on how future research should employ communication strategies to improve the informed consent processes. © The Author 2016. Published by Oxford University Press.

Linguistic Strategies for Improving Informed Consent in Clinical Trials Among Low Health Literacy Patients

PubMed Central

Neil, Jordan M.; Strekalova, Yulia A.; Sarge, Melanie A.

2017-01-01

Abstract Background: Improving informed consent to participate in randomized clinical trials (RCTs) is a key challenge in cancer communication. The current study examines strategies for enhancing randomization comprehension among patients with diverse levels of health literacy and identifies cognitive and affective predictors of intentions to participate in cancer RCTs. Methods: Using a post-test-only experimental design, cancer patients (n = 500) were randomly assigned to receive one of three message conditions for explaining randomization (ie, plain language condition, gambling metaphor, benign metaphor) or a control message. All statistical tests were two-sided. Results: Health literacy was a statistically significant moderator of randomization comprehension (P = .03). Among participants with the lowest levels of health literacy, the benign metaphor resulted in greater comprehension of randomization as compared with plain language (P = .04) and control (P = .004) messages. Among participants with the highest levels of health literacy, the gambling metaphor resulted in greater randomization comprehension as compared with the benign metaphor (P = .04). A serial mediation model showed a statistically significant negative indirect effect of comprehension on behavioral intention through personal relevance of RCTs and anxiety associated with participation in RCTs (P < .001). Conclusions: The effectiveness of metaphors for explaining randomization depends on health literacy, with a benign metaphor being particularly effective for patients at the lower end of the health literacy spectrum. The theoretical model demonstrates the cognitive and affective predictors of behavioral intention to participate in cancer RCTs and offers guidance on how future research should employ communication strategies to improve the informed consent processes. PMID:27794035

Comparing the effect of a decision aid plus patient navigation with usual care on colorectal cancer screening completion in vulnerable populations: study protocol for a randomized controlled trial.

PubMed

Brenner, Alison T; Getrich, Christina M; Pignone, Michael; Rhyne, Robert L; Hoffman, Richard M; McWilliams, Andrew; de Hernandez, Brisa Urquieta; Weaver, Mark A; Tapp, Hazel; Harbi, Khalil; Reuland, Daniel

2014-07-08

Screening can reduce colorectal cancer (CRC) incidence and mortality. However, screening is underutilized in vulnerable patient populations, particularly among Latinos. Patient-directed decision aids can increase CRC screening knowledge, self-efficacy, and intent; however, their effect on actual screening test completion tends to be modest. This is probably because decision aids do not address some of the patient-specific barriers that prevent successful completion of CRC screening in these populations. These individual barriers might be addressed though patient navigation interventions. This study will test a combined decision aid and patient navigator intervention on screening completion in diverse populations of vulnerable primary care patients. We will conduct a multisite, randomized controlled trial with patient-level randomization. Planned enrollment is 300 patients aged 50 to 75 years at average CRC risk presenting for appointments at two primary clinics in North Carolina and New Mexico. Intervention participants will view a video decision aid immediately before the clinic visit. The 14 to 16 minute video presents information about fecal occult blood tests and colonoscopy and will be viewed on a portable computer tablet in English or Spanish. Clinic-based patient navigators are bilingual and bicultural and will provide both face-to-face and telephone-based navigation. Control participants will view an unrelated food safety video and receive usual care. The primary outcome is completion of a CRC screening test at six months. Planned subgroup analyses include examining intervention effectiveness in Latinos, who will be oversampled. Secondarily, the trial will evaluate the intervention effects on knowledge of CRC screening, self-efficacy, intent, and patient-provider communication. The study will also examine whether patient ethnicity, acculturation, language preference, or health insurance status moderate the intervention effect on CRC screening. This pragmatic randomized controlled trial will test a combined decision aid and patient navigator intervention targeting CRC screening completion. Findings from this trial may inform future interventions and implementation policies designed to promote CRC screening in vulnerable patient populations and to reduce screening disparities. ClinicalTrials.gov NCT02054598.

Effect of Daikenchuto (TJ-100) on gastrointestinal symptoms following laparoscopic colectomy in patients with colon cancer: study protocol for a randomized controlled trial.

PubMed

Hoshino, Nobuaki; Kawada, Kenji; Hida, Koya; Wada, Toshiaki; Takahashi, Ryo; Yoshitomi, Mami; Sakai, Yoshiharu

2017-11-21

Postoperative paralytic ileus can be a difficult complication for both surgeons and patients. Causes and treatments have been discussed for more than two centuries, but have not yet been fully resolved. Daikenchuto (TJ-100, DKT) is a traditional Japanese herbal medicine. Recently, some beneficial mechanisms of DKT to relieve paralytic ileus have been reported. DKT can suppress inflammation, increase intestinal blood flow, and accelerate bowel movements. Therefore, we have designed a randomized controlled trial to investigate the effects of DKT on postoperative gastrointestinal symptoms following laparoscopic colectomy in patients with left-sided colon cancer at a single institution. As primary endpoints, the following outcomes will be evaluated: (i) grade of abdominal pain determined using the numeric rating scale (NRS), (ii) grade of abdominal distention determined using the NRS, and (iii) quality of life determined using the Gastrointestinal Quality Life Index (GIQLI). As secondary endpoints, the following will be evaluated: (i) postoperative nutritional status (Onodera's Prognostic Nutritional Index (PNI) and the Controlling Nutritional Status score (CONUT score)), (ii) duration to initial flatus, (iii) duration to initial defecation, (iv) bowel gas volume, (v) character of stool (Bristol Stool Form Scale), (vi) defecation frequency per day, (vii) postoperative complications (Clavien-Dindo classification), (viii) length of postoperative hospital stay, and (ix) metabolites in the stool and blood. This trial is an open-label study, and needs to include 40 patients (20 patients per group) and is expected to span 2 years. To our knowledge, this is the first randomized controlled trial to investigate the effects of DKT on postoperative subjective outcomes (i.e., postoperative quality of life) following laparoscopic colectomy as primary endpoints. Exploratory metabolomics analysis of metabolites in stool and blood will be conducted in this trial, which previously has only been performed in a few human studies. The study aims to guide a future full-scale pragmatic randomized trial to assess the overall effectiveness of DKT to improve the postoperative quality of life following laparoscopic colectomy. UMIN-CTR (Japan), UMIN000023318 . Registered on 25 July 2016.

Dose-response effects of aerobic exercise on energy compensation in postmenopausal women: combined results from two randomized controlled trials.

PubMed

McNeil, J; Brenner, D R; Courneya, K S; Friedenreich, C M

2017-08-01

Despite the clear health benefits of exercise, exercised-induced weight loss is often less than expected. The term 'exercise energy compensation' is used to define the amount of weight loss below what is expected for the amount of exercise energy expenditure. We examined the dose-response effects of exercise volume on energy compensation in postmenopausal women. Data from Alberta Physical Activity and Breast Cancer Prevention (ALPHA) and Breast Cancer and Exercise Trial in Alberta (BETA) were combined for the present analysis. The ALPHA and BETA trials were two-centred, two-armed, 12-month randomized controlled trials. The ALPHA trial included 160 participants randomized to 225 min per week of aerobic exercise, and the BETA trial randomized 200 participants to each 150 and 300 min per week of aerobic exercise. All participants were aged 50-74 years, moderately inactive (<90 min per week of exercise), had no previous cancer diagnosis and a body mass index between 22 and 40 kg m -2 . Energy compensation was based on changes in body composition (dual-energy X-ray absorptiometry scan) and estimated exercise energy expenditure from completed exercise volume. Associations between Δenergy intake, ΔVO 2peak and Δphysical activity time with energy compensation were assessed. No differences in energy compensation were noted between interventions. However, there were large inter-individual differences in energy compensation between participants; 9.4% experienced body composition changes that were greater than expected based on exercise energy expenditure, 64% experienced some degree of energy compensation and 26.6% experienced weight gain based on exercise energy expenditure. Increases in VO 2peak were associated with reductions in energy compensation (β=-3.44 ml kg -1  min -1 , 95% confidence interval for β=-4.71 to -2.17 ml kg -1  min -1 ; P=0.0001). Large inter-individual differences in energy compensation were noted, despite no differences between activity doses. In addition, increases in VO 2peak were associated with lower energy compensation. Future studies are needed to identify behavioral and metabolic factors that may contribute to this large inter-individual variability in energy compensation.

Clinical development of mTOR inhibitors in breast cancer

PubMed Central

2014-01-01

The mammalian target of rapamycin (mTOR) pathway is a central pathway that regulates mRNA translation, protein synthesis, glucose metabolism, lipid synthesis and autophagy, and is involved in malignant transformation. Several randomized trials have shown that the use of mTOR inhibitors could improve patient outcome with hormone receptor-positive or human epidermal growth factor receptor-2-positive breast cancer. This review analyzes new perspectives from these trials. Preclinical studies have suggested that the mTOR pathway may play a role in the resistance to hormone therapy, trastuzumab and chemotherapy for breast cancer. This concept has been tested in clinical trials for neoadjuvant treatment and for metastatic breast cancer patients. Also, much effort has gone into the identification of biomarkers that will allow for more precise stratification of patients. Findings from these studies will provide indispensable tools for the design of future clinical trials and identify new perspectives and challenges for researchers and clinicians. PMID:25189767

[Position paper on the results of Symplicity HTN-3 trial. Grupo de estudio de la hipertensión arterial resistente].

PubMed

Azpiri-López, José Ramón; Assad-Morell, José Luis; Ponce de León-Martínez, Enrique; Monreal-Puente, Rogelio; Dávila-Bortoni, Adrián; Vázquez-Díaz, Luis Alberto; Treviño-Frutos, Ramón Javier; Barrera-Oranday, Félix; Del Angel-Soto, Juan Gustavo; Martínez, José Guadalupe; Arellano-Torres, Marcelo

2015-01-01

Renal artery denervation has shown to be an effective treatment for resistant hypertension. Symplicity HTN 1 and 2 trials showed in small and uncontrolled groups, significant systolic blood pressure reductions down to 30 mm Hg. Symplicity HTN-3, a double blind, randomized, placebo controlled clinical trial shaded this initial enthusiasm. Surprisingly, their results showed that renal denervation has a similar effect to placebo. Pre-specified subgroup analysis showed that non-black race individuals, younger than 65 years and with normal renal function, had a statistically significant systolic blood pressure decrease. This manuscript critically appraises the Symplicity HTN-3 trial, proposing possible explanations for the results. Also declares our group position and future actions regarding renal denervation. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Emerging Evidence of Thresholds for Beneficial Effects from Vitamin D Supplementation.

PubMed

Scragg, Robert

2018-05-03

Publications from clinical trials of vitamin D supplementation have increased substantially over the last 15 years. Yet, despite the growing number of randomized controlled trials, meta-analyses of these studies have drawn inconsistent conclusions. Many meta-analyses assume that vitamin D is a pharmacological agent, and give scant consideration of it being a nutrient. This limits their potential to detect beneficial effects in participants with vitamin D deficiency. An increasing body of evidence from both observational studies and clinical trials supports the presence of thresholds in vitamin D status below which disease risk increases and vitamin supplementation has beneficial effects. Future supplementation trials which seek to replicate these findings should recruit sufficient numbers of participants with low vitamin D levels, and not give low-dose vitamin D to the placebo group. If the presence of vitamin D thresholds for beneficial effects is confirmed, this would strengthen the need for vitamin D fortification of foods.

Oral contraceptives may alter the detection of emotions in facial expressions.

PubMed

Hamstra, Danielle A; De Rover, Mischa; De Rijk, Roel H; Van der Does, Willem

2014-11-01

A possible effect of oral contraceptives on emotion recognition was observed in the context of a clinical trial with a corticosteroid. Users of oral contraceptives detected significantly fewer facial expressions of sadness, anger and disgust than non-users. This was true for trial participants overall as well as for those randomized to placebo. Although it is uncertain whether this is an effect of oral contraceptives or a pre-existing difference, future studies on the effect of interventions should control for the effects of oral contraceptives on emotional and cognitive outcomes. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Nurse-led telecoaching of people with type 2 diabetes in primary care: rationale, design and baseline data of a randomized controlled trial.

PubMed

Odnoletkova, Irina; Goderis, Geert; Nobels, Frank; Aertgeerts, Bert; Annemans, Lieven; Ramaekers, Dirk

2014-02-04

Despite the efforts of the healthcare community to improve the quality of diabetes care, about 50% of people with type 2 diabetes do not reach their treatment targets, increasing the risk of future micro-and macro-vascular complications. Diabetes self-management education has been shown to contribute to better disease control. However, it is not known which strategies involving educational programs are cost-effective. Telehealth applications might support chronic disease management. Transferability of successful distant patient self-management support programs to the Belgian setting needs to be confirmed by studies of a high methodological quality. "The COACH Program" was developed in Australia as target driven educational telephone delivered intervention to support people with different chronic conditions. It proved to be effective in patients with coronary heart disease after hospitalization. Clinical and cost-effectiveness of The COACH Program in people with type 2 diabetes in Belgium needs to be assessed. Randomized controlled trial in patients with type 2 diabetes. Patients were selected based on their medication consumption data and were recruited by their sickness fund. They were randomized to receive either usual care plus "The COACH Program" or usual care alone. The study will assess the difference in outcomes between groups. The primary outcome measure is the level of HbA1c. The secondary outcomes are: Total Cholesterol, LDL-Cholesterol, HDL-Cholesterol, Triglycerides, Blood Pressure, body mass index, smoking status; proportion of people at target for HbA1c, LDL-Cholesterol and Blood Pressure; self-perceived health status, diabetes-specific emotional distress and satisfaction with diabetes care. The follow-up period is 18 months. Within-trial and modeled cost-utility analyses, to project effects over life-time horizon beyond the trial duration, will be undertaken from the perspective of the health care system if the intervention is effective. The study will enhance our understanding of the potential of telehealth in diabetes management in Belgium. Research on the clinical effectiveness and the cost-effectiveness is essential to support policy makers in future reimbursement and implementation decisions.

Internet-Delivered Exposure Therapy for Fibromyalgia: A Randomized Controlled Trial.

PubMed

Hedman-Lagerlöf, Maria; Hedman-Lagerlöf, Erik; Axelsson, Erland; Ljótsson, Brjánn; Engelbrektsson, Johanna; Hultkrantz, Sofia; Lundbäck, Karolina; Björkander, Daniel; Wicksell, Rikard K; Flink, Ida; Andersson, Erik

2018-06-01

Fibromyalgia (FM) is a common and disabling chronic pain disorder, for which existing pharmacological and psychological treatments have yet yielded insufficient effects. Previous literature has shown that exposure therapy may be an effective treatment for chronic pain. This study constitutes the first randomized controlled trial evaluating exposure therapy for FM. A total of 140 participants with diagnosed FM were randomized to a 10-week Internet-delivered exposure treatment (iExp; n=70) or a waitlist control condition (WLC; n=70). Primary outcome measure were FM symptoms and impact, and secondary outcome measures were fatigue, disability, quality of life, pain-related distress and avoidance behaviors, insomnia, depression, and anxiety. Data retention was high (100% data completion at posttreatment for primary outcome, 96% at 6-month follow-up and 94% at 12-month follow-up). Results showed that participants in the iExp group made large and superior improvements compared with WLC on FM symptoms and impact (B, -1.93; z, -10.14; P<0.001, between-group Cohen d=0.90), as well as all secondary outcomes (between-group Cohen d ranging from 0.44 to 1.38) with sustained results. We conclude that iExp seems to be an efficacious treatment for FM compared with no treatment, and the results also highlight the potential increase of accessibility by using the Internet format to deliver psychological treatments for these patients. Future trials with active control conditions are warranted.

Nifedipine as a uterine relaxant for external cephalic version: a randomized controlled trial.

PubMed

Kok, Marjolein; Bais, Joke M; van Lith, Jan M; Papatsonis, Dimitri M; Kleiverda, Gunilla; Hanny, Dahrs; Doornbos, Johannes P; Mol, Ben W; van der Post, Joris A

2008-08-01

To estimate the effectiveness of nifedipine as a uterine relaxant during external cephalic version to correct breech presentation. In this randomized, double-blind, placebo-controlled trial, women with a singleton fetus in breech presentation and a gestational age of 36 weeks or more were eligible for enrollment. Participating women received two doses of either nifedipine 10 mg or placebo, 30 and 15 minutes before the external cephalic version attempt. The primary outcome was a cephalic-presenting fetus immediately after the procedure. Secondary outcome measures were cephalic presentation at delivery, mode of delivery, and adverse events. A sample size of 292 was calculated to provide 80% power to detect a 17% improvement of the external cephalic version success rate, assuming a placebo group rate of 40% and alpha of .05. Outcome data for 310 of 320 randomly assigned participants revealed no significant difference in external cephalic version success rates between treatment (42%) and control group (37%) (relative risk 1.1, 95%; 95% confidence interval 0.85-1.5). The cesarean delivery rate was 51% in the treatment group and 46% in the control group (relative risk 1.1, 95% confidence interval 0.88-1.4). Nifedipine did not significantly improve the success of external cephalic version. Future use of nifedipine to improve the outcome of external cephalic version should be limited to large clinical trials.

Does the use of consumer health information technology improve outcomes in the patient self-management of diabetes? A meta-analysis and narrative review of randomized controlled trials.

PubMed

Or, Calvin K L; Tao, Da

2014-05-01

To assess whether the use of consumer health information technologies (CHITs) improves outcomes in the patient self-management of diabetes. The evidence from randomized controlled trials (RCTs) on the effects of CHITs on patient outcomes was analyzed using either meta-analysis or a narrative synthesis approach. A systematic search of seven electronic databases was conducted to identify relevant reports of RCTs for the analysis. In the meta-analyses, standardized mean differences in patient outcomes were calculated and random-effects models were applied in cases where the heterogeneity of the results was moderate or high, otherwise fixed-effects models were used. Sixty-two studies, representing 67 RCTs, met the inclusion criteria. The results of the meta-analyses showed that the use of CHITs was associated with significant reductions in HbA1c, blood pressure, total cholesterol, and triglycerides levels when compared with the usual care. The findings from the narrative synthesis indicated that only a small proportion of the trials reported positive effects of CHITs on patient outcomes. The use of CHITs in supporting diabetes self-management appears to have potential benefits for patients' self-management of diabetes. However, the effectiveness of the technologies in improving patient outcomes still awaits confirmation in future studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effectiveness and safety of cryotherapy after arthroscopic anterior cruciate ligament reconstruction. A systematic review of the literature.

PubMed

Martimbianco, Ana Luiza Cabrera; Gomes da Silva, Brenda Nazaré; de Carvalho, Alan Pedrosa Viegas; Silva, Valter; Torloni, Maria Regina; Peccin, Maria Stella

2014-11-01

Cryotherapy is widely used in rehabilitation; however, its effectiveness after anterior cruciate ligament (ACL) reconstruction remains uncertain. To investigate the effectiveness and safety of cryotherapy following ACL reconstruction through a systematic review, randomized and quasi-randomized clinical trials were searched in the databases: MEDLINE, EMBASE, CENTRAL, PEDro, SportDiscus, CINAHL, LILACS (June 2013). The primary outcomes measures were pain, edema and adverse events; the secondary outcomes were knee function, analgesic medication use, range of motion, blood loss, hospital stay, quality of life and patient satisfaction. The methodological quality of studies was evaluated using the Cochrane Collaboration risk-of-bias tool. Ten trials (a total of 573 patients) were included. Results of meta-analysis showed that the use of cold compression devices produced a significant reduction in pain scores 48 h after surgery (p < 0.00001), compared to no cryotherapy. The risk for adverse events did not differ between patients receiving cryotherapy versus no treatment (p = 1.00). The limited evidence currently available is insufficient to draw definitive conclusions on the effectiveness of cryotherapy for other outcomes. There is a need for well designed, good quality randomized trials to answer other questions related to this intervention and increase the precision of future systematic reviews. Copyright © 2014 Elsevier Ltd. All rights reserved.

Homeopathy for attention-deficit/hyperactivity disorder: a pilot randomized-controlled trial.

PubMed

Jacobs, Jennifer; Williams, Anna-Leila; Girard, Christine; Njike, Valentine Yanchou; Katz, David

2005-10-01

The aim of this study was to carry out a preliminary trial evaluating the effectiveness of homeopathy in the treatment of attention-deficit/hyperactivity disorder (ADHD). This work was a randomized, double-blind, placebo-controlled trial. This study was conducted in a private homeopathic clinic in the Seattle metropolitan area. Subjects included children 6-12 years of age meeting Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria for ADHD. Forty-three subjects were randomized to receive a homeopathic consultation and either an individualized homeopathic remedy or placebo. Patients were seen by homeopathic physicians every 6 weeks for 18 weeks. Outcome measures included the Conner's Global Index-Parent, Conner's Global Index- Teacher, Conner's Parent Rating Scale-Brief, Continuous Performance Test, and the Clinical Global Impression Scale. There were no statistically significant differences between homeopathic remedy and placebo groups on the primary or secondary outcome variables. However, there were statistically and clinically significant improvements in both groups on many of the outcome measures. This pilot study provides no evidence to support a therapeutic effect of individually selected homeopathic remedies in children with ADHD. A therapeutic effect of the homeopathic encounter is suggested and warrants further evaluation. Future studies should be carried out over a longer period of time and should include a control group that does not receive the homeopathic consultation. Comparison to conventional stimulant medication for ADHD also should be considered.

Cognitive Analytic Therapy for Bipolar Disorder: A Pilot Randomized Controlled Trial.

PubMed

Evans, Mark; Kellett, Stephen; Heyland, Simon; Hall, Jo; Majid, Shazmin

2017-01-01

The evidence base for treatment of bipolar affective disorder (BD) demands the evaluation of new psychotherapies in order to broaden patient choice. This study reports on the feasibility, safety, helpfulness and effectiveness of cognitive analytic therapy (CAT). In a pilot randomized controlled trial, BD patients in remission were randomized to either receiving 24 sessions of CAT (n = 9) or treatment as usual (n = 9) and were assessed in terms of symptoms, functioning and service usage over time. In the CAT arm no adverse events occurred, 8/9 completed treatment, 5/8 attended all 24 sessions and 2/8 were categorized as recovered. The most common helpful event during CAT was recognition of patterns in mood variability, with helpfulness themes changing according to phase of therapy. No major differences were found when comparing the arms over time in terms of service usage or psychometric outcomes. The study suggests that conducting further research into the effectiveness of CAT in treating BD is warranted and guidance regarding future trials is provided. Copyright © 2016 John Wiley & Sons, Ltd. Treating BD with CAT appears feasible and safe. Retaining fidelity to the reformulation, recognition and revision structure of CAT appears useful. Participants stated that across the phases of CAT, focussing on patterns of mood variability was consistently helpful. Copyright © 2016 John Wiley & Sons, Ltd.

Glycemic impact of non-nutritive sweeteners: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Nichol, Alexander D; Holle, Maxwell J; An, Ruopeng

2018-05-15

Nonnutritive sweeteners (NNSs) are zero- or low-calorie alternatives to nutritive sweeteners, such as table sugars. A systematic review and meta-analysis of randomized controlled trials was conducted to quantitatively synthesize existing scientific evidence on the glycemic impact of NNSs. PubMed and Web of Science databases were searched. Two authors screened the titles and abstracts of candidate publications. The third author was consulted to resolve discrepancies. Twenty-nine randomized controlled trials, with a total of 741 participants, were included and their quality assessed. NNSs under examination included aspartame, saccharin, steviosides, and sucralose. The review followed the PRISMA guidelines. Meta-analysis was performed to estimate and track the trajectory of blood glucose concentrations over time after NNS consumption, and to test differential effects by type of NNS and participants' age, weight, and disease status. In comparison with the baseline, NNS consumption was not found to increase blood glucose level, and its concentration gradually declined over the course of observation following NNS consumption. The glycemic impact of NNS consumption did not differ by type of NNS but to some extent varied by participants' age, body weight, and diabetic status. NNS consumption was not found to elevate blood glucose level. Future studies are warranted to assess the health implications of frequent and chronic NNS consumption and elucidate the underlying biological mechanisms.

Narcolepsy: current treatment options and future approaches

PubMed Central

Billiard, Michel

2008-01-01

The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy. PMID:18830438

Early skin-to-skin contact for mothers and their healthy newborn infants.

PubMed

Moore, E R; Anderson, G C; Bergman, N

2007-07-18

Mother-infant separation postbirth is common in Western culture. Early skin-to-skin contact (SSC) begins ideally at birth and involves placing the naked baby, covered across the back with a warm blanket, prone on the mother's bare chest. According to mammalian neuroscience, the intimate contact inherent in this place (habitat) evokes neurobehaviors ensuring fulfillment of basic biological needs. This time may represent a psychophysiologically 'sensitive period' for programming future behavior. To assess the effects of early SSC on breastfeeding, behavior, and physiological adaptation in healthy mother-newborn dyads. Cochrane Pregnancy and Childbirth Group's and Neonatal Group's Trials Registers (August 2006), Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 2), MEDLINE (1976 to 2006). Randomized and quasi-randomized clinical trials comparing early SSC with usual hospital care. We independently assessed trial quality and extracted data. Study authors were contacted for additional information. Thirty studies involving 1925 participants (mother-infant dyads), were included. Data from more than two trials were available for only 8-of-64 outcome measures. We found statistically significant and positive effects of early SSC on breastfeeding at one to four months postbirth (10 trials; 552 participants) (odds ratio (OR) 1.82, 95% confidence interval (CI) 1.08 to 3.07), and breastfeeding duration (seven trials; 324 participants) (weighted mean difference (WMD) 42.55, 95% CI -1.69 to 86.79). Trends were found for improved summary scores for maternal affectionate love/touch during observed breastfeeding (four trials; 314 participants) (standardized mean difference (SMD) 0.52, 95% CI 0.07 to 0.98) and maternal attachment behavior (six trials; 396 participants) (SMD 0.52, 95% CI 0.31 to 0.72) with early SSC. SSC infants cried for a shorter length of time (one trial; 44 participants) (WMD -8.01, 95% CI -8.98 to -7.04). Late preterm infants had better cardio-respiratory stability with early SSC (one trial; 35 participants) (WMD 2.88, 95% CI 0.53 to 5.23). No adverse effects were found. Limitations included methodological quality, variations in intervention implementation, and outcome variability. The intervention may benefit breastfeeding outcomes, early mother-infant attachment, infant crying and cardio-respiratory stability, and has no apparent short or long-term negative effects. Further investigation is recommended. To facilitate meta-analysis, future research should be done using outcome measures consistent with those in the studies included here. Published reports should clearly indicate if the intervention was SSC and include means, standard deviations, exact probability values, and data to measure intervention dose.

Assessments of the quality of randomized controlled trials published in International Journal of Urology from 1994 to 2011.

PubMed

Cho, Hee Ju; Chung, Jae Hoon; Jo, Jung Ki; Kang, Dong Hyuk; Cho, Jeong Man; Yoo, Tag Keun; Lee, Seung Wook

2013-12-01

Randomized controlled trials are one of the most reliable resources for assessing the effectiveness and safety of medical treatments. Low quality randomized controlled trials carry a large bias that can ultimately impair the reliability of their conclusions. The present study aimed to evaluate the quality of randomized controlled trials published in International Journal of Urology by using multiple quality assessment tools. Randomized controlled trials articles published in International Journal of Urology were found using the PubMed MEDLINE database, and qualitative analysis was carried out with three distinct assessment tools: the Jadad scale, the van Tulder scale and the Cochrane Collaboration Risk of Bias Tool. The quality of randomized controlled trials was analyzed by publication year, type of subjects, intervention, presence of funding and whether an institutional review board reviewed the study. A total of 68 randomized controlled trial articles were published among a total of 1399 original articles in International Journal of Urology. Among these randomized controlled trials, 10 (2.70%) were from 1994 to 1999, 23 (4.10%) were from 2000 to 2005 and 35 (4.00%) were from 2006 to 2011 (P = 0.494). On the assessment with the Jadad and van Tulder scale, the numbers and percentage of high quality randomized controlled trials increased over time. The studies that had institutional review board reviews, funding resources or that were carried out in multiple institutions had an increased percentage of high quality articles. The numbers and percentage of high-quality randomized controlled trials published in International Journal of Urology have increased over time. Furthermore, randomized controlled trials with funding resources, institutional review board reviews or carried out in multiple institutions have been found to be of higher quality compared with others not presenting these features. © 2013 The Japanese Urological Association.

A Quantitative Assessment of the Reporting Quality of Herbal Medicine Research: The Road to Improvement.

PubMed

Naumann, Ken

2018-02-01

To quantify different aspects of the quality of reporting of herbal medicine clinical trials, to determine how that quality is affecting the conclusions of meta-analyses, and to target areas for improvement in future herbal medicine research reporting. The Electronic databases PubMed, Academic Search Premier, ScienceDirect, and Alt HealthWatch were searched for meta-analyses of herbal medicines in refereed journals and Cochrane Reviews in the years 2000-2004 and 2010-2014. The search was limited to meta-analyses of randomized controlled trials involving humans and published in English. Judgments and descriptions within the meta-analyses were used to report on risks of bias in the included clinical trials and the meta-analyses themselves. Out of 3264 citations, 9 journal-published meta-analyses were selected from 2000 to 2004, 116 from 2010 to 2014, and 44 Cochrane Reviews from 2010 to 2014. Across both time frames and categories of publication, <42% of the trials included in the meta-analyses described adequate randomization; <19% described concealment methods; <26% described double blinding; <29% described outcome assessment blinding, ≤53% discussed incomplete data, and <36% were nonselective in their reporting. Less than 54% of trials reported on adverse events and 64% of meta-analyses did not include a single trial with a low risk of bias. Taxonomic verification and chemical characterization of test products were infrequent in trials. Only 40% of meta-analyses considered publication bias and, of those that did, 90% found evidence for it. Cochrane Reviews were more likely than other sources to make negative conclusions of efficacy or to defer conclusions because of the absence of high quality trials. Meta-analyses of herbal medicines include a significant number of clinical trials that do not meet the recommended standards for clinical trial reporting. This quantitative assessment identified significant publication bias and other bias risks that may be due to inadequate trial design or incomplete reporting of outcomes. Suggested improvements to herbal medicine clinical trial reporting are discussed.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis.

PubMed

Papachristou, Georgios I; Machicado, Jorge D; Stevens, Tyler; Goenka, Mahesh Kumar; Ferreira, Miguel; Gutierrez, Silvia C; Singh, Vikesh K; Kamal, Ayesha; Gonzalez-Gonzalez, Jose A; Pelaez-Luna, Mario; Gulla, Aiste; Zarnescu, Narcis O; Triantafyllou, Konstantinos; Barbu, Sorin T; Easler, Jeffrey; Ocampo, Carlos; Capurso, Gabriele; Archibugi, Livia; Cote, Gregory A; Lambiase, Louis; Kochhar, Rakesh; Chua, Tiffany; Tiwari, Subhash Ch; Nawaz, Haq; Park, Walter G; de-Madaria, Enrique; Lee, Peter J; Wu, Bechien U; Greer, Phil J; Dugum, Mohannad; Koutroumpakis, Efstratios; Akshintala, Venkata; Gougol, Amir

2017-01-01

We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

Renal denervation in the management of resistant hypertension: current evidence and perspectives.

PubMed

Jin, Yu; Persu, Alexandre; Staessen, Jan A

2013-09-01

Catheter-based renal denervation has emerged as a novel treatment modality for resistant hypertension. This review summarizes the current evidence on this procedure in treatment of resistant hypertension, limitations of available evidence and questions to be answered. The SYMPLICITY studies showed that renal denervation is feasible in treating resistant hypertension, but failed to provide conclusive evidence on the size and durability of the antihypertensive, renal and sympatholytic effects, as well as the long-term safety. The definition of resistant hypertension was loose in the SYMPLICITY studies and the management of resistant hypertension was suboptimal. Future studies should have a randomized design and enroll truly resistant hypertension patients by excluding secondary hypertension, white-coat hypertension and nonadherent patients. Questions to be addressed by the ongoing and future trials include the long-term efficacy and safety of this procedure, identification of responders and uncovering of the underlying mechanisms. Only well-designed, randomized clinical trials addressing the limitations of the SYMPLICITY studies will be able to demonstrate whether renal denervation is an efficacious treatment modality in resistant hypertension and in which patients. For now, renal denervation remains an experimental procedure and should only be offered to truly resistant hypertensive patients in a research context after careful selection.

Determinants of Dropout and Nonadherence in a Dementia Prevention Randomized Controlled Trial: The Prevention of Dementia by Intensive Vascular Care Trial.

PubMed

Beishuizen, Cathrien R L; Coley, Nicola; Moll van Charante, Eric P; van Gool, Willem A; Richard, Edo; Andrieu, Sandrine

2017-07-01

To explore and compare sociodemographic, clinical, and neuropsychiatric determinants of dropout and nonadherence in older people participating in an open-label cluster-randomized controlled trial-the Prevention of Dementia by Intensive Vascular care (preDIVA) trial-over 6 years. Secondary analysis. One hundred sixteen general practices in the Netherlands. Community-dwelling individuals aged 70 to 78 (N = 2,994). Nurse-led multidomain intervention targeting cardiovascular risk factors to prevent dementia. The associations between participant baseline sociodemographic (age, sex, education), clinical (medical history, disability, cardiovascular risk), neuropsychiatric (depressive symptoms (Geriatric Depression Scale-15), and cognitive (Mini-Mental State Examination)) characteristics and dropout from the trial and nonadherence to the trial intervention were explored using multilevel logistic regression models. Older age, poorer cognitive function, more symptoms of depression, and greater disability were the most important determinants of dropout of older people. The presence of cardiovascular risk factors was not associated with dropout but was associated with nonadherence. Being overweight was a risk factor for nonadherence, whereas people with high blood pressure or a low level of physical exercise adhered better to the intervention. The association between poorer cognitive function and symptoms of depression and dropout was stronger in the control group than in the intervention group, and vice versa for increased disability. In a large dementia prevention trial with 6-year follow-up, dropout was associated with older age, poorer cognitive function, symptoms of depression, and disability at baseline. These findings can help to guide the design of future dementia prevention trials in older adults. The associations found between cardiovascular risk factors and nonadherence need to be confirmed in other older populations receiving cardiovascular prevention interventions. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

High flow nasal cannula oxygen versus noninvasive ventilation in adult acute respiratory failure: a systematic review of randomized-controlled trials.

PubMed

Beng Leong, Lim; Wei Ming, Ng; Wei Feng, Lee

2018-06-19

We reviewed the use of noninvasive ventilation (NIV) versus high flow nasal cannula (HFNC) oxygen in adult acute respiratory failure (ARF). We searched major databases and included randomized trials comparing at least NIV with HFNC or NIV+HFNC with NIV in ARF. Primary outcomes included intubation/re-intubation rates. Secondary outcomes were ICU mortality and morbidities. Five trials were included; three compared HFNC with NIV, one compared HFNC, NIV and oxygen whereas one compared HFNC+NIV with NIV. Patients had hypoxaemic ARF (PaO2/FiO2≤300 mmHg). Heterogeneity prevented result pooling. Three and two studies had superiority and noninferiority design, respectively. Patients were postcardiothoracic surgery, mixed medical/surgical patients and those with pneumonia. Two trials were conducted after extubation, two before intubation and one during intubation. Three trials reported intubation/re-intubation rates as the primary outcomes. The other two trials reported the lowest peripheral capillary oxygen saturation readings during bronchoscopy or intubation. In the former three trials, the odds ratio for intubation/re-intubation rates between HFNC versus the NIV group ranged from 0.80 (95% confidence interval: 0.54-1.19) to 1.65 (95% confidence interval: 0.96-2.84). In the latter two trials, only one reported a difference in the lowest peripheral capillary oxygen saturation between NIV+HFNC versus the NIV group during intubation [100% (interquartile range: 95-100) vs. 96% (interquartile range: 92-99); P=0.029]. The secondary outcomes included differences in ICU mortality and patient tolerability, favouring HFNC, were conflicting, but highlighted future research directions. These include patients with hypercapneic ARF, more severe hypoxaemia (PaO2/FiO2≤200 mmHg), a superiority design, an oxygen arm and patient-centred outcomes.

A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy.

PubMed

Dirksen, A; Dijkman, J H; Madsen, F; Stoel, B; Hutchison, D C; Ulrik, C S; Skovgaard, L T; Kok-Jensen, A; Rudolphus, A; Seersholm, N; Vrooman, H A; Reiber, J H; Hansen, N C; Heckscher, T; Viskum, K; Stolk, J

1999-11-01

We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha(1)-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV(1) between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin augmentation therapy. The patients were randomized to either alpha(1)-antitrypsin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr. Self-administered spirometry performed every morning and evening at home showed no significant difference in decline of FEV(1) between treatment and placebo. Each year, the degree of emphysema was quantified by the 15th percentile point of the lung density histogram derived from computed tomography (CT). The loss of lung tissue measured by CT (mean +/- SEM) was 2.6 +/- 0.41 g/L/yr for placebo as compared with 1.5 +/- 0.41 g/L/yr for alpha(1)-antitrypsin infusion (p = 0.07). Power analysis showed that this protective effect would be significant in a similar trial with 130 patients. This is in contrast to calculations based on annual decline of FEV(1) showing that 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr.

Protocol for a Systematic Review and Meta-Analysis of Lithium, Anticonvulsive or atypical antipsychotic Drugs for Treatment of Refractory Obsessive-Compulsive Disorder.

PubMed

Soleimani, R; Jalali, M M; Keshtkar, A; Jalali, S M

2017-01-01

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that causes significant distress to the afflicted individual. About half of OCD patients treated with an adequate trial of serotonin reuptake inhibitors fail to fully respond to treatment and continue to exhibit significant symptoms. Therefore, there is a need for other agents to alleviate the symptoms of these disorders. In spite of considerable research including numerous randomized controlled trials and systematic reviews, there exists uncertainty regarding what treatments are effective. In this systematic review, we evaluated the efficacy of mood stabilizers in treatment-refractory OCD. We conducted a meta-analysis of all randomized clinical trials evaluating lithium, anticonvulsive agents or atypical antipsychotic drugs for OCD to determine which therapies show more effective than a placebo, in reducing obsessive-compulsive symptoms. We acquired eligible studies through a systematic search of Cochrane Central Registry of Controlled Trials, MEDLINE, EMBASE, PsycINFO, Scopus, ProQuest and Google scholar. We conducted meta-analyses to establish the effect of lithium, anticonvulsive agents, or atypical antipsychotic drugs on patient-important outcomes when possible. To assess relative effects of treatments, we constructed a random effect model. Our review was the first to evaluate all treatments for OCD, to provide the relative effectiveness of lithium, anticonvulsive agents, or atypical antipsychotic drugs, and prioritize patient-important outcomes with a focus on functional gains. Our review facilitated the evidence-based management of patients with resistant OCD, and identified the key areas for future research.

Dronabinol for the Treatment of Cannabis Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Levin, Frances R.; Mariani, John J.; Brooks, Daniel J.; Pavlicova, Martina; Cheng, Wendy; Nunes, Edward

2011-01-01

Cannabis dependence is a substantial public health problem. Behavioral treatments have shown promise, but there are no effective medications for cannabis dependence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, in treating cannabis dependence. 156 cannabis-dependent adults were enrolled in a randomized, double-blind, placebo-controlled, 12-week trial. After a 1-week placebo lead-in phase, participants were randomized to receive dronabinol 20 mg twice a day or placebo. Doses were maintained until the end of week 8 and then tapered off over 2 weeks. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline followback method. There was no significant difference between treatment groups in the proportion of participants who achieved 2 weeks of abstinence at the end of the maintenance phase (dronabinol: 17.7%; placebo: 15.6%). Although both groups showed a reduction in marijuana use over time, there were no differences between the groups. Treatment retention was significantly higher at the end of the maintenance phase on dronabinol (77%), compared to placebo (61%) (P = .02), and withdrawal symptoms were significantly lower on dronabinol than placebo (P= .02). This is the first trial using an agonist substitution strategy for treatment of cannabis dependence. Dronabinol showed promise, it was well-tolerated, and improved treatment retention and withdrawal symptoms. Future trials might test higher doses, combinations of dronabinol with other medications with complementary mechanisms, or with more potent behavioral interventions. PMID:21310551

Effect of Compression Devices on Preventing Deep Vein Thrombosis Among Adult Trauma Patients: A Systematic Review.

PubMed

Ibrahim, Mona; Ahmed, Azza; Mohamed, Warda Yousef; El-Sayed Abu Abduo, Somaya

2015-01-01

Trauma is the leading cause of death in Americans up to 44 years old each year. Deep vein thrombosis (DVT) is a significant condition occurring in trauma, and prophylaxis is essential to the appropriate management of trauma patients. The incidence of DVT varies in trauma patients, depending on patients' risk factors, modality of prophylaxis, and methods of detection. However, compression devices and arteriovenous (A-V) foot pumps prophylaxis are recommended in trauma patients, but the efficacy and optimal use of it is not well documented in the literature. The aim of this study was to review the literature on the effect of compression devices in preventing DVT among adult trauma patients. We searched through PubMed, CINAHL, and Cochrane Central Register of Controlled Trials for eligible studies published from 1990 until June 2014. Reviewers identified all randomized controlled trials that satisfied the study criteria, and the quality of included studies was assessed by Cochrane risk of bias tool. Five randomized controlled trials were included with a total of 1072 patients. Sequential compression devices significantly reduced the incidence of DVT in trauma patients. Also, foot pumps were more effective in reducing incidence of DVT compared with sequential compression devices. Sequential compression devices and foot pumps reduced the incidence of DVT in trauma patients. However, the evidence is limited to a small sample size and did not take into account other confounding variables that may affect the incidence of DVT in trauma patients. Future randomized controlled trials with larger probability samples to investigate the optimal use of mechanical prophylaxis in trauma patients are needed.

From randomized controlled trials to evidence grading schemes: current state of evidence-based practice in social sciences.

PubMed

Boruch, Robert; Rui, Ning

2008-11-01

With the advance of web search and navigation technology, enormous amount of information, non-information, and misinformation may be obtained in milliseconds in response to questions about 'what works' in social sciences. Today, policy makers in non-medical public service arenas are under increasing pressure to make sound decisions based on scientific evidence. Some of these decisions are a matter of legal requirement. This paper shows how such movements are closely aligned with the evolution of organizations that develop and apply evidence standards and evidence grading schemes within the social science communities. The current state of evidence-based practice in social sciences is examined by reviewing the latest development of randomized trials and evidence grading schemes in the fields of education, criminal justice, and social welfare. Studies conducted under the auspices of the Campbell Collaboration and What Works Clearinghouse are used to illustrate ingredients of evidence grading schemes, graphic display of results of systematic reviews, and discrepancies of evidence derived from randomized trials and non-experimental trials. Furthermore, it is argued that the use of evidence on 'what works' depends on the potential users' awareness, understanding of the evidence, as well as their capacity and willingness to use it. Awareness and understanding depends on the world wide web and its augmentations, while capacity and willingness depends more on incentives to use good evidence and on political and ethical values. Implications for the future development of evidence grading organizations are discussed. © 2008 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

RandomizEd controlled trial for pre-operAtive dose-escaLation BOOST in locally advanced rectal cancer (RECTAL BOOST study): study protocol for a randomized controlled trial.

PubMed

Burbach, J P Maarten; Verkooijen, Helena M; Intven, Martijn; Kleijnen, Jean-Paul J E; Bosman, Mirjam E; Raaymakers, Bas W; van Grevenstein, Wilhelmina M U; Koopman, Miriam; Seravalli, Enrica; van Asselen, Bram; Reerink, Onne

2015-02-22

Treatment for locally advanced rectal cancer (LARC) consists of chemoradiation therapy (CRT) and surgery. Approximately 15% of patients show a pathological complete response (pCR). Increased pCR-rates can be achieved through dose escalation, thereby increasing the number patients eligible for organ-preservation to improve quality of life (QoL). A randomized comparison of 65 versus 50Gy with external-beam radiation alone has not yet been performed. This trial investigates pCR rate, clinical response, toxicity, QoL and (disease-free) survival in LARC patients treated with 65Gy (boost + chemoradiation) compared with 50Gy standard chemoradiation (sCRT). This study follows the 'cohort multiple randomized controlled trial' (cmRCT) design: rectal cancer patients are included in a prospective cohort that registers clinical baseline, follow-up, survival and QoL data. At enrollment, patients are asked consent to offer them experimental interventions in the future. Eligible patients-histologically confirmed LARC (T3NxM0 <1 mm from mesorectal fascia, T4NxM0 or TxN2M0) located ≤10 cm from the anorectal transition who provided consent for experimental intervention offers-form a subcohort (n = 120). From this subcohort, a random sample is offered the boost prior to sCRT (n = 60), which they may accept or refuse. Informed consent is signed only after acceptance of the boost. Non-selected patients in the subcohort (n = 60) undergo sCRT alone and are not notified that they participate in the control arm until the trial is completed. sCRT consists of 50Gy (25 × 2Gy) with concomitant capecitabine. The boost (without chemotherapy) is given prior to sCRT and consists of 15 Gy (5 × 3Gy) delivered to the gross tumor volume (GTV). The primary endpoint is pCR (TRG 1). Secondary endpoints include acute grade 3-4 toxicity, good pathologic response (TRG 1-2), clinical response, surgical complications, QoL and (disease-free) survival. Data is analyzed by intention to treat. The boost is delivered prior to sCRT so that GTV adjustment for tumor shrinkage during sCRT is not necessary. Small margins also aim to limit irradiation of healthy tissue. The cmRCT design provides opportunity to overcome common shortcomings of classic RCTs, such as slow recruitment, disappointment-bias in control arm patients and poor generalizability. The Netherlands Trials Register NL46051.041.13. Registered 22 August 2013. ClinicalTrials.gov NCT01951521 . Registered 18 September 2013.

On the Use of Local Assessments for Monitoring Centrally Reviewed Endpoints with Missing Data in Clinical Trials*

PubMed Central

Brummel, Sean S.; Gillen, Daniel L.

2014-01-01

Due to ethical and logistical concerns it is common for data monitoring committees to periodically monitor accruing clinical trial data to assess the safety, and possibly efficacy, of a new experimental treatment. When formalized, monitoring is typically implemented using group sequential methods. In some cases regulatory agencies have required that primary trial analyses should be based solely on the judgment of an independent review committee (IRC). The IRC assessments can produce difficulties for trial monitoring given the time lag typically associated with receiving assessments from the IRC. This results in a missing data problem wherein a surrogate measure of response may provide useful information for interim decisions and future monitoring strategies. In this paper, we present statistical tools that are helpful for monitoring a group sequential clinical trial with missing IRC data. We illustrate the proposed methodology in the case of binary endpoints under various missingness mechanisms including missing completely at random assessments and when missingness depends on the IRC’s measurement. PMID:25540717

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

PubMed

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

2013-08-01

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

Commentary: considerations for using the 'Trials within Cohorts' design in a clinical trial of an investigational medicinal product.

PubMed

Bibby, Anna C; Torgerson, David J; Leach, Samantha; Lewis-White, Helen; Maskell, Nick A

2018-01-08

The 'trials within cohorts' (TwiC) design is a pragmatic approach to randomised trials in which trial participants are randomly selected from an existing cohort. The design has multiple potential benefits, including the option of conducting multiple trials within the same cohort. To date, the TwiC design methodology been used in numerous clinical settings but has never been applied to a clinical trial of an investigational medicinal product (CTIMP). We have recently secured the necessary approvals to undertake the first CTIMP using the TwiC design. In this paper, we describe some of the considerations and modifications required to ensure such a trial is compliant with Good Clinical Practice and international clinical trials regulations. We advocate using a two-stage consent process and using the consent stages to explicitly differentiate between trial participants and cohort participants who are providing control data. This distinction ensured compliance but had consequences with respect to costings, recruitment and the trial assessment schedule. We have demonstrated that it is possible to secure ethical and regulatory approval for a CTIMP TwiC. By including certain considerations at the trial design stage, we believe this pragmatic and efficient methodology could be utilised in other CTIMPs in future.

Upper limb robot-assisted therapy in cerebral palsy: a single-blind randomized controlled trial.

PubMed

Gilliaux, Maxime; Renders, Anne; Dispa, Delphine; Holvoet, Dominique; Sapin, Julien; Dehez, Bruno; Detrembleur, Christine; Lejeune, Thierry M; Stoquart, Gaëtan

2015-02-01

Several pilot studies have evoked interest in robot-assisted therapy (RAT) in children with cerebral palsy (CP). To assess the effectiveness of RAT in children with CP through a single-blind randomized controlled trial. Sixteen children with CP were randomized into 2 groups. Eight children performed 5 conventional therapy sessions per week over 8 weeks (control group). Eight children completed 3 conventional therapy sessions and 2 robot-assisted sessions per week over 8 weeks (robotic group). For both groups, each therapy session lasted 45 minutes. Throughout each RAT session, the patient attempted to reach several targets consecutively with the REAPlan. The REAPlan is a distal effector robot that allows for displacements of the upper limb in the horizontal plane. A blinded assessment was performed before and after the intervention with respect to the International Classification of Functioning framework: body structure and function (upper limb kinematics, Box and Block test, Quality of Upper Extremity Skills Test, strength, and spasticity), activities (Abilhand-Kids, Pediatric Evaluation of Disability Inventory), and participation (Life Habits). During each RAT session, patients performed 744 movements on average with the REAPlan. Among the variables assessed, the smoothness of movement (P < .01) and manual dexterity assessed by the Box and Block test (P = .04) improved significantly more in the robotic group than in the control group. This single-blind randomized controlled trial provides the first evidence that RAT is effective in children with CP. Future studies should investigate the long-term effects of this therapy. © The Author(s) 2014.

Neurodevelopmental Outcomes of Extremely Preterm Infants Randomized to Stress Dose Hydrocortisone

PubMed Central

Parikh, Nehal A.; Kennedy, Kathleen A.; Tyson, Jon E.

2015-01-01

Objective To compare the effects of stress dose hydrocortisone therapy with placebo on survival without neurodevelopmental impairments in high-risk preterm infants. Study Design We recruited 64 extremely low birth weight (birth weight ≤1000g) infants between the ages of 10 and 21 postnatal days who were ventilator-dependent and at high-risk for bronchopulmonary dysplasia. Infants were randomized to a tapering 7-day course of stress dose hydrocortisone or saline placebo. The primary outcome at follow-up was a composite of death, cognitive or language delay, cerebral palsy, severe hearing loss, or bilateral blindness at a corrected age of 18–22 months. Secondary outcomes included continued use of respiratory therapies and somatic growth. Results Fifty-seven infants had adequate data for the primary outcome. Of the 28 infants randomized to hydrocortisone, 19 (68%) died or survived with impairment compared with 22 of the 29 infants (76%) assigned to placebo (relative risk: 0.83; 95% CI, 0.61 to 1.14). The rates of death for those in the hydrocortisone and placebo groups were 31% and 41%, respectively (P = 0.42). Randomization to hydrocortisone also did not significantly affect the frequency of supplemental oxygen use, positive airway pressure support, or need for respiratory medications. Conclusions In high-risk extremely low birth weight infants, stress dose hydrocortisone therapy after 10 days of age had no statistically significant effect on the incidence of death or neurodevelopmental impairment at 18–22 months. These results may inform the design and conduct of future clinical trials. Trial Registration ClinicalTrials.gov NCT00167544 PMID:26376074

Review of Yoga Therapy During Cancer Treatment

PubMed Central

Danhauer, Suzanne C.; Addington, Elizabeth L.; Sohl, Stephanie J.; Chaoul, Alejandro; Cohen, Lorenzo

2017-01-01

Purpose Reviews of yoga research that distinguish results of trials conducted during (versus after) cancer treatment are needed to guide future research and clinical practice. We therefore conducted a review of non-randomized studies and randomized controlled trials of yoga interventions for children and adults undergoing treatment for any cancer type. Methods Studies were identified via research databases and reference lists. Inclusion criteria: (1) children or adults undergoing cancer treatment; (2) intervention stated as yoga or component of yoga; and (3) publication in English in peer-reviewed journals through October 2015. Exclusion criteria: (1) samples receiving hormone therapy only; (2) interventions involving only meditation; and (3) yoga delivered within broader cancer recovery or mindfulness-based stress reduction programs. Results Results of non-randomized (adult: n=8, pediatric: n=4) and randomized controlled trials (adult: n=13, pediatric: n=0) conducted during cancer treatment are summarized separately by age group. Findings most consistently support improvement in psychological outcomes (e.g., depression, distress, anxiety). Several studies also found that yoga enhanced quality of life, though further investigation is needed to clarify domain-specific efficacy (e.g., physical, social, cancer-specific). Regarding physical and biomedical outcomes, evidence increasingly suggests that yoga ameliorates sleep and fatigue; additional research is needed to advance preliminary findings for other treatment sequelae and stress/immunity biomarkers. Conclusions Among adults undergoing cancer treatment, evidence supports recommending yoga for improving psychological outcomes, with potential for also improving physical symptoms. Evidence is insufficient to evaluate the efficacy of yoga in pediatric oncology. We describe suggestions for strengthening yoga research methodology to inform clinical practice guidelines. PMID:28064385

Outcome of the Vaginal Infections and Prematurity Study: results of a clinical trial of erythromycin among pregnant women colonized with group B streptococci.

PubMed

Klebanoff, M A; Regan, J A; Rao, A V; Nugent, R P; Blackwelder, W C; Eschenbach, D A; Pastorek, J G; Williams, S; Gibbs, R S; Carey, J C

1995-05-01

Our purpose was to determine whether erythromycin treatment of pregnant women colonized with group B streptococci would reduce the occurrence of low birth weight (< 2500 gm) and preterm (< 37 completed weeks) birth. In a double-blind clinical trial, 938 carriers of group B streptococci were randomized to receive erythromycin base (333 mg three times a day) or matching placebo beginning during the third trimester and before 30 weeks and continuing for 10 weeks or until 35 weeks 6 days of pregnancy. Pregnancy outcomes were available for 97% of randomized women; 14% of subjects withdrew from the trial. Birth weight < 2500 gm occurred in 8.6% of the erythromycin and 6.1% of the placebo recipients (relative risk 1.4, 0.9 to 2.2, p = 0.16). Preterm delivery occurred in 11.4% of women randomized to erythromycin and in 12.3% randomized to placebo (relative risk 0.9, 95% confidence limits 0.6 to 1.3, p = 0.65). Greater benefit of erythromycin in reducing these outcomes was not observed among women reporting the best compliance. In this study of pregnant women colonized with group B streptococci treatment with erythromycin was not shown to be effective at prolonging gestation or reducing low birth weight. Greater than anticipated complicating factors, including spontaneous clearance of the organism, use of nontrial antibiotics, and density of colonization, may have resulted in population sizes too small to detect a benefit of treatment. Future studies should take these factors into account in determining sample sizes.

PROSPERA: a randomized, controlled trial evaluating rasagiline in progressive supranuclear palsy.

PubMed

Nuebling, Georg; Hensler, Mira; Paul, Sabine; Zwergal, Andreas; Crispin, Alexander; Lorenzl, Stefan

2016-08-01

To date, pharmacological treatment options for progressive supranuclear palsy (PSP), a neurodegenerative tauopathy, are limited. The MAO-B inhibitor rasagiline has shown neuroprotective effects in preclinical models of neurodegeneration. To evaluate the safety, tolerability and therapeutic effect of rasagiline on symptom progression in PSP. In this 1-year randomized, double-blind, placebo-controlled trial, 44 patients fulfilling the NINDS-PSP criteria were randomized to 1 mg/d rasagiline or placebo. The combined primary endpoint included symptom progression as measured by the PSP rating scale (PSP-RS) and the requirement of L-dopa rescue medication. Secondary endpoints included Schwab and England Activities of Daily Living (SEADL), Montgomery-Åsberg Depression Rating Scale, Mini Mental State Examination, Frontal Assessment Battery and posturographic measurements. Of the 44 patients randomized, 26 completed the trial per protocol. Rasagiline was well tolerated, with a slight increase of known side effects (hallucinations, ventricular extrasystoles). No effect on the primary endpoint (p = 0.496) was detected. Symptom progression averaged at 11.2 (rasagiline) and 10.8 (placebo) points per year (ΔPSP-RS). No difference was seen in SEADL, depression, cognitive function, frontal executive function and posturographic measurements. Post hoc analyses of PSP-RS subdomains indicate a potential beneficial effect in the "limb motor" subdomain, whereas performance appeared lower in the "mentation" and "history" subdomains in the treatment group. While rasagiline is well tolerated in PSP, a beneficial effect on overall symptom progression was not detected. Post hoc analyses suggest the implementation of more specific endpoints in future studies.

Theta oscillations promote temporal sequence learning.

PubMed

Crivelli-Decker, Jordan; Hsieh, Liang-Tien; Clarke, Alex; Ranganath, Charan

2018-05-17

Many theoretical models suggest that neural oscillations play a role in learning or retrieval of temporal sequences, but the extent to which oscillations support sequence representation remains unclear. To address this question, we used scalp electroencephalography (EEG) to examine oscillatory activity over learning of different object sequences. Participants made semantic decisions on each object as they were presented in a continuous stream. For three "Consistent" sequences, the order of the objects was always fixed. Activity during Consistent sequences was compared to "Random" sequences that consisted of the same objects presented in a different order on each repetition. Over the course of learning, participants made faster semantic decisions to objects in Consistent, as compared to objects in Random sequences. Thus, participants were able to use sequence knowledge to predict upcoming items in Consistent sequences. EEG analyses revealed decreased oscillatory power in the theta (4-7 Hz) band at frontal sites following decisions about objects in Consistent sequences, as compared with objects in Random sequences. The theta power difference between Consistent and Random only emerged in the second half of the task, as participants were more effectively able to predict items in Consistent sequences. Moreover, we found increases in parieto-occipital alpha (10-13 Hz) and beta (14-28 Hz) power during the pre-response period for objects in Consistent sequences, relative to objects in Random sequences. Linear mixed effects modeling revealed that single trial theta oscillations were related to reaction time for future objects in a sequence, whereas beta and alpha oscillations were only predictive of reaction time on the current trial. These results indicate that theta and alpha/beta activity preferentially relate to future and current events, respectively. More generally our findings highlight the importance of band-specific neural oscillations in the learning of temporal order information. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of whole soy and purified isoflavone daidzein on renal function--a 6-month randomized controlled trial in equol-producing postmenopausal women with prehypertension.

PubMed

Liu, Zhao-min; Ho, Suzanne C; Chen, Yu-ming; Tang, Nelson; Woo, Jean

2014-09-01

The aim of the study was to examine the long-term effect of commonly used whole soy foods (soy flour) and purified daidzein (one major isoflavone and the precursor of equol) on renal function among prehypertensive postmenopausal women who are also equol producers, a population most likely to benefit from soy intervention. This was a 6-month double-blind, randomized, placebo-controlled trial. Two hundred seventy eligible Chinese women were randomized to either one of the three treatments: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group) or 40 g low-fat milk powder (placebo group) daily each for 6 months. Fasting blood and 24-h urine samples were collected at the beginning and end of trial. Serum creatinine, cystatin C, urea, angiotensin-converting enzyme, minerals and 24-h urinary creatinine and minerals were analyzed. Estimated glomerular filtration rate (eGFR) was calculated with the Cockcroft-Gault and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Two hundred fifty-three subjects completed the study according to the protocol. Urinary isoflavones indicated good compliance of participants. No significant changes were observed in most of renal parameters, however, there was a less decrease in eGFRcockcroft in 6-month change (p=0.044) and %change (p=0.031) with whole soy intake relative to milk placebo. Subgroup analysis among women with lowered renal function suggested whole soy consumption tended to improve markers of renal function relative to control. Six-month consumption of whole soy tended to have a modest improvement of renal function in prehypertensive postmenopausal women with lowered renal function. Future trials in subjects with more declined renal function are necessary. The trial was registered in ClinicalTrials.gov with identifier of NCT01270737. (URL: http://clinicaltrials.gov/ct2/show/NCT01270737). Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

An Herbal Drug, Gongjin-dan, Ameliorates Acute Fatigue Caused by Short-Term Sleep-Deprivation: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Clinical Trial.

PubMed

Son, Mi Ju; Im, Hwi-Jin; Ku, Boncho; Lee, Jun-Hwan; Jung, So Young; Kim, Young-Eun; Lee, Sung Bae; Kim, Jun Young; Son, Chang-Gue

2018-01-01

Introduction: Gongjin-dan (GJD) is an herbal drug commonly used in Korea and China to combat fatigue, but there are only few clinical studies on its effectiveness and experimental studies on its mechanism of action, and no randomized controlled trial of GJD on the efficacy and mechanism of action has been reported. Here, we performed an exploratory study to evaluate both questions regarding GJD use in humans. Methods: A randomized, double-blinded, placebo-controlled, crossover clinical trial was conducted in the Republic of Korea. Healthy male participants were recruited and randomly allocated to groups receiving GJD-placebo or placebo-GJD in sequence. Fatigue was artificially induced by sleep deprivation for 2 nights. The primary outcome was a change in serum cortisol level; levels of biomarkers for stress hormones as well as oxidative stress and immunologic factors were also assessed, and questionnaires on fatigue and sleep quality were conducted. Results: Twelve and 11 participants were assigned to the GJD-placebo and placebo-GJD groups, respectively. Of all 23 participants, depending on crossover design, we analyzed a total of 20 participants for GJD, and 21 for placebo. An increase in serum cortisol appeared to be attenuated by GJD administration ( p = 0.25), but the effect was not statistically significant; a similar pattern was observed in salivary cortisol levels ( p = 0.14). Overall, GJD showed a tendency to reduce fatigue according to the Brief Fatigue Inventory (BFI, p = 0.07) and the Fatigue Severity Scale (FSS, p = 0.13) questionnaires. BFI and FSS scores in the first stage (before the crossover), however, were significantly improved (BFI, p = 0.02; FSS, p = 0.05) after GJD treatment (relative to placebo). GJD also seemed to improve sleep quality as assessed by the Leeds Sleep Evaluation Questionnaire ( p = 0.06), with a significant improvement specifically in the condition "Getting To Sleep" ( p = 0.02). Five participants experienced minor adverse events, but no adverse events were specific to the GJD administration period. Conclusions: This trial produced the first clinical evidence that GJD might have anti-fatigue properties, especially under sleep deprivation; however, the investigation of cortisol-mediated mechanisms requires further larger-scale studies in the future. World Health Organization International Clinical Trials Registry Platform KCT0001681 (http://apps.who.int/trialsearch/Trial2.aspx?TrialID=KCT0001681).

Antibiotics or probiotics as preventive measures against ventilator-associated pneumonia: a literature review

PubMed Central

2011-01-01

Introduction Mechanically ventilated critically ill patients frequently develop ventilator-associated pneumonia (VAP), a life-threatening complication. Proposed preventive measures against VAP include, but are not restricted to, selective decontamination of the digestive tract (SDD), selective oropharyngeal decontamination (SOD) and the use of probiotics. Probiotics are live bacteria that could have beneficial effects on the host by altering gastrointestinal flora. Similar to SDD and SOD, a prescription of probiotics aims at the prevention of secondary colonization of the upper and/or lower digestive tract. Methods We performed a literature review to describe the differences and similarities between SDD/SOD and probiotic preventive strategies, focusing on (a) efficacy, (b) risks, and (c) the routing of these strategies. Results Reductions in the incidence of VAP have been achieved with SDD and SOD. Two large randomized controlled trials even showed reduced mortality with these preventive strategies. Randomized controlled trials of probiotic strategies also showed a reduction of the incidence of VAP, but trials were too small to draw firm conclusions. Preventive strategies with antibiotics and probiotics may be limited due to the risk of emerging resistance to the locally applied antibiotics and the risk of probiotic-related infections, respectively. The majority of trials of SDD and SOD did not exhaustively address the issue of emerging resistance. Likewise, trials of probiotic strategies did not adequately address the risk of colonization with probiotics and probiotic-related infection. In studies of SDD and SOD the preventive strategy aimed at decontamination of the oral cavity, throat, stomach and intestines, and the oral cavity and throat, respectively. In the vast majority of studies of probiotic therapy the preventive strategy aimed at decontamination of the stomach and intestines. Conclusions Prophylactic use of antibiotics in critically ill patients is effective in reducing the incidence of VAP. Probiotic strategies deserve consideration in future well-powered trials. Future studies are needed to determine if preventive antibiotic and probiotic strategies are safe with regard to development of antibiotic resistance and probiotic infections. It should be determined whether the efficacy of probiotics improves when these agents are provided to the mouth and the intestines simultaneously. PMID:21232110

Management of oral lesions in HIV-positive patients.

PubMed

Baccaglini, Lorena; Atkinson, Jane C; Patton, Lauren L; Glick, Michael; Ficarra, Giuseppe; Peterson, Douglas E

2007-03-01

HIV/AIDS is currently the leading cause of death in Africa and the fourth leading cause of death worldwide. This systematic review of the literature was conducted to evaluate the evidence for treatment of the most common oral lesions associated with HIV: oral candidiasis with or without oropharyngeal involvement (OPC), oral hairy leukoplakia (OHL), recurrent aphthous-like ulcerations (RAU), oral Kaposi's sarcoma (OKS), orolabial herpes simplex infection (HSV), oral herpes zoster infection (VZV), intraoral or perioral warts (HPV), and HIV-associated periodontal diseases. Treatment of HIV-associated salivary gland disease is addressed in a different section of this World Workshop. We found the largest body of evidence for treatment of OPC in HIV patients. Future trials will be needed to test drugs currently in development for treatment of Candida strains that are resistant to existing therapies. There were no double blind, placebo-controlled randomized clinical trials (RCT) for topical treatment of OHL, and only one RCT for systemic treatment of the lesion with desciclovir. Systemic thalidomide was the only drug tested in RCT for treatment or prevention of RAU. Only 1 double-blind RCT comparing vinblastine and sodium tetradecyl sulfate was identified for localized treatment of OKS. Three drugs (famciclovir, acyclovir, and valaciclovir) were shown to be effective in randomized, double-blind trials for treatment or suppression of mucocutaneous HSV lesions in HIV patients. In all 3 trials, the effects of these medications on orolabial HSV lesions were not reported separately. There were no double-blind, placebo-controlled RCT testing topical treatments for orolabial HSV lesions in HIV patients. No trials testing treatments of oral VZV were identified. There were no double-blind, placebo-controlled RCT for treatment of HIV-associated intraoral or perioral warts or periodontal diseases. In conclusion, there is a need for well-designed RCTs to assess the safety and efficacy of topical and systemic treatments of most oral mucosal and perioral lesions in HIV patients. There is also a need to develop newer drugs for treatment of resistant fungal and viral microorganisms. Finally, standardized outcome measures should be developed for future clinical trials to allow comparisons of studies using different populations.

SMS text message reminders to improve infant vaccination coverage in Guatemala: A pilot randomized controlled trial.

PubMed

Domek, Gretchen J; Contreras-Roldan, Ingrid L; O'Leary, Sean T; Bull, Sheana; Furniss, Anna; Kempe, Allison; Asturias, Edwin J

2016-05-05

Patient reminder systems are an evidence-based way to improve childhood vaccination rates but are difficult to implement in low- and middle-income countries (LMICs). Short Message Service (SMS) texts may offer a potential low-cost solution, especially in LMICs where mobile phones are becoming more ubiquitous. To determine if an SMS-based vaccination reminder system aimed at improving completion of the infant primary immunization series is feasible and acceptable in Guatemala. A pilot randomized controlled trial was conducted at two public health clinics in Guatemala City. Infants aged 8-14 weeks presenting for the first dose of the primary immunization series were enrolled in March-April 2013. Participants randomized into the intervention received three SMS reminders one week before the second and third dose. A follow-up acceptability survey was administered to both groups. The participation rate was 86.8% (321/370); 8 did not own a cell phone and 12 could not use SMS. 96.9% of intervention parents were sent at least one SMS reminder prior to visit 2 and 96.3% prior to visit 3. Both intervention and usual care participants had high rates of vaccine and visit completion, with a non-statistically significant higher percentage of children in the intervention completing both visit 2 (95.0% vs. 90.1%, p=.12) and visit 3 (84.4% vs. 80.7%, p=.69). More intervention vs. usual care parents agreed that SMS reminders would be helpful for remembering appointments (p<.0001), agreed to being interested in receiving future SMS reminders (p<.0001), and said that they would be willing to pay for future SMS reminders (p=.01). This proof of concept evaluation showed that a new application of SMS technology is feasible to implement in a LMIC with high user satisfaction. Larger studies with modifications in the SMS system are needed to determine effectiveness (Clinical Trial Registry NCT01663636). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of a Mobile Phone Intervention on Quitting Smoking in a Young Adult Population of Smokers: Randomized Controlled Trial Study Protocol

PubMed Central

Struik, Laura Louise; Hammond, David; Guindon, G Emmanuel; Norman, Cameron D; Whittaker, Robyn; Burns, Catherine M; Grindrod, Kelly A; Brown, K Stephen

2015-01-01

Background Tobacco use remains the number one cause of preventable chronic disease and death in developed countries worldwide. In North America, smoking rates are highest among young adults. Despite that the majority of young adult smokers indicate wanting to quit, smoking rates among this age demographic have yet to decline. Helping young adults quit smoking continues to be a public health priority. Digital mobile technology presents a promising medium for reaching this population with smoking cessation interventions, especially because young adults are the heaviest users of this technology. Objective The primary aim of this trial is to determine the effectiveness of an evidence-informed mobile phone app for smoking cessation, Crush the Crave, on reducing smoking prevalence among young adult smokers. Methods A parallel randomized controlled trial (RCT) with two arms will be conducted in Canada to evaluate Crush the Crave. In total, 1354 young adult smokers (19 to 29 years old) will be randomized to receive the evidence-informed mobile phone app, Crush the Crave, or an evidence-based self-help guide known as “On the Road to Quitting” (control) for a period of 6 months. The primary outcome measure is a 30-day point prevalence of abstinence at the 6-month follow-up. Secondary outcomes include a 7-day point prevalence of abstinence, number of quit attempts, reduction in consumption of cigarettes, self-efficacy, satisfaction, app utilization metrics, and use of smoking cessation services. A cost-effectiveness analysis is included. Results This trial is currently open for recruitment. The anticipated completion date for the study is April 2016. Conclusions This randomized controlled trial will provide the evidence to move forward on decision making regarding the inclusion of technology-based mobile phone interventions as part of existing smoking cessation efforts made by health care providers. Evidence from the trial will also inform the development of future apps, provide a deeper understanding of the factors that drive change in smoking behavior using an app, and improve the design of cessation apps. This trial is among the first to assess the effect of a comprehensive and evidence-informed mHealth smoking cessation app on a large sample of young adult smokers. Strengths of the trial include the high-quality research design and in-depth assessment of the implementation of the intervention. If effective, the trial has the potential to demonstrate that including mHealth technology as a population-based intervention strategy can cost-effectively reach a greater proportion of the population and help young adult smokers to quit. Trial Registration ClinicalTrials.gov NCT01983150; http://clinicaltrials.gov/ct2/show/NCT01983150 (Archived by WebCite at http://www.webcitation.org/6VGyc0W0i). PMID:25599695

Early skin-to-skin contact for mothers and their healthy newborn infants.

PubMed

Moore, Elizabeth R; Anderson, Gene C; Bergman, Nils; Dowswell, Therese

2012-05-16

Mother-infant separation postbirth is common in Western culture. Early skin-to-skin contact (SSC) begins ideally at birth and involves placing the naked baby, head covered with a dry cap and a warm blanket across the back, prone on the mother's bare chest. According to mammalian neuroscience, the intimate contact inherent in this place (habitat) evokes neurobehaviors ensuring fulfillment of basic biological needs. This time may represent a psychophysiologically 'sensitive period' for programming future physiology and behavior. To assess the effects of early SSC on breastfeeding, physiological adaptation, and behavior in healthy mother-newborn dyads. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2011), made personal contact with trialists, and consulted the bibliography on kangaroo mother care (KMC) maintained by Dr. Susan Ludington. Randomized controlled trials comparing early SSC with usual hospital care. We independently assessed trial quality and extracted data. Study authors were contacted for additional information. Thirty-four randomized controlled trials were included involving 2177 participants (mother-infant dyads). Data from more than two trials were available for only eight outcome measures. For primary outcomes, we found a statistically significant positive effect of early SSC on breastfeeding at one to four months postbirth (13 trials; 702 participants) (risk ratio (RR) 1.27, 95% confidence interval (CI) 1.06 to 1.53, and SSC increased breastfeeding duration (seven trials; 324 participants) (mean difference (MD) 42.55 days, 95% CI -1.69 to 86.79) but the results did not quite reach statistical significance (P = 0.06). Late preterm infants had better cardio-respiratory stability with early SSC (one trial; 31 participants) (MD 2.88, 95% CI 0.53 to 5.23). Blood glucose 75 to 90 minutes following the birth was significantly higher in SSC infants (two trials, 94 infants) (MD 10.56 mg/dL, 95% CI 8.40 to 12.72).The overall methodological quality of trials was mixed, and there was high heterogeneity for some outcomes. Limitations included methodological quality, variations in intervention implementation, and outcomes. The intervention appears to benefit breastfeeding outcomes, and cardio-respiratory stability and decrease infant crying, and has no apparent short- or long-term negative effects. Further investigation is recommended. To facilitate meta-analysis, future research should be done using outcome measures consistent with those in the studies included here. Published reports should clearly indicate if the intervention was SSC with time of initiation and duration and include means, standard deviations and exact probability values.

The Evidence for the Role of Nutraceuticals in the Management of Pediatric Migraine: a Review.

PubMed

Orr, Serena L

2018-04-04

Nutraceuticals are a form of complementary and alternative medicine that is commonly used by children and adolescents with migraine. In this review, observational studies, randomized controlled trials, systematic reviews, and meta-analyses on the efficacy and safety of single compound nutraceuticals for the management of migraine in children and adolescents were identified through a literature search of MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials. Twenty-one studies were reviewed, of which 11 were observational studies, 7 were randomized controlled trials, and 3 were systematic reviews. Six different nutraceuticals were included in the review: vitamin D, riboflavin, coenzyme Q10, magnesium, butterbur, and polyunsaturated fatty acids. All but three of the studies assessed the role of nutraceuticals in migraine prevention, while three studies evaluated the role of intravenous magnesium for acute migraine management. Overall, the quality and size of the studies were limited. Due to low quality evidence and limited studies, no definite conclusions can be drawn on the efficacy of nutraceuticals for the treatment of pediatric migraine. Future studies are warranted in order to establish evidence upon which to define the role of nutraceuticals in this patient population.

Randomized Trial of Two Dissemination Strategies for a Skin Cancer Prevention Program in Aquatic Settings

PubMed Central

Escoffery, Cam; Elliott, Tom; Nehl, Eric J.

2015-01-01

Objectives. We compared 2 strategies for disseminating an evidence-based skin cancer prevention program. Methods. We evaluated the effects of 2 strategies (basic vs enhanced) for dissemination of the Pool Cool skin cancer prevention program in outdoor swimming pools on (1) program implementation, maintenance, and sustainability and (2) improvements in organizational and environmental supports for sun protection. The trial used a cluster-randomized design with pools as the unit of intervention and outcome. The enhanced group received extra incentives, reinforcement, feedback, and skill-building guidance. Surveys were collected in successive years (2003–2006) from managers of 435 pools in 33 metropolitan areas across the United States participating in the Pool Cool Diffusion Trial. Results. Both treatment groups improved their implementation of the program, but pools in the enhanced condition had significantly greater overall maintenance of the program over 3 summers of participation. Furthermore, pools in the enhanced condition established and maintained significantly greater sun-safety policies and supportive environments over time. Conclusions. This study found that more intensive, theory-driven dissemination strategies can significantly enhance program implementation and maintenance of health-promoting environmental and policy changes. Future research is warranted through longitudinal follow-up to examine sustainability. PMID:25521872

Potential Expanded Indications for Neprilysin Inhibitors

PubMed Central

Riddell, Elizabeth; Vader, Justin M.

2017-01-01

Purpose of review The goal of this article is to review potential expanded indications for neprilysin inhibitors. This article reviews the rationale and design for ongoing and future trials of sacubitril/valsartan in cardiovascular and non-cardiovascular disease. Recent findings Randomized trial data are lacking for use of sacubitril/valsartan in acute heart failure and advanced heart failure. Mechanistic data from animal studies suggest a role for neprilysin inhibition in the treatment of post-myocardial infarction systolic dysfunction and heart failure with preserved ejection fraction. Beyond the cardiovascular system, renal and neurological function may be impacted by neprilysin inhibition. Forthcoming randomized trials will address the clinical impact of sacubitril/valsartan on these conditions. Summary Neprolysin inhibition with sacubitril/valsartan offers a new therapeutic strategy with a broad range of potential therapeutic actions. In PARADIGM-HF, the combination of neprolysin and RAAS inhibition was proven to be superior to enalapril for patients with stable NYHA class II–III heart failure and reduced left ventricular ejection fraction. Preliminary data suggests it may also have a role in other cardiovascular and non-cardiovascular disease. Several ongoing and planned studies will determine the extent of its benefit for these other indications. PMID:28281174

Randomized trial of an uncertainty self-management telephone intervention for patients awaiting liver transplant.

PubMed

Bailey, Donald E; Hendrix, Cristina C; Steinhauser, Karen E; Stechuchak, Karen M; Porter, Laura S; Hudson, Julie; Olsen, Maren K; Muir, Andrew; Lowman, Sarah; DiMartini, Andrea; Salonen, Laurel Williams; Tulsky, James A

2017-03-01

We tested an uncertainty self-management telephone intervention (SMI) with patients awaiting liver transplant and their caregivers. Participants were recruited from four transplant centers and completed questionnaires at baseline, 10, and 12 weeks from baseline (generally two and four weeks after intervention delivery, respectively). Dyads were randomized to either SMI (n=56) or liver disease education (LDE; n=59), both of which involved six weekly telephone sessions. SMI participants were taught coping skills and uncertainty management strategies while LDE participants learned about liver function and how to stay healthy. Outcomes included illness uncertainty, uncertainty management, depression, anxiety, self-efficacy, and quality of life. General linear models were used to test for group differences. No differences were found between the SMI and LDE groups for study outcomes. This trial offers insight regarding design for future interventions that may allow greater flexibility in length of delivery beyond our study's 12-week timeframe. Our study was designed for the time constraints of today's clinical practice setting. This trial is a beginning point to address the unmet needs of these patients and their caregivers as they wait for transplants that could save their lives. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

SieveSifter: a web-based tool for visualizing the sieve analyses of HIV-1 vaccine efficacy trials.

PubMed

Fiore-Gartland, Andrew; Kullman, Nicholas; deCamp, Allan C; Clenaghan, Graham; Yang, Wayne; Magaret, Craig A; Edlefsen, Paul T; Gilbert, Peter B

2017-08-01

Analysis of HIV-1 virions from participants infected in a randomized controlled preventive HIV-1 vaccine efficacy trial can help elucidate mechanisms of partial protection. By comparing the genetic sequence of viruses from vaccine and placebo recipients to the sequence of the vaccine itself, a technique called 'sieve analysis', one can identify functional specificities of vaccine-induced immune responses. We have created an interactive web-based visualization and data access tool for exploring the results of sieve analyses performed on four major preventive HIV-1 vaccine efficacy trials: (i) the HIV Vaccine Trial Network (HVTN) 502/Step trial, (ii) the RV144/Thai trial, (iii) the HVTN 503/Phambili trial and (iv) the HVTN 505 trial. The tool acts simultaneously as a platform for rapid reinterpretation of sieve effects and as a portal for organizing and sharing the viral sequence data. Access to these valuable datasets also enables the development of novel methodology for future sieve analyses. Visualization: http://sieve.fredhutch.org/viz . Source code: https://github.com/nkullman/SIEVE . Data API: http://sieve.fredhutch.org/data . agartlan@fredhutch.org. © The Author(s) 2017. Published by Oxford University Press.

A process for Decision-making after Pilot and feasibility Trials (ADePT): development following a feasibility study of a complex intervention for pelvic organ prolapse

PubMed Central

2013-01-01

Background Current Medical Research Council (MRC) guidance on complex interventions advocates pilot trials and feasibility studies as part of a phased approach to the development, testing, and evaluation of healthcare interventions. In this paper we discuss the results of a recent feasibility study and pilot trial for a randomized controlled trial (RCT) of pelvic floor muscle training for prolapse (ClinicalTrials.gov: NCT01136889). The ways in which researchers decide to respond to the results of feasibility work may have significant repercussions for both the nature and degree of tension between internal and external validity in a definitive trial. Methods We used methodological issues to classify and analyze the problems that arose in the feasibility study. Four centers participated with the aim of randomizing 50 women. Women were eligible if they had prolapse of any type, of stage I to IV, and had a pessary successfully fitted. Postal questionnaires were administered at baseline, 6 months, and 7 months post-randomization. After identifying problems arising within the pilot study we then sought to locate potential solutions that might minimize the trade-off between a subsequent explanatory versus pragmatic trial. Results The feasibility study pointed to significant potential problems in relation to participant recruitment, features of the intervention, acceptability of the intervention to participants, and outcome measurement. Finding minimal evidence to support our decision-making regarding the transition from feasibility work to a trial, we developed a systematic process (A process for Decision-making after Pilot and feasibility Trials (ADePT)) which we subsequently used as a guide. The process sought to: 1) encourage the systematic identification and appraisal of problems and potential solutions; 2) improve the transparency of decision-making processes; and 3) reveal the tensions that exist between pragmatic and explanatory choices. Conclusions We have developed a process that may aid researchers in their attempt to identify the most appropriate solutions to problems identified within future pilot and feasibility RCTs. The process includes three key steps: a decision about the type of problem, the identification of all solutions (whether addressed within the intervention, trial design or clinical context), and a systematic appraisal of these solutions. PMID:24160371

Esophageal cancer management controversies: Radiation oncology point of view

PubMed Central

Tai, Patricia; Yu, Edward

2014-01-01

Esophageal cancer treatment has evolved from single modality to trimodality therapy. There are some controversies of the role, target volumes and dose of radiotherapy (RT) in the literature over decades. The present review focuses primarily on RT as part of the treatment modalities, and highlight on the RT volume and its dose in the management of esophageal cancer. The randomized adjuvant chemoradiation (CRT) trial, intergroup trial (INT 0116) enrolled 559 patients with resected adenocarcinoma of the stomach or gastroesophageal junction. They were randomly assigned to surgery plus postoperative CRT or surgery alone. Analyses show robust treatment benefit of adjuvant CRT in most subsets for postoperative CRT. The Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) used a lower RT dose of 41.4 Gray in 23 fractions with newer chemotherapeutic agents carboplatin and paclitaxel to achieve an excellent result. Target volume of external beam radiation therapy and its coverage have been in debate for years among radiation oncologists. Pre-operative and post-operative target volumes are designed to optimize for disease control. Esophageal brachytherapy is effective in the palliation of dysphagia, but should not be given concomitantly with chemotherapy or external beam RT. The role of brachytherapy in multimodality management requires further investigation. On-going studies of multidisciplinary treatment in locally advanced cancer include: ZTOG1201 trial (a phase II trial of neoadjuvant and adjuvant CRT) and QUINTETT (a phase III trial of neoadjuvant vs adjuvant therapy with quality of life analysis). These trials hopefully will shed more light on the future management of esophageal cancer. PMID:25132924

A Randomized Controlled Trial of the Group-Based Modified Story Memory Technique in TBI

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0726 TITLE: A Randomized Controlled Trial of the Group -Based Modified Story Memory Technique in TBI PRINCIPAL...2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Randomized Controlled Trial of the Group -Based Modified Story Memory Technique in TBI 5b. GRANT...forthcoming, The current study addresses this need through a double blind, placebo- controlled , randomized clinical trial (RCT) of a group

Active video games: the mediating effect of aerobic fitness on body composition

PubMed Central

2012-01-01

Background Increased understanding of why and how physical activity impacts on health outcomes is needed to increase the effectiveness of physical activity interventions. A recent randomized controlled trial of an active video game (PlayStation EyeToy™) intervention showed a statistically significant treatment effect on the primary outcome, change from baseline in body mass index (BMI), which favored the intervention group at 24 weeks. In this short paper we evaluate the mediating effects of the secondary outcomes. Objective To identify mediators of the effect of an active video games intervention on body composition. Methods Data from a two-arm parallel randomized controlled trial of an active video game intervention (n = 322) were analyzed. The primary outcome was change from baseline in BMI. A priori secondary outcomes were considered as potential mediators of the intervention on BMI, including aerobic fitness (VO2Max), time spent in moderate-to-vigorous physical activity (MVPA), and food snacking at 24 weeks. Results Only aerobic fitness at 24 weeks met the conditions for mediation, and was a significant mediator of BMI. Conclusion Playing active video games can have a positive effect on body composition in overweight or obese children and this effect is most likely mediated through improved aerobic fitness. Future trials should examine other potential mediators related to this type of intervention. Trial registration Australian New Zealand Clinical Trials Registry Website: http://www.anzctr.org.au Study ID number: ACTRN12607000632493 PMID:22554052

Effectiveness of adjunct psychotherapy for cancer treatment: a review.

PubMed

Chen, YokeYong; Ahmad, Mahadir

2018-05-16

Psychotherapies were offered to alleviate psychological and physical symptoms; however, most psychological interventions were only delivered after cancer treatment. Newly diagnosed cancer patients experienced psychological distress while waiting for treatments. This review paper focused on randomized control trial studies, aimed to investigate the effectiveness of psychological intervention among newly diagnosed cancer patients. Eight randomized control trial papers were found in recent 10 years period through electronic database. A moderate to large effect size was detected on the outcomes, ranging from 0.43 to 0.89. This indicated that psychological-based prehabilitation with standard care yielded better outcomes than standard care alone. Psychological-based prehabilitation provides evidence in its effectiveness to reduce psychological distress, functional impairment, recurrence of cancer, numbers of immune reactivity and sleeping quality; however, inconsistent with longer survival result among cancer patients. In conclusion, psychological-based prehabilitation before cancer treatment is necessary for better treatment outcome, and future research is needed to investigate more directly the outcome.

Use of personalized Dynamic Treatment Regimes (DTRs) and Sequential Multiple Assignment Randomized Trials (SMARTs) in mental health studies

PubMed Central

Liu, Ying; ZENG, Donglin; WANG, Yuanjia

2014-01-01

Summary Dynamic treatment regimens (DTRs) are sequential decision rules tailored at each point where a clinical decision is made based on each patient’s time-varying characteristics and intermediate outcomes observed at earlier points in time. The complexity, patient heterogeneity, and chronicity of mental disorders call for learning optimal DTRs to dynamically adapt treatment to an individual’s response over time. The Sequential Multiple Assignment Randomized Trial (SMARTs) design allows for estimating causal effects of DTRs. Modern statistical tools have been developed to optimize DTRs based on personalized variables and intermediate outcomes using rich data collected from SMARTs; these statistical methods can also be used to recommend tailoring variables for designing future SMART studies. This paper introduces DTRs and SMARTs using two examples in mental health studies, discusses two machine learning methods for estimating optimal DTR from SMARTs data, and demonstrates the performance of the statistical methods using simulated data. PMID:25642116

Ameliorating Patient Stigma Amongst Staff Working With Personality Disorder: Randomized Controlled Trial of Self-Management Versus Skills Training.

PubMed

Clarke, Sue; Taylor, Georgina; Bolderston, Helen; Lancaster, Joanna; Remington, Bob

2015-11-01

Patients diagnosed with a personality disorder (PD) are often stigmatized by the healthcare staff who treat them. This study aimed to compare the impact on front-line staff of a self-management Acceptance and Commitment Therapy-based training intervention (ACTr) with a knowledge- and skills-based Dialectical Behaviour Training intervention (DBTr). A service-based randomized controlled trial was conducted comparing the effects of 2-day ACTr (N = 53) and DBTr (N = 47) staff workshops over 6 months. Primary outcome measures were staff attitudes towards patients and staff-patient relationships. For both interventions, staff attitudes, therapeutic relationship, and social distancing all improved pre- to postintervention, and these changes were maintained at 6-month follow-up. Although offering different resources to staff, both ACTr and DBTr were associated with an improved disposition towards PD patients. Future research could evaluate a combined approach, both for staff working with PD patients and those working with other stigmatized groups.

Future directions in physical activity intervention research: expanding our focus to sedentary behaviors, technology, and dissemination.

PubMed

Lewis, Beth A; Napolitano, Melissa A; Buman, Matthew P; Williams, David M; Nigg, Claudio R

2017-02-01

Despite the increased health risks of a sedentary lifestyle, only 49 % of American adults participate in physical activity (PA) at the recommended levels. In an effort to move the PA field forward, we briefly review three emerging areas of PA intervention research. First, new intervention research has focused on not only increasing PA but also on decreasing sedentary behavior. Researchers should utilize randomized controlled trials, common terminology, investigate which behaviors should replace sedentary behaviors, evaluate long-term outcomes, and focus across the lifespan. Second, technology has contributed to an increase in sedentary behavior but has also led to innovative PA interventions. PA technology research should focus on large randomized trials with evidence-based components, explore social networking and innovative apps, improve PA monitoring, consider the lifespan, and be grounded in theory. Finally, in an effort to maximize public health impact, dissemination efforts should address the RE-AIM model, health disparities, and intervention costs.

A randomized controlled trial of a telehealth parenting intervention: A mixed-disability trial.

PubMed

Hinton, Sharon; Sheffield, Jeanie; Sanders, Matthew R; Sofronoff, Kate

2017-06-01

The quality of parenting a child receives has a major impact on development, wellbeing and future life opportunities. This study examined the efficacy of Triple P Online - Disability (TPOL-D) a telehealth intervention for parents of children with a disability. Ninety-eight parents and carers of children aged 2-12 years diagnosed with a range of developmental, intellectual and physical disabilities were randomly assigned to either the intervention (51) or treatment-as-usual (47) control group. At post-intervention parents receiving the TPOL-D intervention demonstrated significant improvements in parenting practices and parenting self-efficacy, however a significant change in parent-reported child behavioral and emotional problems was not detected. At 3-month follow up intervention gains were maintained and/or enhanced. A significant decrease in parent-reported child behavioral and emotional problems was also detected at this time. The results indicate that TPOL-D is a promising telehealth intervention for a mixed-disability group. Copyright © 2017 Elsevier Ltd. All rights reserved.

Future directions in physical activity intervention research: expanding our focus to sedentary behaviors, technology, and dissemination

PubMed Central

Napolitano, Melissa A.; Buman, Matthew P.; Williams, David M.; Nigg, Claudio R.

2016-01-01

Despite the increased health risks of a sedentary lifestyle, only 49 % of American adults participate in physical activity (PA) at the recommended levels. In an effort to move the PA field forward, we briefly review three emerging areas of PA intervention research. First, new intervention research has focused on not only increasing PA but also on decreasing sedentary behavior. Researchers should utilize randomized controlled trials, common terminology, investigate which behaviors should replace sedentary behaviors, evaluate long-term outcomes, and focus across the lifespan. Second, technology has contributed to an increase in sedentary behavior but has also led to innovative PA interventions. PA technology research should focus on large randomized trials with evidence-based components, explore social networking and innovative apps, improve PA monitoring, consider the lifespan, and be grounded in theory. Finally, in an effort to maximize public health impact, dissemination efforts should address the RE-AIM model, health disparities, and intervention costs. PMID:27722907

Randomized Trials on Consider This, a Tailored, Internet-Delivered Smoking Prevention Program for Adolescents

PubMed Central

Buller, David B.; Borland, Ron; Woodall, W. Gill; Hall, John R.; Hines, Joan M.; Burris-Woodall, Patricia; Cutter, Gary R.; Miller, Caroline; Balmford, James; Starling, Randall; Ax, Bryan; Saba, Laura

2015-01-01

The Internet may be an effective medium for delivering smoking prevention to children. Consider This, an Internet-based program, was hypothesized to reduce expectations concerning smoking and smoking prevalence. Group-randomized pretest-posttest controlled trials were conducted in Australia (n = 2,077) and the United States (n = 1,234) in schools containing Grades 6 through 9. Australian children using Consider This reported reduced 30-day smoking prevalence. This reduction was mediated by decreased subjective norms. The amount of program exposure was low in many classes, but program use displayed a dose-response relationship with reduced smoking prevalence. American children only reported lower expectations for smoking in the future. Intervening to prevent smoking is a challenge, and this data suggest small benefits from an Internet-based program that are unlikely to be of practical significance unless increased by improved implementation. Implementation remains the major challenge to delivering interventions via the Internet, both for health educators and researchers. PMID:17114331

Cerebellar transcranial direct current stimulation in patients with ataxia: A double-blind, randomized, sham-controlled study.

PubMed

Benussi, Alberto; Koch, Giacomo; Cotelli, Maria; Padovani, Alessandro; Borroni, Barbara

2015-10-01

Numerous studies have highlighted the possibility of modulating the excitability of cerebellar circuits using transcranial direct current stimulation. The present study investigated whether a single session of cerebellar anodal transcranial direct current stimulation could improve symptoms in patients with ataxia. Nineteen patients with ataxia underwent a clinical and functional evaluation pre- and post-double-blind, randomized, sham, or anodal transcranial direct current stimulation. There was a significant interaction between treatment and time on the Scale for the Assessment and Rating of Ataxia, on the International Cooperative Ataxia Rating Scale, on the 9-Hole Peg Test, and on the 8-Meter Walking Time (P < 0.001). At the end of the sessions, all performance scores were significantly different in the sham trial, compared to the intervention trial. A single session of anodal cerebellar transcranial direct current stimulation can transiently improve symptoms in patients with ataxia and might represent a promising tool for future rehabilitative approaches. © 2015 International Parkinson and Movement Disorder Society.

Treatment selection in a randomized clinical trial via covariate-specific treatment effect curves.

PubMed

Ma, Yunbei; Zhou, Xiao-Hua

2017-02-01

For time-to-event data in a randomized clinical trial, we proposed two new methods for selecting an optimal treatment for a patient based on the covariate-specific treatment effect curve, which is used to represent the clinical utility of a predictive biomarker. To select an optimal treatment for a patient with a specific biomarker value, we proposed pointwise confidence intervals for each covariate-specific treatment effect curve and the difference between covariate-specific treatment effect curves of two treatments. Furthermore, to select an optimal treatment for a future biomarker-defined subpopulation of patients, we proposed confidence bands for each covariate-specific treatment effect curve and the difference between each pair of covariate-specific treatment effect curve over a fixed interval of biomarker values. We constructed the confidence bands based on a resampling technique. We also conducted simulation studies to evaluate finite-sample properties of the proposed estimation methods. Finally, we illustrated the application of the proposed method in a real-world data set.

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

PubMed

Koley, Munmun; Saha, Subhranil; Ghosh, Shubhamoy

2015-07-01

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

Using the Internet to promote physical activity: a randomized trial of intervention delivery modes.

PubMed

Steele, Rebekah; Mummery, W Kerry; Dwyer, Trudy

2007-07-01

A growing number of the population are using the Internet for health information, such as physical activity (PA). The aim of this study was to examine the effectiveness of delivery modes for a behavior change program targeting PA. A randomized trial was conducted with 192 subjects randomly allocated to either a face-to-face, Internet-mediated, or Internet-only arm of a 12-wk intervention. Subjects included inactive adults with Internet access. The primary outcome variable was self-reported PA, assessed at four time points. The results showed no group x time interaction for PA F(6, 567) = 1.64, p > 0.05, and no main effect for group F(2, 189) = 1.58, p > 0.05. However, a main effect for time F(3, 567) = 75.7, p < 0.01 was observed for each group. All groups were statistically equivalent immediately post-intervention (p < 0.05), but not at the follow-up time points (p > 0.05). The Internet-mediated and Internet-only groups showed similar increases in PA to the face-to-face group immediately post-intervention. This study provides evidence in support of the Internet in the delivery of PA interventions and highlights avenues for future research.

Supporting Adolescent Orphan Girls to Stay in School as HIV Risk Prevention: Evidence From a Randomized Controlled Trial in Zimbabwe

PubMed Central

Cho, Hyunsan; Rusakaniko, Simbarashe; Iritani, Bonita; Mapfumo, John; Halpern, Carolyn

2011-01-01

Objectives. Using a randomized controlled trial in rural eastern Zimbabwe, we tested whether comprehensive support to keep orphan adolescent girls in school could reduce HIV risk. Methods. All orphan girls in grade 6 in 25 primary schools were invited to participate in the study in fall 2007 (n = 329). Primary schools were randomized to condition. All primary schools received a universal daily feeding program; intervention participants received fees, uniforms, and a school-based helper to monitor attendance and resolve problems. We conducted annual surveys and collected additional information on school dropout, marriage, and pregnancy rates. We analyzed data using generalized estimating equations over 3 time points, controlling for school and age at baseline. Results. The intervention reduced school dropout by 82% and marriage by 63% after 2 years. Compared with control participants, the intervention group reported greater school bonding, better future expectations, more equitable gender attitudes, and more concerns about the consequences of sex. Conclusions. We found promising evidence that comprehensive school support may reduce HIV risk for orphan girls. Further study, including assessment of dose response, cost benefit, and HIV and herpes simplex virus 2 biomarker measurement, is warranted. PMID:21493943

Heterogeneous Suppression of Sequential Effects in Random Sequence Generation, but Not in Operant Learning.

PubMed

Shteingart, Hanan; Loewenstein, Yonatan

2016-01-01

There is a long history of experiments in which participants are instructed to generate a long sequence of binary random numbers. The scope of this line of research has shifted over the years from identifying the basic psychological principles and/or the heuristics that lead to deviations from randomness, to one of predicting future choices. In this paper, we used generalized linear regression and the framework of Reinforcement Learning in order to address both points. In particular, we used logistic regression analysis in order to characterize the temporal sequence of participants' choices. Surprisingly, a population analysis indicated that the contribution of the most recent trial has only a weak effect on behavior, compared to more preceding trials, a result that seems irreconcilable with standard sequential effects that decay monotonously with the delay. However, when considering each participant separately, we found that the magnitudes of the sequential effect are a monotonous decreasing function of the delay, yet these individual sequential effects are largely averaged out in a population analysis because of heterogeneity. The substantial behavioral heterogeneity in this task is further demonstrated quantitatively by considering the predictive power of the model. We show that a heterogeneous model of sequential dependencies captures the structure available in random sequence generation. Finally, we show that the results of the logistic regression analysis can be interpreted in the framework of reinforcement learning, allowing us to compare the sequential effects in the random sequence generation task to those in an operant learning task. We show that in contrast to the random sequence generation task, sequential effects in operant learning are far more homogenous across the population. These results suggest that in the random sequence generation task, different participants adopt different cognitive strategies to suppress sequential dependencies when generating the "random" sequences.

SMART DOCS: A New Patient-Centered Outcomes and Coordinated-Care Management Approach for the Future Practice of Sleep Medicine

PubMed Central

Kushida, Clete A.; Nichols, Deborah A.; Holmes, Tyson H.; Miller, Ric; Griffin, Kara; Cardell, Chia-Yu; Hyde, Pamela R.; Cohen, Elyse; Manber, Rachel; Walsh, James K.

2015-01-01

The practice of medicine is currently undergoing a transformation to become more efficient, cost-effective, and patient centered in its delivery of care. The aim of this article is to stimulate discussion within the sleep medicine community in addressing these needs by our approach as well as other approaches to sleep medicine care. The primary goals of the Sustainable Methods, Algorithms, and Research Tools for Delivering Optimal Care Study (SMART DOCS) are: (1) to introduce a new Patient-Centered Outcomes and Coordinated-Care Management (PCCM) approach for the future practice of sleep medicine, and (2) to test the PCCM approach against a Conventional Diagnostic and Treatment Outpatient Medical Care (CONV) approach in a randomized, two-arm, single-center, long-term, comparative effectiveness trial. The PCCM approach is integrated into a novel outpatient care delivery model for patients with sleep disorders that includes the latest technology, allowing providers to obtain more accurate and rapid diagnoses and to make evidence-based treatment recommendations, while simultaneously enabling patients to have access to personalized medical information and reports regarding their diagnosis and treatment so that they can make more informed health care decisions. Additionally, the PCCM approach facilitates better communication between patients, referring primary care physicians, sleep specialists, and allied health professionals so that providers can better assist patients in achieving their preferred outcomes. A total of 1,506 patients 18 y or older will be randomized to either the PCCM or CONV approach and will be followed for at least 1 y with endpoints of improved health care performance, better health, and cost control. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT02037438. Citation: Kushida CA, Nichols DA, Holmes TH, Miller R, Griffin K, Cardell CY, Hyde PR, Cohen E, Manber R, Walsh JK. SMART DOCS: a new patient-centered outcomes and coordinated-care management approach for the future practice of sleep medicine. SLEEP 2015;38(2):315–326. PMID:25409112

Hierarchy of evidence: differences in results between non-randomized studies and randomized trials in patients with femoral neck fractures.

PubMed

Bhandari, Mohit; Tornetta, Paul; Ellis, Thomas; Audige, Laurent; Sprague, Sheila; Kuo, Jonathann C; Swiontkowski, Marc F

2004-01-01

There have been a number of non-randomized studies comparing arthroplasty with internal fixation in patients with femoral neck fractures. However, there remains considerable debate about whether the results of non-randomized studies are consistent with the results of randomized, controlled trials. Given the economic burden of hip fractures, it remains essential to identify therapies to improve outcomes; however, whether data from non-randomized studies of an intervention should be used to guide patient care remains unclear. We aimed to determine whether the pooled results of mortality and revision surgery among non-randomized studies were similar to those of randomized trials in studies comparing arthroplasty with internal fixation in patients with femoral neck fractures. We conducted a Medline search from 1969 to June 2002, identifying both randomized and non-randomized studies comparing internal fixation with arthroplasty in patients with femoral neck fractures. Additional strategies to identify relevant articles included Cochrane database, SCISEARCH, textbooks, annual meeting programs, and content experts. We abstracted information on mortality and revision rates in each study and compared the pooled results between non-randomized and randomized studies. In addition, we explored potential reasons for dissimilar results between the two study designs. We identified 140 citations that addressed the general topic of comparison of arthroplasty and internal fixation for hip fracture. Of these, 27 studies met the eligibility criteria, 13 of which were non-randomized studies and 14 of which were randomized trials. Mortality data was available in all 13 non-randomized studies ( n=3108 patients) and in 12 randomized studies ( n=1767 patients). Non-randomized studies overestimated the risk of mortality by 40% when compared with the results of randomized trials (relative risk 1.44 vs 1.04, respectively). Information on revision risk was available in 9 non-randomized studies ( n=2764 patients) and all 14 randomized studies ( n=1901 patients). Both estimates from non-randomized and randomized studies revealed a significant reduction in the risk of revision surgery with arthroplasty compared with internal fixation (relative risk 0.38 vs 0.23, respectively). The reduction in the risk of revision surgery with arthroplasty compared with internal fixation was 62% for non-randomized studies and 77% for randomized trials. Thus, non-randomized studies underestimated the relative benefit of arthroplasty by 19.5%. Non-randomized studies with point estimates of relative risk similar to the pooled estimate for randomized trials all controlled for patient age, gender, and fracture displacement in their comparisons of mortality. We were unable to identify reasons for differences in the revision rate results between the study designs. Similar to other reports in medical subspecialties, non-randomized studies provided results dissimilar to randomized trials of arthroplasty vs internal fixation for mortality and revision rates in patients with femoral neck fractures. Investigators should be aware of these discrepancies when evaluating the merits of alternative surgical interventions, especially when both randomized trials and non-randomized comparative studies are available.

Methodological reporting of randomized controlled trials in major hepato-gastroenterology journals in 2008 and 1998: a comparative study

PubMed Central

2011-01-01

Background It was still unclear whether the methodological reporting quality of randomized controlled trials (RCTs) in major hepato-gastroenterology journals improved after the Consolidated Standards of Reporting Trials (CONSORT) Statement was revised in 2001. Methods RCTs in five major hepato-gastroenterology journals published in 1998 or 2008 were retrieved from MEDLINE using a high sensitivity search method and their reporting quality of methodological details were evaluated based on the CONSORT Statement and Cochrane Handbook for Systematic Reviews of interventions. Changes of the methodological reporting quality between 2008 and 1998 were calculated by risk ratios with 95% confidence intervals. Results A total of 107 RCTs published in 2008 and 99 RCTs published in 1998 were found. Compared to those in 1998, the proportion of RCTs that reported sequence generation (RR, 5.70; 95%CI 3.11-10.42), allocation concealment (RR, 4.08; 95%CI 2.25-7.39), sample size calculation (RR, 3.83; 95%CI 2.10-6.98), incomplete outecome data addressed (RR, 1.81; 95%CI, 1.03-3.17), intention-to-treat analyses (RR, 3.04; 95%CI 1.72-5.39) increased in 2008. Blinding and intent-to-treat analysis were reported better in multi-center trials than in single-center trials. The reporting of allocation concealment and blinding were better in industry-sponsored trials than in public-funded trials. Compared with historical studies, the methodological reporting quality improved with time. Conclusion Although the reporting of several important methodological aspects improved in 2008 compared with those published in 1998, which may indicate the researchers had increased awareness of and compliance with the revised CONSORT statement, some items were still reported badly. There is much room for future improvement. PMID:21801429

Gender research in the National Institute on Drug Abuse National Treatment Clinical Trials Network: a summary of findings.

PubMed

Greenfield, Shelly F; Rosa, Carmen; Putnins, Susan I; Green, Carla A; Brooks, Audrey J; Calsyn, Donald A; Cohen, Lisa R; Erickson, Sarah; Gordon, Susan M; Haynes, Louise; Killeen, Therese; Miele, Gloria; Tross, Susan; Winhusen, Theresa

2011-09-01

The National Institute of Drug Abuse's National Drug Abuse Treatment Clinical Trials Network (CTN) was established to foster translation of research into practice in substance abuse treatment settings. The CTN provides a unique opportunity to examine in multi-site, translational clinical trials, the outcomes of treatment interventions targeting vulnerable subgroups of women; the comparative effectiveness of gender-specific protocols to reduce risk behaviors; and gender differences in clinical outcomes. To review gender-related findings from published CTN clinical trials and related studies from January 2000 to March 2010. CTN studies were selected for review if they focused on treatment outcomes or services for special populations of women with substance use disorders (SUDs) including those with trauma histories, pregnancy, co-occurring eating and other psychiatric disorders, and HIV risk behaviors; or implemented gender-specific protocols. The CTN has randomized 11,500 participants (41% women) across 200 clinics in 24 randomized controlled trials in community settings, of which 4 have been gender-specific. This article summarizes gender-related findings from CTN clinical trials and related studies, focusing on trauma histories, pregnancy, co-occurring eating and other psychiatric disorders, and HIV risk behaviors. These published studies have expanded the evidence base regarding interventions for vulnerable groups of women with SUDs as well as gender-specific interventions to reduce HIV risk behaviors in substance-using men and women. The results also underscore the complexity of accounting for gender in the design of clinical trials and analysis of results. To fully understand the relevance of gender-specific moderators and mediators of outcome, it is essential that future translational studies adopt more sophisticated approaches to understanding and measuring gender-relevant factors and plan sample sizes that are adequate to support more nuanced analytic methods.

Patient-centered clinical trials.

PubMed

Chaudhuri, Shomesh E; Ho, Martin P; Irony, Telba; Sheldon, Murray; Lo, Andrew W

2018-02-01

We apply Bayesian decision analysis (BDA) to incorporate patient preferences in the regulatory approval process for new therapies. By assigning weights to type I and type II errors based on patient preferences, the significance level (α) and power (1-β) of a randomized clinical trial (RCT) for a new therapy can be optimized to maximize the value to current and future patients and, consequently, to public health. We find that for weight-loss devices, potentially effective low-risk treatments have optimal αs larger than the traditional one-sided significance level of 5%, whereas potentially less effective and riskier treatments have optimal αs below 5%. Moreover, the optimal RCT design, including trial size, varies with the risk aversion and time-to-access preferences and the medical need of the target population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Primary angioplasty: the past, the present and the future.

PubMed

Oomman, A; Ramachandran, P

2001-09-01

Primary angioplasty (PTCA) in acute myocardial infarction has many theoretical advantages including better antegrade flow and reduced intracranial haemorrhage. However the improvement in the mortality and morbidity of primary angioplasty in the randomized trials from sophisticated centres has not been translated to the community setting. Primary PTCA is a suitable alternative to thrombolytic therapy if performed in a timely fashion by persons skilled in the procedure in a suitable laboratory. It is also recommended in patients with cardiogenic shock and in those with contraindications to thrombolytic therapy. Combination of thrombolytics and glycoprotein IIb/IIIa inhibitors with primary angioplasty may form the reperfusion strategy of the future.

Randomized clinical trials and observational studies in the assessment of drug safety.

PubMed

Sawchik, J; Hamdani, J; Vanhaeverbeek, M

2018-05-01

Randomized clinical trials are considered as the preferred design to assess the potential causal relationships between drugs or other medical interventions and intended effects. For this reason, randomized clinical trials are generally the basis of development programs in the life cycle of drugs and the cornerstone of evidence-based medicine. Instead, randomized clinical trials are not the design of choice for the detection and assessment of rare, delayed and/or unexpected effects related to drug safety. Moreover, the highly homogeneous populations resulting from restrictive eligibility criteria make randomized clinical trials inappropriate to describe comprehensively the safety profile of drugs. In that context, observational studies have a key added value when evaluating the benefit-risk balance of the drugs. However, observational studies are more prone to bias than randomized clinical trials and they have to be designed, conducted and reported judiciously. In this article, we discuss the strengths and limitations of randomized clinical trials and of observational studies, more particularly regarding their contribution to the knowledge of medicines' safety profile. In addition, we present general recommendations for the sensible use of observational data. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Consolidative autologous hematopoietic stem-cell transplantation in first remission for non-Hodgkin lymphoma: current indications and future perspective.

PubMed

Iams, Wade; Reddy, Nishitha M

2014-10-01

The non-Hodgkin lymphomas (NHLs) are a heterogeneous group of diseases with variable clinical outcomes. Autologous hematopoietic stem-cell transplantation (ASCT) as frontline, consolidative therapy has been evaluated based upon histological subtype of NHL. In this review, we summarize the major clinical trials guiding the use of frontline ASCT in NHL. With the constantly changing landscape of upfront therapy and multiple promising novel agents, the ability to conduct randomized trials to evaluate the benefit of consolidative ASCT is not only challenging but may be considered by some an inept utilization of resources. Our recommendation for consolidative ASCT is based on analyzing the current available data.

Intention-to-treat analysis and accounting for missing data in orthopaedic randomized clinical trials.

PubMed

Herman, Amir; Botser, Itamar Busheri; Tenenbaum, Shay; Chechick, Ahron

2009-09-01

The intention-to-treat principle implies that all patients who are randomized in a clinical trial should be analyzed according to their original allocation. This means that patients crossing over to another treatment group and patients lost to follow-up should be included in the analysis as a part of their original group. This principle is important for preserving the randomization scheme, which is the basis for correct inference in any randomized trial. In this study, we examined the use of the intention-to-treat principle in recently published orthopaedic clinical trials. We surveyed eight leading orthopaedic journals for randomized clinical trials published between January 2005 and August 2008. We determined whether the intention-to-treat principle was implemented and, if so, how it was used in each trial. Specifically, we ascertained which methods were used to account for missing data. Our search yielded 274 randomized clinical trials, and the intention-to-treat principle was used in ninety-six (35%) of them. There were significant differences among the journals with regard to the use of the intention-to-treat principle. The relative number of trials in which the principle was used increased each year. The authors adhered to the strict definition of the intention-to-treat principle in forty-five of the ninety-six studies in which it was claimed that this principle had been used. In forty-four randomized trials, patients who had been lost to follow-up were excluded from the final analysis; this practice was most notable in studies of surgical interventions. The most popular method of adjusting for missing data was the "last observation carried forward" technique. In most of the randomized clinical trials published in the orthopaedic literature, the investigators did not adhere to the stringent use of the intention-to-treat principle, with the most conspicuous problem being a lack of accounting for patients lost to follow-up. This omission might introduce bias to orthopaedic randomized clinical trials and their analysis.

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

PubMed

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

2011-12-05

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

Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all.

PubMed

Papageorgiou, Spyridon N; Antonoglou, Georgios N; Sándor, George K; Eliades, Theodore

2017-01-01

A priori registration of randomized clinical trials is crucial to the transparency and credibility of their findings. Aim of this study was to assess the frequency with which registered and completed randomized trials in orthodontics are published. We searched ClinicalTrials.gov and ISRCTN for registered randomized clinical trials in orthodontics that had been completed up to January 2017 and judged the publication status and date of registered trials using a systematic protocol. Statistical analysis included descriptive statistics, chi-square or Fisher exact tests, and Kaplan-Meier survival estimates. From the 266 orthodontic trials registered up to January 2017, 80 trials had been completed and included in the present study. Among these 80 included trials, the majority (76%) were registered retrospectively, while only 33 (41%) were published at the time. The median time from completion to publication was 20.1 months (interquartile range: 9.1 to 31.6 months), while survival analysis indicated that less than 10% of the trials were published after 5 years from their completion. Finally, 22 (28%) of completed trials remain unpublished even after 5 years from their completion. Publication rates of registered randomized trials in orthodontics remained low, even 5 years after their completion date.

Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all

PubMed Central

Antonoglou, Georgios N.; Sándor, George K.; Eliades, Theodore

2017-01-01

A priori registration of randomized clinical trials is crucial to the transparency and credibility of their findings. Aim of this study was to assess the frequency with which registered and completed randomized trials in orthodontics are published. We searched ClinicalTrials.gov and ISRCTN for registered randomized clinical trials in orthodontics that had been completed up to January 2017 and judged the publication status and date of registered trials using a systematic protocol. Statistical analysis included descriptive statistics, chi-square or Fisher exact tests, and Kaplan-Meier survival estimates. From the 266 orthodontic trials registered up to January 2017, 80 trials had been completed and included in the present study. Among these 80 included trials, the majority (76%) were registered retrospectively, while only 33 (41%) were published at the time. The median time from completion to publication was 20.1 months (interquartile range: 9.1 to 31.6 months), while survival analysis indicated that less than 10% of the trials were published after 5 years from their completion. Finally, 22 (28%) of completed trials remain unpublished even after 5 years from their completion. Publication rates of registered randomized trials in orthodontics remained low, even 5 years after their completion date. PMID:28777820

Effect of a mobile phone intervention on quitting smoking in a young adult population of smokers: randomized controlled trial study protocol.

PubMed

Baskerville, Neill Bruce; Struik, Laura Louise; Hammond, David; Guindon, G Emmanuel; Norman, Cameron D; Whittaker, Robyn; Burns, Catherine M; Grindrod, Kelly A; Brown, K Stephen

2015-01-19

Tobacco use remains the number one cause of preventable chronic disease and death in developed countries worldwide. In North America, smoking rates are highest among young adults. Despite that the majority of young adult smokers indicate wanting to quit, smoking rates among this age demographic have yet to decline. Helping young adults quit smoking continues to be a public health priority. Digital mobile technology presents a promising medium for reaching this population with smoking cessation interventions, especially because young adults are the heaviest users of this technology. The primary aim of this trial is to determine the effectiveness of an evidence-informed mobile phone app for smoking cessation, Crush the Crave, on reducing smoking prevalence among young adult smokers. A parallel randomized controlled trial (RCT) with two arms will be conducted in Canada to evaluate Crush the Crave. In total, 1354 young adult smokers (19 to 29 years old) will be randomized to receive the evidence-informed mobile phone app, Crush the Crave, or an evidence-based self-help guide known as "On the Road to Quitting" (control) for a period of 6 months. The primary outcome measure is a 30-day point prevalence of abstinence at the 6-month follow-up. Secondary outcomes include a 7-day point prevalence of abstinence, number of quit attempts, reduction in consumption of cigarettes, self-efficacy, satisfaction, app utilization metrics, and use of smoking cessation services. A cost-effectiveness analysis is included. This trial is currently open for recruitment. The anticipated completion date for the study is April 2016. This randomized controlled trial will provide the evidence to move forward on decision making regarding the inclusion of technology-based mobile phone interventions as part of existing smoking cessation efforts made by health care providers. Evidence from the trial will also inform the development of future apps, provide a deeper understanding of the factors that drive change in smoking behavior using an app, and improve the design of cessation apps. This trial is among the first to assess the effect of a comprehensive and evidence-informed mHealth smoking cessation app on a large sample of young adult smokers. Strengths of the trial include the high-quality research design and in-depth assessment of the implementation of the intervention. If effective, the trial has the potential to demonstrate that including mHealth technology as a population-based intervention strategy can cost-effectively reach a greater proportion of the population and help young adult smokers to quit. ClinicalTrials.gov NCT01983150; http://clinicaltrials.gov/ct2/show/NCT01983150 (Archived by WebCite at http://www.webcitation.org/6VGyc0W0i).

Mindful Yoga for women with metastatic breast cancer: design of a randomized controlled trial.

PubMed

Carson, James W; Carson, Kimberly M; Olsen, Maren K; Sanders, Linda; Porter, Laura S

2017-03-13

Women with metastatic breast cancer (MBC) have average life expectancies of about 2 years, and report high levels of disease-related symptoms including pain, fatigue, sleep disturbance, psychological distress, and functional impairment. There is growing recognition of the limitations of medical approaches to managing such symptoms. Yoga is a mind-body discipline that has demonstrated a positive impact on psychological and functional health in early stage breast cancer patients and survivors, but has not been rigorously studied in advanced cancer samples. This randomized controlled trial examines the feasibility and initial efficacy of a Mindful Yoga program, compared with a social support condition that controls for attention, on measures of disease-related symptoms such as pain and fatigue. The study will be completed by December 2017. Sixty-five women with MBC age ≥ 18 are being identified and randomized with a 2:1 allocation to Mindful Yoga or a support group control intervention. The 120-min intervention sessions take place weekly for 8 weeks. The study is conducted at an urban tertiary care academic medical center located in Durham, North Carolina. The primary feasibility outcome is attendance at intervention sessions. Efficacy outcomes include pain, fatigue, sleep quality, psychological distress, mindfulness and functional capacity at post-intervention, 3-month follow-up, and 6-month follow-up. In this article, we present the challenges of designing a randomized controlled trial with long-term follow-up among women with MBC. These challenges include ensuring adequate recruitment including of minorities, limiting and controlling for selection bias, tailoring of the yoga intervention to address special needs, and maximizing adherence and retention. This project will provide important information regarding yoga as an intervention for women with advanced cancer, including preliminary data on the psychological and functional effects of yoga for MBC patients. This investigation will also establish rigorous methods for future research into yoga as an intervention for this population. ClinicalTrials.gov identifer: NCT01927081 , registered August 16, 2013.

Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial.

PubMed

Zhong, Linda L D; Cheng, Chung Wah; Chan, Yawen; Chan, King Hong; Lam, Ting Wa; Chen, Xiao Rui; Wong, Chi Tak; Wu, Justin C Y; Bian, Zhao Xiang

2013-11-04

Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine interventions in the future. NCT01695850.

Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials.

PubMed

Berry-Kravis, Elizabeth; Des Portes, Vincent; Hagerman, Randi; Jacquemont, Sébastien; Charles, Perrine; Visootsak, Jeannie; Brinkman, Marc; Rerat, Karin; Koumaras, Barbara; Zhu, Liansheng; Barth, Gottfried Maria; Jaecklin, Thomas; Apostol, George; von Raison, Florian

2016-01-13

Fragile X syndrome (FXS), the most common cause of inherited intellectual disability and autistic spectrum disorder, is typically caused by transcriptional silencing of the X-linked FMR1 gene. Work in animal models has described altered synaptic plasticity, a result of the up-regulation of metabotropic glutamate receptor 5 (mGluR5)-mediated signaling, as a putative downstream effect. Post hoc analysis of a randomized, placebo-controlled, crossover phase 2 trial suggested that the selective mGluR5 antagonist mavoglurant improved behavioral symptoms in FXS patients with completely methylated FMR1 genes. We present the results of two phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of mavoglurant in FXS, designed to confirm this result in adults (n = 175, aged 18 to 45 years) and adolescents (n = 139, aged 12 to 17 years). In both trials, participants were stratified by methylation status and randomized to receive mavoglurant (25, 50, or 100 mg twice daily) or placebo over 12 weeks. Neither of the studies achieved the primary efficacy end point of improvement on behavioral symptoms measured by the Aberrant Behavior Checklist-Community Edition using the FXS-specific algorithm (ABC-C(FX)) after 12 weeks of treatment with mavoglurant. The safety and tolerability profile of mavoglurant was as previously described, with few adverse events. Therefore, under the conditions of our study, we could not confirm the mGluR theory of FXS nor the ability of the methylation state of the FMR1 promoter to predict mavoglurant efficacy. Preclinical results suggest that future clinical trials might profitably explore initiating treatment in a younger population with longer treatment duration and longer placebo run-ins and identifying new markers to better assess behavioral and cognitive benefits. Copyright © 2016, American Association for the Advancement of Science.

Large multi-centre pilot randomized controlled trial testing a low-cost, tailored, self-help smoking cessation text message intervention for pregnant smokers (MiQuit).

PubMed

Naughton, Felix; Cooper, Sue; Foster, Katharine; Emery, Joanne; Leonardi-Bee, Jo; Sutton, Stephen; Jones, Matthew; Ussher, Michael; Whitemore, Rachel; Leighton, Matthew; Montgomery, Alan; Parrott, Steve; Coleman, Tim

2017-07-01

To estimate the effectiveness of pregnancy smoking cessation support delivered by short message service (SMS) text message and key parameters needed to plan a definitive trial. Multi-centre, parallel-group, single-blinded, individual randomized controlled trial. Sixteen antenatal clinics in England. Four hundred and seven participants were randomized to the intervention (n = 203) or usual care (n = 204). Eligible women were < 25 weeks gestation, smoked at least one daily cigarette (> 5 pre-pregnancy), were able to receive and understand English SMS texts and were not already using text-based cessation support. All participants received a smoking cessation leaflet; intervention participants also received a 12-week programme of individually tailored, automated, interactive, self-help smoking cessation text messages (MiQuit). Seven smoking outcomes, including validated continuous abstinence from 4 weeks post-randomization until 36 weeks gestation, design parameters for a future trial and cost-per-quitter. Using the validated, continuous abstinence outcome, 5.4% (11 of 203) of MiQuit participants were abstinent versus 2.0% (four of 204) of usual care participants [odds ratio (OR) = 2.7, 95% confidence interval (CI) = 0.93-9.35]. The Bayes factor for this outcome was 2.23. Completeness of follow-up at 36 weeks gestation was similar in both groups; provision of self-report smoking data was 64% (MiQuit) and 65% (usual care) and abstinence validation rates were 56% (MiQuit) and 61% (usual care). The incremental cost-per-quitter was £133.53 (95% CI = -£395.78 to 843.62). There was some evidence, although not conclusive, that a text-messaging programme may increase cessation rates in pregnant smokers when provided alongside routine NHS cessation care. © 2017 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Lung Function in Rural Guatemalan Women Before and After a Chimney Stove Intervention to Reduce Wood Smoke Exposure: Results From the Randomized Exposure Study of Pollution Indoors and Respiratory Effects and Chronic Respiratory Effects of Early Childhood Exposure to Respirable Particulate Matter Study.

PubMed

Guarnieri, Michael; Diaz, Esperanza; Pope, Daniel; Eisen, Ellen A; Mann, Jennifer; Smith, Kirk R; Smith-Sivertsen, Tone; Bruce, Nigel G; Balmes, John R

2015-11-01

COPD is the third most frequent cause of death globally, with much of this burden attributable to household biomass smoke exposure in developing countries. As biomass smoke exposure is also associated with cardiovascular disease, lower respiratory infection, lung cancer, and cataracts, it presents an important target for public health intervention. Lung function in Guatemalan women exposed to wood smoke from open fires was measured throughout the Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) stove intervention trial and continued during the Chronic Respiratory Effects of Early Childhood Exposure to Respirable Particulate Matter (CRECER) cohort study. In RESPIRE, early stove households received a chimney woodstove at the beginning of the 18-month trial, and delayed stove households received a stove at trial completion. Personal exposure to wood smoke was assessed with exhaled breath carbon monoxide (CO) and personal CO tubes. Change in lung function between intervention groups and as a function of wood smoke exposure was assessed using random effects models. Of 306 women participating in both studies, acceptable spirometry was collected in 129 early stove and 136 delayed stove households (n = 265), with a mean follow-up of 5.6 years. Despite reduced wood smoke exposures in early stove households, there were no significant differences in any of the measured spirometric variables during the study period (FEV1, FVC, FEV1/FVC ratio, and annual change) after adjustment for confounding. In these young Guatemalan women, there was no association between lung function and early randomization to a chimney stove or personal wood smoke exposure. Future stove intervention trials should incorporate cleaner stoves, longer follow-up, or potentially susceptible groups to identify meaningful differences in lung function.

Randomized clinical trials in dentistry: Risks of bias, risks of random errors, reporting quality, and methodologic quality over the years 1955–2013

PubMed Central

Armijo-Olivo, Susan; Cummings, Greta G.; Amin, Maryam; Flores-Mir, Carlos

2017-01-01

Objectives To examine the risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions and the development of these aspects over time. Methods We included 540 randomized clinical trials from 64 selected systematic reviews. We extracted, in duplicate, details from each of the selected randomized clinical trials with respect to publication and trial characteristics, reporting and methodologic characteristics, and Cochrane risk of bias domains. We analyzed data using logistic regression and Chi-square statistics. Results Sequence generation was assessed to be inadequate (at unclear or high risk of bias) in 68% (n = 367) of the trials, while allocation concealment was inadequate in the majority of trials (n = 464; 85.9%). Blinding of participants and blinding of the outcome assessment were judged to be inadequate in 28.5% (n = 154) and 40.5% (n = 219) of the trials, respectively. A sample size calculation before the initiation of the study was not performed/reported in 79.1% (n = 427) of the trials, while the sample size was assessed as adequate in only 17.6% (n = 95) of the trials. Two thirds of the trials were not described as double blinded (n = 358; 66.3%), while the method of blinding was appropriate in 53% (n = 286) of the trials. We identified a significant decrease over time (1955–2013) in the proportion of trials assessed as having inadequately addressed methodological quality items (P < 0.05) in 30 out of the 40 quality criteria, or as being inadequate (at high or unclear risk of bias) in five domains of the Cochrane risk of bias tool: sequence generation, allocation concealment, incomplete outcome data, other sources of bias, and overall risk of bias. Conclusions The risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions have improved over time; however, further efforts that contribute to the development of more stringent methodology and detailed reporting of trials are still needed. PMID:29272315

Randomized clinical trials in dentistry: Risks of bias, risks of random errors, reporting quality, and methodologic quality over the years 1955-2013.

PubMed

Saltaji, Humam; Armijo-Olivo, Susan; Cummings, Greta G; Amin, Maryam; Flores-Mir, Carlos

2017-01-01

To examine the risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions and the development of these aspects over time. We included 540 randomized clinical trials from 64 selected systematic reviews. We extracted, in duplicate, details from each of the selected randomized clinical trials with respect to publication and trial characteristics, reporting and methodologic characteristics, and Cochrane risk of bias domains. We analyzed data using logistic regression and Chi-square statistics. Sequence generation was assessed to be inadequate (at unclear or high risk of bias) in 68% (n = 367) of the trials, while allocation concealment was inadequate in the majority of trials (n = 464; 85.9%). Blinding of participants and blinding of the outcome assessment were judged to be inadequate in 28.5% (n = 154) and 40.5% (n = 219) of the trials, respectively. A sample size calculation before the initiation of the study was not performed/reported in 79.1% (n = 427) of the trials, while the sample size was assessed as adequate in only 17.6% (n = 95) of the trials. Two thirds of the trials were not described as double blinded (n = 358; 66.3%), while the method of blinding was appropriate in 53% (n = 286) of the trials. We identified a significant decrease over time (1955-2013) in the proportion of trials assessed as having inadequately addressed methodological quality items (P < 0.05) in 30 out of the 40 quality criteria, or as being inadequate (at high or unclear risk of bias) in five domains of the Cochrane risk of bias tool: sequence generation, allocation concealment, incomplete outcome data, other sources of bias, and overall risk of bias. The risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions have improved over time; however, further efforts that contribute to the development of more stringent methodology and detailed reporting of trials are still needed.

Impact of Vitamin D Replacement on Markers of Glucose Metabolism and Cardio-Metabolic Risk in Women with Former Gestational Diabetes--A Double-Blind, Randomized Controlled Trial.

PubMed

Yeow, Toh Peng; Lim, Shueh Lin; Hor, Chee Peng; Khir, Amir S; Wan Mohamud, Wan Nazaimoon; Pacini, Giovanni

2015-01-01

Gestational Diabetes Mellitus (GDM) and vitamin D deficiency are related to insulin resistance and impaired beta cell function, with heightened risk for future development of diabetes. We evaluated the impact of vitamin D supplementation on markers of glucose metabolism and cardio metabolic risk in Asian women with former GDM and hypovitaminosis D. In this double blind, randomized controlled trial, 26 participants were randomized to receive either daily 4000 IU vitamin D3 or placebo capsules. 75 g Oral Glucose Tolerance Test (OGTT) and biochemistry profiles were performed at baseline and 6 month visits. Mathematical models, using serial glucose, insulin and C peptide measurements from OGTT, were employed to calculate insulin sensitivity and beta cell function. Thirty three (76%) women with former GDM screened had vitamin D level of <50 nmol/L at baseline. Supplementation, when compared with placebo, resulted in increased vitamin D level (+51.1 nmol/L vs 0.2 nmol/L, p<0.001) and increased fasting insulin (+20% vs 18%, p = 0.034). The vitamin D group also demonstrated a 30% improvement in disposition index and an absolute 0.2% (2 mmol/mol) reduction in HbA1c. There was no clear change in insulin sensitivity or markers of cardio metabolic risk. This study highlighted high prevalence of vitamin D deficiency among Asian women with former GDM. Six months supplementation with 4000 IU of vitamin D3 safely restored the vitamin D level, improved basal pancreatic beta-cell function and ameliorated the metabolic state. There was no effect on markers of cardio metabolic risk. Further mechanistic studies exploring the role of vitamin D supplementation on glucose homeostasis among different ethnicities may be needed to better inform future recommendations for these women with former GDM at high risk of both hypovitaminosis D and future diabetes.

Active video games: the mediating effect of aerobic fitness on body composition.

PubMed

Maddison, Ralph; Mhurchu, Cliona Ni; Jull, Andrew; Prapavessis, Harry; Foley, Louise S; Jiang, Yannan

2012-05-03

Increased understanding of why and how physical activity impacts on health outcomes is needed to increase the effectiveness of physical activity interventions. A recent randomized controlled trial of an active video game (PlayStation EyeToy™) intervention showed a statistically significant treatment effect on the primary outcome, change from baseline in body mass index (BMI), which favored the intervention group at 24 weeks. In this short paper we evaluate the mediating effects of the secondary outcomes. To identify mediators of the effect of an active video games intervention on body composition. Data from a two-arm parallel randomized controlled trial of an active video game intervention (n = 322) were analyzed. The primary outcome was change from baseline in BMI. A priori secondary outcomes were considered as potential mediators of the intervention on BMI, including aerobic fitness (VO2Max), time spent in moderate-to-vigorous physical activity (MVPA), and food snacking at 24 weeks. Only aerobic fitness at 24 weeks met the conditions for mediation, and was a significant mediator of BMI. Playing active video games can have a positive effect on body composition in overweight or obese children and this effect is most likely mediated through improved aerobic fitness. Future trials should examine other potential mediators related to this type of intervention. Australian New Zealand Clinical Trials Registry Website: http://www.anzctr.org.au. Study ID number: ACTRN12607000632493.

Perspectives of health care professionals on the facilitators and barriers to the implementation of a stroke rehabilitation guidelines cluster randomized controlled trial.

PubMed

Munce, Sarah E P; Graham, Ian D; Salbach, Nancy M; Jaglal, Susan B; Richards, Carol L; Eng, Janice J; Desrosiers, Johanne; MacKay-Lyons, Marilyn; Wood-Dauphinee, Sharon; Korner-Bitensky, Nicol; Mayo, Nancy E; Teasell, Robert W; Zwarenstein, Merrick; Mokry, Jennifer; Black, Sandra; Bayley, Mark T

2017-06-26

The Stroke Canada Optimization of Rehabilitation by Evidence Implementation Trial (SCORE-IT) was a cluster randomized controlled trial that evaluated two knowledge translation (KT) interventions for the promotion of the uptake of best practice recommendations for interventions targeting upper and lower extremity function, postural control, and mobility. Twenty rehabilitation centers across Canada were randomly assigned to either the facilitated or passive KT intervention. The objective of the current study was to understand the factors influencing the implementation of the recommended treatments and KT interventions from the perspective of nurses, occupational therapists and physical therapists, and clinical managers following completion of the trial. A qualitative descriptive approach involving focus groups was used. Thematic analysis was used to understand the factors influencing the implementation of the recommended treatments and KT interventions. The Clinical Practice Guidelines Framework for Improvement guided the analysis. Thirty-three participants were interviewed from 11 of the 20 study sites (6 sites from the facilitated KT arm and 5 sites from the passive KT arm). The following factors influencing the implementation of the recommended treatments and KT interventions emerged: facilitation, agreement with the intervention - practical, familiarity with the recommended treatments, and environmental factors, including time and resources. Each of these themes includes the sub-themes of facilitator and/or barrier. Improved team communication and interdisciplinary collaboration emerged as an unintended outcome of the trial across both arms in addition to a facilitator to the implementation of the treatment recommendations. Facilitation was identified as a facilitator to implementation of the KT interventions in the passive KT intervention arm despite the lack of formally instituted facilitators in this arm of the trial. This is one of the first studies to examine the factors influencing the implementation of stroke recommendations and associated KT interventions within the context of a trial. Findings highlight the important role of self-selected facilitators to implementation efforts. Future research should seek to better understand the specific characteristics of facilitators that are associated with successful implementation and clinical outcomes, especially within the context of stroke rehabilitation.

SESOTHO trial ("Switch Either near Suppression Or THOusand") - switch to second-line versus WHO-guided standard of care for unsuppressed patients on first-line ART with viremia below 1000 copies/mL: protocol of a multicenter, parallel-group, open-label, randomized clinical trial in Lesotho, Southern Africa.

PubMed

Amstutz, Alain; Nsakala, Bienvenu Lengo; Vanobberghen, Fiona; Muhairwe, Josephine; Glass, Tracy Renée; Achieng, Beatrice; Sepeka, Mamorena; Tlali, Katleho; Sao, Lebohang; Thin, Kyaw; Klimkait, Thomas; Battegay, Manuel; Labhardt, Niklaus Daniel

2018-02-12

The World Health Organization (WHO) recommends viral load (VL) measurement as the preferred monitoring strategy for HIV-infected individuals on antiretroviral therapy (ART) in resource-limited settings. The new WHO guidelines 2016 continue to define virologic failure as two consecutive VL ≥1000 copies/mL (at least 3 months apart) despite good adherence, triggering switch to second-line therapy. However, the threshold of 1000 copies/mL for defining virologic failure is based on low-quality evidence. Observational studies have shown that individuals with low-level viremia (measurable but below 1000 copies/mL) are at increased risk for accumulation of resistance mutations and subsequent virologic failure. The SESOTHO trial assesses a lower threshold for switch to second-line ART in patients with sustained unsuppressed VL. In this multicenter, parallel-group, open-label, randomized controlled trial conducted in Lesotho, patients on first-line ART with two consecutive unsuppressed VL measurements ≥100 copies/mL, where the second VL is between 100 and 999 copies/mL, will either be switched to second-line ART immediately (intervention group) or not be switched (standard of care, according to WHO guidelines). The primary endpoint is viral resuppression (VL < 50 copies/mL) 9 months after randomization. We will enrol 80 patients, giving us 90% power to detect a difference of 35% in viral resuppression between the groups (assuming two-sided 5% alpha error). For our primary analysis, we will use a modified intention-to-treat set, with those lost to care, death, or crossed over considered failure to resuppress, and using logistic regression models adjusted for the prespecified stratification variables. The SESOTHO trial challenges the current WHO guidelines, assessing an alternative, lower VL threshold for patients with unsuppressed VL on first-line ART. This trial will provide data to inform future WHO guidelines on VL thresholds to recommend switch to second-line ART. ClinicalTrials.gov ( NCT03088241 ), registered May 05, 2017.

Micro-Randomized Trials: An Experimental Design for Developing Just-in-Time Adaptive Interventions

PubMed Central

Klasnja, Predrag; Hekler, Eric B.; Shiffman, Saul; Boruvka, Audrey; Almirall, Daniel; Tewari, Ambuj; Murphy, Susan A.

2015-01-01

Objective This paper presents an experimental design, the micro-randomized trial, developed to support optimization of just-in-time adaptive interventions (JITAIs). JITAIs are mHealth technologies that aim to deliver the right intervention components at the right times and locations to optimally support individuals’ health behaviors. Micro-randomized trials offer a way to optimize such interventions by enabling modeling of causal effects and time-varying effect moderation for individual intervention components within a JITAI. Methods The paper describes the micro-randomized trial design, enumerates research questions that this experimental design can help answer, and provides an overview of the data analyses that can be used to assess the causal effects of studied intervention components and investigate time-varying moderation of those effects. Results Micro-randomized trials enable causal modeling of proximal effects of the randomized intervention components and assessment of time-varying moderation of those effects. Conclusions Micro-randomized trials can help researchers understand whether their interventions are having intended effects, when and for whom they are effective, and what factors moderate the interventions’ effects, enabling creation of more effective JITAIs. PMID:26651463

Preoperative endoscopic versus percutaneous transhepatic biliary drainage in potentially resectable perihilar cholangiocarcinoma (DRAINAGE trial): design and rationale of a randomized controlled trial.

PubMed

Wiggers, Jimme K; Coelen, Robert J S; Rauws, Erik A J; van Delden, Otto M; van Eijck, Casper H J; de Jonge, Jeroen; Porte, Robert J; Buis, Carlijn I; Dejong, Cornelis H C; Molenaar, I Quintus; Besselink, Marc G H; Busch, Olivier R C; Dijkgraaf, Marcel G W; van Gulik, Thomas M

2015-02-14

Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage. The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality. The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma. Netherlands Trial Register [ NTR4243 , 11 October 2013].

Occupational rehabilitation programs for musculoskeletal pain and common mental health disorders: study protocol of a randomized controlled trial

PubMed Central

2014-01-01

Background Long-term sick leave has considerably negative impact on the individual and society. Hence, the need to identify effective occupational rehabilitation programs is pressing. In Norway, group based occupational rehabilitation programs merging patients with different diagnoses have existed for many years, but no rigorous evaluation has been performed. The described randomized controlled trial aims primarily to compare two structured multicomponent inpatient rehabilitation programs, differing in length and content, with a comparative cognitive intervention. Secondarily the two inpatient programs will be compared with each other, and with a usual care reference group. Methods/design The study is designed as a randomized controlled trial with parallel groups. The Social Security Office performs monthly extractions of sick listed individuals aged 18–60 years, on sick leave 2–12 months, with sick leave status 50% - 100% due to musculoskeletal, mental or unspecific disorders. Sick-listed persons are randomized twice: 1) to receive one of two invitations to participate in the study or not receive an invitation, where the latter “untouched” control group will be monitored for future sick leave in the National Social Security Register, and 2) after inclusion, to a Long or Short inpatient multicomponent rehabilitation program (depending on which invitation was sent) or an outpatient cognitive behavioral therapy group comparative program. The Long program consists of 3 ½ weeks with full rehabilitation days. The Short program consists of 4 + 4 full days, separated by two weeks, in which a workplace visit will be performed if desirable. Three areas of rehabilitation are targeted: mental training, physical training and work-related problem solving. The primary outcome is number of sick leave days. Secondary outcomes include time until full sustainable return to work, health related quality of life, health related behavior, functional status, somatic and mental health, and perceptions of work. In addition, health economic evaluation will be performed, and the implementation of the interventions, expectations and experiences of users and service providers will be investigated with different qualitative methods. Trial registration ClinicalTrials.gov: NCT01926574. PMID:24735616

Use of Bayesian Decision Analysis to Minimize Harm in Patient-Centered Randomized Clinical Trials in Oncology.

PubMed

Montazerhodjat, Vahid; Chaudhuri, Shomesh E; Sargent, Daniel J; Lo, Andrew W

2017-09-14

Randomized clinical trials (RCTs) currently apply the same statistical threshold of alpha = 2.5% for controlling for false-positive results or type 1 error, regardless of the burden of disease or patient preferences. Is there an objective and systematic framework for designing RCTs that incorporates these considerations on a case-by-case basis? To apply Bayesian decision analysis (BDA) to cancer therapeutics to choose an alpha and sample size that minimize the potential harm to current and future patients under both null and alternative hypotheses. We used the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database and data from the 10 clinical trials of the Alliance for Clinical Trials in Oncology. The NCI SEER database was used because it is the most comprehensive cancer database in the United States. The Alliance trial data was used owing to the quality and breadth of data, and because of the expertise in these trials of one of us (D.J.S.). The NCI SEER and Alliance data have already been thoroughly vetted. Computations were replicated independently by 2 coauthors and reviewed by all coauthors. Our prior hypothesis was that an alpha of 2.5% would not minimize the overall expected harm to current and future patients for the most deadly cancers, and that a less conservative alpha may be necessary. Our primary study outcomes involve measuring the potential harm to patients under both null and alternative hypotheses using NCI and Alliance data, and then computing BDA-optimal type 1 error rates and sample sizes for oncology RCTs. We computed BDA-optimal parameters for the 23 most common cancer sites using NCI data, and for the 10 Alliance clinical trials. For RCTs involving therapies for cancers with short survival times, no existing treatments, and low prevalence, the BDA-optimal type 1 error rates were much higher than the traditional 2.5%. For cancers with longer survival times, existing treatments, and high prevalence, the corresponding BDA-optimal error rates were much lower, in some cases even lower than 2.5%. Bayesian decision analysis is a systematic, objective, transparent, and repeatable process for deciding the outcomes of RCTs that explicitly incorporates burden of disease and patient preferences.

Use of Bayesian Decision Analysis to Minimize Harm in Patient-Centered Randomized Clinical Trials in Oncology

PubMed Central

Montazerhodjat, Vahid; Chaudhuri, Shomesh E.; Sargent, Daniel J.

2017-01-01

Importance Randomized clinical trials (RCTs) currently apply the same statistical threshold of alpha = 2.5% for controlling for false-positive results or type 1 error, regardless of the burden of disease or patient preferences. Is there an objective and systematic framework for designing RCTs that incorporates these considerations on a case-by-case basis? Objective To apply Bayesian decision analysis (BDA) to cancer therapeutics to choose an alpha and sample size that minimize the potential harm to current and future patients under both null and alternative hypotheses. Data Sources We used the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database and data from the 10 clinical trials of the Alliance for Clinical Trials in Oncology. Study Selection The NCI SEER database was used because it is the most comprehensive cancer database in the United States. The Alliance trial data was used owing to the quality and breadth of data, and because of the expertise in these trials of one of us (D.J.S.). Data Extraction and Synthesis The NCI SEER and Alliance data have already been thoroughly vetted. Computations were replicated independently by 2 coauthors and reviewed by all coauthors. Main Outcomes and Measures Our prior hypothesis was that an alpha of 2.5% would not minimize the overall expected harm to current and future patients for the most deadly cancers, and that a less conservative alpha may be necessary. Our primary study outcomes involve measuring the potential harm to patients under both null and alternative hypotheses using NCI and Alliance data, and then computing BDA-optimal type 1 error rates and sample sizes for oncology RCTs. Results We computed BDA-optimal parameters for the 23 most common cancer sites using NCI data, and for the 10 Alliance clinical trials. For RCTs involving therapies for cancers with short survival times, no existing treatments, and low prevalence, the BDA-optimal type 1 error rates were much higher than the traditional 2.5%. For cancers with longer survival times, existing treatments, and high prevalence, the corresponding BDA-optimal error rates were much lower, in some cases even lower than 2.5%. Conclusions and Relevance Bayesian decision analysis is a systematic, objective, transparent, and repeatable process for deciding the outcomes of RCTs that explicitly incorporates burden of disease and patient preferences. PMID:28418507

Investigation of the contextual interference effect in the manipulation of the motor parameter of over-all force.

PubMed

Goodwin, J E; Meeuwsen, H J

1996-12-01

This investigation examined the contextual interference effect when manipulating over-all force in a golf-putting task. Undergraduate women (N = 30) were randomly assigned to a Random, Blocked-Random, or Blocked practice condition and practiced golf putting from distances of 2.43 m, 3.95 m, and 5.47 m during acquisition. Subjects in the Random condition practiced trials in a quasirandom sequence and those in the Blocked-Random condition practiced trials initially in a blocked sequence with the remainder of the trials practiced in a quasirandom sequence. In the Blocked condition subjects practiced trials in a blocked sequence. A 24-hr. transfer test consisted of 30 trials with 10 trials each from 1.67 m, 3.19 m, and 6.23 m. Transfer scores supported the Magill and Hall (1990) hypothesis that, when task variations involve learning parameters of a generalized motor program, the benefit of random practice over blocked practice would not be found.

Three controlled trials of interventions to increase recruitment to a randomized controlled trial of mobile phone based smoking cessation support.

PubMed

Free, Caroline; Hoile, Elizabeth; Robertson, Steven; Knight, Rosemary

2010-06-01

Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment. We report three controlled trials of interventions to increase recruitment to the Txt2stop trial. To evaluate: Trial 1. The impact on registrations of a text message regarding an online registration facility; Trial 2. The impact on randomizations of sending pound5 with a covering letter to those eligible to join the trial; Trial 3. The impact on randomizations of text messages containing quotes from existing participants. Single blind controlled trials with allocation concealment. Trial 1: A text message regarding our new online registration facility; Trial 2: A letter with pound5 enclosed; Trial 3: A series of four text messages containing quotes from participants. The control group in each trial received standard Txt2stop procedures. Trial 1: 3.6% (17/470) of the intervention group and 1.1% (5/467) of the control group registered for the trial, risk difference 2.5% (95% CI 0.6-4.5). 0% (0/ 470) of the intervention group and 0.2% (1/467) of the control group registered successfully online, risk difference -0.2 (95% CI -0.6-0.2); Trial 2: 4.5% (11/246) of the intervention group and 0.4% (1/245) of the control group were randomized into the Txt2stop trial, risk difference 4.0% (95% CI 1.4-6.7); Trial 3: 3.5% (14/405) of the intervention group and 0% (0/406) of the control group were randomized into the Txt2stop trial, risk difference 3.5 (95% CI 1.7-5.2). There were no baseline data available for trial 1. Allocation of participant IDs in trials 2 and 3 were systematic. Sending a text message about an online registration facility increased registrations to Txt2stop, but did not increase online registrations. Sending a pound5 reimbursement for participants' time and sending text messages containing quotes from existing participants increased randomizations into the Txt2stop trial. Clinical Trials 2010; 7: 265-273. http://ctj.sagepub.com.

Short-term outcomes of extracorporeal shock wave therapy for the treatment of chronic non-calcific tendinopathy of the supraspinatus: a double-blind, randomized, placebo-controlled trial

PubMed Central

2012-01-01

Background There is evidence supporting the use of extracorporeal shock wave therapy (ESWT) in calcific tendinopathy of the rotator cuff, but the best current evidence does not support its use in non-calcifying tendinopathy. We conducted a randomized placebo-controlled trial to investigate the efficacy and safety of low energy ESWT for non-calcifying tendinopathy of the rotator cuff. Methods 20 patients with non-calcifying supraspinatus tendinopathy (NCST) were randomized to an active or a sham treatment group. Physical, blood, roentgenographic, and MRI examinations of the shoulder were conducted to verify that patients met the inclusion and exclusion criteria. These examinations were repeated six and twelve weeks after treatments. Effectiveness was determined by comparison of the mean improvement in the Constant and Murley score (CMS) between the treatment and the placebo groups at three months. Safety was assessed by analyzing the number and severity of adverse events. Results All the patients completed the investigation protocol. At the final follow-up, significant improvement in the total CMS score and most of the CMS subscales was observed in the ESWT group when compared to the baseline values. Significantly higher total CMS, and significantly higher scores for CMS pain and ROM were observed in the ESWT group when compared to the placebo. No serious adverse events were noted after ESWT. Conclusions Patients suffering from NCST may benefit from low energy ESWT, at least in short-term. The application protocol of ESWT is likely to play a key-role in a successful treatment. Future investigations should be undertaken on the long-term effects of this technique for the treatment of NCST. Trial registration Current Controlled Trials ISRCTN41236511 PMID:22672772

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

Evaluation of a Decision Aid for Women with Epilepsy Who Are Considering Pregnancy: A Randomized Controlled Trial.

PubMed

McGrath, Amanda; Sharpe, Louise; Lah, Suncica; Parratt, Kaitlyn

2017-07-01

For many women with epilepsy (WWE), decision making about pregnancy is complicated by considerations such as the potential teratogenicity of antiepileptic drugs, offspring risk of epilepsy, seizure occurrence during pregnancy, and the challenges of parenting amidst poorly controlled seizures. This proof-of-concept, randomized controlled trial aimed to evaluate a decision aid (DA) developed to help WWE decide if they should start or enlarge their families. Seventy-nine WWE of childbearing age were recruited from Epilepsy Action Australia between October and November 2013 and randomized to receive the intervention (the DA) or not, and to complete a set of questionnaires pre- and post- intervention. The DA, delivered as a PDF booklet, provided balanced evidence-based information about options, risks and benefits, including probabilities; as well as steps for clarifying values and considering options within one's personal situation. Compared with the control group, the DA group had statistically significant improvements in knowledge about pregnancy and epilepsy (Cohen's d = 1.24; 95%CI = 0.77 to 1.83) and reduced decisional conflict (Cohen's d = 0.59; 95%CI = 0.21 to 0.99). Changes in decision self-efficacy, certainty of choice, patient-practitioner communication abilities and value congruence with choice were comparable between the DA and control group. Importantly, women's decisions about motherhood were not biased towards either direction, and there were no adverse effects on depression or anxiety. All women who received the DA indicated they would recommend it to other WWE. The DA has the potential to serve as a useful support tool for WWE who are considering motherhood. Future research is needed to test the DA in clinical settings with guidance from a health professional. The trial was registered with the Australian New Zealand Clinical Trials Registry (ID ACTRN12613001082796).

A Safety Run-in and Randomized Phase II Study of Cilengitide Combined with Chemoradiation for Newly Diagnosed Glioblastoma (NABTT 0306)

PubMed Central

Nabors, L. Burt; Mikkelsen, Tom; Hegi, Monika E.; Ye, Xiaubu; Batchelor, Tracy; Lesser, Glenn; Peereboom, David; Rosenfeld, Myrna R.; Olsen, Jeff; Brem, Steve; Fisher, Joy D.; Grossman, Stuart A.

2012-01-01

Background Cilengitide is a selective integrin inhibitor that is well tolerated and has demonstrated biological activity in patients with recurrent malignant glioma. The primary objectives of this randomized phase II trial were to determine safety and efficacy of cilengitide when combined with radiation and temozolomide for newly diagnosed glioblastoma (GBM) and to select a dose for comparative clinical testing. Methods A total of 112 patients were accrued. Eighteen patients received standard RT+TMZ with cilengitide in a safety run-in phase followed by a randomized phase II with ninety-four patients assigned to either 500 or 2000 mg dose groups. The trial was designed to estimate overall survival benefit when compared with the NABTT internal historical control or the published EORTC 26981 data. Results Cilengitide at all doses studied was well tolerated with radiation and temozolomide. The median survival was 19.7 months for all patients, 17.4 months for those receiving the 500 mg dose, 20.8 months for those receiving the 2000mg dose, 30 months for patients with methylated MGMT promoters and 17.4 months for unmethylated patients. For patients ages 70 and younger, the median survival and survival at 24 months was superior to that observed in the EORTC trial (20.7 months vs 14.6 months and 41% vs 27% (p=0.008) respectively). Conclusions Cilengitide is well tolerated when combined with standard chemoradiation and may improve survival for patients newly diagnosed with GBM regardless of MGMT status. From an efficacy and safety standpoint, future trials of this agent in this population should utilize the 2000 mg dose. PMID:22517399

Prospective Dutch colorectal cancer cohort: an infrastructure for long-term observational, prognostic, predictive and (randomized) intervention research.

PubMed

Burbach, J P M; Kurk, S A; Coebergh van den Braak, R R J; Dik, V K; May, A M; Meijer, G A; Punt, C J A; Vink, G R; Los, M; Hoogerbrugge, N; Huijgens, P C; Ijzermans, J N M; Kuipers, E J; de Noo, M E; Pennings, J P; van der Velden, A M T; Verhoef, C; Siersema, P D; van Oijen, M G H; Verkooijen, H M; Koopman, M

2016-11-01

Systematic evaluation and validation of new prognostic and predictive markers, technologies and interventions for colorectal cancer (CRC) is crucial for optimizing patients' outcomes. With only 5-15% of patients participating in clinical trials, generalizability of results is poor. Moreover, current trials often lack the capacity for post-hoc subgroup analyses. For this purpose, a large observational cohort study, serving as a multiple trial and biobanking facility, was set up by the Dutch Colorectal Cancer Group (DCCG). The Prospective Dutch ColoRectal Cancer cohort is a prospective multidisciplinary nationwide observational cohort study in the Netherlands (yearly CRC incidence of 15 500). All CRC patients (stage I-IV) are eligible for inclusion, and longitudinal clinical data are registered. Patients give separate consent for the collection of blood and tumor tissue, filling out questionnaires, and broad randomization for studies according to the innovative cohort multiple randomized controlled trial design (cmRCT), serving as an alternative study design for the classic RCT. Objectives of the study include: 1) systematically collected long-term clinical data, patient-reported outcomes and biomaterials from daily CRC practice; and 2) to facilitate future basic, translational and clinical research including interventional and cost-effectiveness studies for both national and international research groups with short inclusion periods, even for studies with stringent inclusion criteria. Seven months after initiation 650 patients have been enrolled, eight centers participate, 15 centers await IRB approval and nine embedded cohort- or cmRCT-designed studies are currently recruiting patients. This cohort provides a unique multidisciplinary data, biobank, and patient-reported outcomes collection initiative, serving as an infrastructure for various kinds of research aiming to improve treatment outcomes in CRC patients. This comprehensive design may serve as an example for other tumor types.

Engineering Online and In-Person Social Networks for Physical Activity: A Randomized Trial.

PubMed

Rovniak, Liza S; Kong, Lan; Hovell, Melbourne F; Ding, Ding; Sallis, James F; Ray, Chester A; Kraschnewski, Jennifer L; Matthews, Stephen A; Kiser, Elizabeth; Chinchilli, Vernon M; George, Daniel R; Sciamanna, Christopher N

2016-12-01

Social networks can influence physical activity, but little is known about how best to engineer online and in-person social networks to increase activity. The purpose of this study was to conduct a randomized trial based on the Social Networks for Activity Promotion model to assess the incremental contributions of different procedures for building social networks on objectively measured outcomes. Physically inactive adults (n = 308, age, 50.3 (SD = 8.3) years, 38.3 % male, 83.4 % overweight/obese) were randomized to one of three groups. The Promotion group evaluated the effects of weekly emailed tips emphasizing social network interactions for walking (e.g., encouragement, informational support); the Activity group evaluated the incremental effect of adding an evidence-based online fitness walking intervention to the weekly tips; and the Social Networks group evaluated the additional incremental effect of providing access to an online networking site for walking as well as prompting walking/activity across diverse settings. The primary outcome was mean change in accelerometer-measured moderate-to-vigorous physical activity (MVPA), assessed at 3 and 9 months from baseline. Participants increased their MVPA by 21.0 min/week, 95 % CI [5.9, 36.1], p = .005, at 3 months, and this change was sustained at 9 months, with no between-group differences. Although the structure of procedures for targeting social networks varied across intervention groups, the functional effect of these procedures on physical activity was similar. Future research should evaluate if more powerful reinforcers improve the effects of social network interventions. The trial was registered with the ClinicalTrials.gov (NCT01142804).

Cost-Effectiveness of an Internet-Delivered Treatment for Substance Abuse: Data from a Multisite Randomized Controlled Trial

PubMed Central

Murphy, Sean M.; Campbell, Aimee N. C.; Ghitza, Udi E.; Kyle, Tiffany L.; Bailey, Genie L.; Nunes, Edward V.; Polsky, Daniel

2016-01-01

Background Substance misuse and excessive alcohol consumption are major public health issues. Internet-based interventions for substance use disorders (SUDs) are a relatively new method for addressing barriers to access and supplementing existing care. This study examines cost-effectiveness in a multisite, randomized trial of an internet-based version of the community reinforcement approach (CRA) with contingency management (CM) known as the Therapeutic Education System (TES). Methods Economic evaluation of the 12-week trial with follow-up at 24 and 36 weeks. 507 individuals who were seeking therapy for alcohol or other substance use disorders at 10 outpatient community-based treatment programs were recruited and randomized to either treatment as usual (TAU) or TES+TAU. Sub-analyses were completed on participants with a poorer prognosis (i.e., those not abstinent at study entry). Results From the provider’s perspective, TES+TAU as it was implemented in this study costs $278 (SE=87) more than TAU alone after 12 weeks. The quality-adjusted life years gained by TES+TAU and TAU were similar; however, TES+TAU has at least a 95% chance of being considered cost-effective for providers and payers with willingness-to-pay thresholds as low as $20,000 per abstinent year. Findings for the subgroup not abstinent at study entry are slightly more favorable. Conclusions With regard to the clinical outcome of abstinence, our cost-effectiveness findings of TES+TAU compare favorably to those found elsewhere in the CM literature. The analyses performed here serve as an initial economic framework for future studies integrating technology into SUD therapy. Clinical trial registration NCT01104805. PMID:26880594

Preoperative flap-site injection with ropivacaine and epinephrine in BABA robotic and endoscopic thyroidectomy safely reduces postoperative pain: A CONSORT-compliant double-blinded randomized controlled study (PAIN-BREKOR trial).

PubMed

Lee, Joon-Hyop; Suh, Yong Joon; Song, Ra-Yeong; Yi, Jin Wook; Yu, Hyeong Won; Kwon, Hyungju; Choi, June Young; Lee, Kyu Eun

2017-06-01

Clinical trials on bilateral axillo-breast approach (BABA) thyroidectomy show that levobupivacaine and ropivacaine significantly reduce postoperative pain, but they focused on BABA robotic thyroidectomy only and did not identify specific sites of significant pain relief. Our objective was to assess the pain reduction at various sites and safety of ropivacaine-epinephrine flap injection in BABA thyroidectomy. This prospective double-blinded randomized controlled trial was conducted in compliance with the revised CONSORT statement (ClinicalTrials.gov registration no. NCT02112370). Patients were randomized into the ropivacaine-epinephrine arm or control (normal saline) arm. From January 2014 to May 2016, 148 patients participated. The primary endpoint was site-specific pain, as measured by numeric rating scale 12 hours after surgery. The ropivacaine-epinephrine group exhibited significantly less swallowing difficulty (P = .008), anterior neck pain (P = .016), and right (P = .019) and left (P = .035) chest pain. Secondary endpoints were systolic (P = .402), diastolic (P = .827) blood pressure, and pulse rate (P = .397) after injection before incision and during surgery. The vital signs of the groups just after injection did not differ. During surgery, the ropivacaine-epinephrine patients had higher pulse rates (99 ± 13.3 vs 88 ± 16.1, P < .001) but within normal range. There were no adverse events such as postoperative nausea and vomiting. There was no significant difference in pain scores in either patient group between patients who underwent robotic or endoscopic interventions. BABA flap-site injection with ropivacaine and epinephrine mix before incision effectively and safely reduced postoperative pain. Future studies should focus on tailoring ropivacaine and epinephrine dosage for individuals.

Motor/Prefrontal Transcranial Direct Current Stimulation (tDCS) Following Lumbar Surgery Reduces Postoperative Analgesia Use.

PubMed

Glaser, John; Reeves, Scott T; Stoll, William David; Epperson, Thomas I; Hilbert, Megan; Madan, Alok; George, Mark S; Borckardt, Jeffrey J

2016-05-01

Randomized, controlled pilot trial. The present study is the first randomized, double-blind, sham-controlled pilot clinical trial of transcranial direct current stimulation (tDCS) for pain and patient-controlled analgesia (PCA) opioid usage among patients receiving spine surgery. Lumbar spinal surgeries are common, and while pain is often a complaint that precedes surgical intervention, the procedures themselves are associated with considerable postoperative pain lasting days to weeks. Adequate postoperative pain control is an important factor in determining recovery and new analgesic strategies are needed that can be used adjunctively to existing strategies potentially to reduce reliance on opioid analgesia. Several novel brain stimulation technologies including tDCS are beginning to demonstrate promise as treatments for a variety of pain conditions. Twenty-seven patients undergoing lumbar spine procedures at Medical University of South Carolina were randomly assigned to receive four 20-minute sessions of real or sham tDCS during their postsurgical hospital stay. Patient-administered hydromorphone usage was tracked along with numeric rating scale pain ratings. The effect of tDCS on the slope of the cumulative PCA curve was significant (P < 0.001) and tDCS was associated with a 23% reduction in PCA usage. In the real tDCS group a 31% reduction was observed in pain-at-its-least ratings from admission to discharge (P = 0.027), but no other changes in numeric rating scale pain ratings were significant in either group. The present pilot trial is the first study to demonstrate an opioid sparing effect of tDCS after spine surgical procedures. Although this was a small pilot trial in a heterogeneous sample of spinal surgery patients, a moderate effect-size was observed for tDCS, suggesting that future work in this area is warranted. 2.

Stress as a seizure precipitant: Identification, associated factors, and treatment options.

PubMed

McKee, Heather R; Privitera, Michael D

2017-01-01

Stress is a common and important seizure precipitant reported by epilepsy patients. Studies to date have used different methodologies to identify relationships between epilepsy and stress. Several studies have identified anxiety, depression, and childhood trauma as being more common in patients with epilepsy who report stress as a seizure precipitant compared to patients with epilepsy who did not identify stress as a seizure precipitant. In one survey study it was found that a majority of patients with stress-triggered seizures had used some type of stress reduction method on their own and, of those who tried this, an even larger majority felt that these methods improved their seizures. Additionally, small to moderate sized prospective trials, including randomized clinical trials, using general stress reduction methods have shown promise in improving outcomes in patients with epilepsy, but results on seizure frequency have been inconsistent. Based on these studies, we recommend that when clinicians encounter patients who report stress as a seizure precipitant, these patients should be screened for a treatable mood disorder. Furthermore, although seizure reduction with stress reduction methods has not been proven in a randomized controlled trial, other important endpoints like quality of life were improved. Therefore, recommending stress reduction methods to patients with epilepsy appears to be a reasonable low risk adjunctive to standard treatments. The current review highlights the need for future research to help further clarify biological mechanisms of the stress-seizure relationship and emphasizes the need for larger randomized controlled trials to help develop evidence based treatment recommendations for our epilepsy patients. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Randomized placebo-controlled trial of CDB-2914 in new users of a levonorgestrel-releasing intrauterine system shows only short-lived amelioration of unscheduled bleeding

PubMed Central

Warner, P.; Guttinger, A.; Glasier, A.F.; Lee, R.J.; Nickerson, S.; Brenner, R.M.; Critchley, H.O.D.

2010-01-01

BACKGROUND The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive. However, during early months of use unscheduled vaginal bleeding is common, sometimes leading to discontinuation. This study aimed to determine whether intermittent administration of progesterone receptor modulator CDB-2914 would suppress unscheduled bleeding during the first 4 months after insertion of the LNG-IUS. METHODS CDB-2914 150 mg, in divided doses, or placebo tablets, were administered over three consecutive days starting on Days 21, 49 and 77 after LNG-IUS insertion, in a double-blind randomized controlled trial of women aged 19–49 years, newly starting use of LNG-IUS. Daily bleeding diaries were completed for 6 months, and summarized across blocks as percentage days bleeding/spotting (BS%). RESULTS Of 69 women randomized to receive CDB-2914, and 67 placebo, 61 and 55, respectively, completed the trial. BS% decreased with time in both arms, but showed a much steeper treatment-phase gradient in the placebo arm (P < 0.0001), so that a benefit of CDB-2914 in the 28 days after first treatment (−11% points, 95% CI −19 to −2), converted to a disadvantage by 64 days after the third treatment (+10% points, 95% CI 1–18). CONCLUSIONS The effect of CDB-2914 on BS% was initially beneficial but then by third treatment was disadvantageous. Nevertheless, only 3% (4/136) of all women discontinued LNG-IUS. These findings give insight into possible mechanisms and suggest future research directions. ISRCTN Trial no. ISRCTN58283041; EudraCT no. 2006-006511-72. PMID:19897857

Knowledge, Attitudes, and Experiences of HIV Pre-Exposure Prophylaxis (PrEP) Trial Participants in Botswana.

PubMed

Toledo, Lauren; McLellan-Lemal, Eleanor; Henderson, Faith L; Kebaabetswe, Poloko M

2015-03-01

Recent clinical trials have shown that a daily dose of oral TDF/FTC pre-exposure prophylaxis (PrEP) is effective in reducing human immunodeficiency (HIV) risk. Understanding trial participants' perspectives about retention and PrEP adherence is critical to inform future PrEP trials and the scale-up and implementation of PrEP programs. We analyzed 53 in-depth interviews conducted in April 2010 with participants in the TDF2 study, a Phase 3, randomized, double-blind, placebo-controlled clinical trial of daily oral TDF/FTC with heterosexual men and women in Francistown and Gaborone, Botswana. We examined participants' knowledge, attitudes, and experiences of the trial, identified facilitators and barriers to enrollment and retention, and compared participant responses by study site, sex, and study drug adherence. Our findings point to several factors to consider for participant retention and adherence in PrEP trials and programs, including conducting pre-enrollment education and myth reduction counseling, providing accurate estimates of participant obligations and side effect symptoms, ensuring participant understanding of the effects of non-adherence, gauging personal commitment and interest in study outcomes, and developing a strong external social support network for participants.

Application of implantable hemodynamic monitoring in the management of patients with diastolic heart failure: a subgroup analysis of the COMPASS-HF trial.

PubMed

Zile, Michael R; Bourge, Robert C; Bennett, Tom D; Stevenson, Lynne Warner; Cho, Yong K; Adamson, Philip B; Aaron, Mark F; Aranda, Juan M; Abraham, William T; Smart, Frank W; Kueffer, Fred J

2008-12-01

Nearly half of all patients with chronic heart failure (HF) have a normal ejection fraction (EF), and abnormal diastolic function (ie, diastolic heart failure [DHF]). However, appropriate management of DHF patients remains a difficult and uncertain challenge. The Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial was designed to evaluate whether an implantable hemodynamic monitor (IHM) was safe and effective in reducing the number of heart failure-related events (HFRE) in patients with chronic HF. The current study presents data on a prespecified and planned subgroup analysis from the COMPASS-HF trial: 70 patients with an EF > or =50% (ie, DHF). As such, this represents a subgroup analysis of the COMPASS-HF Trial. DHF patients were randomized to IHM-guided care (treatment) vs. standard care (control) for 6 months. All 70 patients received optimal medical therapy, but the hemodynamic information from the IHM was used to guide patient management only in the treatment group. The HFRE rate in DHF patients randomized to treatment was 0.58 events/6 months compared with DHF patients randomized to control, which was 0.73 events/6 months; this represented a 20% nonsignificant reduction in the overall HFRE rate in the treatment group (95% CI = -46, 56, P = .66). There was a 29% nonsignificant reduction in the relative risk of a HF hospitalization in the DHF patients randomized to treatment compared with DHF patients randomized to control (95% CI = -69, 70, P = .43). The IHM was shown to be safe and was associated with a very low system-related and procedure-related complication rate in DHF patients. However, in this subgroup analysis limited to 70 DHF patients, the addition IHM-guided care did not significantly lower the rate of HFR events. The results of this subgroup analysis in DHF patients, for whom there are currently no proven, effective management strategies, will be used to design future studies defining the effects of IHM-guided care in patients with DHF.

CERAMENT treatment of fracture defects (CERTiFy): protocol for a prospective, multicenter, randomized study investigating the use of CERAMENT™ BONE VOID FILLER in tibial plateau fractures

PubMed Central

2014-01-01

Background Bone graft substitutes are widely used for reconstruction of posttraumatic bone defects. However, their clinical significance in comparison to autologous bone grafting, the gold-standard in reconstruction of larger bone defects, still remains under debate. This prospective, randomized, controlled clinical study investigates the differences in pain, quality of life, and cost of care in the treatment of tibia plateau fractures-associated bone defects using either autologous bone grafting or bioresorbable hydroxyapatite/calcium sulphate cement (CERAMENT™|BONE VOID FILLER (CBVF)). Methods/Design CERTiFy (CERament™ Treatment of Fracture defects) is a prospective, multicenter, controlled, randomized trial. We plan to enroll 136 patients with fresh traumatic depression fractures of the proximal tibia (types AO 41-B2 and AO 41-B3) in 13 participating centers in Germany. Patients will be randomized to receive either autologous iliac crest bone graft or CBVF after reduction and osteosynthesis of the fracture to reconstruct the subchondral bone defect and prevent the subsidence of the articular surface. The primary outcome is the SF-12 Physical Component Summary at week 26. The co-primary endpoint is the pain level 26 weeks after surgery measured by a visual analog scale. The SF-12 Mental Component Summary after 26 weeks and costs of care will serve as key secondary endpoints. The study is designed to show non-inferiority of the CBVF treatment to the autologous iliac crest bone graft with respect to the physical component of quality of life. The pain level at 26 weeks after surgery is expected to be lower in the CERAMENT bone void filler treatment group. Discussion CERTiFy is the first randomized multicenter clinical trial designed to compare quality of life, pain, and cost of care in the use of the CBVF and the autologous iliac crest bone graft in the treatment of tibia plateau fractures. The results are expected to influence future treatment recommendations. Trial registration number ClinicalTrials.gov: NCT01828905 PMID:24606670

Aerobic training for improved memory in patients with stress-related exhaustion: a randomized controlled trial.

PubMed

Eskilsson, Therese; Slunga Järvholm, Lisbeth; Malmberg Gavelin, Hanna; Stigsdotter Neely, Anna; Boraxbekk, Carl-Johan

2017-09-02

Patients with stress-related exhaustion suffer from cognitive impairments, which often remain after psychological treatment or work place interventions. It is important to find effective treatments that can address this problem. Therefore, the aim of this study was to investigate the effects on cognitive performance and psychological variables of a 12-week aerobic training program performed at a moderate-vigorous intensity for patients with exhaustion disorder who participated in a multimodal rehabilitation program. In this open-label, parallel, randomized and controlled trial, 88 patients diagnosed with exhaustion disorder participated in a 24-week multimodal rehabilitation program. After 12 weeks in the program the patients were randomized to either a 12-week aerobic training intervention or to a control group with no additional training. Primary outcome measure was cognitive function, and secondary outcome measures were psychological health variables and aerobic capacity. In total, 51% patients in the aerobic training group and 78% patients in the control group completed the intervention period. The aerobic training group significantly improved in maximal oxygen uptake and episodic memory performance. No additional improvement in burnout, depression or anxiety was observed in the aerobic group compared with controls. Aerobic training at a moderate-vigorous intensity within a multimodal rehabilitation program for patients with exhaustion disorder facilitated episodic memory. A future challenge would be the clinical implementation of aerobic training and methods to increase feasibility in this patient group. ClinicalTrials.gov: NCT03073772 . Retrospectively registered 21 February 2017.

A Randomized Double-Blind Placebo-Controlled Trial of Fruit and Vegetable Concentrates on Intermediate Biomarkers in Head and Neck Cancer

PubMed Central

Datta, Mridul; Shaw, Edward G.; Lesser, Glenn J.; Case, L. Douglas; Vitolins, Mara Z.; Schneider, Charles; Frizzell, Bart; Sullivan, Christopher; Lively, Mark; Franzmann, Elizabeth; Hu, Jennifer J.

2017-01-01

Background. Head and neck cancer (HNC) patients are at an increased risk for developing second primary tumors (SPTs). Diets rich in fruits and vegetables (FVs) may lower HNC risk. FV concentrates may offer a potential alternative to increasing FV intake. Methods. We conducted a randomized, double-blind, placebo-controlled trial to evaluate whether Juice PLUS+ (JP; a commercial product with multiple FV concentrates) has an effect on p27 and Ki-67, biomarkers associated with the risk of SPTs. During 2004-2008, we randomized 134 HNC patients to 12 weeks of JP (n = 72) or placebo (n = 62). Oral cavity mucosal biopsies and whole blood were obtained at baseline and after 12 weeks. All participants were given the opportunity to receive JP for 5 years following the end of the intervention period, and they were followed yearly for the development of SPTs. Results. After 12 weeks, patients on JP had significantly higher serum α-carotene (P = .009), β-carotene (P < .0001), and lutein (P = .003) but did not differ significantly in p27 (P = .23) or Ki-67 (P = .95). JP use following the initial 12-week trial was not significantly associated with SPT prevention. Conclusions. Despite increased serum micronutrient levels, our results do not suggest a clinical benefit of JP in HNC patients. Future studies should focus on longer intervention periods and/or modified supplement formulations with demonstrated chemopreventive properties. PMID:28102098

The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Shi, Zhao-feng; Song, Tie-bing; Xie, Juan; Yan, Yi-quan

2017-01-01

Background Atopic dermatitis (AD) has become a common skin disease that requires systematic and comprehensive treatment to achieve adequate clinical control. Traditional Chinese medicines and related treatments have shown clinical effects for AD in many studies. But the systematic reviews and meta-analyses for them are lacking. Objective The systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were conducted to evaluate the efficacy and safety of traditional Chinese medicines and related treatments for AD treatment. Methods Randomized controlled trials (RCTs) were searched based on standardized searching rules in eight medical databases from the inception up to December 2016 and a total of 24 articles with 1,618 patients were enrolled in this meta-analysis. Results The results revealed that traditional Chinese medicines and related treatments did not show statistical differences in clinical effectiveness, SCORAD amelioration, and SSRI amelioration for AD treatment compared with control group. However, EASI amelioration of traditional Chinese medicines and related treatments for AD was superior to control group. Conclusion We need to make conclusion cautiously for the efficacy and safety of traditional Chinese medicine and related treatment on AD therapy. More standard, multicenter, double-blind randomized controlled trials (RCTs) of traditional Chinese medicine and related treatment for AD were required to be conducted for more clinical evidences providing in the future. PMID:28713436

Design of the multicenter standardized supervised exercise training intervention for the claudication: exercise vs endoluminal revascularization (CLEVER) study.

PubMed

Bronas, Ulf G; Hirsch, Alan T; Murphy, Timothy; Badenhop, Dalynn; Collins, Tracie C; Ehrman, Jonathan K; Ershow, Abby G; Lewis, Beth; Treat-Jacobson, Diane J; Walsh, M Eileen; Oldenburg, Niki; Regensteiner, Judith G

2009-11-01

The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice.

Review of Recent Methodological Developments in Group-Randomized Trials: Part 1—Design

PubMed Central

Li, Fan; Gallis, John A.; Prague, Melanie; Murray, David M.

2017-01-01

In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have highlighted the developments of the past 13 years in design with a companion article to focus on developments in analysis. As a pair, these articles update the 2004 review. We have discussed developments in the topics of the earlier review (e.g., clustering, matching, and individually randomized group-treatment trials) and in new topics, including constrained randomization and a range of randomized designs that are alternatives to the standard parallel-arm GRT. These include the stepped-wedge GRT, the pseudocluster randomized trial, and the network-randomized GRT, which, like the parallel-arm GRT, require clustering to be accounted for in both their design and analysis. PMID:28426295

Review of Recent Methodological Developments in Group-Randomized Trials: Part 1-Design.

PubMed

Turner, Elizabeth L; Li, Fan; Gallis, John A; Prague, Melanie; Murray, David M

2017-06-01

In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have highlighted the developments of the past 13 years in design with a companion article to focus on developments in analysis. As a pair, these articles update the 2004 review. We have discussed developments in the topics of the earlier review (e.g., clustering, matching, and individually randomized group-treatment trials) and in new topics, including constrained randomization and a range of randomized designs that are alternatives to the standard parallel-arm GRT. These include the stepped-wedge GRT, the pseudocluster randomized trial, and the network-randomized GRT, which, like the parallel-arm GRT, require clustering to be accounted for in both their design and analysis.

Estimation of treatment efficacy with complier average causal effects (CACE) in a randomized stepped wedge trial.

PubMed

Gruber, Joshua S; Arnold, Benjamin F; Reygadas, Fermin; Hubbard, Alan E; Colford, John M

2014-05-01

Complier average causal effects (CACE) estimate the impact of an intervention among treatment compliers in randomized trials. Methods used to estimate CACE have been outlined for parallel-arm trials (e.g., using an instrumental variables (IV) estimator) but not for other randomized study designs. Here, we propose a method for estimating CACE in randomized stepped wedge trials, where experimental units cross over from control conditions to intervention conditions in a randomized sequence. We illustrate the approach with a cluster-randomized drinking water trial conducted in rural Mexico from 2009 to 2011. Additionally, we evaluated the plausibility of assumptions required to estimate CACE using the IV approach, which are testable in stepped wedge trials but not in parallel-arm trials. We observed small increases in the magnitude of CACE risk differences compared with intention-to-treat estimates for drinking water contamination (risk difference (RD) = -22% (95% confidence interval (CI): -33, -11) vs. RD = -19% (95% CI: -26, -12)) and diarrhea (RD = -0.8% (95% CI: -2.1, 0.4) vs. RD = -0.1% (95% CI: -1.1, 0.9)). Assumptions required for IV analysis were probably violated. Stepped wedge trials allow investigators to estimate CACE with an approach that avoids the stronger assumptions required for CACE estimation in parallel-arm trials. Inclusion of CACE estimates in stepped wedge trials with imperfect compliance could enhance reporting and interpretation of the results of such trials.

Clinical trial designs for rare diseases: studies developed and discussed by the International Rare Cancers Initiative.

PubMed

Bogaerts, Jan; Sydes, Matthew R; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie; Sclafani, Francesco; Hatcher, Helen; Earl, Helena; Ray-Coquard, Isabelle; Paul, James; Blay, Jean-Yves; Whelan, Jeremy; Panageas, Kathy; Wheatley, Keith; Harrington, Kevin; Licitra, Lisa; Billingham, Lucinda; Hensley, Martee; McCabe, Martin; Patel, Poulam M; Carvajal, Richard; Wilson, Richard; Glynne-Jones, Rob; McWilliams, Rob; Leyvraz, Serge; Rao, Sheela; Nicholson, Steve; Filiaci, Virginia; Negrouk, Anastassia; Lacombe, Denis; Dupont, Elisabeth; Pauporté, Iris; Welch, John J; Law, Kate; Trimble, Ted; Seymour, Matthew

2015-02-01

The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional--usually randomized--clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Trials can be designed using a wide array of possibilities. There is no 'one size fits all' solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Ethics of Randomized Controlled Trials in Social Settings: Can Social Trials Be Scientifically Promising and Must There Be Equipoise?

ERIC Educational Resources Information Center

Fives, Allyn; Russell, Daniel W.; Canavan, John; Lyons, Rena; Eaton, Patricia; Devaney, Carmel; Kearns, Norean; O'Brien, Aoife

2015-01-01

In a randomized controlled trial (RCT), treatments are assigned randomly and treatments are withheld from participants. Is it ethically permissible to conduct an RCT in a social setting? This paper addresses two conditions for justifying RCTs: that there should be a state of equipoise and that the trial should be scientifically promising.…

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

PubMed

Kahan, Brennan C

2016-12-13

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

Delivering successful randomized controlled trials in surgery: Methods to optimize collaboration and study design.

PubMed

Blencowe, Natalie S; Cook, Jonathan A; Pinkney, Thomas; Rogers, Chris; Reeves, Barnaby C; Blazeby, Jane M

2017-04-01

Randomized controlled trials in surgery are notoriously difficult to design and conduct due to numerous methodological and cultural challenges. Over the last 5 years, several UK-based surgical trial-related initiatives have been funded to address these issues. These include the development of Surgical Trials Centers and Surgical Specialty Leads (individual surgeons responsible for championing randomized controlled trials in their specialist fields), both funded by the Royal College of Surgeons of England; networks of research-active surgeons in training; and investment in methodological research relating to surgical randomized controlled trials (to address issues such as recruitment, blinding, and the selection and standardization of interventions). This article discusses these initiatives more in detail and provides exemplar cases to illustrate how the methodological challenges have been tackled. The initiatives have surpassed expectations, resulting in a renaissance in surgical research throughout the United Kingdom, such that the number of patients entering surgical randomized controlled trials has doubled.

Effects of a Financial Incentive on Health Researchers’ Response to an Online Survey: a Randomized Controlled Trial

PubMed Central

Petticrew, Mark; Calnan, Mike; Nazareth, Irwin

2010-01-01

Background Nonresponse to questionnaires can affect the validity of surveys and introduce bias. Offering financial incentives can increase response rates to postal questionnaires, but the effect of financial incentives on response rates to online surveys is less clear. Objective As part of a survey, we aimed to test whether knowledge of a financial incentive would increase the response rate to an online questionnaire. Methods A randomized controlled trial of 485 UK-based principal investigators of publicly funded health services and population health research. Participants were contacted by email and invited to complete an online questionnaire via an embedded URL. Participants were randomly allocated to groups with either “knowledge of” or “no knowledge of” a financial incentive (£10 Amazon gift voucher) to be provided on completion of the survey. At the end of the study, gift vouchers were given to all participants who completed the questionnaire regardless of initial randomization status. Four reminder emails (sent from the same email address as the initial invitation) were sent out to nonrespondents at one, two, three, and four weeks; a fifth postal reminder was also undertaken. The primary outcome measure for the trial was the response rate one week after the second reminder. Response rate was also measured at the end of weeks one, two, three, four, and five, and after a postal reminder was sent. Results In total, 243 (50%) questionnaires were returned (232 completed, 11 in which participation was declined). One week after the second reminder, the response rate in the “knowledge” group was 27% (66/244) versus 20% (49/241) in the “no knowledge” group (χ21 = 3.0, P = .08). The odds ratio for responding among those with knowledge of an incentive was 1.45 (95% confidence interval [CI] 0.95 - 2.21). At the third reminder, participants in the “no knowledge” group were informed about the incentive, ending the randomized element of the study. However we continued to follow up all participants, and from reminder three onwards, no significant differences were observed in the response rates of the two groups. Conclusions Knowledge of a financial incentive did not significantly increase the response rate to an online questionnaire. Future surveys should consider including a randomized element to further test the utility of offering incentives of other types and amounts to participate in online questionnaires. Trial Registration ISRCTN59912797; http://www.controlled-trials.com/ISRCTN59912797 (Archived by WebCite at http://www.webcitation.org/5iPPLbT7s) PMID:20457556

Cinnamomum zeylanicum (Ceylon cinnamon) as a potential pharmaceutical agent for type-2 diabetes mellitus: study protocol for a randomized controlled trial.

PubMed

Ranasinghe, Priyanga; Galappaththy, Priyadarshani; Constantine, Godwin Roger; Jayawardena, Ranil; Weeratunga, Hasitha Dhananjaya; Premakumara, Sirimal; Katulanda, Prasad

2017-09-29

Previous studies have explored the anti-diabetic effects of Cinnamomum cassia extract in vivo and in vitro. However, there are no studies at present exploring the effects of the indigenous species of Sri Lankan cinnamon (Cinnamomum zeylanicum) in patients with diabetes mellitus. The present study aims to evaluate the potential effects of Cinnamomum zeylanicum extract as a pharmaceutical agent in patients with type-2 diabetes mellitus. The study will be conducted as a randomized, double-blind, placebo-controlled clinical trial for a period of 4 months at the Medical Clinic, University Medical Unit, National Hospital of Sri Lanka. A total of 210 subjects with diabetes, in three equal groups, will be recruited for the study. The patients will be randomized in a 1:1:1 ratio according to the method of block randomization and the subjects will be randomly and equally assigned into two test groups (n = 70 each) and one placebo group (n = 70). The population will be stratified at randomization based on age, gender and disease severity. The treatment drug is a capsule containing Cinnamomum zeylanicum extract as the active ingredient and the placebo capsule will contain lactose monohydrate. Two doses of Cinnamomum zeylanicum extracts (250 mg and 500 mg of the cinnamon extract) will be used. The study drugs will be double blinded to both investigators and participants. The visits and the evaluations will be done as follows: screening (visit 0), 1 month (visit 1), 2 months (visit 2), 3 months (visit 3) and 4 months (visit 4). The following primary outcome measures will be evaluated: glycosylated hemoglobin (HbA 1 c), fasting plasma glucose (FPG) and serum insulin. Secondary outcome measures include: Body Mass Index (BMI) and other anthropometric parameters, blood pressure, total cholesterol, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) and triglycerides (TAG). Data will be analyzed using SPSS version 14. We describe the protocol for a clinical trial design evaluating the effects of Cinnamomum zeylanicum (Ceylon cinnamon) in patients with type-2 diabetes mellitus. The result of the present study, positive or negative, should provide a step change in the evidence guiding current and future policies regarding the use of cinnamon dietary supplementation in patients with diabetes. Sri Lanka Clinical Trials Registry (SLCTR), identifier: SLCTR/2017/010 ( http://slctr.lk/trials/714 ). Registered on 5 April 2017; study protocol version 3.1 21 March 2017.

A Randomized Controlled Trial to Test the Effectiveness of an Immersive 3D Video Game for Anxiety Prevention among Adolescents

PubMed Central

Scholten, Hanneke; Malmberg, Monique; Lobel, Adam; Engels, Rutger C. M. E.; Granic, Isabela

2016-01-01

Adolescent anxiety is debilitating, the most frequently diagnosed adolescent mental health problem, and leads to substantial long-term problems. A randomized controlled trial (n = 138) was conducted to test the effectiveness of a biofeedback video game (Dojo) for adolescents with elevated levels of anxiety. Adolescents (11–15 years old) were randomly assigned to play Dojo or a control game (Rayman 2: The Great Escape). Initial screening for anxiety was done on 1,347 adolescents in five high schools; only adolescents who scored above the “at-risk” cut-off on the Spence Children Anxiety Survey were eligible. Adolescents’ anxiety levels were assessed at pre-test, post-test, and at three month follow-up to examine the extent to which playing Dojo decreased adolescents’ anxiety. The present study revealed equal improvements in anxiety symptoms in both conditions at follow-up and no differences between Dojo and the closely matched control game condition. Latent growth curve models did reveal a steeper decrease of personalized anxiety symptoms (not of total anxiety symptoms) in the Dojo condition compared to the control condition. Moderation analyses did not show any differences in outcomes between boys and girls nor did age differentiate outcomes. The present results are of importance for prevention science, as this was the first full-scale randomized controlled trial testing indicated prevention effects of a video game aimed at reducing anxiety. Future research should carefully consider the choice of control condition and outcome measurements, address the potentially high impact of participants’ expectations, and take critical design issues into consideration, such as individual- versus group-based intervention and contamination issues. PMID:26816292

Evaluation of a specialized oncology nursing supportive care intervention in newly diagnosed breast and colorectal cancer patients following surgery: a cluster randomized trial.

PubMed

Sussman, Jonathan; Bainbridge, Daryl; Whelan, Timothy J; Brazil, Kevin; Parpia, Sameer; Wiernikowski, Jennifer; Schiff, Susan; Rodin, Gary; Sergeant, Myles; Howell, Doris

2018-05-01

Better coordination of supportive services during the early phases of cancer care has been proposed to improve the care experience of patients. We conducted a randomized trial to test a community-based nurse-led coordination of care intervention in cancer patients. Surgical practices were cluster randomized to a control group involving usual care practices or a standardized nursing intervention consisting of an in-person supportive care assessment with ongoing support to meet identified needs, including linkage to community services. Newly diagnosed breast and colorectal cancer patients within 7 days of cancer surgery were eligible. The primary outcome was the patient-reported outcome (PRO) of continuity of care (CCCQ) measured at 3 weeks. Secondary outcomes included unmet supportive care needs (SCNS), quality of life (EORTC QLQ-C30), health resource utilization, and level of uncertainty with care trajectory (MUIS) at 3 and/or 8 weeks. A total of 121 breast and 72 colorectal patients were randomized through 28 surgical practices. There was a small improvement in the informational domain of continuity of care (difference 0.29 p = 0.05) and a trend to less emergency room use (15.8 vs 7.1%) (p = 0.07). There were no significant differences between groups on unmet need, quality of life, or uncertainty. We did not find substantial gaps in the PROs measured immediately following surgery for breast and colorectal cancer patients. The results of this study support a more targeted approach based on need and inform future research focused on improving navigation during the initial phases of cancer treatment. ClinicalTrials.gov Identifier: NCT00182234. SONICS-Effectiveness of Specialist Oncology Nursing.

Teaching tobacco dependence treatment and counseling skills during medical school: rationale and design of the Medical Students helping patients Quit tobacco (MSQuit) group randomized controlled trial

PubMed Central

Hayes, Rashelle B.; Geller, Alan; Churchill, Linda; Jolicoeur, Denise; Murray, David M.; Shoben, Abigail; David, Sean P.; Adams, Michael; Okuyemi, Kola; Fauver, Randy; Gross, Robin; Leone, Frank; Xiao, Rui; Waugh, Jonathan; Crawford, Sybil; Ockene, Judith K.

2014-01-01

INTRODUCTION Physician-delivered tobacco treatment using the 5As is clinically recommended, yet its use has been limited. Lack of adequate training and confidence to provide tobacco treatment are cited as leading reasons for limited 5A use. Tobacco dependence treatment training while in medical school is recommended, but is minimally provided. The MSQuit trial (Medical Students helping patients Quit tobacco) aims to determine if a multi-modal and theoretically-guided tobacco educational intervention will improve tobacco dependence treatment skills (i.e. 5As) among medical students. METHODS/DESIGN 10 U.S. medical schools were pair-matched and randomized in a group-randomized controlled trial to evaluate whether a multi-modal educational (MME) intervention compared to traditional education (TE) will improve observed tobacco treatment skills. MME is primarily composed of TE approaches (i.e. didactics) plus a 1st year web-based course and preceptor-facilitated training during a 3rd year clerkship rotation. The primary outcome measure is an objective score on an Objective Structured Clinical Examination (OSCE) tobacco-counseling smoking case among 3rd year medical students from schools who implemented the MME or TE. DISCUSSION MSQuit is the first randomized to evaluate whether a tobacco treatment educational intervention implemented during medical school will improve medical students’ tobacco treatment skills. We hypothesize that the MME intervention will better prepare students in tobacco dependence treatment as measured by the OSCE. If a comprehensive tobacco treatment educational learning approach is effective, while also feasible and acceptable to implement, then medical schools may substantially influence skill development and use of the 5As among future physicians. PMID:24486635

Review of yoga therapy during cancer treatment.

PubMed

Danhauer, Suzanne C; Addington, Elizabeth L; Sohl, Stephanie J; Chaoul, Alejandro; Cohen, Lorenzo

2017-04-01

Reviews of yoga research that distinguish results of trials conducted during (versus after) cancer treatment are needed to guide future research and clinical practice. We therefore conducted a review of non-randomized studies and randomized controlled trials of yoga interventions for children and adults undergoing treatment for any cancer type. Studies were identified via research databases and reference lists. Inclusion criteria were the following: (1) children or adults undergoing cancer treatment, (2) intervention stated as yoga or component of yoga, and (3) publication in English in peer-reviewed journals through October 2015. Exclusion criteria were the following: (1) samples receiving hormone therapy only, (2) interventions involving meditation only, and (3) yoga delivered within broader cancer recovery or mindfulness-based stress reduction programs. Results of non-randomized (adult n = 8, pediatric n = 4) and randomized controlled trials (adult n = 13, pediatric n = 0) conducted during cancer treatment are summarized separately by age group. Findings most consistently support improvement in psychological outcomes (e.g., depression, distress, anxiety). Several studies also found that yoga enhanced quality of life, though further investigation is needed to clarify domain-specific efficacy (e.g., physical, social, cancer-specific). Regarding physical and biomedical outcomes, evidence increasingly suggests that yoga ameliorates sleep and fatigue; additional research is needed to advance preliminary findings for other treatment sequelae and stress/immunity biomarkers. Among adults undergoing cancer treatment, evidence supports recommending yoga for improving psychological outcomes, with potential for also improving physical symptoms. Evidence is insufficient to evaluate the efficacy of yoga in pediatric oncology. We describe suggestions for strengthening yoga research methodology to inform clinical practice guidelines.

Physical Activity Self-Management and Coaching Compared to Social Interaction in Huntington Disease: Results From the ENGAGE-HD Randomized, Controlled Pilot Feasibility Trial

PubMed Central

Quinn, Lori; Drew, Cheney; Kelson, Mark; Trubey, Rob; McEwan, Kirsten; Jones, Carys; Townson, Julia; Dawes, Helen; Tudor-Edwards, Rhiannon; Rosser, Anne; Hood, Kerenza

2017-01-01

Abstract Background. Self-management and self-efficacy for physical activity is not routinely considered in neurologic rehabilitation. Objective. This study assessed feasibility and outcomes of a 14-week physical activity self-management and coaching intervention compared with social contact in Huntington disease (HD) to inform the design of a future full-scale trial. Design. Assessor blind, multisite, randomized pilot feasibility trial. Setting. Participants were recruited and assessed at baseline, 16 weeks following randomization, and then again at 26 weeks in HD specialist clinics with intervention delivery by trained coaches in the participants’ homes. Patients and Intervention. People with HD were allocated to the ENGAGE-HD physical activity coaching intervention or a social interaction intervention. Measurements. Eligibility, recruitment, retention, and intervention participation were determined at 16 weeks. Other outcomes of interest included measures of mobility, self-efficacy, physical activity, and disease-specific measures of motor and cognition. Fidelity and costs for both the physical activity and social comparator interventions were established. Results. Forty percent (n = 46) of eligible patients were enrolled; 22 were randomized to the physical intervention and 24 to social intervention. Retention rates in the physical intervention and social intervention were 77% and 92%, respectively. Minimum participation criteria were achieved by 82% of participants in the physical intervention and 100% in the social intervention. There was no indication of between-group treatment effects on function; however, increases in self-efficacy for exercise and self-reported levels of physical activity in the physical intervention lend support to our predefined intervention logic model. Limitations. The use of self-report measures may have introduced bias. Conclusions. An HD physical activity self-management and coaching intervention is feasible and worthy of further investigation. PMID:28371942

A Randomized Controlled Trial of Mentoring Interventions for Underrepresented Minorities.

PubMed

Lewis, Vivian; Martina, Camille A; McDermott, Michael P; Trief, Paula M; Goodman, Steven R; Morse, Gene D; LaGuardia, Jennifer G; Sharp, Daryl; Ryan, Richard M

2016-07-01

To conduct a randomized controlled trial to evaluate the effects of different mentoring interventions on the basic psychological need satisfaction of underrepresented minorities and women in academia. Participants were 150 mentor/protégé dyads from three academic medical centers and eight other colleges and universities in western and central New York, randomized from 2010 to 2013 into mentor training (using principles of self-determination theory); peer mentoring for protégés; mentor training and peer mentoring for protégés combined; or control/usual practice. Protégé participants were graduate students, fellows, and junior faculty who were from underrepresented groups based on race, ethnicity, gender, or disability.The primary analysis was a comparison of intervention effects on changes in protégés' satisfaction of their basic psychological needs (competence, autonomy, and relatedness) with their mentor. They completed a well-validated, online questionnaire every two months for one year. There was no significant effect at the end of one year of either mentor training or peer mentoring on protégés' psychological basic need satisfaction with mentor specifically or at work in general. Exploratory analyses showed a significant effect of the mentor-based intervention on the protégés' overall psychological need satisfaction with their mentor at two months, the time point closest to completing mentor training. This randomized controlled trial showed a potential short-term effect of mentor training on changing basic psychological need satisfaction of underrepresented scholars with their mentors. Despite the lack of sustained effect of either mentor training or peer mentoring, these short-term changes suggest feasibility and potential for future study.

CITRUS, cervical cancer screening trial by randomization of HPV testing intervention for upcoming screening: Design, methods and baseline data of 18,471 women.

PubMed

Morisada, Tohru; Teramoto, Katsuhiro; Takano, Hirokuni; Sakamoto, Ikuko; Nishio, Hiroshi; Iwata, Takashi; Hashi, Akihiko; Katoh, Ryohei; Okamoto, Aikou; Sasaki, Hiroshi; Nakatani, Eiji; Teramukai, Satoshi; Aoki, Daisuke

2017-10-01

To assess the efficacy of screening with concurrent liquid-based cytology and human papillomavirus (HPV) testing for primary cervical cancer screening, we initiated a randomized trial entitled CervIcal cancer screening Trial by Randomization of HPV testing intervention for Upcoming Screening (CITRUS). Between June 2013 and March 2015, women aged 30-64 years of age who participated in a regular cervical cancer screening program (every 2 years) were invited to enrollment of our study. After giving their informed consent, 18,402 women were randomly assigned to liquid-based cytology as the control group (n=9145) or to HPV DNA testing with liquid-based cytology as the intervention group (n=9257). We subsequently compared the incidence rate of cervical intraepithelial neoplasia (CIN), the rate of false positive tests and the rate of overdiagnosis, as well as assessing the risks and benefits of receiving screening for women in both groups. The primary outcome of our study was the incidence of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) during the study period of around 6 years. In the control group, 97.9% of women were NILM, and 2.06% ASC-US or worse (ASC-US+). In the intervention group, 87.13% of women were NILM/HPV negative, 0.72% ASC-US/HPV negative, 10.34% NILM/HPV positive, 0.69% ASC-US/HPV positive, 0.90% worse than ASC-US/either HPV. Positive HPV testing was not linearly related to age in our study. Insights from CITRUS will provide future prospects for cervical cancer screening focused on the use of HPV testing in Japan. NCT01895517, UMIN000010843, TRIUC1312. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Pilot Randomized Clinical Trial of Intermittent Occlusion Therapy Liquid Crystal Glasses versus Traditional Patching for Treatment of Moderate Unilateral Amblyopia

PubMed Central

Wang, Jingyun; Neely, Daniel E.; Galli, Jay; Schliesser, Joshua; Graves, April; Damarjian, Tina G.; Kovarik, Jessica; Bowsher, James; Smith, Heather A.; Donaldson, Dana; Haider, Kathryn M.; Roberts, Gavin J.; Sprunger, Derek T.; Plager, David A.

2017-01-01

INTRODUCTION This pilot study was designed to compare the effectiveness of intermittent occlusion therapy (IO-Therapy) using liquid crystal glasses versus continuous occlusion therapy using traditional adhesive patches for treating amblyopia. DESIGN A randomized controlled trial. Children 3–8 years of age with previously untreated, moderate, unilateral amblyopia (visual acuity of 20/40 to 20/100 in the amblyopic eye) were enrolled. Amblyopia was associated with strabismus, anisometropia, or both. All subjects had worn optimal refractive correction (if needed) for at least 12 weeks without improvement. Subjects were randomized into two treatment groups: a 4-hour IO-Therapy Group with liquid crystal glasses (Amblyz™), set at 30-second opaque/transparent intervals (occluded 50% of wear time) or a 2-hour continuous Patching Group (occluded 100% of wear time). For each patient, visual acuity was measured with the ATS-HOTV method before and after 12 weeks of treatment. RESULTS At the conclusion of the first 12 week-treatment interval, data from 34 patients were available for analysis. Amblyopic eye visual acuity improvement from baseline was 0.15±0.12 (95% CI=0.09 to 0.15) logMAR in the IO-Therapy Group (N=19) and 0.15±0.11 (95% CI=0.1 to 0.15) logMAR in the Patching Group (N=15). Improvements in both groups were significant. The difference between groups was not statistically significant (P=0.73). No adverse effects were reported. CONCLUSION In this pilot study, IO-Therapy with Amblyz liquid crystal glasses is not inferior to adhesive patching and is a promising alternative treatment for children 3–8 years of age with moderate amblyopia. A larger randomized clinical trial is needed to confirm results in future. PMID:27418249

Design, randomization and methodology of the TriAtiva Program to reduce obesity in school children in Southern Brazil.

PubMed

Friedrich, Roberta R; Caetano, Lisandrea C; Schiffner, Mariana D; Wagner, Mário B; Schuch, Ilaine

2015-04-11

The prevalence of child obesity in Brazil has increased rapidly in recent decades. There is, therefore, an urgent need to develop effective strategies to prevent and control child obesity. In light of these considerations, an intervention program with a focus on nutrition education and physical activity was developed for to prevent and control obesity in schools. The intervention was called the TriAtiva Program: Education, Nutrition and Physical Activity. This article describes the design, randomization and method used to evaluate the TriAtiva program. This randomized controlled cluster trial was performed in 12 municipal schools in the city of Porto Alegre/RS (six schools in the intervention group and six control schools) which offered first- through fourth grade, during one school year. The TriAtiva Program was implemented through educational activities related to healthy eating and physical activity, creating an environment which promoted student health while involving the school community and student families. The primary outcome of the present study was body mass, while its secondary outcomes were waist circumference, percent body fat, blood pressure and behavioural variables such as eating habits and physical activity levels, as well as the prevalence, incidence and remission rates of obesity. The intervention was developed based on a comprehensive review of controlled trials of similar design. The TriAtiva Program: Education, Nutrition and Physical Activity was the first study in Southern Brazil to use a randomized controlled design to evaluate an intervention involving both nutrition education and physical activity in schools. Our results will contribute to the development of future interventions aimed at preventing and controlling child obesity in schools, especially in Brazil. Brazilian Clinical Trials Registry (REBEC) number RBR2xx2z4.

Creative music therapy to promote brain structure, function, and neurobehavioral outcomes in preterm infants: a randomized controlled pilot trial protocol.

PubMed

Haslbeck, Friederike Barbara; Bucher, Hans-Ulrich; Bassler, Dirk; Hagmann, Cornelia

2017-01-01

Preterm birth is associated with increased risk of neurological impairment and deficits in cognition, motor function, and behavioral problems. Limited studies indicate that multi-sensory experiences support brain development in preterm infants. Music appears to promote neurobiological processes and neuronal learning in the human brain. Creative music therapy (CMT) is an individualized, interactive therapeutic approach based on the theory and methods of Nordoff and Robbins. CMT may promote brain development in preterm infants via concurrent interaction and meaningful auditory stimulation. We hypothesize that preterm infants who receive creative music therapy during neonatal intensive care admission will have developmental benefits short- and long-term brain function. A prospective, randomized controlled single-center pilot trial involving 60 clinically stable preterm infants under 32 weeks of gestational age is conducted in preparation for a multi-center trial. Thirty infants each are randomized to either standard neonatal intensive care or standard care with CMT. Music therapy intervention is approximately 20 min in duration three times per week. A trained music therapist sings for the infants in lullaby style, individually entrained and adjusted to the infant's rhythm and affect. Primary objectives of this study are feasibility of protocol implementation and investigating the potential mechanism of efficacy for this new intervention. To examine the effect of this new intervention, non-invasive, quantitative magnetic resonance imaging (MRI) methods at corrected age and standardized neurodevelopmental assessments using the Bayley Scales of Infant and Toddler Development third edition at a corrected age of 24 months and Kaufman Assessment Battery for Children at 5 years will be performed. All assessments will be performed and analyzed by blinded experts. To our knowledge, this is the first randomized controlled clinical trial to systematically examine possible effects of creative music therapy on short- and long-term brain development in preterm infants. This project lies at the interface of music therapy, neuroscience, and medical imaging. New insights into the potential role and impact of music on brain function and development may be elucidated. If such a low-cost, low-risk intervention is demonstrated in a future multi-center trial to be effective in supporting brain development in preterm neonates, findings could have broad clinical implications for this vulnerable patient population. ClinicalTrials.gov, NCT02434224.

Dose–response effects of aerobic exercise on energy compensation in postmenopausal women: combined results from two randomized controlled trials

PubMed Central

McNeil, J; Brenner, D R; Courneya, K S; Friedenreich, C M

2017-01-01

Background/objectives: Despite the clear health benefits of exercise, exercised-induced weight loss is often less than expected. The term ‘exercise energy compensation’ is used to define the amount of weight loss below what is expected for the amount of exercise energy expenditure. We examined the dose–response effects of exercise volume on energy compensation in postmenopausal women. Participants/methods: Data from Alberta Physical Activity and Breast Cancer Prevention (ALPHA) and Breast Cancer and Exercise Trial in Alberta (BETA) were combined for the present analysis. The ALPHA and BETA trials were two-centred, two-armed, 12-month randomized controlled trials. The ALPHA trial included 160 participants randomized to 225 min per week of aerobic exercise, and the BETA trial randomized 200 participants to each 150 and 300 min per week of aerobic exercise. All participants were aged 50–74 years, moderately inactive (<90 min per week of exercise), had no previous cancer diagnosis and a body mass index between 22 and 40 kg m−2. Energy compensation was based on changes in body composition (dual-energy X-ray absorptiometry scan) and estimated exercise energy expenditure from completed exercise volume. Associations between Δenergy intake, ΔVO2peak and Δphysical activity time with energy compensation were assessed. Results: No differences in energy compensation were noted between interventions. However, there were large inter-individual differences in energy compensation between participants; 9.4% experienced body composition changes that were greater than expected based on exercise energy expenditure, 64% experienced some degree of energy compensation and 26.6% experienced weight gain based on exercise energy expenditure. Increases in VO2peak were associated with reductions in energy compensation (β=−3.44 ml kg−1 min−1, 95% confidence interval for β=−4.71 to −2.17 ml kg−1 min−1; P=0.0001). Conclusions: Large inter-individual differences in energy compensation were noted, despite no differences between activity doses. In addition, increases in VO2peak were associated with lower energy compensation. Future studies are needed to identify behavioral and metabolic factors that may contribute to this large inter-individual variability in energy compensation. PMID:28360432

A randomized, controlled study of a healthy corner store initiative on the purchases of urban, low-income youth

PubMed Central

Lent, Michelle R.; Veur, Stephanie S. Vander; McCoy, Tara A.; Wojtanowski, Alexis C.; Sandoval, Brianna; Sherman, Sandy; Komaroff, Eugene; Foster, Gary D.

2014-01-01

Objective Although many initiatives exist to improve the availability of healthy foods in corner stores, few randomized trials have assessed their effects. This study evaluated, in a randomized, controlled trial, the effects of a first-generation healthy corner store intervention on students’ food and beverage purchases over a two-year period. Design and Methods Participants (n=767) were 4th-6th grade students. Ten schools and their nearby corner stores (n=24) were randomly assigned to the healthy corner store intervention or an assessment-only control. Intercept surveys directly assessed the nutritional characteristics of students’ corner store purchases at baseline, 1 and 2 years. Students’ weight and heights were measured at baseline, 1 and 2 years. Results There were no differences in energy content per intercept purchased from control or intervention schools at year 1 (p=0.12) or 2 (p=0.58). There were no differences between control and intervention students in BMI-z score (year 1, p=0.83; year 2, p=0. 98) or obesity prevalence (year 1, p=0.96; year 2, p=0.58). Conclusions A healthy corner store initiative did not result in significant changes in the energy content of corner store purchases or in continuous or categorical measures of obesity. These data will help to inform future interventions. PMID:25311881

Lumbar Sympathetic Plexus Block as a Treatment for Postamputation Pain: Methodology for a Randomized Controlled Trial.

PubMed

McCormick, Zachary L; Hendrix, Andrew; Dayanim, David; Clay, Bryan; Kirsling, Amy; Harden, Norman

2018-03-08

We present a technical protocol for rigorous assessment of patient-reported outcomes and psychophysical testing relevant to lumbar sympathetic blocks for the treatment of postamputation pain (PAP). This description is intended to inform future prospective investigation. Series of four participants from a blinded randomized sham-controlled trial. Tertiary, urban, academic pain medicine center. Four participants with a single lower limb amputation and associated chronic PAP. Participants were randomized to receive a lumbar sympathetic block with 0.25% bupivacaine or sham needle placement. Patient-rated outcome measures included the numerical rating scale (NRS) for pain, the McGill Pain Questionnaire-Short Form, Center for Epidemiological Studies Depression Scale, Pain and Anxiety Symptoms Scale-short version, and Pain Disability Index (PDI). Psychophysical and biometric testing was also performed, which included vibration sensation testing, pinprick sensation testing, brush sensation testing, Von Frey repeated weighted pinprick sensation, and thermal quantitative sensory testing. In the four described cases, treatment of PAP with a single lumbar sympathetic block but not sham intervention resulted in reduction of both residual limb pain and phantom limb pain as well as perceived disability on the PDI at three-month follow-up. An appropriately powered randomized controlled study using this methodology may not only aid in determining the possible clinical efficacy of lumbar sympathetic block in PAP, but could also improve our understanding of underlying pathophysiologic mechanisms of PAP.

The Effect of the Time of Injection of Intrathecal Analgesia on the Length of Early and Advanced Labor

DTIC Science & Technology

1999-10-01

Recommendations for future studies include a prospective randomized clinical trial to examine the effect of the timing of intrathecal narcotic...population and in clinical practice. Friedman (1978) Intrathecal Analgesia 7 however, does provide averages and upper statistical limits for the first and...morphine into the subarchnoid space of rats produced potent analgesia (Wang, 1977). These effects were then clinically applied in man for the relief of

Evidence-based medicine in plastic surgery: where did it come from and where is it going?

PubMed

Ricci, Joseph A; Desai, Naman S

2014-05-01

Evidence-based medicine, particularly randomized controlled trials, influence many of the daily decisions within plastic surgery as well as nearly every other medical specialty, and will continue to play a larger role in medicine in the future. Even though it is certainly not a new idea, evidence-based medicine continues to remain a hot topic among members of the healthcare community. As evidence-based medicine continues to grow and evolve, it is becoming more important for all physicians to understand the fundamentals of evidence-based medicine: how evidence-based medicine has changed, and how to successfully incorporate it into the daily practice of medicine. Admittedly, the wide acceptance and implementation of evidence-based medicine has been slower in surgical fields such as plastic surgery given the difficulty in performing large scale blinded randomized controlled trials due to the inherent nature of a surgical intervention as a treatment modality. Despite these challenges, the plastic surgery literature has recently begun to respond to the demand for more evidence-based medicine. Today's plastic surgeons are making a concerted embrace evidence-based medicine by increasing the amount of out of high-level clinical evidence and should be encouraged to continue to further their endeavors in the field of evidence-based medicine in the future. © 2014 Chinese Cochrane Center, West China Hospital of Sichuan University and Wiley Publishing Asia Pty Ltd.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis

PubMed Central

Papachristou, Georgios I.; Machicado, Jorge D.; Stevens, Tyler; Goenka, Mahesh Kumar; Ferreira, Miguel; Gutierrez, Silvia C.; Singh, Vikesh K.; Kamal, Ayesha; Gonzalez-Gonzalez, Jose A.; Pelaez-Luna, Mario; Gulla, Aiste; Zarnescu, Narcis O.; Triantafyllou, Konstantinos; Barbu, Sorin T.; Easler, Jeffrey; Ocampo, Carlos; Capurso, Gabriele; Archibugi, Livia; Cote, Gregory A.; Lambiase, Louis; Kochhar, Rakesh; Chua, Tiffany; Tiwari, Subhash Ch.; Nawaz, Haq; Park, Walter G.; de-Madaria, Enrique; Lee, Peter J.; Wu, Bechien U.; Greer, Phil J.; Dugum, Mohannad; Koutroumpakis, Efstratios; Akshintala, Venkata; Gougol, Amir

2017-01-01

Background We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. Methods The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Results Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. Conclusion APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials. PMID:28042246

Effective Strategies to Recruit Young Adults Into the TXT2BFiT mHealth Randomized Controlled Trial for Weight Gain Prevention

PubMed Central

Balestracci, Kate; Wong, Annette TY; Hebden, Lana; McGeechan, Kevin; Denney-Wilson, Elizabeth; Harris, Mark F; Phongsavan, Philayrath; Bauman, Adrian; Allman-Farinelli, Margaret

2015-01-01

Background Younger adults are difficult to engage in preventive health, yet in Australia they are gaining more weight and increasing in waist circumference faster than middle-to-older adults. A further challenge to engaging 18- to 35-year-olds in interventions is the limited reporting of outcomes of recruitment strategies. Objective This paper describes the outcomes of strategies used to recruit young adults to a randomized controlled trial (RCT), healthy lifestyle mHealth program, TXT2BFiT, for prevention of weight gain. The progression from enquiry through eligibility check to randomization into the trial and the costs of recruitment strategies are reported. Factors associated with nonparticipation are explored. Methods Participants were recruited either via letters of invitation from general practitioners (GPs) or via electronic or print advertisements, including Facebook and Google—social media and advertising—university electronic newsletters, printed posters, mailbox drops, and newspapers. Participants recruited from GP invitation letters had an appointment booked with their GP for eligibility screening. Those recruited from other methods were sent an information pack to seek approval to participate from their own GP. The total number and source of enquiries were categorized according to eligibility and subsequent completion of steps to enrolment. Cost data and details of recruitment strategies were recorded. Results From 1181 enquiries in total from all strategies, 250 (21.17%) participants were randomized. A total of 5311 invitation letters were sent from 12 GP practices—16 participating GPs. A total of 131 patients enquired with 68 participants randomized (68/74 of those eligible, 92%). The other recruitment methods yielded the remaining 182 randomized participants. Enrolment from print media was 26% of enquiries, from electronic media was 20%, and from other methods was 3%. Across all strategies the average cost of recruitment was Australian Dollar (AUD) $139 per person. The least expensive modality was electronic (AUD $37), largely due to a free feature story on one university Web home page, despite Facebook advertising costing AUD $945 per enrolment. The most expensive was print media at AUD $213 and GP letters at AUD $145 per enrolment. Conclusions The research indicated that free electronic media was the most cost-effective strategy, with GP letters the least expensive of the paid strategies in comparison to the other strategies. This study is an important contribution for future research into efficacy, translation, and implementation of cost-effective programs for the prevention of weight gain in young adults. Procedural frameworks for recruitment protocols are required, along with systematic reporting of recruitment strategies to reduce unnecessary expenditure and allow for valuable public health prevention programs to go beyond the research setting. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000924853; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362872 (Archived by WebCite at http://www.webcitation.org/6YpNfv1gI). PMID:26048581

The importance of preservation of the ethical principle of equipoise in the design of clinical trials: relative impact of the methodological quality domains on the treatment effect in randomized controlled trials.

PubMed

Djulbegovic, Benjamin; Cantor, Alan; Clarke, Mike

2003-01-01

Previous research has identified methodological problems in the design and conduct of randomized trials that could, if left unaddressed, lead to biased results. In this report we discuss one such problem, inadequate control intervention, and argue that it can be by far the most important design characteristic of randomized trials in overestimating the effect of new treatments. Current guidelines for the design and reporting of randomized trials, such as the Consolidated Standards of Reporting Trials (CONSORT) statement, do not address the choice of the comparator intervention. We argue that an adequate control intervention can be selected if people designing a trial explicitly take into consideration the ethical principle of equipoise, also known as "the uncertainty principle."

Review of Recent Methodological Developments in Group-Randomized Trials: Part 2-Analysis.

PubMed

Turner, Elizabeth L; Prague, Melanie; Gallis, John A; Li, Fan; Murray, David M

2017-07-01

In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have updated that review with developments in analysis of the past 13 years, with a companion article to focus on developments in design. We discuss developments in the topics of the earlier review (e.g., methods for parallel-arm GRTs, individually randomized group-treatment trials, and missing data) and in new topics, including methods to account for multiple-level clustering and alternative estimation methods (e.g., augmented generalized estimating equations, targeted maximum likelihood, and quadratic inference functions). In addition, we describe developments in analysis of alternative group designs (including stepped-wedge GRTs, network-randomized trials, and pseudocluster randomized trials), which require clustering to be accounted for in their design and analysis.

Run-Reversal Equilibrium for Clinical Trial Randomization

PubMed Central

Grant, William C.

2015-01-01

In this paper, we describe a new restricted randomization method called run-reversal equilibrium (RRE), which is a Nash equilibrium of a game where (1) the clinical trial statistician chooses a sequence of medical treatments, and (2) clinical investigators make treatment predictions. RRE randomization counteracts how each investigator could observe treatment histories in order to forecast upcoming treatments. Computation of a run-reversal equilibrium reflects how the treatment history at a particular site is imperfectly correlated with the treatment imbalance for the overall trial. An attractive feature of RRE randomization is that treatment imbalance follows a random walk at each site, while treatment balance is tightly constrained and regularly restored for the overall trial. Less predictable and therefore more scientifically valid experiments can be facilitated by run-reversal equilibrium for multi-site clinical trials. PMID:26079608

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

PubMed Central

2011-01-01

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

Patient and Physician Views about Protocolized Dialysis Treatment in Randomized Trials and Clinical Care

PubMed Central

Kraybill, Ashley; Dember, Laura M.; Joffe, Steven; Karlawish, Jason; Ellenberg, Susan S.; Madden, Vanessa; Halpern, Scott D.

2016-01-01

Background Pragmatic trials comparing standard-of-care interventions may improve the quality of care for future patients, but raise ethical questions about limitations on decisional autonomy. We sought to understand how patients and physicians view and respond to these questions in the contexts of pragmatic trials and of usual clinical care. Methods We conducted scenario-based, semi-structured interviews with 32 patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis in outpatient dialysis units and with 24 nephrologists. Each participant was presented with two hypothetical scenarios in which a protocolized approach to hemodialysis treatment time was adopted for the entire dialysis unit as part of a clinical trial or a new clinical practice. Results A modified grounded theory analysis revealed three major themes: 1) the value of research, 2) the effect of protocolized care on patient and physician autonomy, and 3) information exchange between patients and physicians, including the mechanism of consent. Most patients and physicians were willing to relinquish decisional autonomy and were more willing to relinquish autonomy for research purposes than in clinical care. Patients’ concerns towards clinical trials were tempered by their desires for certainty for a positive outcome and for physician validation. Patients tended to believe that being informed about research was more important than the actual mechanism of consent, and most were content with being able to opt out from participating. Conclusions This qualitative study suggests the general acceptability of a pragmatic clinical trial comparing standard-of-care interventions that limits decisional autonomy for nephrologists and patients receiving hemodialysis. Future studies are needed to determine whether similar findings would emerge among other patients and providers considering other standard-of-care trials. PMID:27833931

Patient and Physician Views about Protocolized Dialysis Treatment in Randomized Trials and Clinical Care.

PubMed

Kraybill, Ashley; Dember, Laura M; Joffe, Steven; Karlawish, Jason; Ellenberg, Susan S; Madden, Vanessa; Halpern, Scott D

2016-01-01

Pragmatic trials comparing standard-of-care interventions may improve the quality of care for future patients, but raise ethical questions about limitations on decisional autonomy. We sought to understand how patients and physicians view and respond to these questions in the contexts of pragmatic trials and of usual clinical care. We conducted scenario-based, semi-structured interviews with 32 patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis in outpatient dialysis units and with 24 nephrologists. Each participant was presented with two hypothetical scenarios in which a protocolized approach to hemodialysis treatment time was adopted for the entire dialysis unit as part of a clinical trial or a new clinical practice. A modified grounded theory analysis revealed three major themes: 1) the value of research, 2) the effect of protocolized care on patient and physician autonomy, and 3) information exchange between patients and physicians, including the mechanism of consent. Most patients and physicians were willing to relinquish decisional autonomy and were more willing to relinquish autonomy for research purposes than in clinical care. Patients' concerns towards clinical trials were tempered by their desires for certainty for a positive outcome and for physician validation. Patients tended to believe that being informed about research was more important than the actual mechanism of consent, and most were content with being able to opt out from participating. This qualitative study suggests the general acceptability of a pragmatic clinical trial comparing standard-of-care interventions that limits decisional autonomy for nephrologists and patients receiving hemodialysis. Future studies are needed to determine whether similar findings would emerge among other patients and providers considering other standard-of-care trials.

Short and Long Term Effects of Left and Bilateral Repetitive Transcranial Magnetic Stimulation in Schizophrenia Patients with Auditory Verbal Hallucinations: A Randomized Controlled Trial

PubMed Central

Bais, Leonie; Vercammen, Ans; Stewart, Roy; van Es, Frank; Visser, Bert; Aleman, André; Knegtering, Henderikus

2014-01-01

Background Repetitive transcranial magnetic stimulation of the left temporo-parietal junction area has been studied as a treatment option for auditory verbal hallucinations. Although the right temporo-parietal junction area has also shown involvement in the genesis of auditory verbal hallucinations, no studies have used bilateral stimulation. Moreover, little is known about durability effects. We studied the short and long term effects of 1 Hz treatment of the left temporo-parietal junction area in schizophrenia patients with persistent auditory verbal hallucinations, compared to sham stimulation, and added an extra treatment arm of bilateral TPJ area stimulation. Methods In this randomized controlled trial, 51 patients diagnosed with schizophrenia and persistent auditory verbal hallucinations were randomly allocated to treatment of the left or bilateral temporo-parietal junction area or sham treatment. Patients were treated for six days, twice daily for 20 minutes. Short term efficacy was measured with the Positive and Negative Syndrome Scale (PANSS), the Auditory Hallucinations Rating Scale (AHRS), and the Positive and Negative Affect Scale (PANAS). We included follow-up measures with the AHRS and PANAS at four weeks and three months. Results The interaction between time and treatment for Hallucination item P3 of the PANSS showed a trend for significance, caused by a small reduction of scores in the left group. Although self-reported hallucination scores, as measured with the AHRS and PANAS, decreased significantly during the trial period, there were no differences between the three treatment groups. Conclusion We did not find convincing evidence for the efficacy of left-sided rTMS, compared to sham rTMS. Moreover, bilateral rTMS was not superior over left rTMS or sham in improving AVH. Optimizing treatment parameters may result in stronger evidence for the efficacy of rTMS treatment of AVH. Moreover, future research should consider investigating factors predicting individual response. Trial Registration Dutch Trial Register NTR1813 PMID:25329799

Pyridostigmine bromide versus fludrocortisone in the treatment of orthostatic hypotension in Parkinson's disease - a randomized controlled trial.

PubMed

Schreglmann, S R; Büchele, F; Sommerauer, M; Epprecht, L; Kägi, G; Hägele-Link, S; Götze, O; Zimmerli, L; Waldvogel, D; Baumann, C R

2017-04-01

Evidence for effective treatment options for orthostatic hypotension (OH) in Parkinson's disease (PD) is scarce. Elevation of cholinergic tone with pyridostigmine bromide has been reported as a way to improve blood pressure (bp) regulation in neurogenic hypotension without causing supine hypertension. This was a double-centre, double-blind, randomized, active-control, crossover, phase II non-inferiority trial of pyridostigmine bromide for OH in PD (clinicaltrials.gov NCT01993680). Patients with confirmed OH were randomized to 14 days 3 × 60 mg/day pyridostigmine bromide or 1 × 0.2 mg/day fludrocortisone before crossover. Outcome was measured by peripheral and central bp monitoring during the Schellong manoeuvre and questionnaires. Thirteen participants were enrolled between April 2013 and April 2015 with nine participants completing each trial arm. Repeated measures comparison showed a significant 37% improvement with fludrocortisone for the primary outcome diastolic bp drop on orthostatic challenge (baseline 22.9 ± 13.6 vs. pyridostigmine bromide 22.1 ± 17.0 vs. fludrocortisone 14.0 ± 12.6 mmHg; P = 0.04), whilst pyridostigmine bromide had no effect. Fludrocortisone caused an 11% peripheral systolic supine bp rise (baseline 128.4 ± 12.8 vs. pyridostigmine bromide 130.4 ± 18.3 vs. fludrocortisone 143.2 ± 10.1 mmHg; P = 0.01) but no central mean arterial supine bp rise (baseline 107.2 ± 7.8 vs. pyridostigmine bromide 97.0 ± 12.0 vs. fludrocortisone 107.3 ± 6.3 mmHg; P = 0.047). Subjective OH severity, motor score and quality of life remained unchanged by both study interventions. Pyridostigmine bromide is inferior to fludrocortisone in the treatment of OH in PD. This trial provides first objective evidence of the efficacy of 0.2 mg/day fludrocortisone for OH in PD, causing minor peripheral but no central supine hypertension. In addition to peripheral bp, future trials should include central bp measurements, known to correlate more closely with cardiovascular risk. © 2017 EAN.

Family planning to promote physical activity: a randomized controlled trial protocol.

PubMed

Quinlan, Alison; Rhodes, Ryan E; Blanchard, Chris M; Naylor, Patti-Jean; Warburton, Darren E R

2015-10-05

Physical activity is associated with the reduction of several chronic conditions in adults. Additionally, physical activity is extremely important for children for their development and cognitive functioning and also to create a physically active lifestyle that continues into adulthood. Despite the known benefits of physical activity, only one in five adults are achieving the public health recommendations of 150 minutes of moderate-to-vigorous physical activity per week and only 13 % of boys and 6 % of girls between the ages of 5 and 17 years are meeting the guidelines of 60 minutes per day. This study aims to evaluate whether a planning condition improves adherence to regular physical activity compared to an education-only control condition among families. Families are eligible if there is at least one child between the ages of 6 and 12 years who is not meeting the Canadian Physical Activity Guidelines. A six-month longitudinal randomized controlled trial will be used to compare the two conditions. Materials will be delivered at baseline with 'booster' sessions at six weeks and three months. Participants will be assessed at baseline and at six months with a fitness test, as well as questionnaires and accelerometery at baseline, six weeks, three months and six months. A total of 137 families have been recruited thus far from Greater Victoria. This study is ongoing and recruitment will continue until December 2015 with the target goal of reaching 160 families. This protocol describes the implementation of a randomized controlled trial that utilizes planning strategies to try and increase physical activity among families. Research findings could be useful in public health in providing effective strategies to families to help decrease sedentary lifestyles. Additionally, findings may help to inform future interventions aimed at increasing physical activity among families. This trial was registered on June 5, 2012 with the Clinical Trials Registry maintained by the National Library of Medicine at the National Institutes of Health. The registration ID is NCT01882192.

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.

Developing leadership capacity for guideline use: a pilot cluster randomized control trial.

PubMed

Gifford, Wendy A; Davies, Barbara L; Graham, Ian D; Tourangeau, Ann; Woodend, A Kirsten; Lefebre, Nancy

2013-02-01

The importance of leadership to influence nurses' use of clinical guidelines has been well documented. However, little is known about how to develop and evaluate leadership interventions for guideline use. The purpose of this study was to pilot a leadership intervention designed to influence nurses' use of guideline recommendations when caring for patients with diabetic foot ulcers in home care nursing. This paper reports on the feasibility of implementing the study protocol, the trial findings related to nursing process outcomes, and leadership behaviors. A mixed methods pilot study was conducted with a post-only cluster randomized controlled trial and descriptive qualitative interviews. Four units were randomized to control or experimental groups. Clinical and management leadership teams participated in a 12-week leadership intervention (workshop, teleconferences). Participants received summarized chart audit data, identified goals for change, and created a team leadership action. Criteria to assess feasibility of the protocol included: design, intervention, measures, and data collection procedures. For the trial, chart audits compared differences in nursing process outcomes. 8-item nursing assessments score. Secondary outcome: 5-item score of nursing care based on goals for change identified by intervention participants. Qualitative interviews described leadership behaviors that influenced guideline use. Conducting this pilot showed some aspects of the study protocol were feasible, while others require further development. Trial findings observed no significant difference in the primary outcome. A significant increase was observed in the 5-item score chosen by intervention participants (p = 0.02). In the experimental group more relations-oriented leadership behaviors, audit and feedback and reminders were described as leadership strategies. Findings suggest that a leadership intervention has the potential to influence nurses' use of guideline recommendations, but further work is required to refine the intervention and outcome measures. A taxonomy of leadership behaviors is proposed to inform future research. © 2012 The authors. World Views on Evidence-Based Nursing © Sigma Theta Tau International.

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

Physical and psychologic effects of aromatherapy inhalation on pregnant women: a randomized controlled trial.

PubMed

Igarashi, Toshiko

2013-10-01

Stress reduction care is important for pregnant women to decrease obstetric complications and children's health problems after birth. The aim of this study is to clarify the physical and psychologic effects of inhalation aromatherapy on pregnant women. Essential oils with high linalool and linalyl acetate content that may be used during pregnancy were selected and among these, and the one preferred by the participant was used. This was a prospective, randomized, controlled trial. This trial was performed at a gynecology outpatient department in a hospital in Kyoto, Japan. The study included pregnant women in week 28 of a single pregnancy with a normal course. Participants were randomly assigned into an aromatherapy group and a control group. They were seated in the resting, seated position for 10 minutes. During the latter 5 minutes of each 10-minute session, aromatherapy inhalation was performed for the aromatherapy group. Before and after the intervention, the Profile of Mood States (POMS) was measured. During the trial, the heart-rate fluctuations were measured for the autonomic nervous system regulation. A total of 13 pregnant women participated in the trial. Seven (7) participants were assigned to the aromatherapy group and 6 participants to the control group. The results of the POMS were such that based on an intragroup comparison, significant differences were observed in the Tension-Anxiety score (p<0.05) and the Anger-Hostility score (p<0.05), and the respective improvements observed were due to aromatherapy. The results of the autonomic nervous system regulation were such that based on an intragroup comparison within the aromatherapy group, the parasympathetic nerve activity increased significantly (p<0.05). Aromatherapy inhalation using essential oils containing linalyl acetate and linalool was found to be effective for the POMS and parasympathetic nerve activity, based on an intragroup comparison. However, based on a comparison between the groups, no substantial difference was observed; hence, further study is necessary in the future.

Feasibility of Pilates exercise to decrease falls risk: a pilot randomized controlled trial in community-dwelling older people.

PubMed

Barker, Anna L; Talevski, Jason; Bohensky, Megan A; Brand, Caroline A; Cameron, Peter A; Morello, Renata T

2016-10-01

To evaluate the feasibility of Pilates exercise in older people to decrease falls risk and inform a larger trial. Pilot Randomized controlled trial. Community physiotherapy clinic. A total of 53 community-dwelling people aged ⩾60 years (mean age, 69.3 years; age range, 61-84). A 60-minute Pilates class incorporating best practice guidelines for exercise to prevent falls, performed twice weekly for 12 weeks. All participants received a letter to their general practitioner with falls risk information, fall and fracture prevention education and home exercises. Indicators of feasibility included: acceptability (recruitment, retention, intervention adherence and participant experience survey); safety (adverse events); and potential effectiveness (fall, fall injury and injurious fall rates; standing balance; lower limb strength; and flexibility) measured at 12 and 24 weeks. Recruitment was achievable but control group drop-outs were high (23%). Of the 20 participants who completed the intervention, 19 (95%) attended ⩾75% of the classes and reported classes were enjoyable and would recommend them to others. The rate of fall injuries at 24 weeks was 42% lower and injurious fall rates 64% lower in the Pilates group, however, was not statistically significant (P = 0.347 and P = 0.136). Standing balance, lower-limb strength and flexibility improved in the Pilates group relative to the control group (P < 0.05). Estimates suggest a future definitive study would require 804 participants to detect a difference in fall injury rates. A definitive randomized controlled trial analysing the effect of Pilates in older people would be feasible and is warranted given the acceptability and potential positive effects of Pilates on fall injuries and fall risk factors. The protocol for this study is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN1262000224820). © The Author(s) 2015.

Impact of e-learning on nurses' and student nurses knowledge, skills, and satisfaction: a systematic review and meta-analysis.

PubMed

Lahti, Mari; Hätönen, Heli; Välimäki, Maritta

2014-01-01

To review the impact of e-learning on nurses' and nursing student's knowledge, skills and satisfaction related to e-learning. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to assess the impact of e-learning on nurses' and nursing student's knowledge, skills and satisfaction. Electronic databases including MEDLINE (1948-2010), CINAHL (1981-2010), Psychinfo (1967-2010) and Eric (1966-2010) were searched in May 2010 and again in December 2010. All RCT studies evaluating the effectiveness of e-learning and differentiating between traditional learning methods among nurses were included. Data was extracted related to the purpose of the trial, sample, measurements used, index test results and reference standard. An extraction tool developed for Cochrane reviews was used. Methodological quality of eligible trials was assessed. 11 trials were eligible for inclusion in the analysis. We identified 11 randomized controlled trials including a total of 2491 nurses and student nurses'. First, the random effect size for four studies showed some improvement associated with e-learning compared to traditional techniques on knowledge. However, the difference was not statistically significant (p=0.39, MD 0.44, 95% CI -0.57 to 1.46). Second, one study reported a slight impact on e-learning on skills, but the difference was not statistically significant, either (p=0.13, MD 0.03, 95% CI -0.09 to 0.69). And third, no results on nurses or student nurses' satisfaction could be reported as the statistical data from three possible studies were not available. Overall, there was no statistical difference between groups in e-learning and traditional learning relating to nurses' or student nurses' knowledge, skills and satisfaction. E-learning can, however, offer an alternative method of education. In future, more studies following the CONSORT and QUOROM statements are needed to evaluate the effects of these interventions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Implementing an evidence-based computerized decision support system to improve patient care in a general hospital: the CODES study protocol for a randomized controlled trial.

PubMed

Moja, Lorenzo; Polo Friz, Hernan; Capobussi, Matteo; Kwag, Koren; Banzi, Rita; Ruggiero, Francesca; González-Lorenzo, Marien; Liberati, Elisa Giulia; Mangia, Massimo; Nyberg, Peter; Kunnamo, Ilkka; Cimminiello, Claudio; Vighi, Giuseppe; Grimshaw, Jeremy; Bonovas, Stefanos

2016-07-07

Computerized decision support systems (CDSSs) are information technology-based software that provide health professionals with actionable, patient-specific recommendations or guidelines for disease diagnosis, treatment, and management at the point-of-care. These messages are intelligently filtered to enhance the health and clinical care of patients. CDSSs may be integrated with patient electronic health records (EHRs) and evidence-based knowledge. We designed a pragmatic randomized controlled trial to evaluate the effectiveness of patient-specific, evidence-based reminders generated at the point-of-care by a multi-specialty decision support system on clinical practice and the quality of care. We will include all the patients admitted to the internal medicine department of one large general hospital. The primary outcome is the rate at which medical problems, which are detected by the decision support software and reported through the reminders, are resolved (i.e., resolution rates). Secondary outcomes are resolution rates for reminders specific to venous thromboembolism (VTE) prevention, in-hospital all causes and VTE-related mortality, and the length of hospital stay during the study period. The adoption of CDSSs is likely to increase across healthcare systems due to growing concerns about the quality of medical care and discrepancy between real and ideal practice, continuous demands for a meaningful use of health information technology, and the increasing use of and familiarity with advanced technology among new generations of physicians. The results of our study will contribute to the current understanding of the effectiveness of CDSSs in primary care and hospital settings, thereby informing future research and healthcare policy questions related to the feasibility and value of CDSS use in healthcare systems. This trial is seconded by a specialty trial randomizing patients in an oncology setting (ONCO-CODES). ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02577198?term=NCT02577198&rank=1.

Chelation therapy after the Trial to Assess Chelation Therapy: results of a unique trial

PubMed Central

Avila, Maria D.; Escolar, Esteban; Lamas, Gervasio A.

2014-01-01

Purpose of review EDTA chelation therapy has been in off-label use for the treatment of atherosclerosis. We review the results of the first large-scale randomized trial of this treatment. Recent findings The trial to assess chelation therapy was a $30 million National Institutes of Health-funded study of the safety and efficacy of EDTA-based chelation infusions in 1708 post-myocardial infarction (MI) patients. The trial to assess chelation therapy demonstrated a significant (P = 0.035) 18% reduction in a combined primary endpoint of death, MI, stroke, coronary revascularization, or hospitalization for angina. In diabetic patients the benefit was more extreme, with a 41% relative reduction in risk (P = 0.0002) and a 43% reduction in total mortality (P = 0.011). Safety data were favorable. A reduction of oxidative stress by chelation of toxic metals has been proposed as a possible mechanism of action. Summary Recent research suggests that EDTA chelation may be a well-tolerated and effective treatment for post-MI patients. Future replication and mechanistic studies are important prior to implementation in all post-MI patients. PMID:25023079

The Long-Term Oxygen Treatment Trial for Chronic Obstructive Pulmonary Disease: Rationale, Design, and Lessons Learned.

PubMed

Yusen, Roger D; Criner, Gerard J; Sternberg, Alice L; Au, David H; Fuhlbrigge, Anne L; Albert, Richard K; Casaburi, Richard; Stoller, James K; Harrington, Kathleen F; Cooper, J Allen D; Diaz, Philip; Gay, Steven; Kanner, Richard; MacIntyre, Neil; Martinez, Fernando J; Piantadosi, Steven; Sciurba, Frank; Shade, David; Stibolt, Thomas; Tonascia, James; Wise, Robert; Bailey, William C

2018-01-01

The Long-Term Oxygen Treatment Trial demonstrated that long-term supplemental oxygen did not reduce time to hospital admission or death for patients who have stable chronic obstructive pulmonary disease and resting and/or exercise-induced moderate oxyhemoglobin desaturation, nor did it provide benefit for any other outcome measured in the trial. Nine months after initiation of patient screening, after randomization of 34 patients to treatment, a trial design amendment broadened the eligible population, expanded the primary outcome, and reduced the goal sample size. Within a few years, the protocol underwent minor modifications, and a second trial design amendment lowered the required sample size because of lower than expected treatment group crossover rates. After 5.5 years of recruitment, the trial met its amended sample size goal, and 1 year later, it achieved its follow-up goal. The process of publishing the trial results brought renewed scrutiny of the study design and the amendments. This article expands on the previously published design and methods information, provides the rationale for the amendments, and gives insight into the investigators' decisions about trial conduct. The story of the Long-Term Oxygen Treatment Trial may assist investigators in future trials, especially those that seek to assess the efficacy and safety of long-term oxygen therapy. Clinical trial registered with clinicaltrials.gov (NCT00692198).

Ageism in Studies on the Management of Osteoporosis.

PubMed

McGarvey, Caoimhe; Coughlan, Tara; O'Neill, Desmond

2017-07-01

To review the literature to assess whether the fact that osteoporosis is chiefly considered a disease of the older population was reflected in research in the area of the management of osteoporosis and to determine the extent of ageism in studies on the management of osteoporosis. Review. All randomized control trials on the management of osteoporosis entered in the Cochrane Library Database that reported mean age were included. Exclusion criteria were also examined. Of 284 randomized control trials identified, 102 were eligible for inclusion. Older adult trail participants. Mean age of participants and exclusion criteria used were analyzed. The mean age of all participants was 64.0, despite the fact that the average age at hip fracture is 83 for women and 84 for men. Overall, the mean age of those presenting with hip fractures is 84.8. Twenty-four (23%) of the 102 trials used older age as an exclusion factor. Other exclusion factors were long time since menopause, impaired cardiac or pulmonary function, dependent in ambulation, any severe comorbidity, dementia or any cognitive impairment, recent history of peptic ulcer disease or erosive gastric disease, uncontrolled hypertension, and psychiatric illness. These data show a distinct difference between the mean age of participants in studies of the management of osteoporosis and the mean age of those presenting with hip fractures. Given that osteoporosis is the leading cause of hip fractures, this finding could have a significant effect on future studies in this area. It would follow that future research should include a cohort of an age that is more reflective of those most likely to experience the adverse effects of osteoporosis. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Emergency management of severe hyperkalemia: Guideline for best practice and opportunities for the future.

PubMed

Rossignol, Patrick; Legrand, Matthieu; Kosiborod, Mikhail; Hollenberg, Steven M; Peacock, W Frank; Emmett, Michael; Epstein, Murray; Kovesdy, Csaba P; Yilmaz, Mehmet Birhan; Stough, Wendy Gattis; Gayat, Etienne; Pitt, Bertram; Zannad, Faiez; Mebazaa, Alexandre

2016-11-01

Hyperkalemia is a common electrolyte disorder, especially in chronic kidney disease, diabetes mellitus, or heart failure. Hyperkalemia can lead to potentially fatal cardiac dysrhythmias, and it is associated with increased mortality. Determining whether emergency therapy is warranted is largely based on subjective clinical judgment. The Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT) aimed to evaluate the current knowledge pertaining to the emergency treatment of hyperkalemia. The INI-CRCT developed a treatment algorithm reflecting expert opinion of best practices in the context of current evidence, identified gaps in knowledge, and set priorities for future research. We searched PubMed (to August 4, 2015) for consensus guidelines, reviews, randomized clinical trials, and observational studies, limited to English language but not by publication date. Treatment approaches are based on small studies, anecdotal experience, and traditional practice patterns. The safety and real-world effectiveness of standard therapies remain unproven. Prospective research is needed and should include studies to better characterize the population, define the serum potassium thresholds where life-threatening arrhythmias are imminent, assess the potassium and electrocardiogram response to standard interventions. Randomized, controlled trials are needed to test the safety and efficacy of new potassium binders for the emergency treatment of severe hyperkalemia in hemodynamically stable patients. Existing emergency treatments for severe hyperkalemia are not supported by a compelling body of evidence, and they are used inconsistently across institutions, with potentially significant associated side effects. Further research is needed to fill knowledge gaps, and definitive clinical trials are needed to better define optimal management strategies, and ultimately to improve outcomes in these patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using a UK Virtual Supermarket to Examine Purchasing Behavior Across Different Income Groups in the United Kingdom: Development and Feasibility Study

PubMed Central

Waterlander, Wilma Elzeline; Rayner, Mike; Scarborough, Peter

2017-01-01

Background The majority of food in the United Kingdom is purchased in supermarkets, and therefore, supermarket interventions provide an opportunity to improve diets. Randomized controlled trials are costly, time-consuming, and difficult to conduct in real stores. Alternative approaches of assessing the impact of supermarket interventions on food purchases are needed, especially with respect to assessing differential impacts on population subgroups. Objective The aim of this study was to assess the feasibility of using the United Kingdom Virtual Supermarket (UKVS), a three-dimensional (3D) computer simulation of a supermarket, to measure food purchasing behavior across income groups. Methods Participants (primary household shoppers in the United Kingdom with computer access) were asked to conduct two shopping tasks using the UKVS and complete questionnaires on demographics, food purchasing habits, and feedback on the UKVS software. Data on recruitment method and rate, completion of study procedure, purchases, and feedback on usability were collected to inform future trial protocols. Results A total of 98 participants were recruited, and 46 (47%) fully completed the study procedure. Low-income participants were less likely to complete the study (P=.02). Most participants found the UKVS easy to use (38/46, 83%) and reported that UKVS purchases resembled their usual purchases (41/46, 89%). Conclusions The UKVS is likely to be a useful tool to examine the effects of nutrition interventions using randomized controlled designs. Feedback was positive from participants who completed the study and did not differ by income group. However, retention was low and needs to be addressed in future studies. This study provides purchasing data to establish sample size requirements for full trials using the UKVS. PMID:28993301

Rates and determinants of informed consent: a case study of an international thromboprophylaxis trial.

PubMed

Smith, Orla M; McDonald, Ellen; Zytaruk, Nicole; Foster, Denise; Matte, Andrea; Clarke, France; Meade, Laurie; O'Callaghan, Nicole; Vallance, Shirley; Galt, Pauline; Rajbhandari, Dorrilyn; Rocha, Marcelo; Mehta, Sangeeta; Ferguson, Niall D; Hall, Richard; Fowler, Robert; Burns, Karen; Qushmaq, Ismael; Ostermann, Marlies; Heels-Ansdell, Diane; Cook, Deborah

2013-02-01

Successful completion of randomized trials depends upon efficiently and ethically screening patients and obtaining informed consent. Awareness of modifiable barriers to obtaining consent may inform ongoing and future trials. The objective of this study is to describe and examine determinants of consent rates in an international heparin thromboprophylaxis trial (Prophylaxis for ThromboEmbolism in Critical Care Trial, clinicaltrials.gov NCT00182143). Throughout the 4-year trial, research personnel approached eligible critically ill patients or their substitute decision makers for informed consent. Whether consent was obtained or declined was documented daily. The trial was conducted in 67 centers in 6 countries. A total of 3764 patients were randomized. The overall consent rate was 82.2% (range, 50%-100%) across participating centers. Consent was obtained from substitute decision makers and patients in 90.1% and 9.9% of cases, respectively. Five factors were independently associated with consent rates. Research coordinators with more experience achieved higher consent rates (odds ratio [OR], 3.43; 95% confidence interval, 2.42-4.86; P < .001 for those with >10 years of experience). Consent rates were higher in smaller intensive care units with less than 15 beds compared with intensive care units with 15 to 20 beds, 21 to 25 beds, and greater than 25 beds (all ORs, <0.5; P < .001) and were higher in centers with more than 1 full-time research staff (OR, 1.95; 95% confidence interval, 1.28-2.99; P < .001). Consent rates were lower in centers affiliated with the Canadian Critical Care Trials Group or the Australian and New Zealand Intensive Care Society Clinical Trials Group compared with other centers (OR, 0.57; 95% confidence interval, 0.42-0.77; P < .001). Finally, consent rates were highest during the pilot trial, lowest during the initiation of the full trial, and increased over years of recruitment (P < .001). Characteristics of study centers, research infrastructure, and experience were important factors associated with successfully procuring informed consent to participate in this thromboprophylaxis trial. Copyright © 2013 Elsevier Inc. All rights reserved.

Reporting of participant flow diagrams in published reports of randomized trials

PubMed Central

2011-01-01

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

Bayesian network meta-analysis for cluster randomized trials with binary outcomes.

PubMed

Uhlmann, Lorenz; Jensen, Katrin; Kieser, Meinhard

2017-06-01

Network meta-analysis is becoming a common approach to combine direct and indirect comparisons of several treatment arms. In recent research, there have been various developments and extensions of the standard methodology. Simultaneously, cluster randomized trials are experiencing an increased popularity, especially in the field of health services research, where, for example, medical practices are the units of randomization but the outcome is measured at the patient level. Combination of the results of cluster randomized trials is challenging. In this tutorial, we examine and compare different approaches for the incorporation of cluster randomized trials in a (network) meta-analysis. Furthermore, we provide practical insight on the implementation of the models. In simulation studies, it is shown that some of the examined approaches lead to unsatisfying results. However, there are alternatives which are suitable to combine cluster randomized trials in a network meta-analysis as they are unbiased and reach accurate coverage rates. In conclusion, the methodology can be extended in such a way that an adequate inclusion of the results obtained in cluster randomized trials becomes feasible. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of life skills building education and micronutrient supplements provided from preconception versus the standard of care on low birth weight births among adolescent and young Pakistani women (15-24 years): a prospective, population-based cluster-randomized trial.

PubMed

Baxter, Jo-Anna B; Wasan, Yaqub; Soofi, Sajid B; Suhag, Zamir; Bhutta, Zulfiqar A

2018-05-31

Risk factors known to impact maternal and newborn nutrition and health can exist from adolescence. If an undernourished adolescent girl becomes pregnant, her own health and pregnancy are at an increased risk for adverse outcomes. Offering preconception care from adolescence could provide an opportunity for health and nutrition promotion to improve one's own well-being, as well as future pregnancy outcomes and the health of the next generation. The Matiari emPowerment and Preconception Supplementation (MaPPS) Trial is a population-based two-arm, cluster-randomized, controlled trial of life skills building education and multiple micronutrient supplementation provided in a programmatic context to evaluate the impact on pre-identified nutrition and health outcomes among adolescent and young women (15-24 years) in Matiari district Pakistan, and the infants born to them within the context of the trial. The primary aim is to assess the effect of the intervention on the prevalence of low birth weight births (< 2500 g). The intervention includes bi-monthly life skills building education provided from preconception, and supplementation with multiple micronutrients during preconception (twice-weekly), pregnancy (daily), and post-partum (daily to 6 months). The standard of care includes non-regulated community-based health sessions and daily iron and folic acid supplementation during pregnancy. Additional outcome information will also be collected at set time periods. Among participants, these relate to nutrition (anthropometry, nutritional status), morbidity, and mortality. Among infants, these include birth outcomes (stillbirth, preterm birth, length of gestation, small for gestational age, birth defects), anthropometry, morbidity, and mortality. Preconception care from adolescence that includes interventions targeting life skills development and nutrition is suggested to be important to improving the health and nutrition of adolescent and young women and their future offspring. This study is expected to offer insight into providing such an intervention both within a programmatic context and with an extended exposure period prior to conception. The MaPPS Trial was registered retrospectively on clinicaltrials.gov (Identifier: NCT03287882 ) on September 19, 2017.

Future orientation and smoking cessation: secondary analysis of data from a smoking cessation trial.

PubMed

Beenstock, Jane; Lindson-Hawley, Nicola; Aveyard, Paul; Adams, Jean

2014-10-01

To examine the association between future orientation (how individuals consider and value outcomes in the future) and smoking cessation at 4 weeks and 6 months post quit-date in individuals enrolled in a smoking cessation study. Cohort analysis of randomized controlled trial data. UK primary care. Adults aged ≥18 years smoking ≥15 cigarettes daily, prepared to quit in the next 2 weeks. Future orientation was measured prior to quitting and at 4 weeks post-quitting using the Consideration of Future Consequences Scale. Smoking cessation at 4 weeks and 6 months was confirmed biochemically. Those lost to follow-up were assumed to not be abstinent. Potential confounders adjusted for were: age, gender, educational attainment, nicotine dependence and longest previous period quit. A total of 697 participants provided data at baseline; 422 provided information on future orientation at 4 weeks. There was no evidence of an association between future orientation at baseline and abstinence at 4 weeks [adjusted odds ratio (aOR) = 1.05, 95% confidence intervals (CI) 0.80-1.38] or 6 months (aOR = 0.85, 95% CI = 0.60-1.20). There was no change in future orientation from baseline to 4 weeks and no evidence that the change differed between those who were and were not quit at 4 weeks (adjusted regression coefficient = -0.04, 95% CI = -0.16 to 0.08). In smokers who are prepared to quit in the next 2 weeks, the extent of future orientation is unlikely to be a strong predictor of quitting over 4 weeks or 6 months and any increase in future orientation following quitting is likely to be small. © 2014 Society for the Study of Addiction.

Does it matter what you call it? A randomized trial of language used to describe palliative care services.

PubMed

Maciasz, R M; Arnold, R M; Chu, E; Park, S Y; White, D B; Vater, L B; Schenker, Y

2013-12-01

Integration of palliative care into oncology practice remains suboptimal. Misperceptions about the meaning of palliative care may negatively impact utilization. We assessed whether the term and/or description of palliative care services affected patient views. 2x2 between-subject randomized factorial telephone survey of 169 patients with advanced cancer. Patients were randomized into one of four groups that differed by name (supportive care vs. palliative care) and description (patient-centered vs. traditional). Main outcomes (0-10 Likert scale) were patient understanding, impressions, perceived need, and intended use of services. When compared to palliative care, the term supportive care was associated with better understanding (7.7 vs. 6.8; p = 0.021), more favorable impressions (8.4 vs. 7.3; p = 0.002), and higher future perceived need (8.6 vs. 7.7; p = 0.017). There was no difference in outcomes between traditional and patient-centered descriptions. In adjusted linear regression models, the term supportive care remained associated with more favorable impressions (p = 0.003) and higher future perceived need (p = 0.022) when compared to palliative care. Patients with advanced cancer view the name supportive care more favorably than palliative care. Future efforts to integrate principles of palliative medicine into oncology may require changing impressions of palliative care or substituting the term supportive care.

Factors Associated With Time to Site Activation, Randomization, and Enrollment Performance in a Stroke Prevention Trial.

PubMed

Demaerschalk, Bart M; Brown, Robert D; Roubin, Gary S; Howard, Virginia J; Cesko, Eldina; Barrett, Kevin M; Longbottom, Mary E; Voeks, Jenifer H; Chaturvedi, Seemant; Brott, Thomas G; Lal, Brajesh K; Meschia, James F; Howard, George

2017-09-01

Multicenter clinical trials attempt to select sites that can move rapidly to randomization and enroll sufficient numbers of patients. However, there are few assessments of the success of site selection. In the CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trials), we assess factors associated with the time between site selection and authorization to randomize, the time between authorization to randomize and the first randomization, and the average number of randomizations per site per month. Potential factors included characteristics of the site, specialty of the principal investigator, and site type. For 147 sites, the median time between site selection to authorization to randomize was 9.9 months (interquartile range, 7.7, 12.4), and factors associated with early site activation were not identified. The median time between authorization to randomize and a randomization was 4.6 months (interquartile range, 2.6, 10.5). Sites with authorization to randomize in only the carotid endarterectomy study were slower to randomize, and other factors examined were not significantly associated with time-to-randomization. The recruitment rate was 0.26 (95% confidence interval, 0.23-0.28) patients per site per month. By univariate analysis, factors associated with faster recruitment were authorization to randomize in both trials, principal investigator specialties of interventional radiology and cardiology, pre-trial reported performance >50 carotid angioplasty and stenting procedures per year, status in the top half of recruitment in the CREST trial, and classification as a private health facility. Participation in StrokeNet was associated with slower recruitment as compared with the non-StrokeNet sites. Overall, selection of sites with high enrollment rates will likely require customization to align the sites selected to the factor under study in the trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02089217. © 2017 American Heart Association, Inc.

[Methodological quality evaluation of randomized controlled trials for traditional Chinese medicines for treatment of sub-health].

PubMed

Zhao, Jun; Liao, Xing; Zhao, Hui; Li, Zhi-Geng; Wang, Nan-Yue; Wang, Li-Min

2016-11-01

To evaluate the methodological quality of the randomized controlled trials(RCTs) for traditional Chinese medicines for treatment of sub-health, in order to provide a scientific basis for the improvement of clinical trials and systematic review. Such databases as CNKI, CBM, VIP, Wanfang, EMbase, Medline, Clinical Trials, Web of Science and Cochrane Library were searched for RCTS for traditional Chinese medicines for treatment of sub-health between the time of establishment and February 29, 2016. Cochrane Handbook 5.1 was used to screen literatures and extract data, and CONSORT statement and CONSORT for traditional Chinese medicine statement were adopted as the basis for quality evaluation. Among the 72 RCTs included in this study, 67 (93.05%) trials described the inter-group baseline data comparability, 39(54.17%) trials described the unified diagnostic criteria, 28(38.89%) trials described the unified standards of efficacy, 4 (5.55%) trials mentioned the multi-center study, 19(26.38%) trials disclosed the random distribution method, 6(8.33%) trials used the random distribution concealment, 15(20.83%) trials adopted the method of blindness, 3(4.17%) study reported the sample size estimation in details, 5 (6.94%) trials showed a sample size of more than two hundred, 19(26.38%) trials reported the number of withdrawal, defluxion cases and those lost to follow-up, but only 2 trials adopted the ITT analysis,10(13.89%) trials reported the follow-up results, none of the trial reported the test registration and the test protocol, 48(66.7%) trials reported all of the indicators of expected outcomes, 26(36.11%) trials reported the adverse reactions and adverse events, and 4(5.56%) trials reported patient compliance. The overall quality of these randomized controlled trials for traditional Chinese medicines for treatment of sub-health is low, with methodological defects in different degrees. Therefore, it is still necessary to emphasize the correct application of principles such as blindness, randomization and control in RCTs, while requiring reporting in accordance with international standards. Copyright© by the Chinese Pharmaceutical Association.

Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.

PubMed

Muller, Julius; Parizotto, Eneida; Antrobus, Richard; Francis, James; Bunce, Campbell; Stranks, Amanda; Nichols, Marshall; McClain, Micah; Hill, Adrian V S; Ramasamy, Adaikalavan; Gilbert, Sarah C

2017-06-08

Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis. Twenty-one volunteers participated in an influenza challenge trial. We calculated the daily sum of scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 h post challenge was profiled on Illumina HT12v4 microarrays. Changes in gene expression most strongly correlated with DSS were selected to train a Random Forest model and tested on two independent test sets consisting of 41 individuals profiled on a different microarray platform and 33 volunteers assayed by qRT-PCR. 1456 probes are significantly associated with DSS at 1% false discovery rate. We selected 19 genes with the largest fold change to train a random forest model. We observed good concordance between predicted and actual scores in the first test set (r = 0.57; RMSE = -16.1%) with the greatest agreement achieved on samples collected approximately 72 h post challenge. Therefore, we assayed samples collected at baseline and 72 h post challenge in the second test set by qRT-PCR and observed good concordance (r = 0.81; RMSE = -36.1%). We developed a 19-gene qRT-PCR panel to predict DSS, validated on two independent datasets. A transcriptomics based panel could provide a more objective measure of symptom scoring in future influenza challenge studies. Trial registration Samples were obtained from a clinical trial with the ClinicalTrials.gov Identifier: NCT02014870, first registered on December 5, 2013.

Do Contemporary Randomized Controlled Trials Meet ESMO Thresholds for Meaningful Clinical Benefit?

PubMed

Del Paggio, J C; Azariah, B; Sullivan, R; Hopman, W M; James, F V; Roshni, S; Tannock, I F; Booth, C M

2017-01-01

The European Society for Medical Oncology (ESMO) recently released a magnitude of clinical benefit scale (ESMO-MCBS) for systemic therapies for solid cancers. Here, we evaluate contemporary randomized controlled trials (RCTs) against the proposed ESMO thresholds for meaningful clinical benefit. RCTs evaluating systemic therapy for breast cancer, nonsmall cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer published 2011-2015 were reviewed. Data were abstracted regarding trial characteristics and outcomes, and these were applied to the ESMO-MCBS. We also determined whether RCTs were designed to detect an effect that would meet clinical benefit as defined by the ESMO-MCBS. About 277 eligible RCTs were included (40% breast, 31% NSCLC, 22% CRC, 6% pancreas). Median sample size was 532 and 83% were funded by industry. Among all 277 RCTs, the experimental therapy was statistically superior to the control arm in 138 (50%) trials: results of only 31% (43/138) of these trials met the ESMO-MCBS clinical benefit threshold. RCTs with curative intent were more likely to meet clinically meaningful thresholds than those with palliative intent [61% (19/31) versus 22% (24/107), P < 0.001]. Among the 226 RCTs for which the ESMO-MCBS could be applied, 31% (70/226) were designed to detect an effect size that could meet ESMO-MCBS thresholds. Less than one-third of contemporary RCTs with statistically significant results meet ESMO thresholds for meaningful clinical benefit, and this represents only 15% of all published trials. Investigators, funding agencies, regulatory agencies, and industry should adopt more stringent thresholds for meaningful benefit in the design of future RCTs. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Intravenous iron isomaltoside 1000 (Monofer®) reduces postoperative anaemia in preoperatively non-anaemic patients undergoing elective or subacute coronary artery bypass graft, valve replacement or a combination thereof: a randomized double-blind placebo-controlled clinical trial (the PROTECT trial).

PubMed

Johansson, P I; Rasmussen, A S; Thomsen, L L

2015-10-01

This trial explores whether intravenous iron isomaltoside 1000 (Monofer®) results in a better regeneration of haemoglobin levels and prevents anaemia compared to placebo in preoperative non-anaemic patients undergoing cardiac surgery. The trial is a prospective, double-blind, comparative, placebo-controlled trial of 60 non-anaemic patients undergoing cardiac surgery. The patients were randomized 1:1 to either 1000 mg intravenous iron isomaltoside 1000 administered perioperatively by infusion or placebo. Mean preoperative haemoglobin in the active treatment group was 14·3 g/dl vs. 14·0 g/dl in the placebo group. At discharge 5 days after surgery, haemoglobin levels were reduced to 10·7 and 10·5 g/dl, respectively. One month after surgery, haemoglobin concentration had increased to an average of 12·6 g/dl vs. 11·8 g/dl (p = 0·012) and significantly more patients were non-anaemic in the intravenous iron isomaltoside 1000-treated group compared to the placebo group (38·5% vs. 8·0%; p = 0·019). There were no differences in side-effects between the groups. A single perioperative 1000 mg dose of intravenous iron isomaltoside 1000 significantly increased the haemoglobin level and prevented anaemia 4 weeks after surgery, with a short-term safety profile similar to placebo. Future trials on potential clinical benefits of preoperative treatment with intravenous iron in non-anaemic patients are needed. © 2015 The Authors ISBT Science Series published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.

Improving Language Comprehension in Preschool Children with Language Difficulties: A Cluster Randomized Trial

ERIC Educational Resources Information Center

Hagen, Åste M.; Melby-Lervåg, Monica; Lervåg, Arne

2017-01-01

Background: Children with language comprehension difficulties are at risk of educational and social problems, which in turn impede employment prospects in adulthood. However, few randomized trials have examined how such problems can be ameliorated during the preschool years. Methods: We conducted a cluster randomized trial in 148 preschool…

A Randomized Trial of Telephone Psychotherapy and Pharmacotherapy for Depression: Continuation and Durability of Effects

ERIC Educational Resources Information Center

Ludman, Evette J.; Simon, Gregory E.; Tutty, Steve; Von Korff, Michael

2007-01-01

Randomized trial evidence and expert guidelines are mixed regarding the value of combined pharmacotherapy and psychotherapy as initial treatment for depression. This study describes long-term results of a randomized trial (N = 393) evaluating telephone-based cognitive-behavioral therapy (CBT) plus care management for primary care patients…

Breast Cancer Screening by Physical Examination: Randomized Trial in the Phillipines

DTIC Science & Technology

2005-10-01

J -4327 TITLE: Breast Cancer Screening by Physical Examination: Randomized Trial in the Phillipines...Examination: Randomized Trial in the 5a. CONTRACT NUMBER Phillipines 5b. GRANT NUMBER DAMD17-94- J -4327 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Grant DAMD17-94- J -4327 3 Table of

Weighted re-randomization tests for minimization with unbalanced allocation.

PubMed

Han, Baoguang; Yu, Menggang; McEntegart, Damian

2013-01-01

Re-randomization test has been considered as a robust alternative to the traditional population model-based methods for analyzing randomized clinical trials. This is especially so when the clinical trials are randomized according to minimization, which is a popular covariate-adaptive randomization method for ensuring balance among prognostic factors. Among various re-randomization tests, fixed-entry-order re-randomization is advocated as an effective strategy when a temporal trend is suspected. Yet when the minimization is applied to trials with unequal allocation, fixed-entry-order re-randomization test is biased and thus compromised in power. We find that the bias is due to non-uniform re-allocation probabilities incurred by the re-randomization in this case. We therefore propose a weighted fixed-entry-order re-randomization test to overcome the bias. The performance of the new test was investigated in simulation studies that mimic the settings of a real clinical trial. The weighted re-randomization test was found to work well in the scenarios investigated including the presence of a strong temporal trend. Copyright © 2013 John Wiley & Sons, Ltd.

Omega-3 polyunsaturated fatty acids for cardiovascular diseases: present, past and future.

PubMed

Watanabe, Yasuhiro; Tatsuno, Ichiro

2017-08-01

Large-scale epidemiological studies on Greenlandic, Canadian and Alaskan Eskimos have examined the health benefits of omega-3 fatty acids consumed as part of the diet, and found statistically significant relative reduction in cardiovascular risk in people consuming omega-3 fatty acids. Areas covered: This article reviews studies on omega-3 fatty acids during the last 50 years, and identifies issues relevant to future studies on cardiovascular (CV) risk. Expert commentary: Although a meta-analysis of large-scale prospective cohort studies and randomized studies reported that fish and fish oil consumption reduced coronary heart disease-related mortality and sudden cardiac death, omega-3 fatty acids have not yet been shown to be effective in secondary prevention trials on patients with multiple cardiovascular disease (CVD) risk factors. The ongoing long-term CV interventional outcome studies investigate high-dose, prescription-strength omega-3 fatty acids. The results are expected to clarify the potential role of omega-3 fatty acids in reducing CV risk. The anti-inflammatory properties of omega-3 fatty acids are also important. Future clinical trials should also focus on the role of these anti-inflammatory mediators in human arteriosclerotic diseases as well as inflammatory diseases.

Acceptability and performance of the menstrual cup in South Africa: a randomized crossover trial comparing the menstrual cup to tampons or sanitary pads.

PubMed

Beksinska, Mags E; Smit, Jenni; Greener, Ross; Todd, Catherine S; Lee, Mei-ling Ting; Maphumulo, Virginia; Hoffmann, Vivian

2015-02-01

In low-income settings, many women and girls face activity restrictions during menses, owing to lack of affordable menstrual products. The menstrual cup (MC) is a nonabsorbent reusable cup that collects menstrual blood. We assessed the acceptability and performance of the MPower® MC compared to pads or tampons among women in a low-resource setting. We conducted a randomized two-period crossover trial at one site in Durban, South Africa, between January and November 2013. Participants aged 18-45 years with regular menstrual cycles were eligible for inclusion if they had no intention of becoming pregnant, were using an effective contraceptive method, had water from the municipal system as their primary water source, and had no sexually transmitted infections. We used a computer-generated randomization sequence to assign participants to one of two sequences of menstrual product use, with allocation concealed only from the study investigators. Participants used each method over three menstrual cycles (total 6 months) and were interviewed at baseline and monthly follow-up visits. The product acceptability outcome compared product satisfaction question scores using an ordinal logistic regression model with individual random effects. This study is registered on the South African Clinical Trials database: number DOH-27-01134273. Of 124 women assessed, 110 were eligible and randomly assigned to selected menstrual products. One hundred and five women completed all follow-up visits. By comparison to pads/tampons (usual product used), the MC was rated significantly better for comfort, quality, menstrual blood collection, appearance, and preference. Both of these comparative outcome measures, along with likelihood of continued use, recommending the product, and future purchase, increased for the MC over time. MC acceptance in a population of novice users, many with limited experience with tampons, indicates that there is a pool of potential users in low-resource settings.

The Surgical Treatments Outcomes Project for Dysfunctional Uterine Bleeding: summary of an Agency for Health Research and Quality-sponsored randomized trial of endometrial ablation versus hysterectomy for women with heavy menstrual bleeding.

PubMed

Munro, Malcolm G; Dickersin, Kay; Clark, Melissa A; Langenberg, Patricia; Scherer, Roberta W; Frick, Kevin D

2011-04-01

Surgical Treatments Outcomes Project for Dysfunctional Uterine Bleeding is an agency for the Healthcare Research and Quality project built around a multicenter randomized clinical trial comparing hysterectomy and endometrial ablation (EA) for the treatment of heavy menstrual bleeding unrelated to structural causes. For inclusion, women self-defined their complaint, and the endometrial cavity was evaluated to exclude structural lesions. The primary outcomes were bleeding and major problem "solved" at 24 months, with length of institutional stay, surgical complications, quality of life, and reoperation included as secondary outcomes. Also measured was the baseline economic impact of heavy menstrual bleeding. The randomized controlled trial enrolled 237 women. Institutional stay was longer, and perioperative adverse events were more common and severe for those randomized to hysterectomy. At 24 months, 94.4% and 84.9% of women randomized to hysterectomy and EA, respectively, considered their major problem to be solved; at 48 months, the numbers were similar at 98.0% and 85.1%. Postprocedure quality-of-life measures (SF-36, EuroQOL) improved similarly in both groups, but reoperation was more common for women undergoing EA (34, or 30.9%, at 60 mo), with most (32 of 34) selecting hysterectomy.At baseline, women reported missed work as well as activity and leisure limitations. Excess monetary costs were $306 per patient-year (95% CI, $30-$1,872). Excess work and home management loss costs were $2,152 (95% CI, $1,862-$2,479). It was estimated that successful treatment, regardless of the type of intervention, could result in a gain of 1.8 quality-adjusted life years. Future studies will examine and compare the impact of the study interventions on economic outcomes. © 2011 by The North American Menopause Society

The feasibility and acceptability of conducting a trial of specialist medical care and the Lightning Process in children with chronic fatigue syndrome: feasibility randomized controlled trial (SMILE study)

PubMed Central

2013-01-01

Background Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is relatively common in children with limited evidence for treatment. The Phil Parker Lightning Process (LP) is a trademarked intervention, which >250 children use annually. There are no reported studies investigating the effectiveness or possible side effects of LP. Methods The trial population was drawn from the Bath and Bristol NHS specialist paediatric CFS or ME service. The study was designed as a pilot randomized trial with children (aged 12 to 18 years) comparing specialist medical care with specialist medical care plus the Lightning Process. Integrated qualitative methodology was used to explore the feasibility and acceptability of the recruitment, randomization and interventions. Results A total of 56 children were recruited from 156 eligible children (1 October 2010 to 16 June 2012). Recruitment, randomization and both interventions were feasible and acceptable. Participants suggested changes to improve feasibility and acceptability and we incorporated the following in the trial protocol: stopped collecting 6-week outcomes; introduced a second reminder letter; used phone calls to collect primary outcomes from nonresponders; informed participants about different approaches of each intervention and changed our recommendation for the primary outcome for the full study from school attendance to disability (SF-36 physical function subscale) and fatigue (Chalder Fatigue Scale). Conclusions Conducting randomized controlled trials (RCTs) to investigate an alternative treatment such as LP is feasible and acceptable for children with CFS or ME. Feasibility studies that incorporate qualitative methodology enable changes to be made to trial protocols to improve acceptability to participants. This is likely to improve recruitment rate and trial retention. Trial registration Feasibility study first randomization: 29 September 2010. Trial registration: Current Controlled Trials ISRCTN81456207 (31 July 2012). Full trial first randomization: 19 September 2012. PMID:24304689

Quality of life after whole brain radiotherapy compared with radiosurgery of the tumor bed: results from a randomized trial.

PubMed

Kepka, L; Tyc-Szczepaniak, D; Osowiecka, K; Sprawka, A; Trąbska-Kluch, B; Czeremszynska, B

2018-02-01

A recent randomized trial (NCT01535209) demonstrated no difference in neurocognitive function between stereotactic radiotherapy of the tumor bed (SRT-TB) and whole brain radiotherapy (WBRT) in patients with resected single brain metastasis. Patients treated with SRT-TB had lower overall survival compared with the WBRT arm. Here, we compared the health-related quality of life (HRQOL) in patients who received WBRT vs. SRT-TB. A self-reported questionnaire was used to assess HRQOL (EORTC QLQ-C30 with the QLQ-BN20 module) before RT, 2 months after RT, and every 3 months thereafter. HRQOL results are presented as mean scores and compared between groups. Of 59 randomized patients, 37 (64%) were eligible for HRQOL analysis, 15 received SRT-TB, and 22 had WBRT. There were no differences between groups in global health status and main function scales/symptoms (except for drowsiness and appetite loss, which were worse with WBRT 2 months after RT). Global health status decreased 2 and 5 months after RT, but significantly only for SRT-TB (p = 0.025). Physical function decreased significantly 5 months after SRT-TB (p = 0.008). Future uncertainty worsened after RT, but significantly only for SRT-TB after 2 months (p = 0.036). Patients treated with WBRT had significant worsening of appetite, hair loss, and drowsiness after treatment. Despite higher symptom burden after WBRT attributed to the side effects of RT (such as appetite loss, drowsiness, and hair loss), global health status, physical functioning, and future uncertainty favored WBRT compared with SRT-TB. This may be related to the compromised brain tumor control with omission of WBRT.

Changing health behaviors to improve health outcomes after angioplasty: a randomized trial of net present value versus future value risk communication.

PubMed

Charlson, M E; Peterson, J C; Boutin-Foster, C; Briggs, W M; Ogedegbe, G G; McCulloch, C E; Hollenberg, J; Wong, C; Allegrante, J P

2008-10-01

Patients who have undergone angioplasty experience difficulty modifying at-risk behaviors for subsequent cardiac events. The purpose of this study was to test whether an innovative approach to framing of risk, based on 'net present value' economic theory, would be more effective in behavioral intervention than the standard 'future value approach' in reducing cardiovascular morbidity and mortality following angioplasty. At baseline, all patients completed a health assessment, received an individualized risk profile and selected risk factors for modification. The intervention randomized patients into two varying methods for illustrating positive effects of behavior change. For the experimental group, each selected risk factor was assigned a numeric biologic age (the net present value) that approximated the relative potential to improve current health status and quality of life when modifying that risk factor. In the control group, risk reduction was framed as the value of preventing future health problems. Ninety-four percent of patients completed 2-year follow-up. There was no difference between the rates of death, stroke, myocardial infarction, Class II-IV angina or severe ischemia (on non-invasive testing) between the net present value group and the future value group. Our results show that a net present risk communication intervention did not result in significant differences in health outcomes.

Feasibility study of the effects of art as a creative engagement intervention during stroke rehabilitation on improvement of psychosocial outcomes: study protocol for a single blind randomized controlled trial: the ACES study.

PubMed

Morris, Jacqui H; Kelly, Chris; Toma, Madalina; Kroll, Thilo; Joice, Sara; Mead, Gillian; Donnan, Peter; Williams, Brian

2014-09-28

Benefits of art participation after stroke are becoming increasingly recognized. Qualitative studies suggest that participation in visual arts creative engagement interventions (CEIs) during rehabilitation after stroke may improve mood, self-esteem, hope and some aspects of physical recovery. This study examines the feasibility of undertaking a randomized controlled trial of a CEI delivered by artists within in-patient stroke rehabilitation to test effectiveness. This trial is a two arm, single-blind, randomized controlled feasibility trial within in-patient stroke rehabilitation. We will recruit 80 patients receiving stroke rehabilitation in two stroke units in a health board area of Scotland (40 patients in each arm). Intervention arm participants will receive a visual-arts based CEI facilitated by experienced artists. Artists will follow an intervention protocol with specific components that enable participants to set, achieve and review artistic goals. Participants will receive up to eight intervention sessions, four within a group and four one-to-one with the artist. Control group participants will receive usual care only.Data collection will occur at baseline, post-intervention and three-month follow-up. Stroke-related health status is the primary outcome; mood, self-esteem, self-efficacy, perceived recovery control and hope are secondary outcomes. Semi-structured interviews will be conducted with purposively selected patients, artists and healthcare staff to elicit views and experiences of the intervention and feasibility and acceptability of trial processes. Recruitment rates, retention rates and patient preference for art participation will also be collected. Data will indicate, with confidence intervals, the proportion of patients choosing or refusing participation in the CEI and will allow calculation of recruitment rates for a future definitive trial. Summary data will indicate potential variability, magnitude and direction of difference between groups. Findings will inform sample size calculations for a definitive trial. Thematic analysis of qualitative data will be managed using the Framework Approach. Framework is an analytical approach for qualitative data, commonly used in policy and medical research. If shown to demonstrate effects, this intervention has the potential to address aspects of stroke recovery previously. Not routinely addressed in rehabilitation. Registered with Clinical Trials.Gov: NCT02085226 on 6th March 2014.

Rationale, design, and methodology of a trial evaluating three models of care for HCV treatment among injection drug users on opioid agonist therapy.

PubMed

Akiyama, Matthew J; Agyemang, Linda; Arnsten, Julia H; Heo, Moonseong; Norton, Brianna L; Schackman, Bruce R; Linas, Benjamin P; Litwin, Alain H

2018-02-09

People who inject drugs (PWID) constitute 60% of the approximately 5 million people in the U.S. infected with hepatitis C virus (HCV). Treatment of PWID is complex due to addiction, mental illness, poverty, homelessness, lack of positive social support, poor adherence-related skills, low motivation and knowledge, and poor access to and trust in the health care system. New direct-acting antiviral medications are available for HCV with high cure rates and few side effects. The life expectancy and economic benefits of new HCV treatments will not be realized unless we determine optimal models of care for the majority of HCV-infected patients. The purpose of this study is to evaluate the effectiveness of directly observed therapy and group treatment compared with self-administered individual treatment in a large, urban opioid agonist therapy clinic setting in the Bronx, New York. In this randomized controlled trial 150 PWID with chronic HCV were recruited from opioid agonist treatment (OAT) clinics and randomized to one of three models of onsite HCV treatment in OAT: 1) modified directly observed therapy; 2) group treatment; or 3) control - self-administered individual treatment. Participants were age 18 or older, HCV genotype 1, English or Spanish speaking, treatment naïve (or treatment experienced after 12/3/14), willing to receive HCV treatment onsite, receiving methadone or buprenorphine at the medication window at least once per week, and able to provide informed consent. Outcomes of interest include adherence (as measured by self-report and electronic blister packs), HCV treatment completion, sustained virologic response, drug resistance, and cost-effectiveness. This paper describes the design and rationale of a randomized controlled trial comparing three models of care for HCV therapy delivered in an opioid agonist treatment program. Our trial will be critical to rigorously identify models of care that result in high adherence and cure rates. Use of blister pack technology will help us determine the role of adherence in successful cure of HCV. Moreover, the trial methodology outlined here can serve as a template for the development of future programs and studies among HCV-infected drug users receiving opioid agonist therapy, as well as the cost-effectiveness of such programs. This trial was registered with ClinicalTrials.gov ( NCT01857245 ). Trial registration was obtained prospectively on May 20th, 2013.